WorldWideScience

Sample records for salvage pathway studies

  1. Structural basis for feedback inhibition of the deoxyribonucleoside salvage pathway: Studies of the Drosophila deoxyribonucleoside kinase

    DEFF Research Database (Denmark)

    Mikkelsen, N.E.; Johansson, K.; Karlsson, A.

    2003-01-01

    Deoxyribonucleoside kinases are feedback inhibited by the final products of the salvage pathway, the deoxyribonucleoside triphosphates. In the present study, the mechanism of feedback inhibition is presented based on the crystal structure of a complex between the fruit fly deoxyribonucleoside...... kinase and its feedback inhibitor deoxythymidine triphosphate. The inhibitor was found to be bound as a bisubstrate inhibitor with its nucleoside part in the nucleoside binding site and with its phosphate groups partially occupying the phosphate donor site. The overall structure of the enzyme...... and to the primary base, Glu52, that normally is positioned close to the 5'-OH of the substrate deoxyribose....

  2. Bacterial variations on the methionine salvage pathway

    Directory of Open Access Journals (Sweden)

    Haas Dieter

    2004-03-01

    Full Text Available Abstract Background The thiomethyl group of S-adenosylmethionine is often recycled as methionine from methylthioadenosine. The corresponding pathway has been unravelled in Bacillus subtilis. However methylthioadenosine is subjected to alternative degradative pathways depending on the organism. Results This work uses genome in silico analysis to propose methionine salvage pathways for Klebsiella pneumoniae, Leptospira interrogans, Thermoanaerobacter tengcongensis and Xylella fastidiosa. Experiments performed with mutants of B. subtilis and Pseudomonas aeruginosa substantiate the hypotheses proposed. The enzymes that catalyze the reactions are recruited from a variety of origins. The first, ubiquitous, enzyme of the pathway, MtnA (methylthioribose-1-phosphate isomerase, belongs to a family of proteins related to eukaryotic intiation factor 2B alpha. mtnB codes for a methylthioribulose-1-phosphate dehydratase. Two reactions follow, that of an enolase and that of a phosphatase. While in B. subtilis this is performed by two distinct polypeptides, in the other organisms analyzed here an enolase-phosphatase yields 1,2-dihydroxy-3-keto-5-methylthiopentene. In the presence of dioxygen an aci-reductone dioxygenase yields the immediate precursor of methionine, ketomethylthiobutyrate. Under some conditions this enzyme produces carbon monoxide in B. subtilis, suggesting a route for a new gaseous mediator in bacteria. Ketomethylthiobutyrate is finally transaminated by an aminotransferase that exists usually as a broad specificity enzyme (often able to transaminate aromatic aminoacid keto-acid precursors or histidinol-phosphate. Conclusion A functional methionine salvage pathway was experimentally demonstrated, for the first time, in P. aeruginosa. Apparently, methionine salvage pathways are frequent in Bacteria (and in Eukarya, with recruitment of different polypeptides to perform the needed reactions (an ancestor of a translation initiation factor and Ru

  3. Reconstitution of an efficient thymidine salvage pathway in Saccharomyces cerevisiae

    Science.gov (United States)

    Vernis, Laurence; Piskur, Jure; Diffley, John F. X.

    2003-01-01

    The budding yeast Saccharomyces cerevisiae is unable to incorporate exogenous nucleosides into DNA. We have made a number of improvements to existing strategies to reconstitute an efficient thymidine salvage pathway in yeast. We have constructed strains that express both a nucleoside kinase as well as an equilibrative nucleoside transporter. By also deleting the gene encoding thymidylate synthase (CDC21) we have constructed strains that are entirely dependent upon exogenous thymidine for viability and that can grow with normal kinetics at low thymidine concentrations. Using this novel approach, we show that depletion of a single deoxyribonucleoside causes reversible arrest of cells in S phase with concomitant phosphorylation and activation of the S phase checkpoint kinase, Rad53. We show that this strain also efficiently incorporates the thymidine analogue, BrdU, into DNA and can be used for pulse–chase labelling. PMID:14500848

  4. Essential role of Bordetella NadC in a quinolinate salvage pathway for NAD biosynthesis.

    Science.gov (United States)

    Brickman, Timothy J; Suhadolc, Ryan J; McKelvey, Pamela J; Armstrong, Sandra K

    2017-02-01

    Nicotinamide adenine dinucleotide (NAD) is produced via de novo biosynthesis pathways and by salvage or recycling routes. The classical Bordetella bacterial species are known to be auxotrophic for nicotinamide or nicotinic acid. This study confirmed that Bordetella bronchiseptica, Bordetella pertussis and Bordetella parapertussis have the recycling/salvage pathway genes pncA and pncB, for use of nicotinamide or nicotinic acid, respectively, for NAD synthesis. Although these Bordetellae lack the nadA and nadB genes needed for de novo NAD biosynthesis, remarkably, they have one de novo pathway gene, nadC, encoding quinolinate phosphoribosyltransferase. Genomic analyses of taxonomically related Bordetella and Achromobacter species also indicated the presence of an 'orphan' nadC and the absence of nadA and nadB. When supplied as the sole NAD precursor, quinolinate promoted B. bronchiseptica growth, and the ability to use it required nadC. Co-expression of Bordetella nadC with the nadB and nadA genes of Paraburkholderia phytofirmans allowed B. bronchiseptica to grow in the absence of supplied pyridines, indicative of de novo NAD synthesis and functional confirmation of Bordetella NadC activity. Expression of nadC in B. bronchiseptica was influenced by nicotinic acid and by a NadQ family transcriptional repressor, indicating that these organisms prioritize their use of pyridines for NAD biosynthesis. © 2016 John Wiley & Sons Ltd.

  5. Functional identification of APIP as human mtnB, a key enzyme in the methionine salvage pathway.

    Directory of Open Access Journals (Sweden)

    Camille Mary

    Full Text Available The methionine salvage pathway is widely distributed among some eubacteria, yeast, plants and animals and recycles the sulfur-containing metabolite 5-methylthioadenosine (MTA to methionine. In eukaryotic cells, the methionine salvage pathway takes place in the cytosol and usually involves six enzymatic activities: MTA phosphorylase (MTAP, EC 2.4.2.28, 5'-methylthioribose-1-phosphate isomerase (mtnA, EC 5.3.1.23, 5'-methylthioribulose-1-phosphate dehydratase (mtnB, EC: 4.2.1.109, 2,3-dioxomethiopentane-1-phosphate enolase/phosphatase (mtnC, EC 3.1.3.77, aci-reductone dioxygenase (mtnD, EC 1.13.11.54 and 4-methylthio-2-oxo-butanoate (MTOB transaminase (EC 2.6.1.-. The aim of this study was to complete the available information on the methionine salvage pathway in human by identifying the enzyme responsible for the dehydratase step. Using a bioinformatics approach, we propose that a protein called APIP could perform this role. The involvement of this protein in the methionine salvage pathway was investigated directly in HeLa cells by transient and stable short hairpin RNA interference. We show that APIP depletion specifically impaired the capacity of cells to grow in media where methionine is replaced by MTA. Using a Shigella mutant auxotroph for methionine, we confirm that the knockdown of APIP specifically affects the recycling of methionine. We also show that mutation of three potential phosphorylation sites does not affect APIP activity whereas mutation of the potential zinc binding site completely abrogates it. Finally, we show that the N-terminal region of APIP that is missing in the short isoform is required for activity. Together, these results confirm the involvement of APIP in the methionine salvage pathway, which plays a key role in many biological functions like cancer, apoptosis, microbial proliferation and inflammation.

  6. Nucleotide metabolism in Lactococcus lactis: Salvage pathways of exogenous pyrimidines

    DEFF Research Database (Denmark)

    Martinussen, Jan; Andersen, Paal Skytt; Hammer, Karin

    1994-01-01

    By measuring enzyme activities in crude extracts and studying the effect of toxic analogs (5-fluoropyrimidines) on cell growth, the metabolism of pyrimidines in Lactococcus lactis was analyzed. Pathways by which uracil, uridine, deoxyuridine, cytidine, and deoxycytidine are metabolized in L. lact...

  7. Quantitation of NAD+ biosynthesis from the salvage pathway in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Sporty, J; Lin, S; Kato, M; Ognibene, T; Stewart, B; Turteltaub, K; Bench, G

    2009-02-18

    Nicotinamide adenine dinucleotide (NAD{sup +}) is synthesized via two major pathways in prokaryotic and eukaryotic systems: the de novo biosynthesis pathway from tryptophan precursors, or by the salvage biosynthesis pathway from either extracellular nicotinic acid or various intracellular NAD{sup +} decomposition products. NAD{sup +} biosynthesis via the salvage pathway has been linked to an increase in yeast replicative lifespan under calorie restriction (CR). However, the relative contribution of each pathway to NAD{sup +} biosynthesis under both normal and CR conditions is not known. Here, we have performed lifespan, NAD{sup +} and NADH (the reduced form of NAD{sup +}) analyses on BY4742 wild type, NAD+ salvage pathway knockout (npt1{Delta}), and NAD+ de novo pathway knockout (qpt1{Delta}) yeast strains cultured in media containing either 2% glucose (normal growth) or 0.5% glucose (CR). We have utilized {sup 14}C labeled nicotinic acid in the culture media combined with HPLC speciation and both UV and {sup 14}C detection to quantitate the total amounts of NAD{sup +} and NADH and the amounts derived from the salvage pathway. We observe that wild type and qpt1{Delta} yeast exclusively utilize extracellular nicotinic acid for NAD{sup +} and NADH biosynthesis under both the 2% and 0.5% glucose growth conditions suggesting that the de novo pathway plays little role if a functional salvage pathway is present. We also observe that NAD{sup +} concentrations decrease in all three strains under CR. However, unlike the wild type strain, NADH concentrations do not decrease and NAD{sup +}:NADH ratios do not increase under CR for either knockout strain. Lifespan analyses reveal that CR results in a lifespan increase of approximately 25% for the wild type and qpt1{Delta} strains, while no increase in lifespan is observed for the npt1{Delta} strain. In combination these data suggest that having a functional salvage pathway is more important than the absolute levels of NAD

  8. A Key Enzyme of the NAD+Salvage Pathway in Thermus thermophilus: Characterization of Nicotinamidase and the Impact of Its Gene Deletion at High Temperatures.

    Science.gov (United States)

    Taniguchi, Hironori; Sungwallek, Sathidaphorn; Chotchuang, Phatcharin; Okano, Kenji; Honda, Kohsuke

    2017-09-01

    NAD (NAD + ) is a cofactor related to many cellular processes. This cofactor is known to be unstable, especially at high temperatures, where it chemically decomposes to nicotinamide and ADP-ribose. Bacteria, yeast, and higher organisms possess the salvage pathway for reconstructing NAD + from these decomposition products; however, the importance of the salvage pathway for survival is not well elucidated, except for in pathogens lacking the NAD + de novo synthesis pathway. Herein, we report the importance of the NAD + salvage pathway in the thermophilic bacterium Thermus thermophilus HB8 at high temperatures. We identified the gene encoding nicotinamidase (TTHA0328), which catalyzes the first reaction of the NAD + salvage pathway. This recombinant enzyme has a high catalytic activity against nicotinamide ( K m of 17 μM, k cat of 50 s -1 , k cat / K m of 3.0 × 10 3 s -1 · mM -1 ). Deletion of this gene abolished nicotinamide deamination activity in crude extracts of T. thermophilus and disrupted the NAD + salvage pathway in T. thermophilus Disruption of the salvage pathway led to the severe growth retardation at a higher temperature (80°C), owing to the drastic decrease in the intracellular concentrations of NAD + and NADH. IMPORTANCE NAD + and other nicotinamide cofactors are essential for cell metabolism. These molecules are unstable and decompose, even under the physiological conditions in most organisms. Thermophiles can survive at high temperatures where NAD + decomposition is, in general, more rapid. This study emphasizes that NAD + instability and its homeostasis can be one of the important factors for thermophile survival in extreme temperatures. Copyright © 2017 American Society for Microbiology.

  9. Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzenberg, Johannes [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, Los Angeles, CA (United States); Medical University of Vienna, Department of Pediatrics, Vienna (Austria); Radu, Caius G.; Tran, Andrew Q.; Phelps, Michael E.; Satyamurthy, Nagichettiar [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, Los Angeles, CA (United States); Benz, Matthias; Fueger, Barbara; Czernin, Johannes; Schiepers, Christiaan [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, Los Angeles, CA (United States); Witte, Owen N. [David Geffen School of Medicine, University of California, Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, Los Angeles, CA (United States)

    2011-04-15

    Deoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway involved in the production and maintenance of a balanced pool of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis. dCK phosphorylates and therefore activates nucleoside analogs such as cytarabine, gemcitabine, decitabine, cladribine, and clofarabine that are used routinely in cancer therapy. Imaging probes that target dCK might allow stratifying patients into likely responders and nonresponders with dCK-dependent prodrugs. Here we present the biodistribution and radiation dosimetry of three fluorinated dCK substrates, {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC, developed for positron emission tomography (PET) imaging of dCK activity in vivo. PET studies were performed in nine healthy human volunteers, three for each probe. After a transmission scan, the radiopharmaceutical was injected intravenously and three sequential emission scans acquired from the base of the skull to mid-thigh. Regions of interest encompassing visible organs were drawn on the first PET scan and copied to the subsequent scans. Activity in target organs was determined and absorbed dose estimated with OLINDA/EXM. The standardized uptake value was calculated for various organs at different times. Renal excretion was common to all three probes. Bone marrow had higher uptake for L-{sup 18}F-FAC and L-{sup 18}F-FMAC than {sup 18}F-FAC. Prominent liver uptake was seen in L-{sup 18}F-FMAC and L-{sup 18}F-FAC, whereas splenic activity was highest for {sup 18}F-FAC. Muscle uptake was also highest for {sup 18}F-FAC. The critical organ was the bladder wall for all three probes. The effective dose was 0.00524, 0.00755, and 0.00910 mSv/MBq for {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC, respectively. The biodistribution of {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC in humans reveals similarities and differences. Differences may be explained by different probe

  10. Implementation salvage experiences from the Melbourne diabetes prevention study

    Directory of Open Access Journals (Sweden)

    Dunbar James

    2012-09-01

    Full Text Available Abstract Background Many public health interventions based on apparently sound evidence from randomised controlled trials encounter difficulties when being scaled up within health systems. Even under the best of circumstances, implementation is exceedingly difficult. In this paper we will describe the implementation salvage experiences from the Melbourne Diabetes Prevention Study, which is a randomised controlled trial of the effectiveness and cost-effectiveness nested in the state-wide Life! Taking Action on Diabetes program in Victoria, Australia. Discussion The Melbourne Diabetes Prevention Study sits within an evolving larger scale implementation project, the Life! program. Changes that occurred during the roll-out of that program had a direct impact on the process of conducting this trial. The issues and methods of recovery the study team encountered were conceptualised using an implementation salvage strategies framework. The specific issues the study team came across included continuity of the state funding for Life! program and structural changes to the Life! program which consisted of adjustments to eligibility criteria, referral processes, structure and content, as well as alternative program delivery for different population groups. Staff turnover, recruitment problems, setting and venue concerns, availability of potential participants and participant characteristics were also identified as evaluation roadblocks. Each issue and corresponding salvage strategy is presented. Summary The experiences of conducting such a novel trial as the preliminary Melbourne Diabetes Prevention Study have been invaluable. The lessons learnt and knowledge gained will inform the future execution of this trial in the coming years. We anticipate that these results will also be beneficial to other researchers conducting similar trials in the public health field. We recommend that researchers openly share their experiences, barriers and challenges when

  11. Characterization of NAD salvage pathways and their role in virulence in Streptococcus pneumoniae

    Science.gov (United States)

    Johnson, Michael D. L.; Echlin, Haley; Dao, Tina H.

