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Sample records for initiated early alterations

  1. The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation

    Directory of Open Access Journals (Sweden)

    K.A. Sagar

    2015-12-01

    Full Text Available Marijuana (MJ use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n = 24 and late onset (age 16 or later; n = 26, and 34 healthy control participants (HCs. All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth.

  2. Understanding the Early Years (UEY) Initiative

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    Human Resources and Social Development Canada, 2007

    2007-01-01

    Internal Audit Services conducted an Early Implementation Review of the Understanding the Early Years (UEY) Initiative in 2006-07. This review is intended to provide assurance to senior management that program delivery has been established appropriately in order to meet its objectives and highlight any areas that require focused management…

  3. Early detection of chemotherapy-refractory patients by monitoring textural alterations in diffuse optical spectroscopic images

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J., E-mail: Gregory.Czarnota@sunnybrook.ca [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Vorauer, Eric [Department of Medical Physics, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Chin, Lee [Department of Radiation Oncology, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Physics, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Tran, William T. [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Wright, Frances C. [Division of General Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Surgery, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Gandhi, Sonal [Division of Medical Oncology, Sunnybrook Health Sciences Centre, and Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Yaffe, Martin J. [Physical Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario M4N 3M5 (Canada)

    2015-11-15

    Purpose: Changes in textural characteristics of diffuse optical spectroscopic (DOS) functional images, accompanied by alterations in their mean values, are demonstrated here for the first time as early surrogates of ultimate treatment response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC). NAC, as a standard component of treatment for LABC patient, induces measurable heterogeneous changes in tumor metabolism which were evaluated using DOS-based metabolic maps. This study characterizes such inhomogeneous nature of response development, by determining alterations in textural properties of DOS images apparent at early stages of therapy, followed later by gross changes in mean values of these functional metabolic maps. Methods: Twelve LABC patients undergoing NAC were scanned before and at four times after treatment initiation, and tomographic DOS images were reconstructed at each time. Ultimate responses of patients were determined clinically and pathologically, based on a reduction in tumor size and assessment of residual tumor cellularity. The mean-value parameters and textural features were extracted from volumetric DOS images for several functional and metabolic parameters prior to the treatment initiation. Changes in these DOS-based biomarkers were also monitored over the course of treatment. The measured biomarkers were applied to differentiate patient responses noninvasively and compared to clinical and pathologic responses. Results: Responding and nonresponding patients demonstrated different changes in DOS-based textural and mean-value parameters during chemotherapy. Whereas none of the biomarkers measured prior the start of therapy demonstrated a significant difference between the two patient populations, statistically significant differences were observed at week one after treatment initiation using the relative change in contrast/homogeneity of seven functional maps (0.001 < p < 0.049), and mean value of water

  4. Adults with initial metabolic syndrome have altered muscle deoxygenation during incremental exercise.

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    Machado, Alessandro da Costa; Barbosa, Thales Coelho; Kluser Sales, Allan Robson; de Souza, Marcio Nogueira; da Nóbrega, Antonio Claudio Lucas; Silva, Bruno Moreira

    2017-02-01

    Reduced aerobic power is independently associated with metabolic syndrome (MetS) incidence and prevalence in adults. This study investigated whether muscle deoxygenation (proxy of microvascular O 2 extraction) during incremental exercise is altered in MetS and associated with reduced oxygen consumption ( V˙O 2peak ). Twelve men with initial MetS (no overt diseases and medication-naive; mean ± SD, age 38 ± 7 years) and 12 healthy controls (HCs) (34 ± 7 years) completed an incremental cycling test to exhaustion, in which pulmonary ventilation and gas exchange (metabolic analyzer), as well as vastus lateralis deoxygenation (near infrared spectroscopy), were measured. Subjects with MetS, in contrast to HCs, showed lower V˙O 2peak normalized to total lean mass, similar V˙O 2 response to exercise, and earlier break point (BP) in muscle deoxygenation. Consequently, deoxygenation slope from BP to peak exercise was greater. Furthermore, absolute V˙O 2peak was positively associated with BP in correlations adjusted for total lean mass. MetS, without overt diseases, altered kinetics of muscle deoxygenation during incremental exercise, particularly at high-intensity exercise. Therefore, the balance between utilization and delivery of O 2 within skeletal muscle is impaired early in MetS natural history, which may contribute to the reduction in aerobic power. © 2017 The Obesity Society.

  5. Analysis of early initiating event(s) in radiation-induced thymic lymphomagenesis

    International Nuclear Information System (INIS)

    Muto, Masahiro; Ying Chen; Kubo, Eiko; Mita, Kazuei

    1996-01-01

    Since the T cell receptor rearrangement is a sequential process and unique to the progeny of each clone, we investigated the early initiating events in radiation-induced thymic lymphomagenesis by comparing the oncogenic alterations with the pattern of γ T cell receptor (TCR) rearrangements. We reported previously that after leukemogenic irradiation, preneoplastic cells developed, albeit infrequently, from thymic leukemia antigen-2 + (TL-2 + ) thymocytes. Limited numbers of TL-2 + cells from individual irradiated B10.Thy-1.1 mice were injected into B10.Thy-1.2 mice intrathymically, and the common genetic changes among the donor-type T cell lymphomas were investigated with regard to p53 gene and chromosome aberrations. The results indicated that some mutations in the p53 gene had taken place in these lymphomas, but there was no common mutation among the donor-type lymphomas from individual irradiated mice, suggesting that these mutations were late-occurring events in the process of oncogenesis. On the other hand, there were common chromosome aberrations or translocations such as trisomy 15, t(7F; 10C), t(1A; 13D) or t(6A; XB) among the donor-type lymphomas derived from half of the individual irradiated mice. This indicated that the aberrations/translocations, which occurred in single progenitor cells at the early T cell differentiation either just before or after γ T cell receptor rearrangements, might be important candidates for initiating events. In the donor-type lymphomas from the other half of the individual irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after γ TCR rearrangements. (author)

  6. Early versus late initiation of epidural analgesia for labour.

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    Sng, Ban Leong; Leong, Wan Ling; Zeng, Yanzhi; Siddiqui, Fahad Javaid; Assam, Pryseley N; Lim, Yvonne; Chan, Edwin S Y; Sia, Alex T

    2014-10-09

    Pain during childbirth is arguably the most severe pain some women may experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour. Many women have concerns regarding its safety. Furthermore, epidural services and anaesthetic support may not be available consistently across all centres. Observational data suggest that early initiation of epidural may be associated with an increased risk of caesarean section, but the same findings were not seen in recent randomised controlled trials. More recent guidelines suggest that in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labour. The choice of analgesic technique, agent, and dosage is based on many factors, including patient preference, medical status, and contraindications. There is no systematically reviewed evidence on the maternal and foetal outcomes and safety of this practice. This systematic review aimed to summarise the effectiveness and safety of early initiation versus late initiation of epidural analgesia in women. We considered the obstetric and fetal outcomes relevant to women and side effects of the treatments, including risk of caesarean section, instrumental birth and time to birth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 February 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (January 1966 to February 2014), Embase (January 1980 to February 2014) and reference lists of retrieved studies. We included all randomised controlled trials involving women undergoing epidural labour analgesia that compared early initiation versus late initiation of epidural labour analgesia. Two review authors independently assessed trials for inclusion, extracted the data and assessed the trial quality. Data were checked for accuracy. We included nine studies with a total of 15,752 women.The overall risk of bias of

  7. Early Sex Work Initiation and Violence against Female Sex Workers in Mombasa, Kenya.

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    Parcesepe, Angela M; L'Engle, Kelly L; Martin, Sandra L; Green, Sherri; Suchindran, Chirayath; Mwarogo, Peter

    2016-12-01

    Between 20 and 40 % of female sex workers (FSWs) began sex work before age 18. Little is known concerning whether early initiation of sex work impacts later experiences in adulthood, including violence victimization. This paper examines the relationship between early initiation of sex work and violence victimization during adulthood. The sample included 816 FSWs in Mombasa, Kenya, recruited from HIV prevention drop-in centers who were 18 years or older and moderate-risk drinkers. Early initiation was defined as beginning sex work at 17 or younger. Logistic regression modeled recent violence as a function of early initiation, adjusting for drop-in center, age, education, HIV status, supporting others, and childhood abuse. Twenty percent of the sample reported early initiation of sex work. Although both early initiators and other FSWs reported commonly experiencing recent violence, early initiators were significantly more likely to experience recent physical and sexual violence and verbal abuse from paying partners. Early initiation was not associated with physical or sexual violence from non-paying partners. Many FSWs begin sex work before age 18. Effective interventions focused on preventing this are needed. In addition, interventions are needed to prevent violence against all FSWs, in particular, those who initiated sex work during childhood or adolescence.

  8. CDKL5 alterations lead to early epileptic encephalopathy in both genders.

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    Liang, Jao-Shwann; Shimojima, Keiko; Takayama, Rumiko; Natsume, Jun; Shichiji, Minobu; Hirasawa, Kyoko; Imai, Kaoru; Okanishi, Tohru; Mizuno, Seiji; Okumura, Akihisa; Sugawara, Midori; Ito, Tomoshiro; Ikeda, Hiroko; Takahashi, Yukitoshi; Oguni, Hirokazu; Imai, Katsumi; Osawa, Makiko; Yamamoto, Toshiyuki

    2011-10-01

    Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

  9. Water in the Early Solar System: Infrared Studies of Aqueously Altered and Minimally Processed Asteroids

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    McAdam, Margaret M.

    This thesis investigates connections between low albedo asteroids and carbonaceous chondrite meteorites using spectroscopy. Meteorites and asteroids preserve information about the early solar system including accretion processes and parent body processes active on asteroids at these early times. One process of interest is aqueous alteration. This is the chemical reaction between coaccreted water and silicates producing hydrated minerals. Some carbonaceous chondrites have experienced extensive interactions with water through this process. Since these meteorites and their parent bodies formed close to the beginning of the Solar System, these asteroids and meteorites may provide clues to the distribution, abundance and timing of water in the Solar nebula at these times. Chapter 2 of this thesis investigates the relationships between extensively aqueously altered meteorites and their visible, near and mid-infrared spectral features in a coordinated spectral-mineralogical study. Aqueous alteration is a parent body process where initially accreted anhydrous minerals are converted into hydrated minerals in the presence of coaccreted water. Using samples of meteorites with known bulk properties, it is possible to directly connect changes in mineralogy caused by aqueous alteration with spectral features. Spectral features in the mid-infrared are found to change continuously with increasing amount of hydrated minerals or degree of alteration. Building on this result, the degrees of alteration of asteroids are estimated in a survey of new asteroid data obtained from SOFIA and IRTF as well as archived the Spitzer Space Telescope data. 75 observations of 73 asteroids are analyzed and presented in Chapter 4. Asteroids with hydrated minerals are found throughout the main belt indicating that significant ice must have been present in the disk at the time of carbonaceous asteroid accretion. Finally, some carbonaceous chondrite meteorites preserve amorphous iron-bearing materials

  10. Structural Alterations of the Glomerular Wall And Vessels in Early ...

    African Journals Online (AJOL)

    Structural Alterations of the Glomerular Wall And Vessels in Early Stages of Diabetes Mellitus: Light and Transmission Electron Microscopic Study. ... The second group of 20 (the experimental group) was injected intraperitoneally by a single dose of streptozotocin to induce hyperglycemia. Rats were sacrificed after ten days, ...

  11. Early visual cortex reflects initiation and maintenance of task set

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    Elkhetali, Abdurahman S.; Vaden, Ryan J.; Pool, Sean M.

    2014-01-01

    The human brain is able to process information flexibly, depending on a person's task. The mechanisms underlying this ability to initiate and maintain a task set are not well understood, but they are important for understanding the flexibility of human behavior and developing therapies for disorders involving attention. Here we investigate the differential roles of early visual cortical areas in initiating and maintaining a task set. Using functional Magnetic Resonance Imaging (fMRI), we characterized three different components of task set-related, but trial-independent activity in retinotopically mapped areas of early visual cortex, while human participants performed attention demanding visual or auditory tasks. These trial-independent effects reflected: (1) maintenance of attention over a long duration, (2) orienting to a cue, and (3) initiation of a task set. Participants performed tasks that differed in the modality of stimulus to be attended (auditory or visual) and in whether there was a simultaneous distractor (auditory only, visual only, or simultaneous auditory and visual). We found that patterns of trial-independent activity in early visual areas (V1, V2, V3, hV4) depend on attended modality, but not on stimuli. Further, different early visual areas play distinct roles in the initiation of a task set. In addition, activity associated with maintaining a task set tracks with a participant's behavior. These results show that trial-independent activity in early visual cortex reflects initiation and maintenance of a person's task set. PMID:25485712

  12. Preterm birth and structural brain alterations in early adulthood

    Directory of Open Access Journals (Sweden)

    Chiara Nosarti

    2014-01-01

    Full Text Available Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM and white matter (WM maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks and 43 term-born controls aged 19–20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001. WM volume in posterior corpus

  13. Preterm birth and structural brain alterations in early adulthood

    OpenAIRE

    Nosarti, Chiara; Nam, Kie Woo; Walshe, Muriel; Murray, Robin M.; Cuddy, Marion; Rifkin, Larry; Allin, Matthew P.G.

    2014-01-01

    Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT) birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM) and white matter (WM) maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM) we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks) and 43 term-born controls aged 19–20 years, and their association w...

  14. Genetic alterations in hepatocellular carcinoma: An update

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    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC. PMID:27895396

  15. The Early College High School Initiative: An Overview of Five Evaluation Years

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    Berger, Andrea; Adelman, Nancy; Cole, Susan

    2010-01-01

    In 2002, the Bill & Melinda Gates Foundation started the Early College High School Initiative (ECHSI). Through this initiative, more than 200 Early College Schools (ECSs) opened by fall 2009. All of the schools aim to provide underserved students access to college classes while in high school. This article will provide an overview of the first 6…

  16. Quantification of nanoscale density fluctuations by electron microscopy: probing cellular alterations in early carcinogenesis

    International Nuclear Information System (INIS)

    Pradhan, Prabhakar; Damania, Dhwanil; Turzhitsky, Vladimir; Subramanian, Hariharan; Backman, Vadim; Joshi, Hrushikesh M; Dravid, Vinayak P; Roy, Hemant K; Taflove, Allen

    2011-01-01

    Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed

  17. Alteration of gene expression by alcohol exposure at early neurulation.

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    Zhou, Feng C; Zhao, Qianqian; Liu, Yunlong; Goodlett, Charles R; Liang, Tiebing; McClintick, Jeanette N; Edenberg, Howard J; Li, Lang

    2011-02-21

    We have previously demonstrated that alcohol exposure at early neurulation induces growth retardation, neural tube abnormalities, and alteration of DNA methylation. To explore the global gene expression changes which may underline these developmental defects, microarray analyses were performed in a whole embryo mouse culture model that allows control over alcohol and embryonic variables. Alcohol caused teratogenesis in brain, heart, forelimb, and optic vesicle; a subset of the embryos also showed cranial neural tube defects. In microarray analysis (accession number GSM9545), adopting hypothesis-driven Gene Set Enrichment Analysis (GSEA) informatics and intersection analysis of two independent experiments, we found that there was a collective reduction in expression of neural specification genes (neurogenin, Sox5, Bhlhe22), neural growth factor genes [Igf1, Efemp1, Klf10 (Tieg), and Edil3], and alteration of genes involved in cell growth, apoptosis, histone variants, eye and heart development. There was also a reduction of retinol binding protein 1 (Rbp1), and de novo expression of aldehyde dehydrogenase 1B1 (Aldh1B1). Remarkably, four key hematopoiesis genes (glycophorin A, adducin 2, beta-2 microglobulin, and ceruloplasmin) were absent after alcohol treatment, and histone variant genes were reduced. The down-regulation of the neurospecification and the neurotrophic genes were further confirmed by quantitative RT-PCR. Furthermore, the gene expression profile demonstrated distinct subgroups which corresponded with two distinct alcohol-related neural tube phenotypes: an open (ALC-NTO) and a closed neural tube (ALC-NTC). Further, the epidermal growth factor signaling pathway and histone variants were specifically altered in ALC-NTO, and a greater number of neurotrophic/growth factor genes were down-regulated in the ALC-NTO than in the ALC-NTC embryos. This study revealed a set of genes vulnerable to alcohol exposure and genes that were associated with neural tube

  18. Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

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    Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U; Gruber, Leonhard; Zebeli, Qendrim

    2016-01-01

    A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

  19. Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum

    Science.gov (United States)

    Humer, Elke; Khol-Parisini, Annabella; Metzler-Zebeli, Barbara U.; Gruber, Leonhard; Zebeli, Qendrim

    2016-01-01

    A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous) cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10), medium (n = 8), and high (n = 12) lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows. PMID:27383746

  20. Alterations of the Lipid Metabolome in Dairy Cows Experiencing Excessive Lipolysis Early Postpartum.

    Directory of Open Access Journals (Sweden)

    Elke Humer

    Full Text Available A decrease in insulin sensitivity enhances adipose tissue lipolysis helping early lactation cows counteracting their energy deficit. However, excessive lipolysis poses serious health risks for cows, and its underlying mechanisms are not clearly understood. The present study used targeted ESI-LC-MS/MS-based metabolomics and indirect insulin sensitivity measurements to evaluate metabolic alterations in the serum of dairy cows of various parities experiencing variable lipolysis early postpartum. Thirty (12 primiparous and 18 multiparous cows of Holstein Friesian and Simmental breeds, fed the same diet and kept under the same management conditions, were sampled at d 21 postpartum and classified as low (n = 10, medium (n = 8, and high (n = 12 lipolysis groups, based on serum concentration of nonesterified fatty acids. Overall, excessive lipolysis in the high group came along with impaired estimated insulin sensitivity and characteristic shifts in acylcarnitine, sphingomyelin, phosphatidylcholine and lysophospholipid metabolome profiles compared to the low group. From the detected phosphatidylcholines mainly those with diacyl-residues showed differences among lipolysis groups. Furthermore, more than half of the detected sphingomyelins were increased in cows experiencing high lipomobilization. Additionally, strong differences in serum acylcarnitines were noticed among lipolysis groups. The study suggests an altered serum phospholipidome in dairy cows associated with an increase in certain long-chain sphingomyelins and the progression of disturbed insulin function. In conclusion, the present study revealed 37 key metabolites as part of alterations in the synthesis or breakdown of sphingolipids and phospholipids associated with lowered estimated insulin sensitivity and excessive lipolysis in early-lactating cows.

  1. Outcome of Early Initiation of Peritoneal Dialysis in Patients with End-Stage Renal Failure

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    Oh, Kook-Hwan; Hwang, Young-Hwan; Cho, Jung-Hwa; Kim, Mira; Ju, Kyung Don; Joo, Kwon Wook; Kim, Dong Ki; Kim, Yon Su; Ahn, Curie

    2012-01-01

    Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone. PMID:22323864

  2. Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda

    Directory of Open Access Journals (Sweden)

    Sempa Joseph

    2012-09-01

    Full Text Available Abstract Background Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART at CD4+ T cell (CD4 count below 350 cell/μl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250–350 cell/μl (early versus Methods Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/μl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/μl. All costs and benefits were discounted at 3% annually. Results Treatment delay varied from 6–18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33–3.10 disability adjusted life years (DALY’s per patient. Lifetime treatment costs were $4,300–$5,248 for early initiation and $3,940–$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260–$270. Conclusions In HIV-positive patients presenting with CD4 count between 250-350 cells/μl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.

  3. Improving early detection initiatives: a qualitative study exploring perspectives of older people and professionals.

    Science.gov (United States)

    Lette, Manon; Stoop, Annerieke; Lemmens, Lidwien C; Buist, Yvette; Baan, Caroline A; de Bruin, Simone R

    2017-06-23

    A wide range of initiatives on early detection and intervention have been developed to proactively identify problems related to health and wellbeing in (frail) older people, with the aim of supporting them to live independently for as long as possible. Nevertheless, it remains unclear what the best way is to design such initiatives and how older people's needs and preferences can be best addressed. This study aimed to address this gap in the literature by exploring: 1) older people's perspectives on health and living environment in relation to living independently at home; 2) older people's needs and preferences in relation to initiating and receiving care and support; and 3) professionals' views on what would be necessary to enable the alignment of early detection initiatives with older people's own needs and preferences. In this qualitative study, we conducted semi-structured interviews with 36 older people and 19 professionals in proactive elderly care. Data were analysed using the framework analysis method. From the interviews with older people important themes in relation to health and living environment emerged, such as maintaining independence, appropriate housing, social relationships, a supporting network and a sense of purpose and autonomy. Older people preferred to remain self-sufficient, and they would rather not ask for help for psychological or social problems. However, the interviews also highlighted that they were not always able or willing to anticipate future needs, which can hinder early detection or early intervention. At the same time, professionals indicated that older people tend to over-estimate their self-reliance and therefore advocated for early detection and intervention, including social and psychological issues. Older people have a broad range of needs in different domains of life. Discrepancies exist between older people and professionals with regard to their views on timing and scope of early detection initiatives. This study aimed

  4. Early smoking initiation and associated factors among in-school ...

    African Journals Online (AJOL)

    Objective: This report examines the prevalence and common correlates of early smoking initiation among male and female school children across seven African countries. Method: The total sample included 17,725 school children aged 13 to 15 years from nationally representative samples in seven African countries.

  5. Early-Life Persistent Vitamin D Deficiency Alters Cardiopulmonary Responses to Particulate Matter-Enhanced Atmospheric Smog in Adult Mice

    Science.gov (United States)

    This study demonstrates that early-life persistent vitamin D deficiency alters the cardiopulmonary response to smog in mice and may increase risk of adverse effects. Early life nutritional deficiencies can lead to increased cardiovascular susceptibility to environme...

  6. Accuracy of the initial diagnosis among patients with an acutely altered mental status

    OpenAIRE

    Sporer, KA; Solares, M; Edward, JD; Wang, W; Alan, HBW; Robert, MR

    2013-01-01

    Objectives: The objectives of this prospective observational study were to: (1) determine the accuracy of physician diagnosis in patients with an acutely altered mental status (AMS) within the first 20 min of emergency department (ED) presentation; and (2) access if physician confidence in early diagnosis correlates with accuracy of diagnosis. Methods: A prospective observational convenience study was conducted of 112 adult patients who presented to an urban county ED with AMS (Glasgow Coma S...

  7. Early smoking initiation, sexual behavior and reproductive health - a large population-based study of Nordic women

    DEFF Research Database (Denmark)

    Hansen, Bo Terning; Kjaer, Susanne Krüger; Plum, Christian Edinger Munk

    2010-01-01

    To investigate associations between early smoking initiation, risk-taking behavior and reproductive health.......To investigate associations between early smoking initiation, risk-taking behavior and reproductive health....

  8. Early Microbes Modify Immune System Development and Metabolic Homeostasis-The "Restaurant" Hypothesis Revisited.

    Science.gov (United States)

    Nash, Michael J; Frank, Daniel N; Friedman, Jacob E

    2017-01-01

    The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the "Restaurant" hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate's gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.

  9. Label-free Raman spectroscopy provides early determination and precise localization of breast cancer-colonized bone alterations.

    Science.gov (United States)

    Zhang, Chi; Winnard, Paul T; Dasari, Sidarth; Kominsky, Scott L; Doucet, Michele; Jayaraman, Swaathi; Raman, Venu; Barman, Ishan

    2018-01-21

    Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones - significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer.

  10. Early Microbes Modify Immune System Development and Metabolic Homeostasis—The “Restaurant” Hypothesis Revisited

    Science.gov (United States)

    Nash, Michael J.; Frank, Daniel N.; Friedman, Jacob E.

    2017-01-01

    The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research. PMID:29326657

  11. Early Childhood Depression and Alterations in the Trajectory of Gray Matter Maturation in Middle Childhood and Early Adolescence.

    Science.gov (United States)

    Luby, Joan L; Belden, Andy C; Jackson, Joshua J; Lessov-Schlaggar, Christina N; Harms, Michael P; Tillman, Rebecca; Botteron, Kelly; Whalen, Diana; Barch, Deanna M

    2016-01-01

    The trajectory of cortical gray matter development in childhood has been characterized by early neurogenesis and volume increase, peaking at puberty followed by selective elimination and myelination, resulting in volume loss and thinning. This inverted U-shaped trajectory, as well as cortical thickness, has been associated with cognitive and emotional function. Synaptic pruning-based volume decline has been related to experience-dependent plasticity in animals. To date, there have been no data to inform whether and how childhood depression might be associated with this trajectory. To examine the effects of early childhood depression, from the preschool age to the school age period, on cortical gray matter development measured across 3 waves of neuroimaging from late school age to early adolescence. Data were collected in an academic research setting from September 22, 2003, to December 13, 2014, on 193 children aged 3 to 6 years from the St Louis, Missouri, metropolitan area who were observed for up to 11 years in a longitudinal behavioral and neuroimaging study of childhood depression. Multilevel modeling was applied to explore the association between the number of childhood depression symptoms and prior diagnosis of major depressive disorder and the trajectory of gray matter change across 3 scan waves. Data analysis was conducted from October 29, 2014, to September 28, 2015. Volume, thickness, and surface area of cortical gray matter measured using structural magnetic resonance imaging at 3 scan waves. Of the 193 children, 90 had a diagnosis of major depressive disorder; 116 children had 3 full waves of neuroimaging scans. Findings demonstrated marked alterations in cortical gray matter volume loss (slope estimate, -0.93 cm³; 95% CI, -1.75 to -0.10 cm³ per scan wave) and thinning (slope estimate, -0.0044 mm; 95% CI, -0.0077 to -0.0012 mm per scan wave) associated with experiencing an episode of major depressive disorder before the first magnetic resonance

  12. Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.

    Science.gov (United States)

    Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale

    2018-04-01

    To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.

  13. A randomised controlled trial of early initiation of oral feeding after ...

    African Journals Online (AJOL)

    A randomised controlled trial of early initiation of oral feeding after Caesarean ... The outcome measures were rate of ileus symptoms, post operative presence of ... more rapid recovery and expressed their interest in earlier hospital discharge.

  14. Early Microbes Modify Immune System Development and Metabolic Homeostasis—The “Restaurant” Hypothesis Revisited

    Directory of Open Access Journals (Sweden)

    Michael J. Nash

    2017-12-01

    Full Text Available The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD. This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.

  15. Initial Treatment for Nonsyndromic Early-Life Epilepsy: An Unexpected Consensus.

    Science.gov (United States)

    Shellhaas, Renée A; Berg, Anne T; Grinspan, Zachary M; Wusthoff, Courtney J; Millichap, John J; Loddenkemper, Tobias; Coryell, Jason; Saneto, Russell P; Chu, Catherine J; Joshi, Sucheta M; Sullivan, Joseph E; Knupp, Kelly G; Kossoff, Eric H; Keator, Cynthia; Wirrell, Elaine C; Mytinger, John R; Valencia, Ignacio; Massey, Shavonne; Gaillard, William D

    2017-10-01

    There are no evidence-based guidelines on the preferred approach to treating early-life epilepsy. We examined initial therapy selection in a contemporary US cohort of children with newly diagnosed, nonsyndromic, early-life epilepsy (onset before age three years). Seventeen pediatric epilepsy centers participated in a prospective cohort study of children with newly diagnosed epilepsy with onset under 36 months of age. Details regarding demographics, seizure types, and initial medication selections were obtained from medical records. About half of the 495 enrolled children with new-onset, nonsyndromic epilepsy were less than 12 months old at the time of diagnosis (n = 263, 53%) and about half (n = 260, 52%) had epilepsy with focal features. Of 464 who were treated with monotherapy, 95% received one of five drugs: levetiracetam (n = 291, 63%), oxcarbazepine (n = 67, 14%), phenobarbital (n = 57, 12%), topiramate (n = 16, 3.4%), and zonisamide (n = 13, 2.8%). Phenobarbital was prescribed first for 50 of 163 (31%) infants less than six months old versus seven of 300 (2.3%) of children six months or older (P epilepsy presentation (focal, generalized, mixed/uncertain). Between the first and second treatment choices, 367 (74%) of children received levetiracetam within the first year after diagnosis. Without any specific effort, the pediatric epilepsy community has developed an unexpectedly consistent approach to initial treatment selection for early-life epilepsy. This suggests that a standard practice is emerging and could be utilized as a widely acceptable basis of comparison in future drug studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Early maternal alcohol consumption alters hippocampal DNA methylation, gene expression and volume in a mouse model.

    Directory of Open Access Journals (Sweden)

    Heidi Marjonen

    Full Text Available The adverse effects of alcohol consumption during pregnancy are known, but the molecular events that lead to the phenotypic characteristics are unclear. To unravel the molecular mechanisms, we have used a mouse model of gestational ethanol exposure, which is based on maternal ad libitum ingestion of 10% (v/v ethanol for the first 8 days of gestation (GD 0.5-8.5. Early neurulation takes place by the end of this period, which is equivalent to the developmental stage early in the fourth week post-fertilization in human. During this exposure period, dynamic epigenetic reprogramming takes place and the embryo is vulnerable to the effects of environmental factors. Thus, we hypothesize that early ethanol exposure disrupts the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and life-long changes in brain structure and function. Genome-wide analysis of gene expression in the mouse hippocampus revealed altered expression of 23 genes and three miRNAs in ethanol-exposed, adolescent offspring at postnatal day (P 28. We confirmed this result by using two other tissues, where three candidate genes are known to express actively. Interestingly, we found a similar trend of upregulated gene expression in bone marrow and main olfactory epithelium. In addition, we observed altered DNA methylation in the CpG islands upstream of the candidate genes in the hippocampus. Our MRI study revealed asymmetry of brain structures in ethanol-exposed adult offspring (P60: we detected ethanol-induced enlargement of the left hippocampus and decreased volume of the left olfactory bulb. Our study indicates that ethanol exposure in early gestation can cause changes in DNA methylation, gene expression, and brain structure of offspring. Furthermore, the results support our hypothesis of early epigenetic origin of alcohol-induced disorders: changes in gene regulation may have already taken place in embryonic stem cells and therefore can be seen in

  17. Early childhood predictors of age of initiation to use of cannabis: a birth prospective study.

    Science.gov (United States)

    Hayatbakhsh, Reza; Williams, Gail M; Bor, William; Najman, Jake M

    2013-05-01

    Early age of cannabis use predicts subsequent illicit drug abuse and other psychosocial problems. Identification of factors associated with early cannabis use may contribute to the development of preventive interventions. This study aimed to examine the early life predictors of age of initiation to cannabis. Data were from Mater Hospital and University of Queensland Study of Pregnancy, a population-based prospective birth cohort study. Participants were a cohort of 3488 young adults who self-reported frequency and age of onset of cannabis use at the 21 year follow up. Of 3488 young adults, 48.9% (51.8% men and 46.4% women) reported having ever used cannabis. For those who had ever used cannabis, age of onset had mean and median of 15.8 and 16.0 years, respectively. In multivariate analysis child's gender, change in maternal marital status, quality of marital relationship, maternal cigarette smoking and alcohol consumption and maternal depression when the child was 5 years statistically significantly predicted age of initiation to cannabis use. The present study explores the impact of early childhood factors associated with age of onset of cannabis use. It is suggested that the family environment within which children are reared, including factors such as parents' marital circumstances, has a major influence on initiation to cannabis use in adolescence. Research is needed to disentangle the pathways of association between these early life factors and early initiation to use of cannabis. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  18. A Qualitative Study of the Context of Child and Adolescent Substance Use Initiation and Patterns of Use in the First Year for Early and Later Initiators.

    Directory of Open Access Journals (Sweden)

    Sharon Kingston

    Full Text Available Individuals who initiate substance use before high school are at higher risk of negative outcomes. Eighty-six young adults between the ages of 18 and 28 participated in semi-structured qualitative interviews focused on the circumstances surrounding participants' first use of substances and their pattern of use in the year following initiation in order to investigate similarities and differences between early versus later initiators. Initiation and use among early initiators were more likely to be encouraged by poor parental monitoring or active facilitation of use by parents. Early initiators were more likely to report risky patterns of use such as daily use and using alone. The data suggest that interventions targeting this population should focus on improving parental monitoring and decreasing positive parental attitudes toward adolescent substance use and efforts to increase identification and intervention by middle school staff to reach youth from high-risk families.

  19. Initiation of an early-stage plasma during picosecond laser ablation of solids

    International Nuclear Information System (INIS)

    Mao, Samuel S.; Mao, Xianglei; Greif, Ralph; Russo, Richard E.

    2000-01-01

    Picosecond time-resolved images of plasma initiation were recorded during pulsed-laser ablation of metal targets in an air atmosphere. An early-stage plasma was observed to form before the release of a material vapor plume. Close to the target surface, interferometry measurements indicate that the early-stage plasma has an electron number density on the order of 10 20 cm -3 . The longitudinal expansion of the ionization front for this plasma has a velocity 10 9 cm/s, during the laser pulse. In contrast, a material--vapor plume forms approximately 200 ps after the laser pulse, and it moves away from the target at 10 6 cm/s. The experimental observations of the early-stage plasma were simulated by using a theoretical model based on a two-fluids description of laser plasmas. The results indicate that the initiation of the plasma is due to air breakdown assisted by electron emission from the target

  20. Predictors of Cigarette Smoking Initiation in Early, Middle, and Late Adolescence.

    Science.gov (United States)

    O'Loughlin, Jennifer; O'Loughlin, Erin K; Wellman, Robert J; Sylvestre, Marie-Pierre; Dugas, Erika N; Chagnon, Miguel; Dutczak, Hartley; Laguë, Johanne; McGrath, Jennifer J

    2017-09-01

    Little is known about age-related differences in risk factors for cigarette smoking initiation. We identified predictors of initiation in early, middle, and late adolescence from among sociodemographic factors, indicators of smoking in the social environment, psychological characteristics, lifestyle indicators, and perceived need for cigarettes. Data were drawn from a longitudinal study of 1,801 children recruited at age 10-11 years from 29 elementary schools in Montreal, Canada. Multivariable logistic regression within a generalized estimating equations framework was used to identify predictors among never smokers across three 2-year windows: age 11-13 years (n = 1,221); age 13-15 years (n = 737); and age 15-17 years (n = 690). Among the 18 risk factors investigated, two differed across age. Friends' smoking, a strong risk factor in early adolescence (odds ratio [95% confidence interval] = 5.78 [3.90-8.58]), lost potency in late adolescence (1.83 [1.31-2.57]). Depressive symptoms, a risk factor in early and middle adolescence (1.60 [1.26-2.02] and 1.92 [1.45-2.54], respectively), were inversely associated in late adolescence (.76 [.58-1.00]). Sex, TV viewing, and weight-related goals were not associated with initiation at any age. All other factors were significant in two or three age groups. Most risk factors for smoking initiation were stable across age. Tobacco control interventions may be robust for risk factors across age groups and may not need adjustment. At all ages, interventions should focus on eliminating smoking in the social environment and on reducing the availability of tobacco products. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  1. Selective alterations of neurons and circuits related to early memory loss in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    María eLlorens-Martín

    2014-05-01

    Full Text Available A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD. The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC. Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII→dentate gyrus→CA3→CA1 and monosynaptic (ECIII→CA1 circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits.

  2. Correlates of Early versus Later Initiation into Sex Work in Two Mexico–U.S. Border Cities

    Science.gov (United States)

    Loza, Oralia; Strathdee, Steffanie A.; Lozada, Remedios; Staines, Hugo; Ojeda, Victoria D.; Martínez, Gustavo A.; Amaro, Hortensia; Patterson, Thomas L.

    2009-01-01

    Purpose To examine correlates of early initiation into sex work in two Mexico–U.S. border cities. Methods Female sex workers (FSWs) ≥18 years without known HIV infection living in Tijuana and Ciudad Juarez who had recent unprotected sex with clients underwent baseline interviews. Correlates of initiation into sex work before age 18 were identified with logistic regression. Results Of 920 FSWs interviewed in Tijuana (N=474) and Ciudad Juarez (N=446), 9.8% (N=90) were early initiators (<18 years) into sex work. Median age of entry into sex work was 26 years (range: 6–58). After adjusting for age, compared to older initiators, early initiators were more likely to use inhalants (21.1% vs 9.6%, p=0.002), initiate sex work to pay for alcohol (36.7% vs 18.4%, p<.001), report abuse as a child (42.2% vs 18.7%, p<.0001), and they were less likely to be migrants (47.8% vs 62.3%, p=0.02). Factors independently associated with early initiation included inhalant use (adjOR=2.39), initiating sex work to pay for alcohol (adjOR=1.88) and history of child abuse (adjOR=2.92). Factors associated with later initiation included less education (adjOR=0.43 per 5-year increase), migration (adjOR=0.47), and initiating sex work for better pay (adjOR=0.44) or to support children (adjOR=0.03). Conclusions Different pathways for entering sex work are apparent among younger versus older females in the Mexico–U.S. border region. Among girls, interventions are needed to prevent inhalant use and child abuse and to offer coping skills; among older initiators, income-generating strategies, childcare, and services for migrants may help to delay or prevent entry into sex work. PMID:20123256

  3. Initial and follow-up MRI in a case of early diagnosed Reye's syndrome

    International Nuclear Information System (INIS)

    Ozdoba, C.; Pfenninger, J.; Schroth, G.

    1997-01-01

    Early MRI in a case of clinically established Reye's syndrome confirmed CT findings of compressed ventricles and additionally demonstrated signal alterations in the thalamus, mesencephalon and pons. On follow-up MRI the pontine lesion had vanished by 1 week later, while the thalamic lesion persisted for more than 2 months. The patient, however, recovered without neurological sequelae. (orig.). With 3 figs

  4. Timing of First Antenatal Care (ANC) and Inequalities in Early Initiation of ANC in Nepal.

    Science.gov (United States)

    Paudel, Yuba Raj; Jha, Trishna; Mehata, Suresh

    2017-01-01

    The provision and uptake of quality and timely antenatal care (ANC) is an essential element of efforts to improve health outcomes for women and newborn babies. Antenatal consultations assist in early identification and treatment of complications during pregnancy. This study aimed to provide an information on distribution and inequalities in early initiation of ANC in Nepal. The distribution and inequalities in the early initiation of ANC were examined using Nepal Demographic and Health Surveys 2011. Bivariate and multivariate logistic regression was used to assess inequalities. Overall, 70% of the women had started their first ANC at 4 month or earlier. Among participants who had never attended school, just more than half (52%) received first ANC at 4 months or earlier, while majority of participants (97%) who had received higher education received first ANC at recommended time. Similarly, 89% of those from richest quintile and 48% of those from poorest quintile received first ANC at recommended time. In adjusted analysis, women from richest wealth quintile were significantly more likely to initiate ANC early (AOR: 3.74, 95% CI: 2.31-6.05) compared to the poorest. Similarly, women with higher level education were significantly more likely (AOR: 11.40, 95% CI: 5.05-25.73) to initiate ANC early compared to women who had never attended school. A significantly lower odds of early ANC take up was observed among madhesi other caste (AOR: 0.56, 95% CI: 0.35-0.90) compared to brahmin/chhetri women. Women whose pregnancy was unwanted were significantly less likely to attend first ANC at 4 months or early (AOR: 0.73, 95% CI: 0.58-0.93) in comparison to women whose pregnancy was wanted. The differences in the recommended timing of initiation of ANC were evident among women with different educational, economic levels, and caste/ethnic groups. Rural women were less likely to have checkups as per guidelines. The findings suggest to a need of interventions to raise female

  5. Timing of First Antenatal Care (ANC and Inequalities in Early Initiation of ANC in Nepal

    Directory of Open Access Journals (Sweden)

    Yuba Raj Paudel

    2017-09-01

    Full Text Available BackgroundThe provision and uptake of quality and timely antenatal care (ANC is an essential element of efforts to improve health outcomes for women and newborn babies. Antenatal consultations assist in early identification and treatment of complications during pregnancy. This study aimed to provide an information on distribution and inequalities in early initiation of ANC in Nepal.MethodsThe distribution and inequalities in the early initiation of ANC were examined using Nepal Demographic and Health Surveys 2011. Bivariate and multivariate logistic regression was used to assess inequalities.FindingsOverall, 70% of the women had started their first ANC at 4 month or earlier. Among participants who had never attended school, just more than half (52% received first ANC at 4 months or earlier, while majority of participants (97% who had received higher education received first ANC at recommended time. Similarly, 89% of those from richest quintile and 48% of those from poorest quintile received first ANC at recommended time. In adjusted analysis, women from richest wealth quintile were significantly more likely to initiate ANC early (AOR: 3.74, 95% CI: 2.31–6.05 compared to the poorest. Similarly, women with higher level education were significantly more likely (AOR: 11.40, 95% CI: 5.05–25.73 to initiate ANC early compared to women who had never attended school. A significantly lower odds of early ANC take up was observed among madhesi other caste (AOR: 0.56, 95% CI: 0.35–0.90 compared to brahmin/chhetri women. Women whose pregnancy was unwanted were significantly less likely to attend first ANC at 4 months or early (AOR: 0.73, 95% CI: 0.58–0.93 in comparison to women whose pregnancy was wanted.ConclusionThe differences in the recommended timing of initiation of ANC were evident among women with different educational, economic levels, and caste/ethnic groups. Rural women were less likely to have checkups as per guidelines. The findings

  6. The importance of skin-to-skin contact for early initiation of breastfeeding in Nigeria and Bangladesh.

    Science.gov (United States)

    Singh, Kavita; Khan, Shane M; Carvajal-Aguirre, Liliana; Brodish, Paul; Amouzou, Agbessi; Moran, Allisyn

    2017-12-01

    Skin-to-skin contact (SSC) between mother and newborn offers numerous protective effects, however it is an intervention that has been under-utilized. Our objectives are to understand which newborns in Bangladesh and Nigeria receive SSC and whether SSC is associated with the early initiation of breastfeeding. Demographic and Health Survey (DHS) data were used to study the characteristics of newborns receiving SSC for non-facility births in Nigeria (DHS 2013) and for both facility and non-facility births in Bangladesh (DHS 2014). Multivariable logistic regression was used to study the association between SSC and early initiation of breastfeeding after controlling for key socio-demographic, maternal and newborn-related factors. Only 10% of newborns in Nigeria and 26% of newborns in Bangladesh received SSC. In the regression models, SSC was significantly associated with the early initiation of breastfeeding in both countries (OR = 1.42, 95% CI 1.15-1.76 for Nigeria; OR = 1.27, 95% CI 1.04-1.55, for Bangladesh). Findings from the regression analysis for Bangladesh revealed that newborns born by Cesarean section had a 67% lower odds of early initiation of breastfeeding than those born by normal delivery (OR = 0.33, 95% CI 0.26-0.43). Also in Bangladesh newborns born in a health facility had a 30% lower odds of early initiation of breastfeeding than those born in non-facility environments (OR = 0.70, 95% CI 0.53-0.92). Early initiation of breastfeeding was significantly associated with parity, urban residence and wealth in Nigeria. Geographic area was significant in the regression analyses for both Bangladesh and Nigeria. Coverage of SSC is very low in the two countries, despite its benefits for newborns without complications. SSC has the potential to save newborn lives. There is a need to prioritize training of health providers on the implementation of essential newborn care including SSC. Community engagement is also needed to ensure that all women and

  7. Early Initiation of Antenatal Care and Factors Associated with Early Antenatal Care Initiation at Health Facilities in Southern Ethiopia

    Directory of Open Access Journals (Sweden)

    Mengesha Boko Geta

    2017-01-01

    Full Text Available Antenatal care (ANC is care given to pregnant mothers to timely identify and mitigate pregnancy related problems that can harm mother or fetus. Most of Ethiopian mothers present late for ANC. The aim of this paper was to assess determinants of early antenatal care initiation among pregnant women. Mothers attending Shebedino District Health Centers for ANC between January 12 and February 18, 2015, were invited to the study. Multistage sampling technique and structured questionnaire were used to collect data by trained data collectors. Univariate and bivariate analysis were conducted to study the association between explanatory and outcome variable. Out of 608 women, 132 [21.71%] had their first ANC within the recommended time [before or at 3 months]. Media access [AOR = 2.11 95% CI 1.00, 3.22], knowledge about the correct time of ANC booking [AOR = 4.49 95% CI 2.47, 6.16], and having been advised to book within 12 weeks [AOR = 4.14 95% CI 3.80, 5.21] were determinants of first-trimester booking. Health professionals and care providers should provide full information, advice, and appropriate care about early ANC for every eligible mother.

  8. Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats.

    Science.gov (United States)

    Sofronova, Svetlana I; Gaynullina, Dina K; Shvetsova, Anastasia A; Borzykh, Anna A; Selivanova, Ekaterina K; Kostyunina, Daria S; Sharova, Anna P; Martyanov, Andrey A; Tarasova, Olga S

    2017-11-01

    The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α 1 -adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. © 2017 Society for Endocrinology.

  9. Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

    Science.gov (United States)

    Grégoire, Laurent; Caparos, Serge; Leblanc, Carole-Anne; Brisson, Benoit; Blanchette, Isabelle

    2018-01-01

    This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD) and no abuse participants. We focused particularly on an early wave (C1/P1), the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms) of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD) suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology. PMID:29379428

  10. Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

    Directory of Open Access Journals (Sweden)

    Laurent Grégoire

    2018-01-01

    Full Text Available This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD and no abuse participants. We focused particularly on an early wave (C1/P1, the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology.

  11. Sucrose exposure in early life alters adult motivation and weight gain.

    Directory of Open Access Journals (Sweden)

    Cristianne R M Frazier

    2008-09-01

    Full Text Available The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.

  12. Sucrose exposure in early life alters adult motivation and weight gain.

    Science.gov (United States)

    Frazier, Cristianne R M; Mason, Peggy; Zhuang, Xiaoxi; Beeler, Jeff A

    2008-09-17

    The cause of the current increase in obesity in westernized nations is poorly understood but is frequently attributed to a 'thrifty genotype,' an evolutionary predisposition to store calories in times of plenty to protect against future scarcity. In modern, industrialized environments that provide a ready, uninterrupted supply of energy-rich foods at low cost, this genetic predisposition is hypothesized to lead to obesity. Children are also exposed to this 'obesogenic' environment; however, whether such early dietary experience has developmental effects and contributes to adult vulnerability to obesity is unknown. Using mice, we tested the hypothesis that dietary experience during childhood and adolescence affects adult obesity risk. We gave mice unlimited or no access to sucrose for a short period post-weaning and measured sucrose-seeking, food consumption, and weight gain in adulthood. Unlimited access to sucrose early in life reduced sucrose-seeking when work was required to obtain it. When high-sugar/high-fat dietary options were made freely-available, however, the sucrose-exposed mice gained more weight than mice without early sucrose exposure. These results suggest that early, unlimited exposure to sucrose reduces motivation to acquire sucrose but promotes weight gain in adulthood when the cost of acquiring palatable, energy dense foods is low. This study demonstrates that early post-weaning experience can modify the expression of a 'thrifty genotype' and alter an adult animal's response to its environment, a finding consistent with evidence of pre- and peri-natal programming of adult obesity risk by maternal nutritional status. Our findings suggest the window for developmental effects of diet may extend into childhood, an observation with potentially important implications for both research and public policy in addressing the rising incidence of obesity.

  13. Intervening to promote early initiation of breastfeeding in the LDR.

    Science.gov (United States)

    Komara, Carol; Simpson, Diana; Teasdale, Carla; Whalen, Gaye; Bell, Shay; Giovanetto, Laurie

    2007-01-01

    To evaluate the effectiveness of an interventional protocol for the early initiation of breastfeeding that would remove barriers in the labor, delivery, recovery (LDR) unit. Descriptive design using 100 postpartum mothers who were interviewed before discharge at a large university hospital in the south-central United States. Descriptive statistics were used for analysis. The protocol was effective for initiating breastfeeding, and breastfeeding increased from 53% to 66%. When barriers to breastfeeding are reduced in the LDR setting, women will breastfeed. It is possible that reducing hospital barriers to breastfeeding in the LDR can also set the stage for sustained breastfeeding during hospitalization and for less supplementation with formula.

  14. Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

    Directory of Open Access Journals (Sweden)

    Rubén Díaz-Rúa

    2016-11-01

    Full Text Available Background: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC is a promising tool to identify subjects at risk of developing diet-related diseases. Objective: We analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF and high-protein (HP diets. Design: We administered HF and HP diets (4 months to adult Wistar rats in isocaloric conditions to a control diet, mainly to avoid overweight associated with the intake of hyperlipidic diets and, thus, to be able to characterise markers of metabolically obese normal-weight (MONW syndrome. PBMC samples were collected at different time points of dietary treatment and expression of relevant energy homeostatic genes analysed by real-time reverse transcription-polymerase chain reaction. Serum parameters related with metabolic syndrome, as well as fat deposition in liver, were also analysed. Results: The most outstanding results were those obtained for the expression of the lipolytic gene carnitine palmitoyltransferase 1a (Cpt1a. Cpt1a expression in PBMC increased after only 1 month of exposure to both unbalanced diets, and this increased expression was maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a expression was altered even in the absence of increased body weight but correlated with alterations such as higher insulin resistance, alteration of serum lipid profile and, particularly, increased fat deposition in liver, a feature characteristic of metabolic syndrome, which was even observed in animals fed with HP diet. Conclusions: We propose Cpt1a gene expression analysis in PBMC as an early biomarker of metabolic alterations associated with MONW phenotype due to the intake of isocaloric HF diets, as

  15. Statewide Quality Improvement Initiative to Reduce Early Elective Deliveries and Improve Birth Registry Accuracy.

    Science.gov (United States)

    Kaplan, Heather C; King, Eileen; White, Beth E; Ford, Susan E; Fuller, Sandra; Krew, Michael A; Marcotte, Michael P; Iams, Jay D; Bailit, Jennifer L; Bouchard, Jo M; Friar, Kelly; Lannon, Carole M

    2018-04-01

    To evaluate the success of a quality improvement initiative to reduce early elective deliveries at less than 39 weeks of gestation and improve birth registry data accuracy rapidly and at scale in Ohio. Between February 2013 and March 2014, participating hospitals were involved in a quality improvement initiative to reduce early elective deliveries at less than 39 weeks of gestation and improve birth registry data. This initiative was designed as a learning collaborative model (group webinars and a single face-to-face meeting) and included individual quality improvement coaching. It was implemented using a stepped wedge design with hospitals divided into three balanced groups (waves) participating in the initiative sequentially. Birth registry data were used to assess hospital rates of nonmedically indicated inductions at less than 39 weeks of gestation. Comparisons were made between groups participating and those not participating in the initiative at two time points. To measure birth registry accuracy, hospitals conducted monthly audits comparing birth registry data with the medical record. Associations were assessed using generalized linear repeated measures models accounting for time effects. Seventy of 72 (97%) eligible hospitals participated. Based on birth registry data, nonmedically indicated inductions at less than 39 weeks of gestation declined in all groups with implementation (wave 1: 6.2-3.2%, Pinitiative, they saw significant decreases in rates of early elective deliveries as compared with wave 3 (control; P=.018). All waves had significant improvement in birth registry accuracy (wave 1: 80-90%, P=.017; wave 2: 80-100%, P=.002; wave 3: 75-100%, Pinitiative enabled statewide spread of change strategies to decrease early elective deliveries and improve birth registry accuracy over 14 months and could be used for rapid dissemination of other evidence-based obstetric care practices across states or hospital systems.

  16. Early evaluation of renal hemodynamic alterations in type I diabetes mellitus with duplex ultrasound

    Directory of Open Access Journals (Sweden)

    Saif Aasem

    2010-01-01

    Full Text Available To evaluate the role of renal duplex ultrasonography in the detection of early alte-ration of renal blood flow in type I diabetic patients, we studied with duplex ultrasound 32 patients with type I diabetes mellitus (19 males, 13 females, age range 8-19 years and 35 age and sex-matched controls. The resistivity indices (RIs and pulsatility indices (PIs of the main renal as well as intra-renal arteries were calculated. Compared with the healthy control subjects, diabetic patients had significantly higher resistivity indices (RIs in the intrarenal (segmental, arcuate and interlobar ar-teries (P= 0.001. The study, also revealed a significantly positive correlation between the RIs in the intrarenal arteries in diabetics and the albumin/creatinine ratio (r= 0.54, 0.52 and 0.51 respectively, glycated hemoglobin (r= 0.61, 0.59 and 0.63 respectively, as well as the estimated GFR (e-GFR (r= 0.53, 0.51 and 0.57 respectively. We conclude that the current study documented early intra-renal hemodynamic alterations in the form of pathologically elevated intrarenal RIs. This denotes the potential usefulness of duplex evaluation of the intrarenal arteries, as a noninvasive procedure, for monitoring type 1 diabetic patients to predict those at risk of diabetic nephropathy.

  17. Preparing beginning reading teachers: An experimental comparison of initial early literacy field experiences

    OpenAIRE

    Al Otaiba, Stephanie; Lake, Vickie E.; Greulich, Luana; Folsom, Jessica S.; Guidry, Lisa

    2012-01-01

    This randomized-control trial examined the learning of preservice teachers taking an initial Early Literacy course in an early childhood education program and of the kindergarten or first grade students they tutored in their field experience. Preservice teachers were randomly assigned to one of two tutoring programs: Book Buddies and Tutor Assisted Intensive Learning Strategies (TAILS), which provided identical meaning-focused instruction (shared book reading), but differed ...

  18. Early sex work initiation and condom use among alcohol-using female sex workers in Mombasa, Kenya: a cross-sectional analysis.

    Science.gov (United States)

    Parcesepe, Angela M; L'Engle, Kelly L; Martin, Sandra L; Green, Sherri; Suchindran, Chirayath; Mwarogo, Peter

    2016-12-01

    Early initiation of sex work is prevalent among female sex workers (FSWs) worldwide. The objectives of this study were to investigate if early initiation of sex work was associated with: (1) consistent condom use, (2) condom negotiation self-efficacy or (3) condom use norms among alcohol-using FSWs in Mombasa, Kenya. In-person interviews were conducted with 816 FSWs in Mombasa, Kenya. Sample participants were: recruited from HIV prevention drop-in centres, 18 years or older and moderate risk drinkers. Early initiation was defined as first engaging in sex work at 17 years or younger. Logistic regression modelled outcomes as a function of early initiation, adjusting for drop-in centre, years in sex work, supporting others and HIV status. FSWs who initiated sex work early were significantly less likely to report consistent condom use with paying sex partners compared with those who initiated sex work in adulthood. There was no significant difference between groups in consistent condom use with non-paying sex partners. FSWs who initiated sex work early endorsed less condom negotiation self-efficacy with paying sex partners compared with FSWs who did not initiate sex work early. Findings highlight a need for early intervention for at-risk youth and adolescent FSWs, particularly in relation to HIV sexual risk behaviours. Evidence-based interventions for adolescent FSWs or adult FSWs who began sex work in adolescence should be developed, implemented and evaluated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. Altered Natural Killer Cell Subsets in Seropositive Arthralgia and Early Rheumatoid Arthritis Are Associated with Autoantibody Status

    NARCIS (Netherlands)

    Chalan, Paulina; Bijzet, Johan; Kroesen, Bart-Jan; Boots, Annemieke M. H.; Brouwer, Elisabeth

    Objective. The role of natural killer (NK) cells in the immunopathogenesis of rheumatoid arthritis (RA) is unclear. Therefore, numerical and functional alterations of CD56(dim) and CD56(bright) NK cells in the early stages of RA development were studied. Methods. Whole blood samples from newly

  20. Early Substance Use Initiation and Suicide Ideation and Attempts among School-Aged Adolescents in Four Pacific Island Countries in Oceania

    Directory of Open Access Journals (Sweden)

    Karl Peltzer

    2015-09-01

    Full Text Available This study aimed to investigate the correlations between early initiation (<12 years of smoking cigarettes, alcohol use, and drug use (cannabis with suicidal ideation and suicide attempts in school-aged adolescents in four Pacific Island countries in Oceania. The sample included 6540 adolescents (≤13 to ≥16 years old from Kiribati, Samoa, Solomon Islands, and Vanuatu. Bivariate and multivariable analyses were conducted to assess the association between pre-adolescent substance use initiation and suicidal ideation and suicide attempts. Results indicate a prevalence of 25.8% suicidal ideation in the past 12 months (ranging from 17.2% in Vanuatu to 34.7% in Kiribati and 34.9% suicide attempts in the past 12 months (ranging from 23.5% in Vanuatu to 62.0% in Samoa. The prevalence of early cigarette smoking initiation was 15.7%, early alcohol initiation 13.8%, and early drug use initiation was 12.9%. Students who reported pre-adolescent substance use initiation, compared with non-substance users, were more likely reporting suicidal ideation and suicide attempts. The concurrent initiation of cigarette smoking, alcohol, and drug use should be targeted in early prevention programmes in order to prevent possible subsequent suicidal behaviours.

  1. Gray and white matter alterations in early HIV-infected patients: Combined voxel-based morphometry and tract-based spatial statistics.

    Science.gov (United States)

    Wang, Bo; Liu, Zhenyu; Liu, Jiaojiao; Tang, Zhenchao; Li, Hongjun; Tian, Jie

    2016-06-01

    To investigate both the gray matter (GM) and whiter matter (WM) alterations in a homogeneous cohort of early HIV-infected patients by combining voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS). Twenty-six HIV and 26 control subjects enrolled in this study with 3D T1 and diffusion-tensor imaging acquired on a 3.0T Siemens scanner. Group differences in regional GM were assessed using VBM analysis, while differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and relative anisotropy (RD) of WM were evaluated using TBSS analysis. After that, interactions between GM changes and white matter alterations were investigated by using a correlation analysis. The HIV-infected patients displayed decreased GM volume, mainly located in the bilateral frontal cortices, bilateral anterior cingulate cortex, and left supplementary motor area (P 0.05). Our results indicate that structural brain alterations occurred early in HIV-infected patients. The current study may shed further light on the potential brain effects of HIV. J. Magn. Reson. Imaging 2016;43:1474-1483. © 2015 Wiley Periodicals, Inc.

  2. Diethylnitrosamine initiation does not alter clofibric acid-induced hepatocarcinogenesis in the rat.

    Science.gov (United States)

    Michel, Cecile; Desdouets, Chantal; Slaoui, Mohamed; Isaacs, Kevin Robert; Roberts, Ruth Angela; Boitier, Eric

    2007-09-01

    Clofibric acid (CLO) is a nongenotoxic hepatocarcinogen in rodents that causes altered hepatocellular foci and/or neoplasms. Initiation by DNA-damaging agents such as diethylnitrosamine (DEN) accelerates focus and tumor appearance and could therefore significantly contribute to shortening of the regulatory 2-year rodent carcinogenicity bioassays. However, it is crucial to evaluate the histological and molecular impact of initiation with DEN on hepatocarcinogenesis promoted by CLO. Male F344 rats were given a single nonnecrogenic injection of DEN (0 or 30 mg/kg) followed by Control diet or CLO (5000 ppm) in diet for up to 20 months. Histopathology and gene expression profiling were performed in liver tumors and surrounding nontumoral liver tissues. The molecular signature of DEN was characterized and its histopathological and immunohistopathological effects on focus and tumor types were also determined. Although foci and tumors appeared earlier in the DEN+CLO-treated group compared to the group treated with CLO alone, DEN had little impact on gene expression in nontumoral tissues since the gene expression profiles were highly similar between Control and DEN-treated rats, and DEN+CLO- and CLO-treated rats. Finally, tumors obtained from DEN+CLO and CLO-treated groups displayed highly correlated gene expression profiles (r>0.83, independently of the time-point). The pathways involved in tumor development revealed by Gene Ontology functional analysis are similar when driven either by spontaneous initiation or by a chemically induced initiation step. Our work described here may contribute to the design optimization of shorter preclinical tests for the evaluation of the nongenotoxic hepatocarcinogenic potential of drugs under development.

  3. Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting.

    Science.gov (United States)

    Goldenberg, Shira M; Chettiar, Jill; Simo, Annick; Silverman, Jay G; Strathdee, Steffanie A; Montaner, Julio S G; Shannon, Kate

    2014-01-01

    To explore factors associated with early sex work initiation and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Baseline data (2010-2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. SWs completed a questionnaire and HIV/sexually transmitted infection testing. Using multivariate logistic regression, we identified associations with early sex work initiation (prostitution arrests among adult SWs. Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian born [adjusted odds ratio (AOR): 6.8, 95% confidence interval (CI): 2.42 to 19.02], inject drugs (AOR: 1.6, 95% CI: 1.0 to 2.5), and to have worked for a manager (AOR: 2.22, 95% CI: 1.3 to 3.6) or been coerced into sex work (AOR: 2.3, 95% CI: 1.14 to 4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3 to 3.2) and prostitution arrests (AOR: 2.0, 95% CI: 1.3 to 3.2). Adolescent sex work initiation is concentrated among marginalized, drug, and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs.

  4. Microgravity alters protein phosphorylation changes during initiation of sea urchin sperm motility

    Science.gov (United States)

    Tash, J. S.; Bracho, G. E.

    1999-01-01

    European Space Agency (ESA) studies demonstrated that bull sperm swim with higher velocity in microgravity (microG) than at 1 G. Coupling between protein phosphorylation and sperm motility during activation in microG and at 1 G was examined in the ESA Biorack on two space shuttle missions. Immotile sperm were activated to swim (86-90% motility) at launch +20 h by dilution into artificial seawater (ASW). Parallel ground controls were performed 2 h after the flight experiment. Activation after 0, 30, and 60 s was terminated with electrophoresis sample buffer and samples analyzed for phosphoamino acids by Western blotting. Phosphorylation of a 130-kDa phosphothreonine-containing protein (FP130) occurred three to four times faster in microG than at 1 G. A 32-kDa phosphoserine-containing protein was significantly stimulated at 30 s but returned to 1 G control levels at 60 s. The rate of FP130 phosphorylation in microG was attenuated by D2O, suggesting that changes in water properties participate in altering signal transduction. Changes in FP130 phosphorylation triggered by the egg peptide speract were delayed in microG. These results demonstrate that previously observed effects of microG on sperm motility are coupled to changes in phosphorylation of specific flagellar proteins and that early events of sperm activation and fertilization are altered in microG.

  5. Ocean acidification alters early successional coral reef communities and their rates of community metabolism.

    Directory of Open Access Journals (Sweden)

    Sam H C Noonan

    Full Text Available Ocean acidification is expected to alter community composition on coral reefs, but its effects on reef community metabolism are poorly understood. Here we document how early successional benthic coral reef communities change in situ along gradients of carbon dioxide (CO2, and the consequences of these changes on rates of community photosynthesis, respiration, and light and dark calcification. Ninety standardised benthic communities were grown on PVC tiles deployed at two shallow-water volcanic CO2 seeps and two adjacent control sites in Papua New Guinea. Along the CO2 gradient, both the upward facing phototrophic and the downward facing cryptic communities changed in their composition. Under ambient CO2, both communities were dominated by calcifying algae, but with increasing CO2 they were gradually replaced by non-calcifying algae (predominantly green filamentous algae, cyanobacteria and macroalgae, which increased from ~30% to ~80% cover. Responses were weaker in the invertebrate communities, however ascidians and tube-forming polychaetes declined with increasing CO2. Differences in the carbonate chemistry explained a far greater amount of change in communities than differences between the two reefs and successional changes from five to 13 months, suggesting community successions are established early and are under strong chemical control. As pH declined from 8.0 to 7.8, rates of gross photosynthesis and dark respiration of the 13-month old reef communities (upper and cryptic surfaces combined significantly increased by 10% and 20%, respectively, in response to altered community composition. As a consequence, net production remained constant. Light and dark calcification rates both gradually declined by 20%, and low or negative daily net calcification rates were observed at an aragonite saturation state of <2.3. The study demonstrates that ocean acidification as predicted for the end of this century will strongly alter reef communities, and

  6. Parental divorce and initiation of alcohol use in early adolescence.

    Science.gov (United States)

    Jackson, Kristina M; Rogers, Michelle L; Sartor, Carolyn E

    2016-06-01

    Parental divorce/separation is among the most commonly endorsed adverse childhood events. It has been shown to increase subsequent risk of alcohol dependence and problems across adolescence and early adulthood, but its influence on early stages of alcohol involvement has only recently been explored. In the present study, we examined whether time to first full drink was accelerated among youth who experienced parental divorce/separation. To determine specificity of risk, models controlled for perceived stress as well as family history of alcoholism, current parental drinking, and internalizing and externalizing problems. Developmental specificity in terms of timing of both parental divorce and first drink was also examined. Participants were 931 middle-school students (488 girls, 443 boys) who were enrolled in a prospective study on drinking initiation and progression (52% female; 23% non-White, 11% Hispanic). Students indicated whether and at what age they had consumed a full drink of alcohol. Parental divorce/separation was coded from a parent-reported life-events inventory and was grouped based on age experienced (ages 0-5, ages 6-9, age 10+). Cox proportional hazard models showed increased risk for onset of drinking as a function of divorce/separation, even controlling for stress, parental alcohol involvement, and psychopathology. There was no evidence for developmental specificity of the divorce/separation effect based on when it occurred nor in timing of first drink. However, the effect of parental divorce/separation on initiation was magnified at higher levels of parental drinking. Given the rates of parental divorce/separation and its association with increased risk of early drinking, investigation of the mechanisms underlying this link is clearly warranted. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  7. Early sex work initiation independently elevates odds of HIV infection and police arrest among adult sex workers in a Canadian setting

    Science.gov (United States)

    GOLDENBERG, Shira M.; CHETTIAR, Jill; SIMO, Annick; SILVERMAN, Jay G.; STRATHDEE, Steffanie A.; MONTANER, Julio; SHANNON, Kate

    2014-01-01

    Objectives To explore factors associated with early sex work initiation, and model the independent effect of early initiation on HIV infection and prostitution arrests among adult sex workers (SWs). Design Baseline data (2010–2011) were drawn from a cohort of SWs who exchanged sex for money within the last month and were recruited through time-location sampling in Vancouver, Canada. Analyses were restricted to adults ≥18 years old. Methods SWs completed a questionnaire and HIV/STI testing. Using multivariate logistic regression, we identified associations with early sex work initiation (prostitution arrests among adult SWs. Results Of 508 SWs, 193 (38.0%) reported early sex work initiation, with 78.53% primarily street-involved SWs and 21.46% off-street SWs. HIV prevalence was 11.22%, which was 19.69% among early initiates. Early initiates were more likely to be Canadian-born (Adjusted Odds Ratio (AOR): 6.8, 95% Confidence Interval (CI): 2.42–19.02), inject drugs (AOR: 1.6, 95%CI: 1.0–2.5), and to have worked for a manager (AOR: 2.22, 95%CI: 1.3–3.6) or been coerced into sex work (AOR: 2.3, 95%CI: 1.14–4.44). Early initiation retained an independent effect on increased risk of HIV infection (AOR: 2.5, 95% CI: 1.3–3.2) and prostitution arrests (AOR: 2.0, 95%CI: 1.3–3.2). Conclusions Adolescent sex work initiation is concentrated among marginalized, drug and street-involved SWs. Early initiation holds an independent increased effect on HIV infection and criminalization of adult SWs. Findings suggest the need for evidence-based approaches to reduce harm among adult and youth SWs. PMID:23982660

  8. Paediatric early warning scores on a children's ward: a quality improvement initiative.

    LENUS (Irish Health Repository)

    Ennis, Linda

    2014-09-09

    The aim of this quality improvement initiative was to incorporate a paediatric early warning score (PEWS) and track and trigger system in the routine care of children in an acute general children\\'s ward at a regional hospital in the Republic of Ireland. In the absence of a nationally recommended specific PEWS strategy, a local plan was developed. The experience of structuring and implementing the PEWS and track and trigger system is presented in this article. Data from the first year of use were collected to evaluate the clinical utility and effectiveness of this system. In the busy acute children\\'s service, the PEWS initiative was found to benefit processes of early detection, prompt referral and timely, appropriate management of children at potential risk of clinical deterioration. Nursing staff were empowered and supported to communicate concerns immediately and to seek rapid medical review, according to an agreed PEWS escalation plan. Outcomes were significantly improved.

