WorldWideScience

Sample records for hoxc8 early enhancer

  1. Normal proliferation and differentiation of Hoxc-8 transgenic chondrocytes in vitro

    Directory of Open Access Journals (Sweden)

    Mello Maria

    2003-04-01

    Full Text Available Abstract Background Hox genes encode transcription factors that are involved in pattern formation in the skeleton, and recent evidence suggests that they also play a role in the regulation of endochondral ossification. To analyze the role of Hoxc-8 in this process in more detail, we applied in vitro culture systems, using high density cultures of primary chondrocytes from neonatal mouse ribs. Results Cultured cells were characterized on the basis of morphology (light microscopy and production of cartilage-specific extracellular matrix (sulfated proteoglycans and type II Collagen. Hypertrophy was demonstrated by increase in cell size, alkaline phosphatase activity and type X Collagen immunohistochemistry. Proliferation was assessed by BrdU uptake and flow cytometry. Unexpectedly, chondrocytes from Hoxc-8 transgenic mice, which exhibit delayed cartilage maturation in vivo 1, were able to proliferate and differentiate normally in our culture systems. This was the case even though freshly isolated Hoxc-8 transgenic chondrocytes exhibited significant molecular differences as measured by real-time quantitative PCR. Conclusions The results demonstrate that primary rib chondrocytes behave similar to published reports for chondrocytes from other sources, validating in vitro approaches for studies of Hox genes in the regulation of endochondral ossification. Our analysis of cartilage-producing cells from Hoxc-8 transgenic mice provides evidence that the cellular phenotype induced by Hoxc-8 overexpression in vivo is reversible in vitro.

  2. The third helix of the murine Hoxc8 homeodomain facilitates protein transduction in mammalian cells

    International Nuclear Information System (INIS)

    Kong, Kyoung-Ah; Gadi, Jogeswar; Park, Hyoung Woo; Bok, Jinwoong; Kim, Myoung Hee

    2008-01-01

    Previously, we have demonstrated that purified Hoxc8 homeoprotein has the ability to penetrate the cellular membrane and can be transduced efficiently into COS-7 cells. Moreover, the Hoxc8 protein is able to form a complex with DNA molecules in vitro and helps the DNA be delivered intracellularly, serving as a gene delivery vehicle. Here, we further analyzed the membrane transduction activity of Hoxc8 protein and provide the evidence that the 16 amino acid (a.a.191-206, 2.23 kDa) third helix of murine Hoxc8 protein is an efficient protein transduction domain (PTD). When the 16 amino acid peptide was fused at the carboxyl terminal of enhanced green fluorescence protein (EGFP), the fusion proteins were transduced efficiently into the primary pig fetal fibroblast cells. The transduction efficiency increased in a concentration-dependent manner up to 1 μM, and appeared to plateau above a concentration of 1 μM. When tandem multimers of PTD, EGFP-PTD(2), EGFP-PTD(3), EGFP-PTD(4), and EGFP-PTD(5), were analyzed at 500 nM of concentration, the penetrating efficiency increased in a dose-dependent manner. As the number of PTDs increased, the EGFP signal also increased, although the signal maintained plateau after EGFP-PTD(3). These results indicate that the 16 amino acid third helix is the key element responsible for the membrane transduction activity of Hoxc8 proteins, and further suggest that the small peptide could serve as a therapeutic delivery vehicle for large cargo proteins

  3. Expression of cartilage developmental genes in Hoxc8- and Hoxd4-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Claudia Kruger

    2010-02-01

    Full Text Available Hox genes encode transcription factors, which regulate skeletal patterning and chondrocyte differentiation during the development of cartilage, the precursor to mature bone. Overexpression of the homeobox transcription factors Hoxc8 and Hoxd4 causes severe cartilage defects due to delay in cartilage maturation. Matrix metalloproteinases (MMPs, bone morphogenetic proteins (BMPs and fibroblastic growth factors (FGFs are known to play important roles in skeletal development and endochondral bone formation and remodeling. In order to investigate whether these molecules are aberrantly expressed in Hoxc8- and/or Hoxd4-transgenic cartilage, we performed quantitative RT-PCR on chondrocytes from Hox-transgenic mice. Gene expression levels of Bmp4, Fgf8, Fgf10, Mmp9, Mmp13, Nos3, Timp3, Wnt3a and Wnt5a were altered in Hoxc8-transgenic chondrocytes, and Fgfr3, Ihh, Mmp8, and Wnt3a expression levels were altered in Hoxd4-transgenic chondrocytes, respectively. Notably, Wnt3a expression was elevated in Hoxc8- and reduced in Hoxd4-transgenic cartilage. These results suggest that both transcription factors affect cartilage maturation through different molecular mechanisms, and provide the basis for future studies into the role of these genes and possible interactions in pathogenesis of cartilage defects in Hoxc8- and Hoxd4-transgenic mice.

  4. Mouse Homologue of the Schizophrenia Susceptibility Gene ZNF804A as a Target of Hoxc8

    Directory of Open Access Journals (Sweden)

    Hyun Joo Chung

    2010-01-01

    Full Text Available Using a ChIP-cloning technique, we identified a Zinc finger protein 804a (Zfp804a as one of the putative Hoxc8 downstream target genes. We confirmed binding of Hoxc8 to an intronic region of Zfp804a by ChIP-PCR in F9 cells as well as in mouse embryos. Hoxc8 upregulated Zfp804a mRNA levels and augmented minimal promoter activity in vitro. In E11.5 mouse embryos, Zfp804a and Hoxc8 were coexpressed. Recent genome-wide studies identified Zfp804a (or ZNF804A in humans as a plausible marker for schizophrenia, leading us to hypothesize that this embryogenic regulatory control might also exert influence in development of complex traits such as psychosis.

  5. Molecular characterization of HOXC8 gene and methylation status analysis of its exon 1 associated with the length of cashmere fiber in Liaoning cashmere goat.

    Science.gov (United States)

    Bai, Wen L; Wang, Jiao J; Yin, Rong H; Dang, Yun L; Wang, Ze Y; Zhu, Yu B; Cong, Yu Y; Deng, Liang; Guo, Dan; Wang, Shi Q; Yang, Shu H; Xue, Hui L

    2017-02-01

    Homeobox protein Hox-C8 (HOXC8) is a member of Hox family. It is expressed in the dermal papilla of the skin and is thought to be associated with the hair inductive capacity of dermal papilla cells. In the present study, we isolated and characterized a full-length open reading frame of HOXC8 cDNA from the skin tissue of Liaoning cashmere goat, as well as, established a phylogenetic relationship of goat HOXC8 with that of other species. Also, we investigated the effect of methylation status of HOXC8 exon 1 at anagen secondary hair follicle on the cashmere fiber traits in Liaoning cashmere goat. The sequence analysis indicated that the obtained cDNA was 1134-bp in length containing a complete ORF of 729-bp. It encoded a peptide of 242 amino acid residues in length. The structural analysis indicated that goat HOXC8 contained a typical homeobox domain. The phylogenetic analysis revealed that Capra hircus HOXC8 had a closer genetic relationship with that of Ovis aries, followed by Bos Taurus and Bubalus bubalis. The methylation analysis suggested that the methylation degree of HOXC8 exon 1 in anagen secondary hair follicle might be involved in regulating the growth of cashmere fiber in Liaoning cashmere goat. Our results provide new evidence for understanding the molecular structural and evolutionary characteristics of HOXC8 in Liaoning cashmere goat, as well as, for further insight into the role of methylation degree of HOXC8 exon 1 regulates the growth of cashmere fiber in goat.

  6. Long Noncoding RNA HOXC-AS1 Suppresses Ox-LDL-Induced Cholesterol Accumulation Through Promoting HOXC6 Expression in THP-1 Macrophages.

    Science.gov (United States)

    Huang, Chuan; Hu, Yan-Wei; Zhao, Jing-Jing; Ma, Xin; Zhang, Yuan; Guo, Feng-Xia; Kang, Chun-Min; Lu, Jing-Bo; Xiu, Jian-Cheng; Sha, Yan-Hua; Gao, Ji-Juan; Wang, Yan-Chao; Li, Pan; Xu, Bang-Ming; Zheng, Lei; Wang, Qian

    2016-11-01

    Atherosclerosis is a common pathological basis of cardiovascular disease, which remains the leading cause of mortality. Long noncoding RNAs (lncRNAs) are newly studied non-protein-coding RNAs involved in gene regulation, but how lncRNAs exert regulatory effect on atherosclerosis remains unclear. In this study, we found that lncRNA HOXC cluster antisense RNA 1 (HOXC-AS1) and homeobox C6 (HOXC6) were downregulated in carotid atherosclerosis by performing microarray analysis. The results were verified in atherosclerotic plaques and normal arterial intima tissues by quantitative reverse transcription PCR and western blot analysis. Lentivirus-mediated overexpression of HOXC-AS1 induced HOXC6 expression at mRNA and protein levels in THP-1 macrophages. Besides, oxidized low-density lipoprotein (Ox-LDL) decreased expression of HOXC-AS1 and HOXC6 in a time-dependent manner. Induction of cholesterol accumulation by Ox-LDL could be partly suppressed by overexpression of HOXC-AS1.

  7. DNA Methylation and the HOXC6 Paradox in Prostate Cancer

    International Nuclear Information System (INIS)

    Vinarskaja, Anna; Yamanaka, Masanori; Ingenwerth, Marc; Schulz, Wolfgang A.

    2011-01-01

    Overexpression of the classical homeobox transcription factor HOXC6 is frequent in prostate cancers and correlates with adverse clinical parameters. Since surprisingly many HOXC6 target genes are downregulated in prostate cancer, it has been posited that oncogenic effects of HOXC6 in prostate cancer may be unmasked by concurrent epigenetic downregulation of target genes exerting tumor suppressive effects. To test this hypothesis, we have studied the expression of three HOXC6 target genes, CNTN1 (encoding a cell adhesion protein), DKK3 and WIF1 (encoding WNT growth factor antagonists) as well as DNA methylation of DKK3 and WIF1. HOXC6 upregulation and association with poor prognosis were confirmed in our tissue series. The three target genes were each significantly downregulated in cancer tissues and expression of each one correlated inversely with that of HOXC6. Cases with lower WIF1 expression showed significantly earlier recurrence (p = 0.021), whereas no statistical significance was reached for CNTN1 and DKK3. Hypermethylation of DKK3 or WIF1 gene promoters was observed in a subset of cancers with downregulated expression, but was often weak. Our data support the hypothesis that HOXC6 target genes exerting tumor-suppressive effects are epigenetically downregulated in prostate cancer, but DNA methylation appears to follow or bolster rather than to cause their transcriptional inactivation

  8. Bisphenol-A induces expression of HOXC6, an estrogen-regulated homeobox-containing gene associated with breast cancer.

    Science.gov (United States)

    Hussain, Imran; Bhan, Arunoday; Ansari, Khairul I; Deb, Paromita; Bobzean, Samara A M; Perrotti, Linda I; Mandal, Subhrangsu S

    2015-06-01

    HOXC6 is a homeobox-containing gene associated with mammary gland development and is overexpressed in variety of cancers including breast and prostate cancers. Here, we have examined the expression of HOXC6 in breast cancer tissue, investigated its transcriptional regulation via estradiol (E2) and bisphenol-A (BPA, an estrogenic endocrine disruptor) in vitro and in vivo. We observed that HOXC6 is differentially over-expressed in breast cancer tissue. E2 induces HOXC6 expression in cultured breast cancer cells and in mammary glands of Sprague Dawley rats. HOXC6 expression is also induced upon exposure to BPA both in vitro and in vivo. Estrogen-receptor-alpha (ERα) and ER-coregulators such as MLL-histone methylases are bound to the HOXC6 promoter upon exposure to E2 or BPA and that resulted in increased histone H3K4-trimethylation, histone acetylation, and recruitment of RNA polymerase II at the HOXC6 promoter. HOXC6 overexpression induces expression of tumor growth factors and facilitates growth 3D-colony formation, indicating its potential roles in tumor growth. Our studies demonstrate that HOXC6, which is a critical player in mammary gland development, is upregulated in multiple cases of breast cancer, and is transcriptionally regulated by E2 and BPA, in vitro and in vivo. Published by Elsevier B.V.

  9. Role of Hoxc genes in the development of the limb integumentary organ (nail, claw, or hoof).

    Science.gov (United States)

    Lasierra, Maria Angeles Ros; Fernández-Guerrero, Marc; Delisle, Lucille; Yakushiji-Kaminatsui, Nayuta; Darbellay, Fabrice; Pérez-Gómez, Rocío; Duboule, Denis

    2018-04-01

    The developing vertebrate limb has long proved as an excellent system for studying the mechanisms involved in pattern formation and morphogenesis and more recently in transcriptional regulation and morphological evolution. To elucidate the stage-specific expression profiles of the components of the developing limb, we have generated the temporal transcriptome of the limb progenitors and of the overlying ectoderm separately. Our study has uncovered a collinear activation of Hoxc genes in the limb ectoderm that we have validated by in situ hybridization. However, while members of the HoxA and HoxD clusters show complex and dynamic patterns of expression during limb development that correlate with the morphology of the different limb segments, no specific function for the HoxC or HoxB clusters has been identified ( 1 - 3 ). To investigate the function of Hoxc genes in the limb ectoderm, we have reexamined the HoxC cluster null mice. Remarkably, and despite exhibiting normal terminal phalanges, these mice didn't form claws (anonychia). Morphological and immunohistochemical analysis identified a failure in the differentiation of the main components of the nail/claw organ. To unravel the transcriptional regulation of Hoxc genes in the limb ectoderm, we used the ATACseq technique. Using this approach, we identified two putative regulatory regions which activity was tested in mouse transgenic enhancer assays. It is currently considered that Hox genes have played a key role in the evolution of morphological traits, probably associated with changes in their regulatory landscapes ( 4 ). Given that the form and size of the distal limb integumentary organ (nail, claw or hoof) correlates with that of the distal phalanx and that the development of hooves was a major innovation in the evolution of a cursorial lifestyle, we are also exploring the possible implication of Hoxc genes in the nail/claw/hoof transition. This abstract is from the Experimental Biology 2018 Meeting. There

  10. The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and nail differentiation.

    Science.gov (United States)

    Potter, Christopher S; Pruett, Nathanael D; Kern, Michael J; Baybo, Mary Ann; Godwin, Alan R; Potter, Kathleen A; Peterson, Ron L; Sundberg, John P; Awgulewitsch, Alexander

    2011-04-01

    Among the Hox genes, homeobox C13 (Hoxc13) has been shown to be essential for proper hair shaft differentiation, as Hoxc13 gene-targeted (Hoxc13(tm1Mrc)) mice completely lack external hair. Because of the remarkable overt phenotypic parallels to the Foxn1(nu) (nude) mutant mice, we sought to determine whether Hoxc13 and forkhead box N1 (Foxn1) might act in a common pathway of hair follicle (HF) differentiation. We show that the alopecia exhibited by both the Hoxc13(tm1Mrc) and Foxn1(nu) mice is because of strikingly similar defects in hair shaft differentiation and that both mutants suffer from a severe nail dystrophy. These phenotypic similarities are consistent with the extensive overlap between Hoxc13 and Foxn1 expression patterns in the HF and the nail matrix. Furthermore, DNA microarray analysis of skin from Hoxc13(tm1Mrc) mice identified Foxn1 as significantly downregulated along with numerous hair keratin genes. This Foxn1 downregulation apparently reflects the loss of direct transcriptional control by HOXC13 as indicated by our results obtained through co-transfection and chromatin immunoprecipitation (ChIP) assays. As presented in the discussion, these data support a regulatory model of keratinocyte differentiation in which HOXC13-dependent activation of Foxn1 is part of a regulatory cascade controlling the expression of terminal differentiation markers.

  11. HOXC9-Induced Differentiation in Neuroblastoma Development

    Science.gov (United States)

    2014-10-01

    by HOXC9-binding peaks with the motif-finding program MEME revealed that the most enriched binding motif (T/ATTTAT, E value = 1.6e-35) corresponds to...sequences from predicted peak summits and ran MEME for identify- ing statistically overrepresented motifs. We performed MAST to search motifs in the

  12. A Novel Homozygous Missense Mutation in HOXC13 Leads to Autosomal Recessive Pure Hair and Nail Ectodermal Dysplasia.

    Science.gov (United States)

    Li, Xiaoxiao; Orseth, Meredith Lee; Smith, J Michael; Brehm, Mary Abigail; Agim, Nnenna Gebechi; Glass, Donald Alexander

    2017-03-01

    Pure hair and nail ectodermal dysplasia (PHNED) is a rare disorder that presents with hypotrichosis and nail dystrophy while sparing other ectodermal structures such as teeth and sweat glands. We describe a homozygous novel missense mutation in the HOXC13 gene that resulted in autosomal recessive PHNED in a Hispanic child. The mutation c.812A>G (p.Gln271Arg) is located within the DNA-binding domain of the HOXC13 gene, cosegregates within the family, and is predicted to be maximally damaging. This is the first reported case of a missense HOXC13 mutation resulting in PHNED and the first reported case of PHNED identified in a North American family. Our findings illustrate the critical role of HOXC13 in human hair and nail development. © 2017 Wiley Periodicals, Inc.

  13. YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues.

    Science.gov (United States)

    Liu, Ming; Zhao, Shuangyun; Lin, Qingjie; Wang, Xiu-Ping

    2015-04-01

    Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family.

    Science.gov (United States)

    Khan, Anwar Kamal; Muhammad, Noor; Aziz, Abdul; Khan, Sher Alam; Shah, Khadim; Nasir, Abdul; Khan, Muzammil Ahmad; Khan, Saadullah

    2017-04-12

    Pure hair and nail ectodermal dysplasia (PHNED) is a congenital disorder of hair abnormalities and nail dysplasia. Both autosomal recessive and dominant inheritance fashion of PHNED occurs. In literature, to date, five different forms of PHNED have been reported at molecular level, having three genes known and two loci with no gene yet. In this study, a four generations consanguineous family of Pakistani origin with autosomal recessive PHNED was investigated. Affected members exhibited PHNED phenotypes with involvement of complete hair loss and nail dysplasia. To screen for mutation in the genes (HOXC13, KRT74, KRT85), its coding exons and exons-intron boundaries were sequenced. The 3D models of normal and mutated HOXC13 were predicted by using homology modeling. Through investigating the family to known loci, the family was mapped to ectodermal dysplasia 9 (ECTD9) loci with genetic address of 12q13.13. Mutation screening revealed a novel missense mutation (c.929A > C; p.Asn310Thr) in homeobox DNA binding domain of HOXC13 gene in affected members of the family. Due to mutation, loss of hydrogen bonding and difference in potential energy occurs, which may resulting in alteration of protein function. This is the first mutation reported in homeodomain, while 5 th mutation reported in HOXC13 gene causing PHNED.

  15. Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

    Science.gov (United States)

    Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

    2016-01-01

    Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms

  16. Early Gadolinium Enhancement for Determination of Area at Risk

    DEFF Research Database (Denmark)

    Hammer-Hansen, Sophia; Leung, Steve W; Hsu, Li-Yueh

    2017-01-01

    OBJECTIVES: The aim of this study was to determine whether early gadolinium enhancement (EGE) by cardiac magnetic resonance (CMR) in a canine model of reperfused myocardial infarction depicts the area at risk (AAR) as determined by microsphere blood flow analysis. BACKGROUND: It remains controver......OBJECTIVES: The aim of this study was to determine whether early gadolinium enhancement (EGE) by cardiac magnetic resonance (CMR) in a canine model of reperfused myocardial infarction depicts the area at risk (AAR) as determined by microsphere blood flow analysis. BACKGROUND: It remains...... requires pathological validation. METHODS: Eleven dogs underwent 2 h of coronary artery occlusion and 48 h of reperfusion before imaging at 1.5-T. EGE imaging was performed 3 min after contrast administration with coverage of the entire left ventricle. Late gadolinium enhancement imaging was performed...... on native T1 and T2 maps. The size of EGE was significantly greater than the infarct by triphenyltetrazolium chloride (44.1 ± 15.8% vs. 20.7 ± 14.4%; p gadolinium enhancement (44.1 ± 15.8% vs. 23.5 ± 12.7%; p

  17. The embryonic genes Dkk3, Hoxd8, Hoxd9 and Tbx1 identify muscle types in a diet-independent and fiber-type unrelated way

    Directory of Open Access Journals (Sweden)

    Boekschoten Mark V

    2010-03-01

    Full Text Available Abstract Background The mouse skeletal muscle is composed of four distinct fiber types that differ in contractile function, number of mitochondria and metabolism. Every muscle type has a specific composition and distribution of the four fiber types. To find novel genes involved in specifying muscle types, we used microarray analysis to compare the gastrocnemius with the quadriceps from mice fed a low fat diet (LFD or high fat diet (HFD for 8 weeks. Additional qPCR analysis were performed in the gastrocnemius, quadriceps and soleus muscle from mice fed an LFD or HFD for 20 weeks. Results In mice fed the 8-week LFD 162 genes were differentially expressed in the gastrocnemius vs. the quadriceps. Genes with the strongest differences in expression were markers for oxidative fiber types (e.g. Tnni1 and genes which are known to be involved in embryogenesis (Dkk3, Hoxd8,Hoxd9 and Tbx1. Also Dkk2, Hoxa5, Hoxa10, Hoxc9, Hoxc10, Hoxc6 and Tbx15 were detectably, but not differentially expressed in adult muscle tissue. Expression of differentially expressed genes was not influenced by an 8-week or 20-week HFD. Comparing gastrocnemius, quadriceps and soleus, expression of Hoxd8 and Hoxd9 was not related with expression of markers for the four different fiber types. We found that the expression of both Hoxd8 and Hoxd9 was much higher in the gastrocnemius than in the quadriceps or soleus, whereas the expression of Dkk3 was high in quadriceps, but low in both gastrocnemius and soleus. Finally, expression of Tbx1 was high in quadriceps, intermediate in soleus and low in gastrocnemius. Conclusions We found that genes from the Dkk family, Hox family and Tbx family are detectably expressed in adult mouse muscle. Interestingly, expression of Dkk3, Hoxd8, Hoxd9 and Tbx1 was highly different between gastrocnemius, quadriceps and soleus. In fact, every muscle type showed a unique combination of expression of these four genes which was not influenced by diet. Altogether

  18. Evaluation of the early enhancement of coronary atherosclerotic plaque by contrast-enhanced MR angiography

    Energy Technology Data Exchange (ETDEWEB)

    Li Tao [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhao Xihai [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Liu Xin [Paul C. Lauterbur Biomedical Imaging Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen 518067 (China); Gao Jianhua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Zhao Shaohong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Li Xin; Zhou Weihua [Department of Radiology, The General Hospital of Chinese People' s Armed Police Forces, Number 69, Yong Ding Road, Hai Dian District, Beijing (China); Cai Zulong [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China); Zhang Weiguo [Cardiovascular and Neurological Consulting Institute, 6771 San Fernando, Irving, TX 75039 (United States); Yang Li, E-mail: Yangli301@yahoo.com [Department of Radiology, Chinese People' s Liberation Army General Hospital, Number 28, Fu Xing Road, Hai Dian District, Beijing (China)

    2011-10-15

    Purpose: To evaluate the early enhancement of coronary atherosclerotic plaque using contrast-enhanced MR angiography (CE-MRA) and investigate the association between unstable angina pectoris (UAP) and early enhancement of the plaque. Methods: Forty-one patients presenting with angina pectoris and demonstrating single-vessel disease with non-calcified plaque and significant coronary stenosis ({>=}50%) on CTA were consecutively recruited for coronary CE-MRA. Contrast-to-noise ratio of the culprit plaque guided by CTA was measured on a cross-sectional multi-planar reconstruction image of the plaque on both pre- and post-CE-MRA. A 50% increasing of CNR was defined as plaque enhancement. The association between early enhancement of the plaques and UAP was analyzed. Results: Thirty-seven non-calcified plaques with significant coronary stenosis were detected in the 37 patients on MRA. 4 subjects were excluded because coronary atherosclerotic plaques were inadequate for identification on MRA. Of the 37 patients, 18 patients had UAP and other 19 patients presented stable angina pectoris (SAP). Of the 37 plaques on CE-MRA, 13 and 24 plaques presented early enhancement and no enhancement, respectively. Of the 13 early-enhanced plaques, 11 (85%) and 2 (15%) were found in the patients with UAP and SAP, respectively (p < 0.01). Of the 37 patients, 11 (61%) with UAP and 2 (11%) with SAP had early-enhanced plaques, respectively (p < 0.01). Conclusion: CE-MRA allows detection of early enhancement of coronary atherosclerotic plaque. The early enhancement is common in unstable angina and could be a sign of vulnerability.

  19. Enhanced human papillomavirus type 8 oncogene expression levels are crucial for skin tumorigenesis in transgenic mice

    International Nuclear Information System (INIS)

    Hufbauer, M.; Lazic, D.; Akguel, B.; Brandsma, J.L.; Pfister, H.; Weissenborn, S.J.

    2010-01-01

    Human papillomavirus 8 (HPV8) is involved in skin cancer development in epidermodysplasia verruciformis patients. Transgenic mice expressing HPV8 early genes (HPV8-CER) developed papillomas, dysplasias and squamous cell carcinomas. UVA/B-irradiation and mechanical wounding of HPV8-CER mouse skin led to prompt papilloma induction in about 3 weeks. The aim of this study was to analyze the kinetics and level of transgene expression in response to skin irritations. Transgene expression was already enhanced 1 to 2 days after UVA/B-irradiation or tape-stripping and maintained during papilloma development. The enhanced transgene expression could be assigned to UVB and not to UVA. Papilloma development was thus always paralleled by an increased transgene expression irrespective of the type of skin irritation. A knock-down of E6 mRNA by tattooing HPV8-E6-specific siRNA led to a delay and a lower incidence of papilloma development. This indicates that the early increase of viral oncogene expression is crucial for induction of papillomatosis.

  20. Associative Learning during Early Adulthood Enhances Later Memory Retention in Honeybees

    Science.gov (United States)

    Arenas, Andrés; Fernández, Vanesa M.; Farina, Walter M.

    2009-01-01

    Background Cognitive experiences during the early stages of life play an important role in shaping the future behavior in mammals but also in insects, in which precocious learning can directly modify behaviors later in life depending on both the timing and the rearing environment. However, whether olfactory associative learning acquired early in the adult stage of insects affect memorizing of new learning events has not been studied yet. Methodology Groups of adult honeybee workers that experienced an odor paired with a sucrose solution 5 to 8 days or 9 to 12 days after emergence were previously exposed to (i) a rewarded experience through the offering of scented food, or (ii) a non-rewarded experience with a pure volatile compound in the rearing environment. Principal Findings Early rewarded experiences (either at 1–4 or 5–8 days of adult age) enhanced retention performance in 9–12-day-conditioned bees when they were tested at 17 days of age. The highest retention levels at this age, which could not be improved with prior rewarded experiences, were found for memories established at 5–8 days of adult age. Associative memories acquired at 9–12 days of age showed a weak effect on retention for some pure pre-exposed volatile compounds; whereas the sole exposure of an odor at any younger age did not promote long-term effects on learning performance. Conclusions The associative learning events that occurred a few days after adult emergence improved memorizing in middle-aged bees. In addition, both the timing and the nature of early sensory inputs interact to enhance retention of new learning events acquired later in life, an important matter in the social life of honeybees. PMID:19956575

  1. Associative learning during early adulthood enhances later memory retention in honeybees.

    Directory of Open Access Journals (Sweden)

    Andrés Arenas

    Full Text Available BACKGROUND: Cognitive experiences during the early stages of life play an important role in shaping the future behavior in mammals but also in insects, in which precocious learning can directly modify behaviors later in life depending on both the timing and the rearing environment. However, whether olfactory associative learning acquired early in the adult stage of insects affect memorizing of new learning events has not been studied yet. METHODOLOGY: Groups of adult honeybee workers that experienced an odor paired with a sucrose solution 5 to 8 days or 9 to 12 days after emergence were previously exposed to (i a rewarded experience through the offering of scented food, or (ii a non-rewarded experience with a pure volatile compound in the rearing environment. PRINCIPAL FINDINGS: Early rewarded experiences (either at 1-4 or 5-8 days of adult age enhanced retention performance in 9-12-day-conditioned bees when they were tested at 17 days of age. The highest retention levels at this age, which could not be improved with prior rewarded experiences, were found for memories established at 5-8 days of adult age. Associative memories acquired at 9-12 days of age showed a weak effect on retention for some pure pre-exposed volatile compounds; whereas the sole exposure of an odor at any younger age did not promote long-term effects on learning performance. CONCLUSIONS: The associative learning events that occurred a few days after adult emergence improved memorizing in middle-aged bees. In addition, both the timing and the nature of early sensory inputs interact to enhance retention of new learning events acquired later in life, an important matter in the social life of honeybees.

  2. Chromosomal Alterations and Gene Expression Changes Associated with the Progression of Leukoplakia to Advanced Gingivobuccal Cancer

    Directory of Open Access Journals (Sweden)

    Priyanka G. Bhosale

    2017-06-01

    Full Text Available We present an integrative genome-wide analysis that can be used to predict the risk of progression from leukoplakia to oral squamous cell carcinoma (OSCC arising in the gingivobuccal complex (GBC. We find that the genomic and transcriptomic profiles of leukoplakia resemble those observed in later stages of OSCC and that several changes are associated with this progression, including amplification of 8q24.3, deletion of 8p23.2, and dysregulation of DERL3, EIF5A2, ECT2, HOXC9, HOXC13, MAL, MFAP5 and NELL2. Comparing copy number profiles of primary tumors with and without lymph-node metastasis, we identify alterations associated with metastasis, including amplifications of 3p26.3, 8q24.21, 11q22.1, 11q22.3 and deletion of 8p23.2. Integrative analysis reveals several biomarkers that have never or rarely been reported in previous OSCC studies, including amplifications of 1p36.33 (attributable to MXRA8, 3q26.31 (EIF5A2, 9p24.1 (CD274, and 12q13.2 (HOXC9 and HOXC13. Additionally, we find that amplifications of 1p36.33 and 11q22.1 are strongly correlated with poor clinical outcome. Overall, our findings delineate genomic changes that can be used in treatment management for patients with potentially malignant leukoplakia and OSCC patients with higher risk of lymph-node metastasis.

  3. MR imaging of the early rheumatoid arthritis: usefulness of contrast enhanced fat suppressed SPGR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Mi; Joo, Kyung Bin; Kim, Seong Tae; Hahm, Chang Kok [College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    1995-06-15

    To evaluate value of post-contrast 3-Dimensional fat suppressed Spoiled GRASS (FS SPGR) in detecting subtle bony erosion and tenosynovitis of hands and wrists due to early rheumatoid arthritis. Fourteen MR imagings of the hands and wrists were performed in 7 early rheumatoid arthritis without any abnormalities in plain radiography and in 7 healthy volunteers. All subjects underwent MR sequence of coronal 3D FS SPGR with and without contrast enhancement in 1.5T MR unit. We evaluated the number of the bony erosion and tenosynovitis respectively in pre-and post-contrast FS SPGR images. The abnormal enhancing areas were not demonstrated in 7 healthy volunteers. Seven patients had 25 bony erosions in pre-contrast FS SPGR and 52 bony erosions with tenosynovitis (n = 10) in post-contrast FS SPGR. Enhancing joint spaces were shown in 8 cases. Post-contrast FS SPGR was better than pre-contrast FS SPGR in the evaluation of early rheumatoid arthritis and is valuable as a baseline study.

  4. MR imaging of the early rheumatoid arthritis: usefulness of contrast enhanced fat suppressed SPGR imaging

    International Nuclear Information System (INIS)

    Kim, Sun Mi; Joo, Kyung Bin; Kim, Seong Tae; Hahm, Chang Kok

    1995-01-01

    To evaluate value of post-contrast 3-Dimensional fat suppressed Spoiled GRASS (FS SPGR) in detecting subtle bony erosion and tenosynovitis of hands and wrists due to early rheumatoid arthritis. Fourteen MR imagings of the hands and wrists were performed in 7 early rheumatoid arthritis without any abnormalities in plain radiography and in 7 healthy volunteers. All subjects underwent MR sequence of coronal 3D FS SPGR with and without contrast enhancement in 1.5T MR unit. We evaluated the number of the bony erosion and tenosynovitis respectively in pre-and post-contrast FS SPGR images. The abnormal enhancing areas were not demonstrated in 7 healthy volunteers. Seven patients had 25 bony erosions in pre-contrast FS SPGR and 52 bony erosions with tenosynovitis (n = 10) in post-contrast FS SPGR. Enhancing joint spaces were shown in 8 cases. Post-contrast FS SPGR was better than pre-contrast FS SPGR in the evaluation of early rheumatoid arthritis and is valuable as a baseline study

  5. Early versus late GD-DTPA MRI enhancement in experimental glioblastomas.

    Science.gov (United States)

    Farace, Paolo; Tambalo, Stefano; Fiorini, Silvia; Merigo, Flavia; Daducci, Alessandro; Nicolato, Elena; Conti, Giamaica; Degrassi, Anna; Sbarbati, Andrea; Marzola, Pasquina

    2011-03-01

    To compare early versus late enhancement in two glioblastoma models characterized by different infiltrative/edematous patterns. Three weeks after inoculation into nude mice of U87MG and U251 cells, T1-weighted images were acquired early (10.5 min), intermediate (21 min) and late (30.5 min) after a bolus injection of Gd-DTPA at 300 μ mol/kg dosage. EARLY(TH) and LATE(TH) were the corresponding volumes with an enhancement higher than a threshold TH, defined by the mean (μ) and standard deviation (σ) on a contralateral healthy area. ADD(TH) was the enhancing volume found in LATE(TH) but not in EARLY(TH). T2 imaging of both tumors was performed, and T2 mapping of U251. In all tumors, LATE(TH) was significantly higher than EARLY(TH) for TH ranging from μ+σ to μ+5σ. The ADD(TH) /EARLY(TH) ratio was not significantly different when U251 and U87MG tumors were compared. In the U87MG tumors, some enhancement was observed outside the regularly demarcated T2-hyperintense area. In the U251 tumors, irregularly T2 demarcated, a large portion of ADD(μ+3σ) had normal T2 values. At histology, U251 showed a higher infiltrative pattern than U87MG. In these models, the increase over time in the enhancing volume did not depend on the different infiltrative/edematous patterns and was not closely related with edema. Copyright © 2011 Wiley-Liss, Inc.

  6. Korelasi Jumlah Streptococcus mutans (S. mutans dan Level Ekspresi Interlukin 8 (IL-8 pada Severe Early Childhood Caries

    Directory of Open Access Journals (Sweden)

    Muhammad Luthfi

    2015-12-01

    Full Text Available Karies gigi pada anak usia dini merupakan masalah kesehatan yang sangat serius karena merupakan penyakit infeksi kronis yang menular. Dalam beberapa tahun terakhir pandangan tentang neutrofil telah berubah secara dramatis. Neutrofil tidak hanya berperan sebagai pembunuh mikroba melalui proses fagositosis, pelepasan reactive oxigen species (ROS dan peptida antimikrobialnya tetapi neutrofil turut mengatur aktifasi respon imun. Interleukin-8 (IL-8 berfungsi sebagai aktivator kuat dan kemoatraktan neutrofil oleh karena itu IL-8 merupakan mediator kunci dalam migrasi neutrofil ke lokasi peradangan dan infeksi. Untuk menganalisis hubungan dari jumlah S. mutans dan ekspresi IL-8 neutrofil saliva pada anak usia dini bebas karies dan severe early childhood caries (S-ECC. Perlakuan dilakukan pada dua kelompok yaitu isolasi dan menghitung jumlah S. mutans pada sampel saliva dan sampel hasil kumur dengan NaCl 1,5% yang diisolasi neutrofilnya kemudian dianalisis ekspresi IL-8 menggunakan flow cytometry dari 20 anak bebas karies dan 20 anak severe early childhood caries. Hasil nilai rata-rata diketahui bahwa jumlah S. mutans anak usia dini bebas karies lebih rendah (513.500,00±185.565,28 CFU/ml dibandingkan dengan S-ECC (977.000,00±222.500,15 CFU/ml, sedangkan ekspresi IL-8 neutrofil saliva anak usia dini bebas karies lebih tinggi (3,31±0,50 dibandingkan dengan S-ECC (2,95+0,56. Penurunan ekspresi IL-8 neutrofil saliva kemungkinan sebagai penyebab meningkatnya jumlah S. mutans pada S-ECC. Correlation of Streptococcus mutans (S. mutans Level and Interleukin 8 (IL-8 Expressions of Salivary Neutrophils in Severe Early Childhood Caries. Early childhood caries is a very serious health problem because it is a chronic infectious disease that is contagious. Dental caries begins after the primary teeth grow and develop on the tooth surface very quickly and progressively. In recent years the views of neutrophils have changed dramatically. Neutrophils

  7. Early discrimination of nasopharyngeal carcinoma based on tissue deoxyribose nucleic acid surface-enhanced Raman spectroscopy analysis

    Science.gov (United States)

    Qiu, Sufang; Li, Chao; Lin, Jinyong; Xu, Yuanji; Lu, Jun; Huang, Qingting; Zou, Changyan; Chen, Chao; Xiao, Nanyang; Lin, Duo; Chen, Rong; Pan, Jianji; Feng, Shangyuan

    2016-12-01

    Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573 cm-1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.8%, 92.3%, and 87.9% for early NPC, advanced NPC, and normal nasopharyngeal tissue DNA, respectively. In this exploratory study, we demonstrated the potential of SERS for early detection of NPC based on the DNA molecular study of biopsy tissues.

  8. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Early election for Group 1, Phase II boilers. 76.8 Section 76.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1...

  9. Contrast-enhanced FLAIR in the early diagnosis of infectious meningitis

    International Nuclear Information System (INIS)

    Splendiani, Alesssandra; Puglielli, Edoardo; Amicis, Rosanna De; Masciocchi, Carlo; Gallucci, Massimo; Necozione, Stefano

    2005-01-01

    We investigated the accuracy of MRI in the early diagnosis of infectious meningitis with emphasis on the value of gadolinium-enhanced fluid-attenuated inversion recovery (FLAIR) sequence. Twenty-seven patients with clinical suspicion of infectious meningitis were included. MRI was performed within 3 h of clinical evaluation. For all patients, T1-weighted spin-echo, dual-echo T2-weighted fast-spin-echo and FLAIR sequences were performed, followed by gadolinium-enhanced T1-weighted spin-echo and FLAIR sequences. Final diagnosis was based on the clinical findings and the analysis of cerebrospinal fluid, obtained by lumbar puncture after the MRI. Infectious meningitis was confirmed in 12 patients. In all of these patients of the plain studies, FLAIR was positive in only four patients. MRI gadolinium-enhanced FLAIR showed abnormal meningeal enhancement in all 12 patients, while gadolinium-enhanced T1-weighted spin-echo was positive only in six cases. There were no false-positive or false-negative results. It is concluded that MRI could have an important role in the early screening for infectious meningitis, provided a gadolinium-enhanced FLAIR sequence is used. (orig.)

  10. Contrast-enhanced FLAIR in the early diagnosis of infectious meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Splendiani, Alesssandra; Puglielli, Edoardo; Amicis, Rosanna De; Masciocchi, Carlo; Gallucci, Massimo [University of L' Aquila, Department of Radiology, L' Aquila (Italy); Necozione, Stefano [University of L' Aquila, Department of Statistic, L' Aquila (Italy)

    2005-08-01

    We investigated the accuracy of MRI in the early diagnosis of infectious meningitis with emphasis on the value of gadolinium-enhanced fluid-attenuated inversion recovery (FLAIR) sequence. Twenty-seven patients with clinical suspicion of infectious meningitis were included. MRI was performed within 3 h of clinical evaluation. For all patients, T1-weighted spin-echo, dual-echo T2-weighted fast-spin-echo and FLAIR sequences were performed, followed by gadolinium-enhanced T1-weighted spin-echo and FLAIR sequences. Final diagnosis was based on the clinical findings and the analysis of cerebrospinal fluid, obtained by lumbar puncture after the MRI. Infectious meningitis was confirmed in 12 patients. In all of these patients of the plain studies, FLAIR was positive in only four patients. MRI gadolinium-enhanced FLAIR showed abnormal meningeal enhancement in all 12 patients, while gadolinium-enhanced T1-weighted spin-echo was positive only in six cases. There were no false-positive or false-negative results. It is concluded that MRI could have an important role in the early screening for infectious meningitis, provided a gadolinium-enhanced FLAIR sequence is used. (orig.)

  11. Increased blood 8-hydroxy-2-deoxyguanosine levels in methamphetamine users during early abstinence.

    Science.gov (United States)

    Huang, Ming-Chyi; Lai, Ying-Ching; Lin, Shih-Ku; Chen, Chun-Hsin

    2018-01-01

    Reactive oxygen species (ROS) are thought to play a role in the adverse physical and mental consequences of methamphetamine usage. The oxidative DNA adduct 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a well-known biomarker of ROS-induced DNA damage. Currently, there is insufficient clinical information about methamphetamine-induced oxidative DNA damage. This study examined differences in blood levels of 8-OHdG between methamphetamine users and non-users as well as alterations in 8-OHdG levels after 2 weeks of methamphetamine abstinence. We recruited 182 methamphetamine users (78.6% of male) and 71 healthy controls (95.8% of male). Baseline serum 8-OHdG levels were measured in both groups using a competitive enzyme-linked immunosorbent assay. In methamphetamine users, 8-OHdG levels were measured again 2 weeks after baseline measurement. The results showed that methamphetamine users had significantly higher 8-OHdG levels (0.34 ± 0.13 ng/mL) than healthy controls (0.30 ± 0.08 ng/mL) (p users and post-abstinence interval, age of the first methamphetamine use, duration of methamphetamine use, or history of frequent methamphetamine use. Our findings suggest that methamphetamine users had an enhanced level of oxidative damage, which did not normalize during early abstinence. Future studies are required to determine the effects of long-term methamphetamine abstinence and potential confounders on 8-OHdG levels in methamphetamine users.

  12. CT findings of pancreatic carcinoma. Evaluation with the combined method of early enhancement CT and high dose enhancement CT

    International Nuclear Information System (INIS)

    Itoh, Shigeki; Endo, Tokiko; Isomura, Takayuki; Ishigaki, Takeo; Ikeda, Mitsuru; Senda, Kouhei.

    1995-01-01

    Computed tomographic (CT) findings of pancreatic ductal adenocarcinoma were studied with the combined method of early enhancement CT and high dose enhancement CT in 72 carcinomas. Common Findings were change in pancreatic contour, abnormal attenuation in a tumor and dilatation of the main pancreatic duct. The incidence of abnormal attenuation and dilatation of the main pancreatic duct and bile duct was constant regardless of tumor size. The finding of hypoattenuation at early enhancement CT was most useful for demonstrating a carcinoma. However, this finding was negative in ten cases, five of which showed inhomogenous hyperattenuation at high dose enhancement CT. The detection of change in pancreatic contour and dilatation of the main pancreatic duct was most frequent at high dose enhancement CT. The finding of change in pancreatic contour and/or abnormal attenuation in a tumor could be detected in 47 cases at plain CT, 66 at early enhancement CT and 65 at high dose enhancement CT. Since the four cases in which neither finding was detected by any CT method showed dilatated main pancreatic duct, there was no case without abnormal CT findings. This combined CT method will be a reliable diagnostic technique in the imaging of pancreatic carcinoma. (author)

  13. Delayed enhanced MRI in intraparenchymal tumors

    International Nuclear Information System (INIS)

    Eguchi, Takahiko; Morimoto, Tetsuya; Takeshima, Toshikazu

    1991-01-01

    Delayed enhanced MRI was performed on 20 intraparenchymal tumors, and these findings were compared with those of early enhanced MRI. Using the spin-echo technique (SE: 400-500/20 msec), early scans were obtained 5 minutes, and delayed scans were obtained 60 minutes, after the intravenous injection of 0.1 nmol of gadolinium-DTPA/Kg. We discussed the changes in the delayed scan with regard to the change in the pattern of enhancement and the boundary of enhancement. In these twenty intraparenchymal tumors, there were three low-grade astrocytomas, two anaplastic astrocytomas, seven glioblastomas, and eight metastatic tumors. The changes in the enhanced pattern showed three types as follows: Type I: heterogeneous enhancement in both early and delayed scans; Type II: heterogeneous enhancement in early scan and homogeneous enhancement in delayed scan; Type III: homogeneous enhancement in both early and delayed scans. Most malignant tumors, such as glioblastomas (6/8), anaplastic astrocytomas (2/2), and metastatic tumors (7/8), revealed Type I, although low-grade astrocytomas showed Type II (3/2) and Type III (1/3). The heterogeneous enhancement in delayed scan was found in malignant tumors and in low-grade astrocytoma; even if the early scan revealed heterogeneous enhancement, the delayed scan showed homogeneous enhancement. In the delayed scan, most enhanced boundaries spread out of the boundaries in the early scan. Glioblastomas spread markedly in the delayed scan, although none of the low-grade astrocytomas, anaplastic astrocytomas, or metastases revealed marked spreading. We called these marked increases in the delayed scan a 'spreading sign' and thought that this sign was specific to glioblastomas. Recently some authors have emphasized the usefulness of serial scans. Delayed enhanced MRI 60 minutes after the administration of a contrast medium was here found also to be useful for the accurate diagnosis for brain tumors. (author)

  14. Early events governing memory CD8+ T-cell differentiation.

    Science.gov (United States)

    Obar, Joshua J; Lefrançois, Leo

    2010-08-01

    Understanding the regulation of the CD8(+) T-cell response and how protective memory cells are generated has been intensely studied. It is now appreciated that a naive CD8(+) T cell requires at least three signals to mount an effective immune response: (i) TCR triggering, (ii) co-stimulation and (iii) inflammatory cytokines. Only recently have we begun to understand the molecular integration of those signals and how early events regulate the fate decisions of the responding CD8(+) T cells. This review will discuss the recent findings about both the extracellular and intracellular factors that regulate the destiny of responding CD8(+) T cells.

  15. Early-Life Phthalate Exposure and Adiposity at 8 Years of Age.

    Science.gov (United States)

    Shoaff, Jessica; Papandonatos, George D; Calafat, Antonia M; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P; Yolton, Kimberly; Braun, Joseph M

    2017-09-11

    Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022.

  16. Experimental study of Gadofluorine M enhancement in early diagnosis of radiation brain injury by MRI in rats

    International Nuclear Information System (INIS)

    Bai Shoumin; Liao Chengde; Guo Ruomi; Huang Ying; Liang Biling; Shen Jun; Lu Taixiang

    2011-01-01

    Objective: To explore the value of Gadofluorine M, a novel MRI enhancement agent,in the diagnosis the early radiation brain injury. Methods: Seventy-two Wistar rats were randomly divided into 5 equal groups. To establish the radiation injury model, the rat's posterior brain was irradiated with 0 (blank controls), 25, 35, 45, 55, and 65 Gy, respectively. After irradiation MR plain scanning and Gadofluorine M enhancement scanning (after the T1WI and T2WI scanning Gf at the dosage of 0.1 mmol/kg was injected intravenously and scanning was performed again 12 h later) were performed once a week for 8 weeks. Another 12 rats were randomly divided into 2 equal groups to exposure to 55 and 65 Gy, respectively, and MR scanning was performed once a week for 8 weeks since the third week after MR. After T1WI and T2WI scanning Gd-DTPA was injected intravenously, MR was conducted again 30 min later, and Gf was injected intravenously (Gd-DTPA enhancement and Gf enhancement contrast). The MR image and the pixel count were compared. Since the third week 2 rats from the Gf enhancement scanning group and 1 rat from the Gd-DTPA enhancement and Gf enhancement contrast were killed after MR with their brains taken out to undergo pathological examination. Results: No abnormal signal changes were found in MRI in 25 and 35 Gy groups within 2 months after irradiation. A high signal in the Gf enhancement T1WI image was found in 45, 55, and 65 Gy groups within the period of 4-6 weeks after radiation. The signal intensity was significantly higher than that of the control, 25, and 35 Gy groups (F=2.15, P<0.05). The emerge time of this signal was negatively correlated with the dose of radiation (r =-0.62, P<0.05). When there was no obvious change was found by Gd-DTPA enhancement, a high signal representing change of injury could be found in Gf enhancement in the same rat. The signal intensity was significantly enhanced in Gf enhancement compared to the Gd-DTPA enhancement (F=2.74, P<0

  17. Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography

    Science.gov (United States)

    Pan, Y. T.; Xie, T. Q.; Du, C. W.; Bastacky, S.; Meyers, S.; Zeidel, M. L.

    2003-12-01

    We report an experimental study of the possibility of enhancing early bladder cancer diagnosis with fluorescence-image-guided endoscopic optical coherence tomography (OCT). After the intravesical instillation of a 10% solution of 5-aminolevulinic acid, simultaneous fluorescence imaging (excitation of 380-420 nm, emission of 620-700 nm) and OCT are performed on rat bladders to identify the photochemical and morphological changes associated with uroepithelial tumorigenesis. The preliminary results of our ex vivo study reveal that both fluorescence and OCT can identify early uroepithelial cancers, and OCT can detect precancerous lesions (e.g., hyperplasia) that fluorescence may miss. This suggests that a cystoscope combining 5-aminolevulinic acid fluorescence and OCT imaging has the potential to enhance the efficiency and sensitivity of early bladder cancer diagnosis.

  18. Septic liver - Clinical relevance of early inhomogeneous enhancement of the liver in patients with acute pyelonephritis

    Energy Technology Data Exchange (ETDEWEB)

    Han, Ga Jin; Lee, Nam Kyung; Kim, Suk [Dept. of Radiology, Biomedical Research Inst., Pusan National Univ. Hospital, Pusan National Univ. School of Medicine, Busan (Korea, Republic of)], e-mail: kimsuk@medimail.co.kr; Kim, Tae Un [Dept. of Radiology, Pusan National Univ. Yangsan Hospital, Pusan National Univ. School of Medicine, Yangsan (Korea, Republic of); Song, Sang Heon [Dept. of Internal Medicine, Biomedical Research Inst., Pusan National Univ. Hospital, Pusan National Univ. School of Medicine, Busan (Korea, Republic of); Kim, Hyun Sung; Jo, Hong Jae [Dept. of Surgery, Biomedical Research Inst., Pusan National Univ. Hospital, Pusan National Univ. School of Medicine, Busan (Korea, Republic of)

    2013-10-15

    Background: CT scans of patients with febrile illness occasionally show hepatobiliary changes, although infection does not originate in the hepatobiliary system. These findings may cause radiologists and clinicians to misrecognize hepatobiliary diseases and initiate an inappropriate treatment. Thus, it is important to recognize hepatobiliary CT findings in cases of extrahepatobiliary infectious disease. Purpose: To evaluate extrarenal CT manifestations in patients with acute pyelonephritis and to determine the correlation between these extrarenal CT findings and septic liver based on laboratory parameters of sepsis. Material and Methods: This study included 157 retrospectively identified patients with confirmed acute pyelonephritis based on CT imaging and urine test, and who had also undergone multi-phase dynamic contrast-enhanced CT scan. Two radiologists reviewed CT findings including early inhomogeneous enhancement of the liver, periportal low density and gallbladder edema, which were correlated with laboratory data including liver function enzymes, albumin, C-reactive protein, white blood cell count, and results of a blood culture by using the Fisher's exact test and Mann-Whitney U test. Results: Forty-six patients (29.3%) showed early inhomogeneous enhancement of the liver, which was associated with increased C-reactive protein (P < 0.001), a positive blood culture (P < 0.005), and decreased albumin level (P < 0.002). The periportal low density and gallbladder wall edema were noted in 15 patients (9.6%) and six patients (3.8%), respectively. These two CT findings were significantly associated with only decreased albumin level (P < 0.001 and P < 0.040). Conclusion: Early inhomogeneous enhancement of the liver in patients with acute pyelonephritis was significantly associated with increased CRP level, a positive blood culture and decreased albumin level, reflecting sepsis and sepsis-associated liver dysfunction, requiring rapid and appropriate intensive

  19. Septic liver - Clinical relevance of early inhomogeneous enhancement of the liver in patients with acute pyelonephritis

    International Nuclear Information System (INIS)

    Han, Ga Jin; Lee, Nam Kyung; Kim, Suk; Kim, Tae Un; Song, Sang Heon; Kim, Hyun Sung; Jo, Hong Jae

    2013-01-01

    Background: CT scans of patients with febrile illness occasionally show hepatobiliary changes, although infection does not originate in the hepatobiliary system. These findings may cause radiologists and clinicians to misrecognize hepatobiliary diseases and initiate an inappropriate treatment. Thus, it is important to recognize hepatobiliary CT findings in cases of extrahepatobiliary infectious disease. Purpose: To evaluate extrarenal CT manifestations in patients with acute pyelonephritis and to determine the correlation between these extrarenal CT findings and septic liver based on laboratory parameters of sepsis. Material and Methods: This study included 157 retrospectively identified patients with confirmed acute pyelonephritis based on CT imaging and urine test, and who had also undergone multi-phase dynamic contrast-enhanced CT scan. Two radiologists reviewed CT findings including early inhomogeneous enhancement of the liver, periportal low density and gallbladder edema, which were correlated with laboratory data including liver function enzymes, albumin, C-reactive protein, white blood cell count, and results of a blood culture by using the Fisher's exact test and Mann-Whitney U test. Results: Forty-six patients (29.3%) showed early inhomogeneous enhancement of the liver, which was associated with increased C-reactive protein (P < 0.001), a positive blood culture (P < 0.005), and decreased albumin level (P < 0.002). The periportal low density and gallbladder wall edema were noted in 15 patients (9.6%) and six patients (3.8%), respectively. These two CT findings were significantly associated with only decreased albumin level (P < 0.001 and P < 0.040). Conclusion: Early inhomogeneous enhancement of the liver in patients with acute pyelonephritis was significantly associated with increased CRP level, a positive blood culture and decreased albumin level, reflecting sepsis and sepsis-associated liver dysfunction, requiring rapid and appropriate intensive

  20. Helical CT finding of carotid-cavernous fistula: a sign of early enhancing superior ophthalmic vein

    International Nuclear Information System (INIS)

    Kim, Jae Hyung; Na, Dong Gyu; Byun, Hong Sik; Ryoo, Jae Wook

    2000-01-01

    The purpose of this study was to determine the diagnostic value of a sign of early enhancing superior ophthalmic vein (SOV), as seen on helical CT images in patients with carotid-cavernous fistula (CCF). This study involved 16 patients with CCF and 28 control patients. Axial CT images with scanning delays of 30 seconds following bolus injection of contrast material (90 mL, 3 mL/sec) were obtained, and this procedure was followed by coronal CT imaging. To determine the presence or absence of early enhancement or, dilatation of the SOV, bulging of the cavernous sinus, and enlargement of extraocular muscle, CT images were analysed by three observers in a blinded, random manner. Early enhancement of SOV was determined to be present where enhancement of the SOV was similar to or stronger than that of the ipsilateral posterior cerebral artery. A sign of early enhancing SOV was seen in 14 of the 16 patients with CCF but in no control patients (88% sensitivity and 100% specificity). The respective sensitivity and specificity of other CT features were 71% and 100% (dilatation of the SOV, as seen on axial images), 60% and 83% (dilatation of the SOV, as seen on coronal images), 71% and 89% (dilatation of the cavernous sinus), and 65% and 98% (enlargement of extraocular muscle). A sign of early enhancing SOV is a characteristic and specific CT finding of CCF, and is useful for the diagnosis of CCF. (author)

  1. Short-term exposure to oleandrin enhances responses to IL-8 by increasing cell surface IL-8 receptors

    Science.gov (United States)

    Raviprakash, Nune; Manna, Sunil Kumar

    2014-01-01

    BACKGROUND AND PURPOSE One of the first steps in host defence is the migration of leukocytes. IL-8 and its receptors are a chemokine system essential to such migration. Up-regulation of these receptors would be a viable strategy to treat dysfunctional host defence. Here, we studied the effects of the plant glycoside oleandrin on responses to IL-8 in a human monocytic cell line. EXPERIMENTAL APPROACH U937 cells were incubated with oleandrin (1-200 ng mL−1) for either 1 h (pulse) or for 24 h (non-pulse). Apoptosis; activation of NF-κB, AP-1 and NFAT; calcineurin activity and IL-8 receptors (CXCR1 and CXCR2) were measured using Western blotting, RT-PCR and reporter gene assays. KEY RESULTS Pulse exposure to oleandrin did not induce apoptosis or cytoxicity as observed after non-pulse exposure. Pulse exposure enhanced activation of NF-κB induced by IL-8 but not that induced by TNF-α, IL-1, EGF or LPS. Exposure to other apoptosis-inducing compounds (azadirachtin, resveratrol, thiadiazolidine, or benzofuran) did not enhance activation of NF-κB. Pulse exposure to oleandrin increased expression of IL-8 receptors and chemotaxis, release of enzymes and activation of NF-κB, NFAT and AP-1 along with increased IL-8-mediated calcineurin activation, and wound healing. Pulse exposure increased numbers of cell surface IL-8 receptors. CONCLUSIONS AND IMPLICATIONS Short-term (1 h; pulse) exposure to a toxic glycoside oleandrin, enhanced biological responses to IL-8 in monocytic cells, without cytoxicity. Pulse exposure to oleandrin could provide a viable therapy for those conditions where leukocyte migration is defective. PMID:24172227

  2. Radiofrequency ablation of liver cancer: early evaluation of therapeutic response with contrast-enhanced ultrasonography

    International Nuclear Information System (INIS)

    Choi, Dong Gil; Lim, Hyo K.; Lee, Won Jae; Kim, Seung Hoon; Kim, Min Ju; Kim, Seung Kwon; Jang, Kyung Mi; Lee, Ji Yeon; Lim, Jae Hoon

    2004-01-01

    The early assessment of the therapeutic response after percutaneous radiofrequency (RF) ablation is important, in order to correctly decide whether further treatment is necessary. The residual unablated tumor is usually depicted on contrast-enhanced multiphase helical computed tomography (CT) as a focal enhancing structure during the arterial and portal venous phases. Contrast-enhanced color Doppler and power Doppler ultrasonography (US) have also been used to detect residual tumors. Contrast-enhanced gray-scale US, using a harmonic technology which has recently been introduced, allows for the detection of residual tumors after ablation, without any of the blooming or motion artifacts usually seen on contrast-enhanced color or power Doppler US. Based on our experience and reports in the literature, we consider that contrast-enhanced gray-scale harmonic US constitutes a reliable alternative to contrast-enhanced multiphase CT for the early evaluation of the therapeutic response to RF ablation for liver cancer. This technique was also useful in targeting any residual unablated tumors encountered during additional ablation

  3. Evaluation of F8-TNF-α in Models of Early and Progressive Metastatic Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Bernhard Robl

    2017-06-01

    Full Text Available The targeted delivery of tumor necrosis factor-α (TNF-α with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas. Here, we investigated F8-TNF in a syngeneic K7 M2–derived orthotopic model of osteosarcoma as a treatment against pulmonary metastases, the most frequent cause of osteosarcoma-related death. Immunofluorescence on human osteosarcoma tissue confirmed the presence of EDA in primary tumors (PTs as well as metastases. In mice, the efficacy of F8-TNF against PTs and early pulmonary metastases was evaluated. Intratibial PT growth was not affected by F8-TNF, yet early micrometastases were reduced possibly due to an F8-TNF–dependent attraction of pulmonary CD4+, CD8+, and natural killer cells. Furthermore, immunofluorescence revealed stronger expression of EDA in early pulmonary metastases compared with PT tissue. To study progressing pulmonary metastases, a hind limb amputation model was established, and the efficacy of F8-TNF, alone or combined with doxorubicin, was investigated. Despite the presence of EDA in metastases, no inhibition of progressive metastatic growth was detected. No significant differences in numbers of CD4+ or CD8+ cells or F4/80+ and Ly6G+ myeloid-derived cells were observed, although a strong association between metastatic growth and presence of pulmonary Ly6G+ myeloid-derived cells was detected. In summary, these findings demonstrate the potential of F8-TNF in activating the immune system and reducing early metastatic growth yet suggest a lack of efficacy of F8-TNF alone or combined with doxorubicin against progressing osteosarcoma metastases.

  4. Evaluation of F8-TNF-α in Models of Early and Progressive Metastatic Osteosarcoma.

    Science.gov (United States)

    Robl, Bernhard; Botter, Sander Martijn; Boro, Aleksandar; Meier, Daniela; Neri, Dario; Fuchs, Bruno

    2017-06-01

    The targeted delivery of tumor necrosis factor-α (TNF-α) with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA) domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas. Here, we investigated F8-TNF in a syngeneic K7 M2-derived orthotopic model of osteosarcoma as a treatment against pulmonary metastases, the most frequent cause of osteosarcoma-related death. Immunofluorescence on human osteosarcoma tissue confirmed the presence of EDA in primary tumors (PTs) as well as metastases. In mice, the efficacy of F8-TNF against PTs and early pulmonary metastases was evaluated. Intratibial PT growth was not affected by F8-TNF, yet early micrometastases were reduced possibly due to an F8-TNF-dependent attraction of pulmonary CD4 + , CD8 + , and natural killer cells. Furthermore, immunofluorescence revealed stronger expression of EDA in early pulmonary metastases compared with PT tissue. To study progressing pulmonary metastases, a hind limb amputation model was established, and the efficacy of F8-TNF, alone or combined with doxorubicin, was investigated. Despite the presence of EDA in metastases, no inhibition of progressive metastatic growth was detected. No significant differences in numbers of CD4 + or CD8 + cells or F4/80 + and Ly6G + myeloid-derived cells were observed, although a strong association between metastatic growth and presence of pulmonary Ly6G + myeloid-derived cells was detected. In summary, these findings demonstrate the potential of F8-TNF in activating the immune system and reducing early metastatic growth yet suggest a lack of efficacy of F8-TNF alone or combined with doxorubicin against progressing osteosarcoma metastases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Elevated interleukin-8 enhances prefrontal synaptic transmission in mice with persistent inflammatory pain

    Directory of Open Access Journals (Sweden)

    Cui Guang-bin

    2012-02-01

    Full Text Available Abstract Background Interleukin-8 (IL-8 is known for its roles in inflammation and plays critical roles in the development of pain. Its expression increases in the brain after peripheral inflammation. Prefrontal cortex, including the anterior cingulate cortex (ACC, is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission, however, little is known about the expression of IL-8 and its role in the enhanced ACC synaptic transmission in animals with persistent inflammatory pain. Findings In the present study, we examined IL-8 expression in the ACC, somatosensory cortex (SSC, and the dorsal horn of lumbar spinal cord following hind-paw administration of complete Freund's adjuvant (CFA in mice and its effects on the ACC synaptic transmission. Quantification of IL-8 at protein level (by ELISA revealed enhanced expression in the ACC and spinal cord during the chronic phases of CFA-induced peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that IL-8 significantly enhanced synaptic transmission through increased probability of neurotransmitter release in the ACC slice. ACC local infusion of repertaxin, a non-competitive allosteric blocker of IL-8 receptors, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in mice. Conclusions Our findings suggest that up-regulation of IL-8 in the ACC partly attributable to the enhanced prefrontal synaptic transmission in the mice with persistent inflammatory pain.

  6. Comparative transcriptome analyses indicate molecular homology of zebrafish swimbladder and mammalian lung.

    Directory of Open Access Journals (Sweden)

    Weiling Zheng

    Full Text Available The fish swimbladder is a unique organ in vertebrate evolution and it functions for regulating buoyancy in most teleost species. It has long been postulated as a homolog of the tetrapod lung, but the molecular evidence is scarce. In order to understand the molecular function of swimbladder as well as its relationship with lungs in tetrapods, transcriptomic analyses of zebrafish swimbladder were carried out by RNA-seq. Gene ontology classification showed that genes in cytoskeleton and endoplasmic reticulum were enriched in the swimbladder. Further analyses depicted gene sets and pathways closely related to cytoskeleton constitution and regulation, cell adhesion, and extracellular matrix. Several prominent transcription factor genes in the swimbladder including hoxc4a, hoxc6a, hoxc8a and foxf1 were identified and their expressions in developing swimbladder during embryogenesis were confirmed. By comparison of enriched transcripts in the swimbladder with those in human and mouse lungs, we established the resemblance of transcriptome of the zebrafish swimbladder and mammalian lungs. Based on the transcriptomic data of zebrafish swimbladder, the predominant functions of swimbladder are in its epithelial and muscular tissues. Our comparative analyses also provide molecular evidence of the relatedness of the fish swimbladder and mammalian lung.

  7. Feedback Seeking in Early Adolescence: Self-Enhancement or Self-Verification?

    Science.gov (United States)

    Rosen, Lisa H.; Principe, Connor P.; Langlois, Judith H.

    2013-01-01

    The authors examined whether early adolescents ("N" = 90) solicit self-enhancing feedback (i.e., positive feedback) or self-verifying feedback (i.e., feedback congruent with self-views, even when these views are negative). Sixth, seventh, and eighth graders first completed a self-perception measure and then selected whether to receive…

  8. Enhanced musical rhythmic perception in Turkish early and late learners of German

    Directory of Open Access Journals (Sweden)

    Maria Paula eRoncaglia-Denissen

    2013-09-01

    Full Text Available As language rhythm relies partly on general acoustic properties, such as intensity and duration, mastering two languages with distinct rhythmic properties (i.e., stress position may enhance musical rhythm perception. We investigated whether second language (L2 competence affects musical rhythm aptitude in Turkish early (TELG and late learners (TLLG of German in comparison to German monolingual speakers (GMC. To account for inter-individual differences, we measured participants’ short-term and working memory capacity, melodic aptitude, and time they spent listening to music. Both L2 speaker groups perceived rhythmic variations significantly better than monolinguals. No differences were found between early and late learners’ performances. Our findings suggest that mastering two languages with different rhythmic properties enhances musical rhythm perception, providing further evidence of cognitive share between language and music.

  9. A SINE-derived element constitutes a unique modular enhancer for mammalian diencephalic Fgf8.

    Directory of Open Access Journals (Sweden)

    Akiko Nakanishi

    Full Text Available Transposable elements, including short interspersed repetitive elements (SINEs, comprise nearly half the mammalian genome. Moreover, they are a major source of conserved non-coding elements (CNEs, which play important functional roles in regulating development-related genes, such as enhancing and silencing, serving for the diversification of morphological and physiological features among species. We previously reported a novel SINE family, AmnSINE1, as part of mammalian-specific CNEs. One AmnSINE1 locus, named AS071, showed an enhancer property in the developing mouse diencephalon. Indeed, AS071 appears to recapitulate the expression of diencephalic fibroblast growth factor 8 (Fgf8. Here we established three independent lines of AS071-transgenic mice and performed detailed expression profiling of AS071-enhanced lacZ in comparison with that of Fgf8 across embryonic stages. We demonstrate that AS071 is a distal enhancer that directs Fgf8 expression in the developing diencephalon. Furthermore, enhancer assays with constructs encoding partially deleted AS071 sequence revealed a unique modular organization in which AS071 contains at least three functionally distinct sub-elements that cooperatively direct the enhancer activity in three diencephalic domains, namely the dorsal midline and the lateral wall of the diencephalon, and the ventral midline of the hypothalamus. Interestingly, the AmnSINE1-derived sub-element was found to specify the enhancer activity to the ventral midline of the hypothalamus. To our knowledge, this is the first discovery of an enhancer element that could be separated into respective sub-elements that determine regional specificity and/or the core enhancing activity. These results potentiate our understanding of the evolution of retroposon-derived cis-regulatory elements as well as the basis for future studies of the molecular mechanism underlying the determination of domain-specificity of an enhancer.

  10. Dendritic cells modulate burn wound healing by enhancing early proliferation.

    Science.gov (United States)

    Vinish, Monika; Cui, Weihua; Stafford, Eboni; Bae, Leon; Hawkins, Hal; Cox, Robert; Toliver-Kinsky, Tracy

    2016-01-01

    Adequate wound healing is vital for burn patients to reduce the risk of infections and prolonged hospitalization. Dendritic cells (DCs) are antigen presenting cells that release cytokines and are central for the activation of innate and acquired immune responses. Studies have showed their presence in human burn wounds; however, their role in burn wound healing remains to be determined. This study investigated the role of DCs in modulating healing responses within the burn wound. A murine model of full-thickness contact burns was used to study wound healing in the absence of DCs (CD11c promoter-driven diphtheria toxin receptor transgenic mice) and in a DC-rich environment (using fms-like tyrosine kinase-3 ligand, FL- a DC growth factor). Wound closure was significantly delayed in DC-deficient mice and was associated with significant suppression of early cellular proliferation, granulation tissue formation, wound levels of TGFβ1 and formation of CD31+ vessels in healing wounds. In contrast, DC enhancement significantly accelerated early wound closure, associated with increased and accelerated cellular proliferation, granulation tissue formation, and increased TGFβ1 levels and CD31+ vessels in healing wounds. We conclude that DCs play an important role in the acceleration of early wound healing events, likely by secreting factors that trigger the proliferation of cells that mediate wound healing. Therefore, pharmacological enhancement of DCs may provide a therapeutic intervention to facilitate healing of burn wounds. © 2016 by the Wound Healing Society.

  11. 8-aminoadenosine enhances radiation-induced cell death in human lung carcinoma A549 cells

    International Nuclear Information System (INIS)

    Meike, Shunsuke; Yamamori, Tohru; Yasui, Hironobu; Eitaki, Masato; Inanami, Osamu; Matsuda, Akira

    2011-01-01

    The combination of a chemotherapeutic agent and radiation is widely applied to enhance cell death in solid tumor cells in cancer treatment. The purine analogue 8-aminoadenosine (8-NH 2 -Ado) is known to be a transcription inhibitor that has proved very effective in multiple myeloma cell lines and primary indolent leukemia cells. In this report, to examine whether 8-NH 2 -Ado had the ability to enhance the radiation-induced cell killing in solid tumor cells, human lung adenocarcinoma A549 cells were irradiated in the presence and absence of 8-NH 2 -Ado. 8-NH 2 -Ado significantly increased reproductive cell death and apoptosis in A549 cells exposed to X-rays. When peptide inhibitors against caspase-3, -8, and -9 were utilized to evaluate the involvement of caspases, all inhibitors suppressed the enhancement of radiation-induced apoptosis, suggesting that not only mitochondria-mediated apoptotic signal transduction pathways but also death receptor-mediated pathways were involved in this enhancement of apoptosis. In addition, in the cells exposed to the treatment combining X-irradiation and 8-NH 2 -Ado, reduction of the intracellular ATP concentration was essential for survival, and down-regulation of the expression of antiapoptotic proteins such as survivin and X-linked inhibitor of apoptosis protein (XIAP) was observed. These results indicate that 8-NH 2 -Ado has potential not only as an anti-tumor drug for leukemia and lymphoma but also as a radiosensitizing agent for solid tumors. (author)

  12. Transplacental transmission of Bluetongue virus serotype 8 in ewes in early and mid gestation

    NARCIS (Netherlands)

    Sluijs, van der M.; Timmermans, M.; Moulin, V.; Vonk Noordegraaf, C.; Vrijenhoek, M.; Debyser, I.; Smit, de A.J.; Moormann, R.J.M.

    2011-01-01

    The ability of Bluetongue virus serotype 8 (BTV-8) originating from the 2006 European outbreak to cross the ovine placenta during early and mid gestation was investigated in two separate experiments. In the first experiment, 16 ewes were infected with BTV-8 at 70–75 days gestation. The foetuses were

  13. Neutral Polymer Micelle Carriers with pH-Responsive, Endosome-Releasing Activity Modulate Antigen Trafficking to Enhance CD8 T-Cell Responses

    Science.gov (United States)

    Keller, Salka; Wilson, John T; Patilea, Gabriela I; Kern, Hanna B; Convertine, Anthony J; Stayton, Patrick S

    2014-01-01

    draining lymph nodes. As early as 90 min post injection ova-micelle conjugates were associated with 28% and 55% of dendritic cells and macrophages, respectively. After 24 h, conjugates preferentially associated with dendritic cells, affording 30-, 3-, and 3-fold enhancements in uptake relative to free protein, physical mixture, and the non pH-responsive conjugate controls, respectively. These results demonstrate the potential of pH-responsive polymeric micelles for use in vaccine applications that rely on CD8+ T cell activation. PMID:24698946

  14. Neutral polymer micelle carriers with pH-responsive, endosome-releasing activity modulate antigen trafficking to enhance CD8(+) T cell responses.

    Science.gov (United States)

    Keller, Salka; Wilson, John T; Patilea, Gabriela I; Kern, Hanna B; Convertine, Anthony J; Stayton, Patrick S

    2014-10-10

    in the draining lymph nodes. As early as 90min post injection, ova-micelle conjugates were associated with 28% and 55% of dendritic cells and macrophages, respectively. After 24h, conjugates preferentially associated with dendritic cells, affording 30-, 3-, and 3-fold enhancements in uptake relative to free protein, physical mixture, and the non-pH-responsive conjugate controls, respectively. These results demonstrate the potential of pH-responsive polymeric micelles for use in vaccine applications that rely on CD8(+) T cell activation. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Fiber optic probe enabled by surface-enhanced Raman scattering for early diagnosis of potential acute rejection of kidney transplant

    Science.gov (United States)

    Chi, Jingmao; Chen, Hui; Tolias, Peter; Du, Henry

    2014-06-01

    We have explored the use of a fiber-optic probe with surface-enhanced Raman scattering (SERS) sensing modality for early, noninvasive and, rapid diagnosis of potential renal acute rejection (AR) and other renal graft dysfunction of kidney transplant patients. Multimode silica optical fiber immobilized with colloidal Ag nanoparticles at the distal end was used for SERS measurements of as-collected urine samples at 632.8 nm excitation wavelength. All patients with abnormal renal graft function (3 AR episodes and 2 graft failure episodes) who were clinically diagnosed independently show common unique SERS spectral features in the urines collected just one day after transplant. SERS-based fiber-optic probe has excellent potential to be a bedside tool for early diagnosis of kidney transplant patients for timely medical intervention of patients at high risk of transplant dysfunction.

  16. 12 CFR 714.8 - Are the early payment provisions, or interest rate provisions, applicable in leasing arrangements?

    Science.gov (United States)

    2010-01-01

    ... provisions, or interest rate provisions, applicable in leasing arrangements? You are not subject to the early... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Are the early payment provisions, or interest rate provisions, applicable in leasing arrangements? 714.8 Section 714.8 Banks and Banking NATIONAL...

  17. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu

    2014-01-01

    To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells.

  18. Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

    International Nuclear Information System (INIS)

    Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J.

    2014-01-01

    To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 mark on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells

  19. Natural killer cells promote early CD8 T cell responses against cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Scott H Robbins

    2007-08-01

    Full Text Available Understanding the mechanisms that help promote protective immune responses to pathogens is a major challenge in biomedical research and an important goal for the design of innovative therapeutic or vaccination strategies. While natural killer (NK cells can directly contribute to the control of viral replication, whether, and how, they may help orchestrate global antiviral defense is largely unknown. To address this question, we took advantage of the well-defined molecular interactions involved in the recognition of mouse cytomegalovirus (MCMV by NK cells. By using congenic or mutant mice and wild-type versus genetically engineered viruses, we examined the consequences on antiviral CD8 T cell responses of specific defects in the ability of the NK cells to control MCMV. This system allowed us to demonstrate, to our knowledge for the first time, that NK cells accelerate CD8 T cell responses against a viral infection in vivo. Moreover, we identify the underlying mechanism as the ability of NK cells to limit IFN-alpha/beta production to levels not immunosuppressive to the host. This is achieved through the early control of cytomegalovirus, which dramatically reduces the activation of plasmacytoid dendritic cells (pDCs for cytokine production, preserves the conventional dendritic cell (cDC compartment, and accelerates antiviral CD8 T cell responses. Conversely, exogenous IFN-alpha administration in resistant animals ablates cDCs and delays CD8 T cell activation in the face of NK cell control of viral replication. Collectively, our data demonstrate that the ability of NK cells to respond very early to cytomegalovirus infection critically contributes to balance the intensity of other innate immune responses, which dampens early immunopathology and promotes optimal initiation of antiviral CD8 T cell responses. Thus, the extent to which NK cell responses benefit the host goes beyond their direct antiviral effects and extends to the prevention of innate

  20. Accurate late gadolinium enhancement prediction by early T1- based quantitative synthetic mapping

    Energy Technology Data Exchange (ETDEWEB)

    Dijk, Randy van; Harst, Pim van der [University of Groningen, University Medical Centre Groningen, Centre for Medical Imaging, Groningen (Netherlands); University of Groningen, University Medical Centre Groningen, Department of Cardiology, Groningen (Netherlands); Kuijpers, Dirkjan [University of Groningen, University Medical Centre Groningen, Centre for Medical Imaging, Groningen (Netherlands); Department of Cardiovascular Imaging HMC-Bronovo, The Hague (Netherlands); Kaandorp, Theodorus A.M.; Dijkman, Paul R.M. van [Department of Cardiovascular Imaging HMC-Bronovo, The Hague (Netherlands); Vliegenthart, Rozemarijn [University of Groningen, University Medical Center Groningen, Department of Radiology, Groningen (Netherlands); Oudkerk, Matthijs [University of Groningen, University Medical Centre Groningen, Centre for Medical Imaging, Groningen (Netherlands); University Medical Center Groningen, Center for Medical Imaging, Groningen (Netherlands)

    2018-02-15

    Early synthetic gadolinium enhancement (ESGE) imaging from post-contrast T1 mapping after adenosine stress-perfusion cardiac magnetic resonance (CMR) was compared to conventional late gadolinium enhancement (LGE) imaging for assessing myocardial scar. Two hundred fourteen consecutive patients suspected of myocardial ischaemia were referred for stress-perfusion CMR. Myocardial infarct volume was quantified on a per-subsegment basis in both synthetic (2-3 min post-gadolinium) and conventional (9 min post-gadolinium) images by two independent observers. Sensitivity, specificity, PPV and NPV were calculated on a per-patient and per-subsegment basis. Both techniques detected 39 gadolinium enhancement areas in 23 patients. The median amount of scar was 2.0 (1.0-3.1) g in ESGE imaging and 2.2 (1.1-3.1) g in LGE imaging (p=0.39). Excellent correlation (r=0.997) and agreement (mean absolute difference: -0.028±0.289 ml) were found between ESGE and LGE images. Sensitivity, specificity, PPV and NPV of ESGE imaging were 96 (78.9-99.9), 99 (97.1-100.0)%, 96 (76.5-99.4) and 99.5 (96.6-99.9) in patient-based and 99 (94.5-100.0), 100 (99.9-100.0)%, 97.0 (91.3-99.0) and 100.0 (99.8-100.0) in subsegment-based analysis. ESGE based on post-contrast T1 mapping after adenosine stress-perfusion CMR imaging shows excellent agreement with conventional LGE imaging for assessing myocardial scar, and can substantially shorten clinical acquisition time. (orig.)

  1. Accurate late gadolinium enhancement prediction by early T1- based quantitative synthetic mapping

    International Nuclear Information System (INIS)

    Dijk, Randy van; Harst, Pim van der; Kuijpers, Dirkjan; Kaandorp, Theodorus A.M.; Dijkman, Paul R.M. van; Vliegenthart, Rozemarijn; Oudkerk, Matthijs

    2018-01-01

    Early synthetic gadolinium enhancement (ESGE) imaging from post-contrast T1 mapping after adenosine stress-perfusion cardiac magnetic resonance (CMR) was compared to conventional late gadolinium enhancement (LGE) imaging for assessing myocardial scar. Two hundred fourteen consecutive patients suspected of myocardial ischaemia were referred for stress-perfusion CMR. Myocardial infarct volume was quantified on a per-subsegment basis in both synthetic (2-3 min post-gadolinium) and conventional (9 min post-gadolinium) images by two independent observers. Sensitivity, specificity, PPV and NPV were calculated on a per-patient and per-subsegment basis. Both techniques detected 39 gadolinium enhancement areas in 23 patients. The median amount of scar was 2.0 (1.0-3.1) g in ESGE imaging and 2.2 (1.1-3.1) g in LGE imaging (p=0.39). Excellent correlation (r=0.997) and agreement (mean absolute difference: -0.028±0.289 ml) were found between ESGE and LGE images. Sensitivity, specificity, PPV and NPV of ESGE imaging were 96 (78.9-99.9), 99 (97.1-100.0)%, 96 (76.5-99.4) and 99.5 (96.6-99.9) in patient-based and 99 (94.5-100.0), 100 (99.9-100.0)%, 97.0 (91.3-99.0) and 100.0 (99.8-100.0) in subsegment-based analysis. ESGE based on post-contrast T1 mapping after adenosine stress-perfusion CMR imaging shows excellent agreement with conventional LGE imaging for assessing myocardial scar, and can substantially shorten clinical acquisition time. (orig.)

  2. Feedback Seeking in Early Adolescence: Self-Enhancement or Self-Verification?

    OpenAIRE

    Rosen, Lisa H.; Principe, Connor P.; Langlois, Judith H.

    2012-01-01

    The authors examined whether early adolescents (N = 90) solicit self-enhancing feedback (i.e., positive feedback) or self-verifying feedback (i.e., feedback congruent with self-views, even when these views are negative). Sixth, seventh, and eighth graders first completed a self-perception measure and then selected whether to receive positive or negative feedback from an unknown peer in different domains of self. Results were consistent with self-verification theory; adolescents who perceived ...

  3. Mammography combined with breast dynamic contrast-enhanced-magnetic resonance imaging for the diagnosis of early breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yakun He; Guohui Xu; Jin Ren; Bin Feng; Xiaolei Dong; Hao Lu; Changjiu He

    2016-01-01

    Objective The aim of this study was to investigate the application of mammography combined with breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the diagnosis of early breast cancer. Methods Mammography and DCE-MRI were performed for 120 patients with breast cancer (malignant, 102; benign; 18). Results The sensitivity of mammography for early diagnosis of breast cancer was 66.67%, specificity was 77.78%, and accuracy was 68.33%. The sensitivity of MRI for early diagnosis of breast cancer was 94.12%, specificity was 88.89%, and accuracy was 93.33%. However, the sensitivity of mammography combined with DCE-MRI volume imaging with enhanced water signal (VIEWS) scanning for early diagnosis of breast cancer was 97.06%, specificity was 94.44%, and accuracy was 96.67%. Conclusion Mammography combined with DCE-MRI increased the sensitivity, specificity, and accuracy of diagnosing early breast cancer.

  4. Non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI as a predictor of outcomes for early-stage HCC.

    Science.gov (United States)

    Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Sone, Yasuhiro; Maeda, Atsuyuki; Kaneoka, Yuji

    2015-01-01

    In patients with hepatocellular carcinoma (HCC), gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) often identifies non-hypervascular hypointense hepatic nodules during the hepatobiliary phase, but their prognostic significance is unclear. We conducted a prospective observational study to investigate the impact of non-hypervascular hypointense hepatic nodules detected by Gd-EOB-DTPA-enhanced MRI on the outcome of patients with early-stage HCC. Post-treatment recurrence and survival rates were analyzed in 138 patients with non-recurrent, early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0 or A] and Child-Pugh A liver function according to the presence of non-hypervascular hypointense nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Non-hypervascular hypointense hepatic nodules were detected in 51 (37.0%) patients with early-stage HCC on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrence rates were significantly higher in patients with non-hypervascular hypointense nodules (p DTPA-enhanced MRI was independently associated with an increased recurrence rate, independent of tumor progression or treatment (p = 0.0005). The survival rate was significantly lower in patients with non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI (p = 0.0108). In patients with early-stage typical HCC (BCLC 0 or A), the presence of concurrent non-hypervascular hypointense hepatic nodules in the hepatobiliary phase of pretreatment Gd-EOB-DTPA-enhanced MRI is an indicator of higher likelihood of recurrence after treatment and may be a marker for unfavorable outcome.

  5. Implementing an innovative intervention to increase research capacity for enhancing early psychosis care in Indonesia.