    2015-01-01

    NAD is a necessary cofactor present in all living cells. Some bacteria cannot de novo synthesize NAD and must use the salvage pathway to import niacin or nicotinamide riboside via substrate importers NiaX and PnuC, respectively. Although homologues of these two importers and their substrates have been identified in other organisms, limited data exist in Streptococcus pneumoniae, specifically, on its effect on overall virulence. Here, we sought to characterize the substrate specificity of NiaX and PnuC in Str. pneumoniae TIGR4 and the contribution of these proteins to virulence of the pathogen. Although binding affinity of each importer for nicotinamide mononucleotide may overlap, we found NiaX to specifically import nicotinamide and nicotinic acid, and PnuC to be primarily responsible for nicotinamide riboside import. Furthermore, a pnuC mutant is completely attenuated during both intranasal and intratracheal infections in mice. Taken together, these findings underscore the importance of substrate salvage in pneumococcal pathogenesis and indicate that PnuC could potentially be a viable small-molecule therapeutic target to alleviate disease progression in the host. PMID:26311256

  12. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1.

    Science.gov (United States)

    Nakahata, Yasukazu; Sahar, Saurabh; Astarita, Giuseppe; Kaluzova, Milota; Sassone-Corsi, Paolo

    2009-05-01

    Many metabolic and physiological processes display circadian oscillations. We have shown that the core circadian regulator, CLOCK, is a histone acetyltransferase whose activity is counterbalanced by the nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase SIRT1. Here we show that intracellular NAD+ levels cycle with a 24-hour rhythm, an oscillation driven by the circadian clock. CLOCK:BMAL1 regulates the circadian expression of NAMPT (nicotinamide phosphoribosyltransferase), an enzyme that provides a rate-limiting step in the NAD+ salvage pathway. SIRT1 is recruited to the Nampt promoter and contributes to the circadian synthesis of its own coenzyme. Using the specific inhibitor FK866, we demonstrated that NAMPT is required to modulate circadian gene expression. Our findings in mouse embryo fibroblasts reveal an interlocked transcriptional-enzymatic feedback loop that governs the molecular interplay between cellular metabolism and circadian rhythms.

  13. The FORECAST study - Focal recurrent assessment and salvage treatment for radiorecurrent prostate cancer.

    Science.gov (United States)

    Kanthabalan, A; Shah, T; Arya, M; Punwani, S; Bomanji, J; Haroon, A; Illing, R O; Latifoltojar, A; Freeman, A; Jameson, C; van der Meulen, J; Charman, S; Emberton, M; Ahmed, H U

    2015-09-01

    One-third of men may experience biochemical failure by 8years following radical radiotherapy for localised prostate cancer. Over 90% of men are started on androgen deprivation therapy (ADT) which is non-curative and confers systemic side-effects. Focal salvage therapy (FST) limits collateral tissue damage and may improve therapeutic ratios. In order to deliver FST, distant disease must be ruled-out and intra-prostatic disease must be accurately detected, localised and characterised. FORECAST - Focal Recurrent Assessment and Salvage Treatment - is a study designed to evaluate a novel imaging-based diagnostic and therapeutic complex intervention pathway for men who fail radiotherapy. Men with biochemical failure following radical prostate radiotherapy, prior to salvage therapy will be recruited. They will undergo whole-body multi-parametric MRI (WB-MRI), choline PET/CT, bone-scan and pelvic-mpMRI and then MRI transperineal-targeted biopsies (MRI-TB) and Transperineal Template Prostate Mapping Biopsy (TPM). Those suitable for FST will undergo either high intensity focused ultrasound (HIFU) or cryotherapy. Primary outcome measures: a) the accuracy of WB-MRI to detect distant metastatic disease; b) accuracy of prostate mpMRI in local detection of radiorecurrent prostate cancer; c) detection accuracy of MRI-TB; and d) rate of urinary incontinence following FST. Focal salvage therapy may confer lower rates of morbidity whilst retaining disease control. In order to deliver FST, intra- and extra-prostatic disease must be detected early and localised accurately. Novel diagnostic techniques including WB-MRI and MRI-TB may improve the detection of distant and local disease whilst reducing healthcare burdens compared with current imaging and biopsy strategies. Copyright © 2015. Published by Elsevier Inc.

  14. Metabolic Fate of Fumarate, a Side Product of the Purine Salvage Pathway in the Intraerythrocytic Stages of Plasmodium falciparum*

    Science.gov (United States)

    Bulusu, Vinay; Jayaraman, Vijay; Balaram, Hemalatha

    2011-01-01

    In aerobic respiration, the tricarboxylic acid cycle is pivotal to the complete oxidation of carbohydrates, proteins, and lipids to carbon dioxide and water. Plasmodium falciparum, the causative agent of human malaria, lacks a conventional tricarboxylic acid cycle and depends exclusively on glycolysis for ATP production. However, all of the constituent enzymes of the tricarboxylic acid cycle are annotated in the genome of P. falciparum, which implies that the pathway might have important, yet unidentified biosynthetic functions. Here we show that fumarate, a side product of the purine salvage pathway and a metabolic intermediate of the tricarboxylic acid cycle, is not a metabolic waste but is converted to aspartate through malate and oxaloacetate. P. falciparum-infected erythrocytes and free parasites incorporated [2,3-14C]fumarate into the nucleic acid and protein fractions. 13C NMR of parasites incubated with [2,3-13C]fumarate showed the formation of malate, pyruvate, lactate, and aspartate but not citrate or succinate. Further, treatment of free parasites with atovaquone inhibited the conversion of fumarate to aspartate, thereby indicating this pathway as an electron transport chain-dependent process. This study, therefore, provides a biosynthetic function for fumarate hydratase, malate quinone oxidoreductase, and aspartate aminotransferase of P. falciparum. PMID:21209090

  15. Psychosocial reactions to upper extremity limb salvage: A cross-sectional study.

    Science.gov (United States)

    Sposato, Lindsay; Yancosek, Kathleen; Lospinoso, Josh; Cancio, Jill

    2017-08-09

    Descriptive cross-sectional survey study. Limb salvage spares an extremity at risk for amputation after a major traumatic injury. Psychosocial recovery for individuals with lower extremity limb salvage has been discussed in the literature. However, to date, psychosocial reactions for individuals with upper extremity (UE) limb salvage have not been examined. To determine which factors may influence psychosocial adaptation to UE limb salvage. Participants (n = 30; 28 males) were adults (mean, 30.13; range, 18-61) who sustained an UE limb salvage from a traumatic event. Adaptation was measured using a modified version of the Reactions to Impairment and Disability Inventory. A linear mixed-effects regression found that worse psychosocial adaptation was associated with having less than a college degree, being less than 6 months post-injury, being older than 23 years, and having more pain. Dominant hand injuries were found to influence poor adaptation on the denial Reactions to Impairment and Disability Inventory subscale only. The results of this study indicate that there is potential for nonadaptive reactions and psychological distress with certain variables in UE limb salvage. Therapists may use these results to anticipate which clients may be at risk for poor psychosocial outcomes. This study indicates the need for early consideration to factors that affect psychological prognosis for the UE limb salvage population. However, future research is indicated to better understand the unique psychosocial challenges and needs of these individuals. 4. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  16. MtnBD is a multifunctional fusion enzyme in the methionine salvage pathway of Tetrahymena thermophila.

    Directory of Open Access Journals (Sweden)

    Toshihiro Nakano

    Full Text Available To recycle reduced sulfur to methionine in the methionine salvage pathway (MSP, 5-methylthioribulose-1-phosphate is converted to 2-keto-4-methylthiobutyrate, the methionine precursor, by four steps; dehydratase, enolase, phosphatase, and dioxygenase reactions (catalyzed by MtnB, MtnW, MtnX and MtnD, respectively, in Bacillus subtilis. It has been proposed that the MtnBD fusion enzyme in Tetrahymena thermophila catalyzes four sequential reactions from the dehydratase to dioxygenase steps, based on the results of molecular biological analyses of mutant yeast strains with knocked-out MSP genes, suggesting that new catalytic function can be acquired by fusion of enzymes. This result raises the question of how the MtnBD fusion enzyme can catalyze four very different reactions, especially since there are no homologous domains for enolase and phosphatase (MtnW and MtnX, respectively, in B. subtilis in the peptide. Here, we tried to identify the domains responsible for catalyzing the four reactions using recombinant proteins of full-length MtnBD and each domain alone. UV-visible and ¹H-NMR spectral analyses of reaction products revealed that the MtnB domain catalyzes dehydration and enolization and the MtnD domain catalyzes dioxygenation. Contrary to a previous report, conversion of 5-methylthioribulose-1-phosphate to 2-keto-4-methylthiobutyrate was dependent on addition of an exogenous phosphatase from B. subtilis. This was observed for both the MtnB domain and full-length MtnBD, suggesting that MtnBD does not catalyze the phosphatase reaction. Our results suggest that the MtnB domain of T. thermophila MtnBD acquired the new function to catalyze both the dehydratase and enolase reactions through evolutionary gene mutations, rather than fusion of MSP genes.

  17. Metabolic engineering of Escherichia coli to produce 2'-fucosyllactose via salvage pathway of guanosine 5'-diphosphate (GDP)-l-fucose.

    Science.gov (United States)

    Chin, Young-Wook; Seo, Nari; Kim, Jae-Han; Seo, Jin-Ho

    2016-11-01

    2'-Fucosyllactose (2-FL) is one of the key oligosaccharides in human milk. In the present study, the salvage guanosine 5'-diphosphate (GDP)-l-fucose biosynthetic pathway from fucose was employed in engineered Escherichia coli BL21star(DE3) for efficient production of 2-FL. Introduction of the fkp gene coding for fucokinase/GDP-l-fucose pyrophosphorylase (Fkp) from Bacteroides fragilis and the fucT2 gene encoding α-1,2-fucosyltransferase from Helicobacter pylori allows the engineered E. coli to produce 2-FL from fucose, lactose and glycerol. To enhance the lactose flux to 2-FL production, the attenuated, and deleted mutants of β-galactosidase were employed. Moreover, the 2-FL yield and productivity were further improved by deletion of the fucI-fucK gene cluster coding for fucose isomerase (FucI) and fuculose kinase (FucK). Finally, fed-batch fermentation of engineered E. coli BL21star(DE3) deleting lacZ and fucI-fucK, and expressing fkp and fucT2 resulted in 23.1 g/L of extracellular concentration of 2-FL and 0.39 g/L/h productivity. Biotechnol. Bioeng. 2016;113: 2443-2452. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Characterization of an fungal l-fucokinase involved in Mortierella alpina GDP-l-fucose salvage pathway.

    Science.gov (United States)

    Wang, Hongchao; Zhang, Chen; Chen, Haiqin; Yang, Qin; Zhou, Xin; Gu, Zhennan; Zhang, Hao; Chen, Wei; Chen, Yong Q

    2016-08-01

    GDP-l-fucose functions as a biological donor for fucosyltransferases, which are required for the catalysis of l-fucose to various acceptor molecules including oligosaccharides, glycoproteins and glycolipids. Mortierella alpina is one of the highest lipid-producing fungi and can biosynthesis GDP-l-fucose in the de novo pathway. Analysis of the M. alpina genome suggests that there is a gene encoding l-fucokinase (FUK) for the conversion of fucose to l-fucose-1-phosphate in the GDP-l-fucose salvage pathway, which has never been found in fungi before. This gene was characterized to explore its role in GDP-l-fucose synthesis. The yield of GDP-l-fucose is relatively higher in lipid accumulation phase (0.096 mg per g cell) than that in cell multiplication phase (0.074 mg per g cell) of M. alpina Additionally, the transcript level of FUK is up regulated by nitrogen exhaustion when M. alpina starts to accumulate lipid, highlights the functional significance of FUK in the GDP-l-fucose biosynthesis in M. alpina Gene encoding FUK was expressed heterologously in Escherichia coli and the resulting protein was purified to homogeneity. The product of FUK reaction was analyzed by liquid chromatography and mass spectrometry. Kinetic parameters and other properties of FUK were investigated. Comparative analyses between the FUK protein and other homologous proteins were performed. To our knowledge, this study is the first to report a comprehensive characterization of FUK in a fungus. Mortierella alpina could be used as an alternative source for the production of GDP-l-fucose. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Single-institution comparative study on the outcomes of salvage cryotherapy versus salvage robotic prostatectomy for radio-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Anup Vora

    2016-03-01

    Conclusion: While recurrences from primary radiotherapy for prostate cancer do occur, there is no consensus on its management. In our experience, salvage procedures were generally safe and effective. Both salvage cryotherapy and salvage prostatectomy allow for adequate cancer control with minimal toxicity.

  20. Powerful methods to establish chromosomal markers in Lactococcus lactis: an analysis of pyrimidine salvage pathway mutants obtained by positive selections

    DEFF Research Database (Denmark)

    Martinussen, Jan; Hammer, Karin

    1995-01-01

    Using different 5-fluoropyrimidine analogues, positive selection procedures for obtaining mutants blocked in pyrimidine and purine salvage genes of Lactococcus lactis were established. Strains lacking the following enzyme activities due to mutations in the corresponding genes were isolated: uracil...... of many related lactic acid bacteria....

  1. Genes of the thymidine salvage pathway: thymine-7-hydroxylase from a Rhodotorula glutinis cDNA library and iso-orotate decarboxylase from Neurospora crassa.

    Science.gov (United States)

    Smiley, Jeffrey A; Kundracik, Melisa; Landfried, Daniel A; Barnes, Vincient R; Axhemi, Armend A

    2005-05-25

    Genes for two enzymes in the thymidine salvage pathway, thymine-7-hydroxylase (THase; official name thymine dioxygenase) and iso-orotate decarboxylase (IDCase) have been isolated from fungal sources. THase was isolated from a Rhodotorula glutinis cDNA library using a degenerate oligonucleotide based on the published amino acid sequence. The coding sequence was transferred to an Escherichia coli expression system, from which recombinant THase activity was measured using 14C-labeled thymine. The THase sequence shows an almost complete avoidance of codons ending in A or T: 95.8% GC content is present in the third position of codons. A connection between this codon bias and the role of the thymidine salvage pathway in pyrimidine metabolism is proposed. The THase sequence is similar to Group I Fe+2-dependent, alphaKG-dependent dioxygenases. The R. glutinis THase gene was used to locate the probable THase genes in the sequenced genomes of Neurospora crassa and Aspergillus nidulans. The genes neighboring THase in these two genomes are similar to each other, and are similar to the mammalian 2-amino-3-carboxymuconate-6-semialdhyde decarboxylase (ACMSD), leading to their identification as IDCase genes. The N. crassa version was isolated by PCR of genomic DNA, and IDCase activity was measured in recombinant E. coli carrying this gene. A new family of decarboxylases, using similar substrates, is identified by virtue of the protein sequence similarity.

  2. Genes of the de novo and salvage biosynthesis pathways of vitamin B6 are regulated under oxidative stress in the plant pathogen Rhizoctonia solani

    Directory of Open Access Journals (Sweden)

    Jamil eSamsatly

    2016-01-01

    Full Text Available B6 is recognized as an important cofactor required for numerous metabolic enzymes, and has been shown to act as an antioxidant and play a role in stress responses. It can be synthesized through two different routes: salvage and de novo pathways. However, little is known about the possible function of the vitamin B6 pathways in the fungal plant pathogen Rhizoctonia solani. Using genome walking, the de novo biosynthetic pathway genes; RsolPDX1 and RsolPDX2 and the salvage biosynthetic pathway gene, RsolPLR were sequenced. The predicted amino acid sequences of the three genes had high degree of similarity to other fungal PDX1, PDX2, and PLR proteins and are closely related to other R. solani anastomosis groups. We also examined their regulation when subjected to ROS stress inducers, the superoxide generator paraquat, or H2O2, and compared it to the well-known antioxidant genes, catalase and glutathione-S-transferase (GST. The genes were differentially regulated with substantial transcript levels as high as 33 fold depending on the gene and type of stress reflecting that differences in the type of damage induced by ROS. Exogenous addition of the vitamers PN or PLP in culture medium significantly induced the transcription of the vitamin B6 de novo encoding genes as early as 0.5 hour post treatment (HPT. On the other hand, transcription of RsolPLR was vitamer-specific; a down regulation upon supplementation of PN and upregualtion with PLP. Our results suggest that accumulation of ROS in R. solani mycelia was linked to transcriptional regulation of the three genes and R. solani vitamin B6 biosynthesis machinery could be implicated similar to catalases and GST as an antioxidant stress protector against oxidative stress.