  9. Gender difference in early initiation of methamphetamine use among current methamphetamine users in Muse, Northern Shan State, Myanmar.

    Science.gov (United States)

    Saw, Yu Mon; Saw, Thu Nandar; Yasuoka, Junko; Chan, Nyein; Kham, Nang Pann Ei; Khine, Wint; Cho, Su Myat; Jimba, Masamine

    2017-05-08

    Globally, methamphetamine (MA) use is a significant public health concern due to unprecedented health effects of its use. However, gender similarities and differences in early age of MA initiation and its risk factors among current MA users have been understudied in a developing country setting. A community-based, cross-sectional study was conducted using a computer assisted self-interviewing program from January to March 2013 in Muse, Northern Shan State, Myanmar. A total of 1362 (775 male and 587 female) self-reported current MA users aged between 18 and 35 years were recruited using respondent-driven sampling. Two gender-stratified multiple logistic regression models (models I and II) were done for analysis. For similarities, 73.0% of males and 60.5% of females initiated MA before their 18th birthday. The early age of MA initiation was positively associated with the reasons and places of the first time MA use among both genders. For differences, males [hazard ratio 1.35; 95% confidence interval, 1.18-1.54] had a significantly higher risk than females to initiate MA at earlier age. Among male users, participants who had bisexual/homosexual preferences were more likely to initiate MA use earlier. In contrast, female users who exchanged sex for money and/or drugs were more likely to initiate MA in earlier age. More than 60.0% of male and female participants initiated MA use early; however, males initiated use earlier than females. Although similarities were found among both genders, differences found in key risk factors for early age MA initiation suggest that gender-specific, MA prevention programs are urgently needed in Myanmar.

  10. Improvement of Early Antenatal Care Initiation: The Effects of Training Local Health Volunteers in the Community.

    Science.gov (United States)

    Liabsuetrakul, Tippawan; Oumudee, Nurlisa; Armeeroh, Masuenah; Nima, Niamina; Duerahing, Nurosanah

    2018-01-01

    Although antenatal care (ANC) coverage has been increasing in low- and middle-income countries, the adherence to the ANC initiation standards at gestational age ANC initiation by training the existing local health volunteers (LHVs) in 3 southernmost provinces of Thailand. A clustered nonrandomized intervention study was conducted from November 2012 to February 2014. One district of each province was selected to be the study intervention districts for that province. A total of 124 LHVs in the intervention districts participated in the knowledge-counseling intervention. It was organized as half-day workshop using 2 training modules each comprising a 30-minute lecture followed by counseling practice in pairs for 1 hour. Outcome was the rate of early ANC initiation among women giving birth, and its association with intervention, meeting an LHV, and months after training was analyzed. Of 6677 women, 3178 and 3499 women were in the control and intervention groups, respectively. Rates of early ANC were significantly improved after the intervention (adjusted odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.17-1.43, P ANC. Training LHVs in communities by knowledge-counseling intervention significantly improved early ANC initiation, but the magnitude of change was still limited.

  11. Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

    KAUST Repository

    Diaz-Rua, Ruben

    2016-11-23

    Background: Research on biomarkers that provide early information about the development of future metabolic alterations is an emerging discipline. Gene expression analysis in peripheral blood mononuclear cells (PBMC) is a promising tool to identify subjects at risk of developing diet-related diseases.

  12. Early endocrine alterations reflect prolonged stress and relate to one year functional outcome in patients with severe brain injury

    DEFF Research Database (Denmark)

    Marina, Djordje; Klose, Marianne; Nordenbo, Annette

    2015-01-01

    OBJECTIVE: Severe brain injury poses a risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective was to assess the pattern and prevalence...

  13. Secretory activity and cell cycle alteration of alveolar type II cells in the early and late phase after irradiation

    International Nuclear Information System (INIS)

    Willner, Jochen; Vordermark, Dirk; Schmidt, Michael; Gassel, Andreamaria; Flentje, Michael; Wirtz, Hubert

    2003-01-01

    Purpose: Type II cells and the surfactant system have been proposed to play a central role in pathogenesis of radiation pneumonitis. We analyzed the secretory function and proliferation parameters of alveolar type II cells in the early (until 24 h) and late phase (1-5 weeks) after irradiation (RT) in vitro and in vivo. Methods and Materials: Type II cells were isolated from rats according to the method of Dobbs. Stimulation of secretion was induced with terbutaline, adenosine triphosphate (ATP), and 12-O-tetradecanoylphorbol-13-acetate (TPA) for a 2-h period. Determination of secretion was performed using 3 H-labeled phosphatidylcholine. For the early-phase analysis, freshly isolated and adherent type II cells were irradiated in vitro with 9-21 Gy (stepwise increase of 3 Gy). Secretion stimulation was initiated 1, 6, 24, and 48 h after RT. For late-phase analysis, type II cells were isolated 1-5 weeks after 18 Gy whole lung or sham RT. Each experiment was repeated at least fivefold. Flow cytometry was used to determine cell cycle distribution and proliferating cell nuclear antigen index. Results: During the early-phase (in vitro) analysis, we found a normal stimulation of surfactant secretion in irradiated, as well as unirradiated, cells. No change in basal secretion and no dose effect were seen. During the late phase, 1-5 weeks after whole lung RT, we observed enhanced secretory activity for all secretagogues and a small increase in basal secretion in Weeks 3 and 4 (pneumonitis phase) compared with controls. The total number of isolated type II cells, as well as the rate of viable cells, decreased after the second post-RT week. Cell cycle alterations suggesting an irreversible G 2 /M block occurred in the second post-RT week and did not resolve during the observation period. The proliferating cell nuclear antigen index of type II cells from irradiated rats did not differ from that of controls. Conclusion: In contrast to literature data, we observed no direct

  14. Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism

    Directory of Open Access Journals (Sweden)

    Chomiak Taylor

    2010-08-01

    Full Text Available Abstract Background Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking. Results We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA in vivo. Brain sections obtained from postnatal rat pups treated with VPA in vivo revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour. Conclusions The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.

  15. Early detection of multiple sclerosis: MR findings during the initial manifestations of multiple sclerosis

    International Nuclear Information System (INIS)

    Schoerner, W.; Baum, K.; Henkes, H.; Girke, W.; Felix, R.; Klinikum Rudolf Virchow, Berlin

    1988-01-01

    The MR results in 21 patients showing the initial manifestations of multiple sclerosis (MS) were compared with those in 45 patients with a long history of MS. As in the old cases, MR proved a very sensitive technique during the early manifestations, with abnormal findings in 20 out of 21 patients. The relatively characteristic MR findings in long-standing MS (predominant peri-ventricular involvement with a relatively typical pattern) was seen in the early stages is only rare cases. The value of MR during the initial manifestations of MS is in cases where the clinical findings are not conclusive and laboratory diagnosis (evoked potentials, CSF findings) are indefinite. In these patients the finding of multiple lesions in the brain can confirm the suspected diagnosis of MS. (orig.) [de

  16. Sustainable Professional Learning for Early Childhood Educators: Lessons from an Australia-Wide Mental Health Promotion Initiative

    Science.gov (United States)

    Askell-Williams, Helen; Murray-Harvey, Rosalind

    2016-01-01

    New policy initiatives, such as those concerned with promoting young children's positive mental health, highlight the need for good quality professional education in the early childhood education and care sector. However, although a wealth of literature exists from the school sector, little is known about professional education in early childhood…

  17. Family instability and early initiation of sexual activity in Western Kenya.

    Science.gov (United States)

    Goldberg, Rachel E

    2013-04-01

    Epidemiological, economic, and social forces have produced high levels of volatility in family and household structure for young people growing up in sub-Saharan Africa in recent decades. However, scholarship on the family to date has not examined the influence of this family instability on young people's well-being. The current study employs unique life history calendar data from Western Kenya to investigate the relationship between instability in caregiving and early initiation of sexual activity. It draws on a body of work on parental union instability in the United States, and examines new dimensions of family change. Analyses reveal a positive association between transitions in primary caregiver and the likelihood of early sexual debut that is rapidly manifested following caregiver change and persists for a short period. The association is strongest at early ages, and there is a cumulative effect of multiple caregiver changes. The results highlight the importance of studying family stability in sub-Saharan Africa, as distinct from family structure, and for attention to dimensions such as age and recency.

  18. Starting young: sexual initiation and HIV prevention in early adolescence.

    Science.gov (United States)

    Dixon-Mueller, Ruth

    2009-02-01

    The rising numbers of new HIV infections among young people ages 15-24 in many developing countries, especially among young women, signal an urgent need to identify and respond programmatically to behaviors and situations that contribute to the spread of HIV and other sexually transmitted infections in early adolescence. Quantitative and qualitative studies of the sexual knowledge and practices of adolescents age 14 and younger reveal that substantial numbers of boys and girls in many countries engage in unprotected heterosexual vaginal intercourse--by choice or coercion--before their 15th birthdays. Early initiation into male-male or male-female oral and/or anal sex is also documented in some populations. Educational, health, and social programs must reach 10-14-year-olds as well as older adolescents with the information, skills, services, and supplies (condoms, contraceptives) they need to negotiate their own protection from unwanted and/or unsafe sexual practices and to respect the rights of others.

  19. Differences in Microbiota Membership along the Gastrointestinal Tract of Piglets and Their Differential Alterations Following an Early-Life Antibiotic Intervention

    Directory of Open Access Journals (Sweden)

    Chunlong Mu

    2017-05-01

    Full Text Available Early-life antibiotic interventions can change the predisposition to disease by disturbing the gut microbiota. However, the impact of antibiotics on gut microbiota in the gastrointestinal tract is not completely understood, although antibiotic-induced alterations in the distal gut have been reported. Here, employing a piglet model, the microbial composition was analyzed by high-throughput 16S rRNA gene sequencing and PICRUSt predictions of metagenome function. The present study showed clear spatial variation of microbial communities in the stomach and intestine, and found that the administration of antibiotics (a mixture of olaquindox, oxytetracycline calcium, kitasamycin in early life caused markedly differential alterations in the compartmentalized microbiota, with major alterations in their spatial variation in the lumen of the stomach and small intestine. In piglets fed an antibiotic-free diet, most of the variation in microbial communities was concentrated in gut segments and niches (lumen/mucosa. The microbial diversity was higher in the lumen of stomach and duodenum than that in ileum. The early-life antibiotic intervention decreased the abundance of some Lactobacillus species and increased the abundance of potentially pathogenic Streptococcus suis in the lumen of the stomach and small intestine. Interestingly, the intervention increased the abundance of Treponema only in the colonic lumen and that of Faecalibacterium only in the ileal mucosa. Furthermore, the antibiotic intervention exerted location-specific effects on the functional potential involved in the phosphotransferase system (decreased sucrose phosphotransferase in the stomach and antibiotic-resistance genes (increased in the colon. These results point to an early-life antibiotic-induced dramatic and location-specific shift in the gut microbiota, with profound impact in the foregut and less impact in the hindgut. Collectively, these findings provide new insights into the

  20. Early Caffeine Prophylaxis and Risk of Failure of Initial Continuous Positive Airway Pressure in Very Low Birth Weight Infants.

    Science.gov (United States)

    Patel, Ravi M; Zimmerman, Kanecia; Carlton, David P; Clark, Reese; Benjamin, Daniel K; Smith, P Brian

    2017-11-01

    To test the hypothesis that early caffeine treatment on the day of birth, compared with later treatment in very low birth weight (VLBW, caffeine in the first week of life. We used multivariable conditional logistic regression to compare the risk of CPAP failure, defined as invasive mechanical ventilation or surfactant therapy on DOL 1-6, by timing of caffeine treatment as either early (initiation on DOL 0) or routine (initiation on DOL 1-6). We identified 11 133 infants; 4528 (41%) received early caffeine and 6605 (59%) received routine caffeine. Median gestational age was lower in the early caffeine group, 29 weeks (25th, 75th percentiles; 28, 30) vs the routine caffeine group, 30 weeks (29, 31); P caffeine groups: 22% vs 21%; adjusted OR = 1.05 (95% CI: 0.93, 1.18). Early caffeine treatment on the day of birth was not associated with a decreased risk of CPAP failure in the first week of life for VLBW infants initially treated with CPAP. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Mild myelin disruption elicits early alteration in behavior and proliferation in the subventricular zone.

    Science.gov (United States)

    Gould, Elizabeth A; Busquet, Nicolas; Shepherd, Douglas; Dietz, Robert M; Herson, Paco S; Simoes de Souza, Fabio M; Li, Anan; George, Nicholas M; Restrepo, Diego; Macklin, Wendy B

    2018-02-13

    Myelin, the insulating sheath around axons, supports axon function. An important question is the impact of mild myelin disruption. In the absence of the myelin protein proteolipid protein (PLP1), myelin is generated but with age, axonal function/maintenance is disrupted. Axon disruption occurs in Plp1 -null mice as early as 2 months in cortical projection neurons. High-volume cellular quantification techniques revealed a region-specific increase in oligodendrocyte density in the olfactory bulb and rostral corpus callosum that increased during adulthood. A distinct proliferative response of progenitor cells was observed in the subventricular zone (SVZ), while the number and proliferation of parenchymal oligodendrocyte progenitor cells was unchanged. This SVZ proliferative response occurred prior to evidence of axonal disruption. Thus, a novel SVZ response contributes to the region-specific increase in oligodendrocytes in Plp1 -null mice. Young adult Plp1- null mice exhibited subtle but substantial behavioral alterations, indicative of an early impact of mild myelin disruption. © 2018, Gould et al.

  2. Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker of diet-related metabolic alterations

    KAUST Repository

    Diaz Rua, Ruben; Palou, Andreu; Oliver, Paula

    2016-01-01

    subjects at risk of developing diet-related diseases.Objective: We analysed PBMC expression of key energy homeostasis-related genes in a time-course analysis in order to find out early markers of metabolic alterations due to sustained intake of high-fat (HF) and highprotein (HP) diets.Design: We administered HF and HP diets (4 months) to adult Wistar rats in isocaloric conditions to a control diet, mainly to avoid overweight associated with the intake of hyperlipidic diets and, thus, to be able to characterise markers of metabolically obese normal-weight (MONW) syndrome. PBMC samples were collected at different time points of dietary treatment and expression of relevant energy homeostatic genes analysed by real-time reverse transcription-polymerase chain reaction. Serum parameters related with metabolic syndrome, as well as fat deposition in liver, were also analysed.Results: The most outstanding results were those obtained for the expression of the lipolytic gene carnitine palmitoyltransferase 1a (Cpt1a). Cpt1a expression in PBMC increased after only 1 month of exposure to both unbalanced diets, and this increased expression was maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a expression was altered even in the absence of increased body weight but correlated with alterations such as higher insulin resistance, alteration of serum lipid profile and, particularly, increased fat deposition in liver, a feature characteristic of metabolic syndrome, which was even observed in animals fed with HP diet.Conclusions: We propose Cpt1a gene expression analysis in PBMC as an early biomarker of metabolic alterations associated with MONW phenotype due to the intake of isocaloric HF diets, as well as a marker of increased risk of metabolic diseases

  3. Socio-economic status and time trends associated with early ART initiation following primary HIV infection in Montreal, Canada: 1996 to 2015.

    Science.gov (United States)

    Mehraj, Vikram; Cox, Joseph; Lebouché, Bertrand; Costiniuk, Cecilia; Cao, Wei; Li, Taisheng; Ponte, Rosalie; Thomas, Réjean; Szabo, Jason; Baril, Jean-Guy; Trottier, Benoit; Côté, Pierre; LeBlanc, Roger; Bruneau, Julie; Tremblay, Cécile; Routy, Jean-Pierre

    2018-02-01

    Guidelines regarding antiretroviral therapy (ART) initiation in HIV infection have varied over time, with the 2015 World Health Organization recommendation suggesting ART initiation at the time of diagnosis regardless of CD4 T-cell counts. Herein, we investigated the influence of socio-demographic and clinical factors in addition to time trends on early ART initiation among participants of the Montreal Primary HIV Infection Study. The Montreal Primary HIV Infection Study is a prospective cohort established in three community medical centres (CMCs) and two university medical centres (UMCs). Recently diagnosed HIV-infected adults were categorized as receiving early (vs. delayed) ART if ART was initiated within 180 days of the baseline visit. Associations between early ART initiation and socio-demographic, socio-economic and behavioural information were examined. Independent associations of factors linked with early ART initiation were determined using multivariable binary logistic regression analysis. A total of 348 participants had a documented date of HIV acquisition of age of participants was 35 (28; 42) years and the majority were male (96%), having paid employment (63%), men who have sex with men (MSM) (78%) and one to four sexual partners in the last three months (70%). Participants presented with a median IQR HIV plasma viral load of 4.6 (3.7; 5.3) log 10 copies/ml, CD4 count of 510 (387; 660) cells/μl and were recruited in CMCs (52%) or UMCs (48%). Early ART initiation was observed in 47% of the participants and the trend followed a V-shaped curve with peaks in 1996 to 1997 (89%) and 2013 to 2015 (88%) with a dip in 2007 to 2009 (22%). Multivariable analyses showed that having a paid employment adjusted odds ratio (aOR: 2.43; 95% CI: 1.19, 4.95), lower CD4 count (aOR per 50 cell increase: 0.93; 95% CI: 0.87, 0.99) and care at UMCs (aOR: 2.03; 95% CI: 1.06 to 3.90) were independently associated with early ART initiation. Early ART initiation during primary

  4. Altered Dynamic Postural Control during Step Turning in Persons with Early-Stage Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jooeun Song

    2012-01-01

    Full Text Available Persons with early-stage Parkinson’s disease (EPD do not typically experience marked functional deficits but may have difficulty with turning tasks. Studies evaluating turning have focused on individuals in advanced stages of the disease. The purpose of this study was to compare postural control strategies adopted during turning in persons with EPD to those used by healthy control (HC subjects. Fifteen persons with EPD, diagnosed within 3 years, and 10 HC participated. Participants walked 4 meters and then turned 90°. Dynamic postural control was quantified as the distance between the center of pressure (COP and the extrapolated center of mass (eCOM. Individuals with EPD demonstrated significantly shorter COP-eCOM distances compared to HC. These findings suggest that dynamic postural control during turning is altered even in the early stages of PD.

  5. Multislice quantitative computed tomography allows early detection of bone mineral density alterations induced by atherogenic diet in a growing rat experimental model

    International Nuclear Information System (INIS)

    Gubert, M.J.; Monforte, F.; Calo, C.; Lylyk, P.; Friedman, M.F.; Gamba, C.A.

    2012-01-01

    Purpose. To demonstrate the utility of Multislice Quantitative Computed Tomography (MS-QCT) in the early detection of mandibular bone mineral density (BMD) alterations induced by an atherogenic diet in a growing rat experimental model. Materials and Methods. Male weanling Wistar rats (n =16) were divided by body weight (Wt) into 2 groups: control (C) and experimental (E), with no significant differences in the mean initial Wt (p>0.05). C was fed rodent stock diet ad libitum, and E an atherogenic diet for 3 weeks (3w). Zoometry (body weight and length) and diet intake (g/100g rat/day) were monitored. At 3 w in serum (mg/dL) lipidlipoprotein profile was studied: total cholesterol (t-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C) and MSQCT (Philips 64 CT, quantified with the eFilm Workstation 2.1) in seven mandibular areas (MA): n. 1 to 4: from chin to mandibular foramen, n. 5: coronoid process, n. 6: condylar process, n. 7: angular process. Statistics: Pearson's correlation between BMD in each MA and serum t-C. p 0.05). Correlation coefficients (r) and their significance levels (p) were relevant in 5/7 MA. MA1:-0.580 (p=0.019), MA2:-0.709 (p=0.002), MA3:-0.635 (p=0.008), MA5:-0.674 (p=0.004), MA6:-0.564 (p=0.023). Conclusions. These results suggest that MS-QCT is an imaging diagnostic method that allows the early detection of mandible bone architecture alterations induced by an atherogenic diet. Inverse correlation between BMD and t-C would indicate an association between an atherogenic diet intake and potential temporomandibular disorders. (authors)

  6. Purine-related metabolites and their converting enzymes are altered in frontal, parietal and temporal cortex at early stages of Alzheimer's disease pathology.

    Science.gov (United States)

    Alonso-Andrés, Patricia; Albasanz, José Luis; Ferrer, Isidro; Martín, Mairena

    2018-01-24

    Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer's disease (AD) and in age-matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered. 5'-NT is reduced in membranes and cytosol in FC mainly at early stages but not in PC, and only at advanced stages in cytosol in TC. ADA activity is decreased in AD when considered as a whole but increased at early stages in TC. Finally, PNP activity is increased only in TC at early stages. Purine metabolism alterations occur at early stages of AD independently of neurofibrillary tangles and β-amyloid plaques. Alterations are stage dependent and region dependent, the latter showing opposite patterns in FC compared with PC and TC. Adenosine is the most affected of the assessed purines. © 2018 International Society of Neuropathology.

  7. Frameworks for Change: Four Recurrent Themes for Quality in Early Childhood Curriculum Initiatives

    Science.gov (United States)

    Burgess, Jennifer; Fleet, Alma

    2009-01-01

    This paper reports on the first phase of a case study that investigated how early childhood teachers experience organisational change. As one of three levels of quality improvement, State government-funded curriculum initiatives were developed with an aim to promote change. Three curriculum documents, one each focusing on literacy, pedagogy and…

  8. Prenatal cigarette smoke exposure and early initiation of multiple substance use.

    Science.gov (United States)

    Goldschmidt, Lidush; Cornelius, Marie D; Day, Nancy L

    2012-06-01

    Earlier studies have shown a relation between prenatal cigarette smoke exposure (PCSE) and offspring initiation of tobacco use. No prior study has examined the association between PCSE and early initiation of multiple substances (EIMS) including marijuana and alcohol in addition to tobacco. We investigated the association between PCSE and multiple substance use during adolescence. Pregnant women attending an urban prenatal clinic were selected to participate in the prospective longitudinal study based on their substance use. This study is based on the 16-year follow-up phase and consists of 579 mother-offspring dyads. The women were of lower socioeconomic status, 54% were Black, and 53% reported smoking cigarettes. 52% of the offspring were female. EIMS is a measure of the number of substances initiated prior to age 16 by the adolescents; it ranged from 0 (no initiation, N = 166) to 3 (all, N = 162). Adolescents exposed to tobacco during first trimester of gestation were 1.4 times more likely to initiate multiple substances by age 16 than the nonexposed group. PCSE was a significant predictor of EIMS after controlling for other prenatal exposures, home environment, and demographic characteristics, using ordinal polytomous logistic regression. Other risk factors of EIMS were maternal and adolescent depression, less strict and less involved parenting, offspring attention problems, and lack of participation in a youth club. There is a significant relation between PCSE and adolescent's EIMS.

  9. Wet, Carbonaceous Asteroids: Altering Minerals, Changing Amino Acids

    Science.gov (United States)

    Taylor, G. J.

    2011-04-01

    Many carbonaceous chondrites contain alteration products from water-rock interactions at low temperature and organic compounds. A fascinating fact known for decades is the presence in some of them of an assortment of organic compounds, including amino acids, sometimes called the building blocks of life. Murchison and other CM carbonaceous chondrites contain hundreds of amino acids. Early measurements indicated that the amino acids in carbonaceous chondrites had equal proportions of L- and D-structures, a situation called racemic. This was in sharp contrast to life on Earth, which heavily favors L- forms. However, beginning in 1997, John Cronin and Sandra Pizzarello (Arizona State University) found L- excesses in isovaline and several other amino acids in the Murchison carbonaceous chondrite. In 2009, Daniel Glavin and Jason Dworkin (Astrobiology Analytical Lab, Goddard Space Flight Center) reported the first independent confirmation of L-isovaline excesses in Murchison using a different analytical technique than employed by Cronin and Pizzarello. Inspired by this work, Daniel Glavin, Michael Callahan, Jason Dworkin, and Jamie Elsila (Astrobiology Analytical Lab, Goddard Space Flight Center), have done an extensive study of the abundance and symmetry of amino acids in carbonaceous chondrites that experienced a range of alteration by water in their parent asteroids. The results show that amino acids are more abundant in the less altered meteorites, implying that aqueous processing changes the mix of amino acids. They also confirmed the enrichment in L-structures of some amino acids, especially isovaline, confirming earlier work. The authors suggest that aqueously-altered planetesimals might have seeded the early Earth with nonracemic amino acids, perhaps explaining why life from microorganisms to people use only L- forms to make proteins. The initial imbalance caused by non-biologic processes in wet asteroids might have been amplified by life on Earth. Alternatively

  10. Personality Characteristics, Early Maladaptive Schema and Family Function in Couples Initiating for Divorce Versus Non-Initiating Ones

    Directory of Open Access Journals (Sweden)

    محسن دهقانی

    2017-03-01

    Full Text Available Decision for divorce depends on various personal and interpersonal variables. Personality characteristics and early maladaptive schema as two individual, and family function, as an interpersonal variable would play crucial role in helping people to cope with problems in life. A sample of 285 couples (147 initiator, and 138 noninitiator were recruited in the family courts, and residential districts in Tehran. They completed a battery of questionnaire including NEO (five factor personality questionnaire, short form of early maladaptive schema questionnaire (YSR, and McMaster family assessment device (FAD. Groups were matched based on age, education level, social economic status, and years of marriage. Results indicated statistical significant differences between two groups in personality characteristics (neuroticism, openness to new experiences, agreeableness and consciousness early maladaptive schemas (emotional deprivation, rejection, distrust, pessimism and emotional inhibition, and family function (problem solving, roles, and behavioral control. The result of regression logistic analysis showed that 34 to 45 percent of dependent variable predicted by these 12 independent variable. As such, it seems that there is a need to attend the factors would play a role both at primary prevention level and secondary level that psychologists and counselors could consider when providing mental health services.

  11. Early Prediction of Outcome in Advanced Head-and-Neck Cancer Based on Tumor Blood Volume Alterations During Therapy: A Prospective Study

    International Nuclear Information System (INIS)

    Cao Yue; Popovtzer, Aron; Li, Diana; Chepeha, Douglas B.; Moyer, Jeffrey S.; Prince, Mark E.; Worden, Francis; Teknos, Theodoros; Bradford, Carol; Mukherji, Suresh K.; Eisbruch, Avraham

    2008-01-01

    Purpose: To assess whether alterations in tumor blood volume (BV) and blood flow (BF) during the early course of chemo-radiotherapy (chemo-RT) for head-and-neck cancer (HNC) predict treatment outcome. Methods and Materials: Fourteen patients receiving concomitant chemo-RT for nonresectable, locally advanced HNC underwent dynamic contrast-enhanced (DCE) MRI scans before therapy and 2 weeks after initiation of chemo-RT. The BV and BF were quantified from DCE MRI. Preradiotherapy BV and BF, as well as their changes during RT, were evaluated separately in the primary gross tumor volume (GTV) and nodal GTV for association with outcomes. Results: At a median follow-up of 10 months (range, 5-27 months), 9 patients had local-regional controlled disease. One patient had regional failure, 3 had local failures, and 1 had local-regional failure. Reduction in tumor volume after 2 weeks of chemo-RT did not predict for local control. In contrast, the BV in the primary GTV after 2 weeks of chemo-RT was increased significantly in the local control patients compared with the local failure patients (p < 0.03). Conclusions: Our data suggest that an increase in available primary tumor blood for oxygen extraction during the early course of RT is associated with local control, thus yielding a predictor with potential to modify treatment. These findings require validation in larger studies

  12. Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

    Science.gov (United States)

    Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

    2012-07-31

    For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

  13. Alcohol use initiation is associated with changes in personality trait trajectories from early adolescence to young adulthood.

    Science.gov (United States)

    Blonigen, Daniel M; Durbin, C Emily; Hicks, Brian M; Johnson, Wendy; McGue, Matt; Iacono, William G

    2015-11-01

    Recent work has demonstrated the codevelopment of personality traits and alcohol use characteristics from early adolescence to young adulthood. Few studies, however, have tested whether alcohol use initiation impacts trajectories of personality over this time period. We examined the effect of alcohol use initiation on personality development from early adolescence to young adulthood. Participants were male (nmen = 2,350) and female (nwomen = 2,618) twins and adoptees from 3 community-based longitudinal studies conducted at the Minnesota Center for Twin and Family Research. Data on personality traits of Positive Emotionality (PEM; Well-being), Negative Emotionality (NEM; Stress Reaction, Alienation, and Aggression), and Constraint (CON; Control and Harm Avoidance)-assessed via the Multidimensional Personality Questionnaire (MPQ)-and age of first drink were collected for up to 4 waves spanning ages 10 to 32. Alcohol use initiation was associated with significant decreases in levels of Well-being and CON traits, most notably Control; and significant increases in levels of all NEM traits, particularly Aggression. In general, the effects of alcohol use initiation on personality traits were moderated by gender and enhanced among those with earlier age of first drink. From early adolescence to young adulthood, alcohol use initiation predicts deviations from normative patterns of personality maturation. Such findings offer a potential mechanism underlying the codevelopment of personality traits and alcohol use characteristics during this formative period of development. Copyright © 2015 by the Research Society on Alcoholism.

  14. Altered lysosome distribution is an early neuropathological event in neurological forms of Gaucher disease.

    Science.gov (United States)

    Zigdon, Hila; Meshcheriakova, Anna; Farfel-Becker, Tamar; Volpert, Giora; Sabanay, Helena; Futerman, Anthony H

    2017-03-01

    In the lysosomal storage disorder Gaucher disease (GD), glucosylceramide (GlcCer) accumulates due to the defective activity of glucocerebrosidase. A subset of GD patients develops neuropathology. We now show mislocalization of Limp2-positive puncta and a large reduction in the number of Lamp1-positive puncta, which are associated with impaired tubulin. These changes occur at an early stage in animal models of GD, prior to development of overt symptoms and considerably earlier than neuronal loss. Altered lysosomal localization and cytoskeleton disruption precede the neuroinflammatory pathways, axonal dystrophy and neuronal loss previously characterized in neuronal forms of GD. © 2017 Federation of European Biochemical Societies.

  15. Patient satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy in women with diabetes

    DEFF Research Database (Denmark)

    Secher, A L; Madsen, A B; Nielsen, Lene Ringholm

    2012-01-01

    of initial monitoring). Ten women (15%) did not wish to use continuous glucose monitoring again in pregnancy. Main causes behind early removal of continuous glucose monitoring were self-reported skin irritation, technical problems and continuous glucose monitoring inaccuracy. No differences were found......Aim: To evaluate self-reported satisfaction and barriers to initiating real-time continuous glucose monitoring in early pregnancy among women with pregestational diabetes. Methods: Fifty-four women with Type 1 diabetes and 14 women with Type 2 diabetes were offered continuous glucose monitoring...

  16. Early Stress History Alters Serum Insulin-Like Growth Factor-1 and Impairs Muscle Mitochondrial Function in Adult Male Rats.

    Science.gov (United States)

    Ghosh, S; Banerjee, K K; Vaidya, V A; Kolthur-Seetharam, U

    2016-09-01

    Early-life adversity is associated with an enhanced risk for adult psychopathology. Psychiatric disorders such as depression exhibit comorbidity for metabolic dysfunction, including obesity and diabetes. However, it is poorly understood whether, besides altering anxiety and depression-like behaviour, early stress also evokes dysregulation of metabolic pathways and enhances vulnerability for metabolic disorders. We used the rodent model of the early stress of maternal separation (ES) to examine the effects of early stress on serum metabolites, insulin-like growth factor (IGF)-1 signalling, and muscle mitochondrial content. Adult ES animals exhibited dyslipidaemia, decreased serum IGF1 levels, increased expression of liver IGF binding proteins, and a decline in the expression of specific metabolic genes in the liver and muscle, including Pck1, Lpl, Pdk4 and Hmox1. These changes occurred in the absence of alterations in body weight, food intake, glucose tolerance, insulin tolerance or insulin levels. ES animals also exhibited a decline in markers of muscle mitochondrial content, such as mitochondrial DNA levels and expression of TFAM (transcription factor A, mitochondrial). Furthermore, the expression of several genes involved in mitochondrial function, such as Ppargc1a, Nrf1, Tfam, Cat, Sesn3 and Ucp3, was reduced in skeletal muscle. Adult-onset chronic unpredictable stress resulted in overlapping and distinct consequences from ES, including increased circulating triglyceride levels, and a decline in the expression of specific metabolic genes in the liver and muscle, with no change in the expression of genes involved in muscle mitochondrial function. Taken together, our results indicate that a history of early adversity can evoke persistent changes in circulating IGF-1 and muscle mitochondrial function and content, which could serve to enhance predisposition for metabolic dysfunction in adulthood. © 2016 British Society for Neuroendocrinology.

  17. Domestication-driven Gossypium profilin 1 (GhPRF1) gene transduces early flowering phenotype in tobacco by spatial alteration of apical/floral-meristem related gene expression.

    Science.gov (United States)

    Pandey, Dhananjay K; Chaudhary, Bhupendra

    2016-05-13

    Plant profilin genes encode core cell-wall structural proteins and are evidenced for their up-regulation under cotton domestication. Notwithstanding striking discoveries in the genetics of cell-wall organization in plants, little is explicit about the manner in which profilin-mediated molecular interplay and corresponding networks are altered, especially during cellular signalling of apical meristem determinacy and flower development. Here we show that the ectopic expression of GhPRF1 gene in tobacco resulted in the hyperactivation of apical meristem and early flowering phenotype with increased flower number in comparison to the control plants. Spatial expression alteration in CLV1, a key meristem-determinacy gene, is induced by the GhPRF1 overexpression in a WUS-dependent manner and mediates cell signalling to promote flowering. But no such expression alterations are recorded in the GhPRF1-RNAi lines. The GhPRF1 transduces key positive flowering regulator AP1 gene via coordinated expression of FT4, SOC1, FLC1 and FT1 genes involved in the apical-to-floral meristem signalling cascade which is consistent with our in silico profilin interaction data. Remarkably, these positive and negative flowering regulators are spatially controlled by the Actin-Related Protein (ARP) genes, specifically ARP4 and ARP6 in proximate association with profilins. This study provides a novel and systematic link between GhPRF1 gene expression and the flower primordium initiation via up-regulation of the ARP genes, and an insight into the functional characterization of GhPRF1 gene acting upstream to the flowering mechanism. Also, the transgenic plants expressing GhPRF1 gene show an increase in the plant height, internode length, leaf size and plant vigor. Overexpression of GhPRF1 gene induced early and increased flowering in tobacco with enhanced plant vigor. During apical meristem determinacy and flower development, the GhPRF1 gene directly influences key flowering regulators through ARP

  18. Glial alterations from early to late stages in a model of Alzheimer's disease: Evidence of autophagy involvement in Aβ internalization.

    Science.gov (United States)

    Pomilio, Carlos; Pavia, Patricio; Gorojod, Roxana Mayra; Vinuesa, Angeles; Alaimo, Agustina; Galvan, Veronica; Kotler, Monica Lidia; Beauquis, Juan; Saravia, Flavia

    2016-02-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease without effective therapy. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. The identification of early cell responses and of brain areas involved could help to design new successful treatments. Hence, we studied early alterations of hippocampal glia and their progression during the neuropathology in PDAPP-J20 transgenic mice, AD model, at 3, 9, and 15 months (m) of age. At 3 m, before deposits formation, microglial Iba1+ cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus, alterations appearing later on stratum radiatum. Iba1 immunohistochemistry revealed increased cell density and immunoreactive area in PDAPP mice from 9 m onward selectively in the hilus, in coincidence with prominent amyloid Congo red + deposition. At pre-plaque stages, GFAP+ astroglia showed density alterations while, at an advanced age, the presence of deposits was associated with important glial volume changes and apparently being intimately involved in amyloid degradation. Astrocytes around plaques were strongly labeled for LC3 until 15 m in Tg mice, suggestive of increased autophagic flux. Moreover, β-Amyloid fibrils internalization by astrocytes in in vitro conditions was dependent on autophagy. Co-localization of Iba1 with ubiquitin or p62 was exclusively found in microglia contacting deposits from 9 m onward, suggesting torpid autophagy. Our work characterizes glial changes at early stages of the disease in PDAPP-J20 mice, focusing on the hilus as an especially susceptible hippocampal subfield, and provides evidence that glial autophagy could play a role in amyloid processing at advanced stages. © 2015 Wiley Periodicals, Inc.

  19. Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis

    NARCIS (Netherlands)

    Gori, Andrea; Tincati, Camilla; Rizzardini, Giuliano; Torti, Carlo; Quirino, Tiziana; Haarman, Monique; Ben Amor, Kaouther; van Schaik, Jacqueline; Vriesema, Aldwin; Knol, Jan; Marchetti, Giulia; Welling, Gjalt; Clerici, Mario

    Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the

  20. Alterations of parenchymal microstructure, neuronal connectivity and cerebrovascular resistance at adolescence following mild to moderate traumatic brain injury in early development.

    Science.gov (United States)

    Parent, Maxime; Li, Ying; Santhakumar, Vijayalakshmi; Hyder, Fahmeed; Sanganahalli, Basavaraju G; Kannurpatti, Sridhar

    2018-06-01

    TBI is a leading cause of morbidity in children. To investigate outcome of early developmental TBI during adolescence, a rat model of fluid percussion injury was developed, where previous work reported deficits in sensorimotor behavior and cortical blood flow at adolescence. 1 Based on the non-localized outcome, we hypothesized that multiple neurophysiological components of brain function, namely neuronal connectivity, synapse/axonal microstructural integrity and neurovascular function are altered and magnetic resonance imaging (MRI) methods could be used to determine regional alterations. Adolescent outcomes of developmental TBI were studied 2-months after injury, using functional MRI (fMRI) and Diffusion Tensor Imaging (DTI). fMRI based resting state functional connectivity (RSFC), representing neural connectivity, was significantly altered between sham and TBI. RSFC strength decreased in the cortex, hippocampus and thalamus accompanied by decrease in the spatial extent of their corresponding RSFC networks and inter-hemispheric asymmetry. Cerebrovascular reactivity to arterial CO2 changes diminished after TBI across both hemispheres, with a more pronounced decrease in the ipsilateral hippocampus, thalamus and motor cortex. DTI measures of fractional anisotropy (FA) and apparent diffusion coefficient (ADC), reporting on axonal and microstructural integrity of the brain, indicated similar inter-hemispheric asymmetry, with highest change in the ipsilateral hippocampus and regions adjoining the ipsilateral thalamus, hypothalamus and amygdala. TBI-induced corpus callosal microstructural alterations indicated measurable changes in inter-hemispheric structural connectivity. Hippocampus, thalamus and select cortical regions were most consistently affected in multiple imaging markers. The multi-modal MRI results demonstrate cortical and subcortical alterations in neural connectivity, cerebrovascular resistance and parenchymal microstructure in the adolescent brain

  1. Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

    Directory of Open Access Journals (Sweden)

    Sinha Sanjeev

    2012-07-01

    Full Text Available Abstract Background For antiretroviral therapy (ART naive human immunodeficiency virus (HIV infected adults suffering from tuberculosis (TB, there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART after starting antituberculosis treatment (ATT, in order to minimize mortality, HIV disease progression, and adverse events. Methods In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART and 62 after 8-12 weeks (delayed ART of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045. Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05. Rates of adverse events were similar. Interpretation Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Trial registration CTRI/2011/12/002260

  2. Penile alterations at early stage of type 1 diabetes in rats

    Directory of Open Access Journals (Sweden)

    Mingfang Tao

    Full Text Available ABSTRACT Objective Diabetes affects the erectile function significantly. However, the penile alterations in the early stage of diabetes in experimental animal models have not been well studied. We examined the changes of the penis and its main erectile components in diabetic rats. Materials and methods Male Sprague-Dawley rats were divided into 2 groups: streptozotocin (STZ-induced diabetics and age-matched controls. Three or nine weeks after diabetes induction, the penis was removed for immunohistochemical staining of smooth muscle and neuronal nitric oxide synthase (nNOS in midshaft penile tissues. The cross-sectional areas of the whole midshaft penis and the corpora cavernosa were quantified. The smooth muscle in the corpora cavernosa and nNOS in the dorsal nerves were quantified. Results The weight, but not the length, of the penis was lower in diabetics. The cross-sectional areas of the total midshaft penis and the corpora cavernosa were lower in diabetic rats compared with controls 9 weeks, but not 3 weeks after diabetes induction. The cross-sectional area of smooth muscle in the corpora cavernosa as percentage of the overall area of the corpora cavernosa was lower in diabetic rats than in controls 9 weeks, but not 3 weeks after diabetes induction. Percentage change of nNOS in dorsal nerves was similar at 3 weeks, and has a decreased trend at 9 weeks in diabetic rats compared with controls. Conclusions Diabetes causes temporal alterations in the penis, and the significant changes in STZ rat model begin 3-9 weeks after induction. Further studies on the reversibility of the observed changes are warranted.

  3. Functional Connectivity Alterations between Networks and Associations with Infant Immune Health within Networks in HIV Infected Children on Early Treatment: A Study at 7 Years

    Directory of Open Access Journals (Sweden)

    Jadrana T. F. Toich

    2018-01-01

    Full Text Available Although HIV has been shown to impact brain connectivity in adults and youth, it is not yet known to what extent long-term early antiretroviral therapy (ART may alter these effects, especially during rapid brain development in early childhood. Using both independent component analysis (ICA and seed-based correlation analysis (SCA, we examine the effects of HIV infection in conjunction with early ART on resting state functional connectivity (FC in 7 year old children. HIV infected (HIV+ children were from the Children with HIV Early Antiretroviral Therapy (CHER trial and all initiated ART before 18 months; uninfected children were recruited from an interlinking vaccine trial. To better understand the effects of current and early immune health on the developing brain, we also investigated among HIV+ children the association of FC at 7 years with CD4 count and CD4%, both in infancy (6–8 weeks and at scan. Although we found no differences within any ICA-generated resting state networks (RSNs between HIV+ and uninfected children (27 HIV+, 18 uninfected, whole brain connectivity to seeds located at RSN connectivity peaks revealed several loci of FC differences, predominantly from seeds in midline regions (posterior cingulate cortex, paracentral lobule, cuneus, and anterior cingulate. Reduced long-range connectivity and increased short-range connectivity suggest developmental delay. Within the HIV+ children, clinical measures at age 7 years were not associated with FC values in any of the RSNs; however, poor immune health during infancy was associated with localized FC increases in the somatosensory, salience and basal ganglia networks. Together these findings suggest that HIV may affect brain development from its earliest stages and persist into childhood, despite early ART.

  4. Vulnerability to Peer Influence: A Moderated Mediation Study of Early Adolescent Alcohol Use Initiation

    Science.gov (United States)

    Trucco, Elisa M.; Colder, Craig R.; Wieczorek, William F.

    2011-01-01

    Affiliation with deviant peers is a correlate of adolescent alcohol use; however, the mechanism accounting for this association remains unclear, particularly with respect to initiation of alcohol use in early adolescence. This prospective study examines perceived peer attitudes and use as a mediator between peer delinquency and initiation of alcohol use, and how parenting may moderate vulnerability to this risk pathway. Participants included 371 11–13 year-old adolescents (55.5% female, 83.0% Caucasian). Results suggested that high levels of peer delinquency prospectively predicted perceived peer approval and use of alcohol and that peer approval and use of alcohol prospectively predicted initiation of alcohol use. Thus, reinforcement and modeling alcohol use appear to be important mechanisms by which delinquent peers influence the initiation of drinking. There was no support for parental warmth or control as moderators of peer influence. PMID:21420241

  5. Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children.

    Science.gov (United States)

    Landgraf, Kathrin; Rockstroh, Denise; Wagner, Isabel V; Weise, Sebastian; Tauscher, Roy; Schwartze, Julian T; Löffler, Dennis; Bühligen, Ulf; Wojan, Magdalena; Till, Holger; Kratzsch, Jürgen; Kiess, Wieland; Blüher, Matthias; Körner, Antje

    2015-04-01

    Accumulation of fat mass in obesity may result from hypertrophy and/or hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in adults. Here we assessed early alterations in AT biology and function by comprehensive experimental and clinical characterization of 171 AT samples from lean and obese children aged 0 to 18 years. We show an increase in adipocyte size and number in obese compared with lean children beginning in early childhood. These alterations in AT composition in obese children were accompanied by decreased basal lipolytic activity and significantly enhanced stromal vascular cell proliferation in vitro, potentially underlying the hypertrophy and hyperplasia seen in obese children, respectively. Furthermore, macrophage infiltration, including the formation of crown-like structures, was increased in AT of obese children from 6 years on and was associated with higher hs-CRP serum levels. Clinically, adipocyte hypertrophy was not only associated with leptin serum levels but was highly and independently correlated with HOMA-IR as a marker of insulin resistance in children. In summary, we show that adipocyte hypertrophy is linked to increased inflammation in AT in obese children, thereby providing evidence that obesity-associated AT dysfunction develops in early childhood and is related to insulin resistance. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. Early initiation of breastfeeding among mothers of children under the age of 24 months in Southern Ethiopia

    NARCIS (Netherlands)

    Beyene, Misrak Getnet; Geda, Nigatu Regassa; Habtewold, Tesfa Dejenie; Assen, Zuriash Mengistu

    2017-01-01

    BACKGROUND: The early initiation of breastfeeding (EIBF), or timely initiation of breastfeeding, is the proportion of children put to the breast within one hour of birth. It is an important strategy for reducing perinatal and infant morbidity and mortality, but it remains under practiced in

  7. Natural history of bleeding and characteristics of early bleeders among warfarin initiators – a cohort study in Finland

    Directory of Open Access Journals (Sweden)

    Rikala M

    2016-02-01

    Full Text Available Maria Rikala,1 Helena Kastarinen,1,2 Pekka Tiittanen,1 Risto Huupponen,1,3 Maarit Jaana Korhonen1,4,5 1Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, 2Social Insurance Institution, Regional Office for Eastern and Northern Finland, Kuopio, 3Unit of Clinical Pharmacology, Turku University Hospital, 4Department of Public Health, University of Turku, Turku, Finland; 5Division of Pharmaceutical Outcomes and Policy, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, NC, USA Aims: The demand for oral anticoagulant therapy will continue to increase in the future along with the aging of the population. This study aimed to determine the rate of bleeding requiring hospitalization and to characterize early bleeders among persons initiating warfarin therapy. Characterization of those most susceptible to early bleeding is important in order to increase the safety of warfarin initiation. Patients and methods: Using data from nationwide health registers, we identified persons initiating warfarin therapy between January 1, 2009 and June 30, 2012, n=101,588, and followed them until hospitalization for bleeding, death, or administrative end of the study (December 31, 2012. We defined early bleeders as persons with a bleeding requiring hospitalization within 30 days since warfarin initiation. Results: The rate of hospitalization for bleeding during a median follow-up of 1.9 years was 2.6% per person-year (95% confidence interval [CI] 2.5%–2.7%, with a peak within the first 30 days of warfarin initiation (6.5% per person-year, 95% CI 6.0%–7.1%. In a multivariable Cox proportional hazards regression analysis, early bleeders were characterized by prior bleeding (<180 days before initiation, hazard ratio [HR] =13.7, 95% CI 10.9–17.1; during 180 days–7 years before initiation, HR =1.48, 95% CI 1.15–1.90, male sex (HR =1.32, 95% CI 1.10–1.57, older age (HR =1.13, 95% CI 1.04–1

  8. Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

    Science.gov (United States)

    Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

    2018-01-01

    There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

  9. Glial Alterations From Early to Late Stages in a Model of Alzheimer’s Disease: Evidence of Autophagy Involvement in Aβ Internalization

    Science.gov (United States)

    Pomilio, Carlos; Pavia, Patricio; Gorojod, Roxana Mayra; Vinuesa, Angeles; Alaimo, Agustina; Galvan, Veronica; Kotler, Monica Lidia; Beauquis, Juan; Saravia, Flavia

    2017-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disease without effective therapy. Brain amyloid deposits are classical histopathological hallmarks that generate an inflammatory reaction affecting neuronal and glial function. The identification of early cell responses and of brain areas involved could help to design new successful treatments. Hence, we studied early alterations of hippocampal glia and their progression during the neuropathology in PDAPP-J20 transgenic mice, AD model, at 3, 9, and 15 months (m) of age. At 3 m, before deposits formation, microglial Iba1 + cells from transgenic mice already exhibited signs of activation and larger soma size in the hilus, alterations appearing later on stratum radiatum. Iba1 immunohistochemistry revealed increased cell density and immunoreactive area in PDAPP mice from 9 m onward selectively in the hilus, in coincidence with prominent amyloid Congo red + deposition. At pre-plaque stages, GFAP+ astroglia showed density alterations while, at an advanced age, the presence of deposits was associated with important glial volume changes and apparently being intimately involved in amyloid degradation. Astrocytes around plaques were strongly labeled for LC3 until 15 m in Tg mice, suggestive of increased autophagic flux. Moreover, β-Amyloid fibrils internalization by astrocytes in in vitro conditions was dependent on autophagy. Co-localization of Iba1 with ubiquitin or p62 was exclusively found in microglia contacting deposits from 9 m onward, suggesting torpid autophagy. Our work characterizes glial changes at early stages of the disease in PDAPP-J20 mice, focusing on the hilus as an especially susceptible hippocampal subfield, and provides evidence that glial autophagy could play a role in amyloid processing at advanced stages. PMID:26235241

  10. Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study

    International Nuclear Information System (INIS)

    Cherkezyan, Lusik; Backman, Vadim; Stypula-Cyrus, Yolanda; Subramanian, Hariharan; White, Craig; Dela Cruz, Mart; Wali, Ramesh K; Goldberg, Michael J; Bianchi, Laura K; Roy, Hemant K

    2014-01-01

    Nuclear alterations are a well-known manifestation of cancer. However, little is known about the early, microscopically-undetectable stages of malignant transformation. Based on the phenomenon of field cancerization, the tissue in the field of a tumor can be used to identify and study the initiating events of carcinogenesis. Morphological changes in nuclear organization have been implicated in the field of colorectal cancer (CRC), and we hypothesize that characterization of chromatin alterations in the early stages of CRC will provide insight into cancer progression, as well as serve as a biomarker for early detection, risk stratification and prevention. For this study we used transmission electron microscopy (TEM) images of nuclei harboring pre-neoplastic CRC alterations in two models: a carcinogen-treated animal model of early CRC, and microscopically normal-appearing tissue in the field of human CRC. We quantify the chromatin arrangement using approaches with two levels of complexity: 1) binary, where chromatin is separated into areas of dense heterochromatin and loose euchromatin, and 2) grey-scale, where the statistics of continuous mass-density distribution within the nucleus is quantified by its spatial correlation function. We established an increase in heterochromatin content and clump size, as well as a loss of its characteristic peripheral positioning in microscopically normal pre-neoplastic cell nuclei. Additionally, the analysis of chromatin density showed that its spatial distribution is altered from a fractal to a stretched exponential. We characterize quantitatively and qualitatively the nanoscale structural alterations preceding cancer development, which may allow for the establishment of promising new biomarkers for cancer risk stratification and diagnosis. The findings of this study confirm that ultrastructural changes of chromatin in field carcinogenesis represent early neoplastic events leading to the development of well

  11. Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Kyle Farmer

    2015-08-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA, or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0 and LPC (18:1, which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD.

  12. Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection.

    Science.gov (United States)

    Qi, Yuhua; Cui, Lunbiao; Ge, Yiyue; Shi, Zhiyang; Zhao, Kangchen; Guo, Xiling; Yang, Dandan; Yu, Hao; Cui, Lan; Shan, Yunfeng; Zhou, Minghao; Wang, Hua; Lu, Zuhong

    2012-12-28

    Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.

  13. Predictors of early breastfeeding initiation among mothers of children under 24 months of age in rural part of West Ethiopia.

    Science.gov (United States)

    Hailemariam, Tsedeke Wolde; Adeba, Emiru; Sufa, Alem

    2015-10-21

    The World Health Organization recommends initiation of breastfeeding within the first hour after childbirth. In developing countries alone, early initiation of breastfeeding could save as many as 1.45 million lives each year by reducing deaths mainly due to diarrheal disorders and lower respiratory tract infections in children. The current study aimed to determine the rate and the predictors of breastfeeding initiation in East Wollega Zones of West Ethiopia. A community-based, cross-sectional study was conducted from April to May 2014 among 594 mothers who had children less than 24 months. Multi stage cluster sampling method was used to select the study population. Eligible mothers were invited to interview using pretested questionnaires to gather data regarding sociodemographics, health-related variables, breastfeeding initiation, and current breastfeeding practices. A multivariable logistic regression analysis was used to identify independent predictors of early initiation of breastfeeding after controlling for confounding variables. A sample of 593 mothers was included in the study. Breastfeeding was initiated by 83.1 % of mothers within the first hour of childbirth. Being a housewife (AOR (95 % CI) = 2.48 (1.54- 3.99)) and infant received colostrum (AOR (95 % CI) =2.22 (1.08-4.55)) were significant positive predictors for early breastfeeding initiation as revealed by logistic regression. The multivariable logistic regression analysis showed that the mothers who had no radio and/or TV in the household (AOR (95 % CI = 0.55 (0.35-0.88)), were not exposure to health information (AOR (95 % CI) = 0.44 (0.25-0.75)), and infants were provided with prelacteal feeds (AOR (95 % CI)=0.30 (0.14-0.65)) were less likely to initiate breastfeeding. The rate of timely initiation of breastfeeding was high. Breastfeeding promotion program is essential to encourage the practice of timely initiation of breastfeeding, and reduce the practice of providing prelacteal

  14. Experimental Alteration of Basalt to Support Interpretation of Remote Sensing and In Situ Meausrements from Mars

    Science.gov (United States)

    Bell, M. S.

    2014-01-01

    Major occurrences of hydrous alteration minerals on Mars have been found in Noachian impact craters formed in basaltic targets and detected using visible/near infrared (VNIR) spectroscopy. Until recently phyllosilicates were detected only in craters in the southern hemisphere [1, 2]. However, it has been reported that at least nine craters in the northern plains apparently excavated thick layers of lava and sediment to expose phyllosilicates [3] as well. The MER (Mars Exploration Rovers) rovers previously reported results of in situ measurement indicating the presence of alteration minerals on Mars [4,5] and it was recently reported that the Mars Curiosity rover has detected alteration phases in situ at Yellowknife Bay in Gale crater as well [6,7]. An important discovery for Mars geochronology is that the Chemistry and Mineralogy (CheMin) x-ray diffraction (XRD) instrument on Curiosity detected phyllosilicates indicating that phyllosilicate formation on Mars extended beyond the Noachian Epoch [8]. These discoveries indicate that Mars was globally altered by water in the past but does not constrain formation conditions for alteration phase occurrences, which have important implications for the evolution of the surface and the biological potential on Mars. Understanding the alteration assemblages produced by a range of conditions is vital for the interpretation of phyllosilicate spectral signatures as well as in situ measurements and to decipher the environment and evolution of early Mars. The martian surface has been intensely altered by meteorite impacts whose effects include brecciation and melting of target materials as well as the initiation of hydrothermal circulation in a hydrous target [9,10,11,12]. Impact effects may facilitate aqueous alteration of a basaltic target because the rate of silicate dissolution is a function of the degree of crystallinity, surface area, and temperature. The resultant alteration mineralogies from shocked basaltic target material

  15. Reasons for delaying or engaging in early sexual initiation among adolescents in Nigeria

    Directory of Open Access Journals (Sweden)

    Ankomah A

    2011-09-01

    Full Text Available Augustine Ankomah1, Fatima Mamman-Daura2, Godpower Omoregie1, Jennifer Anyanti11Society for Family Health, Abuja; 2Pathfinder International/Nigeria, Kaduna Field Office, Kaduna, NigeriaBackground: Annually, over 1 million births in Nigeria are to teenage mothers. Many of these pregnancies are unwanted and these mothers are also exposed to the risk of human immunodeficiency virus (HIV infection. Sexual abstinence is a critical preventative health strategy. Several quantitative studies in Nigeria have identified the correlates and determinants of early sex, yet few have explored in depth the underlying reasons for early sex. This paper explores both the key factors that motivate some unmarried young people to engage in early sex and reasons why some delay.Methods: This qualitative study was based on data from 30 focus group discussions held with unmarried 14- to 19-year-olds in four geographically and culturally dispersed Nigerian states. Focus groups were stratified by sexual experience to capture variations among different subgroups.Results: Several reasons for early premarital sex were identified. The “push” factors included situations where parents exposed young female adolescents to street trading. “Pull” factors, particularly for males, included the pervasive viewing of locally produced movies, peer pressure and, for females, transactional sex (where adolescent girls exchange sex for gifts, cash, or other favors. Also noted were overtly coercive factors, including rape. There were also myths and misconceptions that “justified” early sexual initiation. Reasons cited for delay included religious injunction against premarital sex; disease prevention (especially HIV/acquired immunodeficiency syndrome; fear of pregnancy, and linked to this, the fear of dropping out of school; and, for females, the fear of bringing shame to the family, which could lead to their inability to get a "good" husband in the future.Conclusion: The differences

  16. History of pancreaticoduodenectomy: early misconceptions, initial milestones and the pioneers.

    Science.gov (United States)

    Are, Chandrakanth; Dhir, Mashaal; Ravipati, Lavanya

    2011-06-01

    Pancreaticoduodenectomy is one of the most challenging surgical procedures which requires the highest level of surgical expertise. This procedure has constantly evolved over the years through the meticulous efforts of a number of surgeons before reaching its current state. This review navigates through some of the early limitations and misconceptions and highlights the initial milestones which laid the foundation of this procedure. The current review also provides a few excerpts from the lives and illuminates on some of the seminal contributions of the three great surgeons: William Stewart Halsted, Walther Carl Eduard Kausch and Allen Oldfather Whipple. These surgeons pioneered the nascent stages of this procedure and paved the way for the modern day pancreaticoduodenectomy. © 2011 International Hepato-Pancreato-Biliary Association.

  17. Alterations in right posterior hippocampus in early blind individuals

    DEFF Research Database (Denmark)

    Chebat, Daniel-Robert; Chen, Jan-Kai; Schneider, Fabien

    2007-01-01

    This study compares hippocampal volumes of early blind and sex/age-matched sighted controls through volumetric and localization analyses. Early blind individuals showed a significantly smaller right posterior hippocampus compared with controls. No differences in total hippocampal volumes were fou...... of the posterior hippocampus in early blind individuals suggests the implication of this region in visual spatial memory. Udgivelsesdato: 2007-Mar-5......This study compares hippocampal volumes of early blind and sex/age-matched sighted controls through volumetric and localization analyses. Early blind individuals showed a significantly smaller right posterior hippocampus compared with controls. No differences in total hippocampal volumes were found...

  18. The role of scheduled second TACE in early-stage hepatocellular carcinoma with complete response to initial TACE

    Directory of Open Access Journals (Sweden)

    Jung Hee Kim

    2017-03-01

    Full Text Available Background/Aims We investigated the outcomes of early-stage hepatocellular carcinoma (HCC patients who showed a complete response (CR to initial transarterial chemoembolization (TACE, with a focus on the role of scheduled TACE repetition. Methods A total of 178 patients with early-stage HCC who were initially treated with TACE and showed a CR based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST criteria on one month follow-up computed tomography (CT were analyzed. Among them, 90 patients underwent scheduled repetition of TACE in the absence of viable tumor on CT. Results During a median follow-up period of 4.6 years (range: 0.4-8.8 years, mortality was observed in 71 patients (39.9%. The overall recurrence-free and local recurrence-free survival rates at 1 year were 44.4% and 56.2%. In the multivariable model, scheduled repetition of TACE was an independent factor associated with survival (hazard ratio [95% confidence interval]: 0.56 [0.34-0.93], P=0.025. When stratified using Barcelona clinic liver cancer (BCLC stage, scheduled repetition of TACE was associated with a favorable survival rate in BCLC stage A patients, but not in BCLC 0 patients. Conclusions Scheduled repetition of TACE was associated with better survival for early-stage HCC patients showing a CR after initial TACE, especially in BCLC stage A patients.

  19. Absence of early epileptiform abnormalities predicts lack of seizures on continuous EEG.

    Science.gov (United States)

    Shafi, Mouhsin M; Westover, M Brandon; Cole, Andrew J; Kilbride, Ronan D; Hoch, Daniel B; Cash, Sydney S

    2012-10-23

    To determine whether the absence of early epileptiform abnormalities predicts absence of later seizures on continuous EEG monitoring of hospitalized patients. We retrospectively reviewed 242 consecutive patients without a prior generalized convulsive seizure or active epilepsy who underwent continuous EEG monitoring lasting at least 18 hours for detection of nonconvulsive seizures or evaluation of unexplained altered mental status. The findings on the initial 30-minute screening EEG, subsequent continuous EEG recordings, and baseline clinical data were analyzed. We identified early EEG findings associated with absence of seizures on subsequent continuous EEG. Seizures were detected in 70 (29%) patients. A total of 52 patients had their first seizure in the initial 30 minutes of continuous EEG monitoring. Of the remaining 190 patients, 63 had epileptiform discharges on their initial EEG, 24 had triphasic waves, while 103 had no epileptiform abnormalities. Seizures were later detected in 22% (n = 14) of studies with epileptiform discharges on their initial EEG, vs 3% (n = 3) of the studies without epileptiform abnormalities on initial EEG (p monitoring is necessary.

  20. In vivo high-resolution 7 Tesla MRI shows early and diffuse cortical alterations in CADASIL.

    Science.gov (United States)

    De Guio, François; Reyes, Sonia; Vignaud, Alexandre; Duering, Marco; Ropele, Stefan; Duchesnay, Edouard; Chabriat, Hugues; Jouvent, Eric

    2014-01-01

    Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease (SVD). The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin's scale ≤1 and Mini Mental State Examination (MMSE) ≥24). Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male) and 24 controls (54.8±11.0 years, 42% male). Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models. MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls. Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.

  1. In vivo high-resolution 7 Tesla MRI shows early and diffuse cortical alterations in CADASIL.

    Directory of Open Access Journals (Sweden)

    François De Guio

    Full Text Available Recent data suggest that early symptoms may be related to cortex alterations in CADASIL (Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy, a monogenic model of cerebral small vessel disease (SVD. The aim of this study was to investigate cortical alterations using both high-resolution T2* acquisitions obtained with 7 Tesla MRI and structural T1 images with 3 Tesla MRI in CADASIL patients with no or only mild symptomatology (modified Rankin's scale ≤1 and Mini Mental State Examination (MMSE ≥24.Complete reconstructions of the cortex using 7 Tesla T2* acquisitions with 0.7 mm isotropic resolution were obtained in 11 patients (52.1±13.2 years, 36% male and 24 controls (54.8±11.0 years, 42% male. Seven Tesla T2* within the cortex and cortical thickness and morphology obtained from 3 Tesla images were compared between CADASIL and control subjects using general linear models.MMSE, brain volume, cortical thickness and global sulcal morphology did not differ between groups. By contrast, T2* measured by 7 Tesla MRI was significantly increased in frontal, parietal, occipital and cingulate cortices in patients after correction for multiple testing. These changes were not related to white matter lesions, lacunes or microhemorrhages in patients having no brain atrophy compared to controls.Seven Tesla MRI, by contrast to state of the art post-processing of 3 Tesla acquisitions, shows diffuse T2* alterations within the cortical mantle in CADASIL whose origin remains to be determined.

  2. Among Early Appearing Non-Motor Signs of Parkinson’s Disease, Alteration of Olfaction but Not Electroencephalographic Spectrum Correlates with Motor Function

    Directory of Open Access Journals (Sweden)

    Vitalii V. Cozac

    2017-10-01

    Full Text Available Olfactory decline is a frequent and early non-motor symptom in Parkinson’s disease (PD, which is increasingly used for diagnostic purposes. Another early appearing sign of PD consists in electroencephalographic (EEG alterations. The combination of olfactory and EEG assessment may improve the identification of patients with early stages of PD. We hypothesized that olfactory capacity would be correlated with EEG alterations and motor and cognitive impairment in PD patients. To the best of our knowledge, the mutual influence of both markers of PD—olfactory decrease and EEG changes—was not studied before. We assessed the function of odor identification using olfactory “Screening 12 Test” (“Sniffin’ Sticks®”, between two samples: patients with PD and healthy controls (HC. We analyzed correlations between the olfactory function and demographical parameters, Unified Parkinson’s Disease Rating Scale (UPDRS-III, cognitive task performance, and spectral alpha/theta ratio (α/θ. In addition, we used receiver operating characteristic-curve analysis to check the classification capacity (PD vs HC of olfactory function, α/θ, and a combined marker (olfaction and α/θ. Olfactory capacity was significantly decreased in PD patients, and correlated with age, disease duration, UPDRS-III, and with items of UPDRS-III related to gait and axial rigidity. In HC, olfaction correlated with age only. No correlation with α/θ was identified in both samples. Combined marker showed the largest area under the curve. In addition to EEG, the assessment of olfactory function may be a useful tool in the early characterization and follow-up of PD.

  3. Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

    Directory of Open Access Journals (Sweden)

    Qi Yuhua

    2012-12-01

    Full Text Available Abstract Background Pulmonary tuberculosis (TB is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP, varicella-zoster virus (VZV and enterovirus (EV were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated. Following qRT-PCR confirmation and receiver operational curve (ROC analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC value range, 0.711-0.848. Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.

  4. Early stress is associated with alterations in the orbitofrontal cortex: a tensor-based morphometry investigation of brain structure and behavioral risk.

    Science.gov (United States)

    Hanson, Jamie L; Chung, Moo K; Avants, Brian B; Shirtcliff, Elizabeth A; Gee, James C; Davidson, Richard J; Pollak, Seth D

    2010-06-02

    Individuals who experience early adversity, such as child maltreatment, are at heightened risk for a broad array of social and health difficulties. However, little is known about how this behavioral risk is instantiated in the brain. Here we examine a neurobiological contribution to individual differences in human behavior using methodology appropriate for use with pediatric populations paired with an in-depth measure of social behavior. We show that alterations in the orbitofrontal cortex among individuals who experienced physical abuse are related to social difficulties. These data suggest a biological mechanism linking early social learning to later behavioral outcomes.

  5. Subtoxic Alterations in Hepatocyte-Derived Exosomes: An Early Step in Drug-Induced Liver Injury?

    Science.gov (United States)

    Holman, Natalie S; Mosedale, Merrie; Wolf, Kristina K; LeCluyse, Edward L; Watkins, Paul B

    2016-06-01

    Drug-induced liver injury (DILI) is a significant clinical and economic problem in the United States, yet the mechanisms that underlie DILI remain poorly understood. Recent evidence suggests that signaling molecules released by stressed hepatocytes can trigger immune responses that may be common across DILI mechanisms. Extracellular vesicles released by hepatocytes, principally hepatocyte-derived exosomes (HDEs), may constitute one such signal. To examine HDE alterations as a function of drug-induced stress, this work utilized prototypical hepatotoxicant acetaminophen (APAP) in male Sprague-Dawley (SD) rats, SD rat hepatocytes, and primary human hepatocytes. HDE were isolated using ExoQuick precipitation reagent and analyzed by quantification of the liver-specific RNAs albumin and microRNA-122 (miR-122). In vivo, significant elevations in circulating exosomal albumin mRNA were observed at subtoxic APAP exposures. Significant increases in exosomal albumin mRNA were also observed in primary rat hepatocytes at subtoxic APAP concentrations. In primary human hepatocytes, APAP elicited increases in both exosomal albumin mRNA and exosomal miR-122 without overt cytotoxicity. However, the number of HDE produced in vitro in response to APAP did not increase with exosomal RNA quantity. We conclude that significant drug-induced alterations in the liver-specific RNA content of HDE occur at subtoxic APAP exposures in vivo and in vitro, and that these changes appear to reflect selective packaging rather than changes in exosome number. The current findings demonstrate that translationally relevant HDE alterations occur in the absence of overt hepatocellular toxicity, and support the hypothesis that HDE released by stressed hepatocytes may mediate early immune responses in DILI. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones.