    Science.gov (United States)

    Renwick, L; Irmansyah; Keliat, B A; Lovell, K; Yung, A

    2017-11-01

    WHAT IS KNOWN ON THE TOPIC?: In low- and middle-income settings (LMICs) such as Indonesia, the burden from psychotic illness is significant due to large gaps in treatment provision Mental health workers and community nurses are a growing workforce requiring new evidence to support practice and enhanced roles and advanced competencies among UK mental health nurses also requires greater research capacity Research capacity building projects can strengthen research institutions, enhance trial capacity, improve quality standards and improve attitudes towards the importance of health research. WHAT THIS PAPER ADDS?: Delivering innovative, cross-cultural workshops to enhance research capacity to multidisciplinary, early career researchers in Indonesia and the UK are rated highly by attendees Supporting people in this way helps them to gain competitive grant funding to complete their own research which can improve the health of the population To our knowledge, there are no other studies reporting the attainment of grant income as a successful outcome of international research partnerships for mental health nursing so our finding is novel. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This method could be implemented to improve networking and collaboration between UK academics and early career researchers in other lower- and middle-income settings This strategy can also strengthen existing partnerships among early career researchers in the UK to meet the demands for greater research mentorship and leadership among mental health nurses and enhance nurses capabilities to contribute to evidence for practice. Aim To strengthen research capacity for nurses and early career researchers in Indonesia and the UK to develop a local evidence base in Indonesia to inform policy and improve the nation's health. These strategies can strengthen research institutions, enhance trial capacity, improve quality standards and improve attitudes towards the importance of health research. Methods Four

  6. Enhancing Famine Early Warning Systems with Improved Forecasts, Satellite Observations and Hydrologic Simulations

    Science.gov (United States)

    Funk, C. C.; Verdin, J.; Thiaw, W. M.; Hoell, A.; Korecha, D.; McNally, A.; Shukla, S.; Arsenault, K. R.; Magadzire, T.; Novella, N.; Peters-Lidard, C. D.; Robjohn, M.; Pomposi, C.; Galu, G.; Rowland, J.; Budde, M. E.; Landsfeld, M. F.; Harrison, L.; Davenport, F.; Husak, G. J.; Endalkachew, E.

    2017-12-01

    Drought early warning science, in support of famine prevention, is a rapidly advancing field that is helping to save lives and livelihoods. In 2015-2017, a series of extreme droughts afflicted Ethiopia, Southern Africa, Eastern Africa in OND and Eastern Africa in MAM, pushing more than 50 million people into severe food insecurity. Improved drought forecasts and monitoring tools, however, helped motivate and target large and effective humanitarian responses. Here we describe new science being developed by a long-established early warning system - the USAID Famine Early Warning Systems Network (FEWS NET). FEWS NET is a leading provider of early warning and analysis on food insecurity. FEWS NET research is advancing rapidly on several fronts, providing better climate forecasts and more effective drought monitoring tools that are being used to support enhanced famine early warning. We explore the philosophy and science underlying these successes, suggesting that a modal view of climate change can support enhanced seasonal prediction. Under this modal perspective, warming of the tropical oceans may interact with natural modes of variability, like the El Niño-Southern Oscillation, to enhance Indo-Pacific sea surface temperature gradients during both El Niño and La Niña-like climate states. Using empirical data and climate change simulations, we suggest that a sequence of droughts may commence in northern Ethiopia and Southern Africa with the advent of a moderate-to-strong El Niño, and then continue with La Niña/West Pacific related droughts in equatorial eastern East Africa. Scientifically, we show that a new hybrid statistical-dynamic precipitation forecast system, the FEWS NET Integrated Forecast System (FIFS), based on reformulations of the Global Ensemble Forecast System weather forecasts and National Multi-Model Ensemble (NMME) seasonal climate predictions, can effectively anticipate recent East and Southern African drought events. Using cross-validation, we

  7. Dynamic contrast-enhanced 3-T magnetic resonance imaging: a method for quantifying disease activity in early polyarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Navalho, Marcio [Faculdade de Medicina da Universidade de Lisboa, Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon (Portugal); Hospital da Luz, Radiology Department, Lisbon (Portugal); Hospital da Luz, Centro de Imagiologia, Lisbon (Portugal); Resende, Catarina [Hospital da Luz, Rheumatology Department, Lisbon (Portugal); Hospital de Santa Maria, Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal); Rodrigues, Ana Maria; Fonseca, Joao Eurico; Canhao, Helena [Faculdade de Medicina da Universidade de Lisboa, Rheumatology Research Unit, Instituto de Medicina Molecular, Lisbon (Portugal); Hospital de Santa Maria, Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal); Gaspar, Augusto [Hospital da Luz, Radiology Department, Lisbon (Portugal); Campos, Jorge [Hospital de Santa Maria, Radiology Department, Centro Hospitalar de Lisboa Norte, EPE, Lisbon (Portugal)

    2012-01-15

    To determine whether measurement of synovial enhancement and thickness quantification parameters with 3.0-Tesla magnetic resonance imaging (3-T MRI) can reliably quantify disease activity in patients with early polyarthritis. Eighteen patients (16 women, 2 men; mean age 46 years) with early polyarthritis with less than 12 months of symptoms were included. MRI examination using 3-T device was performed by a new approach including both wrists and hands simultaneously in the examination field-of-view. MRI scoring of disease activity included quantification of synovial enhancement with simple measurements such as rate of early enhancement (REE; REE{sub 57} = S{sub 57}/S{sub 200}, where S{sub 57} and S{sub 200} are the signal intensities 57 s and 200 s after gadolinium injection) and rate of relative enhancement (RE; RE = S{sub 200} - S{sub 0}). Both wrists and hands were scored according to the Rheumatoid Arthritis MRI Scoring System (RAMRIS) for synovitis. Disease activity was clinically assessed by the 28-joint Disease Activity Score (DAS28). DAS28 score was strongly correlated with RE (r = 0.8331, p < 0.0001), REE (r = 0.8112, p < 0.0001), and RAMRIS score for synovitis (r = 0.7659, p < 0.0002). An REE score above 0.778 accurately identified patients with clinically active disease (sensitivity 92%; specificity 67%; p < 0.05). A statistically significant difference was observed in the RE, REE, and RAMRIS scores for synovitis between patients with active and inactive disease (p < 0.05). Our findings support the use of 3-T dynamic contrast-enhanced MRI for precise quantification of disease activity and for discriminating active disease from inactive disease in early polyarthritis. (orig.)

  8. Dynamic gadolinium-enhanced subtraction MR imaging - a simple technique for the early diagnosis of Legg-Calve-Perthes disease: preliminary results

    International Nuclear Information System (INIS)

    Sebag, G.; Ducou Le Pointe, H.; Klein, I.; Maiza, D.; Mazda, K.; Bensahel, H.; Hassan, M.

    1997-01-01

    To determine whether the simple technique of dynamic gadolinium-enhanced subtraction MR imaging, which is available on standard MR units, can detect ischemia of the femoral head in children with early Legg-Calve-Perthes disease (LCP). Bone perfusion of eight hips in four patients (mean age 7.5 years) was studied using dynamic gadolinium-enhanced substraction MR imaging at the onset of proven LCP (with initial negative plain films). Enhancement of subtracted images was compared with that on standard MR images and with bone scintigraphy findings. Subtraction MR imaging depicted ischemia as a widespread absence of enhancement and was in good agreement with bone scintigraphy. The subtraction technique improved the sensitivity and the specificity of MR imaging in two children. Furthermore, subtraction MR imaging allowed recognition of the pattern of early reperfusion. Our preliminary results indicate that dynamic gadolinium-enhanced subtraction MRI is a simple and promising means of early recognition of ischemia in LCP. (orig.)

  9. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    Science.gov (United States)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-06-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  10. Tobacco randomly inserted tt8 differenly enhance light signals and flavonoid accumulation

    International Nuclear Information System (INIS)

    Sompornpailin, K.; Kanthang, S.

    2015-01-01

    The individual lines of tobacco over-expressing TT8, a bHLH gene, were constructed and cultured under tissue culture condition radiating with photosynthetically activation radiation (PAR) or PAR+UVA. They were compared to wild type (WT). Leaf of treated plants was extracted and analyzed for flavonoid accumulations using a spectrophotometer. The extract of TT8 plants significantly contained flavone, flavonol and anthocyanin level, higher than the WT extract did. The petal extracts of mature transgenic under PAR had a similar absorbance profile of each substance, but these extracts had higher flavonoid contents than the leaf extracts did. All flavonoid subgroups and p-coumaric acid biosynthesis were significantly enhanced after the additional UVA radiation to plant. This UVA condition slightly stimulated an accumulation of these substances in normal plant. Some transgenic greatly increased flavonoid accumulation in responding to PAR+UVA, but the others were slightly different compared to WT. The distinct insertion site is directly affected TT8 gene expression. Transgenic seeds had a dark brown color more than WT seed, which indicated high content of polymer flavonoids (proanthocyanins). This over-expressing TT8 in transgenic tobacco may directly or indirectly enhance the signal transductions of PAR and UVA and raise up flavonoid accumulation. (author)

  11. Early-enhancing non-neoplastic lesions on gadolinium-enhanced MRI of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Kanematsu, M. E-mail: masa-gif@umin.ac.jp; Kondo, H.; Semelka, R.C.; Matsuo, M.; Goshima, S.; Hoshi, H.; Moriyama, N.; Itai, Y

    2003-10-01

    AIM: To assess the frequency, cause, and significance of early-enhancing, non-neoplastic (EN) lesions on gadolinium-enhanced magnetic resonance imaging (MRI) of the liver performed for the detection of malignant hepatic tumours. MATERIALS AND METHODS: From September 1997 to September 2000, we reviewed the images of 125 patients, suspected of having hepatic tumours, in whom (1) gadolinium-enhanced triphasic dynamic gradient-recalled-echo (GRE) imaging in addition to unenhanced T1- and T2-weighted MRI was performed, (2) conventional angiography and combination computed tomography (CT) hepatic arteriography and CT during arterial portography were performed within 2 weeks of the MRI, and (3) definitive surgery within 2 weeks of the MRI or follow-up study by means of intravenously contrast-enhanced CT or MRI in 10 months or more was performed. Angiographic studies were correlated to determine the underlying causes of the EN lesions. RESULTS: We found 78 EN lesions in 36 patients (29%), ranging in size from 4 and 50 mm (mean, 12.2 mm). From the MR reports, our radiologists had prospectively diagnosed EN lesions as probable malignant tumours in eight (10%), possible malignant tumours in 36 (46%), and probable non-neoplastic lesion in 34 (44%). EN lesions were found in 27 of 81 (33%) cirrhotic patients and in nine of 44 (20%) non-cirrhotic patients. Fifty-one EN lesions (65%) were located along the liver edge. The shape was circular in 42 (54%), oval in 14 (18%), irregular in 12 (15%), wedge-shaped in seven (9%), and fan-shaped in three (4%). Twenty EN lesions (26%) appeared slightly hyperintense on T2-weighted images. The causes were non-neoplastic arterio-portal shunting in 48 (62%), cystic venous drainage in four (5%), rib compression in four (5%), aberrant right gastric venous drainage in two (3%), and unknown in 20 (26%). CONCLUSION: Over half the number of EN lesions were caused by non-neoplastic arterio-portal shunting, occasionally showing slight hyperintensity on

  12. A Glycolipid Adjuvant, 7DW8-5, Enhances CD8+ T Cell Responses Induced by an Adenovirus-Vectored Malaria Vaccine in Non-Human Primates

    OpenAIRE

    Padte, Neal N.; Boente-Carrera, Mar; Andrews, Chasity D.; McManus, Jenny; Grasperge, Brooke F.; Gettie, Agegnehu; Coelho-dos-Reis, Jordana G.; Li, Xiangming; Wu, Douglass; Bruder, Joseph T.; Sedegah, Martha; Patterson, Noelle; Richie, Thomas L.; Wong, Chi-Huey; Ho, David D.

    2013-01-01

    A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer), enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent ad...

  13. 1st International Early Research Career Enhancement School

    CERN Document Server

    Klimov, Valentin; Rybina, Galina

    2016-01-01

    This book presents cutting-edge research focused on current challenges towards the realization of Biologically Inspired intelligent agents, or Cognitive Architectures (BICA). The chapters are written by both world-recognized experts (including Antonio Chella, Olivier Georgeon, Oliver Kutz, Antonio Lieto, David Vernon, Paul Verschure, and others) and young researchers. Together, they constitute a good mixture of new findings with tutorial-based reviews and position papers, all presented at the First International Early Research Career Enhancement School on Biologically Inspired Cognitive Architectures (FIERCES on BICA 2016), held April 21-24 in Moscow, Russia. Most works included here cross boundaries between disciplines: from neuroscience to social science, from cognitive science to robotics, and from bioengineering to artificial intelligence. A special emphasis is given to novel solutions to urgent problems that have been resisting traditional approaches for decades. Intended for providing readers with an up...

  14. Enhanced MRI in patients with facial palsy; Study of time-related enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Yanagida, Masahiro; Kato, Tsutomu; Ushiro, Koichi; Kitajiri, Masanori; Yamashita, Toshio; Kumazawa, Tadami; Tanaka, Yoshimasa (Kansai Medical School, Moriguchi, Osaka (Japan))

    1991-03-01

    We performed Gd-DTPA-enhanced magnetic resonance imaging (MRI) examinations at several stages in 40 patients with peripheral facial nerve palsy (Bell's palsy and Ramsay-Hunt syndrome). In 38 of the 40 patients, one and more enhanced region could be seen in certain portion of the facial nerve in the temporal bone on the affected side, whereas no enhanced regions were seen on the intact side. Correlations between the timing of the MRI examination and the location of the enhanced regions were analysed. In all 6 patients examined by MRI within 5 days after the onset of facial nerve palsy, enhanced regions were present in the meatal portion. In 3 of the 8 patients (38%) examined by MRI 6 to 10 days after the onset of facial palsy, enhanced areas were seen in both the meatal and labyrinthine portions. In 8 of the 9 patients (89%) tested 11 to 20 days after the onset of palsy, the vertical portion was enhanced. In the 12 patients examined by MRI 21 to 40 days after the onset of facial nerve palsy, the meatal portion was not enhanced while the labyrinthine portion, the horizontal portion and the vertical portion were enhanced in 5 (42%), 8 (67%) and 11 (92%), respectively. Enhancement in the vertical portion was observed in all 5 patients examined more than 41 days after the onset of facial palsy. These results suggest that the central portion of the facial nerve in the temporal bone tends to be enhanced in the early stage of facial nerve palsy, while the peripheral portion is enhanced in the late stage. These changes of Gd-DTPA enhanced regions in the facial nerve may suggest dromic degeneration of the facial nerve in peripheral facial nerve palsy. (author).

  15. High Frequency of CD8 Positive Lymphocyte Infiltration Correlates with Lack of Lymph Node Involvement in Early Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Silvio Däster

    2014-01-01

    Full Text Available Aims. A trend towards local excision of early rectal cancers has prompted us to investigate if immunoprofiling might help in predicting lymph node involvement in this subgroup. Methods. A tissue microarray of 126 biopsies of early rectal cancer (T1 and T2 was stained for several immunomarkers of the innate and the adaptive immune response. Patients’ survival and nodal status were analyzed and correlated with infiltration of the different immune cells. Results. Of all tested markers, only CD8 (P=0.005 and TIA-1 (P=0.05 were significantly more frequently detectable in early rectal cancer biopsies of node negative as compared to node positive patients. Although these two immunomarkers did not display prognostic effect “per se,” CD8+ and, marginally, TIA-1 T cell infiltration could predict nodal involvement in univariate logistic regression analysis (OR 0.994; 95% CI 0.992–0.996; P=0.009 and OR 0.988; 95% CI 0.984–0.994; P=0.05, resp.. An algorithm significantly predicting the nodal status in early rectal cancer based on CD8 together with vascular invasion and tumor border configuration could be calculated (P<0.00001. Conclusion. Our data indicate that in early rectal cancers absence of CD8+ T-cell infiltration helps in predicting patients’ nodal involvement.

  16. The Arabidopsis NF-YA3 and NF-YA8 genes are functionally redundant and are required in early embryogenesis.

    Directory of Open Access Journals (Sweden)

    Monica Fornari

    Full Text Available Nuclear factor Y (NF-Y is a trimeric transcription factor composed of three distinct subunits called NF-YA, NF-YB and NF-YC. In Arabidopsis thaliana, NF-Y subunits are known to play roles in many processes, such as gametogenesis, embryogenesis, seed development, drought resistance, ABA signaling, flowering time, primary root elongation, Endoplasmic Reticulum (ER stress response and blue light responses. Here, we report that the closely related NF-YA3 and NF-YA8 genes control early embryogenesis. Detailed GUS and in situ analyses showed that NF-YA3 and NF-YA8 are expressed in vegetative and reproductive tissues with the highest expression being during embryo development from the globular to the torpedo embryo stage. Plants from the nf-ya3 and nf-ya8 single mutants do not display any obvious phenotypic alteration, whereas nf-ya3 nf-ya8 double mutants are embryo lethal. Morphological analyses showed that the nf-ya3 nf-ya8 embryos fail to undergo to the heart stage and develop into abnormal globular embryos with both proembryo and suspensor characterized by a disordered cell cluster with an irregular shape, suggesting defects in embryo development. The suppression of both NF-YA3 and NF-YA8 gene expression by RNAi experiments resulted in defective embryos that phenocopied the nf-ya3 nf-ya8 double mutants, whereas complementation experiments partially rescued the abnormal globular nf-ya3 nf-ya8 embryos, confirming that NF-YA3 and NF-YA8 are required in early embryogenesis. Finally, the lack of GFP expression of the auxin responsive DR5rev::GFP marker line in double mutant embryos suggested that mutations in both NF-YA3 and NF-YA8 affect auxin response in early developing embryos. Our findings indicate that NF-YA3 and NF-YA8 are functionally redundant genes required in early embryogenesis of Arabidopsis thaliana.

  17. Hox code in embryos of Chinese soft-shelled turtle Pelodiscus sinensis correlates with the evolutionary innovation in the turtle.

    Science.gov (United States)

    Ohya, Yoshie Kawashima; Kuraku, Shigehiro; Kuratani, Shigeru

    2005-03-15

    Turtles have the most unusual body plan of the amniotes, with a dorsal shell consisting of modified ribs. Because this morphological change in the ribs can be described as an axial-level specific alteration, the evolution of the turtle carapace should depend on changes in the Hox code. To identify turtle-specific changes in developmental patterns, we cloned several Hox genes from the Chinese soft-shelled turtle, Pelodiscus sinensis, examined their expression patterns during embryogenesis, and compared them with those of chicken and mouse embryos. We detected possibly turtle-specific derived traits in Hoxc-6 expression, which is restricted to the paraxial part of the embryo; in the expression of Hoxa-5 and Hoxb-5, the transcripts of which were detected only at the cervical level; and in Hoxc-8 and Hoxa-7 expression, which is shifted anteriorly relative to that of the other two amniote groups. From the known functions of the Hox orthologs in model animals, these P. sinensis-specific changes apparently correlate with specializations in the turtle-specific body plan. Copyright 2005 Wiley-Liss, Inc.

  18. A glycolipid adjuvant, 7DW8-5, enhances CD8+ T cell responses induced by an adenovirus-vectored malaria vaccine in non-human primates.

    Science.gov (United States)

    Padte, Neal N; Boente-Carrera, Mar; Andrews, Chasity D; McManus, Jenny; Grasperge, Brooke F; Gettie, Agegnehu; Coelho-dos-Reis, Jordana G; Li, Xiangming; Wu, Douglass; Bruder, Joseph T; Sedegah, Martha; Patterson, Noelle; Richie, Thomas L; Wong, Chi-Huey; Ho, David D; Vasan, Sandhya; Tsuji, Moriya

    2013-01-01

    A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer), enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent adjuvant effect on a candidate human malaria vaccine in the more relevant non-human primate (NHP) model, prior to committing to clinical development. The candidate human malaria vaccine, AdPfCA (NMRC-M3V-Ad-PfCA), consists of two non-replicating recombinant adenoviral (Ad) vectors, one expressing the circumsporozoite protein (CSP) and another expressing the apical membrane antigen-1 (AMA1) of Plasmodium falciparum. In several phase 1 clinical trials, AdPfCA was well tolerated and demonstrated immunogenicity for both humoral and cell-mediated responses. In the study described herein, 25 rhesus macaques received prime and boost intramuscular (IM) immunizations of AdPfCA alone or with an ascending dose of 7DW8-5. Our results indicate that 7DW8-5 is safe and well-tolerated and provides a significant enhancement (up to 9-fold) in malaria-specific CD8+ T-cell responses after both priming and boosting phases, supporting further clinical development.

  19. A glycolipid adjuvant, 7DW8-5, enhances CD8+ T cell responses induced by an adenovirus-vectored malaria vaccine in non-human primates.

    Directory of Open Access Journals (Sweden)

    Neal N Padte

    Full Text Available A key strategy to a successful vaccine against malaria is to identify and develop new adjuvants that can enhance T-cell responses and improve protective immunity. Upon co-administration with a rodent malaria vaccine in mice, 7DW8-5, a recently identified novel analog of α-galactosylceramide (α-GalCer, enhances the level of malaria-specific protective immune responses more strongly than the parent compound. In this study, we sought to determine whether 7DW8-5 could provide a similar potent adjuvant effect on a candidate human malaria vaccine in the more relevant non-human primate (NHP model, prior to committing to clinical development. The candidate human malaria vaccine, AdPfCA (NMRC-M3V-Ad-PfCA, consists of two non-replicating recombinant adenoviral (Ad vectors, one expressing the circumsporozoite protein (CSP and another expressing the apical membrane antigen-1 (AMA1 of Plasmodium falciparum. In several phase 1 clinical trials, AdPfCA was well tolerated and demonstrated immunogenicity for both humoral and cell-mediated responses. In the study described herein, 25 rhesus macaques received prime and boost intramuscular (IM immunizations of AdPfCA alone or with an ascending dose of 7DW8-5. Our results indicate that 7DW8-5 is safe and well-tolerated and provides a significant enhancement (up to 9-fold in malaria-specific CD8+ T-cell responses after both priming and boosting phases, supporting further clinical development.

  20. Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

    Directory of Open Access Journals (Sweden)

    Patrik Htun

    Full Text Available Since patients with phenylketonuria (PKU have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT and ß-stiffness index] and platelet activation.In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation. CIMT was measured bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of CIMTleft and CIMTright.Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group.Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients.

  1. Fish-Free Diet in Patients with Phenylketonuria Is Not Associated with Early Atherosclerotic Changes and Enhanced Platelet Activation.

    Science.gov (United States)

    Htun, Patrik; Nee, Jens; Ploeckinger, Ursula; Eder, Klaus; Geisler, Tobias; Gawaz, Meinrad; Bocksch, Wolfgang; Fateh-Moghadam, Suzanne

    2015-01-01

    Since patients with phenylketonuria (PKU) have to follow a lifelong restriction of natural protein to lower phenylalanine-intake, they never eat fish. This diet may lead to a chronic deficit of omega-3 and omega-6 fatty acids with the risk of early atherosclerotic changes. The aim of the study was to analyse the fatty acid profile of PKU patients and to correlate the results with surrogate markers of early atherosclerotic changes [enhanced carotid intima media thickness (CIMT) and ß-stiffness index] and platelet activation. In 43 PKU patients and in 58 healthy controls we prospectively examined the fatty acid profile, CIMT, ß-stiffness index and platelet activation (flow cytometric determination of markers of platelet activation). CIMT was measured bilaterally by ultrasound. CIMTmean was defined as the mean value of the sum of CIMTleft and CIMTright. Despite of lower HDL-cholesterol and higher triglyceride concentrations in the PKU group, there was no significant difference in the omega-6 or omega-3 fatty acid profile, CIMT, ß-stiffness index between both groups. Platelet activation was not enhanced in the PKU group. Fish-free diet does not induce early atherosclerotic changes or enhanced platelet activation in PKU patients.

  2. Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.

    Directory of Open Access Journals (Sweden)

    Jonathan Göke

    2011-12-01

    Full Text Available Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.

  3. Enhancing early consolidation of human episodic memory by theta EEG neurofeedback.

    Science.gov (United States)

    Rozengurt, Roman; Shtoots, Limor; Sheriff, Aviv; Sadka, Ofir; Levy, Daniel A

    2017-11-01

    Consolidation of newly formed memories is readily disrupted, but can it be enhanced? Given the prominent role of hippocampal theta oscillations in memory formation and retrieval, we hypothesized that upregulating theta power during early stages of consolidation might benefit memory stability and persistence. We used EEG neurofeedback to enable participants to selectively increase theta power in their EEG spectra following episodic memory encoding, while other participants engaged in low beta-focused neurofeedback or passively viewed a neutral nature movie. Free recall assessments immediately following the interventions, 24h later and 7d later all indicated benefit to memory of theta neurofeedback, relative to low beta neurofeedback or passive movie-viewing control conditions. The degree of benefit to memory was correlated with the extent of theta power modulation, but not with other spectral changes. Theta enhancement may provide optimal conditions for stabilization of new hippocampus-dependent memories. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment.

    Science.gov (United States)

    Chen, Aiping; Zhang, Yonghui; Meng, Gang; Jiang, Dengxu; Zhang, Hailin; Zheng, Meihong; Xia, Mao; Jiang, Aiqin; Wu, Junhua; Beltinger, Christian; Wei, Jiwu

    2017-07-12

    There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8 + NKG2D + cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8 + NKG2D + cells, mediated by at least three distinct mechanisms. First, MV-Edm infection compelled HCC cells to express the specific NKG2D ligands MICA/B, which may contribute to the activation of CD8 + NKG2D + cells. Second, MV-Edm-infected HCC cells stimulated CD8 + NKG2D + cells to express high level of FasL resulting in enhanced induction of apoptosis. Third, intratumoural administration of MV-Edm enhanced infiltration of intravenously injected CD8 + NKG2D + cells. Moreover, we found that MV-Edm and adoptive CD8 + NKG2D + cells, either administered alone or combined, upregulated the immune suppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in HCC. Elimination of IDO1 by fludarabine enhanced antitumour responses. Taken together, our data provide a novel and clinically relevant strategy for treatment of HCC.

  5. Contrast-enhanced fat- suppression MR imaging of avascular necrosis of femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Tae Kyoung; Shim, Jae Chan; Lee, Ghi Jai; Jeon, Jeong Dong; Bang, Sun Woo; Kim, Ho Kyun [College of Medicine, Inje University, Seoul (Korea, Republic of)

    2000-02-01

    To evaluate the findings and role of contrast-enhanced fat suppression MR imaging in avascular necrosis (AVN) of the femoral head. In 15 patients with AVN of the femoral head, MR T1-weighted and T2-weighted images and contrast-enhanced fat-suppression T1-weighted images were obtained, and the findings were reviewed. Early and advanced groups were classified on the basis of clinical findings and imaging, and the enhancement pattern was classified as either type I, rim enhancement; type II, surrounding diffuse enhancement; type III, intralesional enhancement; or type IV, II + III. Twenty-four cases of AVN of the femoral head were detected; in nine patients, lesions were bilateral. Eight cases occurred in the early group and 16 in the advanced. All eight in the early group showed the 'double line sign' on T2-weighted images, with a type-I enhancement pattern. In the advanced group, type II (8/16) and type IV (8/16) enhancement patterns were seen. Among the cases showing the type-IV pattern, the intralesional enhancing area showed low signal intensity on T1-weighted images and isosignal intensity on T2-weighted in one case, and low signal intensity on T2-weighted in one case, and low signal intensity on T1-weighted images and high signal intensity on T2-weighted in the other cases. There was no difference in the extent of the disease before and after enhancement. Contrast-enhanced fat-suppression MR images may be helpful in evaluating the extent of AVN of the femoral head and predicting the histopathologic findings of the disease. (author)

  6. Contrast-enhanced fat- suppression MR imaging of avascular necrosis of femoral head

    International Nuclear Information System (INIS)

    Oh, Tae Kyoung; Shim, Jae Chan; Lee, Ghi Jai; Jeon, Jeong Dong; Bang, Sun Woo; Kim, Ho Kyun

    2000-01-01

    To evaluate the findings and role of contrast-enhanced fat suppression MR imaging in avascular necrosis (AVN) of the femoral head. In 15 patients with AVN of the femoral head, MR T1-weighted and T2-weighted images and contrast-enhanced fat-suppression T1-weighted images were obtained, and the findings were reviewed. Early and advanced groups were classified on the basis of clinical findings and imaging, and the enhancement pattern was classified as either type I, rim enhancement; type II, surrounding diffuse enhancement; type III, intralesional enhancement; or type IV, II + III. Twenty-four cases of AVN of the femoral head were detected; in nine patients, lesions were bilateral. Eight cases occurred in the early group and 16 in the advanced. All eight in the early group showed the 'double line sign' on T2-weighted images, with a type-I enhancement pattern. In the advanced group, type II (8/16) and type IV (8/16) enhancement patterns were seen. Among the cases showing the type-IV pattern, the intralesional enhancing area showed low signal intensity on T1-weighted images and isosignal intensity on T2-weighted in one case, and low signal intensity on T2-weighted in one case, and low signal intensity on T1-weighted images and high signal intensity on T2-weighted in the other cases. There was no difference in the extent of the disease before and after enhancement. Contrast-enhanced fat-suppression MR images may be helpful in evaluating the extent of AVN of the femoral head and predicting the histopathologic findings of the disease. (author)

  7. Guanfacine enhances inhibitory control and attentional shifting in early abstinent cocaine-dependent individuals.

    Science.gov (United States)

    Fox, Helen; Sofuoglu, Mehmet; Sinha, Rajita

    2015-03-01

    Attenuation of adrenergic drive and cognitive enhancement, via stimulation of alpha2 pre- and post-synaptic receptors, may selectively enhance executive performance in early abstinent cocaine-dependent individuals. As these cognitive processes underpin important treatment-related behaviors, the alpha2 agonist, guanfacine HCl, may represent an effective pharmaco-therapeutic intervention. Twenty-five early abstinent cocaine-dependent individuals were administered a battery of neurocognitive tasks on entry into treatment (baseline) and again following 3 weeks of either placebo or guanfacine treatment (up to 3 mg). Tasks included: Stop Signal, Stroop, 3-Dimentional Intra-dimensional/Extra-dimensional (IDED) task, Spatial Working Memory (SWM), Paired Associates Learning (PAL), Verbal Fluency and the Rey Auditory Verbal Learning Test (RAVLT). Compared with placebo, the guanfacine group demonstrated attenuated anxiety and negative affect as well as improved performance on selective executive tests. This included fewer directional errors on the stop signal task, fewer errors on the extra-dimensional shift component of the IDED task and better attentional switching during verbal fluency. Guanfacine did not improve strategic working memory or peripheral memory. Guanfacine improves selective cognitive processes which may underlie salient treatment-related regulatory behaviors. Alpha2 agonists may therefore represent important agents for cocaine dependence. © The Author(s) 2015.

  8. Predicting Readmission at Early Hospitalization Using Electronic Clinical Data: An Early Readmission Risk Score.

    Science.gov (United States)

    Tabak, Ying P; Sun, Xiaowu; Nunez, Carlos M; Gupta, Vikas; Johannes, Richard S

    2017-03-01

    Identifying patients at high risk for readmission early during hospitalization may aid efforts in reducing readmissions. We sought to develop an early readmission risk predictive model using automated clinical data available at hospital admission. We developed an early readmission risk model using a derivation cohort and validated the model with a validation cohort. We used a published Acute Laboratory Risk of Mortality Score as an aggregated measure of clinical severity at admission and the number of hospital discharges in the previous 90 days as a measure of disease progression. We then evaluated the administrative data-enhanced model by adding principal and secondary diagnoses and other variables. We examined the c-statistic change when additional variables were added to the model. There were 1,195,640 adult discharges from 70 hospitals with 39.8% male and the median age of 63 years (first and third quartile: 43, 78). The 30-day readmission rate was 11.9% (n=142,211). The early readmission model yielded a graded relationship of readmission and the Acute Laboratory Risk of Mortality Score and the number of previous discharges within 90 days. The model c-statistic was 0.697 with good calibration. When administrative variables were added to the model, the c-statistic increased to 0.722. Automated clinical data can generate a readmission risk score early at hospitalization with fair discrimination. It may have applied value to aid early care transition. Adding administrative data increases predictive accuracy. The administrative data-enhanced model may be used for hospital comparison and outcome research.

  9. Gadoxetate disodium-enhanced MR imaging: Differentiation between early-enhancing non-tumorous lesions and hypervascular hepatocellular carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Goshima, Satoshi, E-mail: gossy@par.odn.ne.jp [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Kanematsu, Masayuki [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Department of Radiology Services, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Watanabe, Haruo; Kondo, Hiroshi; Mizuno, Nozomi; Kawada, Hiroshi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Shiratori, Yoshimune [Department of Medical Informatics, Gifu University School of Medicine, Gifu (Japan); Onozuka, Minoru [Department of Physiology and Neuroscience, Kanagawa Dental College, Yokosuka (Japan); Moriyama, Noriyuki [Research Center for Cancer Prevention and Screening, National Cancer Center Hospital, Tsukiji (Japan); Bae, Kyongtae T. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

    2011-08-15

    Purpose: To retrospectively assess imaging features that help differentiate early-enhancing non-tumorous (EN) hepatic lesions from hepatocellular carcinomas (HCCs) on gadoxetate disodium-enhanced MR imaging. Materials and methods: Our institutional review board approved this retrospective study. We reviewed the studies of 158 patients (92 men and 65 women; age range: 29-91; mean age: 65.6 years) with chronic liver damage, who underwent gadoxetate disodium-enhanced MR imaging at 3T MR scanner. Hypervascular lesions identified during the hepatic artery phase were selected for a study cohort. The location, shape, size (maximum diameter and maximum area), and contrast enhancement signal intensity characteristics of the lesions were evaluated, then compared between the EN and HCC lesions. Results: A total of 65 EN lesions (range: 3-60 mm, mean: 13.6 {+-} 10.6 mm) from 35 patients and 33 HCCs (range: 9-61 mm, mean: 19.3 {+-} 12.6 mm) from 20 patients were identified. Lesions were more frequently round or oval in shape for HCCs (n = 29; 88%) than ENs (n = 26; 40%) (P < 0.01). Unexpectedly, some ENs (n = 12; 18%) showed hypointensity on hepatocyte-phase, and 6 (50%) of them were T2 hyperintense. For lesions smaller than 2 cm (9 ENs and 21 HCCs) on hepatic arterial-phase images, the mean area of hypointensity in hepatocyte-phase (54.2 {+-} 33.1 mm{sup 2}) was significantly smaller than those of the corresponding hyperintensity in hepatic arterial-phase (97.1 {+-} 42.0 mm{sup 2}) for EN lesions (P = 0.019), whereas no significant difference in area was found for HCCs. Conclusion: EN lesions may occasionally present with hypointensity during the hepatocyte-phase; presenting a diagnostic dilemma. In this situation, EN lesions may be differentiated from HCCs when a hypointense area in hepatocyte-phase is smaller than the corresponding hypervascular area in hepatic-arterial phase.

  10. Subendometrial enhancement and peritumoral enhancement for assessing endometrial cancer on dynamic contrast enhanced MR imaging

    International Nuclear Information System (INIS)

    Fujii, Shinya; Kido, Aki; Baba, Tsukasa; Fujimoto, Koji; Daido, Sayaka; Matsumura, Noriomi; Konishi, Ikuo; Togashi, Kaori

    2015-01-01

    Highlights: •We have assessed the peritumoral enhancement (PTE), which mimics SEE on DCE. •We evaluated the diagnostic accuracy of SEE for the myometrial invasion and the frequency of PTE. •We assessed the relationship between these enhancements and important pathologic factors. •PTE Type 1 is the main factor causing the overestimation of myometrial invasion using SEE on DCE. •PTE Type 2 correlates the myometrial invasion and may play an important role in the diagnosis of LVSI. -- Abstract: Objectives: To evaluate the diagnostic accuracy of subendometrial enhancement (SEE) in assessing the myometrial invasion in endometrial cancer, the frequency and clinical significance of peritumoral enhancement (PTE) on dynamic contrast enhanced (DCE) imaging. Materials and methods: MR images of 147 patients with endometrial cancer were retrospectively analyzed for intact SEE and PTEs: Type 1, a focal early enhancement peritumorally, and Type 2, an irregular thin-layered early intense enhancement peritumorally. Two radiologists independently assessed intact SEE and PTEs on DCE imaging and compared the lesions by the presence and depth of myometrial invasion, grade, lymphovascular space involvement (LVSI), and lymph node metastasis. The relationship between SEE, PTEs, and each factor was analyzed using univariate and multivariate analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for SEE. Results: The sensitivity, specificity, PPV, NPV and diagnostic accuracy for myometrial invasion based on SEE disruption on DCE were 96.6%, 32.1–46.4%, 85.8–88.5%, 69.2–76.5%, and 84.4–87.1%. According to multivariate analysis, SEE significantly predicted myometrial invasion (p < 0.0001). PTE Type 2 significantly predicted myometrial invasion presence (p < 0.05) and depth (p < 0.01). Conclusion: Diagnosis of myometrial invasion only by using SEE might be difficult on DCE-MRI due to the

  11. Subendometrial enhancement and peritumoral enhancement for assessing endometrial cancer on dynamic contrast enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Shinya [Division of Radiology, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, Yonago (Japan); Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Kido, Aki, E-mail: akikido@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Baba, Tsukasa [Departments of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Fujimoto, Koji; Daido, Sayaka [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Matsumura, Noriomi; Konishi, Ikuo [Departments of Gynecology and Obstetrics, Graduate School of Medicine, Kyoto University, Kyoto (Japan); Togashi, Kaori [Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto (Japan)

    2015-04-15

    Highlights: •We have assessed the peritumoral enhancement (PTE), which mimics SEE on DCE. •We evaluated the diagnostic accuracy of SEE for the myometrial invasion and the frequency of PTE. •We assessed the relationship between these enhancements and important pathologic factors. •PTE Type 1 is the main factor causing the overestimation of myometrial invasion using SEE on DCE. •PTE Type 2 correlates the myometrial invasion and may play an important role in the diagnosis of LVSI. -- Abstract: Objectives: To evaluate the diagnostic accuracy of subendometrial enhancement (SEE) in assessing the myometrial invasion in endometrial cancer, the frequency and clinical significance of peritumoral enhancement (PTE) on dynamic contrast enhanced (DCE) imaging. Materials and methods: MR images of 147 patients with endometrial cancer were retrospectively analyzed for intact SEE and PTEs: Type 1, a focal early enhancement peritumorally, and Type 2, an irregular thin-layered early intense enhancement peritumorally. Two radiologists independently assessed intact SEE and PTEs on DCE imaging and compared the lesions by the presence and depth of myometrial invasion, grade, lymphovascular space involvement (LVSI), and lymph node metastasis. The relationship between SEE, PTEs, and each factor was analyzed using univariate and multivariate analyses. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated for SEE. Results: The sensitivity, specificity, PPV, NPV and diagnostic accuracy for myometrial invasion based on SEE disruption on DCE were 96.6%, 32.1–46.4%, 85.8–88.5%, 69.2–76.5%, and 84.4–87.1%. According to multivariate analysis, SEE significantly predicted myometrial invasion (p < 0.0001). PTE Type 2 significantly predicted myometrial invasion presence (p < 0.05) and depth (p < 0.01). Conclusion: Diagnosis of myometrial invasion only by using SEE might be difficult on DCE-MRI due to the

  12. Enhancing Community Based Early Warning Systems in Nepal with Flood Forecasting Using Local and Global Models

    Science.gov (United States)

    Dugar, Sumit; Smith, Paul; Parajuli, Binod; Khanal, Sonu; Brown, Sarah; Gautam, Dilip; Bhandari, Dinanath; Gurung, Gehendra; Shakya, Puja; Kharbuja, RamGopal; Uprety, Madhab

    2017-04-01

    % probability of exceeding the Medium Level Alert in two days. Rainfall stations upstream of the West Rapti catchment recorded heavy rainfall on 26 July, and localized forecasts from the probabilistic model at 8 am suggested that the water level would cross a pre-determined warning level in the next 3 hours. The Flood Forecasting Section at DHM issued a flood advisory, and disseminated SMS flood alerts to more than 13,000 at-risk people residing along the floodplains. Water levels crossed the danger threshold (5.4 meters) at 11 am, peaking at 8.15 meters at 10 pm. Extension of the warning lead time from probabilistic forecasts was significant in minimising the risk to lives and livelihoods as communities gained extra time to prepare, evacuate and respond. Likewise, longer timescale forecasts from GLoFAS could be potentially linked with no-regret early actions leading to improved preparedness and emergency response. These forecasting tools have contributed to enhance the effectiveness and efficiency of existing community based systems, increasing the lead time for response. Nevertheless, extensive work is required on appropriate ways to interpret and disseminate probabilistic forecasts having longer (2-14 days) and shorter (3-5 hours) time horizon for operational deployment as there are numerous uncertainties associated with predictions.

  13. Detection of Enhanced Central Mass-to-light Ratios in Low-mass Early-type Galaxies: Evidence for Black Holes?

    Science.gov (United States)

    Pechetti, Renuka; Seth, Anil; Cappellari, Michele; McDermid, Richard; den Brok, Mark; Mieske, Steffen; Strader, Jay

    2017-11-01

    We present dynamical measurements of the central mass-to-light ratio (M/L) of a sample of 27 low-mass early-type {{ATLAS}}3{{D}} galaxies. We consider all {{ATLAS}}3{{D}} galaxies with 9.7 text{}}M/L{{s}} are higher than dynamical {\\text{}}M/L{{s}} derived at larger radii and stellar population estimates of the galaxy centers in ˜80% of galaxies, with a median enhancement of ˜14% and a statistical significance of 3.3σ. We show that the enhancement in the central M/L is best described either by the presence of black holes in these galaxies or by radial initial mass function variations. Assuming a black hole model, we derive black hole masses for the sample of galaxies. In two galaxies, NGC 4458 and NGC 4660, the data suggest significantly overmassive black holes, while in most others only upper limits are obtained. We also show that the level of M/L enhancements we see in these early-type galaxy nuclei are consistent with the larger enhancements seen in ultracompact dwarf galaxies (UCDs), supporting the scenario where massive UCDs are created by stripping galaxies of these masses.

  14. Enhancing early detection of exotic pests in agricultural and forest ecosystems using an urban-gradient framework.

    Science.gov (United States)

    Colunga-Garcia, Manuel; Magarey, Roger A; Haack, Robert A; Gage, Stuart H; Qi, Jiaquo

    2010-03-01

    Urban areas are hubs of international transport and therefore are major gateways for exotic pests. Applying an urban gradient to analyze this pathway could provide insight into the ecological processes involved in human-mediated invasions. We defined an urban gradient for agricultural and forest ecosystems in the contiguous United States to (1) assess whether ecosystems nearer more urbanized areas were at greater risk of invasion, and (2) apply this knowledge to enhance early detection of exotic pests. We defined the gradient using the tonnage of imported products in adjacent urban areas and their distance to nearby agricultural or forest land. County-level detection reports for 39 exotic agricultural and forest pests of major economic importance were used to characterize invasions along the gradient. We found that counties with more exotic pests were nearer the urban end of the gradient. Assuming that the exotic species we analyzed represent typical invaders, then early detection efforts directed at 21-26% of U.S. agricultural and forest land would likely be able to detect 70% of invaded counties and 90% of the selected species. Applying an urban-gradient framework to current monitoring strategies should enhance early detection efforts of exotic pests, facilitating optimization in allocating resources to areas at greater risk of future invasions.

  15. HIV screening at health facilities and community pharmacies in Kenya : Enhancing test uptake and early diagnosis

    NARCIS (Netherlands)

    Mugo, P.M.

    2017-01-01

    Despite a tremendous scale-up of antiretroviral therapy, as many as 54% of HIV-infected persons globally remain undiagnosed hence are not on treatment. This thesis presents findings from a series of studies conducted in Coastal Kenya aiming to enhance HIV test uptake and early diagnosis. We found

  16. Early dynamic imaging in "6"8Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions

    International Nuclear Information System (INIS)

    Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Warwitz, Boris; Scarpa, Lorenza; Roig, Llanos Geraldo; Kendler, Dorota; Guggenberg, Elisabeth von; Virgolini, Irene Johanna; Fritz, Josef; Bektic, Jasmin; Horninger, Wolfgang

    2017-01-01

    PET/CT with "6"8Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60 min after injection. This study sought to verify whether early dynamic "6"8Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. Eighty consecutive PC patients referred to "6"8Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60 min post injection early dynamic imaging of the pelvis in the first 8 min after tracer injection was performed. SUV_m_a_x of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. A total of 55 lesions consistent with malignancy on 60 min whole body imaging exhibited also pathologic "6"8Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3 min, whereas urinary bladder activity was absent within the first 3 min of dynamic imaging in all patients. Suv_m_a_x was significantly higher in PC lesions in the first 6 min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. Early dynamic imaging in "6"8Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic bladder accumulation

  17. Early Spring Post-Fire Snow Albedo Dynamics in High Latitude Boreal Forests Using Landsat-8 OLI Data

    Science.gov (United States)

    Wang, Zhuosen; Erb, Angela M.; Schaaf, Crystal B.; Sun, Qingsong; Liu, Yan; Yang, Yun; Shuai, Yanmin; Casey, Kimberly A.; Roman, Miguel O.

    2016-01-01

    Taking advantage of the improved radiometric resolution of Landsat-8 OLI which, unlike previous Landsat sensors, does not saturate over snow, the progress of fire recovery progress at the landscape scale (less than 100 m) is examined. High quality Landsat-8 albedo retrievals can now capture the true reflective and layered character of snow cover over a full range of land surface conditions and vegetation densities. This new capability particularly improves the assessment of post-fire vegetation dynamics across low- to high-burn severity gradients in Arctic and boreal regions in the early spring, when the albedos during recovery show the greatest variation. We use 30 m resolution Landsat-8 surface reflectances with concurrent coarser resolution (500 m) MODIS high quality full inversion surface Bidirectional Reflectance Distribution Functions (BRDF) products to produce higher resolution values of surface albedo. The high resolution full expression shortwave blue sky albedo product performs well with an overall RMSE of 0.0267 between tower and satellite measures under both snow-free and snow-covered conditions. While the importance of post-fire albedo recovery can be discerned from the MODIS albedo product at regional and global scales, our study addresses the particular importance of early spring post-fire albedo recovery at the landscape scale by considering the significant spatial heterogeneity of burn severity, and the impact of snow on the early spring albedo of various vegetation recovery types. We found that variations in early spring albedo within a single MODIS gridded pixel can be larger than 0.6. Since the frequency and severity of wildfires in Arctic and boreal systems is expected to increase in the coming decades, the dynamics of albedo in response to these rapid surface changes will increasingly impact the energy balance and contribute to other climate processes and physical feedback mechanisms. Surface radiation products derived from Landsat-8 data will

  18. Photothermal-enhanced catalysis in core-shell plasmonic hierarchical Cu7S4 microsphere@zeolitic imidazole framework-8.

    Science.gov (United States)

    Wang, Feifan; Huang, Yanjie; Chai, Zhigang; Zeng, Min; Li, Qi; Wang, Yuan; Xu, Dongsheng

    2016-12-01

    Conventional semiconductor photocatalysis based on band-edge absorption remains inefficient due to the limited harvesting of solar irradiation and the complicated surface/interface chemistry. Herein, novel photothermal-enhanced catalysis was achieved in a core-shell hierarchical Cu 7 S 4 nano-heater@ZIF-8 heterostructures via near-infrared localized surface plasmon resonance. Our results demonstrated that both the high surface temperature of the photothermal Cu 7 S 4 core and the close-adjacency of catalytic ZIF-8 shell contributed to the extremely enhanced catalytic activity. Under laser irradiation (1450 nm, 500 mW), the cyclocondensation reaction rate increased 4.5-5.4 fold compared to that of the process at room temperature, in which the 1.6-1.8 fold enhancement was due to the localized heating effect. The simulated sunlight experiments showed a photothermal activation efficiency (PTAE) of 0.07%, further indicating the validity of photothermal catalysis based on the plasmonic semiconductor nanomaterials. More generally, this approach provides a platform to improve reaction activity with efficient utilization of solar energy, which can be readily extended to other green-chemistry processes.

  19. Utility of Gd-EOB-DTPA-Enhanced MRI in Diagnosing Small Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Soo Ryang Kim

    2009-07-01

    Full Text Available We describe an 8-mm hepatocellular carcinoma (HCC with hepatitis C virus-related cirrhosis in a 74-year-old woman. Ultrasound (US revealed an 8-mm hyperechoic nodule in segment 6 of the liver. Contrast-enhanced computed tomography (CT and US revealed no hypervascularity in the early phase and no washout in the late phase and the Kupffer phase, respectively. CT during arteriography revealed no hypervascularity and CT during arterial portography disclosed no perfusion defect. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI revealed no hypervascularity in the early phase, but disclosed a defect in the hepatobiliary phase. Histologically, the nodule was diagnosed as well-differentiated HCC characterized by more than two-fold the cellularity of the non-tumorous area, with a high nuclear:cytoplasmic ratio, increased cytoplasmic eosinophilia, fatty change, and slight cell atypia with an irregular thin trabecular pattern. Our case demonstrates the utility of Gd-EOB-DTPA-enhanced MRI in the diagnosis of small HCC.

  20. Human mesenchymal stromal cells enhance the immunomodulatory function of CD8+CD28− regulatory T cells

    Science.gov (United States)

    Liu, Qiuli; Zheng, Haiqing; Chen, Xiaoyong; Peng, Yanwen; Huang, Weijun; Li, Xiaobo; Li, Gang; Xia, Wenjie; Sun, Qiquan; Xiang, Andy Peng

    2015-01-01

    One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on the other subsets of Treg cells. Herein, we studied the effects of MSCs on CD8+CD28− Treg cells and found that the MSCs could not only increase the proportion of CD8+CD28− T cells, but also enhance CD8+CD28−T cells' ability of hampering naive CD4+ T-cell proliferation and activation, decreasing the production of IFN-γ by activated CD4+ T cells and inducing the apoptosis of activated CD4+ T cells. Mechanistically, the MSCs affected the functions of the CD8+CD28− T cells partially through moderate upregulating the expression of IL-10 and FasL. The MSCs had no distinct effect on the shift from CD8+CD28+ T cells to CD8+CD28− T cells, but did increase the proportion of CD8+CD28− T cells by reducing their rate of apoptosis. In summary, this study shows that MSCs can enhance the regulatory function of CD8+CD28− Treg cells, shedding new light on MSCs-mediated immune regulation. PMID:25482073

  1. Enhanced adhesion of early endothelial progenitor cells to radiation-induced senescence-like vascular endothelial cells in vitro

    International Nuclear Information System (INIS)

    Sermsathanasawadi, N.; Inoue, Yoshinori; Iwai, Takehisa; Ishii, Hideto; Yoshida, Masayuki; Igarashi, Kaori; Miura, Masahiko

    2009-01-01

    The effects of ionizing radiation (IR) on tumor neovascularization are still unclear. We previously reported that vascular endothelial cells (ECs) expressing the IR-induced senescence-like (IRSL) phenotype exhibit a significant decrease in angiogenic activity in vitro. In this study, we examined the effects of the IRSL phenotype on adhesion to early endothelial progenitor cells (early EPCs). Adhesion of human peripheral blood-derived early EPCs to human umbilical vein endothelial cells (HUVECs) expressing the IRSL phenotype was evaluated by an adhesion assay under static conditions. It was revealed that the IRSL HUVECs supported significantly more adhesion of early EPCs than normal HUVECs. Expressions of ICAM-1, VCAM-1 and E-selectin were up-regulated in IRSL HUVECs. Pre-treatment of IRSL HUVECs with adhesion-blocking monoclonal antibodies against E-selectin and VCAM-1 significantly reduced early EPC adhesion to IRSL HUVECs, suggesting a potential role for the E-selectin and VCAM-1 in the adhesion between IRSL ECs and early EPCs. Therefore, the IRSL phenotype expressed in ECs may enhance neovascularization via increased homing of early EPCs. Our findings are first to implicate the complex effects of this phenotype on tumor neovascularization following irradiation. (author)

  2. Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence.

    Science.gov (United States)

    Ibáñez, Lourdes; López-Bermejo, Abel; Díaz, Marta; Marcos, Maria Victoria; de Zegher, Francis

    2011-08-01

    Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS). The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS. This was a randomized, open-label study over 7 yr. The study was conducted at a university hospital. Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr. Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr). Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr). None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr. In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche.

  3. Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells.

    Science.gov (United States)

    Tršan, Tihana; Vuković, Kristina; Filipović, Petra; Brizić, Ana Lesac; Lemmermann, Niels A W; Schober, Kilian; Busch, Dirk H; Britt, William J; Messerle, Martin; Krmpotić, Astrid; Jonjić, Stipan

    2017-08-01

    Designing CD8 + T-cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 + T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. CMV vector expressing RAE-1γ potentiated expansion of KLRG1 + CD8 + T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long-term maintenance of epitope-specific CD8 + T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8 + T-cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8 + T-cell sensitive tumors. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Infusing Early Childhood Mental Health into Early Intervention Services

    Science.gov (United States)

    Grabert, John C.

    2009-01-01

    This article describes the process of enhancing early childhood mental health awareness and skills in non-mental health staff. The author describes a pilot training model, conducted the U.S. Army's Early Intervention Services, that involved: (a) increasing early childhood mental health knowledge through reflective readings, (b) enhancing…

  5. Monodispersed ZIF-8 particles with enhanced performance for CO2 adsorption and heterogeneous catalysis

    Science.gov (United States)

    Guan, Yebin; Shi, Juanjuan; Xia, Ming; Zhang, Jun; Pang, Zhenfeng; Marchetti, Alessandro; Wang, Xiaohong; Cai, Jingsong; Kong, Xueqian

    2017-11-01

    Monodispersed zeolitic imidazolate frameworks (ZIFs) were prepared with a simple method using dimethylsulfoxide (DMSO) as solvent. This method yields ZIF-8 nanoparticles with a narrow particle size distribution of 90-110 nm and the dispersion is highly stable against agglomeration. These particles have larger nanosized porosity and enhanced CO2 adsorption capability compared to ZIF-8 prepared with different solvents such as methanol or N, N-dimethyl formamide. Their uniform size and surface chemistry also lead to superior performance in the Knoevenagel condensation reactions. The ZIF-8 nanoparticles possess high thermal stability up to 550 °C and the preparation steps are easy for scaling up which are favorable for industrial applications.

  6. Differentiation between early rheumatoid arthritis patients and healthy persons by conventional and dynamic contrast-enhanced magnetic resonance imaging

    DEFF Research Database (Denmark)

    Axelsen, Mette Bjørndal; Ejbjerg, B J; Hetland, M L

    2014-01-01

    OBJECTIVES: To identify the magnetic resonance imaging (MRI) parameter that best differentiates healthy persons and patients with early rheumatoid arthritis (RA), and to investigated responsiveness to treatment of various MRI parameters. METHOD: Conventional MRI and dynamic contrast-enhanced (DCE...

  7. Early Appropriate Care: A Protocol to Standardize Resuscitation Assessment and to Expedite Fracture Care Reduces Hospital Stay and Enhances Revenue.

    Science.gov (United States)

    Vallier, Heather A; Dolenc, Andrea J; Moore, Timothy A

    2016-06-01

    We hypothesized that a standardized protocol for fracture care would enhance revenue by reducing complications and length of stay. Prospective consecutive series. Level 1 trauma center. Two hundread and fifty-three adult patients with a mean age of 40.7 years and mean Injury Severity Score of 26.0. Femur, pelvis, or spine fractures treated surgically. Hospital and professional charges and collections were analyzed. Fixation was defined as early (<36 hours) or delayed. Complications and hospital stay were recorded. Mean charges were US $180,145 with a mean of US $66,871 collected (37%). The revenue multiplier was US $59,882/$6989 (8.57), indicating hospital collection of US $8.57 for every professional dollar, less than half of which went to orthopaedic surgeons. Delayed fracture care was associated with more intensive care unit (4.5 vs. 9.4) and total hospital days (9.4 vs. 15.3), with mean loss of actual revenue US $6380/patient delayed (n = 47), because of the costs of longer length of stay. Complications were associated with the highest expenses: mean of US $291,846 charges and US $101,005 collections, with facility collections decreased by 5.1%. An uncomplicated course of care was associated with the most favorable total collections: (US $60,017/$158,454 = 38%) and the shortest mean stay (8.7 days). Facility collections were nearly 9 times more than professional collections. Delayed fixation was associated with more complications, and facility collections decreased 5% with a complication. Furthermore, delayed fixation was associated with longer hospital stay, accounting for US $300K more in actual costs during the study. A standardized protocol to expedite definitive fixation enhances the profitability of the trauma service line. Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.

  8. Enhanced MRI in patients with facial palsy

    International Nuclear Information System (INIS)

    Yanagida, Masahiro; Kato, Tsutomu; Ushiro, Koichi; Kitajiri, Masanori; Yamashita, Toshio; Kumazawa, Tadami; Tanaka, Yoshimasa

    1991-01-01

    We performed Gd-DTPA-enhanced magnetic resonance imaging (MRI) examinations at several stages in 40 patients with peripheral facial nerve palsy (Bell's palsy and Ramsay-Hunt syndrome). In 38 of the 40 patients, one and more enhanced region could be seen in certain portion of the facial nerve in the temporal bone on the affected side, whereas no enhanced regions were seen on the intact side. Correlations between the timing of the MRI examination and the location of the enhanced regions were analysed. In all 6 patients examined by MRI within 5 days after the onset of facial nerve palsy, enhanced regions were present in the meatal portion. In 3 of the 8 patients (38%) examined by MRI 6 to 10 days after the onset of facial palsy, enhanced areas were seen in both the meatal and labyrinthine portions. In 8 of the 9 patients (89%) tested 11 to 20 days after the onset of palsy, the vertical portion was enhanced. In the 12 patients examined by MRI 21 to 40 days after the onset of facial nerve palsy, the meatal portion was not enhanced while the labyrinthine portion, the horizontal portion and the vertical portion were enhanced in 5 (42%), 8 (67%) and 11 (92%), respectively. Enhancement in the vertical portion was observed in all 5 patients examined more than 41 days after the onset of facial palsy. These results suggest that the central portion of the facial nerve in the temporal bone tends to be enhanced in the early stage of facial nerve palsy, while the peripheral portion is enhanced in the late stage. These changes of Gd-DTPA enhanced regions in the facial nerve may suggest dromic degeneration of the facial nerve in peripheral facial nerve palsy. (author)

  9. Computed Tomography Assessment of Ablation Zone Enhancement in Patients With Early-Stage Lung Cancer After Stereotactic Ablative Radiotherapy.

    Science.gov (United States)

    Moore, William; Chaya, Yair; Chaudhry, Ammar; Depasquale, Britney; Glass, Samantha; Lee, Susan; Shin, James; Mikhail, George; Bhattacharji, Priya; Kim, Bong; Bilfinger, Thomas

    2015-01-01

    Stereotactic ablative radiotherapy (SABR) offers a curative treatment for lung cancer in patients who are marginal surgical candidates. However, unlike traditional surgery the lung cancer remains in place after treatment. Thus, imaging follow-up for evaluation of recurrence is of paramount importance. In this retrospective designed Institutional Review Board-approved study, follow-up contrast-enhanced computed tomography (CT) exams were performed on sixty one patients to evaluate enhancement pattern in the ablation zone at 1, 3, 6, and 12 months after SABR. Eleven patients had recurrence within the ablation zone after SABR. The postcontrast enhancement in the recurrence group showed a washin and washout phenomenon, whereas the radiation-induced lung injury group showed continuous enhancement suggesting an inflammatory process. The textural feature of the ablation zone of enhancement and perfusion as demonstrated in computed tomography nodule enhancement may allow early differentiation of recurrence from radiation-induced lung injury in patients' status after SABR or primary lung cancer.

  10. Enhancing international collaboration among early-career researchers

    Science.gov (United States)

    Carroll, Jennifer K; Albada, Akke; Farahani, Mansoureh; Lithner, Maria; Neumann, Melanie; Sandhu, Harbinder; Shepherd, Heather L

    2010-01-01

    Objective The European Association of Communication in Healthcare (EACH) Early Career Researchers Network (ECRN) aims are to (1) promote international collaboration among young investigators and (2) provide a support network for future innovative communication research projects. In October 2009, Miami, USA at a workshop facilitated by the ECRN at the International Conference on Communication in Healthcare (ICCH) hosted by the American Academy of Communication in Healthcare we explored common facilitators and challenges faced by early career researchers in health communication research. Methods Attendees introduced themselves, their research area(s) of interest, and listed one facilitator and one barrier for their career development. EACH ECRN members then led a discussion of facilitators and challenges encountered in communication research projects and career development. We discussed potential collaboration opportunities, future goals, and activities. Results Having supportive collegial relationships, institutional support, job security, and funding are critical facilitators for early career investigators. Key challenges include difficulty with time management and prioritizing, limited resources, and contacts. Conclusion International collaboration among early career researchers is a feasible and effective means to address important challenges, by increasing opportunities for professional support and networking, problem-solving, discussion of data, and ultimately publishing. Practice Implications Future AACH-EACH Early Career Researcher Networks should continue to build collaborations by developing shared research projects, papers, and other scholarly products. PMID:20663630

  11. Enhancing pattern of gastric carcinoma at dynamic incremental CT: correlation with gross and histologic findings

    International Nuclear Information System (INIS)

    Shin, Hong Seop; Lee, Dong Ho; Kim, Yoon Hwa; Ko, Young Tae; Lim, Joo Won; Yoon, Yup

    1996-01-01

    To evaluate the enhancing pattern of gastric carcinomas at dynamic incremental CT and to correlate it with pathologic findings. We retrospectively evaluated the enhancement pattern of stomach cancer on dynamic incremental CT of the 78 patients. All the lesions had been pathologically proved after surgery. The enhancement pattern was categorized as good or poor in the early phase;homogeneous, heterogeneous or ring enhancement;the presence or absence of delayed enhancement. There were 16 cases of early gastric cancer (EGC), and 62 cases of advanced gastric cancer(AGC). The Borrmann type of AGC were 1(n=1), 2(n=20), 3=(n=32), 4(n=8) and 5(n=1). The histologic patterns of AGC were tubular(n=49), signet ring cell(n=10), and mucinous(n=3). The enhancing patterns were compared with gross and histologic findings and delayed enhancement was correlated with pathologic evidence of desmoplasia. Good enhancement of tumor was seen in 24/41cases (58.5%) with AGC Borrmann type 3-5, in 6/21(28.6%) with AGC Borrmann type 1-2, and in 3/16(18.8%) with EGC (P<.05). By histologic pattern, good enhancement of tumor was seen in 8/10(80%) with signet ring cell type, in 21/49(42.9%) with tubular type, and in 1/3(33.3%) with mucinous type(P<.05). EGC was homogeneously enhanced in 14/16cases (87.5%), but AGC was heterogeneously enhanced in 33/62(53.2%), respectively(P<.01). There was no significant correlation between delayed enhancement and the presence of desmoplasia. AGC Borrmann type 3-5 and signet ring cell type have a tendency to show good enhancement and EGC is more homogeneously enhanced at dynamic incremental CT

  12. EXCESS OPTICAL ENHANCEMENT OBSERVED WITH ARCONS FOR EARLY CRAB GIANT PULSES

    Energy Technology Data Exchange (ETDEWEB)

    Strader, M. J.; Mazin, B. A.; Spiro Jaeger, G. V.; Gwinn, C. R.; Meeker, S. R.; Szypryt, P.; Van Eyken, J. C.; Marsden, D.; Walter, A. B.; Ulbricht, G. [Department of Physics, University of California, Santa Barbara, CA 93106 (United States); Johnson, M. D. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); O' Brien, K. [Department of Physics, University of Oxford, Denys Wilkinson Building, Keble Road, Oxford OX1 3RH (United Kingdom); Stoughton, C. [Fermilab Center for Particle Astrophysics, Batavia, IL 60510 (United States); Bumble, B. [NASA Jet Propulsion Laboratory, 4800 Oak Grove Drive, Pasadena, CA 91125 (United States)

    2013-12-10

    We observe an extraordinary link in the Crab pulsar between the enhancement of an optical pulse and the timing of the corresponding giant radio pulse. At optical through infrared wavelengths, our observations use the high time resolution of ARray Camera for Optical to Near-IR Spectrophotometry, a unique superconducting energy-resolving photon-counting array at the Palomar 200 inch telescope. At radio wavelengths, we observe with the Robert C. Byrd Green Bank Telescope and the Green Bank Ultimate Pulsar Processing Instrument backend. We see an 11.3% ± 2.5% increase in peak optical flux for pulses that have an accompanying giant radio pulse arriving near the peak of the optical main pulse, in contrast to a 3.2% ± 0.5% increase when an accompanying giant radio pulse arrives soon after the optical peak. We also observe that the peak of the optical main pulse is 2.8% ± 0.8% enhanced when there is a giant radio pulse accompanying the optical interpulse. We observe no statistically significant spectral differences between optical pulses accompanied by and not accompanied by giant radio pulses. Our results extend previous observations of optical-radio correlation to the time and spectral domains. Our refined temporal correlation suggests that optical and radio emission are indeed causally linked, and the lack of spectral differences suggests that the same mechanism is responsible for all optical emission.

  13. EXCESS OPTICAL ENHANCEMENT OBSERVED WITH ARCONS FOR EARLY CRAB GIANT PULSES

    International Nuclear Information System (INIS)

    Strader, M. J.; Mazin, B. A.; Spiro Jaeger, G. V.; Gwinn, C. R.; Meeker, S. R.; Szypryt, P.; Van Eyken, J. C.; Marsden, D.; Walter, A. B.; Ulbricht, G.; Johnson, M. D.; O'Brien, K.; Stoughton, C.; Bumble, B.

    2013-01-01

    We observe an extraordinary link in the Crab pulsar between the enhancement of an optical pulse and the timing of the corresponding giant radio pulse. At optical through infrared wavelengths, our observations use the high time resolution of ARray Camera for Optical to Near-IR Spectrophotometry, a unique superconducting energy-resolving photon-counting array at the Palomar 200 inch telescope. At radio wavelengths, we observe with the Robert C. Byrd Green Bank Telescope and the Green Bank Ultimate Pulsar Processing Instrument backend. We see an 11.3% ± 2.5% increase in peak optical flux for pulses that have an accompanying giant radio pulse arriving near the peak of the optical main pulse, in contrast to a 3.2% ± 0.5% increase when an accompanying giant radio pulse arrives soon after the optical peak. We also observe that the peak of the optical main pulse is 2.8% ± 0.8% enhanced when there is a giant radio pulse accompanying the optical interpulse. We observe no statistically significant spectral differences between optical pulses accompanied by and not accompanied by giant radio pulses. Our results extend previous observations of optical-radio correlation to the time and spectral domains. Our refined temporal correlation suggests that optical and radio emission are indeed causally linked, and the lack of spectral differences suggests that the same mechanism is responsible for all optical emission

  14. Aldimine Formation Reaction, the First Step of the Maillard Early-phase Reaction, Might be Enhanced in Variant Hemoglobin, Hb Himeji.

    Science.gov (United States)

    Koga, Masafumi; Inada, Shinya; Shimizu, Sayoko; Hatazaki, Masahiro; Umayahara, Yutaka; Nishihara, Eijun

    2015-01-01

    Hb Himeji (β140Ala→Asp) is known as a variant hemoglobin in which glycation is enhanced and HbA1c measured by immunoassay shows a high value. The phenomenon of enhanced glycation in Hb Himeji is based on the fact that the glycation product of variant hemoglobin (HbX1c) shows a higher value than HbA1c. In this study, we investigated whether aldimine formation reaction, the first step of the Maillard early-phase reaction, is enhanced in Hb Himeji in vitro. Three non-diabetic subjects with Hb Himeji and four non-diabetic subjects without variant hemoglobin were enrolled. In order to examine aldimine formation reaction, whole blood cells were incubated with 500 mg/dl of glucose at 37°C for 1 hour and were analyzed by high-performance liquid chromatography. Both HbA1c and HbX1c were not increased in this condition. After incubation with glucose, labile HbA1c (LA1c) fraction increased in the controls (1.1±0.3%). In subjects with Hb Himeji increases in the labile HbX1c (LX1c) fraction as well as the LA1c fraction were observed, and the degree of increase in the LX1c fraction was significantly higher than that of the LA1c fraction (1.8±0.1% vs. 0.5±0.2%, Preaction might be enhanced in Hb Himeji in vitro. The 140th amino acid in β chain of hemoglobin is suggested to be involved in aldimine formation reaction. © 2015 by the Association of Clinical Scientists, Inc.

  15. An EG-VEGF-dependent decrease in homeobox gene NKX3.1 contributes to cytotrophoblast dysfunction: a possible mechanism in human fetal growth restriction.

    Science.gov (United States)

    Murthi, P; Brouillet, S; Pratt, A; Borg, Aj; Kalionis, B; Goffin, F; Tsatsaris, V; Munaut, C; Feige, Jj; Benharouga, M; Fournier, T; Alfaidy, N

    2015-07-21

    Idiopathic fetal growth restriction (FGR) is frequently associated with placental insufficiency. Previous reports have provided evidence that EG-VEGF (endocrine gland derived-vascular endothelial growth factor), a placental secreted protein, is expressed during the first trimester of pregnancy, controls both trophoblast proliferation and invasion, and its increased expression is associated with human FGR. In this study, we hypothesise that EG-VEGF-dependent change in placental homeobox gene expressions contribute to trophoblast dysfunction in idiopathic FGR. The changes in EG-VEGF-dependent homeobox gene expressions were determined using a Homeobox gene cDNA array on placental explants of 8-12 weeks' gestation after stimulation with EG-VEGF in vitro for 24 hours. The Homeobox gene array identified a >5-fold increase in HOXA9, HOXC8, HOXC10, HOXD1, HOXD8, HOXD9 and HOXD11, while NKX 3.1 showed a >2 fold-decrease in mRNA expression compared to untreated controls. Homeobox gene NKX3.1 was selected as a candidate because it is a downstream target of EG-VEGF and its expression and functional role are largely unknown in control and idiopathic FGR-affected placentae. Real-time PCR and immunoblotting showed a significant decrease in NKX3.1 mRNA and protein levels, respectively, in placentae from FGR compared to control pregnancies. Gene inactivation in vitro using short-interference RNA specific for NKX3.1 demonstrated an increase in BeWo cell differentiation and a decrease in HTR8-SVneo proliferation. We conclude that the decreased expression of homeobox gene NKX3.1 down-stream of EG-VEGF may contribute to the trophoblast dysfunction associated with idiopathic FGR pregnancies.

  16. Texture Segregation Causes Early Figure Enhancement and Later Ground Suppression in Areas V1 and V4 of Visual Cortex.

    Science.gov (United States)

    Poort, Jasper; Self, Matthew W; van Vugt, Bram; Malkki, Hemi; Roelfsema, Pieter R

    2016-10-01

    Segregation of images into figures and background is fundamental for visual perception. Cortical neurons respond more strongly to figural image elements than to background elements, but the mechanisms of figure-ground modulation (FGM) are only partially understood. It is unclear whether FGM in early and mid-level visual cortex is caused by an enhanced response to the figure, a suppressed response to the background, or both.We studied neuronal activity in areas V1 and V4 in monkeys performing a texture segregation task. We compared texture-defined figures with homogeneous textures and found an early enhancement of the figure representation, and a later suppression of the background. Across neurons, the strength of figure enhancement was independent of the strength of background suppression.We also examined activity in the different V1 layers. Both figure enhancement and ground suppression were strongest in superficial and deep layers and weaker in layer 4. The current-source density profiles suggested that figure enhancement was caused by stronger synaptic inputs in feedback-recipient layers 1, 2, and 5 and ground suppression by weaker inputs in these layers, suggesting an important role for feedback connections from higher level areas. These results provide new insights into the mechanisms for figure-ground organization. © The Author 2016. Published by Oxford University Press.

  17. Dynamic contrast-enhanced computed tomography to assess early activity of cetuximab in squamous cell carcinoma of the head and neck

    International Nuclear Information System (INIS)

    Schmitz, Sandra; Rommel, Denis; Michoux, Nicolas; Lhommel, Renaud; Hanin, François-Xavier; Duprez, Thierry; Machiels, Jean-Pascal

    2015-01-01

    Cetuximab, a monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR), has demonstrated activity in various tumor types. Using dynamic contrast-enhanced computed tomography (DCE-CT), we investigated the early activity of cetuximab monotherapy in previously untreated patients with squamous cell carcinoma of the head and neck (SCCHN). Treatment-naïve patients with SCCHN received cetuximab for 2 weeks before curative surgery. Treatment activity was evaluated by DCE-CT at baseline and before surgery. Tumor vascular and interstitial characteristics were evaluated using the Brix two-compartment kinetic model. Modifications of the perfusion parameters (blood flow F p , extravascular space v e , vascular space v p , and transfer constant PS) were assessed between both time points. DCE data were compared to FDG-PET and histopathological examination obtained simultaneously. Plasmatic vascular markers were investigated at different time points. Fourteen patients had evaluable DCE-CT parameters at both time points. A significant increase in the extravascular extracellular space v e accessible to the tracer was observed but no significant differences were found for the other kinetic parameters (F p , v p or PS). Significant correlations were found between DCE parameters and the other two modalities. Plasmatic VEGF, PDGF-BB and IL-8 decreased as early as 2 hours after cetuximab infusion. Early activity of cetuximab on tumor interstitial characteristics was detected by DCE-CT. Modifications of plasmatic vascular markers are not sufficient to confirm anti-angiogenic cetuximab activity in vivo. Further investigation is warranted to determine to what extent DCE-CT parameters are modified and to evaluate whether they are able to predict treatment outcome

  18. Feedback Seeking in Early Adolescence: Self-Enhancement or Self-Verification?

    Science.gov (United States)

    Rosen, Lisa H; Principe, Connor P; Langlois, Judith H

    2013-02-13

    The authors examined whether early adolescents ( N = 90) solicit self-enhancing feedback (i.e., positive feedback) or self-verifying feedback (i.e., feedback congruent with self-views, even when these views are negative). Sixth, seventh, and eighth graders first completed a self-perception measure and then selected whether to receive positive or negative feedback from an unknown peer in different domains of self. Results were consistent with self-verification theory; adolescents who perceived themselves as having both strengths and weaknesses were more likely to seek negative feedback regarding a self-perceived weakness compared to a self-perceived strength. The authors found similar support for self-verification processes when they considered the entire sample regardless of perceived strengths and weaknesses; hierarchical linear modeling (HLM) examined the predictive power of ratings of self-perceived ability, certainty, and importance on feedback seeking for all participants and provided additional evidence of self-verification strivings in adolescence.

  19. Thickening and enhancement of multiple cranial nerves in conjunction with cystic white matter lesions in early infantile Krabbe disease

    Energy Technology Data Exchange (ETDEWEB)

    Beslow, Lauren A.; Boennemann, Carsten G. [Children' s Hospital of Philadelphia, Division of Neurology, Philadelphia, PA (United States); Schwartz, Erin S. [Children' s Hospital of Philadelphia, Division of Neuroradiology, Philadelphia, PA (United States)

    2008-06-15

    We present serial MR findings in a child ultimately diagnosed with the early infantile form of Krabbe disease. MR showed typical features of Krabbe disease including cerebellar and brainstem hyperintensity, periventricular and deep white matter hyperintensity, and cerebral atrophy. In addition, the combination of both enlargement and enhancement of multiple cranial nerves in conjunction with unusual cystic lesions adjacent to the frontal horns of the lateral ventricles was previously unreported and expands the spectrum of imaging findings in early Krabbe disease. (orig.)

  20. Coping Expectancies, Not Enhancement Expectancies, Mediate Trauma Experience Effects on Problem Alcohol Use: A Prospective Study From Early Childhood to Adolescence.

    Science.gov (United States)

    Jester, Jennifer M; Steinberg, Davia B; Heitzeg, Mary M; Zucker, Robert A

    2015-09-01

    The relationship between experiencing trauma and increased alcohol consumption has been well established. Exposure to childhood trauma has been linked to both early onset of drinking and problematic substance use. However, the mechanisms underlying this relationship remain unclear. The results of early work suggested that drinking to relieve negative affect (i.e., drinking to cope) was driving this connection. However, the findings of more recent work suggest that drinking might be used to enhance positive affect as a way of addressing the aftereffects of early trauma. The current study looked at these two drinking expectancies as indirect pathways between the experience in early childhood of living in a home with parental violence and peak alcohol use in emerging adulthood. Participants were 1,064 children and their parents involved in a longitudinal community study of children at high risk for the development of alcoholism and a community contrast group of those at lower risk. Baseline assessment was at age 3-5 years, self-reports of internalizing behavior and drinking expectancies were obtained at age 12-14, and drinking measures were assessed at age 18-20. Results indicated that coping expectancy was a mediator of the relationship between early childhood trauma and later peak alcohol use, whereas enhancement expectancy was not. Children living in homes with parental violence were more likely to develop ineffective coping strategies, such as using alcohol to decrease negative affect. These results support the self-medication theory. They also demonstrate the long-term effects of early life experience on drinking behavior in early adulthood.

  1. Comparison of human memory CD8 T cell responses to adenoviral early and late proteins in peripheral blood and lymphoid tissue.

    Directory of Open Access Journals (Sweden)

    Amita Joshi

    Full Text Available Treatment of invasive adenovirus (Ad disease in hematopoietic stem cell transplant (SCT recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977 and late protein hexon (H-892 were compared in peripheral blood (PB and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and exhibited lower levels of the activation marker CD25 but higher proliferative potential than PB T cells. Finally, in parallel with the kinetics of mRNA expression, P-977-specific CTLs lysed targets as early as 8 hrs post infection. In contrast, H-892-specific CTLs did not kill unless infected fibroblasts were pretreated with IFN-γ to up regulate HLA class I antigens, and cytotoxicity was delayed until 16-24 hours. These data show that, in contrast to hexon CTLs, central memory type DNA polymerase CTLs dominate the lymphoid compartment and kill fibroblasts earlier after infection without requiring exogenous IFN-γ. Thus, use of CTLs targeted to both early and late Ad proteins may improve the efficacy of immunotherapy for life-threatening Ad disease in SCT recipients.

  2. Musicians' Enhanced Neural Differentiation of Speech Sounds Arises Early in Life: Developmental Evidence from Ages 3 to 30

    Science.gov (United States)

    Strait, Dana L.; O'Connell, Samantha; Parbery-Clark, Alexandra; Kraus, Nina

    2014-01-01

    The perception and neural representation of acoustically similar speech sounds underlie language development. Music training hones the perception of minute acoustic differences that distinguish sounds; this training may generalize to speech processing given that adult musicians have enhanced neural differentiation of similar speech syllables compared with nonmusicians. Here, we asked whether this neural advantage in musicians is present early in life by assessing musically trained and untrained children as young as age 3. We assessed auditory brainstem responses to the speech syllables /ba/ and /ga/ as well as auditory and visual cognitive abilities in musicians and nonmusicians across 3 developmental time-points: preschoolers, school-aged children, and adults. Cross-phase analyses objectively measured the degree to which subcortical responses differed to these speech syllables in musicians and nonmusicians for each age group. Results reveal that musicians exhibit enhanced neural differentiation of stop consonants early in life and with as little as a few years of training. Furthermore, the extent of subcortical stop consonant distinction correlates with auditory-specific cognitive abilities (i.e., auditory working memory and attention). Results are interpreted according to a corticofugal framework for auditory learning in which subcortical processing enhancements are engendered by strengthened cognitive control over auditory function in musicians. PMID:23599166

  3. Contrast enhanced MR imaging of postoperative medulloblastoma in childhood: emphasis on meningeal enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Choong Gon; Kim, In One; Kim, Woo Sun; Kim, Ho Chul; Yeon, Kyung Mo [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1993-03-15

    To differentiate the postoperative changes from the recurrence of tumor and to evaluate MR imaging of early postoperative leptomeningeal seeding in medulloblastoma, We have retrospectively analysed 34 cases of MR images of 17 patients who were confirmed as medulloblastoma by histopathology. Noncontrast and postcontrast T1 weighted MR images were obtained in all patients. In 11 patients follow-up MR was done more than once (average: 1.5 times) and average interval of MR imaging was 6 months. The timing of 34 MR images was as follow: 6 case within 2 months, 9 cases between 2 months and 1 year, 19 cases more than 1 year after surgery respectively. MR images within 2 month after surgery revealed contrast enhancement at operation site and adjacent meninges, hemorrhage, residual tumor. In patients who had no evidence of tumor recurrence, these early postoperative changes were markedly decreased within 6 month after surgery. MR images obtained more than 1 year after surgery showed no abnormal contrast enhancement or mild focal dural enhancement at operation site. Diffuse moderate dural enhancement was noted in one patient who had the history of post-surgical subdural hemorrhage. In six patients with tumor recurrences which were detected from as early as 9 months to 6 years after surgery, the findings of recurrence included leptomeningeal enhancement of brain stem and cerebellar surface at early stage, variable sized enhancing leptomeningeal nodules, linear or irregular sulcus obliterating enhancing lesions, enhancing mass at primary or metastatic site. We have concluded that leptomeningeal enhancement detected after 6 months of surgery is an important MR finding suggesting the possibility of tumor recurrence. Small nodular and linear enhancement of leptomeninges at brainstem or cerebellar surface is considered as the early manifestation of intracranial tumor seeding.

  4. Contrast enhanced MR imaging of postoperative medulloblastoma in childhood: emphasis on meningeal enhancement

    International Nuclear Information System (INIS)

    Choi, Choong Gon; Kim, In One; Kim, Woo Sun; Kim, Ho Chul; Yeon, Kyung Mo

    1993-01-01

    To differentiate the postoperative changes from the recurrence of tumor and to evaluate MR imaging of early postoperative leptomeningeal seeding in medulloblastoma, We have retrospectively analysed 34 cases of MR images of 17 patients who were confirmed as medulloblastoma by histopathology. Noncontrast and postcontrast T1 weighted MR images were obtained in all patients. In 11 patients follow-up MR was done more than once (average: 1.5 times) and average interval of MR imaging was 6 months. The timing of 34 MR images was as follow: 6 case within 2 months, 9 cases between 2 months and 1 year, 19 cases more than 1 year after surgery respectively. MR images within 2 month after surgery revealed contrast enhancement at operation site and adjacent meninges, hemorrhage, residual tumor. In patients who had no evidence of tumor recurrence, these early postoperative changes were markedly decreased within 6 month after surgery. MR images obtained more than 1 year after surgery showed no abnormal contrast enhancement or mild focal dural enhancement at operation site. Diffuse moderate dural enhancement was noted in one patient who had the history of post-surgical subdural hemorrhage. In six patients with tumor recurrences which were detected from as early as 9 months to 6 years after surgery, the findings of recurrence included leptomeningeal enhancement of brain stem and cerebellar surface at early stage, variable sized enhancing leptomeningeal nodules, linear or irregular sulcus obliterating enhancing lesions, enhancing mass at primary or metastatic site. We have concluded that leptomeningeal enhancement detected after 6 months of surgery is an important MR finding suggesting the possibility of tumor recurrence. Small nodular and linear enhancement of leptomeninges at brainstem or cerebellar surface is considered as the early manifestation of intracranial tumor seeding

  5. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    Science.gov (United States)

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Orthostatic intolerance and the cardiovascular response to early postoperative mobilization

    DEFF Research Database (Denmark)

    Bundgaard-Nielsen, M; Jørgensen, Christoffer Calov; Jørgensen, T B

    2009-01-01

    BACKGROUND: A key element in enhanced postoperative recovery is early mobilization which, however, may be hindered by orthostatic intolerance, that is, an inability to sit or stand because of symptoms of cerebral hypoperfusion as intolerable dizziness, nausea and vomiting, feeling of heat...... of orthostatic intolerance. In contrast, 8 (50%) and 2 (12%) patients were orthostatic intolerant at 6 and approximately 22 h after surgery, respectively. Before surgery, SAP, DAP, and TPR increased (P0.05) and Scv(O2) decreased (P... the preoperative evaluation (P>0.05). CONCLUSIONS: The early postoperative postural cardiovascular response is impaired after radical prostatectomy with a risk of orthostatic intolerance, limiting early postoperative mobilization. The pathogenic mechanisms include both impaired TPR and CO responses....