  3. Extension and grading of osteomyelitis are not related to limb salvage in Charcot neuropathic osteoarthropathy: A cohort prospective study.

    Science.gov (United States)

    Dalla Paola, Luca; Carone, Anna; Baglioni, Marco; Boscarino, Giulio; Vasilache, Lucian

    2016-01-01

    Charcot neuropathic osteoarthropathy (CN) represents a complication for diabetic patients which involves a progressive alteration of the osteoarticular apparatus with high risk of amputation. The aim of the study was to assess whether the localization of CN and the extent or grading of the osteomyelitis have an influence on the rate of limb salvage and the time to recovery. We treated a diabetic population affected by CN complicated by ulceration and widespread osteomyelitic involvement. All patients were treated surgically to eliminate infected tissues, stabilize and correct the bone deformities. Histopathological and microbiological analyses were carried out on the bone specimens. Thirty-three patients affected by CN complicated by large osteomyelitic involvement of midfoot and/or ankle were treated between January 2010 and May 2014. The mean follow-up was 409,35 ± 154,06 days. Thirty patients had complete recovery (90.91%) at the end of follow-up. No difference in limb salvage rate and time to recovery was observed when stratifying the population according to CN localization, extent and grading of osteomyelitis. In this cohort prospective study we observed a high percentage of limb salvage in patients affected by CN complicated by diffuse midfoot/hindfoot osteomyelitis. The localization of Charcot deformity and the extent/stage of osteomyelitis did not change the rate of limb salvage. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Thermotoga lettingae Can Salvage Cobinamide To Synthesize Vitamin B12

    Science.gov (United States)

    Butzin, Nicholas C.; Secinaro, Michael A.; Swithers, Kristen S.; Gogarten, J. Peter

    2013-01-01

    We recently reported that the Thermotogales acquired the ability to synthesize vitamin B12 by acquisition of genes from two distantly related lineages, Archaea and Firmicutes (K. S. Swithers et al., Genome Biol. Evol. 4:730–739, 2012). Ancestral state reconstruction suggested that the cobinamide salvage gene cluster was present in the Thermotogales' most recent common ancestor. We also predicted that Thermotoga lettingae could not synthesize B12 de novo but could use the cobinamide salvage pathway to synthesize B12. In this study, these hypotheses were tested, and we found that Tt. lettingae did not synthesize B12 de novo but salvaged cobinamide. The growth rate of Tt. lettingae increased with the addition of B12 or cobinamide to its medium. It synthesized B12 when the medium was supplemented with cobinamide, and no B12 was detected in cells grown on cobinamide-deficient medium. Upstream of the cobinamide salvage genes is a putative B12 riboswitch. In other organisms, B12 riboswitches allow for higher transcriptional activity in the absence of B12. When Tt. lettingae was grown with no B12, the salvage genes were upregulated compared to cells grown with B12 or cobinamide. Another gene cluster with a putative B12 riboswitch upstream is the btuFCD ABC transporter, and it showed a transcription pattern similar to that of the cobinamide salvage genes. The BtuF proteins from species that can and cannot salvage cobinamides were shown in vitro to bind both B12 and cobinamide. These results suggest that Thermotogales species can use the BtuFCD transporter to import both B12 and cobinamide, even if they cannot salvage cobinamide. PMID:24014541

  5. TEXTILE SALVAGE

    CERN Multimedia

    Relations with the Host States Service

    2002-01-01

    Readers are reminded that Geneva's agency for salvaging used clothing, other textiles and old shoes (Coordination d'oeuvres d'entraide pour la récupération de vêtements, textiles et chaussures usagés dans le canton de Genève) has a container in the car park outside CERN's Meyrin site. In 2001, 1000 tonnes of such items were collected in the Canton of Geneva (as compared with 840 tonnes in 2000), of which 4460 kg came from the container outside the Meyrin site. The operation's organisers (Caritas, Centre Social Protestant, the Geneva Section of the Swiss Red Cross, Terre des Hommes, the Geneva branch of Terre des Hommes Suisse and Emmaüs, Geneva) would like to thank all those who have donated clothing or otherwise supported their campaign. Relations with the Host States Service Tel. 72848 http://www.cern.ch/relations/

  6. [Case-control study on treating severe tibial open fractures by amputation and limb salvage].

    Science.gov (United States)

    Jiang, Xing-jie; Zhang, Feng; Zhao, Jian; Cao, Yong; Chen, Xiang-dong; Yao, Yu

    2014-12-01

    To compare mid-term clinical outcomes between amputation and limb salvage in treating severe open tibial fractures with type Gustilo III B, III C. From July 2007 to June 2010,68 patients with severe open tibial fractures with type Gustilo III B, III C treated by amputation and limb salvage were retrospectively analyzed. In amputation group, there were 26 males and 12 females with an average age of (44.9±16.3) years old; and 21 cases were type Gustilo (III B, 17 cases were Gustilo III C; amputation were performed in accordance with soft tissue injury degree of shank, fracture types and surgical exploration. In limb salvageg group, there were 21 males and 9 females with an average age of (43.5±14.7) years old; and 23 cases were type Gustilo III B, 7 cases were Gustilo III C; the method of internal fixation and and wound healing were performed in accordance with patients's specific condition. Operative time, blood loss, hospital stay and postoperative infection was compared between two groups; time of loading and rate of return to work was compared; VAS scoring was used to evaluate condition of pain; SF-36 health queationaire was used to assess postoperative life quality. Totally 60 patients were followed up (33 cases in amputation group and 27 cases in limb salvage group) with an average time of 49.1 months. Operative time, blood loss, hospital stay and postoperative infection in amputation and limb salvage group respectively was (109.0±25.7) min, (245.0±58.6) min; (168.0±49.0) ml, (311.0±137.0) ml; (13.8±2.7) d, (28.8±13.1) d; 7.9%, 36.7%. At the final following-up, there was no significance meaning between two groups in VAS scoring and rate of return to work, but time of loading in amputation group was shorter than that of in limb salvage group. Physiological function in amputation group was better than limb salvage group, while body pain was worse; and there was no signicance meaning in psychological health between two groups. Amputation and limb salvage

  7. Molecular cloning of a novel glucuronokinase/putative pyrophosphorylase from zebrafish acting in an UDP-glucuronic acid salvage pathway.

    Directory of Open Access Journals (Sweden)

    Roman Gangl

    Full Text Available In animals, the main precursor for glycosaminoglycan and furthermore proteoglycan biosynthesis, like hyaluronic acid, is UDP-glucuronic acid, which is synthesized via the nucleotide sugar oxidation pathway. Mutations in this pathway cause severe developmental defects (deficiency in the initiation of heart valve formation. In plants, UDP-glucuronic acid is synthesized via two independent pathways. Beside the nucleotide sugar oxidation pathway, a second minor route to UDP-glucuronic acid exist termed the myo-inositol oxygenation pathway. Within this myo-inositol is ring cleaved into glucuronic acid, which is subsequently converted to UDP-glucuronic acid by glucuronokinase and UDP-sugar pyrophosphorylase. Here we report on a similar, but bifunctional enzyme from zebrafish (Danio rerio which has glucuronokinase/putative pyrophosphorylase activity. The enzyme can convert glucuronic acid into UDP-glucuronic acid, required for completion of the alternative pathway to UDP-glucuronic acid via myo-inositol and thus establishes a so far unknown second route to UDP-glucuronic acid in animals. Glucuronokinase from zebrafish is a member of the GHMP-kinase superfamily having unique substrate specificity for glucuronic acid with a Km of 31 ± 8 µM and accepting ATP as the only phosphate donor (Km: 59 ± 9 µM. UDP-glucuronic acid pyrophosphorylase from zebrafish has homology to bacterial nucleotidyltransferases and requires UTP as nucleosid diphosphate donor. Genes for bifunctional glucuronokinase and putative UDP-glucuronic acid pyrophosphorylase are conserved among some groups of lower animals, including fishes, frogs, tunicates, and polychaeta, but are absent from mammals. The existence of a second pathway for UDP-glucuronic acid biosynthesis in zebrafish likely explains some previous contradictory finding in jekyll/ugdh zebrafish developmental mutants, which showed residual glycosaminoglycans and proteoglycans in knockout mutants of UDP

  8. Neoadjuvant chemotherapy combined with limb salvage surgery in patients with limb osteosarcoma of Enneking stage II: a retrospective study

    Directory of Open Access Journals (Sweden)

    Yuan G

    2017-05-01

    Full Text Available Guangke Yuan,1,2 Jingming Chen,2 Dongjin Wu,1 Chunzheng Gao1 1Department of Orthopedics, The Second Hospital of Shandong University, Jinan, 2Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong, People’s Republic of China Objective: To explore the effect of neoadjuvant chemotherapy combined with limb salvage surgery in patients with limb osteosarcoma of Enneking stage II. Patients and methods: Medical records of 98 patients who met the inclusion criteria were retrospectively analyzed. Of these patients, 56 cases who received neoadjuvant chemotherapy combined with limb salvage surgery were listed as group A, while another 42 patients who received limb salvage surgery combined with adjuvant chemotherapy were listed as group B. The recurrence and metastasis rate, survival rate, limb function and incidence of adverse reactions were compared between the two groups. Results: All 98 patients completed the treatment in this study. Baseline characteristics showed no significant differences between group A and group B, including age, gender, tumor location, maximum tumor diameter and Enneking stage (all P>0.05. The total metastasis and recurrence rate of group A was significantly lower than that of group B (25.0% vs 47.6%, χ2=5.419, P=0.020. The Kaplan–Meier method showed that progression-free survival (PFS (log-rank χ2=4.014, P=0.045 and overall survival (OS (log-rank χ2=3.859, P=0.049 of group A were both significantly higher than those of group B. There was no significant difference in the incidence of grades III–IV adverse reactions between the two groups (all P>0.05. The excellent and good rate of limb function in group A was significantly higher than that in group B (83.9% vs 66.7%, χ2=3.982, P=0.046. Conclusion: Neoadjuvant chemotherapy combined with limb salvage surgery for patients with Enneking stage IIA or IIB limb osteosarcoma patients has better efficacy and can significantly improve limb function of

  9. Membrane-type 1 matrix metalloproteinase cytoplasmic tail binding protein-1 (MTCBP-1) acts as an eukaryotic aci-reductone dioxygenase (ARD) in the methionine salvage pathway.

    Science.gov (United States)

    Hirano, Wakako; Gotoh, Isamu; Uekita, Takamasa; Seiki, Motoharu

    2005-06-01

    MTCBP-1 was identified as a protein that binds the cytoplasmic tail of membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14). Since MTCBP-1 has a putative beta-barrel structure, it is presumably a member of the recently proposed cupin superfamily that contains tremendously diverged functions of proteins in spite of their well-conserved beta-barrel structure. MTCBP-1 shows significant homology to the bacterial aci-reductone dioxygenase (ARD) in the cupin family, which is an enzyme in the methionine salvage pathway (MTA cycle). Since it is difficult to speculate the functions of cupin proteins simply based on their sequence homology, we examined whether the eukaryotic ARD homologs surely function in the methionine metabolism. Under sulfur-depleted conditions, yeast could grow when substrate of MTA cycle was provided. Disruption of the yeast ARD homolog, YMR009w gene, abolished ability of the cells to grow in this culture condition. Re-expression of either the YMR009w or MTCBP-1 gene restored the cell growth. Mutation analysis revealed that the glutamic acid residue in the beta-barrel fold and the N-terminal extension from the beta-barrel fold were found to be important for the activity to restore the growth. Thus, MTCBP-1 isolated as a binding protein for MT1-MMP was demonstrated to function as an ARD-like enzyme in the MTA cycle in yeast.

  10. Is Salvage of Recently Infected Breast Implant After Breast Augmentation or Reconstruction Possible? An Experimental Study.

    Science.gov (United States)

    Castus, P; Heymans, O; Melin, P; Renwart, L; Henrist, C; Hayton, E; Mordon, S; Leclère, F M

    2018-01-23

    could allow reinsertion of an infected implant when peri-prosthetic infection occurs early after breast augmentation or breast reconstruction and when a salvage procedure is indicated. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  11. Salmonella typhimurium PtsJ is a novel MocR-like transcriptional repressor involved in regulating the vitamin B6 salvage pathway.

    Science.gov (United States)

    Tramonti, Angela; Milano, Teresa; Nardella, Caterina; di Salvo, Martino L; Pascarella, Stefano; Contestabile, Roberto

    2017-02-01

    The vitamin B6 salvage pathway, involving pyridoxine 5'-phosphate oxidase (PNPOx) and pyridoxal kinase (PLK), recycles B6 vitamers from nutrients and protein turnover to produce pyridoxal 5'-phosphate (PLP), the catalytically active form of the vitamin. Regulation of this pathway, widespread in living organisms including humans and many bacteria, is very important to vitamin B6 homeostasis but poorly understood. Although some information is available on the enzymatic regulation of PNPOx and PLK, little is known on their regulation at the transcriptional level. In the present work, we identified a new MocR-like regulator, PtsJ from Salmonella typhimurium, which controls the expression of the pdxK gene encoding one of the two PLKs expressed in this organism (PLK1). Analysis of pdxK expression in a ptsJ knockout strain demonstrated that PtsJ acts as a transcriptional repressor. This is the first case of a MocR-like regulator acting as repressor of its target gene. Expression and purification of PtsJ allowed a detailed characterisation of its effector and DNA-binding properties. PLP is the only B6 vitamer acting as effector molecule for PtsJ. A DNA-binding region composed of four repeated nucleotide sequences is responsible for binding of PtsJ to its target promoter. Analysis of binding stoichiometry revealed that protein subunits/DNA molar ratio varies from 4 : 1 to 2 : 1, depending on the presence or absence of PLP. Structural characteristics of DNA transcriptional factor-binding sites suggest that PtsJ binds DNA according to a different model with respect to other characterised members of the MocR subgroup. © 2016 Federation of European Biochemical Societies.

  12. How to salvage a salvage endoprosthesis.

    Science.gov (United States)

    Haldar, Anil; Kantharuban, Shanjitha; Sharma, Aadhar; Davidson, Jerome A; Briggs, Timothy W R

    2016-01-17

    Custom-made endoprostheses can be linked to existing well-fixed implants in the treatment of complex periprosthetic femoral fractures. By adopting this salvage approach, secure implants can be retained in favour of patients undergoing more tissue disruptive procedures such as total femoral replacements. In this piece, we present a unique case illustrating a salvage strategy for treating a failed cement-linked salvage endoprosthesis, a complex scenario which to our knowledge has never before been reported. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

  13. Protection of the Environment and the International Salvage ...

    African Journals Online (AJOL)

    This article focuses on the International Salvage Convention and the protection of the environment in salvage operations. The article traces the evolution and history of the law of Salvage to its present status by using the UK as a case study. In essence, the article seeks to ascertain the extent of current international regime ...