    Directory of Open Access Journals (Sweden)

    Po-Chin Huang

    Full Text Available Previous studies revealed that phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of phthalate exposure on thyroid hormones during early pregnancy.We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl phthalate (MEP, mono-(2-ethyl-5-carboxypentyl phthalate (MECPP, mono-(2-ethylhexyl phthalate (MEHP, mono-butyl phthalate (MnBP, of 9 phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4, free T4, and thyroid-binding globulin (TBG.Three phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%, MnBP (81% and MECPP (86%. Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other phthalates of phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = -5.41; p-value = 0.012; n = 97 in pregnant women using Bonferroni correction.We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations.

  7. Breastfeeding Initiation and Duration in First-Time Mothers: Exploring the Impact of Father Involvement in the Early Post-Partum Period

    Directory of Open Access Journals (Sweden)

    Theresa Hunter

    2014-12-01

    Full Text Available Background: The early post-partum period is a crucial time for breastfeeding support. Mothers who have physical and emotional support during this period are more likely to be successful in breastfeeding. This study examined the relationship between father involvement and support for breast feeding initiation and duration in first-time mothers. Methods: Overall, 146 women who attended a childbirth education class or breastfeeding course at BABS were asked to fill out the Childbirth Experiences Survey, which explored key topics such as (1 breastfeeding initiation, (2 early post-partum breastfeeding, (3 breastfeeding plan, (4 post-partum breastfeeding support and (5 breast feeding duration. This was a voluntary self-reported questionnaire. The surveys were completed by the mothers during the post-partum period. Results: 45.9% (n=67 of mothers received helped from their husband or partner with breastfeeding while in the hospital, while 54.1% (n=79 of mothers did not receive support from their partners. Mothers who received early post-partum breastfeeding support were more likely to continue breastfeeding after leaving the hospital. Conclusion: First-time mothers who identified as having breastfeeding support from their partners, the infant’s father, during the early post-partum period were more likely to initiate breastfeeding and had longer breastfeeding durations.

  8. Multiple populations within globular clusters in Early-type galaxies Exploring their effect on stellar initial mass function estimates

    Science.gov (United States)

    Chantereau, W.; Usher, C.; Bastian, N.

    2018-05-01

    It is now well-established that most (if not all) ancient globular clusters host multiple populations, that are characterised by distinct chemical features such as helium abundance variations along with N-C and Na-O anti-correlations, at fixed [Fe/H]. These very distinct chemical features are similar to what is found in the centres of the massive early-type galaxies and may influence measurements of the global properties of the galaxies. Additionally, recent results have suggested that M/L variations found in the centres of massive early-type galaxies might be due to a bottom-heavy stellar initial mass function. We present an analysis of the effects of globular cluster-like multiple populations on the integrated properties of early-type galaxies. In particular, we focus on spectral features in the integrated optical spectrum and the global mass-to-light ratio that have been used to infer variations in the stellar initial mass function. To achieve this we develop appropriate stellar population synthesis models and take into account, for the first time, an initial-final mass relation which takes into consideration a varying He abundance. We conclude that while the multiple populations may be present in massive early-type galaxies, they are likely not responsible for the observed variations in the mass-to-light ratio and IMF sensitive line strengths. Finally, we estimate the fraction of stars with multiple populations chemistry that come from disrupted globular clusters within massive ellipticals and find that they may explain some of the observed chemical patterns in the centres of these galaxies.

  9. The analysis of initial cranial CT of early hematoma enlargement in spontaneous intracerebral hemorrhage

    OpenAIRE

    BEI Yu-zhang; CHEN Ben-yang; QI Hao-bo; ZHOU Zheng-ping; LI Yu-bo

    2012-01-01

    Objective To investigate the predictive effect of initial cranial CT on early hematoma enlargement in spontaneous intracerebral hemorrhage. Methods Three hundred patients with spontaneous intracerebral hemorrhage within 6 hours after onset were studied. Chi-square test and logistic regression analysis were used to detect the related factors which may indicate hematoma enlargement. Results Sixty-one (20.33% ) patients presented hematoma enlargement on cranial CT. Single factor and multivariate...

  10. Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

    Science.gov (United States)

    Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

    2018-02-07

    have not yet been detected. Structural and functional network metrics of regions related to reward, memory, and sensory performance were strongly correlated with the cognitive outcome. The use of animal models is essential for the early identification of these alterations and can contribute to the development of early biomarkers of the disease based on MRI connectomics.

  11. 1H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

    International Nuclear Information System (INIS)

    Zhang, Ying; Lin, Lianjie; Xu, Yanbin; Lin, Yan; Jin, Yu; Zheng, Changqing

    2013-01-01

    Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ( 1 H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected to multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC

  12. Early history of military radiology

    International Nuclear Information System (INIS)

    Eisenberg, R.L.

    1991-01-01

    This paper reports that soon after Roentgen's discovery, physicians in the armed services of the major powers grasped the importance of x-ray sin military surgery. By May of 1896, radiographic examinations were being performed on Italian soldiers returning from the ill-fated Ethiopian campaign. Initially, radiographs were used for foreign body localization and the detection of fractures; later, a full range of diagnostic services was offered. The early challenges of obtaining x-ray examinations in the field - fragility of tubes and plates, mobility of machines and patients, and unpredictability of radiation dosage - became the basis for innovations that would fundamentally alter the daily practice of radiology in civilian life

  13. Alterations in mtDNA, gastric carcinogenesis and early diagnosis.

    Science.gov (United States)

    Rodrigues-Antunes, S; Borges, B N

    2018-05-26

    Gastric cancer remains one of the most prevalent cancers in the world. Due to this, efforts are being made to improve the diagnosis of this neoplasm and the search for molecular markers that may be involved in its genesis. Within this perspective, the mitochondrial DNA is considered as a potential candidate, since it has several well documented changes and is readily accessible. However, numerous alterations have been reported in mtDNA, not facilitating the visualization of which alterations and molecular markers are truly involved with gastric carcinogenesis. This review presents a compilation of the main known changes relating mtDNA to gastric cancer and their clinical significance.

  14. Modelling glass alteration in an altered argillaceous environment

    International Nuclear Information System (INIS)

    Bildstein, O.; Trotignon, L.; Pozo, C.; Jullien, M.

    2007-01-01

    The long term behaviour of materials such as glass, steel and clay has been investigated in the context of deep geological disposal of radioactive wastes. The interactions between vitrified wastes, canister corrosion products (CPs) and clay are studied using a modified version of the reaction-transport code Crunch, especially looking at pH changes and possible cementation at the interface with the clayey materials. These perturbations may indeed affect the lifetime of glass matrix in deep repositories, e.g., high pH enhances the rate of glass alteration. This work focuses on the argillite of Bure. The calculations were performed at 323 K with a glass alteration rate switching from a high initial rate to a residual rate according to the sorption capacity of CPs. The time at which this sorption capacity is saturated is crucial to the system in terms of wastes package lifetime. The results show that the glass alteration imposes a high pH value at the interface with CPs and clay: up to a value of 9.2, compared to 7.3 which is the initial pH value in the argillite. Experimental data show that the rate of glass alteration is much higher in such pH conditions. For a R7T7-type glass, the rate is about five times higher at pH 9 than at pH 7. This pH perturbation migrates through the clayey domain as a result of the migration of mobile elements such as boron and sodium, and despite the existence of strong pH buffers in the argillite. The cementation of porosity at the interface between glass and clay is predicted by the model due to the massive precipitation of iron corrosion products and glass alteration products. At this point of the evolution of the system, the pH starts to decrease and the alteration rate of the glass could be significantly reduced. This porosity clogging effect is difficult to confirm by experiments especially since existing data on short term experiments tend to show a pervasive precipitation of silica in the domain instead of a localized precipitation

  15. Mapping advanced argillic alteration at Cuprite, Nevada, using imaging spectroscopy

    Science.gov (United States)

    Swayze, Gregg A.; Clark, Roger N.; Goetz, Alexander F.H.; Livo, K. Eric; Breit, George N.; Kruse, Fred A.; Sutley, Stephen J.; Snee, Lawrence W.; Lowers, Heather A.; Post, James L.; Stoffregen, Roger E.; Ashley, Roger P.

    2014-01-01

    Mineral maps based on Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data were used to study late Miocene advanced argillic alteration at Cuprite, Nevada. Distributions of Fe-bearing minerals, clays, micas, sulfates, and carbonates were mapped using the Tetracorder spectral-shape matching system. The Al content of white micas increases toward altered areas and near intrusive rocks. Alunite composition varies from pure K to intimate mixtures of Na-K endmembers with subpixel occurrences of huangite, the Ca analogue of alunite. Intimately mixed Na-K alunite marks areas of relatively lower alteration temperature, whereas co-occurring Na-alunite and dickite may delineate relict hydrothermal conduits. The presence of dickite, halloysite, and well-ordered kaolinite, but absence of disordered kaolinite, is consistent with acidic conditions during hydrothermal alteration. Partial lichen cover on opal spectrally mimics chalcedony, limiting its detection to lichen-free areas. Pods of buddingtonite are remnants of initial quartz-adularia-smectite alteration. Thus, spectral maps provide a synoptic view of the surface mineralogy, and define a previously unrecognized early steam-heated hydrothermal event.Faulting and episodes of hydrothermal alteration at Cuprite were intimately linked to upper plate movements above the Silver Peak-Lone Mountain detachment and growth, collapse, and resurgence of the nearby Stonewall Mountain volcanic complex between 8 and 5 Ma. Isotopic dating indicates that hydrothermal activity started at least by 7.61 Ma and ended by about 6.2 Ma. Spectral and stable isotope data suggest that Cuprite is a late Miocene low-sulfidation adularia-sericite type hot spring deposit overprinted by late-stage, steam-heated advanced argillic alteration formed along the margin of the Stonewall Mountain caldera.

  16. Growing and Supporting the Student and Early Career Pipeline in Earth and Space Sciences - A Spotlight on New AGU Initiatives

    Science.gov (United States)

    Hankin, E. R.; Williams, B. M.; Asher, P. M.; Furukawa, H.; Holm Adamec, B.; Lee, M.; Cooper, P.

    2015-12-01

    The American Geophysical Union (AGU) is home to more than 60,000 scientists from 139 countries. Included in this membership are approximately 20,000 (34%) student and early career members. Many well-established programs within AGU provide a dynamic forum for Earth and Space scientists to advance research, collaborate across disciplines, and communicate the importance and impact of science to society regardless of career stage—programs such as AGU publications, scientific meetings and conferences, honors and recognition, and other educational and scientific forums. Additionally, many AGU program initiatives focusing specifically on supporting student and early career scientists and the global talent pool pipeline ones are actively underway. These include both new and long-standing programs. This presentation will describe (1) the overall demographics and needs in Earth and Space sciences, and (2) AGU's coordinated series of programs designed to help attract, retain and support student and early career scientists—with an emphasis on new programmatic activities and initiatives targeting improved diversity. Included in this presentation are a description of the AGU BrightSTaRS Program, the AGU Berkner Program for international students, a newly established AGU Student & Early Career Conference, the AGU Virtual Poster Showcase initiative, the AGU Meeting Mentor program, and GeoLEAD—an umbrella program being jointly built by a coalition of societies to help address Earth and space sciences talent pool needs.

  17. Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis.

    Science.gov (United States)

    Diniz, Lúcio Ricardo Leite; Portella, Viviane Gomes; da Silva Alves, Kerly Shamira; Araújo, Pâmella Cristina da Costa; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Cavalcante de Albuquerque, Aline Alice; Coelho-de-Souza, Andrelina Noronha; Leal-Cardoso, José Henrique

    2018-01-01

    Nonspecific and delayed diagnosis of neurologic damage contributes to the development of neuropathies in patients with severe sepsis. The present study assessed the electrophysiologic parameters related to the excitability and conductibility of sciatic and vagus nerves during early stages of sepsis. Twenty-four hours after sepsis induced by cecal ligation and puncture (CLP) model, sciatic and vagus nerves of septic (CLP group) and control (sham group) rats were removed, and selected electric stimulations were applied to measure the parameters of the first and second components of the compound action potential. The first component originated from fibers with motor and sensory functions (Types A α and A β fibers) with a large conduction velocity (70-120 m/s), and the second component originated from fibers (Type A γ ) with sensorial function. To evaluate the presence of sensorial alterations, the sensitivity to non-noxious mechanical stimuli was measured by using the von Frey test. Hematoxylin and eosin staining of the nerves was performed. We observed an increase of rheobase followed by a decrease in the first component amplitude and a higher paw withdrawal threshold in response to the application of von Frey filaments in sciatic nerves from the CLP group compared to the sham group. Differently, a decrease in rheobase and an increase in the first component amplitude of vagal C fibers from CLP group were registered. No significant morphologic alteration was observed. Our data showed that the electrophysiologic alterations in peripheral nerves vary with the fiber type and might be identified in the first 24 h of sepsis, before clinical signs of neuromuscular disorders.

  18. Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV.

    Science.gov (United States)

    Nichols, Sharon L; Bethel, James; Kapogiannis, Bill G; Li, Tiandong; Woods, Steven P; Patton, E Doyle; Ren, Weijia; Thornton, Sarah E; Major-Wilson, Hanna O; Puga, Ana M; Sleasman, John W; Rudy, Bret J; Wilson, Craig M; Garvie, Patricia A

    2016-04-01

    Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18-24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4 treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.

  19. Early initiation of sexual activity: a risk factor for sexually transmitted diseases, HIV infection, and unwanted pregnancy among university students in China

    Directory of Open Access Journals (Sweden)

    Ravari Shahrzad

    2009-04-01

    Full Text Available Abstract Background To explore any association between the timing of the initiation of sexual activity and sexual behaviors and risks among university students in China. Methods Data were derived from a cross-sectional study on sexual behavior among university students conducted in Ningbo municipality, China, at the end of 2003. Students completed a self-administered, structured questionnaire. Of 1981 sexually active male students, 1908 (96.3% completed the item for timing of the initiation of sexual activity and were included in bivariate trend analyses and multiple logistic regression analyses to compare the association between this timing and sexual behavior and risks. Results Male early sexual initiators had a significantly higher risk profile, including a significantly higher proportion reporting non-regular partners (i.e., casual or commercial partners, multiple partners, diagnosis with a sexually transmitted disease (STD, partner history of pregnancy, partner history of induced abortion, and less condom and oral contraceptive use, compared with late initiators. Multivariate analyses confirmed the increased likelihood of these risks in early initiators versus late initiators, other than partner type during the last year. Conclusion Our results showed that, compared to late initiators, people who initiated sexual activity early engaged in more risky behaviors that could lead to elevated risks of unwanted pregnancies and STDs or human immunodeficiency virus infection. Sex-education strategies should be focused on an earlier age, should include advice on delaying the age of first sexual activity, and should target young people who continue to take sexual risks.

  20. Verbal Semantics Drives Early Anticipatory Eye Movements during the Comprehension of Verb-Initial Sentences.

    Science.gov (United States)

    Sauppe, Sebastian

    2016-01-01

    Studies on anticipatory processes during sentence comprehension often focus on the prediction of postverbal direct objects. In subject-initial languages (the target of most studies so far), however, the position in the sentence, the syntactic function, and the semantic role of arguments are often conflated. For example, in the sentence "The frog will eat the fly" the syntactic object ("fly") is at the same time also the last word and the patient argument of the verb. It is therefore not apparent which kind of information listeners orient to for predictive processing during sentence comprehension. A visual world eye tracking study on the verb-initial language Tagalog (Austronesian) tested what kind of information listeners use to anticipate upcoming postverbal linguistic input. The grammatical structure of Tagalog allows to test whether listeners' anticipatory gaze behavior is guided by predictions of the linear order of words, by syntactic functions (e.g., subject/object), or by semantic roles (agent/patient). Participants heard sentences of the type "Eat frog fly" or "Eat fly frog" (both meaning "The frog will eat the fly") while looking at displays containing an agent referent ("frog"), a patient referent ("fly") and a distractor. The verb carried morphological marking that allowed the order and syntactic function of agent and patient to be inferred. After having heard the verb, listeners fixated on the agent irrespective of its syntactic function or position in the sentence. While hearing the first-mentioned argument, listeners fixated on the corresponding referent in the display accordingly and then initiated saccades to the last-mentioned referent before it was encountered. The results indicate that listeners used verbal semantics to identify referents and their semantic roles early; information about word order or syntactic functions did not influence anticipatory gaze behavior directly after the verb was heard. In this verb-initial language, event semantics

  1. Verbal semantics drives early anticipatory eye movements during the comprehension of verb-initial sentences

    Directory of Open Access Journals (Sweden)

    Sebastian eSauppe

    2016-02-01

    Full Text Available Studies on anticipatory processes during sentence comprehension often focus on the prediction of postverbal direct objects. In subject-initial languages (the target of most studies so far, however, the position in the sentence, the syntactic function, and the semantic role of arguments are often conflated. For example, in the sentence The frog will eat the fly the syntactic object (fly is at the same time also the last word and the patient argument of the verb. It is therefore not apparent which kind of information listeners orient to for predictive processing during sentence comprehension. A visual world eye tracking study on the verb-initial language Tagalog (Austronesian tested what kind of information listeners use to anticipate upcoming postverbal linguistic input. The grammatical structure of Tagalog allows to test whether listeners' anticipatory gaze behavior is guided by predictions of the linear order of words, by syntactic functions (e.g., subject/object, or by semantic roles (agent/patient. Participants heard sentences of the type Eat frog fly or Eat fly frog (both meaning The frog will eat the fly while looking at displays containing an agent referent (frog, a patient referent (fly and a distractor. The verb carried morphological marking that allowed the order and syntactic function of agent and patient to be inferred. After having heard the verb, listeners fixated on the agent irrespective of its syntactic function or position in the sentence. While hearing the first-mentioned argument, listeners fixated on the corresponding referent in the display accordingly and then initiated saccades to the last-mentioned referent before it was encountered. The results indicate that listeners used verbal semantics to identify referents and their semantic roles early; information about word order or syntactic functions did not influence anticipatory gaze behavior directly after the verb was heard. In this verb-initial language, event semantics

  2. Challenges in Initiating Antiretroviral Therapy in 2010

    Directory of Open Access Journals (Sweden)

    Cécile L Tremblay

    2010-01-01

    Full Text Available Many clinical trials have shown that initiating antiretroviral therapy (ART at higher rather than lower CD4 T cell-positive counts results in survival benefit. Early treatment can help prevent end-organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti-retroviral agents and cardiovascular disease. As the HIV-positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient’s preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed-dose antiretroviral drug combinations can facilitate adherence.

  3. Effects of Companies’ Initiatives to Reduce Early Retirement Among Older Workers

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    Tove Midtsundstad

    2012-08-01

    Full Text Available Although active ageing policy and practice vary between countries, we believe that knowledge about the effects of Norwegian companies’ initiatives to delay early retirement is of interest for all countries striving to increase the employment rates of older workers. Since the agreement on a more inclusive working life (IW agreement was signed in 2001, the Norwegian government and social partners have encouraged companies to develop a more senior-friendly policy and implement special measures to retain older workers. In this article, we evaluate the effects of such measures. Our research question is, have preventive measures offered by companies to employees aged 62 years and older contributed to reduced rates of early retirement? We use a ‘difference-in-differences’ approach and examine whether measures at the company level to counteract early retirement actually affect older employees’ retirement decisions, controlling for different individual and enterprise factors. This is done by comparing changes and differences in the individual likelihood of early retirement on the contractual pension (AFP scheme and disability pension in the period 2002–2007 among employees 62 years of age in businesses with and without the corresponding preventive measures/instruments. The analyses show that the likelihood that a 62-year-old worker will retire on the AFP scheme has increased from 2002 to 2007. This applies equally to 62-year-old employees in enterprises that have enacted special measures to retain older workers as well as 62-year-olds in enterprises that have not enacted any such measures. On the other hand, the likelihood that a 62-year-old worker will retire because of disability decreased from 2002 to 2007, among employees in both the intervention enterprises and the control enterprises. However, when controlling for other relevant characteristics of individuals and enterprises, the analysis indicates that the measures as such have had no

  4. Misalignments of purpose and power in an early Canadian interprofessional education initiative.

    Science.gov (United States)

    Whyte, Sarah; Paradis, Elise; Cartmill, Carrie; Kuper, Ayelet; Boon, Heather; Hart, Corinne; Razack, Saleem; Pipher, Mandy; Whitehead, Cynthia R

    2017-12-01

    Interprofessional education (IPE) has been widely incorporated into health professional curricula and accreditation standards despite an arguably thin base of evidence regarding its clinical effects, theoretical underpinnings, and social implications. To better understand how and why IPE first took root, but failed to grow, this study examines one of the earliest documented IPE initiatives, which took place at the University of British Columbia between 1960 and 1975. We examined a subset of 110 texts (academic literature, grey literature, and unpublished records) from a larger study that uses Critical Discourse Analysis to trace the emergence of IPE in Canada. We asked how IPE was promoted and received, by whom, for what purposes, and to what effects. Our analysis demonstrates that IPE was promoted as a response to local challenges for the Faculty of Medicine as well as national challenges for Canada's emerging public healthcare system. These dual exigencies enabled the IPE initiative, but they shaped it in somewhat divergent ways: the former gave rise to its core component (a health sciences centre) and the latter its ultimate purpose (increasing the role of non-medical professions in primary care). Reception of the initiative was complicated by a further tension: nurses and allied health professionals were sometimes represented as independent experts with unique knowledge and skills, and sometimes as assistants or substitutes for medical doctors. We relate the successes and frustrations of this early initiative to particular (mis)alignments of purpose and relationships of power, some of which continue to enable and constrain IPE today.

  5. Early efficacy of the ketogenic diet is not affected by initial body mass index percentile.

    Science.gov (United States)

    Shull, Shastin; Diaz-Medina, Gloria; Wong-Kisiel, Lily; Nickels, Katherine; Eckert, Susan; Wirrell, Elaine

    2014-05-01

    Predictors of the ketogenic diet's success in treating pediatric intractable epilepsy are not well understood. The aim of this study was to determine whether initial body mass index and weight percentile impact early efficacy of the traditional ketogenic diet in children initiating therapy for intractable epilepsy. This retrospective study included all children initiating the ketogenic diet at Mayo Clinic, Rochester from January 2001 to December 2010 who had body mass index (children ≥2 years of age) or weight percentile (those diet initiation and seizure frequency recorded at diet initiation and one month. Responders were defined as achieving a >50% seizure reduction from baseline. Our cohort consisted of 48 patients (20 male) with a median age of 3.1 years. There was no significant correlation between initial body mass index or weight percentile and seizure frequency reduction at one month (P = 0.72, r = 0.26 and P = 0.91, r = 0.03). There was no significant association between body mass index or weight percentile quartile and responder rates (P = 0.21 and P = 0.57). Children considered overweight or obese at diet initiation (body mass index or weight percentile ≥85) did not have lower responder rates than those with body mass index or weight percentiles ketogenic diet. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Early initiation of alcohol consumption by adolescents in reconstructed families may be explained by parenting style

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    Iakunchykova, Olena

    2011-05-01

    Full Text Available BACKGROUND. Literature about risk factors of alcohol use points at the association between alcohol use and parenting style. This study investigates the relationship between family structure of adolescents in Ukraine and their initiation of alcohol use with parenting style as a mediating variable.METHODS: Pooled data from the repeated cross-sectional nationally representative survey of classes in Ukrainian secondary schools with target group of all 15-16 year old students, held in 1999, 2003, and 2007, were used for this analysis. Complete data were available for 11019 participants. Main exposures were family structure (full, single parent and reconstructed and perceptions of the relationships with mother and father, rule-setting, control, and support provided by parents. Outcome measure was age when students started consuming alcohol.RESULTS: In bivariate analysis, children in reconstructed families had higher risk for initiating alcohol use at age of 13 or younger (odds ratio 1.37, confidence interval 1,15-1,63 compared to full families. In reconstructed families, adolescents were more likely to be dissatisfied with their relationships with mother compared to intact family structure (8.7% vs. 4.7% and dissatisfied with their relationships with father compared to intact family structure (19,8% vs. 9,1%. Parental support was lacking in higher proportion of reconstructed families, compared to intact family structure (20.7% vs. 15.1%. In the multivariate analysis, controlling for relationship with mother and father, support received from parents, and socio-demographic characteristics, the association between family structure and alcohol drinking initiation was attenuated.CONCLUSIONS: Children in reconstructed families have higher risk of early drinking initiation. This study also supports the hypothesis that dissatisfaction with relationships with parents and lack of support received from parents may mediate the association between family structure

  7. Quantitative Proteomics Analysis of Altered Protein Expression in the Placental Villous Tissue of Early Pregnancy Loss Using Isobaric Tandem Mass Tags

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    Xiaobei Ni

    2014-01-01

    Full Text Available Many pregnant women suffer miscarriages during early gestation, but the description of these early pregnancy losses (EPL can be somewhat confusing because of the complexities of early development. Thus, the identification of proteins with different expression profiles related to early pregnancy loss is essential for understanding the comprehensive pathophysiological mechanism. In this study, we report a gel-free tandem mass tags- (TMT- labeling based proteomic analysis of five placental villous tissues from patients with early pregnancy loss and five from normal pregnant women. The application of this method resulted in the identification of 3423 proteins and 19647 peptides among the patient group and the matched normal control group. Qualitative and quantitative proteomic analysis revealed 51 proteins to be differentially abundant between the two groups (≥1.2-fold, Student's t-test, P<0.05. To obtain an overview of the biological functions of the proteins whose expression levels altered significantly in EPL group, gene ontology analysis was performed. We also investigated the twelve proteins with a difference over 1.5-fold using pathways analysis. Our results demonstrate that the gel-free TMT-based proteomic approach allows the quantification of differences in protein expression levels, which is useful for obtaining molecular insights into early pregnancy loss.

  8. Anatomical correlates of cognitive functions in early Parkinson's disease patients.

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    Roberta Biundo

    Full Text Available Cognitive deficits may occur early in Parkinson's disease (PD but the extent of cortical involvement associated with cognitive dysfunction needs additional investigations. The aim of our study is to identify the anatomical pattern of cortical thickness alterations in patients with early stage PD and its relationship with cognitive disability.We recruited 29 PD patients and 21 healthy controls. All PD patients performed an extensive neuropsychological examination and 14 were diagnosed with mild cognitive impairment (PD-MCI. Surface-based cortical thickness analysis was applied to investigate the topographical distribution of cortical and subcortical alterations in early PD compared with controls and to assess the relationship between cognition and regional cortical changes in PD-MCI.Overall PD patients showed focal cortical (occipital-parietal areas, orbito-frontal and olfactory areas and subcortical thinning when compared with controls. PD-MCI showed a wide spectrum of cognitive deficits and related significant regional thickening in the right parietal-frontal as well as in the left temporal-occipital areas.Our results confirm the presence of changes in grey matter thickness at relatively early PD stage and support previous studies showing thinning and atrophy in the neocortex and subcortical regions. Relative cortical thickening in PD-MCI may instead express compensatory neuroplasticity. Brain reserve mechanisms might first modulate cognitive decline during the initial stages of PD.

  9. Does interspecific competition alter effects of early season ozone exposure on plants from wet grasslands? Results of a three-year experiment in open-top chambers

    NARCIS (Netherlands)

    Tonneijck, A.E.G.; Franzaring, J.; Brouwer, G.; Metselaar, K.; Dueck, T.A.

    2004-01-01

    Chronic effects of ozone on wet grassland species early in the growing season might be altered by interspecific competition. Individual plants of Holcus lanatus, Lychnis flos-cuculi, Molinia caerulea and Plantago lanceolata were grown in monocultures and in mixed cultures with Agrostis capillaris.

  10. Transhepatic Balloon Dilatation of Early Biliary Strictures in Pediatric Liver Transplantation: Successful Initial and Mid-Term Outcome

    International Nuclear Information System (INIS)

    Belenky, Alexander; Mor, Eytan; Bartal, Gabriel; Atar, Eli; Shapiro, Riki; Bar-Nathan, Nathan; Bachar, Gil N.

    2004-01-01

    Purpose: To evaluate the initial and mid-term outcomes of transhepatic balloon dilatation for the treatment of early biliary strictures in lateral left-segment liver transplants in young children.Methods: Between April 1997 and May 2001, seven children aged 9 months to 6 years with nine benign strictures in left-segment liver grafts were treated percutaneously. Sessions of two or three dilations were performed three or four times at average intervals of 10-20 days. In each session, the biliary stenoses were gradually dilated using balloons of 3-7 mm. Follow-up ranged from 12 to 54 months (mean 27 months, median 12 months). Clinical success was defined as resolution of the stenosis, normalization of liver enzymes and lack of clinical symptoms. Results: Technical success was achieved in all nine strictures. Hemobilia occurred in one patient and was successfully treated. On follow-up, all patients had complete clinical recovery with normalization of liver function and imaging of patent bile ducts. Conclusion: Balloon dilatation is an effective and relatively safe method for the treatment of early biliary strictures in left-segment liver transplantation in young children. We recommend this approach as the initial treatment for early strictures. Metal stents or surgery should be reserved for patients with late appearance of strictures or failure of balloon dilatation

  11. Increased Pre- and Early-Adolescent Stress in Youth with a Family History of Substance Use Disorder and Early Substance Use Initiation.

    Science.gov (United States)

    Charles, Nora E; Mathias, Charles W; Acheson, Ashley; Bray, Bethany C; Ryan, Stacy R; Lake, Sarah L; Liang, Yuanyuan; Dougherty, Donald M

    2015-10-01

    Individuals with a family history of substance use disorders (Family History Positive) are more likely to have early-onset substance use (i.e., prior to age 15), which may contribute to their higher rates of substance use disorders. One factor that may differentiate Family History Positive youth who engage in early-onset substance use from other Family History Positive youth is exposure to stressors. The aim of this study was to quantify how exposure to stressors from age 11-15 varies as a function of family history of substance use disorders and early-onset substance use. Self-reported stressors were prospectively compared in a sample of predominately (78.9%) Hispanic youth that included 68 Family History Positive youth (50% female) who initiated substance use by age 15 and demographically matched non-users with (n = 136; 52.9% female) and without (n = 75; 54.7% female) family histories of substance use disorders. Stressors were assessed at 6-month intervals for up to 4 years. Both the severity of stressors and the degree to which stressors were caused by an individual's own behavior were evaluated. All three groups differed from one another in overall exposure to stressors and rates of increase in stressors over time, with Family History Positive youth who engaged in early-onset substance use reporting the greatest exposure to stressors. Group differences were more pronounced for stressors caused by the participants' behavior. Family History Positive users had higher cumulative severity of stressors of this type, both overall and across time. These results indicate greater exposure to stressors among Family History Positive youth with early-onset substance use, and suggest that higher rates of behavior-dependent stressors may be particularly related to early-onset use.

  12. The developmental progression of age 14 behavioral disinhibition, early age of sexual initiation, and subsequent sexual risk-taking behavior.

    Science.gov (United States)

    Samek, Diana R; Iacono, William G; Keyes, Margaret A; Epstein, Marina; Bornovalova, Marina A; McGue, Matt

    2014-07-01

    Research has demonstrated a consistent relationship between early sexual experience and subsequent sexual risk-taking behaviors. We hypothesized that this relationship is due to a general predisposition toward behavioral disinhibition (BD), and that relationships among BD, early sex, and subsequent risky sexual behavior may be influenced by common genetic influences for males and common environmental influences for females. A prospective sample of 1,512 same-sex adolescent twins (50.2% female) was used. Adolescent BD was measured by clinical symptom counts of conduct disorder, oppositional defiant disorder, and self-reported delinquent behavior (age 14). Age of sexual initiation was defined as first age of consensual oral or penetrative sex (mean age ~17). Adult risky sexual behavior was defined by sexual behaviors under the influence of drugs and alcohol and number of casual sexual partners in the past year (age 24). Multivariate analyses showed evidence for substantial common genetic variance among age 14 BD, age at sexual initiation, and adult risky sexual behavior for males, but not females. There was no significant difference in the degree of common environmental influence on these variables for females compared to males. Notably, age of sexual initiation was not significantly correlated with age 24 risky sexual behavior for females. The relationship between early sex and later risky sex can be better understood through a general liability toward BD, which is influenced primarily by genetic factors for males. The association between age 14 BD and age of sexual initiation was influenced through a combination of genetic and environmental factors for females; however, age of sexual initiation does not appear to be a salient predictor of adult women’s sexual risk-taking behavior. Findings suggest that prevention programs aimed at reducing sexual risk behavior might target youth exhibiting BD by age 14, particularly males. More research is needed on what predicts

  13. Determinants of HIV-induced brain changes in three different periods of the early clinical course: A data mining analysis

    Directory of Open Access Journals (Sweden)

    Bokai Cao

    2015-01-01

    Full Text Available To inform an understanding of brain status in HIV infection, quantitative imaging measurements were derived at structural, microstructural and macromolecular levels in three different periods of early infection and then analyzed simultaneously at each stage using data mining. Support vector machine recursive feature elimination was then used for simultaneous analysis of subject characteristics, clinical and behavioral variables, and immunologic measures in plasma and CSF to rank features associated with the most discriminating brain alterations in each period. The results indicate alterations beginning in initial infection and in all periods studied. The severity of immunosuppression in the initial virus host interaction was the most highly ranked determinant of earliest brain alterations. These results shed light on the initial brain changes induced by a neurotropic virus and their subsequent evolution. The pattern of ongoing alterations occurring during and beyond the period in which virus is suppressed in the systemic circulation supports the brain as a viral reservoir that may preclude eradication in the host. Data mining capabilities that can address high dimensionality and simultaneous analysis of disparate information sources have considerable utility for identifying mechanisms underlying onset of neurological injury and for informing new therapeutic targets.

  14. Neuroanatomical Alterations in Patients with Early Stage of Unilateral Pulsatile Tinnitus: A Voxel-Based Morphometry Study

    Directory of Open Access Journals (Sweden)

    Yawen Liu

    2018-01-01

    Full Text Available During the past several years, the rapid development of neuroimaging techniques has contributed greatly in the noninvasive imaging studies of tinnitus. The aim of the present study was to explore the brain anatomical alterations in patients with right-sided unilateral pulsatile tinnitus (PT in the early stage of PT symptom using voxel-based morphometry (VBM analysis. Twenty-four patients with right-sided pulsatile tinnitus and 24 age- and gender-matched normal controls were recruited to this study. Structural image data preprocessing was performed using VBM8 toolbox. Tinnitus Handicap Inventory (THI score was acquired in the tinnitus group to assess the severity of tinnitus and tinnitus-related distress. Two-sample t-test and Pearson’s correlation analysis were used in statistical analysis. Patients with unilateral pulsatile tinnitus had significantly increased gray matter (GM volume in bilateral superior temporal gyrus compared with the normal controls. However, the left cerebellum posterior lobe, left frontal superior orbital lobe (gyrus rectus, right middle occipital gyrus (MOG, and bilateral putamen showed significantly decreased brain volumes. This was the first study which demonstrated the features of neuroanatomical changes in patients with unilateral PT during their early stages of the symptom.

  15. Early social deprivation impairs pair bonding and alters serum corticosterone and the NAcc dopamine system in mandarin voles.

    Science.gov (United States)

    Yu, Peng; An, Shucheng; Tai, Fadao; Wang, Jianli; Wu, Ruiyong; Wang, Bo

    2013-12-01

    Early life stress has a long-term negative impact on emotion, learning, memory and adult sexual behavior, and these deficits most likely impair pair bonding. Here, we investigated whether early social deprivation (ED) affects the formation of pair bonds in socially monogamous mandarin voles (Microtus mandarinus). In a partner preference test (PPT), ED-reared adult females and males did not show a preference for their partner, spent more time exploring the cage of an unfamiliar animal and directed high levels of aggression toward unfamiliar animals. In social interaction test, ED increased exploring behavior only in females, but increased movement around the partner and reduced inactivity in both males and females. Three days of cohabitation did not alter serum corticosterone levels in ED-reared males, but increased corticosterone levels in males that received bi-parental care (PC). Interestingly, serum corticosterone levels in ED- and PC-reared females declined after cohabitation. ED significantly increased basal serum corticosterone levels in males, but had no effect on females. ED significantly up-regulated the levels of dopamine and the mRNA expression of dopamine 1-type receptor (D1R) in the nucleus accumbens (NAcc) in females and males. ED suppressed dopamine 2-type receptor mRNA (D2R) expression in females, but increased this in males. After three days of cohabitation, levels of D1R mRNA and D2R mRNA expression changed in opposite directions in PC-reared voles, but in the same direction in ED-reared males, and only the expression of D2R mRNA increased in ED-reared females. Our results indicate that early social deprivation inhibits pair bonding at adulthood. This inhibition is possibly associated with sex-specific alterations in serum corticosterone, levels of dopamine and mRNA expression of two types of dopamine receptors in the NAcc. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Psychosocial predictors of sexual initiation and high-risk sexual behaviors in early adolescence

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    Schwab-Stone Mary

    2007-11-01

    Full Text Available Abstract Background This longitudinal study examined psychosocial factors associated with risky sexual behavior in early adolescence. Methods Data were collected through a self-report survey, the Social and Health Assessment (SAHA, which was administered in three waves between 2001 and 2003 to a cohort of incoming sixth grade students in the public school system (149 classes at 17 middle and high schools, N = 1,175 of a small northeastern city in the United States. We first examined whether internalizing and externalizing problems in sixth grade, and the rate of change in these factors during middle school, were predictive of sexual initiation two years later, when most of the sample was in eighth grade. We then assessed whether internalizing and externalizing problems in sixth grade, and the rate of change in these factors during middle school, were predictive of engaging in high risk sexual behavior over the subsequent two years. Results Externalizing factors are more predictive of sexual risk in early adolescence than are internalizing factors. Specifically, substance use and violent delinquency over the course of middle school were associated with higher, while anxiety with lower, sexual initiation rates during middle school. Additionally, increased substance use over the course of middle school was associated with greater likelihood of engaging in high risk sexual behavior. Conclusion By identifying particular psychosocial risk factors among young adolescents, the findings of this study have implications for designing multi-dimensional programs aimed at preventing health-compromising sexual behavior among young teens.

  17. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    International Nuclear Information System (INIS)

    Herring, M.J.; Putney, L.F.; St George, J.A.; Avdalovic, M.V.; Schelegle, E.S.; Miller, L.A.; Hyde, D.M.

    2015-01-01

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O 3 ) or HDMA/ozone (HDMA + O 3 ) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O 3 alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)

  18. An fMRI-study of locally oriented perception in autism: altered early visual processing of the block design test.

    Science.gov (United States)

    Bölte, S; Hubl, D; Dierks, T; Holtmann, M; Poustka, F

    2008-01-01

    Autism has been associated with enhanced local processing on visual tasks. Originally, this was based on findings that individuals with autism exhibited peak performance on the block design test (BDT) from the Wechsler Intelligence Scales. In autism, the neurofunctional correlates of local bias on this test have not yet been established, although there is evidence of alterations in the early visual cortex. Functional MRI was used to analyze hemodynamic responses in the striate and extrastriate visual cortex during BDT performance and a color counting control task in subjects with autism compared to healthy controls. In autism, BDT processing was accompanied by low blood oxygenation level-dependent signal changes in the right ventral quadrant of V2. Findings indicate that, in autism, locally oriented processing of the BDT is associated with altered responses of angle and grating-selective neurons, that contribute to shape representation, figure-ground, and gestalt organization. The findings favor a low-level explanation of BDT performance in autism.

  19. Chronophin activation is necessary in Doxorubicin-induced actin cytoskeleton alteration.

    Science.gov (United States)

    Lee, Su Jin; Park, Jeen Woo; Kang, Beom Sik; Lee, Dong-Seok; Lee, Hyun-Shik; Choi, Sooyoung; Kwon, Oh-Shin

    2017-06-01

    Although doxorubicin (Dox)-induced oxidative stress is known to be associated with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals, but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations, resulting in central stress fiber disruption at early time points and cell periphery cortical actin formation at a later stage, in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In addition, a novel interaction between CIN and 14-3-3ζ was detected in the absence of Dox treatment. We demonstrated that CIN activity is quite contrary to 14-3-3ζ binding, and the interaction leads to enhanced phosphorylated cofilin levels. Therefore, initial CIN activation regulation could be critical in Dox-induced actin cytoskeleton remodeling through RhoA/cofilin signaling. [BMB Reports 2017; 50(6): 335-340].

  20. Are Persistent Early Onset Child Conduct Problems Predicted by the Trajectories and Initial Levels of Discipline Practices?

    Science.gov (United States)

    Lorber, Michael F.; Slep, Amy M. Smith

    2015-01-01

    In the present investigation we focused on 2 broad sets of questions: Do parental overreactivity, laxness, and corporal punishment show evidence of normative change in early to middle childhood? Are persistently elevated child conduct problems (CPs) associated with deviations from normative changes in, as well as high initial levels of, discipline…

  1. [Markers for early detection of alterations in carbohydrate metabolism after acute myocardial infarction].

    Science.gov (United States)

    de Gea-García, J H; Benali, L; Galcerá-Tomás, J; Padilla-Serrano, A; Andreu-Soler, E; Melgarejo-Moreno, A; Alonso-Fernández, N

    2014-03-01

    Undiagnosed abnormal glucose metabolism is often seen in patients admitted with acute myocardial infarction, although there is no consensus on which patients should be studied with a view to establishing an early diagnosis. The present study examines the potential of certain variables obtained upon admission to diagnose abnormal glucose metabolism. A prospective cohort study was carried out. The Intensive Care Unit of Arrixaca University Hospital (Murcia), Spain. A total of 138 patients admitted to the Intensive Care Unit with acute myocardial infarction and without known or de novo diabetes mellitus. After one year, oral glucose tolerance testing was performed. Clinical and laboratory test parameters were recorded upon admission and one year after discharge. Additionally, after one year, oral glucose tolerance tests were made, and a study was made of the capacity of the variables obtained at admission to diagnose diabetes, based on the ROC curves and multivariate analysis. Of the 138 patients, 112 (72.5%) had glucose metabolic alteration, including 16.7% with diabetes. HbA1c was independently associated with a diagnosis of diabetes (RR: 7.28, 95%CI 1.65 to 32.05, P = .009), and showed the largest area under the ROC curve for diabetes (0.81, 95%CI 0.69 to 0.92, P = .001). In patients with acute myocardial infarction, HbA1c helps identify those individuals with abnormal glucose metabolism after one year. Thus, its determination in this group of patients could be used to identify those subjects requiring a more exhaustive study in order to establish an early diagnosis. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  2. Feasibility of Early-Initiated Progressive Resistance Training after Total Hip Replacement

    DEFF Research Database (Denmark)

    Mikkelsen, Lone Ramer; Mechlenburg, Inger; Petersen, Annemette Krintel

    during the exercises were measured at each training session. Isometric muscle strength was measured before and 4 weeks after the THR. Findings / Results: Pain during exercises and resting pain before and after each training session was unchanged or decreased during the 4 weeks of training. Averaged...... across exercises pain during training decreased from 3.6 (sd: 2.8) at the first session to 1.52 (sd: 1.8) VAS-mm at the last session, ptraining load increased progressively for all 4 exercises during the 4 weeks of training. For example: 2nd, 5th and 8th training session. Hip......Background: Muscle atrophy, reduced hip muscle strength and function are documented within the first weeks after Total Hip Replacement (THR). Purpose / Aim of Study: The purpose of this study was to evaluate the feasibility of early-initiated progressive resistance training (PRT) after THR...

  3. Early adolescent adversity inflates threat estimation in females and promotes alcohol use initiation in both sexes.

    Science.gov (United States)

    Walker, Rachel A; Andreansky, Christopher; Ray, Madelyn H; McDannald, Michael A

    2018-06-01

    Childhood adversity is associated with exaggerated threat processing and earlier alcohol use initiation. Conclusive links remain elusive, as childhood adversity typically co-occurs with detrimental socioeconomic factors, and its impact is likely moderated by biological sex. To unravel the complex relationships among childhood adversity, sex, threat estimation, and alcohol use initiation, we exposed female and male Long-Evans rats to early adolescent adversity (EAA). In adulthood, >50 days following the last adverse experience, threat estimation was assessed using a novel fear discrimination procedure in which cues predict a unique probability of footshock: danger (p = 1.00), uncertainty (p = .25), and safety (p = .00). Alcohol use initiation was assessed using voluntary access to 20% ethanol, >90 days following the last adverse experience. During development, EAA slowed body weight gain in both females and males. In adulthood, EAA selectively inflated female threat estimation, exaggerating fear to uncertainty and safety, but promoted alcohol use initiation across sexes. Meaningful relationships between threat estimation and alcohol use initiation were not observed, underscoring the independent effects of EAA. Results isolate the contribution of EAA to adult threat estimation, alcohol use initiation, and reveal moderation by biological sex. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  4. Initiatives on early detection and intervention to proactively identify health and social problems in older people: experiences from the Netherlands.

    Science.gov (United States)

    Lette, Manon; Baan, Caroline A; van den Berg, Matthijs; de Bruin, Simone R

    2015-10-30

    Over the last years, several initiatives on early detection and intervention have been put in place to proactively identify health and social problems in (frail) older people. An overview of the initiatives currently available in the Netherlands is lacking, and it is unknown whether they meet the preferences and needs of older people. Therefore, the objectives of this study were threefold: 1. To identify initiatives on early detection and intervention for older people in the Netherlands and compare their characteristics; 2. To explore the experiences of professionals with these initiatives; and 3. To explore to what extent existing initiatives meet the preferences and needs of older people. We performed a qualitative descriptive study in which we conducted semi-structured interviews with seventeen experts in preventive elderly care and three group interviews with volunteer elderly advisors. Data were analysed using the framework analysis method. We identified eight categories of initiatives based on the setting (e.g. general practitioner practice, hospital, municipality) in which they were offered. Initiatives differed in their aims and target groups. The utilization of peers to identify problems and risks, as was done by some initiatives, was seen as a strength. Difficulties were experienced with identifying the target group that would benefit from proactive delivery of care and support most, and with addressing prevalent issues among older people (e.g. psychosocial issues, self-reliance issues). Although there is a broad array of initiatives available, there is a discrepancy between supply and demand. Current initiatives insufficiently address needs of (frail) older people. More insight is needed in "what should be done by whom, for which target group and at what moment", in order to improve current practice in preventive elderly care.

  5. Early life exposure to allergen and ozone results in altered development in adolescent rhesus macaque lungs

    Energy Technology Data Exchange (ETDEWEB)

    Herring, M.J.; Putney, L.F.; St George, J.A. [California National Primate Research Center, Davis, CA (United States); Avdalovic, M.V. [Department of Internal Medicine, Division of Pulmonary and Critical Care, University of California, Davis, CA (United States); Schelegle, E.S.; Miller, L.A. [California National Primate Research Center, Davis, CA (United States); Hyde, D.M., E-mail: dmhyde@ucdavis.edu [California National Primate Research Center, Davis, CA (United States)

    2015-02-15

    In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergen (HDMA), ozone (O{sub 3}) or HDMA/ozone (HDMA + O{sub 3}) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O{sub 3} alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)

  6. Rates and determinants of early initiation of breastfeeding and exclusive breast feeding at 42 days postnatal in six low and middle-income countries: A prospective cohort study.

    Science.gov (United States)

    Patel, Archana; Bucher, Sherri; Pusdekar, Yamini; Esamai, Fabian; Krebs, Nancy F; Goudar, Shivaprasad S; Chomba, Elwyn; Garces, Ana; Pasha, Omrana; Saleem, Sarah; Kodkany, Bhalachandra S; Liechty, Edward A; Kodkany, Bhala; Derman, Richard J; Carlo, Waldemar A; Hambidge, K; Goldenberg, Robert L; Althabe, Fernando; Berrueta, Mabel; Moore, Janet L; McClure, Elizabeth M; Koso-Thomas, Marion; Hibberd, Patricia L

    2015-01-01

    Early initiation of breastfeeding after birth and exclusive breastfeeding through six months of age confers many health benefits for infants; both are crucial high impact, low-cost interventions. However, determining accurate global rates of these crucial activities has been challenging. We use population-based data to describe: (1) rates of early initiation of breastfeeding (defined as within 1 hour of birth) and of exclusive breastfeeding at 42 days post-partum; and (2) factors associated with failure to initiate early breastfeeding and exclusive breastfeeding at 42 days post-partum. Prospectively collected data from women and their live-born infants enrolled in the Global Network's Maternal and Newborn Health Registry between January 1, 2010-December 31, 2013 included women-infant dyads in 106 geographic areas (clusters) at 7 research sites in 6 countries (Kenya, Zambia, India [2 sites], Pakistan, Argentina and Guatemala). Rates and risk factors for failure to initiate early breastfeeding were investigated for the entire cohort and rates and risk factors for failure to maintain exclusive breastfeeding was assessed in a sub-sample studied at 42 days post-partum. A total of 255,495 live-born women-infant dyads were included in the study. Rates and determinants for the exclusive breastfeeding sub-study at 42 days post-partum were assessed from among a sub-sample of 105,563 subjects. Although there was heterogeneity by site, and early initiation of breastfeeding after delivery was high, the Pakistan site had the lowest rates of early initiation of breastfeeding. The Pakistan site also had the highest rate of lack of exclusive breastfeeding at 42 days post-partum. Across all regions, factors associated with failure to initiate early breastfeeding included nulliparity, caesarean section, low birth weight, resuscitation with bag and mask, and failure to place baby on the mother's chest after delivery. Factors associated with failure to achieve exclusive breastfeeding

  7. The EGU Seismology Division Early Career Scientist Representative team and its initiatives

    Science.gov (United States)

    Parisi, Laura; Ermert, Laura; Gualtieri, Lucia; Spieker, Kathrin; Van Noten, Koen; Agius, Matthew R.; Mai, P. Martin

    2017-04-01

    Since 2014, the Seismology Division (SM) of the European Geosciences Union (EGU) has its Early Career Scientist (ECS) representative to reach out to its numerous 'younger' members. In April 2016, a new team of representatives joined the Division. We are a vivid team of early career scientists, representing both (either) PhD students and post-doctoral researchers working in different seismological disciplines and different countries. The initiatives of the SM ECS-rep team have various aims: (1) to motivate the ECSs to get involved in activities and initiatives of the EGU and the Seismology Division, (2) to promote the research of ECSs, (3) to discuss issues concerning seismologists during this particular stage of their career, (4) to share ideas on how to promote equality between scientists and (5) to improve on the public dissemination of scientific knowledge. In an effort to reach out to experienced and ECS seismologists more effectively and to continuously encourage to voice their ideas by contributing and following our initiatives, a blog and social media pages dedicated to seismology and earthquake trivia are run by the team. Weekly posts are published on the blog and shared on the social media regarding scientific and social aspects of seismology. One of the major contributions recently introduced to the blog is the "Paper of the Month" series where experienced seismologists write about recent or classical - must read - seismology articles. We also aim to organise and promote social and scientific events. During the EGU General Assembly 2016 a social event was held in Vienna allowing ECS to network with peers in an informal environment. Given the success of this event, a similar event will be organized during the General Assembly 2017. Also, similar to previous years, a short course on basic seismology for non seismologists will be requested and offered to all ECSs attending the General Assembly. Finally, a workshop dedicated entirely to ECSs seismologists

  8. Sensory Deprivation during Early Postnatal Period Alters the Density of Interneurons in the Mouse Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Hiroshi Ueno

    2015-01-01

    Full Text Available Early loss of one sensory system can cause improved function of other sensory systems. However, both the time course and neuronal mechanism of cross-modal plasticity remain elusive. Recent study using functional MRI in humans suggests a role of the prefrontal cortex (PFC in cross-modal plasticity. Since this phenomenon is assumed to be associated with altered GABAergic inhibition in the PFC, we have tested the hypothesis that early postnatal sensory deprivation causes the changes of inhibitory neuronal circuit in different regions of the PFC of the mice. We determined the effects of sensory deprivation from birth to postnatal day 28 (P28 or P58 on the density of parvalbumin (PV, calbindin (CB, and calretinin (CR neurons in the prelimbic, infralimbic, and dorsal anterior cingulate cortices. The density of PV and CB neurons was significantly increased in layer 5/6 (L5/6. Moreover, the density of CR neurons was higher in L2/3 in sensory deprived mice compared to intact mice. These changes were more prominent at P56 than at P28. These results suggest that long-term sensory deprivation causes the changes of intracortical inhibitory networks in the PFC and the changes of inhibitory networks in the PFC may contribute to cross-modal plasticity.

  9. Children's Alcohol Initiation: An Analytic Overview

    Science.gov (United States)

    Ward, Bernadette; Snow, Pamela; Aroni, Rosalie

    2010-01-01

    Many parents support the "supervised introduction" of alcohol to children. While initiation to regular alcohol consumption in early adolescence has been linked with alcohol-related problems in adult life, the findings from these studies cannot be extrapolated to early childhood. The definition of initiation to alcohol in early childhood is often…

  10. Early transcriptional changes in cardiac mitochondria during chronic doxorubicin exposure and mitigation by dexrazoxane in mice

    Energy Technology Data Exchange (ETDEWEB)

    Vijay, Vikrant; Moland, Carrie L.; Han, Tao; Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lee, Taewon [Department of Mathematics, Korea University, Sejong (Korea, Republic of); Herman, Eugene H. [Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850-9734 (United States); Jenkins, G. Ronald [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Cummings, Connie A. [UltraPath Imaging, 2228 Page Road, Durham, NC 27703 (United States); Gao, Yuan; Cao, Zhijun; Yu, Li-Rong [Biomarkers and Alternative Models Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

    2016-03-15

    Identification of early biomarkers of cardiotoxicity could help initiate means to ameliorate the cardiotoxic actions of clinically useful drugs such as doxorubicin (DOX). Since DOX has been shown to target mitochondria, transcriptional levels of mitochondria-related genes were evaluated to identify early candidate biomarkers in hearts of male B6C3F{sub 1} mice given a weekly intravenous dose of 3 mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively). Also, a group of mice was pretreated (intraperitoneally) with the cardio-protectant, dexrazoxane (DXZ; 60 mg/kg) 30 min before each weekly dose of DOX or SAL. At necropsy a week after the last dose, increased plasma concentrations of cardiac troponin T (cTnT) were detected at 18 and 24 mg/kg cumulative DOX doses, whereas myocardial alterations were observed only at the 24 mg/kg dose. Of 1019 genes interrogated, 185, 109, 140, 184, and 451 genes were differentially expressed at 6, 9, 12, 18, and 24 mg/kg cumulative DOX doses, respectively, compared to concurrent SAL-treated controls. Of these, expression of 61 genes associated with energy metabolism and apoptosis was significantly altered before and after occurrence of myocardial injury, suggesting these as early genomics markers of cardiotoxicity. Much of these DOX-induced transcriptional changes were attenuated by pretreatment of mice with DXZ. Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. This information on early transcriptional changes during DOX treatment may be useful in designing cardioprotective strategies targeting mitochondria. - Highlights: • Altered mitochondria-related gene expression before heart injury by doxorubicin • Dexrazoxane mitigated doxorubicin-induced early expression changes in mitochondria. • Dexrazoxane completely ameliorated doxorubicin-induced pathology in mouse heart.

  11. Alterations in biomechanical properties and microstructure of colon wall in early-stage experimental colitis.

    Science.gov (United States)

    Gong, Xiaohui; Xu, Xiaojuan; Lin, Sisi; Cheng, Yu; Tong, Jianhua; Li, Yongyu

    2017-08-01

    The aim of the current study was to investigate the effects of early-stage dextran sodium sulfate (DSS)-induced mouse colitis on the biomechanical properties and microstructure of colon walls. In the present study, colitis was induced in 8-week-old mice by the oral administration of DSS, and then 10 control and 10 experimental colitis samples were harvested. Uniaxial tensile tests were performed to measure the ultimate tensile strength and ultimate stretches of colon tissues. In addition, histological investigations were performed to characterize changes in the microstructure of the colon wall following treatment. The results revealed that the ultimate tensile stresses were 232±33 and 183±25 kPa for the control and DSS groups, respectively (P=0.001). Ultimate stretches at rupture for the control and DSS groups were 1.43±0.04 and 1.51±0.06, respectively (P=0.006). However, there was no statistically significant difference in tissue stiffness between the two groups. Histological analysis demonstrated high numbers of inflammatory cells infiltrated into the stroma in the DSS group, leading to significant submucosa edema. Hyperplasia was also identified in the DSS-treated submucosa, causing a disorganized microstructure within the colon wall. Furthermore, a large number of collagen fibers in the DSS-treated muscular layer were disrupted, and fiber bundles were thinner when compared with the control group. In conclusion, early-stage experimental colitis alters the mechanical properties and microstructural characteristics of the colon walls, further contributing to tissue remodeling in the pathological process.

  12. FDG PET/CT in initial staging and early response to chemotherapy assessment of paediatric rhabdomyosarcomas

    International Nuclear Information System (INIS)

    Eugene, T.; Ansquer, C.; Oudoux, A.; Carlier, T.; Kraeber-Bodere, T.; Bodet-Milin, C.; Corradini, N.; Thomas, C.; Dupas, B.

    2010-01-01

    Purpose: The objective of this study was to retrospectively evaluate the impact of positron emission tomography/computed tomography (PET/CT) using fluorine-18-fluorodeoxyglucose (FDG), in comparison with conventional imaging modalities (CIM), for initial staging and early therapy assessment in paediatric rhabdomyosarcoma. Patients and methods: Prior to treatment, 18 patients (age range, 9 months to 18 years) with histologically proven rhabdomyosarcoma underwent FDG PET/CT in addition to CIM (magnetic resonance imaging of primary site, whole body CT and bone scintigraphy). After three courses of chemotherapy, 12 patients underwent FDG PET/CT in addition to CIM. RECIST criteria and visual analysis of FDG uptake were used for assessment of response. The standard of reference was determined by an interdisciplinary tumor board based on imaging material, histopathology and follow-up data (median = 5 years). Results: PET/CT sensitivity was superior to CIM's concerning lymph node involvement (100% versus 83%, respectively) and metastases detection (100% versus 50%, respectively). PET/CT results changed therapeutic management in 11% of cases. After three courses of chemotherapy, the rate of complete response was 66% with PET/CT versus 8% with CIM. Five percent of patients relapsed during follow-up (median = 5 years). Conclusion: This study confirms that PET/CT depicts important additional information in initial staging of paediatric rhabdomyosarcomas and suggests a superior prognostic value of PET/CT in early response to chemotherapy assessment. (authors)

  13. Early canine plaque biofilms: characterization of key bacterial interactions involved in initial colonization of enamel.

    Directory of Open Access Journals (Sweden)

    Lucy J Holcombe

    Full Text Available Periodontal disease (PD is a significant problem in dogs affecting between 44% and 63.6% of the population. The main etiological agent for PD is plaque, a microbial biofilm that colonizes teeth and causes inflammation of the gingiva. Understanding how this biofilm initiates on the tooth surface is of central importance in developing interventions against PD. Although the stages of plaque development on human teeth have been well characterized little is known about how canine plaque develops. Recent studies of the canine oral microbiome have revealed distinct differences between the canine and human oral environments and the bacterial communities they support, particularly with respect to healthy plaque. These differences mean knowledge about the nature of plaque formation in humans may not be directly translatable to dogs. The aim of this study was to identify the bacterial species important in the early stages of canine plaque formation in vivo and then use isolates of these species in a laboratory biofilm model to develop an understanding of the sequential processes which take place during the initial colonization of enamel. Supra-gingival plaque samples were collected from 12 dogs at 24 and 48 hour time points following a full mouth descale and polish. Pyrosequencing of the 16S rDNA identified 134 operational taxonomic units after statistical analysis. The species with the highest relative abundance were Bergeyella zoohelcum, Neisseria shayeganii and a Moraxella species. Streptococcal species, which tend to dominate early human plaque biofilms, had very low relative abundance. In vitro testing of biofilm formation identified five primary colonizer species, three of which belonged to the genus Neisseria. Using these pioneer bacteria as a starting point, viable two and three species communities were developed. Combining in vivo and in vitro data has led us to construct novel models of how the early canine plaque biofilm develops.

  14. Coherent Active-Sterile Neutrino Flavor Transformation in the Early Universe

    Science.gov (United States)

    Kishimoto, Chad T.; Fuller, George M.; Smith, Christel J.

    2006-10-01

    We solve the problem of coherent Mikheyev-Smirnov-Wolfenstein resonant active-to-sterile neutrino flavor conversion driven by an initial lepton number in the early Universe. We find incomplete destruction of the lepton number in this process and a sterile neutrino energy distribution with a distinctive cusp and high energy tail. These features imply alteration of the nonzero lepton number primordial nucleosynthesis paradigm when there exist sterile neutrinos with rest masses ms˜1eV. This could result in better light element probes of (constraints on) these particles.

  15. Coherent Active-Sterile Neutrino Flavor Transformation in the Early Universe

    International Nuclear Information System (INIS)

    Kishimoto, Chad T.; Fuller, George M.; Smith, Christel J.

    2006-01-01

    We solve the problem of coherent Mikheyev-Smirnov-Wolfenstein resonant active-to-sterile neutrino flavor conversion driven by an initial lepton number in the early Universe. We find incomplete destruction of the lepton number in this process and a sterile neutrino energy distribution with a distinctive cusp and high energy tail. These features imply alteration of the nonzero lepton number primordial nucleosynthesis paradigm when there exist sterile neutrinos with rest masses m s ∼1 eV. This could result in better light element probes of (constraints on) these particles

  16. Early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats.

    Directory of Open Access Journals (Sweden)

    Emmanuel Somm

    Full Text Available Poor fetal growth, also known as intrauterine growth restriction (IUGR, is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN. Physiological (glucose and insulin tolerance, morphometric (automated tissue image analysis and transcriptomic (quantitative PCR approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.

  17. A survey of critical care nurses' practices and perceptions surrounding early intravenous antibiotic initiation during septic shock.

    Science.gov (United States)

    Roberts, Russel J; Alhammad, Abdullah M; Crossley, Lindsay; Anketell, Eric; Wood, LeeAnn; Schumaker, Greg; Garpestad, Erik; Devlin, John W

    2017-08-01

    Delays in antibiotic administration after severe sepsis recognition increases mortality. While physician and pharmacy-related barriers to early antibiotic initiation have been well evaluated, those factors that affect the speed by which critical care nurses working in either the emergency department or the intensive care unit setting initiate antibiotic therapy remains poorly characterized. To evaluate the knowledge, practices and perceptions of critical care nurses regarding antibiotic initiation in patients with newly recognised septic shock. A validated survey was distributed to 122 critical care nurses at one 320-bed academic institution with a sepsis protocol advocating intravenous(IV) antibiotic initiation within 1hour of shock recognition. Among 100 (82%) critical care nurses responding, nearly all (98%) knew of the existence of the sepsis protocol. However, many critical care nurses stated they would optimise blood pressure [with either fluid (38%) or both fluid and a vasopressor (23%)] before antibiotic initiation. Communicated barriers to rapid antibiotic initiation included: excessive patient workload (74%), lack of awareness IV antibiotic(s) ordered (57%) or delivered (69%), need for administration of multiple non-antibiotic IV medications (54%) and no IV access (51%). Multiple nurse-related factors influence IV antibiotic(s) initiation speed and should be incorporated into sepsis quality improvement efforts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

    Science.gov (United States)

    Grinsztejn, Beatriz; Hosseinipour, Mina C; Ribaudo, Heather J; Swindells, Susan; Eron, Joseph; Chen, Ying Q; Wang, Lei; Ou, San-San; Anderson, Maija; McCauley, Marybeth; Gamble, Theresa; Kumarasamy, Nagalingeshwaran; Hakim, James G; Kumwenda, Johnstone; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; de Melo, Marineide Gonçalves; Mayer, Kenneth H; Eshleman, Susan H; Piwowar-Manning, Estelle; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Sanne, Ian; Gallant, Joel; Hoffman, Irving; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David; Essex, Max; Havlir, Diane; Cohen, Myron S

    2014-01-01

    Summary Background Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. Methods The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. Findings 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group

  19. Abrogation of Early Apoptosis Does Not Alter Late Inhibition of Hippocampal Neurogenesis After Irradiation

    International Nuclear Information System (INIS)

    Li Yuqing; Aubert, Isabelle; Wong, C. Shun

    2010-01-01

    Purpose: Irradiation of the adult brain results in acute apoptosis of neural progenitors and vascular endothelial cells, as well as late dysfunction of neural progenitors and inhibition of neurogenesis. We sought to determine whether the early apoptotic response has a causative role in late inhibition of neurogenesis after cranial irradiation. Methods and Materials: Using a genetic approach with p53 and smpd1 transgenic mice and a pharmacologic approach with basic fibroblast growth factor (bFGF) to abrogate the early apoptotic response, we evaluated the late inhibition of neurogenesis in the hippocampal dentate gyrus after cranial irradiation. Results: In dentate gyrus, subgranular neural progenitors underwent p53-dependent apoptosis within 24 h after irradiation. Despite a near abrogation of neural progenitor apoptosis in p53-/- mice, the reduction in newborn neurons in dentate gyrus at 9 weeks after irradiation in p53-/- mice was not different from that observed in wildtype controls. Endothelial cell apoptosis after radiation is mediated by membrane damage initiated by activation of acid sphingomyelinase (ASMase). Deletion of the smpd1 gene (which encodes ASMase) attenuated the apoptotic response of endothelial cells. At 9 weeks after irradiation, the inhibition of hippocampal neurogenesis was not rescued by ASMase deficiency. Intravenous administration of bFGF protected both endothelial cells and neural progenitors against radiation-induced apoptosis. There was no protection against inhibition of neurogenesis at 9 weeks after irradiation in bFGF-treated mice. Conclusion: Early apoptotic death of neural progenitors, endothelial cells, or both does not have a causative association with late inhibition of neurogenesis after irradiation.

  20. Preparing beginning reading teachers: An experimental comparison of initial early literacy field experiences.

    Science.gov (United States)

    Al Otaiba, Stephanie; Lake, Vickie E; Greulich, Luana; Folsom, Jessica S; Guidry, Lisa

    2012-01-01

    This randomized-control trial examined the learning of preservice teachers taking an initial Early Literacy course in an early childhood education program and of the kindergarten or first grade students they tutored in their field experience. Preservice teachers were randomly assigned to one of two tutoring programs: Book Buddies and Tutor Assisted Intensive Learning Strategies (TAILS), which provided identical meaning-focused instruction (shared book reading), but differed in the presentation of code-focused skills. TAILS used explicit, scripted lessons, and the Book Buddies required that code-focused instruction take place during shared book reading. Our research goal was to understand which tutoring program would be most effective in improving knowledge about reading, lead to broad and deep language and preparedness of the novice preservice teachers, and yield the most successful student reading outcomes. Findings indicate that all pre-service teachers demonstrated similar gains in knowledge, but preservice teachers in the TAILS program demonstrated broader and deeper application of knowledge and higher self-ratings of preparedness to teach reading. Students in both conditions made similar comprehension gains, but students tutored with TAILS showed significantly stronger decoding gains.