  7. Assessment of renal perfusion with contrast-enhanced ultrasound: Preliminary results in early diabetic nephropathies.

    Science.gov (United States)

    Dong, Yi; Wang, Wen-Ping; Lin, Pan; Fan, Peili; Mao, Feng

    2016-01-01

    We performed a prospective study to evaluate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of renal cortex perfusion in patients suspected of early diabetic nephropathies (DN), with the estimated GFR (MDRD equation) as the gold standard. The study protocol was approved by the hospital review board; each patient gave written informed consent. Our study included 46 cases (21 males and 25 females, mean age 55.6 ± 4.14 years) of clinical confirmed early DN patients. After intravenous bolus injection of 1 ml sulfur hexafluoride microbubbles of ultrasound contrast agent, real time CEUS of renal cortex was performed successively using a 2-5 MHz convex probe. Time-intensity curves (TICs) and quantitative indexes were created with Qlab software. Receiver operating characteristic (ROC) curves were used to predict the diagnostic criteria of CEUS quantitative indexes, and their diagnostic efficiencies were compared with resistance index (RI) and peak systolic velocity (PSV) of renal segmental arteries by chi square test. Our control group included forty-five healthy volunteers. Difference was considered statistically significant with P  0.05). CEUS might be helpful to improve early diagnosis of DN by quantitative analyses. AUC and DPI might be valuable quantitative indexes.

  8. IHH and FGF8 coregulate elongation of digit primordia.

    Science.gov (United States)

    Zhou, Jian; Meng, Junwei; Guo, Shengzhen; Gao, Bo; Ma, Gang; Zhu, Xuming; Hu, Jianxin; Xiao, Yue; Lin, Chuwen; Wang, Hongsheng; Ding, Lusheng; Feng, Guoyin; Guo, Xizhi; He, Lin

    2007-11-23

    In the developing limb bud, digit pattern arises from anterior-posterior (A-P) positional information which is provided by the concentration gradient of SHH. However, the mechanisms of translating early asymmetry into morphological form are still unclear. Here, we examined the ability of IHH and FGF8 signaling to regulate digital chondrogenesis, by implanting protein-loaded beads in the interdigital space singly and in combination. We found that IHH protein induced an elongated digit and that FGF8 protein blocked the terminal phalange formation. Molecular marker analysis showed that IHH expanded Sox9 expression in mesenchymal cells possibly through up-regulated FGF8 expression. Application of both IHH and FGF8 protein induced a large terminal phalange. These results suggest that both enhanced IHH and FGF8 signaling are required for the development of additional cartilage element in limbs. IHH and FGF8 maybe play different roles and act synergistically to promote chondrogenesis during digit primordia elongation.

  9. Solo/Trio8, a membrane-associated short isoform of Trio, modulates endosome dynamics and neurite elongation.

    Science.gov (United States)

    Sun, Ying-Jie; Nishikawa, Kaori; Yuda, Hideki; Wang, Yu-Lai; Osaka, Hitoshi; Fukazawa, Nobuna; Naito, Akira; Kudo, Yoshihisa; Wada, Keiji; Aoki, Shunsuke

    2006-09-01

    With DNA microarrays, we identified a gene, termed Solo, that is downregulated in the cerebellum of Purkinje cell degeneration mutant mice. Solo is a mouse homologue of rat Trio8-one of multiple Trio isoforms recently identified in rat brain. Solo/Trio8 contains N-terminal sec14-like and spectrin-like repeat domains followed by a single guanine nucleotide exchange factor 1 (GEF1) domain, but it lacks the C-terminal GEF2, immunoglobulin-like, and kinase domains that are typical of Trio. Solo/Trio8 is predominantly expressed in Purkinje neurons of the mouse brain, and expression begins following birth and increases during Purkinje neuron maturation. We identified a novel C-terminal membrane-anchoring domain in Solo/Trio8 that is required for enhanced green fluorescent protein-Solo/Trio8 localization to early endosomes (positive for both early-endosome antigen 1 [EEA1] and Rab5) in COS-7 cells and primary cultured neurons. Solo/Trio8 overexpression in COS-7 cells augmented the EEA1-positive early-endosome pool, and this effect was abolished via mutation and inactivation of the GEF domain or deletion of the C-terminal membrane-anchoring domain. Moreover, primary cultured neurons transfected with Solo/Trio8 showed increased neurite elongation that was dependent on these domains. These results suggest that Solo/Trio8 acts as an early-endosome-specific upstream activator of Rho family GTPases for neurite elongation of developing Purkinje neurons.

  10. Increased amygdala reactivity following early life stress: a potential resilience enhancer role.

    Science.gov (United States)

    Yamamoto, Tetsuya; Toki, Shigeru; Siegle, Greg J; Takamura, Masahiro; Takaishi, Yoshiyuki; Yoshimura, Shinpei; Okada, Go; Matsumoto, Tomoya; Nakao, Takashi; Muranaka, Hiroyuki; Kaseda, Yumiko; Murakami, Tsuneji; Okamoto, Yasumasa; Yamawaki, Shigeto

    2017-01-18

    Amygdala hyper-reactivity is sometimes assumed to be a vulnerability factor that predates depression; however, in healthy people, who experience early life stress but do not become depressed, it may represent a resilience mechanism. We aimed to test these hypothesis examining whether increased amygdala activity in association with a history of early life stress (ELS) was negatively or positively associated with depressive symptoms and impact of negative life event stress in never-depressed adults. Twenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS. Mood change and amygdala reactivity were increased in never-depressed participants who reported ELS compared to participants who reported no ELS. Yet, increased amygdala reactivity lowered effects of ELS on depressive symptoms and negative life events stress. Amygdala reactivity also had positive functional connectivity with the bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory recall. Increased amygdala activity in those with ELS was associated with decreased symptoms and increased neural features, consistent with emotion regulation, suggesting that preservation of robust amygdala reactions may reflect a stress buffering or resilience enhancing factor against depression and negative stressful events.

  11. Ammonia-treated porous carbon derived from ZIF-8 for enhanced CO{sub 2} adsorption

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Xiancheng [School of Energy Science and Engineering, Central South University, Changsha 410083, Hunan (China); Li, Liqing, E-mail: liqingli@hotmail.com [School of Energy Science and Engineering, Central South University, Changsha 410083, Hunan (China); Wang, Shaobin [Department of Chemical Engineering, Curtin University, GPO Box U1987, Perth 6845, WA (Australia); Lu, Mingming [Department of Civil and Environmental Engineering, University of Cincinnati, Cincinnati, OH 45221 (United States); Li, Hailong; Ma, Weiwu [School of Energy Science and Engineering, Central South University, Changsha 410083, Hunan (China); Keener, Tim C. [Department of Civil and Environmental Engineering, University of Cincinnati, Cincinnati, OH 45221 (United States)

    2016-04-30

    Graphical abstract: The role of nitrogen species in increasing CO{sub 2} adsorption capacity has been explained with the mechanisms of base–acid interaction, as well as hydrogen bonds interaction. - Highlights: • A porous carbon (ZC) was prepared at 900 °C using ZIF-8 as a solid template for CO{sub 2} adsorption. • The ZC was further treated by ammonia functionalization to improve CO{sub 2} uptake. • The detailed interaction mechanism between N-containing groups and CO{sub 2} molecules is elucidated. - Abstract: A porous carbon (ZC) was prepared at 900 °C using zeolitic imidazolate framework-8 (ZIF-8) as a solid template for CO{sub 2} adsorption. The ZC was further treated by ammonia functionalization to improve CO{sub 2} uptake. The textural and surface characteristics of ZC samples were determined by X-ray diffraction (XRD), N{sub 2} adsorption, Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). It was revealed that ammonia treatment at 600 °C considerably enhanced the specific surface area and N-content of ZC. However, the pyrrolic-N group was decreased, yet the pyridinic-N group was increased with an increased temperature. The pyrrolic-N significantly enhanced CO{sub 2} adsorption. The ammonia treatment, on the one hand, increases the alkalinity of ZC sample and the base–acid interaction between N-containing functional groups with CO{sub 2}. On the other hand, the ammonia treatment increased pyrrolic-N group (NH) into carbon surface facilitating the hydrogen-bonding interactions between proton of pyrrolic-N and CO{sub 2} molecules.

  12. Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Leach, M.O.; Orton, M. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Morgan, B. [Univ. of Leicester, College of Medicine, Biological Sciences and Psychology, Leicester (United Kingdom); Tofts, P.S. [Brighton and Sussex Medical School, Univ. of Sussex, Clinical Imaging Sciences Centre, Sussex (United Kingdom); Buckley, D.L. [University of Leeds, Division of Medical Physics, Leeds (United Kingdom); Huang, W. [Oregon Health and Science Univ., Advanced Imaging Research Centre, Portland, OR (United States); Horsfield, M.A. [Medical Physics Section, Leicester Royal Infirmary, Dept. of Cardiovascular Sciences, Leicester (United Kingdom); Chenevert, T.L. [Univ. of Michigan Health System, Ann Arbor, MI (United States); Collins, D.J. [Royal Marsden Hospital NHS Foundation Trust, Cancer Research UK and EPSRC Cancer Imaging Centre, Sutton, Surrey (United Kingdom); Jackson, A. [Univ. of Manchester, Wolfson Molecular Imaging Centre, Withington, Manchester, M20 3LJ (United Kingdom); Lomas, D. [Univ. of Cambridge, Dept. of Radiology, Cambridge (United Kingdom); Whitcher, B. [Unit 2 Greenways Business Park, Mango Solutions, Chippenham (United Kingdom); Clarke, L. [Cancer Imaging Program, Imaging Technology Development Branch, Rockville, MD (United States); Plummer, R. [Univ. of Newcastle Upon Tyne, The Medical School, Medical Oncology, Northern Inst. for Cancer Research, Newcastle Upon Tyne (United Kingdom); Judson, I. [Royal Marsden Hospital, Sutton, Surrey (United Kingdom); Jones, R. [Beatson West of Scotland Cancer Centre, Glasgow (United Kingdom); Alonzi, R. [Mount Vernon Cancer Centre, Northwood (United Kingdom); Brunner, T. [Gray Inst. for Radiation, Oncology and Biology, Oxford (United Kingdom); Koh, D.M. [Royal Marsden NHS Foundation Trust, Diagnostic Radiology, Sutton, Surrey (United Kingdom)] [and others

    2012-07-15

    Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. (orig.)

  13. Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time.

    Directory of Open Access Journals (Sweden)

    Ingrid M M Schellens

    Full Text Available BACKGROUND: T-cell immunity is thought to play an important role in controlling HIV infection, and is a main target for HIV vaccine development. HIV-specific central memory CD8(+ and CD4(+ T cells producing IFNgamma and IL-2 have been associated with control of viremia and are therefore hypothesized to be truly protective and determine subsequent clinical outcome. However, the cause-effect relationship between HIV-specific cellular immunity and disease progression is unknown. We investigated in a large prospective cohort study involving 96 individuals of the Amsterdam Cohort Studies with a known date of seroconversion whether the presence of cytokine-producing HIV-specific CD8(+ T cells early in infection was associated with AIDS-free survival time. METHODS AND FINDINGS: The number and percentage of IFNgamma and IL-2 producing CD8(+ T cells was measured after in vitro stimulation with an overlapping Gag-peptide pool in T cells sampled approximately one year after seroconversion. Kaplan-Meier survival analysis and Cox proportional hazard models showed that frequencies of cytokine-producing Gag-specific CD8(+ T cells (IFNgamma, IL-2 or both shortly after seroconversion were neither associated with time to AIDS nor with the rate of CD4(+ T-cell decline. CONCLUSIONS: These data show that high numbers of functional HIV-specific CD8(+ T cells can be found early in HIV infection, irrespective of subsequent clinical outcome. The fact that both progressors and long-term non-progressors have abundant T cell immunity of the specificity associated with low viral load shortly after seroconversion suggests that the more rapid loss of T cell immunity observed in progressors may be a consequence rather than a cause of disease progression.

  14. Perfusion of surgical cavity wall enhancement in early post-treatment MR imaging may stratify the time-to-progression in glioblastoma.

    Directory of Open Access Journals (Sweden)

    Ji Eun Park

    Full Text Available To determine if perfusion in surgical cavity wall enhancement (SCWE obtained in early post-treatment MR imaging can stratify time-to-progression (TTP in glioblastoma.This study enrolled 60 glioblastoma patients with more than 5-mm-thick SCWEs as detected on contrast-enhanced MR imaging after concurrent chemoradiation therapy. Two independent readers categorized the shape and perfusion state of SCWEs as nodular or non-nodular and as having positive or negative perfusion compared with the contralateral grey matter on arterial spin labeling (ASL. The perfusion fraction on ASL within the contrast-enhancing lesion was calculated. The independent predictability of TTP was analyzed using the Kaplan-Meier method and Cox proportional hazards modelling.The perfusion fraction was higher in the non-progression group, significantly for reader 2 (P = 0.03 and borderline significantly for reader 1 (P = 0.08. A positive perfusion state and (P = 0.02 a higher perfusion fraction of the SCWE were found to become an independent predictor of longer TTP (P = 0.001 for reader 1 and P < 0.001 for reader 2. The contrast enhancement pattern did not become a TTP predictor.Assessment of perfusion in early post-treatment MR imaging can stratify TTP in patients with glioblastoma for adjuvant temozolomide therapy. Positive perfusion in SCWEs can become a predictor of a longer TTP.

  15. Reminiscence spike in reading recall between the ages of 8–11: The influence of early memories on attitudes and actions

    Directory of Open Access Journals (Sweden)

    Margaret Freestone

    2016-12-01

    Full Text Available An investigation into the recalled reading of 31 environmental educators has uncovered a potential link between early reading and pro-environmental attitudes. The recalled books are not only from the recognised “reminiscence bump” of adolescence and early adulthood, but there also appears to be a spike in recall of books within the 8–11-year reading age group. This 8–11-year age group, also known as middle childhood is recognised within other disciplines as being an influential or significant time for learning. The discovery of these earlier memories from stories and their ongoing influence highlights the potential of incidental learning and pre-adolescent attitude formation.

  16. Change in contrast enhancement of HCC on 1-month follow-up CT after local radiotherapy: An early predictor of final treatment response

    International Nuclear Information System (INIS)

    Kim, Eun Young; Choi, Dongil; Lim, Do Hoon; Lee, Won Jae; Yoo, Byung Chul; Paik, Seung Woon

    2009-01-01

    Background: The purpose of this study was to evaluate the change in contrast enhancement of HCC on 1-month follow-up CT after local radiotherapy (RT) as an early predictor of final treatment response. Materials: Fifty patients who underwent local RT for HCCs had both pre-RT and post-RT CT scans including 1-month follow-up CT. We assessed the final treatment response by using the change in maximal tumor size on 6-12-month follow-up CT scan after RT. We also evaluated the change in tumor enhancement between pre-RT and 1-month follow-up CT scans. Results: A final treatment response was achieved in 27 (54%) of 50 patients, who showed either a complete response (n = 11) or a partial response (n = 16). Compared with non-responsive patients (n = 23), responsive patients showed a significant decrease in tumor enhancement on 1-month follow-up CT after RT in both objective and subjective analyses (each P < 0.001). Conclusion: The change in contrast enhancement of HCC seen on the 1-month follow-up CT in patients after local RT may be used as an early predictor of final treatment response.

  17. Early diagnosis of influenza virus a using surface-enhanced Raman scattering-based lateral flow assay

    International Nuclear Information System (INIS)

    Park, Hyun Ji; Choo, Jae Bum; Yang, Sung Chul

    2016-01-01

    We report a surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) kit for the rapid diagnosis of influenza virus A. Influenza virus A is highly infectious and causes acute respiratory diseases. Therefore, it is important to diagnose the virus early to prevent a pandemic and to provide appropriate treatment to the patient and vaccination of high-risk individuals. Conventional diagnostic tests, including virus cell culture and real-time polymerase chain reaction, take longer than 1 day to confirm the disease. In contrast, a commercially available rapid influenza diagnostic test can detect the infection within 30 min, but it is hard to confirm viral infection using only this test because of its low sensitivity. Therefore, the development of a rapid and simple test for the early diagnosis of influenza infection is urgently needed. To resolve these problems, we developed a SERS-based LFA kit in which the gold nanoparticles in the commercial rapid kit were replaced with SERS-active nano tags. It is possible to quantitatively detect the influenza virus A with high sensitivity by measuring the enhanced Raman signal of these SERS nano tags on the LFA strip. The limit of detection (LOD) using our proposed SERS-based LFA kit was estimated to be 1.9 × 10"4 PFU/mL, which is approximately one order of magnitude more sensitive than the LOD determined from the colorimetric LFA kit

  18. Early diagnosis of influenza virus a using surface-enhanced Raman scattering-based lateral flow assay

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyun Ji; Choo, Jae Bum [Dept. of Bionano Technology, Hanyang University, Ansan (Korea, Republic of); Yang, Sung Chul [School of Architectural Engineering, Hongik University, Sejong (Korea, Republic of)

    2016-12-15

    We report a surface-enhanced Raman scattering (SERS)-based lateral flow assay (LFA) kit for the rapid diagnosis of influenza virus A. Influenza virus A is highly infectious and causes acute respiratory diseases. Therefore, it is important to diagnose the virus early to prevent a pandemic and to provide appropriate treatment to the patient and vaccination of high-risk individuals. Conventional diagnostic tests, including virus cell culture and real-time polymerase chain reaction, take longer than 1 day to confirm the disease. In contrast, a commercially available rapid influenza diagnostic test can detect the infection within 30 min, but it is hard to confirm viral infection using only this test because of its low sensitivity. Therefore, the development of a rapid and simple test for the early diagnosis of influenza infection is urgently needed. To resolve these problems, we developed a SERS-based LFA kit in which the gold nanoparticles in the commercial rapid kit were replaced with SERS-active nano tags. It is possible to quantitatively detect the influenza virus A with high sensitivity by measuring the enhanced Raman signal of these SERS nano tags on the LFA strip. The limit of detection (LOD) using our proposed SERS-based LFA kit was estimated to be 1.9 × 10{sup 4} PFU/mL, which is approximately one order of magnitude more sensitive than the LOD determined from the colorimetric LFA kit.

  19. Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-α-positive human cells

    International Nuclear Information System (INIS)

    Singleton, David W.; Feng, Yuxin; Yang, Jun; Puga, Alvaro; Lee, Adrian V.; Khan, Sohaib A.

    2006-01-01

    Bisphenol-A (BPA) shows proliferative actions in uterus and mammary glands and may influence the development of male and female reproductive tracts in utero or during early postnatal life. Because of its ability to function as an estrogen receptor (ER) agonist, BPA has the potential to disrupt normal endocrine signaling through regulation of ER target genes. Some genes are regulated by both estradiol (E2) and BPA, but those exclusive to either agent have not been described. Using a yeast strain incorporating a vitellogenin A2 ERE-LacZ reporter gene into the genome, we found that BPA induced expression of the reporter in colonies transformed with the ERα expression plasmid, illustrating BPA-mediated regulation within a chromatin context. Additionally, a reporter gene transiently transfected into the endometrial cancer (Ishikawa) cell line also showed BPA activity, although at 100-fold less potency than E2. To compare global gene expression in response to BPA and E2, we used a variant of the MCF-7 breast cancer cell line stably expressing HA-tagged ERα. Cultures were treated for 3 h with an ethanol vehicle, E2 (10 -8 M), or BPA (10 -6 M), followed by isolation of RNA and microarray analysis with the human U95A probe array (Affymetrix, Santa Clara, CA, USA). More than 300 genes were changed 2-fold or more by either or both agents, with roughly half being up-regulated and half down-regulated. A number of growth- and development-related genes, such as HOXC1 and C6, Wnt5A, Frizzled, TGFβ-2, and STAT inhibitor 2, were found to be affected exclusively by BPA. We used quantitative real-time PCR to verify regulation of the HOXC6 gene, which showed decreased expression of approximately 2.5-fold by BPA. These results reveal novel effects by BPA and E2, raising interesting possibilities regarding the role of endocrine disruptors in sexual development

  20. Enhancements to and characterization of the very early time electromagnetic (VETEM) prototype instrument and applications to shallow subsurface imaging at sites in the DOE complex. 1998 annual progress report

    International Nuclear Information System (INIS)

    Chew, W.C.; Wright, D.L.

    1998-01-01

    'The objective of this project is to enhance the state-of-the-art of electromagnetic imaging of the shallow (0 to 5 m) subsurface in electrically conductive media where ground penetrating radar (GPR) provides insufficient penetration and time domain electromagnetic (TEM) systems provide insufficient resolution. This objective is being pursued by instrumentation enhancements to the existing very early time electromagnetic (VETEM) system coupled with physical and numerical modeling. Success in this endeavor will improve the speed and accuracy of waste pit and trench location and characterization, and could have additional applications to shallow DNAPL and LNAPL spill and cleanup monitoring, clay cap integrity assessment, and landfill stabilization monitoring. This could result in significant savings in time and money during characterization, remediation, and decommissioning of facilities. This report summarizes accomplishments after 8 months of a three-year project. The authors have focused mainly on instrumentation and numerical modeling during this time.'

  1. IL-2 Enhances Gut Homing Potential of Human Naive Regulatory T Cells Early in Life.

    Science.gov (United States)

    Hsu, Peter S; Lai, Catherine L; Hu, Mingjing; Santner-Nanan, Brigitte; Dahlstrom, Jane E; Lee, Cheng Hiang; Ajmal, Ayesha; Bullman, Amanda; Arbuckle, Susan; Al Saedi, Ahmed; Gacis, Lou; Nambiar, Reta; Williams, Andrew; Wong, Melanie; Campbell, Dianne E; Nanan, Ralph

    2018-06-15

    Recent evidence suggests early environmental factors are important for gut immune tolerance. Although the role of regulatory T (Treg) cells for gut immune homeostasis is well established, the development and tissue homing characteristics of Treg cells in children have not been studied in detail. In this article, we studied the development and homing characteristics of human peripheral blood Treg cell subsets and potential mechanisms inducing homing molecule expression in healthy children. We found contrasting patterns of circulating Treg cell gut and skin tropism, with abundant β7 integrin + Treg cells at birth and increasing cutaneous lymphocyte Ag (CLA + ) Treg cells later in life. β7 integrin + Treg cells were predominantly naive, suggesting acquisition of Treg cell gut tropism early in development. In vitro, IL-7 enhanced gut homing but reduced skin homing molecule expression in conventional T cells, whereas IL-2 induced a similar effect only in Treg cells. This effect was more pronounced in cord compared with adult blood. Our results suggest that early in life, naive Treg cells may be driven for gut tropism by their increased sensitivity to IL-2-induced β7 integrin upregulation, implicating a potential role of IL-2 in gut immune tolerance during this critical period of development. Copyright © 2018 by The American Association of Immunologists, Inc.

  2. Enhancing early postnatal care: findings from a major reform of maternity care in three Australian hospitals.

    Science.gov (United States)

    Yelland, Jane; Krastev, Ann; Brown, Stephanie

    2009-08-01

    four hospitals comprising a health network in Melbourne, Australia, implemented a range of initiatives aimed at enhancing women's experiences of postnatal maternity care. to compare women's views and experiences of early postnatal care before and after implementation of maternity enhancement initiatives. 'before and after' study design incorporating two postal surveys of recent mothers (baseline and post-implementation). four hospitals in Melbourne, Australia. Analysis of postnatal outcomes was confined to three hospitals where the initiatives were fully operational. 1256 women participated in the baseline survey in 1999 (before implementing the initiative) and 1050 women responded to the post-implementation survey in 2001. the response to the 1999 baseline survey was 65.3% (1256/1922) and to the 2001 post-implementation survey 57.4% (1050/1829). Comparative analysis revealed a statistically significant improvement in overall ratings of hospital postnatal care; the level of advice and support received in relation to discharge and going home; the sensitivity of caregivers; and the proportion of women receiving domiciliary care after discharge. There was little change in the time women spent in hospital after birth between the two survey time-points. Over 90% of women reported one or more health problems in the first 3 months postpartum. The proportion of women reporting physical or emotional health problems between the two surveys did not change. mainstream maternity care can be restructured to improve women's experiences of early postnatal care. maternity service providers should consider a multi-faceted approach to reorienting postnatal services and improving women's experiences of care. Approaches worthy of consideration include attempts to ensure consistency and continuity of care through staffing arrangements, guidelines and protocols; an emphasis on planning for postnatal care during pregnancy; the use of evidence to inform both consumer information and advice

  3. Measurement of L-XRF cross-sections and Coster–Kronig enhancement factors for {sup 62}Sm at excitation energies 6.8, 7.4 and 8 KeV

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, R., E-mail: rajiv_005@rediffmail.com [Department of Physics, HCTM Technical Campus, Kaithal, Haryana 136027 (India); Rani, A., E-mail: anita_teotia@rediffmail.com [Department of Physics, University P.G. College Kurukshetra, Kurukshetra University, Kurukshetra, Haryana 136119 (India); Singh, R.M. [Department of Physics, Ch. Devi Lal University, Sirsa, Haryana 125055 (India); Tiwari, M.K.; Singh, A.K. [X-ray Optics Section, Indus Synchrotron Utilization Division, Raja Ramanna Centre for Advanced Technology, Indore, Madhya Pradesh 452013 (India)

    2016-05-15

    Highlights: • L XRF production cross-sections for {sup 62}Sm at excitation energies 6.8, 7.4 and 8 KeV were measured. • Synchrotron radiations with Peltier cooled Si(Li) detector was employed. • Experimental L XRF cross sections are in good agreement with the theoretical estimations of Puri’s data. • The present study was also carried out to examine the effect of Coster - Kronig transitions on L XRF cross section. • The measured enhancement factors are found to be smaller than the theoretical estimations. - Abstract: L{sub ℓ}, L{sub α} and L{sub β} XRF production cross-sections were measured for {sup 62}Sm at excitation energies i.e. 6.8 KeV, 7.4 KeV and 8 KeV using synchrotron radiations. Experimental measurements were also carried out to examine the effect of Coster–Kronig transitions (non-radiative transitions) on fluorescence cross section for the L{sub i} (i = 1, 2, 3) X-ray lines. The experimental cross-sections with greater accuracy and better signal to noise ratio can be measured using a polarized monoenergetic excitation beam and a high resolution detector system. A Peltier cooled vortex solid state detector with energy resolution of 138 eV at 5.959 keV X-ray was employed. Experimentally measured cross-sections have been compared with the theoretical predictions with the data of M.O. Krause [J. Phys. Chem. Ref. Data 8 (1979) 307], J.L. Campbell [At. Data Nucl. Data Tables 85 (2003) 291] and S. Puri et al. [X-Ray Spectrom. 22 (1993) 358]. The measured enhancement factors were found to be smaller than the theoretically calculated values.

  4. Suppressive and enhancing effects in early visual cortex during illusory shape perception: A comment on.

    Science.gov (United States)

    Moors, Pieter

    2015-01-01

    In a recent functional magnetic resonance imaging study, Kok and de Lange (2014) observed that BOLD activity for a Kanizsa illusory shape stimulus, in which pacmen-like inducers elicit an illusory shape percept, was either enhanced or suppressed relative to a nonillusory control configuration depending on whether the spatial profile of BOLD activity in early visual cortex was related to the illusory shape or the inducers, respectively. The authors argued that these findings fit well with the predictive coding framework, because top-down predictions related to the illusory shape are not met with bottom-up sensory input and hence the feedforward error signal is enhanced. Conversely, for the inducing elements, there is a match between top-down predictions and input, leading to a decrease in error. Rather than invoking predictive coding as the explanatory framework, the suppressive effect related to the inducers might be caused by neural adaptation to perceptually stable input due to the trial sequence used in the experiment.

  5. A Case Study of the Use of Internet Photobook Technology to Enhance Early Childhood "Scientist" Identity

    Science.gov (United States)

    Katz, Phyllis

    2011-10-01

    There are many influences on a child's identity. Photobook technology purposefully prepared around science explorations presents a modern opportunity to repeatedly trigger memories that reinforce the "me, as scientist" viewpoint. Semi-structured interviews at 6 and 8 years of age were conducted with a child who was the subject of a photobook of everyday science activities to gain insights into his thinking about the nature of science and how he interprets his younger self participating. Interview data were recorded, transcribed and analyzed using dimensions from the previously established parameters for the nature of science. The child's statements about his participation in the photos were matched to these dimensions to consider how he sees himself "doing science" through his early years. Preliminary findings suggest that the child recognizes elements of science and regards himself as an active participant. In both interviews, the child reinforces these views by the opportunity to revisit the experiences in the photobook. Affective components may motivate further science involvement as well: the child enjoyed the time and attention that the photos and discussion provided; the child took pride in being the subject of a book. This case study suggests that there is a fertile field of research to investigate how, for whom, and in what ways internet photobook technology may enhance a child's developing identity as capable science explorer.

  6. Chronological observation in early radiation myelopathy of the cervical spinal cord; Gadolinium-enhanced MRI findings in two cases

    Energy Technology Data Exchange (ETDEWEB)

    Hirota, Saeko; Yoshida, Shoji; Soejima, Toshinori (Hyogo Medical Center for Adults, Akashi (Japan)) (and others)

    Gd-enhanced MR images of two patients with clinically and histopathologically diagnosed chronic progressive radiation myelitis (CPRM) were observed chronologically. One of them had had nasopharyngeal cancer and received radiotherapy at a dose of 100 Gy to the C1-2 level of the spinal cord. She developed CPRM 25 months after the termination of radiotherapy. The other had had malignant lymphoma originating from the tonsil and received chemoradiotherapy. The dose delivered to her cervical spinal cord was 40 Gy, and she developed CPRM 30 months later. Gd-enhanced MRI in the early phase revealed a small crescent-shaped nidus with or without a very small central nonenhanced area in both cases. Enhancement was not great. At that time, patients noticed only the inability to perceive pain and temperature or paresthesia in the opposite side. In a few months, MRI revealed a much more strongly enhanced and larger nidus with enlargement of a central nonenhanced area accompanied by long segmental cord enlargement. The patients' neurological symptoms had also progressed, with hemiparesis developing, for example. (author).

  7. Carcinoma of the cervix. Value of dynamic magnetic resonance imaging in assessing early stromal invasion

    International Nuclear Information System (INIS)

    Kojima, Yumi; Aoki, Yoichi; Kase, Hiroaki; Kodama, Shoji; Tanaka, Kenichi

    1998-01-01

    The purpose of this study was to assess the accuracy of contrast-enhanced magnetic resonance imaging (dynamic MR imaging) in the evaluation of preinvasive and early invasive cancer of the cervix. Twenty-nine women with untreated squamous cell carcinoma of the cervix with either no stromal invasion or early stromal invasion underwent pretreatment MR imaging and dynamic MR imaging within 4 weeks of surgical evaluation. The images were evaluated for tumor detection and compared with results of histologic examination of the surgical specimens. The lesions in 17 cases with histologically proven stromal invasion of 4 mm or greater were detected with dynamic MR imaging, whereas lesions in only 8 of these cases were detected with T2 imaging. In 9 cases with stromal invasion between 4.0 mm and 5.0 mm, lesions were represented as early phase focal enhancement on dynamic MR images, but not detected on T2-weighted images. In the 12 cases with less than 4 mm stromal invasion, no lesions were visualized on either T2-weighted images or dynamic MR images, except in 1 case of glandular involvement without stromal invasion that appeared as enhancement on early-phase dynamic MR imaging. Dynamic MR imaging detected more lesions of early stromal invasion in pretreatment imaging for cervical cancer than nonenhanced MR imaging. (author)

  8. Transcriptome Profile Analysis of Mechanisms of Black and White Plumage Determination in Black-Bone Chicken

    Directory of Open Access Journals (Sweden)

    Shigang Yu

    2018-05-01

    Full Text Available Background/Aims: Melanin is a major and ubiquitous component of plumage colouration, and patterns of melanin pigmentation in birds are extremely varied. However, the molecular mechanism of pigmentation in avian plumage is still largely unknown. Methods: To elucidate the molecular mechanisms involved in the formation of black and white plumage, this study takes advantage of high-throughput sequencing technology to compare differences in the transcriptome between black and white chicken feather bulbs. In total, we constructed six cDNA libraries from black (Group B and white (Group W feather bulbs in the dorsal plumage of Muchuan black-boned chickens. Results: A comparison between Groups B and W revealed 61 differentially expressed genes, with 47 displaying higher, and 14 displaying lower, levels of expression in white feather bulbs. Our results revealed a set of candidate genes and two potential metabolic pathways involved in black-bone chicken plumage melanogenesis. These include four homeobox genes (HOXB9, HOXC8, HOXA9, and HOXC 9, two glutathione (GSH metabolism-related genes (CHAC1 and GPX3, and the transforming growth factor beta (TGF-β signalling pathway. Two known genes, TYR and MITF, were also shown to play a role in melanin formation. Conclusion: our data provide a valuable resource for discovering genes important in plumage melanin formation and will help further elucidate the molecular mechanisms for black and white plumage.

  9. Noncanonical Expression of a Murine Cytomegalovirus Early Protein CD8 T-Cell Epitope as an Immediate Early Epitope Based on Transcription from an Upstream Gene

    Directory of Open Access Journals (Sweden)

    Annette Fink

    2014-02-01

    Full Text Available Viral CD8 T-cell epitopes, represented by viral peptides bound to major histocompatibility complex class-I (MHC-I glycoproteins, are often identified by “reverse immunology”, a strategy not requiring biochemical and structural knowledge of the actual viral protein from which they are derived by antigen processing. Instead, bioinformatic algorithms predicting the probability of C-terminal cleavage in the proteasome, as well as binding affinity to the presenting MHC-I molecules, are applied to amino acid sequences deduced from predicted open reading frames (ORFs based on the genomic sequence. If the protein corresponding to an antigenic ORF is known, it is usually inferred that the kinetic class of the protein also defines the phase in the viral replicative cycle during which the respective antigenic peptide is presented for recognition by CD8 T cells. We have previously identified a nonapeptide from the predicted ORFm164 of murine cytomegalovirus that is presented by the MHC-I allomorph H-2 Dd and that is immunodominant in BALB/c (H-2d haplotype mice. Surprisingly, although the ORFm164 protein gp36.5 is expressed as an Early (E phase protein, the m164 epitope is presented already during the Immediate Early (IE phase, based on the expression of an upstream mRNA starting within ORFm167 and encompassing ORFm164.

  10. Enhanced neutrophil chemotactic activity after bronchial challenge in subjects with grain dust-induced asthma.

    Science.gov (United States)

    Park, H S; Jung, K S

    1998-03-01

    There have been few reports suggesting involvement of neutrophils in induction of bronchoconstriction after inhalation of grain dust. To understand the role of neutrophils in pathogenesis of grain dust-induced asthma. We observed serum neutrophil chemotactic activity during grain dust-bronchoprovocation tests in six asthmatic subjects with positive bronchial challenges (group I). They were compared with those of six symptomatic subjects from the same workplace with negative bronchial challenges (group II). After grain dust inhalation, serum neutrophil chemotactic activity significantly increased at 30 minutes (P = .028), and then decreased to baseline level at 240 minutes (P = .028) in five subjects of group I having isolated early asthmatic responses. Enhanced neutrophil chemotactic activity was persistent for up to 240 minutes in one asthmatic subject having both early and late asthmatic responses. There was, however, no significant change in serum neutrophil chemotactic activity during bronchial challenges in subjects of group II. Pre-incubation of sera with anti-interleukin-8 (IL-8) antibody did not affect the neutrophil chemotactic activity results of group I subjects. These results suggest that enhanced neutrophil chemotactic activity distinct from IL-8 may contribute to significant bronchoconstriction induced by grain dust.

  11. Expression of antimicrobial peptides and interleukin-8 during early stages of inflammation: An experimental gingivitis study.

    Science.gov (United States)

    Dommisch, H; Staufenbiel, I; Schulze, K; Stiesch, M; Winkel, A; Fimmers, R; Dommisch, J; Jepsen, S; Miosge, N; Adam, K; Eberhard, J

    2015-12-01

    In the oral cavity, the epithelial surface is constantly exposed to a number of different microorganisms that are organized in a well-structured biofilm. The aim of this study was to monitor gingival expression of antimicrobial peptides (AMPs) and interleukin-8 (IL-8) in an early gingivitis model. Experimental gingivitis was allowed to develop in healthy volunteers (n = 17). Bleeding on probing (BOP%) and gingival crevicular fluid volume (GCF) were assessed at baseline and day 1, 3, 5, 7 and 14. Expression of AMPs (human beta-defensin-2, hBD-2; CC-chemokine ligand 20, CCL20; psoriasin, pso/S100A7) and IL-8 was analyzed by immunohistochemistry in gingival biopsies. In addition, hBD-2 and IL-8 protein expression was monitored in GCF using the ELISA technology. Experimental gingivitis gradually developed with an increase in BOP scores and GCF volume over time. In GCF, elevated concentrations of hBD-2 and IL-8 were monitored at day 1, 5 and 7 (p ≤ 0.0002). Immunohistochemical analysis of gingival sections demonstrated increased staining for hBD-2 at day 3, whereas the CCL20, pso/S100A7, and IL-8 expression was increased at later time points (p gingival inflammation. Differential temporal expression for AMPs may ensure a constant antimicrobial activity against changes in the bacterial composition of the growing dental biofilm. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Early Progressive Strength Training to Enhance Recovery After Fast-Track Total Knee Arthroplasty

    DEFF Research Database (Denmark)

    Jakobsen, Thomas Linding; Kehlet, Henrik; Husted, Henrik

    2014-01-01

    different interventions: 7 weeks of supervised physical rehabilitation with PST (PST group) and without PST (CON group) commenced early after fast-track TKA. The primary outcome was the maximal distance walked in 6 minutes (6-minute walk test). Secondary outcomes were lower extremity strength and power......, knee joint effusion and range of motion, knee pain, and self-reported disability and quality of life. All outcome measures were assessed before TKA (baseline) and 4, 8, and 26 weeks after TKA. RESULTS: There was no statistically significant difference between the PST and CON groups in the change score...

  13. Evaluation of delayed contrast-enhanced CT scan in diagnosing hilar cholangiocarcinoma

    International Nuclear Information System (INIS)

    Li Jianding; Liang Chenyang; Zhang Hua; Zhang Yuezhen; Li Rui

    2001-01-01

    Objective: To assess the diagnostic value of delayed CT contrast enhancement patterns in hilar cholangiocarcinoma based on two-phased dynamic incremental CT scanning. Methods: Fifty-two patients with suspected hilar tumor and bile duct obstruction underwent spiral CT scan. The scan time for one revolution of the X-ray tube was 1 second. To elucidate the delay time for optimal imaging, all proved cholangiocarcinoma with delayed (6, 8, 10, 15, 20, 30 minutes) post-equilibrium-phase contrast-enhanced CT scans were acquired with unenhanced, dynamic contrast-enhanced, and delayed images. Degree of delayed enhancement was compared with that of surrounding liver parenchyma. Results: (1) 8-15 minutes after IV injection of contrast material was the delay time for optimal imaging. (2) Of 29 cholangiocarcinomas, the early CT showed hypo-attenuating (lower than that of liver parenchyma) in 23 tumors, iso-attenuating (equal to that of the liver) in 4 tumors, and hyper-attenuating (higher than that of liver) in 2 tumors. The delayed CT scan showed iso-attenuating in 8 tumors, hyper-attenuating in 21 tumors, and no hypo-attenuating. Most of delay imaging of hilar cholangiocarcinoma may appear hyper-attenuating (U = -4.3073, P 2 = 9.09, P < 0.01). Conclusion: When assessing hilar tumor, delayed CT contrast enhancement patterns based on two-phase dynamic incremental CT scans is useful in the detection and characterization of hilar cholangiocarcinoma

  14. Encoding audio motion: spatial impairment in early blind individuals

    Directory of Open Access Journals (Sweden)

    Sara eFinocchietti

    2015-09-01

    Full Text Available The consequence of blindness on auditory spatial localization has been an interesting issue of research in the last decade providing mixed results. Enhanced auditory spatial skills in individuals with visual impairment have been reported by multiple studies, while some aspects of spatial hearing seem to be impaired in the absence of vision. In this study, the ability to encode the trajectory of a 2 dimensional sound motion, reproducing the complete movement, and reaching the correct end-point sound position, is evaluated in 12 early blind individuals, 8 late blind individuals, and 20 age-matched sighted blindfolded controls. Early blind individuals correctly determine the direction of the sound motion on the horizontal axis, but show a clear deficit in encoding the sound motion in the lower side of the plane. On the contrary, late blind individuals and blindfolded controls perform much better with no deficit in the lower side of the plane. In fact the mean localization error resulted 271 ± 10 mm for early blind individuals, 65 ± 4 mm for late blind individuals, and 68 ± 2 mm for sighted blindfolded controls.These results support the hypothesis that i it exists a trade-off between the development of enhanced perceptual abilities and role of vision in the sound localization abilities of early blind individuals, and ii the visual information is fundamental in calibrating some aspects of the representation of auditory space in the brain.

  15. Enhancing early engagement with mental health services by young people

    Directory of Open Access Journals (Sweden)

    Burns J

    2014-11-01

    Full Text Available Jane Burns, Emma Birrell Young and Well Cooperative Research Centre, Abbotsford, VIC, Australia Abstract: International studies have shown that the prevalence of mental illness, and the fundamental contribution it make to the overall disease burden, is greatest in children and young people. Despite this high burden, adolescents and young adults are the least likely population group to seek help or to access professional care for mental health problems. This issue is particularly problematic given that untreated, or poorly treated, mental disorders are associated with both short- and long-term functional impairment, including poorer education and employment opportunities, potential comorbidity, including drug and alcohol problems, and a greater risk for antisocial behavior, including violence and aggression. This cycle of poor mental health creates a significant burden for the young person, their family and friends, and society as a whole. Australia is enviably positioned to substantially enhance the well-being of young people, to improve their engagement with mental health services, and – ultimately – to improve mental health. High prevalence but potentially debilitating disorders, such as depression and anxiety, are targeted by the specialized youth mental health service, headspace: the National Youth Mental Health Foundation and a series of Early Psychosis Prevention and Intervention Centres, will provide early intervention specialist services for low prevalence, complex illnesses. Online services, such as ReachOut.com by Inspire Foundation, Youthbeyondblue, Kids Helpline, and Lifeline Australia, and evidence-based online interventions, such as MoodGYM, are also freely available, yet a major challenge still exists in ensuring that young people receive effective evidence-based care at the right time. This article describes Australian innovation in shaping a comprehensive youth mental health system, which is informed by an evidence

  16. Evolutionary history of the alpha2,8-sialyltransferase (ST8Sia) gene family: tandem duplications in early deuterostomes explain most of the diversity found in the vertebrate ST8Sia genes.

    Science.gov (United States)

    Harduin-Lepers, Anne; Petit, Daniel; Mollicone, Rosella; Delannoy, Philippe; Petit, Jean-Michel; Oriol, Rafael

    2008-09-23

    The animal sialyltransferases, which catalyze the transfer of sialic acid to the glycan moiety of glycoconjugates, are subdivided into four families: ST3Gal, ST6Gal, ST6GalNAc and ST8Sia, based on acceptor sugar specificity and glycosidic linkage formed. Despite low overall sequence identity between each sialyltransferase family, all sialyltransferases share four conserved peptide motifs (L, S, III and VS) that serve as hallmarks for the identification of the sialyltransferases. Currently, twenty subfamilies have been described in mammals and birds. Examples of the four sialyltransferase families have also been found in invertebrates. Focusing on the ST8Sia family, we investigated the origin of the three groups of alpha2,8-sialyltransferases demonstrated in vertebrates to carry out poly-, oligo- and mono-alpha2,8-sialylation. We identified in the genome of invertebrate deuterostomes, orthologs to the common ancestor for each of the three vertebrate ST8Sia groups and a set of novel genes named ST8Sia EX, not found in vertebrates. All these ST8Sia sequences share a new conserved family-motif, named "C-term" that is involved in protein folding, via an intramolecular disulfide bridge. Interestingly, sequences from Branchiostoma floridae orthologous to the common ancestor of polysialyltransferases possess a polysialyltransferase domain (PSTD) and those orthologous to the common ancestor of oligosialyltransferases possess a new ST8Sia III-specific motif similar to the PSTD. In osteichthyans, we have identified two new subfamilies. In addition, we describe the expression profile of ST8Sia genes in Danio rerio. Polysialylation appeared early in the deuterostome lineage. The recent release of several deuterostome genome databases and paralogons combined with synteny analysis allowed us to obtain insight into events at the gene level that led to the diversification of the ST8Sia genes, with their corresponding enzymatic activities, in both invertebrates and vertebrates. The

  17. Evolutionary history of the alpha2,8-sialyltransferase (ST8Sia gene family: Tandem duplications in early deuterostomes explain most of the diversity found in the vertebrate ST8Sia genes

    Directory of Open Access Journals (Sweden)

    Petit Jean-Michel

    2008-09-01

    Full Text Available Abstract Background The animal sialyltransferases, which catalyze the transfer of sialic acid to the glycan moiety of glycoconjugates, are subdivided into four families: ST3Gal, ST6Gal, ST6GalNAc and ST8Sia, based on acceptor sugar specificity and glycosidic linkage formed. Despite low overall sequence identity between each sialyltransferase family, all sialyltransferases share four conserved peptide motifs (L, S, III and VS that serve as hallmarks for the identification of the sialyltransferases. Currently, twenty subfamilies have been described in mammals and birds. Examples of the four sialyltransferase families have also been found in invertebrates. Focusing on the ST8Sia family, we investigated the origin of the three groups of α2,8-sialyltransferases demonstrated in vertebrates to carry out poly-, oligo- and mono-α2,8-sialylation. Results We identified in the genome of invertebrate deuterostomes, orthologs to the common ancestor for each of the three vertebrate ST8Sia groups and a set of novel genes named ST8Sia EX, not found in vertebrates. All these ST8Sia sequences share a new conserved family-motif, named "C-term" that is involved in protein folding, via an intramolecular disulfide bridge. Interestingly, sequences from Branchiostoma floridae orthologous to the common ancestor of polysialyltransferases possess a polysialyltransferase domain (PSTD and those orthologous to the common ancestor of oligosialyltransferases possess a new ST8Sia III-specific motif similar to the PSTD. In osteichthyans, we have identified two new subfamilies. In addition, we describe the expression profile of ST8Sia genes in Danio rerio. Conclusion Polysialylation appeared early in the deuterostome lineage. The recent release of several deuterostome genome databases and paralogons combined with synteny analysis allowed us to obtain insight into events at the gene level that led to the diversification of the ST8Sia genes, with their corresponding enzymatic

  18. Legislative change enabling use of early part-time sick leave enhanced return to work and work participation in Finland.

    Science.gov (United States)

    Viikari-Juntura, Eira; Virta, Lauri J; Kausto, Johanna; Autti-Rämö, Ilona; Martimo, Kari-Pekka; Laaksonen, Mikko; Leinonen, Taina; Husgafvel-Pursiainen, Kirsti; Burdorf, Alex; Solovieva, Svetlana

    2017-09-01

    Objectives The aim of the study was to assess the effectiveness of the use of part-time sick leave at the early (first 12 weeks) stage of work disability due to mental disorder or musculoskeletal disease on sustained return to work (RTW) and overall work participation. Methods In a nation-wide register-based quasi-experimental study, we compared sustained RTW (ie, ≥28 consecutive days at work) and 2-year work participation between the part- and full-time sickness absence (SA) benefit groups (N=1878 in each group) using propensity-score matching. Persons who received partial or full SA benefit due to musculoskeletal diseases or mental disorders between January 1, 2010 and December 31, 2011 were eligible as cases or controls, respectively. Results A higher proportion showed sustained RTW after part- compared to full-time sick leave [absolute risk difference 8.0%, 95% confidence interval (95% CI) 5.3-10.9]. Moreover, the proportion of time at work was at a 10.5% higher level in the part- compared to full-time sick leave group. The prevalence of full disability retirement was almost three-fold among the full- compared to part-time sick leave group, whereas partial disability retirement was 4.5-fold more prevalent in the part- compared to full-time sick leave group. Conclusions The use of part-time sick leave during the first three months of SA enhances RTW and overall work participation during two years among persons with mental disorders and musculoskeletal diseases. The prescription of part-time sick leave can be recommended at an early stage of work disability.

  19. The Mitochondrion-Located Protein OsB12D1 Enhances Flooding Tolerance during Seed Germination and Early Seedling Growth in Rice

    Directory of Open Access Journals (Sweden)

    Dongli He

    2014-07-01

    Full Text Available B12D belongs to a function unknown subgroup of the Balem (Barley aleurone and embryo proteins. In our previous work on rice seed germination, we identified a B12D-like protein encoded by LOC_Os7g41350 (named OsB12D1. OsB12D1 pertains to an ancient protein family with an amino acid sequence highly conserved from moss to angiosperms. Among the six OsB12Ds, OsB12D1 is one of the major transcripts and is primarily expressed in germinating seed and root. Bioinformatics analyses indicated that OsB12D1 is an anoxic or submergence resistance-related gene. RT-PCR results showed OsB12D1 is induced remarkably in the coleoptiles or roots by flooding during seed germination and early seedling growth. The OsB12D1-overexpressed rice seeds could protrude radicles in 8 cm deep water, further exhibiting significant flooding tolerance compared to the wild type. Moreover, this tolerance was not affected by the gibberellin biosynthesis inhibitor paclobutrazol. OsB12D1 was identified in the mitochondrion by subcellular localization analysis and possibly enhances electron transport through mediating Fe and oxygen availability under flooded conditions. This work indicated that OsB12D1 is a promising gene that can help to enhance rice seedling establishment in farming practices, especially for direct seeding.

  20. Facile in situ solvothermal method to synthesize MWCNT/SnIn4S8 composites with enhanced visible light photocatalytic activity

    International Nuclear Information System (INIS)

    Ding, Chaoying; Tian, Li; Liu, Bo; Liang, Qian; Li, Zhongyu; Xu, Song; Liu, Qiaoli; Lu, Dayong

    2015-01-01

    Highlights: • MWCNT/SnIn 4 S 8 composites were facilely fabricated via in situ solvothermal method. • MWCNT/SnIn 4 S 8 composites exhibited significantly enhanced visible-light activity. • MWCNT/SnIn 4 S 8 composites showed remarkable visible light photocatalytic activity. • MWCNT/SnIn 4 S 8 composites exhibited excellent photo-stability. • Possible photocatalytic mechanism under visible-light irradiation was proposed. - Abstract: Superior photocatalytic activity could be achieved by multi-walled carbon nanotube (MWCNT) incorporated in the porous assembly of marigold-like SnIn 4 S 8 heterostructures synthesized by a flexible in-situ solvothermal method. The as-prepared MWCNT/SnIn 4 S 8 composites were well-characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM) and UV–vis diffuse reflectance spectroscopy (DRS). The photocatalytic properties of the as-prepared samples were tested by photo-degradation of aqueous malachite green (MG) under the irradiation of visible light. It was found that the MWCNT/SnIn 4 S 8 composites showed enhanced visible light photocatalytic activity for dye degradation, and an optimum photocatalytic activity was observed over 3.0 wt.% MWCNT incorporated SnIn 4 S 8 composites. The superior photocatalytic activity of MWCNT/SnIn 4 S 8 composites could be ascribed to the existence of MWCNT which could serve as a good electron acceptor, mediator as well as the co-catalyst for dye degradation. The synergistic effect between SnIn 4 S 8 and MWCNT in the composites facilitated the interfacial charge transfer driven by the excitation of SnIn 4 S 8 under visible-light irradiation. Furthermore, a possible mechanism for the photocatalytic degradation of MWCNT/SnIn 4 S 8 composites was also discussed

  1. Diagnostic Value of Early-Phase-Enhanced Computed Tomography for the Differentiation of Pulmonary Metastases from Hepatocellular Carcinoma and Primary Lung Cancer

    International Nuclear Information System (INIS)

    Choi, Joon-Il; Jung, Dae Chul; Kim, Min-Ju; Hong, Eun Kyung; Park, Joong-Won; Kim, Chang-Min; Choi, Hyuck Jae; Jang, Yun-Jin

    2009-01-01

    Background: The lung is the most common site of distant metastases from hepatocellular carcinoma. Correct differentiation between metastatic hepatocellular carcinoma of the lung and primary lung cancer is sometimes difficult without biopsy. Purpose: To evaluate the usefulness of measuring the attenuations of pulmonary nodules on early-phase contrast-enhanced computed tomography (CT) for the differentiation of pulmonary metastases from hepatocellular carcinoma and primary lung cancer. Material and Methods: Thirteen patients with pulmonary metastases from hepatocellular carcinoma (nine men, four women; age 53.9±14.2 years, range 16-70 years) and 25 patients with primary lung cancer (14 men, 11 women; age 62.2±9.4 years, range 43-72 years) were retrospectively evaluated. Contrast-enhanced scans were obtained 35 s after commencing intravenous injection of contrast medium. Attenuation values and the size of the pulmonary nodules were measured on contrast-enhanced CT scans. CT and clinical features were analyzed with regard to age, sex, body surface area of the patients, the attenuation values and size of the nodules, and CT machines using univariate analysis (Fisher's exact test for binary data sets and the Mann-Whitney U test for continuous data sets). Multiple linear regression analysis was used to eliminate confounding factors. Results: The mean attenuation value of metastatic pulmonary nodules from hepatocellular carcinoma (75.7±24.9 HU) was higher than that of primary lung cancer nodules (45.8±14.4 HU) (P<0.01). Other variables such as age, sex, body surface area of the patients, CT device, and nodule size were not significant variables on multiple regression analysis. When a cut-off value of 75 HU was applied, the positive predictive value for diagnosing metastatic nodules from hepatocellular carcinoma was 100%. Conclusion: Pending confirmation in a large study, our findings suggest that there is a difference in contrast enhancement between pulmonary

  2. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

    Science.gov (United States)

    Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-10-13

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.

  3. Enhanced Early Neuronal Processing of Food Pictures in Anorexia Nervosa: A Magnetoencephalography Study

    Directory of Open Access Journals (Sweden)

    Lauren R. Godier

    2016-01-01

    Full Text Available Neuroimaging studies in Anorexia Nervosa (AN have shown increased activation in reward and cognitive control regions in response to food, and a behavioral attentional bias (AB towards food stimuli is reported. This study aimed to further investigate the neural processing of food using magnetoencephalography (MEG. Participants were 13 females with restricting-type AN, 14 females recovered from restricting-type AN, and 15 female healthy controls. MEG data was acquired whilst participants viewed high- and low-calorie food pictures. Attention was assessed with a reaction time task and eye tracking. Time-series analysis suggested increased neural activity in response to both calorie conditions in the AN groups, consistent with an early AB. Increased activity was observed at 150 ms in the current AN group. Neuronal activity at this latency was at normal level in the recovered group; however, this group exhibited enhanced activity at 320 ms after stimulus. Consistent with previous studies, analysis in source space and behavioral data suggested enhanced attention and cognitive control processes in response to food stimuli in AN. This may enable avoidance of salient food stimuli and maintenance of dietary restraint in AN. A later latency of increased activity in the recovered group may reflect a reversal of this avoidance, with source space and behavioral data indicating increased visual and cognitive processing of food stimuli.

  4. S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.

    Science.gov (United States)

    Bektik, Emre; Dennis, Adrienne; Pawlowski, Gary; Zhou, Chen; Maleski, Danielle; Takahashi, Satoru; Laurita, Kenneth R; Deschênes, Isabelle; Fu, Ji-Dong

    2018-05-04

    Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of 5-ethynyl-20-deoxyuridine (EdU)⁺/α-myosin heavy chain (αMHC)-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP low cells. However, S-phase synchronization did not enhance the reprogramming with a polycistronic-viral vector, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

  5. Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy

    DEFF Research Database (Denmark)

    Mogensen, Marie Benzon; Hansen, Martin Lundsgaard; Henriksen, Birthe Merete

    2017-01-01

    Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective...... study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured....... Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy...

  6. Effect of calcium-binding protein S100A8 expression on early phase of radiation pulmonary fibrosis

    International Nuclear Information System (INIS)

    Rao Yalan; Li Ming; Cong Yue; Li Fengsheng; Chen Xiaohua; Dong Bo; Zhang Junquan; Gao Ling; Mao Bingzhi

    2008-01-01

    The study explores the expression and effect of calcium-binding protein S100A8 on early phase of radiation pulmonary fibrosis via in vivo and in vitro experiments. In vivo experiment, the thoracic regions of rats were irradiated under 20Gy 60 Co γ-rays to establish radiation pulmonary fibrosis. After irradiation, the lung specimens of the sacrificed rats were separately harvested by the ends of the first, second, and fourth weeks respectively. The protein expression of S100A8 was tested through immunohistochemistry, the mRNA expression of S100A8 and its heterodimeric S100A9 were investigated by RT-PCR method. In vitro experiment, RT-PCR method was also applied to measure the mRNA expression of S100A8 in mouse macrophage cell line RAW264.7 after γ-rays irradiation and/or lipopolysaccharide (LPS). It shows that the protein expression of S100A8 was increased in the plasma of lung macrophages samples and the mRNA expression of S100A8 and S100A9 was also increased in the lung tissue samples in four weeks after irradiation in vivo experiment. And in vitro experiment it shows that the cooperation between γ-rays and LPS can increase the mRNA expression of S100A8 in RAW264.7. These phenomena suggest that S100A8 can exert the chemotactic activity, participate in the inflammatory response, and influence the establishment of radiation pulmonary fibrosis. (authors)

  7. Fibroadenomas of the breast: histopathological/dynamic contrast-enhanced MR correlation

    Energy Technology Data Exchange (ETDEWEB)

    Gilles, R. [Dept. of Radiology, Inst. Gustave Roussy, 94 - Villejuif (France)]|[CIERM, Hopital Bicetre, 94 - Le Kremin-Bicetre (France); Garnier, C. [Dept. of Radiology, Inst. Gustave Roussy, 94 - Villejuif (France)]|[CIERM, Hopital Bicetre, 94 - Le Kremin-Bicetre (France); Meingan, P. [Dept. of Radiology, Inst. Gustave Roussy, 94 - Villejuif (France)]|[CIERM, Hopital Bicetre, 94 - Le Kremin-Bicetre (France); Zemoura, L. [Dept. of Histopathology C, Inst. Gustave Roussy, 94 - Villejuif (France); Lucidarme, O. [Dept. of Radiology, Hopital Salpetriere, 75 - Paris (France); Guinebretiere, J.M. [Dept. of Histopathology C, Inst. Gustave Roussy, 94 - Villejuif (France); Tardivon, A.A. [Dept. of Radiology, Inst. Gustave Roussy, 94 - Villejuif (France)]|[CIERM, Hopital Bicetre, 94 - Le Kremin-Bicetre (France); Arriagada, R. [Breast Cancer Study Group, Inst. Gustave Roussy, 94 - Villejuif, (France)

    1995-12-31

    A total of 22 women with fibroadenomas had preoperative dynamic MR study (T1-weighted images every 47 s after injection of Gd-DOTA). Their age, hormonal status, breast MR studies and histopathological slides were retrospectively reviewed. Eleven pre- (n = 2) or post-menopausal (n = 9) women showed no early contrast enhancement. The absence of early contrast enhancement correlated with hyalin stromal component. Eleven pre- (n = 7) or post-menopausal (n = 4) women showed focal (n = 9) or diffuse (n = 2) early contrast enhancement. Early focal contrast enhancement correlated with myxoid (n = 9), mixed hyalin/myxoid (n = 1) or hyalin (n = 1) fibroadenomas. Early diffuse contrast enhancement of the breast correlated with myxoid (n = 1) or hyalin (n = 1) stromal component associated with proliferative fibrocystic disease of the breast parenchyma. The presence of contrast enhancement correlated with myxoid fibroadenomas, whereas absence of contrast enhancement correlated with hyalin fibroadenomas. As hyalin fibroadenomas occurs in post-menopausal women, the diagnostic accuracy of dynamic MRI may be improved in this age group. (orig.)

  8. Fibroadenomas of the breast: histopathological/dynamic contrast-enhanced MR correlation

    International Nuclear Information System (INIS)

    Gilles, R.; Garnier, C.; Meingan, P.; Zemoura, L.; Lucidarme, O.; Guinebretiere, J.M.; Tardivon, A.A.; Arriagada, R.

    1995-01-01

    A total of 22 women with fibroadenomas had preoperative dynamic MR study (T1-weighted images every 47 s after injection of Gd-DOTA). Their age, hormonal status, breast MR studies and histopathological slides were retrospectively reviewed. Eleven pre- (n = 2) or post-menopausal (n = 9) women showed no early contrast enhancement. The absence of early contrast enhancement correlated with hyalin stromal component. Eleven pre- (n = 7) or post-menopausal (n = 4) women showed focal (n = 9) or diffuse (n = 2) early contrast enhancement. Early focal contrast enhancement correlated with myxoid (n = 9), mixed hyalin/myxoid (n 1) or hyalin (n = 1) fibroadenomas. Early diffuse contrast enhancement of the breast correlated with myxoid (n = 1) or hyalin (n = 1) stromal component associated with proliferative fibrocystic disease of the breast parenchyma. The presence of contrast enhancement correlated with myxoid fibroadenomas, whereas absence of contrast enhancement correlated with hyalin fibroadenomas. As hyalin fibroadenomas occurs in post-menopausal women, the diagnostic accuracy of dynamic MRI may be improved in this age group. (orig.)

  9. Pattern of Breast Cancer Distribution in Ghana: A Survey to Enhance Early Detection, Diagnosis, and Treatment

    Directory of Open Access Journals (Sweden)

    Frank Naku Ghartey Jnr

    2016-01-01

    Full Text Available Background. Nearly 70% of women diagnosed with breast cancer in Ghana are in advanced stages of the disease due especially to low awareness, resulting in limited treatment success and high death rate. With limited epidemiological studies on breast cancer in Ghana, the aim of this study is to assess and understand the pattern of breast cancer distribution for enhancing early detection and treatment. Methods. We randomly selected and screened 3000 women for clinical palpable breast lumps and used univariate and bivariate analysis for description and exploration of variables, respectively, in relation to incidence of breast cancer. Results. We diagnosed 23 (0.76% breast cancer cases out of 194 (6.46% participants with clinically palpable breast lumps. Seventeen out of these 23 (0.56% were premenopausal (<46.6 years with 7 (0.23% being below 35 years. With an overall breast cancer incidence of 0.76% in this study, our observation that about 30% of these cancer cases were below 35 years may indicate a relative possible shift of cancer burden to women in their early thirties in Ghana, compared to Western countries. Conclusion. These results suggest an age adjustment for breast cancer screening to early twenties for Ghanaian women and the need for a nationwide breast cancer screening to understand completely the pattern of breast cancer distribution in Ghana.

  10. Calcium dips enhance volatile emission of cold-stored 'Fuji Kiku-8' apples.

    Science.gov (United States)

    Ortiz, Abel; Echeverría, Gemma; Graell, Jordi; Lara, Isabel

    2009-06-10

    Despite the relevance of volatile production for overall quality of apple (Malus x domestica Borkh.) fruit, only a few studies have focused on the effects of calcium treatments on this quality attribute. In this work, 'Fuji Kiku-8' apples were harvested at commercial maturity, dipped in calcium chloride (2%, w/v), stored at 1 degrees C and 92% relative humidity for 4 or 7 months under either air or ultralow oxygen (ULO; 1 kPa of O(2)/2 kPa of CO(2)), and placed subsequently at 20 degrees C. Ethylene production, standard quality parameters, emission of volatile compounds, and the activities of some related enzymes were assessed 7 days thereafter. Calcium concentration was higher in CaCl(2)-treated than in untreated fruit, suggesting that the treatment was effective in introducing calcium into the tissues. Higher calcium contents were concomitant with higher flesh firmness and titratable acidity after storage. Furthermore, calcium treatment led to increased production of volatiles in middle-term stored apples, probably arising from enhanced supply of precursors for ester production as a consequence of increased pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) activities. After long-term storage, higher volatile emission might have arisen also from the enhancement of alcohol o-acyltransferase (AAT) activity, which was increased as a result of calcium treatment. In addition to storage period, the effects of calcium treatment were also partially dependent on storage atmosphere and more noticeable for fruit stored in air.

  11. Cognitive behavioural therapy attenuates the enhanced early facial stimuli processing in social anxiety disorders: an ERP investigation.

    Science.gov (United States)

    Cao, Jianqin; Liu, Quanying; Li, Yang; Yang, Jun; Gu, Ruolei; Liang, Jin; Qi, Yanyan; Wu, Haiyan; Liu, Xun

    2017-07-28

    Previous studies of patients with social anxiety have demonstrated abnormal early processing of facial stimuli in social contexts. In other words, patients with social anxiety disorder (SAD) tend to exhibit enhanced early facial processing when compared to healthy controls. Few studies have examined the temporal electrophysiological event-related potential (ERP)-indexed profiles when an individual with SAD compares faces to objects in SAD. Systematic comparisons of ERPs to facial/object stimuli before and after therapy are also lacking. We used a passive visual detection paradigm with upright and inverted faces/objects, which are known to elicit early P1 and N170 components, to study abnormal early face processing and subsequent improvements in this measure in patients with SAD. Seventeen patients with SAD and 17 matched control participants performed a passive visual detection paradigm task while undergoing EEG. The healthy controls were compared to patients with SAD pre-therapy to test the hypothesis that patients with SAD have early hypervigilance to facial cues. We compared patients with SAD before and after therapy to test the hypothesis that the early hypervigilance to facial cues in patients with SAD can be alleviated. Compared to healthy control (HC) participants, patients with SAD had more robust P1-N170 slope but no amplitude effects in response to both upright and inverted faces and objects. Interestingly, we found that patients with SAD had reduced P1 responses to all objects and faces after therapy, but had selectively reduced N170 responses to faces, and especially inverted faces. Interestingly, the slope from P1 to N170 in patients with SAD was flatter post-therapy than pre-therapy. Furthermore, the amplitude of N170 evoked by the facial stimuli was correlated with scores on the interaction anxiousness scale (IAS) after therapy. Our results did not provide electrophysiological support for the early hypervigilance hypothesis in SAD to faces, but

  12. Exogenous glucagon-like peptide-1 reduces body weight and cholecystokinin-8 enhances this reduction in diet-induced obese male rats.

    Science.gov (United States)

    Mhalhal, Thaer R; Washington, Martha C; Newman, Kayla; Heath, John C; Sayegh, Ayman I

    2017-10-01

    The sites of action regulating meal size (MS) and intermeal interval (IMI) length by glucagon like peptide-1 (7-36) (GLP-1 (7-36)) and cholecystokinin-8 (CCK-8) reside in the areas supplied by the two major branches of the abdominal aorta, celiac and cranial mesenteric arteries. We hypothesized that infusing GLP-1 near those sites reduces body weight (BW) and adding CCK-8 to this infusion enhances the reduction. Here, we measured BW in diet-induced obese (DIO) male rats maintained and tested on normal rat chow and infused with saline, GLP-1 (0.5nmol/kg) and GLP-1+CCK-8 (0.5nmol/kg each) in the aorta once daily for 21days. We found that GLP-1 and GLP-1+CCK-8 decrease BW relative to saline vehicle and GLP-1+CCK-8 reduced it more than GLP-1 alone. Reduction of BW by GLP-1 alone was accompanied by decreased 24-h food intake, first MS, duration of first meal and number of meals, and an increase in latency to first meal. Reduction of BW by the combination of the peptides was accompanied by decrease 24-h food intake, first MS, duration of first meal and number of meals, and increase in the IMI length, satiety ratio and latency to first meal. In conclusion, GLP-1 reduces BW and CCK-8 enhances this reduction if the peptides are given near their sites of action. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Contrast-Enhanced Endoscopic Ultrasonography for Pancreatic Tumors

    Directory of Open Access Journals (Sweden)

    Yasunobu Yamashita

    2015-01-01

    Full Text Available Objectives. To investigate the usefulness of contrast-enhanced endoscopic ultrasonography (CE-EUS for histological differentiation of pancreatic tumors. Methods. CE-EUS was performed for consecutive patients having a pancreatic solid lesion, and tumors were classified into three vascular patterns (hypervascular, isovascular, and hypovascular at two time phases (early-phase and late-phase. Correlation between vascular patterns and histopathology of resected pancreatic cancer (PC tissues was ascertained. Results. The final diagnoses of 147 examined tumors were PC (n=109, inflammatory mass (n=11, autoimmune pancreatitis (n=9, neuroendocrine tumor (n=8, and others (n=10. In late-phase images, 104 of 109 PCs had the hypovascular pattern, for a diagnostic sensitivity and specificity of 94% and 71%, respectively. Of 28 resected PCs, 10 had isovascular, and 18 hypovascular, patterns on the early-phase image. Early-phase isovascular PCs were more likely to be differentiated than were early-phase hypovascular PCs (6 well and 4 moderately differentiated versus 3 well, 14 moderately, and 1 poorly differentiated, P=0.028. Immunostaining revealed that hypovascular areas of early-phase images reflected heterogeneous tumor cells with fibrous tissue, necrosis, and few vessels. Conclusion. CE-EUS could be useful for distinguishing PC from other solid pancreatic lesions and for histological differentiation of PCs.

  14. Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Poghosyan, Anna, E-mail: pannagos@yahoo.com; Patel, Jamie K.; Clifford, Rachel L.; Knox, Alan J., E-mail: alan.knox@nottingham.ac.uk

    2016-08-05

    Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.

  15. Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

    International Nuclear Information System (INIS)

    Poghosyan, Anna; Patel, Jamie K.; Clifford, Rachel L.; Knox, Alan J.

    2016-01-01

    Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors of bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.

  16. Impaired 8-Hydroxyguanine Repair Activity of MUTYH Variant p.Arg109Trp Found in a Japanese Patient with Early-Onset Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Kazuya Shinmura

    2014-01-01

    Full Text Available Purpose. The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP, which is characterized by colorectal multiple polyps and carcinoma(s. However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients. Methods. Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing. Results. Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19*  MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19* and p.Arg109Trp corresponded to p.Arg5* and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5* is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays. Conclusion. These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19* and p.Arg109Trp MUTYH variants are associated with functional impairments.

  17. Dual-energy computed tomography for the assessment of early treatment effects of regorafenib in a preclinical tumor model: comparison with dynamic contrast-enhanced CT and conventional contrast-enhanced single-energy CT

    International Nuclear Information System (INIS)

    Knobloch, Gesine; Hamm, Bernd; Jost, Gregor; Pietsch, Hubertus; Huppertz, Alexander

    2014-01-01

    The potential diagnostic value of dual-energy computed tomography (DE-CT) compared to dynamic contrast-enhanced CT (DCE-CT) and conventional contrast-enhanced CT (CE-CT) in the assessment of early regorafenib treatment effects was evaluated in a preclinical setting. A rat GS9L glioma model was examined with contrast-enhanced dynamic DE-CT measurements (80 kV/140 kV) for 4 min before and on days 1 and 4 after the start of daily regorafenib or placebo treatment. Tumour time-density curves (0-240 s, 80 kV), DE-CT (60 s) derived iodine maps and the DCE-CT (0-30 s, 80 kV) based parameters blood flow (BF), blood volume (BV) and permeability (PMB) were calculated and compared to conventional CE-CT (60 s, 80 kV). The regorafenib group showed a marked decrease in the tumour time-density curve, a significantly lower iodine concentration and a significantly lower PMB on day 1 and 4 compared to baseline, which was not observed for the placebo group. CE-CT showed a significant decrease in tumour density on day 4 but not on day 1. The DE-CT-derived iodine concentrations correlated with PMB and BV but not with BF. DE-CT allows early treatment monitoring, which correlates with DCE-CT. Superior performance was observed compared to single-energy CE-CT. circle Regorafenib treatment response was evaluated by CT in a rat tumour model. (orig.)

  18. Dual-energy computed tomography for the assessment of early treatment effects of regorafenib in a preclinical tumor model: comparison with dynamic contrast-enhanced CT and conventional contrast-enhanced single-energy CT

    Energy Technology Data Exchange (ETDEWEB)

    Knobloch, Gesine; Hamm, Bernd [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Jost, Gregor; Pietsch, Hubertus [Bayer Healthcare, MR and CT Contrast Media Research, Berlin (Germany); Huppertz, Alexander [Imaging Science Institute Charite - Siemens, Berlin (Germany)

    2014-08-15

    The potential diagnostic value of dual-energy computed tomography (DE-CT) compared to dynamic contrast-enhanced CT (DCE-CT) and conventional contrast-enhanced CT (CE-CT) in the assessment of early regorafenib treatment effects was evaluated in a preclinical setting. A rat GS9L glioma model was examined with contrast-enhanced dynamic DE-CT measurements (80 kV/140 kV) for 4 min before and on days 1 and 4 after the start of daily regorafenib or placebo treatment. Tumour time-density curves (0-240 s, 80 kV), DE-CT (60 s) derived iodine maps and the DCE-CT (0-30 s, 80 kV) based parameters blood flow (BF), blood volume (BV) and permeability (PMB) were calculated and compared to conventional CE-CT (60 s, 80 kV). The regorafenib group showed a marked decrease in the tumour time-density curve, a significantly lower iodine concentration and a significantly lower PMB on day 1 and 4 compared to baseline, which was not observed for the placebo group. CE-CT showed a significant decrease in tumour density on day 4 but not on day 1. The DE-CT-derived iodine concentrations correlated with PMB and BV but not with BF. DE-CT allows early treatment monitoring, which correlates with DCE-CT. Superior performance was observed compared to single-energy CE-CT. circle Regorafenib treatment response was evaluated by CT in a rat tumour model. (orig.)

  19. Enhancement of 8-methoxypsoralen topical delivery via nanosized niosomal vesicles: Formulation development, in vitro and in vivo evaluation of skin deposition.

    Science.gov (United States)

    Kassem, Ahmed Alaa; Abd El-Alim, Sameh Hosam; Asfour, Marwa Hasanein

    2017-01-30

    The aim of the present study is to enhance the skin penetration and deposition of 8-methoxypsoraln (8-MOP) via niosomal vesicles to increase its local efficacy and safety. 8-MOP niosomes were prepared by the thin film hydration method using Span 60 or Span 40 along with cholesterol at five different molar ratios. The obtained vesicles revealed high entrapment efficiencies (83.04-89.90%) with nanometric vesicle diameters (111.1-198.8nm) of monodisperse distribution (PDI=0.145-0.216), zeta potential values <-48.3mV and spherical morphology under transmission electron microscopy. Optimized niosomal formulations depicted a biphasic in vitro release pattern in phosphate buffer (pH 5.5)/ethanol (7:3v/v) and displayed good physical stability after storage for 6 months at room (20-25°C) and refrigeration (4-8°C) temperatures. The two optimized formulations were incorporated in 5% sodium carboxy methylcellulose based hydrogel matrix which showed optimum pH values (7.37-7.39), pseudoplastic with thixotropic rheological behavior and more retarded 8-MOP release, by 23.82 and 14.89%, compared to niosomal vesicles after 24h. In vitro drug permeation and deposition studies, using rat skins, revealed promoted penetration and accumulation of 8-MOP after 8h. The skin penetration was further confirmed in vivo by confocal laser scanning microscopy, after 2h application period using rhodamine-loaded niosomal hydrogels compared to plain rhodamine hydrogel, as a florescence marker. Therefore, enhanced permeation and skin deposition of 8-MOP delivered by niosomes may help in improving the efficacy and safety of long-term treatment with 8-MOP. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Early life vaccination

    DEFF Research Database (Denmark)

    Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria

    2016-01-01

    Intracellular pathogens represent a serious threat during early life. Importantly, even though the immune system of newborns may be characterized as developmentally immature, with a propensity to develop Th2 immunity, significant CD8+ T-cell responses may still be elicited in the context of optimal...... the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...

  1. Enhancement pattern of hilar cholangiocarcinoma: Contrast-enhanced ultrasound versus contrast-enhanced computed tomography

    International Nuclear Information System (INIS)

    Xu Huixiong; Chen Lida; Xie Xiaoyan; Xie Xiaohua; Xu Zuofeng; Liu Guangjian; Lin Manxia; Wang Zhu; Lu Mingde

    2010-01-01

    Objective: To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). Methods: Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated. Results: In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT (P = 0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT (P = 0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P > 0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination (P = 0.125). Conclusion: The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.

  2. Enhancement pattern of hilar cholangiocarcinoma: Contrast-enhanced ultrasound versus contrast-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Xu Huixiong, E-mail: xuhuixiong@hotmail.co [Department of Medical Ultrasonics, The First Affiliated Hospital, Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080 (China); Chen Lida; Xie Xiaoyan; Xie Xiaohua; Xu Zuofeng; Liu Guangjian; Lin Manxia; Wang Zhu [Department of Medical Ultrasonics, The First Affiliated Hospital, Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080 (China); Lu Mingde, E-mail: lumd@21cn.co [Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou 510080 (China)

    2010-08-15

    Objective: To compare the enhancement pattern of hilar cholangiocarcinoma on contrast-enhanced ultrasound (CEUS) with that on contrast-enhanced computed tomography (CECT). Methods: Thirty-two consecutive patients with pathologically proven hilar cholangiocarcinomas were evaluated by both low mechanical index CEUS and CECT. The enhancement feature of the tumor, portal vein infiltration, and lesion conspicuity on them was investigated. Results: In the arterial phase, the numbers of the lesions showing hyperenhancement, isoenhancement, and hypoenhancement, were 14 (43.8%), 14 (43.8%), and 4 (12.6%), on CEUS, and 12 (37.5%), 9 (28.1%), and 11 (34.4%), on CECT (P = 0.162). In portal phase, the numbers of the lesions showing hypoenhancement, isoenhancement, and hyperenhancement were 30 (93.8%), 1 (3.1%), and 1 (3.1%), on CEUS, and 23 (71.9%), 8 (25.0%), and 1 (3.1%), on CECT (P = 0.046). The detection rates for portal vein infiltration were 84.2% (16/19) for baseline ultrasound, 89.5% (17/19) for CEUS, and 78.9% (15/19) for CECT (all P > 0.05 between every two groups). CEUS significantly improved the lesion conspicuity in comparison with CECT. CEUS and CECT made correct diagnoses in 30 (93.8%) and 25 (78.1%) lesions prior to pathological examination (P = 0.125). Conclusion: The enhancement pattern of hilar cholangiocarcinoma on CEUS was similar with that on CECT in arterial phase, whereas in portal phase hilar cholangiocarcinoma shows hypoenhancement more likely on CEUS. CEUS and CECT lead to similar results in evaluating portal vein infiltration and diagnosis of this entity.

  3. Contrast-Enhanced Ultrasound and Near-Infrared Spectroscopy of the Neonatal Bowel: Novel, Bedside, Noninvasive, and Radiation-Free Imaging for Early Detection of Necrotizing Enterocolitis.

    Science.gov (United States)

    Al-Hamad, Suzanne; Hackam, David J; Goldstein, Seth D; Huisman, Thierry A G M; Darge, Kassa; Hwang, Misun

    2018-05-31

    Despite extensive research and improvements in the field of neonatal care, the morbidity and mortality associated with necrotizing enterocolitis (NEC) have remained unchanged over the past three decades. Early detection of ischemia and necrotic bowel is vital in improving morbidity and mortality associated with NEC; however, strategies for predicting and preventing NEC are lacking. Contrast-enhanced ultrasound (CEUS) and near-infrared spectroscopy (NIRS) are novel techniques in pediatrics that have been proven as safe modalities. CEUS has benefits over conventional ultrasound (US) by its improved real-time evaluation of the micro- and macrovascularities of normally and abnormally perfused tissue. US has been implemented as a useful adjunct to X-ray for earlier evaluation of NEC. NIRS is another noninvasive technique that has shown promise in improving early detection of NEC. The purpose of this article is to review the current understanding of changes in bowel perfusion in NEC, discuss the accuracy of abdominal US in detecting NEC, and explain how the use of CEUS and NIRS will enhance the precise and early detection of altered/pathological bowel wall perfusion in the initial development and course of NEC. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Quantification of synovitis in the cranio-cervical region: Dynamic contrast enhanced and diffusion weighted magnetic resonance imaging in early rheumatoid arthritis-A feasibility follow up study

    Energy Technology Data Exchange (ETDEWEB)

    Jeromel, M., E-mail: miran.jeromel@gmail.com [Institute of Radiology, Department for Neuroradiology, University Medical Centre Ljubljana, Zaloska cesta 2, 1000 Ljubljana (Slovenia); Jevtic, V., E-mail: vladimir.jevtic@mf.uni-lj.si [Medical Faculty Ljubljana, Vrazov trg 2, 1104 Ljubljana (Slovenia); Sersa, I., E-mail: igor.sersa@ijs.si [Jozef Stefan Institute, Jamova cesta 39, 1000 Ljubljana (Slovenia); Ambrozic, A., E-mail: ales.ambrozic@mf.uni-lj.si [Department of Rheumatology, University Medical Centre Ljubljana, Vodnikova 62, 1000 Ljubljana (Slovenia); Tomsic, M., E-mail: matija.tomsic@kclj.si [Department of Rheumatology, University Medical Centre Ljubljana, Vodnikova 62, 1000 Ljubljana (Slovenia)

    2012-11-15

    Objective: To test the feasibility of dynamic contrast enhanced (DCEI) and diffusion weighted (DWI) magnetic resonance imaging (MRI) for quantifying synovitis of the cranio-cervical (C-C) region in patients with early rheumatoid arthritis (RA) and neck pain at the beginning and at a six month follow up. Methods: 27 patients with duration of RA of less than 24 months and neck pain were studied with standard qualitative MRI evaluation and two quantitative MRI methods (DCEI and DWI) at the level of atlantoaxial joints. Rate of early enhancement (REE), enhancement gradient (Genh) and apparent diffusion coefficient (ADC) were extracted from DCEI and DWI data. MRI was coupled with clinical assessment and radiographic imaging. Results: Using standard qualitative MRI evaluation, unequivocal active synovitis (grade 2 or 3 contrast enhancement) was proved in 16 (59%) patients at baseline and 14 (54%) at follow up. DCEI and DWI measurements confirmed active synovitis in 25 (93%) patients at baseline and 24 (92%) at follow up. Average REE, Genh and ADC values decreased during follow up, however the difference was not statistically significant (p > 0.05). Both qualitative and quantitative MRI methods confirmed active inflammatory disease in the C-C region following therapy although all clinical criteria showed signs of improvement of the peripheral disease. Conclusions: The study proved the feasibility of DCEI and DWI MRI for quantifying synovitis of the C-C region in patients with early RA and neck pain. Both techniques can be used as additional method for evaluation of synovitis of the C-C region in RA.

  5. Quantification of synovitis in the cranio-cervical region: Dynamic contrast enhanced and diffusion weighted magnetic resonance imaging in early rheumatoid arthritis—A feasibility follow up study

    International Nuclear Information System (INIS)

    Jeromel, M.; Jevtič, V.; Serša, I.; Ambrožič, A.; Tomšič, M.

    2012-01-01

    Objective: To test the feasibility of dynamic contrast enhanced (DCEI) and diffusion weighted (DWI) magnetic resonance imaging (MRI) for quantifying synovitis of the cranio-cervical (C-C) region in patients with early rheumatoid arthritis (RA) and neck pain at the beginning and at a six month follow up. Methods: 27 patients with duration of RA of less than 24 months and neck pain were studied with standard qualitative MRI evaluation and two quantitative MRI methods (DCEI and DWI) at the level of atlantoaxial joints. Rate of early enhancement (REE), enhancement gradient (Genh) and apparent diffusion coefficient (ADC) were extracted from DCEI and DWI data. MRI was coupled with clinical assessment and radiographic imaging. Results: Using standard qualitative MRI evaluation, unequivocal active synovitis (grade 2 or 3 contrast enhancement) was proved in 16 (59%) patients at baseline and 14 (54%) at follow up. DCEI and DWI measurements confirmed active synovitis in 25 (93%) patients at baseline and 24 (92%) at follow up. Average REE, Genh and ADC values decreased during follow up, however the difference was not statistically significant (p > 0.05). Both qualitative and quantitative MRI methods confirmed active inflammatory disease in the C-C region following therapy although all clinical criteria showed signs of improvement of the peripheral disease. Conclusions: The study proved the feasibility of DCEI and DWI MRI for quantifying synovitis of the C-C region in patients with early RA and neck pain. Both techniques can be used as additional method for evaluation of synovitis of the C-C region in RA.