  14. Synthesizing and Salvaging NAD+: Lessons Learned from Chlamydomonas reinhardtii

    Science.gov (United States)

    Lin, Huawen; Kwan, Alan L.; Dutcher, Susan K.

    2010-01-01

    The essential coenzyme nicotinamide adenine dinucleotide (NAD+) plays important roles in metabolic reactions and cell regulation in all organisms. Bacteria, fungi, plants, and animals use different pathways to synthesize NAD+. Our molecular and genetic data demonstrate that in the unicellular green alga Chlamydomonas NAD+ is synthesized from aspartate (de novo synthesis), as in plants, or nicotinamide, as in mammals (salvage synthesis). The de novo pathway requires five different enzymes: L-aspartate oxidase (ASO), quinolinate synthetase (QS), quinolate phosphoribosyltransferase (QPT), nicotinate/nicotinamide mononucleotide adenylyltransferase (NMNAT), and NAD+ synthetase (NS). Sequence similarity searches, gene isolation and sequencing of mutant loci indicate that mutations in each enzyme result in a nicotinamide-requiring mutant phenotype in the previously isolated nic mutants. We rescued the mutant phenotype by the introduction of BAC DNA (nic2-1 and nic13-1) or plasmids with cloned genes (nic1-1 and nic15-1) into the mutants. NMNAT, which is also in the de novo pathway, and nicotinamide phosphoribosyltransferase (NAMPT) constitute the nicotinamide-dependent salvage pathway. A mutation in NAMPT (npt1-1) has no obvious growth defect and is not nicotinamide-dependent. However, double mutant strains with the npt1-1 mutation and any of the nic mutations are inviable. When the de novo pathway is inactive, the salvage pathway is essential to Chlamydomonas for the synthesis of NAD+. A homolog of the human SIRT6-like gene, SRT2, is upregulated in the NS mutant, which shows a longer vegetative life span than wild-type cells. Our results suggest that Chlamydomonas is an excellent model system to study NAD+ metabolism and cell longevity. PMID:20838591

  15. Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia.

    Science.gov (United States)

    Badoux, Xavier C; Keating, Michael J; Wen, Sijin; Wierda, William G; O'Brien, Susan M; Faderl, Stefan; Sargent, Rachel; Burger, Jan A; Ferrajoli, Alessandra

    2013-02-10

    Lenalidomide is an immunomodulatory drug active as salvage therapy for chronic lymphocytic leukemia (CLL). We combined lenalidomide with rituximab to improve response rates in patients with relapsed or refractory CLL. Fifty-nine adult patients (age 42 to 82 years) with relapsed or refractory CLL were enrolled onto a phase II study of lenalidomide and rituximab. Patients had received prior fludarabine-based therapy or chemoimmunotherapy. Rituximab (375 mg/m(2) intravenously) was administered weekly during cycle one and on day 1 of cycles three to 12. Lenalidomide was started on day 9 of cycle one at 10 mg orally and administered daily continuously. Each cycle was 28 days. Rituximab was administered for 12 cycles; lenalidomide could continue indefinitely if patients benefitted clinically. The overall response rate was 66%, including 12% complete responses and 12% nodular partial remissions. Time to treatment failure was 17.4 months. Median overall survival has not been reached; estimated survival at 36 months is 71%. The most common grade 3 or 4 toxicity was neutropenia (73% of patients). Fourteen patients (24%) experienced a grade 3 to 4 infection or febrile episode. There was one episode of grade 3 tumor lysis; one patient experienced renal failure during the first cycle of therapy, and one venous thromboembolic event occurred during the study. The combination of lenalidomide and rituximab is active in patients with recurrent CLL and warrants further investigation.

  16. Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study

    Directory of Open Access Journals (Sweden)

    Viale Giuseppe

    2008-07-01

    Full Text Available Abstract Background The vinka-alkaloyd vinorelbine is a potentially valuable treatment in patients with HER2-positive, trastuzumab-resistant advanced breast cancer. We sought to document the clinical activity of vinorelbine-based salvage treatments in this clinical setting. Methods We analyzed a cohort of 424 consecutive women receiving trastuzumab-based therapy for HER2-positive advanced breast cancer. Of these, 299 were identified as progressing during the initial trastuzumab-based treatment, and 77 received vinorelbine-based therapy as first salvage treatment. Central review of pathological specimens revealed that 70 patients had HER2-amplification detected by FISH. For these patients we determined overall response rate (ORR = complete-CR + partial-PR and clinical benefit (CB = CR+PR+ Stable disease lasting at least 6 months, time to progression (TTP and overall survival (OS from the initiation of vinorelbine-based salvage therapy. Results In 60 patients who were evaluable for tumor response, ORR and CB rates were 28% (95% C.I. 18%-41% and 50% (95% C.I. 38%-62%, respectively. Median follow-up from the initiation of salvage therapy was 15 months (range 1–63 months. Median TTP and OS were 7.1 months (95% C.I. 6.6–7.7 months and 21 months (95% C.I. 14.3–27.7 months, respectively. No differences in clinical outcomes were observed according to whether vinorelbine was administered as a single agent or in combination with other cytostatics, or whether trastuzumab was stopped or continued beyond disease progression. Conclusion our findings suggests that vinorelbine-based combinations are active and should be further evaluated in studies conducted in trastuzumab-resistant patients, including those evaluating newer HER2-targeting agents.

  17. Salvage Radiation Therapy Dose Response for Biochemical Failure of Prostate Cancer After Prostatectomy—A Multi-Institutional Observational Study

    Energy Technology Data Exchange (ETDEWEB)

    Pisansky, Thomas M., E-mail: pisansky.thomas@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Agrawal, Shree [Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Hamstra, Daniel A. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Koontz, Bridget F. [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Liauw, Stanley L. [Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois (United States); Efstathiou, Jason A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Michalski, Jeff M. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abramowitz, Matthew C.; Pollack, Alan [Department of Radiation Oncology, University of Miami, Miami, Florida (United States); Anscher, Mitchell S. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Moghanaki, Drew [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Hunter Holmes McGuire Veterans Administration Medical Center, Richmond, Virginia (United States); Den, Robert B. [Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Stephans, Kevin L. [Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio (United States); Zietman, Anthony L. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lee, W. Robert [Department of Radiation Oncology, Duke Cancer Institute, Durham, North Carolina (United States); Kattan, Michael W. [Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio (United States); and others

    2016-12-01

    Purpose: To determine whether a dose-response relationship exists for salvage radiation therapy (RT) of biochemical failure after prostatectomy for prostate cancer. Methods and Materials: Individual data from 1108 patients who underwent salvage RT at 10 academic centers were pooled. The cohort was enriched for selection criteria more likely associated with tumor recurrence in the prostate bed (margin positive and pre-RT prostate-specific antigen [PSA] level of ≤2.0 ng/mL) and without the confounding of planned androgen suppression. The cumulative incidence of biochemical failure and distant metastasis over time was computed, and competing risks hazard regression models were used to investigate the association between potential predictors and these outcomes. The association of radiation dose with outcomes was the primary focus. Results: With a 65.2-month follow-up duration, the 5- and 10-year estimates of freedom from post-RT biochemical failure (PSA level >0.2 ng/mL and rising) was 63.5% and 49.8%, respectively, and the cumulative incidence of distant metastasis was 12.4% by 10 years. A Gleason score of ≥7, higher pre-RT PSA level, extraprostatic tumor extension, and seminal vesicle invasion were associated with worse biochemical failure and distant metastasis outcomes. A salvage radiation dose of ≥66.0 Gy was associated with a reduced cumulative incidence of biochemical failure, but not of distant metastasis. Conclusions: The use of salvage radiation doses of ≥66.0 Gy are supported by evidence presented in the present multicenter pooled analysis of individual patient data. The observational reporting method, limited sample size, few distant metastasis events, modest follow-up duration, and elective use of salvage therapy might have diminished the opportunity to identify an association between the radiation dose and this endpoint.

  18. Limb salvage surgery

    Directory of Open Access Journals (Sweden)

    Dinesh Kadam

    2013-01-01

    Full Text Available The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy.

  19. Quantitative and qualitative evaluation of blood salvaged after extracorporeal circulation (ECC) in paediatric heart surgery. Study of biochemical, morphological and structural variations of RBC after ECC and after salvaging of ECC circuit priming blood.

    Science.gov (United States)

    Calza, G; Zannini, L; Lerzo, F; Nitti, P; Mangraviti, S; Perutelli, P; Porlezza, M

    2000-06-01

    The salvaging of ECC circuit priming blood is essential for reducing the morbidity related to homologous blood transfusions and the importance of this technique is inversely proportionate to the age and weight of the child. In infants, the washing and centrifugation of blood not only drastically reduce the risk of contracting blood-transmitted diseases and cut management costs, but are also of considerable hemodynamic importance, producing a rapid normalization of the patient's hematocrit and hemoglobin and balancing the O2 consumption/demand ratio. The marketing of miniaturized salvagin devices with 55 ml bowls by Dideco has made possible the recovery of small quantities of blood, so as to normalise the hematic crisis and permit the application of total hemodilution in low-weight patients. The salvaged blood shows an average hematocrit of 52.7+/-9.7% (max 68.1%) and an average hemoglobin of 17.6 +/- 2.9 g/dl (max 20.7 g/dl), and maintains its structural components, osmotic resistance, concentration of intraerythrocytic hemoglobin and mean corpuscular hemoglobin all intact. Washing with isoosmotic and isoionic hydroelectrolytic solutions normalizes the ionic situation in the post-operative period and activated blood salvaging after Extracorporeal Circulation. The use of solutions without nutritional substances results however in a considerable fall in the number of enzymes in the intraerythrocytic metabolic glucide chain (G6PDH: -40.7 +/- 14.3% p<0.001), (PK: -23.8 +/- 20.5% p<0.03). This drop may be responsible for erythrocytic morphological alterations (echinocytic change) and probably for the release of hemoglobin from the red blood cells. Washing with isoionic, isoosmotic solutions containing G5% and adenine could, at least in theory, improve the quality of the salvaged blood, by normalizing the morphology and the volume of the RBC and by increasing the hematocrit.

  20. Salvage hypospadias repairs

    Directory of Open Access Journals (Sweden)

    Sripathi V

    2008-01-01

    Full Text Available Aim: Review of our experience and to develop an algorithm for salvage procedures in the management of hypospadias cripples and treatment of urethral strictures following hypospadias repair. Methods: This is a retrospective review of hypospadias surgeries over a 41-month period. Out of a total 168 surgeries, 20 were salvage/re-operative repairs. In three children a Duplay repair was feasible, while in four others a variety of single-stage repairs could be done. The repair was staged in seven children - buccal mucosal grafts (BMGs in five, buccal mucosal tube in one, and skin graft in one. Five children with dense strictures were managed by dorsal BMG inlay grafting in one, vascularized tunical onlay grafting on the ventrum in one, and a free tunical patch in one. Three children were treated by internal urethrotomy and stenting for four weeks with a poor outcome. Results: The age of children ranged from 1.5-15 years (mean 4.5. Follow-up ranged from 3 months to 3.5 years. Excellent results were obtained in 10 children (50% with a well-surfaced erect penis and a slit-like meatus. Glans closure could not be achieved and meatus was coronal in three. Two children developed fistulae following a Duplay repair and following a staged BMG. Three repairs failed completely - a composite repair broke down, a BMG tube stenosed with a proximal leak, and a stricture recurred with loss of a ventral free tunical graft. Conclusions: In salvage procedures performed on hypospadias cripples, a staged repair with buccal mucosa as an inlay in the first stage followed by tubularization 4-6 months later provides good results. A simple algorithm to plan corrective surgery in failed hypospadias cases and obtain satisfactory results is devised.

  1. Can Orthopedic Oncologists Predict Functional Outcome in Patients with Sarcoma after Limb Salvage Surgery in the Lower Limb? A Nationwide Study

    Directory of Open Access Journals (Sweden)

    Sjoerd Kolk

    2014-01-01

    Full Text Available Accurate predictions of functional outcome after limb salvage surgery (LSS in the lower limb are important for several reasons, including informing the patient preoperatively and, in some cases, deciding between amputation and LSS. This study aimed to elucidate the correlation between surgeon-predicted and patient-reported functional outcome of LSS in the Netherlands. Twenty-three patients (between six months and ten years after surgery and five independent orthopedic oncologists completed the Toronto Extremity Salvage Score (TESS and the RAND-36 physical functioning subscale (RAND-36 PFS. The orthopedic oncologists made their predictions based on case descriptions (including MRI scans that reflected the preoperative status. The correlation between patient-reported and surgeon-predicted functional outcome was “very poor” to “poor” on both scores (r2 values ranged from 0.014 to 0.354. Patient-reported functional outcome was generally underestimated, by 8.7% on the TESS and 8.3% on the RAND-36 PFS. The most difficult and least difficult tasks on the RAND-36 PFS were also the most difficult and least difficult to predict, respectively. Most questions had a “poor” intersurgeon agreement. It was difficult to accurately predict the patient-reported functional outcome of LSS. Surgeons’ ability to predict functional scores can be improved the most by focusing on accurately predicting more demanding tasks.

  2. Prospective 2-years follow-up quality of life study after infrageniculate bypass surgery for limb salvage: lasting improvements only in non-diabetic patients.

    Science.gov (United States)

    Engelhardt, M; Bruijnen, H; Scharmer, C; Wohlgemuth, W A; Willy, C; Wölfle, K D

    2008-07-01

    To assess health-related quality of life (HRQoL) up to 24 months after successful infrageniculate bypass surgery for limb-threatening ischaemia. 89 patients with infrageniculate bypass surgery for limb-salvage were studied. HRQoL was assessed using the Short Form (SF)-36v1 questionnaire before, 6, 12, and 24 months after revascularisation. 47 patients (53%) with intact limb and functioning graft were assessed after 24 months, 27 patients (30%) died, further 7 required secondary amputation, 3 suffered irremediable graft occlusion, and 4 were lost to follow-up. The 24-months HRQoL-values were significantly improved in 4 domains: physical functioning (pdiabetics compared to non-diabetics throughout follow-up. Maximum improvement of HRQoL was delayed in diabetics (12 months vs. 6 months) and less pronounced. After 24 months non-diabetic patients maintained improvement in 5 domains and diabetic patients only in bodily pain. Improvement in HRQoL is sustained for more than 12 months after successful infrageniculate bypass surgery. Therefore, an aggressive approach towards revascularisation seems to be justified from the patient's perspective. However, this benefit in quality of life is less in diabetic patients, despite similar limb-salvage rates.

  3. intraoperative blood salvage and autotransfusion in thf ...

    African Journals Online (AJOL)

    Objective: To review the role of intraoperative blood salvage and autologous blood transfusion in the management of ruptured ectopic pregnancy. Data sources: A complete review of relevant current and old literature using the MEDLINE search strategy. Study selection: Papers were selected for their relevance to the topic.

  4. Limb Salvage After Bone Cancer

    Science.gov (United States)

    ... usually done at least yearly. Life-long follow-up by an orthopedic surgeon is recommended. Promoting Health after Limb Salvage Physical and occupational therapy play an important role in successful rehabilitation after limb salvage surgery. Both passive and active ...

  5. Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

    Science.gov (United States)

    Mateos, F A; Puig, J G; Jiménez, M L; Fox, I H

    1987-03-01

    We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with [8-14C]adenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme-deficient patients and 6.0 +/- 0.7% (mean +/- SE) in four normal subjects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 10(6) cpm/g creatinine in both patients and to 4.73 +/- 0.69 X 10(6) cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 398 +/- 86% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 microM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xanthinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predominance of this urinary purine compound in xanthinuria.