  1. Early adverse life events are associated with altered brain network architecture in a sex- dependent manner

    Directory of Open Access Journals (Sweden)

    Arpana Gupta, PhD

    2017-12-01

    Full Text Available Introduction: Early adverse life events (EALs increase the risk for chronic medical and psychiatric disorders by altering early neurodevelopment. The aim of this study was to examine associations between EALs and network properties of core brain regions in the emotion regulation and salience networks, and to test the influence of sex on these associations. Methods: Resting-state functional and diffusion tensor magnetic resonance imaging were obtained in healthy individuals (61 men, 63 women. Functional and anatomical network properties of centrality and segregation were calculated for the core regions of the two networks using graph theory. Moderator analyses were applied to test hypotheses. Results: The type of adversity experienced influences brain wiring differently, as higher general EALs were associated with decreased functional and anatomical centrality in salience and emotion regulation regions, while physical and emotional EALs were associated with increased anatomical centrality and segregation in emotion regulation regions. Sex moderated the associations between EALs and measures of centrality; with decreased centrality of salience and emotion regulation regions with increased general EALs in females, and increased centrality in salience regions with higher physical and emotional EALs in males. Increased segregation of salience regions was associated with increased general EALs in males. Centrality of the amygdala was associated with physical symptoms, and segregation of salience regions was correlated with higher somatization in men only. Conclusions: Emotion regulation and salience regions are susceptible to topological brain restructuring associated with EALs. The male and female brains appear to be differently affected by specific types of EALs. Keywords: Early adverse traumatic life events, Centrality, Segregation, Network metrics, Moderating effects of sex, Emotion regulation network, Salience network

  2. A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury

    DEFF Research Database (Denmark)

    Karvellas, Constantine J; Farhat, Maha R; Sajjad, Imran

    2011-01-01

    Introduction: Our aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI). Methods: Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web ...

  3. What do we really know about early diagenesis of non-marine carbonates?

    Science.gov (United States)

    De Boever, Eva; Brasier, Alexander T.; Foubert, Anneleen; Kele, Sándor

    2017-11-01

    Non-marine carbonate rocks including cave, spring, stream, calcrete and lacustrine-palustrine sediments, are susceptible to early diagenetic processes. These can profoundly alter the carbonate fabric and affect paleoclimatic proxies. This review integrates recent insights into diagenesis of non-marine carbonates and in particular the variety of early diagenetic processes, and presents a conceptual framework to address them. With ability to study at smaller and smaller scales, down to nanometers, one can now observe diagenesis taking place the moment initial precipitates have formed, and continuing thereafter. Diagenesis may affect whole rocks, but it typically starts in nano- and micro-environments. The potential for diagenetic alteration depends on the reactivity of the initial precipitate, commonly being metastable phases like vaterite, Ca-oxalates, hydrous Mg-carbonates and aragonite with regard to the ambient fluid. Furthermore, organic compounds commonly play a crucial role in hosting these early transformations. Processes like neomorphism (inversion and recrystallization), cementation and replacement generally result in an overall coarsening of the fabric and homogenization of the wide range of complex, primary microtextures. If early diagenetic modifications are completed in a short time span compared to the (annual to millennial) time scale of interest, then recorded paleoenvironmental signals and trends could still acceptably reflect original, depositional conditions. However, even compact, non-marine carbonate deposits may behave locally and temporarily as open systems to crystal-fluid exchange and overprinting of one or more geochemical proxies is not unexpected. Looking to the future, relatively few studies have examined the behaviour of promising geochemical records, such as clumped isotope thermometry and (non-conventional) stable isotopes, in well-constrained diagenetic settings. Ongoing and future in-vitro and in-situ experimental approaches will

  4. Neuronal redox imbalance results in altered energy homeostasis and early postnatal lethality.

    Science.gov (United States)

    Maity-Kumar, Gandhari; Thal, Dietmar R; Baumann, Bernd; Scharffetter-Kochanek, Karin; Wirth, Thomas

    2015-07-01

    Redox imbalance is believed to contribute to the development and progression of several neurodegenerative disorders. Our aim was to develop an animal model that exhibits neuron-specific oxidative stress in the CNS to study the consequences and eventually find clues regarding the pathomechanisms of oxidative insults in neuronal homeostasis. We therefore generated a novel neuron-specific superoxide dismutase 2 (SOD2)-deficient mouse by deleting exon 3 of the SOD2 gene using CamKIIα promoter-driven Cre expression. These neuron-specific SOD2 knockout (SOD2(nko)) mice, although born at normal frequencies, died at the age of 4 weeks with critical growth retardation, severe energy failure, and several neurologic phenotypes. In addition, SOD2(nko) mice exhibited severe neuronal alterations such as reactive astrogliosis, neuronal cell cycle inhibition, and induction of apoptosis. JNK activation and stabilization of p53, as a result of reactive oxygen species accumulation, are most likely the inducers of neuronal apoptosis in SOD2(nko) mice. It is remarkable that hypothalamic regulation of glucose metabolism was affected, which in turn induced necrotic brain lesions in SOD2(nko) mice. Taken together, our findings suggest that exclusive deficiency of SOD2 in neurons results in an impaired central regulation of energy homeostasis that leads to persistent hypoglycemia, hypoglycemia-related neuropathology, and an early lethality of the mutant mice. © FASEB.

  5. Impact of nutritional stress on early embryonic survival

    Directory of Open Access Journals (Sweden)

    Sukanta Mondal

    2015-09-01

    Full Text Available Background: Low reproductive efficiency is the most critical problem faced by the livestock industry across the globe. Early embryonic loss is one the major cause of poor reproductive efficiency resulting in delayed pregnancy, fewer calves born, reduced milk production, slower genetic progress and substantial financial loss to the beef or dairy industry. The establishment of pregnancy results from the interaction between the embryo and the dam and is the culmination of a series of events initiated with development of the follicle and gametes. Among numerous internal and external factors nutrition has the potency to alter the micro-environment of the oocyte and the embryo, making it more hostile to optimal fertilization and pre-implantation embryonic growth. Understanding the impact of nutritional stress on oocyte function, embryo development and reciprocal signaling networks between the embryo and uterus will lead to alleviation of the problems of early embryonic mortality.

  6. Entropy Growth in the Early Universe and Confirmation of Initial Big Bang Conditions

    Science.gov (United States)

    Beckwith, Andrew

    2009-09-01

    This paper shows how increased entropy values from an initially low big bang level can be measured experimentally by counting relic gravitons. Furthermore the physical mechanism of this entropy increase is explained via analogies with early-universe phase transitions. The role of Jack Ng's (2007, 2008a, 2008b) revised infinite quantum statistics in the physics of gravitational wave detection is acknowledged. Ng's infinite quantum statistics can be used to show that ΔS~ΔNgravitons is a startmg point to the increasing net universe cosmological entropy. Finally, in a nod to similarities AS ZPE analysis, it is important to note that the resulting ΔS~ΔNgravitons ≠ 1088, that in fact it is much lower, allowing for evaluating initial graviton production as an emergent field phenomena, which may be similar to how ZPE states can be used to extract energy from a vacuum if entropy is not maximized. The rapid increase in entropy so alluded to without near sudden increases to 1088 may be enough to allow successful modeling of relic graviton production for entropy in a manner similar to ZPE energy extraction from a vacuum state.

  7. Alteration, age, and emplacement of the Tangihua Complex ophiolite, New Zealand

    International Nuclear Information System (INIS)

    Nicholson, K.N.; Black, P.M.; Picard, C.; Cooper, P.; Hall, C.M.; Itaya, T.

    2007-01-01

    The Tangihua Complex, New Zealand, represents an upper sequence of Late Cretaceous oceanic crustal material: massive basalt flows, pillow lavas, and dolerites. Three phases of alteration are preserved within the complex, each characterised by zeolite precipitation, which correlate to stratigraphic position. The mylonitised sole contains greenschist assemblages (c. 325 degrees C) grading upwards into the initial phase of alteration (250-300 degrees C), and is characterised by actinolite, epidote, albite, and Na-rich zeolites. This phase is cut by lower temperature veins of chlorite-smectite and Ca-rich zeolites. The final alteration phase ( + and Ca 2+ rich minerals, including apophyllite and calcite. Disruption of Ar/Ar spectra around 50 Ma correlate with rifting in the Loyalty Basin and initiation of obduction along the Loyalty-Three Kings Ridge system. We suggest that these events resulted in initial dismemberment, alteration, and movement of the ophiolite, whereas Ar/Ar plateaux at 25-35 Ma correspond to ophiolite emplacement and the last phases of alteration. (author). 49 refs., 5 figs., 3 tabs

  8. Physiological alterations associated with intrauterine growth restriction in fetal pigs: Causes and insights for nutritional optimization.

    Science.gov (United States)

    Wang, Junjun; Feng, Cuiping; Liu, Ting; Shi, Meng; Wu, Guoyao; Bazer, Fuller W

    2017-09-01

    Intrauterine growth restriction (IUGR) remains a major problem in swine production since the associated low birth weight leads to high rates of pre-weaning morbidity and mortality plus permanent retardation of growth and development. Complex biological events-including genetics, epigenetics, maternal maturity, maternal nutrition, placenta efficiency, uterine capacity, and other environmental factors-can affect fetal growth and development during late gestation, as well as maturity of oocytes, duration of estrus, and both implantation and placentation of conceptuses in uteri of sows. Understanding the physiological changes related to initiation and progress of IUGR are, therefore, of great importance to formulate nutritional strategies that can mitigate IUGR in gilts and sows. Altering the nutritional status of sows prior to mating and during early-, mid-, and late-gestation may be effective at increasing the uniformity of oocytes and conceptuses, decreasing variation among conceptuses during elongation and implantation, and preventing increases in within-litter variation in fetal weights during late gestation. This review summarizes current progress on physiological alterations responsible for IUGR fetuses, as well as possible nutritional interventions to prevent the initiation and continuation of IUGR in gilts and sows. © 2017 Wiley Periodicals, Inc.

  9. INITIAL BREEDING MATERIAL OF VEGETABLE BEAN FOR DEVELOPMENT OF EARLY-RIPENING VARIETIES IN NORTH PART OF FOREST STEPPE OF THE UKRAINE

    Directory of Open Access Journals (Sweden)

    E. N. Grishenko

    2015-01-01

    Full Text Available The collection of vegetable bean varieties was screened for duration of vegetative and interstage periods. The initial breeding material as a source of early-ripeness was selected.

  10. Longitudinal Associations Among Religiousness, Delay Discounting, and Substance Use Initiation in Early Adolescence.

    Science.gov (United States)

    Kim-Spoon, Jungmeen; McCullough, Michael E; Bickel, W K; Farley, Julee P; Longo, Gregory S

    2015-03-01

    Prior research indicates that religiousness is related negatively to adolescent health risk behaviors, yet how such protective effects operate is not well understood. This study examined the longitudinal associations among organizational and personal religiousness, delay discounting, and substance use initiation (alcohol, cigarette, and marijuana use). The sample comprised 106 early adolescents (10-13 years of age, 52% female) who were not using substances at Time 1. Path analyses suggested that high levels of personal religiousness at Time 1 were related to low levels of substance use at Time 2 (2.4 years later), mediated by low levels of delay discounting. Delay discounting appears to be an important contributor to the protective effect of religiousness on the development of substance use among adolescents.

  11. Altered frontal cortical volume and decision making in adolescent cannabis users

    Directory of Open Access Journals (Sweden)

    John C Churchwell

    2010-12-01

    Full Text Available Anticipating future outcomes is central to decision making and a failure to consider long-term consequences may lead to impulsive choices. Adolescence is a vulnerable period during which underdeveloped prefrontal cortical systems may contribute to poor judgment, impulsive choices, and substance abuse. Conversely, substance abuse during this period may alter neural systems involved in decision making and lead to greater impulsivity. Although a broad neural network which supports decision making undergoes extensive change during adolescent development, one region that may be critical is the medial prefrontal cortex. Altered functional integrity of this region may be specifically related to reward perception, substance abuse, and dependence. In the present investigation, we acquired structural magnetic resonance images (MRI, using a 3T Siemens Trio scanner, from 18 cannabis abusing adolescents (CA; 2 female and 16 male subjects; mean age, 17.7 years; range 16-19 years and 18 healthy controls (HC; 6 female and 12 male subjects; mean age, 17.2 years; range 16-19 years. In order to measure medial orbital prefrontal cortex (moPFC morphology related to substance abuse and impulsivity, semi-automated cortical reconstruction and volumetric segmentation of MRIs was performed with FreeSurfer. Impulsivity was evaluated with the Barratt Impulsiveness Scale (BIS. Our results indicate that cannabis abusing adolescents have decreased right moPFC volume compared to controls, p =.01, d = .92, CI.95 = .21, 1.59. Cannabis abusing adolescents also show decreased future orientation, as indexed by the BIS nonplanning subscale, when compared to controls, p = .01, d = .89, CI.95 = .23, 1.55. Moreover, total moPFC volume was positively correlated with age of first use (18 = .49, p < .03, suggesting that alterations in this region may be related to initiation of cannabis use or that early initiation may lead to reduced moPFC volume.

  12. A different view on the checkerboard? Alterations in early and late visually evoked EEG potentials in Asperger observers.

    Directory of Open Access Journals (Sweden)

    Juergen Kornmeier

    Full Text Available BACKGROUND: Asperger Autism is a lifelong psychiatric condition with highly circumscribed interests and routines, problems in social cognition, verbal and nonverbal communication, and also perceptual abnormalities with sensory hypersensitivity. To objectify both lower-level visual and cognitive alterations we looked for differences in visual event-related potentials (EEG between Asperger observers and matched controls while they observed simple checkerboard stimuli. METHODS: In a balanced oddball paradigm checkerboards of two checksizes (0.6° and 1.2° were presented with different frequencies. Participants counted the occurrence times of the rare fine or rare coarse checkerboards in different experimental conditions. We focused on early visual ERP differences as a function of checkerboard size and the classical P3b ERP component as an indicator of cognitive processing. RESULTS: We found an early (100-200 ms after stimulus onset occipital ERP effect of checkerboard size (dominant spatial frequency. This effect was weaker in the Asperger than in the control observers. Further a typical parietal/central oddball-P3b occurred at 500 ms with the rare checkerboards. The P3b showed a right-hemispheric lateralization, which was more prominent in Asperger than in control observers. DISCUSSION: The difference in the early occipital ERP effect between the two groups may be a physiological marker of differences in the processing of small visual details in Asperger observers compared to normal controls. The stronger lateralization of the P3b in Asperger observers may indicate a stronger involvement of the right-hemispheric network of bottom-up attention. The lateralization of the P3b signal might be a compensatory consequence of the compromised early checksize effect. Higher-level analytical information processing units may need to compensate for difficulties in low-level signal analysis.

  13. Early life nutrition, epigenetics and programming of later life disease.

    Science.gov (United States)

    Vickers, Mark H

    2014-06-02

    The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA) and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how these effects may be

  14. Early Life Nutrition, Epigenetics and Programming of Later Life Disease

    Directory of Open Access Journals (Sweden)

    Mark H. Vickers

    2014-06-01

    Full Text Available The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how

  15. Leverage of an Existing Cervical Cancer Prevention Service Platform to Initiate Breast Cancer Control Services in Zambia: Experiences and Early Outcomes

    Directory of Open Access Journals (Sweden)

    Leeya F. Pinder

    2017-09-01

    Full Text Available Purpose: In 2005, the Cervical Cancer Prevention Program in Zambia (CCPPZ was implemented and has since provided cervical cancer screen-and-treat services to more than 500,000 women. By leveraging the successes and experiences of the CCPPZ, we intended to build capacity for the early detection and surgical treatment of breast cancer. Methods: Our initiative sought to build capacity for breast cancer care through the (1 formation of a breast cancer advocacy alliance to raise awareness, (2 creation of resource-appropriate breast cancer care training curricula for mid- and high-level providers, and (3 implementation of early detection and treatment capacity within two major health care facilities. Results: Six months after the completion of the initiative, the following outcomes were documented: Breast health education and clinical breast examination (CBE services were successfully integrated into the service platforms of four CCPPZ clinics. Two new breast diagnostic centers were opened, which provided access to breast ultrasound, ultrasound-guided core needle biopsy, and needle aspiration. Breast health education and CBE were provided to 1,955 clients, 167 of whom were evaluated at the two diagnostic centers; 55 of those evaluated underwent core-needle biopsy, of which 17 were diagnosed with invasive cancer. Newly trained surgeons performed six sentinel lymph node mappings, eight sentinel lymph node dissections, and 10 breast conservation surgeries (lumpectomies. Conclusion: This initiative successfully established clinical services in Zambia that are critical for the early detection and surgical management of breast cancer.

  16. The effects of pre-natal-, early-life- and indirectly-initiated exposures to maximum adversities on the course of schizophrenia.

    Science.gov (United States)

    Levine, Stephen Z; Levav, Itzhak; Yoffe, Rinat; Pugachova, Inna

    2014-09-01

    The effects of pre-natal-, early-life- and indirectly-initiated exposures to protracted maximum adversity on the course of schizophrenia are unknown. To compare the aforementioned Holocaust directly exposed subgroups with an indirectly exposed subgroup on the course of schizophrenia. The study population were: Israeli Jews in-uterus or born in Nazi-occupied or dominated European nations by the end of the persecution of the Jews, who were alive in 1950, and who had a last discharge diagnosis of schizophrenia in the Israel National Psychiatric Case Registry by 2013 (N=4933). The population was disaggregated into subgroups who (1) migrated after WWII and who had (1a) pre-natal (n=584, 11.8%) and (1b) early-life (n=3709, 75.2%) initiated exposures to the maximum adversities of the Holocaust, and (2) indirectly exposed individuals to the Holocaust who migrated before the Nazi-era persecution begun (n=640, 13%). Recurrent event survival analyses were computed to examine the psychiatric re-hospitalization risk of the study subgroups, unadjusted and adjusted for age of onset of the disorder and sex. The pre-natal initiated exposure subgroup had a significantly (pPoland-born individuals, the years 1922 and 1935; and followed at least 10 years and to the year 2000. Pre-natal initiated exposure to the maximal adversity of the holocaust constitutes a consistent risk factor for a worse course of schizophrenia, a possible byproduct of neurodevelopment disruptions induced by maternal stress and/or famine and/or infections. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  18. Initiation of genome instability and preneoplastic processes through loss of Fhit expression.

    Directory of Open Access Journals (Sweden)

    Joshua C Saldivar

    Full Text Available Genomic instability drives tumorigenesis, but how it is initiated in sporadic neoplasias is unknown. In early preneoplasias, alterations at chromosome fragile sites arise due to DNA replication stress. A frequent, perhaps earliest, genetic alteration in preneoplasias is deletion within the fragile FRA3B/FHIT locus, leading to loss of Fhit protein expression. Because common chromosome fragile sites are exquisitely sensitive to replication stress, it has been proposed that their clonal alterations in cancer cells are due to stress sensitivity rather than to a selective advantage imparted by loss of expression of fragile gene products. Here, we show in normal, transformed, and cancer-derived cell lines that Fhit-depletion causes replication stress-induced DNA double-strand breaks. Using DNA combing, we observed a defect in replication fork progression in Fhit-deficient cells that stemmed primarily from fork stalling and collapse. The likely mechanism for the role of Fhit in replication fork progression is through regulation of Thymidine kinase 1 expression and thymidine triphosphate pool levels; notably, restoration of nucleotide balance rescued DNA replication defects and suppressed DNA breakage in Fhit-deficient cells. Depletion of Fhit did not activate the DNA damage response nor cause cell cycle arrest, allowing continued cell proliferation and ongoing chromosomal instability. This finding was in accord with in vivo studies, as Fhit knockout mouse tissue showed no evidence of cell cycle arrest or senescence yet exhibited numerous somatic DNA copy number aberrations at replication stress-sensitive loci. Furthermore, cells established from Fhit knockout tissue showed rapid immortalization and selection of DNA deletions and amplifications, including amplification of the Mdm2 gene, suggesting that Fhit loss-induced genome instability facilitates transformation. We propose that loss of Fhit expression in precancerous lesions is the first step in the

  19. Early Childhood Workforce Index, 2016

    Science.gov (United States)

    Whitebook, Marcy; McLean, Caitlin; Austin, Lea J. E.

    2016-01-01

    The State of the Early Childhood Workforce (SECW) Initiative is a groundbreaking multi-year project to shine a steady spotlight on the nation's early childhood workforce. The SECW Initiative is designed to challenge entrenched ideas and policies that maintain an inequitable and inadequate status quo for early educators and for the children and…

  20. The Early-Career Development of Science Teachers from Initial Training Onwards: The Advantages of a Multifaceted Five-Year Programme

    Science.gov (United States)

    Clarke, Julian; Howarth, Sue; King, Chris; Perry, John; Tas, Maarten; Twidle, John; Warhurst, Adrian; Garrett, Caro

    2014-01-01

    If a programme were to be devised for the early-career development of science teachers, what might such a programme look like? This was the focus of a meeting of science educators interested in developing such a structure, from the start of initial teacher training onwards. The contributions, modified and written up here, include a suggested…

  1. Early initiation of alcohol drinking, cigarette smoking, and sexual intercourse linked to suicidal ideation and attempts: findings from the 2006 Korean Youth Risk Behavior Survey.

    Science.gov (United States)

    Kim, Dong-Sik; Kim, Hyun-Sun

    2010-01-01

    This study examined the association between early initiation of problem behaviors (alcohol drinking, cigarette smoking, and sexual intercourse) and suicidal behaviors (suicidal ideation and suicide attempts), and explored the effect of concurrent participation in these problem behaviors on suicidal behaviors among Korean adolescent males and females. Data were obtained from the 2006 Korean Youth Risk Behavior Survey, a nationally representative sample of middle and high school students (32,417 males and 31,467 females) in grades seven through twelve. Bivariate and multivariate logistic analyses were conducted. Several important covariates, such as age, family living structure, household economic status, academic performance, current alcohol drinking, current cigarette smoking, current butane gas or glue sniffing, perceived body weight, unhealthy weight control behaviors, subjective sleep evaluation, and depressed mood were included in the analyses. Both male and female preteen initiators of each problem behavior were at greater risk for suicidal behaviors than non-initiators, even after controlling for covariates. More numerous concurrent problematic behaviors were correlated with greater likelihood of seriously considering or attempting suicide among both males and females. This pattern was more clearly observed in preteen than in teen initiators although the former and latter were engaged in the same frequency of problem behavior. Early initiation of alcohol drinking, cigarette smoking, and sexual intercourse, particularly among preteens, represented an important predictor of later suicidal ideation and suicide attempts in both genders. Thus, early preventive intervention programs should be developed and may reduce the potential risks for subsequent suicidal behaviors.

  2. Psychosocial factors associated with early initiation and frequency of antenatal care (ANC) visits in a rural and urban setting in South Africa: a cross-sectional survey.

    Science.gov (United States)

    Muhwava, Lorrein Shamiso; Morojele, Neo; London, Leslie

    2016-01-25

    Late booking and infrequent antenatal care (ANC) are common but avoidable patient-related risk factors for maternal deaths in South Africa. The aim of the study was to examine the association of psychosocial factors with early initiation of ANC and adequate frequency of attendance of ANC clinics among women in an urban and rural location in South Africa. Data from a 2006 cross-sectional household survey of 363 women from the rural Western Cape and 466 women from urban Gauteng provinces of South Africa for risk of alcohol-exposed pregnancy were analysed. We examined associations between psychosocial variables (self-esteem, cultural influences, religiosity, social capital, social support, pregnancy desire (wanted versus unwanted pregnancy), partner characteristics and mental health) and both early ANC first visit (before 16 weeks) and adequate frequency of ANC visits (4 or more visits) for respondents' last pregnancy. Overall prevalence among urban women of early ANC initiation was 46% and 84% for adequate ANC frequency. Overall prevalence among rural women of early ANC initiation was 45% and 78% for adequate ANC frequency. After adjusting for clustering, psychosocial factors associated with early ANC initiation in the urban site were being employed (OR 1.6; 95% CI 1.0-2.5) and wanted pregnancy (OR 1.8; 95% CI 1.1-3.0). For the rural site, early ANC initiation was significantly associated with being married (OR 1.93; 95% CI 1.0-3.6) but inversely associated with high religiosity (OR 0.5; 95% CI 0.3-0.8). Adequate frequency of ANC attendance in the rural site was associated with wanted pregnancy (OR 4.2; 95% CI 1.9-9.3) and the father of the child being present in the respondent's life (OR 3.0; 95% CI 1.0-9.0) but inversely associated with having a previous miscarriage (OR 0.4; 95% CI 0.2-0.8). There were no significant associations between adequate ANC attendance and the psychosocial factors in the urban site. The majority of women from both sites attended ANC

  3. Early-onset sleep defects in Drosophila models of Huntington's disease reflect alterations of PKA/CREB signaling

    Science.gov (United States)

    Gonzales, Erin D.; Tanenhaus, Anne K.; Zhang, Jiabin; Chaffee, Ryan P.; Yin, Jerry C.P.

    2016-01-01

    Huntington's disease (HD) is a progressive neurological disorder whose non-motor symptoms include sleep disturbances. Whether sleep and activity abnormalities are primary molecular disruptions of mutant Huntingtin (mutHtt) expression or result from neurodegeneration is unclear. Here, we report Drosophila models of HD exhibit sleep and activity disruptions very early in adulthood, as soon as sleep patterns have developed. Pan-neuronal expression of full-length or N-terminally truncated mutHtt recapitulates sleep phenotypes of HD patients: impaired sleep initiation, fragmented and diminished sleep, and nighttime hyperactivity. Sleep deprivation of HD model flies results in exacerbated sleep deficits, indicating that homeostatic regulation of sleep is impaired. Elevated PKA/CREB activity in healthy flies produces patterns of sleep and activity similar to those in our HD models. We were curious whether aberrations in PKA/CREB signaling were responsible for our early-onset sleep/activity phenotypes. Decreasing signaling through the cAMP/PKA pathway suppresses mutHtt-induced developmental lethality. Genetically reducing PKA abolishes sleep/activity deficits in HD model flies, restores the homeostatic response and extends median lifespan. In vivo reporters, however, show dCREB2 activity is unchanged, or decreased when sleep/activity patterns are abnormal, suggesting dissociation of PKA and dCREB2 occurs early in pathogenesis. Collectively, our data suggest that sleep defects may reflect a primary pathological process in HD, and that measurements of sleep and cAMP/PKA could be prodromal indicators of disease, and serve as therapeutic targets for intervention. PMID:26604145

  4. Caesarean section delivery and breastfeeding initiation at the ...

    African Journals Online (AJOL)

    Background: Caesarean section (CS) presents a challenge for early breastfeeding of the newborn infant. It is expected that with the Baby Friendly Hospital Initiative (BFHI), mothers who deliver by CS can be helped to initiate breastfeeding early. Objectives: This study aims to determine the time of initiation of breastfeeding in ...

  5. Congenital heart malformations induced by hemodynamic altering surgical interventions

    Directory of Open Access Journals (Sweden)

    Madeline eMidgett

    2014-08-01

    Full Text Available Embryonic heart formation results from a dynamic interplay between genetic and environmental factors. Blood flow during early embryonic stages plays a critical role in heart development, as interactions between flow and cardiac tissues generate biomechanical forces that modulate cardiac growth and remodeling. Normal hemodynamic conditions are essential for proper cardiac development, while altered blood flow induced by surgical manipulations in animal models result in heart defects similar to those seen in humans with congenital heart disease. This review compares the altered hemodynamics, changes in tissue properties, and cardiac defects reported after common surgical interventions that alter hemodynamics in the early chick embryo, and shows that interventions produce a wide spectrum of cardiac defects. Vitelline vein ligation and left atrial ligation decrease blood pressure and flow; and outflow tract banding increases blood pressure and flow velocities. These three surgical interventions result in many of the same cardiac defects, which indicate that the altered hemodynamics interfere with common looping, septation and valve formation processes that occur after intervention and that shape the four-chambered heart. While many similar defects develop after the interventions, the varying degrees of hemodynamic load alteration among the three interventions also result in varying incidence and severity of cardiac defects, indicating that the hemodynamic modulation of cardiac developmental processes is strongly dependent on hemodynamic load.

  6. Altered hypothalamic protein expression in a rat model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    Full Text Available Huntington's disease (HD is a neurodegenerative disorder, which is characterized by progressive motor impairment and cognitive alterations. Changes in energy metabolism, neuroendocrine function, body weight, euglycemia, appetite function, and circadian rhythm can also occur. It is likely that the locus of these alterations is the hypothalamus. We used the HD transgenic (tg rat model bearing 51 CAG repeats, which exhibits similar HD symptomology as HD patients to investigate hypothalamic function. We conducted detailed hypothalamic proteome analyses and also measured circulating levels of various metabolic hormones and lipids in pre-symptomatic and symptomatic animals. Our results demonstrate that there are significant alterations in HD rat hypothalamic protein expression such as glial fibrillary acidic protein (GFAP, heat shock protein-70, the oxidative damage protein glutathione peroxidase (Gpx4, glycogen synthase1 (Gys1 and the lipid synthesis enzyme acylglycerol-3-phosphate O-acyltransferase 1 (Agpat1. In addition, there are significant alterations in various circulating metabolic hormones and lipids in pre-symptomatic animals including, insulin, leptin, triglycerides and HDL, before any motor or cognitive alterations are apparent. These early metabolic and lipid alterations are likely prodromal signs of hypothalamic dysfunction. Gaining a greater understanding of the hypothalamic and metabolic alterations that occur in HD, could lead to the development of novel therapeutics for early interventional treatment of HD.

  7. Elucidation of Altered Pathways in Tumor-Initiating Cells of Triple-Negative Breast Cancer: A Useful Cell Model System for Drug Screening.

    Science.gov (United States)

    Christensen, Anne G; Ehmsen, Sidse; Terp, Mikkel G; Batra, Richa; Alcaraz, Nicolas; Baumbach, Jan; Noer, Julie B; Moreira, José; Leth-Larsen, Rikke; Larsen, Martin R; Ditzel, Henrik J

    2017-08-01

    of pathways associated with cell viability, and CSCs are the major differences between tumor-initiating and nontumorigenic cells independent of their epithelial-like/mesenchymal-like phenotype. These altered pathways may provide targets for future drug development to eliminate CSCs, and the cell model may be a useful tool in such drug screenings. Stem Cells 2017;35:1898-1912. © 2017 AlphaMed Press.

  8. Maternal Dexamethasone Exposure Alters Synaptic Inputs to Gonadotropin-Releasing Hormone Neurons in the Early Postnatal Rat

    Directory of Open Access Journals (Sweden)

    Wei Ling Lim

    2016-08-01

    Full Text Available Maternal dexamethasone (DEX; a glucocorticoid receptor agonist exposure delays pubertal onset and alters reproductive behaviour in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP under the control of GnRH promoter. Pregnant females were administered with DEX (0.1mg/kg or vehicle (VEH, water daily during gestation day 13-20. Confocal imaging was used to examine the spine density of EGFP-GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP-GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0 males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the post synaptic marker molecule, post-synaptic density 95 was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.

  9. Effect of low dose electron beam irradiation on the alteration layer formed during nuclear glass leaching

    Energy Technology Data Exchange (ETDEWEB)

    Mougnaud, S., E-mail: sarah.mougnaud@gmail.com [CEA Marcoule, DEN, DTCD, SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Tribet, M. [CEA Marcoule, DEN, DTCD, SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Renault, J.-P. [NIMBE, CNRS, CEA, Université Paris Saclay, CEA Saclay, 91191 Gif-sur-Yvette cedex (France); Jollivet, P. [CEA Marcoule, DEN, DTCD, SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France); Panczer, G. [Institut Lumière Matière, UMR 5306, Université Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne cedex (France); Charpentier, T. [NIMBE, CNRS, CEA, Université Paris Saclay, CEA Saclay, 91191 Gif-sur-Yvette cedex (France); Jégou, C. [CEA Marcoule, DEN, DTCD, SECM, BP 17171, 30207 Bagnols-sur-Cèze cedex (France)

    2016-12-15

    This investigation concerns borosilicate glass leaching mechanisms and the evolution of alteration layer under electron beam irradiation. A simple glass doped with rare earth elements was selected in order to access mechanistic and structural information and better evaluate the effects of irradiation. It was fully leached in initially pure water at 90 °C and at high glass surface area to solution volume ratio (S/V = 20 000 m{sup −1}) in static conditions. Under these conditions, the system quickly reaches the residual alteration rate regime. A small particle size fraction (2–5 μm) was sampled in order to obtain a fairly homogeneous altered material enabling the use of bulk characterization methods. External irradiations with 10 MeV electrons up to a dose of 10 MGy were performed either before or after leaching, to investigate respectively the effect of initial glass irradiation on its alteration behavior and the irradiation stability of the alteration layer. Glass dissolution rate was analyzed by regular leachate samplings and the alteration layer structure was characterized by Raman, luminescence (continuous or time-resolved), and {sup 29}Si MAS NMR and EPR spectroscopy. It was shown that the small initial glass evolutions under irradiation did not induce any modification of the leaching kinetic nor of the structure of the alteration layer. The alteration process seemed to “smooth over” the created defects. Otherwise, the alteration layer and initial glass appeared to have different behaviors under irradiation. No Eu{sup 3+} reduction was detected in the alteration layer after irradiation and the defect creation efficiency was much lower than for initial glass. This can possibly be explained by the protective role of pore water contained in the altered material (∼20%). Moreover, a slight depolymerization of the silicon network of the altered glass under irradiation with electrons was evidenced, whereas in the initial glass it typically

  10. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    International Nuclear Information System (INIS)

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-01-01

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life

  11. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    Energy Technology Data Exchange (ETDEWEB)

    Miki, Takanori, E-mail: mikit@med.kagawa-u.ac.jp [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Kusaka, Takashi [Department of Pediatrics, Faculty of Medicine, Kagawa University (Japan); Warita, Katsuhiko [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Yokoyama, Toshifumi [Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University (Japan); Jamal, Mostofa [Department of Forensic Medicine, Faculty of Medicine, Kagawa University (Japan); Ueki, Masaaki [Department of Anesthesia, Nishiwaki Municipal Hospital (Japan); Yakura, Tomiko; Tamai, Motoki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan); Sumitani, Kazunori [Department of Medical Education, Faculty of Medicine, Kagawa University (Japan); Hosomi, Naohisa [Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences (Japan); Takeuchi, Yoshiki [Department of Anatomy and Neurobiology, Faculty of Medicine, Kagawa University (Japan)

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  12. Altered growth pattern, not altered growth per se, is the hallmark of early lesions preceding cancer development.

    Science.gov (United States)

    Doratiotto, S; Marongiu, F; Faedda, S; Pani, P; Laconi, E

    2009-01-01

    Many human solid cancers arise from focal proliferative lesions that long precede the overt clinical appearance of the disease. The available evidence supports the notion that cancer precursor lesions are clonal in origin, and this notion forms the basis for most of the current theories on the pathogenesis of neoplastic disease. In contrast, far less attention has been devoted to the analysis of the phenotypic property that serves to define these focal lesions, i.e. their altered growth pattern. In fact, the latter is often considered a mere morphological by-product of clonal growth, with no specific relevance in the process. In the following study, evidence will be presented to support the concept that focal growth pattern is an inherent property of altered cells, independent of clonal growth; furthermore, it will be discussed how such a property, far from being merely descriptive, might indeed play a fundamental role in the sequence of events leading to the development of cancer. Within this paradigm, the earliest steps of neoplasia should be considered and analysed as defects in the mechanisms of tissue pattern formation.

  13. Early initiation of night-time NIV in an outpatient setting: a randomized non-inferiority study in ALS patients.

    Science.gov (United States)

    Bertella, Enrica; Banfi, Paolo; Paneroni, Mara; Grilli, Silvia; Bianchi, Luca; Volpato, Eleonora; Vitacca, Michele

    2017-12-01

    In patients with amyotrophic lateral sclerosis (ALS), non-invasive ventilation (NIV) is usually initiated in an in-hospital regime. We investigated if NIV initiated in an outpatient setting can be as effective in terms of patients' acceptance/adherence. We also evaluated factors predicting NIV acceptance and adherence and disease progression. Prospective randomized study. Outpatient versus inpatient rehabilitation. ALS patients. ALS patients were randomized to two groups for NIV initiation: outpatients versus inpatients. At baseline (T0), end of NIV trial program (T1) and after 3 months from T1 (T2), respiratory function tests, blood gas analysis, and sleep study were performed. At T1, we assessed: NIV acceptance (>4 h/night), and dyspnea symptoms (day/night) by Visual analogue scale (VAS), staff and patients' experience (how difficult NIV was to accept, how difficult ventilator was to manage, satisfaction); at T2: NIV adherence (>120 h/month) and patients' experience. Fifty patients participated. There were no differences in acceptance failure (P=0.733) or adherence failure (P=0.529). At T1, outpatients had longer hours of nocturnal ventilation (PNIV acceptance/adherence failure. There were no between-group differences in progression of respiratory impairment, symptoms and sleep quality. Early outpatient initiation of NIV in ALS is as effective as inpatient initiation.

  14. Public health implications of altered puberty timing

    DEFF Research Database (Denmark)

    Golub, M.S.; Collman, G.W.; Foster, P.M.

    2008-01-01

    sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated...

  15. An alter-centric perspective on employee innovation: The importance of alters' creative self-efficacy and network structure.

    Science.gov (United States)

    Grosser, Travis J; Venkataramani, Vijaya; Labianca, Giuseppe Joe

    2017-09-01

    While most social network studies of employee innovation behavior examine the focal employees' ("egos'") network structure, we employ an alter-centric perspective to study the personal characteristics of employees' network contacts-their "alters"-to better understand employee innovation. Specifically, we examine how the creative self-efficacy (CSE) and innovation behavior of employees' social network contacts affects their ability to generate and implement novel ideas. Hypotheses were tested using a sample of 144 employees in a U.S.-based product development organization. We find that the average CSE of alters in an employee's problem solving network is positively related to that employee's innovation behavior, with this relationship being mediated by these alters' average innovation behavior. The relationship between the alters' average innovation behavior and the employee's own innovation behavior is strengthened when these alters have less dense social networks. Post hoc results suggest that having network contacts with high levels of CSE also leads to an increase in ego's personal CSE 1 year later in cases where the employee's initial level of CSE was relatively low. Implications for theory and practice are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. Development of gypsum alteration on marble and limestone

    Science.gov (United States)

    McGee, E.S.

    1996-01-01

    Blackened alteration crusts of gypsum plus particulates that form on sheltered areas on marble and limestone buildings pose a challenge for rehabilitation and cleaning. Fresh marble and limestone samples exposed at monitored exposure sites present conditions of simple geometry and well-documented exposures but have short exposure histories (one to five years). The gypsum alteration crusts that develop on these samples provide insight into the early stages and rate of alteration crust formation. Alteration crusts from buildings give a longer, but less well known exposure history and present much more complex surfaces for gypsum accumulation. Integrated observations and measurements of alteration crusts from exposure samples and from buildings identify four factors that are important in the formation and development of alteration crusts on marble and limestone: (1) pollution levels, (2) exposure to rain or washing, (3) geometry of exposure of the stone surface, and (4) permeability of the stone. The combination of these factors contributes to both the distribution and the physical characteristics of the gypsum crusts which may affect cleaning decisions.

  17. Early initiation of new oral anticoagulants in acute stroke and TIA patients with nonvalvular atrial fibrillation.

    Science.gov (United States)

    Shibazaki, Kensaku; Kimura, Kazumi; Aoki, Junya; Saji, Naoki; Sakai, Kenichiro

    2013-08-15

    The aim of this study was to investigate whether early initiation of new oral anticoagulants (NOAC) for acute stroke or transient ischemic attack (TIA) patients with nonvalvular atrial fibrillation (NVAF) are safe. Between March 2011 and September 2012, stroke or TIA patients with NVAF who started NOAC within 2 weeks were enrolled retrospectively. Symptomatic intracerebral hemorrhage (ICH), hemorrhagic transformation (HT) on T2*-weighted MRI, recurrence of stroke or TIA, systemic embolism and any bleeding complications after initiation of NOAC were evaluated. 41 patients (25 males; mean age 76.2 years) started NOAC; of which, 39 (95%) patients had stroke, and 2 (5%) had TIA. The median (interquartile range) interval from onset to treatment with NOAC was 2 (1-6) days. Symptomatic ICH was not observed. HT on initial T2* and new HT on follow-up T2* were 5 (12%) and 11 (31%), but it was asymptomatic. Of 5 patients who had HT on the initial T2*, enlargement of hemorrhage on follow-up T2* (hemorrhagic infarction (HI) Type 1→HI Type 2) was observed in 1 patient, but it was asymptomatic. None of the patients had recurrent stroke or TIA, systemic embolism, and any bleeding complications. The NOAC may be safe in acute stroke or TIA patients with NVAF. A large, prospective study is needed to confirm this. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Early cell adhesion events differ between osteoporotic and non-osteoporotic osteoblasts.

    Science.gov (United States)

    Perinpanayagam, H; Zaharias, R; Stanford, C; Brand, R; Keller, J; Schneider, G

    2001-11-01

    In osteoporosis, the regenerative capacity of bone is compromised, which may involve altered osteoblast (OB) activity. This could be attributed to an inappropriate synthesis and assembly of an extracellular matrix (ECM), altered cell adhesion to the ECM, or be due to inappropriate downstream activation of adhesion-mediated signaling cascades through proteins such as focal adhesion kinase (FAK). The purpose of our study was to compare early adhesion-mediated events using previously described and characterized clinically derived OBs obtained from human patients undergoing major joint arthroplasty for osteoporosis or osteoarthritis. The presence or absence of osteoporosis was established with a radiographic index. Using light microscopy and crystal violet staining, we show that OB cells derived from sites of osteoporosis do not attach and spread as well as non-osteoporotic (OP) OB cells. OP cells initially have a more rounded morphology, and show significantly less (P attachment to serum-coated tissue culture plastic over a 24 h time period. Immunofluorescent labeling after 24 h of attachment showed that OP OB focal adhesions (FAs) and stress fibers were less defined, and that the OP cells were smaller and had a more motile phenotype. When normalized protein lysates were Western blotted for phosphotyrosine (PY) a band corresponding to pp125FAK was identified. FAK tyrosine phosphorylation was evident at 6 h in both the OP and non-OP OBs, but decreased or was absent through 24 h in OP OBs. These results suggest early adhesion-mediated events, such as cell adhesion, attachment, and FAK signaling via PY may be altered in OP OBs.

  19. Initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases

    International Nuclear Information System (INIS)

    Scott, R.E.; Maercklein, P.B.

    1985-01-01

    A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G 1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G 1 states. The results establish that a slow dosage of 254 nm UV irradiation selectivity and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defect proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the inhibition of carcinogenesis. These observations support a concept that the initiation of carcinogenesis involves multiple phases

  20. Early Smoking, Education, and Labor Market Performance

    NARCIS (Netherlands)

    Palali, Ali

    2015-01-01

    This study investigates the effects of early smoking on educational attainment and labor market performance. The results show that early smoking adversely affects educational attainment and initial labor market performance, but only for males. The effect of early smoking on initial labor market

  1. Alteration in neonatal nutrition causes perturbations in hypothalamic neural circuits controlling reproductive function.

    Science.gov (United States)

    Caron, Emilie; Ciofi, Philippe; Prevot, Vincent; Bouret, Sebastien G

    2012-08-15

    It is increasingly accepted that alterations of the early life environment may have lasting impacts on physiological functions. In particular, epidemiological and animal studies have indicated that changes in growth and nutrition during childhood and adolescence can impair reproductive function. However, the precise biological mechanisms that underlie these programming effects of neonatal nutrition on reproduction are still poorly understood. Here, we used a mouse model of divergent litter size to investigate the effects of early postnatal overnutrition and undernutrition on the maturation of hypothalamic circuits involved in reproductive function. Neonatally undernourished females display attenuated postnatal growth associated with delayed puberty and defective development of axonal projections from the arcuate nucleus to the preoptic region. These alterations persist into adulthood and specifically affect the organization of neural projections containing kisspeptin, a key neuropeptide involved in pubertal activation and fertility. Neonatal overfeeding also perturbs the development of neural projections from the arcuate nucleus to the preoptic region, but it does not result in alterations in kisspeptin projections. These studies indicate that alterations in the early nutritional environment cause lasting and deleterious effects on the organization of neural circuits involved in the control of reproduction, and that these changes are associated with lifelong functional perturbations.

  2. Gestational methylazoxymethanol exposure leads to NMDAR dysfunction in hippocampus during early development and lasting deficits in learning.

    Science.gov (United States)

    Snyder, Melissa A; Adelman, Alicia E; Gao, Wen-Jun

    2013-01-01

    The N-methyl-D-aspartate (NMDA) receptor has long been associated with learning and memory processes as well as diseased states, particularly in schizophrenia (SZ). Additionally, SZ is increasingly recognized as a neurodevelopmental disorder with cognitive impairments often preceding the onset of psychosis. However, the cause of these cognitive deficits and what initiates the pathological process is unknown. Growing evidence has implicated the glutamate system and, in particular, N-methyl-D-aspartate receptor (NMDAR) dysfunction in the pathophysiology of SZ. Yet, the vast majority of SZ-related research has focused on NMDAR function in adults leaving the role of NMDARs during development uncharacterized. We used the prenatal methylazoxymethanol acetate (MAM, E17) exposure model to determine the alterations of NMDAR protein levels and function, as well as associated cognitive deficits during development. We found that MAM-exposed animals have significantly altered NMDAR protein levels and function in the juvenile and adolescent hippocampus. Furthermore, these changes are associated with learning and memory deficits in the Morris Water Maze. Thus, in the prenatal MAM-exposure SZ model, NMDAR expression and function is altered during the critical period of hippocampal development. These changes may be involved in disease initiation and cognitive impairment in the early stage of SZ.

  3. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission

    DEFF Research Database (Denmark)

    Arora, Tulika; Velagapudi, Vidya; Pournaras, Dimitri J

    2015-01-01

    -surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery....... The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic......Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were...

  4. Pore Pressure Distribution and Flank Instability in Hydrothermally Altered Stratovolcanoes

    Science.gov (United States)

    Ball, J. L.; Taron, J.; Hurwitz, S.; Reid, M. E.

    2015-12-01

    Field and geophysical investigations of stratovolcanoes with long-lived hydrothermal systems commonly reveal that initially permeable regions (such as brecciated layers of pyroclastic material) can become both altered and water-bearing. Hydrothermal alteration in these regions, including clay formation, can turn them into low-permeability barriers to fluid flow, which could increase pore fluid pressures resulting in flank slope instability. We examined elevated pore pressure conditions using numerical models of hydrothermal flow in stratovolcanoes, informed by geophysical data about internal structures and deposits. Idealized radially symmetric meshes were developed based on cross-sectional profiles and alteration/permeability structures of Cascade Range stratovolcanoes. We used the OpenGeoSys model to simulate variably saturated conditions in volcanoes heated only by regional heat fluxes, as well as 650°C intrusions at two km depth below the surface. Meteoric recharge was estimated from precipitation rates in the Cascade Range. Preliminary results indicate zones of elevated pore pressures form: 1) where slopes are underlain by continuous low-permeability altered layers, or 2) when the edifice has an altered core with saturated, less permeable limbs. The first scenario might control shallow collapses on the slopes above the altered layers. The second could promote deeper flank collapses that are initially limited to the summit and upper slopes, but could progress to the core of an edifice. In both scenarios, pore pressures can be further elevated by shallow intrusions, or evolve over longer time scales under forcing from regional heat flux. Geometries without confining low-permeability layers do not show these pressure effects. Our initial scenarios use radially symmetric models, but we are also simulating hydrothermal flow under real 3D geometries with asymmetric subsurface structures (Mount Adams). Simulation results will be used to inform 3D slope

  5. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia.

    Science.gov (United States)

    Kesby, James P; Cui, Xiaoying; Burne, Thomas H J; Eyles, Darryl W

    2013-01-01

    Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

  6. Altered dopamine ontogeny in the developmentally vitamin D deficient rat and its relevance to schizophrenia

    Directory of Open Access Journals (Sweden)

    James P. Kesby

    2013-07-01

    Full Text Available Schizophrenia is a heterogeneous group of disorders with unknown aetiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesised that abnormal dopamine signalling in the adult patient may result from altered dopamine signalling during foetal brain development. Environmental and genetic risk factors can be modelled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the aetiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD deficiency. DVD-deficient adult rats display an altered behavioural profile in response to dopamine releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters dopamine metabolism in the developing brain. We speculate such alterations in foetal brain development may change the trajectory of dopamine neuron ontogeny to induce the behavioural abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in dopamine ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.

  7. Chlorite alteration in aqueous solutions and uranium removal by altered chlorite

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eungyeong; Ahn, Hyangsig [Department of Earth and Environmental Sciences, Korea University, Anam-dong, Seongbuk-gu, Seoul 02841 (Korea, Republic of); Jo, Ho Young, E-mail: hyjo@korea.ac.kr [Department of Earth and Environmental Sciences, Korea University, Anam-dong, Seongbuk-gu, Seoul 02841 (Korea, Republic of); Ryu, Ji-Hun; Koh, Yong-Kwon [Korea Atomic Energy Research Institute, 1045 Daedeokdaero, Yuseong-gu, Daejeon 34057 (Korea, Republic of)

    2017-04-05

    Highlights: • Chlorite alteration and the U removal capacity of altered chlorite were investigated. • Initial pH affected more chlorite dissolution than ionic strength. • Chlorite dissolution at pH{sub o} = 3–8 was inversely proportional to the U removal capacity. • Chlorite dissolution at pH{sub o} = 10 was proportional to the U removal capacity. • The formation of Fe-containing secondary minerals affected the U removal capacity. - Abstract: Chlorite alteration and the U removal capacity of altered chlorite were investigated. Batch kinetic dissolution tests using clinochlore CCa-2 were conducted for 60 days in aqueous solutions of various pHs and ionic strengths. Batch sorption tests using these altered chlorite samples were conducted for 48 h with natural groundwater containing 3.06 × 10{sup −6} M U. Chlorite dissolution was influenced more by pH{sub o} than by the ionic strength of the solution. TEM analysis revealed Fe(oxy)hydroxide aggregates in the solid residue from the batch dissolution test with 0.1 M NaClO{sub 4} solution at pH{sub o} = 10. The U removal capacity of the reacted chlorite samples at pH{sub o} = 6–10 was higher than that of the reacted chlorite samples at pH{sub o} = 3. The degree of dissolution of chlorite samples reacted at pH{sub o} = 3–8 was inversely proportional to the U removal capacity, but that of chlorite samples reacted at pH{sub o} = 10 was proportional to the U removal capacity. The positive correlation between the U removal capacity and degree of chlorite dissolution at pH{sub o} = 10 might be due to the formation of Fe-containing secondary minerals and changes in the reactive sites.

  8. Uranium-induced sensory alterations in the zebrafish Danio rerio

    Energy Technology Data Exchange (ETDEWEB)

    Faucher, K., E-mail: kfaucher@hotmail.fr [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France); Floriani, M.; Gilbin, R.; Adam-Guillermin, C. [Laboratoire d' ecotoxicologie des radionucleides (LECO), Institut de Radioprotection et Surete Nucleaire, Centre de Cadarache, Batiment 186, BP3, 13115 Saint Paul lez Durance (France)

    2012-11-15

    The effect of chronic exposure to uranium ions (UO{sub 2}{sup 2+}) on sensory tissues including the olfactory and lateral line systems was investigated in zebrafish (Danio rerio) using scanning electron microscopy. The aim of this study was to determine whether exposure to uranium damaged sensory tissues in fish. The fish were exposed to uranium at the concentration of 250 {mu}g l{sup -1} for 10 days followed by a depuration period of 23 days. Measurements of uranium uptake in different fish organs: olfactory rosettes and bulbs, brain, skin, and muscles, were also determined by ICP-AES and ICP-MS during the entire experimental period. The results showed that uranium displayed a strong affinity for sensory structures in direct contact with the surrounding medium, such as the olfactory and lateral line systems distributed on the skin. A decreasing gradient of uranium concentration was found: olfactory rosettes > olfactory bulbs > skin > muscles > brain. At the end of the experiment, uranium was present in non-negligible quantities in sensory tissues. In parallel, fish exposed to uranium showed severe sensory tissue alterations at the level of the olfactory and lateral line systems. In both sensory systems, the gross morphology was altered and the sensory hair cells were significantly damaged very early after the initiation of exposure (from the 3rd day). At the end of the experiment, after 23 days of depuration, the lateral line system still displayed slight tissue alterations, but approximately 80% of the neuromasts in this system had regenerated. In contrast, the olfactory system took more time to recover, as more than half of the olfactory rosettes observed remained destroyed at the end of the experiment. This study showed, for the first time, that uranium is able to damage fish sensory tissues to such an extent that tissue regeneration is delayed.

  9. Effect of prenatal education on breastfeeding initiation and exclusive ...

    African Journals Online (AJOL)

    Background: The prevalence of breastfeeding initiation and exclusive breastfeeding is low globally in both developing and developed countries despite the promotion interventions on breastfeeding rates in early infancy. In Ethiopia, the proportion of women who practiced early breastfeeding initiation (EBI) and exclusive ...

  10. Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.

    Science.gov (United States)

    Weiss, Lukas; Melchardt, Thomas; Egle, Alexander; Grabmer, Christoph; Greil, Richard; Tinhofer, Inge

    2011-05-15

    Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. 2010 American Cancer Society.

  11. Very early disease manifestations of macular telangiectasia type 2

    NARCIS (Netherlands)

    Issa, P.C.; Heeren, T.F.C.; Kupitz, E.H.; Holz, F.G.; Berendschot, T.T.J.M.

    Background: To report very early morphologic and functional alterations in patients with macular telangiectasia type 2. Methods: Patients with asymmetric disease manifestations, in whom retinal alterations characteristic for macular telangiectasia type 2 were present in one but not in the apparently

  12. Hydrothermal alteration in the Matok Igneous Complex, Southern Marginal Zone of the Limpopo Belt, South Africa

    International Nuclear Information System (INIS)

    Sieber, T.; Van Reenen, D.D.; Barton, J.M.

    1991-01-01

    Ductile shear zones associated with the 2700 to 2650 Ma Limpopo Orogeny locally contained gold mineralization. Some of these shear zones were reactivated under brittle conditions and contain zones of hydrothermal alteration that are of potential economic significance. Within the approximately 2670 Ma Matok Complex, two examples of this shear zone controlled alteration are exposed, the Dwars River and Sand River alteration zones. The granitic rocks of this Complex experienced early selective sericitization of plagioclase and the subsequent development of perthitic porphyroblasts. This early regional alteration was overprinted along brittle shear zones by pervasive propylitization and vein controlled quartz-albite alteration. The setting, composition, and the age of the Matok Complex make it a possible source for Archaean gold mineralization. The Dwars River and Sand River alteration zones are characterized by the absence of significant gold mineralization. The pattern of wall-rock alteration indicates that the hydrothermal processes were different from typical Archaean lode gold deposits. P-T conditions during the shear-zone controlled alteration were less than 400 degrees C and 1,9 - 2,8 kb. The shear zone hosted alteration could have taken place anytime between emplacement of the Matok Complex and about 1315 Ma ago. 35 refs., 10 figs., 4 tabs

  13. Theoretical cell alteration model in the context of carcinogenesis

    International Nuclear Information System (INIS)

    Walsh, P.J.

    1976-01-01

    A model incorporating cell survival and alteration is used to discuss the general nature of cellular response to a toxic agent. Cell division and repair are discussed as regards their influence on dose-response relationships to bone-seeking radionuclides. The application of the model in its present form to specific biologic end points depends on the assumption that such end points are the result of some initial alteration

  14. Expectations Do Not Alter Early Sensory Processing during Perceptual Decision-Making.

    Science.gov (United States)

    Rungratsameetaweemana, Nuttida; Itthipuripat, Sirawaj; Salazar, Annalisa; Serences, John T

    2018-06-13

    Two factors play important roles in shaping perception: the allocation of selective attention to behaviorally relevant sensory features, and prior expectations about regularities in the environment. Signal detection theory proposes distinct roles of attention and expectation on decision-making such that attention modulates early sensory processing, whereas expectation influences the selection and execution of motor responses. Challenging this classic framework, recent studies suggest that expectations about sensory regularities enhance the encoding and accumulation of sensory evidence during decision-making. However, it is possible, that these findings reflect well documented attentional modulations in visual cortex. Here, we tested this framework in a group of male and female human participants by examining how expectations about stimulus features (orientation and color) and expectations about motor responses impacted electroencephalography (EEG) markers of early sensory processing and the accumulation of sensory evidence during decision-making (the early visual negative potential and the centro-parietal positive potential, respectively). We first demonstrate that these markers are sensitive to changes in the amount of sensory evidence in the display. Then we show, counter to recent findings, that neither marker is modulated by either feature or motor expectations, despite a robust effect of expectations on behavior. Instead, violating expectations about likely sensory features and motor responses impacts posterior alpha and frontal theta oscillations, signals thought to index overall processing time and cognitive conflict. These findings are inconsistent with recent theoretical accounts and suggest instead that expectations primarily influence decisions by modulating post-perceptual stages of information processing. SIGNIFICANCE STATEMENT Expectations about likely features or motor responses play an important role in shaping behavior. Classic theoretical

  15. Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells

    Science.gov (United States)

    Mimeault, Murielle; Batra, Surinder K

    2013-01-01

    Accumulating lines of experimental evidence have revealed that hypoxia-inducible factors, HIF-1α and HIF-2α, are key regulators of the adaptation of cancer- and metastasis-initiating cells and their differentiated progenies to oxygen and nutrient deprivation during cancer progression under normoxic and hypoxic conditions. Particularly, the sustained stimulation of epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), stem cell factor (SCF) receptor KIT, transforming growth factor-β receptors (TGF-βRs) and Notch and their downstream signalling elements such as phosphatidylinositol 3′-kinase (PI3K)/Akt/molecular target of rapamycin (mTOR) may lead to an enhanced activity of HIFs. Moreover, the up-regulation of HIFs in cancer cells may also occur in the hypoxic intratumoral regions formed within primary and secondary neoplasms as well as in leukaemic cells and metastatic prostate and breast cancer cells homing in the hypoxic endosteal niche of bone marrow. The activated HIFs may induce the expression of numerous gene products such as induced pluripotency-associated transcription factors (Oct-3/4, Nanog and Sox-2), glycolysis- and epithelial-mesenchymal transition (EMT) programme-associated molecules, including CXC chemokine receptor 4 (CXCR4), snail and twist, microRNAs and angiogenic factors such as vascular endothelial growth factor (VEGF). These gene products in turn can play critical roles for high self-renewal ability, survival, altered energy metabolism, invasion and metastases of cancer cells, angiogenic switch and treatment resistance. Consequently, the targeting of HIF signalling network and altered metabolic pathways represents new promising strategies to eradicate the total mass of cancer cells and improve the efficacy of current therapies against aggressive and metastatic cancers and prevent disease relapse. PMID:23301832

  16. Excessive Sensory Stimulation during Development Alters Neural Plasticity and Vulnerability to Cocaine in Mice.

    Science.gov (United States)

    Ravinder, Shilpa; Donckels, Elizabeth A; Ramirez, Julian S B; Christakis, Dimitri A; Ramirez, Jan-Marino; Ferguson, Susan M

    2016-01-01

    Early life experiences affect the formation of neuronal networks, which can have a profound impact on brain function and behavior later in life. Previous work has shown that mice exposed to excessive sensory stimulation during development are hyperactive and novelty seeking, and display impaired cognition compared with controls. In this study, we addressed the issue of whether excessive sensory stimulation during development could alter behaviors related to addiction and underlying circuitry in CD-1 mice. We found that the reinforcing properties of cocaine were significantly enhanced in mice exposed to excessive sensory stimulation. Moreover, although these mice displayed hyperactivity that became more pronounced over time, they showed impaired persistence of cocaine-induced locomotor sensitization. These behavioral effects were associated with alterations in glutamatergic transmission in the nucleus accumbens and amygdala. Together, these findings suggest that excessive sensory stimulation in early life significantly alters drug reward and the neural circuits that regulate addiction and attention deficit hyperactivity. These observations highlight the consequences of early life experiences and may have important implications for children growing up in today's complex technological environment.

  17. Metabolic system alterations in pancreatic cancer patient serum: potential for early detection

    International Nuclear Information System (INIS)

    Ritchie, Shawn A; Jin, Wei; Sajobi, Tolulope T; Jayasinghe, Dushmanthi; Chitou, Bassirou; Yamazaki, Yasuyo; White, Thayer; Goodenowe, Dayan B; Akita, Hirofumi; Takemasa, Ichiro; Eguchi, Hidetoshi; Pastural, Elodie; Nagano, Hiroaki; Monden, Morito; Doki, Yuichiro; Mori, Masaki

    2013-01-01

    The prognosis of pancreatic cancer (PC) is one of the poorest among all cancers, due largely to the lack of methods for screening and early detection. New biomarkers for identifying high-risk or early-stage subjects could significantly impact PC mortality. The goal of this study was to find metabolic biomarkers associated with PC by using a comprehensive metabolomics technology to compare serum profiles of PC patients to healthy control subjects. A non-targeted metabolomics approach based on high-resolution, flow-injection Fourier transform ion cyclotron resonance mass spectrometry (FI-FTICR-MS) was used to generate comprehensive metabolomic profiles containing 2478 accurate mass measurements from the serum of Japanese PC patients (n=40) and disease-free subjects (n=50). Targeted flow-injection tandem mass spectrometry (FI-MS/MS) assays for specific metabolic systems were developed and used to validate the FI-FTICR-MS results. A FI-MS/MS assay for the most discriminating metabolite discovered by FI-FTICR-MS (PC-594) was further validated in two USA Caucasian populations; one comprised 14 PCs, six intraductal papillary mucinous neoplasims (IPMN) and 40 controls, and a second comprised 1000 reference subjects aged 30 to 80, which was used to create a distribution of PC-594 levels among the general population. FI-FTICR-MS metabolomic analysis showed significant reductions in the serum levels of metabolites belonging to five systems in PC patients compared to controls (all p<0.000025). The metabolic systems included 36-carbon ultra long-chain fatty acids, multiple choline-related systems including phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, as well as vinyl ether-containing plasmalogen ethanolamines. ROC-AUCs based on FI-MS/MS of selected markers from each system ranged between 0.93 ±0.03 and 0.97 ±0.02. No significant correlations between any of the systems and disease-stage, gender, or treatment were observed. Biomarker PC-594 (an ultra long

  18. Hyperintense signal alteration in the suprapatellar fat pad on MRI is associated with degeneration of the patellofemoral joint over 48 months. Data from the Osteoarthritis Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Schwaiger, Benedikt J.; Gersing, Alexandra S. [University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Technical University of Munich, Department of Radiology, Klinikum Rechts der Isar, Munich (Germany); Mbapte Wamba, John; Facchetti, Luca; Link, Thomas M. [University of California, San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Nevitt, Michael C.; McCulloch, Charles E. [University of California, Department of Epidemiology and Biostatistics, San Francisco, CA (United States)

    2018-03-15

    To analyze associations of suprapatellar fat pad (SPFP) hyperintense signal alterations and mass effect with progression of patellofemoral osteoarthritis (OA) and clinical symptoms over 48 months. Subjects from the Osteoarthritis Initiative (n = 426; 51.8 ± 3.8 years; 49.8% women) without radiographic tibiofemoral OA underwent 3T-MRI of their right knees and clinical evaluation using the Knee Injury and Osteoarthritis Outcome Score at baseline and at 48 months. Elevated SPFP signal was assessed on intermediate-weighted, fat-saturated turbo spin-echo (TSE) images. Mass effect was defined as a convex posterior contour. Patellofemoral cartilage, bone marrow lesions (BML), and subchondral cysts were assessed using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations of SPFP imaging findings with MRI and clinical progression were assessed using general linear models and logistic regressions. Baseline SPFP signal alterations were found in 51% of the subjects (n = 217), of whom 11% (n = 23) additionally had a mass effect. Progression of cartilage lesions was significantly higher in subjects with signal alteration versus without (adjusted mean increases, 95% CI; patella: 0.29, -0.07 to 0.64 vs -0.04, -0.40 to 0.31; p < 0.001; trochlea: 0.47, 0.16 to 0.77 vs 0.31, 0.01 to 0.61; p = 0.007). BML progression was also more likely in subjects with signal alteration (OR 1.75, 95% CI 1.09 to 2.82; p = 0.021). Mass effect was not associated with joint degeneration and SPFP findings were not associated with clinical worsening (p > 0.18 for all). Patellofemoral joint degeneration over 48 months was significantly increased in subjects with SPFP signal alteration, suggesting an association between SPFP abnormalities and the progression of patellofemoral OA. (orig.)

  19. Hyperintense signal alteration in the suprapatellar fat pad on MRI is associated with degeneration of the patellofemoral joint over 48 months. Data from the Osteoarthritis Initiative

    International Nuclear Information System (INIS)

    Schwaiger, Benedikt J.; Gersing, Alexandra S.; Mbapte Wamba, John; Facchetti, Luca; Link, Thomas M.; Nevitt, Michael C.; McCulloch, Charles E.

    2018-01-01

    To analyze associations of suprapatellar fat pad (SPFP) hyperintense signal alterations and mass effect with progression of patellofemoral osteoarthritis (OA) and clinical symptoms over 48 months. Subjects from the Osteoarthritis Initiative (n = 426; 51.8 ± 3.8 years; 49.8% women) without radiographic tibiofemoral OA underwent 3T-MRI of their right knees and clinical evaluation using the Knee Injury and Osteoarthritis Outcome Score at baseline and at 48 months. Elevated SPFP signal was assessed on intermediate-weighted, fat-saturated turbo spin-echo (TSE) images. Mass effect was defined as a convex posterior contour. Patellofemoral cartilage, bone marrow lesions (BML), and subchondral cysts were assessed using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations of SPFP imaging findings with MRI and clinical progression were assessed using general linear models and logistic regressions. Baseline SPFP signal alterations were found in 51% of the subjects (n = 217), of whom 11% (n = 23) additionally had a mass effect. Progression of cartilage lesions was significantly higher in subjects with signal alteration versus without (adjusted mean increases, 95% CI; patella: 0.29, -0.07 to 0.64 vs -0.04, -0.40 to 0.31; p < 0.001; trochlea: 0.47, 0.16 to 0.77 vs 0.31, 0.01 to 0.61; p = 0.007). BML progression was also more likely in subjects with signal alteration (OR 1.75, 95% CI 1.09 to 2.82; p = 0.021). Mass effect was not associated with joint degeneration and SPFP findings were not associated with clinical worsening (p > 0.18 for all). Patellofemoral joint degeneration over 48 months was significantly increased in subjects with SPFP signal alteration, suggesting an association between SPFP abnormalities and the progression of patellofemoral OA. (orig.)

  20. Does menopausal hormone therapy reduce myocardial infarction risk if initiated early after menopause? A population-based case-control study.