  6. An adverse early life environment can enhance stress resilience in adulthood.

    Science.gov (United States)

    Santarelli, Sara; Zimmermann, Christoph; Kalideris, Georgia; Lesuis, Sylvie L; Arloth, Janine; Uribe, Andrés; Dournes, Carine; Balsevich, Georgia; Hartmann, Jakob; Masana, Mercè; Binder, Elisabeth B; Spengler, Dietmar; Schmidt, Mathias V

    2017-04-01

    Chronic stress is a major risk factor for depression. Interestingly, not all individuals develop psychopathology after chronic stress exposure. In contrast to the prevailing view that stress effects are cumulative and increase stress vulnerability throughout life, the match/mismatch hypothesis of psychiatric disorders. The match/mismatch hypothesis proposes that individuals who experience moderate levels of early life psychosocial stress can acquire resilience to renewed stress exposure later in life. Here, we have tested this hypothesis by comparing the developmental effects of 2 opposite early life conditions, when followed by 2 opposite adult environments. Male Balb/c mice were exposed to either adverse early life conditions (limited nesting and bedding material) or a supportive rearing environment (early handling). At adulthood, the animals of each group were either housed with an ovariectomized female (supportive environment) or underwent chronic social defeat stress (socially adverse environment) for 3 weeks. At the end of the adult manipulations, all of the animals were returned to standard housing conditions. Then, we compared the neuroendocrine, behavioral and molecular effects of the interaction between early and adult environment. Our study shows that early life adversity does not necessarily result in increased vulnerability to stress. Specific endophenotypes, like hypothalamic-pituitary-adrenal axis activity, anxiety-related behavior and glucocorticoid receptor expression levels in the hippocampus were not significantly altered when adversity is experienced during early life and in adulthood, and are mainly affected by either early life or adult life adversity alone. Overall our data support the notion that being raised in a stressful environment prepares the offspring to better cope with a challenging adult environment and emphasize the role of early life experiences in shaping adult responsiveness to stress. Copyright © 2017 Elsevier Ltd. All rights

  7. Enhanced tocopherol levels during early germination events in Chamaerops humilis var. humilis seeds.

    Science.gov (United States)

    Siles, Laura; Alegre, Leonor; Tijero, Verónica; Munné-Bosch, Sergi

    2015-10-01

    Most angiosperms accumulate vitamin E in the form of tocopherols in seeds, exerting a protective antioxidant role. However, several palm trees principally accumulate tocotrienols, rather than tocopherols, in seeds, as it occurs in other monocots. To unravel the protective role of either tocopherols or tocotrienols against lipid peroxidation during seed germination in Chamaerops humilis var. humilis; seed viability, natural and induced germination capacity, seed water content, malondialdehyde levels (as an indicator of the extent of lipid peroxidation) and vitamin E levels (including both tocopherols and tocotrienols) were examined at various germination phases in a simulated, natural seed bank. At the very early stages of germination (operculum removal), malondialdehyde levels increased 2.8-fold, to decrease later up to 74%, thus indicating a transient lipid peroxidation at early stages of germination. Tocopherol levels were absent in quiescent seeds and did not increase during operculum removal, but increased later presumably dampening malondialdehyde accumulation. Thereafter, tocopherols continued increasing, while lipid peroxidation levels decreased. By contrast, tocotrienols levels remained constant or even decreased as germination progressed, showing no correlation with lipid peroxidation levels. We hypothesize that despite their high tocotrienol content, seeds synthesize tocopherols during germination to protect lipids from peroxidation events. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma.

    Science.gov (United States)

    Dhabhar, Firdaus S; Saul, Alison N; Daugherty, Christine; Holmes, Tyson H; Bouley, Donna M; Oberyszyn, Tatiana M

    2010-01-01

    In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposure would enhance protective immunity and increase resistance to SCC. Control and short-term stress groups were treated identically except that the short-term stress group was restrained (2.5h) before each of nine UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of the 10-week UV exposure protocol. Tumors were measured weekly, and tissue collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and immunohistochemistry. Compared to controls, the short-term stress group showed greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors (weeks 11-26). These results suggest that activation of short-term stress physiology increased chemokine expression and T cell trafficking and/or function during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated immunity that is crucial for resistance to SCC. Therefore, the physiological fight-or-flight stress response and its adjuvant-like immuno-enhancing effects, may provide a novel and important mechanism for enhancing immune system mediated tumor-detection/elimination that merits further investigation.

  9. Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Fogg, Mark; Murphy, John R.; Lorch, Jochen; Posner, Marshall; Wang, Fred

    2013-01-01

    Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. - Highlights: • Viral proteins are tumor antigens in Epstein–Barr virus associated Nasopharyngeal Carcinoma. • CD8+ T cell responses against EBV proteins EBNA-1 and LMP2 are suppressed in NPC patients. • T regulatory cells are responsible for suppressing EBV immunity in NPC patients. • Depletion of Tregs with Ontak can rescue EBV-specific CD8+ T cell responses in NPC patients. • This clinically approved drug may be effective for enhancing anti-tumor immunity in NPC patients

  10. Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fogg, Mark [Department of Medicine, Brigham and Women' s Hospital (United States); Murphy, John R. [Departments of Medicine and Microbiology, Boston University School of Medicine, Boston, MA 02118 (United States); Lorch, Jochen; Posner, Marshall [Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Wang, Fred, E-mail: fwang@research.bwh.harvard.edu [Department of Medicine, Brigham and Women' s Hospital (United States); Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 (United States)

    2013-07-05

    Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. - Highlights: • Viral proteins are tumor antigens in Epstein–Barr virus associated Nasopharyngeal Carcinoma. • CD8+ T cell responses against EBV proteins EBNA-1 and LMP2 are suppressed in NPC patients. • T regulatory cells are responsible for suppressing EBV immunity in NPC patients. • Depletion of Tregs with Ontak can rescue EBV-specific CD8+ T cell responses in NPC patients. • This clinically approved drug may be effective for enhancing anti-tumor immunity in NPC patients.

  11. Early alveolar and systemic mediator release in patients at different risks for ARDS after multiple trauma.

    Science.gov (United States)

    Raymondos, Konstantinos; Martin, Michael U; Schmudlach, Tanja; Baus, Stefan; Weilbach, Christian; Welte, Tobias; Krettek, Christian; Frink, Michael; Hildebrand, Frank

    2012-02-01

    Alveolar IL-8 has been reported to early identify patients at-risk to develop ARDS. However, it remains unknown how alveolar IL-8 is related to pulmonary and systemic inflammation in patients predisposed for ARDS. We studied 24 patients 2-6h after multiple trauma. Patients with IL-8 >200 pg/ml in bronchoalveolar lavage (BAL) were assigned to the group at high risk for ARDS (H, n = 8) and patients with BAL IL-8 mediators. The enhanced alveolar and systemic inflammation associated with alveolar IL-8 release should be considered to identify high-risk patients for pulmonary complications after multiple trauma to adjust surgical and other treatment strategies to the individual risk profile. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Rhizospheric Bacterial Strain Brevibacterium casei MH8a Colonizes Plant Tissues and Enhances Cd, Zn, Cu Phytoextraction by White Mustard.

    Science.gov (United States)

    Płociniczak, Tomasz; Sinkkonen, Aki; Romantschuk, Martin; Sułowicz, Sławomir; Piotrowska-Seget, Zofia

    2016-01-01

    Environmental pollution by heavy metals has become a serious problem in the world. Phytoextraction, which is one of the plant-based technologies, has attracted the most attention for the bioremediation of soils polluted with these contaminants. The aim of this study was to determine whether the multiple-tolerant bacterium, Brevibacterium casei MH8a isolated from the heavy metal-contaminated rhizosphere soil of Sinapis alba L., is able to promote plant growth and enhance Cd, Zn, and Cu uptake by white mustard under laboratory conditions. Additionally, the ability of the rifampicin-resistant spontaneous mutant of MH8a to colonize plant tissues and its mechanisms of plant growth promotion were also examined. In order to assess the ecological consequences of bioaugmentation on autochthonous bacteria, the phospholipid fatty acid (PLFA) analysis was used. The MH8a strain exhibited the ability to produce ammonia, 1-amino-cyclopropane-1-carboxylic acid deaminase, indole 3-acetic acid and HCN but was not able to solubilize inorganic phosphate and produce siderophores. Introduction of MH8a into soil significantly increased S. alba biomass and the accumulation of Cd (208%), Zn (86%), and Cu (39%) in plant shoots in comparison with those grown in non-inoculated soil. Introduced into the soil, MH8a was able to enter the plant and was found in the roots and leaves of inoculated plants thus indicating its endophytic features. PLFA analysis revealed that the MH8a that was introduced into soil had a temporary influence on the structure of the autochthonous bacterial communities. The plant growth-promoting features of the MH8a strain and its ability to enhance the metal uptake by white mustard and its long-term survival in soil as well as its temporary impact on autochthonous microorganisms make the strain a suitable candidate for the promotion of plant growth and the efficiency of phytoextraction.

  13. Dynamic contrast-enhanced MR of the prostatic cancer and benign prostatic hyperplasia: correlation with angiogenesis

    International Nuclear Information System (INIS)

    Ni Xinchu; Shen Junkang; Lu Zhian; Zhou Lijuan; Yang Xiaochun; Wang Guanzhong; Zhang Caiyuan; Wang Shuizhen; Qian Minghui; Chan Yuxi; Qian Nong; Xiang Jianpo; Pan Changjie; Rong Weiliang; Chen Jianguo

    2005-01-01

    Objective: To evaluate the role of dynamic contrast-enhanced magnetic resonance imaging (MRI) in the diagnose of prostatic cancer and benign prostatic hyperplasia (BPH), and to determine the correlation between dynamic MRI findings with angiogenesis. Methods: Thirty-two cases of prostatic cancer and 40 cases of BPH underwent dynamic contrast-enhanced MRI. All the patients in this study were diagnosed by histopathology. The results of dynamic contrast-enhanced MRI were evaluated by early-phase enhancement parameters and time-signal intensity curves (SI-T curves), and the curves were classified according to their shapes as type I, which had steady enhancement; type II, plateau of signal intensity; and type III, washout of signal intensity. The pathologic specimens of region of interest (ROI ) were obtained, and HE staining, immunohistochemical vascular endothelial growth factor (VEGF), and microvessel density (MVD) measurements were performed. The relationships among dynamic contrast-enhanced MRI features, VEGF, and MVD expression were analyzed. Results: In the early-phase enhancement parameters of dynamic contrast-enhanced MRI, onset time, maximum signal intensity, and early-phase enhancement rate differed between prostatic cancer and BPH (P<0.01, 0.05, 0.01), but there were some overlaps between them. The intermediate and late post-contrast periods were characterized with the lesion SI-T curves. The SI-T curve of prostatic cancer was mainly type III (21 cases). Type II could be seen in both prostatic cancer (8 cases) and BPH (19 cases). Type I most appeared in BPH (18 cases). The distributions proved to have significant difference (P<0.001). The mean VEGF and MVD level of 32 prostatic cancer patients were significantly higher than those of 40 BPH patients (P<0.001). MVD level of prostatic cancer and BPH showed an association with VEGF level (P<0.01). The maximum signal intensity and early-phase enhancement rate in both prostatic cancer and BPH showed an association

  14. Functional weight-bearing mobilization after Achilles tendon rupture enhances early healing response: a single-blinded randomized controlled trial.

    Science.gov (United States)

    Valkering, Kars P; Aufwerber, Susanna; Ranuccio, Francesco; Lunini, Enricomaria; Edman, Gunnar; Ackermann, Paul W

    2017-06-01

    Functional weight-bearing mobilization may improve repair of Achilles tendon rupture (ATR), but the underlying mechanisms and outcome were unknown. We hypothesized that functional weight-bearing mobilization by means of increased metabolism could improve both early and long-term healing. In this prospective randomized controlled trial, patients with acute ATR were randomized to either direct post-operative functional weight-bearing mobilization (n = 27) in an orthosis or to non-weight-bearing (n = 29) plaster cast immobilization. During the first two post-operative weeks, 15°-30° of plantar flexion was allowed and encouraged in the functional weight-bearing mobilization group. At 2 weeks, patients in the non-weight-bearing cast immobilization group received a stiff orthosis, while the functional weight-bearing mobilization group continued with increased range of motion. At 6 weeks, all patients discontinued immobilization. At 2 weeks, healing metabolites and markers of procollagen type I (PINP) and III (PIIINP) were examined using microdialysis. At 6 and 12 months, functional outcome using heel-rise test was assessed. Healing tendons of both groups exhibited increased levels of metabolites glutamate, lactate, pyruvate, and of PIIINP (all p bearing mobilization group demonstrated significantly higher concentrations of glutamate compared to the non-weight-bearing cast immobilization group (p = 0.045).The upregulated glutamate levels were significantly correlated with the concentrations of PINP (r = 0.5, p = 0.002) as well as with improved functional outcome at 6 months (r = 0.4; p = 0.014). Heel-rise tests at 6 and 12 months did not display any differences between the two groups. Functional weight-bearing mobilization enhanced the early healing response of ATR. In addition, early ankle range of motion was improved without the risk of Achilles tendon elongation and without altering long-term functional outcome. The relationship between

  15. Perturbed CD8+ T cell TIGIT/CD226/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals

    DEFF Research Database (Denmark)

    Tauriainen, Johanna; Scharf, Lydia; Frederiksen, Juliet

    2017-01-01

    HIV-specific CD8+ T cells demonstrate an exhausted phenotype associated with increased expression of inhibitory receptors, decreased functional capacity, and a skewed transcriptional profile, which are only partially restored by antiretroviral treatment (ART). Expression levels of the inhibitory...... and displayed a diminished expression of CD226. Furthermore, expression of PVR was increased on CD4+ T cells, especially T follicular helper (Tfh) cells, in HIV-infected lymph nodes. These results depict a skewing of the TIGIT/CD226 axis from CD226 co-stimulation towards TIGIT-mediated inhibition of CD8+ T...... increased over time despite early initiation of ART. HIV-specific CD8+ T cells were almost exclusively TIGIT+, had an inverse expression of the transcription factors T-bet and Eomes and co-expressed PD-1, CD160 and 2B4. HIV-specific TIGIThi cells were negatively correlated with polyfunctionality...

  16. Birth weight and postnatal growth in preterm born children are associated with cortisol in early infancy, but not at age 8 years.

    Science.gov (United States)

    Ruys, Charlotte A; van der Voorn, Bibian; Lafeber, Harrie N; van de Lagemaat, Monique; Rotteveel, Joost; Finken, Martijn J J

    2017-08-01

    Preterm birth has been associated with altered hypothalamic-pituitary-adrenal (HPA-) axis activity as well as cardiometabolic diseases and neurodevelopmental impairments later in life. We assessed cortisol from term age to age 8 y in children born preterm, to explore the development of HPA-axis activity in association with intrauterine and early-postnatal growth until 6 mo. corrected age. In 152 children born at a gestational age ≤32 wks. and/or with a birth weight ≤1,500g, random serum cortisol was assessed at term age (n=150), 3 mo. (n=145) and 6 mo. corrected age (n=144), and age 8 y (n=59). Salivary cortisol was assessed at age 8 y (n=75): prior to bedtime, at awakening, 15min after awakening, and before lunch. Cortisol was analyzed in association with birth weight-standard deviation score (SDS), being born small for gestational age (SGA), and combinations of intrauterine and postnatal growth: appropriate for gestational age (AGA) with or without growth restriction (AGA GR+ or AGA GR-) at 6 mo. corrected age, and SGA with or without catch-up growth (SGA CUG+ or SGA CUG-) at 6 mo. corrected age. Cross-sectional associations at all time points were analyzed using linear regression, and longitudinal associations were analyzed using generalized estimating equations. Longitudinally, birth weight-SDS was associated with cortisol (β [95%CI]): lower cortisol over time was seen in infants with a birth weight ≤-2 SDS (-50.69 [-94.27; -7.11], p=0.02), infants born SGA (-29.70 [-60.58; 1.19], p=0.06), AGA GR+ infants (-55.10 [-106.02; -4.17], p=0.03) and SGA CUG- infants (-61.91 [-104.73; -19.10], p=0.01). In cross-sectional analyses at age 8 y, no associations were found between either serum or salivary cortisol and birth weight-SDS, SGA-status, or growth from birth to 6 mo. corrected age. In children born preterm, poor intrauterine and postnatal growth were associated with lower cortisol in early infancy, but not at age 8 y. Even though HPA-axis activity no longer

  17. Enhanced interleukin-8 production in THP-1 human monocytic cells by lipopolysaccharide from oral microorganisms and granulocyte-macrophage colony-stimulating factor.

    Science.gov (United States)

    Baqui, A A; Meiller, T F; Falkler, W A

    1999-10-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been used to assist in bone marrow recovery during cancer chemotherapy. Interleukin-8 (IL-8) plays an important role in macrophage mediated inflammatory processes including exacerbation of periodontal diseases, one of the most common complications in GM-CSF receiving cancer patients. The effect of GM-CSF supplementation on IL-8 production was investigated in a human monocyte cell line THP-1, stimulated with lipopolysaccharide extracted from two oral microorganisms, Porphyromonas gingivalis and Fusobacterium nucleatum. Resting THP-1 cells were treated with lipopolysaccharide (1 microgram/ml) of P. gingivalis or F. nucleatum and/or GM-CSF (50 IU/ml) for varying time periods. The production of IL-8 in THP-1 cells was measured by a solid-phase enzyme-linked immunosorbent assay (ELISA). A very low level of the cytokine IL-8 was produced constitutive in THP-1 cells. Starting from 8 h of treatment and afterwards GM-CSF alone significantly increased IL-8 production in THP-1 cells. Lipopolysaccharide (1 microgram/ml) extracts from either F. nucleatum or P. gingivalis amplified IL-8 production 500-800 times in comparison to resting THP-1 cells. When lipopolysaccharide of F. nucleatum or P. gingivalis was supplemented with 50 IU/ml of GM-CSF, there was a statistically significant enhanced production of IL-8 by THP-1 cells after 1 day to 7 days of treatment as compared with lipopolysaccharide treatment alone. GM-CSF (50 IU/ml) also significantly increased IL-8 production from 2-7 days of treatment of THP-1 cells when supplemented with a positive control, phorbol-12-myristate-13 acetate (PMA), as compared to PMA treatment alone. These investigations using the in vitro THP-1 human monocyte cell model indicate that there may be an increase in the response on a cellular level to oral endotoxin following GM-CSF therapy as evidenced by enhanced production of the tissue-reactive inflammatory cytokine, IL-8.

  18. Loss of heterozygosity at D8S262: an early genetic event of hepatocarcinogenesis.

    Science.gov (United States)

    Zhu, Qiao; Gong, Li; Liu, Xiaoyan; Wang, Jun; Ren, Pin; Zhang, Wendong; Yao, Li; Han, Xiujuan; Zhu, Shaojun; Lan, Miao; Li, Yanhong; Zhang, Wei

    2015-06-16

    Hepatocellular carcinoma (HCC) is a multi-factor, multi-step, multi-gene and complicated process resulting from the accumulation of sequential genetic and epigenetic alterations. An important change among them is from precancerous lesions to HCC. However, only few studies have been reported about the sequential genetic changes during hepatocarcinogenesis. We observed firstly molecular karyotypes of 10 matched HCC using Affymetrix single-nucleotide polymorphism (SNP) 6.0 arrays, and found chromosomal fragments with high incidence (more than 70%) of loss of heterozygosity (LOH). Then, we selected 28 microsatellite markers at some gene spanning these chromosomal fragments, and examined the frequency of LOH of 128 matched HCC and 43 matched precancerous lesions-dysplastic nodules (DN) by a PCR-based analysis. Finally, we investigated the expression of proteins encoded by these genes in HCC, DN and the surrounding hepatic tissues. The result of Affymetrix SNP6.0 arrays demonstrated that more than 70% (7/10) cases had chromosomal fragment deletion on 4q13.3-35.1, 8p23.2-21.2, 16q11.2-24.3, and 17p13.3-12. Among 28 microsatellite markers selected, LOH frequencies at D8S262 for DN and HCC were found to be the highest, 51.2% and 72.7%, respectively. Immunohistochemically, the positive rate of its adjacent gene CSMD1 in HCC, DN, and the surrounding hepatic tissues were 27.3% (35/128), 75% (33/44), and 82% (105/128), respectively. LOH at D8S262 may be associated with an early genetic event of hepatocarcinogenesis, and a predictor for the monitor and prevention of HCC. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1557074981159099 .

  19. Sulfur Geochemistry of a Lacustrine Record from Taiwan Reveals Enhanced Marine Aerosol Input during the Early Holocene.

    Science.gov (United States)

    Ding, Xiaodong; Li, Dawei; Zheng, Liwei; Bao, Hongyan; Chen, Huei-Fen; Kao, Shuh-Ji

    2016-12-12

    Lacustrine record of marine aerosol input has rarely been documented. Here, we present the sulfur geochemistry during the last deglaciation and early Holocene of a sediment core retrieved from the Dongyuan Lake in southern Taiwan. An unusually high sulfur peak accompanying pyrite presence is observed at 10.5 ka BP. Such high sulfur content in lacustrine record is unusual. The δ 34 S of sulfur varied from +9.5 to + 17.1‰ with two significant positive shifts at 10.5 and 9.4 ka BP. The sources of sulfur and potential processes involving the sulfur isotope variation including bacterial sulfate reduction, volcanic emissions, in-catchment sulfide oxidation and marine aerosol input are discussed. Enhanced marine aerosol input is the most likely explanation for such sulfur peaks and δ 34 S shifts. The positive δ 34 S shifts appeared concurrently with the maximum landslide events over Taiwan resulted from enhanced typhoon activities. The synchronicity among records suggests that increased typhoon activities promoted sea spray, and consequently enhanced the marine aerosol input with 34 S-enriched sulfate. Our sulfur geochemistry data revealed sea spray history and marine influence onto terrestrial environment at coastal regions. Wider coverage of spatial-temporal lacustrine sulfur geochemistry record is needed to validate the applicability of sulfur proxy in paleoenvironmental research.

  20. The effect of excess expression of GFP in a novel heart-specific green fluorescence zebrafish regulated by nppa enhancer at early embryonic development.

    Science.gov (United States)

    Huang, Wen; Deng, Yun; Dong, Wei; Yuan, Wuzhou; Wan, Yongqi; Mo, Xiaoyan; Li, Yongqing; Wang, Zequn; Wang, Yuequn; Ocorr, Karen; Zhang, Bo; Lin, Shuo; Wu, Xiushan

    2011-02-01

    In order to study the impalpable effect of GFP in homozygous heart-specific GFP-positive zebrafish during the early stage, the researchers analyzed the heart function of morphology and physiology at the first 3 days after fertilization. This zebrafish line was produced by a large-scale Tol2 transposon mediated enhancer trap screen that generated a transgenic zebrafish with a heart-specific expression of green fluorescent protein (GFP)-tagged under control of the nppa enhancer. In situ hybridization experiments showed that the nppa:GFP line faithfully recapitulated both the spatial and temporal expressions of the endogenous nppa. Green fluorescence was intensively and specifically expressed in the myocardial cells located both in the heart chambers and in the atrioventricular canal. The embryonic heart of nppa:GFP line developed normally compared with those in the wild type. There was no difference between the nappa:GFP and wild type lines with respect to heart rate, overall size, ejection volume, and fractional shortening. Thus the excess expression of GFP in this transgenic line seemed to exert no detrimental effects on zebrafish hearts during the early stages.

  1. Diagnostic Accuracy of Dynamic Contrast Enhanced Magnetic Resonance Imaging in Characterizing Lung Masses

    Science.gov (United States)

    Inan, Nagihan; Arslan, Arzu; Donmez, Muhammed; Sarisoy, Hasan Tahsin

    2016-01-01

    Background Imaging plays a critical role not only in the detection, but also in the characterization of lung masses as benign or malignant. Objectives To determine the diagnostic accuracy of dynamic magnetic resonance imaging (MRI) in the differential diagnosis of benign and malignant lung masses. Patients and Methods Ninety-four masses were included in this prospective study. Five dynamic series of T1-weighted spoiled gradient echo (FFE) images were obtained, followed by a T1-weighted FFE sequence in the late phase (5th minutes). Contrast enhancement patterns in the early (25th second) and late (5th minute) phase images were evaluated. For the quantitative evaluation, signal intensity (SI)-time curves were obtained and the maximum relative enhancement, wash-in rate, and time-to-peak enhancement of masses in both groups were calculated. Results The early phase contrast enhancement patterns were homogeneous in 78.2% of the benign masses, while heterogeneous in 74.4% of the malignant tumors. On the late phase images, 70.8% of the benign masses showed homogeneous enhancement, while most of the malignant masses showed heterogeneous enhancement (82.4%). During the first pass, the maximum relative enhancement and wash-in rate values of malignant masses were significantly higher than those of the benign masses (P = 0.03 and 0.04, respectively). The cutoff value at 15% yielded a sensitivity of 85.4%, specificity of 61.2%, and positive predictive value of 68.7% for the maximum relative enhancement. Conclusion Contrast enhancement patterns and SI-time curve analysis of MRI are helpful in the differential diagnosis of benign and malignant lung masses. PMID:27703654

  2. Social recovery therapy in combination with early intervention services for enhancement of social recovery in patients with first-episode psychosis (SUPEREDEN3): a single-blind, randomised controlled trial.

    Science.gov (United States)

    Fowler, David; Hodgekins, Jo; French, Paul; Marshall, Max; Freemantle, Nick; McCrone, Paul; Everard, Linda; Lavis, Anna; Jones, Peter B; Amos, Tim; Singh, Swaran; Sharma, Vimal; Birchwood, Max

    2018-01-01

    activity of 8·1 h (95% CI 2·5-13·6; p=0·0050) compared with early intervention services alone. No adverse events were deemed attributable to study therapy. Our findings show a clinically important benefit of enhanced social recovery on structured activity in patients with first-episode psychosis who received social recovery therapy plus early intervention services. Social recovery therapy might be useful in improving functional outcomes in people with first-episode psychosis, particularly in individuals not motivated to engage in existing psychosocial interventions targeting functioning, or who have comorbid difficulties preventing them from doing so. National Institute for Health Research. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

  3. Early detection of temporomandibular joint arthritis in children with juvenile idiopathic arthritis - the role of contrast-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kalle, Thekla von; Stuber, Tina; Winkler, Peter [Olgahospital Klinikum Stuttgart, Pediatric Radiology, Radiologisches Institut, Stuttgart (Germany); Maier, Jan; Hospach, Toni [Olgahospital Klinikum Stuttgart, Pediatric Rheumatology, Stuttgart (Germany)

    2015-03-01

    Early treatment of temporomandibular joint (TMJ) arthritis is crucial in children with juvenile idiopathic arthritis (JIA) to prevent permanent functional impairment. As involvement of TMJs is often asymptomatic, contrast-enhanced MRI is regarded as the most sensitive noninvasive diagnostic tool. To evaluate the degree of contrast enhancement in TMJs of children and adolescents with JIA in comparison to normal controls from a previous study. Dynamic contrast-enhanced MRI of 50 children and adolescents with JIA (6.3 to 18 years of age; mean: 12 years) were retrospectively analysed. We assessed morphological abnormalities and postcontrast time-intensity curves of the soft joint tissue and the mandibular condyle. Ratios were calculated to quantify postcontrast signal intensities (SI) in relation to precontrast SI at initial (1 min postcontrast) and maximum (6 min postcontrast) increase. Time-intensity curves followed similar biphasic patterns in normal and pathological joints. In joints with morphological signs of arthritis, mean SI ratios were on average higher than in normal joints of the reference group, but ranges of values widely overlapped. Arthritis: mean initial increase of SI 62% (±2 S.D. 18-105%), mean maximum SI 106% higher than precontrast (±2 S.D. 46-166%). Normal: mean initial increase of SI 49% (±2 S.D. 14- 85%), mean maximum of SI 73% (±2 S.D. 23-123%). Given this considerable overlap of results in dynamic contrast-enhanced MRI, the degree of contrast enhancement alone did not allow differentiation between TMJs with and without signs of inflammation. Thickening of the soft joint tissue seems to remain the earliest sign to reliably indicate TMJ arthritis. (orig.)

  4. The CD8 and CD4 T-cell response against Kaposi's sarcoma-associated herpesvirus is skewed towards early and late lytic antigens.

    Directory of Open Access Journals (Sweden)

    Rebecca C Robey

    Full Text Available Kaposi's sarcoma-associated herpesvirus (KSHV is causally related to Kaposi's sarcoma (KS, the most common malignancy in untreated individuals with HIV/AIDS. The adaptive T-cell immune response against KSHV has not been fully characterized. To achieve a better understanding of the antigenic repertoire of the CD8 and CD4 T-cell responses against KSHV, we constructed a library of lentiviral expression vectors each coding for one of 31 individual KSHV open reading frames (ORFs. We used these to transduce monocyte-derived dendritic cells (moDCs isolated from 14 KSHV-seropositive (12 HIV-positive and 7 KSHV-seronegative (4 HIV-positive individuals. moDCs were transduced with up to 3 KSHV ORFs simultaneously (ORFs grouped according to their expression during the viral life cycle. Transduced moDCs naturally process the KSHV genes and present the resulting antigens in the context of MHC class I and II. Transduced moDCs were cultured with purified autologous T cells and the CD8 and CD4 T-cell proliferative responses to each KSHV ORF (or group was assessed using a CFSE dye-based assay. Two pools of early lytic KSHV genes ([ORF8/ORF49/ORF61] and [ORF59/ORF65/K4.1] were frequently-recognized targets of both CD8 and CD4 T cells from KSHV seropositive individuals. One pool of late lytic KSHV genes ([ORF28/ORF36/ORF37] was a frequently-recognized CD8 target and another pool of late genes ([ORF33/K1/K8.1] was a frequently-recognized CD4 target. We report that both the CD8 and CD4 T-cell responses against KSHV are skewed towards genes expressed in the early and late phases of the viral lytic cycle, and identify some previously unknown targets of these responses. This knowledge will be important to future immunological investigations into KSHV and may eventually lead to the development of better immunotherapies for KSHV-related diseases.

  5. Subchronic JP-8 jet fuel exposure enhances vulnerability to noise-induced hearing loss in rats.

    Science.gov (United States)

    Fechter, L D; Fisher, J W; Chapman, G D; Mokashi, V P; Ortiz, P A; Reboulet, J E; Stubbs, J E; Lear, A M; McInturf, S M; Prues, S L; Gearhart, C A; Fulton, S; Mattie, D R

    2012-01-01

    Both laboratory and epidemiological studies published over the past two decades have identified the risk of excess hearing loss when specific chemical contaminants are present along with noise. The objective of this study was to evaluate the potency of JP-8 jet fuel to enhance noise-induced hearing loss (NIHL) using inhalation exposure to fuel and simultaneous exposure to either continuous or intermittent noise exposure over a 4-wk exposure period using both male and female Fischer 344 rats. In the initial study, male (n = 5) and female (n = 5) rats received inhalation exposure to JP-8 fuel for 6 h/d, 5 d/wk for 4 wk at concentrations of 200, 750, or 1500 mg/m³. Parallel groups of rats also received nondamaging noise (constant octave band noise at 85 dB(lin)) in combination with the fuel, noise alone (75, 85, or 95 dB), or no exposure to fuel or noise. Significant concentration-related impairment of auditory function measured by distortion product otoacoustic emissions (DPOAE) and compound action potential (CAP) threshold was seen in rats exposed to combined JP-8 plus noise exposure when JP-8 levels of 1500 mg/m³ were presented with trends toward impairment seen with 750 mg/m³ JP-8 + noise. JP-8 alone exerted no significant effect on auditory function. In addition, noise was able to disrupt the DPOAE and increase auditory thresholds only when noise exposure was at 95 dB. In a subsequent study, male (n = 5 per group) and female (n = 5 per group) rats received 1000 mg/m³ JP-8 for 6 h/d, 5 d/wk for 4 wk with and without exposure to 102 dB octave band noise that was present for 15 min out of each hour (total noise duration 90 min). Comparisons were made to rats receiving only noise, and thosereceiving no experimental treatment. Significant impairment of auditory thresholds especially for high-frequency tones was identified in the male rats receiving combined treatment. This study provides a basis for estimating excessive hearing loss under

  6. Enhanced vaccine-induced CD8+ T cell responses to malaria antigen ME-TRAP by fusion to MHC class ii invariant chain.

    Directory of Open Access Journals (Sweden)

    Alexandra J Spencer

    Full Text Available The orthodox role of the invariant chain (CD74; Ii is in antigen presentation to CD4+ T cells, but enhanced CD8+ T cells responses have been reported after vaccination with vectored viral vaccines encoding a fusion of Ii to the antigen of interest. In this study we assessed whether fusion of the malarial antigen, ME-TRAP, to Ii could increase the vaccine-induced CD8+ T cell response. Following single or heterologous prime-boost vaccination of mice with a recombinant chimpanzee adenovirus vector, ChAd63, or recombinant modified vaccinia virus Ankara (MVA, higher frequencies of antigen-specific CD4+ and CD8+ T cells were observed, with the largest increases observed following a ChAd63-MVA heterologous prime-boost regimen. Studies in non-human primates confirmed the ability of Ii-fusion to augment the T cell response, where a 4-fold increase was maintained up to 11 weeks after the MVA boost. Of the numerous different approaches explored to increase vectored vaccine induced immunogenicity over the years, fusion to the invariant chain showed a consistent enhancement in CD8+ T cell responses across different animal species and may therefore find application in the development of vaccines against human malaria and other diseases where high levels of cell-mediated immunity are required.

  7. Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function

    Directory of Open Access Journals (Sweden)

    Brendan E. Russ

    2017-12-01

    Full Text Available Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs, we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+ chromatin signature upon differentiation. This unique TE subset exhibited characteristics of poised enhancers in the naive CD8+ T cell subset and demonstrated enrichment for transcription factor binding motifs known to be important for virus-specific CD8+ T cell differentiation. These data provide insights into the establishment and maintenance of the gene transcription profiles that define each stage of virus-specific T cell differentiation.

  8. Use of biosolids to enhance rangeland forage quality.

    Science.gov (United States)

    McFarland, Michael J; Vasquez, Issaak Romero; Vutran, MaiAnh; Schmitz, Mark; Brobst, Robert B

    2010-05-01

    Biosolids land application was demonstrated to be a potentially cost-effective means for restoring forage productivity and enhancing soil-moisture-holding capacity on disturbed rangelands. By land-applying aerobically digested, anaerobically digested, composted, and lime-stabilized biosolids on rangeland test plots at rates of up to 20 times (20X) the estimated nitrogen-based agronomic rate, forage yields were found to increase from 132.8 kg/ha (118.2 lb/ac) (control plots) to 1182.3 kg/ha (1052.8 lb/ac). Despite the environmental benefits associated with increased forage yield (e.g., reduced soil erosion, improved drainage, and enhanced terrestrial carbon sequestration), the type of forage generated both before and after biosolids land application was found to be dominated by invasive weeds, all of which were characterized as having fair to poor nutritional value. Opportunistic and shallow rooting invasive weeds not only have marginal nutritional value, they also limit the establishment of native perennial grasses and thus biodiversity. Many of the identified invasive species (e.g., Cheatgrass) mature early, a characteristic that significantly increases the fuel loads that support the increased frequency and extent of western wildfires.

  9. Contrast medium-enhanced MRI findings and changes over time in stage I tuberculous meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Oztoprak, I. [Department of Radiology Cumhuriyet University Faculty of Medicine, 58140 Sivas (Turkey)], E-mail: oztoprak@cumhuriyet.edu.tr; Guemues, C.; Oztoprak, B. [Department of Radiology Cumhuriyet University Faculty of Medicine, 58140 Sivas (Turkey); Engin, A. [Department of Infectious Diseases, Cumhuriyet University Faculty of Medicine, Sivas (Turkey)

    2007-12-15

    Aim: To demonstrate the detailed imaging characteristics of early tuberculous meningitis (TBM) and changes over time on standard gadolinium-enhanced, T1-weighted magnetic resonance imaging (MRI) images. Materials and methods: Contrast-enhanced, T1-weighted, spin-echo MRI images of 26 patients with early TBM were evaluated retrospectively. Meningeal enhancement characteristics were categorized according to distribution and pattern as diffuse, focal, linear, nodular, and mixed. Results: We found that 35% of patients had diffuse meningeal enhancement and 65% of cases had focal meningeal enhancement. There was a predilection for focal meningeal enhancement in basal pial areas, the interpeduncular fossa being the most common. In six patients with diffuse meningeal enhancement admitted to hospital relatively early after the onset of symptoms, the type of meningeal enhancement later changed to the focal form. Conclusion: Reactive diffuse meningeal enhancement occurs in the early period of TBM on contrast medium-enhanced T1-weighted MR images, but later becomes limited to basal areas.

  10. Contrast medium-enhanced MRI findings and changes over time in stage I tuberculous meningitis

    International Nuclear Information System (INIS)

    Oztoprak, I.; Guemues, C.; Oztoprak, B.; Engin, A.

    2007-01-01

    Aim: To demonstrate the detailed imaging characteristics of early tuberculous meningitis (TBM) and changes over time on standard gadolinium-enhanced, T1-weighted magnetic resonance imaging (MRI) images. Materials and methods: Contrast-enhanced, T1-weighted, spin-echo MRI images of 26 patients with early TBM were evaluated retrospectively. Meningeal enhancement characteristics were categorized according to distribution and pattern as diffuse, focal, linear, nodular, and mixed. Results: We found that 35% of patients had diffuse meningeal enhancement and 65% of cases had focal meningeal enhancement. There was a predilection for focal meningeal enhancement in basal pial areas, the interpeduncular fossa being the most common. In six patients with diffuse meningeal enhancement admitted to hospital relatively early after the onset of symptoms, the type of meningeal enhancement later changed to the focal form. Conclusion: Reactive diffuse meningeal enhancement occurs in the early period of TBM on contrast medium-enhanced T1-weighted MR images, but later becomes limited to basal areas

  11. Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Piludu, Francesca; Vidiri, Antonello [Regina Elena National Cancer Institute, Radiology and Diagnostic Imaging Department, Rome (Italy); Marzi, Simona [Regina Elena National Cancer Institute, Medical Physics Laboratory, Rome (Italy); Pace, Andrea; Villani, Veronica [Regina Elena National Cancer Institute, Neurology Division, Rome (Italy); Fabi, Alessandra [Regina Elena National Cancer Institute, Oncology Department, Rome (Italy); Carapella, Carmine Maria [Regina Elena National Cancer Institute, Oncologic Surgery Department, Rome (Italy); Terrenato, Irene [Regina Elena National Cancer Institute, Biostatistics-Scientific Direction, Rome (Italy); Antenucci, Anna [Regina Elena National Cancer Institute, Clinical Pathology, Rome (Italy)

    2015-12-15

    The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V{sub tot}), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V{sub CE-T1} and V{sub NON-CE-T1}, respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K{sup trans} maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. Responding patients showed a larger reduction in V{sub NON-CE-T1} after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K{sup trans}, after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V{sub tot} was predictive of overall survival (OS), while V{sub CE-T1} showed a tendency of correlation with OS. Tumor subvolumes with increased nIAUGC and K{sup trans} showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation. (orig.)

  12. Rhizospheric bacterial strain Brevibacterium casei MH8a colonizes plant tissues and enhances Cd, Zn, Cu phytoextraction by white mustard

    Directory of Open Access Journals (Sweden)

    Tomasz ePłociniczak

    2016-02-01

    Full Text Available Environmental pollution by heavy metals has become a serious problem in the world. Phytoextraction, which is one of the plant-based technologies, has attracted the most attention for the bioremediation of soils polluted with these contaminants.The aim of this study was to determine whether the multiple-tolerant bacterium, Brevibacterium casei MH8a isolated from the heavy metal-contaminated rhizosphere soil of Sinapis alba L., is able to promote plant growth and enhance Cd, Zn and Cu uptake by white mustard under laboratory conditions. Additionally, the ability of the rifampicin-resistant spontaneous mutant of MH8a to colonize plant tissues and its mechanisms of plant growth promotion were also examined. In order to assess the ecological consequences of bioaugmentation on autochthonous bacteria, the phospholipid fatty acid (PLFA analysis was used. The MH8a strain exhibited the ability to produce ammonia, 1-amino-cyclopropane-1-carboxylic acid deaminase, indole 3-acetic acid and HCN but was not able to solubilize inorganic phosphate and produce siderophores. Introduction of MH8a into soil significantly increased S. alba biomass and the accumulation of Cd (208%, Zn (86% and Cu (39% in plant shoots in comparison with those grown in non-inoculated soil. Introduced into the soil, MH8a was able to enter the plant and was found in the roots and leaves of inoculated plants thus indicating its endophytic features. PLFA analysis revealed that the MH8a that was introduced into soil had a temporary influence on the structure of the autochthonous bacterial communities. The plant growth-promoting features of the MH8a strain and its ability to enhance the metal uptake by white mustard and its long-term survival in soil as well as its temporary impact on autochthonous microorganisms make the strain a suitable candidate for the promotion of plant growth and the efficiency of phytoextraction.

  13. The performance review of EEWS(Earthquake Early Warning System) about Gyeongju earthquakes with Ml 5.1 and Ml 5.8 in Korea

    Science.gov (United States)

    Park, Jung-Ho; Chi, Heon-Cheol; Lim, In-Seub; Seong, Yun-Jeong; Park, Jihwan

    2017-04-01

    EEW(Earthquake Early Warning) service to the public has been officially operated by KMA (Korea Meteorological Administration) from 2015 in Korea. For the KMA's official EEW service, KIGAM has adopted ElarmS from UC Berkeley BSL and modified local magnitude relation, 1-D travel time curves and association procedures with real time waveform from about 201 seismic stations of KMA, KIGAM, KINS and KEPRI. There were two moderate size earthquakes with magnitude Ml 5.1 and Ml 5.8 close to Gyeongju city located at the southeastern part of Korea on Sep. 12. 2016. We have checked the performance of EEWS(Earthquake Early Warning System) named as TrigDB by KIGAM reviewing of these two Gyeongju earthquakes. The nearest station to epicenters of two earthquakes Ml 5.1(35.7697 N, 129.1904 E) and Ml 5.8(35.7632 N, 129.1898 E) was MKL which detected P phases in about 2.1 and 3.6 seconds after the origin times respectively. The first events were issued in 6.3 and 7.0 seconds from each origin time. Because of the unstable results on the early steps due to very few stations and unexpected automated analysis, KMA has the policy to wait for more 20 seconds for confirming the reliability. For these events KMA published EEW alarms in about 26 seconds after origin times with M 5.3 and M 5.9 respectively.

  14. Hox gene clusters in the Indonesian coelacanth, Latimeria menadoensis

    Science.gov (United States)

    Koh, Esther G. L.; Lam, Kevin; Christoffels, Alan; Erdmann, Mark V.; Brenner, Sydney; Venkatesh, Byrappa

    2003-01-01

    The Hox genes encode transcription factors that play a key role in specifying body plans of metazoans. They are organized into clusters that contain up to 13 paralogue group members. The complex morphology of vertebrates has been attributed to the duplication of Hox clusters during vertebrate evolution. In contrast to the single Hox cluster in the amphioxus (Branchiostoma floridae), an invertebrate-chordate, mammals have four clusters containing 39 Hox genes. Ray-finned fishes (Actinopterygii) such as zebrafish and fugu possess more than four Hox clusters. The coelacanth occupies a basal phylogenetic position among lobe-finned fishes (Sarcopterygii), which gave rise to the tetrapod lineage. The lobe fins of sarcopterygians are considered to be the evolutionary precursors of tetrapod limbs. Thus, the characterization of Hox genes in the coelacanth should provide insights into the origin of tetrapod limbs. We have cloned the complete second exon of 33 Hox genes from the Indonesian coelacanth, Latimeria menadoensis, by extensive PCR survey and genome walking. Phylogenetic analysis shows that 32 of these genes have orthologs in the four mammalian HOX clusters, including three genes (HoxA6, D1, and D8) that are absent in ray-finned fishes. The remaining coelacanth gene is an ortholog of hoxc1 found in zebrafish but absent in mammals. Our results suggest that coelacanths have four Hox clusters bearing a gene complement more similar to mammals than to ray-finned fishes, but with an additional gene, HoxC1, which has been lost during the evolution of mammals from lobe-finned fishes. PMID:12547909

  15. Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair

    Science.gov (United States)

    Liu, Fan; Chen, Yan; Zhu, Gu; Hysi, Pirro G; Wu, Sijie; Adhikari, Kaustubh; Breslin, Krystal; Pośpiech, Ewelina; Hamer, Merel A; Peng, Fuduan; Muralidharan, Charanya; Acuna-Alonzo, Victor; Canizales-Quinteros, Samuel; Bedoya, Gabriel; Gallo, Carla; Poletti, Giovanni; Rothhammer, Francisco; Bortolini, Maria Catira; Gonzalez-Jose, Rolando; Zeng, Changqing; Xu, Shuhua; Jin, Li; Uitterlinden, André G; Ikram, M Arfan; van Duijn, Cornelia M; Nijsten, Tamar; Walsh, Susan; Branicki, Wojciech; Wang, Sijia; Ruiz-Linares, Andrés; Spector, Timothy D; Martin, Nicholas G; Medland, Sarah E; Kayser, Manfred

    2018-01-01

    Abstract Shape variation of human head hair shows striking variation within and between human populations, while its genetic basis is far from being understood. We performed a series of genome-wide association studies (GWASs) and replication studies in a total of 28 964 subjects from 9 cohorts from multiple geographic origins. A meta-analysis of three European GWASs identified 8 novel loci (1p36.23 ERRFI1/SLC45A1, 1p36.22 PEX14, 1p36.13 PADI3, 2p13.3 TGFA, 11p14.1 LGR4, 12q13.13 HOXC13, 17q21.2 KRTAP, and 20q13.33 PTK6), and confirmed 4 previously known ones (1q21.3 TCHH/TCHHL1/LCE3E, 2q35 WNT10A, 4q21.21 FRAS1, and 10p14 LINC00708/GATA3), all showing genome-wide significant association with hair shape (P < 5e-8). All except one (1p36.22 PEX14) were replicated with nominal significance in at least one of the 6 additional cohorts of European, Native American and East Asian origins. Three additional previously known genes (EDAR, OFCC1, and PRSS53) were confirmed at the nominal significance level. A multivariable regression model revealed that 14 SNPs from different genes significantly and independently contribute to hair shape variation, reaching a cross-validated AUC value of 0.66 (95% CI: 0.62–0.70) and an AUC value of 0.64 in an independent validation cohort, providing an improved accuracy compared with a previous model. Prediction outcomes of 2504 individuals from a multiethnic sample were largely consistent with general knowledge on the global distribution of hair shape variation. Our study thus delivers target genes and DNA variants for future functional studies to further evaluate the molecular basis of hair shape in humans. PMID:29220522

  16. Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair.

    Science.gov (United States)

    Liu, Fan; Chen, Yan; Zhu, Gu; Hysi, Pirro G; Wu, Sijie; Adhikari, Kaustubh; Breslin, Krystal; Pospiech, Ewelina; Hamer, Merel A; Peng, Fuduan; Muralidharan, Charanya; Acuna-Alonzo, Victor; Canizales-Quinteros, Samuel; Bedoya, Gabriel; Gallo, Carla; Poletti, Giovanni; Rothhammer, Francisco; Bortolini, Maria Catira; Gonzalez-Jose, Rolando; Zeng, Changqing; Xu, Shuhua; Jin, Li; Uitterlinden, André G; Ikram, M Arfan; van Duijn, Cornelia M; Nijsten, Tamar; Walsh, Susan; Branicki, Wojciech; Wang, Sijia; Ruiz-Linares, Andrés; Spector, Timothy D; Martin, Nicholas G; Medland, Sarah E; Kayser, Manfred

    2018-02-01

    Shape variation of human head hair shows striking variation within and between human populations, while its genetic basis is far from being understood. We performed a series of genome-wide association studies (GWASs) and replication studies in a total of 28 964 subjects from 9 cohorts from multiple geographic origins. A meta-analysis of three European GWASs identified 8 novel loci (1p36.23 ERRFI1/SLC45A1, 1p36.22 PEX14, 1p36.13 PADI3, 2p13.3 TGFA, 11p14.1 LGR4, 12q13.13 HOXC13, 17q21.2 KRTAP, and 20q13.33 PTK6), and confirmed 4 previously known ones (1q21.3 TCHH/TCHHL1/LCE3E, 2q35 WNT10A, 4q21.21 FRAS1, and 10p14 LINC00708/GATA3), all showing genome-wide significant association with hair shape (P 5e-8). All except one (1p36.22 PEX14) were replicated with nominal significance in at least one of the 6 additional cohorts of European, Native American and East Asian origins. Three additional previously known genes (EDAR, OFCC1, and PRSS53) were confirmed at the nominal significance level. A multivariable regression model revealed that 14 SNPs from different genes significantly and independently contribute to hair shape variation, reaching a cross-validated AUC value of 0.66 (95% CI: 0.62-0.70) and an AUC value of 0.64 in an independent validation cohort, providing an improved accuracy compared with a previous model. Prediction outcomes of 2504 individuals from a multiethnic sample were largely consistent with general knowledge on the global distribution of hair shape variation. Our study thus delivers target genes and DNA variants for future functional studies to further evaluate the molecular basis of hair shape in humans. © The Author(s) 2017. Published by Oxford University Press.

  17. Enhancement pattern of small hepatic hemangioma: findings on multiphase spiral CT and dynamic MRI

    International Nuclear Information System (INIS)

    Choi, Byung In; Lee, Seung Koo; Kim, Myeong Jin; Chung, Jae Joon; Yoo, Hyung Sik; Lee, Jong Tae

    1999-01-01

    To compare the enhancement characteristics of small hemangiomas seen on multiphase spiral CT and dynamic MR imaging. Thirteen patients with 20 hepatic hemangiomas less than 25mm in diameter underwent both multiphase spiral CT and dynamic MR imaging. All lesions were assigned to one of three classified into 3 categories according to the enhancement pattern seen on multiphase spiral CT : typical delayed pooling, atypical early enhancement, or continuous low attenuation. The enhancement patterns seen on spiral CT and on dynamic MRI were correlated. On CT scans, ten lesions (50%) showed delayed pooling. Six (30%) showed early arterial enhancement and four (20%) showed continuous low attenuation. On delayed-phase MRI, all lesions showed delayed high signal intensity compared to adjacent liver parenchyma. Four of six lesions with early enhancement on CT showed peripheral globular enhancement on early arterial-phase MRI. On multiphase spiral CT scans, small hemangiomas can show variable atypical enhancement features. In this situation, contrast-enhanced dynamic MRI is helpful for the diagnosis of hemangiomas

  18. Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ.

    Science.gov (United States)

    Trsan, Tihana; Busche, Andreas; Abram, Maja; Wensveen, Felix M; Lemmermann, Niels A; Arapovic, Maja; Babic, Marina; Tomic, Adriana; Golemac, Mijo; Brinkmann, Melanie M; Jäger, Wiebke; Oxenius, Annette; Polic, Bojan; Krmpotic, Astrid; Messerle, Martin; Jonjic, Stipan

    2013-10-08

    Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes. Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell-based vaccines.

  19. NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Blandine C Mercier

    Full Text Available Pattern recognition receptors (PRR, like Toll-like receptors (TLR and NOD-like receptors (NLR, are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic ligand for NOD1, has a direct impact on both murine and human CD8 T cells, increasing proliferation and effector functions of cells activated via their T cell receptor (TCR. This effect is dependent on the adaptor molecule RIP2 and is associated with an increased activation of the NF-κB, JNK and p38 signaling pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our results indicate that NOD1 might function as an alternative costimulatory receptor in CD8 T cells. Our study provides new insights into the function of NLR in T cells and extends to NOD1 the recent concept that PRR stimulation can directly control T cell functions.

  20. Nanoscale control of Ag nanostructures for plasmonic fluorescence enhancement of near-infrared dyes

    KAUST Repository

    Xie, Fang

    2013-05-23

    Potential utilization of proteins for early detection and diagnosis of various diseases has drawn considerable interest in the development of protein-based detection techniques. Metal induced fluorescence enhancement offers the possibility of increasing the sensitivity of protein detection in clinical applications. We report the use of tunable plasmonic silver nanostructures for the fluorescence enhancement of a near-infrared (NIR) dye (Alexa Fluor 790). Extensive fluorescence enhancement of ∼2 orders of magnitude is obtained by the nanoscale control of the Ag nanostructure dimensions and interparticle distance. These Ag nanostructures also enhanced fluorescence from a dye with very high quantum yield (7.8 fold for Alexa Fluor 488, quantum efficiency (Qy) = 0.92). A combination of greatly enhanced excitation and an increased radiative decay rate, leading to an associated enhancement of the quantum efficiency leads to the large enhancement. These results show the potential of Ag nanostructures as metal induced fluorescence enhancement (MIFE) substrates for dyes in the NIR "biological window" as well as the visible region. Ag nanostructured arrays fabricated by colloidal lithography thus show great potential for NIR dye-based biosensing applications. [Figure not available: see fulltext.] © 2013 Tsinghua University Press and Springer-Verlag Berlin Heidelberg.

  1. Longitudinal functional brain imaging study in early course schizophrenia before and after cognitive enhancement therapy.

    Science.gov (United States)

    Keshavan, Matcheri S; Eack, Shaun M; Prasad, Konasale M; Haller, Chiara S; Cho, Raymond Y

    2017-05-01

    Schizophrenia is characterized by impaired -social and non social cognition both of which lead to functional deficits. These deficits may benefit from cognitive remediation, but the neural underpinnings of such improvements have not been clearly delineated. We conducted a functional magnetic resonance (fMRI) study in early course schizophrenia patients randomly assigned to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) and treated for two years. Imaging data over three time points including fMRI blood oxygen level dependent (BOLD) data were acquired during performance of a cognitive control paradigm, the Preparing to Overcome Prepotency (POP) task, and functional connectivity data, were analyzed. During the two years of treatment, CET patients showed a continual increase in BOLD activity in the right dorsolateral prefrontal cortex (DLPFC), whereas EST patients tended to show no change in prefrontal brain function throughout treatment. Increases in right DLPFC activity were modestly associated with improved neurocognition (β = .14, p = .041), but not social cognition. Functional connectivity analyses showed reduced connectivity between the DLPFC and the anterior cingulate cortex (ACC) in CET compared to EST over the two years of treatment, which was associated with neurocognitive improvement. These findings suggest that CET leads to enhanced neural activity in brain regions mediating cognitive control and increased efficiency in prefrontal circuits; such changes may be related to the observed therapeutic effects of CET on neurocognitive function. Copyright © 2017. Published by Elsevier Inc.

  2. Image processing of early gastric cancer cases

    International Nuclear Information System (INIS)

    Inamoto, Kazuo; Umeda, Tokuo; Inamura, Kiyonari

    1992-01-01

    Computer image processing was used to enhance gastric lesions in order to improve the detection of stomach cancer. Digitization was performed in 25 cases of early gastric cancer that had been confirmed surgically and pathologically. The image processing consisted of grey scale transformation, edge enhancement (Sobel operator), and high-pass filtering (unsharp masking). Grey scale transformation improved image quality for the detection of gastric lesions. The Sobel operator enhanced linear and curved margins, and consequently, suppressed the rest. High-pass filtering with unsharp masking was superior to visualization of the texture pattern on the mucosa. Eight of 10 small lesions (less than 2.0 cm) were successfully demonstrated. However, the detection of two lesions in the antrum, was difficult even with the aid of image enhancement. In the other 15 lesions (more than 2.0 cm), the tumor surface pattern and margin between the tumor and non-pathological mucosa were clearly visualized. Image processing was considered to contribute to the detection of small early gastric cancer lesions by enhancing the pathological lesions. (author)

  3. Luminescent Enhancement of Na+ and Sm3+ Co-doping Reddish Orange SrCa3Si2O8 Phosphors

    Science.gov (United States)

    Chun, Fengjun; Zhang, Binbin; Li, Wen; Liu, Honggang; Deng, Wen; Chu, Xiang; Osman, Hanan; Zhang, Haitao; Yang, Weiqing

    2018-04-01

    Reddish orange SrCa3Si2O8 phosphors, prepared by the facile solid state reaction method, are a luminescent enhancement of Na+ and Sm3+ co-doping luminescent material. Na+ was designed to compensate the charge imbalance of Sm3+ ion substituting for the Sr2+ ion of orthorhombic SrCa3Si2O8 crystals. The results suggest that Na+ can effectively enhance the luminescent intensity of the reddish orange light peaked at about 562 nm (4 G 5/2 → 6 H 5/2), 600 nm (4 G 5/2 → 6 H 7/2) and 645 nm (4 G 5/2 → 6 H 9/2) excited by the near ultraviolet excited light 404 nm (4 L 13/2 → 6 H 5/2). The energy transfer has been further verified by the florescence lifetime. Additionally, the luminescent lifetime τ of as-grown phosphors was separated into two parts, a rapid lifetime and a slow lifetime. The average lifetime results ranged from 2.098 to 1.329 ms which were influenced by the concentration of Sm3+ doping. The systematic researches of as-grown phosphors have clearly suggested a potential application for white-light-emitting diodes ( w-LEDs).

  4. Early serum interleukin-8 evaluation may prove useful in localizing abnormally implanted human gestations after in vitro fertilization.

    Science.gov (United States)

    Morelli, Sara S; Keegan, Debbra A; Krey, Lewis C; Katz, Joseph; Liu, Mengling; Noyes, Nicole

    2008-12-01

    To determine whether early measurement of the serum cytokines interleukin-2 receptor (IL-2R), IL-6, and IL-8 along with human chorionic gonadotropin (hCG) and progesterone (P(4)) can differentiate an ectopic from an intrauterine gestation. Retrospective analysis. University-based fertility center. 75 women who underwent treatment with in vitro fertilization (IVF) and subsequently had an ectopic gestation (n = 15), spontaneous abortion (SAB) (n = 30), or term delivery (TD) (n = 30). Serum samples were obtained 14 (day 28) and 21 (day 35) days after oocyte retrieval. Serum concentrations of IL-2R, IL-6, IL-8, P(4), and hCG. Median hCG readings on day 28 and day 35 were statistically significantly lower in the ectopic gestation group than in those with spontaneous abortion or term delivery. On day 28, median IL-8 levels were lower in the ectopic gestation group when compared with all intrauterine gestations combined. No statistically significant differences in IL-2R or IL-6 levels were noted between groups. Despite P(4) supplementation, median day-35 P(4) levels were lower in ectopic gestation than in the spontaneous abortion and term delivery cycles. In the setting of a rise or plateau in hCG levels, low day-28 IL-8 and day-35 P(4) levels suggested an extrauterine implantation. This assay combination may facilitate earlier diagnosis of an ectopic gestation when pregnancy location is unclear.

  5. Myocardial enhancement pattern in patients with acute myocardial infarction on two-phase contrast-enhanced Ecg-gated multidetector-row computed tomography

    International Nuclear Information System (INIS)

    Ko, S.M.; Seo, J.B.; Hong, M.K.; Do, K.H.; Lee, S.H.; Lee, J.S.; Song, J.W.; Park, S.J.; Park, S.W.; Lim, T.H.

    2006-01-01

    Aim: To evaluate the myocardial enhancement pattern of the left ventricle on two-phase contrast-enhanced electrocardiogram (ECG)-gated multidetector computed tomography (MDCT) images in patients with acute myocardial infarction (AMI). METHODS: Two-phase contrast-enhanced ECG-gated MDCT examinations were performed in 16 patients with AMI. The presence, location and pattern of myocardial enhancement were evaluated. MDCT findings were compared with the catheter angiographic results. RESULTS: Subendocardial (n=9) or transmural (n=6) area of early perfusion defects of the myocardium was detected in 15 of 16 patients (94%) on early-phase CT images. Variable delayed myocardial enhancement patterns on late-phase CT images were observed in 12 patients (75%): (1) subendocardial residual perfusion defect and subepicardial late enhancement (n=6); (2) transmural late enhancement (n=1); (3) isolated subendocardial late enhancement (n=1); and (4) isolated subendocardial residual perfusion defect (n=2). On catheter angiography, 14 of 15 corresponding coronary arteries showed significant stenosis. CONCLUSION: Variable abnormal myocardial enhancement pattern was seen on two-phase, contrast-enhanced ECG-gated MDCT in patients with AMI. Assessment of myocardial attenuation on CT angiography gives additional information of the location and extent of infarction

  6. Enhanced Glycogen Storage of a Subcellular Hot Spot in Human Skeletal Muscle during Early Recovery from Eccentric Contractions

    Science.gov (United States)

    Nielsen, Joachim; Farup, Jean; Rahbek, Stine Klejs; de Paoli, Frank Vincenzo; Vissing, Kristian

    2015-01-01

    Unaccustomed eccentric exercise is accompanied by muscle damage and impaired glucose uptake and glycogen synthesis during subsequent recovery. Recently, it was shown that the role and regulation of glycogen in skeletal muscle are dependent on its subcellular localization, and that glycogen synthesis, as described by the product of glycogen particle size and number, is dependent on the time course of recovery after exercise and carbohydrate availability. In the present study, we investigated the subcellular distribution of glycogen in fibers with high (type I) and low (type II) mitochondrial content during post-exercise recovery from eccentric contractions. Analysis was completed on five male subjects performing an exercise bout consisting of 15 x 10 maximal eccentric contractions. Carbohydrate-rich drinks were subsequently ingested throughout a 48 h recovery period and muscle biopsies for analysis included time points 3, 24 and 48 h post exercise from the exercising leg, whereas biopsies corresponding to prior to and at 48 h after the exercise bout were collected from the non-exercising, control leg. Quantitative imaging by transmission electron microscopy revealed an early (post 3 and 24 h) enhanced storage of intramyofibrillar glycogen (defined as glycogen particles located within the myofibrils) of type I fibers, which was associated with an increase in the number of particles. In contrast, late in recovery (post 48 h), intermyofibrillar, intramyofibrillar and subsarcolemmal glycogen in both type I and II fibers were lower in the exercise leg compared with the control leg, and this was associated with a smaller size of the glycogen particles. We conclude that in the carbohydrate-supplemented state, the effect of eccentric contractions on glycogen metabolism depends on the subcellular localization, muscle fiber’s oxidative capacity, and the time course of recovery. The early enhanced storage of intramyofibrillar glycogen after the eccentric contractions may

  7. The ABA receptor PYL8 promotes lateral root growth by enhancing MYB77-dependent transcription of auxin-responsive genes.

    Science.gov (United States)

    Zhao, Yang; Xing, Lu; Wang, Xingang; Hou, Yueh-Ju; Gao, Jinghui; Wang, Pengcheng; Duan, Cheng-Guo; Zhu, Xiaohong; Zhu, Jian-Kang

    2014-06-03

    The phytohormone abscisic acid (ABA) regulates plant growth, development, and abiotic stress responses. ABA signaling is mediated by a group of receptors known as the PYR1/PYL/RCAR family, which includes the pyrabactin resistance 1-like protein PYL8. Under stress conditions, ABA signaling activates SnRK2 protein kinases to inhibit lateral root growth after emergence from the primary root. However, even in the case of persistent stress, lateral root growth eventually recovers from inhibition. We showed that PYL8 is required for the recovery of lateral root growth, following inhibition by ABA. PYL8 directly interacted with the transcription factors MYB77, MYB44, and MYB73. The interaction of PYL8 and MYB77 increased the binding of MYB77 to its target MBSI motif in the promoters of multiple auxin-responsive genes. Compared to wild-type seedlings, the lateral root growth of pyl8 mutant seedlings and myb77 mutant seedlings was more sensitive to inhibition by ABA. The recovery of lateral root growth was delayed in pyl8 mutant seedlings in the presence of ABA, and the defect was rescued by exposing pyl8 mutant seedlings to the auxin IAA (3-indoleacetic acid). Thus, PYL8 promotes lateral root growth independently of the core ABA-SnRK2 signaling pathway by enhancing the activities of MYB77 and its paralogs, MYB44 and MYB73, to augment auxin signaling. Copyright © 2014, American Association for the Advancement of Science.

  8. Contrast between hypervascularized liver lesions and hepatic parenchyma. Early dynamic PET versus contrast-enhanced CT

    International Nuclear Information System (INIS)

    Freesmeyer, M.; Winkens, T.; Schierz, J.-H.

    2014-01-01

    To detect hypervascularized liver lesions, early dynamic (ED) 18 F-FDG PET may be an alternative when contrast-enhanced (CE) imaging is infeasible. This retrospective pilot analysis compared contrast between such lesions and liver parenchyma, an important objective image quality variable, in ED PET versus CE CT. Twenty-eight hypervascularized liver lesions detected by CE CT [21 (75%) hepatocellular carcinomas; mean (range) diameter 4.9 ± 3.5 (1-14) cm] in 20 patients were scanned with ED PET. Using regions of interest, maximum and mean lesional and parenchymal signals at baseline, arterial and venous phases were calculated for ED PET and CE CT. Lesional/parenchymal signal ratio was significantly higher (P < 0.005) with ED PET versus CE CT at the arterial phase and similar between the methods at the venous phase. In liver imaging, ED PET generates greater lesional-parenchymal contrast during the arterial phase than does CE CT; these observations should be formally, prospectively evaluated. (author)

  9. Contrast-enhanced MRI features in the early diagnosis of Juvenile Idiopathic Arthritis

    International Nuclear Information System (INIS)

    Hemke, Robert; Maas, Mario; Kuijpers, Taco W.; Schonenberg-Meinema, Dieneke; Nusman, Charlotte M.; Rossum, Marion A.J. van; Berg, J.M. van den; Dolman, Koert M.

    2015-01-01

    To determine whether clinical, laboratory or Magnetic Resonance Imaging (MRI) measures differentiate Juvenile Idiopathic Arthritis (JIA) from other forms of active childhood arthritis. We prospectively collected data of 80 treatment-naive patients clinically suspected of JIA with active non-infectious arthritis of (at least) one knee for <12 months duration. Upon presentation patients underwent clinical and laboratory assessments and contrast-enhanced MRI. MRI was not used as a diagnostic criterion. Forty-four (55 %) patients were clinically diagnosed with JIA, whereas in 36 (45 %) patients the diagnosis of JIA was discarded on clinical or laboratory findings. MRI-based synovitis was present in 27 (61.4 %) JIA patients and in 7 (19.4 %) non-JIA patients (P < 0.001). Five factors (male gender, physician's global assessment of overall disease activity, joints with limited range of motion, HLA-B27, MRI-based synovitis) were associated with the onset of JIA. In multivariate analysis MRI-based synovitis proved to be independently associated with JIA (OR 6.58, 95 % CI 2.36-18.33). In patients with MRI-based synovitis, the RR of having JIA was 3.16 (95 % CI 1.6-6.4). The presence of MRI-based synovitis is associated with the clinical onset of JIA. Physical examination could be supported by MRI, particularly to contribute in the early differentiation of different forms of non-infectious childhood arthritis. (orig.)

  10. Contrast-enhanced MRI features in the early diagnosis of Juvenile Idiopathic Arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Hemke, Robert; Maas, Mario [University of Amsterdam, Department of Radiology Academic Medical Center, Amsterdam (Netherlands); Kuijpers, Taco W.; Schonenberg-Meinema, Dieneke [University of Amsterdam, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children' s Hospital AMC, Amsterdam (Netherlands); Nusman, Charlotte M. [University of Amsterdam, Department of Radiology Academic Medical Center, Amsterdam (Netherlands); University of Amsterdam, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children' s Hospital AMC, Amsterdam (Netherlands); Rossum, Marion A.J. van; Berg, J.M. van den [University of Amsterdam, Department of Pediatric Hematology, Immunology, Rheumatology and Infectious Disease, Emma Children' s Hospital AMC, Amsterdam (Netherlands); Department of Pediatric Rheumatology, Reade, Amsterdam (Netherlands); Dolman, Koert M. [Department of Pediatric Rheumatology, Reade, Amsterdam (Netherlands); St. Lucas Andreas Hospital, Department of Pediatrics, Amsterdam (Netherlands)

    2015-11-15

    To determine whether clinical, laboratory or Magnetic Resonance Imaging (MRI) measures differentiate Juvenile Idiopathic Arthritis (JIA) from other forms of active childhood arthritis. We prospectively collected data of 80 treatment-naive patients clinically suspected of JIA with active non-infectious arthritis of (at least) one knee for <12 months duration. Upon presentation patients underwent clinical and laboratory assessments and contrast-enhanced MRI. MRI was not used as a diagnostic criterion. Forty-four (55 %) patients were clinically diagnosed with JIA, whereas in 36 (45 %) patients the diagnosis of JIA was discarded on clinical or laboratory findings. MRI-based synovitis was present in 27 (61.4 %) JIA patients and in 7 (19.4 %) non-JIA patients (P < 0.001). Five factors (male gender, physician's global assessment of overall disease activity, joints with limited range of motion, HLA-B27, MRI-based synovitis) were associated with the onset of JIA. In multivariate analysis MRI-based synovitis proved to be independently associated with JIA (OR 6.58, 95 % CI 2.36-18.33). In patients with MRI-based synovitis, the RR of having JIA was 3.16 (95 % CI 1.6-6.4). The presence of MRI-based synovitis is associated with the clinical onset of JIA. Physical examination could be supported by MRI, particularly to contribute in the early differentiation of different forms of non-infectious childhood arthritis. (orig.)

  11. Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice

    Directory of Open Access Journals (Sweden)

    LaFerla Frank M

    2005-10-01

    Full Text Available Abstract Background Alzheimer's disease is a complex neurodegenerative disorder characterized pathologically by a temporal and spatial progression of beta-amyloid (Aβ deposition, neurofibrillary tangle formation, and synaptic degeneration. Inflammatory processes have been implicated in initiating and/or propagating AD-associated pathology within the brain, as inflammatory cytokine expression and other markers of inflammation are pronounced in individuals with AD pathology. The current study examines whether inflammatory processes are evident early in the disease process in the 3xTg-AD mouse model and if regional differences in inflammatory profiles exist. Methods Coronal brain sections were used to identify Aβ in 2, 3, and 6-month 3xTg-AD and non-transgenic control mice. Quantitative real-time RT-PCR was performed on microdissected entorhinal cortex and hippocampus tissue of 2, 3, and 6-month 3xTg-AD and non-transgenic mice. Microglial/macrophage cell numbers were quantified using unbiased stereology in 3xTg-AD and non-transgenic entorhinal cortex and hippocampus containing sections. Results We observed human Aβ deposition at 3 months in 3xTg-AD mice which is enhanced by 6 months of age. Interestingly, we observed a 14.8-fold up-regulation of TNF-α and 10.8-fold up-regulation of MCP-1 in the entorhinal cortex of 3xTg-AD mice but no change was detected over time in the hippocampus or in either region of non-transgenic mice. Additionally, this increase correlated with a specific increase in F4/80-positive microglia and macrophages in 3xTg-AD entorhinal cortex. Conclusion Our data provide evidence for early induction of inflammatory processes in a model that develops amyloid and neurofibrillary tangle pathology. Additionally, our results link inflammatory processes within the entorhinal cortex, which represents one of the earliest AD-affected brain regions.

  12. A mammalian conserved element derived from SINE displays enhancer properties recapitulating Satb2 expression in early-born callosal projection neurons.

    Directory of Open Access Journals (Sweden)

    Kensuke Tashiro

    Full Text Available Short interspersed repetitive elements (SINEs are highly repeated sequences that account for a significant proportion of many eukaryotic genomes and are usually considered "junk DNA". However, we previously discovered that many AmnSINE1 loci are evolutionarily conserved across mammalian genomes, suggesting that they may have acquired significant functions involved in controlling mammalian-specific traits. Notably, we identified the AS021 SINE locus, located 390 kbp upstream of Satb2. Using transgenic mice, we showed that this SINE displays specific enhancer activity in the developing cerebral cortex. The transcription factor Satb2 is expressed by cortical neurons extending axons through the corpus callosum and is a determinant of callosal versus subcortical projection. Mouse mutants reveal a crucial function for Sabt2 in corpus callosum formation. In this study, we compared the enhancer activity of the AS021 locus with Satb2 expression during telencephalic development in the mouse. First, we showed that the AS021 enhancer is specifically activated in early-born Satb2(+ neurons. Second, we demonstrated that the activity of the AS021 enhancer recapitulates the expression of Satb2 at later embryonic and postnatal stages in deep-layer but not superficial-layer neurons, suggesting the possibility that the expression of Satb2 in these two subpopulations of cortical neurons is under genetically distinct transcriptional control. Third, we showed that the AS021 enhancer is activated in neurons projecting through the corpus callosum, as described for Satb2(+ neurons. Notably, AS021 drives specific expression in axons crossing through the ventral (TAG1(-/NPY(+ portion of the corpus callosum, confirming that it is active in a subpopulation of callosal neurons. These data suggest that exaptation of the AS021 SINE locus might be involved in enhancement of Satb2 expression, leading to the establishment of interhemispheric communication via the corpus callosum

  13. Enhanced startle reflexivity during presentation of visual nurture cues in young adults who experienced parental divorce in early childhood.

    Science.gov (United States)

    Hengesch, Xenia; Larra, Mauro F; Finke, Johannes B; Blumenthal, Terry D; Schächinger, Hartmut

    2017-10-01

    Adverse childhood experiences (ACE) may influence stress and affective processing in adulthood. Animal and human studies show enhanced startle reflexivity in adult participants with ACE. This study examined the impact of one of the most common ACE, parental divorce, on startle reflexivity in adulthood. Affective modulation of acoustically-elicited startle eye blink was assessed in a group of 23 young adults with self-reported history of parental divorce, compared to an age- and sex-matched control group (n=18). Foreground pictures were either aversive (e.g. mutilation and injury), standard appetitive (e.g. erotic, recreational sport), or nurture pictures (e.g. related to early life, parental care), intermixed with neutral pictures (e.g. household objects), and organized in three valence blocks delivered in a balanced, pseudo-randomized sequence. During picture viewing startle eye blinks were elicited by binaural white noise bursts (50ms, 105 dB) via headphones and recorded at the left orbicularis oculi muscle via EMG. A significant interaction of group×picture valence (p=0.01) was observed. Contrast with controls revealed blunted startle responsiveness of the ACE group during presentation of aversive pictures, but enhanced startle during presentation of nurture-related pictures. No group differences were found during presentation of standard appetitive pictures. ACE participants rated nurture pictures as more arousing (p=0.02) than did control participants. Results suggest that divorce in childhood led to altered affective context information processing in early adulthood. When exposed to unpleasant (vs. neutral) pictures participants with ACE showed less startle potentiation than controls. Nurture context, however, potentiated startle in ACE participants, suggesting visual cuing to activate protective behavioral responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. miR-150-Mediated Foxo1 Regulation Programs CD8+ T Cell Differentiation.

    Science.gov (United States)

    Ban, Young Ho; Oh, Se-Chan; Seo, Sang-Hwan; Kim, Seok-Min; Choi, In-Pyo; Greenberg, Philip D; Chang, Jun; Kim, Tae-Don; Ha, Sang-Jun

    2017-09-12

    MicroRNA (miR)-150 is a developmental regulator of several immune-cell types, but its role in CD8 + T cells is largely unexplored. Here, we show that miR-150 regulates the generation of memory CD8 + T cells. After acute virus infection, miR-150 knockout (KO) mice exhibited an accelerated differentiation of CD8 + T cells into memory cells and improved production of effector cytokines. Additionally, miR-150 KO CD8 + T cells displayed an enhanced recall response and improved protection against infections with another virus and bacteria. We found that forkhead box O1 (Foxo1) and T cell-specific transcription factor 1 (TCF1) are upregulated during the early activation phase in miR-150 KO CD8 + T cells and that miR-150 directly targets and suppresses Foxo1. These results suggest that miR-150-mediated suppression of Foxo1 regulates the balance between effector and memory cell differentiation, which might aid in the development of improved vaccines and T cell therapeutics. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Suppressive and Enhancing Effects in Early Visual Cortex during Illusory Shape Perception: A Comment on Kok and de Lange (2014

    Directory of Open Access Journals (Sweden)

    Pieter Moors

    2015-02-01

    Full Text Available In a recent functional magnetic resonance imaging study, Kok and de Lange (2014 observed that BOLD activity for a Kanizsa illusory shape stimulus, in which pacmen-like inducers elicit an illusory shape percept, was either enhanced or suppressed relative to a nonillusory control configuration depending on whether the spatial profile of BOLD activity in early visual cortex was related to the illusory shape or the inducers, respectively. The authors argued that these findings fit well with the predictive coding framework, because top-down predictions related to the illusory shape are not met with bottom-up sensory input and hence the feedforward error signal is enhanced. Conversely, for the inducing elements, there is a match between top-down predictions and input, leading to a decrease in error. Rather than invoking predictive coding as the explanatory framework, the suppressive effect related to the inducers might be caused by neural adaptation to perceptually stable input due to the trial sequence used in the experiment.

  16. Transmission of clonal hepatitis C virus genomes reveals the dominant but transitory role of CD8¿ T cells in early viral evolution

    DEFF Research Database (Denmark)

    Callendret, Benoît; Bukh, Jens; Eccleston, Heather B

    2011-01-01

    occurred slowly over several years of chronic infection. Together these observations indicate that during acute hepatitis C, virus evolution was driven primarily by positive selection pressure exerted by CD8(+) T cells. This influence of immune pressure on viral evolution appears to subside as chronic......The RNA genome of the hepatitis C virus (HCV) diversifies rapidly during the acute phase of infection, but the selective forces that drive this process remain poorly defined. Here we examined whether Darwinian selection pressure imposed by CD8(+) T cells is a dominant force driving early amino acid...... replacement in HCV viral populations. This question was addressed in two chimpanzees followed for 8 to 10 years after infection with a well-defined inoculum composed of a clonal genotype 1a (isolate H77C) HCV genome. Detailed characterization of CD8(+) T cell responses combined with sequencing of recovered...

  17. Endoscopic tattooing of early colon carcinoma enhances detection of lymph nodes most prone to harbor tumor burden.

    Science.gov (United States)

    Aldecoa, Iban; Montironi, Carla; Planell, Nuria; Pellise, Maria; Fernandez-Esparrach, Gloria; Gines, Angels; Delgado, Salvadora; Momblan, Dulce; Moreira, Leticia; Lopez-Ceron, Maria; Rakislova, Natalia; Martinez-Palli, Graciela; Balust, Jaume; Bombi, Josep Antoni; de Lacy, Antonio; Castells, Antoni; Balaguer, Francesc; Cuatrecasas, Miriam

    2017-02-01

    Colorectal cancer (CRC) screening programs result in the detection of early-stage asymptomatic carcinomas suitable to be surgically cured. Lymph nodes (LN) from early CRC are usually small and may be difficult to collect. Still, at least 12 LNs should be analyzed from colectomies, to ensure a reliable pN0 stage. Presurgical endoscopic tattooing improves LN procurement. In addition, molecular detection of occult LN tumor burden in histologically pN0 CRC patients is associated with a decreased survival rate. We aimed to study the impact of presurgical endoscopic tattooing on the molecular detection of LN tumor burden in early colon neoplasms. A prospective cohort study from a CRC screening-based population was performed at a tertiary academic hospital. LNs from colectomies with and without preoperative endoscopic tattooing were assessed by two methods, hematoxylin and eosin (HE), and RT-LAMP, to detect tumor cytokeratin 19 (CK19) mRNA. We compared the amount of tumor burden and LN yields from tattooed and non-tattooed specimens. HE and RT-LAMP analyses of 936 LNs were performed from 71 colectomies containing early carcinomas and endoscopically unresectable adenomas (8 pT0, 17 pTis, 27 pT1, 19 pT2); 47 out of 71 (66.2 %) were tattooed. Molecular positivity correlated with the presence of tattoo in LN [p < 0.001; OR 3.1 (95 % CI 1.7-5.5)]. A significantly higher number of LNs were obtained in tattooed specimens (median 17 LN vs. 14.5 LN; p = 0.019). Endoscopic tattooing enables the analysis of those LNs most prone to harbor tumor cells and improves the number of LN harvested.

  18. STAT3 Regulates Proliferation and Survival of CD8+ T Cells: Enhances Effector Responses to HSV-1 Infection, and Inhibits IL-10+ Regulatory CD8+ T Cells in Autoimmune Uveitis

    Directory of Open Access Journals (Sweden)

    Cheng-Rong Yu

    2013-01-01

    Full Text Available STAT3 regulates CD4+ T cell survival and differentiation. However, its effects on CD8+ T cells are not well understood. Here, we show that in comparison to WT CD8+ T cells, STAT3-deficient CD8+ T cells exhibit a preactivated memory-like phenotype, produce more IL-2, proliferate faster, and are more sensitive to activation-induced cell death (AICD. The enhanced proliferation and sensitivity to AICD correlated with downregulation of class-O forkhead transcription factors (FoxO1, FoxO3A, , , Bcl-2, OX-40, and upregulation of FasL, Bax, and Bad. We examined whether STAT3-deficient CD8+ T cells can mount effective response during herpes simplex virus (HSV-1 infection and experimental autoimmune uveitis (EAU. Compared to WT mice, HSV-1-infected STAT3-deficient mice (STAT3KO produced less IFN- and virus-specific KLRG-1+ CD8+ T cells. STAT3KO mice are also resistant to EAU and produced less IL-17-producing Tc17 cells. Resistance of STAT3KO to EAU correlated with marked expansion of IL-10-producing regulatory CD8+ T cells (CD8-Treg implicated in recovery from autoimmune encephalomyelitis. Thus, increases of IL-6-induced STAT3 activation observed during inflammation may inhibit expansion of CD8-Tregs, thereby impeding recovery from uveitis. These results suggest that STAT3 is a potential therapeutic target for upregulating CD8+ T cell-mediated responses to viruses and suggest the successful therapeutic targeting of STAT3 as treatment for uveitis, derived, in part, from promoting CD8-Treg expansion.

  19. The mutation frequency of 8-oxo-7,8 dihydroguanine (8-oxoG) situated in a multiply damaged site: comparison of a single and two closely opposed 8-oxodG in Escherichia coli

    International Nuclear Information System (INIS)

    Malyarchuk, S.G.; Youngblood, R.C.; Landry, A.M.; Quillin, E.; Harrison, L.

    2003-01-01

    Full text: A multiply damaged site (MDS) is defined as >= two lesions within a distance of 10-15 base pairs (bp). MDS generated by ionizing radiation contains oxidative base damage, and in vitro studies have indicated that if the base damage is less than 3 bp apart, repair of one lesion is inhibited until repair of the lesion in the opposite strand is completed. Inhibition of repair could result in an increase in the mutation frequency of the base damage. We have designed an assay to determine whether a closely opposed lesion causes an increase in adenine insertion opposite an 8-oxodG in bacteria. The double-stranded oligonucleotides (with no damage, each single 8-oxodG or the MDS) were ligated into the firefly luciferase coding region of a reporter vector and transformed into wild type or MutY-deficient bacteria. The MDS contained an 8-oxodG in the transcribed strand (T) and a second 8-oxodG immediately 5' to this lesion in the non-transcribed strand (NT). During two rounds of replication, insertion of adenine opposite the 8-oxodG in the T or NT strand results in a translation termination codon at position 444 or 445, respectively. In wild-type bacteria, we detected a translation stop at a frequency of 0.15% (codon 444) and 0.09% (codon 445) with a single 8-oxodG in the T or NT strand, respectively. This was enhanced ∼3 fold when single lesions were replicated in MutY-deficient bacteria. Positioning an 8-oxodG in the T strand within the MDS enhanced the mutation frequency by ∼2 fold in wild-type bacteria and 8 fold in Mut Y-deficient bacteria, while the mutation frequency of the 8-oxodG in the NT strand increased by 6 fold in Mut Y-deficient bacteria. This enhancement of mutation frequency supports the in vitro MDS studies, which demonstrated the inability of base excision repair to completely repair closely opposed lesions

  20. Missed pancreatic ductal adenocarcinoma: Assessment of early imaging findings on prediagnostic magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Kyung Mi; Kim, Seong Hyun, E-mail: sh6453.kim@samsung.com; Kim, Young Kon; Song, Kyoung Doo; Lee, Soon Jin; Choi, Dongil

    2015-08-15

    Highlights: • MR imaging was superior to CT for the detection of early PDAC. • A focal lesion with no MPD interruption is common MR finding of early PDAC. • A mean volume doubling time of early PDAC was about five months. - Abstract: Objective: To investigate the early imaging findings and growth rate of pancreatic ductal adenocarcinoma (PDAC), and to assess whether MR imaging detects early PDAC better than CT. Materials and methods: The institutional review board approved this retrospective study and waived the requirement for informed consent. Twenty-two patients were included, and two radiologists, by consensus, assessed the presence of focal lesions, interruption of the main pancreatic duct (MPD), MPD dilatation, and pancreatitis, volume doubling time (VDT) of PDAC on prediagnostic MR imaging. Two other observers independently reviewed three image sets (CT images, unenhanced MR images, and unenhanced and contrast-enhanced MR images) for the detection of early PDAC. Paired Wilcoxon signed rank test and receiver operating characteristic (ROC) curve analysis were used for statistical analyses. Results: In 20 (90.9%) patients, prediagnostic MR exams showed abnormality, and all of them showed focal lesions on the first abnormal prediagnostic MR exams. Thirteen lesions (65%) showed no MPD interruption and one lesion (5%) was accompanied by pancreatitis. The mean VDT of PDAC was 151.7 days (range, 18.3–417.8 days). Diagnostic performance of unenhanced MR images (Az, 0.971–0.989) and combined unenhanced and contrast-enhanced MR images (Az, 0.956–0.963) was significantly better than that of CT images (Az, 0.565–0.583; p < 0.01) for both observers, Conclusion: The most common early imaging finding of PDAC on prediagnostic MR exams was a focal lesion with no MPD interruption with a mean volume doubling time of five months. MR imaging was superior to CT for the detection of early PDAC.