  6. Salvage therapy for locally recurrent prostate cancer after radiation.

    Science.gov (United States)

    Marcus, David M; Canter, Daniel J; Jani, Ashesh B; Dobbs, Ryan W; Schuster, David M; Carthon, Bradley C; Rossi, Peter J

    2012-12-01

    External beam radiotherapy (EBRT) is widely utilized as primary therapy for clinically localized prostate cancer. For patients who develop locally recurrent disease after EBRT, local salvage therapy may be indicated. The primary modalities for local salvage treatment in this setting include radical prostatectomy, cryotherapy, and brachytherapy. To date, there is little data describing outcomes and toxicity associated with each of these salvage modalities. A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. We focused on prospective trials and multi-institutional retrospective series in order to identify the highest level of evidence describing these therapies. The majority of reports describing the use of local salvage treatment for recurrent prostate cancer after EBRT are single-institution, retrospective reports, although small prospective studies are available for salvage cryotherapy and salvage brachytherapy. Clinical outcomes and toxicity for each modality vary widely across studies, which is likely due to the heterogeneity of patient populations, treatment techniques, and definitions of failure. In general, most studies demonstrate that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. As there are no randomized trials comparing salvage treatment modalities for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis, with careful consideration of each patient's disease characteristics and tolerance for the risks of treatment. Additional data, ideally from prospective randomized trials, is needed to guide decision making for patients with local recurrence after EBRT failure.

  7. Limb salvage in tibial hemimelia.

    Science.gov (United States)

    Eamsobhana, Perajit; Kaewpornsawan, Kamolporn

    2012-09-01

    To study the results of treatment of tibial hemimelia with limb salvage procedure in term of patient satisfaction, clinical results and complications. From 1993 to 2007 the authors treated six cases of tibial hemimelia with limb salvage procedures. Three legs of type Ia and four legs of type IV tibial hemimelia classified by Jones classification. The age at the operation ranged from 2 to 11 years. For type Ia cases, the Brown procedure,foot centralization and ilizarov lengthening of the fibula were used to correct limb length discrepancy. For type IV the foot centralization, soft tissue release and ilizarov lengthening were used to correct limb length discrepancy. The follow-up range from 4 to 10 years. In two patients with type Ia, one patient could bear weight without gait aids, the other walked with orthosis and axillary crutch because this patient had bilateral Ia type and knee instability with progressive flexion contracture due to weakness of the quadriceps muscle. All patients with type IV can walk independently without gait aids. Three patients were performed limb lengthening. One case was fibular lengthening following Brown procedure in Ia type. Two cases were tibial lengthening in type IV The mean lengthening was 5.1 cm. Mean lengthening index was 2.4. Satisfactory functional and cosmetic results were achieved in all patients with partial deficiency, whereas in patients with completely deficiency of the limbs, none of the 3 knees treated by fibular transfer achieved a satisfactory functional result because of insufficient quadriceps strength, progressive knee flexion contracture and persistent ligamentous instability. Nevertheless, in these 3 legs, all patients were ultimately able to withstand weight bearing. Patients and families were satisfied even though patients must have multiple surgery to correct deformities of the foot and the knee joint, as well as leg-length discrepancy and also a prolong treatment time. Limb salvage procedure in tibial

  8. Impacts of salvage logging on biodiversity: a meta-analysis.

    Science.gov (United States)

    Thorn, Simon; Bässler, Claus; Brandl, Roland; Burton, Philip J; Cahall, Rebecca; Campbell, John L; Castro, Jorge; Choi, Chang-Yong; Cobb, Tyler; Donato, Daniel C; Durska, Ewa; Fontaine, Joseph B; Gauthier, Sylvie; Hebert, Christian; Hothorn, Torsten; Hutto, Richard L; Lee, Eun-Jae; Leverkus, Alexandro B; Lindenmayer, David B; Obrist, Martin K; Rost, Josep; Seibold, Sebastian; Seidl, Rupert; Thom, Dominik; Waldron, Kaysandra; Wermelinger, Beat; Winter, Maria-Barbara; Zmihorski, Michal; Müller, Jörg

    2018-01-01

    Logging to "salvage" economic returns from forests affected by natural disturbances has become increasingly prevalent globally. Despite potential negative effects on biodiversity, salvage logging is often conducted, even in areas otherwise excluded from logging and reserved for nature conservation, inter alia because strategic priorities for post-disturbance management are widely lacking.A review of the existing literature revealed that most studies investigating the effects of salvage logging on biodiversity have been conducted less than 5 years following natural disturbances, and focused on non-saproxylic organisms.A meta-analysis across 24 species groups revealed that salvage logging significantly decreases numbers of species of eight taxonomic groups. Richness of dead wood dependent taxa (i.e. saproxylic organisms) decreased more strongly than richness of non-saproxylic taxa. In contrast, taxonomic groups typically associated with open habitats increased in the number of species after salvage logging.By analysing 134 original species abundance matrices, we demonstrate that salvage logging significantly alters community composition in 7 of 17 species groups, particularly affecting saproxylic assemblages.Synthesis and applications. Our results suggest that salvage logging is not consistent with the management objectives of protected areas. Substantial changes, such as the retention of dead wood in naturally disturbed forests, are needed to support biodiversity. Future research should investigate the amount and spatio-temporal distribution of retained dead wood needed to maintain all components of biodiversity.

  9. Evaluation of hemolysis in microcatheter directed blood infusion at different flow rates for transarterial salvage reperfusion: In-vitro study.

    Science.gov (United States)

    Froelich, Jens J; Ray, Udayan; Monkhorst, Jessica; Marwick, Thomas H; Hardikar, Ashutosh; Harle, Robin; Carr, Michael W

    2015-01-01

    Microcatheter directed blood reperfusion is an endovascular salvage option for acute cerebral artery occlusions. It has not been investigated whether this technique may be associated with hemolysis. Analysis of hemolysis during blood infusion through different microcatheters and infusion rates to assess related risks. Four microcatheters with different inner diameters were perfused with blood samples at three infusion rates. Hemolytic markers including lactate-dehydrogenase (LDH) and haptoglobin were analyzed. Samples before and after blood infusion were compared using Student's t-test. Flow-related degree of hemolysis was analyzed with regression analysis. Resulting shear stress was calculated and correlated with LDH and haptoglobin. Significant increase of LDH and decrease of haptoglobin was found after blood reperfusion through small microcatheters at progressive flow rates (pflow rates (p>0.05). Correlation between shear stress, LDH and haptoglobin was r=0.86 and r=0.75, respectively. Progressive hemolysis occurs during blood perfusion of small lumen microcatheters at increasing flow rates. This phenomenon may be related to turbulent flow, exposure time and increased shear stress. Larger microcatheters did not induce hemolysis and may be the preferred choice for stroke reperfusion.

  10. Residual tumor after the salvage surgery is the major risk factors for primary treatment failure in malignant ovarian germ cell tumors: A retrospective study of single institution

    Directory of Open Access Journals (Sweden)

    Park Jong Sup

    2011-10-01

    Full Text Available Abstract Background Malignant ovarian germ cell tumors are rare, and knowledge of their prognostic factors is limited, with little available randomized data. This study was conducted to evaluate the clinicopathologic characteristics of malignant ovarian germ cell tumors and to determine the association of their prognostic factors to primary treatment failure. Methods The medical records of 57 patients with stages I to IV malignant ovarian germ cell tumor were retrospectively reviewed, and their clinicopathologic and treatment-related data were collected and analyzed. Results The median age at the diagnosis was 23.3 years (range: 8-65 years, and the median follow-up period was 108 months (range: 48-205 months. The histological types of the tumors were immature teratoma (n = 24, dysgerminoma (n = 20, endodermal sinus tumor (n = 8, mixed germ cell tumor (n = 4, and choriocarcinoma (n = 1. 66.7% of the patients had stage I disease; 5.2%, stage II; 26.3%, stage III; and 1.8%, stage IV. After the initial surgery, 49 patients (86% received cisplatin-based chemotherapy. The five-year survival rate was 96.5%. There were six primary treatment failures, with two of the patients dying of the disease, and the median time to the recurrence was 8 months. The histological diagnosis (P P = 0.0052, elevation of beta-hCG (P = 0.0134, operation methods (P = 0.0006, and residual tumor after the salvage surgery (P P = 0.0011, Hazard ratio = 29.046, 95% Confidence interval 3.832-220.181. Conclusion Most malignant ovarian germ cell tumors have excellent prognoses with primary treatment, and good reproductive outcomes can be expected. Because primary treatment failure is associated with the residual disease after the salvage surgery, knowledge of the presence or absence of this risk factor may be helpful in risk stratification and individualization of adjuvant therapy in malignant ovarian germ cell tumors. Further large-scale prospective studies to confirm these results

  11. Pyridine metabolism in tea plants: salvage, conjugate formation and catabolism.

    Science.gov (United States)

    Ashihara, Hiroshi; Deng, Wei-Wei

    2012-11-01

    Pyridine compounds, including nicotinic acid and nicotinamide, are key metabolites of both the salvage pathway for NAD and the biosynthesis of related secondary compounds. We examined the in situ metabolic fate of [carbonyl-(14)C]nicotinamide, [2-(14)C]nicotinic acid and [carboxyl-(14)C]nicotinic acid riboside in tissue segments of tea (Camellia sinensis) plants, and determined the activity of enzymes involved in pyridine metabolism in protein extracts from young tea leaves. Exogenously supplied (14)C-labelled nicotinamide was readily converted to nicotinic acid, and some nicotinic acid was salvaged to nicotinic acid mononucleotide and then utilized for the synthesis of NAD and NADP. The nicotinic acid riboside salvage pathway discovered recently in mungbean cotyledons is also operative in tea leaves. Nicotinic acid was converted to nicotinic acid N-glucoside, but not to trigonelline (N-methylnicotinic acid), in any part of tea seedlings. Active catabolism of nicotinic acid was observed in tea leaves. The fate of [2-(14)C]nicotinic acid indicates that glutaric acid is a major catabolite of nicotinic acid; it was further metabolised, and carbon atoms were finally released as CO(2). The catabolic pathway observed in tea leaves appears to start with the nicotinic acid N-glucoside formation; this pathway differs from catabolic pathways observed in microorganisms. Profiles of pyridine metabolism in tea plants are discussed.

  12. Cell Salvage Used in Scoliosis Surgery: Is It Really Effective?

    Science.gov (United States)

    Liu, Jia-Ming; Fu, Bi-Qi; Chen, Wen-Zhao; Chen, Jiang-Wei; Huang, Shan-Hu; Liu, Zhi-Li

    2017-05-01

    Scoliosis surgery usually is associated with large volume of intraoperative blood loss, and cell salvage is used commonly to filter and retranfusion autologous blood to patients. The efficacy of using cell salvage in scoliosis surgery, however, is still controversial. The purpose of this study is to make clear that intraoperative use of cell salvage is effective to decrease the volume of perioperative allogenic blood transfusion in scoliosis surgery. A meta-analysis was conducted to identify the relevant studies from PubMed, Embase, Medline, Cochrane library, and Google scholar until July 2016. All randomized trials and controlled clinical studies comparing the clinical outcomes of using cell salvage versus noncell salvage in scoliosis surgery were retrieved for the meta-analysis. The data were analyzed by RevMan 5.3. A total of 7 studies with 562 patients were included in this meta-analysis. Based on the analysis, the volumes of perioperative and postoperative allogenic red blood cell (RBC) transfusion in cell salvage group were significantly less than those in control group (P = 0.04 and P = 0.01); however, no significant difference was detected in the amount of intraoperative allogenic RBC transfusion and the risk of patients needing allogenic blood transfusion between the 2 groups (P = 0.14 and P = 0.61). Both the hemoglobin and hematocrit levels on the first day after surgery were significantly greater in cell salvage group than those in control group (P = 0.002 and P scoliosis surgery and increased the hemoglobin and hematocrit levels on the first day postoperatively. In addition, it seemed not to increase the rate of transfusion complications during the surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. A randomized controlled trial to evaluate antiretroviral salvage therapy guided by rules-based or phenotype-driven HIV-1 genotypic drug-resistance interpretation with or without concentration-controlled intervention: the Resistance and Dosage Adapted Regimens (RADAR) study.

    Science.gov (United States)

    Torti, Carlo; Quiros-Roldan, Eugenia; Regazzi, Mario; De Luca, Andrea; Mazzotta, Francesco; Antinori, Andrea; Ladisa, Nicoletta; Micheli, Valeria; Orani, Anna; Patroni, Andrea; Villani, Paola; Lo Caputo, Sergio; Moretti, Francesca; Di Giambenedetto, Simona; Castelnuovo, Filippo; Maggi, Paolo; Tinelli, Carmine; Carosi, Giampiero

    2005-06-15

    It is not well defined whether concentration-controlled intervention (CCI) and rules-based human immunodeficiency virus (HIV) type 1 genotype drug-resistance interpretation (GI) or virtual phenotype drug-resistance interpretation (VPI) may improve the outcome of HIV salvage therapy. In a prospective, randomized, controlled trial, patients were randomized (on a factorial basis) to change treatment after either GI or VPI, and they then were further randomized to the control arm (no CCI) or the CCI arm. Protease inhibitor (PI) and nonnucleoside reverse-transcriptase inhibitor (NNRTI) trough concentration (Ctrough) values were determined at weeks 1, 4, 12, and 24 of the study. Among 230 patients, virological benefit (defined by an HIV RNA load of receipt of a regimen that contained PIs boosted with ritonavir was an independent predictor of virological response. The present study did not support the routine use of CCI for patients undergoing salvage treatment, probably as a result of existing difficulties associated with its clinical application. However, a higher Ctrough value appeared to be correlated with treatment response. No major differences were found between VPI or GI when they are used together with expert advice for the selection of salvage treatment combinations.

  14. Estimate of myocardial salvage in late presentation acute myocardial infarction by comparing functional and perfusion abnormalities in predischarge gated SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Sotgia, Barbara; Sciagra, Roberto; Pupi, Alberto [University of Florence, Nuclear Medicine Unit, Department of Clinical Physiopathology, Florence (Italy); Parodi, Guido; Antoniucci, David [Careggi Hospital, Division of Cardiology, Florence (Italy); Kastrati, Adnan; Schoemig, Albert [Technische Universitaet, Deutsches Herzzentrum, Munich (Germany)

    2008-05-15

    We hypothesized that, because of persistent stunning, the extent of post-treatment functional abnormalities detected using gated single-photon emission computed tomography (SPECT) could be representative of the initial risk area in acute myocardial infarction (AMI) treated by reperfusion therapy. In 48 AMI patients, we acquired two {sup 99m}Tc-sestamibi gated SPECT studies (at admission with tracer injection before treatment and at discharge 5 to 10 days later). We assessed the myocardial salvage defined by the admission minus predischarge summed rest score, and we compared it with the value obtained by subtracting the extent of perfusion defect from the extent of wall motion or wall thickening abnormalities in predischarge gated SPECT. Myocardial salvage was expressed as salvage index (salvaged myocardium divided by initial risk area). There was a good correlation between summed rest score salvage index and wall motion (Spearman's {rho} = 0.754, p < 0.0001) or wall thickening salvage index (Spearman's {rho} = 0.798, p < 0.0001). The wall thickening salvage index was able to classify correctly the patients that had a summed rest score salvage index {>=} 0.10 with 73% sensitivity, 88% specificity, and 83% accuracy. The wall motion salvage index was highly sensitive (91%) but poorly specific (13%, p < 0.002 vs wall thickening salvage index) and less accurate (69%, p < 0.05 vs wall thickening salvage index). {sup 99m}Tc-sestamibi gated SPECT allows assessing myocardial salvage using only post-treatment data. The salvage index derived using wall thickening as surrogate of admission perfusion defect correlates well with the salvage index measured by comparing pre- and post-treatment perfusion defects. (orig.)

  15. Factors associated with failed hardware salvage in high-risk patients after microsurgical lower extremity reconstruction.