    Science.gov (United States)

    Carrasquilla, Germán D; Berglund, Anita; Gigante, Bruna; Landgren, Britt-Marie; de Faire, Ulf; Hallqvist, Johan; Leander, Karin

    2015-06-01

    This study aims to assess whether the timing of menopausal hormone therapy initiation in relation to onset of menopause and hormone therapy duration is associated with myocardial infarction risk. This study was based on the Stockholm Heart Epidemiology Program, a population-based case-control study including 347 postmenopausal women who had experienced a nonfatal myocardial infarction and 499 female control individuals matched for age and residential area. Odds ratios (with 95% CIs) for myocardial infarction were calculated using logistic regression. Early initiation of hormone therapy (within 10 y of onset of menopause or before age 60 y), compared with never use, was associated with an odds ratio of 0.87 (95% CI, 0.58-1.30) after adjustments for lifestyle factors, body mass index, and socioeconomic status. For late initiation of hormone therapy, the corresponding odds ratio was 0.97 (95% CI, 0.53-1.76). For hormone therapy duration of 5 years or more, compared with never use, the adjusted odds ratio was 0.64 (95% CI, 0.35-1.18). For hormone therapy duration of less than 5 years, the odds ratio was 0.97 (95% CI, 0.63-1.48). Neither the timing of hormone therapy initiation nor the duration of therapy is significantly associated with myocardial infarction risk.

  1. Autoradiography in Studying the Alteration of Rocks; L'Autoradiographie dans l'Etude de l'Alteration des Roches

    Energy Technology Data Exchange (ETDEWEB)

    Leveque, P.; Vigneaux, M. [Institut de Geologie du Bassin d' Aquitaine, Faculte des Sciences de l' Universite de Bordeaux (France)

    1967-06-15

    The alteration of rocks intended for use as the foundations of large-scale civil-engineering projects, for building construction and for rock piling has been studied and numerous tests carried out; some of these tests have been standardized in varying degrees. The conventional method of autoradiography has been used to develop one of the processes for estimating alteration due, in particular, to thermal shocks. By using {sup 35}S and {sup 32}P, the authors were able to follow the progressive alteration of different rocks in the form of microfissurations. This process is considerably more accurate than that based solely on utilization of the characteristics of rocks in normal or polarized light. In addition, it permits absolute comparison of the initial microfissuration conditions of the sample and the microfissuration found after an increasing number of thermal shock cycles. The results of the process are given in the paper. (author) [French] L'alterabilite des roches destinees, soit a des fondations de grands travaux de genie civil, soit a la construction d'immeubles, soit enfin a l'etablissement d'enrochements, a fait l'objet de nombreux essais dont certains ont ete normalises, ou tout au moins ont subi un debut de normalisation. Un des procedes de determination du processus d'alteration du notamment aux chocs thermiques a ete mis au point a partir de la methode classique d'autoradiographie. L'utilisation de {sup 35}S et de {sup 32}P a permis de suivre la progression de l'alteration par microfissuration dans des roches diverses. Ce procede est notablement plus precis que celui qui est fonde sur la seule utilisation des caracteristiques des roches en lumiere naturelle ou polarisee. De plus, il permet la comparaison en valeur absolue de l'etat de microfissuration initial de l'echantillon avec la microfissuration obtenue apres un nombre croissant de cycles de chocs thermiques. Les resultats obtenus grace a ce procede sont donnes dans le memoire. (author)

  2. Early Jurassic Carbon and Sodium Sequestration in a CAMP basalt flow

    Science.gov (United States)

    Block, K. A.; Puffer, J. H.

    2017-12-01

    The initial HTQ-type CAMP Orange Mountain Basalt flow, as well as related pillowed flows and the overlying Preakness flows, locally underwent substantial and well documented albitization, chloritization, and sulphate, carbonate, and zeolite mineralization. Layers representing at least 25 vol % of the Orange Mountain Basalt have undergone a major net increase in sodium and carbon content and a major redistribution of magnesium and calcium. Most alteration occurred during the development of a widespread early Jurassic geothermal system similar to the active system of Iceland. In both cases alteration was controlled by active circulation of basin brines through vesicular layers during rapid burial at temperatures that were kept elevated by recurring magmatism. Whole rock Na2O levels typically increased from 2.2 wt. % in unaltered layers to 3.2 wt. % in vesicular layers, and commonly reached levels exceeding 5 wt. %. The environmental implications of the removal of such massive amounts of sodium from the geothermal system on the chlorine budget and the salt content of Early Jurassic lakes are currently being evaluated. Massive amounts of carbon sequestration from the geothermal system may have mitigated an increased burden on the early Jurassic atmosphere where geothermal CO2 may have otherwise been vented at hot springs or solfataras. Calcite amygdules typically account for 5 to 10 vol. % of the vesiculated layers amounting to 66 to 132 kg of CO2 per m3 of basalt. If 25 vol. % of the 160 thick Orange Mountain Basalt is vesiculated that would equate to about 2640 to 5280 kg of CO2 per m2 of basalt. The full extent of calcite enrichment across the entire CAMP province, however, has not yet been determined.

  3. Altered Cellular Metabolism Drives Trained Immunity.

    Science.gov (United States)

    Sohrabi, Yahya; Godfrey, Rinesh; Findeisen, Hannes M

    2018-04-04

    Exposing innate immune cells to an initial insult induces a long-term proinflammatory response due to metabolic and epigenetic alterations which encompass an emerging new concept called trained immunity. Recent studies provide novel insights into mechanisms centered on metabolic reprogramming which induce innate immune memory in hematopoietic stem cells and monocytes. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. The "Internet of Things" and "industrial production" as part of the early identification initiative of the German Federal Ministry of Education and Research (BMBF)

    OpenAIRE

    Dworschak, Bernd; Zaiser, Helmut; Achtenhagen, Claudia

    2013-01-01

    The main objective of the German Federal Ministry of Education and Research's initiative for early identification of skill needs is to pinpoint the skills and qualifications required for the new skill requirements emerging from impending changes in the world of work and for which widespread demand may well grow over the next three to five years. Three projects relevant to the “Internet of Things”, which is one focus of the initiative, were completed inthe fields of logistics, industrial produ...

  5. Initial mass function for early-type stars in starburst galaxies

    International Nuclear Information System (INIS)

    Sekiguchi, K.; Anderson, K.S.

    1987-01-01

    The IMF slope of early-type stars in starburst galaxies is investigated using IUE observations and a technique that utilizes mass-linewidth relations for early-type stars. Fourteen low-resolution IUE spectra of eight starburst galaxies and three H II region galaxies are used to obtain line-strength ratios Si IV(1400 A)/C IV(1550 A). These are compared to model line ratios, and indicate that the average IMF slope for OB stars in these intense star-formation regions is appreciably flatter than that of the solar neighborhood. 46 references

  6. Early Results of Medicare's Bundled Payment Initiative for a 90-Day Total Joint Arthroplasty Episode of Care.

    Science.gov (United States)

    Iorio, Richard; Clair, Andrew J; Inneh, Ifeoma A; Slover, James D; Bosco, Joseph A; Zuckerman, Joseph D

    2016-02-01

    In 2011 Medicare initiated a Bundled Payment for Care Improvement (BPCI) program with the goal of introducing a payment model that would "lead to higher quality, more coordinated care at a lower cost to Medicare." A Model 2 bundled payment initiative for Total Joint Replacement (TJR) was implemented at a large, tertiary, urban academic medical center. The episode of care includes all costs through 90 days following discharge. After one year, data on 721 Medicare primary TJR patients were available for analysis. Average length of stay (LOS) was decreased from 4.27 days to 3.58 days (Median LOS 3 days). Discharges to inpatient facilities decreased from 71% to 44%. Readmissions occurred in 80 patients (11%), which is slightly lower than before implementation. The hospital has seen cost reduction in the inpatient component over baseline. Early results from the implementation of a Medicare BPCI Model 2 primary TJR program at this medical center demonstrate cost-savings. IV economic and decision analyses-developing an economic or decision model. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Proteomic analysis on the alteration of protein expression in the early-stage placental villous tissue of electromagnetic fields associated with cell phone exposure.

    Science.gov (United States)

    Luo, Qiong; Jiang, Ying; Jin, Min; Xu, Jian; Huang, He-Feng

    2013-09-01

    To explore the possible adverse effects and search for cell phone electromagnetic field (EMF)-responsive proteins in human early reproduction, a proteomics approach was employed to investigate the changes in protein expression profile induced by cell phone EMF in human chorionic tissues of early pregnancy in vivo. Volunteer women about 50 days pregnant were exposed to EMF at the average absorption rate of 1.6 to 8.8 W/kg for 1 hour with the irradiation device placed 10 cm away from the umbilicus at the midline of the abdomen. The changes in protein profile were examined using 2-dimensional electrophoresis (2-DE). Up to 15 spots have yielded significant change at least 2- to 2.5-folds up or down compared to sham-exposed group. Twelve proteins were identified- procollagen-proline, eukaryotic translation elongation factor 1 delta, chain D crystal structure of human vitamin D-binding protein, thioredoxin-like 3, capping protein, isocitrate dehydrogenase 3 alpha, calumenin, Catechol-O-methyltransferase protein, proteinase inhibitor 6 (PI-6; SerpinB6) protein, 3,2-trans-enoyl-CoA isomerase protein, chain B human erythrocyte 2,3-bisphosphoglycerate mutase, and nucleoprotein. Cell phone EMF might alter the protein profile of chorionic tissue of early pregnancy, during the most sensitive stage of the embryos. The exposure to EMF may cause adverse effects on cell proliferation and development of nervous system in early embryos. Furthermore, 2-DE coupled with mass spectrometry is a promising approach to elucidate the effects and search for new biomarkers for environmental toxic effects.

  8. Marijuana exposure and pulmonary alterations in primates.

    Science.gov (United States)

    Fligiel, S E; Beals, T F; Tashkin, D P; Paule, M G; Scallet, A C; Ali, S F; Bailey, J R; Slikker, W

    1991-11-01

    As part of a large multidisciplinary study, we examined lungs from 24 periadolescent male rhesus monkeys that were sacrificed seven months after daily marijuana smoke inhalation of 12 months duration. Animals were divided into four exposure groups: A) high-dose (one marijuana cigarette 7 days/week), B) low-dose (one marijuana cigarette 2 days/week and sham smoke 5 days/week), C) placebo (one extracted marijuana cigarette 7 days/week), and D) sham (sham smoke 7 days/week). Lungs, removed intact, were formalin inflated, sectioned and examined. Several pathological alterations, including alveolitis, alveolar cell hyperplasia and granulomatous inflammation, were found with higher frequency in all cigarette-smoking groups. Other alterations, such as bronchiolitis, bronchiolar squamous metaplasia and interstitial fibrosis, were found most frequently in the marijuana-smoking groups. Alveolar cell hyperplasia with focal atypia was seen only in the marijuana-smoking animals. These changes represent mostly early alterations of small airways. Additional follow-up studies are needed to determine their long-term prognostic significance.

  9. Genomic and Epigenomic Alterations in Cancer.

    Science.gov (United States)

    Chakravarthi, Balabhadrapatruni V S K; Nepal, Saroj; Varambally, Sooryanarayana

    2016-07-01

    Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. Early evolution and dynamics of Earth from a molten initial stage

    Science.gov (United States)

    Louro Lourenço, Diogo; Tackley, Paul J.

    2016-04-01

    It is now well established that most of the terrestrial planets underwent a magma ocean stage during their accretion. On Earth, it is probable that at the end of accretion, giant impacts like the hypothesised Moon-forming impact, together with other sources of heat, melted a substantial part of the mantle. The thermal and chemical evolution of the resulting magma ocean most certainly had dramatic consequences on the history of the planet. Considerable research has been done on magma oceans using simple 1-D models (e.g.: Abe, PEPI 1997; Solomatov, Treat. Geophys. 2007; Elkins-Tanton EPSL 2008). However, some aspects of the dynamics may not be adequately addressed in 1-D and require the use of 2-D or 3-D models. Moreover, new developments in mineral physics that indicate that melt can be denser than solid at high pressures (e.g.: de Koker et al., EPSL 2013) can have very important impacts on the classical views of the solidification of magma oceans (Labrosse et al., Nature 2007). The goal of our study is to understand and characterize the influence of melting on the long-term thermo-chemical evolution of rocky planet interiors, starting from an initial molten state (magma ocean). Our approach is to model viscous creep of the solid mantle, while parameterizing processes that involve melt as previously done in 1-D models, including melt-solid separation at all melt fractions, the use of an effective diffusivity to parameterize turbulent mixing, coupling to a parameterized core heat balance and a radiative surface boundary condition. These enhancements have been made to the numerical code StagYY (Tackley, PEPI 2008). We present results for the evolution of an Earth-like planet from a molten initial state to present day, while testing the effect of uncertainties in parameters such as melt-solid density differences, surface heat loss and efficiency of turbulent mixing. Our results show rapid cooling and crystallization until the rheological transition then much slower

  11. Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE.

    Science.gov (United States)

    Christy, Alison L; Walker, Margaret E; Hessner, Martin J; Brown, Melissa A

    2013-05-01

    The meninges are often considered inert tissues that house the CSF and provide protection for the brain and spinal cord. Yet emerging data demonstrates that they are also active sites of immune responses. Furthermore, the blood-CSF barrier surrounding meningeal blood vessels, together with the blood-brain barrier (BBB), is postulated to serve as a gateway for the pathological infiltration of immune cells into the CNS in multiple sclerosis (MS). Our previous studies using mast cell-deficient (Kit(W/Wv)) mice demonstrated that mast cells resident in the dura mater and pia mater exacerbate experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, by facilitating CNS inflammatory cell influx. Here we examined the underlying mechanisms that mediate these effects. We demonstrate that there are dramatic alterations in immune associated gene expression in the meninges in pre-clinical disease, including those associated with mast cell and neutrophil function. Meningeal mast cells are activated within 24 h of disease induction, but do not directly compromise CNS vascular integrity. Rather, through production of TNF, mast cells elicit an early influx of neutrophils, cells known to alter vascular permeability, into the meninges. These data add to the growing evidence that inflammation in the meninges precedes CNS immune cell infiltration and establish that mast cells are among the earliest participants in these disease-initiating events. We hypothesize that mast cell-dependent neutrophil recruitment and activation in the meninges promotes early breakdown of the local BBB and CSF-blood barrier allowing initial immune cell access to the CNS. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Detection of early metabolic alterations in the ocular fundus of diabetic patients by time-resolved autofluorescence of endogenous fluorophores

    Science.gov (United States)

    Schweitzer, D.; Klemm, M.; Quick, S.; Deutsch, L.; Jentsch, S.; Hammer, M.; Dawczynski, J.; Kloos, C. H.; Mueller, U. A.

    2011-07-01

    Measurements of time-resolved autofluorescence (FLIM) at the human ocular fundus of diabetic patients permit the detection of early pathologic alterations before signs of diabetic retinopathy are visible. The measurements were performed by the Jena Fluorescence Lifetime Laser Scanner Ophthalmoscope applying time-correlated single photon counting (TCSPC) in two spectral channels (K1: 490-560 nm, K2:560-700ps). The fluorescence was excited by 70 ps pulses (FWHM) at 448 nm. The decay of fluorescence intensity was triple-exponentially approximated. The frequency of amplitudes, lifetimes, and relative contributions was compared in fields of the same size and position in healthy subjects and in diabetic patients. The most sensitive parameter was the lifetime T2 in the short-wavelength channel, which corresponds to the neuronal retina. The changes in lifetime point to a loss of free NADH and an increased contribution of protein-bound NADH in the pre-stage of diabetic retinopathy.

  13. Alterations in Circulating miRNA Levels following Early-Stage Estrogen Receptor-Positive Breast Cancer Resection in Post-Menopausal Women

    DEFF Research Database (Denmark)

    Kodahl, Annette R; Zeuthen, Pernille; Binder, Harald

    2014-01-01

    INTRODUCTION: Circulating microRNAs (miRNAs) exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings. The aim of this study was to investigate changes in the levels of specific circulating miRNA following breast cancer surgery and evaluate whether these altera...... and could potentially be used to monitor whether all cancer cells have been removed at surgery and/or, subsequently, whether the patients develop recurrence.......INTRODUCTION: Circulating microRNAs (miRNAs) exhibit remarkable stability and may serve as biomarkers in several clinical cancer settings. The aim of this study was to investigate changes in the levels of specific circulating miRNA following breast cancer surgery and evaluate whether...... these alterations were also observed in an independent data set. METHODS: Global miRNA analysis was performed on prospectively collected serum samples from 24 post-menopausal women with estrogen receptor-positive early-stage breast cancer before surgery and 3 weeks after tumor resection using global LNA...

  14. Exercise is More Effective at Altering Gut Microbial Composition and Producing Stable Changes in Lean Mass in Juvenile versus Adult Male F344 Rats.

    Directory of Open Access Journals (Sweden)

    Agnieszka Mika

    Full Text Available The mammalian intestine harbors a complex microbial ecosystem that influences many aspects of host physiology. Exposure to specific microbes early in development affects host metabolism, immune function, and behavior across the lifespan. Just as the physiology of the developing organism undergoes a period of plasticity, the developing microbial ecosystem is characterized by instability and may also be more sensitive to change. Early life thus presents a window of opportunity for manipulations that produce adaptive changes in microbial composition. Recent insights have revealed that increasing physical activity can increase the abundance of beneficial microbial species. We therefore investigated whether six weeks of wheel running initiated in the juvenile period (postnatal day 24 would produce more robust and stable changes in microbial communities versus exercise initiated in adulthood (postnatal day 70 in male F344 rats. 16S rRNA gene sequencing was used to characterize the microbial composition of juvenile versus adult runners and their sedentary counterparts across multiple time points during exercise and following exercise cessation. Alpha diversity measures revealed that the microbial communities of young runners were less even and diverse, a community structure that reflects volatility and malleability. Juvenile onset exercise altered several phyla and, notably, increased Bacteroidetes and decreased Firmicutes, a configuration associated with leanness. At the genus level of taxonomy, exercise altered more genera in juveniles than in the adults and produced patterns associated with adaptive metabolic consequences. Given the potential of these changes to contribute to a lean phenotype, we examined body composition in juvenile versus adult runners. Interestingly, exercise produced persistent increases in lean body mass in juvenile but not adult runners. Taken together, these results indicate that the impact of exercise on gut microbiota

  15. Temperament Alters Susceptibility to Negative Peer Influence in Early Adolescence

    Science.gov (United States)

    Mrug, Sylvie; Madan, Anjana; Windle, Michael

    2012-01-01

    The role of deviant peers in adolescent antisocial behavior has been well documented, but less is known about individual differences in susceptibility to negative peer influence. This study examined whether specific temperament dimensions moderate the prospective relationship between peer deviance and delinquent behavior in early adolescence.…

  16. Neural Alterations in Acquired Age-Related Hearing Loss

    Directory of Open Access Journals (Sweden)

    Raksha Anand Mudar

    2016-06-01

    Full Text Available Hearing loss is one of the most prevalent chronic health conditions in older adults. Growing evidence suggests that hearing loss is associated with reduced cognitive functioning and incident dementia. In this mini-review, we briefly examine literature on anatomical and functional alterations in the brains of adults with acquired age-associated hearing loss, which may underlie the cognitive consequences observed in this population, focusing on studies that have used structural and functional magnetic resonance imaging, diffusion tensor imaging, and event-related electroencephalography. We discuss structural and functional alterations observed in the temporal and frontal cortices and the limbic system. These neural alterations are discussed in the context of common cause, information-degradation, and sensory-deprivation hypotheses, and we suggest possible rehabilitation strategies. Although we are beginning to learn more about changes in neural architecture and functionality related to age-associated hearing loss, much work remains to be done. Understanding the neural alterations will provide objective markers for early identification of neural consequences of age-associated hearing loss and for evaluating benefits of intervention approaches.

  17. Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.

    Science.gov (United States)

    Abida, Wassim; Armenia, Joshua; Gopalan, Anuradha; Brennan, Ryan; Walsh, Michael; Barron, David; Danila, Daniel; Rathkopf, Dana; Morris, Michael; Slovin, Susan; McLaughlin, Brigit; Curtis, Kristen; Hyman, David M; Durack, Jeremy C; Solomon, Stephen B; Arcila, Maria E; Zehir, Ahmet; Syed, Aijazuddin; Gao, Jianjiong; Chakravarty, Debyani; Vargas, Hebert Alberto; Robson, Mark E; Joseph, Vijai; Offit, Kenneth; Donoghue, Mark T A; Abeshouse, Adam A; Kundra, Ritika; Heins, Zachary J; Penson, Alexander V; Harris, Christopher; Taylor, Barry S; Ladanyi, Marc; Mandelker, Diana; Zhang, Liying; Reuter, Victor E; Kantoff, Philip W; Solit, David B; Berger, Michael F; Sawyers, Charles L; Schultz, Nikolaus; Scher, Howard I

    2017-07-01

    A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in the disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic non-castrate, and metastatic castration-resistant prostate cancer (CRPC). Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was employed to identify single nucleotide variations, small insertions and deletions, copy number alterations and structural rearrangements in over 300 cancer-related genes in tumors and matched normal blood. We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair (DDR), PI3K, and MAP kinase pathways. 27% of patients harbored a germline or a somatic alteration in a DDR gene that may predict for response to PARP inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, while ATM alterations were specifically enriched in CRPC. Through genomic profiling of prostate tumors representing the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis and castration-resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer, for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.

  18. Primitive Liquid Water of the Solar System in an Aqueous Altered Carbonaceous Chondrite

    Science.gov (United States)

    Tsuchiyama, A.; Miyake, A.; Kitayama, A.; Matsuno, J.; Takeuchi, A.; Uesugi, K.; Suzuki, Y.; Nakano, T.; Zolensky, M. E.

    2016-01-01

    Non-destructive 3D observations of the aqueous altered CM chondrite Sutter's Mill using scanning imaging x-ray microscopy (SIXM) showed that some of calcite and enstatite grains contain two-phase inclusion, which is most probably composed of liquid water and bubbles. This water should be primitive water responsible for aqueous alteration in an asteroid in the early solar system.

  19. Lower limb ice application alters ground reaction force during gait initiation

    Directory of Open Access Journals (Sweden)

    Thiago B. Muniz

    2015-04-01

    Full Text Available BACKGROUND: Cryotherapy is a widely used technique in physical therapy clinics and sports. However, the effects of cryotherapy on dynamic neuromuscular control are incompletely explained. OBJECTIVES: To evaluate the effects of cryotherapy applied to the calf, ankle and sole of the foot in healthy young adults on ground reaction forces during gait initiation. METHOD: This study evaluated the gait initiation forces, maximum propulsion, braking forces and impulses of 21 women volunteers through a force platform, which provided maximum and minimum ground reaction force values. To assess the effects of cooling, the task - gait initiation - was performed before ice application, immediately after and 30 minutes after removal of the ice pack. Ice was randomly applied on separate days to the calf, ankle and sole of the foot of the participants. RESULTS: It was demonstrated that ice application for 30 minutes to the sole of the foot and calf resulted in significant changes in the vertical force variables, which returned to their pre-application values 30 minutes after the removal of the ice pack. Ice application to the ankle only reduced propulsion impulse. CONCLUSIONS: These results suggest that although caution is necessary when performing activities that require good gait control, the application of ice to the ankle, sole of the foot or calf in 30-minute intervals may be safe even preceding such activities.

  20. Early blindness alters the spatial organization of verbal working memory.

    Science.gov (United States)

    Bottini, Roberto; Mattioni, Stefania; Collignon, Olivier

    2016-10-01

    Several studies suggest that serial order in working memory (WM) is grounded on space. For a list of ordered items held in WM, items at the beginning of the list are associated with the left side of space and items at the end of the list with the right side. This suggests that maintaining items in verbal WM is performed in strong analogy to writing these items down on a physical whiteboard for later consultation (The Mental Whiteboard Hypothesis). What drives this spatial mapping of ordered series in WM remains poorly understood. In the present study we tested whether visual experience is instrumental in establishing the link between serial order in WM and spatial processing. We tested early blind (EB), late blind (LB) and sighted individuals in an auditory WM task. Replicating previous studies, left-key responses were faster for early items in the list whereas later items facilitated right-key responses in the sighted group. The same effect was observed in LB individuals. In contrast, EB participants did not show any association between space and serial position in WM. These results suggest that early visual experience plays a critical role in linking ordered items in WM and spatial representations. The analogical spatial structure of WM may depend in part on the actual experience of using spatially organized devices (e.g., notes, whiteboards) to offload WM. These practices are largely precluded to EB individuals, who instead rely to mnemonic devices that are less spatially organized (e.g., recordings, vocal notes). The way we habitually organize information in the external world may bias the way we organize information in our WM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Does interspecific competition alter effects of early season ozone exposure on plants from wet grasslands? Results of a three-year experiment in open-top chambers.

    Science.gov (United States)

    Tonneijck, A E G; Franzaring, J; Brouwer, G; Metselaar, K; Dueck, Th A

    2004-09-01

    Chronic effects of ozone on wet grassland species early in the growing season might be altered by interspecific competition. Individual plants of Holcus lanatus, Lychnis flos-cuculi, Molinia caerulea and Plantago lanceolata were grown in monocultures and in mixed cultures with Agrostis capillaris. Mesocosms were exposed to charcoal-filtered air plus 25 nl l(-1) ozone (CF+25), non-filtered air (NF), non-filtered air plus 25 nl l(-1) ozone (NF+25) and non-filtered air plus 50 nl l(-1) ozone (NF+50) early in the growing seasons of 2000 through 2002. Ozone-enhanced senescence and visible foliar injury were recorded on some of the target plants in the first year only. Ozone effects on biomass production were minimal and plant response to ozone did not differ between monocultures and mixed cultures. After three years, above-ground biomass of the plants in mixed culture compared to monocultures was three times greater for H. lanatus and two to four times smaller for the other species.

  2. Does interspecific competition alter effects of early season ozone exposure on plants from wet grasslands? Results of a three-year experiment in open-top chambers

    International Nuclear Information System (INIS)

    Tonneijck, A.E.G.; Franzaring, J.; Brouwer, G.; Metselaar, K.; Dueck, Th.A.

    2004-01-01

    Chronic effects of ozone on wet grassland species early in the growing season might be altered by interspecific competition. Individual plants of Holcus lanatus, Lychnis flos-cuculi, Molinia caerulea and Plantago lanceolata were grown in monocultures and in mixed cultures with Agrostis capillaris. Mesocosms were exposed to charcoal-filtered air plus 25 nl l -1 ozone (CF + 25), non-filtered air (NF), non-filtered air plus 25 nl l -1 ozone (NF + 25) and non-filtered air plus 50 nl l -1 ozone (NF + 50) early in the growing seasons of 2000 through 2002. Ozone-enhanced senescence and visible foliar injury were recorded on some of the target plants in the first year only. Ozone effects on biomass production were minimal and plant response to ozone did not differ between monocultures and mixed cultures. After three years, above-ground biomass of the plants in mixed culture compared to monocultures was three times greater for H. lanatus and two to four times smaller for the other species

  3. Rare earth impact on glass structure and alteration kinetics

    International Nuclear Information System (INIS)

    Molieres, E.

    2012-01-01

    This work is related to the question of the geological deep repository of high-level waste glass. These wastes include fission products and minor actinides, elements which can be simulated by rare earths. As new glass compositions could enable increased rare earth concentrations, it is crucial to know and understand rare earth impact on glass structure on the one hand, and on glass alteration kinetics or their incorporation into an altered layer. This work studied simplified borosilicate glasses in order to limit synergetic effects between rare earths and other elements. Various complementary techniques were used to characterize pristine and altered glasses (solid-high resolution NMR, Raman spectroscopy, fluorescence, SIMS, SAXS). Firstly, the structural role of a rare earth is discussed and is compared to a calcium cation. The local environment of rare earths is also probed. Secondly, rare earth (nature and concentration) impact on several alteration regimes was studied (initial rate, rate drop). Then, after alteration, rare earth elements being retained within the altered layer, the structural impact of rare earth elements (and their local environment) in this alteration layer was also investigated. (author) [fr

  4. The Early Identity Exploration Scale-a measure of initial exploration in breadth during early adolescence.

    Science.gov (United States)

    Kłym, Maria; Cieciuch, Jan

    2015-01-01

    The existing models and measurement instruments concerning identity appear to primarily focus on adolescence and early adulthood, and studies extending identity research to younger stages of life are scarce. There has been a particular lack of instruments measuring the early stages of identity formation, especially the process of exploration, which has been portrayed as a central process during this particular period of life. Our aim is to help fill the gap in the literature and facilitate further studies of the exploration process by providing an appropriate instrument to measure exploration in breadth during early adolescence. As a coherent and mature sense of identity is closely associated with psychosocial well-being, an effective identity exploration scale will enable researchers to assess the predictors of young adolescents' well-being. We propose a model of identity exploration domains based on the literature and considering 12 exploration domains: physical appearance, free time, family, work, boyfriend-girlfriend relationships, own opinion formation, perception of own place in the life cycle, self-reflection, future, future family, outlook on life, and attitude toward rules. The study was conducted on a group of N = 454 adolescents (50% males, M age = 13.04, SD = 0.98). Both reliability and structural validity, as verified by confirmatory factor analysis were satisfactory. The instrument is invariant across gender groups at the scalar level of measurement invariance.

  5. Molecular alterations in early gastric carcinomas. No apparent correlation with Helicobacter pylori status

    NARCIS (Netherlands)

    Blok, P.; Craanen, M. E.; Offerhaus, G. J.; Dekker, W.; Kuipers, E. J.; Meuwissen, S. G.; Tytgat, G. N.

    1999-01-01

    Data on the differences in molecular profile between H pylori-positive and H pylori-negative early gastric carcinomas, if any, are almost nonexistent. We therefore investigated whether molecular differences can be observed between H pylori-positive and H pylori-negative early gastric carcinomas.

  6. Implications of Eocene-age Philippine Sea and forearc basalts for initiation and early history of the Izu-Bonin-Mariana arc

    Science.gov (United States)

    Yogodzinski, Gene M.; Bizimis, Michael; Hickey-Vargas, Rosemary; McCarthy, Anders; Hocking, Benjamin D.; Savov, Ivan P.; Ishizuka, Osamu; Arculus, Richard

    2018-05-01

    Whole-rock isotope ratio (Hf, Nd, Pb, Sr) and trace element data for basement rocks at ocean drilling Sites U1438, 1201 and 447 immediately west of the KPR (Kyushu-Palau Ridge) are compared to those of FAB (forearc basalts) previously interpreted to be the initial products of IBM subduction volcanism. West-of-KPR basement basalts (drill sites U1438, 1201, 447) and FAB occupy the same Hf-Nd and Pb-Pb isotopic space and share distinctive source characteristics with εHf mostly > 16.5 and up to εHf = 19.8, which is more radiogenic than most Indian mid-ocean ridge basalts (MORB). Lead isotopic ratios are depleted, with 206Pb/204Pb = 17.8-18.8 accompanying relatively high 208Pb/204Pb, indicating an Indian-MORB source unlike that of West Philippine Basin plume basalts. Some Sr isotopes show affects of seawater alteration, but samples with 87Sr/86Sr 8.0 appear to preserve magmatic compositions and also indicate a common source for west-of-KPR basement and FAB. Trace element ratios resistant to seawater alteration (La/Yb, Lu/Hf, Zr/Nb, Sm/Nd) in west-of-KPR basement are generally more depleted than normal MORB and so also appear similar to FAB. At Site U1438, only andesite sills intruding sedimentary rocks overlying the basement have subduction-influenced geochemical characteristics (εNd ∼ 6.6, εHf ∼ 13.8, La/Yb > 2.5, Nd/Hf ∼ 9). The key characteristic that unites drill site basement rocks west of KPR and FAB is the nature of their source, which is more depleted in lithophile trace elements than average MORB but with Hf, Nd, and Pb isotope ratios that are common in MORB. The lithophile element-depleted nature of FAB has been linked to initiation of IBM subduction in the Eocene, but Sm-Nd model ages and errorchron relationships in Site U1438 basement indicate that the depleted character of the rocks is a regional characteristic that was produced well prior to the time of subduction initiation and persists today in the source of modern IBM arc volcanic rocks with

  7. Early indicators and risk factors for ethical issues in clinical practice.

    Science.gov (United States)

    Pavlish, Carol; Brown-Saltzman, Katherine; Hersh, Mary; Shirk, Marilyn; Nudelman, Olga

    2011-03-01

    Nurses in all clinical settings encounter ethical issues that frequently lead to moral distress. This critical incident study explored nurses' descriptions of ethically difficult situations to identify risk factors and early indicators of ethical conflicts. Employing the critical incident technique, researchers developed a questionnaire that collected information on ethically difficult situations, their risk factors and early indicators, nurse actions, and situational outcomes. Two nurse researchers independently analyzed and categorized data using a constant comparison technique. Most of the ethically difficult situations pertained to end-of-life care for children and adults. Conflicts in interpersonal relationships were prevalent. Nurses were especially moved by patient and family suffering and concerned about patient vulnerability, harm-benefit ratio, and patient autonomy. Researchers discovered risk factor categories for patients, families, healthcare providers, and health systems. Additionally, researchers found subcategories in six major categories of early indicators: signs of conflict, patient suffering, nurse distress, ethics violation, unrealistic expectations, and poor communication. Nurses are keenly aware of pertinent risk factors and early indicators of unfolding ethical conflicts. Many nurses reported feeling powerless in the face of ethical conflict. Research that develops interventions to strengthen nurses' voices in ethically difficult situation is warranted. Nurses are in a key position to identify patient situations with a high risk for ethical conflict. Initiating early ethics consultation and interventions can alter the course of pending conflicts and diminish the potential for patient and family suffering and nurses' moral distress. © 2011 Sigma Theta Tau International.

  8. High initiation and long duration of breastfeeding despite absence of early skin-to-skin contact in Karen refugees on the Thai-Myanmar border: a mixed methods study.

    Science.gov (United States)

    White, Adrienne L; Carrara, Verena I; Paw, Moo Kho; Malika; Dahbu, Colleypaw; Gross, Mechthild M; Stuetz, Wolfgang; Nosten, Francois H; McGready, Rose

    2012-12-13

    Early skin-to-skin contact (SSC) after birth is recommended as part of the United Nations Children's Fund (UNICEF) baby friendly health initiative to promote optimum breastfeeding. This paper reports rates of breastfeeding initiation and duration in a low resource environment, where early SSC is not practised, and explores views of pregnant women and midwives surrounding breastfeeding and swaddling. Data from records from a single hospital on the Thai-Myanmar border where refugee women gave birth during a one-year period (2010) were used to determine breastfeeding initiation rates and the time of the first breastfeed, and duration of breastfeeding of the previous alive child in multigravidae. Focus group discussions (FGD) were conducted to obtain information from pregnant women attending antenatal care about their intended or previous duration of breastfeeding and views on breastfeeding. Interviews with local midwives explored reasons for high rates of breastfeeding in this setting and the practice of newborn swaddling. Of 1404 live births in 2010 in Maela refugee camp there were 982 evaluable mother-newborn pairs, including 80 infants born before 37 weeks gestation. Initiation of breastfeeding within the first hour after birth and exclusive breastfeeding at discharge in term mother-newborn pairs was 91.2% (823/902) and 99.3% (896/902); and before 37 weeks gestation, 48.8% (39/80) and 98.8% (79/80). Reported duration of previous breastfeeding was 19 (range 2 to 72) months.During FGD all primigravidae (n = 17) intended to breastfeed and all multigravidae (n = 33) had previously breastfed; expected or previous duration of feeding was for more than one year or longer. The major theme identified during FGD was breastfeeding is "good". Women stated their intention to breastfeed with certainty. This certainty was echoed during the interviews with midwifery staff. SSC requires a delay in early swaddling that in Karen people, with animistic beliefs, could risk loss

  9. Initiation to scientific literacy in early years of elementary school: contributions of a didactic sequence

    Directory of Open Access Journals (Sweden)

    Juliana Pinto Viecheneski

    2013-12-01

    Full Text Available This article presents the results of a research professional, which was developed in the context of the early years of elementary school, from the application of a didactic sequence, with a view to initiation of scientific literacy of students in the literacy process of language. The methodological approach was qualitative, interpretative nature. The subjects were the students of 1st year 1st Cycle of Basic Education in a public school in Ponta Grossa - PR. The data were collected through observation, application of diagnostic testing, audio recordings, photographs, written records, illustrations and posttest. The theory History Cultural Development made the analysis of pedagogical actions and reflections on them. The main results indicate that the activities of the instructional sequence, contributed to the progressive advancement of the students' knowledge in relation to the area of science and basic scientific literacy, and also contributed to make learning the language more contextualized and interdisciplinary. It is noted that this work requires a teacher to assume the role of mediator between the scientific and the children, as well as requires the understanding that, as the subject entered the technological means, students in the early years have a right to access scientific culture. In this perspective, respecting the level of development of the children, the teacher can provide challenges and mediations necessary for the gradual construction of scientific knowledge, the first years of elementary school.

  10. HEALTH SERVICES AND IT’S UTILIZATION RELATED TO EXCLUSIVE BREASTFEEDING AND EARLY BREASTFEEDING INITIATION PROGRAM IN WEST JAVA PROVINCE

    Directory of Open Access Journals (Sweden)

    Nur Handayani Utami

    2015-01-01

    Full Text Available AbstractDespite the essential benefit of early initiation of breastfeeding and exclusive breast feeding during the first six months, the practice was still low. Health services and personnel play important role have not optimal yet in breast feeding. The aim of this study was to review the provision of health services and it’s utilization related to early breastfeeding initiation and exclusive breastfeeding practices in West Java province. This study was an analysis of the Indonesian Health Facility Survey (Rifaskes 2011 and the Basic Health Survey (Riskesdas 2010. It analyzed 45 public hospitals  and  997  primary  health  centers  in  West  Java  Province  from  HFS  and  285  infants (0-6 months in West Java province from Riskesdas. It supplemented with qualitative data that obtained from in-depth interviews with the representatives from central government, Provincial Health Office, District Health Office (DHO, public health centers and hospitals in Bandung city and Bogor district, West Java. This study revealed that a number of gaps related to breastfeeding services  in  PHC  and  hospitals  were  still  found.  One  of  the  influential  factors  that  hindering  the breastfeeding services in health services was the absence of local policy regarding early initiation of breastfeeding and exclusive breastfeeding practices in West Java Province. The limitation of human resources, facilities and specific budget were also become the obstacles in the implementation of the breastfeeding program. This study implied that most of community already utilized the maternal and child’s heath care. This study indicated the importance of health services and support from health professionals for successful of breastfeeding. Thus the strong commitment of health personnels as well as the policy makers was really needed.Keywords : early initiation of breastfeeding; exclusive breastfeeding; health facilities; utilization

  11. Heart rate profile during exercise in patients with early repolarization.

    Science.gov (United States)

    Cay, Serkan; Cagirci, Goksel; Atak, Ramazan; Balbay, Yucel; Demir, Ahmet Duran; Aydogdu, Sinan

    2010-09-01

    Both early repolarization and altered heart rate profile are associated with sudden death. In this study, we aimed to demonstrate an association between early repolarization and heart rate profile during exercise. A total of 84 subjects were included in the study. Comparable 44 subjects with early repolarization and 40 subjects with normal electrocardiogram underwent exercise stress testing. Resting heart rate, maximum heart rate, heart rate increment and decrement were analyzed. Both groups were comparable for baseline characteristics including resting heart rate. Maximum heart rate, heart rate increment and heart rate decrement of the subjects in early repolarization group had significantly decreased maximum heart rate, heart rate increment and heart rate decrement compared to control group (all P decrement (multiple-adjusted OR of the risk of presence of early repolarization was 2.98 (95%CI 1.21-7.34) (P = 0.018) and 7.73 (95%CI 2.84-21.03) (P decrement compared to higher levels, respectively. Subjects with early repolarization have altered heart rate profile during exercise compared to control subjects. This can be related to sudden death.

  12. Timescales and settings for alteration of chondritic meteorites

    Energy Technology Data Exchange (ETDEWEB)

    Krot, A N; Hutcheon, I D; Brearley, A J; Pravdivtseva, O V; Petaev, M I; Hohenberg, C M

    2005-11-16

    Most groups of chondritic meteorites experienced diverse styles of secondary alteration to various degrees that resulted in formation of hydrous and anhydrous minerals (e.g., phyllosilicates, magnetite, carbonates, ferrous olivine, hedenbergite, wollastonite, grossular, andradite, nepheline, sodalite, Fe,Ni-carbides, pentlandite, pyrrhotite, Ni-rich metal). Mineralogical, petrographic, and isotopic observations suggest that the alteration occurred in the presence of aqueous solutions under variable conditions (temperature, water/rock ratio, redox conditions, and fluid compositions) in an asteroidal setting, and, in many cases, was multistage. Although some alteration predated agglomeration of the final chondrite asteroidal bodies (i.e. was pre-accretionary), it seems highly unlikely that the alteration occurred in the solar nebula, nor in planetesimals of earlier generations. Short-lived isotope chronologies ({sup 26}Al-{sup 26}Mg, {sup 53}Mn-{sup 53}Cr, {sup 129}I-{sup 129}Xe) of the secondary minerals indicate that the alteration started within 1-2 Ma after formation of the Ca,Al-rich inclusions and lasted up to 15 Ma. These observations suggest that chondrite parent bodies must have accreted within the first 1-2 Ma after collapse of the protosolar molecular cloud and provide strong evidence for an early onset of aqueous activity on these bodies.

  13. Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning

    NARCIS (Netherlands)

    J.A. Cabrera (Jesús); E.A. Ziemba (Elizabeth); L.H. Colbert (Lisa); L.B. Anderson (Lorraine); W.J. Sluiter (Wim); D.J.G.M. Duncker (Dirk); T.A. Butterick (Tammy); J. Sikora (Joseph); H.B. Ward (Herbert B.); R.F. Kelly (Rosemary); E.O. McFalls (Edward)

    2012-01-01

    textabstractAltered expression of mitochondrial electron transport proteins has been shown in early preconditioned myocardial tissue. We wished to determine whether these alterations persist in the Second Window of Protection (SWOP) and if so, whether a favorable energetic state is facilitated

  14. The Practices, Perceptions, and Beliefs of Traditional Birth Attendants Regarding Early Breastfeeding Initiation in Zimbabwe: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Gladys Mugadza

    2018-04-01

    Full Text Available Background & aim: Early breastfeeding initiation (EBFI defined as giving breast milk within the first hours following birth, which is recommended as a simple strategy for the enhancement of neonatal health and survival. This descriptive qualitative study was conducted to explore the practices, perceptions and beliefs of renowned traditional birth attendants (TBA regarding EBFI in Chipinge rural community, Zimbabwe. Methods: The study population was selected through purposive sampling technique. One-on-one interview was conducted for the purpose of unearthing sensitive issues regarding EBFI. The data were collected using an unstructured in-depth interview to explore the practices, perceptions, and beliefs regarding EBFI. Data analysis was carried out using thematic analysis. To this end, the data were presented in thematic categories using the deductive approach and coded into subthemes, which were then merged into themes. The trustworthiness of the study was enhanced through credibility, dependability, confirmability and transferability. Results: The emerged themes included EBFI preparation, EBFI and significance of colostrum, and determinants of EBFI. The findings revealed that EBFI was not only related to physical and emotional interactions, but also associated with a totality of the person, involving sociocultural ties. The EBFI is viewed as a predictor of maternal sociocultural integrity and the legitimacy of the newborn. In the context under study, failure to breastfeed or to initiate breastfeeding early is thought to be a result of the mother’s past immorality. Breastfeeding in Chipinge community goes beyond the mother-baby interaction. Conclusion: It encompasses the whole person,  that is the physical, social, cultural and spiritual ties. Under this condition, the mother should testify and undergo a ritual cleansing to rectify the problem.

  15. Temporal and spatial distribution of alteration, mineralization and fluid inclusions in the transitional high-sulfidation epithermal-porphyry copper system at Red Mountain, Arizona

    Science.gov (United States)

    Lecumberri-Sanchez, Pilar; Newton, M. Claiborne; Westman, Erik C.; Kamilli, Robert J.; Canby, Vertrees M.; Bodnar, Robert J.

    2013-01-01

    Red Mountain, Arizona, is a Laramide porphyry Cu system (PCD) that has experienced only a modest level of erosion compared to most other similar deposits in the southwestern United States. As a result, the upper portion of the magmatic–hydrothermal system, which represents the transition from shallower high-sulfidation epithermal mineralization to deeper porphyry Cu mineralization, is well preserved. Within the Red Mountain system, alteration, mineralization and fluid inclusion assemblages show a systematic distribution in both time and space. Early-potassic alteration (characterized by the minerals biotite and magnetite) is paragenetically earlier than late-potassic alteration (K-feldspar–anhydrite) and both are followed by later phyllic (sericite–pyrite) alteration. Advanced argillic alteration (pyrophyllite–alunite–other clay minerals) is thought to be coeval with or postdate phyllic alteration. Minerals characteristic of advanced argillic alteration are present in the near surface. Phyllic alteration extends to greater depths compared to advanced argillic alteration. Early-potassic and late-potassic alteration are only observed in the deepest part of the system. Considerable overlap of phyllic alteration with both early-potassic and late-potassic alteration zones is observed. The hypogene mineralization contains 0.4–1.2% Cu and is spatially and temporally related to the late-potassic alteration event. Molybdenum concentration is typically In the deepest part of the system, an early generation of low-to-moderate density and salinity liquid + vapor inclusions with opaque daughter minerals is followed in time by halite-bearing inclusions that also contain opaque daughter minerals indicating that an early intermediate-density magmatic fluid evolved to a high-density, high-salinity mineralizing fluid. The increase in density and salinity of fluids with time observed in the deeper parts of the system may be the result of immiscibility (“boiling”) of

  16. Nitrogen alters carbon dynamics during early succession in boreal forest

    Science.gov (United States)

    Steven D. Allison; Tracy B. Gartner; Michelle C. Mack; Krista McGuire; Kathleen. Treseder

    2010-01-01

    Boreal forests are an important source of wood products, and fertilizers could be used to improve forest yields, especially in nutrient poor regions of the boreal zone. With climate change, fire frequencies may increase, resulting in a larger fraction of the boreal landscape present in early successional stages. Since most fertilization studies have focused on mature...

  17. Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

    Science.gov (United States)

    Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

    2015-01-01

    Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia – before severe fat loss – in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34–42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition. PMID:25457061

  18. Altered Evoked Gamma-Band Responses Reveal Impaired Early Visual Processing in ADHD Children

    Science.gov (United States)

    Lenz, Daniel; Krauel, Kerstin; Flechtner, Hans-Henning; Schadow, Jeanette; Hinrichs, Hermann; Herrmann, Christoph S.

    2010-01-01

    Neurophysiological studies yield contrary results whether attentional problems of patients with attention-deficit/hyperactivity disorder (ADHD) are related to early visual processing deficits or not. Evoked gamma-band responses (GBRs), being among the first cortical responses occurring as early as 90 ms after visual stimulation in human EEG, have…

  19. Flight initiation and maintenance deficits in flies with genetically altered biogenic amine levels

    OpenAIRE

    Brembs, Björn; Christiansen, F.; Pflüger, J.; Duch, C.

    2007-01-01

    Insect flight is one of the fastest, most intense and most energy-demanding motor behaviors. It is modulated on multiple levels by the biogenic amine octopamine. Within the CNS, octopamine acts directly on the flight central pattern generator, and it affects motivational states. In the periphery, octopamine sensitizes sensory receptors, alters muscle contraction kinetics, and enhances flight muscle glycolysis. This study addresses the roles for octopamine and its precursor tyramine in flight ...

  20. Hydrothermal alteration in Dumoga Barat, Bolaang Mongondow area North Sulawesi

    International Nuclear Information System (INIS)

    Agus Harjanto' Sutanto; Sutarto; Achmad Subandrio; I Made Suasta; Juanito Salamat; Giri Hartono; Putu Suputra; I Gde Basten; Muhammad Fauzi; Rosdiana

    2016-01-01

    Bolaang Mongondow is located in central north Sulawesi arm, which is composed of Neogen magmatic arc and potentially contain economic minerals. This condition is behind the research purpose to study the mineral resources potencies. Research aim is to study alteration caused by hydrothermal process and its relation with gold (Au) deposit based on field study and laboratory analysis. Methodologies used for the research are literature study, geological survey, rocks sampling, laboratory analysis, and data processing. Research area is a multiply diorite intrusion complex. Andesite, volcaniclastic rocks, and dacite, the older rocks, were intruded by this complex. Later, dacitic tuff, volcanic sandstone, and alluvium deposited above them. There are three measured and mapped major faults heading NE-SW crossed by E-W fault and NW-SE fault lately crossed all the older faults. Early stage hydrothermal alteration related to the existence of young quartz diorite, showing alteration stage from the potassic center to distal prophylatic. Final stage hydrothermal alteration consist of argilic, advanced argilic, and silica-clay mineral±magnetite±chlorite alteration overlapping the earlier alteration. Mineralization of Cu-Au±Ag in central part of research area or Tayap-Kinomaligan area is mostly associated with potassic altered young quartz diorite and crossed by parallel and stock worked quartz-magnetite-chalcopyrite±bornite vein. (author)

  1. Olanzapine Overdose in a Pin Point Pupil with Altered Sensorium

    Directory of Open Access Journals (Sweden)

    Naresh Midha

    2017-09-01

    Full Text Available Background:Olanzapine is a highly tolerable and easily affordable atypical antipsychotic drug which has been commonly prescribed in both inpatient and outpatient settings for several mental disorders. Olanzapine overdose is commonly seen in psychiatric patients, who attempt suicide by intoxicating themselves with their own prescribed medications. Increased olanzapine use is associated with increased incidence of overdosing. Case Presentation:We are reporting a case of olanzapine overdosage as a cause of pinpoint pupils and altered sensorium with exclusion of other differentials. The mainstay of managementof olanzapine overdose is general supportive and symptomatic measures. Discussion: Pinpoint pupils with altered sensorium and agitation are always an alarming situation for a clinician, because of differentials like organophosphorus poisoning, pontine hemorrhage and opium overdosing. Due to olanzapine overdosage, similar clinical picture can be confusing in the emergency department and early identification of such cases is helpful to decrease the risk of fatality. Conclusion: This case highlights the significance of olanzapine overdosing as a differential diagnosis for patients presented with altered sensorium and pinpoint pupils in the emergency department. Olanzapine overdosage is associated with high morbidity and mortality. Although there is no specific antidote for olanzapine overdose, appropriate history, assessment and early diagnosis are very useful for the better outcome.

  2. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission.

    Directory of Open Access Journals (Sweden)

    Tulika Arora

    Full Text Available Roux-en-Y gastric bypass (RYGB is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3, which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.

  3. Whole transcriptome profiling of maize during early somatic embryogenesis reveals altered expression of stress factors and embryogenesis-related genes.

    Directory of Open Access Journals (Sweden)

    Stella A G D Salvo

    Full Text Available Embryogenic tissue culture systems are utilized in propagation and genetic engineering of crop plants, but applications are limited by genotype-dependent culture response. To date, few genes necessary for embryogenic callus formation have been identified or characterized. The goal of this research was to enhance our understanding of gene expression during maize embryogenic tissue culture initiation. In this study, we highlight the expression of candidate genes that have been previously regarded in the literature as having important roles in somatic embryogenesis. We utilized RNA based sequencing (RNA-seq to characterize the transcriptome of immature embryo explants of the highly embryogenic and regenerable maize genotype A188 at 0, 24, 36, 48, and 72 hours after placement of explants on tissue culture initiation medium. Genes annotated as functioning in stress response, such as glutathione-S-transferases and germin-like proteins, and genes involved with hormone transport, such as PINFORMED, increased in expression over 8-fold in the study. Maize genes with high sequence similarity to genes previously described in the initiation of embryogenic cultures, such as transcription factors BABY BOOM, LEAFY COTYLEDON, and AGAMOUS, and important receptor-like kinases such as SOMATIC EMBRYOGENESIS RECEPTOR LIKE KINASES and CLAVATA, were also expressed in this time course study. By combining results from whole genome transcriptome analysis with an in depth review of key genes that play a role in the onset of embryogenesis, we propose a model of coordinated expression of somatic embryogenesis-related genes, providing an improved understanding of genomic factors involved in the early steps of embryogenic culture initiation in maize and other plant species.

  4. 18F-FDG PET and MRS of the early stages of subacute sclerosing panencephalitis in a child with a normal initial MRI

    International Nuclear Information System (INIS)

    Seo, Yeong-Seon; Jung, Da-Eun; Kim, Ho-Sung

    2010-01-01

    In subacute sclerosing panencephalitis (SSPE), conventional MRI findings have been reported. However, in the early clinical stages, imaging studies can appear normal. Moreover, with no history of infant measles infection, the diagnosis of SSPE can only be arrived at after extensive investigation that must eliminate a number of neurodegenerative diseases. We report here on 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) and magnetic resonance spectroscopy (MRS) findings in a 14-year-old girl with a normal initial MRI who had not contracted measles. Although 18 F-FDG PET and MRS are not specific or diagnostic for SSPE, these techniques can demonstrate substantial metabolic impairments when MRI findings show no obvious abnormalities, as is often the case in the early stages of this disease. (orig.)

  5. 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

  6. Inflation with generalized initial conditions

    International Nuclear Information System (INIS)

    Albrecht, A.; Brandenberger, R.; Matzner, R.

    1987-01-01

    In many current models of the early Universe a scalar field phi which is only very weakly coupled to other quantum fields is used to generate inflation. In such models there are no forces which could thermalize the scalar field, and previous assumptions about its preinflation ''initial'' conditions must be abandoned. In this paper the onset of inflation is studied classically for more general initial conditions of the scalar field configuration. In particular, initial conditions with a nonvanishing spatial average of phi, with phi chosen at random in each initial horizon volume, and with random initial momenta are considered. We identify and discuss several mechanisms that can drive these more general initial conditions toward an inflationary state. The analysis is done in one spatial dimension

  7. Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

    Science.gov (United States)

    Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

    2014-08-01

    Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

  8. Early Effects of Altered Gravity Environments on Plant Cell Growth and Cell Proliferation: Characterization of Morphofunctional Nucleolar Types in an Arabidopsis Cell Culture System

    Energy Technology Data Exchange (ETDEWEB)

    Manzano, Ana I.; Herranz, Raúl; Manzano, Aránzazu [Centro de Investigaciones Biológicas (CSIC), Madrid (Spain); Loon, Jack J. W. A. van [Department of Oral and Maxillofacial Surgery/Oral Pathology, Dutch Experiment Support Center, VU University Medical Center, Amsterdam (Netherlands); Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam (Netherlands); ESA-ESTEC, TEC-MMG, Noordwijk (Netherlands); Medina, F. Javier, E-mail: fjmedina@cib.csic.es [Centro de Investigaciones Biológicas (CSIC), Madrid (Spain)

    2016-02-05

    Changes in the cell growth rate of an in vitro cellular system in Arabidopsis thaliana induced by short exposure to an altered gravity environment have been estimated by a novel approach. The method consisted of defining three structural nucleolar types which are easy and reliable indicators of the ribosome biogenesis activity and, consequently, of protein biosynthesis, a parameter strictly correlated to cell growth in this cellular system. The relative abundance of each nucleolar type was statistically assessed in different conditions of gravity. Samples exposed to simulated microgravity for 200 min showed a significant decrease in nucleolar activity compared to 1g controls, whereas samples exposed to hypergravity (2g) for the same period showed nucleolar activity slightly increased. These effects could be considered as an early cellular response to the environmental alteration, given the short duration of the treatment. The functional significance of the structural data was validated by a combination of several different well-known parameters, using microscopical, flow cytometry, qPCR, and proteomic approaches, which showed that the decreased cell growth rate was decoupled from an increased cell proliferation rate under simulated microgravity, and the opposite trend was observed under hypergravity. Actually, not all parameters tested showed the same quantitative changes, indicating that the response to the environmental alteration is time-dependent. These results are in agreement with previous observations in root meristematic cells and they show the ability of plant cells to produce a response to gravity changes, independently of their integration into plant organs.

  9. Communication Ambassadors-an Australian Social Media Initiative to Develop Communication Skills in Early Career Scientists.

    Science.gov (United States)

    Wang, Jack T H; Power, Cheryl J; Kahler, Charlene M; Lyras, Dena; Young, Paul R; Iredell, Jonathan; Robins-Browne, Roy

    2018-01-01

    Science communication is a skill set to be developed through ongoing interactions with different stakeholders across a variety of platforms. Opportunities to engage the general public are typically reserved for senior scientists, but the use of social media in science communication allows all scientists to instantaneously disseminate their findings and interact with online users. The Communication Ambassador program is a social media initiative launched by the Australian Society for Microbiology to expand the online presence and science communication portfolios of early-career scientists. Through their participation in the program, a rotating roster of Australian microbiologists have broadened the online reach of the Society's social media channels as well as their own professional networks by attending and live-tweeting microbiology events throughout the year. We present the Communication Ambassador program as a case study of coordinated social media activity in science communication to the general public, and describe the potential for its applications in science education and training.

  10. Proteomic identification of early salicylate- and flg22-responsive redox-sensitive proteins in Arabidopsis

    KAUST Repository

    Liu, Peng

    2015-02-27

    Accumulation of reactive oxygen species (ROS) is one of the early defense responses against pathogen infection in plants. The mechanism about the initial and direct regulation of the defense signaling pathway by ROS remains elusive. Perturbation of cellular redox homeostasis by ROS is believed to alter functions of redox-sensitive proteins through their oxidative modifications. Here we report an OxiTRAQ-based proteomic study in identifying proteins whose cysteines underwent oxidative modifications in Arabidopsis cells during the early response to salicylate or flg22, two defense pathway elicitors that are known to disturb cellular redox homeostasis. Among the salicylate- and/or flg22-responsive redox-sensitive proteins are those involved in transcriptional regulation, chromatin remodeling, RNA processing, post-translational modifications, and nucleocytoplasmic shuttling. The identification of the salicylate-/flg22-responsive redox-sensitive proteins provides a foundation from which further study can be conducted toward understanding biological significance of their oxidative modifications during the plant defense response.

  11. The relative contribution of genes and environment to alcohol use in early adolescents: are similar factors related to initiation of alcohol use and frequency of drinking?

    NARCIS (Netherlands)

    Poelen, Evelien A. P.; Derks, Eske M.; Engels, Rutger C. M. E.; van Leeuwe, Jan F. J.; Scholte, Ron H. J.; Willemsen, Gonneke; Boomsma, Dorret I.

    2008-01-01

    The present study assessed the relative contribution of genes and environment to individual differences in initiation of alcohol use and frequency of drinking among early adolescents and examined the extent to which the same genetic and environmental factors influence both individual differences in

  12. The Relative Contribution of Genes and Environment to Alcohol Use in Early Adolescents : Are Similar Factors Related to Initiation of Alcohol Use and Frequency of Drinking?

    NARCIS (Netherlands)

    Poelen, E.A.P.; Derks, E.M.; Engels, R.C.M.E.; Scholte, R.H.J.; Willemsen, A.H.M.; Boomsma, D.I.

    2008-01-01

    Background: The present study assessed the relative contribution of genes and environment to individual differences in initiation of alcohol use and frequency of drinking among early adolescents and examined the extent to which the same genetic and environmental factors influence both individual

  13. The relative contribution of genes and environment to alcohol use in early adolescents: Are similar factors related to initiation of alcohol use and frequency of drinking?

    NARCIS (Netherlands)

    Poelen, E.A.P.; Derks, E.M.; Engels, R.C.M.E.; Leeuwe, J.F.J.; Scholte, R.H.J.; Willemsen, G.; Boomsma, D.I.

    2008-01-01

    Background: The present study assessed the relative contribution of genes and environment to individual differences in initiation of alcohol use and frequency of drinking among early adolescents and examined the extent to which the same genetic and environmental factors influence both individual

  14. Predicting early epidurals: association of maternal, labor, and neonatal characteristics with epidural analgesia initiation at a cervical dilation of 3 cm or less.

    Science.gov (United States)

    Moore, Albert R; Shan, William Li Pi; Hatzakorzian, Roupen

    2013-01-01

    Retrospective studies have associated early epidural analgesia with cesarean delivery, but prospective studies do not demonstrate a causal relationship. This suggests that there are other variables associated with early epidural analgesia that increase the risk of cesarean delivery. This study was undertaken to determine the characteristics associated with early epidural analgesia initiation. Information about women delivering at 37 weeks or greater gestation with epidural analgesia, who were not scheduled for cesarean delivery, was extracted from the McGill Obstetric and Neonatal Database. Patients were grouped into those who received epidural analgesia at a cervical dilation of ≤3 cm and >3 cm. Univariable and multivariable logistic regression was used to determine the maternal, neonatal, and labor characteristics that increased the risk of inclusion in the early epidural group. Of the 13,119 patients analyzed, multivariable regression demonstrated odds ratios (OR) of 2.568, 5.915 and 10.410 for oxytocin augmentation, induction, and dinoprostone induction of labor (P analgesia (OR 0.780, P analgesia (P neonatal weight (OR 0.943, P analgesia. Labor augmentation and induction, nulliparity, rupture of membranes spontaneously and before labor starts, increasing maternal weight, and decreasing neonatal weight are associated with early epidural analgesia. Many of these variables are also associated with cesarean delivery.

  15. Effects of Early Serotonin Programming on Fear Response, Memory and Aggression

    Science.gov (United States)

    The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter development of serotonergic circuitry, altering behaviors mediated by 5-HT signaling, including memory, fear and aggression. The present study was desi...

  16. Workshop initial report: Expanding the geoscience pipeline by connecting educators with early career IODP scientists

    Science.gov (United States)

    Lewis, J. C.; Cooper, S. K.; Hovan, S. A.; Leckie, R. M.; White, L. D.

    2017-12-01

    The U.S. is facing challenges in attracting, retaining and diversifying the workforce in the geosciences. A likely contributing factor is the homogeneity of the pool of mentors/role models available both within the workforce and in the U.S. professoriate. Another probable factor is "exposure gaps" among U.S. student populations; i.e., differing access to engaging facets of science, technology, engineering and mathematics (STEM). In response, we organized an 18-day School of Rock workshop onboard the International Ocean Discovery Program (IODP) drilling vessel JOIDES Resolution during a July 2017 transit in the western Pacific. Our objectives were diversity driven, focusing on measures to broaden participation at all levels (i.e., K-12, undergraduate and beyond) in innovative ways (e.g., from place-base curriculum to longitudinal peer mentoring through extracurricular STEM communities). To accomplish this, we designed a recruiting scheme to attract pairs of participants, specifically a teacher from a diverse community and a nearby early-career scientist with an interest in IODP science. By partnering in this way we sought to foster connections that might not naturally emerge, and therein to establish new mechanisms for increased engagement, broader recruitment, enhanced support, and improved retention of students from underrepresented communities in STEM education. We report on initial workshop outcomes that include new curriculum proposals, nascent funding proposals, and innovative connections among secondary educators and early-career scientists. Survey results of our participants gauge the expected impacts of the workshop on perceptions and on plans for future actions aimed at broadening participation.

  17. Who Gets Early Tracheostomy?

    Science.gov (United States)

    Shaw, Joshua J.

    2015-01-01

    BACKGROUND: Although the benefits of early tracheostomy in patients dependent on ventilators are well established, the reasons for variation in time from intubation to tracheostomy remain unclear. We identified clinical and demographic disparities in time to tracheostomy. METHODS: We performed a level 3 retrospective prognostic study by querying the University HealthSystem Consortium (2007-2010) for adult patients receiving a tracheostomy after initial intubation. Time to tracheostomy was designated early ( 10 days). Cohorts were stratified by time to tracheostomy and compared using univariate tests of association and multivariable adjusted models. RESULTS: A total of 49,191 patients underwent tracheostomy after initial intubation: 42% early (n = 21,029) and 58% late (n = 28,162). On both univariate and multivariable analyses, women, blacks, Hispanics, and patients receiving Medicaid were less likely to receive an early tracheostomy. Patients in the early group also experienced lower rates of mortality (OR, 0.84; 95% CI, 0.79-0.88). CONCLUSIONS: Early tracheostomy was associated with increased survival. Yet, there were still significant disparities in time to tracheostomy according to sex, race, and type of insurance. Application of evidence-based algorithms for tracheostomy may reduce unequal treatment and improve overall mortality rates. Additional research into this apparent bias in referral/rendering of tracheostomy is needed. PMID:26313324

  18. Early Right Ventricular Apical Pacing-Induced Gene Expression Alterations Are Associated with Deterioration of Left Ventricular Systolic Function

    Directory of Open Access Journals (Sweden)

    Haiyan Xu

    2017-01-01

    Full Text Available The chronic high-dose right ventricular apical (RVA pacing may have deleterious effects on left ventricular (LV systolic function. We hypothesized that the expression changes of genes regulating cardiomyocyte energy metabolism and contractility were associated with deterioration of LV function in patients who underwent chronic RVA pacing. Sixty patients with complete atrioventricular block and preserved ejection fraction (EF who underwent pacemaker implantation were randomly assigned to either RVA pacing (n=30 group or right ventricular outflow tract (RVOT pacing (n=30 group. The mRNA levels of OPA1 and SERCA2a were significantly lower in the RVA pacing group at 1 month’s follow-up (both p<0.001. Early changes in the expression of selected genes OPA1 and SERCA2a were associated with deterioration in global longitudinal strain (GLS that became apparent months later (p=0.002 and p=0.026, resp. The altered expressions of genes that regulate cardiomyocyte energy metabolism and contractility measured in the peripheral blood at one month following pacemaker implantation were associated with subsequent deterioration in LV dyssynchrony and function in patients with preserved LVEF, who underwent RVA pacing.

  19. Early Trypanosoma cruzi Infection Reprograms Human Epithelial Cells

    Directory of Open Access Journals (Sweden)

    María Laura Chiribao

    2014-01-01

    Full Text Available Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response, a great number of transcription factors (including the majority of NFκB family members, and host metabolism (cholesterol, fatty acids, and phospholipids. These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination.

  20. Initial Assessment of Whiplash Patients

    Directory of Open Access Journals (Sweden)

    R Gunzburg

    2003-01-01

    Full Text Available The article looks at how for severe trauma, the outcome of treatment depends on the initial medical care. This has now also been accepted for whiplash associated disorders, underlining the importance of a proper initial assessment. Once major injury has been excluded and the diagnosis of whiplash associated disorder has been established, the initial treatment of whiplash in the emergency room can be started. The four key points to remember are described, including reassuring the patient about evolution, no soft collar, nonsteroidal anti-inflammatory drugs and early mobilisation.

  1. Does interspecific competition alter effects of early season ozone exposure on plants from wet grasslands? Results of a three-year experiment in open-top chambers

    Energy Technology Data Exchange (ETDEWEB)

    Tonneijck, A.E.G.; Franzaring, J.; Brouwer, G.; Metselaar, K.; Dueck, Th.A

    2004-09-01

    Chronic effects of ozone on wet grassland species early in the growing season might be altered by interspecific competition. Individual plants of Holcus lanatus, Lychnis flos-cuculi, Molinia caerulea and Plantago lanceolata were grown in monocultures and in mixed cultures with Agrostis capillaris. Mesocosms were exposed to charcoal-filtered air plus 25 nl l{sup -1} ozone (CF + 25), non-filtered air (NF), non-filtered air plus 25 nl l{sup -1} ozone (NF + 25) and non-filtered air plus 50 nl l{sup -1} ozone (NF + 50) early in the growing seasons of 2000 through 2002. Ozone-enhanced senescence and visible foliar injury were recorded on some of the target plants in the first year only. Ozone effects on biomass production were minimal and plant response to ozone did not differ between monocultures and mixed cultures. After three years, above-ground biomass of the plants in mixed culture compared to monocultures was three times greater for H. lanatus and two to four times smaller for the other species.