  1. Value of early follow-up CT in paediatric tuberculous meningitis

    International Nuclear Information System (INIS)

    Andronikou, Savvas; Wieselthaler, Nicky; Smith, Bruce; Douis, Hassan; Fieggen, A. Graham; Toorn, Ronald van; Wilmshurst, Jo

    2005-01-01

    The value of CT in the diagnosis of tuberculous meningitis (TBM) in children is well reported. Follow-up CT scanning for these patients is, however, not well described and, in particular, the value of early follow-up CT has not been addressed for children with TBM. To assess the value of early follow-up CT in children with TBM in identifying diagnostic, prognostic and therapeutically relevant features of TBM. A retrospective 4-year review of CT scans performed within 1 week and 1 month of initial CT in children with proven (CSF culture-positive) and probable TBM (CSF profile-positive but culture-negative) and comparison with initial CT for the diagnostic, prognostic and therapeutic CT features of TBM. The CT scans of 50 children were included (19 ''definite'' TBM; 31 ''probable'' TBM). Of these, 30 had CT scans performed within 1 week of the initial CT. On initial CT, 44 patients had basal enhancement. Only 24 patients had contrast medium-enhanced follow-up scans. Important findings include: 8 of 29 patients (who were not shunted) developed new hydrocephalus. New infarcts developed in 24 patients; 45% of those who did not have infarction initially developed new infarcts. Three of the six patients who did not show basal enhancement on initial scans developed this on the follow-up scans, while in seven patients with pre-existing basal enhancement this became more pronounced. Two patients developed hyperdensity in the cisterns on non-contrast medium scans. Eight patients developed a diagnostic triad of features. Three patients developed CT features of TBM where there was none on the initial scans. Early follow-up CT is useful in making a diagnosis of TBM by demonstrating features that were not present initially and by demonstrating more sensitive, obvious or additional features of TBM. In addition, follow-up CT is valuable as a prognostic indicator as it demonstrates additional infarcts which may have developed or become more visible since the initial study. Lastly

  2. Value of early follow-up CT in paediatric tuberculous meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Andronikou, Savvas [University of Cape Town, Department of Radiology, Cape Town (South Africa); Wieselthaler, Nicky; Smith, Bruce; Douis, Hassan [Red Cross Children' s Hospital, Department of Paediatric Radiology, School of Child and Adolescent Health, Cape Town (South Africa); Fieggen, A. Graham; Toorn, Ronald van; Wilmshurst, Jo [Red Cross Children' s Hospital, Department of Paediatric Radiology, School of Child and Adolescent Health, Cape Town (South Africa); Red Cross Children' s Hospital, Department of Neurosciences, School of Child and Adolescent Health, Cape Town (South Africa)

    2005-11-01

    The value of CT in the diagnosis of tuberculous meningitis (TBM) in children is well reported. Follow-up CT scanning for these patients is, however, not well described and, in particular, the value of early follow-up CT has not been addressed for children with TBM. To assess the value of early follow-up CT in children with TBM in identifying diagnostic, prognostic and therapeutically relevant features of TBM. A retrospective 4-year review of CT scans performed within 1 week and 1 month of initial CT in children with proven (CSF culture-positive) and probable TBM (CSF profile-positive but culture-negative) and comparison with initial CT for the diagnostic, prognostic and therapeutic CT features of TBM. The CT scans of 50 children were included (19 ''definite'' TBM; 31 ''probable'' TBM). Of these, 30 had CT scans performed within 1 week of the initial CT. On initial CT, 44 patients had basal enhancement. Only 24 patients had contrast medium-enhanced follow-up scans. Important findings include: 8 of 29 patients (who were not shunted) developed new hydrocephalus. New infarcts developed in 24 patients; 45% of those who did not have infarction initially developed new infarcts. Three of the six patients who did not show basal enhancement on initial scans developed this on the follow-up scans, while in seven patients with pre-existing basal enhancement this became more pronounced. Two patients developed hyperdensity in the cisterns on non-contrast medium scans. Eight patients developed a diagnostic triad of features. Three patients developed CT features of TBM where there was none on the initial scans. Early follow-up CT is useful in making a diagnosis of TBM by demonstrating features that were not present initially and by demonstrating more sensitive, obvious or additional features of TBM. In addition, follow-up CT is valuable as a prognostic indicator as it demonstrates additional infarcts which may have developed or become more

  3. Identification of immediate early gene products of bovine herpes virus 1 (BHV-1) as dominant antigens recognized by CD8 T cells in immune cattle

    DEFF Research Database (Denmark)

    Hart, Jane; MacHugh, Niall D.; Sheldrake, Tara

    2017-01-01

    candidate viral gene products with CD8 T-cell lines from 3 BHV-1-immune cattle of defined MHC genotypes identified 4 antigens, including 3 immediate early (IE) gene products (ICP4, ICP22 and Circ) and a tegument protein (UL49). Identification of the MHC restriction specificities revealed that the antigens...... cases refined, the identity of the epitopes. Analyses of the epitope specificity of the CD8 T-cell lines showed that a large component of the response is directed against these IE epitopes. The results indicate that these IE gene products are dominant targets of the CD8 T-cell response in BHV...

  4. On grand unified SU(8)sub(L) x SU(8)sub(R) model

    International Nuclear Information System (INIS)

    Pirogov, Yu.F.

    1980-01-01

    In the model of early chiral grand unification SU(8)sub(L)xSU(8)sub(R) with intermediate symmetry hierarchies the radiation corrections for sinsup(2)thetasub(W)(μ) and α(μ) are calculated and unification mass M 8 is found in the one loop approximation with Higgs fields contribution being neglected. It is shown that there exists a natural hierarchy, leading to the decrease of sinsup(2)thetasub(W)(Msub(W)) down to the value sinsup(2)thetasub(W)=1/5-1/4 and simultaneous decrease of M 8 down to M 8 =(10 6 -10 7 ) GeV as compared with the values when there is no hierarchy [ru

  5. Enhanced discriminative stimulus effects of Δ(9)-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys.

    Science.gov (United States)

    McMahon, Lance R

    2016-08-01

    Cannabidiol, a therapeutic with potential serotonin (5-hydroxytryptamine; 5-HT) 5-HT1A receptor agonist activity, is the second most prevalent cannabinoid in Cannabis after Δ(9)-THC. The extent to which cannabidiol modifies the effects of Δ(9)-THC has not been firmly established, especially with respect to abuse-related effects in rhesus monkeys where previously antagonistic interactions have been reported for some behavioral outcomes. Cannabidiol and the 5-HT1A receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) were tested in two separate discrimination assays in rhesus monkeys. One group (n=6) discriminated Δ(9)-tetrahydrocannabinol (Δ(9)-THC; 0.1mg/kg i.v.); a second group (n=6) discriminated the cannabinoid antagonist rimonabant (1mg/kg i.v.) while receiving Δ(9)-THC daily (1mg/kg/12hs.c.). Responding was maintained under a fixed ratio 5 schedule of stimulus-shock termination. Both training drugs dose-dependently increased the percentage of responses on the respective drug-associated levers. Cannabidiol (up to 17.8mg/kg) and 8-OH-DPAT (up to 0.178mg/kg) did not substitute for either training drug; however, both significantly increased the potency of Δ(9)-THC to produce discriminative stimulus effects. Moreover, 8-OH-DPAT significantly attenuated the discriminative stimulus effects of rimonabant, whereas cannabidiol did not modify the rimonabant discriminative stimulus. These results, which are consistent with cannabidiol lacking CB1 receptor agonist or antagonist activity in vivo, demonstrate enhancement of the effects of Δ(9)-THC by cannabidiol, albeit at cannabidiol amounts larger than those in Cannabis or cannabidiol-based therapeutics (nabiximols). In addition to showing that cannabidiol and a 5-HT1A receptor agonist have overlapping behavioral effects, the current results suggest that 5-HT1A agonism enhances the CB1 receptor-mediated effects of Δ(9)-THC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Enhanced discriminative stimulus effects of Δ9-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys

    Science.gov (United States)

    McMahon, Lance R.

    2016-01-01

    Background Cannabidiol, a therapeutic with potential serotonin (5-hydroxytryptamine; 5-HT) 5-HT1A receptor agonist activity, is the second most prevalent cannabinoid in Cannabis after Δ9-THC. The extent to which cannabidiol modifies the effects of Δ9-THC has not been firmly established, especially with respect to abuse-related effects in rhesus monkeys where previously antagonistic interactions have been reported for some behavioral outcomes. Methods Cannabidiol and the 5-HT1A receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) were tested in two separate discrimination assays in rhesus monkeys. One group (n=6) discriminated Δ9-tetrahydrocannabinol (Δ9-THC; 0.1 mg/kg i.v.); a second group (n=6) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) while receiving Δ9-THC daily (1 mg/kg/12 h s.c.). Responding was maintained under a fixed ratio 5 schedule of stimulus-shock termination. Results Both training drugs dose-dependently increased the percentage of responses on the respective drug-associated levers. Cannabidiol (up to 17.8 mg/kg) and 8-OH-DPAT (up to 0.178 mg/kg) did not substitute for either training drug; however, both significantly increased the potency of Δ9-THC to produce discriminative stimulus effects. Moreover, 8-OH-DPAT significantly attenuated the discriminative stimulus effects of rimonabant, whereas cannabidiol did not modify the rimonabant discriminative stimulus. Conclusions These results, which are consistent with cannabidiol lacking CB1 receptor agonist or antagonist activity in vivo, demonstrate enhancement of the effects of Δ9-THC by cannabidiol, albeit at cannabidiol amounts larger than those in Cannabis or cannabidiol-based therapeutics (nabiximols). In addition to showing that cannabidiol and a 5-HT1A receptor agonist have overlapping behavioral effects, the current results suggest that 5-HT1A agonism enhances the CB1 receptor-mediated effects of Δ9-THC. PMID:27289270

  7. Interferon Regulator Factor 8 (IRF8 Limits Ocular Pathology during HSV-1 Infection by Restraining the Activation and Expansion of CD8+ T Cells.

    Directory of Open Access Journals (Sweden)

    Lin Sun

    Full Text Available Interferon Regulatory Factor-8 (IRF8 is constitutively expressed in monocytes and B cell lineages and plays important roles in immunity to pathogens and cancer. Although IRF8 expression is induced in activated T cells, the functional relevance of IRF8 in T cell-mediated immunity is not well understood. In this study, we used mice with targeted deletion of Irf8 in T-cells (IRF8KO to investigate the role of IRF8 in T cell-mediated responses during herpes simplex virus 1 (HSV-1 infection of the eye. In contrast to wild type mice, HSV-1-infected IRF8KO mice mounted a more robust anti-HSV-1 immune response, which included marked expansion of HSV-1-specific CD8+ T cells, increased infiltration of inflammatory cells into the cornea and trigeminal ganglia (TG and enhanced elimination of virus within the trigeminal ganglion. However, the consequence of the enhanced immunological response was the development of ocular inflammation, limbitis, and neutrophilic infiltration into the cornea of HSV-1-infected IRF8KO mice. Surprisingly, we observed a marked increase in virus-specific memory precursor effector cells (MPEC in IRF8KO mice, suggesting that IRF8 might play a role in regulating the differentiation of effector CD8+ T cells to the memory phenotype. Together, our data suggest that IRF8 might play a role in restraining excess lymphocyte proliferation. Thus, modulating IRF8 levels in T cells can be exploited therapeutically to prevent immune-mediated ocular pathology during autoimmune and infectious diseases of the eye.

  8. Effects of low dose gamma radiation on the early growth of red pepper and the resistance to subsquent high dose of radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. S.; Baek, M. H.; Kim, D. H.; Lee, Y. K. [KAERI, Taejon (Korea, Republic of); Lee, Y. B. [Chungnam National Univ., Taejon (Korea, Republic of)

    2001-05-01

    Red pepper (capsicum annuum L. cv. Jokwang and cv. Johong) seeds were irradiated with the dose of 0{approx}50 Gy to investigated the effect of the low dose gamma radiation on the early growth and resistance to subsequent high dose of radiation. The effect of the low dose gamma radiation on the early growth and resistance to subsequenct high dose of radiation were enhanced in Johong cultivar but not in Jokwang cultivar. Germination rate and early growth of Johong cultivar were noticeably increased at 4 Gy-, 8 Gy- and 20 Gy irradiation group. Resistance to subsequent high dose of radiation of Johong cultivar were increased at almost all of the low dose irradiation group. Especially it was highest at 4 Gy irradiation group. The carotenoid contents and enzyme activity on the resistance to subsequent high dose of radiation of Johong cultivar were increased at the 4 Gy and 8 Gy irradiation group.

  9. Digital Learning As Enhanced Learning Processing? Cognitive Evidence for New insight of Smart Learning.

    Science.gov (United States)

    Di Giacomo, Dina; Ranieri, Jessica; Lacasa, Pilar

    2017-01-01

    Large use of technology improved quality of life across aging and favoring the development of digital skills. Digital skills can be considered an enhancing to human cognitive activities. New research trend is about the impact of the technology in the elaboration information processing of the children. We wanted to analyze the influence of technology in early age evaluating the impact on cognition. We investigated the performance of a sample composed of n. 191 children in school age distributed in two groups as users: high digital users and low digital users. We measured the verbal and visuoperceptual cognitive performance of children by n. 8 standardized psychological tests and ad hoc self-report questionnaire. Results have evidenced the influence of digital exposition on cognitive development: the cognitive performance is looked enhanced and better developed: high digital users performed better in naming, semantic, visual memory and logical reasoning tasks. Our finding confirms the data present in literature and suggests the strong impact of the technology using not only in the social, educational and quality of life of the people, but also it outlines the functionality and the effect of the digital exposition in early age; increased cognitive abilities of the children tailor digital skilled generation with enhanced cognitive processing toward to smart learning.

  10. Interleukin 8 in progression of hormone-dependent early breast cancer

    Indian Academy of Sciences (India)

    The only way to perceive the real clinical course of disease and the prognostic significance of potential biomarkers is follow-up of patients who did not receive any kind of adjuvant therapy. Many studies have confirmed high levels ofinterleukin 8 (IL8) in HER2-enriched and basal-like (ER–) primary breast tumours, but less is ...

  11. Radiofrequency ablation of renal tumours: diagnostic accuracy of contrast-enhanced ultrasound for early detection of residual tumour

    International Nuclear Information System (INIS)

    Hoeffel, Christine; Pousset, Maud; Elie, Caroline; Timsit, Marc-Olivier; Mejean, Arnaud; Merran, Samuel; Tranquart, Francois; Khairoune, Ahmed; Helenon, Olivier; Correas, Jean-Michel; Joly, Dominique; Richard, Stephane

    2010-01-01

    To evaluate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in the early detection of residual tumour after radiofrequency ablation (RFA) of renal tumours. Patients referred to our institution for RFA of renal tumours prospectively underwent CEUS and computed tomography (CT) or magnetic resonance imaging (MRI) before, within 1 day and 6 weeks after treatment. Identification of residual tumour was assessed by three blinded radiologists. Reference standard was CT/MRI performed at least 1 year after RFA. A total of 66 renal tumours in 43 patients (median age 62 years; range 44-71.5) were studied. Inter-reader agreement (κ value) was 0.84 for CEUS. Prevalence of residual disease was 19%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), respectively, were as follows: 64% [confidence interval (CI) 39-84], 98% [CI 91-100], 82% [CI 52-95] and 92% [CI 83-97] on 24-h CEUS; 79% [CI 52-92], 100% [CI 94-100], 100% [CI 74-100] and 95% [CI 87-100] on 6-week CEUS; 79% [CI 52-92], 95% [CI 86-98], 79% [CI 52-92] and 95% [CI 86-98] on 24-h CT/MRI; and 100% [CI 72-100], 98% [CI 90-100], 91% [CI 62-98] and 100% [CI 93-100] on 6-week CT/MRI. CEUS has high specificity for the early diagnosis of residual tumour after renal RFA. (orig.)

  12. Enhancing Research and Practice in Early Childhood through Formative and Design Experiments

    Science.gov (United States)

    Bradley, Barbara A.; Reinking, David

    2011-01-01

    This article describes formative and design experiments and how they can advance research and instructional practices in early childhood education. We argue that this relatively new approach to education research closes the gap between research and practice, and it addresses limitations that have been identified in early childhood research. We…

  13. Evaluation of sacroiliitis: contrast-enhanced MRI with subtraction technique

    Energy Technology Data Exchange (ETDEWEB)

    Algin, Oktay; Gokalp, Gokhan; Baran, Bulent; Ocakoglu, Gokhan; Yazici, Zeynep [Uludag University, Medical Faculty, Department of Radiology, Gorukle, Bursa (Turkey)

    2009-10-15

    The purpose of the study was to investigate the diagnostic value of contrast-enhanced MRI using the subtraction technique in the detection of active sacroiliitis. Magnetic resonance imaging was performed in 8 asymptomatic volunteers and 50 patients with clinically suspected active sacroiliitis. On precontrast MR images, T1-weighted spin-echo images with and without fat saturation (T1WFS and T1W), STIR and 3D-FLASH images with fat saturation were obtained in the semicoronal plane using a 1.5 Tesla imager. Postcontrast MRI was performed using the same T1WFS sequence as before contrast injection for all volunteers and patients. Postcontrast images were subtracted from fat-suppressed precontrast images. Enhancement within the joint space and bone marrow was considered to demonstrate active sacroiliitis. In 50 patients (100 sacroiliac joints [SIJs]), 40 (76 SIJs) were considered to have active sacroiliitis based on MR images. Bone marrow edema was present in 33 patients (62 SIJs) on STIR images. Routine MRI allowed identification of contrast enhancement in SIJs on postcontrast T1WFS images in 31 patients (49 SIJs). Contrast enhancement was observed in 40 patients (76 SIJs) who were examined by MRI using the subtraction technique. Contrast enhancement was significantly more conspicuous on subtraction images than on non-subtracted postcontrast T1WFS images (Mann-Whitney U test, p<0.001). Contrast-enhanced MRI with subtraction technique may be useful for early detection of active sacroiliitis. (orig.)

  14. Impact of Maternal HIV Seroconversion during Pregnancy on Early Mother to Child Transmission of HIV (MTCT Measured at 4-8 Weeks Postpartum in South Africa 2011-2012: A National Population-Based Evaluation.

    Directory of Open Access Journals (Sweden)

    Thu-Ha Dinh

    Full Text Available Mother-to-child transmission of HIV (MTCT depends on the timing of HIV infection. We estimated HIV-seroconversion during pregnancy (HSP after having a HIV-negative result antenatally, and its contribution to early MTCT in South Africa (SA.Between August 2011 and March 2012, we recruited a nationally representative sample of mother-infant pairs with infants aged 4-to-8 weeks from 578 health facilities. Data collection included mother interviews, child health-card reviews, and infant dried-blood-spots sample (iDBS. iDBS were tested for HIV antibodies and HIV-deoxyribonucleic-acid (HIV-DNA. HSP was defined as maternal self-report of an HIV-negative test during this pregnancy, no documented use of antiretroviral drugs and a matched HIV sero-positive iDBS. We used 20 imputations from a uniform distribution for time from reported antenatal HIV-negative result to delivery to estimate time of HSP. Early MTCT was defined based on detection of HIV-DNA in iDBS. Estimates were adjusted for clustering, nonresponse, and weighted by SA's 2011 live-births.Of 9802 mother-infant pairs, 2738 iDBS were HIV sero-positive, including 212 HSP, resulting in a nationally weighted estimate of 3.3% HSP (95% Confidence Interval: 2.8%-3.8%. Median time of HIV-seroconversion was 32.8weeks gestation;28.3% (19.7%- 36.9% estimated to be >36 weeks. Early MTCT was 10.7% for HSP (6.2%-16.8% vs. 2.2% (1.7%-2.8% for mothers with known HIV-positive status. Although they represent 2.2% of all mothers and 6.7% of HIV-infected mothers, HSP accounted for 26% of early MTCT. Multivariable analysis indicated the highest risk for HSP was among women who knew the baby's father was HIV-infected (adjusted-hazard ratio (aHR 4.71; 1.49-14.99, or who had been screened for tuberculosis (aHR 1.82; 1.43-2.32.HSP risk is high and contributes significantly to early MTCT. Identification of HSP by repeat-testing at 32 weeks gestation, during labor, 6 weeks postpartum, in tuberculosis-exposed women, and in

  15. Impact of Maternal HIV Seroconversion during Pregnancy on Early Mother to Child Transmission of HIV (MTCT) Measured at 4-8 Weeks Postpartum in South Africa 2011-2012: A National Population-Based Evaluation

    Science.gov (United States)

    Dinh, Thu-Ha; Delaney, Kevin P.; Goga, Ameena; Jackson, Debra; Lombard, Carl; Woldesenbet, Selamawit; Mogashoa, Mary; Pillay, Yogan; Shaffer, Nathan

    2015-01-01

    Background Mother-to-child transmission of HIV (MTCT) depends on the timing of HIV infection. We estimated HIV-seroconversion during pregnancy (HSP) after having a HIV-negative result antenatally, and its contribution to early MTCT in South Africa (SA). Methods and Findings Between August 2011 and March 2012, we recruited a nationally representative sample of mother-infant pairs with infants aged 4-to-8 weeks from 578 health facilities. Data collection included mother interviews, child health-card reviews, and infant dried-blood-spots sample (iDBS). iDBS were tested for HIV antibodies and HIV-deoxyribonucleic-acid (HIV-DNA). HSP was defined as maternal self-report of an HIV-negative test during this pregnancy, no documented use of antiretroviral drugs and a matched HIV sero-positive iDBS. We used 20 imputations from a uniform distribution for time from reported antenatal HIV-negative result to delivery to estimate time of HSP. Early MTCT was defined based on detection of HIV-DNA in iDBS. Estimates were adjusted for clustering, nonresponse, and weighted by SA’s 2011 live-births. Results Of 9802 mother-infant pairs, 2738 iDBS were HIV sero-positive, including 212 HSP, resulting in a nationally weighted estimate of 3.3% HSP (95% Confidence Interval: 2.8%-3.8%). Median time of HIV-seroconversion was 32.8weeks gestation;28.3% (19.7%- 36.9%) estimated to be >36 weeks. Early MTCT was 10.7% for HSP (6.2%-16.8%) vs. 2.2% (1.7%-2.8%) for mothers with known HIV-positive status. Although they represent 2.2% of all mothers and 6.7% of HIV-infected mothers, HSP accounted for 26% of early MTCT. Multivariable analysis indicated the highest risk for HSP was among women who knew the baby’s father was HIV-infected (adjusted-hazard ratio (aHR) 4.71; 1.49-14.99), or who had been screened for tuberculosis (aHR 1.82; 1.43-2.32). Conclusions HSP risk is high and contributes significantly to early MTCT. Identification of HSP by repeat-testing at 32 weeks gestation, during labor, 6

  16. The role of intrahepatic CD3 +/CD4 −/CD8 − double negative T (DN T) cells in enhanced acetaminophen toxicity

    International Nuclear Information System (INIS)

    Getachew, Yonas; Cusimano, Frank A.; James, Laura P.; Thiele, Dwain L.

    2014-01-01

    The role of the immune system, specifically NK, NKT and CD3 cells, in acetaminophen (APAP) induced liver injury remains inconsistently defined. In the present study, wild type (C57BL/6J) mice and granzyme B deficient (GrB −/−) mice were treated with acetaminophen to assess the role of the immune system in acute liver injury. Doses of acetaminophen that induced sub lethal liver injury in wild type mice unexpectedly produced fatal hepatotoxicity in granzyme B deficient (GrB −/−) mice. Analysis revealed that GrB −/− mice had an increased population of intrahepatic CD3 (+), CD4 (−), and CD8 (−) lymphocytes expressing the CD69 activation marker and Fas ligand. Depletion of these cells in the GrB −/− and wild type mice made them less susceptible to APAP injury, while depletion of NK1.1 (+) cells or both CD4 (+) and CD8 (+) T cells failed to provide the same hepatoprotection. Transfer of the GrB −/− IHLs further exacerbated liver injury and increased mortality in wild type mice but not in LRP/LPR mice, lacking fas expression. Conclusions: Acetaminophen toxicity is enhanced by the presence of activated, FasL expressing intrahepatic CD3 (+), CD4 (−), CD8 (−), NK1.1 (−) T cells. Depletion of these cells from GrB −/− mice and wild type mice greatly reduces mortality and improves the course of liver injury recovery. - Highlights: • Intrahepatic lymphocytes (IHLs) from GrB −/− mice harbor activated DNT cells. • IHLs from GrB −/− mice exhibit enhanced Fas ligand expression. • Acetaminophen toxicity is enhanced by activated, FasL expressing DNT cells

  17. The role of intrahepatic CD3 +/CD4 −/CD8 − double negative T (DN T) cells in enhanced acetaminophen toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Getachew, Yonas, E-mail: yonas.getachew@utsouthwestern.edu [Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9151 (United States); Cusimano, Frank A. [Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9151 (United States); James, Laura P. [Department of Pediatrics, University of Arkansas, Little Rock, AR (United States); Thiele, Dwain L. [Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9151 (United States)

    2014-10-15

    The role of the immune system, specifically NK, NKT and CD3 cells, in acetaminophen (APAP) induced liver injury remains inconsistently defined. In the present study, wild type (C57BL/6J) mice and granzyme B deficient (GrB −/−) mice were treated with acetaminophen to assess the role of the immune system in acute liver injury. Doses of acetaminophen that induced sub lethal liver injury in wild type mice unexpectedly produced fatal hepatotoxicity in granzyme B deficient (GrB −/−) mice. Analysis revealed that GrB −/− mice had an increased population of intrahepatic CD3 (+), CD4 (−), and CD8 (−) lymphocytes expressing the CD69 activation marker and Fas ligand. Depletion of these cells in the GrB −/− and wild type mice made them less susceptible to APAP injury, while depletion of NK1.1 (+) cells or both CD4 (+) and CD8 (+) T cells failed to provide the same hepatoprotection. Transfer of the GrB −/− IHLs further exacerbated liver injury and increased mortality in wild type mice but not in LRP/LPR mice, lacking fas expression. Conclusions: Acetaminophen toxicity is enhanced by the presence of activated, FasL expressing intrahepatic CD3 (+), CD4 (−), CD8 (−), NK1.1 (−) T cells. Depletion of these cells from GrB −/− mice and wild type mice greatly reduces mortality and improves the course of liver injury recovery. - Highlights: • Intrahepatic lymphocytes (IHLs) from GrB −/− mice harbor activated DNT cells. • IHLs from GrB −/− mice exhibit enhanced Fas ligand expression. • Acetaminophen toxicity is enhanced by activated, FasL expressing DNT cells.

  18. Metal plasmon enhanced europium complex luminescence

    International Nuclear Information System (INIS)

    Liu Feng; Aldea, Gabriela; Nunzi, Jean-Michel

    2010-01-01

    The plasmon enhanced luminescence of a rare-earth complex Tris(6, 6, 7, 7, 8, 8, 8-heptafluoro-2, 2-dimethyl-3, 5-octanedionato) europium (Eu(fod) 3 ) was investigated. A polyvinyl alcohol (PVA) thin film was successfully adopted as a spacer to separate the Eu complex from the silver island film (SIF), and five-fold enhancement of the radiative decay rate of the Eu complex on SIF was demonstrated based on the luminescence intensity and lifetime measurement. Investigation of the distance dependent luminescence indicates that 7 nm is an optimal distance for SIF enhanced Eu luminescence. Plasmon enhanced rare-earth luminescence based on an organic film spacer would find potential applications in plasmon enhanced organic light emitting diode (OLED) devices.

  19. Blocking of PDL-1 interaction enhances primary and secondary CD8 T cell response to herpes simplex virus-1 infection.

    Directory of Open Access Journals (Sweden)

    Rudragouda Channappanavar

    Full Text Available The blocking of programmed death ligand-1 (PDL-1 has been shown to enhance virus-specific CD8 T cell function during chronic viral infections. Though, how PDL-1 blocking at the time of priming affects the quality of CD8 T cell response to acute infections is not well understood and remains controversial. This report demonstrates that the magnitude of the primary and secondary CD8 T cell responses to herpes simplex virus-1 (HSV-1 infection is subject to control by PDL-1. Our results showed that after footpad HSV-1 infection, PD-1 expression increases on immunodominant SSIEFARL peptide specific CD8 T cells. Additionally, post-infection, the level of PDL-1 expression also increases on CD11c+ dendritic cells. Intraperitoneal administration of anti-PDL-1 monoclonal antibody given one day prior to and three days after cutaneous HSV-1 infection, resulted in a marked increase in effector and memory CD8 T cell response to SSIEFARL peptide. This was shown by measuring the quantity and quality of SSIEFARL-specific CD8 T cells by making use of ex-vivo assays that determine antigen specific CD8 T cell function, such as intracellular cytokine assay, degranulation assay to measure cytotoxicity and viral clearance. Our results are discussed in terms of the beneficial effects of blocking PDL-1 interactions, while giving prophylactic vaccines, to generate a more effective CD8 T cell response to viral infection.

  20. Numerical modeling of an enhanced very early time electromagnetic (VETEM) prototype system

    Science.gov (United States)

    Cui, T.J.; Chew, W.C.; Aydiner, A.A.; Wright, D.L.; Smith, D.V.; Abraham, J.D.

    2000-01-01

    In this paper, two numerical models are presented to simulate an enhanced very early time electromagnetic (VETEM) prototype system, which is used for buried-object detection and environmental problems. Usually, the VETEM system contains a transmitting loop antenna and a receiving loop antenna, which run on a lossy ground to detect buried objects. In the first numerical model, the loop antennas are accurately analyzed using the Method of Moments (MoM) for wire antennas above or buried in lossy ground. Then, Conjugate Gradient (CG) methods, with the use of the fast Fourier transform (FFT) or MoM, are applied to investigate the scattering from buried objects. Reflected and scattered magnetic fields are evaluated at the receiving loop to calculate the output electric current. However, the working frequency for the VETEM system is usually low and, hence, two magnetic dipoles are used to replace the transmitter and receiver in the second numerical model. Comparing these two models, the second one is simple, but only valid for low frequency or small loops, while the first modeling is more general. In this paper, all computations are performed in the frequency domain, and the FFT is used to obtain the time-domain responses. Numerical examples show that simulation results from these two models fit very well when the frequency ranges from 10 kHz to 10 MHz, and both results are close to the measured data.

  1. Integr8: enhanced inter-operability of European molecular biology databases.

    Science.gov (United States)

    Kersey, P J; Morris, L; Hermjakob, H; Apweiler, R

    2003-01-01

    The increasing production of molecular biology data in the post-genomic era, and the proliferation of databases that store it, require the development of an integrative layer in database services to facilitate the synthesis of related information. The solution of this problem is made more difficult by the absence of universal identifiers for biological entities, and the breadth and variety of available data. Integr8 was modelled using UML (Universal Modelling Language). Integr8 is being implemented as an n-tier system using a modern object-oriented programming language (Java). An object-relational mapping tool, OJB, is being used to specify the interface between the upper layers and an underlying relational database. The European Bioinformatics Institute is launching the Integr8 project. Integr8 will be an automatically populated database in which we will maintain stable identifiers for biological entities, describe their relationships with each other (in accordance with the central dogma of biology), and store equivalences between identified entities in the source databases. Only core data will be stored in Integr8, with web links to the source databases providing further information. Integr8 will provide the integrative layer of the next generation of bioinformatics services from the EBI. Web-based interfaces will be developed to offer gene-centric views of the integrated data, presenting (where known) the links between genome, proteome and phenotype.

  2. Early ontogeny of the central benzodiazepine receptor in human embryos and fetuses

    Energy Technology Data Exchange (ETDEWEB)

    Hebebrand, J.; Hofmann, D.; Reichelt, R.; Schnarr, S.; Knapp, M.; Propping, P.; Foedisch, H.J.

    1988-01-01

    The early ontogeny of the central benzodiazepine receptor (BZR) was investigated in human embryos and fetuses between 7 and 26 weeks of gestation. Brain tissue was gained from terminated pregnancies or spontaneous abortions. Binding studies, which were performed with /sup 3/H-flunitrazepam (FNZ), revealed that specific benzodiazepine binding is already detectable at an embryonal age of 7 weeks post conception. Binding at this early stage can be displaced potently by clonazepam and the inverse agonist ..beta..-CCE. Additionally, /sup 3/H-FNZ binding is enhanced by GABA. Thus, benzodiazepine binding is of the central type. Receptor density increases steeply in whole brain between weeks 8 and 11 of gestation. In frontal cortex receptor density increases gradually between weeks 12 and 26 of gestation. No specific fetal disease entity (including trisomy 21) was consistently associated with exceptionally high or low B/sub max/-values.

  3. Silencing of OSBP-related protein 8 (ORP8) modifies the macrophage transcriptome, nucleoporin p62 distribution, and migration capacity

    International Nuclear Information System (INIS)

    Béaslas, Olivier; Vihervaara, Terhi; Li, Jiwei; Laurila, Pirkka-Pekka; Yan, Daoguang; Olkkonen, Vesa M.

    2012-01-01

    ORP8 is an oxysterol/cholesterol binding protein anchored to the endoplasmic reticulum and the nuclear envelope, and is abundantly expressed in the macrophage. We created and characterized mouse RAW264.7 macrophages with ORP8 stably silenced using shRNA lentiviruses. A microarray transcriptome and gene ontology pathway analysis revealed significant alterations in several nuclear pathways and ones associated with centrosome and microtubule organization. ORP8 knockdown resulted in increased expression and altered subcellular distribution of an interaction partner of ORP8, nucleoporin NUP62, with an intranuclear localization aspect and association with cytoplasmic vesicular structures and lamellipodial edges of the cells. Moreover, ORP8 silenced cells displayed enhanced migration, and a more pronounced microtubule cytoskeleton than controls expressing a non-targeting shRNA. ORP8 was shown to compete with Exo70 for interaction with NUP62, and NUP62 knockdown abolished the migration enhancement of ORP8-silenced cells, suggesting that the endogenous ORP8 suppresses migration via binding to NUP62. As a conclusion, the present study reveals new, unexpected aspects of ORP8 function in macrophages not directly involving lipid metabolism, but rather associated with nuclear functions, microtubule organization, and migration capacity. -- Highlights: ► The phenotype of Raw264.7 macrophage with ORP8 silenced is characterized. ► ORP8 silencing alters mRNA levels of nuclear and microtubule/centrosome pathways. ► ORP8 silencing results in increased expression and altered distribution of NUP62. ► ORP8 silenced macrophages show enhanced migration and altered microtubule cytoskeleton. ► ORP8 competes in vitro with Exo70 for binding to NUP62.

  4. Early Career Boot Camp: a novel mechanism for enhancing early career development for psychologists in academic healthcare.

    Science.gov (United States)

    Foran-Tuller, Kelly; Robiner, William N; Breland-Noble, Alfiee; Otey-Scott, Stacie; Wryobeck, John; King, Cheryl; Sanders, Kathryn

    2012-03-01

    The purpose of this article is to describe a pilot mentoring program for Early Career Psychologists (ECPs) working in Academic Health Centers (AHCs) and synthesize the lessons learned to contribute to future ECP and AHC career development training programs. The authors describe an early career development model, named the Early Career Boot Camp. This intensive experience was conducted as a workshop meant to build a supportive network and to provide mentorship and survival tools for working in AHCs. Four major components were addressed: professional effectiveness, clinical supervision, strategic career planning, and academic research. Nineteen attendees who were currently less than 5 years post completion of doctoral graduate programs in psychology participated in the program. The majority of boot camp components were rated as good to excellent, with no component receiving below average ratings. Of the components offered within the boot camp, mentoring and research activities were rated the strongest, followed by educational activities, challenges in AHCS, and promotion and tenure. The article describes the purpose, development, implementation, and assessment of the program in detail in an effort to provide an established outline for future organizations to utilize when mentoring ECPs.

  5. Enhanced production of bacitracin by a mutant strain bacillus licheniformis UV-MN-HN-8 (enhanced bacitracin production by mutagenesis)

    International Nuclear Information System (INIS)

    Aftab, M.N.; Ikram-ul-Haq; Baig, S.

    2010-01-01

    The present study is focused on the improvement of Bacillus licheniformis through random mutagenesis to obtain mutant having enhanced production of bacitracin. Many isolates of Bacillus licheniformis were isolated and the isolate GP-40 produced maximum bacitracin production (16 +- 0.72 IU/mL). Treatment of Bacillus licheniformis GP-40 with ultraviolet (UV) radiations increased bacitracin production to 29 +- 0.69 IU/mL. Similarly, treatment of vegetative cells of GP-40 with chemicals like N-methyl N'-nitro N-nitroso guanidine (MNNG) and Nitrous acid (HNO/sub 2/) increased bacitracin production to 35 +- 1.35 IU/mL and 29 +- 0.89 IU/mL respectively. Studies regarding the combined effect of UV and chemical treatment on parental cells exhibited significantly higher titers of bacitracin with maximum bacitracin production reached to 47.6 +- 0.92 IU/mL. An increase of 2.97 fold production of bacitracin in comparison to wild type was observed. Mutant strain was highly stable and produced consistent yield of bacitracin even after 15 generations. On the basis of kinetic variables, notably mu (h-/sup 1/)max, Yp/x, qp, Qp and Qx mutant strain B. licheniformis UV-MN-HN-8 was found to be a hyper producer of bacitracin. (author)

  6. Monitoring early response to chemoradiotherapy with "1"8F-FMISO dynamic PET in head and neck cancer

    International Nuclear Information System (INIS)

    Grkovski, Milan; Beattie, Bradley J.; O'Donoghue, Joseph A.; Humm, John L.; Lee, Nancy Y.; Riaz, Nadeem; Leeman, Jonathan E.; Schoeder, Heiko; Carlin, Sean D.

    2017-01-01

    There is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of "1"8F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC. Seventy-two HNC patients underwent FMISO dPET scans in a customized immobilization mask (0-30 min dynamic acquisition, followed by 10 min static acquisitions starting at ∝95 min and ∝160 min post-injection) at baseline and early into treatment where patients have already received one cycle of chemotherapy and anywhere from five to ten fractions of 2 Gy per fraction radiation therapy. Voxelwise pharmacokinetic modeling was conducted using an irreversible one-plasma two-tissue compartment model to calculate surrogate biomarkers of tumor hypoxia (k_3 and Tumor-to-Blood Ratio (TBR)), perfusion (K_1) and FMISO distribution volume (DV). Additionally, Tumor-to-Muscle Ratios (TMR) were derived by visual inspection by an experienced nuclear medicine physician, with TMR > 1.2 defining hypoxia. One hundred and thirty-five lesions in total were analyzed. TBR, k_3 and DV decreased on early response scans, while no significant change was observed for K_1. The k_3 -TBR correlation decreased substantially from baseline scans (Pearson's r = 0.72 and 0.76 for mean intratumor and pooled voxelwise values, respectively) to early response scans (Pearson's r = 0.39 and 0.40, respectively). Both concordant and discordant examples of changes in intratumor k_3 and TBR were identified; the latter partially mediated by the change in DV. In 13 normoxic patients according to visual analysis (all having lesions with TMR = 1.2), subvolumes were identified where k_3 indicated the presence of hypoxia. Pharmacokinetic modeling of FMISO dynamic PET reveals a more detailed characterization of the

  7. Effectiveness and Cost Efficiency of Different Surveillance Components for Proving Freedom and Early Detection of Disease: Bluetongue Serotype 8 in Cattle as Case Study for Belgium, France and the Netherlands.

    Science.gov (United States)

    Welby, S; van Schaik, G; Veldhuis, A; Brouwer-Middelesch, H; Peroz, C; Santman-Berends, I M; Fourichon, C; Wever, P; Van der Stede, Y

    2017-12-01

    Quick detection and recovery of country's freedom status remain a constant challenge in animal health surveillance. The efficacy and cost efficiency of different surveillance components in proving the absence of infection or (early) detection of bluetongue serotype 8 in cattle populations within different countries (the Netherlands, France, Belgium) using surveillance data from years 2006 and 2007 were investigated using an adapted scenario tree model approach. First, surveillance components (sentinel, yearly cross-sectional and passive clinical reporting) within each country were evaluated in terms of efficacy for substantiating freedom of infection. Yearly cross-sectional survey and passive clinical reporting performed well within each country with sensitivity of detection values ranging around 0.99. The sentinel component had a sensitivity of detection around 0.7. Secondly, how effective the components were for (early) detection of bluetongue serotype 8 and whether syndromic surveillance on reproductive performance, milk production and mortality data available from the Netherlands and Belgium could be of added value were evaluated. Epidemic curves were used to estimate the timeliness of detection. Sensitivity analysis revealed that expected within-herd prevalence and number of herds processed were the most influential parameters for proving freedom and early detection. Looking at the assumed direct costs, although total costs were low for sentinel and passive clinical surveillance components, passive clinical surveillance together with syndromic surveillance (based on reproductive performance data) turned out most cost-efficient for the detection of bluetongue serotype 8. To conclude, for emerging or re-emerging vectorborne disease that behaves such as bluetongue serotype 8, it is recommended to use passive clinical and syndromic surveillance as early detection systems for maximum cost efficiency and sensitivity. Once an infection is detected and eradicated

  8. Dynamic Contrast Enhanced MRI Can Monitor the Very Early Inflammatory Treatment Response upon Intra-Articular Steroid Injection in the Knee Joint: A Case Report with Review of the Literature

    DEFF Research Database (Denmark)

    Boesen, Mikael; Kubassova, Olga; Cimmino, Marco A

    2011-01-01

    Dynamic contrast-enhanced MRI in inflammatory arthritis, especially in conjunction with computer-aided analysis using appropriate dedicated software, seems to be a highly sensitive tool for monitoring the early inflammatory treatment response in patients with rheumatoid arthritis. This paper give...... a review of the current knowledge of the emerging technique. The potential of the technique is demonstrated and discussed in the context of a case report following the early effect of an intra-articular steroid injection in a patient with rheumatoid arthritis flare in the knee....

  9. Enhanced PL and EL properties of Alq3/nano-TiO2 with the modification of 8-vinyl POSS

    Science.gov (United States)

    Li, Jie; Xie, Bing; Xia, Kai; Zhao, Chunmao; Li, Yingchun; Hu, Shengliang

    2018-04-01

    In this study, tris (8-hydroxyquinoline) aluminum/nano-titanium dioxide (Alq3/nano-TiO2) composites were synthesized using a simply in-situ process with 8-vinyl polyhedral oligomeric silsesquioxane (POSS) as a modifier. The as-prepared Alq3/nano-TiO2 composites were characterized by X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS) and ultraviolet visible (UV-vis) absorption spectra. The effect of modification on luminescence properties for the samples was studied by photoluminescence (PL) spectra, electroluminescence (EL) spectra and time-resolved luminescence decay curves. Organic light emitting diodes (OLEDs) with the corresponded emitting layer structure were investigated. The results show that the amphiphilicity of the 8-vinyl POSS leads to well-dispersion state of the nano-TiO2 in the Alq3. Adding a proper weight percentage of 8-vinyl POSS is beneficial for the PL and EL properties enhancement of the composites. OLED using the Alq3/nano-TiO2 with 1 wt% 8-vinyl POSS emitting layer has the low turn-on voltage (4.7 V at 1 cd/m2), high maximum luminance (7463 cd/m2 at 8.75 V), and high luminous efficiency (1.13 cd/A at 100 mA/cm2). Adding 1 wt% 8-vinyl POSS in Alq3/nano-TiO2 can increase the EL intensity by a factor of 37.1 at 8 V. These values are better than those for OLEDs using the Alq3 emitting layer. The increase in luminance and current efficiency stability can be attributed to the energy transfer process between the Alq3 and the nano-TiO2, and the suppression of the self-quenching by caged 8-vinyl POSS molecules.

  10. Volume 9 No. 8 November 2009 1712 ENHANCEMENT OF THE ...

    African Journals Online (AJOL)

    2009-11-08

    Nov 8, 2009 ... Acid detergent fiber (ADF) was determined by the method of Goering & Van Soest. [8]. .... source of crude protein, like urea or ammonia [16]. ..... Rivers B Factors affecting the enzymatic hydrolysis of bagasse and rice straw.

  11. MRI in predication of early hemorrhagic transformation after acute stroke

    International Nuclear Information System (INIS)

    Guo Gang; Wu Renhua; Mikulis, D.J.

    2007-01-01

    Objective: To investigate the relationship among early parenchymal enhancement, post- gadolinium (Gd) hyperintense middle cerebral artery (HMCA), and subsequent hemorrhagic transformation (HT) in patients with hyperacute ischemic stroke. Methods: Twenty-four consecutive patients with ischemic stroke who underwent MRI within 6 h [(4.3±1.4) h] of symptom onset were retrospectively reviewed. All of these patients underwent at least one follow-up MRI or non-enhanced CT study at 2 to 7 days. Post-Gd T 1 WI were analyzed for parenchymal enhancement and hyperintense MCA. Gradient echo MRI and CT were used for assessment of HT. Results: Ten patients developed HT on follow-up imaging (hemorrhagic group). Early parenchymal enhancement was found in 6 patients with HT (P 1 WI after Gd-DTPA administration are independent predictors of subsequent HT. (authors)

  12. Earth's early biosphere

    Science.gov (United States)

    Des Marais, D. J.

    1998-01-01

    Understanding our own early biosphere is essential to our search for life elsewhere, because life arose on Earth very early and rocky planets shared similar early histories. The biosphere arose before 3.8 Ga ago, was exclusively unicellular and was dominated by hyperthermophiles that utilized chemical sources of energy and employed a range of metabolic pathways for CO2 assimilation. Photosynthesis also arose very early. Oxygenic photosynthesis arose later but still prior to 2.7 Ga. The transition toward the modern global environment was paced by a decline in volcanic and hydrothermal activity. These developments allowed atmospheric O2 levels to increase. The O2 increase created new niches for aerobic life, most notably the more advanced Eukarya that eventually spawned the megascopic fauna and flora of our modern biosphere.

  13. Targeting Hydrothermal Alterations Utilizing LANDSAT-8 Andaster Data in Shahr-E Iran

    Science.gov (United States)

    Safari, M.; Pour, A. B.; Maghsoudi, A.; Hashim, M.

    2017-10-01

    Shahr-e-Babak tract of the Kerman metalogenic belt is one of the most potential segments of Urumieh-Dokhtar (Sahand-Bazman) magmatic arc. This area encompasses several porphyry copper deposits in exploration, development and exploitation hierarchy. The aim of this study is to map hydrothermal alterations caused by early Cenozoic magmatic intrusions in Shahr-e-Babak area. To this purpose, mineral mapping methods including band combinations, ratios and multiplications as well as PCA and MNF data space transforms in SWIR and VNIR for both ASTER and OLI sensors. Alteration zones according to spectral signatures of each type of alteration mineral assemblages such as argillic, phyllic and propylitic are successfully mapped. For enhancing the target areas false color composites and HSI-RGB color space transform are performed on developed band combinations. Previous studies have proven the robust application of ASTER in geology and mineral exploration; nonetheless, the results of this investigation prove applicability of OLI sensor from landsat-8 for alteration mapping. According to the results, evidently OLI sensor data can accurately map alteration zones. Additionally, the 12-bit quantization of OLI data is its privilege over 8-bit data of ASTER in VNIR and SWIR, thus OLI high quality results, which makes it easy to distinguish targets with enhanced color contrast between the altered and unaltered rocks.

  14. Co-stimulation through 4-1BB/CD137 improves the expansion and function of CD8(+ melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy.

    Directory of Open Access Journals (Sweden)

    Jessica Ann Chacon

    Full Text Available Adoptive T-cell therapy (ACT using tumor-infiltrating lymphocytes (TIL can induce tumor regression in up to 50% or more of patients with unresectable metastatic melanoma. However, current methods to expand melanoma TIL, especially the "rapid expansion protocol" (REP were not designed to enhance the generation of optimal effector-memory CD8(+ T cells for infusion. One approach to this problem is to manipulate specific co-stimulatory signaling pathways to enhance CD8(+ effector-memory T-cell expansion. In this study, we determined the effects of activating the TNF-R family member 4-1BB/CD137, specifically induced in activated CD8(+ T cells, on the yield, phenotype, and functional activity of expanded CD8(+ T cells during the REP. We found that CD8(+ TIL up-regulate 4-1BB expression early during the REP after initial TCR stimulation, but neither the PBMC feeder cells in the REP or the activated TIL expressed 4-1BB ligand. However, addition of an exogenous agonistic anti-4-1BB IgG4 (BMS 663513 to the REP significantly enhanced the frequency and total yield of CD8(+ T cells as well as their maintenance of CD28 and increased their anti-tumor CTL activity. Gene expression analysis found an increase in bcl-2 and survivin expression induced by 4-1BB that was associated with an enhanced survival capability of CD8(+ post-REP TIL when re-cultured in the absence or presence of cytokines. Our findings suggest that adding an agonistic anti-4-1BB antibody during the time of TIL REP initiation produces a CD8(+ T cell population capable of improved effector function and survival. This may greatly improve TIL persistence and anti-tumor activity in vivo after adoptive transfer into patients.

  15. Silencing of OSBP-related protein 8 (ORP8) modifies the macrophage transcriptome, nucleoporin p62 distribution, and migration capacity

    Energy Technology Data Exchange (ETDEWEB)

    Beaslas, Olivier; Vihervaara, Terhi [Minerva Foundation Institute for Medical Research, FI-00290 Helsinki (Finland); Li, Jiwei [Department of Biology, Jinan University, Guangzhou 510632 (China); Laurila, Pirkka-Pekka [FIMM, Institute for Molecular Medicine Finland, FI-00290 Helsinki (Finland); National Institute for Health and Welfare, Public Health Genomics Unit, FI-00290 Helsinki (Finland); Yan, Daoguang [Department of Biology, Jinan University, Guangzhou 510632 (China); Olkkonen, Vesa M., E-mail: vesa.olkkonen@helsinki.fi [Minerva Foundation Institute for Medical Research, FI-00290 Helsinki (Finland); Institute of Biomedicine, Anatomy, University of Helsinki, FI-00014 (Finland)

    2012-09-10

    ORP8 is an oxysterol/cholesterol binding protein anchored to the endoplasmic reticulum and the nuclear envelope, and is abundantly expressed in the macrophage. We created and characterized mouse RAW264.7 macrophages with ORP8 stably silenced using shRNA lentiviruses. A microarray transcriptome and gene ontology pathway analysis revealed significant alterations in several nuclear pathways and ones associated with centrosome and microtubule organization. ORP8 knockdown resulted in increased expression and altered subcellular distribution of an interaction partner of ORP8, nucleoporin NUP62, with an intranuclear localization aspect and association with cytoplasmic vesicular structures and lamellipodial edges of the cells. Moreover, ORP8 silenced cells displayed enhanced migration, and a more pronounced microtubule cytoskeleton than controls expressing a non-targeting shRNA. ORP8 was shown to compete with Exo70 for interaction with NUP62, and NUP62 knockdown abolished the migration enhancement of ORP8-silenced cells, suggesting that the endogenous ORP8 suppresses migration via binding to NUP62. As a conclusion, the present study reveals new, unexpected aspects of ORP8 function in macrophages not directly involving lipid metabolism, but rather associated with nuclear functions, microtubule organization, and migration capacity. -- Highlights: Black-Right-Pointing-Pointer The phenotype of Raw264.7 macrophage with ORP8 silenced is characterized. Black-Right-Pointing-Pointer ORP8 silencing alters mRNA levels of nuclear and microtubule/centrosome pathways. Black-Right-Pointing-Pointer ORP8 silencing results in increased expression and altered distribution of NUP62. Black-Right-Pointing-Pointer ORP8 silenced macrophages show enhanced migration and altered microtubule cytoskeleton. Black-Right-Pointing-Pointer ORP8 competes in vitro with Exo70 for binding to NUP62.

  16. Accounting Early for Life Long Learning: The AcE Project.

    Science.gov (United States)

    University Coll. Worcester (England). Centre for Research in Early Childhood Education.

    Building upon the work of the Effective Early Learning (EEL) Project in raising the quality of early learning for young children in the United Kingdom, the 3-year Accounting Early for Life Long Learning Project (AcE Project) focuses on enhancing in 3- to 6-year-olds those attitudes and dispositions that are important to life-long learning. This…

  17. Enhancing the Effectiveness of ICT Applications and Tools for ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Enhancing the Effectiveness of ICT Applications and Tools for Disaster ... of disaster management in the Caribbean, including early warning systems and collection ... to enhancing regional strategies to respond to natural hazards using ICTs.

  18. Retromer guides STxB and CD8-M6PR from early to recycling endosomes, EHD1 guides STxB from recycling endosome to Golgi

    Science.gov (United States)

    McKenzie, Jenna E.; Raisley, Brent; Zhou, Xin; Naslavsky, Naava; Taguchi, Tomohiko; Caplan, Steve; Sheff, David

    2012-01-01

    Retrograde trafficking transports proteins, lipids and toxins from the plasma membrane to the Golgi and ER. To reach the Golgi, these cargos must transit the endosomal system, consisting of early endosomes, recycling endosomes, late endosomes and lysosomes. All cargos pass through early endosomes, but may take different routes to the Golgi. Retromer dependent cargos bypass the late endosomes to reach the Golgi. We compared how two very different retromer dependent cargos negotiate the endosomal sorting system. Shiga toxin B, bound to the external layer of the plasma membrane, and chimeric CD8-Mannose-6-Phosphate Receptor, which is anchored via a transmembrane domain. Both appear to pass through the recycling endosome. Ablation of the recycling endosome diverted both of these cargos to an aberrant compartment and prevented them from reaching the Golgi. Once in the recycling endosome, Shiga toxin required EHD1 to traffic to the TGN, while the CD8-Mannose-6-Phosphate Receptor was not significantly dependent on EHD1. Knockdown of retromer components left cargo in the early endosomes, suggesting that it is required for retrograde exit from this compartment. This work establishes the recycling endosome as a required step in retrograde traffic of at least these two retromer dependent cargos. Along this pathway, retromer is associated with EE to recycling endosome traffic, while EHD1 is associated with recycling endosome to TGN traffic of STxB. PMID:22540229

  19. Diagnosis value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Ma Zhoupeng; Zhou Jianjun; Liu Xueling; Wang Chun; Zhang Shunzhuang

    2012-01-01

    Objective: To explore the diagnostic value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma. Methods: Sixty patients who were suspected of clear cell renal cell carcinoma underwent non-enhanced CT and contrast enhancement CT of early interface-phase between cortex -medulla and parenchymal phase on a dual-energy CT. The true non-enhanced kidney CT (TNCT) was performed in a single-energy acquisition mode, but the dual-phase contrast enhancement CT were performed in a dual-energy mode of 80 kV and 140 kV respectively. The virtual non-enhanced CT (VNCT) images were derived from the data of early interface phase using liver virtual non-contrast software. The diagnose according to VNCT combined dual-phase contrast enhancement CT and dual-phase contrast enhancement CT only were made respectively and compared with χ 2 test. Between the true non-contrast CT and the virtual non-contrast CT, the image quality was compared with Wilcoxon test; The radiation dose of volume CT dose index (CTDIvol) and dose length product(DLP) in a single-phase and total examination, the mean CT HU values of the tumours were compared with t test. Results: The accuracy of VNCT combined dual-phase contrast enhancement CT was higher than that of dual-phase contrast enhancement CT only [93.3% (56/60) vs.78.3% (47/60); χ 2 =5.6, P<0.05]. The detective ability (score) of VNCT was near to that of TNCT and the difference was not obvious (Z=0.00, P>0.05). The radiation dose of volume CT dose index (CTDIvol) and dose length product (DLP) in a single phase and total examination of VNCT [(8.85 ± 1.28) mGy, (196.45 ±21.12) mGy·cm, (17.69±2.35) mGy, (392.90±42.25) mGy · cm] were lower than that of TNCT [(10.20 ± 1.44) mGy,(218.29 ± 29.60) mGy · cm, (30.61 ± 3.27) mGy and (654.86 ± 88.81) mGy ·cm], t=4.21, 3.58, 23.63, 16.12 respectively, P<0.05. The mean CT HU values of tumours on VNCT images was higher than that

  20. Enhancement of building operations: A successful approach towards national electrical demand management

    International Nuclear Information System (INIS)

    Al-Mulla, A.; Maheshwari, G.P.; Al-Nakib, D.; ElSherbini, A.; Alghimlas, F.; Al-Taqi, H.; Al-Hadban, Y.

    2013-01-01

    Highlights: • Enhanced building operations were applied for eight large government buildings in Kuwait. • The enhanced building operations led to demand savings of 8.90 MW during the national peak hour. • Nationwide guidelines were developed for implementing the enhanced operations in similar government buildings in Kuwait. • The peak electrical demand reduction is likely to be 488 MW by the year 2030. - Abstract: An approach for managing electrical demand through enhanced building operations in hot climates is evaluated and demonstrated in this paper. The approach focuses on implementing enhanced operations in government buildings, since they are easier to implement and administer. These enhanced operations included early reduction of cooling supply before the end of the occupancy period, improved time-of-day control after occupancy period and reduced lighting. A total of eight government buildings with different construction and system characteristics were selected for implementing these enhanced operations. These buildings have a total air-conditioning area of 4.39 × 10 5 m 2 and a combined peak electrical demand of 29.3 MW. The enhanced operations resulted in demand savings of 8.90 MW during the national peak hour. Temperatures build up inside the buildings were monitored and found to be within acceptable ranges. Guidelines for nationwide implementation in similar buildings were developed based on the results of this work. Implementation is estimated to reduce demand by 488 MW by the year 2030, which amounts to capital savings of $585 million. These projected values would be important to adopt energy efficient policies for the country. Additional reductions in energy and fuel consumption are added benefits, which would result in large financial and environmental savings to the country. Moreover, the enhanced building operations would be an important tool to avoid any blackouts by properly reducing the peak electrical demand as well as operating the

  1. Mitogen-Activated Protein Kinase 8 (MAP3K8) Mediates the Signaling Pathway of Estradiol Stimulating Progesterone Production Through G Protein-Coupled Receptor 30 (GPR30) in Mouse Corpus Luteum.

    Science.gov (United States)

    Liu, Ying; Li, Yueqin; Zhang, Di; Liu, Jiali; Gou, Kemian; Cui, Sheng

    2015-05-01

    The corpus luteum (CL) is a transient endocrine gland developed from the ovulated follicles, and the most important function is to synthesize and secrete progesterone (P(4)), a key hormone to maintain normal pregnancy and estrous cycle in most mammals. It is known that estrogen has a vital role in stimulating P(4) synthesis in CL, but it still remains unclear about the mechanism of estradiol (E(2)) regulating P(4) production in CL. Our results here first show that all of the CL cells express MAPK 8 (MAP3K8), and the MAP3K8 level is much higher at the midstage than at the early and late stages during CL development. The further functional studies show that the forced inhibition of endogenous MAP3K8 by using MAP3K8 small interfering RNA and MAP3K8 signaling inhibitor (MAP3K8i) in the luteal cells significantly block the P(4) synthesis and neutralize the enhancing effect of E(2) on P(4) production in the CL. In addition, our results here demonstrate that the stimulating effect of E(2) on P(4) synthesis relies on the estrogen no-classical protein-coupled receptor 30, and MAP3K8 is involved in mediating the protein-coupled receptor 30signaling of E(2) affecting P(4) synthesis via stimulating ERK phosphorylation. These novel findings are critical for our understanding the ovary physiology and pathological mechanism.

  2. Subcentimeter hypervascular nodules with typical imaging findings of hepatocellular carcinoma on gadoxetic acid-enhanced MRI: Outcomes of early treatment and watchful waiting

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Jung Han; Song, Kyoung Doo; Kim, Seong Hyun [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, 81 Irwon-Ro, Gangnam-Gu, Seoul (Korea, Republic of)

    2017-10-15

    To compare treatment outcomes of subcentimeter hypervascular nodules at high risk for developing into hepatocellular carcinomas (SHNHR) between early treatment and watchful waiting until progression to overt hepatocellular carcinoma (HCC) groups. SHNHRs were defined as subcentimeter hypervascular nodules with the usual imaging features of HCC on gadoxetic acid-enhanced magnetic resonance imaging (MRI). Among 63 patients with 74 SHNHRs, 27 (37 SHNHRs) received early treatment (treatment of < 1 cm nodules), and 36 (37 SHNHRs) underwent watchful waiting until progression to overt HCC. Risk factor analysis was performed for recurrence-free and local recurrence-free survival. Among the 36 patients who adopted watchful waiting, 33 eventually underwent treatment because their SHNHRs progressed to overt HCC. For recurrence-free survival, significant risk factors included number of previous treatments (HR, 1.181; p < 0.001), tumour number (HR, 1.943; p = 0.009), and α-feto protein level (HR, 1.005; p = 0.037) in the multivariate analyses. Treatment strategy was not a significant risk factor for recurrence-free survival. For local recurrence-free survival from the date of treatment, only treatment modality (transarterial chemoembolization) (HR, 6.879; p = 0.002) was a significant risk factor. Recurrence-free survival was not significantly different between early treatment and watchful waiting for SHNHRs. (orig.)

  3. 78 FR 13294 - Enhanced Prudential Standards and Early Remediation Requirements for Foreign Banking...

    Science.gov (United States)

    2013-02-27

    ... Prudential Standards and Early Remediation Requirements for Foreign Banking Organizations and Foreign Nonbank... 166 of the Act for foreign banking organizations and foreign nonbank financial companies supervised by... Prudential Standards and Early Remediation Requirements for Foreign Banking Organizations and Foreign Nonbank...

  4. Early-life risperidone enhances locomotor responses to amphetamine during adulthood.

    Science.gov (United States)

    Lee Stubbeman, Bobbie; Brown, Clifford J; Yates, Justin R; Bardgett, Mark E

    2017-10-05

    Antipsychotic drug prescriptions for pediatric populations have increased over the past 20 years, particularly the use of atypical antipsychotic drugs such as risperidone. Most antipsychotic drugs target forebrain dopamine systems, and early-life antipsychotic drug exposure could conceivably reset forebrain neurotransmitter function in a permanent manner that persists into adulthood. This study determined whether chronic risperidone administration during development modified locomotor responses to the dopamine/norepinephrine agonist, D-amphetamine, in adult rats. Thirty-five male Long-Evans rats received an injection of one of four doses of risperidone (vehicle, .3, 1.0, 3.0mg/kg) each day from postnatal day 14 through 42. Locomotor activity was measured for 1h on postnatal days 46 and 47, and then for 24h once a week over the next two weeks. Beginning on postnatal day 75, rats received one of four doses of amphetamine (saline, .3, 1.0, 3.0mg/kg) once a week for four weeks. Locomotor activity was measured for 27h after amphetamine injection. Rats administered risperidone early in life demonstrated increased activity during the 1 and 24h test sessions conducted prior to postnatal day 75. Taking into account baseline group differences, these same rats exhibited significantly more locomotor activity in response to the moderate dose of amphetamine relative to controls. These results suggest that early-life treatment with atypical antipsychotic drugs, like risperidone, permanently alters forebrain catecholamine function and increases sensitivity to drugs that target such function. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Early oral feeding after pancreatoduodenectomy enhances recovery without increasing morbidity

    Science.gov (United States)

    Gerritsen, Arja; Wennink, Roos A W; Besselink, Marc G H; van Santvoort, Hjalmar C; Tseng, Dorine S J; Steenhagen, Elles; Borel Rinkes, Inne H M; Molenaar, I Quintus

    2014-01-01

    Objective The aim of this study was to evaluate whether a change in the routine feeding strategy applied after pancreatoduodenectomy (PD) from nasojejunal tube (NJT) feeding to early oral feeding improved clinical outcomes. Methods An observational cohort study was performed in 102 consecutive patients undergoing PD. In period 1 (n = 51, historical controls), the routine postoperative feeding strategy was NJT feeding. This was changed to a protocol of early oral feeding with on-demand NJT feeding in period 2 (n = 51, consecutive prospective cohort). The primary outcome was time to resumption of adequate oral intake. Results The baseline characteristics of study subjects in both periods were comparable. In period 1, 98% (n = 50) of patients received NJT feeding, whereas in period 2, 53% (n = 27) of patients did so [for delayed gastric empting (DGE) (n = 20) or preoperative malnutrition (n = 7)]. The time to resumption of adequate oral intake significantly decreased from 12 days in period 1 to 9 days in period 2 (P = 0.015), and the length of hospital stay shortened from 18 days in period 1 to 13 days in period 2 (P = 0.015). Overall, there were no differences in the incidences of complications of Clavien–Dindo Grade III or higher, DGE, pancreatic fistula, postoperative haemorrhage and mortality between the two periods. Conclusions The introduction of an early oral feeding strategy after PD reduced the time to resumption of adequate oral intake and length of hospital stay without negatively impacting postoperative morbidity. PMID:24308458

  6. In situ monitoring of thermal crystallization of ultrathin tris(8-hydroxyquinoline) aluminum films using surface-enhanced Raman scattering.

    Science.gov (United States)

    Muraki, Naoki

    2014-01-01

    Thermal crystallization of 3, 10, and 60 nm-thick tris(8-hydroxyquinoline)aluminum (Alq3) films is studied using surface-enhanced Raman scattering with a constant heating rate. An abrupt higher frequency shift of the quinoline-stretching mode is found to be an indication of a phase transition of Alq3 molecules from amorphous to crystalline. While the 60 nm-thick film shows the same crystallization temperature as a bulk sample, the thinner films were found to have a lower crystallization temperature and slower rate of crystallization. Non-isothermal kinetics analysis is performed to quantify kinetic properties such as the Avrami exponent constants and crystallization rates of ultrathin Alq3 films.

  7. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes

    DEFF Research Database (Denmark)

    Petrovic, Natasa; Walden, Tomas B; Shabalina, Irina G

    2009-01-01

    The recent insight that brown adipocytes and muscle cells share a common origin and in this respect are distinct from white adipocytes has spurred questions concerning the origin and molecular characteristics of the UCP1-expressing cells observed in classic white adipose tissue depots under certain...... physiological or pharmacological conditions. Examining precursors from the purest white adipose tissue depot (epididymal), we report here that chronic treatment with the peroxisome proliferator-activated receptor gamma agonist rosiglitazone promotes not only the expression of PGC-1alpha and mitochondriogenesis...... associated with classic brown adipocytes (Zic1, Lhx8, Meox2, and characteristically PRDM16) or for myocyte-associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain white fat characteristics such as Hoxc9 expression. Co-culture experiments verify that the UCP1-expressing cells...

  8. The Implementation of Traditional Games to Improve the Social Emotional Early Childhood

    Directory of Open Access Journals (Sweden)

    Putu Indah Lestari

    2017-12-01

    Full Text Available The aims of this study was to improve the social emotional early childhood through the traditional game. This research was conducted on the children of group B TK Pradnyandari III Kerobokan in the academic year 2016 / 2017. This research used Classroom Action Research design with observation method. The subjects of this study were 22 children of group B1 TK Pradnyandari III Kerobokan consisting of 11 sons and 11 daughters. The object of research is the application of traditional children's games to increase social emotional early childhood. The results og this research as in Cycle I, 14 children (63.64% reached the completeness learning mastery, 8 children (36.36% had not reached. In Cycle II, 20 children (90,91% reached the learning mastery, leaving only 2 children (9,09% had not reached. The implementation of traditional games can enhance children's social emotional skill. Based on the research findings there was an improvement of 27.27% learning mastery of the children from Cycle I to Cycle II. This means that the application of traditional games can improve children's social emotional development. Traditional games can be piloted in other areas of development skill in early childhood education.

  9. Enhanced erythrocyte antioxidant status following an 8-week aerobic exercise training program in heavy drinkers.

    Science.gov (United States)

    Georgakouli, Kalliopi; Manthou, Eirini; Fatouros, Ioannis G; Georgoulias, Panagiotis; Deli, Chariklia K; Koutedakis, Yiannis; Theodorakis, Yannis; Jamurtas, Athanasios Z

    2018-06-01

    Alcohol-induced oxidative stress is involved in the development and progression of various pathological conditions and diseases. On the other hand, exercise training has been shown to improve redox status, thus attenuating oxidative stress-associated disease processes. The purpose of the present study was to evaluate the effect of an exercise training program that has been previously reported to decrease alcohol consumption on blood redox status in heavy drinkers. In a non-randomized within-subject design, 11 sedentary, heavily drinking men (age: 30.3 ± 3.5 years; BMI: 28.4 ± 0.86 kg/m 2 ) participated first in a control condition for 4 weeks, and then in an intervention where they completed an 8-week supervised aerobic training program of moderate intensity (50-60% of the heart rate reserve). Blood samples were collected in the control condition (pre-, post-control) as well as before, during (week 4 of the training program), and after intervention (week 8 of the training program). Samples were analyzed for total antioxidant capacity (TAC), thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), uric acid (UA), bilirubin, reduced glutathione (GSH), and catalase activity. No significant change in indices of redox status in the pre- and post-control was observed. Catalase activity increased (p program enhanced erythrocyte antioxidant status in heavy drinkers, indicating that aerobic training may attenuate pathological processes caused by alcohol-induced oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. CD4+ T cells are required to contain early extrathoracic TB dissemination and sustain multi-effector functions of CD8+ T and CD3− lymphocytes

    Science.gov (United States)

    Yao, Shuyu; Huang, Dan; Chen, Crystal Y.; Halliday, Lisa; Wang, Richard C.; Chen, Zheng W.

    2014-01-01

    The possibility that CD4+ T cells can act as “innate-like” cells to contain very-early M. tuberculosis (Mtb) dissemination and function as master helpers to sustain multiple effector functions of CD8+ T cells and CD3-negative lymphocytes during development of adaptive immunity against primary tuberculosis(TB) has not been demonstrated. We showed that pulmonary Mtb infection of CD4-depleted macaques surprisingly led to very-early extrathoracic Mtb dissemination, whereas CD4 deficiency clearly resulted in rapid TB progression. CD4 depletion during Mtb infection revealed the ability of CD8+ T cells to compensate and rapidly differentiate to Th17-like/Th1-like, and cytotoxic-like effectors, but these effector functions were subsequently unsustainable due to CD4 deficiency. While CD3-negative non-T lymphocytes in presence of CD4+ T cells developed predominant Th22-like and NK-like (perforin production) responses to Mtb infection, CD4 depletion abrogated these Th22-/NK-like effector functions and favored IL-17 production by CD3-negative lymphocytes. CD4-depleted macaques exhibited no or few pulmonary T effector cells constitutively producing IFN-γ, TNFα, IL-17, IL-22, and perforin at the endpoint of more severe TB, but presented pulmonary IL-4+ T effectors. TB granulomas in CD4-depleted macaques contained fewer IL-22+ and perforin+ cells despite presence of IL-17+ and IL-4+ cells. These results implicate previously-unknown “innate-like” ability of CD4+ T cells to contain extrathoracic Mtb dissemination at very early stage. Data also suggest that CD4+ T cells are required to sustain multiple effector functions of CD8+ T cells and CD3-negative lymphocytes and to prevent rapid TB progression during Mtb infection of nonhuman primates. PMID:24489088

  11. Comparison of early myocardial technetium-99m pyrophosphate uptake to early peaking of creatine kinase and creatine kinase-MB as indicators of early reperfusion in acute myocardial infarction

    International Nuclear Information System (INIS)

    Kondo, M.; Yuzuki, Y.; Arai, H.; Shimizu, K.; Morikawa, M.; Shimono, Y.

    1987-01-01

    The value of technetium-99m pyrophosphate (Tc-99m-PYP) scintigraphy as an indicator of reperfusion 2.8 to 8 hours after the onset of symptoms of acute myocardial infarction was compared with the value of early peak creatine kinase (CK) and CK-MB release within 16 hours after the onset of symptoms. In 29 patients who received thrombolytic therapy, recanalization was seen (group 1) and in 7 it was not (group 2). In 23 patients (79%) in group 1 scintigraphic findings were positive and in all 7 in group 2 they were negative. In 15 patients (52%) in group 1 and 1 patient (14%) in group 2, CK reached its peak level within 16 hours. In 20 patients (69%) in group 1 and 3 (43%) in group 2 the CK-MB level reached a peak within 16 hours. The sensitivity, specificity and predictive accuracy of positive results of early Tc-99m-PYP scintigraphy in predicting the reperfusion were 79%, 100% and 83%. These values are significantly higher than or similar to those of early peaking of CK and CK-MB release. In contrast to measurements of enzyme release, reperfusion data for Tc-99m-PYP scintigraphy are available immediately after thrombolytic therapy. Therefore, early Tc-99m-PYP scintigraphy (3 to 8 hours after onset of symptoms) is valuable as a noninvasive technique for early diagnosis of reperfusion

  12. Transcription factor cooperativity in early adipogenic hotspots and super-enhancers

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Rabiee, Atefeh; Nielsen, Ronni

    2014-01-01

    . Using a combination of advanced proteomics and genomics approaches, we identify ∼12,000 transcription factor hotspots (∼400 bp) in the early phase of adipogenesis, and we find evidence of both simultaneous and sequential binding of transcription factors at these regions. We demonstrate that hotspots...

  13. The diagnostic value of sacroiliac CT for detecting early changes of ankylosing spondylitis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ju Hyun; Park, Ji Seon; Ryu, Kyung Nam [Kyunghee University Medical Center, Seoul (Korea, Republic of); Jin, Wook [East-West Neo Medical Center, Seoul (Korea, Republic of)

    2007-02-15

    We wanted to evaluate the diagnostic value of the various findings on sacroiliac CT for detecting the early changes of ankylosing spondylitis (AS). Between April 2005 and March 2006, 51 sacroiliac CT images with the clinical suspicion of AS, but no definite evidence of AS on the plain radiograph only, were retrospectively reviewed. Finally, 36 patients (mean age: 28.6 years; 34 males and 2 females), who were clinically diagnosed as AS (AS group, n = 26) or they had no evidence of AS (non-AS group, n = 10), were evaluated. Two musculoskeletal radiologists analyzed the presence of marginal irregularity, bony erosion and subchondral sclerosis. A statistical analysis was performed to evaluate the incidence, sensitivity and specificity of each finding. Marginal irregularity was seen in 21 of 26 AS subjects, and in 8 of 10 non-AS subjects. Bony erosion was only seen in 13 of 26 AS subjects. Subchondral sclerosis was observed in 19 of 26 AS subjects and in 8 of 10 non-AS subjects. The sensitivity/specificity for each findings were 72.4%/28.6%, 100%/43.5% and 70.4%/22.2%, respectively. Except for bony erosions, these results showed no statistical significance ({rho} = .006). Bony erosion on CT is a very sensitive finding for the early changes of AS, whereas marginal irregularity or subchondral sclerosis is not so helpful in differentiating AS from non-AS. Attention to these results may further enhance the accurate diagnosis of the early changes in AS.

  14. Intrathecally enhanced spinal CT in the early diagnosis of cerebrospinal fluid-borne metastasis in pediatric patients with primary brain tumors

    International Nuclear Information System (INIS)

    Wang, H.; Rosenbaum, A.E.; Ahn, H.S.; Zinreich, S.J.; Diffley, D.M.; Killmond, T.A.; Strauss, L.C.

    1987-01-01

    Early diagnosis and treatment of asymptomatic intraspinal cerebrospinal fluid-borne metastases can obviate serious sequelae in pediatric patients with known intracranial tumors. MR imaging is a superior imaging modality; however, in very young patients who need general anesthesia for immobilization and also for evaluation of small subarachnoid seedings, the authors found CT to be a valuable alternative. Twelve patients ranging in age from 3 months to 13 years underwent CT screening of the entire spine after intrathecal enhancement with 3-5 ml of metrizamide (100 mg iodine per milliliter) via a lumbar puncture. Intrathecal spinal metastases were found in 67% of the studied patients and even in a patient whose MR imaging examination failed to disclose the lesion

  15. Bacillus amyloliquefaciens TSBSO 3.8, a biosurfactant-producing strain with biotechnological potential for microbial enhanced oil recovery.

    Science.gov (United States)

    Alvarez, Vanessa Marques; Jurelevicius, Diogo; Marques, Joana Montezano; de Souza, Pamella Macedo; de Araújo, Livia Vieira; Barros, Thalita Gonçalves; de Souza, Rodrigo Octavio Mendonça Alves; Freire, Denise Maria Guimarães; Seldin, Lucy

    2015-12-01

    A screening for biosurfactant-producing bacteria was conducted with 217 strains that were isolated from environmental samples contaminated with crude oil and/or petroleum derivatives. Although 19 promising biosurfactant producers were detected, strain TSBSO 3.8, which was identified by molecular methods as Bacillus amyloliquefaciens, drew attention for its production of a high-activity compound that presented an emulsification activity of 63% and considerably decreased surface (28.5 mN/m) and interfacial (11.4 mN/m) tensions in Trypticase Soy Broth culture medium. TSBSO 3.8 growth and biosurfactant production were tested under different physical and chemical conditions to evaluate its biotechnological potential. Biosurfactant production occurred between 0.5% and 7% NaCl, at pH values varying from 6 to 9 and temperatures ranging from 28 to 50 °C. Moreover, biosurfactant properties remained the same after autoclaving at 121 °C for 15 min. The biosurfactant was also successful in a test to simulate microbial enhanced oil recovery (MEOR). Mass spectrometry analysis showed that the surface active compound was a surfactin, known as a powerful biosurfactant that is commonly produced by Bacillus species. The production of a high-efficiency biosurfactant, under some physical and chemical conditions that resemble those experienced in an oil production reservoir, such as high salinities and temperatures, makes TSBSO 3.8 an excellent candidate and creates good expectations for its application in MEOR. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Bovine Lhx8, a Germ Cell-Specific Nuclear Factor, Interacts with Figla.

    Directory of Open Access Journals (Sweden)

    Liyuan Fu

    Full Text Available LIM homeobox 8 (Lhx8 is a germ cell-specific transcription factor essential for the development of oocytes during early oogenesis. In mice, Lhx8 deficiency causes postnatal oocyte loss and affects the expression of many oocyte-specific genes. The aims of this study were to characterize the bovine Lhx8 gene, determine its mRNA expression during oocyte development and early embryogenesis, and evaluate its interactions with other oocyte-specific transcription factors. The bovine Lhx8 gene encodes a protein of 377 amino acids. A splice variant of Lhx8 (Lhx8_v1 was also identified. The predicted bovine Lhx8 protein contains two LIM domains and one homeobox domain. However, one of the LIM domains in Lhx8_v1 is incomplete due to deletion of 83 amino acids near the N terminus. Both Lhx8 and Lhx8_v1 transcripts were only detected in the gonads but none of the somatic tissues examined. The expression of Lhx8 and Lhx8_v1 appears to be restricted to oocytes as none of the transcripts was detectable in granulosa or theca cells. The maternal Lhx8 transcript is abundant in GV and MII stage oocytes as well as in early embryos but disappear by morula stage. A nuclear localization signal that is required for the import of Lhx8 into nucleus was identified, and Lhx8 is predominantly localized in the nucleus when ectopically expressed in mammalian cells. Finally, a novel interaction between Lhx8 and Figla, another transcription factor essential for oogenesis, was detected. The results provide new information for studying the mechanisms of action for Lhx8 in oocyte development and early embryogenesis.

  17. TARGETING HYDROTHERMAL ALTERATIONS UTILIZING LANDSAT-8 ANDASTER DATA IN SHAHR-E-BABAK, IRAN

    Directory of Open Access Journals (Sweden)

    M. Safari

    2017-10-01

    Full Text Available Shahr-e-Babak tract of the Kerman metalogenic belt is one of the most potential segments of Urumieh–Dokhtar (Sahand-Bazman magmatic arc. This area encompasses several porphyry copper deposits in exploration, development and exploitation hierarchy. The aim of this study is to map hydrothermal alterations caused by early Cenozoic magmatic intrusions in Shahr-e-Babak area. To this purpose, mineral mapping methods including band combinations, ratios and multiplications as well as PCA and MNF data space transforms in SWIR and VNIR for both ASTER and OLI sensors. Alteration zones according to spectral signatures of each type of alteration mineral assemblages such as argillic, phyllic and propylitic are successfully mapped. For enhancing the target areas false color composites and HSI-RGB color space transform are performed on developed band combinations. Previous studies have proven the robust application of ASTER in geology and mineral exploration; nonetheless, the results of this investigation prove applicability of OLI sensor from landsat-8 for alteration mapping. According to the results, evidently OLI sensor data can accurately map alteration zones. Additionally, the 12-bit quantization of OLI data is its privilege over 8-bit data of ASTER in VNIR and SWIR, thus OLI high quality results, which makes it easy to distinguish targets with enhanced color contrast between the altered and unaltered rocks.

  18. Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease.

    Science.gov (United States)

    Schaeffer, Evelin L; Forlenza, Orestes V; Gattaz, Wagner F

    2009-01-01

    Alzheimer disease (AD) is the leading cause of dementia in the elderly and has no known cure. Evidence suggests that reduced activity of specific subtypes of intracellular phospholipases A2 (cPLA2 and iPLA2) is an early event in AD and may contribute to memory impairment and neuropathology in the disease. The objective of this study was to review the literature focusing on the therapeutic role of PLA2 stimulation by cognitive training and positive modulators, or of supplementation with arachidonic acid (PLA2 product) in facilitating memory function and synaptic transmission and plasticity in either research animals or human subjects. MEDLINE database was searched (no date restrictions) for published articles using the keywords Alzheimer disease (mild, moderate, severe), mild cognitive impairment, healthy elderly, rats, mice, phospholipase A(2), phospholipid metabolism, phosphatidylcholine, arachidonic acid, cognitive training, learning, memory, long-term potentiation, protein kinases, dietary lipid compounds, cell proliferation, neurogenesis, and neuritogenesis. Reference lists of the identified articles were checked to select additional studies of interest. Overall, the data suggest that PLA2 activation is induced in the healthy brain during learning and memory. Furthermore, learning seems to regulate endogenous neurogenesis, which has been observed in AD brains. Finally, PLA2 appears to be implicated in homeostatic processes related to neurite outgrowth and differentiation in both neurodevelopmental processes and response to neuronal injury. The use of positive modulators of PLA2 (especially of cPLA2 and iPLA2) or supplementation with dietary lipid compounds (e.g., arachidonic acid) in combination with cognitive training could be a valuable therapeutic strategy for cognitive enhancement in early-stage AD.

  19. Suggested MR staging classification of early rheumatoid arthritis at the metacarpophalangeal and proximal interphalangeal joints

    International Nuclear Information System (INIS)

    Scheck, R.J.; Hoischen, S.H.; Willemsen, U.F.; Pfluger, T.; Kueffer, G.; Krueger, K.; Schattenkirchner, M.; Hahn, K.