    Science.gov (United States)

    Patel, Ketan M; Seruya, Mitchel; Franklin, Brenton; Attinger, Christopher E; Ducic, Ivica

    2012-10-01

    Lower extremity hardware salvage remains challenging in patients with complex comorbidities. The purpose of this study was to identify factors associated with failed hardware salvage after microsurgical lower extremity reconstruction. A retrospective, institutional review board-approved review was performed of patients who underwent lower extremity hardware salvage via free tissue transfer from 2004 to 2010. Outcomes were binarized into successful versus failed hardware salvage, with failure defined as nonelective removal. Patient demographics, wound characteristics, microbiology, and pathology were compared. Thirty-four patients underwent lower extremity hardware salvage via free tissue transfer, with an average follow-up of 3.2 years (range, 0.3-7.0 years). Of these patients, 15 (44.1%) had successful hardware salvage and 19 (55.9%) required hardware removal. By demographics, a higher prevalence of multiple comorbidities was found in patients with failed hardware salvage. Wound characteristics revealed a significantly longer time to hardware coverage and longer duration of intravenous antibiotics in failed versus successful hardware salvage patients (38.9 vs 9.3 weeks, P=0.02; 6.5 vs 4.1 weeks, P=0.03, respectively). Initial wound cultures demonstrated a significantly higher frequency of positive growth in patients with failed versus successful hardware salvage (100.0% vs 57.1%, P=0.003). Initial pathology revealed a borderline-significantly higher frequency of chronic osteomyelitis in failed versus successful salvage patients (66.7% vs 33.3%, P=0.08). In this retrospective review of microsurgical lower extremity reconstruction, factors associated with failed hardware salvage included multiple comorbidities, longer time to hardware coverage, increased duration of intravenous antibiotics, positive initial wound cultures, and chronic osteomyelitis on initial pathology.

  16. Trinidad Reservoir Salvage Archaeology, 1968,

    Science.gov (United States)

    1974-10-15

    separated by a small unnamed arroyol TCtC9:186 was im- mediately east and TC:C9:187 was immediately west of the arroyo. The comunity of St. Thomas was...Region, Linco.n. Ireland, Stephen K. and Caryl E. Wood 1973 Trinidad Reservoir Salvage Archaeology: Site TC:C9:20. MS on file at the National Park Service

  17. Comparative genomics of bacterial and plant folate synthesis and salvage: predictions and validations

    Directory of Open Access Journals (Sweden)

    Noiriel Alexandre

    2007-07-01

    Full Text Available Abstract Background Folate synthesis and salvage pathways are relatively well known from classical biochemistry and genetics but they have not been subjected to comparative genomic analysis. The availability of genome sequences from hundreds of diverse bacteria, and from Arabidopsis thaliana, enabled such an analysis using the SEED database and its tools. This study reports the results of the analysis and integrates them with new and existing experimental data. Results Based on sequence similarity and the clustering, fusion, and phylogenetic distribution of genes, several functional predictions emerged from this analysis. For bacteria, these included the existence of novel GTP cyclohydrolase I and folylpolyglutamate synthase gene families, and of a trifunctional p-aminobenzoate synthesis gene. For plants and bacteria, the predictions comprised the identities of a 'missing' folate synthesis gene (folQ and of a folate transporter, and the absence from plants of a folate salvage enzyme. Genetic and biochemical tests bore out these predictions. Conclusion For bacteria, these results demonstrate that much can be learnt from comparative genomics, even for well-explored primary metabolic pathways. For plants, the findings particularly illustrate the potential for rapid functional assignment of unknown genes that have prokaryotic homologs, by analyzing which genes are associated with the latter. More generally, our data indicate how combined genomic analysis of both plants and prokaryotes can be more powerful than isolated examination of either group alone.

  18. Which is the best method of sterilization for recycled bone autograft in limb salvage surgery: a radiological, biomechanical and histopathological study in rabbit.

    Science.gov (United States)

    Yasin, Nor Faissal; Ajit Singh, Vivek; Saad, Marniza; Omar, Effat

    2015-04-15

    Limb salvage surgery is a treatment of choice for sarcomas of the extremities. One of the options in skeletal reconstruction after tumour resection is by using a recycled bone autograft. The present accepted methods of recycling bone autografts include autoclaving, pasteurization and irradiation. At the moment there is lack of studies that compare the effectiveness of various sterilization methods used for recycling bone autografts and their effects in terms of bone incorporation. This study was performed to determine the effects of different methods of sterilization on bone autografts in rabbit by radiological, biomechanical and histopathological evaluations. Fresh rabbit cortical bone is harvested from the tibial diaphysis and sterilized extracorporeally by pasteurization (n = 6), autoclaving (n = 6), irradiation (n = 6) and normal saline as control group (n = 6). The cortical bones were immediately reimplanted after the sterilization process. The subsequent process of graft incorporation was examined over a period of 12 weeks by serial radiographs, biomechanical and histopathological evaluations. Statistical analysis (ANOVA) was performed on these results. Significance level (α) and power (β) were set to 0.05 and 0.90, respectively. Radiographic analysis showed that irradiation group has higher score in bony union compared to other sterilization groups (p = 0.041). ANOVA analysis of 'failure stress', 'modulus' and 'strain to failure' demonstrated no significant differences (p = 0.389) between treated and untreated specimens under mechanical loading. In macroscopic histopathological analysis, the irradiated group has the highest percentage of bony union (91.7 percent). However in microscopic analysis of union, the pasteurization group has significantly higher score (p = 0.041) in callus formation, osteocytes percentage and bone marrow cellularity at the end of the study indicating good union potential. This experimental study shown that both irradiation and

  19. Nucleotide Salvage Deficiencies, DNA Damage and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Michael Fasullo

    2015-04-01

    Full Text Available Nucleotide balance is critically important not only in replicating cells but also in quiescent cells. This is especially true in the nervous system, where there is a high demand for adenosine triphosphate (ATP produced from mitochondria. Mitochondria are particularly prone to oxidative stress-associated DNA damage because nucleotide imbalance can lead to mitochondrial depletion due to low replication fidelity. Failure to maintain nucleotide balance due to genetic defects can result in infantile death; however there is great variability in clinical presentation for particular diseases. This review compares genetic diseases that result from defects in specific nucleotide salvage enzymes and a signaling kinase that activates nucleotide salvage after DNA damage exposure. These diseases include Lesch-Nyhan syndrome, mitochondrial depletion syndromes, and ataxia telangiectasia. Although treatment options are available to palliate symptoms of these diseases, there is no cure. The conclusions drawn from this review include the critical role of guanine nucleotides in preventing neurodegeneration, the limitations of animals as disease models, and the need to further understand nucleotide imbalances in treatment regimens. Such knowledge will hopefully guide future studies into clinical therapies for genetic diseases.

  20. Removing inactive NRTIs in a salvage regimen is safe, maintains virological suppression and reduces treatment costs: 96 weeks post VERITAS study

    Directory of Open Access Journals (Sweden)

    Benoit Trottier

    2014-11-01

    Full Text Available Introduction: In HIV+ patients exhibiting multidrug resistance (MDR, NRTIs often have little activity, increased toxicity, drug interactions and add unnecessary treatment costs. The 48 week VERITAS study demonstrated that these patients can have a safe and effective simplification of salvage regimen by removing inactive NRTIs as determined by genotypic data. Virological, immunological, clinical and financial outcomes were evaluated at an additional 96 weeks of follow-up. Materials and Methods: MDR patients with an undetectable viral load (VL on a stable regimen containing at least four ARVs (including one inactive NRTI were enrolled in an open-label, prospective simplification trial, where one inactive NRTI was removed at baseline (BL. A second NRTI could be removed at week 24 if the regimen contained at least five ARVs at enrolment. Results: 31 male patients participated. The mean length of treatment was 14 years, with a median CD4 count of 525. The BL regimen consisted of 4 ARVs in 22 patients (71% and 5 ARVs in 9 patients (29%. 3TC or FTC was removed in 29 patients (94%, and either AZT or TDF was interrupted in 2 others. Four patients had a second NRTI stopped. One patient was removed at W26 as an active NRTI was removed for creatinine elevation. 30 well-controlled patients continued follow-up after W48. At W144, six patients had additional changes in their ARV regimen. Half were due to toxicity (jaundice, neuropathy and nephrotoxicity while the other half were the result of treatment simplification. None of the patients exhibited virologic failure at the time of treatment change and maintained undetectable VLs throughout the entire follow-up. These six patients had a mean gain of 79 CD4 (p=0.17 compared to baseline. 22 of the 24 patients (92% with no changes in ARV therapy after W48 had undetectable VLs. The other two had confirmed virologic failure, one with genotypic resistance. All 24 had elevated CD4 counts (mean +118 CD4, p<0.0001. No

  1. Salvage of Infected Breast Implants

    Directory of Open Access Journals (Sweden)

    Joon Ho Song

    2017-11-01

    Full Text Available Background Implant-based breast reconstruction is being performed more frequently, and implants are associated with an increased risk of infection. We reviewed the clinical features of cases of implant infection and investigated the risk factors for breast device salvage failure. Methods We retrospectively analyzed 771 patients who underwent implant-based breast reconstruction between January 2010 and December 2016. Age, body mass index, chemotherapy history, radiation exposure, and smoking history were assessed as potential risk factors for postoperative infection. We also evaluated the presence and onset of infection symptoms, wound culture pathogens, and other complications, including seroma, hematoma, and mastectomy skin necrosis. Additionally, we examined the mastectomy type, the use of acellular dermal matrix, the presence of an underlying disease such as hypertension or diabetes, and axillary node dissection. Results The total infection rate was 4.99% (58 of 1,163 cases and the total salvage rate was 58.6% (34 of 58. The postoperative duration to closed suction drain removal was significantly different between the cellulitis and implant removal groups. Staphylococcus aureus infection was most frequently found, with methicillin resistance in 37.5% of the cases of explantation. Explantation after infection was performed more often in patients who had undergone 2-stage expander/implant reconstruction than in those who had undergone direct-to-implant reconstruction. Conclusions Preventing infection is essential in implant-based breast reconstruction. The high salvage rate argues against early implant removal. However, when infection is due to methicillin-resistant S. aureus and the patient’s clinical symptoms do not improve, surgeons should consider implant removal.

  2. Salvage arthrodesis for charcot arthropathy.

    Science.gov (United States)

    Panagakos, Panagiotis; Ullom, Nathan; Boc, Steven F

    2012-01-01

    The principles of fusion of a Charcot joint arise from the assertion that successful fusion requires removal of all cartilage, debris, and sclerotic bone. The authors believe that reconstruction can prevent amputation in patients who have unbraceable or unstable deformities, or recurrent ulcerations. The goal with any Charcot reconstruction procedure is to achieve a plantigrade foot free of ulceration, and to prevent any future collapse, deformity, or ulcerations. The authors strongly believe arthrodesis of unstable joints of the Charcot neuropathic foot can lead to limb salvage and better quality of life. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Outcome and renal function following salvage surgery for bilateral ...

    African Journals Online (AJOL)

    Objective: The aim of this study was to determine the surgical outcomes and renal function following salvage surgery for bilateral Wilms tumor (BWT). Summary background data The challenge for the surgeon treating BWT lies in striking a fine balance between renal preservation and oncological clearance. Methods: This is ...

  4. Windthrow and salvage logging in an old-growth hemlock-northern hardwoods forest

    Science.gov (United States)

    Lang, K.D.; Schulte, L.A.; Guntenspergen, G.R.

    2009-01-01

    Although the initial response to salvage (also known as, post-disturbance or sanitary) logging is known to vary among system components, little is known about longer term forest recovery. We examine forest overstory, understory, soil, and microtopographic response 25 years after a 1977 severe wind disturbance on the Flambeau River State Forest in Wisconsin, USA, a portion of which was salvage logged. Within this former old-growth hemlock-northern hardwoods forest, tree dominance has shifted from Eastern hemlock (Tsuga canadensis) to broad-leaf deciduous species (Ulmus americana, Acer saccharum, Tilia americana, Populus tremuloides, and Betula alleghaniensis) in both the salvaged and unsalvaged areas. While the biological legacies of pre-disturbance seedlings, saplings, and mature trees were initially more abundant in the unsalvaged area, regeneration through root suckers and stump sprouts was common in both areas. After 25 years, tree basal area, sapling density, shrub layer density, and seedling cover had converged between unsalvaged and salvaged areas. In contrast, understory herb communities differed between salvaged and unsalvaged forest, with salvaged forest containing significantly higher understory herb richness and cover, and greater dominance of species benefiting from disturbance, especially Solidago species. Soil bulk density, pH, organic carbon content, and organic nitrogen content were also significantly higher in the salvaged area. The structural legacy of tip-up microtopography remains more pronounced in the unsalvaged area, with significantly taller tip-up mounds and deeper pits. Mosses and some forest herbs, including Athyrium filix-femina and Hydrophyllum virginianum, showed strong positive responses to this tip-up microrelief, highlighting the importance of these structural legacies for understory biodiversity. In sum, although the pathways of recovery differed, this forest appeared to be as resilient to the compound disturbances of windthrow

  5. Hip salvage surgery in cerebral palsy cases: a systematic review.

    Science.gov (United States)

    de Souza, Rafael Carboni; Mansano, Marcelo Valentim; Bovo, Miguel; Yamada, Helder Henzo; Rancan, Daniela Regina; Fucs, Patricia Maria de Moraes Barros; Svartman, Celso; de Assumpção, Rodrigo Montezuma César

    2015-01-01

    Imbalance and muscle spasticity, in association with coxa valga and persistent femoral anteversion, compromises hip development in cases of cerebral palsy and may result in chronic pain and even dislocation. Some of these hips undergo salvage surgery because of the severe impact of their abnormalities in these patients' quality of life. We conducted a systematic review of the literature to compare the results from the main hip salvage techniques applied to these individuals. The literature search focused on studies that evaluated results from hip salvage surgery in cases of cerebral palsy, published from 1970 to 2011, which are present in the Embase, Medline, PubMed, Cochrane Library and SciELO databases. Although the results were not statistically comparable, this systematic review demonstrates that hip salvage surgery should be indicated after individual evaluation on each patient, due to the wide spectrum of presentations of cerebral palsy. Therefore, it seems that no surgical technique is superior to any other. Rather, there are different indications.

  6. Hip salvage surgery in cerebral palsy cases: a systematic review☆

    Science.gov (United States)

    de Souza, Rafael Carboni; Mansano, Marcelo Valentim; Bovo, Miguel; Yamada, Helder Henzo; Rancan, Daniela Regina; Fucs, Patricia Maria de Moraes Barros; Svartman, Celso; de Assumpção, Rodrigo Montezuma César

    2015-01-01

    Imbalance and muscle spasticity, in association with coxa valga and persistent femoral anteversion, compromises hip development in cases of cerebral palsy and may result in chronic pain and even dislocation. Some of these hips undergo salvage surgery because of the severe impact of their abnormalities in these patients’ quality of life. We conducted a systematic review of the literature to compare the results from the main hip salvage techniques applied to these individuals. The literature search focused on studies that evaluated results from hip salvage surgery in cases of cerebral palsy, published from 1970 to 2011, which are present in the Embase, Medline, PubMed, Cochrane Library and SciELO databases. Although the results were not statistically comparable, this systematic review demonstrates that hip salvage surgery should be indicated after individual evaluation on each patient, due to the wide spectrum of presentations of cerebral palsy. Therefore, it seems that no surgical technique is superior to any other. Rather, there are different indications. PMID:26229926

  7. Hip salvage surgery in cerebral palsy cases: a systematic review

    Directory of Open Access Journals (Sweden)

    Rafael Carboni de Souza

    2015-06-01

    Full Text Available Imbalance and muscle spasticity, in association with coxa valga and persistent femoral anteversion, compromises hip development in cases of cerebral palsy and may result in chronic pain and even dislocation. Some of these hips undergo salvage surgery because of the severe impact of their abnormalities in these patients' quality of life. We conducted a systematic review of the literature to compare the results from the main hip salvage techniques applied to these individuals. The literature search focused on studies that evaluated results from hip salvage surgery in cases of cerebral palsy, published from 1970 to 2011, which are present in the Embase, Medline, PubMed, Cochrane Library and SciELO databases. Although the results were not statistically comparable, this systematic review demonstrates that hip salvage surgery should be indicated after individual evaluation on each patient, due to the wide spectrum of presentations of cerebral palsy. Therefore, it seems that no surgical technique is superior to any other. Rather, there are different indications.