  2. Rheumatoid cachexia and other nutritional alterations in rheumatologic diseases.

    Science.gov (United States)

    Hurtado-Torres, Gilberto Fabián; González-Baranda, Lourdes Larisa; Abud-Mendoza, Carlos

    2015-01-01

    The prevalence of nutritional alterations in rheumatologic diseases ranges from 4 to 95%, depending on the detection method used. Formerly described as the single term rheumatoid cachexia, nutritional alterations can currently be grouped and subdivided based on the physiopathological mechanisms involved: chronic disease-related inflammatory conditions (cachexia), malnutrition associated to acute malnutrition inflammatory conditions (protein-caloric malnutrition) and starvation-related malnutrition. Clinical manifestations of malnutrition associated to rheumatic diseases vary from the patient with low weight or overweight and obesity; with lean body mass depletion as well as functional repercussions, and impact of quality of life as a common denominator. Additionally, the associated increase in body fat mass increases the risk for cardiovascular morbidity. A multidisciplinary approach towards rheumatic diseases should include aspects oriented towards prevention, early identification, diagnosis and correction of nutritional alterations. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  3. Epilepsy in patients with GRIN2A alterations

    DEFF Research Database (Denmark)

    von Stülpnagel, Celina; Ensslen, M; Møller, R S

    2017-01-01

    indicate that children with epilepsy due to pathogenic GRIN2A mutations present with different clinical phenotypes and a spectrum of seizure types in the context of a pharmacoresistant epilepsy providing information for clinicians treating children with this form of genetically determined epileptic......OBJECTIVE: To delineate the genetic, neurodevelopmental and epileptic spectrum associated with GRIN2A alterations with emphasis on epilepsy treatment. METHODS: Retrospective study of 19 patients (7 females; age: 1-38 years; mean 10.1 years) with epilepsy and GRIN2A alteration. Genetic variants were...... classified according to the guidelines and recommendations of the American College of Medical Genetics (ACMG). Clinical findings including epilepsy classification, treatment, EEG findings, early childhood development and neurodevelopmental outcome were collected with an electronic questionnaire. RESULTS: 7...

  4. Geochemical behaviour of rare earth elements on metasomatic alteration of volcanic rocks

    International Nuclear Information System (INIS)

    Jordanov, J.A.; Kunov, A.J.

    1987-01-01

    Investigations are carried out on metasomatically altered Paleogene latites in order to follow up the rare earth elements (REE) geochemical behavour. Representative samples of the initial rocks (latites), from propylitized latites and quartz-sericite rocks, as well as from dickite, alumite, diaspore and monoquartzites, are analysed. The results show that REE have a behaviour of moderately mobile elements. They undergo redistribution both in quantity and in the composition of the group. The different concentrations and changes in the ΣREE compared to the initial rocks are observed and direct relationships to the degree of endogenic leaching are made. The REE mobility and redistribution during the metasomatic alterations in the region investigated are controlled by the physical-chemical conditions which play a significant role both in determining the composition of the mineral paragenese and in the fixing of REE. The distribution patterns indicate that REE redistribution in the case of metasomatic alterations is almost isochemical without any supply from hydrothermal solutions

  5. Reduction of initial shock in decadal predictions using a new initialization strategy

    Science.gov (United States)

    He, Yujun; Wang, Bin; Liu, Mimi; Liu, Li; Yu, Yongqiang; Liu, Juanjuan; Li, Ruizhe; Zhang, Cheng; Xu, Shiming; Huang, Wenyu; Liu, Qun; Wang, Yong; Li, Feifei

    2017-08-01

    A novel full-field initialization strategy based on the dimension-reduced projection four-dimensional variational data assimilation (DRP-4DVar) is proposed to alleviate the well-known initial shock occurring in the early years of decadal predictions. It generates consistent initial conditions, which best fit the monthly mean oceanic analysis data along the coupled model trajectory in 1 month windows. Three indices to measure the initial shock intensity are also proposed. Results indicate that this method does reduce the initial shock in decadal predictions by Flexible Global Ocean-Atmosphere-Land System model, Grid-point version 2 (FGOALS-g2) compared with the three-dimensional variational data assimilation-based nudging full-field initialization for the same model and is comparable to or even better than the different initialization strategies for other fifth phase of the Coupled Model Intercomparison Project (CMIP5) models. Better hindcasts of global mean surface air temperature anomalies can be obtained than in other FGOALS-g2 experiments. Due to the good model response to external forcing and the reduction of initial shock, higher decadal prediction skill is achieved than in other CMIP5 models.

  6. Host rock characteristics of uranium deposits of cataclastic-altered granite type

    International Nuclear Information System (INIS)

    Feng Mingyue

    1997-01-01

    The author expounds the host rock characteristics of uranium deposits of cataclastic-altered granite type, i.e., the high initial content of uranium, the high cataclasis of host rocks, the strong alteration of host rocks, the simple composition of host rocks favourable for the leaching of uranium, as well as the low content of harmful associated elements. These characteristics may be regarded as petrological criteria for recognition and prospecting for such type of uranium deposits

  7. Host rock characteristics of uranium deposits of cataclastic-altered granite type

    Energy Technology Data Exchange (ETDEWEB)

    Mingyue, Feng [Beijing Research Inst. of Uranium Geology (China)

    1997-03-01

    The author expounds the host rock characteristics of uranium deposits of cataclastic-altered granite type, i.e., the high initial content of uranium, the high cataclasis of host rocks, the strong alteration of host rocks, the simple composition of host rocks favourable for the leaching of uranium, as well as the low content of harmful associated elements. These characteristics may be regarded as petrological criteria for recognition and prospecting for such type of uranium deposits.

  8. Early environmental predictors of the affective and interpersonal constructs of psychopathy.

    Science.gov (United States)

    Daversa, Maria T

    2010-02-01

    Early childhood maltreatment (i.e., physical, sexual, emotional abuse) and caregiver disruptions are hypothesized to be instrumental in altering the neurobiology of the brain, particularly the amygdala, and contributing to the development of the affective deficits examined in individuals with psychopathy. Exposure to early untoward life events in models of rodent and nonhuman primates changes the neurobiology of the stress response. It is hypothesized that these changes may permanently shape brain regions that mediate stress and emotion and therefore play a role in the etiology of affective disorders in humans. The significance of experience (e.g., the intensity/severity, chronicity/duration, and developmental timing of experiences) and how the accompanying changes in the activity of the hypothalamic-pituitary-adrenocortical system affect alterations in the amygdala are discussed as critical contributors to the etiology of psychopathy. A model is proposed in which early maltreatment experiences contribute to alterations to the amygdala and produce a blunted or dissociative response to stress, a key factor in the affective deficits observed in psychopaths.

  9. Effects of early serotonin programming on behavior and central monoamine concentrations in an avian model

    Science.gov (United States)

    Serotonin (5-HT) acts as a neurogenic compound in the developing brain; however serotonin altering drugs such as SSRIs are often prescribed to pregnant and lactating mothers. Early agonism of 5-HT receptors could alter the development of serotonergic circuitry, altering neurotransmission and behavio...

  10. Temporal Trends in Late Preterm and Early Term Birth Rates in 6 High-Income Countries in North America and Europe and Association With Clinician-Initiated Obstetric Interventions

    DEFF Research Database (Denmark)

    Richards, Jennifer L.; Kramer, Michael S.; Deb-Rinker, Paromita

    2016-01-01

    Importance: Clinicians have been urged to delay the use of obstetric interventions (eg, labor induction, cesarean delivery) until 39 weeks or later in the absence of maternal or fetal indications for intervention. Objective: To describe recent trends in late preterm and early term birth rates in 6......: Use of clinician-initiated obstetric intervention (either labor induction or prelabor cesarean delivery) during delivery. Main Outcomes and Measures: Annual country-specific late preterm (34-36 weeks) and early term (37-38 weeks) birth rates. Results: The study population included 2 415 432 Canadian...... births in 2006-2012 (3.6% late preterm; 18.7% early term); and 25 788 558 US births in 2006-2014 (6.0% late preterm; 26.9% early term). Late preterm birth rates decreased in Norway (3.9% to 3.5%) and the United States (6.8% to 5.7%). Early term birth rates decreased in Norway (17.6% to 16.8%), Sweden (19...

  11. Early life stress, HPA axis adaptation and mechanisms contributing to later health outcomes

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2014-05-01

    Full Text Available Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early life stress can impact on later health but less is known about how early life stress impairs HPA axis activity, contributing to maladaptation of the stress response system. Early life stress exposure (either prenatally or in the early postnatal period can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical and experimental studies have demonstrated that early life stress produces long-term hyper responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviours. Recently, evidence has emerged on early life stress induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1. We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early life stress induced maladaptation of the HPA axis, and its subsequent effects on energy utilisation and expenditure. The effects of positive later environments as a means of ameliorating early life stress induced health deficits, and proposed mechanisms underpinning the interaction between early life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early life stress and later health outcomes will also

  12. Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

    2014-01-01

    Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

  13. Effect of socioeconomic status disparity on child language and neural outcome: how early is early?

    Science.gov (United States)

    Hurt, Hallam; Betancourt, Laura M

    2016-01-01

    It is not news that poverty adversely affects child outcome. The literature is replete with reports of deleterious effects on developmental outcome, cognitive function, and school performance in children and youth. Causative factors include poor nutrition, exposure to toxins, inadequate parenting, lack of cognitive stimulation, unstable social support, genetics, and toxic environments. Less is known regarding how early in life adverse effects may be detected. This review proposes to elucidate "how early is early" through discussion of seminal articles related to the effect of socioeconomic status on language outcome and a discussion of the emerging literature on effects of socioeconomic status disparity on brain structure in very young children. Given the young ages at which such outcomes are detected, the critical need for early targeted interventions for our youngest is underscored. Further, the fiscal reasonableness of initiating quality interventions supports these initiatives. As early life adversity produces lasting and deleterious effects on developmental outcome and brain structure, increased focus on programs and policies directed to reducing the impact of socioeconomic disparities is essential.

  14. The influence of galaxy environment on the stellar initial mass function of early-type galaxies

    Science.gov (United States)

    Rosani, Giulio; Pasquali, Anna; La Barbera, Francesco; Ferreras, Ignacio; Vazdekis, Alexandre

    2018-06-01

    In this paper, we investigate whether the stellar initial mass function (IMF) of early-type galaxies depends on their host environment. To this purpose, we have selected a sample of early-type galaxies from the SPIDER catalogue, characterized their environment through the group catalogue of Wang et al., and used their optical Sloan Digital Sky Survey (SDSS) spectra to constrain the IMF slope, through the analysis of IMF-sensitive spectral indices. To reach a high enough signal-to-noise ratio, we have stacked spectra in velocity dispersion (σ0) bins, on top of separating the sample by galaxy hierarchy and host halo mass, as proxies for galaxy environment. In order to constrain the IMF, we have compared observed line strengths and predictions of MIUSCAT/EMILES synthetic stellar population models, with varying age, metallicity, and `bimodal' (low-mass tapered) IMF slope (Γ _b). Consistent with previous studies, we find that Γ _b increases with σ0, becoming bottom-heavy (i.e. an excess of low-mass stars with respect to the Milky Way like IMF) at high σ0. We find that this result is robust against the set of isochrones used in the stellar population models, as well as the way the effect of elemental abundance ratios is taken into account. We thus conclude that it is possible to use currently state-of-the-art stellar population models and intermediate resolution spectra to consistently probe IMF variations. For the first time, we show that there is no dependence of Γb on environment or galaxy hierarchy, as measured within the 3 arcsec SDSS fibre, thus leaving the IMF as an intrinsic galaxy property, possibly set already at high redshift.

  15. Gene expression alterations associated with outcome in aromatase inhibitor-treated ER+ early-stage breast cancer patients

    DEFF Research Database (Denmark)

    Gravgaard Thomsen, Karina Hedelund; Lyng, Maria Bibi; Elias, Daniel

    2015-01-01

    predictive of outcome of ER+ breast cancer patients treated with AIs are needed. Global gene expression analysis was performed on ER+ primary breast cancers from patients treated with adjuvant AI monotherapy; half experienced recurrence (median follow-up 6.7 years). Gene expression alterations were validated...... by qRT-PCR, and functional studies evaluating the effect of siRNA-mediated gene knockdown on cell growth were performed. Twenty-six genes, including TFF3, DACH1, RGS5, and GHR, were shown to exhibit altered expression in tumors from patients with recurrence versus non-recurrent (fold change ≥1.5, p ....05), and the gene expression alterations were confirmed using qRT-PCR. Ten of these 26 genes could be linked in a network associated with cellular proliferation, growth, and development. TFF3, which encodes for trefoil factor 3 and is an estrogen-responsive oncogene shown to play a functional role in tamoxifen...

  16. Alberta Learning: Early Development Instrument Pilot Project Evaluation.

    Science.gov (United States)

    Meaney, Wanda; Harris-Lorenze, Elayne

    The Early Development Instrument (EDI) was designed by McMaster University to measure the outcomes of childrens early years as they influence their readiness to learn at school. The EDI was piloted in several Canadian cities in recent years through two national initiatives. Building on these initiatives, Alberta Learning piloted the EDI as a…

  17. Exercise-Associated Amenorrhea: Are Altered Leptin Levels an Early Warning Sign?

    Science.gov (United States)

    Warren, Michelle P.; Ramos, Russalind H.; Bronson, Emily M.

    2002-01-01

    Although the exact cause of the female athlete triad (amenorrhea, disordered eating, and osteoporosis) is unknown, recent research implicates leptin, a hormone secreted by adipocytes. Leptin may be an important indicator of nutritional status and may play a role in reproductive function. Physicians who develop a plan for early recognition and…

  18. Early diagnosis of HIV in children below 18 months using DNA PCR test--assessment of the effectiveness of PMTCT interventions and challenges in early initiation of ART in a resource-limited setting.

    Science.gov (United States)

    Gupta, Anil; Singh, Girraj; Kaushik, Pratap; Joshi, Bipin; Kalra, Kamlesh; Chakraborty, Sabyasachi

    2013-04-01

    This study was conducted to assess efficacy of the current Indian Prevention of Mother-to-Child Transmission (PMTCT) protocol in 217 HIV-exposed infants, and to assess challenges in the early initiation of antiretroviral treatment (ART) in 18 (8.3%) infants with HIV, as determined by the HIV-1 DNA polymerase chain reaction (PCR) test at ≥ 6 weeks to ART was initiated in 10 (55.6%) HIV-infected children at a mean ± standard deviation (SD) age of 10.45 ± 4.9 (range: 4-17.5) months; delay resulted in opportunistic infections in one-third of the children. A single-dose nevirapine PMTCT regimen should be replaced by a triple antiretroviral regimen; DBS DNA PCR-positive infants may be given ART, and simultaneously a whole blood specimen should be taken to determine whether ART should be continued.

  19. Limitation of the Predominant-Period Estimator for Earthquake Early Warning and the Initial Rupture of Earthquakes

    Science.gov (United States)

    Yamada, T.; Ide, S.

    2007-12-01

    Earthquake early warning is an important and challenging issue for the reduction of the seismic damage, especially for the mitigation of human suffering. One of the most important problems in earthquake early warning systems is how immediately we can estimate the final size of an earthquake after we observe the ground motion. It is relevant to the problem whether the initial rupture of an earthquake has some information associated with its final size. Nakamura (1988) developed the Urgent Earthquake Detection and Alarm System (UrEDAS). It calculates the predominant period of the P wave (τp) and estimates the magnitude of an earthquake immediately after the P wave arrival from the value of τpmax, or the maximum value of τp. The similar approach has been adapted by other earthquake alarm systems (e.g., Allen and Kanamori (2003)). To investigate the characteristic of the parameter τp and the effect of the length of the time window (TW) in the τpmax calculation, we analyze the high-frequency recordings of earthquakes at very close distances in the Mponeng mine in South Africa. We find that values of τpmax have upper and lower limits. For larger earthquakes whose source durations are longer than TW, the values of τpmax have an upper limit which depends on TW. On the other hand, the values for smaller earthquakes have a lower limit which is proportional to the sampling interval. For intermediate earthquakes, the values of τpmax are close to their typical source durations. These two limits and the slope for intermediate earthquakes yield an artificial final size dependence of τpmax in a wide size range. The parameter τpmax is useful for detecting large earthquakes and broadcasting earthquake early warnings. However, its dependence on the final size of earthquakes does not suggest that the earthquake rupture is deterministic. This is because τpmax does not always have a direct relation to the physical quantities of an earthquake.

  20. NEUTRAL Na IN COMETARY TAILS AS A REMNANT OF EARLY AQUEOUS ALTERATION

    Energy Technology Data Exchange (ETDEWEB)

    Ellinger, Y.; Pauzat, F.; Doronin, M.; Zicler, E. [Laboratoire de Chimie Théorique, Sorbonne Universités, UPMC Univ. Paris 06, CNRS UMR 7616, F-75252 Paris CEDEX 05 (France); Mousis, O. [Laboratoire d’Astrophysique de Marseille (LAM), Aix Marseille Université, CNRS, UMR 7326, F-13388 Marseille (France); Guilbert-Lepoutre, A.; Ali-Dib, M. [Observatoire des Sciences de l’Univers de Besançon, Université de Franche-Comté, Institut UTINAM, CNRS/INSU, UMR 6213, F-35030 Besançon CEDEX (France); Leblanc, F. [LATMOS/IPSL, Sorbonne Universités, UPMC Univ. Paris 06, CNRS UMR 8190, F-75252 Paris CEDEX 05 (France); Doressoundiram, A. [LESIA—Observatoire de Paris, Sorbonne Universités, UPMC Univ. Paris 06, Univ. Paris-Diderot, CNRS UMR 8109, F-92190 Meudon (France)

    2015-03-10

    Observations of comet C/1995O1 Hale-Bopp during the spring of 1997 led to the discovery of a neutral sodium tail whose origin is still not clearly understood. Here, we propose an interpretation for the origin of this sodium tail, which is based upon chemical grounds. Starting from Na{sup +} trapped chemically during the condensation of refractory material in the protosolar nebula to its incorporation in the building blocks of comets and its transfer from refractory to volatile phases in the nucleus due to aqueous alteration, we follow the chemical path of sodium until its transformation into a neutral atom when released from the sublimating cometary ice. We propose that two Na reservoirs should coexist in a comet: one coming from the refractory dust, the other one from the icy matrix. Their relative importance would depend on the extent of the zone where liquid water formed within the nucleus and the time during which water remained liquid, thus favoring the Na{sup +} exchange between rocks and ice. These two key parameters would in turn strongly depend on the thermal history of the comet (amounts of radiogenic nuclides, orbital history, etc.). If our model is correct, the detection of Na originating from water ice would be a testimonial of the past aqueous alteration of the comet or its parent body.

  1. Work Participation and Health Status in Early Osteoarthritis of the Hip and/or Knee : A Comparison Between the Cohort Hip and Cohort Knee and the Osteoarthritis Initiative

    NARCIS (Netherlands)

    Bieleman, H. J.; Oosterveld, F. G. J.; Oostveen, J. C. M.; Reneman, M. F.; Groothoff, J. W.

    Objective. To examine the work participation of Dutch people with early osteoarthritis (OA) in hips or knees and compare this with data from the American Osteoarthritis Initiative (OAI) cohort. The influence of health status and personal factors on work participation was analyzed. Methods. In the

  2. Early identification and intervention in cerebral palsy

    DEFF Research Database (Denmark)

    Herskind, Anna; Greisen, Gorm; Nielsen, Jens Bo

    2015-01-01

    Infants with possible cerebral palsy (CP) are commonly assumed to benefit from early diagnosis and early intervention, but substantial evidence for this is lacking. There is no consensus in the literature on a definition of 'early', but this review focuses on interventions initiated within...

  3. Initial phase of adaptation of Memory Alteration Test (M@T) in a Portuguese sample.

    Science.gov (United States)

    Sousa, Mónica; Pereira, Anabela; Costa, Rui; Rami, Lorena

    2015-01-01

    The Memory Alteration Test is a screening test able to discriminate the amnestic mild cognitive impairment (A-MCI) and mild Alzheimer disease from subjective memory complain group (SMC-G). The aim of this study was to analyze the European Portuguese experimental version of the Memory Alteration Test (M@T-PT). Were described the successive stages of the translation and adaptation procedure used to develop the M@T-PT. The psychometric properties were explored using principal component analysis (PCA) with varimax rotation, internal consistence, convergent validity and receiver operating characteristics (ROC) curves. Chi-squared, ANOVAs and Pearson's correlation were also analyzed. A total of 330 people with an age greater or equal to 54 years old participated. According to their cognitive state they were classified as normal controls (n=28), SMC-G (n=81) or A-MCI (n=221). The PCA for the M@T-PT indicated that the total variance explained by three components was 48.07%. A high internal consistent was obtained (α=0.93). Convergent validity was verified using M@T-PT and Mini-Mental State Examination (r=0.83, psound instrument for use in older people in Portugal. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. The Yekaterinburg headache initiative

    DEFF Research Database (Denmark)

    Lebedeva, Elena R; Olesen, Jes; Osipova, Vera V

    2013-01-01

    for a demonstrational interventional project in Russia, undertaken within the Global Campaign against Headache. The initiative proposes three actions: 1) raise awareness of need for improvement; 2) design and implement a three-tier model (from primary care to a single highly specialized centre with academic affiliation......) for efficient and equitable delivery of headache-related health care; 3) develop a range of educational initiatives aimed at primary-care physicians, non-specialist neurologists, pharmacists and the general public to support the second action. RESULTS AND CONCLUSION: We set these proposals in a context...... of a health-care needs assessment, and as a model for all Russia. We present and discuss early progress of the initiative, justify the investment of resources required for implementation and call for the political support that full implementation requires. The more that the Yekaterinburg headache initiative...

  5. Borosilicate nuclear waste glass alteration kinetics theoretical basis for the kinetic law of nuclear glass alteration

    International Nuclear Information System (INIS)

    Jegou, Ch.; Gin, St.; Advocat, Th.; Vernaz, E.

    1997-01-01

    Work carried out since the early 1980's to predict the long-term behavior of nuclear containment glasses has revealed the inadequacy of existing models, notably in accounting for the fundamental mechanisms involved in some complex systems (e.g. glass-water-clay), inciting us to examine and discuss the theoretical basis for the hypotheses generally assumed in our models. This paper discusses the theoretical basis for the Aagaard-Helgeson law and its application to nuclear glasses. The contribution of other types of kinetic laws is also considered to describe the alteration kinetics of nuclear glasses. (authors)

  6. Identification of early indicators of altered metabolism in normal development using a rodent model system

    Directory of Open Access Journals (Sweden)

    Ashok Daniel Prabakaran

    2018-03-01

    Full Text Available Although the existence of a close relationship between the early maternal developmental environment, fetal size at birth and the risk of developing disease in adulthood has been suggested, most studies, however, employed experimentally induced intrauterine growth restriction as a model to link this with later adult disease. Because embryonic size variation also occurs under normal growth and differentiation, elucidating the molecular mechanisms underlying these changes and their relevance to later adult disease risk becomes important. The birth weight of rat pups vary according to the uterine horn positions. Using birth weight as a marker, we compared two groups of rat pups – lower birth weight (LBW, 5th to 25th percentile and average birth weight (ABW, 50th to 75th percentile – using morphological, biochemical and molecular biology, and genetic techniques. Our results show that insulin metabolism, Pi3k/Akt and Pparγ signaling and the genes regulating growth and metabolism are significantly different in these groups. Methylation at the promoter of the InsII (Ins2 gene and DNA methyltransferase 1 in LBW pups are both increased. Additionally, the Dnmt1 repressor complex, which includes Hdac1, Rb (Rb1 and E2f1, was also upregulated in LBW pups. We conclude that the Dnmt1 repressor complex, which regulates the restriction point of the cell cycle, retards the rate at which cells traverse the G1 or G0 phase of the cell cycle in LBW pups, thereby slowing down growth. This regulatory mechanism mediated by Dnmt1 might contribute to the production of small-size pups and altered physiology and pathology in adult life.

  7. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

    DEFF Research Database (Denmark)

    Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred

    2015-01-01

    BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS: We randomly assigned HIV...... entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients...... in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells...

  8. Alteration of immature sedimentary rocks on Earth and Mars. Recording Aqueous and Surface-atmosphere Processes

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, Kenneth M. [Brown Univ., Providence, RI (United States); Mustard, John F. [Brown Univ., Providence, RI (United States); Salvatore, Mark R. [Arizona State Univ., Mesa, AZ (United States)

    2015-03-05

    The rock alteration and rind formation in analog environments like Antarctica may provide clues to rock alteration and therefore paleoclimates on Mars. Clastic sedimentary rocks derived from basaltic sources have been studied in situ by martian rovers and are likely abundant on the surface of Mars. Moreover, how such rock types undergo alteration when exposed to different environmental conditions is poorly understood compared with alteration of intact basaltic flows. Here we characterize alteration in the chemically immature Carapace Sandstone from Antarctica, a terrestrial analog for martian sedimentary rocks. We employ a variety of measurements similar to those used on previous and current Mars missions. Laboratory techniques included bulk chemistry, powder X-ray diffraction (XRD), hyperspectral imaging and X-ray absorption spectroscopy. Through these methods we find that primary basaltic material in the Carapace Sandstone is pervasively altered to hydrated clay minerals and palagonite as a result of water–rock interaction. A thick orange rind is forming in current Antarctic conditions, superimposing this previous aqueous alteration signature. The rind exhibits a higher reflectance at visible-near infrared wavelengths than the rock interior, with an enhanced ferric absorption edge likely due to an increase in Fe3+ of existing phases or the formation of minor iron (oxy)hydroxides. This alteration sequence in the Carapace Sandstone results from decreased water–rock interaction over time, and weathering in a cold, dry environment, mimicking a similar transition early in martian history. This transition may be recorded in sedimentary rocks on Mars through a similar superimposition mechanism, capturing past climate changes at the hand sample scale. These results also suggest that basalt-derived sediments could have sourced significant volumes of hydrated minerals on early Mars due to their greater permeability compared with intact igneous rocks.

  9. Out of time? - Music, consciousness states and neuropharmacological mechanisms of an altered temporality

    OpenAIRE

    Fachner, Jörg

    2009-01-01

    Drug-induced altered temporality is a well-known effect of cannabis action that is utilised from musicians and music listeners for music appreciation since the early days of jazz. Cannabis has an influence on timing processes at short time scales of hundreds of milliseconds as O’Leary et al (2003) have shown in their tapping studies, proving evidence of an altered cerebellar functioning. This paper will focus on cannabis and its action on timing and aims to discuss selected scientific streams...

  10. {sup 18}F-FDG PET and MRS of the early stages of subacute sclerosing panencephalitis in a child with a normal initial MRI

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Yeong-Seon; Jung, Da-Eun [Ajou University School of Medicine, Department of Pediatrics, Suwon, Kyungki-do (Korea, Republic of); Kim, Ho-Sung [Ajou University School of Medicine, Department of Radiology, Suwon, Kyungki-do (Korea, Republic of)

    2010-11-15

    In subacute sclerosing panencephalitis (SSPE), conventional MRI findings have been reported. However, in the early clinical stages, imaging studies can appear normal. Moreover, with no history of infant measles infection, the diagnosis of SSPE can only be arrived at after extensive investigation that must eliminate a number of neurodegenerative diseases. We report here on {sup 18} F-fluorodeoxyglucose positron emission tomography ({sup 18}F-FDG PET) and magnetic resonance spectroscopy (MRS) findings in a 14-year-old girl with a normal initial MRI who had not contracted measles. Although {sup 18} F-FDG PET and MRS are not specific or diagnostic for SSPE, these techniques can demonstrate substantial metabolic impairments when MRI findings show no obvious abnormalities, as is often the case in the early stages of this disease. (orig.)

  11. Development of the embryonic heat shock response and the impact of repeated thermal stress in early stage lake whitefish (Coregonus clupeaformis) embryos.

    Science.gov (United States)

    Whitehouse, Lindy M; McDougall, Chance S; Stefanovic, Daniel I; Boreham, Douglas R; Somers, Christopher M; Wilson, Joanna Y; Manzon, Richard G

    2017-10-01

    Lake whitefish (Coregonus clupeaformis) embryos were exposed to thermal stress (TS) at different developmental stages to determine when the heat shock response (HSR) can be initiated and if it is altered by exposure to repeated TS. First, embryos were subject to one of three different TS temperatures (6, 9, or 12°C above control) at 4 points in development (21, 38, 60 and 70 days post-fertilisation (dpf)) for 2h followed by a 2h recovery to understand the ontogeny of the HSR. A second experiment explored the effects of repeated TS on the HSR in embryos from 15 to 75 dpf. Embryos were subjected to one of two TS regimes; +6°C TS for 1h every 6 days or +9°C TS for 1h every 6 days. Following a 2h recovery, a subset of embryos was sampled. Our results show that embryos could initiate a HSR via upregulation of heat shock protein 70 (hsp70) mRNA at all developmental ages studied, but that this response varied with age and was only observed with a TS of +9 or +12°C. In comparison, when embryos received multiple TS treatments, hsp70 was not induced in response to the 1h TS and 2h recovery, and a downregulation was observed at 39 dpf. Downregulation of hsp47 and hsp90α mRNA was also observed in early age embryos. Collectively, these data suggest that embryos are capable of initiating a HSR at early age and throughout embryogenesis, but that repeated TS can alter the HSR, and may result in either reduced responsiveness or a downregulation of inducible hsps. Our findings warrant further investigation into both the short- and long-term effects of repeated TS on lake whitefish development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Isotopic and Chemical Evidence for Primitive Aqueous Alteration in the Tagish Lake Meteorite

    Science.gov (United States)

    Sakuma, Keisuke; Hidaka, Hiroshi; Yoneda, Shigekazu

    2018-01-01

    Aqueous alteration is one of the primitive activities that occurred on meteorite parent bodies in the early solar system. The Tagish Lake meteorite is known to show an intense parent body aqueous alteration signature. In this study, quantitative analyses of the alkaline elements and isotopic analyses of Sr and Ba from acid leachates of TL (C2-ungrouped) were performed to investigate effects of aqueous alteration. The main purpose of this study is to search for isotopic evidence of extinct 135Cs from the Ba isotopic analyses in the chemical separates from the Tagish Lake meteorite. Barium isotopic data from the leachates show variable 135Ba isotopic anomalies (ε = ‑2.6 ∼ +3.6) which correlatewith 137Ba and 138Ba suggesting a heterogeneous distribution of s- and r-rich nucleosynthetic components in the early solar system. The 87Rb–87Sr and 135Cs–135Ba decay systems on TL in this study do not provide any chronological information. The disturbance of the TL chronometers is likely a reflection of the selective dissolution of Cs and Rb given the relatively higher mobility of Cs and Rb compared to Ba and Sr, respectively, during fluid mineral interactions.

  13. Apolipoprotein E Allelic Frequency Altered in Women with Early-onset Breast Cancer

    Directory of Open Access Journals (Sweden)

    Tirtsa Porrata-Doria

    2010-01-01

    Full Text Available Among women, the most prevalent type of cancer is breast cancer, affecting 1 out of every 8 women in the United States; in Puerto Rico, 70 out of every 100,000 will develop some type of breast cancer. Therefore, a better understanding of the potential risk factors for breast cancer could lead to the development of early detection tools. A gene that has been proposed as a risk factor in several populations around the world is Apolipoprotein E (apoE. ApoE functions as a mechanism of transport for lipoproteins and cholesterol throughout the body, with 3 main isoforms present in humans (apoE2, apoE3, and apoE4. Whether or not apoE4 is a risk factor for breast cancer remains controversial. Previous studies have either included test subjects of all ages (20–80 or have focused on late-onset (after age 50 breast cancer; none has concentrated specifically on early-onset (aged 50 and younger breast cancer. The objectives of this study was to examine (in a Puerto Rican population the differences in the relative frequency of occurrence of apoE4 in non-breast cancer versus breast cancer patients and to examine, as well, the potential differences of same in early- versus late-onset patients. We found an increased frequency of apoE4 (odds ratio 2.15 only in early-onset breast cancer survivors, which is similar to the findings of those studies that combined or adjusted for age as well as for an association between apoE4 and decreased tumor size. ApoE is also a potential risk factor for long-term cognitive effects after chemotherapy and affects response to hormone replacement. Our data supports the theory that knowing the apoE genotype of women who are at risk of developing breast cancer may be beneficial, as such knowledge would aid in the prediction of tumor size and the development of treatment regimens.

  14. Limbic grey matter changes in early Parkinson's disease.

    Science.gov (United States)

    Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

    2017-05-02

    The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The

  15. Origin of depleted basalts during subduction initiation and early development of the Izu-Bonin-Mariana island arc: Evidence from IODP expedition 351 site U1438, Amami-Sankaku basin

    Science.gov (United States)

    Hickey-Vargas, R.; Yogodzinski, G. M.; Ishizuka, O.; McCarthy, A.; Bizimis, M.; Kusano, Y.; Savov, I. P.; Arculus, R.

    2018-05-01

    The Izu-Bonin-Mariana (IBM) island arc formed following initiation of subduction of the Pacific plate beneath the Philippine Sea plate at about 52 Ma. Site U1438 of IODP Expedition 351 was drilled to sample the oceanic basement on which the IBM arc was constructed, to better understand magmatism prior to and during the subduction initiation event. Site U1438 igneous basement Unit 1 (150 m) was drilled beneath 1460 m of primarily volcaniclastic sediments and sedimentary rock. Basement basalts are microcrystalline to fine-grained flows and form several distinct subunits (1a-1f), all relatively mafic (MgO = 6.5-13.8%; Mg# = 52-83), with Cr = 71-506 ppm and Ni = 62-342 ppm. All subunits are depleted in non-fluid mobile incompatible trace elements. Ratios such as Sm/Nd (0.35-0.44), Lu/Hf (0.19-0.37), and Zr/Nb (55-106) reach the highest values found in MORB, while La/Yb (0.31-0.92), La/Sm (0.43-0.91) and Nb/La (0.39-0.59) reach the lowest values. Abundances of fluid-mobile incompatible elements, K, Rb, Cs and U, vary with rock physical properties, indicating control by post-eruptive seawater alteration, but lowest abundances are typical of fresh, highly depleted MORBs. Mantle sources for the different subunits define a trend of progressive incompatible element depletion. Inferred pressures of magma segregation are 0.6-2.1 GPa with temperatures of 1280-1470 °C. New 40Ar/39Ar dates for Site U1438 basalts averaging 48.7 Ma (Ishizuka et al., 2018) are younger that the inferred age of IBM subduction initiation based on the oldest ages (52 Ma) of IBM forearc basalts (FAB) from the eastern margin of the Philippine Sea plate. FAB are hypothesized to be the first magma type erupted as the Pacific plate subsided, followed by boninites, and ultimately typical arc magmas over a period of about 10 Ma. Site U1438 basalts and IBM FABs are similar, but Site U1438 basalts have lower V contents, higher Ti/V and little geochemical evidence for involvement of slab-derived fluids. We

  16. Early detection of metastases using whole-body MRI for initial staging and routine follow-up of myxoid liposarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Gorelik, Natalia; Reddy, Santhosh Mauvva Venkatesh; Powell, Thomas I. [McGill University Health Center, Department of Diagnostic Radiology, Montreal, Quebec (Canada); Turcotte, Robert E.; Goulding, Krista [McGill University Health Center, Division of Orthopaedic Surgery, Montreal, Quebec (Canada); Jung, Sungmi [McGill University Health Center, Department of Pathology, Montreal, Quebec (Canada); Alcindor, Thierry [McGill University Health Center, Gerald Bronfman Department of Oncology, Division of Medical Oncology, Montreal, Quebec (Canada)

    2018-03-15

    To define the role of whole-body MRI (WBMRI) for initial staging and routine follow-up of myxoid liposarcoma (MLS). A retrospective review of all the patients with MLS who underwent WBMRI for initial staging and routine follow-up at our institution between October 1, 2006, and September 30, 2016 was performed. Patient demographics, clinical presentation, imaging findings, tumor histology, and occurrence and location of metastatic disease were recorded. Thirty-three patients who underwent a total of 150 WBMRI examinations were included in the study. Nine patients (27%) were diagnosed with metastases between 0 and 60 months (median 10; interquartile range, 7-13) from the diagnosis of the primary tumor. The initial site of metastatic disease was extrapulmonary in all patients. Only two patients developed pulmonary metastases, which were diagnosed by CT chest 9 and 29 months after the diagnosis of extrapulmonary metastases. The first metastasis was diagnosed by WBMRI in seven patients (78%), by thoracic CT in one patient, and by abdominal CT in one patient. Eight of nine patients (89%) were asymptomatic at the time of diagnosis of the metastases. In seven patients (78%), WBMRI demonstrated metastases included within the field of view of, but occult on a contemporaneous CT scan. Our 10-year institutional experience demonstrates that WBMRI facilitates early detection of extrapulmonary MLS metastases before the onset of clinical symptoms and pulmonary metastases. WBMRI also depicts extrapulmonary metastases that are occult on CT scans. The current surveillance strategies are insufficient for screening for extrapulmonary MLS metastases. (orig.)

  17. [Depressed mothers: the impact of depression on early interactions. An analysis of Anglo-Saxon studies].

    Science.gov (United States)

    Guedeney, N

    1993-10-01

    Maternal depression remains a public health problem as indicated by many studies focusing on depression in mothers of young children. Although the high prevalence of depression in mothers of infants and young children is now a recognized fact, the detection and management of maternal depression in everyday practice still raises significant problems. This initial review centers on studies providing diagnostic guidelines. The problem of maternal depression and of its impact on the offspring is relevant to the issue of how qualities, abilities, and vulnerabilities are transmitted from one generation to the next. Psychoanalysts, infant psychiatrists, and developmental psychologists show great interest in this field. The current review was restricted to recent Anglo-Saxon studies on depression-related changes in early maternal behavior. The most striking findings are as follows: although depression affects maternal behavior overall, there is considerable variation across mothers; timing alterations (in terms of micro and macro sequences) in mother-child interactions occur in every case and are among the obstacles to harmony and synchronization; subtle alterations in the mother's response to her baby's signals preclude flexibility and anticipation.

  18. Race to the Top--Early Learning Challenge: An Analysis of Impact on IDEIA, Part C Early Intervention Programs

    Science.gov (United States)

    Bohjanen, Sharon L.

    2016-01-01

    Infants and toddlers who live in poverty are more likely to experience developmental delays or disabilities and less likely to access early intervention (EI) services. The federal initiative Race to the Top--Early Learning Challenge (RTT-ELC) was designed to increase access to high quality early learning programs for children at risk for…

  19. Alteration of the retinoblastoma gene locus in radium-exposed individuals

    International Nuclear Information System (INIS)

    Hardwick, J.P.; Schlenker, R.; Huberman, E.

    1991-01-01

    This study was performed to determine if the retinoblastoma suppressor gene was altered in individuals exposed to radium. We analyzed the Rb gene in 30 individuals, 17 of whom were exposed to radium either occupationally or iatrogenically. In the kidney DNA from four of nine radium-exposed individuals, the Rb gene was deleted. Three of these alterations in the Rb gene were internal deletions, which resulted in the absence of Rb mRNA accumulation. These results imply that the Rb gene is susceptible to radium-induced damage and confirm previous showing that radiation preferentially causes genomic deletions. The pronounced alterations in the non-tumorigenic femurs from radium-exposed individuals suggests that in the many years of exposure there was a selection of cells with alterations, presumably because of their growth advantage. Also it implies that deletions of one of the Rb alleles can be one of the events (perhaps an initial one) in the progression of radium-induced sarcomas. 11 refs., 2 figs

  20. Flight behaviour of honey bee (Apis mellifera) workers is altered by initial infections of the fungal parasite Nosema apis

    Science.gov (United States)

    Dosselli, Ryan; Grassl, Julia; Carson, Andrew; Simmons, Leigh W.; Baer, Boris

    2016-01-01

    Honey bees (Apis mellifera) host a wide range of parasites, some being known contributors towards dramatic colony losses as reported over recent years. To counter parasitic threats, honey bees possess effective immune systems. Because immune responses are predicted to cause substantial physiological costs for infected individuals, they are expected to trade off with other life history traits that ultimately affect the performance and fitness of the entire colony. Here, we tested whether the initial onset of an infection negatively impacts the flight behaviour of honey bee workers, which is an energetically demanding behaviour and a key component of foraging activities. To do this, we infected workers with the widespread fungal pathogen Nosema apis, which is recognised and killed by the honey bee immune system. We compared their survival and flight behaviour with non-infected individuals from the same cohort and colony using radio frequency identification tags (RFID). We found that over a time frame of four days post infection, Nosema did not increase mortality but workers quickly altered their flight behaviour and performed more flights of shorter duration. We conclude that parasitic infections influence foraging activities, which could reduce foraging ranges of colonies and impact their ability to provide pollination services. PMID:27827404

  1. Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity.

    Science.gov (United States)

    Schwaiger, Marion; Grinberg, Marianna; Moser, Dirk; Zang, Johannes C S; Heinrichs, Markus; Hengstler, Jan G; Rahnenführer, Jörg; Cole, Steve; Kumsta, Robert

    2016-09-01

    Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.

  2. Modulation of early stress-induced neurobiological changes: a review of behavioural and pharmacological interventions in animal models.

    Science.gov (United States)

    Harrison, E L; Baune, B T

    2014-05-13

    Childhood adversity alters the predisposition to psychiatric disorders later in life. Those with psychiatric conditions and a history of early adversity exhibit a higher incidence of treatment resistance compared with individuals with no such history. Modulation of the influence early stress exerts over neurobiology may help to prevent the development of psychiatric disorders in some cases, while attenuating the extent of treatment resistance in those with established psychiatric disorders. This review aims to critically evaluate the ability of behavioural, environmental and pharmacologic interventions to modulate neurobiological changes induced by early stress in animal models. Databases were systematically searched to locate literature relevant to this review. Early adversity was defined as stress that resulted from manipulation of the mother-infant relationship. Analysis was restricted to animal models to enable characterisation of how a given intervention altered specific neurobiological changes induced by early stress. A wide variety of changes in neurobiology due to early stress are amenable to intervention. Behavioural interventions in childhood, exercise in adolescence and administration of epigenetic-modifying drugs throughout life appear to best modulate cellar and behavioural alterations induced by childhood adversity. Other pharmacotherapies, such as endocannabinoid system modulators, anti-inflammatories and antidepressants can also influence these neurobiological and behavioural changes that result from early stress, although findings are less consistent at present and require further investigation. Further work is required to examine the influence that behavioural interventions, exercise and epigenetic-modifying drugs exert over alterations that occur following childhood stress in human studies, before possible translational into clinical practice is possible.

  3. The role of meniscal tissue in joint protection in early osteoarthritis.

    Science.gov (United States)

    Verdonk, Rene; Madry, Henning; Shabshin, Nogah; Dirisamer, Florian; Peretti, Giuseppe M; Pujol, Nicolas; Spalding, Tim; Verdonk, Peter; Seil, Romain; Condello, Vincenzo; Di Matteo, Berardo; Zellner, Johannes; Angele, Peter

    2016-06-01

    It is widely accepted that partial meniscectomy leads to early onset of osteoarthritis (OA). A strong correlation exists between the amount and location of the resected meniscus and the development of degenerative changes in the knee. On the other hand, osteoarthritic changes of the joint alter the structural and functional integrity of meniscal tissue. These alterations might additionally compromise the limited healing capacity of the meniscus. In young, active patients without cartilage damage, meniscus therapy including partial meniscectomy, meniscus suture, and meniscus replacement has proven beneficial effects in long-term studies. Even in an early osteoarthritic milieu, there is a relevant regenerative potential of the meniscus and the surrounding cartilage. This potential should be taken into account, and meniscal surgery can be performed with the correct timing and the proper indication even in the presence of early OA.

  4. Effect of carbonate chemistry alteration on the early embryonic development of the Pacific oyster (Crassostrea gigas).

    Science.gov (United States)

    Gazeau, Frédéric; Gattuso, Jean-Pierre; Greaves, Mervyn; Elderfield, Henry; Peene, Jan; Heip, Carlo H R; Middelburg, Jack J

    2011-01-01

    Ocean acidification, due to anthropogenic CO₂ absorption by the ocean, may have profound impacts on marine biota. Calcareous organisms are expected to be particularly sensitive due to the decreasing availability of carbonate ions driven by decreasing pH levels. Recently, some studies focused on the early life stages of mollusks that are supposedly more sensitive to environmental disturbances than adult stages. Although these studies have shown decreased growth rates and increased proportions of abnormal development under low pH conditions, they did not allow attribution to pH induced changes in physiology or changes due to a decrease in aragonite saturation state. This study aims to assess the impact of several carbonate-system perturbations on the growth of Pacific oyster (Crassostrea gigas) larvae during the first 3 days of development (until shelled D-veliger larvae). Seawater with five different chemistries was obtained by separately manipulating pH, total alkalinity and aragonite saturation state (calcium addition). Results showed that the developmental success and growth rates were not directly affected by changes in pH or aragonite saturation state but were highly correlated with the availability of carbonate ions. In contrast to previous studies, both developmental success into viable D-shaped larvae and growth rates were not significantly altered as long as carbonate ion concentrations were above aragonite saturation levels, but they strongly decreased below saturation levels. These results suggest that the mechanisms used by these organisms to regulate calcification rates are not efficient enough to compensate for the low availability of carbonate ions under corrosive conditions.

  5. Effect of carbonate chemistry alteration on the early embryonic development of the Pacific oyster (Crassostrea gigas.

    Directory of Open Access Journals (Sweden)

    Frédéric Gazeau

    Full Text Available Ocean acidification, due to anthropogenic CO₂ absorption by the ocean, may have profound impacts on marine biota. Calcareous organisms are expected to be particularly sensitive due to the decreasing availability of carbonate ions driven by decreasing pH levels. Recently, some studies focused on the early life stages of mollusks that are supposedly more sensitive to environmental disturbances than adult stages. Although these studies have shown decreased growth rates and increased proportions of abnormal development under low pH conditions, they did not allow attribution to pH induced changes in physiology or changes due to a decrease in aragonite saturation state. This study aims to assess the impact of several carbonate-system perturbations on the growth of Pacific oyster (Crassostrea gigas larvae during the first 3 days of development (until shelled D-veliger larvae. Seawater with five different chemistries was obtained by separately manipulating pH, total alkalinity and aragonite saturation state (calcium addition. Results showed that the developmental success and growth rates were not directly affected by changes in pH or aragonite saturation state but were highly correlated with the availability of carbonate ions. In contrast to previous studies, both developmental success into viable D-shaped larvae and growth rates were not significantly altered as long as carbonate ion concentrations were above aragonite saturation levels, but they strongly decreased below saturation levels. These results suggest that the mechanisms used by these organisms to regulate calcification rates are not efficient enough to compensate for the low availability of carbonate ions under corrosive conditions.

  6. Mechanisms behind early life nutrition and adult disease outcome

    OpenAIRE

    Velkoska, Elena; Morris, Margaret J

    2011-01-01

    Obesity is increasing around the globe. While adult lifestyle factors undoubtedly contribute to the incidence of obesity and its attendant disorders, mounting evidence suggests that programming of obesity may occur following under- and over-nutrition during development. As hypothalamic control of appetite and energy expenditure is set early in life and can be perturbed by certain exposures such as undernutrition and altered metabolic and hormonal signals, in utero exposure to altered maternal...

  7. Early appendectomy reduces costs in children with perforated appendicitis.

    Science.gov (United States)

    Church, Joseph T; Klein, Edwin J; Carr, Benjamin D; Bruch, Steven W

    2017-12-01

    Perforated appendicitis can be managed with early appendectomy, or nonoperative management followed by interval appendectomy. We aimed to identify the strategy with the lowest health care utilization and cost. We retrospectively reviewed the medical records of all children ≤18 years old with perforated appendicitis admitted to a single institution between January 2009 and March 2016. After excluding immunosuppressed patients and transfers from outside hospitals, we grouped the remaining patients by early or interval appendectomy. Cost accounting data were obtained from our institutional database. The primary outcome was total hospital cost over 2 y from initial admission for appendicitis. Other outcomes analyzed included initial admission costs, number of admissions, emergency room and clinic visits, percutaneous procedures, cross-sectional and overall imaging studies, and length of stay. A total of 203 children with perforated appendicitis were identified. After exclusion of immunosuppressed patients and outside hospital transfers, 94 patients were included in the study. Thirty-nine underwent early appendectomy and 55 initial nonoperative management; of these, 54 underwent elective interval appendectomy. Five of 55 patients (9%) failed initial nonoperative management and required earlier-than-planned appendectomy. Total cost over 2 y was significantly lower with early appendectomy than initial nonoperative management ($19,300 ± 14,300 versus $26,000 ± 17,500; P = 0.05). Early appendectomy resulted in fewer hospital admissions, clinic visits, invasive procedures, and imaging studies. Early appendectomy results in lower hospital costs and less health care utilization compared with initial nonoperative management with elective interval appendectomy. A prospective study will shed more light on this question and can assess the role of nonoperative management without interval appendectomy in children with perforated appendicitis. Copyright © 2017 Elsevier

  8. Changes in nucleosome repeat lengths precede replication in the early replicating metallothionein II gene region of cells synchronized in early S phase

    International Nuclear Information System (INIS)

    D'Anna, J.A.; Tobey, R.A.

    1989-01-01

    Previous investigations showed that inhibition of DNA synthesis by hydroxyurea, aphidicolin, or 5-fluorodeoxyuridine produced large changes in the composition and nucleosome repeat lengths of bulk chromatin. There the authors report results of investigations to determine whether the changes in nucleosome repeat lengths might be localized in the initiated replicons, as postulated. In most experiments, Chinese hamster (line CHO) cells were synchronized in G1, or they were synchronized in early S phase by allowing G1 cells to enter S phase in medium containing 1 mM hydroxyurea or 5 μg mL -1 aphidicolin, a procedure believed to produce an accumulation of initiated replicons that arise from normally early replicating DNA. Measurements of nucleosome repeat lengths of bulk chromatin, the early replicating unexpressed metallothionein II (MTII) gene region, and a later replicating repeated sequence indicate that the changes in repeat lengths occur preferentially in the early replicating MTII gene region as G1 cells enter and become synchronized in early S phase. During that time, the MTII gene region is not replicated nor is there any evidence for induction of MTII messenger RNA. Thus, the results are consistent with the hypothesis that changes in chromatin structure occur preferentially in the early replicating (presumably initiated) replicons at initiation or that changes in chromatin structure can precede replication during inhibition of DNA synthesis. The shortened repeat lengths that precede MTII replication are, potentially, reversible, because they become elongated when the synchronized early S-phase cells are released to resume cell cycle progression

  9. Early phyllosilicates formed by alteration of R7T7 glass in water at 250 deg C

    International Nuclear Information System (INIS)

    Vernaz, E.; Dussossoy, J.L.; Caurel, J.; Crovisier, J.L.

    1991-01-01

    T7T7 glass samples have been altered during periods of one and seven days at 250 deg C in distilled water. Ultramicrotomic thin sections were performed in the outermost part of the glass for a study under analytical transmission electron microscope. After one day the alteration layer is about 5 μm thick. It is made up of sheeted silicated particles, tentatively identified as septechlorite (7 A intervals) mixed with an intercrystalline amorphous matrix of different composition. After seven days the alteration layer is about 11 μm thick. It is made up of sheeted silicated particles of smectite type (10 A intervals). No 7 A particles were found in the seven days sample. This study illustrates the capacity of poorly crystalline phyllosilicates to adapt to the chemical changes in solution. 15 refs., 4 tabs., 2 plates

  10. Dynamic gene expression response to altered gravity in human T cells.

    Science.gov (United States)

    Thiel, Cora S; Hauschild, Swantje; Huge, Andreas; Tauber, Svantje; Lauber, Beatrice A; Polzer, Jennifer; Paulsen, Katrin; Lier, Hartwin; Engelmann, Frank; Schmitz, Burkhard; Schütte, Andreas; Layer, Liliana E; Ullrich, Oliver

    2017-07-12

    We investigated the dynamics of immediate and initial gene expression response to different gravitational environments in human Jurkat T lymphocytic cells and compared expression profiles to identify potential gravity-regulated genes and adaptation processes. We used the Affymetrix GeneChip® Human Transcriptome Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding genes and performed the experiments during a parabolic flight and a suborbital ballistic rocket mission to cross-validate gravity-regulated gene expression through independent research platforms and different sets of control experiments to exclude other factors than alteration of gravity. We found that gene expression in human T cells rapidly responded to altered gravity in the time frame of 20 s and 5 min. The initial response to microgravity involved mostly regulatory RNAs. We identified three gravity-regulated genes which could be cross-validated in both completely independent experiment missions: ATP6V1A/D, a vacuolar H + -ATPase (V-ATPase) responsible for acidification during bone resorption, IGHD3-3/IGHD3-10, diversity genes of the immunoglobulin heavy-chain locus participating in V(D)J recombination, and LINC00837, a long intergenic non-protein coding RNA. Due to the extensive and rapid alteration of gene expression associated with regulatory RNAs, we conclude that human cells are equipped with a robust and efficient adaptation potential when challenged with altered gravitational environments.

  11. Tubular Initial Conditions and Ridge Formation

    Directory of Open Access Journals (Sweden)

    M. S. Borysova

    2013-01-01

    Full Text Available The 2D azimuth and rapidity structure of the two-particle correlations in relativistic A+A collisions is altered significantly by the presence of sharp inhomogeneities in superdense matter formed in such processes. The causality constraints enforce one to associate the long-range longitudinal correlations observed in a narrow angular interval, the so-called (soft ridge, with peculiarities of the initial conditions of collision process. This study's objective is to analyze whether multiform initial tubular structures, undergoing the subsequent hydrodynamic evolution and gradual decoupling, can form the soft ridges. Motivated by the flux-tube scenarios, the initial energy density distribution contains the different numbers of high density tube-like boost-invariant inclusions that form a bumpy structure in the transverse plane. The influence of various structures of such initial conditions in the most central A+A events on the collective evolution of matter, resulting spectra, angular particle correlations and vn-coefficients is studied in the framework of the hydrokinetic model (HKM.

  12. Observations on early and delayed colostomy closure.

    Science.gov (United States)

    Tade, A O; Salami, B A; Ayoade, B A

    2011-06-01

    Traditional treatment of a variety of colorectal pathologies had included a diverting colostomy that was closed eight or more weeks later during a readmission. The aim of this retrospective study was to determine the outcomes of early colostomy closure and delayed colostomy closure in patients with temporary colostomies following traumatic and non-traumatic colorectal pathologies. In this study early colostomy closure was the closure of a colostomy within three weeks of its construction, while delayed colostomy closure referred to closure after 3 weeks. Complete records of the 37 adult patients who had temporary colostomy constructed and closed between Jan. 1997 December 2003 for various colorectal pathologies were studied. Fourteen patients had early colostomy closure while 23 had delayed closure. In the early colostomy closure group there were 10 men and 4 women. The mean age of the patients was 28yr with a range of 18-65yr. Colostomies were closed 9-18 days after initial colostomy construction. There was no mortality. Morbidity rate 28.6% (4 out of 14). There were two faecal fistulas (14.3%). Twenty-three patients had delayed colostomy closure 8 weeks to 18 months after initial colostomy construction. These were patients unfit for early surgery after initial colostomy construction because of carcinoma, significant weight loss, or sepsis. There was no mortality. Morbidity rate was 26.1%. There were 3 faecal fistulas (13.2%). Outcomes following early colostomy closure and delayed closure were comparable. Patients fit for surgery should have early closure whilst patients who may have compromised health should have delayed closure.

  13. Exercise-associated amenorrhea: are altered leptin levels an early warning sign?

    Science.gov (United States)

    Warren, Michelle P; Ramos, Russalind H; Bronson, Emily M

    2002-10-01

    Although the exact cause of the female athlete triad (amenorrhea, disordered eating, and osteoporosis) is unknown, recent research implicates leptin, a hormone that is secreted by adipocytes. Leptin may be an important indicator of nutritional status and may also play a role in reproductive function. Physicians who develop a plan for early recognition and treatment of exercise-induced amenorrhea now may prevent the more serious consequences of osteopenia and osteoporosis later.

  14. Alteration of cell cycle progression by Sindbis virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Ruirong; Saito, Kengo [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Isegawa, Naohisa [Laboratory Animal Center, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Shirasawa, Hiroshi, E-mail: sirasawa@faculty.chiba-u.jp [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan)

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  15. Alteration of cell cycle progression by Sindbis virus infection

    International Nuclear Information System (INIS)

    Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

    2015-01-01

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G 1 phase preferred to proliferate during S/G 2 phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G 1 phase than in cells infected during S/G 2 phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases

  16. Preoperative PET/CT in early-stage breast cancer

    DEFF Research Database (Denmark)

    Bernsdorf, M; Berthelsen, A K; Timmermans-Wielenga, Vera

    2012-01-01

    The aim of this study was to assess the diagnostic and therapeutic impact of preoperative positron emission tomography and computed tomography (PET/CT) in the initial staging of patients with early-stage breast cancer.......The aim of this study was to assess the diagnostic and therapeutic impact of preoperative positron emission tomography and computed tomography (PET/CT) in the initial staging of patients with early-stage breast cancer....

  17. Diagenesis of amorphous organic matter as an essential aspect of genesis and alteration of tabular-type uranium-vanadium deposits, Colorado Plateau

    International Nuclear Information System (INIS)

    Spirakis, C.S.; Hansley, P.L.

    1987-01-01

    Organic matter was the key to the initial concentration of uranium and vanadium (during the sulfate reduction stage of early diagenesis) in all sandstone-hosted, tabular deposits in the Morrison Formation, Colorado Plateau. In deposits rich in amorphous organic matter, as are many in the Grants uranium region (GUR), diagenesis did not proceed beyond sulfate reduction. In contrast, in organic-poor, chlorite deposits of the Henry Mountains district, 13 C- and 18 O-enriched dolomites preserve evidence of a subsequent methanogenic stage. In these and similar organic-poor deposits in the Slick Rock district and in parts of the GUR, aluminosilicate dissolution (including a distinctive, organic-acid-induced etching of garnets) and growth of coarse-grained coffinite, albite, ankerite, and chlorite suggest diagenesis reached the organic acid stage. Temperature and thermal maturation indicators (vitrinite reflectance, type IIb chlorite, ordered illite/smectite, and fluid inclusion data) are consistent with temperatures of organic-acid stage diagenesis (∼ 100 0 C). The localization of these alterations in and around organic-poor, clay-rich ore; the similarities in type and sequence of these alterations to the normal alteration of organic-bearing sediments; the alteration of iron-titanium oxides (attributed to the action of soluble organic complexes) around both organic-rich and organic-poor deposits; and the gradation from organic-rich to organic-poor, chlorite-rich deposits (in GUR) suggest that (1) amorphous organic matter was involved in the genesis of all of these deposits and (2) differences among deposits may reflect varying degrees of diagenesis of the organic matter

  18. Scaling up implementation of ART: Organizational culture and early mortality of patients initiated on ART in Nairobi, Kenya.

    Science.gov (United States)

    Ayah, Richard

    2018-01-01

    Scaling up the antiretroviral (ART) program in Kenya has involved a strategy of using clinical guidelines coupled with decentralization of treatment sites. However decentralization pushes clinical responsibility downwards to health facilities run by lower cadre staff. Whether the organizational culture in health facilities affects the outcomes despite the use of clinical guidelines has not been explored. This study aimed to demonstrate the relationship between organizational culture and early mortality and those lost to follow up (LTFU) among patients enrolled for HIV care. A stratified sample of 31 health facilities in Nairobi County offering ART services were surveyed. Data of patients enrolled on ART and LTFU for the 12 months ending 30th June 2013 were abstracted. Mortality and LTFU were determined and used to rank health facilities. In the facilities with the lowest and highest mortality and LTFU key informant interviews were conducted using a tool adapted from team climate assessment measurement questionnaire and competing value framework tool to assess organizational culture. The strength of association between early mortality, LTFU and organizational culture was tested. Half (51.8%) of the 5,808 patients enrolled into care in 31 health facilities over the 12-month study period were started on ART. Of these 48 (1.6% 95% CI 0.8%-2.4%) died within three months of starting treatment, while a further 125 (4.2% 95% CI 2.1%-6.6%) were LTFU giving an attrition rate of 5.7% (95% CI 3.3%-8.6%). Tuberculosis was the most common comorbidity associated with high early mortality and high LTFU. Organizational culture, specifically an adhocratic type was found to be associated with low early mortality and low LTFU of patients enrolled for HIV care (P = 0.034). The use of ART clinical guidelines in a decentralized health systems are not sufficient to achieve required service delivery outcomes. The attrition rate above would mean 85,000 Kenyans missing care based on current

  19. Early initiation of low-level parenteral dextrose induces an accelerated diabetic phenotype in septic C57BL/6J mice.

    Science.gov (United States)

    Singamsetty, Srikanth; Shah, Faraaz Ali; Guo, Lanping; Watanabe, Yoshio; McDonald, Sherie; Sharma, Rohit; Zhang, Yingze; Alonso, Laura C; O'Donnell, Christopher P; McVerry, Bryan J

    2016-01-01

    Development of hyperglycemia during sepsis is associated with increased morbidity and mortality. Nutritional support is common practice in the intensive care unit, but the metabolic effects are not well understood. The purpose of this study is to determine the effect of early low-level calorie provision on the development of hyperglycemia in a clinically relevant murine model of sepsis. C57BL/6J mice underwent femoral arterial and venous catheterization followed by cecal ligation and puncture (CLP) or sham surgery and low-dose intravenous dextrose or saline infusion. Blood glucose, plasma insulin, and cytokines were measured after 24 h. Additional septic mice underwent hyperinsulinemic-euglycemic clamps or received intravenous insulin concurrent with dextrose to determine whole-body insulin sensitivity and test the efficacy of insulin to reverse hyperglycemia. Neither dextrose infusion nor CLP alone induced hyperglycemia. Early initiation of low-level dextrose in septic mice produced a variable glycemic response: 49% maintained euglycemia (blood glucose dextrose (∼ 20% daily caloric requirements) precipitated hyperglycemia akin to an acute diabetic phenotype in septic mice characterized by decreased insulin sensitivity, decreased insulin secretion, and an increased inflammatory response.

  20. Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats

    Directory of Open Access Journals (Sweden)

    Silvers Janelle M

    2006-04-01

    Full Text Available Abstract Background Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured α2-adrenergic receptor (α2-AR density in adolescent (35-days-old rats, using [3H]RX821002 (5 nM. Results Sex-specific alterations of α2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of α2-AR in parietal cortex. Conclusion These data suggest that prenatal cocaine exposure results in a persistent alteration in forebrain NE systems as indicated by alterations in receptor density. These neurochemical changes may underlie behavioral abnormalities observed in offspring attentional processes following prenatal exposure to cocaine.

  1. SDSS-IV MaNGA: Variation of the Stellar Initial Mass Function in Spiral and Early-type Galaxies

    Science.gov (United States)

    Li, Hongyu; Ge, Junqiang; Mao, Shude; Cappellari, Michele; Long, R. J.; Li, Ran; Emsellem, Eric; Dutton, Aaron A.; Li, Cheng; Bundy, Kevin; Thomas, Daniel; Drory, Niv; Lopes, Alexandre Roman

    2017-04-01

    We perform Jeans anisotropic modeling (JAM) on elliptical and spiral galaxies from the MaNGA DR13 sample. By comparing the stellar mass-to-light ratios estimated from stellar population synthesis and from JAM, we find a systematic variation of the initial mass function (IMF) similar to that in the earlier {{ATLAS}}3{{D}} results. Early-type galaxies (elliptical and lenticular) with lower velocity dispersions within one effective radius are consistent with a Chabrier-like IMF, while galaxies with higher velocity dispersions are consistent with a more bottom-heavy IMF such as the Salpeter IMF. Spiral galaxies have similar systematic IMF variations, but with slightly different slopes and larger scatters, due to the uncertainties caused by the higher gas fractions and extinctions for these galaxies. Furthermore, we examine the effects of stellar mass-to-light ratio gradients on our JAM modeling, and we find that the trends become stronger after considering the gradients.

  2. Impact of Unplanned Care Interruption on CD4 Response Early After ART Initiation in a Nigerian Cohort.

    Science.gov (United States)

    Ahonkhai, Aimalohi A; Adeola, Juliet; Banigbe, Bolanle; Onwuatuelo, Ifeyinwa; Adegoke, Abdulkabir B; Bassett, Ingrid V; Losina, Elena; Freedberg, Kenneth A; Okonkwo, Prosper; Regan, Susan

    The authors conducted a retrospective cohort study of unplanned care interruption (UCI) among adults initiating antiretroviral therapy (ART) from 2009 to 2011 in a Nigerian clinic. The authors used repeated measures regression to model the impact of UCI on CD4 count upon return to care and rate of CD4 change on ART. Among 2496 patients, 83% had 0, 15% had 1, and 2% had ≥2 UCIs. Mean baseline CD4 for those with 0, 1, or ≥2 UCIs was 228/cells/mm 3 , 355/cells/mm 3 , and 392/cells/mm 3 ( P ART, patients with 0 UCI gained 10 cells/µL/mo (95% CI: 7-4). Those with 1 and ≥2 UCIs lost 2 and 5 cells/µL/mo (95% CI: -18 to 13 and -26 to 16). Patients with UCI did not recover from early CD4 losses associated with UCI. Preventing UCI is critical to maximize benefits of ART.

  3. Early alterations in extracellular matrix and transforming growth factor β gene expression in mouse lung indicative of late radiation fibrosis

    International Nuclear Information System (INIS)

    Finkelstein, J.N.; Johnston, C.J.; Baggs, R.; Rubin, P.