    1997-01-01

    Purpose: MRI can demonstrate pathology of joint disease in the early course of rheumatoid arthritis prior to destructions seen on conventional radiographs. In a prospective study, we tried to develop a systematical classification of joint pathology demonstrated by MRI, which would be essential for scoring the course of the disease. Patients and method: Metacarpophalangeal and interphalangeal joints of 48 patients suffering from early rheumatoid arthritis (mean disease duration: 6.4 months) were evaluated by MRI using a high-resolution transmitter-receiver coil. Examinations included 2 mm sliced T 2 -, T 1 - and gadolinium enhanced T 1 -SE sequences in coronal and axial orientation. In consideration of pathological findings on MRI and histopathogenetical pathways of destruction in rheumatoid arthritis a MR-score (0-5) was established. Results: This allowed to score each joint examined: Score 0 (normal) in 47.8%/49.5%, score 1 in 35.5%/50.5%, score 2 in 4.2%/0%, score 3 in 10.8%/0%, score 4 in 1.5%/0% of the metacarpophalangeal/interphalangeal joints, respectively. Conclusions: Using the MR-score a relative individual destruction number can be calculated, which may be used to follow up patients in the early course of rheumatoid arthritis (e.g. drug therapy studies). The presented MR scoring system has to be evaluated further in longitudinal studies and must be correlated to radiographical and clinical findings. (orig.) [de

  20. Beginning Windows 8.1

    CERN Document Server

    Halsey, Mike

    2013-01-01

    Windows 8 has been described by Microsoft as its 'boldest' Windows release ever and the 8.1 update enhances the paradigm further. Beginning Windows 8.1 takes you through the new features and helps you get more out of the familiar to reveal the fullest possibilities for this amazing new operating system. You will learn, with non-technical language used throughout, how to get up and running in the new Windows interface, minimize downtime, maximize productivity, and harness the features you never knew existed to take control of your computer and enjoy the peace of mind and excitement that comes w

  1. Evaluation on changes of early renal function in patients with diabetic nephropathy with contrast-enhanced ultrasound and its clinical significance

    International Nuclear Information System (INIS)

    Guo Xinmin; Jin Hong; Pan Liwen; Chen Hui; Liu Wei; Quan Xianyue

    2013-01-01

    Objective: To quantitatively assess the parameter alteration of renal blood flow in patients with diabetic nephropathy (DN) with the contrast-enhanced ultrasound (CEUS), and to evaluate value of the technique in diagnosis of early renal function changes of DN patients. Methods: 40 diabetic patients were equally divided into two group according to Mogensen's staging criteria: normal albuminuria group (group Ⅰ) and early DN group (group Ⅱ); and 15 cases of healthy volunteers were used as control group (N group) (n=15). All subjects were performed renal CEUS perfusion imaging, and QontraXt image analysis software was applied to select the region of interest (ROI) in the renal cortex. Then the time intensity curve (TIC) and kidney blood perfusion parameters were collected. Results: The renal blood perfusion was clearly shown in real time CEUS; compared with N group, the time to peak (TTP), regional blood volume (RBV), and mean transit time (MTT) of the patients in group Ⅰ were increased, there were significant differences (P<0.05); but there were no significant differences of derived peak intensity (DPI) and regional blood flow (RBF) between two groups (P>0.05). Compared with group Ⅰ and N group, the RBV, TTP and MTT of the patients were increased, the DPI and RBF were reduced in group Ⅱ, there were significant differences (P<0.05). Conclusion: The CEUS technical analysis can be used in evaluating renal abnormality of the DN patients in early period by showing the changes of renal perfusion parameters. (authors)

  2. Dynamic contrast-enhanced MRI evaluates the early response of human head and neck tumor xenografts following anti-EMMPRIN therapy with cisplatin or irradiation.

    Science.gov (United States)

    Kim, Hyunki; Hartman, Yolanda E; Zhai, Guihua; Chung, Thomas K; Korb, Melissa L; Beasley, Timothy M; Zhou, Tong; Rosenthal, Eben L

    2015-10-01

    To assess the early therapeutic effects of anti-EMMPRIN (extracellular matrix metalloprotease inducer) antibody with/without cisplatin or X-ray radiation in head and neck cancer mouse models using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Mice bearing SCC1 (or OSC19) tumor xenografts were treated with anti-EMMPRIN antibody, radiation, cisplatin, or anti-EMMPRIN antibody plus cisplatin (or radiation) for a week (n = 4-5 per group). DCE-MRI was carried out on a 9.4T small animal MR scanner on days 0, 3, and 7, and K(trans) values were averaged in a 0.5-mm-thick peripheral tumor region. Ki67 and CD31 staining were implemented for all tumors after imaging. The K(trans) changes of SCC1 and OSC19 tumors treated with anti-EMMPRIN antibody for 3 days were -18 ± 8% and 4 ± 7%, respectively, which were significantly lower than those of control groups (39 ± 5% and 45 ± 7%; P = 0.0025 and 0.0220, respectively). When cisplatin was added, those were -42 ± 9% and -44 ± 9%, respectively, and with radiation, -45 ± 9% and -27 ± 10%, respectively, which were also significantly lower than those of control groups (P EMMPRIN antibody with/without cisplatin or radiation, the mean K(trans) change for 3 days was significantly correlated with the mean tumor volume change for 7 days (r = 0.74, P = 0.0346), Ki67-expressing cell density (r = 0.96, P = 0.0001), and CD31 density (r = 0.84, P = 0.0084). DCE-MRI might be utilized to assess the early therapeutic effects of anti-EMMPRIN antibody with/without chemotherapy or radiotherapy in head and neck cancer. © 2015 Wiley Periodicals, Inc.

  3. SPL8 Acts Together with the Brassinosteroid-Signaling Component BIM1 in Controlling Arabidopsis thaliana Male Fertility

    Directory of Open Access Journals (Sweden)

    Shuping Xing

    2013-06-01

    Full Text Available The non-miR156 targeted SBP-box gene SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 8 (SPL8, plays an important role in Arabidopsis anther development, where its loss-of-function results in a semi-sterile phenotype. Fully male-sterile plants are obtained when a spl8 loss-of-function mutation is introduced into a 35S:MIR156 genetic background, thereby revealing functional redundancy between SPL8 and miR156-targeted SBP-box genes. Here, we show that BIM1, a gene encoding a bHLH protein involved in brassinosteroid signaling and embryonic patterning, functions redundantly with SPL8 in its requirement for male fertility. Although bim1 single mutants displayed a mild fertility problem due to shortened filaments in some flowers, mutation of BIM1 significantly enhanced the semi-sterile phenotype of the spl8 mutant. Expression of both SPL8 and BIM1 was detected in overlapping expression domains during early anther developmental stages. Our data suggest that in regulating anther development, SPL8 and BIM1 function cooperatively in a common complex or in synergistic pathways. Phylogenetic analysis supports the idea of an evolutionary conserved function for both genes in angiosperm anther development.

  4. Does copepods influence dusky grouper (Epinephelus marginatus early development?

    Directory of Open Access Journals (Sweden)

    Monica Mateus

    2014-06-01

    Full Text Available Good knowledge on the development of early life stages is essential for successful conservation programs of threatened fish species. Diet and rearing system affects early life survival and juvenile quality. Copepods are the natural food of fish larvae in the wild possessing high nutritional value, when compared with live feeds used in aquaculture (rotifers and artemia, and a wide range of size classes. Rearing systems with low water column disturbance and low larval densities enhanced the survival of fragile fish larvae. The aim of this work is to evaluate the effect of the introduction of copepods in the diet of early dusky grouper larvae reared in controlled mesocosm systems using larval development and juvenile quality as indicators. Two feeding protocols were tested, one composed only by rotifers (Brachionus plicatilis, brine shrimp (Artemia spp. and dry feed and the other supplemented with copepods (Paracartia grani from mouth opening (2 day after hatching - DAH to 8 DAH. Feeding behavior, growth, survival, skeletal malformations and digestive enzymes activity was assessed at different developmental stages. The addition of copepods to the early larvae diet of dusky grouper resulted in faster development and higher survival rates. Larvae fed with copepods improved their development. At 20 DAH all larvae reared at the mesocosm with copedods were already at the stage of post-flexion while in the system without copepods this stage was attained later. At 25 DAH only 64% of the larvae were in post flexion in the mesoscosm without copepods. At 30 DAH larvae supplemented with copepods attained an acidic digestion (high specific activity of pepsin earlier than at the system without copepods. In this last system alkaline digestion (trypsin specific activity, characteristic of early larval stages, was significantly higher reinforcing the faster development of larvae fed with copepods. In both systems the incidence of skeletal malformations was low.

  5. Human umbilical-cord-blood mononucleated cells enhance the survival of lethally irradiated mice. Dosage and the window of time

    International Nuclear Information System (INIS)

    Kovalenko, Olga A.; Ende, Norman; Azzam, Edouard I.

    2013-01-01

    The purpose of this study was to evaluate the window of time and dose of human umbilical-cord-blood (HUCB) mononucleated cells necessary for successful treatment of radiation injury in mice. Female A/J mice (27-30 weeks old) were exposed to an absorbed dose of 9-10 Gy of 137 Cs γ-rays delivered acutely to the whole body. They were treated either with 1 × 10 8 or 2 × 10 8 HUCB mononucleated cells at 24-52 h after the irradiation. The antibiotic Levaquin was applied 4 h postirradiation. The increased dose of cord-blood cells resulted in enhanced survival. The enhancement of survival in animals that received 2 × 10 8 HUCB mononucleated cells relative to irradiated but untreated animals was highly significant (P < 0.01). Compared with earlier studies, the increased dose of HUCB mononucleated cells, coupled with early use of an antibiotic, extended the window of time for effective treatment of severe radiation injury from 4 to 24-52 h after exposure. (author)

  6. Effects of Critical Thinking Intervention for Early Childhood Teacher Candidates

    Science.gov (United States)

    Han, Heejeong Sophia; Brown, E. Todd

    2013-01-01

    This study is based on an intervention designed to enhance early childhood teacher candidates' critical thinking abilities. The concept, elements, standards, and traits of critical thinking were integrated into the main course contents, and the effects of the intervention were examined. The results indicated that early childhood teacher…

  7. Genetic adjuvantation of recombinant MVA with CD40L potentiates CD8 T cell mediated immunity

    Directory of Open Access Journals (Sweden)

    Henning eLauterbach

    2013-08-01

    Full Text Available Modified vaccinia Ankara (MVA is a safe and promising viral vaccine vector that is currently investigated in several clinical and pre-clinical trials. In contrast to inactivated or sub-unit vaccines, MVA is able to induce strong humoral as well as cellular immune responses. In order to further improve its CD8 T cell inducing capacity, we genetically adjuvanted MVA with the coding sequence of murine CD40L, a member of the tumor necrosis factor (TNF superfamily. Immunization of mice with this new vector led to strongly enhanced primary and memory CD8 T cell responses. Concordant with the enhanced CD8 T cell response, we could detect stronger activation of dendritic cells and higher systemic levels of innate cytokines (including IL-12p70 early after immunization. Interestingly, acquisition of memory characteristics (i.e., IL-7R expression was accelerated after immunization with MVA-CD40L in comparison to non-adjuvanted MVA. Furthermore, the generated CTLs also showed improved functionality as demonstrated by intracellular cytokine staining and in vivo killing activity. Importantly, the superior CTL response after a single MVA-CD40L immunization was able to protect B cell deficient mice against a fatal infection with ectromelia virus. Taken together, we show that genetic adjuvantation of MVA can change strength, quality and functionality of innate and adaptive immune responses. These data should facilitate a rational vaccine design with a focus on rapid induction of large numbers of CD8 T cells able to protect against specific diseases.

  8. Multimedia support of early literacy learning

    NARCIS (Netherlands)

    Segers, P.C.J.; Verhoeven, L.T.W.

    2002-01-01

    In the present article, the development of a child-friendly computer software program to enhance the early literacy skills of kindergarteners in the Netherlands is described. The ergonomic aspects of designing software for young children are described along with the content of the program in

  9. Variation of oxygen enhancement ratio with radiation dose studies using 8 MeV electron beam

    International Nuclear Information System (INIS)

    Yerol, Narayana; Nairy, Rajesha K.; Sanjeev, Ganesh

    2014-01-01

    The radiobiological effects can be modified by physical, chemical and biological factors. Oxygen is one of the best known modifiers, and the biological effects are greater in the presence of oxygen. Failure to achieve complete response following radiotherapy of large tumors is attributed to the presence of radio-resistant hypoxic cells; therefore clarifying the mechanism of the oxygen effect is important. In the present study, an attempt was made to quantify Oxygen Enhancement Ratio (OER) and variation of OER as a function of dose with experimental and theoretical formulations using Saccharomyces cerevisiae D7, X2180 and rad 52 and 8 MeV electron beam from Microtron accelerator. The single cell stationary-phase cultures were obtained by growing the cells in Yeast extract: Peptone: Dextrose (YEPD) (1%:2%:2%) medium for several generations in stationary phase to a density of approximately 3 x 10 8 cells mL -1 . Cells were washed thrice by centrifugation and re-suspended to a cell concentration of 1 x 10 8 cells mL -1 in a sterile polypropylene vial for irradiation. Hypoxic conditions were achieved by incubating the samples in air tight vials at 30℃ for 30 min prior to irradiation. For euoxic samples, a cell suspension of 1 x 10 6 cells mL -1 was prepared and was thoroughly aerated by mixing before irradiation. Treated and untreated samples were suitably diluted and plated in quadruplicate on YEPD agar medium. Plates were incubated for 2-3 days at 30℃ in dark and normal atmospheric conditions and the colonies were counted. The study confirmed that, the variation of OER with dose depends upon type of cell and repair proficiency of cells. For repair proficient cells OER value has been found to increase with dose, while remain constant for repair deficient cell lines. A theoretical model has been formulated to estimate OER values. The OER value varies from 1.51 to 2.53 for D7, 2.02 to 2.98 for X2180, and 2.58 for rad 52. (author)

  10. Sympathetic activation during early pregnancy in humans

    Science.gov (United States)

    Jarvis, Sara S; Shibata, Shigeki; Bivens, Tiffany B; Okada, Yoshiyuki; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2012-01-01

    Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min−1, 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min−1; main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm−5; P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.−1 min−1; P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml−1, P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml−1, P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications. PMID:22687610

  11. Role of alveolar epithelial Early growth response-1 (Egr-1) in CD8+ T Cell mediated Lung Injury

    Science.gov (United States)

    Ramana, Chilakamarti V.; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung- Joo; Enelow, Richard I.

    2009-01-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8+ T cells in this injury, and have found that the critical effector molecule is TNF-α expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8+ T cell recognition, and demonstrate that the Early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-α– dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection. PMID:19786304

  12. Role of alveolar epithelial early growth response-1 (Egr-1) in CD8+ T cell-mediated lung injury.

    Science.gov (United States)

    Ramana, Chilakamarti V; Cheng, Guang-Shing; Kumar, Aseem; Kwon, Hyung-Joo; Enelow, Richard I

    2009-12-01

    Influenza infection of the distal airways results in severe lung injury, a considerable portion of which is immunopathologic and attributable to the host responses. We have used a mouse model to specifically investigate the role of antiviral CD8(+) T cells in this injury, and have found that the critical effector molecule is TNF-alpha expressed by the T cells upon antigen recognition. Interestingly, the immunopathology which ensues is characterized by significant accumulation of host inflammatory cells, recruited by chemokines expressed by the target alveolar epithelial cells. In this study we analyzed the mechanisms involved in the induction of epithelial chemokine expression triggered by antigen-specific CD8(+) T cell recognition, and demonstrate that the early growth response-1 (Egr-1) transcription factor is rapidly induced in epithelial cells, both in vitro and ex vivo, and that this is a critical regulator of a host of inflammatory chemokines. Genetic deficiency of Egr-1 significantly abrogates both the chemokine expression and the immunopathologic injury associated with T cell recognition, and it directly regulates transcriptional activity of a model CXC chemokine, MIP-2. We further demonstrate that Egr-1 induction is triggered by TNF-alpha-dependent ERK activation, and inhibition of this pathway ablates Egr-1 expression. These findings suggest that Egr-1 may represent an important target in mitigating the immunopathology of severe influenza infection.

  13. Enhanced plastochromanol-8 accumulation during reiterated drought in maize (Zea mays L.).

    Science.gov (United States)

    Fleta-Soriano, Eva; Munné-Bosch, Sergi

    2017-03-01

    Plastochromanol-8 (PC-8) belongs to the group of tocochromanols, and together with tocopherols and carotenoids, might help protect photosystem II from photoinhibition during environmental stresses. Here, we aimed to unravel the time course evolution of PC-8 together with that of vitamin E compounds, in maize (Zea mays L.) plants exposed to reiterated drought. Measurements were performed in plants grown in a greenhouse subjected to two consecutive cycles of drought-recovery. PC-8 contents, which accounted for more than 25% of tocochromanols in maize leaves, increased progressively in response to reiterated drought stress. PC-8 contents paralleled with those of vitamin E, particularly α-tocopherol. Profiling of the stress-related phytohormones (ABA, jasmonic acid and salicylic acid) was consistent with a role of ABA in the regulation of PC-8 and vitamin E biosynthesis during drought stress. Results also suggest that PC-8 may help tocopherols prevent damage to the photosynthetic apparatus. A better knowledge of the ABA-dependent regulation of PC-8 may help us manipulate the contents of this important antioxidant in crops. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Possible role of oceanic heat transport in early Eocene climate

    Science.gov (United States)

    Sloan, L. C.; Walker, J. C.; Moore, T. C. Jr

    1995-01-01

    Increased oceanic heat transport has often been cited as a means of maintaining warm high-latitude surface temperatures in many intervals of the geologic past, including the early Eocene. Although the excess amount of oceanic heat transport required by warm high latitude sea surface temperatures can be calculated empirically, determining how additional oceanic heat transport would take place has yet to be accomplished. That the mechanisms of enhanced poleward oceanic heat transport remain undefined in paleoclimate reconstructions is an important point that is often overlooked. Using early Eocene climate as an example, we consider various ways to produce enhanced poleward heat transport and latitudinal energy redistribution of the sign and magnitude required by interpreted early Eocene conditions. Our interpolation of early Eocene paleotemperature data indicate that an approximately 30% increase in poleward heat transport would be required to maintain Eocene high-latitude temperatures. This increased heat transport appears difficult to accomplish by any means of ocean circulation if we use present ocean circulation characteristics to evaluate early Eocene rates. Either oceanic processes were very different from those of the present to produce the early Eocene climate conditions or oceanic heat transport was not the primary cause of that climate. We believe that atmospheric processes, with contributions from other factors, such as clouds, were the most likely primary cause of early Eocene climate.

  15. The enhanced value of combining conventional and 'omics' analyses in early assessment of drug-induced hepatobiliary injury

    International Nuclear Information System (INIS)

    Ellinger-Ziegelbauer, Heidrun; Adler, Melanie; Amberg, Alexander; Brandenburg, Arnd; Callanan, John J.; Connor, Susan; Fountoulakis, Michael; Gmuender, Hans; Gruhler, Albrecht; Hewitt, Philip; Hodson, Mark; Matheis, Katja A.; McCarthy, Diane; Raschke, Marian; Riefke, Bjoern; Schmitt, Christina S.; Sieber, Max; Sposny, Alexandra; Suter, Laura; Sweatman, Brian

    2011-01-01

    The InnoMed PredTox consortium was formed to evaluate whether conventional preclinical safety assessment can be significantly enhanced by incorporation of molecular profiling ('omics') technologies. In short-term toxicological studies in rats, transcriptomics, proteomics and metabolomics data were collected and analyzed in relation to routine clinical chemistry and histopathology. Four of the sixteen hepato- and/or nephrotoxicants given to rats for 1, 3, or 14 days at two dose levels induced similar histopathological effects. These were characterized by bile duct necrosis and hyperplasia and/or increased bilirubin and cholestasis, in addition to hepatocyte necrosis and regeneration, hepatocyte hypertrophy, and hepatic inflammation. Combined analysis of liver transcriptomics data from these studies revealed common gene expression changes which allowed the development of a potential sequence of events on a mechanistic level in accordance with classical endpoint observations. This included genes implicated in early stress responses, regenerative processes, inflammation with inflammatory cell immigration, fibrotic processes, and cholestasis encompassing deregulation of certain membrane transporters. Furthermore, a preliminary classification analysis using transcriptomics data suggested that prediction of cholestasis may be possible based on gene expression changes seen at earlier time-points. Targeted bile acid analysis, based on LC-MS metabonomics data demonstrating increased levels of conjugated or unconjugated bile acids in response to individual compounds, did not provide earlier detection of toxicity as compared to conventional parameters, but may allow distinction of different types of hepatobiliary toxicity. Overall, liver transcriptomics data delivered mechanistic and molecular details in addition to the classical endpoint observations which were further enhanced by targeted bile acid analysis using LC/MS metabonomics.

  16. Contrast-enhanced dynamic and diffusion-weighted magnetic resonance imaging at 3.0 T to assess early-stage nasopharyngeal carcinoma.

    Science.gov (United States)

    Ni, Liangping; Liu, Ying

    2018-04-01

    The present study aimed to assess early-stage nasopharyngeal carcinoma (NPC) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) at 3.0 T. A total of 44 patients newly diagnosed with NPC were included in the present study. All patients underwent MR examination at 3.0 T using DCE-MRI and DWI. The volume transfer constant ( K trans ), flux rate constant between extravascular extracellular space and plasma ( K ep ), the volume of extravascular extracellular space per unit volume of tissue ( V e ) and the apparent diffusion coefficient (ADC) of tumours were investigated. Furthermore, the correlation between clinical stages and ADC value and K trans were analysed. The diagnostic accuracy of K trans and ADC were estimated using receiver operating characteristic curves. NPC stage correlated positively with K trans and negatively with ADC values. Additionally, tumour K trans negatively correlated with ADC value. The sensitivity and accuracy of combined K trans and ADC in distinguishing between stage II and stage III and stage III and IV were higher than the values of either measurement used separately. The present study suggested that K trans and ADC derived from DCE-MRI and DWI may be useful to detect stage early NPC accurately. K trans and ADC in combination were superior than either alone.

  17. TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy.

    Science.gov (United States)

    Shintani, Nahoko; Siebenrock, Klaus A; Hunziker, Ernst B

    2013-01-01

    Synovial explants furnish an in-situ population of mesenchymal stem cells for the repair of articular cartilage. Although bone morphogenetic protein 2 (BMP-2) induces the chondrogenesis of bovine synovial explants, the cartilage formed is neither homogeneously distributed nor of an exclusively hyaline type. Furthermore, the downstream differentiation of chondrocytes proceeds to the stage of terminal hypertrophy, which is inextricably coupled with undesired matrix mineralization. With a view to optimizing BMP-2-induced chondrogenesis, the modulating influences of fibroblast growth factor 2 (FGF-2) and transforming growth factor beta 1 (TGF-ß1) were investigated. Explants of bovine calf metacarpal synovium were exposed to BMP-2 (200 ng/ml) for 4 (or 6) weeks. FGF-2 (10 ng/ml) or TGF-ß1 (10 ng/ml) was introduced at the onset of incubation and was present either during the first week of culturing alone or throughout its entire course. FGF-2 enhanced the BMP-2-induced increase in metachromatic staining for glycosaminoglycans (GAGs) only when it was present during the first week of culturing alone. TGF-ß1 enhanced not only the BMP-2-induced increase in metachromasia (to a greater degree than FGF-2), but also the biochemically-assayed accumulation of GAGs, when it was present throughout the entire culturing period; in addition, it arrested the downstream differentiation of cells at an early stage of hypertrophy. These findings were corroborated by an analysis of the gene- and protein-expression levels of key cartilaginous markers and by an estimation of individual cell volume. TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants, improves the hyaline-like properties of the neocartilage, and arrests the downstream differentiation of cells at an early stage of hypertrophy. With the prospect of engineering a mature, truly articular type of cartilage in the context of clinical repair, our findings will be of importance in fine-tuning the

  18. TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy.

    Directory of Open Access Journals (Sweden)

    Nahoko Shintani

    Full Text Available Synovial explants furnish an in-situ population of mesenchymal stem cells for the repair of articular cartilage. Although bone morphogenetic protein 2 (BMP-2 induces the chondrogenesis of bovine synovial explants, the cartilage formed is neither homogeneously distributed nor of an exclusively hyaline type. Furthermore, the downstream differentiation of chondrocytes proceeds to the stage of terminal hypertrophy, which is inextricably coupled with undesired matrix mineralization. With a view to optimizing BMP-2-induced chondrogenesis, the modulating influences of fibroblast growth factor 2 (FGF-2 and transforming growth factor beta 1 (TGF-ß1 were investigated.Explants of bovine calf metacarpal synovium were exposed to BMP-2 (200 ng/ml for 4 (or 6 weeks. FGF-2 (10 ng/ml or TGF-ß1 (10 ng/ml was introduced at the onset of incubation and was present either during the first week of culturing alone or throughout its entire course. FGF-2 enhanced the BMP-2-induced increase in metachromatic staining for glycosaminoglycans (GAGs only when it was present during the first week of culturing alone. TGF-ß1 enhanced not only the BMP-2-induced increase in metachromasia (to a greater degree than FGF-2, but also the biochemically-assayed accumulation of GAGs, when it was present throughout the entire culturing period; in addition, it arrested the downstream differentiation of cells at an early stage of hypertrophy. These findings were corroborated by an analysis of the gene- and protein-expression levels of key cartilaginous markers and by an estimation of individual cell volume.TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants, improves the hyaline-like properties of the neocartilage, and arrests the downstream differentiation of cells at an early stage of hypertrophy. With the prospect of engineering a mature, truly articular type of cartilage in the context of clinical repair, our findings will be of importance in fine-tuning the

  19. DART-bid: dose-differentiated accelerated radiation therapy, 1.8 Gy twice daily. High local control in early stage (I/II) non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Zehentmayr, Franz; Wurstbauer, Karl; Deutschmann, Heinz; Sedlmayer, Felix; Fussl, Christoph; Kopp, Peter; Dagn, Karin; Fastner, Gerd; Porsch, Peter; Studnicka, Michael

    2015-01-01

    While surgery is considered standard of care for early stage (I/II), non-small-cell lung cancer (NSCLC), radiotherapy is a widely accepted alternative for medically unfit patients or those who refuse surgery. International guidelines recommend several treatment options, comprising stereotactic body radiation therapy (SBRT) for small tumors, conventional radiotherapy ≥ 60 Gy for larger sized especially centrally located lesions or continuous hyperfractionated accelerated RT (CHART). This study presents clinical outcome and toxicity for patients treated with a dose-differentiated accelerated schedule using 1.8 Gy bid (DART-bid). Between April 2002 and December 2010, 54 patients (median age 71 years, median Karnofsky performance score 70 %) were treated for early stage NSCLC. Total doses were applied according to tumor diameter: 73.8 Gy for 6 cm. The median follow-up was 28.5 months (range 2-108 months); actuarial local control (LC) at 2 and 3 years was 88 %, while regional control was 100 %. There were 10 patients (19 %) who died of the tumor, and 18 patients (33 %) died due to cardiovascular or pulmonary causes. A total of 11 patients (20 %) died intercurrently without evidence of progression or treatment-related toxicity at the last follow-up, while 15 patients (28 %) are alive. Acute esophagitis ≤ grade 2 occurred in 7 cases, 2 patients developed grade 2 chronic pulmonary fibrosis. DART-bid yields high LC without significant toxicity. For centrally located and/or large (> 5 cm) early stage tumors, where SBRT is not feasible, this method might serve as radiotherapeutic alternative to present treatment recommendations, with the need of confirmation in larger cohorts. (orig.) [de

  20. The Role of the Heat Shock Protein B8 (HSPB8 in Motoneuron Diseases

    Directory of Open Access Journals (Sweden)

    Paola Rusmini

    2017-06-01

    Full Text Available Amyotrophic lateral sclerosis (ALS and spinal and bulbar muscular atrophy (SBMA are two motoneuron diseases (MNDs characterized by aberrant protein behavior in affected cells. In familial ALS (fALS and in SBMA specific gene mutations lead to the production of neurotoxic proteins or peptides prone to misfold, which then accumulate in form of aggregates. Notably, some of these proteins accumulate into aggregates also in sporadic ALS (sALS even if not mutated. To prevent proteotoxic stresses detrimental to cells, misfolded and/or aggregated proteins must be rapidly removed by the protein quality control (PQC system. The small heat shock protein B8 (HSPB8 is a chaperone induced by harmful events, like proteasome inhibition. HSPB8 is expressed both in motoneuron and muscle cells, which are both targets of misfolded protein toxicity in MNDs. In ALS mice models, in presence of the mutant proteins, HSPB8 is upregulated both in spinal cord and muscle. HSPB8 interacts with the HSP70 co-chaperone BAG3 and enhances the degradation of misfolded proteins linked to sALS, or causative of fALS and of SBMA. HSPB8 acts by facilitating autophagy, thereby preventing misfolded protein accumulation in affected cells. BAG3 and BAG1 compete for HSP70-bound clients and target them for disposal to the autophagy or proteasome, respectively. Enhancing the selective targeting of misfolded proteins by HSPB8-BAG3-HSP70 to autophagy may also decrease their delivery to the proteasome by the BAG1-HSP70 complex, thereby limiting possible proteasome overwhelming. Thus, approaches aimed at potentiating HSPB8-BAG3 may contribute to the maintenance of proteostasis and may delay MNDs progression.

  1. Early presentation of primary glioblastoma.

    Science.gov (United States)

    Faguer, R; Tanguy, J-Y; Rousseau, A; Clavreul, A; Menei, P

    2014-08-01

    Clinical and neuroimaging findings of glioblastomas (GBM) at an early stage have rarely been described and those tumors are most probably under-diagnosed. Furthermore, their genetic alterations, to our knowledge, have never been previously reported. We report the clinical as well as neuroimaging findings of four early cases of patients with GBM. In our series, early stage GBM occurred at a mean age of 57 years. All patients had seizures as their first symptom. In all early stages, MRI showed a hyperintense signal on T2-weighted sequences and an enhancement on GdE-T1WI sequences. A hyperintense signal on diffusion sequences with a low ADC value was also found. These early observed occurrences of GBM developed rapidly and presented the MRI characteristics of classic GBM within a few weeks. The GBM size was multiplied by 32 in one month. Immunohistochemical analysis indicated the de novo nature of these tumors, i.e. absence of mutant IDH1 R132H protein expression, which is a diagnostic marker of low-grade diffuse glioma and secondary GBM. A better knowledge of early GBM presentation would allow a more suitable management of the patients and may improve their prognosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Expression patterns of Xenopus FGF receptor-like 1/nou-darake in early Xenopus development resemble those of planarian nou-darake and Xenopus FGF8.

    Science.gov (United States)

    Hayashi, Shuichi; Itoh, Mari; Taira, Sumiko; Agata, Kiyokazu; Taira, Masanori

    2004-08-01

    Fibroblast growth factors (FGFs) mediate many cell-to-cell signaling events during early development. Nou-darake (ndk), a gene encoding an FGF receptor (FGFR)-like molecule, was found to be highly and specifically expressed in the head region of the planarian Dugesia japonica, and its functional analyses provided strong molecular evidence for the existence of a brain-inducing circuit based on the FGF signaling pathway. To analyze the role of ndk during vertebrate development, we isolated the Xenopus ortholog of ndk, the vertebrate FGFR-like 1 gene (XFGFRL1). Expression of XFGFRL1/Xndk was first detected in the anterior region at the late gastrula stage and dramatically increased at the early neurula stage in an overall anterior mesendodermal region, including the prechordal plate, paraxial mesoderm, anterior endoderm, and archenteron roof. This anterior expression pattern resembles that of ndk in planarians, suggesting that the expression of FGFRL1/ndk is conserved in evolution between these two distantly diverged organisms. During the tail bud stages, XFGFRL1/Xndk expression was detected in multiple regions, including the forebrain, eyes, midbrain-hindbrain boundary, otic vesicles, visceral arches, and somites. In many of these regions, XFGFRL1/Xndk was coexpressed with XFGF8, indicating that XFGFRL1/Xndk is a member of the XFGF8 synexpression group, which includes sprouty, sef, and isthmin. Copyright 2004 Wiley-Liss, Inc.

  3. Early prediction of adverse events in enhanced recovery based upon the host systemic inflammatory response.

    Science.gov (United States)

    Lane, J C; Wright, S; Burch, J; Kennedy, R H; Jenkins, J T

    2013-02-01

    Early identification of patients experiencing postoperative complications is imperative for successful management. C-reactive protein (CRP) is a nonspecific marker of inflammation used in many specialties to monitor patient condition. The role of CRP measurement early in the elective postoperative colorectal patient is unclear, particularly in the context of enhanced recovery (ERAS). Five hundred and thirty-three consecutive patients who underwent elective colorectal surgery between October 2008 and October 2010 within an established ERAS programme were studied. Patients were separated into a development group of 265 patients and a validation group of 268 patients by chronological order. CRP and white cell count were added to a prospectively maintained ERAS database. The primary outcome of the study was all adverse events (including infective complications, postoperative organ dysfunction and prolonged length of stay) during the initial hospital admission. Significant predictors for adverse events on univariate analysis were submitted to multivariate regression analysis and the resulting model applied to the validation group. The validity and predictive accuracy of the regression model was assessed using receiver operating characteristic curve/area under the curve (AUC) analysis. CRP levels >150 mg/l on postoperative day 2 and a rising CRP on day 3 were independently associated with all adverse events during the hospital admission. A weighted model was applied to the validation group yielding an AUC of 0.65 (95% CI 0.58-0.73) indicating, at best, modest discrimination and predictive accuracy for adverse events. Measurement of CRP in patients after elective colorectal surgery in the first few days after surgery within ERAS can assist in identifying those at risk of adverse events and a prolonged hospital stay. A CRP value of >150 mg/l on day 2 and a rising CRP on day 3 should alert the surgeon to an increased likelihood of such events. © 2012 The Authors

  4. Natural course of early COPD

    Directory of Open Access Journals (Sweden)

    Rhee CK

    2017-02-01

    Full Text Available Chin Kook Rhee,1 Kyungjoo Kim,1 Hyoung Kyu Yoon,2 Jee-Ae Kim,3 Sang Hyun Kim,4 Sang Haak Lee,5 Yong Bum Park,6 Ki-Suck Jung,7 Kwang Ha Yoo,8 Yong Il Hwang7 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Pharmaceutical Policy Evaluation Research Team, Research Institution, 4Big Data Division, Health Insurance Review and Assessment Service, Wonju, 5Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, 6Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background and objective: Few studies have examined the natural course of early COPD. The aim of this study was to observe the natural course of early COPD patients. We also aimed to analyze medical utilization and costs for early COPD during a 6-year period. Methods: Patients with early COPD were selected from Korean National Health and Nutrition Examination Survey (KNHANES data. We linked the KNHANES data of patients with early COPD to National Health Insurance data. Results: A total of 2,397 patients were enrolled between 2007 and 2012. The mean forced expiratory volume in 1 second (FEV1 was 78.6%, and the EuroQol five dimensions questionnaire (EQ-5D index value was 0.9. In total, 110 patients utilized health

  5. Enhanced early visual processing in response to snake and trypophobic stimuli

    NARCIS (Netherlands)

    J.W. van Strien (Jan); Van der Peijl, M.K. (Manja K.)

    2018-01-01

    textabstractBackground: Trypophobia refers to aversion to clusters of holes. We investigated whether trypophobic stimuli evoke augmented early posterior negativity (EPN). Methods: Twenty-four participants filled out a trypophobia questionnaire and watched the random rapid serial presentation of 450

  6. Delayed enhancement of peripheral zone of neurofibromas at magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kurosaki, Y. [Dept. of Radiology, Inst. of Clinical Medicine, Univ. of Tsukuba (Japan); Kuramoto, K. [Dept. of Radiology, Inst. of Clinical Medicine, Univ. of Tsukuba (Japan); Itai, Y. [Dept. of Radiology, Inst. of Clinical Medicine, Univ. of Tsukuba (Japan)

    1996-02-01

    It is well known that bizonal histologic appearance characteristic of neurofibromas are reflected on magnetic resonance (MR) images. We report a case in which a delayed enhanced MR image showed that the entire mass enhanced homogeneously resulting in loss of zonal distinction on early enhanced MR image. (orig.)

  7. Salivary cytokine levels in early gingival inflammation

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

    2017-01-01

    Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte chemoattr......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte...

  8. The diagnostic sensitivity of dengue rapid test assays is significantly enhanced by using a combined antigen and antibody testing approach.

    Directory of Open Access Journals (Sweden)

    Scott R Fry

    2011-06-01

    Full Text Available BACKGROUND: Serological tests for IgM and IgG are routinely used in clinical laboratories for the rapid diagnosis of dengue and can differentiate between primary and secondary infections. Dengue virus non-structural protein 1 (NS1 has been identified as an early marker for acute dengue, and is typically present between days 1-9 post-onset of illness but following seroconversion it can be difficult to detect in serum. AIMS: To evaluate the performance of a newly developed Panbio® Dengue Early Rapid test for NS1 and determine if it can improve diagnostic sensitivity when used in combination with a commercial IgM/IgG rapid test. METHODOLOGY: The clinical performance of the Dengue Early Rapid was evaluated in a retrospective study in Vietnam with 198 acute laboratory-confirmed positive and 100 negative samples. The performance of the Dengue Early Rapid in combination with the IgM/IgG Rapid test was also evaluated in Malaysia with 263 laboratory-confirmed positive and 30 negative samples. KEY RESULTS: In Vietnam the sensitivity and specificity of the test was 69.2% (95% CI: 62.8% to 75.6% and 96% (95% CI: 92.2% to 99.8 respectively. In Malaysia the performance was similar with 68.9% sensitivity (95% CI: 61.8% to 76.1% and 96.7% specificity (95% CI: 82.8% to 99.9% compared to RT-PCR. Importantly, when the Dengue Early Rapid test was used in combination with the IgM/IgG test the sensitivity increased to 93.0%. When the two tests were compared at each day post-onset of illness there was clear differentiation between the antigen and antibody markers. CONCLUSIONS: This study highlights that using dengue NS1 antigen detection in combination with anti-glycoprotein E IgM and IgG serology can significantly increase the sensitivity of acute dengue diagnosis and extends the possible window of detection to include very early acute samples and enhances the clinical utility of rapid immunochromatographic testing for dengue.

  9. Contrast-enhanced MDCT gastrography for detection of early gastric cancer: Initial assessment of “wall-carving image”, a novel volume rendering technique

    International Nuclear Information System (INIS)

    Komori, Masahiro; Kawanami, Satoshi; Tsurumaru, Daisuke; Matsuura, Shuji; Hiraka, Kiyohisa; Nishie, Akihiro; Honda, Hiroshi

    2012-01-01

    Objective: We developed a new volume rendering technique, the CT gastrography wall carving image (WC) technique, which provides a clear visualization of localized enhanced tumors in the gastric wall. We evaluated the diagnostic performance of the WC as an adjunct to conventional images in detecting early gastric cancer (EGC). Materials and methods: Thirty-nine patients with 43 EGCs underwent contrast-enhanced MDCT gastrography for preoperative examination. Two observers independently reviewed the images under three different conditions: term 1, Axial CT; term 2, Axial CT, MPR and VE; and term 3, Axial CT, MPR, VE and WC for the detection of EGC. The accuracy of each condition as reviewed by each of the two observers was evaluated by receiver operating characteristic analysis. Interobserver agreement was calculated using weighted-κ statistics. Results: The best diagnostic performance and interobserver agreement were obtained in term 3. The AUCs of the two observers for terms 1, 2, and 3 were 0.63, 0.73, and 0.84, and 0.57, 0.73, and 0.76, respectively. The interobserver agreement improved from fair at term 1 to substantial at term 3. Conclusions: The addition of WC to conventional MDCT display improved the diagnostic accuracy and interobserver reproducibility for the detection of ECG. WC represents a suitable alternative for the visualization of localized enhanced tumors in the gastric wall.

  10. Children's Early Approaches to Learning and Academic Trajectories through Fifth Grade

    Science.gov (United States)

    Li-Grining, Christine P.; Votruba-Drzal, Elizabeth; Maldonado-Carreno, Carolina; Haas, Kelly

    2010-01-01

    Children's early approaches to learning (ATL) enhance their adaptation to the demands they experience with the start of formal schooling. The current study uses individual growth modeling to investigate whether children's early ATL, which includes persistence, emotion regulation, and attentiveness, explain individual differences in their academic…

  11. Quantitative analysis of enhanced malignant and benign lesions on contrast-enhanced spectral mammography.

    Science.gov (United States)

    Deng, Chih-Ying; Juan, Yu-Hsiang; Cheung, Yun-Chung; Lin, Yu-Ching; Lo, Yung-Feng; Lin, GiGin; Chen, Shin-Cheh; Ng, Shu-Hang

    2018-02-27

    To retrospectively analyze the quantitative measurement and kinetic enhancement among pathologically proven benign and malignant lesions using contrast-enhanced spectral mammography (CESM). We investigated the differences in enhancement between 44 benign and 108 malignant breast lesions in CESM, quantifying the extent of enhancements and the relative enhancements between early (between 2-3 min after contrast medium injection) and late (3-6 min) phases. The enhancement was statistically stronger in malignancies compared to benign lesions, with good performance by the receiver operating characteristic curve [0.877, 95% confidence interval (0.813-0.941)]. Using optimal cut-off value at 220.94 according to Youden index, the sensitivity was 75.9%, specificity 88.6%, positive likelihood ratio 6.681, negative likelihood ratio 0.272 and accuracy 82.3%. The relative enhancement patterns of benign and malignant lesions, showing 29.92 vs 73.08% in the elevated pattern, 7.14 vs 92.86% in the steady pattern, 5.71 vs 94.29% in the depressed pattern, and 80.00 vs 20.00% in non-enhanced lesions (p < 0.0001), respectively. Despite variations in the degree of tumour angiogenesis, quantitative analysis of the breast lesions on CESM documented the malignancies had distinctive stronger enhancement and depressed relative enhancement patterns than benign lesions. Advances in knowledge: To our knowledge, this is the first study evaluating the feasibility of quantifying lesion enhancement on CESM. The quantities of enhancement were informative for assessing breast lesions in which the malignancies had stronger enhancement and more relative depressed enhancement than the benign lesions.

  12. [Present situation and prospect of enhanced recovery after surgery in pancreatic surgery].

    Science.gov (United States)

    Feng, Mengyu; Zhang, Taiping; Zhao, Yupei

    2017-05-25

    Enhanced recovery after surgery is a multimodal perioperative strategy according to the evidence-based medicine and multidisciplinary collaboration, aiming to improve the restoration of functional capacity after surgery by reducing surgical stress, optimal control of pain, early oral diet and early mobilization. Compared with other sub-specialty in general surgery, pancreatic surgery is characterized by complex disease, highly difficult procedure and more postoperative complications. Accordingly, pancreatic surgery shares a slow development in enhanced recovery after surgery. In this review, the feasibility, safety, application progress, prospect and controversy of enhanced recovery after surgery in pancreatic surgery are discussed.

  13. Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants.

    Science.gov (United States)

    Mohamadzadeh, M; Müller, M; Hultsch, T; Enk, A; Saloga, J; Knop, J

    1994-12-01

    To investigate the interleukin-8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensitizer (2,4-dinitrofluorobenzene, 3-n-pentadecylcatechol); (ii) tolerogen (5-methyl-3-n-pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin-8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin-8. Interleukin-8 gene expression was markedly increased upon in vitro stimulation after 1-6 h with contact sensitizers, tolerogen and the irritant. In contrast, interleukin-8 production was not detectable in unstimulated normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin-8 is a response to nonspecific stimuli and may play a critical role in the early response to immunogenic or inflammatory signals in man.

  14. Value of fast dynamic enhanced MR imaging for the differential diagnosis between ovarian fibroma and subserosal leiomyoma

    International Nuclear Information System (INIS)

    Shan Jun; Wang Xiaomei; Xu Jianmin; Xu Hongli; Feng Xiaofeng; Gong Jingshan; Ling Rennan; Rao Zibin

    2004-01-01

    Objective: To study the value of dynamic enhanced MRI in the differential diagnosis between subserosal uterine leiomyoma and ovarian fibroma which were iso-signal and low signal ones on T 2 WI. Methods: Plain and dynamic enhanced MRI findings of 45 patients with histologically proved subserosal leiomyoma or ovarian fibroma were analyzed. There were 35 cases of subserosal leiomyoma and 10 cases of ovarian fibroma. The enhancement index of early phase (100 sec after the contrast medial administration) and the time to peak during 200 sec after the contrast administration (TTP 200 ) were analyzed. Results: On plain scanning, both subserosal leiomyoma and ovarian fibrioma appeared similarly as intrapelvic masses with low signal on T 2 WI. On Gadolinium dynamic enhancement, subserosal leiomyomas showed early and evident enhancement while ovarian fibroma showed delayed and moderate enhancement. The difference of the enhancement index of early phase and TTP 200 was statistically significant (P<0.001). Conclusion: Gadolinium dynamic enhanced MR imaging was helpful in the differential diagnosis between subserosal uterine leiomyoma and ovarian fibroma by the difference in the enhancement pattern

  15. In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells.

    Science.gov (United States)

    Sales, Natiely S; Silva, Jamile R; Aps, Luana R M M; Silva, Mariângela O; Porchia, Bruna F M M; Ferreira, Luís Carlos S; Diniz, Mariana O

    2017-12-19

    In vivo electroporation (EP) has reignited the clinical interest on DNA vaccines as immunotherapeutic approaches to control different types of cancer. EP has been associated with increased immune response potency, but its capacity in influencing immunomodulation remains unclear. Here we evaluated the impact of in vivo EP on the induction of cellular immune responses and therapeutic effects of a DNA vaccine targeting human papillomavirus-induced tumors. Our results demonstrate that association of EP with the conventional intramuscular administration route promoted a more efficient activation of multifunctional and effector memory CD8 + T cells with enhanced cytotoxic activity. Furthermore, EP increased tumor infiltration of CD8 + T cells and avoided tumor recurrences. Finally, our results demonstrated that EP promotes local migration of antigen presenting cells that enhances with vaccine co-delivery. Altogether the present evidences shed further light on the in vivo electroporation action and its impact on the immunogenicity of DNA vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Enhanced photoelectrochemical properties of 100 MeV Si8+ ion irradiated barium titanate thin films

    International Nuclear Information System (INIS)

    Solanki, Anjana; Choudhary, Surbhi; Satsangi, Vibha R.; Shrivastav, Rohit; Dass, Sahab

    2013-01-01

    Highlights: ► Effect of 100 MeV Si 8+ ion irradiation on photoelectrochemical (PEC) properties of BaTiO 3 thin films was studied. ► Films were deposited on Indium doped Tin Oxide (ITO) coated glass by sol–gel spin coating technique. ► Optimal irradiation fluence for best PEC response was 5 × 10 11 ion cm −2 . ► Maximum photocurrent density was observed to be 0.7 mA cm −2 at 0.4 V/SCE. ► Enhanced photo-conversion efficiency was due to maximum negative flatband potential, donor density and lowest resistivity. -- Abstract: Effects of high electronic energy deposition on the structure, surface topography, optical property and photoelectrochemical behavior of barium titanate (BaTiO 3 ) thin films were investigated by irradiating films with 100 MeV Si 8+ ions at different ion fluences in the range of 1 × 10 11 –2 × 10 13 ions cm −2 . BaTiO 3 thin films were deposited on indium tin oxide coated glass substrate by sol gel spin coating method. Irradiation induced modifications in the films were analyzed using the results from XRD, SEM, cross sectional SEM, AFM and UV–Vis spectrometry. Maximum photocurrent density of 0.7 mA cm −2 at 0.4 V/SCE and applied bias hydrogen conversion efficiency (ABPE) of 0.73% was observed for BaTiO 3 film irradiated at 5 × 10 11 ions cm −2 , which can be attributed to maximum negative value of the flatband potential and donor density and lowest resistivity

  17. Postexercise nutrient intake enhances leg protein balance in early postmenopausal women

    DEFF Research Database (Denmark)

    Holm, Lars; Esmarck, Birgitte; Suetta, Charlotte

    2005-01-01

    BACKGROUND: We investigated the effect of nutrient administration after a session of resistance exercise on muscle protein kinetics in six healthy, early postmenopausal women, in a crossover design of random and double-blinded administration of protein and carbohydrate (PC) or placebo (NON). METH...

  18. Clinico-roentgenological characteristic of early stomach neoplasm

    International Nuclear Information System (INIS)

    Golub, G.D.

    1988-01-01

    Peculiarities of clinic and roentgenosemiotics of early stomach neoplasms in patients were analyzed. Roentgenological picture of early stomach neoplasms depends on anatomic growth shape and size of neoplasms, its localization and on manifestation of inflammatory and functional chages accompanying the neoplasm. Application of complex of gastrological examination including roentgenological diagnostic method, gastrofibroscopy and morphological examination of the tissue permits to diagnose early stomach neoplasm in 95,4 % of patients. 8 refs

  19. Early anaerobic metabolisms

    DEFF Research Database (Denmark)

    Canfield, Donald Eugene; Rosing, Minik T; Bjerrum, Christian

    2006-01-01

    probably driven by the cycling of H2 and Fe2+ through primary production conducted by anoxygenic phototrophs. Interesting and dynamic ecosystems would have also been driven by the microbial cycling of sulphur and nitrogen species, but their activity levels were probably not so great. Despite the diversity......Before the advent of oxygenic photosynthesis, the biosphere was driven by anaerobic metabolisms. We catalogue and quantify the source strengths of the most probable electron donors and electron acceptors that would have been available to fuel early-Earth ecosystems. The most active ecosystems were...... of potential early ecosystems, rates of primary production in the early-Earth anaerobic biosphere were probably well below those rates observed in the marine environment. We shift our attention to the Earth environment at 3.8Gyr ago, where the earliest marine sediments are preserved. We calculate, consistent...

  20. Time dependent enhanced resistance against antibiotics & metal salts by planktonic & biofilm form of Acinetobacter haemolyticus MMC 8 clinical isolate

    Directory of Open Access Journals (Sweden)

    Sharvari Vijaykumar Gaidhani

    2014-01-01

    Full Text Available Background & objectives: Available literature shows paucity of reports describing antibiotic and metal resistance profile of biofilm forming clinical isolates of Acinetobacter haemolyticus. The present study was undertaken to evaluate the antibiotic and metal resistance profile of Indian clinical isolate of A. haemolyticus MMC 8 isolated from human pus sample in planktonic and biofilm form. Methods: Antibiotic susceptibility and minimum inhibitory concentration were determined employing broth and agar dilution techniques. Biofilm formation was evaluated quantitatively by microtiter plate method and variation in complex architecture was determined by scanning electron microscopy. Minimum biofilm inhibiting concentration was checked by Calgary biofilm device. Results: Planktonic A. haemolyticus MMC 8 was sensitive to 14 antibiotics, AgNO 3 and HgC1 2 resistant to streptomycin and intermediately resistant to netilmycin and kanamycin. MMC 8 exhibited temporal variation in amount and structure of biofilm. There was 32 - 4000 and 4 - 256 fold increase in antibiotic and metal salt concentration, respectively to inhibit biofilm over a period of 72 h as against susceptible planktonic counterparts. Total viable count in the range of 10 5 -10 6 cfu / ml was observed on plating minimum biofilm inhibiting concentration on Muller-Hinton Agar plate without antimicrobial agents. Biofilm forming cells were several folds more resistant to antibiotics and metal salts in comparison to planktonic cells. Presence of unaffected residual cell population indicated presence of persister cells. Interpretation & conclusions: The results indicate that biofilm formation causes enhanced resistance against antibiotics and metal salts in otherwise susceptible planktonic A. haemolyticus MMC 8.

  1. Presentation of an immunodominant immediate-early CD8+ T cell epitope resists human cytomegalovirus immunoevasion.

    Directory of Open Access Journals (Sweden)

    Stefanie Ameres

    Full Text Available Control of human cytomegalovirus (HCMV depends on CD8+ T cell responses that are shaped by an individual's repertoire of MHC molecules. MHC class I presentation is modulated by a set of HCMV-encoded proteins. Here we show that HCMV immunoevasins differentially impair T cell recognition of epitopes from the same viral antigen, immediate-early 1 (IE-1, that are presented by different MHC class I allotypes. In the presence of immunoevasins, HLA-A- and HLA-B-restricted T cell clones were ineffective, but HLA-C*0702-restricted T cell clones recognized and killed infected cells. Resistance of HLA-C*0702 to viral immunoevasins US2 and US11 was mediated by the alpha3 domain and C-terminal region of the HLA heavy chain. In healthy donors, HLA-C*0702-restricted T cells dominated the T cell response to IE-1. The same HLA-C allotype specifically protected infected cells from attack by NK cells that expressed a corresponding HLA-C-specific KIR. Thus, allotype-specific viral immunoevasion allows HCMV to escape control by NK cells and HLA-A- and HLA-B-restricted T cells, while the virus becomes selectively vulnerable to an immunodominant population of HLA-C-restricted T cells. Our work identifies a T cell population that may be of particular efficiency in HCMV-specific immunotherapy.

  2. Prevalence and characteristics of intravertebral enhancement on contrast-enhanced CT scans in cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Rasselet, Benjamin [Medical Imaging Department and Biostatistics Department, Montpellier University Hospital, 191 Avenue du Doyen Gaston Giraud, 34 295 Montpellier Cedex 5 (France); Larbi, Ahmed; Viala, Pierre [Medical Imaging Department, Nimes University Hospital, 4 rue du Professeur Robert Debré, 30029 Nîmes (France); Molinari, Nicolas [Biostatistics Department, Montpellier University Hospital, 191 Avenue du Doyen Gaston Giraud, 34 295 Montpellier Cedex 5 (France); Tetreau, Raphael [Medical Imaging Department, Montpellier Cancer Institute (ICM), 208 Avenue des Apothicaires, 34298 Montpellier Cedex 5 (France); Faruch-Bilfeld, Marie [Medical Imaging Department, Toulouse University Hospital, Place du Docteur Baylac, 31059 Toulouse Cedex 9 (France); Taourel, Patrice [Medical Imaging Department and Biostatistics Department, Montpellier University Hospital, 191 Avenue du Doyen Gaston Giraud, 34 295 Montpellier Cedex 5 (France); Cyteval, Catherine, E-mail: c-cyteval@chu-montpellier.fr [Medical Imaging Department and Biostatistics Department, Montpellier University Hospital, 191 Avenue du Doyen Gaston Giraud, 34 295 Montpellier Cedex 5 (France)

    2017-01-15

    Highlights: • 2.8% of collateral venous circulation seen on CT scan in a cancer population. • 37% of intravertebral enhancement in this population with collateral venous circulation. • 80.8% of intravertebral enhancements are located between C6 and. • 73% of intravertebral enhancements are located ipsilateral to the injection side. -  Abstract: Study design: This was a single center, retrospective observational study. Objective: to investigate—in a cancer population—the prevalence and hallmarks of intravertebral enhancement (IVE) detected on contrast-enhanced CT. Summary of background data: Intravertebral enhancements secondary to iodinated contrast stagnation have been described. Cancer patients have an increased risk of perivertebral venous thrombosis or stenosis secondary to several risk factors (cancer or drug induced hypercoagulability, deterioration of venous flow linked to catheter insertion, prolonged immobilization). In case of a high density lesion identified on CT, the diagnostic choice between metastasis and contrast media within bone marrow vessels may be an issue, especially as oncologic follow-up CT scans are usually performed with contrast medium injection. Methods: 2572 contrast-enhanced body CT scans performed in cancer patients over 3 months in the medical imaging department of a university hospital were retrospectively reviewed. IVE was sought when paravertebral venous collateral circulation was detected and bone metastasis ruled out and classified as linear or nodular. Their locations within vertebra, their relation to the injection side and the predominant collateral venous network side were evaluated. Results: Sixty-seven (2.8%) patients had a collateral paravertebral venous system and among them 21 had IVE (37%). There were 208 IVE locations involving 75 vertebrae. 199 IVE were linear-shaped (95.7%) and 9 nodular-shaped (4.3%). 80.8% were located between C6 and T4. 88.9% were localized in the vertebral body. 73.1% were located

  3. Prevalence and characteristics of intravertebral enhancement on contrast-enhanced CT scans in cancer patients

    International Nuclear Information System (INIS)

    Rasselet, Benjamin; Larbi, Ahmed; Viala, Pierre; Molinari, Nicolas; Tetreau, Raphael; Faruch-Bilfeld, Marie; Taourel, Patrice; Cyteval, Catherine

    2017-01-01

    Highlights: • 2.8% of collateral venous circulation seen on CT scan in a cancer population. • 37% of intravertebral enhancement in this population with collateral venous circulation. • 80.8% of intravertebral enhancements are located between C6 and. • 73% of intravertebral enhancements are located ipsilateral to the injection side. -  Abstract: Study design: This was a single center, retrospective observational study. Objective: to investigate—in a cancer population—the prevalence and hallmarks of intravertebral enhancement (IVE) detected on contrast-enhanced CT. Summary of background data: Intravertebral enhancements secondary to iodinated contrast stagnation have been described. Cancer patients have an increased risk of perivertebral venous thrombosis or stenosis secondary to several risk factors (cancer or drug induced hypercoagulability, deterioration of venous flow linked to catheter insertion, prolonged immobilization). In case of a high density lesion identified on CT, the diagnostic choice between metastasis and contrast media within bone marrow vessels may be an issue, especially as oncologic follow-up CT scans are usually performed with contrast medium injection. Methods: 2572 contrast-enhanced body CT scans performed in cancer patients over 3 months in the medical imaging department of a university hospital were retrospectively reviewed. IVE was sought when paravertebral venous collateral circulation was detected and bone metastasis ruled out and classified as linear or nodular. Their locations within vertebra, their relation to the injection side and the predominant collateral venous network side were evaluated. Results: Sixty-seven (2.8%) patients had a collateral paravertebral venous system and among them 21 had IVE (37%). There were 208 IVE locations involving 75 vertebrae. 199 IVE were linear-shaped (95.7%) and 9 nodular-shaped (4.3%). 80.8% were located between C6 and T4. 88.9% were localized in the vertebral body. 73.1% were located

  4. Enhanced Effector Function of CD8+ T Cells From Healthy Controls and HIV-Infected Patients Occurs Through Thrombin Activation of Protease-Activated Receptor 1

    Science.gov (United States)

    Hurley, Amanda; Smith, Mindy; Karpova, Tatiana; Hasley, Rebecca B.; Belkina, Natalya; Shaw, Stephen; Balenga, Nariman; Druey, Kirk M.; Nickel, Erin; Packard, Beverly; Imamichi, Hiromi; Hu, Zonghui; Follmann, Dean; McNally, James; Higgins, Jeanette; Sneller, Michael; Lane, H. Clifford; Catalfamo, Marta

    2013-01-01

    Disruption of vascular integrity by trauma and other tissue insults leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these 2 processes. The proinflammatory function of thrombin is mediated by activation of protease-activated receptor 1 (PAR-1). We found that peripheral blood effector memory CD4+ and CD8+ T lymphocytes expressed PAR-1 and that expression was increased in CD8+ T cells from human immunodeficiency virus (HIV)–infected patients. Thrombin enhanced cytokine secretion in CD8+ T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8+ T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and phosphorylated ezrin-radexin-moesin proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines. PMID:23204166

  5. Enhanced effector function of CD8(+) T cells from healthy controls and HIV-infected patients occurs through thrombin activation of protease-activated receptor 1.

    Science.gov (United States)

    Hurley, Amanda; Smith, Mindy; Karpova, Tatiana; Hasley, Rebecca B; Belkina, Natalya; Shaw, Stephen; Balenga, Nariman; Druey, Kirk M; Nickel, Erin; Packard, Beverly; Imamichi, Hiromi; Hu, Zonghui; Follmann, Dean; McNally, James; Higgins, Jeanette; Sneller, Michael; Lane, H Clifford; Catalfamo, Marta

    2013-02-15

    Disruption of vascular integrity by trauma and other tissue insults leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these 2 processes. The proinflammatory function of thrombin is mediated by activation of protease-activated receptor 1 (PAR-1). We found that peripheral blood effector memory CD4(+) and CD8(+) T lymphocytes expressed PAR-1 and that expression was increased in CD8(+) T cells from human immunodeficiency virus (HIV)-infected patients. Thrombin enhanced cytokine secretion in CD8(+) T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8(+) T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and phosphorylated ezrin-radexin-moesin proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines.

  6. Whole-liver MR perfusion imaging in rabbit liver VX2 tumors: early findings of coagulative necrosis after percutaneous ethanol injection therapy

    International Nuclear Information System (INIS)

    Zhang Wanshi; Wang Dong; Meng Limin; Shi Huiping; Song Yunlong; Wu Bing

    2007-01-01

    Objective: To investigate the value of whole-liver MR perfusion imaging (MRPI) for early detection of coagulative necrosis after percutaneous ethanol injection (PEI) in rabbit liver VX 2 tumors. Methods: VX 2 tumor cell suspension was inoculated into rabbit liver and liver VX 2 tumors [diameter of (2.6 ± 0.6) cm] were induced in 10 male rabbits. MR T 1 WI and T 2 WI were performed to monitor the development of the liver tumor on the 2 nd and 3 rd week after inoculation. Whole-liver MRPI was performed in the 10 rabbits with liver VX 2 tumors before and 6 days after PEI therapy (1.0 ml ethanol was injected into the most enhanced tumor region under CT guiding). Signal intensity (SI) values of untreated tumor parts and treated areas 6 days after PEI were recorded respectively. The steepest slope (SS) and bolus arrival time (T0) of SI-time curves were measured. The t-Student test was used in statistical analysis of the data. Results: There was significant difference in MRPI data between untreated tumor parts [T0: (16.0 ± 1.2) s and SS: 38.9 ± 2.2] and treated areas [T0: (50.8 ± 5.9) s and SS: 6.0 ± 1.2] 6 days after PEI(t was 15.8 and -39.6 respectively, P 1 WI and T 2 WI could not show any differences between untreated tumor parts and treated areas. Conclusion: Whole-liver MRPI could detect coagulative necrosis of rabbit liver VX 2 tumors after PEI early. Disappearance of early enhancement can be a potential marker for efficacy of PEI. (authors)

  7. Early detection and assertive community treatment of young psychotics

    DEFF Research Database (Denmark)

    Jørgensen, P; Nordentoft, M; Abel, M B

    2000-01-01

    Recent research indicates that early detection of young persons suffering from psychosis and subsequent intensive intervention enhances treatment response and prognosis, but the data are only preliminary and suggestive....

  8. Windows 8 visual quick tips

    CERN Document Server

    McFedries, Paul

    2012-01-01

    Easy-in, easy-out format covers all the bells and whistles of Windows 8 If you want to learn how to work smarter and faster in Microsoft's Windows 8 operating system, this easy-to-use, compact guide delivers the goods. Designed for visual learners, it features short explanations and full-color screen shots on almost every page, and it's packed with timesaving tips and helpful productivity tricks. From enhancing performance and managing digital content to setting up security and much more, this handy guide will help you get more out of Windows 8. Uses full-color screen shots and short, step-by-

  9. Gd-EOB-DTPA enhanced MRI of the liver: Correlation of relative hepatic enhancement, relative renal enhancement, and liver to kidneys enhancement ratio with serum hepatic enzyme levels and eGFR

    Energy Technology Data Exchange (ETDEWEB)

    Talakic, Emina; Steiner, Jürgen; Kalmar, Peter; Lutfi, Andre [Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9, 8036 Graz (Austria); Quehenberger, Franz [Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Auenbruggerplatz 2, 8036 Graz (Austria); Reiter, Ursula; Fuchsjäger, Michael [Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9, 8036 Graz (Austria); Schöllnast, Helmut, E-mail: helmut.schoellnast@medunigraz.at [Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9, 8036 Graz (Austria)

    2014-04-15

    Objectives: To assess the correlation of relative hepatic enhancement (RHE), relative renal enhancement (RRE) and liver to kidneys enhancement ratio (LKR) with serum hepatic enzyme levels and eGFR in Gd-EOB-DTPA enhanced MRI of the liver and to assess threshold levels for predicting enhancement of the liver parenchyma. Methods: Data of 75 patients who underwent Gd-EOB-DTPA enhanced MRI of the liver were collected. Images were obtained before contrast injection, during the early arterial phase, late arterial phase, venous phase, delayed phase, and hepatobiliary phase which was 20 min after Gd-EOB-DTPA administration. Signal intensity of the liver and the kidneys in all phases was defined using region-of-interest measurements for relative enhancement calculation. Serum hepatic enzyme levels and eGFR were available in all patients. Spearman correlation test was used to test the correlation of RHE, RRE and LKR with serum hepatic enzyme levels and eGFR. Results: In the hepatobiliary phase all serum hepatic enzymes were significantly correlated with RHE; total bilirubin (TBIL) and cholin esterase (CHE) showed strongest correlations. TBIL and CHE were significantly correlated with RRE in the arterial phases. TBIL and CHE were significantly correlated with LKR in the arterial phase and hepatobiliary phase. eGFR showed no correlation. Conclusions: In Gd-EOB-DTPA enhanced MRI, TBIL and CHE levels may predict RHE, RRE and LKR.

  10. Cleanup Verification Package for the 618-8 Burial Ground

    International Nuclear Information System (INIS)

    Appel, M.J.

    2006-01-01

    This cleanup verification package documents completion of remedial action for the 618-8 Burial Ground, also referred to as the Solid Waste Burial Ground No. 8, 318-8, and the Early Solid Waste Burial Ground. During its period of operation, the 618-8 site is speculated to have been used to bury uranium-contaminated waste derived from fuel manufacturing, and construction debris from the remodeling of the 313 Building

  11. Researching the roots of IEEE Region 8

    NARCIS (Netherlands)

    Bastiaans, M.J.

    2013-01-01

    This paper describes the preliminary steps towards the foundation and the early history of IRE Region 9 / IEEE Region 8. The information has been gathered mainly from the archives of the IEEE Benelux Section.

  12. Leptin Enhances Synthesis of Proinflammatory Mediators in Human Osteoarthritic Cartilage—Mediator Role of NO in Leptin-Induced PGE2, IL-6, and IL-8 Production

    Directory of Open Access Journals (Sweden)

    Katriina Vuolteenaho

    2009-01-01

    Full Text Available Obesity is an important risk factor for osteoarthritis (OA in weight-bearing joints, but also in hand joints, pointing to an obesity-related metabolic factor that influences on the pathogenesis of OA. Leptin is an adipokine regulating energy balance, and it has recently been related also to arthritis and inflammation as a proinflammatory factor. In the present paper, the effects of leptin on human OA cartilage were studied. Leptin alone or in combination with IL-1 enhanced the expression of iNOS and COX-2, and production of NO, PGE2, IL-6, and IL-8. The results suggest that the effects of leptin are mediated through activation of transcription factor nuclear factor κB (NF-κB and mitogen-activated protein kinase (MAPK pathway c-Jun NH2-terminal kinase (JNK. Interestingly, inhibition of leptin-induced NO production with a selective iNOS inhibitor 1400 W inhibited also the production of IL-6, IL-8, and PGE2, and this was reversed by exogenously added NO-donor SNAP, suggesting that the effects of leptin on IL-6, IL-8, and PGE2 production are dependent on NO. These findings support the idea of leptin as a factor enhancing the production of proinflammatory factors in OA cartilage and as an agent contributing to the obesity-associated increased risk for osteoarthritis.

  13. Multiproxy evidence for terrestrial and aquatic ecosystem responses during the 8.2 ka cold event as recorded at Højby Sø, Denmark

    DEFF Research Database (Denmark)

    Hede, Mikkel Ulfeldt; Rasmussen, Peter; Noe-Nygaard, Nanna

    2010-01-01

    ecosystems to the 8.2 ka cold event. A reduced pollen production by thermophilous deciduous tree taxa in the period c. 8250–8000 cal yr BP reveal that the forest ecosystem was affected by low temperatures during the summer and winter/early-spring seasons. This finding is consistent with the timing of the 8.......2 ka cold event as registered in the Greenland ice cores. At Højby Sø, the climate anomaly appears to have started 200–250 yr earlier than the 8.2 ka cold event as the lake proxy data provide strong evidence for a precipitation-induced distinct increase in catchment soil erosion beginning around 8500...... cal yr BP. Alteration of the terrestrial environment then resulted in a major aquatic ecosystem change with nutrient enrichment of the lake and enhanced productivity, which lasted until c. 7900 cal yr BP. Keywords: 8.2 ka cold event; Lake sediments; Palaeoclimate; Pollen; Macrofossils; Geochemistry...

  14. Hepatocellular carcinoma treated with transarterial chemoembolization: Evaluation with parametric contrast-enhanced ultrasonography

    Science.gov (United States)

    Moschouris, Hippocrates; Malagari, Katerina; Marinis, Athanasios; Kornezos, Ioannis; Stamatiou, Konstantinos; Nikas, Georgios; Papadaki, Marina Georgiou; Gkoutzios, Panagiotis

    2012-01-01

    AIM: To evaluate the response of hepatocellular carcinoma (HCC) to transarterial chemoembolization (TACE) using a simplified protocol of parametric contrast-enhanced ultrasound (pCEUS). METHODS: Eighteen patients with HCC (18 target tumors, diameter: 2.8-12 cm) were evaluated before, and 20 d after TACE. The distribution and morphology of TACE-induced necrosis in these tumors precluded accurate evaluation by visual assessment or by simple measurements. For pCEUS, a 4.8 mL bolus of SonoVue (Bracco, Milan, Italy) was intravenously administered and analysis of tumor perfusion during the initial phase of enhancement (0-30 s post injection) was performed with dedicated software (Qontrast, Bracco, Milan, Italy). Time-intensity curves were plotted and three parameters were calculated: peak intensity (PI, in percentage %), time to peak (TTP in seconds, s) and area under the curve during wash-in (AUC-WI, in arbitrary units, a.u). Magnetic resonance imaging was the standard imaging modality for post-treatment evaluation. Changes in tumor size were recorded and response was assessed according to response evaluation criteria in solid tumors criteria. RESULTS: A statistically significant decrease in PI and AUC-WI was observed in the treated tumors post TACE; PIpre: 21.5% ± 8.7% (mean ± SD), PIpost: 12.7% ± 6.7%, P < 0.001, AUC-WI pre: 17493 ± 9563 a.u, AUC-WI post: 9585 ± 5494 a.u, P < 0.001. A slight increase in TTP was noted post TACE, but this was not statistically significant; TTP pre: 13.1 ± 4.3 s, TTP post: 13.6 ± 4.2 s , P = 0.058). The changes in the aforementioned parameters were not accompanied by significant tumor shrinkage. CONCLUSION: pCEUS, even when limited to the study of the arterial phase of tumoral enhancement, can detect and quantify early perfusional changes in HCC post TACE. PMID:22937217

  15. Employee well-being, early-retirement intentions, and company performance.

    Science.gov (United States)

    von Bonsdorff, Monika E; Vanhala, Sinikka; Seitsamo, Jorma; Janhonen, Minna; Husman, Päivi

    2010-12-01

    To explore the relationship between employee well-being and early-retirement intentions, and the extent to which early-retirement intentions are associated with company performance. This study is based on cross-sectional survey data on the ageing employees of the Finnish metal industry and retail trade, collected in 2007 (company-level n = 129, employee-level n = 1281). It was analyzed using multinomial logistic and multiple regression analysis. Poor work ability, frequent emotional exhaustion, low organizational commitment, and job control were associated with the prevalence of early-retirement intentions among aging employees in both industries. Metal industry employees' early-retirement intentions were associated with weaker company performance measured by the perceptions of the manager. By enhancing well-being, employees may stay at work for longer rather than retiring early. Early-retirement intentions can be counterproductive for companies.

  16. A novel bacterial transport mechanism of Acinetobacter baumannii via activated human neutrophils through interleukin-8.

    Science.gov (United States)

    Kamoshida, Go; Tansho-Nagakawa, Shigeru; Kikuchi-Ueda, Takane; Nakano, Ryuichi; Hikosaka, Kenji; Nishida, Satoshi; Ubagai, Tsuneyuki; Higashi, Shouichi; Ono, Yasuo

    2016-12-01

    Hospital-acquired infections as a result of Acinetobacter baumannii have become problematic because of high rates of drug resistance. Although neutrophils play a critical role in early protection against bacterial infection, their interactions with A. baumannii remain largely unknown. To elucidate the interactions between A. baumannii and human neutrophils, we cocultured these cells and analyzed them by microscopy and flow cytometry. We found that A. baumannii adhered to neutrophils. We next examined neutrophil and A. baumannii infiltration into Matrigel basement membranes by an in vitro transmigration assay. Neutrophils were activated by A. baumannii, and invasion was enhanced. More interestingly, A. baumannii was transported together by infiltrating neutrophils. Furthermore, we observed by live cell imaging that A. baumannii and neutrophils moved together. In addition, A. baumannii-activated neutrophils showed increased IL-8 production. The transport of A. baumannii was suppressed by inhibiting neutrophil infiltration by blocking the effect of IL-8. A. baumannii appears to use neutrophils for transport by activating these cells via IL-8. In this study, we revealed a novel bacterial transport mechanism that A. baumannii exploits human neutrophils by adhering to and inducing IL-8 release for bacterial portage. This mechanism might be a new treatment target. © Society for Leukocyte Biology.

  17. Acute Sleep Deprivation Enhances Post-Infection Sleep and Promotes Survival during Bacterial Infection in Drosophila

    Science.gov (United States)

    Kuo, Tzu-Hsing; Williams, Julie A.

    2014-01-01

    Study Objectives: Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Setting: Laboratory. Participants: Drosophila melanogaster. Methods and Results: Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Conclusions: Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection. Citation: Kuo TH, Williams JA. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila. SLEEP 2014;37(5):859-869. PMID:24790264

  18. The enhanced electron injection by fluorinated tris-(8-hydroxy-quinolinato) aluminum derivatives in high efficient Si-anode OLEDs

    Energy Technology Data Exchange (ETDEWEB)

    Liu, N. [State Key Laboratory of Silicon Materials, MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Shi, M.M., E-mail: minminshi@zju.edu.c [State Key Laboratory of Silicon Materials, MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Li, Y.Z. [School of Physics, State Key Laboratory for Mesoscopic Physics, Peking University, Beijing 100871 (China); Shi, Y.W. [State Key Laboratory of Silicon Materials, MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China); Ran, G.Z.; Qin, G.G. [School of Physics, State Key Laboratory for Mesoscopic Physics, Peking University, Beijing 100871 (China); Wang, M.; Chen, H.Z. [State Key Laboratory of Silicon Materials, MOE Key Laboratory of Macromolecule Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027 (China)

    2011-02-15

    Fabrication of organic light-emitting diodes (OLEDs) and lasers on silicon substrates is a feasible route to integrate microelectronic chips with optical devices for telecommunications. However, the efficiency of Si-anode based OLEDs is restricted by the imbalance of hole-electron injection because a p-type Si anode owns better hole injection ability than ITO. We have used fluorinated tris-(8-hydroxy-quinolinato) aluminum (FAlq{sub 3}) derivatives to prepare Si-anode based OLEDs. We observed that, when tris-(5-fuloro-8-hydroxyquinolinato) aluminum (5FAlq{sub 3}) is used as the electron-transporting material instead of Alq{sub 3}, the cathode electron injection is enhanced due to its lower lowest unoccupied molecular orbital (LUMO) compared to the Alq{sub 3}. The device can keep the relative carrier balance even when a Si anode capable of stronger hole injection was used. Further optimization of the device structure by introducing 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP) as a hole blocking layer showed significant increase in the device power efficiency from 0.029 to 0.462 lm/W. This indicates that use of fluorinated Alq{sub 3} derivatives is an effective way to improve the performance of Si-anode based OLEDs.

  19. Are gains in decision-making autonomy during early adolescence beneficial for emotional functioning? The case of the United States and china.

    Science.gov (United States)

    Qin, Lili; Pomerantz, Eva M; Wang, Qian

    2009-01-01

    This research examined the role of children's decision-making autonomy in their emotional functioning during early adolescence in the United States and China. Four times over the 7th and 8th grades, 825 American and Chinese children (M = 12.73 years) reported on the extent to which they versus their parents make decisions about issues children often deem as under their authority. Children also reported on their emotional functioning. American children made greater gains over time in decision-making autonomy than did Chinese children. Initial decision-making autonomy predicted enhanced emotional functioning similarly among American and Chinese children. However, gains over time in decision-making autonomy predicted enhanced emotional functioning more in the United States (vs. China) where such gains were normative.

  20. Early Adolescent Sexual Activity: A Developmental Study.

    Science.gov (United States)

    Whitbeck, Les B.; Yoder, Kevin A.; Hoyt, Dan R.; Conger, Rand D.

    1999-01-01

    Examines predictors of early sexual intercourse for a sample of 457 adolescents in grades 8 through 10, from two-parent and single-mother families. Significant decreases were noted in the effect of mother monitoring by 10th grade. The primary predictors of early intercourse were age, opportunity (steady relationship), sexually permissive attitude,…

  1. Interleukin 8 in progression of hormone-dependent early breast cancer

    Indian Academy of Sciences (India)

    2017-04-18

    Apr 18, 2017 ... significance of IL8 in hormone-dependent breast cancer. The aim of this study was to evaluate the prognostic ... types characterized by a particularly poor prognosis (Aceto et al. ... Progesterone receptor status. PRlow. 70. 76.9. PRhigh. 21. 23.1. NA .... (M<88.82 pg/mg) had lower percentage of relapses and.

  2. Irregular vascular pattern by contrast-enhanced ultrasonography and high serum Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level predict poor outcome after successful radiofrequency ablation in patients with early-stage hepatocellular carcinoma.

    Science.gov (United States)

    Takada, Hitomi; Tsuchiya, Kaoru; Yasui, Yutaka; Nakakuki, Natsuko; Tamaki, Nobuharu; Suzuki, Shoko; Nakanishi, Hiroyuki; Itakura, Jun; Takahashi, Yuka; Kurosaki, Masayuki; Asahina, Yasuhiro; Enomoto, Nobuyuki; Izumi, Namiki

    2016-11-01

    Radiofrequency ablation (RFA) is considered the most effective treatment for early-stage hepatocellular carcinoma (HCC) patients unsuitable for resection. However, poor outcome after RFA has occasionally been reported worldwide. To predict such an outcome, we investigated imaging findings using contrast-enhanced ultrasonography (CEUS) with Sonazoid and serum tumor markers before RFA. This study included 176 early-stage HCC patients who had initially achieved successful RFA. Patients were examined using CEUS; their levels of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin before RFA were measured. Sonazoid provided parenchyma-specific contrast imaging and facilitated tumor vascular architecture imaging through maximum intensity projection (MIP). Kaplan-Meier analysis examined cumulative rates of local tumor progression, intrasubsegmental recurrence, and survival; factors associated with these were determined with Cox proportional hazards analysis. Local tumor progression (n = 15), intrasubsegmental recurrence (n = 46), and death (n = 18) were observed. Irregular pattern in MIP classification and serum AFP-L3 level (>10%) before RFA were identified as independent risk factors for local tumor progression and intrasubsegmental recurrence. These two factors were independently associated with poor survival after RFA (irregular pattern in MIP: hazard ratio, (HR) = 8.26; 95% confidence interval, (CI) = 2.24-30.3; P = 0.002 and AFP-L3 > 10%: HR = 2.94; 95% CI = 1.09-7.94; P = 0.033). Irregular MIP pattern by CEUS and high level of serum AFP-L3 were independent risk factors for poor outcome after successful RFA. The Patients with these findings should be considered as special high-risk group in early-stage HCC. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  3. Xiao-Ai-Ping, a TCM Injection, Enhances the Antigrowth Effects of Cisplatin on Lewis Lung Cancer Cells through Promoting the Infiltration and Function of CD8+ T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Wanshuai Li

    2013-01-01

    Full Text Available Objectives. To investigate how Xiao-Ai-Ping injection, a traditional Chinese medicine and an ancillary drug in tumor treatment, enhances the antitumor effects of cisplatin on Lewis lung cancer (LLC cells. Methods. LLC-bearing mice were daily intraperitoneally injected with various doses of cisplatin, Xiao-Ai-Ping, or cisplatin plus Xiao-Ai-Ping, respectively. Body weight and tumor volumes were measured every three days. Results. Combination of Xiao-Ai-Ping and cisplatin yielded significantly better antigrowth and proapoptotic effects on LLC xenografts than sole drug treatment did. In addition, we found that Xiao-Ai-Ping triggered the infiltration of CD8+ T cells, a group of cytotoxic T cells, to LLC xenografts. Furthermore, the mRNA levels of interferon-γ (ifn-γ, perforin-1 (prf-1, and granzyme B (gzmb in CD8+ T cells were significantly increased after combination treatment of Xiao-Ai-Ping and cisplatin. In vitro studies showed that Xiao-Ai-Ping markedly upregulated the mRNA levels of ifn-γ, prf-1, and gzmb in CD8+ T cells in a concentration-dependent manner, suggesting that Xiao-Ai-Ping augments the function of CD8+ T cells. Conclusions. Xiao-Ai-Ping promotes the infiltration and function of CD8+ T cells and thus enhances the antigrowth effects of cisplatin on LLC xenografts, which provides new evidence for the combination of Xiao-Ai-Ping and cisplatin in clinic in China.

  4. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila.

    Science.gov (United States)

    Kuo, Tzu-Hsing; Williams, Julie A

    2014-05-01

    Sleep is known to increase as an acute response to infection. However, the function of this behavioral response in host defense is not well understood. To address this problem, we evaluated the effect of acute sleep deprivation on post-infection sleep and immune function in Drosophila. Laboratory. Drosophila melanogaster. Flies were subjected to sleep deprivation before (early DEP) or after (late DEP) bacterial infection. Relative to a non-deprived control, flies subjected to early DEP had enhanced sleep after infection as well as increased bacterial clearance and survival outcome. Flies subjected to late DEP experienced enhanced sleep following the deprivation period, and showed a modest improvement in survival outcome. Continuous DEP (early and late DEP) throughout infection also enhanced sleep later during infection and improved survival. However, improved survival in flies subjected to late or continuous DEP did not occur until after flies had experienced sleep. During infection, both early and late DEP enhanced NFκB transcriptional activity as measured by a luciferase reporter (κB-luc) in living flies. Early DEP also increased NFκB activity prior to infection. Flies that were deficient in expression of either the Relish or Dif NFκB transcription factors showed normal responses to early DEP. However, the effect of early DEP on post-infection sleep and survival was abolished in double mutants, which indicates that Relish and Dif have redundant roles in this process. Acute sleep deprivation elevated NFκB-dependent activity, increased post-infection sleep, and improved survival during bacterial infection.

  5. FADD cleavage by NK cell granzyme M enhances its self-association to facilitate procaspase-8 recruitment for auto-processing leading to caspase cascade.

    Science.gov (United States)

    Wang, S; Xia, P; Shi, L; Fan, Z

    2012-04-01

    Granzyme M (GzmM), an orphan Gzm, is constitutively and abundantly expressed in innate effector natural killer cells. We previously demonstrated that GzmM induces caspase (casp)-dependent apoptosis and cytochrome c release from mitochondria. We also resolved the crystal structure for GzmM and generated its specific inhibitor. However, how GzmM causes casp activation has not been defined. Here we found that casp-8 is an initiator caspase in GzmM-induced casp cascade, which causes other casp activation and Bid cleavage. GzmM does not directly cleave procaspase-3 and Bid, whose processing is casp dependent. Casp-8 knockdown or deficient cells attenuate or abolish GzmM-induced proteolysis of procaspase-3 and Bid. Extrinsic death receptor pathway adaptor Fas-associated protein with death domain (FADD) contributes to GzmM-induced casp-8 activation. GzmM specifically cleaves FADD after Met 196 to generate truncated FADD (tFADD) that enhances its self-association for oligomerization. The oligomerized tFADD facilitates procaspase-8 recruitment to promote its auto-processing leading to casp activation cascade. FADD-deficient cells abrogate GzmM-induced activation of casp-8 and apoptosis as well as significantly inhibit lymphokine-activated killer cell-mediated cytotoxicity. FADD processing by GzmM can potentiate killing efficacy against tumor cells and intracellular pathogens.

  6. Incorporating Early Learning Strategies in the School Improvement Grants (SIG) Program

    Science.gov (United States)

    Connors-Tadros, Lori; Dunn, Lenay; Martella, Jana; McCauley, Carlas

    2015-01-01

    The Center on Enhancing Early Learning Outcomes (CEELO) and the Center on School Turnaround (CST) collaborated to develop case studies of three selected schools receiving SIG funds that have, with the support of their districts, promoted the use of early childhood programming (PK-3) as a key strategy in their schools' turnaround models. The goal…

  7. An 8-Week Web-Based Weight Loss Challenge With Celebrity Endorsement and Enhanced Social Support: Observational Study

    Science.gov (United States)

    Collins, Clare E; Morgan, Philip J; Callister, Robin

    2013-01-01

    Using GLMM, including weight data for all participants, there was significantly greater (P=.03) 8-week weight loss in SC (–5.1 kg [–5.5 to –4.6 kg] or –6.0%) compared to BLC participants (–4.5 kg [–4.8, –4.2] or –5.0%). Dropout rates were low and consistent across groups (BLC: 17 (1.8%) vs SC: 2 (0.5%), P=.08) and 48.7% (456/936) of BLC and 51.2% (184/379) of SC participants accessed the website at 8 weeks, with no difference between programs (P=.48). SC participants accessed the discussion forums, menu plans, exercise plans, and educational materials significantly more than BLC participants (Pcelebrity personal trainer, as well as a greater energy balance deficit, within a commercial Web-based weight loss program may facilitate greater initial weight loss and engagement with some program components. The results support the need for a more rigorous and prospective evaluation of Web-based weight loss programs that incorporate additional strategies to enhance initial weight loss and engagement, such as a short-term challenge. PMID:23827796

  8. An 8-week web-based weight loss challenge with celebrity endorsement and enhanced social support: observational study.