  8. Psychosocial reactions to upper extremity limb salvage: A case series.

    Science.gov (United States)

    Sposato, Lindsay; Yancosek, Kathleen; Cancio, Jill

    2017-11-30

    Case series. A salvaged limb is one that has undergone a major traumatic injury, followed by repeated surgical attempts in order to avoid amputation. Psychological recovery for individuals with lower extremity limb salvage has been examined in a number of studies. However, psychosocial reactions for individuals with upper extremity (UE) limb salvage are understudied in the literature. The purpose of this study was to explore the process of psychosocial adaptation for 3 trauma cases after UE limb salvage. The Reactions to Impairment and Disability Inventory was used to assess psychosocial adaptation. Physical function outcomes (pain, range of motion, edema, sensation, and dexterity) are presented. The Disabilities of the Arm, Shoulder, and Hand measure was used to assess perceived disability. Medical and rehabilitation history are discussed for each case, in order to provide in-depth understanding of the impact of these injuries. Reactions to injury varied across the cases; however, outcomes suggest that psychosocial adaptation may be influenced by the experience of pain, the ability to participate in valued roles and activities, and having a supportive social network. For this population, therapists may consider emphasizing pain management, focusing on client-centered goals and interventions, and facilitating peer support. Providers should closely monitor patients for signs of poor adaptation, such as hand-hiding behaviors. This study is among the first to examine psychological outcomes for the UE limb salvage population. Future research would be beneficial to provide deeper understanding of the psychosocial challenges for these individuals. Copyright © 2017 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  9. Vascular complications and microvascular free flap salvage: the role of thrombolytic agents.

    Science.gov (United States)

    Chang, Eric I; Mehrara, Babak J; Festekjian, Jaco H; Da Lio, Andrew L; Crisera, Christopher A

    2011-10-01

    Vascular thrombosis with flap loss is the most dreaded complication of microvascular free tissue transfer. Thrombolytic agents such as tissue plasminogen activator have been used clinically for free flap salvage in cases of pedicle thrombosis. Yet, there is a paucity of data in the literature validating the benefit of their use. A retrospective review of the breast reconstruction free flap database was performed at a single institution between the years of 1991-2010. The incidence of vascular complications (arterial and/or venous thrombosis) was examined to determine the role of adjuvant thrombolytic therapy in flap salvage. Pathologic examination was used to determine the incidence of fat necrosis after secondary revision procedures. Seventy-four cases were identified during the study period. In 41 cases, revision of the anastamoses was performed alone without thrombolytics with 38 cases of successful flap salvage (92.7%). In 33 cases, anastamotic revision was performed with adjuvant thrombolytic therapy, and successful flap salvage occurred in 28 of these cases (84.8%). Thrombolysis did not appear to significantly affect flap salvage. Interestingly, only two of the salvaged flaps that had received thrombolysis developed fat necrosis, whereas 11 of the nonthrombolysed flaps developed some amount fat necrosis (7.1% vs. 28.9%, P dissolution of thrombi in the microvasculature with the administration of thrombolytics. Although the use of adjuvant thrombolytic therapy does not appear to impact the rate of flap salvage, their use may have secondary benefits on overall flap outcomes. Copyright © 2011 Wiley-Liss, Inc.

  10. Stable vertical distraction osteogenesis of highly atrophic mandibles after ablative tumour surgery of the oral cavity--a salvage pathway for mandibular reconstruction prior to oral rehabilitation with dental implants.

    Science.gov (United States)

    Adolphs, Nicolai; Sproll, Christoph; Raguse, Jan-Dirk; Nelson, Katja; Heberer, Susanne; Scheifele, Christian; Klein, Martin

    2009-09-01

    Mandibular reconstruction is still a challenge for surgeons. Distraction osteogenesis (DO) might contribute in certain instances to solve this problem. A principal advantage of DO is the expansion of the surrounding soft tissues that accompanies the bony regeneration. In addition there is no donor site morbidity when compared with reconstruction by autologous bone grafting. However its application may be limited by the thinness of the mandible and the attendant fracture risk. This article describes a technique that combines stable internal fixation with vertical distraction of the alveolar ridge in six patients with critical mandibular thickness after ablative surgery for cancer of the oral cavity. Prior to implant insertion for further prosthodontic restoration stable vertical mandibular distraction produced an additional 11-20mm. Improvement of the surrounding soft tissues, especially intraorally was achieved and dental implants were inserted after bony consolidation. This method can be a useful salvage technique for the augmentation of the atrophic mandible in patients who are not able or willing to undergo the risks and disadvantages of established methods such as free autologous bone transfer or microsurgical techniques.

  11. Second-line salvage chemotherapy for transplant-eligible patients with Hodgkin's lymphoma resistant to platinum-containing first-line salvage chemotherapy.

    Science.gov (United States)

    Villa, Diego; Seshadri, Tara; Puig, Noemi; Massey, Christine; Tsang, Richard; Keating, Armand; Crump, Michael; Kuruvilla, John

    2012-05-01

    The management of patients with relapsed or refractory Hodgkin's lymphoma who achieve less than a partial response to first-line salvage chemotherapy is unclear. The objective of this study was to evaluate response and outcomes to second-line salvage and autologous stem cell transplantation in patients not achieving a complete or partial response to platinum-containing first-line salvage chemotherapy. Consecutively referred transplant-eligible patients with relapsed/refractory Hodgkin's lymphoma after primary chemotherapy received gemcitabine, dexamethasone, and cisplatin as first salvage chemotherapy. Those achieving a complete or partial response, and those with a negative gallium scan and stable disease with bulk chemotherapy and autologous stem cell transplantation. Patients with progressive disease or stable disease with a positive gallium scan or bulk ≥ 5 cm were given second salvage chemotherapy with mini-BEAM (carmustine, etoposide, cytarabine, melphalan). Patients who responded (according to the same definition) proceeded to autologous stem cell transplantation. One hundred and thirty-one patients with relapsed/refractory Hodgkin's lymphoma received first-line salvage gemcitabine, dexamethasone, and cisplatin; of these patients 99 had at least a partial response (overall response rate 76%). One hundred and twelve (85.5%) patients proceeded to autologous stem cell transplantation, while the remaining 19 (14.5%) patients received mini-BEAM. Among these 19 patients, six had at least a partial response (overall response rate 32%), and nine proceeded to autologous stem cell transplantation. The remaining ten patients received palliative care. Seven of the nine patients transplanted after mini-BEAM had a subsequent relapse. Patients receiving second salvage mini-BEAM had poor outcomes, with a 5-year progression-free survival rate of 11% and a 5-year overall survival rate of 20%. Patients who require a second salvage regimen to achieve disease control prior to

  12. Targeting a Novel Plasmodium falciparum Purine Recycling Pathway with Specific Immucillins

    Energy Technology Data Exchange (ETDEWEB)

    Ting, L; Shi, W; Lewandowicz, A; Singh, V; Mwakingwe, A; Birck, M R; Taylor Ringia, E A; Bench, G; Madrid, D C; Tyler, P C; Evans, G B; Furneaux, R H; Schramm, V L; Kim, K

    2004-05-19

    Plasmodium falciparum is unable to synthesize purine bases and relies upon purine salvage and purine recycling to meet its purine needs. We report that purines formed as products of the polyamine pathway are recycled in a novel pathway in which 5'-methylthioinosine is generated by adenosine deaminase. The action of P. falciparum purine nucleoside phosphorylase is a convergent step of purine salvage, converting both 5'-methylthioinosine and inosine to hypoxanthine. We used accelerator mass spectrometry to verify that 5'-methylthioinosine is an active nucleic acid precursor in P. falciparum. Prior studies have shown that inhibitors of purine salvage enzymes kill malaria, but potent malaria-specific inhibitors of these enzymes have not previously been described. 5'-methylthio-Immucillin-H, a transition state analogue inhibitor that is selective for malarial over human purine nucleoside phosphorylase, kills P. falciparum in culture. Immucillins are currently in clinical trials for other indications and may have application as antimalarials.

  13. Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO-IMPACT study.

    Science.gov (United States)

    Gore, John L; du Plessis, Marguerite; Santiago-Jiménez, María; Yousefi, Kasra; Thompson, Darby J S; Karsh, Lawrence; Lane, Brian R; Franks, Michael; Chen, David Y T; Bandyk, Mark; Bianco, Fernando J; Brown, Gordon; Clark, William; Kibel, Adam S; Kim, Hyung L; Lowrance, William; Manoharan, Murugesan; Maroni, Paul; Perrapato, Scott; Sieber, Paul; Trabulsi, Edouard J; Waterhouse, Robert; Davicioni, Elai; Lotan, Yair; Lin, Daniel W

    2017-08-01

    Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT. A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results. Patients completed validated surveys on prostate cancer (PCa)-specific decisional effectiveness and PCa-related anxiety. Before the Decipher test, observation was recommended for 89% of patients considering ART and 58% of patients considering SRT. After Decipher testing, 18% (95% confidence interval [95% CI], 12%-25%) of treatment recommendations changed in the ART arm, including 31% among high-risk patients; and 32% (95% CI, 24%-42%) of management recommendations changed in the salvage arm, including 56% among high-risk patients. Decisional Conflict Scale (DCS) scores were better after viewing Decipher test results (ART arm: median DCS before Decipher, 25 and after Decipher, 19 [Pfear of PCa disease recurrence in the ART arm (P = .02) and PCa-specific anxiety in the SRT arm (P = .05) decreased significantly among low-risk patients. Decipher results reported per 5% increase in 5-year metastasis probability were associated with the decision to pursue ART (odds ratio, 1.48; 95% CI, 1.19-1.85) and SRT (odds ratio, 1.41; 95% CI, 1.09-1.81) in multivariable logistic regression analysis. Knowledge of Decipher test results was associated with treatment decision making and improved decisional effectiveness among men with PCa who were considering ART and SRT. Cancer 2017;123:2850-59. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American

  14. Association of Preoperative Nutritional Status with Prognosis in Patients with Esophageal Cancer Undergoing Salvage Esophagectomy.

    Science.gov (United States)

    Sakai, Makoto; Sohda, Makoto; Miyazaki, Tatsuya; Yoshida, Tomonori; Kumakura, Yuji; Honjo, Hiroaki; Hara, Keigo; Ozawa, Daigo; Suzuki, Shigemasa; Tanaka, Naritaka; Yokobori, Takehiko; Kuwano, Hiroyuki

    2018-02-01

    To investigate whether malnutrition is associated with poor prognosis of patients who undergo salvage esophagectomy. We examined the association between the preoperative prognostic nutritional index (PNI) and prognosis of patients who undergo salvage esophagectomy. We conducted a single-center retrospective study and reviewed hospital patient records for tumor characteristics and patient outcomes. Univariate and multivariate survival analyses were carried out using the Cox proportional hazards regression model. Thirty-two patients with esophageal squamous cell carcinoma (ESCC) who underwent salvage esophagectomy between 1998 and 2015 at our Institute were included in this study. Univariate analysis revealed that clinical response (p=0.045), preoperative PNI (pnutritional status is associated with the prognosis of patients undergoing salvage esophagectomy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. A cost-utility analysis of amputation versus salvage for Gustilo type IIIB and IIIC open tibial fractures.

    Science.gov (United States)

    Chung, Kevin C; Saddawi-Konefka, Daniel; Haase, Steven C; Kaul, Gautam

    2009-12-01

    Lower extremity trauma is common. Despite an abundance of literature on severe injuries that can be treated with salvage or amputation, the appropriate management of these injuries remains uncertain. In this situation, a cost-utility analysis is an important tool in providing an evidence-based practice approach to guide treatment decisions. Costs following amputation and salvage were derived from data presented in a study that emerged from the Lower Extremity Assessment Project. The authors extracted relevant data on projected lifetime costs and analyzed them to include discounting and sensitivity analysis by considering patient age. The utilities for the various health states (amputation or salvage, including possible complications) were measured previously using the standard gamble method and a decision tree simulation to determine quality-adjusted life-years. Amputation is more expensive than salvage, independently of varied ongoing prosthesis needs, discount rate, and patient age at presentation. Moreover, amputation yields fewer quality-adjusted life-years than salvage. Salvage is deemed the dominant, cost-saving strategy. Unless the injury is so severe that salvage is not a possibility, based on this economic model, surgeons should consider limb salvage, which will yield lower costs and higher utility when compared with amputation.

  16. [Combination of etoposide, cisplatin and ifosfamide (VPH) in the salvage chemotherapy of relapsing or refractory aggressive malignant lymphoma. Study of 51 patients].

    Science.gov (United States)

    Eghbali, H; Catry-Thomas, I; Soubeyran, P; Bonnel, C; Hoerni, B

    1994-09-01

    Fifty-one patients with non-Hodgkin's lymphoma refractory or relapsing after CHOP-like regimen, underwent a salvage chemotherapy by VPH: etoposide 100 mg/m2/d, D1 to D3, cisplatin 20 mg/m2/d, D1 to D5, ifosfamide 1 g/m2/d D1 to D5, mesna 1.2 g/m2/d D1 to D5, every 4 weeks. Among 46 evaluable patients for efficacy, 21 (45.6%) achieved complete or partial response according to WHO criteria and 25 (54.3%) failed, while five cases (9.8% of all patients) were not evaluable (two initial complete remission before VPH, two early toxic deaths and one confusional syndrome). Thirty-five patients (68.6%) died of lymphoma, three (5.8%) of acute toxicity and 13 (25.5%) are alive: five in complete remission. The toxicity is mainly myelo-suppression, digestive and renal but could be managed as usually. Although the follow-up is short, this regimen appears effective in these circumstances after CHOP failure but it should be used early, before overt chemoresistance. It does not hinder a bone marrow transplantation programme.

  17. Ultra-early versus early salvage androgen deprivation therapy for post-prostatectomy biochemical recurrence in pT2-4N0M0 prostate cancer.