    1994-01-01

    Fibrosis, characterized by the accumulation of collagen, is a late result of thoracic irradiation. The expression of late radiation injury can be found immediately after irradiation by measuring messenger RNA (mRNA) abundance. To determine if extracellular matrix mRNA and transforming growth factor beta abundance was affected acutely after irradiation, the authors measured mRNA levels of collagen I (CI), collagen III (CIII), collagen IV (CIV), fibronectin (FN), and transforming growth factor β (TGFβ 1,2ampersand3 ) in mouse lungs on day 1 and day 14 after graded doses of radiation. C57BL/6 female mice were irradiated with a single dose to the thorax of 5 or 12.5 Gy. Total lung RNA was prepared and immobilized by Northern and slot blotting and hybridized with radiolabelled cDNA probes for CI, CIII, CIV, FN, TGFβ 1,2ampersand3 and a control probe encoding for glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Autoradiographic data were quantified by video densitometry and results normalized to GAPDH. Changes in the expression of CI, CIII, CIV, FN and TGFβ 1,2ampersand3 were observed as early as 1 day after exposure. Through 14 days, changes in mRNA up to 5-fold were seen for any one dose. Dose related changes as high as 10-fold were also evident. The CI:CIII ratio increased gradually for the 5 Gy dose at 14 days postirradiation while the CI:CII ratio for the 12.5 Gy dose decreased by approximately 4-fold as compared to the control. These studies suggest that alterations in expression of extracellular matrix and TGFβ mRNA occur very early after radiation injury even at low doses and may play a role in the development of chronic fibrosis. 37 refs., 6 figs

  4. Integrated Initiating Event Performance Indicators

    International Nuclear Information System (INIS)

    S. A. Eide; Dale M. Rasmuson; Corwin L. Atwood

    2005-01-01

    The U.S. Nuclear Regulatory Commission Industry Trends Program (ITP) collects and analyses industry-wide data, assesses the safety significance of results, and communicates results to Congress and other stakeholders. This paper outlines potential enhancements in the ITP to comprehensively cover the Initiating Events Cornerstone of Safety. Future work will address other cornerstones of safety. The proposed Tier 1 activity involves collecting data on ten categories of risk-significant initiating events, trending the results, and comparing early performance with prediction limits (allowable numbers of events, above which NRC action may occur). Tier 1 results would be used to monitor industry performance at the level of individual categories of initiating events. The proposed Tier 2 activity involves integrating the information for individual categories of initiating events into a single risk-based indicator, termed the Baseline Risk Index for Initiating Events or BRIIE. The BRIIE would be evaluated yearly and compared against a threshold. BRIIE results would be reported to Congress on a yearly basis

  5. Early deprivation, atypical brain development, and internalizing symptoms in late childhood.

    Science.gov (United States)

    Bick, J; Fox, N; Zeanah, C; Nelson, C A

    2017-02-07

    Children exposed to extreme early-life neglect such as in institutional rearing are at heightened risk for developing depression and anxiety disorders, and internalizing problems more broadly. These outcomes are believed to be due to alterations in the development of neural circuitry that supports emotion regulation. The specific neurodevelopmental changes that contribute to these difficulties are largely unknown. This study examined whether microstructural alterations in white matter pathways predicted long-term risk for internalizing problems in institutionally reared children. Data from 69 children were drawn from the Bucharest Early Intervention Project, a randomized clinical trial of foster care for institutionally reared children. White matter was assessed using diffusion tensor imaging (DTI) when children were between 8 and 10years of age. Internalizing symptoms were assessed at the time of the MRI scan, and once children reached 12-14years of age. Results indicated that neglect-associated alterations in the external capsule and corpus callosum partially explained links between institutional rearing status and internalizing symptoms in middle childhood and early adolescence. Findings shed light on neural mechanisms contributing to increased risk for emotional difficulties among children reared in adverse conditions and have implications for prevention and intervention. Copyright © 2015. Published by Elsevier Ltd.

  6. Early and Later Life Stress Alter Brain Activity and Sleep in Rats

    Science.gov (United States)

    Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

    2013-01-01

    Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857

  7. Serious Non-AIDS Conditions in HIV: Benefit of Early ART.

    Science.gov (United States)

    Lundgren, Jens D; Borges, Alvaro H; Neaton, James D

    2018-04-01

    Optimal control of HIV can be achieved by early diagnosis followed by the initiation of antiretroviral therapy (ART). Two large randomised trials (TEMPRANO and START) have recently been published documenting the clinical benefits to HIV-positive adults of early ART initiation. Main findings are reviewed with a focus on serious non-AIDS (SNA) conditions. Data from the two trials demonstrated that initiating ART early in the course of HIV infection resulted in marked reductions in the risk of opportunistic diseases and invasive bacterial infections. This indicates that HIV causes immune impairment in early infection that is remedied by controlling viral replication. Intriguingly, in START, a marked reduction in risk of cancers, both infection-related and unrelated types of cancers, was observed. Like the findings for opportunistic infections, this anti-cancer effect of early ART shows how the immune system influences important pro-oncogenic processes. In START, there was also some evidence suggesting that early ART initiation preserved kidney function, although the clinical consequence of this remains unclear. Conversely, while no adverse effects were evident, the trials did not demonstrate a clear effect on metabolic-related disease outcomes, pulmonary disease, or neurocognitive function. HIV causes immune impairment soon after acquisition of infection. ART reverses this harm at least partially. The biological nature of the immune impairment needs further elucidation, as well as mechanisms and clinical impact of innate immune activation. Based on the findings from TEMPRANO and START, and because ART lowers the risk of onward transmission, ART initiation should be offered to all persons following their diagnosis of HIV.

  8. 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.

  9. Early infection and prognosis after acute stroke

    DEFF Research Database (Denmark)

    Kammersgaard, L P; Jørgensen, H S; Reith, J

    2001-01-01

    Infection is a frequent complication in the early course of acute stroke and may adversely affect stroke outcome. In the present study, we investigate early infection developing in patients within 3 days of admission to the hospital and its independent relation to recovery and stroke outcome....... In addition, we identify predictors for early infections, infection subtypes, and their relation to initial stroke severity....

  10. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Li, Qiuping [Zhongshan Hospital of Fudan University, Shanghai 200032 (China); Yang, Zhiyuan; Wu, Guoqiang [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Gu, Jianxin [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences of Fudan University, Shanghai 200032 (China); Wei, Yuanyan, E-mail: yywei@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Jiang, Jianhai, E-mail: jianhaijiang@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China)

    2010-07-09

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  11. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    International Nuclear Information System (INIS)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan; Li, Qiuping; Yang, Zhiyuan; Wu, Guoqiang; Sun, Shuhui; Gu, Jianxin; Wei, Yuanyan; Jiang, Jianhai

    2010-01-01

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  12. Improving early childhood development and well-being in refugee ...

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

    Improving early childhood development and well-being in refugee and other marginalized countries. Early childhood development research has traditionally focused on single-intervention initiatives and non-refugee populations. This project will generate evidence to support effective, integrated and scalable early childhood ...

  13. Integrated analysis of HPV-mediated immune alterations in cervical cancer.

    Science.gov (United States)

    Chen, Long; Luan, Shaohong; Xia, Baoguo; Liu, Yansheng; Gao, Yuan; Yu, Hongyan; Mu, Qingling; Zhang, Ping; Zhang, Weina; Zhang, Shengmiao; Wei, Guopeng; Yang, Min; Li, Ke

    2018-05-01

    Human papillomavirus (HPV) infection is the primary cause of cervical cancer. HPV-mediated immune alterations are known to play crucial roles in determining viral persistence and host cell transformation. We sought to thoroughly understand HPV-directed immune alterations in cervical cancer by exploring publically available datasets. 130 HPV positive and 7 HPV negative cervical cancer cases from The Cancer Genome Atlas were compared for differences in gene expression levels and functional enrichment. Analyses for copy number variation (CNV) and genetic mutation were conducted for differentially expressed immune genes. Kaplan-Meier analysis was performed to assess survival and relapse differences across cases with or without alterations of the identified immune signature genes. Genes up-regulated in HPV positive cervical cancer were enriched for various gene ontology terms of immune processes (P=1.05E-14~1.00E-05). Integrated analysis of the differentially expressed immune genes identified 9 genes that displayed either CNV, genetic mutation and/or gene expression changes in at least 10% of the cases of HPV positive cervical cancer. Genomic amplification may cause elevated levels of these genes in some HPV positive cases. Finally, patients with alterations in at least one of the nine signature genes overall had earlier relapse compared to those without any alterations. The altered expression of either TFRC or MMP13 may indicate poor survival for a subset of cervical cancer patients (P=1.07E-07). We identified a novel immune gene signature for HPV positive cervical cancer that is potentially associated with early relapse of cervical cancer. Copyright © 2018. Published by Elsevier Inc.

  14. Challenges of Early Years Leadership Preparation: A Comparison between Early and Experienced Early Years Practitioners in England

    Science.gov (United States)

    Mistry, Malini; Sood, Krishan

    2012-01-01

    Leadership has been under-researched in the Early Years (EY) sector of primary schools in England, especially in leading change for professional development. The aim of this paper is to theorise what the leadership culture for EY practitioners looks like, and how Initial Teacher Training providers and schools are preparing practitioners for…

  15. Aerobic Capacities of Early College High School Students

    Science.gov (United States)

    Loflin, Jerry W.

    2014-01-01

    The Early College High School Initiative (ECHSI) was introduced in 2002. Since 2002, limited data, especially student physical activity data, have been published pertaining to the ECHSI. The purpose of this study was to examine the aerobic capacities of early college students and compare them to state and national averages. Early college students…

  16. Can cognitive assessment really discriminate early stages of Alzheimer's and behavioural variant frontotemporal dementia at initial clinical presentation?

    Science.gov (United States)

    Reul, Sophia; Lohmann, Hubertus; Wiendl, Heinz; Duning, Thomas; Johnen, Andreas

    2017-08-09

    Neuropsychological testing is considered crucial for differential diagnosis of Alzheimer's disease (AD) and behavioural variant frontotemporal dementia (bvFTD). In-depth neuropsychological assessment revealed specific dysfunctions in the two dementia syndromes. However, a significant overlap of cognitive impairments exists in early disease stages. We questioned whether a standard neuropsychological assessment at initial clinical presentation can delineate patients with AD versus bvFTD. In a retrospective approach, we evaluated and compared how cognitive profiles assessed at initial clinical presentation predicted the diagnosis of later verified AD (n = 43) and bvFTD (n = 26). Additionally, the neuropsychological standard domains memory, language, visuospatial skills, executive functions, praxis and social cognition were subjected to stepwise discriminant analysis to compare their differential contribution to diagnosis. Regardless of diagnosis, a percentage of patients presented with major deterioration in a wide range of cognitive domains when compared with age-matched normative data. Only few significant differences were detected on the group level: Patients with AD were relatively more impaired in the verbal recall, verbal recognition, figure copy, and surprisingly in the executive subdomains, set shifting and processing speed whereas bvFTD was characterised by more deficits in imitation of face postures. A combination of tests for verbal recall, imitation of limb and face postures, and figure copy showed the greatest discriminatory power. Our results imply that the contribution of a standard neuropsychological assessment is limited for differential diagnosis of AD and bvFTD at initial presentation. In contrast to current clinical guidelines, executive functions are neither particularly nor exclusively impaired in patients with bvFTD when assessed within a standard clinical neuropsychological test battery. The significant overlap of bvFTD and AD

  17. Barriers to timely initiation of breastfeeding among mothers of ...

    African Journals Online (AJOL)

    Routine labour ward and delivery table, specific assignment to the staff in the delivery/ labour rooms help newly delivered mothers initiate breastfeeding early, and empowering the to request for babies are recommended. Keywords: breastfeeding, initiation, barriers. Nigerian Journal of Clinical Practice Vol. 9(1) 2006: 57-64 ...

  18. Bud initiation and optimum harvest date in Brussels sprouts

    NARCIS (Netherlands)

    Everaarts, A.P.; Sukkel, W.

    1999-01-01

    For six cultivars of Brussels sprouts (Brassica oleracea var. gemmifera) with a decreasing degree of earliness, or optimum harvest date, the time of bud initiation was determined during two seasons. Fifty percent of the plants had initiated buds between 60 and 75 days after planting (DAP) in 1994

  19. Complex Foot Injury: Early and Definite Management

    NARCIS (Netherlands)

    Schepers, Tim; Rammelt, Stefan

    2017-01-01

    Complex foot injuries occur infrequently, but are life-changing events. They often present with other injuries as the result of a high-energy trauma. After initial stabilization, early assessment should be regarding salvagability. All treatment strategies are intensive. The initial treatment

  20. Initial response of a rock penetrator

    International Nuclear Information System (INIS)

    Longcope, D.B.; Grady, D.E.

    1977-12-01

    An analysis based on elastic rod theory is given for the early-time axisymmetric response of pointed penetrators. Results of measurements by laser interferometry of the back surface particle velocity of laboratory scale penetrators impacted by sandstone targets are presented. Values of the initial pressure on the penetrator tip are determined which give good agreement between the analytical and experimental results. These initial tip pressures are found to be approximated by the stress-particle velocity Hugoniot for the target material

  1. Correlation between white matter alterations and cognitive function decline in early Alzheimer's disease

    International Nuclear Information System (INIS)

    Ni Hongyan; Qi Ji; Wang Mingshi

    2008-01-01

    Objective: To investigate the effects of early stage Alzheimer's disease (AD) on white matter (WM) integrity using diffusion tensor imaging (DTI) and its relationship with cognitive function decline. Methods: DTI was performed in 32 subjects, including 14 early AD patients and 18 elder controls (ON) with a 1.5 T MR scanner. Fractional anisotropy (FA) and mean diffusivity (b) values were computed and compared for 9 regions of interest (ROI). Eight standard neuropsychological tests were performed and compared between AD and ON to evaluate basic cognitive capacities of AD. Correlation analysis was applied between FA, D values and scores of neuropsychological tests for all subjects. Results: FA significantly decreased in splenium of the corpus callosum and the posterior parietal-temporal region (S2), and (D)-bar significantly increased in the splenium in AD patients (P<0.05). AD patients showed lower scores compared with ON in all neuropsychological tests (P<0.05). FA of the splenium and S2 positively correlated with several tests scores, while D of multiple ROIs negatively correlated with several tests scores (P<0.05). Conclusions: In the early stage of AD, neuropathology has effect not only on cognitive function, but also on white matter structure, and they have strong relationship. AD patients show white matter changes in specific regions, which reflect loss in cortico-cortical connections. (authors)

  2. The transcriptome landscape of early maize meiosis

    Science.gov (United States)

    Meiosis, particularly meiotic recombination, is a major factor affecting yield and breeding of plants. To gain insight into the transcriptome landscape during early initiation steps of meiotic recombination, we profiled early prophase I meiocytes from maize using RNA-seq. Our analyses of genes prefe...

  3. Climate change alters seedling emergence and establishment in an old-field ecosystem.

    Directory of Open Access Journals (Sweden)

    Aimée T Classen

    2010-10-01

    Full Text Available Ecological succession drives large-scale changes in ecosystem composition over time, but the mechanisms whereby climatic change might alter succession remain unresolved. Here, we asked if the effects of atmospheric and climatic change would alter tree seedling emergence and establishment in an old-field ecosystem, recognizing that small shifts in rates of seedling emergence and establishment of different species may have long-term repercussions on the transition of fields to forests in the future.We introduced seeds from three early successional tree species into constructed old-field plant communities that had been subjected for 4 years to altered temperature, precipitation, and atmospheric CO(2 regimes in an experimental facility. Our experiment revealed that different combinations of atmospheric CO(2 concentration, air temperature, and soil moisture altered seedling emergence and establishment. Treatments directly and indirectly affected soil moisture, which was the best predictor of seedling establishment, though treatment effects differed among species.The observed impacts, coupled with variations in the timing of seed arrival, are demonstrated as predictors of seedling emergence and establishment in ecosystems under global change.

  4. Early-life seizures alter synaptic calcium-permeable AMPA receptor function and plasticity

    Science.gov (United States)

    Lippman-Bell, Jocelyn J.; Zhou, Chengwen; Sun, Hongyu; Feske, Joel S.; Jensen, Frances E.

    2016-01-01

    Calcium (Ca2+)-mediated1 signaling pathways are critical to synaptic plasticity. In adults, the NMDA glutamate receptor (NMDAR) represents a major route for activity-dependent synaptic Ca2+ entry. However, during neonatal development, when synaptic plasticity is high, many AMPA glutamate receptors (AMPARs) are also permeable to Ca2+ (CP-AMPAR) due to low GluA2 subunit expression, providing an additional route for activity- and glutamate-dependent Ca2+ influx and subsequent signaling. Therefore, altered hippocampal Ca2+ signaling may represent an age-specific pathogenic mechanism. We thus aimed to assess Ca2+ responses 48 hours after hypoxia-induced neonatal seizures (HS) in postnatal day (P)10 rats, a post-seizure time point at which we previously reported LTP attenuation. We found that Ca2+ responses were higher in brain slices from post-HS rats than in controls and this increase was CP-AMPAR-dependent. To determine whether synaptic CP-AMPAR expression was also altered post-HS, we assessed the expression of GluA2 at hippocampal synapses and the expression of long-term depression (LTD), which has been linked to the presence of synaptic GluA2. Here we report a decrease 48 hours after HS in synaptic GluA2 expression at synapses and LTD in hippocampal CA1. Given the potentially critical role of AMPAR trafficking in disease progression, we aimed to establish whether post-seizure in vivo AMPAR antagonist treatment prevented the enhanced Ca2+ responses, changes in GluA2 synaptic expression, and diminished LTD. We found that NBQX treatment prevents all three of these post-seizure consequences, further supporting a critical role for AMPARs as an age-specific therapeutic target. PMID:27521497

  5. Exposure to dim light at night during early development increases adult anxiety-like responses.

    Science.gov (United States)

    Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

    2014-06-22

    Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

  6. Higher educational status, staying in joint family and early treatment initiation improves quality of life in leprosy: Experiences from and observational study at a tertiary centre in Eastern India

    Directory of Open Access Journals (Sweden)

    Arup Chakraborty

    2015-01-01

    Full Text Available Introduction Leprosy is a chronic infectious disease with various risks of permanent and progressive disabilities as well as deformities. This can lead to social stigma and discrimination. Methodology A cross sectional institution based study was conducted among the patient of a leprosy clinic in a tertiary care center. WHOQOL-BREF questionnaire was used after taking consent from each study individual. Results Majority (69.8% of the patients was male and 41.3% of the study population belonged to below poverty line. Majority (85.7% of the study population were suffering from multi-bacillary type of leprosy. Though Majority (96.8% of the patients was receiving MDT (multi drug therapy regularly but still 33.33% of them were leading a poor quality of life. It has been seen that literacy, family type and time gap between starting of symptoms and initiation of treatment were significantly associated with quality of life. Discussion Different previous studies showed QOL (quality of life was associated with factors like SES (socio economic status, literacy and male gender, the present study revealed higher literacy, staying in the joint family and early treatment initiation helped to improve the QOL. Conclusion Better QOL was associated with higher educational status, good family support and early initiation of treatment among the leprosy patients.

  7. Exposure to bisphenol A in young adult mice does not alter ovulation but does alter the fertilization ability of oocytes

    International Nuclear Information System (INIS)

    Moore-Ambriz, Teresita Rocio; Acuña-Hernández, Deyanira Guadalupe; Ramos-Robles, Brenda; Sánchez-Gutiérrez, Manuel; Santacruz-Márquez, Ramsés; Sierra-Santoyo, Adolfo; Piña-Guzmán, Belem

    2015-01-01

    Follicle growth culminates in ovulation, which allows for the expulsion of fertilizable oocytes and the formation of corpora lutea. Bisphenol A (BPA) is present in many consumer products, and it has been suggested that BPA impairs ovulation; however, the underlying mechanisms are unknown. Therefore, this study first evaluated whether BPA alters ovulation by affecting folliculogenesis, the number of corpora lutea or eggs shed to the oviduct, ovarian gonadotropin responsiveness, hormone levels, and estrous cyclicity. Because it has been suggested (but not directly confirmed) that BPA exerts toxic effects on the fertilization ability of oocytes, a second aim was to evaluate whether BPA impacts the oocyte fertilization rate using an in vitro fertilization assay and mating. The possible effects on early zygote development were also examined. Young adult female C57BL/6J mice (39 days old) were orally dosed with corn oil (vehicle) or 50 μg/kg bw/day BPA for a period encompassing the first three reproductive cycles (12–15 days). BPA exposure did not alter any parameters related to ovulation. Moreover, BPA exposure reduced the percentage of fertilized oocytes after either in vitro fertilization or mating, but it did not alter the zygotic stages. The data indicate that exposure to the reference dose of BPA does not impact ovulation but that it does influence the oocyte quality in terms of its fertilization ability. - Highlights: • Bisphenol A targets the fertilization ability of oocytes. • Bisphenol A does not alter ovulation. • Young adult females may be susceptible to the effects of bisphenol A on fertilization.

  8. Exposure to bisphenol A in young adult mice does not alter ovulation but does alter the fertilization ability of oocytes

    Energy Technology Data Exchange (ETDEWEB)

    Moore-Ambriz, Teresita Rocio; Acuña-Hernández, Deyanira Guadalupe; Ramos-Robles, Brenda [Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, México D.F. 07360, México (Mexico); Sánchez-Gutiérrez, Manuel [Área Académica de Medicina, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo 42000, México (Mexico); Santacruz-Márquez, Ramsés; Sierra-Santoyo, Adolfo [Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN), Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, México D.F. 07360, México (Mexico); Piña-Guzmán, Belem [Instituto Politécnico Nacional-UPIBI, México D.F. 07738, México (Mexico); and others

    2015-12-15

    Follicle growth culminates in ovulation, which allows for the expulsion of fertilizable oocytes and the formation of corpora lutea. Bisphenol A (BPA) is present in many consumer products, and it has been suggested that BPA impairs ovulation; however, the underlying mechanisms are unknown. Therefore, this study first evaluated whether BPA alters ovulation by affecting folliculogenesis, the number of corpora lutea or eggs shed to the oviduct, ovarian gonadotropin responsiveness, hormone levels, and estrous cyclicity. Because it has been suggested (but not directly confirmed) that BPA exerts toxic effects on the fertilization ability of oocytes, a second aim was to evaluate whether BPA impacts the oocyte fertilization rate using an in vitro fertilization assay and mating. The possible effects on early zygote development were also examined. Young adult female C57BL/6J mice (39 days old) were orally dosed with corn oil (vehicle) or 50 μg/kg bw/day BPA for a period encompassing the first three reproductive cycles (12–15 days). BPA exposure did not alter any parameters related to ovulation. Moreover, BPA exposure reduced the percentage of fertilized oocytes after either in vitro fertilization or mating, but it did not alter the zygotic stages. The data indicate that exposure to the reference dose of BPA does not impact ovulation but that it does influence the oocyte quality in terms of its fertilization ability. - Highlights: • Bisphenol A targets the fertilization ability of oocytes. • Bisphenol A does not alter ovulation. • Young adult females may be susceptible to the effects of bisphenol A on fertilization.

  9. Bedfordshire County Structure Plan. Proposed alterations. Results of public consultation. Policy 97: Nuclear waste

    International Nuclear Information System (INIS)

    1984-01-01

    The document refers to Alterations to the County Structure Plan, proposed by Bedfordshire County Council and submitted to the Secretary of State for the Environment. An additional Alteration initiated at the County Council's meeting, dealing with nuclear waste, had not been the subject of prior public consultation. Consultation had since been arranged, and the present document summarises the responses that have been received, and describes the next action to be taken. (U.K.)

  10. Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

    Science.gov (United States)

    Darcy, Justin; Fang, Yimin; Hill, Cristal M; McFadden, Sam; Sun, Liou Y; Bartke, Andrzej

    2016-10-01

    Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice. © 2016 by the Society for Experimental Biology and Medicine.

  11. Early MRI Detection and Closed Bone Graft Epiphysiodesis May Alter the Course of Avascular Necrosis Following Unstable Slipped Capital Femoral Epiphysis.

    Science.gov (United States)

    Napora, Joshua K; Gilmore, Allison; Son-Hing, Jochen P; Grimberg, Dominic C; Thompson, George H; Liu, Raymond W

    2018-04-01

    Unstable slipped capital femoral epiphysis (SCFE) has an increased incidence of avascular necrosis (AVN). Early identification and surgical intervention for AVN may help preserve the femoral head. We retrospectively reviewed 48 patients (50 hips) with unstable SCFE managed between 2000 and 2014. AVN was diagnosed based on 2 different postoperative protocols. Seventeen patients (17 hips) had a scheduled magnetic resonance imaging (MRI) between 1 and 6 months from initial surgery, and the remaining 31 patients (33 hips) were evaluated by plain radiographs alone. If AVN was diagnosed, we offered core decompression and closed bone graft epiphysiodesis (CBGE) to mitigate its affects. At final follow-up, we assessed progression of AVN using the Steinberg classification. Overall 13 hips (26%) with unstable SCFEs developed AVN. MRI revealed AVN in 7 of 17 hips (41%) at a mean of 2.5 months postoperatively (range, 1.0 to 5.2 mo). Six hips diagnosed by MRI received surgical intervention (4 CBGE, 1 free vascularized fibula graft, and 1 repinning due to screw cutout) at a mean of 4.1 months (range, 1.3 to 7.2 mo) postoperatively. None of the 4 patients treated with CBGE within 2 months postoperatively progressed to stage IVC AVN. The 2 patients treated after 4 months postoperatively both progressed to stage VC AVN.Plain radiographs demonstrated AVN in 6 of 33 hips (18%) at a mean of 6.8 months postoperatively (range, 2.1 to 21.1 mo). One patient diagnosed with stage IVB AVN at 2.4 months had screw cutout and received CBGE at 2.5 months from initial pinning. The remaining 5 were not offered surgical intervention. Five of the 6 radiographically diagnosed AVN, including the 1 treated with CBGE, progressed to stage IVC AVN or greater. Although all patients with positive MRI scans developed radiographic AVN, none of the 4 patients treated with CBGE within 2 months after pinning developed grade IVC or greater AVN. Early MRI detection and CBGE may mitigate the effects of AVN after

  12. Study of the alteration of the Vatnajokull volcanic glasses (Iceland). Mechanisms and situation at low temperature

    International Nuclear Information System (INIS)

    Le Gal, X.

    1999-01-01

    Volcanic glasses have been considered for several years to be good analogues of nuclear glasses. The main objective of this study is to look at the long term behaviour of natural glasses subjected to meteoric alteration. Basaltic hyalo-clasts, essentially from Hengill, Husafell and Vatnajokull, in Iceland, were studied. These glasses, ranging from 0.09 to 4 My in age, and altered by meteoric water, are surrounded by alteration layers. In the youngest samples ( 18 O measurements indicate, major modification of the initial glass structure during gel formation. Chemical budgets show that elements are not completely retained by alteration products in such geological environments. (author)

  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. Early life adversities or high fat diet intake reduce cognitive function and alter BDNF signaling in adult rats: Interplay of these factors changes these effects.

    Science.gov (United States)

    Arcego, Danusa Mar; Krolow, Rachel; Lampert, Carine; Toniazzo, Ana Paula; Berlitz, Carolina; Lazzaretti, Camilla; Schmitz, Felipe; Rodrigues, André Felipe; Wyse, Angela T S; Dalmaz, Carla

    2016-05-01

    Environmental factors, like early exposure to stressors or high caloric diets, can alter the early programming of central nervous system, leading to long-term effects on cognitive function, increased vulnerability to cognitive decline and development of psychopathologies later in life. The interaction between these factors and their combined effects on brain structure and function are still not completely understood. In this study, we evaluated long-term effects of social isolation in the prepubertal period, with or without chronic high fat diet access, on memory and on neurochemical markers in the prefrontal cortex of rats. We observed that early social isolation led to impairment in short-term and working memory in adulthood, and to reductions of Na(+),K(+)-ATPase activity and the immunocontent of phospho-AKT, in prefrontal cortex. Chronic exposure to a high fat diet impaired short-term memory (object recognition), and decreased BDNF levels in that same brain area. Remarkably, the association of social isolation with chronic high fat diet rescued the memory impairment on the object recognition test, as well as the changes in BDNF levels, Na(+),K(+)-ATPase activity, MAPK, AKT and phospho-AKT to levels similar to the control-chow group. In summary, these findings showed that a brief social isolation period and access to a high fat diet during a sensitive developmental period might cause memory deficits in adulthood. On the other hand, the interplay between isolation and high fat diet access caused a different brain programming, preventing some of the effects observed when these factors are separately applied. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  15. Development of basic data for modelling the residual alteration rate in aqueous media of AVM nuclear glasses

    International Nuclear Information System (INIS)

    Thien, B.

    2010-01-01

    During their aqueous alteration, AVM French nuclear glasses exhibit a large range of behaviour, in spite of a small range of composition. AVM glasses alteration rates are controlled by two phenomena: (i) precipitation of secondary phases, mostly aluminous hectorites, and (ii) diffusion of water across a more or less protective gel. The magnesium contained in these glasses increases the precipitation of these secondary phases, leading to a partial or total dissolution of the gel layer. This dissolution increases the glass alteration rates. On the other hand, Mg also incorporates in the gel, increasing his passivation properties. The predominance of one of these two phenomena depends on the initial composition of the glass, the pH of the solution, and the alteration conditions. In presence of Bure geological disposal site water (Mg and Ca rich), AVM glasses undergo less alteration than in initially pure water, in spite of larger amounts of secondary phase precipitates. This results from incorporation of calcium in the gel instead of sodium and magnesium, improving its passivating properties. We have adapted the geochemical GRAAL model for AVM glasses. In spite of its limitations, this model allows us to describe the differences of behaviour between these glasses, in function of their composition. Moreover, GRAAL can be proposed as a basis of a future operational model for predicting the alteration of AVM glasses. (author) [fr

  16. The carbonaceous matter in the uraniferous dequartzified and albitized leucogranite of Saraya (Senegal): an example of superimposed hydrothermal alterations

    International Nuclear Information System (INIS)

    Mouthier, B.

    1988-01-01

    Two superimposed early hydrothermal alterations have been recognized in the Proterozoic Saraya leucogranite. Successively are described a major dequartzification leading to an episyenite infilled with carbonaceous matter and sulfate during an interruption of the system, succeeded by a mobilization of U and other elements during an albitization. A dolomite filling up followed by a silicopotassic feed-back alteration, close down the system [fr

  17. Radiation induced early onset of neuro-cognitive changes

    International Nuclear Information System (INIS)

    Kumar, Mayank; Haridas, Seenu; Gupta, Mamta; Trivedi, Richa; Khushu, Subhash; Manda, Kailash

    2012-01-01

    Exposure to ionizing radiations has been shown to cause many detrimental effects. Primarily, the effects observed are broadly classified into hematopoietic syndrome at lower doses, gastrointestinal syndrome and central nervous system dysfunctions at high doses. However, recent studies reported that even at lower doses, there is an effect seen on the nervous system which can be observed as a decline in cognitive abilities. This has been reported in patients undergoing radiotherapy. The cognitive decline, especially in young patients affects development and has been shown to persist for years after the therapy. Thus, the aim of this study was to study and consolidate the early effects of radiation exposure which result in behavioural alterations and cognitive decline. Since, radiation-induced early changes in behavioural functions are poorly understood, therefore, the present investigation aimed to conceptualize and design behavioural test batteries in order to systematically study the immediate alterations in behavioural function following irradiation with a-rays. The behavioural alterations were correlated to changes in the different area of brain like hippocampus, thalamus, hypothalamus and corpus callosum using Diffusion Tensor Imaging (DTI) studies. Present study reported profound changes in behaviour, as well as alterations in the morphology of the brain tissue as perceived by DTI, 48 hours after exposure to ionizing radiations. These changes need to be correlated and clarified further to understand the mechanisms behind the cognitive dysfunctions occurring immediately after radiation exposure as well as to find out a therapeutic window to counteract or reduce the effect of long term cognitive changes following irradiation. (author)

  18. Plug-in Hybrid Initiative

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Angie; Moore, Ray; Rowden, Tim

    2013-09-27

    Our main project objective was to implement Plug-in Electric Vehicles (PEV) and charging infrastructure into our electric distribution service territory and help reduce barriers in the process. Our research demonstrated the desire for some to be early adopters of electric vehicles and the effects lack of education plays on others. The response of early adopters was tremendous: with the initial launch of our program we had nearly 60 residential customers interested in taking part in our program. However, our program only allowed for 15 residential participants. Our program provided assistance towards purchasing a PEV and installation of Electric Vehicle Supply Equipment (EVSE). The residential participants have all come to love their PEVs and are more than enthusiastic about promoting the many benefits of driving electric.

  19. [Environmental and genetic variables related with alterations in language acquisition in early childhood].

    Science.gov (United States)

    Moriano-Gutierrez, A; Colomer-Revuelta, J; Sanjuan, J; Carot-Sierra, J M

    2017-01-01

    A great deal of research has addressed problems in the correct acquisition of language, but with few overall conclusions. The reasons for this lie in the individual variability, the existence of different measures for assessing language and the fact that a complex network of genetic and environmental factors are involved in its development. To review the environmental and genetic variables that have been studied to date, in order to gain a better under-standing of the causes of specific language impairment and create new evidence that can help in the development of screening systems for the early detection of these disorders. The environmental variables related with poorer early child language development include male gender, low level of education of the mother, familial history of problems with language or psychiatric problems, perinatal problems and health problems in early childhood. Bilingualism seems to be a protective factor. Temperament and language are related. Within the genetic factors there are several specific genes associated with language, two of which have a greater influence on its physiological acquisition: FOXP2 and CNTNAP2. The other genes that are most related with specific language disorders are ATP2C2, CMIP, ROBO2, ZNF277 and NOP9. The key to comprehending the development of specific language disorders lies in reaching an understanding of the true role played by genes in the ontogenesis, in the regulation of the different developmental processes, and how this role is modulated by the environment.

  20. Exploiting Epigenetic Alterations in Prostate Cancer.

    Science.gov (United States)

    Baumgart, Simon J; Haendler, Bernard

    2017-05-09

    Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

  1. Exploiting Epigenetic Alterations in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Simon J. Baumgart

    2017-05-01

    Full Text Available Prostate cancer affects an increasing number of men worldwide and is a leading cause of cancer-associated deaths. Beside genetic mutations, many epigenetic alterations including DNA and histone modifications have been identified in clinical prostate tumor samples. They have been linked to aberrant activity of enzymes and reader proteins involved in these epigenetic processes, leading to the search for dedicated inhibitory compounds. In the wake of encouraging anti-tumor efficacy results in preclinical models, epigenetic modulators addressing different targets are now being tested in prostate cancer patients. In addition, the assessment of microRNAs as stratification biomarkers, and early clinical trials evaluating suppressor microRNAs as potential prostate cancer treatment are being discussed.

  2. Early Development of Entrepreneurial Qualities: the Role of Initial Education

    OpenAIRE

    Isobel van der Kuip; Ingrid Verheul

    2003-01-01

    This study attempts to create a better understanding of the role of entrepreneurship education in developing entrepreneurial qualities. Theory and practice are confronted. The paper discusses the extent to which entrepreneurship can be taught, and the way in which it should be taught. The focus is on the phase of initial education.

  3. Study of nuclear glasses alteration gel and synthesis of some model gels; Etude du gel d`alteration des verres nucleaires et synthese de gels modeles

    Energy Technology Data Exchange (ETDEWEB)

    Ricol, S

    1995-10-05

    This work deals with the general problem of alteration of the reference nuclear glass R7T7. Attention is paid particularly to the altered layer formed at the glass surface during alteration process. In opposition to previous works, related essentially to glass dissolution kinetics based on chemical analyses of lixiviated elements, this thesis deals with alteration problems through structural studies of the reference glass and derived gel. This approach allows the determination of mechanisms for the gel formation and a better understanding of the behaviour of glasses towards lixiviation. Both approaches appeared complementary. Based on several spectroscopic techniques, this work showed the particular role of cations such as calcium, zirconium and iron. Studies of silica-based synthetic gels showed the synergic effect of formers cation and of one highly coordinated cation. The variation of the wavenumber related to Si-O-Si asymmetric stretching vibration can be correlated to O/Si ratio for ternary systems Si/Na/Zr. On the contrary, the Si losses of the materials depend on the number of non-bridging oxygen atoms. In the perspective of long-term behaviour, the alteration gel presents better characteristics than initial glass. It is therefore a highly stable material in static conditions. In the same way, synthetic gels are materials with very low solubilities (much lower than the alteration gel) and could be used as confining matrices. (authors). refs., 71 figs., 37 tabs.

  4. Alterations to Bone Mineral Composition as an Early Indication of Osteomyelitis in the Diabetic Foot

    OpenAIRE

    Esmonde-White, Karen A.; Esmonde-White, Francis W.L.; Holmes, Crystal M.; Morris, Michael D.; Roessler, Blake J.

    2013-01-01

    OBJECTIVE Osteomyelitis in the diabetic foot is a major risk factor for amputation, but there is a limited understanding of early-stage infection, impeding limb-preserving diagnoses. We hypothesized that bone composition measurements provide insight into the early pathophysiology of diabetic osteomyelitis. RESEARCH DESIGN AND METHODS Compositional analysis by Raman spectroscopy was performed on bone specimens from patients with a clinical diagnosis of osteomyelitis in the foot requiring surgi...

  5. Aging induced ER stress alters sleep and sleep homeostasis

    Science.gov (United States)

    Brown, Marishka K.; Chan, May T.; Zimmerman, John E.; Pack, Allan I.; Jackson, Nicholas E.; Naidoo, Nirinjini

    2014-01-01

    Alterations in the quality, quantity and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response (UPR). The effectiveness of the adaptive UPR is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of x-box binding protein 1 (XBP1) and upregulation of phosphorylated elongation initiation factor 2 α (p-eIF2α), in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged/sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep/ sleep debt discharge. PMID:24444805

  6. Immune-mediated diseases and microbial exposure in early life

    DEFF Research Database (Denmark)

    Bisgaard, H; Bønnelykke, K; Stokholm, Jacob

    2014-01-01

    The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system...

  7. Complex Foot Injury: Early and Definite Management.

    Science.gov (United States)

    Schepers, Tim; Rammelt, Stefan

    2017-03-01

    Complex foot injuries occur infrequently, but are life-changing events. They often present with other injuries as the result of a high-energy trauma. After initial stabilization, early assessment should be regarding salvagability. All treatment strategies are intensive. The initial treatment includes prevention of progression ischemia/necrosis, prevention of infection, and considering salvage or amputation. Definitive treatment for salvage includes anatomic reconstruction with stable internal fixation and early soft tissue coverage followed by aggressive rehabilitation. Prognosis after complex injuries is hard to predict. The various stages of the treatment are reviewed and recommendations are made. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. An Ancient Transcription Factor Initiates the Burst of piRNA Production During Early Meiosis in Mouse Testes

    Science.gov (United States)

    Li, Xin Zhiguo; Roy, Christian K.; Dong, Xianjun; Bolcun-Filas, Ewelina; Wang, Jie; Han, Bo W.; Xu, Jia; Moore, Melissa J.; Schimenti, John C.; Weng, Zhiping; Zamore, Phillip D.

    2013-01-01

    SUMMARY Animal germ cells produce PIWI-interacting RNAs (piRNAs), small silencing RNAs that suppress transposons and enable gamete maturation. Mammalian transposon-silencing piRNAs accumulate early in spermatogenesis, whereas pachytene piRNAs are produced later during post-natal spermatogenesis and account for >95% of all piRNAs in the adult mouse testis. Mutants defective for pachytene piRNA pathway proteins fail to produce mature sperm, but neither the piRNA precursor transcripts nor the trigger for pachytene piRNA production is known. Here, we show that the transcription factor A-MYB initiates pachytene piRNA production. A-MYB drives transcription of both pachytene piRNA precursor RNAs and the mRNAs for core piRNA biogenesis factors, including MIWI, the protein through which pachytene piRNAs function. A-MYB regulation of piRNA pathway proteins and piRNA genes creates a coherent feed-forward loop that ensures the robust accumulation of pachytene piRNAs. This regulatory circuit, which can be detected in rooster testes, likely predates the divergence of birds and mammals. PMID:23523368

  9. DARK MATTER CONTRACTION AND THE STELLAR CONTENT OF MASSIVE EARLY-TYPE GALAXIES: DISFAVORING 'LIGHT' INITIAL MASS FUNCTIONS

    International Nuclear Information System (INIS)

    Auger, M. W.; Treu, T.; Gavazzi, R.; Bolton, A. S.; Koopmans, L. V. E.; Marshall, P. J.

    2010-01-01

    We use stellar dynamics, strong lensing, stellar population synthesis models, and weak lensing shear measurements to constrain the dark matter (DM) profile and stellar mass in a sample of 53 massive early-type galaxies. We explore three DM halo models (unperturbed Navarro, Frenk, and White (NFW) halos and the adiabatic contraction models of Blumenthal and Gnedin) and impose a model for the relationship between the stellar and virial mass (i.e., a relationship for the star formation efficiency as a function of halo mass). We show that, given our model assumptions, the data clearly prefer a Salpeter-like initial mass function (IMF) over a lighter IMF (e.g., Chabrier or Kroupa), irrespective of the choice of DM halo. In addition, we find that the data prefer at most a moderate amount of adiabatic contraction (Blumenthal adiabatic contraction is strongly disfavored) and are only consistent with no adiabatic contraction (i.e., an NFW halo) if a mass-dependent IMF is assumed, in the sense of a more massive normalization of the IMF for more massive halos.

  10. Altered level of consciousness: evidence-based management in the emergency department [digest].

    Science.gov (United States)

    Song, Joo Lee; Wang, Vincent J; Vazquez, Michelle N

    2017-01-22

    A child who presents to the emergency department with an altered level of consciousness can be clinically unstable and can pose a great diagnostic challenge. The emergency clinician must quickly develop a wide differential of possible etiologies in order to administer potentially life-saving medications or interventions. The history, physical examination, and appropriate diagnostic tests can aid greatly in rapidly narrowing the differential diagnosis. Once initial stabilization, workup, and first-line interventions are completed, most patients who present with unresolved or unidentified altered level of consciousness should be admitted for further evaluation and close monitoring. This issue provides a review of the etiologies of altered level of consciousness as well as guidance for the management and disposition of patients with this condition. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

  11. Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever.

    Science.gov (United States)

    Blohmke, Christoph J; Darton, Thomas C; Jones, Claire; Suarez, Nicolas M; Waddington, Claire S; Angus, Brian; Zhou, Liqing; Hill, Jennifer; Clare, Simon; Kane, Leanne; Mukhopadhyay, Subhankar; Schreiber, Fernanda; Duque-Correa, Maria A; Wright, James C; Roumeliotis, Theodoros I; Yu, Lu; Choudhary, Jyoti S; Mejias, Asuncion; Ramilo, Octavio; Shanyinde, Milensu; Sztein, Marcelo B; Kingsley, Robert A; Lockhart, Stephen; Levine, Myron M; Lynn, David J; Dougan, Gordon; Pollard, Andrew J

    2016-05-30

    Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host-pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. © 2016 Blohmke et al.

  12. Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

    Science.gov (United States)

    Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

    2017-07-20

    Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

  13. The effect of altered gut flora on glucose intolerance in C57BL/6NTac mice

    DEFF Research Database (Denmark)

    Rune, Ida; Ellekilde, Merete; Hansen, Camilla Hartmann Friis

    Recent studies have shown that long term broad spectrum antibiotic treatment improves glucose tolerance in mice. We hypothesize that it is primarily in the early life that altering of the gut microbiota will have an impact on glucose intoleance.....

  14. Sleep Deprivation Alters Choice Strategy Without Altering Uncertainty or Loss Aversion Preferences

    Directory of Open Access Journals (Sweden)

    O'Dhaniel A Mullette-Gillman

    2015-10-01

    Full Text Available Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  15. Sleep deprivation alters choice strategy without altering uncertainty or loss aversion preferences.

    Science.gov (United States)

    Mullette-Gillman, O'Dhaniel A; Kurnianingsih, Yoanna A; Liu, Jean C J

    2015-01-01

    Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD) alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences.

  16. Reduced butyrylcholinesterase activity is an early indicator of trauma-induced acute systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Zivkovic AR

    2016-11-01

    Full Text Available Aleksandar R Zivkovic, Jochen Bender, Thorsten Brenner, Stefan Hofer,* Karsten Schmidt* Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany *These authors contributed equally to this work Purpose: Early diagnosis of systemic inflammatory response syndrome is fundamentally important for an effective and a goal-directed therapy. Various inflammation biomarkers have been used in clinical and experimental practice. However, a definitive diagnostic tool for an early detection of systemic inflammation remains to be identified. Acetylcholine (Ach has been shown to play an important role in the inflammatory response. Serum cholinesterase (butyrylcholinesterase [BChE] is the major Ach hydrolyzing enzyme in blood. The role of this enzyme during inflammation has not yet been fully understood. This study tests whether a reduction in the BChE activity could indicate the onset of the systemic inflammatory response upon traumatic injury. Patients and methods: This observational study measured BChE activity in patients with traumatic injury admitted to the emergency room by using point-of-care-test system (POCT. In addition, the levels of routine inflammation biomarkers during the initial treatment period were measured. Injury Severity Score was used to assess the trauma severity. Results: Altered BChE activity was correlated with trauma severity, resulting in systemic inflammation. Reduction in the BChE activity was detected significantly earlier compared to those of routinely measured inflammatory biomarkers. Conclusion: This study suggests that the BChE activity reduction might serve as an early indicator of acute systemic inflammation. Furthermore, BChE activity, measured using a POCT system, might play an important role in the early diagnosis of the trauma-induced systemic inflammation. Keywords: trauma, injury, early diagnostics, cholinergic, pseudocholinesterase, SIRS

  17. The Stellar Initial Mass Function in Early-type Galaxies from Absorption Line Spectroscopy. I. Data and Empirical Trends

    Science.gov (United States)

    van Dokkum, Pieter G.; Conroy, Charlie

    2012-11-01

    The strength of gravity-sensitive absorption lines in the integrated light of old stellar populations is one of the few direct probes of the stellar initial mass function (IMF) outside of the Milky Way. Owing to the advent of fully depleted CCDs with little or no fringing it has recently become possible to obtain accurate measurements of these features. Here, we present spectra covering the wavelength ranges 0.35-0.55 μm and 0.72-1.03 μm for the bulge of M31 and 34 early-type galaxies from the SAURON sample, obtained with the Low Resolution Imaging Spectrometer on Keck. The signal-to-noise ratio is >~ 200 Å-1 out to 1 μm, which is sufficient to measure gravity-sensitive features for individual galaxies and to determine how they depend on other properties of the galaxies. Combining the new data with previously obtained spectra for globular clusters in M31 and the most massive elliptical galaxies in the Virgo cluster, we find that the dwarf-sensitive Na I λ8183, 8195 doublet and the FeH λ9916 Wing-Ford band increase systematically with velocity dispersion, while the giant-sensitive Ca II λ8498, 8542, 8662 triplet decreases with dispersion. These trends are consistent with a varying IMF, such that galaxies with deeper potential wells have more dwarf-enriched mass functions. In a companion paper, we use a comprehensive stellar population synthesis model to demonstrate that IMF effects can be separated from age and abundance variations and quantify the IMF variation among early-type galaxies.

  18. THE STELLAR INITIAL MASS FUNCTION IN EARLY-TYPE GALAXIES FROM ABSORPTION LINE SPECTROSCOPY. I. DATA AND EMPIRICAL TRENDS

    International Nuclear Information System (INIS)

    Van Dokkum, Pieter G.; Conroy, Charlie

    2012-01-01

    The strength of gravity-sensitive absorption lines in the integrated light of old stellar populations is one of the few direct probes of the stellar initial mass function (IMF) outside of the Milky Way. Owing to the advent of fully depleted CCDs with little or no fringing it has recently become possible to obtain accurate measurements of these features. Here, we present spectra covering the wavelength ranges 0.35-0.55 μm and 0.72-1.03 μm for the bulge of M31 and 34 early-type galaxies from the SAURON sample, obtained with the Low Resolution Imaging Spectrometer on Keck. The signal-to-noise ratio is ∼> 200 Å –1 out to 1 μm, which is sufficient to measure gravity-sensitive features for individual galaxies and to determine how they depend on other properties of the galaxies. Combining the new data with previously obtained spectra for globular clusters in M31 and the most massive elliptical galaxies in the Virgo cluster, we find that the dwarf-sensitive Na I λ8183, 8195 doublet and the FeH λ9916 Wing-Ford band increase systematically with velocity dispersion, while the giant-sensitive Ca II λ8498, 8542, 8662 triplet decreases with dispersion. These trends are consistent with a varying IMF, such that galaxies with deeper potential wells have more dwarf-enriched mass functions. In a companion paper, we use a comprehensive stellar population synthesis model to demonstrate that IMF effects can be separated from age and abundance variations and quantify the IMF variation among early-type galaxies.

  19. Inhibition of autophagy initiation potentiates chemosensitivity in mesothelioma.

    Science.gov (United States)

    Follo, Carlo; Cheng, Yao; Richards, William G; Bueno, Raphael; Broaddus, Virginia Courtney

    2018-03-01

    The benefits of inhibiting autophagy in cancer are still controversial, with differences in outcome based on the type of tumor, the context and the particular stage of inhibition. Here, we investigated the impact of inhibiting autophagy at different stages on chemosensitivity using 3-dimensional (3D) models of mesothelioma, including ex vivo human tumor fragment spheroids. As shown by LC3B accumulation, we successfully inhibited autophagy using either an early stage ULK1/2 inhibitor (MRT 68921) or a late stage inhibitor (hydroxychloroquine). We found that inhibition of autophagy at the early stage, but not at late stage, potentiated chemosensitivity. This effect was seen only in those spheroids with high autophagy and active initiation at steady state. Inhibition of autophagy alone, at either early or late stage, did not cause cell death, showing that the inhibitors were non-toxic and that mesothelioma did not depend on autophagy at baseline, at least over 24 h. Using ATG13 puncta analysis, we found that autophagy initiation identified tumors that are more chemosensitive at baseline and after autophagy inhibition. Our results highlight a potential role of autophagy initiation in supporting mesothelioma cells during chemotherapy. Our work also highlights the importance of testing the inhibition of different stages in order to uncover the role of autophagy and the potential of its modulation in the treatment of cancer. © 2017 Wiley Periodicals, Inc.

  20. Initial management of breastfeeding.

    Science.gov (United States)

    Sinusas, K; Gagliardi, A

    2001-09-15

    Breast milk is widely accepted as the ideal source of nutrition for infants. In order to ensure success in breastfeeding, it is important that it be initiated as early as possible during the neonatal period. This is facilitated by skin-to-skin contact between the mother and infant immediately following birth. When possible, the infant should be allowed to root and latch on spontaneously within the first hour of life. Many common nursery routines such as weighing the infant, administration of vitamin K and application of ocular antibiotics can be safely delayed until after the initial breastfeeding. Postpartum care practices that improve breastfeeding rates include rooming-in, anticipatory guidance about breastfeeding problems and the avoidance of formula supplementation and pacifiers.

  1. Gram negative bacteria are associated with the early stages of necrotizing enterocolitis.

    Directory of Open Access Journals (Sweden)

    Erica M Carlisle

    Full Text Available INTRODUCTION: Necrotizing enterocolitis (NEC affects 5-10% of infants born weighing less than 1500 g. Most models of NEC recapitulate late-stage disease with gut necrosis and elevated inflammatory mediators. Evaluation of NEC at earlier, less lethal stages of disease will allow investigation of initial disease triggers and may advance our understanding of temporal relationships between factors implicated in NEC pathogenesis. In this manuscript, we describe our investigation of early NEC and test the hypothesis that bacteria and inflammatory mediators differ between animals with early NEC and disease free animals. METHODS: On DOL7 C3HeB/FeJ pups were fed liquid formula with 1×10(4 Streptococcus thoraltensis, Serratia marcescens, and Pseudomonas aeruginosa every 3 h. To initiate NEC, pups underwent asphyxia (100% N(2 for 90 s and hypothermia (4°C for 10 min after feeding. Pups were euthanized at 72 h. Intestines were collected for histologic NEC scoring and DNA/RNA extraction. Bacterial populations were identified by 16S rRNA pyrosequencing and principal component analysis (PCA. RNA isolates underwent QRT-PCR for Toll-like Receptor 4 (TLR4 and inducible nitric oxide synthase (iNOS. RESULTS: Despite histologic, intestinal damage in mice with NEC, no gross necrosis was observed suggesting early disease. QRT-PCR yielded no difference between groups in TLR4 or iNOS mRNA levels. PCA demonstrated relative clustering of microbial communities based on presence or absence of NEC. 16S pyrosequencing demonstrated similar phyla between groups (Firmicutes and Proteobacteria predominated in all animals. However, the colonic microbiota of animals with NEC had more Citrobacter (p<0.01, Klebsiella (p<0.05, and Tatumella (p<0.05, while that of animals without NEC had more Streptococcus (p<0.01 and Enterococcus (p<0.01. CONCLUSION: Citrobacter, Klebsiella, and Tatumella are associated with NEC. Differential colonic bacteria were identified despite the lack of

  2. Napping Reduces Emotional Attention Bias during Early Childhood

    Science.gov (United States)

    Cremone, Amanda; Kurdziel, Laura B. F.; Fraticelli-Torres, Ada; McDermott, Jennifer M.; Spencer, Rebecca M. C.

    2017-01-01

    Sleep loss alters processing of emotional stimuli in preschool-aged children. However, the mechanism by which sleep modifies emotional processing in early childhood is unknown. We tested the hypothesis that a nap, compared to an equivalent time spent awake, reduces biases in attention allocation to affective information. Children (n = 43;…

  3. Early management of sepsis with emphasis on early goal directed therapy: AME evidence series 002

    OpenAIRE

    Zhang, Zhongheng; Hong, Yucai; Smischney, Nathan J.; Kuo, Han-Pin; Tsirigotis, Panagiotis; Rello, Jordi; Kuan, Win Sen; Jung, Christian; Robba, Chiara; Taccone, Fabio Silvio; Leone, Marc; Spapen, Herbert; Grimaldi, David; Van Poucke, Sven; Simpson, Steven Q.

    2017-01-01

    Severe sepsis and septic shock are major causes of morbidity and mortality in patients entering the emergency department (ED) or intensive care unit (ICU). Despite substantial efforts to improve patient outcome, treatment of sepsis remains challenging to clinicians. In this context, early goal directed therapy (EGDT) represents an important concept emphasizing both early recognition of sepsis and prompt initiation of a structured treatment algorithm. As part of the AME evidence series on seps...

  4. Solutions to the Cosmic Initial Entropy Problem without Equilibrium Initial Conditions

    Directory of Open Access Journals (Sweden)

    Vihan M. Patel

    2017-08-01

    Full Text Available The entropy of the observable universe is increasing. Thus, at earlier times the entropy was lower. However, the cosmic microwave background radiation reveals an apparently high entropy universe close to thermal and chemical equilibrium. A two-part solution to this cosmic initial entropy problem is proposed. Following Penrose, we argue that the evenly distributed matter of the early universe is equivalent to low gravitational entropy. There are two competing explanations for how this initial low gravitational entropy comes about. (1 Inflation and baryogenesis produce a virtually homogeneous distribution of matter with a low gravitational entropy. (2 Dissatisfied with explaining a low gravitational entropy as the product of a ‘special’ scalar field, some theorists argue (following Boltzmann for a “more natural” initial condition in which the entire universe is in an initial equilibrium state of maximum entropy. In this equilibrium model, our observable universe is an unusual low entropy fluctuation embedded in a high entropy universe. The anthropic principle and the fluctuation theorem suggest that this low entropy region should be as small as possible and have as large an entropy as possible, consistent with our existence. However, our low entropy universe is much larger than needed to produce observers, and we see no evidence for an embedding in a higher entropy background. The initial conditions of inflationary models are as natural as the equilibrium background favored by many theorists.

  5. Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.

    Science.gov (United States)

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne

    2017-11-01

    In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate-dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J-wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds, and also demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  6. Brain viscoelasticity alteration in chronic-progressive multiple sclerosis.

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    Kaspar-Josche Streitberger

    Full Text Available INTRODUCTION: Viscoelastic properties indicate structural alterations in biological tissues at multiple scales with high sensitivity. Magnetic Resonance Elastography (MRE is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. MRE recently revealed that early relapsing-remitting multiple sclerosis (MS is associated with a global decrease of the cerebral mechanical integrity. This study addresses MRE and MR volumetry in chronic-progressive disease courses of MS. METHODS: We determined viscoelastic parameters of the brain parenchyma in 23 MS patients with primary or secondary chronic progressive disease course in comparison to 38 age- and gender-matched healthy individuals by multifrequency MRE, and correlated the results with clinical data, T2 lesion load and brain volume. Two viscoelastic parameters, the shear elasticity μ and the powerlaw exponent α, were deduced according to the springpot model and compared to literature values of relapsing-remitting MS. RESULTS: In chronic-progressive MS patients, μ and α were reduced by 20.5% and 6.1%, respectively, compared to healthy controls. MR volumetry yielded a weaker correlation: Total brain volume loss in MS patients was in the range of 7.5% and 1.7% considering the brain parenchymal fraction. All findings were significant (P<0.001. CONCLUSIONS: Chronic-progressive MS disease courses show a pronounced reduction of the cerebral shear elasticity compared to early relapsing-remitting disease. The powerlaw exponent α decreased only in the chronic-progressive stage of MS, suggesting an alteration in the geometry of the cerebral mechanical network due to chronic neuroinflammation.

  7. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    Energy Technology Data Exchange (ETDEWEB)

    Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  8. A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

    International Nuclear Information System (INIS)

    Xu, D.; Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J.; Ping, J.; Qin, J.; Zhang, C.; Chen, L.B.; Magdalou, J.; Wang, H.

    2012-01-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

  9. Early myelin breakdown following sural nerve crush: a freeze-fracture study

    Directory of Open Access Journals (Sweden)

    Martinez A.M.B.

    2000-01-01

    Full Text Available In this study we describe the early changes of the myelin sheath following surgical nerve crush. We used the freeze-fracture technique to better evaluate myelin alterations during an early stage of Wallerian degeneration. Rat sural nerves were experimentally crushed and animals were sacrificed by transcardiac perfusion 30 h after surgery. Segments of the nerves were processed for routine transmission electron microscopy and freeze-fracture techniques. Our results show that 30 h after the lesion there was asynchrony in the pattern of Wallerian degeneration, with different nerve fibers exhibiting variable degrees of axon disruption. This was observed by both techniques. Careful examination of several replicas revealed early changes in myelin membranes represented by vacuolization and splitting of consecutive lamellae, rearrangement of intramembranous particles and disappearance of paranodal transverse bands associated or not with retraction of paranodal myelin terminal loops from the axolemma. These alterations are compatible with a direct injury to the myelin sheath following nerve crush. The results are discussed in terms of a similar mechanism underlying both axon and myelin breakdown.

  10. Alterations in HIV-1 LTR promoter activity during AIDS progression

    International Nuclear Information System (INIS)

    Hiebenthal-Millow, Kirsten; Greenough, Thomas C.; Bretttler, Doreen B.; Schindler, Michael; Wildum, Steffen; Sullivan, John L.; Kirchhoff, Frank

    2003-01-01

    HIV-1 variants evolving in AIDS patients frequently show increased replicative capacity compared to those present during early asymptomatic infection. It is known that late stage HIV-1 variants often show an expanded coreceptor tropism and altered Nef function. In the present study we investigated whether enhanced HIV-1 LTR promoter activity might also evolve during disease progression. Our results demonstrate increased LTR promoter activity after AIDS progression in 3 of 12 HIV-1-infected individuals studied. Further analysis revealed that multiple alterations in the U3 core-enhancer and in the transactivation-response (TAR) region seem to be responsible for the enhanced functional activity. Our findings show that in a subset of HIV-1-infected individuals enhanced LTR transcription contributes to the increased replicative potential of late stage virus isolates and might accelerate disease progression

  11. Relativistic initial conditions for N-body simulations

    Energy Technology Data Exchange (ETDEWEB)

    Fidler, Christian [Catholic University of Louvain—Center for Cosmology, Particle Physics and Phenomenology (CP3) 2, Chemin du Cyclotron, B-1348 Louvain-la-Neuve (Belgium); Tram, Thomas; Crittenden, Robert; Koyama, Kazuya; Wands, David [Institute of Cosmology and Gravitation, University of Portsmouth, Portsmouth PO1 3FX (United Kingdom); Rampf, Cornelius, E-mail: christian.fidler@uclouvain.be, E-mail: thomas.tram@port.ac.uk, E-mail: rampf@thphys.uni-heidelberg.de, E-mail: robert.crittenden@port.ac.uk, E-mail: kazuya.koyama@port.ac.uk, E-mail: david.wands@port.ac.uk [Institut für Theoretische Physik, Universität Heidelberg, Philosophenweg 16, D–69120 Heidelberg (Germany)

    2017-06-01

    Initial conditions for (Newtonian) cosmological N-body simulations are usually set by re-scaling the present-day power spectrum obtained from linear (relativistic) Boltzmann codes to the desired initial redshift of the simulation. This back-scaling method can account for the effect of inhomogeneous residual thermal radiation at early times, which is absent in the Newtonian simulations. We analyse this procedure from a fully relativistic perspective, employing the recently-proposed Newtonian motion gauge framework. We find that N-body simulations for ΛCDM cosmology starting from back-scaled initial conditions can be self-consistently embedded in a relativistic space-time with first-order metric potentials calculated using a linear Boltzmann code. This space-time coincides with a simple ''N-body gauge'' for z < 50 for all observable modes. Care must be taken, however, when simulating non-standard cosmologies. As an example, we analyse the back-scaling method in a cosmology with decaying dark matter, and show that metric perturbations become large at early times in the back-scaling approach, indicating a breakdown of the perturbative description. We suggest a suitable ''forwards approach' for such cases.

  12. Subcortical functional reorganization due to early blindness.

    Science.gov (United States)

    Coullon, Gaelle S L; Jiang, Fang; Fine, Ione; Watkins, Kate E; Bridge, Holly

    2015-04-01

    Lack of visual input early in life results in occipital cortical responses to auditory and tactile stimuli. However, it remains unclear whether cross-modal plasticity also occurs in subcortical pathways. With the use of functional magnetic resonance imaging, auditory responses were compared across individuals with congenital anophthalmia (absence of eyes), those with early onset (in the first few years of life) blindness, and normally sighted individuals. We find that the superior colliculus, a "visual" subcortical structure, is recruited by the auditory system in congenital and early onset blindness. Additionally, auditory subcortical responses to monaural stimuli were altered as a result of blindness. Specifically, responses in the auditory thalamus were equally strong to contralateral and ipsilateral stimulation in both groups of blind subjects, whereas sighted controls showed stronger responses to contralateral stimulation. These findings suggest that early blindness results in substantial reorganization of subcortical auditory responses. Copyright © 2015 the American Physiological Society.

  13. Effects of Early Neglect Experience on Recognition and Processing of Facial Expressions: A Systematic Review

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    Victoria Doretto

    2018-01-01

    Full Text Available Background: Child neglect is highly prevalent and associated with a series of biological and social consequences. Early neglect may alter the recognition of emotional faces, but its precise impact remains unclear. We aim to review and analyze data from recent literature about recognition and processing of facial expressions in individuals with history of childhood neglect. Methods: We conducted a systematic review using PubMed, PsycINFO, ScIELO and EMBASE databases in the search of studies for the past 10 years. Results: In total, 14 studies were selected and critically reviewed. A heterogeneity was detected across methods and sample frames. Results were mixed across studies. Different forms of alterations to perception of facial expressions were found across 12 studies. There was alteration to the recognition and processing of both positive and negative emotions, but for emotional face processing there was predominance in alteration toward negative emotions. Conclusions: This is the first review to examine specifically the effects of early neglect experience as a prevalent condition of child maltreatment. The results of this review are inconclusive due to methodological diversity, implement of distinct instruments and differences in the composition of the samples. Despite these limitations, some studies support our hypothesis that individuals with history of early negligence may present alteration to the ability to perceive face expressions of emotions. The article brings relevant information that can help in the development of more effective therapeutic strategies to reduce the impact of neglect on the cognitive and emotional development of the child.

  14. Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

    Science.gov (United States)

    Molina-Jiménez, Tania; Limón-Morales, Ofelia; Bonilla-Jaime, Herlinda

    2018-03-01

    Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. 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.

  16. Contributions to early HIV diagnosis among patients linked to care vary by testing venue

    Directory of Open Access Journals (Sweden)

    Trott Alexander T

    2008-06-01

    Full Text Available Abstract Objective Early HIV diagnosis reduces transmission and improves health outcomes; screening in non-traditional settings is increasingly advocated. We compared test venues by the number of new diagnoses successfully linked to the regional HIV treatment center and disease stage at diagnosis. Methods We conducted a retrospective cohort study using structured chart review of newly diagnosed HIV patients successfully referred to the region's only HIV treatment center from 1998 to 2003. Demographics, testing indication, risk profile, and initial CD4 count were recorded. Results There were 277 newly diagnosed patients meeting study criteria. Mean age was 33 years, 77% were male, and 46% were African-American. Median CD4 at diagnosis was 324. Diagnoses were earlier via partner testing at the HIV treatment center (N = 8, median CD4 648, p = 0.008 and with universal screening by the blood bank, military, and insurance companies (N = 13, median CD4 483, p = 0.05 than at other venues. Targeted testing by health care and public health entities based on patient request, risk profile, or patient condition lead to later diagnosis. Conclusion Test venues varied by the number of new diagnoses made and the stage of illness at diagnosis. To improve the rate of early diagnosis, scarce resources should be allocated to maximize the number of new diagnoses at screening venues where diagnoses are more likely to be early or alter testing strategies at test venues where diagnoses are traditionally made late. Efforts to improve early diagnosis should be coordinated longitudinally on a regional basis according to this conceptual paradigm.

  17. Development of potentiometric equipment for the identification of altered dry-cured hams: A preliminary study.

    Science.gov (United States)

    Girón, Joel; Gil-Sánchez, Luís; García-Breijo, Eduardo; Pagán, M Jesús; Barat, José M; Grau, Raúl

    2015-08-01

    Microbiological contamination in dry-cured ham can occur in the early stages of the process, a large number of microorganisms involved in spoilage can produce alterations in the product. These include non-common odours, which are detected at the end of the process by a procedure called "cala", consisting of a sharp instrument punctured in every ham; this is smelled by an expert taster, who classifies hams as good and altered hams. An electronic device would be suitable for this process given the large amount of hams. The present research aims to develop objective equipment based on the potentiometry technique that identifies altered hams. A probe was developed, containing silver, nickel and copper electrodes, and was employed to classify altered and unaltered hams prior to classification by a tester. The results shown lower Ag and higher Cu potential values for altered hams. The differences in potentiometric response reveal a classification model, although further studies are required to obtain a reliable classification model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. 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.

  19. The Relationship between Oxygen Saturation and Color Alteration of a Compromised Skin Flap: Experimental Study on the Rabbit

    Directory of Open Access Journals (Sweden)

    Theddeus O. H. Prasetyono

    2013-09-01

    Full Text Available Background The aim of this study was to collect important data on the time of oxygensaturation change in relation to skin flap color alteration using non-invasive pulse oximetryto evaluate its ability to provide continuous monitoring of skin flap perfusion.Methods An experimental study on the monitoring of blood perfusion of 20 tube-islandgroin flaps of 10 male New Zealand rabbits was performed using pulse oximetry. The animalswere randomly assigned to one of two groups representing a blockage of either arterial orvenous blood flow. The oxygen saturation change and clinical color alteration were monitoredfrom the beginning of vessel clamping until the saturation became undetectable. The resultwas analyzed by the t-test using SSPS ver. 10.0.Results The mean times from the vessel clamping until the saturation became undetectablewere 20.19±2.13 seconds and 74.91±10.57 seconds for the artery and vein clamping groups,respectively. The mean time of the clinical alteration from the beginning of vein clampingwas 34.5±11.72 minutes, while the alteration in flaps with artery clamping could not bedetected until 2.5 hours after clamping.Conclusions The use of neonate-type reusable flex sensor-pulse oximetry is objective andeffective in early detection of arterial and vein blockage. It provides real-time data on vesselocclusion, which in turn will allow for early salvaging. The detection periods of both arterialocclusion and venous congestion are much earlier than the color alteration one may encounterclinically.

  20. The Internationalisation of Early Childhood Education: Case Study from Selected Kindergartens in Bandung, Indonesia

    Science.gov (United States)

    Adriany, Vina

    2018-01-01

    For the past 20 years, early childhood education has undergone changes that have resulted from an alteration in Indonesian socio-political situations. One of the changes has resulted in the emergence of the internationalisation of early childhood education in Indonesia. This paper unpacks the complexity of the process. Three teachers from three…

  1. Preliminary findings demonstrating latent effects of early adolescent marijuana use onset on cortical architecture

    Directory of Open Access Journals (Sweden)

    Francesca M. Filbey

    2015-12-01

    Conclusions: Divergent patterns between current MJ use and elements of cortical architecture were associated with early MJ use onset. Considering brain development in early adolescence, findings are consistent with disruptions in pruning. However, divergence with continued use for many years thereafter suggests altered trajectories of brain maturation during late adolescence and beyond.