    Science.gov (United States)

    Hutchesson, Melinda J; Collins, Clare E; Morgan, Philip J; Callister, Robin

    2013-07-04

    participants, there was significantly greater (P=.03) 8-week weight loss in SC (-5.1 kg [-5.5 to -4.6 kg] or -6.0%) compared to BLC participants (-4.5 kg [-4.8, -4.2] or -5.0%). Dropout rates were low and consistent across groups (BLC: 17 (1.8%) vs SC: 2 (0.5%), P=.08) and 48.7% (456/936) of BLC and 51.2% (184/379) of SC participants accessed the website at 8 weeks, with no difference between programs (P=.48). SC participants accessed the discussion forums, menu plans, exercise plans, and educational materials significantly more than BLC participants (Pendorsement by a celebrity personal trainer, as well as a greater energy balance deficit, within a commercial Web-based weight loss program may facilitate greater initial weight loss and engagement with some program components. The results support the need for a more rigorous and prospective evaluation of Web-based weight loss programs that incorporate additional strategies to enhance initial weight loss and engagement, such as a short-term challenge.

  9. Ozone Enhances Diesel Exhaust Particles (DEP-Induced Interleukin-8 (IL-8 Gene Expression in Human Airway Epithelial Cells through Activation of Nuclear Factors- κB (NF-κB and IL-6 (NF-IL6

    Directory of Open Access Journals (Sweden)

    James Kelley

    2005-12-01

    Full Text Available Ozone, a highly reactive oxidant gas is a major component of photochemical smog. As an inhaled toxicant, ozone induces its adverse effects mainly on the lung. Inhalation of particulate matter has been reported to cause airway inflammation in humans and animals. Furthermore, epidemiological evidence has indicated that exposure to particulate matter (PM2.5-10, including diesel exhaust particles (DEP has been correlated with increased acute and chronic respiratory morbidity and exacerbation of asthma. Previously, exposure to ozone or particulate matter and their effect on the lung have been addressed as separate environmental problems. Ozone and particulate matter may be chemically coupled in the ambient air. In the present study we determined whether ozone exposure enhances DEP effect on interleukin-8 (IL-8 gene expression in human airway epithelial cells. We report that ozone exposure (0.5 ppm x 1 hr significantly increased DEP-induced IL-8 gene expression in A549 cells (117 ± 19 pg/ml, n = 6, p < 0.05 as compared to cultures treated with DEP (100 μg/ml x 4 hr alone (31 ± 3 pg/ml, n = 6, or cultures exposed to purified air (24 ± 6 pg/ml, n = 6. The increased DEP-induced IL-8 gene expression following ozone exposure was attributed to ozone-induced increase in the activity of the transcription factors NF-κB and NF-IL6. The results of the present study indicate that ozone exposure enhances the toxicity of DEP in human airway epithelial cells by augmenting IL-8 gene expression, a potent chemoattractant of neutrophils in the lung.

  10. Early aphasia rehabilitation is associated with functional reactivation of the left inferior frontal gyrus: a pilot study.

    Science.gov (United States)

    Mattioli, Flavia; Ambrosi, Claudia; Mascaro, Lorella; Scarpazza, Cristina; Pasquali, Patrizia; Frugoni, Marina; Magoni, Mauro; Biagi, Laura; Gasparotti, Roberto

    2014-02-01

    Early poststroke aphasia rehabilitation effects and their functional MRI (fMRI) correlates were investigated in a pilot, controlled longitudinal study. Twelve patients with mild/moderate aphasia (8 Broca, 3 anomic, and 1 Wernicke) were randomly assigned to daily language rehabilitation for 2 weeks (starting 2.2 [mean] days poststroke) or no rehabilitation. The Aachen Aphasia Test and fMRI recorded during an auditory comprehension task were performed at 3 time intervals: mean 2.2 (T1), 16.2 (T2), and 190 (T3) days poststroke. Groups did not differ in terms of age, education, aphasia severity, lesions volume, baseline fMRI activations, and in task performance during fMRI across examinations. Rehabilitated patients significantly improved in naming and written language tasks (Paphasia treatment is useful, has durable effects, and may lead to early enhanced recruitment of brain areas, particularly the left inferior frontal gyrus, which persists in the chronic phase.

  11. Enhancing early child care quality and learning for toddlers at risk: the responsive early childhood program.

    Science.gov (United States)

    Landry, Susan H; Zucker, Tricia A; Taylor, Heather B; Swank, Paul R; Williams, Jeffrey M; Assel, Michael; Crawford, April; Huang, Weihua; Clancy-Menchetti, Jeanine; Lonigan, Christopher J; Phillips, Beth M; Eisenberg, Nancy; Spinrad, Tracy L; de Villiers, Jill; de Villiers, Peter; Barnes, Marcia; Starkey, Prentice; Klein, Alice

    2014-02-01

    Despite reports of positive effects of high-quality child care, few experimental studies have examined the process of improving low-quality center-based care for toddler-age children. In this article, we report intervention effects on child care teachers' behaviors and children's social, emotional, behavioral, early literacy, language, and math outcomes as well as the teacher-child relationship. The intervention targeted the use of a set of responsive teacher practices, derived from attachment and sociocultural theories, and a comprehensive curriculum. Sixty-five childcare classrooms serving low-income 2- and 3-year-old children were randomized into 3 conditions: business-as-usual control, Responsive Early Childhood Curriculum (RECC), and RECC plus explicit social-emotional classroom activities (RECC+). Classroom observations showed greater gains for RECC and RECC+ teachers' responsive practices including helping children manage their behavior, establishing a predictable schedule, and use of cognitively stimulating activities (e.g., shared book reading) compared with controls; however, teacher behaviors did not differ for focal areas such as sensitivity and positive discipline supports. Child assessments demonstrated that children in the interventions outperformed controls in areas of social and emotional development, although children's performance in control and intervention groups was similar for cognitive skills (language, literacy, and math). Results support the positive impact of responsive teachers and environments providing appropriate support for toddlers' social and emotional development. Possible explanations for the absence of systematic differences in children's cognitive skills are considered, including implications for practice and future research targeting low-income toddlers.

  12. Early Epstein-Barr Virus Genomic Diversity and Convergence toward the B95.8 Genome in Primary Infection.

    Science.gov (United States)

    Weiss, Eric R; Lamers, Susanna L; Henderson, Jennifer L; Melnikov, Alexandre; Somasundaran, Mohan; Garber, Manuel; Selin, Liisa; Nusbaum, Chad; Luzuriaga, Katherine

    2018-01-15

    Over 90% of the world's population is persistently infected with Epstein-Barr virus. While EBV does not cause disease in most individuals, it is the common cause of acute infectious mononucleosis (AIM) and has been associated with several cancers and autoimmune diseases, highlighting a need for a preventive vaccine. At present, very few primary, circulating EBV genomes have been sequenced directly from infected individuals. While low levels of diversity and low viral evolution rates have been predicted for double-stranded DNA (dsDNA) viruses, recent studies have demonstrated appreciable diversity in common dsDNA pathogens (e.g., cytomegalovirus). Here, we report 40 full-length EBV genome sequences obtained from matched oral wash and B cell fractions from a cohort of 10 AIM patients. Both intra- and interpatient diversity were observed across the length of the entire viral genome. Diversity was most pronounced in viral genes required for establishing latent infection and persistence, with appreciable levels of diversity also detected in structural genes, including envelope glycoproteins. Interestingly, intrapatient diversity declined significantly over time ( P < 0.01), and this was particularly evident on comparison of viral genomes sequenced from B cell fractions in early primary infection and convalescence ( P < 0.001). B cell-associated viral genomes were observed to converge, becoming nearly identical to the B95.8 reference genome over time (Spearman rank-order correlation test; r = -0.5589, P = 0.0264). The reduction in diversity was most marked in the EBV latency genes. In summary, our data suggest independent convergence of diverse viral genome sequences toward a reference-like strain within a relatively short period following primary EBV infection. IMPORTANCE Identification of viral proteins with low variability and high immunogenicity is important for the development of a protective vaccine. Knowledge of genome diversity within circulating viral

  13. Carcinoma of the uterine cervix. High-resolution turbo spin-echo MR imaging with contrast-enhanced dynamic scanning and T2-weighting

    International Nuclear Information System (INIS)

    Abe, Y.; Yamashita, Y.; Namimoto, T.; Takahashi, M.; Katabuchi, H.; Tanaka, N.; Okamura, H.

    1998-01-01

    Purpose: To compare high-resolution contrast-enhanced (Gd-DTPA) dynamic MR imaging with T2-weighted turbo spin-echo (TSE) imaging in the evaluation of uterine cervical carcinoma. Material and Methods: Thirty-two patients with cervical carcinoma underwent MR imaging on a 1.5 T superconductive unit to have the extension of the disease assessed before treatment. A phased-array coil was used in all patients. In 25 patients, surgical confirmation of the diagnosis was obtained after imaging. Radiation therapy was selected for the remaining 7 patients with advanced carcinoma. Qualitative and quantitative image analyses were also performed. Results: The cervical carcinomas showed maximum contrast in the cervical stroma and myometrium in the early dynamic phase. The tumor/cervical-stroma contrast in the early dynamic phase obtained with the T1-weighted TSE technique (contrast-to-noise ratio 22.6) was significantly higher than that obtained in T2-weighted TSE imaging (contrast-to-noise ratio 4.3). In the evaluation of parametrial invasion, the accuracy of T2-weighted imaging was 71.8% and contrast-enhanced dynamic imaging 81.2%. Conclusion: High-resolution contrast-enhanced (Gd-DTPA) dynamic MR imaging in cervical cancer offers improved tumor/cervical-stroma contrast and provides useful information on parametrial invasion. (orig.)

  14. Elevated Social Anxiety among Early Maturing Girls

    Science.gov (United States)

    Blumenthal, Heidemarie; Leen-Feldner, Ellen W.; Babson, Kimberly A.; Gahr, Jessica L.; Trainor, Casey D.; Frala, Jamie L.

    2011-01-01

    Adolescence is a key period in terms of the development of anxiety psychopathology. An emerging literature suggests that early pubertal maturation is associated with enhanced vulnerability for anxiety symptomatology, although few studies have examined this association with regard to social anxiety. Accordingly, the current study was designed to…

  15. The determinants of early retirement in Switzerland

    OpenAIRE

    Dorn, David; Sousa-Poza, Alfonso

    2005-01-01

    In the past decade, Switzerland has experienced a large increase in the number of individuals going into early retirement. This paper examines the determinants of such early retirement using data from the newly implemented social-security module of the 2002 Swiss Labor Force Survey. In the sixteen-month period from January 2001 to April 2002, more than 36,000 older individuals, representing 8% of all workers within nine years of legal retirement age, became early retirees. One of the most imp...

  16. Selective T-cell depletion targeting CD45RA reduces viremia and enhances early T-cell recovery compared with CD3-targeted T-cell depletion.

    Science.gov (United States)

    Triplett, Brandon M; Muller, Brad; Kang, Guolian; Li, Ying; Cross, Shane J; Moen, Joseph; Cunningham, Lea; Janssen, William; Mamcarz, Ewelina; Shook, David R; Srinivasan, Ashok; Choi, John; Hayden, Randall T; Leung, Wing

    2018-02-01

    T-cell depletion (TCD) effectively reduces severe graft-versus-host disease in recipients of HLA-mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory-immunity in the allografts and confer protection against important viral infections in the early post-transplant period. Sixty-seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed. Patients receiving CD45RA-depleted donor grafts had 2000-fold more donor T cells infused, significantly higher T-cell counts at Day +30 post transplant (550/μL vs 10/μL; P depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P = .02). CD45RA-depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T-cell recovery and protection against viremia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Disruption of AtWNK8 Enhances Tolerance of Arabidopsis to Salt and Osmotic Stresses via Modulating Proline Content and Activities of Catalase and Peroxidase

    Directory of Open Access Journals (Sweden)

    Hong Liao

    2013-03-01

    Full Text Available With no lysine kinases (WNKs play important roles in plant growth and development. However, its role in salt and osmotic stress tolerance is unclear. Here, we report that AtWNK8 is mainly expressed in primary root, hypocotyl, stamen and pistil and is induced by NaCl and sorbitol treatment. Compared to the wild-type, the T-DNA knock-out wnk8 mutant was more tolerant to severe salinity and osmotic stresses, as indicated by 27% and 198% more fresh weight in the NaCl and sorbitol treatment, respectively. The wnk8 mutant also accumulated 1.43-fold more proline than the wild-type in the sorbitol treatment. Under NaCl and sorbitol stresses, catalase (CAT activity in wnk8 mutant was 1.92- and 3.7-times of that in Col-0, respectively. Similarly, under salt and osmotic stress conditions, peroxidase (POD activities in wnk8 mutant were 1.81- and 1.58-times of that in Col-0, respectively. Taken together, we revealed that maintaining higher CAT and POD activities might be one of the reasons that the disruption of AtWNK8 enhances the tolerance to salt stress, and accumulating more proline and higher activities of CAT and POD might result in the higher tolerance of WNK8 to osmotic stress.

  18. Bladder transitional cell carcinoma: correlation of contrast enhancement on computed tomography with histological grade and tumour angiogenesis

    International Nuclear Information System (INIS)

    Xie, Q.; Zhang, J.; Wu, P.-H.; Jiang, X.-Q.; Chen, S.-L.; Wang, Q.-L.; Xu, J.; Chen, G.-D.; Deng, J.-H.

    2005-01-01

    AIM: To investigate the correlation between the degree of contrast enhancement of bladder cancer in the early enhanced phase of helical computed tomography (CT) and microvessel density (MVD), vascular endothelial growth factor (VEGF) and histological grade. MATERIALS AND METHODS: Sixty-five patients with transitional cell carcinoma of the bladder were examined by incremental unenhanced CT and helical CT at 40-45 s after initiation of intravenous administration of contrast medium before surgery. The CT density in Hounsfield units of bladder carcinomas were measured in the middle of the maximum diameter section of the cancer lesions on unenhanced and enhanced CT. The degree of contrast enhancement of the tumour was determined as the absolute increase in Hounsfield units. Histological grade, VEGF and MVD were analysed for each cancer. The Pearson and Spearman correlation tests were used to determine the strength of the relationships between CT enhancement and histological grade, VEGF expression and MVD. RESULTS: Different degrees of enhancement were observed in 91 cancers during the early enhanced phase of helical CT. Mean MVDs and mean CT enhancing values of different histological grade groups were statistically different (p<0.001). A positive correlation was found in the CT-enhancing value of bladder cancer and MVD (Pearson correlation test; r=0.938, p<0.001) and histological grade (Spearman rank correlation; r=0.734, p<0.001). VEGF of bladder cancer did not correlate with the change in CT attenuation (Spearman rank correlation; r=0.087, p=0.410) and MVD (Spearman rank correlation, r=0.103, p=0.330). CONCLUSION: In bladder cancer, the degree of contrast enhancement during the early enhanced helical CT is correlated with the MVD and histological grade of tumour. It is possible that MVD is the histopathological basis of early contrast enhancement of bladder cancer

  19. Signalling fiscal stress in the euro area - a country-specific early warning system

    OpenAIRE

    Hernández de Cos, Pablo; Koester, Gerrit B.; Moral-Benito, Enrique; Nickel, Christiane

    2014-01-01

    The sovereign debt crisis in the euro area has increased the interest in early warning indicators, with the aim to indicate the build?up of fiscal stress early on and to facilitate crisis prevention by a timely counteraction of fiscal and macroeconomic policies. This paper presents possible improvements to enhance existing early warning indicators for fiscal stress, especially for the euro area. We show that a country?specific approach could strongly increase the signalling power of early war...

  20. Early warning scores: a sign of deterioration in patients and systems

    LENUS (Irish Health Repository)

    Fox, A

    2015-02-01

    The early warning score is a decision-making tool that has a simple design, yet its implementation in healthcare organisations is proving complex. This article reports the results of a survey that evaluated the nurses’ experiences of using the NEWS (National Early Warning Score) in an acute hospital in Ireland. Staff reported that the NEWS was easy to use, did not increase workload and enhanced their ability to identify deteriorating patients. However, they also identified problems related to doctors’ delayed response times, doctors lack of training in the use of the tool, and a failure by doctors to modify parameters for patients with chronic conditions. NEWS enhances nurses’ role in early detection of patient deterioration but delays in response times by doctors, exposes systematic flaws in healthcare. This suggests that it is not only an indicator of patient deterioration but also of deteriorating healthcare systems.

  1. Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8+ TEM and TRM Cell Responses against Herpesvirus Infection and Disease.

    Science.gov (United States)

    Lopes, Patricia P; Todorov, George; Pham, Thanh T; Nesburn, Anthony B; Bahraoui, Elmostafa; BenMohamed, Lbachir

    2018-04-15

    There is an urgent need for chemical-free and biological-free safe adjuvants to enhance the immunogenicity of vaccines against widespread viral pathogens, such as herpes simplex virus 2 (HSV-2), that infect a large proportion of the world human population. In the present study, we investigated the safety, immunogenicity, and protective efficacy of a laser adjuvant-assisted peptide (LAP) vaccine in the B6 mouse model of genital herpes. This LAP vaccine and its laser-free peptide (LFP) vaccine analog contain the immunodominant HSV-2 glycoprotein B CD8 + T cell epitope (HSV-gB 498-505 ) covalently linked with the promiscuous glycoprotein D CD4 + T helper cell epitope (HSV-gD 49-89 ). Prior to intradermal delivery of the LAP vaccine, the lower-flank shaved skin of B6 or CD11c/eYFP transgenic mice received a topical skin treatment with 5% imiquimod cream and then was exposed for 60 s to a laser, using the FDA-approved nonablative diode. Compared to the LFP vaccine, the LAP vaccine (i) triggered mobilization of dendritic cells (DCs) in the skin, which formed small spots along the laser-treated areas, (ii) induced phenotypic and functional maturation of DCs, (iii) stimulated long-lasting HSV-specific effector memory CD8 + T cells (T EM cells) and tissue-resident CD8 + T cells (T RM cells) locally in the vaginal mucocutaneous tissues (VM), and (iv) induced protective immunity against genital herpes infection and disease. As an alternative to currently used conventional adjuvants, the chemical- and biological-free laser adjuvant offers a well-tolerated, simple-to-produce method to enhance mass vaccination for widespread viral infections. IMPORTANCE Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect a large proportion of the world population. There is an urgent need for chemical-free and biological-free safe adjuvants that would advance mass vaccination against the widespread herpes infections. The present study demonstrates that immunization with a laser

  2. Angiogenesis and dynamic contrast enhanced MRI of benign and malignant breast lesions: preliminary results

    International Nuclear Information System (INIS)

    Liu Peifang; Bao Runxian; Niu Yun; Yu Yong

    2002-01-01

    Objective: To determine whether dynamic contrast enhanced MRI features of early-phase enhancement rate, enhancement amplitude, and signal intensity (SI) time course are associated with the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression of malignant and benign breast lesions. Methods: Thirty-eight patients with histopathologically verified breast lesions underwent dynamic contrast enhanced MRI. SI changes during dynamic scanning were assessed quantitatively. Early-phase enhancement rate and enhancement amplitude were calculated. Time-SI curves of the lesions were obtained and classified according to their shapes as type I (which was steady enhancement to the end of the dynamic data acquisition at 7.5 min), type II (plateau of SI after avid initial contrast enhancement), or type III (washout of SI after avid initial contrast enhancement). the mean MVD and VEGF expression of the lesions were measured with immuno-histochemical staining method in all the histologic specimens by pathologists without the knowledge of the results of the MR examination. The relationships among dynamic contrast enhanced MRI features, MVD, and VEGF expression of benign and malignant breast lesions were analyzed. Results: Histology revealed 21 malignancies and 17 benign lesions. The mean MVD and VEGF expression for 21 malignant lesions were statistically higher than the mean MVD and VEGF expression for 17 benign lesions. High VEGF expression of benign and malignant breast lesions showed an association with increased MVD. Among all 38 lesions, greater (> 60%) MR early-phase enhancement rate and time-SI curve type II and III showed an association with increased MVD and higher VEGF expression level. All the differences mentioned above showed statistical significance except that the difference between VEGF expression and the distribution of curve types had no statistical significance. No significant relationships were observed between the mean of enhancement

  3. Specific role of taurine in the 8-brominated-2'-deoxyguanosine formation.

    Science.gov (United States)

    Asahi, Takashi; Nakamura, Yoshimasa; Kato, Yoji; Osawa, Toshihiko

    2015-11-15

    At the sites of inflammation, hypohalous acids, such as hypochlorous acid and hypobromous acid (HOBr), are produced by myeloperoxidase. These hypohalous acids rapidly react with the primary amino groups to produce haloamines, which are relatively stable and can diffuse long distances and cross the plasma membrane. In this study, we examined the effects of taurine, the most abundant free amino acid in the leukocyte cytosol, on the hypohalous acid-dependent formation of 8-chloro-2'-deoxyguanosine (8-CldG) and 8-bromo-2'-deoxyguanosine (8-BrdG). The reaction of taurine with HOBr yielded taurine bromamine, which is the most stable among other bromamines of amino acids. Taurine also enhanced the bromination of only dG among the four 2'-deoxynucleosides, whereas it inhibited the 8-CldG formation. The specificity of taurine for the enhanced formation of halogenated dG is completely different from that of nicotine, an enhancer of chlorination. The amount of dibrominated taurine (taurine dibromamine) closely correlated with the formation of 8-BrdG, suggesting that taurine dibromamine might be a plausible mediator for the dG bromination in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Infection of Early and Young Callus Tissues of Indica Rice BPT 5204 Enhances Regeneration and Transformation Efficiency

    Directory of Open Access Journals (Sweden)

    P. MANIMARAN

    2013-11-01

    Full Text Available A rapid and reproducible method to develop transgenic plants with enhanced transformation efficiency using Agrobacterium has been developed for the elite indica rice variety BPT 5204. Different rice calli aged from 3 to 30 d were co-cultivated with pre-incubated Agrobacterium suspension culture (LBA4404: pSB1, pCAMBIA1301 and incubated in dark for 3 d. Based on the transient GUS gene expression analysis, 6-day-old young calli showed high transformation frequency followed by 21-day-old ones. Thus, both 6- and 21-day-old calli were used for assessing the stable transformation efficiency. It was observed that the 6-day-old young transformed calli showed about 2-fold higher regeneration frequency when compared with 21-day-old calli. The transformation efficiency was enhanced for young calli to 5.9% compared with 0.8% of the 21-day-old calli. Molecular and genetic analysis of transgenic plants (T0 revealed the presence of 1–2 copies of T-DNA integration in transformants and it follows Mendalian ratio in T1 transgenic plants. From the present study, it was concluded that the development of transgenic rice plants in less duration with high regeneration and transformation efficiency was achieved in BPT 5204 by using 6-day-old young calli as explants.

  5. Value of contrast-enhanced MRI of breast after silicone implant

    International Nuclear Information System (INIS)

    Heinig, A.; Heywang-Koebrunner, S.H.; Viehweg, P.; Spielmann, R.P.; Lampe, D.; Buchmann, J.

    1997-01-01

    Early recognition of recurrence and work-up of clinically indeterminate lesions may be impaired after reconstruction with silicone implants due to superimposition of the implant or to scarring. This study was undertaken to evaluate the use of contrast-enhanced MRI in patients with silicone implant after breast cancer. Contrast-enhanded MRI was offered to 169 patients. Comparative two- to three-view mammography was also performed in 169 patients, as well as comparative sonography in 144 patients. Conventional imaging and clinical examination detected only 8/13 recurrences, whereas 12/13 were detected by MRI. One recurrence had been visible as a strongly enhancing 2-mm dot in a previous examination (2 years before), but was not called. It was therefore counted as false negative. In addition, multicentricity was detected by MRI alone in two of three cases. MRI correctly diagnosed scar tissue in all cases with indeterminate findings. However, due to false-positive calls caused by enhancing granulomas specificity could not be improved. Contrast-enhanded MRI allowed decisive additional information in our study group and improved the sensitivity significantly (concerning all diagnoses). Contrast-enhanded MRI allowed decisive additional information in our study group and improved the sensitivity significantly (concerning all diagnoses). Contrast-enhanded MRI is recommended in patients with diagnostic problems or high risk of recurrence after silicone implants. (orig.) [de

  6. Morphological development and allometric growth patterns of Acipenser persicus Borodin, 1897 (Actinopterygii, Acipenseridae during early development

    Directory of Open Access Journals (Sweden)

    Soheil Eagderi

    2017-06-01

    Full Text Available Morphological development and allometric growth patterns of reared Persian sturgeon, Acipenser persicus, were studied from hatching to 50 days post-hatching (dph. The larvae were sampled, their left sides photographed and seven morphometric characters, including total length, head length, tail length, trunk length, snout length, caudal peduncle and predorsal length were measured. Allometric growth patterns were calculated as a power function of total length and described using the growth coefficient to find important steps in early life history. The total length of the newly hatched larvae and fry were 10.59±0.8 and 38.8±2.9 mm at 1 and 50 dph, respectively. Morphogenesis and differentiation were the highest rates during the first 11 days of early development, i.e. endogenous feeding period. There were higher growth rate of head, snout and tail regions compared with those of other organs from the hatch up to yolk sac absorption, followed by positive or almost isometric patterns, after the begin of exogenous feeding, showing priority to enhance the feeding and swimming capabilities. This study confirmed that most of morphological changes of this species are occurred from hatching until the onset of exogenous feeding i.e. during the lecithotrophic phase.

  7. Effect of contrast-enhanced ultrasound on differential diagnosis of intrahepatic cholangiocarcinoma and arterial phase enhanced hepatic inflammatory lesions

    Institute of Scientific and Technical Information of China (English)

    Shanshan Yin; Qiuli Cui; Kun Yan; Wei Yang; Wei Wu; Liping Bao; Minhua Chen

    2017-01-01

    Objective:To investigate differential diagnosis between intrahepatic cholangiocarcinoma (ICC) and arterial phase enhanced hepatic inflammatory lesions in patients without liver cirrhosis using contrast-enhanced ultrasound (CEUS).Methods:ICC and hepatic inflammatory lesions cases with CEUS and pathological diagnosis between Sep 2013 and Oct 2016 were investigated retrospectively.Imaging features of conventional ultrasound and CEUS were analyzed.The parameters of time intensity curve (TIC),including the arrival time,peak intensity (PI) in the lesions,the starting time for washout,and the intensity difference at 3 min (△I3) after contrast agent infection between the lesion and the liver parenchyma,were compared between ICC and hepatic inflammatory lesions.Results:Twenty-five ICC and fifteen inflammatory patients were included in this study.Seventeen ICC (68.0%) and two inflammatory cases (13.3%) showed bile duct dilatation on conventional ultrasound.Using CEUS,three ICC cases (12.0%) were misdiagnosed as inflammatory lesions and three inflammatory lesions (20.0%) as ICC;two ICC (8.0%) and one inflammatory case (6.7%) could not be made definite diagnosis.Washout started at 34.5±3.5 s and 61.5± 12.9 s for ICC and inflammatory lesions respectively (P<0.001).The intensity difference between lesion and liver parenchyma at 3 min after contrast agent injection was 10.8±3.1 dB in ICC and 4.2±2.3 dB in inflammatory group (P<0.00 1).The sensitivity and specificity differentiating ICC and inflammatory lesions were 76% and 87% if the cut-offvalue of the intensity difference was 7.7 dB.Conclusions:Combined with TIC analysis,and particularly with the characteristic of the early-starting and obvious washout in ICC,CEUS can be useful in differential diagnosis between hepatic inflammatory lesions and ICC.

  8. An SU-8-based microprobe with a nanostructured surface enhances neuronal cell attachment and growth

    Science.gov (United States)

    Kim, Eunhee; Kim, Jin-Young; Choi, Hongsoo

    2017-12-01

    Microprobes are used to repair neuronal injury by recording electrical signals from neuronal cells around the surface of the device. Following implantation into the brain, the immune response results in formation of scar tissue around the microprobe. However, neurons must be in close proximity to the microprobe to enable signal recording. A common reason for failure of microprobes is impaired signal recording due to scar tissue, which is not related to the microprobe itself. Therefore, the device-cell interface must be improved to increase the number of neurons in contact with the surface. In this study, we developed nanostructured SU-8 microprobes to support neuronal growth. Nanostructures of 200 nm diameter and depth were applied to the surface of microprobes, and the attachment and neurite outgrowth of PC12 cells on the microprobes were evaluated. Neuronal attachment and neurite outgrowth on the nanostructured microprobes were significantly greater than those on non-nanostructured microprobes. The enhanced neuronal attachment and neurite outgrowth on the nanostructured microprobes occurred in the absence of an adhesive coating, such as poly- l-lysine, and so may be useful for implantable devices for long-term use. Therefore, nanostructured microprobes can be implanted without adhesive coating, which can cause problems in vivo over the long term.

  9. Ultrasonographic findings of early abortion: suggested predictors

    International Nuclear Information System (INIS)

    Jun, Soon Ae; Ahn, Myoung Ock; Cha, Kwang Yul; Lee, Young Doo

    1992-01-01

    To investigate predictable ultrasonographic findings of early abortion. To investigate objective rules for the screening of abortion. Ultrasonographic examination of 111 early pregnancies between the sixth and ninth week in women who had regular 28 day menstrual cycles was performed. Ultrasonographic measurements of the gestational sac, crown rump length and fetal heart rate were performed using a linear array real time transducer with doppler ultrasonogram. All measurements of 17 early abortions were compared to those of 94 normal pregnancies. Most of early aborted pregnancies were classified correctly by discriminant analysis with G-SAC and CRL (G-SAC=0.5 CRL + 15, sensitivity 76.5%, specificity 96.8%). With the addition of FHR, 94.1% of early abortions could be predicted. In conclusion, ultrasonographic findings of early intrauterine growth retardation, small gestational sac and bradycardia can be predictable signs suggestive of poor prognosis of early pregnancies

  10. Audit of the autoantibody test, EarlyCDT®-lung, in 1600 patients: an evaluation of its performance in routine clinical practice.

    Science.gov (United States)

    Jett, James R; Peek, Laura J; Fredericks, Lynn; Jewell, William; Pingleton, William W; Robertson, John F R

    2014-01-01

    EarlyCDT(®)-Lung may enhance detection of early stage lung cancer by aiding physicians in assessing high-risk patients through measurement of biological markers (i.e., autoantibodies). The test's performance characteristics in routine clinical practice were evaluated by auditing clinical outcomes of 1613 US patients deemed at high risk for lung cancer by their physician, who ordered the EarlyCDT-Lung test for their patient. Clinical outcomes for all 1613 patients who provided HIPAA authorization are reported. Clinical data were collected from each patient's treating physician. Pathology reports when available were reviewed for diagnostic classification. Staging was assessed on histology, otherwise on imaging. Six month follow-up for the positives/negatives was 99%/93%. Sixty-one patients (4%) were identified with lung cancer, 25 of whom tested positive by EarlyCDT-Lung (sensitivity=41%). A positive EarlyCDT-Lung test on the current panel was associated with a 5.4-fold increase in lung cancer incidence versus a negative. Importantly, 57% (8/14) of non-small cell lung cancers detected as positive (where stage was known) were stage I or II. EarlyCDT-Lung has been extensively tested and validated in case-control settings and has now been shown in this audit to perform in routine clinical practice as predicted. EarlyCDT-Lung may be a complementary tool to CT for detection of early lung cancer. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. Intense Adrenal Enhancement: A CT Feature of Cardiogenic Shock

    International Nuclear Information System (INIS)

    Hrabak-Paar, Maja

    2016-01-01

    In this report, images of intense adrenal enhancement in a 79-year-old female patient with right-sided heart failure and severe tricuspid insufficiency are presented. Only two cases of intense adrenal enhancement as a sign of cardiogenic shock were previously reported in the literature. Intense adrenal enhancement could be one of the earliest CT signs of cardiogenic shock. Its presence should be immediately reported to the referring physician as a sign of significant hemodynamic instability warranting early critical-care management

  12. Intense Adrenal Enhancement: A CT Feature of Cardiogenic Shock

    Energy Technology Data Exchange (ETDEWEB)

    Hrabak-Paar, Maja, E-mail: maja.hrabak.paar@mef.hr [University of Zagreb School of Medicine, Department of Diagnostic and Interventional Radiology, University Hospital Center Zagreb (Croatia)

    2016-02-15

    In this report, images of intense adrenal enhancement in a 79-year-old female patient with right-sided heart failure and severe tricuspid insufficiency are presented. Only two cases of intense adrenal enhancement as a sign of cardiogenic shock were previously reported in the literature. Intense adrenal enhancement could be one of the earliest CT signs of cardiogenic shock. Its presence should be immediately reported to the referring physician as a sign of significant hemodynamic instability warranting early critical-care management.

  13. Clinical significance of nerve root enhancement in contrast-enhanced MR imaging of the postoperative lumbar spine

    International Nuclear Information System (INIS)

    Lee, Yeon Soo; Lee, Eun Ja; Kang, Si Won; Choi, Eun Seok; Song, Chang June; Kim, Jong Chul

    2001-01-01

    To determine the significance of nerve root contrast enhancement in patients with residual or recurrent symptomatic postoperative lumbar spine. Eighty-eight patients with 116 postoperative lumbar disc lesions causing radiating back pain underwent enhanced MR imaging. Intradural nerve root enhancement was quantified by pixel measurement, and affected nerve roots were compared before and after contrast administration. Extradural nerve root enhancement was assessed visually, and nerve root enhancement and clinical symptoms were correlated. Associated lesions such as recurrent disc herniation, scar tissue, nerve root thickening and nerve root displacement were also evaluated. Of 26 cases (22.4%) involving intradural nerve root enhancement, 22 (84.6%) showed significant clinical symptoms (p=0.002). and of 59 (50.9%) demonstrating extradural enhancement, clinical symptoms showed significant correlation in 47 (79.7%) (p=0.001). Nerve root enhancement, including eleven cases where this was both intra-and extradural, showed highly significant association with clinical symptoms in 74 of the 116 cases (63.8%) (p=0.000). Among 33 cases (28.4%) of recurrent disc herniation, nerve root enhancement was observed in 28 (84.8%) and in 24 of these 28 (85.7%), significant correlation with clinical symptoms was observed (p=0.000). Where epidural fibrosis was present, correlation between nerve root enhancement and clinical symptoms was not significant (p>0.05). Nerve root thickening and displaced nerve root were, however, significantly associated with symptoms (87.2% and 88.6%, respectively). In patients with postoperative lumbar spine, the association between nerve root enhancement revealed by MRI and clinical symptoms was highly significant

  14. Freedom and Slavery in Early Islamic Time (1st/7th and 2nd/8th centuries

    Directory of Open Access Journals (Sweden)

    Schneider, Irene

    2007-12-01

    Full Text Available This article focuses on two topics: the presumption of freedom in the “literary period” (from the 8th century on and the question of enslavement, sale, bondage or self-dedition of free persons in the “pre-literary period” (7th and 8th centuries. Based on the assumption that the legal practice in Late Antiquity influenced the discussions of the early Muslim jurists I will try to reconstruct the legal discourse of the 1st/7th and 2nd/ 8th centuries and to show that this discourse comprised interesting legal opinions with regard to the sale of children, debt-bondage and the legal position of foundlings. In the legal literature which emerged from the 2nd/8th century the jurists did not, as one would expect, deal intensively with the topic. Thus there is, as will be shown, a certain inconsistency between the lively and controversial discourse in the “pre-literary period” on the topic, which will be reconstructed in this article, and the marginalization of the topic in the legal literature afterwards.

    Este artículo se centra en dos cuestiones: por un lado, la presunción de libertad en el «período literario» (desde el s. VIII en adelante; y, por otro, la cuestión de la esclavización, venta o servidumbre —voluntaria o no— de personas libres en la «época preliteraria» (ss. VII y VIII. Asumiendo de partida la idea de que la práctica legal en la Antigüedad Tardía influyó en las discusiones de los primeros juristas musulmanes, trataré de reconstruir el discurso legal de los siglos I/VII y II/VIII y de mostrar que ese discurso contenía interesantes opiniones legales en relación a la venta de niños, servidumbre por deudas y la situación legal de los huérfanos. En la literatura legal que emergió desde el s. II/VIII los juristas, al contrario de lo que se hubiese esperado, no trataron estas cuestiones intensamente. Tal y

  15. Early stage structural development of prototypical zeolitic imidazolate framework (ZIF) in solution

    Energy Technology Data Exchange (ETDEWEB)

    Terban, Maxwell W.; Banerjee, Debasis; Ghose, Sanjit; Medasani, Bharat K.; Shukla, Anil K.; Legg, Benjamin A.; Zhou, Yufan; Zhu, Zihua; Sushko, Maria L.; De Yoreo, James J.; Liu, Jun; Thallapally, Praveen K.; Billinge, Simon L.

    2018-03-28

    Given the wide-ranging potential applications of metal organic frameworks (MOFs), an emerging imperative is to understand their formation with atomic scale precision. This will aid in designing syntheses for next-generation MOFs with enhanced properties and functionalities. Major challenges are to characterize the early-stage seeds, and the pathways to framework growth, which require synthesis coupled with in situ structural characterization sensitive to nanoscale structures in solution. Here we report measurements of an in situ synthesis of a prototypical MOF, ZIF-8, utilizing synchrotron X-ray atomic pair distribution function (PDF) analysis optimized for sensitivity to dilute species, complemented by mass spectrometry, electron microscopy, and density functional theory calculations. We observe that despite rapid formation of the crystalline product, a high concentration of Zn(2-MeIm)4 (2-MeIm = 2-methylimidazolate) initially forms and persists as stable clusters over long times. A secondary, amorphous phase also pervades during the synthesis, which has a structural similarity to the final ZIF-8 and may act as an intermediate to the final product.

  16. HuR/ELAVL1 RNA binding protein modulates interleukin-8 induction by muco-active ribotoxin deoxynivalenol

    International Nuclear Information System (INIS)

    Choi, Hye Jin; Yang, Hyun; Park, Seong Hwan; Moon, Yuseok

    2009-01-01

    HuR/Elav-like RNA binding protein 1 (ELAVL1) positively regulates mRNA stability of AU-rich elements (ARE)-containing transcript such as pro-inflammatory cytokines. Ribotoxic stresses can trigger the production of pro-inflammatory mediators by enhancing mRNA stability and the transcriptional activity. We investigated the effects of ribotoxin deoxynivalenol (DON) on HuR translocation and its involvement in the regulation of the pro-inflammatory interleukin-8 (IL-8) mRNA stability. Exposure to the muco-active DON induced nuclear export of both endogenous and exogenous HuR RNA binding protein in human intestinal epithelial cells. Moreover, the interference with HuR protein production suppressed ribotoxic DON-induced IL-8 secretion and its mRNA stability. Cytoplasmic HuR protein interacted with IL-8 mRNA and the complex stabilization was due to the presence of 3'-untranslated region of the transcript. Partly in terms of IL-8-modulating transcription factors, HuR protein was demonstrated to be positively and negatively associated with DON-induced early growth response gene 1 (EGR-1) and activating transcription factor 3 (ATF3), respectively. HuR was a critical mechanistic link between ribotoxic stress and the pro-inflammatory cytokine production, and may have a broader functional significance with regard to mucosal insults since ribotoxic stress responses are also produced upon interactions with the diverse environment of gut.

  17. Multiple-Threshold Event Detection and Other Enhancements to the Virtual Seismologist (VS) Earthquake Early Warning Algorithm

    Science.gov (United States)

    Fischer, M.; Caprio, M.; Cua, G. B.; Heaton, T. H.; Clinton, J. F.; Wiemer, S.

    2009-12-01

    The Virtual Seismologist (VS) algorithm is a Bayesian approach to earthquake early warning (EEW) being implemented by the Swiss Seismological Service at ETH Zurich. The application of Bayes’ theorem in earthquake early warning states that the most probable source estimate at any given time is a combination of contributions from a likelihood function that evolves in response to incoming data from the on-going earthquake, and selected prior information, which can include factors such as network topology, the Gutenberg-Richter relationship or previously observed seismicity. The VS algorithm was one of three EEW algorithms involved in the California Integrated Seismic Network (CISN) real-time EEW testing and performance evaluation effort. Its compelling real-time performance in California over the last three years has led to its inclusion in the new USGS-funded effort to develop key components of CISN ShakeAlert, a prototype EEW system that could potentially be implemented in California. A significant portion of VS code development was supported by the SAFER EEW project in Europe. We discuss recent enhancements to the VS EEW algorithm. We developed and continue to test a multiple-threshold event detection scheme, which uses different association / location approaches depending on the peak amplitudes associated with an incoming P pick. With this scheme, an event with sufficiently high initial amplitudes can be declared on the basis of a single station, maximizing warning times for damaging events for which EEW is most relevant. Smaller, non-damaging events, which will have lower initial amplitudes, will require more picks to be declared an event to reduce false alarms. This transforms the VS codes from a regional EEW approach reliant on traditional location estimation (and it requirement of at least 4 picks as implemented by the Binder Earthworm phase associator) to a hybrid on-site/regional approach capable of providing a continuously evolving stream of EEW

  18. In vitro of quantitative MR imaging of early degenerative changes in human articular cartilage

    International Nuclear Information System (INIS)

    Kim, Ok Wha; Lee, Young Jun; Cha, Sung Suk; Hwa, Ryu Ji

    2004-01-01

    To assess the applicability of quantitative MR microscopy for the detection of glycosaminoglycan (GAG) depletion as an early sign of degeneration in the articular cartilage of humans treated by trypsin. Four cartilage-bone blocks were obtained from the patient who had suffered from osteoarthritis of the knee and underwent a total knee replacement arthroscopy. Each articular cartilage segment was resected as to a round disk shape (8 mm in diameter) with a remnant of subchondral bone 1 mm in thickness. Four different culture solutions were prepared, and these solutions were 0.2 mg/ml of trypsin solution (group 1), 1 mM of Gd (DTPA) 2-mixed trypsin solution (group 2), phosphate buffered saline (PBS) (group 3), and 1 mM of Gd (DTPA) 2-mixed PBS (group 4). The cartilages were cultured and then MR imagings were performed every hour for 5 hrs, and we continued the additional cultures of 24 hrs, 36 hrs and 48 hrs. Three imaging sequences were used: T1-weighted spin echo (TR/TE, 450/22), proton density turbo spin echo with fat suppression (TR/TE, 3000/25), and CPMG (Carr-Purcell-Meiboom-Gill) (TR/TE/TI, 760/21-168, 360). MR imaging data were analyzed with pixel-by-pixel comparisons in all groups. The GAG loss in the articular cartilage was increased proportionately to the culture duration. Mean changes of T1 relaxation time were 1.2% for group 1, -1.9% for group 3, -54.7% for group 2 and -64.2% for group 4 (p< 0.05). When comparing by linear profile on the T1-weighted images, SNR increased and T1 relaxation time decreased for group 2 and 4, as the culture duration increased (p< 0.05). On the correlation analysis, there is significant correlation between GAG loss and Gd (DTPA) 2-enhancement for group 2 (p=0.0431), but there was no significant difference for group 4 (p=0.0918). More enhancement with Gd (DTPA) 2-was noted for group 2 than for group 4. Group 2 showed a diffuse enhancement in all the layers of cartilage, but for group 4, prominent enhancement was noted only in

  19. Supersonic gas streams enhance the formation of massive black holes in the early universe.

    Science.gov (United States)

    Hirano, Shingo; Hosokawa, Takashi; Yoshida, Naoki; Kuiper, Rolf

    2017-09-29

    The origin of super-massive black holes in the early universe remains poorly understood. Gravitational collapse of a massive primordial gas cloud is a promising initial process, but theoretical studies have difficulty growing the black hole fast enough. We report numerical simulations of early black hole formation starting from realistic cosmological conditions. Supersonic gas motions left over from the Big Bang prevent early gas cloud formation until rapid gas condensation is triggered in a protogalactic halo. A protostar is formed in the dense, turbulent gas cloud, and it grows by sporadic mass accretion until it acquires 34,000 solar masses. The massive star ends its life with a catastrophic collapse to leave a black hole-a promising seed for the formation of a monstrous black hole. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  20. Dynamic contrast enhanced MRI in the differential diagnosis of adrenal adenomas and malignant adrenal masses

    International Nuclear Information System (INIS)

    Inan, Nagihan; Arslan, Arzu; Akansel, Gur; Anik, Yonca; Balci, N. Cem; Demirci, Ali

    2008-01-01

    Objective: To evaluate the value of dynamic MR imaging in the differential diagnosis of adrenal adenomas and malignant tumors, especially in cases with atypical adenomas. Materials and methods: Sixty-four masses (48 adenomas, 16 malignant tumors) were included in this prospective study. Signal loss of masses was evaluated using chemical shift MR imaging. Five dynamic series of T1-weighted spoiled gradient echo (FFE) images were obtained, with the acquisition starting simultaneously with i.v. contrast administration (0-100 s) followed by a T1-weighted FFE sequence in the late phase (5th minute). Contrast enhancement patterns in the early (25th second) and late (5th minute) phase images were evaluated. For the quantitative evaluation, signal intensity (SI)-time curves were obtained according to the SIs on the 0th, 25th, 50th 75th and 100th second. Also, the wash-in rate, maximum relative enhancement, time-to-peak, and wash-out of contrast at 100 s of masses in both groups were calculated. The statistical significance was determined by Mann-Whitney U test. To evaluate the diagnostic performance of the quantitative tests, receiver operating characteristic (ROC) analysis was performed. Results: Chemical shift MR imaging was able to differentiate 44 out of 48 adenomas (91.7%) from non-adenomas. The 4 adenomas (8.3%) which could not be differentiated from non-adenomas by this technique did not exhibit signal loss on out-of-phase images. With a cut-off value of 30, SI indices of adenomas had a sensitivity of 93.8%, specificity of 100% and a positive predictive value of 100%. On visual evaluation of dynamic MR imaging, early phase contrast enhancement patterns were homogeneous in 75% and punctate in 20,83% of the adenomas; while patchy in 56.25% and peripheral in 25% of the malignant tumors. On the late phase images 58.33% of the adenomas showed peripheral ring-shaped enhancement and 10.41% showed heterogeneous enhancement. All of the malignant masses showed heterogeneous

  1. Early prenatal syphilis

    Directory of Open Access Journals (Sweden)

    Santosh Rathod

    2010-01-01

    Full Text Available Syphilis in pregnancy still remains a challenge despite the availability of adequate diagnostic tests for serological screening and penicillin therapy. We report a case of 2 month old female infant who presented with runny nose, papulosquamous lesions over both palms and soles and perianal erosions since 1 month after birth. Cutaneous examination revealed moist eroded areas in the perianal region and fine scaly lesions over palms and soles. Radiograph of both upper limbs and limbs revealed early periosteal changes in lower end of humerus and lower end of tibia. Diagnosis of early pre-natal syphilis was confirmed by Child′s Serum Rapid Plasma Reagin Antibody test [S.RPR] being positive with 1:64 dilution while that of mother was 1:8.

  2. Early diagnosis of diabetic retinopathy in primary care.

    Science.gov (United States)

    Jimenez-Baez, Maria Valeria; Marquez-Gonzalez, Horacio; Barcenas-Contreras, Rodolfo; Morales Montoya, Carlos; Espinosa-Garcia, Laura Fatima

    2015-01-01

    To evaluate the impact of a strategy for early detection of diabetic retinopathy in patients with type 2 diabetes mellitus (DMT2) in Quintana Roo, México. Study transversal, observational, prospective, analytical, eight primary care units from Mexican Social Security Institute in the northern delegation of the State of Quintana Roo, Mexico were included. A program for early detection of diabetic retinopathy (DR) in adult 376,169 was designed. Were diagnosed 683 cases of type 2 diabetes, in 105 patients randomized was conducted to direct ophthalmoscopy were subjected to a secondary hospital were assigned. Will determine the degree of diabetic retinopathy and macular edema was performed. In population were 55.2% female, mean age 48+11.1 years, 23.8 % had some degree of DR, 28.0% with mild non- proliferative diabetic retinopathy 48.0 % moderate 16.0% and severe and 8.0% showed proliferative diabetic retinopathy. Those over age 30 are 2.8 times more risk of developing DR, OR= 2.8; 95%CI: 0.42-18.0, and OR= 1.7; 95%CI: 1.02-2.95 women. The implementation of programs aimed at the early detection of debilitating conditions such as diabetic retinopathy health impact beneficiaries, effective links between primary care systems and provide second level positive health outcomes for patient diseases.

  3. Effectiveness of a Danish early year preschool program

    DEFF Research Database (Denmark)

    Jensen, Bente; Holm, Anders; Bremberg, Sven

    2013-01-01

    A significant number of studies indicate that early year preschool programs lead to positive long-term effects. Systematic quality improvement of early year preschool may enhance these outcomes. The ASP Program was built on this principle. In this program preschool staff are supported...... in their efforts to critically reflect on current practices and to change these. A randomized controlled study was carried out in Denmark from September 2006 to May 2008. The study encompassed 2323 children in 59 preschools in two municipalities. Children were assessed using the Strength and Difficulties...

  4. Contrast enhancement of cranial lesions in computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lewander, R; Bergstroem, M; Bergvall, U [Kungliga Karolinska Mediko-Kirurgiska Inst., Stockholm (Sweden)

    1978-01-01

    The time course of enhancement in apparently normal brain tissue, edema and focal lesions during 30 to 60 min after intravenous injection of vascular contrast medium was evaluated in a series of 41 pateints with differnt intracranial lesions. The attenuation of apparently normal unenhanced brain tissue varied with the level of the scan, mainly an effect of beam hardening. Different types of enhancement response are discussed in terms of a 3-compartment model. The differential diagnostic potential of contrast enhancement in the early phase needs further evaluation using instruments with short scanning time, while the late phase of enhancement must be recorded with the use of a reliable head fixation to provide reproducibility of repeat measurements.

  5. A New Adjuvant Combined with Inactivated Influenza Enhances Specific CD8 T Cell Response in Mice and Decreases Symptoms in Swine Upon Challenge.

    Science.gov (United States)

    Bouguyon, Edwige; Goncalves, Elodie; Shevtsov, Alexander; Maisonnasse, Pauline; Remyga, Stepan; Goryushev, Oleg; Deville, Sebastien; Bertho, Nicolas; Ben Arous, Juliette

    2015-11-01

    Vaccination is the most effective way to control swine influenza virus (SIV) in the field. Classical vaccines are based on inactivated antigens formulated with an oil emulsion or a polymeric adjuvant. Standard adjuvants enhance the humoral response and orient the immune response toward a Th2 response. An important issue is that current vaccines do not protect against new strains. One approach to improve cross-protection is to enhance Th1 and cytotoxic responses. The development of adjuvants orienting the immune response of inactivated vaccines toward Th1/Cytotoxic responses would be highly beneficial. This study shows that the water in oil in water emulsion adjuvant Montanide™ ISA 201 VG allows the induction of anti-influenza CD8 T cell in mice and induces homologous protection against an H1N1 challenge in swine. Such adjuvants that induce both humoral and cell-mediated immunity could improve the protection conferred by SIV vaccines in the field.

  6. Abducens nerve enhancement demonstrated by multiplanar reconstruction of contrast-enhanced three-dimensional MRI

    International Nuclear Information System (INIS)

    Hosoya, T.; Adachi, M.; Sugai, Y.; Yamaguchi, K.; Yamaguchi, K.; Kato, T.

    2001-01-01

    We describe contrast enhancement of the cisternal portion of the abducens nerve and discuss its clinical significance. We examined 67 patients with ophthalmoplegia using contrast-enhanced 3-dimensional (3D) MRI with multiplanar reconstruction along the nerves and found 16 patients (ten men, six women), aged 10-73 years (mean 34.4 years), with contrast enhancement of the abducens nerve. Of the 36 patients who had an abducens palsy, 14 (39 %) showed contrast enhancement. In the 16 patients, 23 abducens nerves enhanced; 13 were symptomatic and 10 asymptomatic at the time. The causes were disseminated tumour (1), an inflammatory process (3), trauma (2), ischaemia (2) and autoimmune diseases (8), such as the Miller Fisher syndrome, acute ophthalmoparesis, polyneuropathy and multiple sclerosis. Abducens and/or oculomotor nerve enhancement was the only abnormality on MRI in the patients with traumatic or ischaemic neuropathy or autoimmune diseases. There were 14 patients who recovered fully within 1-6 months after treatment, and resolution of the enhancement correlated well with recovery. (orig.)

  7. Abducens nerve enhancement demonstrated by multiplanar reconstruction of contrast-enhanced three-dimensional MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hosoya, T.; Adachi, M.; Sugai, Y. [Dept. of Radiology, Yamagata University School of Medicine (Japan); Yamaguchi, K.; Yamaguchi, K. [Dept. of Ophthalmology, Yamagata University School of Medicine (Japan); Kato, T. [3. Dept. of Internal Medicine, Yamagata University School of Medicine (Japan)

    2001-04-01

    We describe contrast enhancement of the cisternal portion of the abducens nerve and discuss its clinical significance. We examined 67 patients with ophthalmoplegia using contrast-enhanced 3-dimensional (3D) MRI with multiplanar reconstruction along the nerves and found 16 patients (ten men, six women), aged 10-73 years (mean 34.4 years), with contrast enhancement of the abducens nerve. Of the 36 patients who had an abducens palsy, 14 (39 %) showed contrast enhancement. In the 16 patients, 23 abducens nerves enhanced; 13 were symptomatic and 10 asymptomatic at the time. The causes were disseminated tumour (1), an inflammatory process (3), trauma (2), ischaemia (2) and autoimmune diseases (8), such as the Miller Fisher syndrome, acute ophthalmoparesis, polyneuropathy and multiple sclerosis. Abducens and/or oculomotor nerve enhancement was the only abnormality on MRI in the patients with traumatic or ischaemic neuropathy or autoimmune diseases. There were 14 patients who recovered fully within 1-6 months after treatment, and resolution of the enhancement correlated well with recovery. (orig.)

  8. "6"8Gallium-arginine-glycine-aspartic acid and "1"8F-fluorodeoxyglucose position emission tomography/computed tomography in chondroblastic osteosarcoma of the skull

    International Nuclear Information System (INIS)

    Orunmuyi, Akintunde; Modiselle, Moshe; Lengana, Thabo; Ebenhan, Thomas; Vorster, Mariza; Sathekge, Mike

    2017-01-01

    We report the case of a 32 year-old male with Chondroblastic Osteosarcoma of the skull, which was imaged with both "1"8[F]fluorodeoxyglucose ("1"8F-FDG) positron emission tomography/computed tomography (PET/CT) and "6"8Gallium-arginine-glycine-aspartic acid ("6"8Ga-RGD) PET/CT. The "1"8F-FDG PET/CT did not demonstrate the tumour, whereas the "6"8Ga-RGD PET/CT clearly depicted a left-sided frontal tumour. "6"8Ga-RGD PET/CT may be a clinically useful imaging modality for early detection of recurrent osteosarcoma, considering the limitations of "1"8F-FDG PET in a setting of low glycolytic activity

  9. Working memory-driven attention improves spatial resolution: Support for perceptual enhancement.

    Science.gov (United States)

    Pan, Yi; Luo, Qianying; Cheng, Min

    2016-08-01

    Previous research has indicated that attention can be biased toward those stimuli matching the contents of working memory and thereby facilitates visual processing at the location of the memory-matching stimuli. However, whether this working memory-driven attentional modulation takes place on early perceptual processes remains unclear. Our present results showed that working memory-driven attention improved identification of a brief Landolt target presented alone in the visual field. Because the suprathreshold target appeared without any external noise added (i.e., no distractors or masks), the results suggest that working memory-driven attention enhances the target signal at early perceptual stages of visual processing. Furthermore, given that performance in the Landolt target identification task indexes spatial resolution, this attentional facilitation indicates that working memory-driven attention can boost early perceptual processing via enhancement of spatial resolution at the attended location.

  10. Early career professionals: the mission of a task force.

    Science.gov (United States)

    Barnes, G D; Lauw, M N

    2016-07-01

    Early career researchers and clinicians face unique challenges in comparison with more senior colleagues, for instance connecting with expert leaders outside of their own institution to enhance their expertise. As the largest international thrombosis and hemostasis professional society, the ISTH can play a central role in supporting the development of early career professionals. The ISTH Early Career Task Force was formed to improve support for, and encourage collaboration between early career thrombosis and hemostasis researchers and clinicians. These activities include (1) maintaining an online forum for early career ISTH members to connect, promote clinical, research, funding and educational activities, and to generate a sense of community; (2) broaden ISTH's reach with early career professionals in the developing world through promotion of the Reach-the-World fellowships and translating ISTH websites into six languages; (3) encourage early career engagement with ISTH activities, such as guidelines and guidance document processing and online webinar series; and (4) establishing this early career forum series in this journal. The JTH Forum series will highlight the early career perspective on a wide range of issues relevant to this group, and all ISTH early career members are encouraged to contribute. © 2016 International Society on Thrombosis and Haemostasis.

  11. The bimodal distribution spin Seebeck effect enhancement in epitaxial Ni0.65Zn0.35Al0.8Fe1.2O4 thin film

    Science.gov (United States)

    Wang, Hua; Hou, Dazhi; Kikkawa, Takashi; Ramos, Rafael; Shen, Ka; Qiu, Zhiyong; Chen, Yao; Umeda, Maki; Shiomi, Yuki; Jin, Xiaofeng; Saitoh, Eiji

    2018-04-01

    The temperature dependence of the spin Seebeck effect (SSE) in epitaxial Ni0.65Zn0.35Al0.8Fe1.2O4 (NZA ferrite) thin film has been investigated systematically. The SSE at high fields shows a bimodal distribution enhancement from 3 K to 300 K and is well fitted with a double-peak Lorentzian function. We speculate the symmetric SSE enhancement in Pt/NZA ferrite bilayer, which is different from the magnon polarons induced asymmetric spikes in the SSE of Pt/YIG [T. Kikkawa et al. Phys. Rev. Lett. 117, 207203 (2016)], may result from the magnon-phonon interactions occurring at the intersections of the quantized magnon and phonon dispersions. The SSE results are helpful for the investigation of the magnon-phonon interaction in the magnetic ultrathin films.

  12. Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Elham Khanicheh

    Full Text Available BACKGROUND/OBJECTIVES: Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1 with contrast enhanced ultrasound (CEU could assess treatment effects on endothelial phenotype in early atherosclerosis. METHODS: Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day. At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM and control microbubbles (MB(Ctr. Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression. RESULTS: Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM in non-treated animals (MB(VCAM 2±0.3 vs MB(Ctr 0.7±0.2, p<0.01, but not in statin-treated animals (MB(VCAM 0.8±0.2 vs MB(Ctr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MB(VCAM signal. CONCLUSIONS: Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.

  13. The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study

    OpenAIRE

    Lin Cai; Qi Dong; Haijing Niu

    2018-01-01

    Early childhood (7–8 years old) and early adolescence (11–12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological ...

  14. Early career professionals: the mission of a task force

    NARCIS (Netherlands)

    Barnes, G. D.; Lauw, M. N.

    2016-01-01

    Early career researchers and clinicians face unique challenges in comparison with more senior colleagues, for instance connecting with expert leaders outside of their own institution to enhance their expertise. As the largest international thrombosis and hemostasis professional society, the ISTH can

  15. The serotonin transporter and early life stress : Translational perspectives

    NARCIS (Netherlands)

    Houwing, Danielle J; Buwalda, Bauke; Zee, van der Eddy; de Boer, Sietse F; Olivier, Jocelien D A

    2017-01-01

    The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human

  16. Effect of promoting self-esteem by participatory learning process on emotional intelligence among early adolescents.

    Science.gov (United States)

    Munsawaengsub, Chokchai; Yimklib, Somkid; Nanthamongkolchai, Sutham; Apinanthavech, Suporn

    2009-12-01

    To study the effect of promoting self-esteem by participatory learning program on emotional intelligence among early adolescents. The quasi-experimental study was conducted in grade 9 students from two schools in Bangbuathong district, Nonthaburi province. Each experimental and comparative group consisted of 34 students with the lowest score of emotional intelligence. The instruments were questionnaires, Program to Develop Emotional Intelligence and Handbook of Emotional Intelligence Development. The experimental group attended 8 participatory learning activities in 4 weeks to Develop Emotional Intelligence while the comparative group received the handbook for self study. Assessment the effectiveness of program was done by pre-test and post-test immediately and 4 weeks apart concerning the emotional intelligence. Implementation and evaluation was done during May 24-August 12, 2005. Data were analyzed by frequency, percentage, mean, standard deviation, Chi-square, independent sample t-test and paired sample t-test. Before program implementation, both groups had no statistical difference in mean score of emotional intelligence. After intervention, the experimental group had higher mean score of emotional intelligence both immediately and 4 weeks later with statistical significant (p = 0.001 and self-esteem by participatory learning process could enhance the emotional intelligence in early-adolescent. This program could be modified and implemented for early adolescent in the community.

  17. The role of contrast-enhanced endoscopic ultrasound in pancreatic adenocarcinoma

    DEFF Research Database (Denmark)

    Saftoiu, Adrian; Vilmann, Peter; Bhutani, Manoop S

    2016-01-01

    contrast agents for early detection, tridimensional and fusion techniques for enhanced staging and resectability assessment but also novel applications of perfusion imaging for monitoring ablative therapy, improved local detection through EUS-guided sampling of portal vein flow or enhanced drug delivery......Contrast-enhanced endoscopic ultrasound (CE-EUS) allows characterization, differentiation, and staging of focal pancreatic masses. The method has a high sensitivity and specificity for the diagnosis of pancreatic adenocarcinoma which is visualized as hypo-enhanced as compared to the rest...... of the parenchyma while chronic pancreatitis and neuroendocrine tumors are generally either iso-enhanced or hyper-enhanced. The development of contrast-enhanced low mechanical index harmonic imaging techniques used in real time during endoscopic ultrasound (EUS) allowed perfusion imaging and the quantification...

  18. Differential Proteomic Analysis of Syncytiotrophoblast Extracellular Vesicles from Early-Onset Severe Preeclampsia, using 8-Plex iTRAQ Labeling Coupled with 2D Nano LC-MS/MS

    Directory of Open Access Journals (Sweden)

    Hongmei Li

    2015-06-01

    Full Text Available Aims: Previous studies have revealed that the increased shedding of syncytiotrophoblast extracellular vesicles (STBM may lead to preeclampsia (PE. We aimed to identify the proteins carried by STBM and their potential pathological roles in early-onset severe PE. Methods: In this study, we performed a differential proteomic analysis of STBM from early-onset severe PE patients, using iTRAQ isobaric tags and 2D nano LC-MS/MS. STBM were generated by the in vitro explant culture method, and then verified by electron microscopy and western blot analysis. Results: A total of 18 533 unique peptides and 3 317 proteins were identified, 3 292 proteins were quantified. We identified 194 differentially expressed proteins in STBM from early-onset severe PE patients, 122 proteins were up-regulated and 72 proteins were down-regulated. Further bioinformatics analysis revealed that mitochondrion, transmembrane transport and transmembrane transporter activity were the most abundant categories in gene ontology (GO annotation. Glycolysis/ gluconeogenesis, citrate cycle, fatty acid elongation, steroid hormone biosynthesis and oxidative phosphorylation were the five significantly represented pathways. Four differentially expressed proteins (siglec-6, calnexin, CD63 and S100-A8 related to inflammation, coagulation or immunoregulation were independently verified using western blot. Conclusions: The identification of key proteins carried by STBM may serve not only as a basis for better understanding and further exploring the etiology and pathogenesis of PE, but also as potential biomarkers and in providing targets for future therapy in PE, especially in early-onset severe PE(sPE.

  19. Role of salivary matrix metalloproteinase-8 (MMP-8) in chronic periodontitis diagnosis.

    Science.gov (United States)

    Gupta, Namita; Gupta, N D; Gupta, Akash; Khan, Saif; Bansal, Neha

    2015-03-01

    Periodontitis is an inflammatory disease of the periodontium. Any imbalance between the matrix metalloproteinases (MMPs) secreted by neutrophils and tissue inhibitors initiates the destruction of collagen in gum tissue, leading to chronic periodontitis. This study aimed to correlate salivary levels of MMP-8 and periodontal parameters of chronic periodontitis to establish MMP-8 as a noninvasive marker for the early diagnosis of chronic periodontitis. The study involved 40 subjects visiting the periodontic OPD of Dr. Ziauddin Ahmad Dental College and Hospital, located in Aligarh, U.P., India, from 2011 to 2012. The subjects were divided into two groups: group I consisted of 20 periodontally healthy subjects (controls) while group II consisted of 20 patients with chronic periodontitis. Chronic periodontitis was assessed on the basis of several periodontal parameters, including pocket probing depth (PPD), clinical attachment level (CAL), gingival index (GI), and plaque index (PI). Around 3ml of unstimulated and whole expectorated saliva was collected for MMP-8 estimation by ELISA using Quantikine human total MMP-8 immunoassay kits. Data were analyzed using STATISTICA (Windows version 6) software. Salivary MMP-8 levels of groups I and II were 190.91 ± 143.89 ng/ml and 348.26 ± 202.1 ng/ml, respectively. The MMP-8 levels and periodontal status (PPD, CAL, GI, and PI) of groups I and II showed positive and significant correlations (for PPD, r = 0.63, P chronic periodontitis.

  20. Anchor enhanced capsulorraphy in bunionectomies using an L-shaped capsulotomy.

    Science.gov (United States)

    Gould, John S; Ali, Sheriff; Fowler, Rachel; Fleisig, Glenn S

    2003-01-01

    The objective of this study was to investigate potential benefit of a suture anchor-enhanced capsulorraphy in the early maintenance of correction in bunionectomies. We compared, retrospectively, in successive series, the loss of correction of the Hallux Valgus (HV) and intermetatarsal (IM) angle, in those repaired with an L-shaped capsulorraphy enhanced with anchors to those without. Intraoperative and second week postoperative simulated weightbearing anterior posterior (AP) X-rays were used to evaluate results. By using only intraoperative and early postoperative X-rays, we should have effectively eliminated extraneous factors that might have influenced our results. A Total of 106 cases were investigated, 65 of which were repaired using anchors, the remaining 41 without. In the anchor group, 38 underwent a proximal metatarsal concentric shelf osteotomy (CSO)/modified McBride procedure, while the remaining 27 had a distal Chevron correction. In the without-anchor group, 21 had a CSO/modified McBride procedure while 20 underwent the Chevron procedure. In the without-anchor group, the average HV and IM loss of correction was 4.60 degrees (range, -2 to 21 degrees) and 0.6 degrees (range, -1 to 9 degrees) respectively. In the anchor group, the corresponding loss was 2.8 degrees (range, -3 to 17 degrees) and 0.6 degrees (range, -2 to 14 degrees) respectively. These results, when statistically analyzed, demonstrated that while the IM angle change was not statistically significant, the HV angle change was statistically significant, implying that the anchor plays a significant role in maintaining the surgical correction in both the distal Chevron and CSO/ modified McBride bunionectomies.

  1. Appearance of microvascular obstruction on high resolution first-pass perfusion, early and late gadolinium enhancement CMR in patients with acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Redwood Simon

    2009-08-01

    Full Text Available Abstract Background The presence and extent of microvascular obstruction (MO after acute myocardial infarction can be measured by first-pass gadolinium-enhanced perfusion cardiovascular magnetic resonance (CMR or after gadolinium injection with early or late enhancement (EGE/LGE imaging. The volume of MO measured by these three methods may differ because contrast agent diffusion into the MO reduces its apparent extent over time. Theoretically, first-pass perfusion CMR should be the most accurate method to measure MO, but this technique has been limited by lower spatial resolution than EGE and LGE as well as incomplete cardiac coverage. These limitations of perfusion CMR can be overcome using spatio-temporal undersampling methods. The purpose of this study was to compare the extent of MO by high resolution first-pass k-t SENSE accelerated perfusion, EGE and LGE. Methods 34 patients with acute ST elevation myocardial infarction, treated successfully with primary percutaneous coronary intervention (PPCI, underwent CMR within 72 hours of admission. k-t SENSE accelerated first-pass perfusion MR (7 fold acceleration, spatial resolution 1.5 mm × 1.5 mm × 10 mm, 8 slices acquired over 2 RR intervals, 0.1 mmol/kg Gd-DTPA, EGE (1–4 minutes after injection with a fixed TI of 440 ms and LGE images (10–12 minutes after injection, TI determined by a Look-Locker scout were acquired. MO volume was determined for each technique by manual planimetry and summation of discs methodology. Results k-t SENSE first-pass perfusion detected more cases of MO than EGE and LGE (22 vs. 20 vs. 14, respectively. The extent of MO imaged by first-pass perfusion (median mass 4.7 g, IQR 6.7 was greater than by EGE (median mass 2.3 g, IQR 7.1, p = 0.002 and LGE (median mass 0.2 g, IQR 2.4, p = 0.0003. The correlation coefficient between MO mass measured by first-pass perfusion and EGE was 0.91 (p Conclusion The extent of MO following acute myocardial infarction appears larger on

  2. Enhanced early visual processing in response to snake and trypophobic stimuli

    OpenAIRE

    Strien, Jan; Van der Peijl, M.K. (Manja K.)

    2018-01-01

    textabstractBackground: Trypophobia refers to aversion to clusters of holes. We investigated whether trypophobic stimuli evoke augmented early posterior negativity (EPN). Methods: Twenty-four participants filled out a trypophobia questionnaire and watched the random rapid serial presentation of 450 trypophobic pictures, 450 pictures of poisonous animals, 450 pictures of snakes, and 450 pictures of small birds (1800 pictures in total, at a rate of 3 pictures/s). The EPN was scored as the mean ...

  3. Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles

    Energy Technology Data Exchange (ETDEWEB)

    Sugino, Noriko [Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 (Japan); Miura, Yasuo, E-mail: ym58f5@kuhp.kyoto-u.ac.jp [Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 (Japan); Yao, Hisayuki [Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 (Japan); Iwasa, Masaki; Fujishiro, Aya [Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 (Japan); Division of Gastroenterology and Hematology, Shiga University of Medical Science, Shiga 520-2192 (Japan); Fujii, Sumie [Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 (Japan); Hirai, Hideyo [Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 (Japan); Takaori-Kondo, Akifumi [Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Ichinohe, Tatsuo [Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan); Maekawa, Taira [Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507 (Japan)

    2016-01-22

    Bone marrow (BM) microenvironment has a crucial role in supporting hematopoiesis. Here, by using a microarray analysis, we demonstrate that human BM mesenchymal stromal/stem cells (MSCs) in an early osteoinductive stage (e-MSCs) are characterized by unique hematopoiesis-associated gene expression with an enhanced hematopoiesis-supportive ability. In comparison to BM-MSCs without osteoinductive treatment, gene expression in e-MSCs was significantly altered in terms of their cell adhesion- and chemotaxis-related profiles, as identified with Gene Ontology and Gene Set Enrichment Analysis. Noteworthy, expression of the hematopoiesis-associated molecules CXCL12 and vascular cell adhesion molecule 1 was remarkably decreased in e-MSCs. e-MSCs supported an enhanced expansion of CD34{sup +} hematopoietic stem and progenitor cells, and generation of myeloid lineage cells in vitro. In addition, short-term osteoinductive treatment favored in vivo hematopoietic recovery in lethally irradiated mice that underwent BM transplantation. e-MSCs exhibited the absence of decreased stemness-associated gene expression, increased osteogenesis-associated gene expression, and apparent mineralization, thus maintaining the ability to differentiate into adipogenic cells. Our findings demonstrate the unique biological characteristics of e-MSCs as hematopoiesis-regulatory stromal cells at differentiation stage between MSCs and osteoprogenitor cells and have significant implications in developing new strategy for using pharmacological osteoinductive treatment to support hematopoiesis in hematopoietic stem and progenitor cell transplantation. - Highlights: • Human BM-MSCs in an early osteoinductive stage (e-MSCs) support hematopoiesis. • Adhesion- and chemotaxis-associated gene signatures are altered in e-MSCs. • Expression of CXCL12 and VCAM1 is remarkably decreased in e-MSCs. • e-MSCs are at differentiation stage between MSCs and osteoprogenitor cells. • Osteoinductive treatment

  4. Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.

    Directory of Open Access Journals (Sweden)

    Ian A Cockburn

    2010-05-01

    Full Text Available Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization--a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.

  5. Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function.

    Science.gov (United States)

    Geng, Jie; Altman, John D; Krishnakumar, Sujatha; Raghavan, Malini

    2018-05-09

    When complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8 + T cell responses via interaction with the T cell receptor (TCR) and co-receptor CD8. Peptides are generally critical for the stable cell surface expression of HLA-I molecules. However, for HLA-I alleles such as HLA-B*35:01, peptide-deficient (empty) heterodimers are thermostable and detectable on the cell surface. Additionally, peptide-deficient HLA-B*35:01 tetramers preferentially bind CD8 and to a majority of blood-derived CD8 + T cells via a CD8-dependent binding mode. Further functional studies reveal that peptide-deficient conformers of HLA-B*35:01 do not directly activate CD8 + T cells, but accumulate at the immunological synapse in antigen-induced responses, and enhance cognate peptide-induced cell adhesion and CD8 + T cell activation. Together, these findings indicate that HLA-I peptide occupancy influences CD8 binding affinity, and reveal a new set of regulators of CD8 + T cell activation, mediated by the binding of empty HLA-I to CD8. © 2018, Geng et al.

  6. Investigation of the mechanism responsible for the photoluminescence enhancement with Li+ co-doping in highly thermally stable white-emitting Sr8ZnSc(PO4)7:Dy3+ phosphor

    International Nuclear Information System (INIS)

    Gou, Jing; Fan, Jingyan; Luo, Meng; Zuo, Shengnan

    2017-01-01

    The strategy of co-doping Li + was used with the aim of enhancing the emission intensities of Sr 8 ZnSc(PO 4 ) 7 under near ultraviolet excitation. The luminescence enhancement was related to the deep defects V O ¨ which were produced by the introduction of Li + ion. Furthermore, much deep V O ¨ were produced with the incorporation amount of Li + ion increasing. As the sensitizer, the produced deep V O ¨ can effectively tunnelling transfer energy to the nearby activator Dy 3+ resulting in the photoluminescence enhancement in SZSPO:1.5%Dy 3+ ,5%Li + . In addition, its yellow/blue emitting ratio and photoluminescent quantum yields both were improved under longer wavelength excitation. Furthermore, the excellent thermal stability of optimal SZSPO:1.5%Dy 3+ ,5%Li + excelled over commercial phosphor DS-200 below 225 °C. The electroluminescence properties of fabricated ABPD-WLED reach the optimum with V=10 V and I=800 mA (λ ex =365 nm) or 700 mA (λ ex =388 nm), then the bright white luminescence can be obviously observed. These photoluminescence, electroluminescence and thermal properties testified the potential application of Sr 8 ZnSc(PO 4 ) 7 :1.5%Dy 3+ ,5%Li + as a new-style warm-white emitting LEDs phosphor. - Graphical abstract: The mechanism of the luminescence enhancement is consider as that a little amount introduction of Li + ion can produce defects Li Zn ′ and oxygen vacancies V O ¨, and with the incorporation amount of Li + increasing, the more deep V O ¨ are produced. As sensitizer, the productive deeper V O ¨ can effectively tunneling transfer energy to nearby activator Dy 3+ inducing its photoluminescence enhancement.

  7. Web-Based Education Prior to Outpatient Orthopaedic Surgery Enhances Early Patient Satisfaction Scores: A Prospective Randomized Controlled Study.

    Science.gov (United States)

    van Eck, Carola F; Toor, Aneet; Banffy, Michael B; Gambardella, Ralph A

    2018-01-01

    A good patient-surgeon relationship relies on adequate preoperative education and counseling. Several multimedia resources, such as web-based education tools, have become available to enhance aspects of perioperative care. The purpose of this study was to evaluate the effect of an interactive web-based education tool on perioperative patient satisfaction scores after outpatient orthopaedic surgery. It was hypothesized that web-based education prior to outpatient orthopaedic surgery enhances patient satisfaction scores. Randomized controlled trial; Level of evidence, 1. All patients undergoing knee arthroscopy with meniscectomy, chondroplasty, or anterior cruciate ligament reconstruction or shoulder arthroscopy with rotator cuff repair were eligible for inclusion and were randomized to the study or control group. The control group received routine education by the surgeon, whereas the study group received additional web-based education. At the first postoperative visit, all patients completed the OAS CAHPS (Outpatient and Ambulatory Surgery Consumer Assessment of Healthcare Providers and Systems) survey. Differences in patient satisfaction scores between the study and control groups were determined with an independent t test. A total of 177 patients were included (104 [59%] males; mean age, 42 ± 14 years); 87 (49%) patients were randomized to receive additional web-based education. Total patient satisfaction score was significantly higher in the study group (97 ± 5) as compared with the control group (94 ± 8; P = .019), specifically for the OAS CAHPS core measure "recovery" (92 ± 13 vs 82 ± 23; P = .001). Age, sex, race, workers' compensation status, education level, overall health, emotional health, procedure type and complexity, and addition of a video did not influence patient satisfaction scores. Supplemental web-based patient education prior to outpatient orthopaedic surgery enhances patient satisfaction scores.

  8. Influence of first-time mothers' early employment on severe early childhood caries in their child.

    Science.gov (United States)

    Plutzer, Kamila; Keirse, Marc J N C

    2012-01-01

    Aim. To examine whether mothers' early employment status is related to the development of severe early childhood caries in their child. Methods. Questionnaire survey of 429 first-time mothers in metropolitan Adelaide, South Australia, and dental examinations of their child at 20 months of age. Results. At 20 ± 2.5 months of age, 5.6% of children exhibited caries defined as one or more demineralized or cavitated lesions on the upper incisors. Of the mothers, 52.2% had no paid employment, 39.6% were part-time and 8.2% full-time employed. Overall, mothers' participation in the workforce had no influence on the frequency of severe early childhood caries in their child, but there was a significant interaction with family structure. For mothers without employment there was no difference between single, and two-parent families, but children with an employed single mother more frequently had caries than those with a working mother in a two-parent family (P early childhood caries in their child.

  9. Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8 induction in lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Refsnes M

    2014-12-01

    Full Text Available Magne Refsnes, Tonje Skuland, Marit Låg, Per E Schwarze, Johan Øvrevik Department of Air Pollution and Noise, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway Abstract: Different toxic agents have a varying potential to induce the production of the proinflammatory chemokine, CXCL8 (interleukin [IL]-8, in lung cells. A critical question is which mechanisms determine the magnitude and persistence of the CXCL8 responses to different stimuli. To approach this, we compared the potential of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA, and sodium fluoride (NaF to induce CXCL8 responses in A549 cells, with emphasis on the importance of nuclear factor kappa B (NF-κB- and mitogen-activated protein kinase (MAPK signaling. Notably, TPA induced a greater release of CXCL8 than did NaF. Furthermore, TPA induced a strong, rapid, but transient upregulation of CXCL8 messenger (mRNA, whereas NaF induced a weaker, more delayed, but persistent upregulation. With respect to signaling, TPA led to an early, strong, and relatively transient extracellular signal-regulated kinase (ERK1/2 phosphorylation, and a less marked and even more transient phosphorylation of c-jun-N-terminal kinases (JNK1/2 and p38. In contrast, NaF elicited a lower, but relatively sustained increase in phosphorylation of ERK1/2, and a marked phosphorylation of p38 and JNK1/2, with the JNK1/2 response as most transient. Only ERK1/2 inhibition affected the TPA response, whereas inhibition of all the three MAPK cascades reduced NaF-induced CXCL8 release. TPA also induced an early, marked phosphorylation/translocation of p65 (NF-κB, whereas NaF induced slower, less pronounced effects on p65. The CXCL8 responses by TPA and NaF were reduced by p65-siRNA. In conclusion, all MAPK cascades were involved in NaF-induced CXCL8 release, whereas only ERK1/2 activation was involved in response to TPA. Furthermore, NF-κB activation appeared to be

  10. Characterizing Tumor Heterogeneity With Functional Imaging and Quantifying High-Risk Tumor Volume for Early Prediction of Treatment Outcome: Cervical Cancer as a Model

    International Nuclear Information System (INIS)

    Mayr, Nina A.; Huang Zhibin; Wang, Jian Z.; Lo, Simon S.; Fan, Joline M.; Grecula, John C.; Sammet, Steffen; Sammet, Christina L.; Jia Guang; Zhang Jun; Knopp, Michael V.; Yuh, William T.C.

    2012-01-01

    Purpose: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. Methods and Materials: DCE-MRI was performed in 102 stage IB 2 –IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the total volume of tumor voxels with critically low DCE signal intensity ( 20, >13, and >5 cm 3 , respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 × 10 −8 , 2.0 × 10 −8 ) and disease-specific survival (p = 1.9 × 10 −4 , 2.1 × 10 −6 , 2.5 × 10 −7 , respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. Discussion: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2–5 weeks into treatment.

  11. Solitary hepatic infantile hemangioendothelioma: dynamic gadolinium-enhanced MR imaging findings

    International Nuclear Information System (INIS)

    Mortele, Koenraad J.; Vanzieleghem, Bart; Mortele, Bart; Benoit, Yves; Ros, Pablo R.

    2002-01-01

    We report the MRI findings of a solitary hepatic infantile hemangioendothelioma (IHE) diagnosed in a 14-day-old girl. To the best of our knowledge, only one report has illustrated the dynamic gadolinium-enhanced MR imaging features of IHE previously. Compounding the rarity of presentation as a solitary mass, the gadolinium-enhanced MRI appearance in our case is unique, because the IHE showed an early rim-like pseudocapsular enhancement followed by progressive fill-in of the lesion on delayed imaging. (orig.)

  12. Sedimentary evidence for enhanced hydrological cycling in response to rapid carbon release during the early Toarcian oceanic anoxic event

    Science.gov (United States)

    Izumi, Kentaro; Kemp, David B.; Itamiya, Shoma; Inui, Mutsuko

    2018-01-01

    A pronounced excursion in the carbon-isotope composition of biospheric carbon and coeval seawater warming during the early Toarcian (∼183 Ma) has been linked to the large-scale transfer of 12C-enriched carbon to the oceans and atmosphere. A European bias in the distribution of available data means that the precise pattern, tempo and global expression of this carbon cycle perturbation, and the associated environmental responses, remain uncertain. Here, we present a new cm-scale terrestrial-dominated carbon-isotope record through an expanded lower Toarcian section from Japan that displays a negative excursion pattern similar to marine and terrestrial carbon-isotope records documented from Europe. These new data suggest that 12C-enriched carbon was added to the biosphere in at least one rapid, millennial-scale pulse. Sedimentological analysis indicates a close association between the carbon-isotope excursion and high-energy sediment transport and enhanced fluvial discharge. Together, these data support the hypothesis that a sudden strengthening of the global hydrological cycle occurred in direct and immediate response to rapid carbon release and atmospheric warming.

  13. Early mortality and complications in hospitalized adult Californians with acute myeloid leukaemia.

    Science.gov (United States)

    Ho, Gwendolyn; Jonas, Brian A; Li, Qian; Brunson, Ann; Wun, Ted; Keegan, Theresa H M

    2017-06-01

    Few studies have evaluated the impact of complications, sociodemographic and clinical factors on early mortality (death ≤60 days from diagnosis) in acute myeloid leukaemia (AML) patients. Using data from the California Cancer Registry linked to hospital discharge records from 1999 to 2012, we identified patients aged ≥15 years with AML who received inpatient treatment (N = 6359). Multivariate logistic regression analyses were used to assess the association of complications with early mortality, adjusting for sociodemographic factors, comorbidities and hospital type. Early mortality decreased over time (25·3%, 1999-2000; 16·8%, 2011-2012) across all age groups, but was higher in older patients (6·9%, 15-39, 11·4%, 40-54, 18·6% 55-65, and 35·8%, >65 years). Major bleeding [Odds ratio (OR) 1·5, 95% confidence interval (CI) 1·3-1·9], liver failure (OR 1·9, 95% CI 1·1-3·1), renal failure (OR 2·4, 95% CI 2·0-2·9), respiratory failure (OR 7·6, 95% CI 6·2-9·3) and cardiac arrest (OR 15·8, 95% CI 8·7-28·6) were associated with early mortality. Higher early mortality was also associated with single marital status, low neighbourhood socioeconomic status, lack of health insurance and comorbidities. Treatment at National Cancer Institute-designated cancer centres was associated with lower early mortality (OR 0·5, 95% CI 0·4-0·6). In conclusion, organ dysfunction, hospital type and sociodemographic factors impact early mortality. Further studies should investigate how differences in healthcare delivery affect early mortality. © 2017 John Wiley & Sons Ltd.