  2. Aqueous alteration of Japanese simulated waste glass P0798: Effects of alteration-phase formation on alteration rate and cesium retention

    International Nuclear Information System (INIS)

    Inagaki, Y.; Shinkai, A.; Idemistu, K.; Arima, T.; Yoshikawa, H.; Yui, M.

    2006-01-01

    Aqueous alteration tests were performed with a Japanese simulated waste glass P0798 in alkaline solutions as a function of pH or species/concentration of alkaline metals in the solution in order to evaluate the alteration conditions determining whether smectite (2:1 clay mineral) or analcime (zeolite) forms as the major alteration-phase. XRD analysis of the alteration-phases showed that smectite forms at any pH between 9.5 and 12, and analcime forms at pH above 11, though the formation also depends on species and concentrations of alkaline metals in the solution. These results cannot agree with the thermodynamically predicted phase stability, e.g., smectite is more stable than the thermodynamic prediction shows. On the basis of the results of alteration conditions, the alteration tests were performed under smectite forming conditions, where only smectite forms or no crystalline phases form, in order to evaluate the alteration rate and the mechanism of cesium release/retention. The results showed that the glass alteration proceeds slowly in proportion to square root of time under smectite forming conditions, which indicates that the alteration rate can be controlled by a diffusion process. It was suggested that the alteration rate under smectite forming conditions is independent of the pH, alkaline metal species/concentration in the solution and whether smectite actually forms or not. The results also indicated that most of cesium dissolved from the glass can be retained in the alteration-phases by reversible sorption onto smectite or irreversible incorporation into analcime, pollucite or solid solutions of them

  3. A hypothalamic-pituitary-adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion.

    Science.gov (United States)

    Xu, D; Wu, Y; Liu, F; Liu, Y S; Shen, L; Lei, Y Y; Liu, J; Ping, J; Qin, J; Zhang, C; Chen, L B; Magdalou, J; Wang, H

    2012-11-01

    Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic-pituitary-adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Initial intramuscular perfusion pressure predicts early skeletal muscle function following isolated tibial fractures

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    Haas Norbert P

    2008-04-01

    Full Text Available Abstract Background The severity of associated soft tissue trauma in complex injuries of the extremities guides fracture treatment and decisively determines patient's prognosis. Trauma-induced microvascular dysfunction and increased tissue pressure is known to trigger secondary soft tissue damage and seems to adversely affect skeletal muscle function. Methods 20 patients with isolated tibial fractures were included. Blood pressure and compartment pressure (anterior and deep posterior compartment were measured continuously up to 24 hours. Corresponding perfusion pressure was calculated. After 4 and 12 weeks isokinetic muscle peak torque and mean power of the ankle joint in dorsal and plantar flexion were measured using a Biodex dynamometer. Results A significant inverse correlation between the anterior perfusion pressure at 24 hours and deficit in dorsiflexion at 4 weeks was found for both, the peak torque (R = -0.83; p Conclusion The functional relationship between the decrease in intramuscular perfusion pressures and muscle performance in the early rehabilitation period indicate a causative and prognostic role of early posttraumatic microcirculatory derangements and skeletal muscle function. Therapeutic concepts aimed at effective muscle recovery, early rehabilitation, and decreased secondary tissue damage, should consider the maintenance of an adequate intramuscular perfusion pressure.

  5. Arterial alterations in severely obese children with obstructive sleep apnoea.

    Science.gov (United States)

    Dubern, Beatrice; Aggoun, Yacine; Boulé, Michèle; Fauroux, Brigitte; Bonnet, Damien; Tounian, Patrick

    2010-05-03

    Obstructive sleep apnoea (OSA) in obese adults is associated with cardiovascular disease independently of obesity. Vascular alterations exist in children with obesity and may constitute the first stage in the development of adulthood cardiovascular disease. To investigate the relationship between OSA and early arterial alterations in obese children. Cross-sectional study of a prospective cohort. A total of 51 children with severe obesity managed at a teaching hospital outpatient clinic. Polysomnography was performed. We measured the intima-media thickness and incremental elastic modulus (Einc) to assess the mechanical characteristics of the common carotid artery. Arterial endothelial function was evaluated by measuring flow-mediated dilation and glyceryl trinitrate-mediated dilation (GTNMD) of the brachial artery. A total of 24 (47%) children had a desaturation index (DI) >10/h and 7 (14%) had a respiratory event index >10/h. DI >10/h was associated with significantly higher values of Einc (4.0 + or - 0.5 vs. 2.4 + or - 0.4 mm Hg(-1) x 10(3), p=0.003) and GTNMD (18.0 + or - 1.1 vs. 14.1 + or - 1.0 %, p=0.02) after adjustment for age, sex, body mass index, fasting insulin, and leptin. In the univariate analysis, GTNMD correlated positively with DI (r=0.14, p=0.02) after adjustment for age, sex, fasting insulin and leptin. By multivariate analysis with BMI as an additional independent variable, both GTNMD and Einc correlated significantly with DI (beta=0.4, p=0.02 and beta=0.27, p=0.04, respectively). OSA in children is associated with arterial alterations independently from obesity. The increased vasodilation in response to glyceryl trinitrate reflects pre-existing vasoconstriction probably induced by intermittent hypoxia. OSA should be detected early in children with severe obesity.

  6. Prevalence of oral manifestations in soft tissues during early childhood in Brazilian children

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    Maria Cristina Ramos Lima PADOVANI

    2014-08-01

    Full Text Available This study aimed at assessing the prevalence of soft tissue oral manifestations in children during early childhood, according to age group, gender, and site in the oral cavity, and at correlating these oral manifestations with systemic alterations. A cross-sectional study was conducted involving 586 children from 0 to 3 years of age (12.4 ± 11.8 months, 316 (53.9% male and 270 (46.1% female, in the city of Mauá, SP, Brazil. Examination was performed by a single examiner (Kappa Index = 0.90 according to World Health Organization criteria (WHO, 1997.The prevalence of oral manifestations in the soft tissues of children during early childhood was 34.8%. The age group showing statistical significance was 0-1 months old (56.4%. Epstein’s pearls were significantly present (43.2% in 0-1-month-old babies, and gingivitis in 12-24-month-olds (15.9%. The palate was the most affected region (16.7%. Infectious alterations were the most prevalent systemic alteration (20%. An association was observed between the presence of systemic alterations and the occurrence of oral manifestations. The prevalence of oral manifestations was 34.8%, regardless of gender, and was manifested mostly in 0-1-month-old babies. The palate was the most prevalent region, and the majority of oral manifestations were associated with systemic alterations.

  7. Chronic administration during early adulthood does not alter the hormonally-dependent disruptive effects of delta-9-tetrahydrocannabinol (Δ9-THC) on complex behavior in female rats.

    Science.gov (United States)

    Winsauer, Peter J; Sutton, Jessie L

    2014-02-01

    This study examined whether chronic Δ(9)-THC during early adulthood would produce the same hormonally-dependent deficits in learning that are produced by chronic Δ(9)-THC during adolescence. To do this, either sham-operated (intact) or ovariectomized (OVX) female rats received daily saline or 5.6 mg/kg of Δ(9)-THC i.p. for 40 days during early adulthood. Following chronic administration, and a drug-free period to train both a learning and performance task, acute dose-effect curves for Δ(9)-THC (0.56-10 mg/kg) were established in each of the four groups (intact/saline, intact/THC, OVX/saline and OVX/THC). The dependent measures of responding under the learning and performance tasks were the overall response rate and the percentage of errors. Although the history of OVX and chronic Δ(9)-THC in early adulthood did not significantly affect non-drug or baseline behavior under the tasks, acute administration of Δ(9)-THC produced both rate-decreasing and error-increasing effects on learning and performance behavior, and these effects were dependent on their hormone condition. More specifically, both intact groups were more sensitive to the rate-decreasing and error-increasing effects of Δ(9)-THC than the OVX groups irrespective of chronic Δ(9)-THC administration, as there was no significant main effect of chronic treatment and no significant interaction between chronic treatment (saline or Δ(9)-THC) and the dose of Δ(9)-THC administered as an adult. Post mortem examination of 10 brain regions also indicated there were significant differences in agonist-stimulated GTPγS binding across brain regions, but no significant effects of chronic treatment and no significant interaction between the chronic treatment and cannabinoid signaling. Thus, acute Δ(9)-THC produced hormonally-dependent effects on learning and performance behavior, but a period of chronic administration during early adulthood did not alter these effects significantly, which is contrary to what we

  8. Visible light alters yeast metabolic rhythms by inhibiting respiration

    OpenAIRE

    Robertson, James Brian; Davis, Chris R.; Johnson, Carl Hirschie

    2013-01-01

    In some organisms, respiration fluctuates cyclically, and these rhythms can be a sensitive gauge of metabolism. Constant or pulsatile exposure of yeast to visible wavelengths of light significantly alters and/or initiates these respiratory oscillations, revealing a further dimension of the challenges to yeast living in natural environments. Our results also have implications for the use of light as research tools—e.g., for excitation of fluorescence microscopically—even in organisms such as y...

  9. Early histological and functional effects of chronic copper exposure in rat liver.

    Science.gov (United States)

    Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

    2005-10-01

    Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

  10. Arab-American Hookah Smokers: Initiation, and Pros and Cons of Hookah Use.

    Science.gov (United States)

    Kassem, Nada O F; Kassem, Noura O; Jackson, Sheila R; Daffa, Reem M; Liles, Sandy; Hovell, Melbourne F

    2015-09-01

    To examine initiation, pros and cons of hookah tobacco smoking among Arab Americans. In this descriptive cross-sectional study, we recruited a community-based convenience sample of 458 adult Arab-American hookah smokers, mean age 28.4 years, who completed self-administered questionnaires. Irrespective of sex, most participants initiated hookah tobacco use by young adulthood in private homes or hookah lounges influenced by friends and family. Women initiated hookah use later than men. Ever dual smokers (hookah smokers who ever smoked a cigarette) initiated hookah use later than cigarettes; however, early hookah initiators < 18 years initiated hookah and cigarettes concurrently. Participants enjoyed the flavors of hookah tobacco, and complained about coughing, dizziness, and headaches. Early and late initiation of hookah tobacco use warrant prevention programs targeting the youth and older adults in communities, colleges, and middle and high schools that include health education campaigns, and encouragement of voluntary smokefree home rules. Tobacco control policies aimed to prevent initiation of hookah use should include regulation of hookah tobacco flavors, and should target the physical environments in neighborhoods, especially around schools and colleges, to reduce the proliferation of hookah lounges. Dual hookah tobacco and cigarette use warrant continuous monitoring.

  11. Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons.

    Science.gov (United States)

    McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas; Blanco, Cynthia

    2017-05-01

    Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. Copyright © 2017 Endocrine Society.

  12. Alterations in CD200-CD200R1 System during EAE Already Manifest at Presymptomatic Stages

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    Tony Valente

    2017-05-01

    Full Text Available In the brain of patients with multiple sclerosis, activated microglia/macrophages appear in active lesions and in normal appearing white matter. However, whether they play a beneficial or a detrimental role in the development of the pathology remains a controversial issue. The production of pro-inflammatory molecules by chronically activated microglial cells is suggested to contribute to the progression of neurodegenerative processes in neurological disease. In the healthy brain, neurons control glial activation through several inhibitory mechanisms, such as the CD200-CD200R1 interaction. Therefore, we studied whether alterations in the CD200-CD200R1 system might underlie the neuroinflammation in an experimental autoimmune encephalomyelitis (EAE model of multiple sclerosis. We determined the time course of CD200 and CD200R1 expression in the brain and spinal cord of an EAE mouse model from presymptomatic to late symptomatic stages. We also assessed the correlation with associated glial activation, inflammatory response and EAE severity. Alterations in CD200 and CD200R1 expression were mainly observed in spinal cord regions in the EAE model, mostly a decrease in CD200 and an increase in CD200R1 expression. A decrease in the expression of the mRNA encoding a full CD200 protein was detected before the onset of clinical signs, and remained thereafter. A decrease in CD200 protein expression was observed from the onset of clinical signs. By contrast, CD200R1 expression increased at EAE onset, when a glial reaction associated with the production of pro- and anti-inflammatory markers occurred, and continued to be elevated during the pathology. Moreover, the magnitude of the alterations correlated with severity of the EAE mainly in spinal cord. These results suggest that neuronal-microglial communication through CD200-CD200R1 interaction is compromised in EAE. The early decreases in CD200 expression in EAE suggest that this downregulation might also

  13. An Assessment of Dialysis Provider's Attitudes towards Timing of Dialysis Initiation in Canada

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    Bikaramjit S Mann

    2014-04-01

    Full Text Available Background: Physicians' perceptions and opinions may influence when to initiate dialysis. Objective: To examine providers' perspectives and opinions regarding the timing of dialysis initiation. Design: Online survey. Setting: Community and academic dialysis practices in Canada. Participants: A nationally-representative sample of dialysis providers. Measurements and Methods: Dialysis providers opinions assessing reasons to initiate dialysis at low or high eGFR. Responses were obtained using a 9-point Likert scale. Early dialysis was defined as initiation of dialysis in an individual with an eGFR greater than or equal to 10.5 ml/min/m 2 . A detailed survey was emailed to all members of the Canadian Society of Nephrology (CSN in February 2013. The survey was designed and pre-tested to evaluate duration and ease of administration. Results: One hundred and forty one (25% response rate physicians participated in the survey. The majority were from urban, academic centres and practiced in regionally administered renal programs. Very few respondents had a formal policy regarding the timing of dialysis initiation or formally reviewed new dialysis starts (N = 4, 3.1%. The majority of respondents were either neutral or disagreed that late compared to early dialysis initiation improved outcomes (85–88%, had a negative impact on quality of life (89%, worsened AVF or PD use (84–90%, led to sicker patients (83% or was cost effective (61%. Fifty-seven percent of respondents felt uremic symptoms occurred earlier in patients with advancing age or co-morbid illness. Half (51.8% of the respondents felt there was an absolute eGFR at which they would initiate dialysis in an asymptomatic patient. The majority of respondents would initiate dialysis for classic indications for dialysis, such as volume overload (90.1% and cachexia (83.7% however a significant number chose other factors that may lead them to early dialysis initiation including avoiding an emergency (28

  14. Holding the baby: early mother-infant contact after childbirth and outcomes.

    Science.gov (United States)

    Redshaw, Maggie; Hennegan, Julie; Kruske, Sue

    2014-05-01

    to describe the timing, type and duration of initial infant contact and associated demographic and clinical factors in addition to investigating the impact of early contact on breastfeeding and maternal health and well being after birth. data from a recent population survey of women birthing in Queensland, Australia were used to describe the nature of the first hold and associated demographic characteristics. Initial comparisons, with subsequent adjustment for type of birthing facility and mode of childbirth, were used to assess associations between timing, type and duration of initial contact and outcomes. Further analyses were conducted to investigate a dose-response relationship between duration of first contact and outcomes. women who had an unassisted vaginal birth held their infant sooner, and for longer than women who had an assisted vaginal birth or caesarean and were more satisfied with their early contact. Multivariate models showed a number of demographic and clinical interventions contributing to timing, duration and type of first contact with type of birthing facility (public/private), area of residence, and assisted birth as prominent factors. For women who had a vaginal birth; early, skin-to-skin, and longer duration of initial contact were associated with high rates of breastfeeding initiation and breastfeeding at discharge, but not breastfeeding at 13 weeks. Some aspects of early contact were associated with improved maternal well being. However, these associations were not found for women who had a caesarean birth. With longer durations of first contact, a dose-response effect was found for breastfeeding. results of the study provide a description of current practice in Queensland, Australia and factors impacting on early contact. For vaginal births, findings add to the evidence in support of early skin-to-skin contact for an extended period. It is suggested that all research in this area should consider the effects of early contact separately for

  15. Patterns and Timing of Initial Relapse in Patients Subsequently Undergoing Transplantation for Hodgkin's Lymphoma

    International Nuclear Information System (INIS)

    Dhakal, Sughosh; Biswas, Tithi; Liesveld, Jane L.; Friedberg, Jonathan W.; Phillips, Gordon L.; Constine, Louis S.

    2009-01-01

    Purpose: To evaluate the patterns and timing of initial recurrence in patients with Hodgkin's lymphoma (HL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplantation to enhance our understanding of the natural history of this disease and its modern treatment strategies and to direct approaches to disease surveillance. Methods and Materials: The records of 69 patients with HL who had undergone high-dose chemotherapy with autologous stem cell transplantation in our center between May 1992 and June 2006 were analyzed. The initial diagnosis had been made between April 1982 and January 2005 at a median patient age of 33 years (range, 19-65). The patients were segregated according to the initial stage (Stage I-II vs. III-IV). Results: Early-stage HL patients developed a relapse at a median of 2.1 years (range, 0.5-10.3), with 91% of relapses at the initial disease site, 71% of which (65% overall) were only in previously involved sites. Advanced-stage HL patients developed a relapse at a median of 1.5 years (range, 0.6-10.5), with 97% at the initial site, 71% of which (69% overall) were only in previously involved sites. Single-site relapses occurred in 47% of early- vs. 26% of advanced-stage patients, and extranodal relapses occurred in 12% of early- vs. 31% of advanced-stage patients. Conclusions: Almost all patients with HL who develop relapse and subsequently undergo high-dose chemotherapy with autologous stem cell transplantation initially developed recurrence in previously involved disease sites. Early-stage HL relapses often occurred in single sites, and advanced-stage disease relapses were more likely in multiple and extranodal sites. The interval to recurrence was brief, suggesting that the frequency of screening should be the greatest in the early post-therapy years.

  16. Histone deacetylase inhibitors reduce the number of herpes simplex virus-1 genomes initiating expression in individual cells

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    Lev Shapira

    2016-12-01

    Full Text Available Although many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1 fluorescence-expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s. Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA, Suberohydroxamic Acid (SBX, Valporic Acid (VPA and Suberoylanilide Hydoxamic Acid (SAHA. We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the gene expression from the viral genomes. Different cell types (HFF, Vero and U2OS, which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (PML and ATRX, which may explain the lower number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in

  17. Initial amino acid intake influences phosphorus and calcium homeostasis in preterm infants--it is time to change the composition of the early parenteral nutrition.

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    Francesco Bonsante

    Full Text Available Early aggressive parenteral nutrition (PN, consisting of caloric and nitrogen intake soon after birth, is currently proposed for the premature baby. Some electrolyte disturbances, such as hypophosphatemia and hypercalcemia, considered unusual in early life, were recently described while using this PN approach. We hypothesize that, due to its impact on cell metabolism, the initial amino acid (AA amount may specifically influence the metabolism of phosphorus, and consequently of calcium. We aim to evaluate the influence of AA intake on calcium-phosphorus metabolism, and to create a calculation tool to estimate phosphorus needs.Prospective observational study. Phosphate and calcium plasma concentrations and calcium balance were evaluated daily during the first week of life in very preterm infants, and their relationship with nutrition was studied. For this purpose, infants were divided into three groups: high, medium and low AA intake (HAA, MAA, LAA. A calculation formula to assess phosphorus needs was elaborated, with a theoretical model based on AA and calcium intake, and the cumulative deficit of phosphate intake was estimated.154 infants were included. Hypophosphatemia (12.5% and hypercalcemia (9.8% were more frequent in the HAA than in the MAA (4.6% and 4.8% and in the LAA group (0% and 1.9%; both p<0.001.Calcium-phosphorus homeostasis was influenced by the early AA intake. We propose to consider phosphorus and calcium imbalances as being part of a syndrome, related to incomplete provision of nutrients after the abrupt discontinuation of the placental nutrition at birth (PI-ReFeeding syndrome. We provide a simple tool to calculate the optimal phosphate intake. The early introduction of AA in the PN soon after birth might be completed by an early intake of phosphorus, since AA and phosphorus are (along with potassium the main determinants of cellular growth.

  18. Interferon-driven alterations of the host’s amino acid metabolism in the pathogenesis of typhoid fever

    Science.gov (United States)

    Jones, Claire; Waddington, Claire S.; Zhou, Liqing; Hill, Jennifer; Clare, Simon; Mukhopadhyay, Subhankar; Schreiber, Fernanda; Roumeliotis, Theodoros I.; Yu, Lu; Ramilo, Octavio; Sztein, Marcelo B.; Kingsley, Robert A.; Levine, Myron M.

    2016-01-01

    Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever. PMID:27217537

  19. Proteasomes remain intact, but show early focal alteration in their composition in a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; Agar, Jeffrey N; Hong, Yu; Taylor, David M; Minotti, Sandra; Figlewicz, Denise A; Durham, Heather D

    2008-06-01

    In amyotrophic lateral sclerosis caused by mutations in Cu/Zn-superoxide dismutase (SOD1), altered solubility and aggregation of the mutant protein implicates failure of pathways for detecting and catabolizing misfolded proteins. Our previous studies demonstrated early reduction of proteasome-mediated proteolytic activity in lumbar spinal cord of SOD1(G93A) transgenic mice, tissue particularly vulnerable to disease. The purpose of this study was to identify any underlying abnormalities in proteasomal structure. In lumbar spinal cord of pre-symptomatic mice [postnatal day 45 (P45) and P75], normal levels of structural 20S alpha subunits were incorporated into 20S/26S proteasomes; however, proteasomal complexes separated by native gel electrophoresis showed decreased immunoreactivity with antibodies to beta3, a structural subunit of the 20S proteasome core, and beta5, the subunit with chymotrypsin-like activity. This occurred prior to increase in beta5i immunoproteasomal subunit. mRNA levels were maintained and no association of mutant SOD1 with proteasomes was identified, implicating post-transcriptional mechanisms. mRNAs also were maintained in laser captured motor neurons at a later stage of disease (P100) in which multiple 20S proteins are reduced relative to the surrounding neuropil. Increase in detergent-insoluble, ubiquitinated proteins at P75 provided further evidence of stress on mechanisms of protein quality control in multiple cell types prior to significant motor neuron death.

  20. Hospitalist and Internal Medicine Leaders' Perspectives of Early Discharge Challenges at Academic Medical Centers.

    Science.gov (United States)

    Patel, Hemali; Fang, Margaret C; Mourad, Michelle; Green, Adrienne; Wachter, Robert M; Murphy, Ryan D; Harrison, James D

    2018-06-01

    Improving early discharges may improve patient flow and increase hospital capacity. We conducted a national survey of academic medical centers addressing the prevalence, importance, and effectiveness of early-discharge initiatives. We assembled a list of hospitalist and general internal medicine leaders at 115 US-based academic medical centers. We emailed each institutional representative a 30-item online survey regarding early-discharge initiatives. The survey included questions on discharge prioritization, the prevalence and effectiveness of early-discharge initiatives, and barriers to implementation. We received 61 responses from 115 institutions (53% response rate). Forty-seven (77%) "strongly agreed" or "agreed" that early discharge was a priority. "Discharge by noon" was the most cited goal (n = 23; 38%) followed by "no set time but overall goal for improvement" (n = 13; 21%). The majority of respondents reported early discharge as more important than obtaining translators for non-English-speaking patients and equally important as reducing 30-day readmissions and improving patient satisfaction. The most commonly reported factors delaying discharge were availability of postacute care beds (n = 48; 79%) and patient-related transport complications (n = 44; 72%). The most effective early discharge initiatives reported involved changes to the rounding process, such as preemptive identification and early preparation of discharge paperwork (n = 34; 56%) and communication with patients about anticipated discharge (n = 29; 48%). There is a strong interest in increasing early discharges in an effort to improve hospital throughput and patient flow. © 2017 Society of Hospital Medicine.

  1. A developmental perspective on early-life exposure to neurotoxicants.

    Science.gov (United States)

    Bellinger, David C; Matthews-Bellinger, Julia A; Kordas, Katarzyna

    2016-09-01

    Studies of early-life neurotoxicant exposure have not been designed, analyzed, or interpreted in the context of a fully developmental perspective. The goal of this paper is to describe the key principles of a developmental perspective and to use examples from the literature to illustrate the relevance of these principles to early-life neurotoxicant exposures. Four principles are discussed: 1) the effects of early-life neurotoxicant exposure depend on a child's developmental context; 2) deficits caused by early-life exposure initiate developmental cascades that can lead to pathologies that differ from those observed initially; 3) early-life neurotoxicant exposure has intra-familial and intergenerational impacts; 4) the impacts of early-life neurotoxicant exposure influence a child's ability to respond to future insults. The first principle is supported by considerable evidence, but the other three have received much less attention. Incorporating a developmental perspective in studies of early-life neurotoxicant exposures requires prospective collection of data on a larger array of covariates than usually considered, using analytical approaches that acknowledge the transactional processes between a child and the environment and the phenomenon of developmental cascades. Consideration of early-life neurotoxicant exposure within a developmental perspective reveals that many issues remain to be explicated if we are to achieve a deep understanding of the societal health burden associated with early-life neurotoxicant exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Altered retinal microRNA expression profiles in early diabetic retinopathy: an in silico analysis.

    Science.gov (United States)

    Xiong, Fen; Du, Xinhua; Hu, Jianyan; Li, Tingting; Du, Shanshan; Wu, Qiang

    2014-07-01

    MicroRNAs (miRNAs) - as negative regulators of target genes - are associated with various human diseases, but their precise role(s) in diabetic retinopathy (DR) remains to be elucidated. The aim of this study was to elucidate the involvement of miRNAs in early DR using in silico analysis to explore their gene expression patterns. We used the streptozotocin (STZ)-induced diabetic rat to investigate the roles of miRNAs in early DR. Retinal miRNA expression profiles from diabetic versus healthy control rats were examined by miRNA array analysis. Based on several bioinformatic systems, specifically, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we identified signatures of the potential pathological processes, gene functions, and signaling pathways that are influenced by dysregulated miRNAs. We used quantitative real-time polymerase chain reaction (qRT-PCR) to validate six (i.e. those with significant changes in expression levels) of the 17 miRNAs that were detected in the miRNA array. We also describe the significant role of the miRNA-gene network, which is based on the interactions between miRNAs and target genes. GO analysis of the 17 miRNAs detected in the miRNA array analysis revealed the most prevalent miRNAs to be those related to biological processes, olfactory bulb development and axonogenesis. These miRNAs also exert significant influence on additional pathways, including the mitogen-activated protein and calcium signaling pathways. Six of the seventeen miRNAs were chosen for qRT-PCR validation. With the exception of a slight difference in miRNA-350, our results are in close agreement with the differential expressions detected by array analysis. This study, which describes miRNA expression during the early developmental phases of DR, revealed extensive miRNA interactions. Based on both their target genes and signaling pathways, we suggest that miRNAs perform critical regulatory functions during the early stages of DR

  3. Evidence for a constant initial mass function in early-type galaxies based on their X-ray binary populations

    International Nuclear Information System (INIS)

    Peacock, Mark B.; Zepf, Stephen E.; Maccarone, Thomas J.; Kundu, Arunav; Gonzalez, Anthony H.; Lehmer, Bret D.; Maraston, Claudia

    2014-01-01

    A number of recent studies have proposed that the stellar initial mass function (IMF) of early type galaxies varies systematically as a function of galaxy mass, with higher mass galaxies having bottom-heavy IMFs. These bottom-heavy IMFs have more low-mass stars relative to the number of high mass stars, and therefore naturally result in proportionally fewer neutron stars (NSs) and black holes (BHs). In this paper, we specifically predict the variation in the number of BHs and NSs based on the power-law IMF variation required to reproduce the observed mass-to-light ratio trends with galaxy mass. We then test whether such variations are observed by studying the field low-mass X-ray binary (LMXB) populations of nearby early-type galaxies. In these binaries, an NS or BH accretes matter from a low-mass donor star. Their number is therefore expected to scale with the number of BHs and NSs present in a galaxy. We find that the number of LMXBs per K-band light is similar among the galaxies in our sample. These data therefore demonstrate the uniformity of the slope of the IMF from massive stars down to those now dominating the K-band light and are consistent with an invariant IMF. Our results are inconsistent with an IMF which varies from a Kroupa/Chabrier like IMF for low-mass galaxies to a steep power-law IMF (with slope x = 2.8) for high mass galaxies. We discuss how these observations constrain the possible forms of the IMF variations and how future Chandra observations can enable sharper tests of the IMF.

  4. Evidence for a constant initial mass function in early-type galaxies based on their X-ray binary populations

    Energy Technology Data Exchange (ETDEWEB)

    Peacock, Mark B.; Zepf, Stephen E. [Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824 (United States); Maccarone, Thomas J. [Texas Tech University, Physics Department, Box 41051, Lubbock, TX 79409 (United States); Kundu, Arunav [Eureka Scientific, Inc., 2452 Delmer Street, Suite 100 Oakland, CA 94602 (United States); Gonzalez, Anthony H. [Department of Astronomy, University of Florida, Gainesville, FL 32611 (United States); Lehmer, Bret D. [The Johns Hopkins University, Homewood Campus, Baltimore, MD 21218 (United States); Maraston, Claudia, E-mail: mpeacock@msu.edu [Institute of Cosmology and Gravitation, Dennis Sciama Building, Burnaby Road, Portsmouth PO1 3FX (United Kingdom)

    2014-04-01

    A number of recent studies have proposed that the stellar initial mass function (IMF) of early type galaxies varies systematically as a function of galaxy mass, with higher mass galaxies having bottom-heavy IMFs. These bottom-heavy IMFs have more low-mass stars relative to the number of high mass stars, and therefore naturally result in proportionally fewer neutron stars (NSs) and black holes (BHs). In this paper, we specifically predict the variation in the number of BHs and NSs based on the power-law IMF variation required to reproduce the observed mass-to-light ratio trends with galaxy mass. We then test whether such variations are observed by studying the field low-mass X-ray binary (LMXB) populations of nearby early-type galaxies. In these binaries, an NS or BH accretes matter from a low-mass donor star. Their number is therefore expected to scale with the number of BHs and NSs present in a galaxy. We find that the number of LMXBs per K-band light is similar among the galaxies in our sample. These data therefore demonstrate the uniformity of the slope of the IMF from massive stars down to those now dominating the K-band light and are consistent with an invariant IMF. Our results are inconsistent with an IMF which varies from a Kroupa/Chabrier like IMF for low-mass galaxies to a steep power-law IMF (with slope x = 2.8) for high mass galaxies. We discuss how these observations constrain the possible forms of the IMF variations and how future Chandra observations can enable sharper tests of the IMF.

  5. Supporting women with advanced breast cancer: the impact of altered functional status on their social roles.

    Science.gov (United States)

    Chen, Bai Qi Peggy; Parmar, Monica P; Gartshore, Kimberley

    2014-01-01

    Despite early detection of breast cancer and the progress of treatment modalities, metastasis-specific symptoms continue to impact women's functional status and daily living. The aim of this study was to explore the experience of altered functional status and social roles of women with advanced breast cancer. Using qualitative descriptive methodology, semi-structured interviews were conducted with 10 women diagnosed with advanced breast cancer and altered functional status attending a tertiary care cancer centre. Results illustrated the adaptive experience of women living with their illness as they reshaped their social roles to fit with their altered functional status and advanced disease. These findings highlight the opportunity for supportive care nursing interventions to facilitate the behavioural and cognitive transitions that are experienced by women with advanced breast cancer and altered functional status. These results may have implications for women with other advanced chronic diseases, though more research is required.

  6. 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...

  7. Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.

    Science.gov (United States)

    Brown, Marishka K; Chan, May T; Zimmerman, John E; Pack, Allan I; Jackson, Nicholas E; Naidoo, Nirinjini

    2014-06-01

    Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 α, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Permanent alterations in muscarinic receptors and pupil size produced by chronic atropinization in kittens

    International Nuclear Information System (INIS)

    Smith, E.L.; Redburn, D.A.; Harwerth, R.S.; Maguire, G.W.

    1984-01-01

    Chronic mydriasis was induced in six kittens (four monocular, two binocular) and two adult cats (both monocular) by the daily topical application of atropine. Both the kittens and the adult cats were atropinized for a 13-week period with the treatment regimen beginning at the time of eye opening for the kittens. Pupil size measurements, obtained 1 year after the atropinization were discontinued, revealed that, although the pupils of the adult cats were normal, the pupils of the kittens' treated eyes were consistently smaller than pupils in control eyes. The status of the muscarinic receptors in the kittens' irides was investigated using 3 H-QNB binding assays. In comparison with iris muscle homogenates from the control eyes, those from the treated eyes demonstrated an eightfold increase in the number of receptor binding sites. The results indicate that pupil size can be altered permanently by chronic mydriasis initiated early in the life of a kitten and that the permanent change in pupil size may result, in part, from a type of permanent supersensitivity response in the muscle following chronic blockade of muscarinic transmission by atropine

  9. Potential alteration of precipitation chemistry by epiphytic lichens

    Energy Technology Data Exchange (ETDEWEB)

    Lang, G E; Reiners, W A; Heier, R K

    1976-01-01

    Epiphytic lichen growth is abundant on the boles and branches of balsam fir trees at high elevations in New Hampshire. These lichens absorb elements needed for growth from solutions flowing over their surfaces and from direct impaction of water droplets. This study describes how epiphytic lichens and fir needles altered the chemistry of simulated rain water solutions under laboratory conditions. Experiments showed: 1) lichens absorbed ammonium and nitrate from solution; the rate of uptake increased with increasing temperature of the solution, 2) lichens lost calcium, magnesium, and hydrogen to the solution, 3) lichen thalli also initially lost potassium, but in time, net movement was reversed back into the thallus, 4) cation movement increased with increasing temperature, and 5) fir needles responded in a manner similar to that of the lichens, but the amount of change was much less. From these results it seems that epiphytic lichens have potential ecological importance in altering the chemistry of throughfall and stemflow.

  10. FAA Loran early implementation project

    Science.gov (United States)

    1990-03-01

    The Early Implementation Project (EIP), established by FAA Administrator Admiral : Donald C. Engen, was the initial step in the process of Loran integration into the : National Airsace System (NAS). The EIP was designed to give the FAA and the Loran ...

  11. Differential impact of Met receptor gene interaction with early-life stress on neuronal morphology and behavior in mice.

    Science.gov (United States)

    Heun-Johnson, Hanke; Levitt, Pat

    2018-02-01

    Early adversity in childhood increases the risk of anxiety, mood, and post-traumatic stress disorders in adulthood, and specific gene-by-environment interactions may increase risk further. A common functional variant in the promoter region of the gene encoding the human MET receptor tyrosine kinase (rs1858830 ' C' allele) reduces expression of MET and is associated with altered cortical circuit function and structural connectivity. Mice with reduced Met expression exhibit changes in anxiety-like and conditioned fear behavior, precocious synaptic maturation in the hippocampus, and reduced neuronal arbor complexity and synaptogenesis. These phenotypes also can be produced independently by early adversity in wild-type mice. The present study addresses the outcome of combining early-life stress and genetic influences that alter timing of maturation on enduring functional and structural phenotypes. Using a model of reduced Met expression ( Met +/- ) and early-life stress from postnatal day 2-9, social, anxiety-like, and contextual fear behaviors in later life were measured. Mice that experienced early-life stress exhibited impairments in social interaction, whereas alterations in anxiety-like behavior and fear learning were driven by Met haploinsufficiency, independent of rearing condition. Early-life stress or reduced Met expression decreased arbor complexity of ventral hippocampal CA1 pyramidal neurons projecting to basolateral amygdala. Paradoxically, arbor complexity in Met +/- mice was increased following early-life stress, and thus not different from arbors in wild-type mice raised in control conditions. The changes in dendritic morphology are consistent with the hypothesis that the physiological state of maturation of CA1 neurons in Met +/- mice influences their responsiveness to early-life stress. The dissociation of behavioral and structural changes suggests that there may be phenotype-specific sensitivities to early-life stress.

  12. Pukala intrusion, its age and connection to hydrothermal alteration in Orivesi, southwestern Finland

    Directory of Open Access Journals (Sweden)

    Matti Talikka

    2005-01-01

    Full Text Available The Pukala intrusion is situated in the Paleoproterozoic Svecofennian domain of the Fennoscandian Shield in the contact region between the Central Finland Granitoid Complex and the Tampere Belt. The acid subvolcanic intrusion, which is in contact or close to severalaltered domains, mainly consists of porphyritic granodiorite and trondhjemite. The Pukala intrusion was emplaced into volcanic sequence in an island-arc or fore-arc setting before or during the early stages of the main regional deformation phase of the Svecofennian orogeny. On the basis of the geochemical data, the Pukala intrusion is a peraluminous volcanic-arc granitoid. After crystallisation at 1896±3 Ma, multiphase deformation and metamorphismcaused alteration, recrystallisation, and orientation of the minerals, and tilted the intrusion steeply towards south. The 1851±5 Ma U-Pb age for titanite is connected to the late stages of the Svecofennian tectonometamorphic evolution of the region. Several hydrothermally altered domains are located in the felsic and intermediate metavolcanic rocks of the Tampere Belt within less than one kilometre south of the Pukala intrusion. Alteration is divided into three basic types: partial silica alteration, chlorite-sericite±silica alteration, and sericite alteration in shear zones. The first two types probably formed during the emplacement and crystallisation of the Pukala intrusion, and the third is linked to late shearing. Intense sericitisation and comb quartz bands in the contact of theintrusion and the altered domain at Kutemajärvi suggest that the hydrothermal system was driven by the Pukala intrusion.

  13. Barriers to early initiation of antenatal care in a multi-ethnic sample in South Auckland, New Zealand.

    Science.gov (United States)

    Corbett, Sarah; Chelimo, Carol; Okesene-Gafa, Kara

    2014-10-17

    To identify barriers to early initiation of antenatal care amongst pregnant women in South Auckland, New Zealand. Women in late pregnancy (>37 weeks gestation) or who had recently delivered (18 weeks (late bookers). The ethnic composition of the sample was: 43% Pacific Peoples, 20% Maori, 14% Asian, and 21% European or other ethnicities. The multivariate analysis indicated that women were significantly more likely to book late for antenatal care if they had limited resources (OR=1.86; 95% CI=1.17-2.93), no tertiary education (OR=1.96; 95% CI=1.23-3.15), or were not living with a husband/partner (OR=2.34; 95% CI=1.48-3.71). In addition, the odds of late booking for antenatal care was almost six times higher among Maori (OR=5.70; 95% CI=2.57-12.64) and Pacific (OR=5.90; 95% CI=2.83-12.29) women compared to those of European and other ethnicities. Late booking for antenatal care in the Counties Manukau District Health Board area (South Auckland) is associated with sociodemographic factors, social deprivation, and inadequate social support.

  14. Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β) Signaling in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Khin, Sann Sanda [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Pathology Research Unit, Department of Medical Research (Central Myanmar), Naypyitaw, Union of (Myanmar); Kitazawa, Riko [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan); Kondo, Takeshi; Idei, Yuka; Fujimoto, Masayo [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Haraguchi, Ryuma [Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan); Mori, Kiyoshi [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Kitazawa, Sohei, E-mail: kitazawa@m.ehime-u.ac.jp [Kobe University Graduate School of Medicine, Division of Diagnostic Molecular Pathology, Kobe 650-0017 (Japan); Ehime University Graduate School of Medicine, Toon 791-0295, Ehime (Japan)

    2011-03-03

    Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression.

  15. Epigenetic Alteration by DNA Promoter Hypermethylation of Genes Related to Transforming Growth Factor-β (TGF-β) Signaling in Cancer

    International Nuclear Information System (INIS)

    Khin, Sann Sanda; Kitazawa, Riko; Kondo, Takeshi; Idei, Yuka; Fujimoto, Masayo; Haraguchi, Ryuma; Mori, Kiyoshi; Kitazawa, Sohei

    2011-01-01

    Epigenetic alterations in cancer, especially DNA methylation and histone modification, exert a significant effect on the deregulated expression of cancer-related genes and lay an epigenetic pathway to carcinogenesis and tumor progression. Global hypomethylation and local hypermethylation of CpG islands in the promoter region, which result in silencing tumor suppressor genes, constitute general and major epigenetic modification, the hallmark of the neoplastic epigenome. Additionally, methylation-induced gene silencing commonly affects a number of genes and increases with cancer progression. Indeed, cancers with a high degree of methylation (CpG island methylator phenotype/CIMP) do exist and represent a distinct subset of certain cancers including colorectal, bladder and kidney. On the other hand, signals from the microenvironment, especially those from transforming growth factor-β (TGF-β), induce targeted de novo epigenetic alterations of cancer-related genes. While TGF-β signaling has been implicated in two opposite roles in cancer, namely tumor suppression and tumor promotion, its deregulation is also partly induced by epigenetic alteration itself. Although the epigenetic pathway to carcinogenesis and cancer progression has such reciprocal complexity, the important issue is to identify genes or signaling pathways that are commonly silenced in various cancers in order to find early diagnostic and therapeutic targets. In this review, we focus on the epigenetic alteration by DNA methylation and its role in molecular modulations of the TGF-β signaling pathway that cause or underlie altered cancer-related gene expression in both phases of early carcinogenesis and late cancer progression

  16. Correlation of initiating potency of skin carcinogens with potency to induce resistance to terminal differentiation in cultured mouse keratinocytes

    International Nuclear Information System (INIS)

    Kilkenny, A.E.; Morgan, D.; Spangler, E.F.; Yuspa, S.H.

    1985-01-01

    The induction by chemical carcinogens of resistance to terminal differentiation in cultured mouse keratinocytes has been proposed to represent a cellular change associated with the initiation phase of skin carcinogenesis. Previous results with this culture model indicated that the number of differentiation-resistant foci was correlated with the dose and known potency for several chemical carcinogens. Assay conditions were optimized to provide quantitative results for screening a variety of carcinogens for their potency as inducers of foci resistant to terminal differentiation. Eight skin initiators of varying potency and from different chemical classes and ultraviolet light were studied for their activity to induce this alteration in cultured epidermal cells from newborn BALB/c mice. There was an excellent positive correlation for the potency of these agents as initiators in vivo and as inducers of altered differentiation in vitro. The induction of resistant foci was independent of the relative cytotoxic effects of each agent except where cytotoxicity was extensive and reduced the number of foci. The results support the hypothesis that initiation of carcinogenesis in skin results in an alteration in the program of epidermal cell differentiation. The results also suggest that the assay is useful for identifying relative potency classes (strong, moderate, weak) of initiating agents

  17. Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome

    Science.gov (United States)

    Uriarte, Juan J.; Meirelles, Thayna; Gorbenko del Blanco, Darya; Nonaka, Paula N.; Campillo, Noelia; Sarri, Elisabet; Navajas, Daniel; Egea, Gustavo; Farré, Ramon

    2016-01-01

    Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome. PMID:27003297

  18. Neuropeptides as mediators of the early-life impact on the brain; implications for alcohol use disorders

    Directory of Open Access Journals (Sweden)

    Ingrid eNylander

    2012-07-01

    Full Text Available The brain is constantly exposed to external and internal input and to function in an ever-changing environment we are dependent on processes that enable the brain to adapt to new stimuli. Exposure to postnatal environmental stimuli can interfere with vital adaption processes and cause long-term changes in physiological function and behaviour. Early-life alterations in brain function may result in impaired ability to adapt to new situations, in altered sensitivity to challenges later in life and thereby mediate risk or protection for psychopathology such as alcohol use disorders (AUD. In clinical research the studies of mechanisms, mediators and causal relation between early environmental factors and vulnerability to AUD are restricted and attempts are made to find valid animal models for studies of the early-life influence on the brain. This review focuses on rodent models and the effects of adverse and naturalistic conditions on peptide networks within the brain and pituitary gland. Importantly, the consequences of alcohol addiction are not discussed but rather neurobiological alterations that can cause risk consumption and vulnerability to addiction. The article reviews earlier results and includes new data with emphasis on endogenous opioid peptides but also oxytocin and vasopressin. These peptides are vital for developmental processes and it is hypothesized that early-life changes in peptide networks may interfere with neuronal processes and thereby contribute the individual vulnerability for AUD. The summarized results indicate a link between early-life rearing conditions, opioids and ethanol consumption and that the ethanol-induced effects and the treatment with opioid antagonists later in life are dependent on early-life experiences. Endogenous opioids are therefore of interest to further study in the early-life impact on individual differences in vulnerability to AUD and treatment outcome.

  19. Early Dementia Screening

    Directory of Open Access Journals (Sweden)

    Peter K. Panegyres

    2016-01-01

    Full Text Available As the population of the world increases, there will be larger numbers of people with dementia and an emerging need for prompt diagnosis and treatment. Early dementia screening is the process by which a patient who might be in the prodromal phases of a dementing illness is determined as having, or not having, the hallmarks of a neurodegenerative condition. The concepts of mild cognitive impairment, or mild neurocognitive disorder, are useful in analyzing the patient in the prodromal phase of a dementing disease; however, the transformation to dementia may be as low as 10% per annum. The search for early dementia requires a comprehensive clinical evaluation, cognitive assessment, determination of functional status, corroborative history and imaging (including MRI, FDG-PET and maybe amyloid PET, cerebrospinal fluid (CSF examination assaying Aβ1–42, T-τ and P-τ might also be helpful. Primary care physicians are fundamental in the screening process and are vital in initiating specialist investigation and treatment. Early dementia screening is especially important in an age where there is a search for disease modifying therapies, where there is mounting evidence that treatment, if given early, might influence the natural history—hence the need for cost-effective screening measures for early dementia.

  20. The early Earth atmosphere and early life catalysts.

    Science.gov (United States)

    Ramírez Jiménez, Sandra Ignacia

    2014-01-01

    Homochirality is a property of living systems on Earth. The time, the place, and the way in which it appeared are uncertain. In a prebiotic scenario two situations are of interest: either an initial small bias for handedness of some biomolecules arouse and progressed with life, or an initial slight excess led to the actual complete dominance of the known chiral molecules. A definitive answer can probably never be given, neither from the fields of physics and chemistry nor biology. Some arguments can be advanced to understand if homochirality is necessary for the initiation of a prebiotic homochiral polymer chemistry, if this homochirality is suggesting a unique origin of life, or if a chiral template such as a mineral surface is always required to result in an enantiomeric excess. A general description of the early Earth scenario will be presented in this chapter, followed by a general description of some clays, and their role as substrates to allow the concentration and amplification of some of the building blocks of life.

  1. Early Outcomes of Endoscopic Vein Harvesting during the Initial Learning Period

    Directory of Open Access Journals (Sweden)

    Do Yeon Kim

    2015-06-01

    Full Text Available Background: The endoscopic vein harvesting (EVH method has been used in coronary artery bypass surgery in many countries. We started using the EVH method recently, and investigated the results during the early learning period. Methods: Between March 2012 and June 2014, 75 patients (31 patients in the EVH method group, and 44 patients in the open method group who underwent isolated first-time coronary artery bypass grafting using vein grafts were retrospectively analyzed with respect to the early outcomes including graft patency and risk factors for leg wound complications. For assessing the patency of vein graft, we performed coronary computed tomography angiography during the immediate postoperative period and 6 months later. Results: Mean harvesting time of endoscopic method was about 15 minutes. Patency rate during the immediate operative period and the 6-month patency rate were similar between the two groups (postoperative period: EVH 100% vs. open method 94.4%, p=0.493; at 6 months: EVH 93.3% vs. open method 90.9%, p=0.791. Leg wound complications occurred more frequently in the open method group (EVH 3.2% vs. open method 13.6%, p=0.127. According to the analysis, age was an independent risk factor for leg wound complications. Conclusion: EVH is a feasible method even for beginners and can be performed satisfactorily during their learning period.

  2. The Relationship between Oxygen Saturation and Color Alteration of a Compromised Skin Flap: Experimental Study on the Rabbit.

    Science.gov (United States)

    Prasetyono, Theddeus O H; Adianto, Senja

    2013-09-01

    The aim of this study was to collect important data on the time of oxygen saturation change in relation to skin flap color alteration using non-invasive pulse oximetry to evaluate its ability to provide continuous monitoring of skin flap perfusion. An experimental study on the monitoring of blood perfusion of 20 tube-island groin flaps of 10 male New Zealand rabbits was performed using pulse oximetry. The animals were randomly assigned to one of two groups representing a blockage of either arterial or venous blood flow. The oxygen saturation change and clinical color alteration were monitored from the beginning of vessel clamping until the saturation became undetectable. The result was analyzed by the t-test using SSPS ver. 10.0. The mean times from the vessel clamping until the saturation became undetectable were 20.19±2.13 seconds and 74.91±10.57 seconds for the artery and vein clamping groups, respectively. The mean time of the clinical alteration from the beginning of vein clamping was 34.5±11.72 minutes, while the alteration in flaps with artery clamping could not be detected until 2.5 hours after clamping. The use of neonate-type reusable flex sensor-pulse oximetry is objective and effective in early detection of arterial and vein blockage. It provides real-time data on vessel occlusion, which in turn will allow for early salvaging. The detection periods of both arterial occlusion and venous congestion are much earlier than the color alteration one may encounter clinically.

  3. The Relationship between Oxygen Saturation and Color Alteration of a Compromised Skin Flap: Experimental Study on the Rabbit

    Directory of Open Access Journals (Sweden)

    Theddeus O. H. Prasetyono

    2013-09-01

    Full Text Available BackgroundThe aim of this study was to collect important data on the time of oxygen saturation change in relation to skin flap color alteration using non-invasive pulse oximetry to evaluate its ability to provide continuous monitoring of skin flap perfusion.MethodsAn experimental study on the monitoring of blood perfusion of 20 tube-island groin flaps of 10 male New Zealand rabbits was performed using pulse oximetry. The animals were randomly assigned to one of two groups representing a blockage of either arterial or venous blood flow. The oxygen saturation change and clinical color alteration were monitored from the beginning of vessel clamping until the saturation became undetectable. The result was analyzed by the t-test using SSPS ver. 10.0.ResultsThe mean times from the vessel clamping until the saturation became undetectable were 20.19±2.13 seconds and 74.91±10.57 seconds for the artery and vein clamping groups, respectively. The mean time of the clinical alteration from the beginning of vein clamping was 34.5±11.72 minutes, while the alteration in flaps with artery clamping could not be detected until 2.5 hours after clamping.ConclusionsThe use of neonate-type reusable flex sensor-pulse oximetry is objective and effective in early detection of arterial and vein blockage. It provides real-time data on vessel occlusion, which in turn will allow for early salvaging. The detection periods of both arterial occlusion and venous congestion are much earlier than the color alteration one may encounter clinically.

  4. Varied sensitivity to therapy of HIV-1 strains in CD4+ lymphocyte sub-populations upon ART initiation

    Directory of Open Access Journals (Sweden)

    Paxton William A

    2010-12-01

    Full Text Available Abstract Background Although antiretroviral therapy (ART has proven its success against HIV-1, the long lifespan of infected cells and viral latency prevent eradication. In this study we analyzed the sensitivity to ART of HIV-1 strains in naïve, central memory and effector memory CD4+ lymphocyte subsets. Methods From five patients cellular HIV-1 infection levels were quantified before and after initiation of therapy (2-5 weeks. Through sequencing the C2V3 region of the HIV-1 gp120 envelope, we studied the effect of short-term therapy on virus variants derived from naïve, central memory and effector memory CD4+ lymphocyte subsets. Results During short-term ART, HIV-1 infection levels declined in all lymphocyte subsets but not as much as RNA levels in serum. Virus diversity in the naïve and central memory lymphocyte populations remained unchanged, whilst diversity decreased in serum and the effector memory lymphocytes. ART differentially affected the virus populations co-circulating in one individual harboring a dual HIV-1 infection. Changes in V3 charge were found in all individuals after ART initiation with increases within the effector memory subset and decreases found in the naïve cell population. Conclusions During early ART virus diversity is affected mainly in the serum and effector memory cell compartments. Differential alterations in V3 charge were observed between effector memory and naïve populations. While certain cell populations can be targeted preferentially during early ART, some virus strains demonstrate varied sensitivity to therapy, as shown from studying two strains within a dual HIV-1 infected individual.

  5. Correlates of sexual initiation among European adolescents.

    Directory of Open Access Journals (Sweden)

    Pietro Gambadauro

    Full Text Available Sexuality is a physiological component of adolescent development, though early initiation is associated with reproductive health risk. This study aimed at identifying correlates and predictors of sexual initiation in a large multinational cohort of European adolescents.A questionnaire addressing socio-demographics, behaviours, mental health and sexual activity, was delivered to 11,110 adolescents recruited from 168 randomly selected schools in 10 European countries between 2009 and 2011. A follow-up questionnaire was delivered after 12 months. The longitudinal association of baseline risk behaviors, psychological attributes and contextual vulnerabilities, with sexual initiation during follow-up was evaluated through simple and multivariable age/sex stratified logistic regression. Multinomial logistic regression measured the association between predictors and sexual initiation with or without coexisting reproductive risk factors, such as multiple partners or infrequent condom use.Baseline sexual experience was reported by 19.2% of 10,757 respondents (median age 15; IQR 14-15; females 59.6%. This was significantly more frequent among pupils older than 15 (41% and males (20.8%. Of 7,111 pupils without previous experience who were available at follow-up (response rate 81.8%, 17% reported sexual initiation, without differences between females and males. Baseline smoking (age/sex adjusted odds ratio [aOR] 3.63, alcohol use (aOR 2.95, illegal drugs use (aOR 2.72, and poor sleep (aOR 1.71 predicted sexual initiation. Stratified analyses showed a particularly strong association in case of younger and female pupils, and, among girls, when initiation was reported together with multiple partners and/or infrequent condom use. Externalizing (i.e. conduct and hyperactivity symptoms independently predicted sexual initiation. Internalizing difficulties (i.e. emotional and peer problems were negatively associated with early and risky sexual initiation among boys

  6. Early-life adversity-induced long-term epigenetic programming associated with early onset of chronic physical aggression: Studies in humans and animals.

    Science.gov (United States)

    Chistiakov, Dimitry A; Chekhonin, Vladimir P

    2017-06-05

    To examine whether chronic physical aggression (CPA) in adulthood can be epigenetically programmed early in life due to exposure to early-life adversity. Literature search of public databases such as PubMed/MEDLINE and Scopus. Children/adolescents susceptible for CPA and exposed to early-life abuse fail to efficiently cope with stress that in turn results in the development of CPA later in life. This phenomenon was observed in humans and animal models of aggression. The susceptibility to aggression is a complex trait that is regulated by the interaction between environmental and genetic factors. Epigenetic mechanisms mediate this interaction. Subjects exposed to stress early in life exhibited long-term epigenetic programming that can influence their behaviour in adulthood. This programming affects expression of many genes not only in the brain but also in other systems such as neuroendocrine and immune. The propensity to adult CPA behaviour in subjects experienced to early-life adversity is mediated by epigenetic programming that involves long-term systemic epigenetic alterations in a whole genome.

  7. The motivation for very early intervention for infants at high risk for autism spectrum disorders.

    Science.gov (United States)

    Webb, Sara Jane; Jones, Emily J H; Kelly, Jean; Dawson, Geraldine

    2014-02-01

    The first Autism Research Matrix (IACC, 2003) listed the identification of behavioural and biological markers of risk for autism as a top priority. This emphasis was based on the hypothesis that intervention with infants at-risk, at an early age when the brain is developing and before core autism symptoms have emerged, could significantly alter the developmental trajectory of children at risk for the disorder and impact long-range outcome. Research has provided support for specific models of early autism intervention (e.g., Early Start Denver Model) for improving outcomes in young children with autism, based on both behavioural and brain activity measures. Although great strides have been made in ability to identify risk markers for autism in younger infant/toddler samples, how and when to intervene during the prodromal state remains a critical question. Emerging evidence suggests that abnormal brain circuitry in autism precedes altered social behaviours; thus, an intervention designed to promote early social engagement and reciprocity potentially could steer brain development back toward the normal trajectory and remit or reduce the expression of symptoms.

  8. Relation between both oxidative and metabolic-osmotic cell damages and initial injury severity in bombing casualties

    Directory of Open Access Journals (Sweden)

    Vučeljić Marina

    2006-01-01

    Full Text Available Background/Aim. We have recently reported the development of oxidative cell damages in bombing casualties within a very early period after the initial injury. The aim of this study, was to investigate malondialdehyde (MDA, as an indicator of lipid peroxidation, and osmolal gap (OG, as a good indicator of metabolic cell damages and to assess their relationship with the initial severity of the injury in bombing casualties. Methods. The study included the males (n = 52, injured during the bombing with the Injury Severity Score (ISS ranging from 3 to 66. The whole group of casualties was devided into a group of less severely (ISS < 25, n = 24 and a group of severely (ISS ≥ 26, n = 28 injured males. The uninjured volunteers (n = 10 were the controls. Osmolality, MDA, sodium, glucose, urea, creatinine, total bilirubin and total protein levels were measured in the venous blood, sampled daily, within a ten-day period. Results. In both groups of casualties, MDA and OG levels increased, total protein levels decreased, while other parameters were within the control limits. MDA alterations correlated with ISS (r = 0.414, p < 0.01, while a statistically significant correlation between OG and ISS was not obtained. Interestingly, in spite of some differences in MDA and OG trends, at the end of the examined period they were at the similar level in both groups. Conclusion. The initial oxidative damages of the cellular membrane with intracellular metabolic disorders contributed to the gradual development of metabolic-osmotic damages of cells, which, consequently caused the OG increase. In the bombing casualties, oxidative cell damages were dependent on the initial injury severity, while metabolic-osmotic cell damages were not.

  9. Modeling initiation of Ewing sarcoma in human neural crest cells.

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    Cornelia von Levetzow

    2011-04-01

    Full Text Available Ewing sarcoma family tumors (ESFT are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC and/or neural crest (NCSC stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC. Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis.

  10. Mitochondrial Bioenergetics Is Altered in Fibroblasts from Patients with Sporadic Alzheimer's Disease

    Science.gov (United States)

    Pérez, María J.; Ponce, Daniela P.; Osorio-Fuentealba, Cesar; Behrens, Maria I.; Quintanilla, Rodrigo A.

    2017-01-01

    The identification of an early biomarker to diagnose Alzheimer's disease (AD) remains a challenge. Neuropathological studies in animal and AD patients have shown that mitochondrial dysfunction is a hallmark of the development of the disease. Current studies suggest the use of peripheral tissues, like skin fibroblasts as a possibility to detect the early pathological alterations present in the AD brain. In this context, we studied mitochondrial function properties (bioenergetics and morphology) in cultured fibroblasts obtained from AD, aged-match and young healthy patients. We observed that AD fibroblasts presented a significant reduction in mitochondrial length with important changes in the expression of proteins that control mitochondrial fusion. Moreover, AD fibroblasts showed a distinct alteration in proteolytic processing of OPA1, a master regulator of mitochondrial fusion, compared to control fibroblasts. Complementary to these changes AD fibroblasts showed a dysfunctional mitochondrial bioenergetics profile that differentiates these cells from aged-matched and young patient fibroblasts. Our findings suggest that the human skin fibroblasts obtained from AD patients could replicate mitochondrial impairment observed in the AD brain. These promising observations suggest that the analysis of mitochondrial bioenergetics could represent a promising strategy to develop new diagnostic methods in peripheral tissues of AD patients. PMID:29056898

  11. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

  12. Hypothalamic-pituitary-adrenal axis activity and early onset of cannabis use

    NARCIS (Netherlands)

    Huizink, Anja C.; Ferdinand, Robert F.; Ormel, Johan; Verhulst, Frank C.

    2006-01-01

    Aims To identify early onset cannabis users by measuring basal hypothalamic-pituitary-adrenal (HPA) axis activity, which may be a risk factor for early onset substance use when showing low activity. Design In a prospective cohort study, adolescents who initiated cannabis use at an early age (9-12

  13. 77 FR 45471 - White House Initiative on Educational Excellence for African Americans

    Science.gov (United States)

    2012-08-01

    ... programs and services that enable early learning and development of children from birth through age 5; (iii...: (1) the development, implementation, and coordination of educational programs and initiatives at the... House Initiative on Educational Excellence for African Americans By the authority vested in me as...

  14. Early Maladaptive Schemas in a Sample of Airline Pilots seeking Residential Substance Use Treatment: An Initial Investigation.

    Science.gov (United States)

    Shorey, Ryan C; Brasfield, Hope; Anderson, Scott; Stuart, Gregory L

    2014-01-01

    Recent research has begun to examine the early maladaptive schemas of substance abusers, as it is believed that targeting these core beliefs in treatment may result in improved substance use outcomes. One special population that has received scant attention in the research literature, despite high levels of substance use, is airline pilots. The current study examined the early maladaptive schemas of a sample of airline pilots ( n = 64) who were seeking residential treatment for alcohol dependence and whether they differed in early maladaptive schemas from non-pilot substance abusers who were also seeking residential treatment for alcohol dependence ( n = 45). Pre-existing medical records from patients of a residential substance abuse treatment facility were reviewed for the current study. Of the 18 early maladaptive schemas, results demonstrated that pilots scored higher than non-pilots on the early maladaptive schema of unrelenting standards (high internalized standards of behavior), whereas non-pilots scored higher on insufficient self-control (low frustration tolerance and self-control). Early maladaptive schemas may be a relevant treatment target for substance abuse treatment seeking pilots and non-pilots.

  15. Cardiac, Metabolic and Molecular Profiles of Sedentary Rats in the Initial Moment of Obesity

    Directory of Open Access Journals (Sweden)

    Bruno Barcellos Jacobsen

    2017-10-01

    Full Text Available Abstract Background: Different types of high-fat and/or high-energy diets have been used to induce obesity in rodents. However, few studies have reported on the effects observed at the initial stage of obesity induced by high-fat feeding on cardiac functional and structural remodelling. Objective: To characterize the initial moment of obesity and investigate both metabolic and cardiac parameters. In addition, the role of Ca2+ handling in short-term exposure to obesity was verified. Methods: Thirty-day-old male Wistar rats were randomized into two groups (n = 19 each: control (C; standard diet and high-fat diet (HF, unsaturated high-fat diet. The initial moment of obesity was defined by weekly measurement of body weight (BW complemented by adiposity index (AI. Cardiac remodelling was assessed by morphological, histological, echocardiographic and papillary muscle analysis. Ca2+ handling proteins were determined by Western Blot. Results: The initial moment of obesity occurred at the 3rd week. Compared with C rats, the HF rats had higher final BW (4%, body fat (20%, AI (14.5%, insulin levels (39.7%, leptin (62.4% and low-density lipoprotein cholesterol (15.5% but did not exhibit alterations in systolic blood pressure. Echocardiographic evaluation did not show alterations in cardiac parameters. In the HF group, muscles were observed to increase their +dT/dt (C: 52.6 ± 9.0 g/mm2/s and HF: 68.0 ± 17.0 g/mm2/s; p < 0.05. In addition, there was no changes in the cardiac expression of Ca2+ handling proteins. Conclusion: The initial moment of obesity promotes alterations to hormonal and lipid profiles without cardiac damage or changes in Ca2+ handling.

  16. [18F]-Fluoro-Deoxy-Glucose Positron Emission Tomography Scan Should Be Obtained Early in Cases of Autoimmune Encephalitis

    Directory of Open Access Journals (Sweden)

    C. R. Newey

    2016-01-01

    Full Text Available Introduction. Autoimmune encephalitis (AE is a clinically challenging diagnosis with nonspecific neurological symptoms. Prompt diagnosis is important and often relies on neuroimaging. We present a case series of AE highlighting the importance of an early [18F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET scan. Methods. Retrospective review of seven consecutive cases of autoimmune encephalitis. Results. All patients had both magnetic resonance imaging (MRI and FDG-PET scans. Initial clinical presentations included altered mental status and/or new onset seizures. Six cases had serum voltage-gated potassium channel (VGKC antibody and one had serum N-methyl-D-aspartate (NMDA antibody. MRI of brain showed mesial temporal lobe hyperintensity in five cases of VGKC. The other two patients with VGKC or NMDA AE had restiform body hyperintensity on MRI brain or a normal MRI, respectively. Mesial temporal lobe hypermetabolism was noted in three cases on FDG-PET, despite initial unremarkable MRI. Malignancy workup was negative in all patients. Conclusion. A high index of suspicion for AE should be maintained in patients presenting with cognitive symptoms, seizures, and limbic changes on neuroimaging. In cases with normal initial brain MRI, FDG-PET can be positive. Additionally, extralimbic hyperintensity on MRI may also be observed.

  17. [18F]-Fluoro-Deoxy-Glucose Positron Emission Tomography Scan Should Be Obtained Early in Cases of Autoimmune Encephalitis

    Science.gov (United States)

    Sarwal, A.; Hantus, S.

    2016-01-01

    Introduction. Autoimmune encephalitis (AE) is a clinically challenging diagnosis with nonspecific neurological symptoms. Prompt diagnosis is important and often relies on neuroimaging. We present a case series of AE highlighting the importance of an early [18F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan. Methods. Retrospective review of seven consecutive cases of autoimmune encephalitis. Results. All patients had both magnetic resonance imaging (MRI) and FDG-PET scans. Initial clinical presentations included altered mental status and/or new onset seizures. Six cases had serum voltage-gated potassium channel (VGKC) antibody and one had serum N-methyl-D-aspartate (NMDA) antibody. MRI of brain showed mesial temporal lobe hyperintensity in five cases of VGKC. The other two patients with VGKC or NMDA AE had restiform body hyperintensity on MRI brain or a normal MRI, respectively. Mesial temporal lobe hypermetabolism was noted in three cases on FDG-PET, despite initial unremarkable MRI. Malignancy workup was negative in all patients. Conclusion. A high index of suspicion for AE should be maintained in patients presenting with cognitive symptoms, seizures, and limbic changes on neuroimaging. In cases with normal initial brain MRI, FDG-PET can be positive. Additionally, extralimbic hyperintensity on MRI may also be observed. PMID:27559482

  18. Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

    Directory of Open Access Journals (Sweden)

    Manuela Pogliaghi

    Full Text Available During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART.To investigate the impact of infection as early as during primary HIV-1 infection (PHI we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI individuals before and during 48 weeks of cART as compared to healthy controls (n = 23. We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation.Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM, Tissue-like Memory (TLM B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD- phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups.In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized

  19. Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

    Science.gov (United States)

    Pogliaghi, Manuela; Ripa, Marco; Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

    2015-01-01

    During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and

  20. Study of nuclear glasses alteration gel and synthesis of some model gels

    International Nuclear Information System (INIS)

    Ricol, S.

    1995-01-01

    This work deals with the general problem of alteration of the reference nuclear glass R7T7. Attention is paid particularly to the altered layer formed at the glass surface during alteration process. In opposition to previous works, related essentially to glass dissolution kinetics based on chemical analyses of lixiviated elements, this thesis deals with alteration problems through structural studies of the reference glass and derived gel. This approach allows the determination of mechanisms for the gel formation and a better understanding of the behaviour of glasses towards lixiviation. Both approaches appeared complementary. Based on several spectroscopic techniques, this work showed the particular role of cations such as calcium, zirconium and iron. Studies of silica-based synthetic gels showed the synergic effect of formers cation and of one highly coordinated cation. The variation of the wavenumber related to Si-O-Si asymmetric stretching vibration can be correlated to O/Si ratio for ternary systems Si/Na/Zr. On the contrary, the Si losses of the materials depend on the number of non-bridging oxygen atoms. In the perspective of long-term behaviour, the alteration gel presents better characteristics than initial glass. It is therefore a highly stable material in static conditions. In the same way, synthetic gels are materials with very low solubilities (much lower than the alteration gel) and could be used as confining matrices. (authors). refs., 71 figs., 37 tabs