  14. Evaluation of residual hepatocellular carcinoma after transcatheter arterial chemoembolization: Comparison between contrast-enhanced helical CT and contrast-enhanced power doppler ultrasonography

    International Nuclear Information System (INIS)

    Kim, Seung Hoon; Lim, Hyo Keun; Lee, Won Jae

    2001-01-01

    To evaluate the effectiveness of contrast-enhanced helical CT and contrast-enhanced power doppler ultrasonography (PDUS) in assessing the therapeutic effect of transcatheter arterial chemoembolization (TACE) in hepatocellular carcinomas (HCCs). The follow-up contrast-enhanced helical CT and contrast-enhanced PDUS were performed for twenty-nine nodular HCCs from twelve patients previously treated with TACE. We defined the residual HCCs as intratumoral enhancing area on contrast-enhanced helical CT and color signal on contrast-enhanced PDUS. The interval between two examinations was less than 2 weeks (mean, 9 days). Two radiologists evaluated two examinations by consensus, and the results of these two examination were compared with the findings of other examinations including CT, angiography, and/or pathology to calculate the sensitivity, specificity and accuracy of two examinations. Of the 29 HCCs, 20 had residual HCCs whereas no residual HCCs in 9 HCCs on pathologic examination and/or follow-up radiologic study. The sensitivity, sensitivity and accuracy of contrast-enhanced helical CT were 65 (13/20), 89 (8/9), and 72% (21/29) while those of contrast-enhanced PDUS were 100 (20/20), 89 (8/9) and 97% (28/29), respectively. A microbubble contrast-enhanced PDUS was more effective in the detection of residual tumor in HCCs following TACE than contrast-enhanced helical CT.

  15. Early menarche is associated with increased risk of asthma

    DEFF Research Database (Denmark)

    Lieberoth, Sofie; Gade, Elisabeth; Kyvik, Kirsten Ohm

    2015-01-01

    in girls with early menarche compared to girls without early menarche (7.4 vs. 4.5%), OR = 1.71 (1.31-2.22), p increased by 8% (1-15%), p = 0...... in discordant monozygotic and dizygotic twins. CONCLUSION: Early menarche is associated with increased risk of asthma among Danish female twins independently of BMI, age, physical activity, educational level and smoking. Results indicate a complex relationship possibly mediated through innate and non...

  16. Detecting early response to cyclophosphamide treatment of RIF-1 tumors using selective multiple quantum spectroscopy (SelMQC) and dynamic contrast enhanced imaging.

    Science.gov (United States)

    Poptani, Harish; Bansal, Navin; Graham, Robert A; Mancuso, Anthony; Nelson, David S; Glickson, Jerry D

    2003-04-01

    The purpose of this study was to develop a reliable, noninvasive method for early detection of tumor response to therapy that would facilitate optimization of treatment regimens to the needs of the individual patient. In the present study, the effects of cyclophosphamide (Cp, a widely used alkylating agent) were monitored in a murine radiation induced fibrosarcoma (RIF-1) using in vivo (1)H NMR spectroscopy and imaging to evaluate the potential of these techniques towards early detection of treatment response. Steady-state lactate levels and Gd-DTPA uptake kinetics were measured using selective multiple quantum coherence (Sel-MQC) transfer spectroscopy and dynamic contrast enhanced imaging, respectively in RIF-1 tumors before, 24 and 72 h after 300 mg/kg of Cp administration. High-resolution (1)H NMR spectra of perchloric acid extracts of the tumor were correlated with lactate and glucose concentrations determined enzymatically. In vivo NMR experiments showed a decrease in steady-state lactate to water ratios (5.4 +/- 1.6 to 0.6 +/- 0.5, p < 0.05) and an increase in Gd-DTPA uptake kinetics following treatment response. The data indicate that decreases in lactate result from decreased glycolytic metabolism and an increase in tumor perfusion/permeability. Perchloric acid extracts confirmed the lower lactate levels seen in vivo in treated tumors and also indicated a higher glycerophosphocholine/phosphocholine (GPC/PC) integrated intensity ratio (1.39 +/- 0.09 vs 0.97 +/- 0.04, p < 0.01), indicative of increased membrane degradation following Cp treatment. Steady-state lactate levels provide metabolic information that correlates with changes in tumor physiology measured by Gd-DTPA uptake kinetics with high spatial and temporal resolution. Both of these parameters may be useful for monitoring early tumor response to therapy. Copyright 2003 John Wiley & Sons, Ltd.

  17. Polycystic ovary syndrome: dynamic contrast-enhanced ovary MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Erdem, C. Zuhal E-mail: sunarerdem@yahoo.com; Bayar, Ulku; Erdem, L. Oktay; Barut, Aykut; Gundogdu, Sadi; Kaya, Erdal

    2004-07-01

    Objective: to determine the enhancement behaviour of the ovaries in women with polycystic ovary syndrome (PCOS) by dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging and to compare these data with those of normal ovulating controls. Method: 24 women with PCOS and 12 controls underwent DCE-MR imaging. Dynamic images were acquired before and after injection of a contrast bolus at 30 s and the min of 1, 2, 3, 4 and 5. On postprocessing examination: (i) the ovarian volumes; (ii) the signal intensity value of each ovary per dynamic study; (iii) early-phase enhancement rate; (iv) time to peak enhancement (T{sub p}); and (v) percentage of washout of 5th min were determined. Data of the ovaries of the women with PCOS and controls were compared with Mann-Whitney U-test. Results: the mean values of T{sub p} were found to be significantly lower in women with PCOS than in controls (p<0.05). On the other hand, the mean values of ovarian volume, the early-phase enhancement rate, and percentage of washout of 5th min of ovaries were significantly higher in PCOS patients (p<0.05). Examination of the mean signal intensity-time curve revealed the ovaries in women with PCOS showed a faster and greater enhancement and wash-out. Conclusion: the enhancement behaviour of ovaries of women with PCOS may be significantly different from those of control subjects on DCE-MR imaging examination. In our experience, it is a valuable modality to highlight the vascularization changes in ovarian stroma with PCOS. We believe that improved DCE-MR imaging techniques may also provide us additional parameters in the diagnosis and treatment strategies of PCOS.

  18. Polycystic ovary syndrome: dynamic contrast-enhanced ovary MR imaging

    International Nuclear Information System (INIS)

    Erdem, C. Zuhal; Bayar, Ulku; Erdem, L. Oktay; Barut, Aykut; Gundogdu, Sadi; Kaya, Erdal

    2004-01-01

    Objective: to determine the enhancement behaviour of the ovaries in women with polycystic ovary syndrome (PCOS) by dynamic contrast-enhanced magnetic resonance (DCE-MR) imaging and to compare these data with those of normal ovulating controls. Method: 24 women with PCOS and 12 controls underwent DCE-MR imaging. Dynamic images were acquired before and after injection of a contrast bolus at 30 s and the min of 1, 2, 3, 4 and 5. On postprocessing examination: (i) the ovarian volumes; (ii) the signal intensity value of each ovary per dynamic study; (iii) early-phase enhancement rate; (iv) time to peak enhancement (T p ); and (v) percentage of washout of 5th min were determined. Data of the ovaries of the women with PCOS and controls were compared with Mann-Whitney U-test. Results: the mean values of T p were found to be significantly lower in women with PCOS than in controls (p<0.05). On the other hand, the mean values of ovarian volume, the early-phase enhancement rate, and percentage of washout of 5th min of ovaries were significantly higher in PCOS patients (p<0.05). Examination of the mean signal intensity-time curve revealed the ovaries in women with PCOS showed a faster and greater enhancement and wash-out. Conclusion: the enhancement behaviour of ovaries of women with PCOS may be significantly different from those of control subjects on DCE-MR imaging examination. In our experience, it is a valuable modality to highlight the vascularization changes in ovarian stroma with PCOS. We believe that improved DCE-MR imaging techniques may also provide us additional parameters in the diagnosis and treatment strategies of PCOS

  19. Preventability of early vs. late readmissions in an academic medical center.

    Directory of Open Access Journals (Sweden)

    Kelly L Graham

    Full Text Available It is unclear if the 30-day unplanned hospital readmission rate is a plausible accountability metric.Compare preventability of hospital readmissions, between an early period [0-7 days post-discharge] and a late period [8-30 days post-discharge]. Compare causes of readmission, and frequency of markers of clinical instability 24h prior to discharge between early and late readmissions.120 patient readmissions in an academic medical center between 1/1/2009-12/31/2010.Sum-score based on a standard algorithm that assesses preventability of each readmission based on blinded hospitalist review; average causation score for seven types of adverse events; rates of markers of clinical instability within 24h prior to discharge.Readmissions were significantly more preventable in the early compared to the late period [median preventability sum score 8.5 vs. 8.0, p = 0.03]. There were significantly more management errors as causative events for the readmission in the early compared to the late period [mean causation score [scale 1-6, 6 most causal] 2.0 vs. 1.5, p = 0.04], and these errors were significantly more preventable in the early compared to the late period [mean preventability score 1.9 vs 1.5, p = 0.03]. Patients readmitted in the early period were significantly more likely to have mental status changes documented 24h prior to hospital discharge than patients readmitted in the late period [12% vs. 0%, p = 0.01].Readmissions occurring in the early period were significantly more preventable. Early readmissions were associated with more management errors, and mental status changes 24h prior to discharge. Seven-day readmissions may be a better accountability measure.

  20. Prognosis of late versus early ventricular fibrillation in acute myocardial infarction

    DEFF Research Database (Denmark)

    Jensen, G V; Torp-Pedersen, C; Køber, L

    1990-01-01

    VF was not associated with heart failure. When VF was associated with heart failure (secondary VF) early VF had a greater mortality than late VF after 2 and 5 years. Logistic regression analysis showed that heart failure (relative risk 1.9 [1.1 to 3.1]) and cardiogenic shock (relative risk 3.9 [1.......8 to 8.5]) were significant risk factors for in-hospital death. Late VF compared to early VF had no prognostic implication (relative risk 1.0 [0.6 to 1.6]). For patients discharged from the hospital, risk factors were heart failure (1.8 [1.1 to 2.8]) and previous AMI (1.6 [1.3 to 2.1]).(ABSTRACT...... TRUNCATED AT 250 WORDS)...

  1. Interferon-alpha administration enhances CD8+ T cell activation in HIV infection.

    Directory of Open Access Journals (Sweden)

    Maura Manion

    Full Text Available Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation.To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment.The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006. These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy. As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001.Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection.

  2. Redefining early gastric cancer.

    Science.gov (United States)

    Barreto, Savio G; Windsor, John A

    2016-01-01

    The problem is that current definitions of early gastric cancer allow the inclusion of regional lymph node metastases. The increasing use of endoscopic submucosal dissection to treat early gastric cancer is a concern because regional lymph nodes are not addressed. The aim of the study was thus to critically evaluate current evidence with regard to tumour-specific factors associated with lymph node metastases in "early gastric cancer" to develop a more precise definition and improve clinical management. A systematic and comprehensive search of major reference databases (MEDLINE, EMBASE, PubMed and the Cochrane Library) was undertaken using a combination of text words "early gastric cancer", "lymph node metastasis", "factors", "endoscopy", "surgery", "lymphadenectomy" "mucosa", "submucosa", "lymphovascular invasion", "differentiated", "undifferentiated" and "ulcer". All available publications that described tumour-related factors associated with lymph node metastases in early gastric cancer were included. The initial search yielded 1494 studies, of which 42 studies were included in the final analysis. Over time, the definition of early gastric cancer has broadened and the indications for endoscopic treatment have widened. The mean frequency of lymph node metastases increased on the basis of depth of infiltration (mucosa 6% vs. submucosa 28%), presence of lymphovascular invasion (absence 9% vs. presence 53%), tumour differentiation (differentiated 13% vs. undifferentiated 34%) and macroscopic type (elevated 13% vs. flat 26%) and tumour diameter (≤2 cm 8% vs. >2 cm 25%). There is a need to re-examine the diagnosis and staging of early gastric cancer to ensure that patients with one or more identifiable risk factor for lymph node metastases are not denied appropriate chemotherapy and surgical resection.

  3. Emotion improves and impairs early vision.

    Science.gov (United States)

    Bocanegra, Bruno R; Zeelenberg, René

    2009-06-01

    Recent studies indicate that emotion enhances early vision, but the generality of this finding remains unknown. Do the benefits of emotion extend to all basic aspects of vision, or are they limited in scope? Our results show that the brief presentation of a fearful face, compared with a neutral face, enhances sensitivity for the orientation of subsequently presented low-spatial-frequency stimuli, but diminishes orientation sensitivity for high-spatial-frequency stimuli. This is the first demonstration that emotion not only improves but also impairs low-level vision. The selective low-spatial-frequency benefits are consistent with the idea that emotion enhances magnocellular processing. Additionally, we suggest that the high-spatial-frequency deficits are due to inhibitory interactions between magnocellular and parvocellular pathways. Our results suggest an emotion-induced trade-off in visual processing, rather than a general improvement. This trade-off may benefit perceptual dimensions that are relevant for survival at the expense of those that are less relevant.

  4. The Construction Site Project: Transforming Early Childhood Teacher Practice

    Science.gov (United States)

    McNaughton, Kathryn; Krentz, Caroline

    2007-01-01

    The work of Malaguzzi (in Edwards, Gandini, & Forman, 1998; Fraser, 2006) has made the fundamentals of the preschools of Reggio Emilia familiar to many early childhood educators. The article describes an authentic project that enhanced undergraduate and postgraduate participants' understanding of the impact of collaboration, conversation, and…

  5. Carbon-14-labeled 2,3,7,8- and 1,2,7,8-tetrachlorodibenzofuran

    International Nuclear Information System (INIS)

    Gray, A.P.; McClellan, W.J.; Dipinto, V.M.

    1981-01-01

    Both 2,3,7,8- and 1,2,7,8- tetrachlorodibenzofuran -U 14 C, specific activity 57 mCi/mmol, have been obtained in low yield but at > 98% purity via Pschorr cyclization of o-phenoxyaniline -U 14 C, chlorination of the resultant dibenzofuran and separation of the tetrachloro isomers by hplc. The lower yields obtained in the Pschorr cyclization of 'hot' o-phenoxyaniline in comparison with the 'cold' material are postulated to result from enhanced homolytic relative to heterolytic cleavage of the 'hot' diazonium ion leading to a 'hot' free radical which polymerizes. The completely anomalous results observed in the attempted palladium acetate-mediated cyclization of diphenyl ether- U 14 C are likewise interpreted in terms of the intervention of a 'hot' free radical. (author)

  6. Dual phase helical CT: diagnosis value for early pancreatic carcinoma

    International Nuclear Information System (INIS)

    Shen Bingqi; Zhang Ling; Zheng Keguo; Xu Dasheng

    2006-01-01

    Objective: To study dual-phase helical CT for the evaluation of early pancreatic cacinoma. Methods: Dual-phase helical CT was performed on 21 patients with early pancreatic carcinoma. In the enhanced imaging the contrast material was intravenously injected in a dose of 1.5 ml/kg at a rate of 3 ml/s. The image acquisition of the lesion in pancreatic phase (PP) and portal venous phase (PVP) were started at 35 seconds and 65 seconds after the start of the injection respectively. The enhancement of normal pancreas and tumor during the two phases was observed and compared. All data were statistically analyzed. Results: Tumor-pancreas contrast was significantly greater in PP (45.16±113.23) HU than in PVP (23.15±12.44) HU (t=2.13, P<0.01). Conclusion: Dual-phase helical CT scan for pancreas, including the imaging of the pancreatic and portal , venous phase, can be applied as an optimal selection. It can delineate early pancreatic carcinoma clearly and provide more information for the diagnosis of the lesion. The tumor-pancreas contrast was much higher' in PP than in PVP. (authors)

  7. Homologous series of induced early mutants in Indica rice. Pt.3: The relationship between the induction of homologous series of early mutants and its different pedigree

    International Nuclear Information System (INIS)

    Chen Xiulan; Yang Hefeng; He Zhentian; Han Yuepeng; Liu Xueyu

    2002-01-01

    The percentage of homologous series of early mutants (PHSEM) induced by irradiation was closely related to its pedigree. This study showed that PHSEM for varieties with the same pedigree were similar, and there were three different level of dominance (high, low and normal) in the homologous series induced from different pedigree. The PHSEM for varieties derived form distant-relative-parents were higher than that derived from close-relative-parents. There was the dominance pedigree for the induction of homologous series of early mutants. IR8(Peta x DGWG), IR127 (Cpslo x Sigadis) and IR24 (IR8 x IR127) were dominant pedigree, and varieties derived from them could be easily induced the homologous series of early mutants

  8. FUNdamental Movement in Early Childhood.

    Science.gov (United States)

    Campbell, Linley

    2001-01-01

    Noting that the development of fundamental movement skills is basic to children's motor development, this booklet provides a guide for early childhood educators in planning movement experiences for children between 4 and 8 years. The booklet introduces a wide variety of appropriate practices to promote movement skill acquisition and increased…

  9. Contrast enhancement pattern on multidetector CT predicts malignancy in pancreatic endocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Cappelli, Carla [University of Pisa, Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Azienda Ospedaliero-Universitaria Pisana-Radiodiagnostica I, Pisa (Italy); Boggi, Ugo [University of Pisa, General and Transplant Surgery, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Mazzeo, Salvatore; Cervelli, Rosa; Contillo, Benedetta Pontillo; Bartolozzi, Carlo [University of Pisa, Diagnostic and Interventional Radiology, Department of Translational Research and New Technologies in Medicine and Surgery, Pisa (Italy); Campani, Daniela; Funel, Niccola [University of Pisa, Pathology, Department of Surgical, Medical, Molecular and Critical Area Pathology, Pisa (Italy)

    2014-12-02

    Preoperative suspicion of malignancy in pancreatic neuroendocrine tumours (pNETs) is mostly based on tumour size. We retrospectively reviewed the contrast enhancement pattern (CEP) of a series of pNETs on multiphasic multidetector computed tomography (MDCT), to identify further imaging features predictive of lesion aggressiveness. Sixty pNETs, diagnosed in 52 patients, were classified based on CEP as: type A showing early contrast enhancement and rapid wash-out; type B presenting even (B1) or only (B2) late enhancement. All tumours were resected allowing pathologic correlations. Nineteen pNETs showed type A CEP (5-20 mm), 29 type B1 CEP (5-80 mm) and 12 type B2 (15-100 mm). All tumours were classified as well differentiated tumours, 19 were benign (WDt-b), 15 with uncertain behaviour (WDt-u) and 26 carcinomas (WDC). None of A lesions were malignant (12 WDt-b; 7 WDt-u), all B2 lesions were WDC, 7 B1 lesions were WDt-b, 8 WDt-u and 14 WDC; 4/34 (12 %) lesions ≤2cm were WDC. CEP showed correlation with all histological prognostic indicators. Correlating with the lesion grading and other histological prognostic predictors, CEP may preoperatively suggest the behaviour of pNETs, assisting decisions about treatment. Moreover CEP allows recognition of malignant small tumours, incorrectly classified on the basis of their dimension. (orig.)

  10. Contrast enhancement pattern on multidetector CT predicts malignancy in pancreatic endocrine tumours

    International Nuclear Information System (INIS)

    Cappelli, Carla; Boggi, Ugo; Mazzeo, Salvatore; Cervelli, Rosa; Contillo, Benedetta Pontillo; Bartolozzi, Carlo; Campani, Daniela; Funel, Niccola

    2015-01-01

    Preoperative suspicion of malignancy in pancreatic neuroendocrine tumours (pNETs) is mostly based on tumour size. We retrospectively reviewed the contrast enhancement pattern (CEP) of a series of pNETs on multiphasic multidetector computed tomography (MDCT), to identify further imaging features predictive of lesion aggressiveness. Sixty pNETs, diagnosed in 52 patients, were classified based on CEP as: type A showing early contrast enhancement and rapid wash-out; type B presenting even (B1) or only (B2) late enhancement. All tumours were resected allowing pathologic correlations. Nineteen pNETs showed type A CEP (5-20 mm), 29 type B1 CEP (5-80 mm) and 12 type B2 (15-100 mm). All tumours were classified as well differentiated tumours, 19 were benign (WDt-b), 15 with uncertain behaviour (WDt-u) and 26 carcinomas (WDC). None of A lesions were malignant (12 WDt-b; 7 WDt-u), all B2 lesions were WDC, 7 B1 lesions were WDt-b, 8 WDt-u and 14 WDC; 4/34 (12 %) lesions ≤2cm were WDC. CEP showed correlation with all histological prognostic indicators. Correlating with the lesion grading and other histological prognostic predictors, CEP may preoperatively suggest the behaviour of pNETs, assisting decisions about treatment. Moreover CEP allows recognition of malignant small tumours, incorrectly classified on the basis of their dimension. (orig.)

  11. Characterizing Tumor Heterogeneity With Functional Imaging and Quantifying High-Risk Tumor Volume for Early Prediction of Treatment Outcome: Cervical Cancer as a Model

    Energy Technology Data Exchange (ETDEWEB)

    Mayr, Nina A., E-mail: Nina.Mayr@osumc.edu [Department of Radiation Oncology, Ohio State University, Columbus, OH (United States); Huang Zhibin [Department of Radiation Oncology and Department of Physics, East Carolina University, Greenville, NC (United States); Wang, Jian Z. [Department of Radiation Oncology, Ohio State University, Columbus, OH (United States); Lo, Simon S. [Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States); Fan, Joline M. [Department of Molecular Biology, Stanford University, Stanford, CA (United States); Grecula, John C. [Department of Radiation Oncology, Ohio State University, Columbus, OH (United States); Sammet, Steffen [Department of Radiology, University of Chicago, Chicago, IL (United States); Department of Radiology, Ohio State University, Columbus, OH (United States); Sammet, Christina L. [Department of Radiology, University of Chicago, Chicago, IL (United States); Jia Guang; Zhang Jun; Knopp, Michael V.; Yuh, William T.C. [Department of Radiology, Ohio State University, Columbus, OH (United States)

    2012-07-01

    Purpose: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. Methods and Materials: DCE-MRI was performed in 102 stage IB{sub 2}-IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the total volume of tumor voxels with critically low DCE signal intensity (<2.1 compared with precontrast image, determined by previous receiver operator characteristic analysis). FRVs were correlated with treatment outcome (follow-up: 0.2-9.4, mean 6.8 years) and compared with ATVs (Mann-Whitney, Kaplan-Meier, and multivariate analyses). Results: Before and during therapy at 2-2.5 and 4-5 weeks of RT, FRVs >20, >13, and >5 cm{sup 3}, respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 Multiplication-Sign 10{sup -8}, 2.0 Multiplication-Sign 10{sup -8}) and disease-specific survival (p = 1.9 Multiplication-Sign 10{sup -4}, 2.1 Multiplication-Sign 10{sup -6}, 2.5 Multiplication-Sign 10{sup -7}, respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. Discussion: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2

  12. Post-irradiation regeneration of early B-lymphocyte precursor cells in mouse bone marrow

    International Nuclear Information System (INIS)

    Park, Y.-H.; Osmond, D.G.

    1989-01-01

    To examine the sequential development of early B-cell precursors in mouse bone marrow, B-lineage cells have been examined during a wave of post-irradiation regeneration. Cell phenotypes have been defined for (i) terminal deoxynucleotidyl transferase (TdT); (ii) B220 glycoprotein, (iii) μ heavy chains in the cytoplasm (cμ) and at the cell surface (sμ). Three populations of μ - cells (TdT + 14.8 - ; TdT + 14.8 + ; TdT - 14.8 + ) have been proposed to be early B-cell precursors which would give rise to cμ + sμ - pre-B cells and to sμ + B lymphocytes. The timing, cell-size shifts and progressive amplification of the waves of regeneration accord with a dynamic model in which the TdT + 14.8 - , TdT + 14.8 + and TdT - 14.8 + cells form three successive stages in B-cell differentiation before the expression of μ chains, presumptively including the stage of μ chain gene rearrangement. In addition, the results provide an experimental system for the enrichment of early B-cell precursors in mouse bone marrow. (author)

  13. Localized basal meningeal enhancement in tuberculous meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du [University of Stellenbosch, Department of Radiology, Tygerberg Hospital, P.O. BOX 19063, Tygerberg (South Africa)

    2006-11-15

    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  14. Localized basal meningeal enhancement in tuberculous meningitis

    International Nuclear Information System (INIS)

    Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du

    2006-01-01

    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  15. Friends not foes: CTLA-4 blockade and mTOR inhibition cooperate during CD8+ T cell priming to promote memory formation and metabolic readiness.

    Science.gov (United States)

    Pedicord, Virginia A; Cross, Justin R; Montalvo-Ortiz, Welby; Miller, Martin L; Allison, James P

    2015-03-01

    During primary Ag encounter, T cells receive numerous positive and negative signals that control their proliferation, function, and differentiation, but how these signals are integrated to modulate T cell memory has not been fully characterized. In these studies, we demonstrate that combining seemingly opposite signals, CTLA-4 blockade and rapamycin-mediated mammalian target of rapamycin inhibition, during in vivo T cell priming leads to both an increase in the frequency of memory CD8(+) T cells and improved memory responses to tumors and bacterial challenges. This enhanced efficacy corresponds to increased early expansion and memory precursor differentiation of CD8(+) T cells and increased mitochondrial biogenesis and spare respiratory capacity in memory CD8(+) T cells in mice treated with anti-CTLA-4 and rapamycin during immunization. Collectively, these results reveal that mammalian target of rapamycin inhibition cooperates with rather than antagonizes blockade of CTLA-4, promoting unrestrained effector function and proliferation, and an optimal metabolic program for CD8(+) T cell memory. Copyright © 2015 by The American Association of Immunologists, Inc.

  16. Predictive factors for early failure of transarterial embolization in blunt hepatic injury patients

    International Nuclear Information System (INIS)

    Lee, Y.-H.; Wu, C.-H.; Wang, L.-J.; Wong, Y.-C.; Chen, H.-W.; Wang, C.-J.; Lin, B.-C.; Hsu, Y.-P.

    2014-01-01

    Aim: To evaluate the early success of transarterial embolization (TAE) in patients with traumatic liver haemorrhage and to determine independent factors for its failure. Materials and methods: From January 2009 to December 2012, TAE was performed in 48 patients for traumatic liver haemorrhage. Their medical charts were reviewed for demographic information, pre-TAE vital signs and laboratory data, injury grade, type of contrast medium extravasation (CME) at CT, angiography findings, and early failure. “Early failure” was defined as the need for repeated TAE or a laparotomy for hepatic haemorrhage within 4 days after TAE. Variables were compared between the early success and early failure groups. Variables with univariate significance were also analysed using multivariate logistic regression for predictors of early failure. Results: Among 48 liver TAE cases, nine (18.8%) were early failures due to liver haemorrhage. Early failure was associated with injury grade (p = 0.039), major liver injury (grades 4 and 5; p = 0.007), multiple CMEs at angiography (p = 0.031), incomplete TAE (p = 0.002), and elevated heart rate (p = 0.026). Incomplete embolization (OR = 8; p = 0.042), and heart rate >110 beats/min (bpm; OR = 8; p = 0.05) were independent factors for early failure of TAE in the group with major liver injuries. Conclusion: Major hepatic injury is an important factor in early failure. Patients with a heart rate >110 bpm and incomplete embolization in the major injury group have an increased rate of early failure. The success rate of proximal TAE was comparable to that of the more time-consuming, superselective, distal TAE. - Highlights: • Early failure of TAE is associated with a higher grade of liver injury. • Incomplete embolization is more likely to suffer early failure of TAE. • A heart rate greater than 110 bpm is more likely to suffer early failure of TAE. • We recommend proximal embolization to prevent early failure of TAE

  17. Incidence and characteristics of early childhood wheezing, Dhaka, Bangladesh, 2004-2010.

    Science.gov (United States)

    Dawood, Fatimah S; Fry, Alicia M; Goswami, Doli; Sharmeen, Amina; Nahar, Kamrun; Anjali, Bilkis Ara; Rahman, Mustafizur; Brooks, W Abdullah

    2016-06-01

    Early childhood wheezing substantially impacts quality of life in high-income countries, but data are sparse on early childhood wheezing in low-income countries. We estimate wheezing incidence, describe wheezing phenotypes, and explore the contribution of respiratory viral illnesses among children aged accounting for 8,901 episodes (733 [8%] associated with hospitalization); 25% wheezed at work of breathing (OR 1.6, 95%CI 1.4-1.8), and hospitalization (OR 2.0, 95%CI 1.6-2.4). Respiratory viruses were detected in 66% (578/873) of episodes with testing. In urban Bangladesh, early childhood wheezing is common and largely associated with respiratory virus infections. Recurrent wheezing is associated with more severe illness and may predict children who would benefit most from closer follow-up and targeted interventions. Pediatr Pulmonol. 2016;51:588-595. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  18. Early cortical facilitation for emotionally arousing targets during the attentional blink

    Directory of Open Access Journals (Sweden)

    Ihssen Niklas

    2006-07-01

    Full Text Available Abstract Background The present study aimed to investigate the time course of electrocortical facilitation for affectively arousing written words during the so-called 'attentional blink' (AB period in a rapid serial visual presentation (RSVP task. The AB refers to a period of reduced awareness for second-target stimuli following a first target by an interval of about 200–500 ms. Pleasant, neutral, and unpleasant written verbs were used as second targets in an 8.6-Hz RSVP paradigm that contained affectively neutral words as distractors. Replicating and extending behavioral studies, we expected that emotional second targets would be associated with better identification accuracy and greater electrocortical activity, compared with neutral targets. Results The steady-state visual evoked potential was recorded using 129 scalp electrodes. The time-varying energy at the presentation frequency of 8.6 Hz was extracted as a continuous measure of electrocortical activity related to the RSVP stream. Behavioral data showed that at an inter-target interval of 232 ms, the report for emotionally arousing (pleasant and unpleasant words was more accurate than for neutral control words. This result was mirrored by the electrocortical response at posterior sensors, which showed rapid amplitude enhancement (120–270 ms after T2 onset for pleasant and unpleasant targets specifically. Conclusion The present data suggest that identification facilitation for emotionally arousing target words in the AB is related to rapid enhancement of sensory processing. Affectively arousing information is preferentially selected at the level of early perceptual analysis, leading to facilitation at later stages of processing, including consolidation in working memory and visual awareness.

  19. Usefulness of fat-suppressed Gd-enhanced MR imaging of tongue cancer

    International Nuclear Information System (INIS)

    Murakami, Shumei; Fuchihata, Hajime; Yoon, Sukja; Furukawa, Souhei; Kawai, Tadahiko; Kishino, Mitsunobu

    1999-01-01

    To evaluate the usefulness of the fat suppression technique for magnetic resonance imaging of oral tongue cancer. One hundred and fourteen patients underwent both magnetic resonance imaging (MRI) and computed tomography (CT). All patients were clinically diagnosed as having oral tongue cancer shown to be squamous cell carcinoma histopathologically. We used two types of CT and six types of MRI scanning: plain CT, contrast enhanced CT, conventional T1w, conventional PDw, conventional T2w, fat-suppressed (FATS) T1w, Gd-enhanced conventional T1w, and Gd-enhanced FATS T1w images. The focus of our study was Gd-enhanced FATS T1w imaging. Tumor detection rates were as follows: Gd-enhanced FATS T1w MRI, 86.8%; conventional T2w MRI, 71.9%; conventional PDw MRI, 65.8%; Gd-enhanced conventional T1w MRI, 47.4%; contrast enhanced CT, 36.8%; T1w MRI, 20.2%; CT, 10.5%. There were 59 cases in which tumors were detected by Gd-enhanced FATS T1w MRI but not detected by contrast enhanced CT. Gd-enhanced FATS T1w MRI was the best for the tumor detection and Gd-enhanced conventional T1w MRI was not useful in the diagnosis of the tongue cancer. CT imaging must not be the first choice for tumor detection in tongue cancer patients. (author)

  20. NR2B subunit-dependent long-term potentiation enhancement in the rat cortical auditory system in vivo following masking of patterned auditory input by white noise exposure during early postnatal life.

    Science.gov (United States)

    Hogsden, Jennifer L; Dringenberg, Hans C

    2009-08-01

    The composition of N-methyl-D-aspartate (NMDA) receptor subunits influences the degree of synaptic plasticity expressed during development and into adulthood. Here, we show that theta-burst stimulation of the medial geniculate nucleus reliably induced NMDA receptor-dependent long-term potentiation (LTP) of field postsynaptic potentials recorded in the primary auditory cortex (A1) of urethane-anesthetized rats. Furthermore, substantially greater levels of LTP were elicited in juvenile animals (30-37 days old; approximately 55% maximal potentiation) than in adult animals (approximately 30% potentiation). Masking patterned sound via continuous white noise exposure during early postnatal life (from postnatal day 5 to postnatal day 50-60) resulted in enhanced, juvenile-like levels of LTP (approximately 70% maximal potentiation) relative to age-matched controls reared in unaltered acoustic environments (approximately 30%). Rats reared in white noise and then placed in unaltered acoustic environments for 40-50 days showed levels of LTP comparable to those of adult controls, indicating that white noise rearing results in a form of developmental arrest that can be overcome by subsequent patterned sound exposure. We explored the mechanisms mediating white noise-induced plasticity enhancements by local NR2B subunit antagonist application in A1. NR2B subunit antagonists (Ro 25-6981 or ifenprodil) completely reversed white noise-induced LTP enhancement at concentrations that did not affect LTP in adult or age-matched controls. We conclude that white noise exposure during early postnatal life results in the maintenance of juvenile-like, higher levels of plasticity in A1, an effect that appears to be critically dependent on NR2B subunit activation.

  1. Enhanced musical rhythmic perception in Turkish early and late learners of German

    NARCIS (Netherlands)

    Roncaglia-Denissen, M.P.; Schmidt-Kassow, M.; Heine, A.; Vuust, P.; Kotz, S.A.

    2013-01-01

    As language rhythm relies partly on general acoustic properties, such as intensity and duration, mastering two languages with distinct rhythmic properties (i.e., stress position) may enhance musical rhythm perception. We investigated whether competence in a second language (L2) with different

  2. Early perfusion changes within 1 week of systemic treatment measured by dynamic contrast-enhanced MRI may predict survival in patients with advanced hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Bang-Bin; Yu, Chih-Wei; Liang, Po-Chin [National Taiwan University College of Medicine and Hospital, Department of Medical Imaging and Radiology, Taipei City (China); Hsu, Chao-Yu [National Taiwan University College of Medicine and Hospital, Department of Medical Imaging and Radiology, Taipei City (China); Taipei Hospital, Ministry of Health and Welfare, Department of Radiology, New Taipei City (China); Hsu, Chiun; Hsu, Chih-Hung; Cheng, Ann-Lii [National Taiwan University College of Medicine and Hospital, Department of Oncology, Taipei City (China); Shih, Tiffany Ting-Fang [National Taiwan University College of Medicine and Hospital, Department of Medical Imaging and Radiology, Taipei City (China); Taipei City Hospital, Department of Medical Imaging, Taipei City (China); National Taiwan University Hospital, Department of Medical Imaging, Taipei (China)

    2017-07-15

    To correlate early changes in the parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) within 1 week of systemic therapy with overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC). Eighty-nine patients with advanced HCC underwent DCE-MRI before and within 1 week following systemic therapy. The relative changes of six DCE-MRI parameters (Peak, Slope, AUC, Ktrans, Kep and Ve) of the tumours were correlated with OS using the Kaplan-Meier model and the double-sided log-rank test. All patients died and the median survival was 174 days. Among the six DCE-MRI parameters, reductions in Peak, AUC, and Ktrans, were significantly correlated with one another. In addition, patients with a high Peak reduction following treatment had longer OS (P = 0.023) compared with those with a low Peak reduction. In multivariate analysis, a high Peak reduction was an independent favourable prognostic factor in all patients [hazard ratio (HR), 0.622; P = 0.038] after controlling for age, sex, treatment methods, tumour size and stage, and Eastern Cooperative Oncology Group performance status. Early perfusion changes within 1 week following systemic therapy measured by DCE-MRI may aid in the prediction of the clinical outcome in patients with advanced HCC. (orig.)

  3. LUMINOUS SATELLITES OF EARLY-TYPE GALAXIES. I. SPATIAL DISTRIBUTION

    International Nuclear Information System (INIS)

    Nierenberg, A. M.; Auger, M. W.; Treu, T.; Marshall, P. J.; Fassnacht, C. D.

    2011-01-01

    We study the spatial distribution of faint satellites of intermediate redshift (0.1 s = 1.7 +0.9 -0.8 ) that is comparable to the number of Milky Way satellites with similar host-satellite contrast. The average projected radial profile of the satellite distribution is isothermal (γ p = -1.0 +0.3 -0.4 ), which is consistent with the observed central mass density profile of massive early-type galaxies. Furthermore, the satellite distribution is highly anisotropic (isotropy is ruled out at a >99.99% confidence level). Defining φ to be the offset between the major axis of the satellite spatial distribution and the major axis of the host light profile, we find a maximum posterior probability of φ = 0 and |φ| less than 42 0 at the 68% confidence level. The alignment of the satellite distribution with the light of the host is consistent with simulations, assuming that light traces mass for the host galaxy as observed for lens galaxies. The anisotropy of the satellite population enhances its ability to produce the flux ratio anomalies observed in gravitationally lensed quasars.

  4. Characteristics of hypertrophic cardiomyopathy on delayed contrast-enhanced MRI

    International Nuclear Information System (INIS)

    Yan Chaowu; Zhao Shihua; Li Hua; Jiang Shiliang; Lu Minjie; Zhang Yan; Wei Yunqing; Ling Jian; Fang Wei

    2010-01-01

    Objective: To analyze the characteristics of hypertrophic cardiomyopathy (HCM) on delayed contrast-enhanced cardiac magnetic resonance imaging (CMRI). Methods: All patients underwent delayed contrast-enhanced CMRI. The left ventricle was divided into 9 segments to assess the location, extent and function of the hypertrophic segments. The t test was applied for the statistics. Results: Of 154 patients, delayed enhancement of' hypertrophic segment was found in 95 cases and non-delayed enhancement in 59 cases. The thickness and number of hypertrophic segment in patients with delayed enhancement were larger than those with non-delayed enhancement [(24.8±5.5) mm vs (20.4± 3.8) mm, t=3.82, P<0.05; (3.3±1.9) vs (2.4±1.7), t=2.26, P<0.05], and the age was younger [(46.0±15.2) years vs (55.0±11.9) years, t=-3.67, P<0.05]. The diffuse enhancement was found in 62 patients, and confluent enhancement in 33 patients. Confluent enhancement was found in all 14 patients after the alcohol ablation procedure. Conclusion: The age, thickness and number of hypertrophic segments in patients with delayed enhancement are different from those with non-delayed enhancement. (authors)

  5. The Effect of the Degree of Luminal Contrast-Enhancement on CT Measurement of Plaque Size: A Comparison with T1-weighted Magnetic Resonance Imaging

    International Nuclear Information System (INIS)

    Choi, Byoung Wook; Hur, Jin; Lee, Hye Jeong; Kim, Young Jin; Choe, Kyu Ok; Kim, Tae Hoon

    2010-01-01

    We studied early and delayed contrast-enhanced CT to determine the effects of the degree of luminal enhancement on the measurement of plaque size compared to T1-weighted MRI. T1-weighted MRI and a two-phase contrast-enhanced CT was performed in 5 New Zealand white rabbits with atherosclerosis. Early-phase images were acquired during an expected peak enhancement period of the lumen; delayed-phase images were acquired 240 sec after administration of the contrast media. Anteroposterior and lateral luminal diameters (APD, LD), luminal area (LA), total vessel area (TVA), and plaque area (PA) of the aorta were measured on MRI and CT, respectively and compared to each other. A total of 78 slices of the aorta were analyzed. PA, measured on T1-weighted MR images, was significantly greater than PA for both early-phase and delayed-phase CT (p 2 (p 2 (p 2 (p = 0.159) for MRI vs. early-phase CT, MRI vs. delayed-phase CT, and early-phase CT vs. delayed-phase CT, respectively. Different luminal densities by contrast enhancement do not affect the CT measurement of plaque area for the detection of obstructive coronary artery disease

  6. Dietary supplementation with n-3 polyunsaturated fatty acids in early childhood: effects on blood pressure and arterial structure and function at age 8 y.

    Science.gov (United States)

    Ayer, Julian G; Harmer, Jason A; Xuan, Wei; Toelle, Brett; Webb, Karen; Almqvist, Catarina; Marks, Guy B; Celermajer, David S

    2009-08-01

    n-3 Fatty acid supplementation in adults results in cardiovascular benefits. However, the cardiovascular effects of n-3 supplementation in early childhood are unknown. The objective was to evaluate blood pressure (BP) and arterial structure and function in 8-y-old children who had participated in a randomized controlled trial of dietary n-3 and n-6 modification over the first 5 y of life. The children (n = 616; 49% girls) were randomly assigned antenatally to active (n = 312; increase in n-3 intake and decrease in n-6 intake) or control (n = 304) diet interventions implemented from the time of weaning or introduction of solids until 5 y of age. At age 8.0 +/- 0.1 y, BP, carotid intima-media thickness, carotid artery distensibility, augmentation index, and brachial pulse wave velocity were measured in 405 of these children. Venous blood was collected for measurement of plasma fatty acids, lipoproteins, high-sensitivity C-reactive protein, and asymmetric dimethylarginine. Plasma fatty acid concentrations were also assessed during the intervention. Plasma concentrations of n-3 fatty acids were higher and of n-6 were lower in the active than in the control diet group at 18 mo and 3 and 5 y (P n-3 and n-6 fatty acids were similar at 8 y. At 8 y of age, no significant differences were found in BP, carotid intima-media thickness, carotid artery distensibility, augmentation index, asymmetric dimethylarginine, high-sensitivity C-reactive protein, or lipoproteins between diet groups. A dietary supplement intervention to increase n-3 and decrease n-6 intakes from infancy until 5 y does not result in significant improvements in arterial structure and function at age 8 y. This trial was registered at the Australian Clinical Trials Registry as ACTRN012605000042640.

  7. Near Real-Time Browsable Landsat-8 Imagery

    Directory of Open Access Journals (Sweden)

    Cheng-Chien Liu

    2017-01-01

    Full Text Available The successful launch and operation of Landsat-8 extends the remarkable 40-year acquisition of space-based land remote-sensing data. To respond quickly to emergency needs, real-time data are directly downlinked to 17 ground stations across the world on a routine basis. With a size of approximately 1 Gb per scene, however, the standard level-1 product provided by these stations is not able to serve the general public. Users would like to browse the most up-to-date and historical images of their regions of interest (ROI at full-resolution from all kinds of devices without the need for tedious data downloading, decompressing, and processing. This paper reports on the Landsat-8 automatic image processing system (L-8 AIPS that incorporates the function of mask developed by United States Geological Survey (USGS, the pan-sharpening technique of spectral summation intensity modulation, the adaptive contrast enhancement technique, as well as the Openlayers and Google Maps/Earth compatible superoverlay technique. Operation of L-8 AIPS enables the most up-to-date Landsat-8 images of Taiwan to be browsed with a clear contrast enhancement regardless of the cloud condition, and in only one hour’s time after receiving the raw data from the USGS Level 1 Product Generation System (LPGS. For any ROI in Taiwan, all historical Landsat-8 images can also be quickly viewed in time series at full resolution (15 m. The debris flow triggered by Typhoon Soudelor (8 August 2015, as well as the barrier lake formed and the large-scale destruction of vegetation after Typhoon Nepartak (7 July 2016, are given as three examples of successful applications to demonstrate that the gap between the user’s needs and the existing Level-1 product from LPGS can be bridged by providing browsable images in near real-time.

  8. Multiple Roles for UV RESISTANCE LOCUS8 in Regulating Gene Expression and Metabolite Accumulation in Arabidopsis under Solar Ultraviolet Radiation1[W][OA

    Science.gov (United States)

    Morales, Luis O.; Brosché, Mikael; Vainonen, Julia; Jenkins, Gareth I.; Wargent, Jason J.; Sipari, Nina; Strid, Åke; Lindfors, Anders V.; Tegelberg, Riitta; Aphalo, Pedro J.

    2013-01-01

    Photomorphogenic responses triggered by low fluence rates of ultraviolet B radiation (UV-B; 280–315 nm) are mediated by the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8). Beyond our understanding of the molecular mechanisms of UV-B perception by UVR8, there is still limited information on how the UVR8 pathway functions under natural sunlight. Here, wild-type Arabidopsis (Arabidopsis thaliana) and the uvr8-2 mutant were used in an experiment outdoors where UV-A (315–400 nm) and UV-B irradiances were attenuated using plastic films. Gene expression, PYRIDOXINE BIOSYNTHESIS1 (PDX1) accumulation, and leaf metabolite signatures were analyzed. The results show that UVR8 is required for transcript accumulation of genes involved in UV protection, oxidative stress, hormone signal transduction, and defense against herbivores under solar UV. Under natural UV-A irradiance, UVR8 is likely to interact with UV-A/blue light signaling pathways to moderate UV-B-driven transcript and PDX1 accumulation. UVR8 both positively and negatively affects UV-A-regulated gene expression and metabolite accumulation but is required for the UV-B induction of phenolics. Moreover, UVR8-dependent UV-B acclimation during the early stages of plant development may enhance normal growth under long-term exposure to solar UV. PMID:23250626

  9. A new quaternary photoluminescence enhancement system of Eu-N-(o-vanillin)-1,8-diaminonaphthalene-1,10-phenanthroline-Zn and its application in determining trace amounts of europium and zinc.

    Science.gov (United States)

    Zhou, Yunshan; Ahmad, Waqar; An, Yugang; Zhang, Lijuan; Zheng, Xiaorui

    2014-08-01

    A new sensitive quaternary photoluminescence enhancement system has been successfully developed to determine trace amounts of Eu(3+) and Zn(2+). The photoluminescence intensity of Eu - N-(o-vanilin)-1,8-diaminonaphthalene systems was greatly increased by the addition of specific concentrations of 1, 10-phenanthroline and Zn(2+). The excitation and emission wavelengths were 274 and 617 nm, respectively. Under optimal system conditions, the photoluminescence intensity showed a linear response toward Eu(3+) in the range of 5.0 × 10(-6)  ~ 2.0 × 10(-5)  M with a limit of detection (= 2.2 × 10(-9)  M) and the photoluminescence intensity of the system decreased linearly by increasing the Zn(2+) concentration in the range of 5.0 × 10(-8)  ~ 1.0 × 10(-6)  M with a limit of detection (= 8.8 × 10(-11)  M). This system was successfully applied for the determination of trace amounts of Eu(3+) in a high purity La2O3 matrix and in the synthetic rare earth oxide mixture, and of Zn(2+) in a high purity Mg(NO3)2 · 6H2O matrix and in synthetic coexisting ionic matrixes. The energy transfer mechanism, photoluminescence enhancement of the system and interference of other lanthanide ions and common coexisting ions were also studied in detail. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Possible edge effect in enhanced network

    Energy Technology Data Exchange (ETDEWEB)

    Jones, H P; Brown, D R [National Aeronautics and Space Administration, Greenbelt, Md. (USA). Goddard Space Flight Center

    1977-05-01

    K-line observations of enhanced network taken with the NASA/SPO Multichannel Spectrometer on 28 September 1975 in support of OSO-8 are discussed. The data show a correlation between core brightness and asymmetry for spatial scans which cross enhanced network boundaries. The implications of this result concerning mass flow in and near supergranule boundaries are discussed.

  11. Procalcitonin and C-reactive protein as early markers of anastomotic leak after laparoscopic colorectal surgery within an enhanced recovery after surgery (ERAS) program.

    Science.gov (United States)

    Muñoz, José Luis; Alvarez, María Oliva; Cuquerella, Vicent; Miranda, Elena; Picó, Carlos; Flores, Raquel; Resalt-Pereira, Marta; Moya, Pedro; Pérez, Ana; Arroyo, Antonio

    2018-03-08

    C-reactive protein (CRP) and procalcitonin (PCT) have been described as good predictors of anastomotic leak after colorectal surgery, obtaining the highest diagnostic accuracy on the 5th postoperative day. However, if an enhanced recovery after surgery (ERAS) program is performed, early predictors are needed in order to ensure a safe and early discharge. The aim of this study was to investigate the efficacy of CRP, PCT, and white blood cell (WBC) count determined on first postoperative days, in predicting septic complications, especially anastomotic leak, after laparoscopic colorectal surgery performed within an ERAS program. We conducted a prospective study including 134 patients who underwent laparoscopic colorectal surgery within an ERAS program between 2015 and 2017. The primary endpoint investigated was anastomotic leak. CRP, PCT, and WBC count were determined in the blood sample extracted on postoperative day 1 (POD 1), POD 2 and POD 3. Anastomotic leak (AL) was detected in 6 patients (4.5%). Serum levels of CRP and PCT, but not WBC, determined on POD 1, POD 2, and POD 3 were significantly higher in patients who had AL in the postoperative course. Using ROC analysis, the best AUC of the CRP and PCT levels was on POD 3 (0.837 and 0.947, respectively). A CRP cutoff level at 163 mg/l yielded 85% sensitivity, 80% specificity, and 99% negative predictive value (NPV). A PCT cutoff level at 2.5 ng/ml achieved 85% sensitivity, 95% specificity, 44% positive predictive value, and 99% NPV. CRP and PCT are relevant markers for detecting postoperative AL after laparoscopic colorectal surgery. Furthermore, they can ensure an early discharge with a low probability of AL when an ERAS program is performed.

  12. Early prediction of post-thyroidectomy hypocalcemia by early parathyroid hormone measurement.

    Science.gov (United States)

    Yetkin, Gurkan; Citgez, Bulent; Yazici, Pinar; Mihmanli, Mehmet; Sit, Erhan; Uludag, Mehmet

    2016-01-01

    Hypoparathyroidism is the most common complication of total thyroidectomy (TT). Postthyroidectomy hypocalcemia occurs 24 to 48 hours after the operation. It prolongs the length of hospital stay, even though transient in most cases. The aim of this study was to predetermine the patients who may develop postthyroidectomy hypocalcemia by using early postoperative serum intact parathormone (iPTH) and calcium (Ca2+) measurements, and to investigate the effects of early initiated oral calcium and vitamin D treatments on the development of transient hypocalcemia. Patients who underwent TT after initiation of the early iPTH measurement protocol in January 2013 were included into the study group (Group 1, n=202). The control group (Group 2) was composed of 72 patients who underwent TT before the protocol. Prior to the initiation of the protocol, Ca2+ was measured instead of iPTH. In the study group, the serum Ca2+ and iPTH levels were measured before surgery, and 1 and 24-hours after. A calcium level below 8 mg/dL was accepted as biochemical hypocalcaemia, and a iPTH level under 15pg/mL was accepted as hypoparathyroidism. In the study group, patients with below normal iPTH levels were treated with prophylactic oral calcium and vitamin D. In Group 1, 15.8% (n=32) of the patients had hypoparathyroidism on the 1h and 24 h iPTH measurements. There was no statistically difference with regard to PTH levels measured in the postoperative 1st hour and at the 24th hour (p= 0.078). Biochemical hypocalcaemia developed in 16 (7.9%) and 13 (18%) patients in Groups 1 and 2, respectively, 24 hours after thyroidectomy (peffective management of plausible postthyroidectomic hypocalcemia. It yields significantly shorter hospital stay periods. Calcium, Hypoparathyroidism, Postoperative complication, Total thyroidectomy.

  13. Contrast-enhanced dedicated breast CT detection of invasive breast cancer preceding mammographic diagnosis

    Directory of Open Access Journals (Sweden)

    Nicolas D. Prionas, MD, PhD

    2015-01-01

    Full Text Available Dedicated breast computed tomography (bCT generates high-resolution, three-dimensional images of the pendent uncompressed breast. Intravenous iodinated contrast during bCT provides additional physiologic information. In this case, a 10.0-mm invasive ductal carcinoma was visualized using contrast-enhanced breast CT one year before mammographic detection. Mammography four months before bCT was negative. The bCT contrast enhancement pattern closely matched the dynamic contrast-enhanced MRI obtained after diagnosis. Lesion enhancement at contrast-enhanced breast CT matched previously published enhancement values of breast cancer. Contrast-enhanced dedicated bCT provided high-resolution tomographic images and physiologic contrast enhancement data that facilitated the detection of an early breast cancer.

  14. Correlation Between Expression of Recombinant Proteins and Abundance of H3K4Me3 on the Enhancer of Human Cytomegalovirus Major Immediate-Early Promoter.

    Science.gov (United States)

    Soo, Benjamin P C; Tay, Julian; Ng, Shirelle; Ho, Steven C L; Yang, Yuansheng; Chao, Sheng-Hao

    2017-08-01

    Role of epigenetic regulation in the control of gene expression is well established. The impact of several epigenetic mechanisms, such as DNA methylation and histone acetylation, on recombinant protein production in mammalian cells has been investigated recently. Here we investigate the correlation between the selected epigenetic markers and five trastuzumab biosimilar-producing Chinese hamster ovary (CHO) cell lines in which the expression of trastuzumab is driven by human cytomegalovirus (HCMV) major immediate-early (MIE) promoter. We chose the producing clones in which transcription was the determinative step for the production of recombinant trastuzumab. We found that the abundance of trimethylation of histone 3 at lysine 4 (H3K4Me3) on the enhancer of HCMV MIE promoter correlated well with the relative titers of recombinant trastuzumab among the clones. Such close correlation was not observed between the recombinant protein and other epigenetic markers examined in our study. Our results demonstrate that the HCMV MIE enhancer-bound H3K4Me3 epigenetic marker may be used as the epigenetic indicator to predict the relative production of recombinant proteins between the producing CHO cell lines.

  15. Language experience enhances early cortical pitch-dependent responses

    Science.gov (United States)

    Krishnan, Ananthanarayan; Gandour, Jackson T.; Ananthakrishnan, Saradha; Vijayaraghavan, Venkatakrishnan

    2014-01-01

    Pitch processing at cortical and subcortical stages of processing is shaped by language experience. We recently demonstrated that specific components of the cortical pitch response (CPR) index the more rapidly-changing portions of the high rising Tone 2 of Mandarin Chinese, in addition to marking pitch onset and sound offset. In this study, we examine how language experience (Mandarin vs. English) shapes the processing of different temporal attributes of pitch reflected in the CPR components using stimuli representative of within-category variants of Tone 2. Results showed that the magnitude of CPR components (Na-Pb and Pb-Nb) and the correlation between these two components and pitch acceleration were stronger for the Chinese listeners compared to English listeners for stimuli that fell within the range of Tone 2 citation forms. Discriminant function analysis revealed that the Na-Pb component was more than twice as important as Pb-Nb in grouping listeners by language affiliation. In addition, a stronger stimulus-dependent, rightward asymmetry was observed for the Chinese group at the temporal, but not frontal, electrode sites. This finding may reflect selective recruitment of experience-dependent, pitch-specific mechanisms in right auditory cortex to extract more complex, time-varying pitch patterns. Taken together, these findings suggest that long-term language experience shapes early sensory level processing of pitch in the auditory cortex, and that the sensitivity of the CPR may vary depending on the relative linguistic importance of specific temporal attributes of dynamic pitch. PMID:25506127

  16. Development of early communication skills in the first two years of life.

    Science.gov (United States)

    Beuker, Karin T; Rommelse, Nanda N J; Donders, Rogier; Buitelaar, Jan K

    2013-02-01

    The first two years of life is a crucially important period for the development of communication skills. In this study joint attention and language development were monthly assessed between 8 and 24 months of age in a sample of 23 typically developing children to establish the developmental trajectory of specific joint attention skills, to investigate the developmental interrelations of these different joint attention skills with vocabulary size, and to examine whether the order of development of following and directing attention influences the development of other early communication skills such as language. All joint attention skills emerged between 8 and 15 months of age and responsive joint attention skills tend to emerge before initiative joint attention. Early joint attention skills influenced later language development, but not the other way around. Children in whom directing attention with gaze alternation developed early (in age or order) showed a relatively larger early vocabulary growth. A fine grained mapping of the normal development of early communication skills can be helpful in the early detection of abnormalities in these skills. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Australian Early Childhood Educators: From Government Policy to University Practice

    Science.gov (United States)

    Davies, Sharon; Trinidad, Sue

    2013-01-01

    This article provides an overview of the Australian Federal Government initiatives in the area of early childhood with regard to the provision of early childhood education and care. These changes have influenced a Western Australian university to develop an innovative birth to 8 years preservice educator education curriculum. Using an ecological…

  18. Early Predictors of Eating Problems in Preadolescence

    DEFF Research Database (Denmark)

    Munkholm, Anja; Olsen, Else Marie; Rask, Charlotte Ulrikka

    2016-01-01

    Purpose: The epidemiology of childhood eating problems is far from being fully described. The present study aims to explore early predictors of eating behavior problems in preadolescence. Methods: The study sample comprised 1,939 children from the birth cohort study, the Copenhagen Child Cohort...... interval [CI] = 1.13–6.77; p = .03), with overweight at age 11–12 years and low annual household income as strong explanatory factors (OR = 4.79; 95% CI = 2.81–8.17; p early child...

  19. Early inflammatory response in epithelial ovarian tumor cyst fluids

    International Nuclear Information System (INIS)

    Kristjánsdóttir, Björg; Partheen, Karolina; Fung, Eric T; Yip, Christine; Levan, Kristina; Sundfeldt, Karin

    2014-01-01

    Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors

  20. Gd-DTPA enhanced MRI of the brain infarction: correlation between onset of infarction and enhancing patterns

    International Nuclear Information System (INIS)

    Joo, An Young; Kim, Myung Soon; Lee, Sung Soo

    1994-01-01

    To evaluate the correlation between onset of brain infarction and Gd-DTPA enhancing patterns on MRI. We reviewed MRI of 58 lesions in 45 patients with clinically documented brain infarction retrospectively. Axial, coronal and sagittal T1WI (TR/TE 450-520/20), T2WI (TR/TE 2190/90) and Gd-DTPA enhanced T1WI were performed with a 0.5T superconductive MR system. We analyzed Gd-enhancing patterns that were divided into intravascular, meningeal, and parenchymal enhancement. Parenchymal pattern was subdivided into mottled, partial ring like and dense enhancement. Intravascular enhancement was seen at 1-10 days in 30(53%) of 58 infarctions. Meningeal enhancement (13%) was noted at 1-6 days. Parenchymal enhancement (50%) was seen at 2-28 days and subdividing patterns are as follows: The mottled enhancement pattern was seen earlier at 2-8 days and partial ring like or dense enhancement patterns at 5-28 days. After reviewing Gd-enhanced MRI of infarction, the intravascular and meningeal enhancement patterns were earlier than parenchymal enhancement. Among parenchymal patterns, the mottled pattern was seen earlier than partial ring like or dense patterns. In conclusion, Gd-enhancing patterns of brain infarction are useful in estimating the age of infarction including acute infarction

  1. Effect of Cytoflavin on Early Postanesthetic Recovery of Cancer Patients

    Directory of Open Access Journals (Sweden)

    K. F. Fatullayeva

    2008-01-01

    Full Text Available Objective: to evaluate the effect of the metabolic antihypoxant cytoflavin on the course of early postanesthetic recovery in patients operated on for various cancers. Subjects and methods: Fifty-seven patients aged 30 to 65 years, operated on for gynecological cancer, were examined. The patients were divided into 2 groups: 1 28 patients who took cytoflavin and 2 29 who did not. At the end of an operation, the agent was intravenously injected in a dose of 10 ml in a mixture with an equal volume of 0.9% sodium chloride solution. Thiopental sodium was used for initial anesthesia; arduan was employed to maintain muscle relaxation. Neuroleptic analgesia with fentanyl and droperidol or ataralgesia (fentanyl + relanium was applied in both groups. The levels of hemoglobin, glucose, sodium, potassium, calcium, malonic dialdehyde (MDA (Andreyev’s test, antioxidative activity (AOA (Semenov’s test were measured to evaluate the functional state of patients. The rating system for determining the recovery of consciousness, respiration, and motor activity, proposed by Aldret and Kroulik [8], and Bidway’s psychological testing, blood oxygen saturation and cardiac performance monitoring (TRITON, Russia and some others were used to evaluate the efficacy of the drug in the early postanesthetic period. The results were statistically processed using Microsoft Excel and a package of Biostatistics 6.0. Results. The use of cytoflavin at the end of surgery has been established to have a beneficial effect on the early recovery period. This is manifested as shorter recovery of consciousness and respiration mainly in the ataralgesia group; fair oxygen saturation, lower MDA concentrations and higher AOA are revealed. Conclusion. Cytoflavin significantly reduces the recovery of consciousness and adequate respiration and the incidence of the fever, muscle tremor syndrome and fails to favor the occurrence of hypoglycemia. Inclusion of cytoflavin into a complex of

  2. κ-Carrageenan Enhances Lipopolysaccharide-Induced Interleukin-8 Secretion by Stimulating the Bcl10-NF-κB Pathway in HT-29 Cells and Aggravates C. freundii-Induced Inflammation in Mice

    Directory of Open Access Journals (Sweden)

    Wei Wu

    2017-01-01

    Full Text Available Background. The dietary usage of carrageenan as common food additive has increased observably over the last 50 years. But there is substantial controversy about its safety. Methods. We investigated whether the κ-carrageenan could enhance lipopolysaccharide-induced IL-8 expression by studying its actions on the TLR4-NF-κB pathway. The aggravating effect of κ-carrageenan on Citrobacter freundii DBS100-induced intestinal inflammation was also investigated in a mouse model. Results. Our data show that κ-carrageenan pretreatment promoted LPS-induced IL-8 expression in HT-29 cells. Although CD14, MD-2, and TLR4 were upregulated, the binding of LPS was not enhanced. However, the pathway of Bcl10-NF-κB was triggered. Interestingly, κ-carrageenan competitively blocked the binding of FITC-LPS. Furthermore, pretreatment with κ-carrageenan for one week previous to gavage with C. freundii DBS100 markedly aggravated weight loss, mortality, and colonic damage. The secretion of cytokines was unbalanced and the ratio of Tregs was decreased significantly. In addition, κ-carrageenan, together with C. freundii DBS100, enhanced the transcription and secretion of TLR4 and NF-κB. Conclusions. κ-Carrageenan can synergistically activate LPS-induced inflammatory through the Bcl10-NF-κB pathway, as indicated by its aggravation of C. freundii DBS100-induced colitis in mice. General Significance. Our results suggest that κ-carrageenan serves as a potential inflammatory agent that magnifies existing intestinal inflammation.

  3. Centrifugal (inside-out) enhancement of liver hemangiomas: A possible atypical appearance on contrast-enhanced US

    International Nuclear Information System (INIS)

    Bartolotta, Tommaso Vincenzo; Taibbi, Adele; Galia, Massimo; Lo Re, Giuseppe; La Grutta, Ludovico; Grassi, Roberto; Midiri, Massimo

    2007-01-01

    Objective: To report the prevalence and to describe the atypical centrifugal (inside-out) appearance of contrast-enhancement of liver hemangiomas on contrast-enhanced sonography. Materials and methods: Baseline and SonoVue-enhanced ultrasonography of 92 patients with 158 liver hemangiomas - considered atypical at grey-scale examination and confirmed by computed tomography, magnetic resonance imaging and ultrasound follow-up - were reviewed in consensus by two experienced radiologists, who evaluated baseline echogenicity and the dynamic enhancement pattern of each lesion looking for the presence of central enhancing foci in the arterial phase followed by a centrifugal (inside-out) enhancement in the portal-venous and late phases. Results: After administration of SonoVue, 12/158 hemangiomas (7.6%) (size range: 1-7 cm; mean: 3.2 cm) in seven patients (5 women, 2 men; age range: 34-71 years, mean: 50.8 years) showed a central enhancing focus in the arterial phase followed by a centrifugal enhancement in the portal-venous and late phases. In all cases centrifugal enhancement was incomplete at contrast-enhanced sonography, whereas computed tomography and/or magnetic resonance imaging were able to depict a complete and homogeneous fill-in. Conclusion: Radiologist should be aware that centrifugal (inside-out) appearance on contrast-enhanced sonography is a rare but possible feature of liver hemangioma

  4. Centrifugal (inside-out) enhancement of liver hemangiomas: A possible atypical appearance on contrast-enhanced US

    Energy Technology Data Exchange (ETDEWEB)

    Bartolotta, Tommaso Vincenzo [Department of Radiology, University of Palermo, Via Del Vespro 127, 90127 Palermo (Italy)], E-mail: tv.bartolotta@unipa.it; Taibbi, Adele [Department of Radiology, University of Palermo, Via Del Vespro 127, 90127 Palermo (Italy)], E-mail: taibbi_adele@yahoo.it; Galia, Massimo [Department of Radiology, University of Palermo, Via Del Vespro 127, 90127 Palermo (Italy)], E-mail: mgalia@yahoo.com; Lo Re, Giuseppe [Department of Radiology, University of Palermo, Via Del Vespro 127, 90127 Palermo (Italy)], E-mail: giuseppe.lore12@tin.it; La Grutta, Ludovico [Department of Radiology, University of Palermo, Via Del Vespro 127, 90127 Palermo (Italy)], E-mail: lagrutta@mbox.infcom.it; Grassi, Roberto [Institute of Radiology, Second University of Naples, Piazza Miraglia, 80138 Naples (Italy)], E-mail: roberto.grassi@libero.it; Midiri, Massimo [Department of Radiology, University of Palermo, Via Del Vespro 127, 90127 Palermo (Italy)], E-mail: mmidiri@hotmail.com

    2007-12-15

    Objective: To report the prevalence and to describe the atypical centrifugal (inside-out) appearance of contrast-enhancement of liver hemangiomas on contrast-enhanced sonography. Materials and methods: Baseline and SonoVue-enhanced ultrasonography of 92 patients with 158 liver hemangiomas - considered atypical at grey-scale examination and confirmed by computed tomography, magnetic resonance imaging and ultrasound follow-up - were reviewed in consensus by two experienced radiologists, who evaluated baseline echogenicity and the dynamic enhancement pattern of each lesion looking for the presence of central enhancing foci in the arterial phase followed by a centrifugal (inside-out) enhancement in the portal-venous and late phases. Results: After administration of SonoVue, 12/158 hemangiomas (7.6%) (size range: 1-7 cm; mean: 3.2 cm) in seven patients (5 women, 2 men; age range: 34-71 years, mean: 50.8 years) showed a central enhancing focus in the arterial phase followed by a centrifugal enhancement in the portal-venous and late phases. In all cases centrifugal enhancement was incomplete at contrast-enhanced sonography, whereas computed tomography and/or magnetic resonance imaging were able to depict a complete and homogeneous fill-in. Conclusion: Radiologist should be aware that centrifugal (inside-out) appearance on contrast-enhanced sonography is a rare but possible feature of liver hemangioma.

  5. The application of T1 and T2 relaxation time and magnetization transfer ratios to the early diagnosis of patellar cartilage osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Weiwu; Qu, Nan; Lu, Zhihua; Yang, Shixun [Shanghai Jiaotong University, Department of Radiology, Shanghai (China)

    2009-11-15

    We compare the T1 and T2 relaxation times and magnetization transfer ratios (MTRs) of normal subjects and patients with osteoarthritis (OA) to evaluate the ability of these techniques to aid in the early diagnosis and treatment of OA. The knee joints in 11 normal volunteers and 40 patients with OA were prospectively evaluated using T1 relaxation times as measured using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), T2 relaxation times (multiple spin-echo sequence, T2 mapping), and MTRs. The OA patients were further categorized into mild, moderate, and severe OA. The mean T1 relaxation times of the four groups (normal, mild OA, moderate OA, and severe OA) were: 487.3{+-}27.7, 458.0{+-}55.9, 405.9{+-}57.3, and 357.9{+-}36.7 respectively (p<0.001). The mean T2 relaxation times of the four groups were: 37.8{+-}3.3, 44.0{+-}8.5, 50.9{+-}9.5, and 57.4{+-}4.8 respectively (p<0.001). T1 relaxation time decreased and T2 relaxation time increased with worsening degeneration of patellar cartilage. The result of the covariance analysis showed that the covariate age had a significant influence on T2 relaxation time (p<0.001). No significant differences between the normal and OA groups using MTR were noted. T1 and T2 relaxation times are relatively sensitive to early degenerative changes in the patellar cartilage, whereas the MTR may have some limitations with regard to early detection of OA. In addition, The T1 and T2 relaxation times negatively correlate with each other, which is a novel finding. (orig.)

  6. Four Steps for Becoming Familiar with Early Music Standards

    Science.gov (United States)

    Kim, Jinyoung; Robinson, Helen Mele

    2010-01-01

    Music has a profound impact on children's lives, yet it is often overlooked in early childhood classrooms. Music instruction enhances children's spatial-temporal reasoning skills--skills that are crucial to learning math and science. For children who received formal music lessons, there was a positive long-lasting correlation with IQ and academic…

  7. Characterization of the onset of embryonic control and early development in the bovine embryo

    International Nuclear Information System (INIS)

    Barnes, F.L.

    1988-01-01

    Bovine embryos were used to determine if morphological and molecular features of early development are similar to in vivo recovered bovine embryos and to determine at what level early bovine development is regulated. Radiolabeling of IVP embryos and in vivo recovered embryos with 35 S-methionine for SDS-polyacrylamide gel electrophoresis reveals that these embryos are equivalent. Few differences in protein profiles are observed between 1- and early 4-cell embryos. A change in protein profiles begins at the mid 4-cell stage and continues into the 8-cell stage. Few differences in protein profiles are observed between 1- and early 4-cell embryos. A change in protein profiles begins at the mid 4-cell stage and continues into the 8-cell stage. Few differences in protein profiles are observed between late 8-cells and morulae. This transition is α-amanitin sensitive therefore due to de novo embryonic transcription. Embryonic transcription is partially responsible for terminating the post-transcriptionally regulated period of early bovine development. Argentophillic nucleolar organizing regions (Ag-NORs) indicate onset of nucleolar activation. Ag-NORs were absent in 2- and 4-cell IVP embryos and rarely occurred in 8-cell IVP embryos cultured in vitro. IVP 1- and 2-cell embryos cultured to blastocysts in sheep oviducts demonstrated Ag-NORs. Thus the lack of nucleolar activation of IVP embryos cultured in vitro is culture induced between the 2- and 8-cell stage

  8. An 8-Week Ketogenic Low Carbohydrate, High Fat Diet Enhanced Exhaustive Exercise Capacity in Mice.

    Science.gov (United States)

    Ma, Sihui; Huang, Qingyi; Yada, Koichi; Liu, Chunhong; Suzuki, Katsuhiko

    2018-05-25

    Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD) is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.

  9. An 8-Week Ketogenic Low Carbohydrate, High Fat Diet Enhanced Exhaustive Exercise Capacity in Mice

    Directory of Open Access Journals (Sweden)

    Sihui Ma

    2018-05-01

    Full Text Available Current fueling tactics for endurance exercise encourage athletes to ingest a high carbohydrate diet. However, athletes are not generally encouraged to use fat, the largest energy reserve in the human body. A low carbohydrate, high fat ketogenic diet (KD is a nutritional approach ensuring that the body utilizes lipids. Although KD has been associated with weight-loss, enhanced fat utilization in muscle and other beneficial effects, there is currently no clear proof whether it could lead to performance advantage. To evaluate the effects of KD on endurance exercise capacity, we studied the performance of mice subjected to a running model after consuming KD for eight weeks. Weight dropped dramatically in KD-feeding mice, even though they ate more calories. KD-feeding mice showed enhanced running time without aggravated muscle injury. Blood biochemistry and correlation analysis indicated the potential mechanism is likely to be a keto-adaptation enhanced capacity to transport and metabolize fat. KD also showed a potential preventive effect on organ injury caused by acute exercise, although KD failed to exert protection from muscle injury. Ultimately, KD may contribute to prolonged exercise capacity.

  10. Cucurbit[8]uril templated supramolecular ring structure formation and protein assembly modulation

    NARCIS (Netherlands)

    Ramaekers, M.; Wijnands, S.P.W.; van Dongen, J.L.J.; Brunsveld, L.; Dankers, P.Y.W.

    2015-01-01

    The interplay of Phe-Gly-Gly (FGG)-tagged proteins and bivalent FGG-tagged penta(ethylene glycol) as guest molecules with cucurbit[8]uril (Q8) hosts is studied to modulate the supramolecular assembly process. Ring structure formation of the bivalent guest molecule with Q8 leads to enhanced binding

  11. Enhanced Recovery Pathways for Improving Outcomes After Minimally Invasive Gynecologic Oncology Surgery.

    Science.gov (United States)

    Chapman, Jocelyn S; Roddy, Erika; Ueda, Stefanie; Brooks, Rebecca; Chen, Lee-Lynn; Chen, Lee-May

    2016-07-01

    To estimate whether an enhanced recovery after surgery pathway facilitates early recovery and discharge in gynecologic oncology patients undergoing minimally invasive surgery. This was a retrospective case-control study. Consecutive gynecologic oncology patients undergoing laparoscopic or robotic surgery between July 1 and November 5, 2014, were treated on an enhanced recovery pathway. Enhanced recovery pathway components included patient education, multimodal analgesia, opioid minimization, nausea prophylaxis as well as early catheter removal, ambulation, and feeding. Cases were matched in a one-to-two ratio with historical control patients on the basis of surgery type and age. Primary endpoints were length of hospital stay, rates of discharge by noon, 30-day hospital readmission rates, and hospital costs. There were 165 patients included in the final cohort, 55 of whom were enhanced recovery pathway patients. Enhanced recovery patients were more likely to be discharged on postoperative day 1 compared with patients in the control group (91% compared with 60%, Pcontrol patients (P=.03). Postoperative pain scores decreased (2.6 compared with 3.12, P=.03) despite a 30% reduction in opioid use. Average total hospital costs were decreased by 12% in the enhanced recovery group ($13,771 compared with $15,649, P=.01). Readmission rates, mortality, and reoperation rates did not differ between the two groups. An enhanced recovery pathway in patients undergoing gynecologic oncology minimally invasive surgery is associated with significant improvements in recovery time, decreased pain despite reduced opioid use, and overall lower hospital costs.

  12. Resolution enhancement techniques in microscopy

    Science.gov (United States)

    Cremer, Christoph; Masters, Barry R.

    2013-05-01

    We survey the history of resolution enhancement techniques in microscopy and their impact on current research in biomedicine. Often these techniques are labeled superresolution, or enhanced resolution microscopy, or light-optical nanoscopy. First, we introduce the development of diffraction theory in its relation to enhanced resolution; then we explore the foundations of resolution as expounded by the astronomers and the physicists and describe the conditions for which they apply. Then we elucidate Ernst Abbe's theory of optical formation in the microscope, and its experimental verification and dissemination to the world wide microscope communities. Second, we describe and compare the early techniques that can enhance the resolution of the microscope. Third, we present the historical development of various techniques that substantially enhance the optical resolution of the light microscope. These enhanced resolution techniques in their modern form constitute an active area of research with seminal applications in biology and medicine. Our historical survey of the field of resolution enhancement uncovers many examples of reinvention, rediscovery, and independent invention and development of similar proposals, concepts, techniques, and instruments. Attribution of credit is therefore confounded by the fact that for understandable reasons authors stress the achievements from their own research groups and sometimes obfuscate their contributions and the prior art of others. In some cases, attribution of credit is also made more complex by the fact that long term developments are difficult to allocate to a specific individual because of the many mutual connections often existing between sometimes fiercely competing, sometimes strongly collaborating groups. Since applications in biology and medicine have been a major driving force in the development of resolution enhancing approaches, we focus on the contribution of enhanced resolution to these fields.

  13. High Speed PAM -8 Optical Interconnects with Digital Equalization based on Neural Network

    DEFF Research Database (Denmark)

    Gaiarin, Simone; Pang, Xiaodan; Ozolins, Oskars

    2016-01-01

    We experimentally evaluate a high-speed optical interconnection link with neural network equalization. Enhanced equalization performances are shown comparing to standard linear FFE for an EML-based 32 GBd PAM-8 signal after 4-km SMF transmission.......We experimentally evaluate a high-speed optical interconnection link with neural network equalization. Enhanced equalization performances are shown comparing to standard linear FFE for an EML-based 32 GBd PAM-8 signal after 4-km SMF transmission....

  14. An ecological analysis of the effects of deviant peer clustering on sexual promiscuity, problem behavior, and childbearing from early adolescence to adulthood: an enhancement of the life history framework.

    Science.gov (United States)

    Dishion, Thomas J; Ha, Thao; Véronneau, Marie-Hélène

    2012-05-01

    The authors propose that peer relationships should be included in a life history perspective on adolescent problem behavior. Longitudinal analyses were used to examine deviant peer clustering as the mediating link between attenuated family ties, peer marginalization, and social disadvantage in early adolescence and sexual promiscuity in middle adolescence and childbearing by early adulthood. Specifically, 998 youths, along with their families, were assessed at age 11 years and periodically through age 24 years. Structural equation modeling revealed that the peer-enhanced life history model provided a good fit to the longitudinal data, with deviant peer clustering strongly predicting adolescent sexual promiscuity and other correlated problem behaviors. Sexual promiscuity, as expected, also strongly predicted the number of children by ages 22-24 years. Consistent with a life history perspective, family social disadvantage directly predicted deviant peer clustering and number of children in early adulthood, controlling for all other variables in the model. These data suggest that deviant peer clustering is a core dimension of a fast life history strategy, with strong links to sexual activity and childbearing. The implications of these findings are discussed with respect to the need to integrate an evolutionary-based model of self-organized peer groups in developmental and intervention science.

  15. Mechanical Composite of LiNi0.8Co0.15Al0.05O2/Carbon Nanotubes with Enhanced Electrochemical Performance for Lithium-Ion Batteries

    OpenAIRE

    Zhang, Liping; Fu, Ju; Zhang, Chuhong

    2017-01-01

    LiNi0.8Co0.15Al0.05O2/carbon nanotube (NCA/CNT) composite cathode materials are prepared by a facile mechanical grinding method, without damage to the crystal structure and morphology of the bulk. The NCA/CNT composite exhibits enhanced cycling and rate performance compared with pristine NCA. After 60?cycles at a current?rate?of 0.25 C, the reversible capacity of NCA/CNT composite cathode is 181?mAh/g with a discharge retention rate of 96%, considerably higher than the value of pristine NCA (...

  16. Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

    Science.gov (United States)

    Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

    2017-07-01

    Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

  17. Contrast-enhanced magnetic resonance imaging of pulmonary lesions: Description of a technique aiming clinical practice

    International Nuclear Information System (INIS)

    Koenigkam-Santos, Marcel; Optazaite, Elzbieta; Sommer, Gregor; Safi, Seyer; Heussel, Claus Peter; Kauczor, Hans-Ulrich

    2015-01-01

    To propose a technique for evaluation of pulmonary lesions using contrast-enhanced MRI; to assess morphological patterns of enhancement and correlate quantitative analysis with histopathology. Material and methods: Thirty-six patients were prospectively studied. Volumetric-interpolated T1W images were obtained during consecutive breath holds after bolus triggered contrast injection. Volume coverage of first three acquisitions was limited (higher temporal resolution) and last acquisition obtained at 4th min. Two radiologists individually evaluated the patterns of enhancement. Region-of-interest-based signal intensity (SI)-time curves were created to assess quantitative parameters. Results: Readers agreed moderately to substantially concerning lesions’ enhancement pattern. SI-time curves could be created for all lesions. In comparison to benign, malignant lesions showed higher values of maximum enhancement, early peak, slope and 4th min enhancement. Early peak >15% showed 100% sensitivity to detect malignancy, maximum enhancement >40% showed 100% specificity. Conclusions: The proposed technique is robust, simple to perform and can be applied in clinical scenario. It allows visual evaluation of enhancement pattern/progression together with creation of SI-time curves and assessment of derived quantitative parameters. Perfusion analysis was highly sensitive to detect malignancy, in accordance to what is recommended by most recent guidelines on imaging evaluation of pulmonary lesions

  18. Contrast-enhanced magnetic resonance imaging of pulmonary lesions: Description of a technique aiming clinical practice

    Energy Technology Data Exchange (ETDEWEB)

    Koenigkam-Santos, Marcel, E-mail: marcelk46@yahoo.com.br [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); Radiology Department, German Cancer Research Center (Deutsches Krebsforschungszentrum – DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Department of Radiology, University Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes 3900, Campus Universitario Monte Alegre, 14048 900 Ribeirao Preto, Sao Paulo (Brazil); Optazaite, Elzbieta, E-mail: optazaite@andrulis.eu [Diagnostic and Interventional Radiology with Nuclear Medicine, Chest Clinic (Thoraxklinik), University of Heidelberg, Amalienstraße 5, 69126 Heidelberg (Germany); Sommer, Gregor, E-mail: gregor.sommer@usb.ch [Clinic of Radiology and Nuclear Medicine, University Hospital Basel, Petersgraben 4, CH-4031 Basel (Switzerland); Safi, Seyer, E-mail: seyer.safi@gmail.com [Surgery Department, Chest Clinic (Thoraxklinik), University of Heidelberg, Amalienstraße 5, 69126 Heidelberg (Germany); Heussel, Claus Peter, E-mail: heussel@uni-heidelberg.de [Diagnostic and Interventional Radiology with Nuclear Medicine, Chest Clinic (Thoraxklinik), University of Heidelberg, Amalienstraße 5, 69126 Heidelberg (Germany); Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); Kauczor, Hans-Ulrich, E-mail: hans-ulrich.kauczor@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); and others

    2015-01-15

    To propose a technique for evaluation of pulmonary lesions using contrast-enhanced MRI; to assess morphological patterns of enhancement and correlate quantitative analysis with histopathology. Material and methods: Thirty-six patients were prospectively studied. Volumetric-interpolated T1W images were obtained during consecutive breath holds after bolus triggered contrast injection. Volume coverage of first three acquisitions was limited (higher temporal resolution) and last acquisition obtained at 4th min. Two radiologists individually evaluated the patterns of enhancement. Region-of-interest-based signal intensity (SI)-time curves were created to assess quantitative parameters. Results: Readers agreed moderately to substantially concerning lesions’ enhancement pattern. SI-time curves could be created for all lesions. In comparison to benign, malignant lesions showed higher values of maximum enhancement, early peak, slope and 4th min enhancement. Early peak >15% showed 100% sensitivity to detect malignancy, maximum enhancement >40% showed 100% specificity. Conclusions: The proposed technique is robust, simple to perform and can be applied in clinical scenario. It allows visual evaluation of enhancement pattern/progression together with creation of SI-time curves and assessment of derived quantitative parameters. Perfusion analysis was highly sensitive to detect malignancy, in accordance to what is recommended by most recent guidelines on imaging evaluation of pulmonary lesions.

  19. State of Early Child Development Research, Practice, and Policy for Most Vulnerable Children: A Global Perspective

    Science.gov (United States)

    Young, Mary Eming

    2017-01-01

    Interventions to enhance development of children ages 0-6 have profound benefits for children, families, and societies. The benefits are well documented, recognized internationally, and supportive of policies and programs targeting early child development (ECD). Intervening in the early years is a critical first step toward alleviating poverty,…

  20. Deep Surveying of the Transcriptional and Alternative Splicing Signatures for Decidual CD8+ T Cells at the First Trimester of Human Healthy Pregnancy

    Directory of Open Access Journals (Sweden)

    Weihong Zeng

    2018-05-01

    Full Text Available Decidual CD8+ (dCD8 T cells have been proposed to play important roles in immune protection against the invading pathogens and in tolerance toward the growing semi-allogeneic fetus during early pregnancy. However, their phenotypic and functional characteristics remain poorly defined. Here, we performed the first analysis of the transcriptional and alternative splicing (AS signatures for human first-trimester dCD8 T cells using high-throughput mRNA sequencing. Our data revealed that dCD8 T cells have distinct transcriptional and AS landscapes when compared with their autologous peripheral blood CD8+ (pCD8 T counterparts. Furthermore, human dCD8 T cells were observed to contain CD8-Treg and effector-memory T-cell subsets, and display enhanced functionality in terms of degranulation and cytokine production on a per-cell basis. Additionally, we have identified the novel splice junctions that use a high ratio of the non-canonical splicing motif GC-AG and found that AS is not a major contributor to the gene expression-level changes between paired pCD8 and dCD8 T cells. Together, our findings not only provide a comprehensive framework of the transcriptional and AS landscapes but also reveal the functional feature of human dCD8 T cells, which are of great importance in understanding the biology of these cells and the physiology of human healthy pregnancy.