    Science.gov (United States)

    Taguchi, Satoru; Fukuhara, Hiroshi; Azuma, Takeshi; Suzuki, Motofumi; Fujimura, Tetsuya; Nakagawa, Tohru; Ishikawa, Akira; Kume, Haruki; Igawa, Yasuhiko; Homma, Yukio

    2014-10-16

    The optimal timing of salvage androgen deprivation therapy (ADT) for biochemical recurrence after radical prostatectomy is controversial. We compared the outcomes of ultra-early versus early salvage ADT. Among 855 patients undergoing radical prostatectomy at our institution between 2000 and 2012, we identified 121 with adjuvant-treatment-naïve pT2-4N0M0 prostate cancer who received salvage ADT for biochemical recurrence. These patients were divided into an ultra-early salvage ADT group (n = 51), who started salvage ADT before meeting the standardized definition of biochemical recurrence in Japan (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/ml), and an early salvage ADT group (n = 70) who started salvage ADT when they met the definition. The ultra-early ADT group consisted of those who started salvage ADT with a single PSA value ≥0.2 ng/ml (n = 30) or with two consecutive PSA values >0.1 ng/ml and rising (n = 21). The primary endpoint was biochemical recurrence after salvage ADT, defined as a single PSA value ≥0.2 ng/ml after PSA nadir following salvage ADT. Secondary endpoints were clinical metastasis and cancer-specific survival. A Cox proportional hazards model was used for multivariate analysis. The median follow-up was 65.5 months. Biochemical recurrence occurred in one patient (2.0%) in the ultra-early group and in 12 (17.1%) in the early salvage ADT group. Multivariate analysis identified ultra-early salvage ADT and preoperative Gleason score ≤7 as independent negative predictors of biochemical recurrence after salvage ADT. Only one patient in the early salvage ADT group developed clinical metastasis to a left supraclavicular lymph node, and no patient died from prostate cancer during follow-up. The major limitations of this study were its retrospective design, selection bias, and the possibility that the ultra-early salvage ADT group may have included patients without biochemical recurrence. Ultra-early salvage ADT

  18. Peripheral Sympathectomy for Raynaud's Phenomenon: A Salvage Procedure

    Directory of Open Access Journals (Sweden)

    Wen-Her Wang

    2006-10-01

    Full Text Available We retrospectively reviewed the effectiveness of peripheral sympathectomy for severe Raynaud's phenomenon. In this study, a total of 14 digits from six patients with chronic digital ischemic change were included. All patients had pain, ulcer, or gangrenous change in the affected digits and were unresponsive to pharmacologic or other nonsurgical therapies. In all cases, angiography showed multifocal arterial lesions, so microvascular reconstruction was unfeasible. Peripheral sympathectomy was performed as a salvage procedure to prevent digit amputation. The results were analyzed according to reduction of pain, healing of ulcers, and prevention of amputation. In 12 of the 14 digits, the ulcers healed and amputation was avoided. In the other two digits, the ulcers improved and progressive gangrene was limited. As a salvage procedure for Raynaud's phenomenon recalcitrant to conservative treatment, peripheral sympathectomy improves perfusion to ischemic digits and enables amputation to be avoided.

  19. Prognostic implications of immediate PSA response to early salvage radiotherapy.

    Science.gov (United States)

    Turner I I, Robert M; Yabes, Jonathan G; Woldemichael, Elen; Deutsch, Melvin M; Smith, Ryan P; Werner, Robert S; Jacobs, Bruce L; Nelson, Joel B

    2016-12-01

    Up to 25% of men with prostate cancer who undergo radical prostatectomy will recur. In this setting, salvage radiotherapy may cure patients with local recurrence, but is unable to cure those with occult metastatic disease. The objective of this study is to examine how prostate-specific antigen (PSA) response to radiotherapy predicts subsequent disease progression and survival. Using a prospectively populated database of 3089 men who underwent open radical prostatectomy, 212 patients (7%) were identified who received early salvage radiotherapy for biochemical recurrence. The main outcome was time to disease progression after salvage radiotherapy. Patients were stratified by PSA response after radiotherapy: 1) PSA radiotherapy at a median PSA of 0.20 ng/mL (IQR 0.10-0.30 ng/mL). At a median follow up of 47.3 months, a total of 52 (25%) patients experienced disease progression. On multivariable analysis, both persistent PSA (HR 5.12; 95% CI 1.98-13.23) and rising PSA (HR 16.55; 95% CI 6.61-41.48) were associated with increased risk of disease progression compared to those with PSA radiotherapy PSA, Gleason score, margin status, stage, and time to radiotherapy. Only rising PSA was associated with an increased risk of cancer-specific and all-cause mortality. PSA response is associated with the risk of disease progression following salvage radiotherapy. This information can be used to counsel patients on the potential need for additional therapy and identify those at greatest risk for progression and cancer-related mortality.

  20. Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Clausen, Anders R.; Girandon, Lenart; Ali, Ashfaq

    2012-01-01

    Deoxyribonucleotides are the building blocks of DNA and can be synthesized via de novo and salvage pathways. Deoxyribonucleoside kinases (EC 2.7.1.145) salvage deoxyribonucleosides by transfer of a phosphate group to the 5′ of a deoxyribonucleoside. This salvage pathway is well characterized....... Deoxyribonucleoside kinase activities were present in all tissues during all growth stages. In the A. thaliana genome, we identified two types of genes that could encode enzymes which are involved in the salvage of deoxyribonucleosides. Thymidine kinase activity was encoded by two thymidine kinase 1 (EC 2.......7.1.21)‐like genes (AtTK1a and AtTK1b). Deoxyadenosine, deoxyguanosine and deoxycytidine kinase activities were encoded by a single AtdNK gene. T‐DNA insertion lines of AtTK1a and AtTK1b mutant genes had normal growth, although AtTK1a AtTK1b double mutants died at an early stage, which indicates that AtTK1a...

  1. Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Anders Ranegaard Clausen, Anders Ranegaard; Girandon, Lenart; Ali, Ashfaq

    2012-01-01

    Deoxyribonucleotides are the building blocks of DNA and can be synthesized via de novo and salvage pathways. Deoxyribonucleoside kinases (EC 2.7.1.145) salvage deoxyribonucleosides by transfer of a phosphate group to the 5' of a deoxyribonucleoside. This salvage pathway is well characterized....... Deoxyribonucleoside kinase activities were present in all tissues during all growth stages. In the A. thaliana genome, we identified two types of genes that could encode enzymes which are involved in the salvage of deoxyribonucleosides. Thymidine kinase activity was encoded by two thymidine kinase 1 (EC 2.......7.1.21)-like genes (AtTK1a and AtTK1b). Deoxyadenosine, deoxyguanosine and deoxycytidine kinase activities were encoded by a single AtdNK gene. T-DNA insertion lines of AtTK1a and AtTK1b mutant genes had normal growth, although AtTK1a AtTK1b double mutants died at an early stage, which indicates that AtTK1a...

  2. Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Sage, Eva K.; Gehrmann, Mathias; Sedelmayr, Michael [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); Schmid, Thomas E.; Combs, Stephanie E.; Multhoff, Gabriele [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany); Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Partner Site Munich, Munich (Germany); Geinitz, Hans [Johannes Kepler University, Department of Radiation Oncology, Ordensklinikum Linz, Krankenhaus der Barmherzigen Schwestern and Medical Faculty, Linz (Austria); Duma, Marciana N. [Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Klinikum rechts der Isar, Munich (Germany); HelmholtzZentrum Muenchen, Department of Radiation Sciences (DRS), Institute of Innovate Radiotherapy (iRT), Munich (Germany)

    2017-08-15

    Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3{sup +} T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells. (orig.) [German] Die Strahlentherapie (RT) ist eine bewaehrte Behandlung beim primaeren und rezidivierten Prostatakarzinoms. In dieser Studie wurde der Einfluss einer definitiven und Salvage RT auf die Zusammensetzung der Lymphozytensubpopulationen verglichen, um potenzielle Immuneffekte einer RT zu analysieren. In die Studie wurden 33 Prostatakarzinompatienten eingeschlossen

  3. Isavuconazole as salvage therapy for mucormycosis

    Directory of Open Access Journals (Sweden)

    Bianca Graves

    2016-03-01

    Full Text Available Mucormycosis carries a high mortality rate with few therapeutic options available. We describe a man with pulmonary/splenic mucormycosis complicating hypoplastic myelodysplastic syndrome on a background of chronic kidney disease, who achieved a complete response with salvage isavuconazole therapy following intolerance of consecutive courses of liposomal amphotericin and posaconazole therapy.

  4. Metaethics Meets Virtue Epistemology: Salvaging Disagreement ...

    African Journals Online (AJOL)

    Virtue ethics and virtue epistemology shift the focus of evaluation from thin concepts to thick ones. Simon Blackburn has argued that a shift to thick ethical concepts dooms us to talking past one another. I contend that virtue epistemologists can answer. Blackburn's objection, thus salvaging genuine disagreement about the ...

  5. Pathway analysis comparison using Crohn's disease genome wide association studies.

    Science.gov (United States)

    Ballard, David; Abraham, Clara; Cho, Judy; Zhao, Hongyu

    2010-06-28

    The use of biological annotation such as genes and pathways in the analysis of gene expression data has aided the identification of genes for follow-up studies and suggested functional information to uncharacterized genes. Several studies have applied similar methods to genome wide association studies and identified a number of disease related pathways. However, many questions remain on how to best approach this problem, such as whether there is a need to obtain a score to summarize association evidence at the gene level, and whether a pathway, dominated by just a few highly significant genes, is of interest. We evaluated the performance of two pathway-based methods (Random Set, and Binomial approximation to the hypergeometric test) based on their applications to three data sets of Crohn's disease. We consider both the disease status as a phenotype as well as the residuals after conditioning on IL23R, a known Crohn's related gene, as a phenotype. Our results show that Random Set method has the most power to identify disease related pathways. We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways. Our results highlight the need to apply powerful gene score methods prior to pathway enrichment tests, and that controlling for genes that attain genome wide significance enable further biological insight.

  6. Pathway analysis comparison using Crohn's disease genome wide association studies

    Directory of Open Access Journals (Sweden)

    Cho Judy

    2010-06-01

    Full Text Available Abstract Background The use of biological annotation such as genes and pathways in the analysis of gene expression data has aided the identification of genes for follow-up studies and suggested functional information to uncharacterized genes. Several studies have applied similar methods to genome wide association studies and identified a number of disease related pathways. However, many questions remain on how to best approach this problem, such as whether there is a need to obtain a score to summarize association evidence at the gene level, and whether a pathway, dominated by just a few highly significant genes, is of interest. Methods We evaluated the performance of two pathway-based methods (Random Set, and Binomial approximation to the hypergeometric test based on their applications to three data sets of Crohn's disease. We consider both the disease status as a phenotype as well as the residuals after conditioning on IL23R, a known Crohn's related gene, as a phenotype. Results Our results show that Random Set method has the most power to identify disease related pathways. We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways. Conclusions Our results highlight the need to apply powerful gene score methods prior to pathway enrichment tests, and that controlling for genes that attain genome wide significance enable further biological insight.

  7. Salvage robot-assisted radical prostatectomy after brachytherapy: our experience

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2014-11-01

    Full Text Available In case of recurrence of prostate cancer after radiation therapy patient may be offered salvage radical prostatectomy (both open and laparoscopic/robotic, hormone therapy, and a number of alternative techniques such as salvage cryoablation, HIFU-therapy and brachytherapy. Results of monitoring of patients for 10 years after salvage treatment of prostate cancer are known only after salvage prostatectomy. Technically radical prostatectomy after radiation therapy is associated with a large number of complications if compared with primary radical prostatectomy. The most frequent complications after salvage prostatectomy include incontinence, stricture formation of urethrovesical anastomosis, rectal injury, acute urinary retention and infectious complications.

  8. Salvage robot-assisted radical prostatectomy after brachytherapy: our experience

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2014-01-01

    Full Text Available In case of recurrence of prostate cancer after radiation therapy patient may be offered salvage radical prostatectomy (both open and laparoscopic/robotic, hormone therapy, and a number of alternative techniques such as salvage cryoablation, HIFU-therapy and brachytherapy. Results of monitoring of patients for 10 years after salvage treatment of prostate cancer are known only after salvage prostatectomy. Technically radical prostatectomy after radiation therapy is associated with a large number of complications if compared with primary radical prostatectomy. The most frequent complications after salvage prostatectomy include incontinence, stricture formation of urethrovesical anastomosis, rectal injury, acute urinary retention and infectious complications.

  9. Better organized care via care pathways: A multicenter study.

    Directory of Open Access Journals (Sweden)

    Deborah Seys

    Full Text Available An increased need for efficiency and effectiveness in today's healthcare system urges professionals to improve the organization of care. Care pathways are an important tool to achieve this. The overall aim of this study was to analyze if care pathways lead to better organization of care processes. For this, the Care Process Self-Evaluation tool (CPSET was used to evaluate how healthcare professionals perceive the organization of care processes. Based on information from 2692 health care professionals gathered between November 2007 and October 2011 we audited 261 care processes in 108 organizations. Multilevel analysis was used to compare care processes without and with care pathways and analyze if care pathways led to better organization of care processes. A significant difference between care processes with and without care pathways was found. A care pathway in use led to significant better scores on the overall CPSET scale (p<0.001 and its subscales, "coordination of care" (p<0.001 and "follow-up of care" (p<0.001. Physicians had the highest score on the overall CPSET scale and the five subscales. Care processes organized by care pathways had a 2.6 times higher probability that the care process was well-organized. In around 75% of the cases a care pathway led to better organized care processes. Care processes supported by care pathways were better organized, but not all care pathways were well-organized. Managers can use care pathways to make healthcare professionals more aware of their role in the organization of the care process.

  10. Folate metabolic pathways in Leishmania

    Science.gov (United States)

    Vickers, Tim J.; Beverley, Stephen M.

    2012-01-01

    Trypanosomatid parasitic protozoans of the genus Leishmania are autotrophic for both folate and unconjugated pteridines. Leishmania salvage these metabolites from their mammalian hosts and insect vectors through multiple transporters. Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), which reduces both folates and unconjugated pteridines. PTR1 can act as a metabolic bypass of DHFR inhibition, reducing the effectiveness of existing antifolate drugs. Leishmania possess a reduced set of folate-dependent metabolic reactions and can salvage many of the key products of folate metabolism from their hosts. For example, they lack purine synthesis, which normally requires 10-formyltetrahydrofolate, and instead rely on a network of purine salvage enzymes. Leishmania elaborate at least three pathways for the synthesis of the key metabolite 5,10-methylene-tetrahydrofolate, required for the synthesis of thymidylate, and for 10-formyltetrahydrofolate, whose presumptive function is for methionyl-tRNAMet formylation required for mitochondrial protein synthesis. Genetic studies have shown that the synthesis of methionine using 5-methyltetrahydrofolate is dispensable, as is the activity of the glycine cleavage complex, probably due to redundancy with serine hydroxymethyltransferase. Although not always essential, the loss of several folate metabolic enzymes results in attenuation or loss of virulence in animal models, and a null DHFR-TS mutant has been used to induce protective immunity. The folate metabolic pathway provides numerous opportunities for targeted chemotherapy, with strong potential for ‘repurposing’ of compounds developed originally for treatment of human cancers or other infectious agents. PMID:22023442

  11. Simulation and Analysis of Passive Rolling Compensation of High Sea Salvage System

    Directory of Open Access Journals (Sweden)

    Lin Liqun

    2017-01-01

    Full Text Available Method and device of a flexible interception and salvage system was introduced in this paper. In order to study the effect of wave motion on salvage operation, we proposed a passive wave compensation scheme that utilizes a combination of variable-pitch cylinders and accumulators, and established the mathematical vibration model of the rolling motion of the salvage compensation system. With the relationships between the stiffness coefficient and the accumulator parametric of passive compensated gas-liquid system, we determined the effective compensation stiffness range through Mathematica simulation analysis. The relationship between the roll displacement of the salvage arm and the initial volume Vo of the accumulator has been analysed. The results show that the accumulatorVo in a certain range has a great influence on the passive compensation. However, when the volume is greater than 20m3, the compensation effect is weakened, and tend to a certain value, irrespective of the passive system accumulator volume capacity, it does not achieve full compensation. The results have important guidance on the design and optimization of rolling passive compensation of the practical high sea salvage system.

  12. Outcomes After Severe Distal Tibia, Ankle, and/or Foot Trauma: Comparison of Limb Salvage Versus Transtibial Amputation (OUTLET).

    Science.gov (United States)

    Bosse, Michael J; Teague, David; Reider, Lisa; Gary, Joshua L; Morshed, Saam; Seymour, Rachel B; Toledano, James; Cannada, Lisa K; Steverson, Barbara; Scharfstein, Daniel O; Luly, Jason; MacKenzie, Ellen J

    2017-04-01

    Severe foot and ankle injuries are complex and challenging to treat, often requiring multiple operations to salvage the limb contributing to a prolonged healing period. There is some evidence to suggest that early amputation for some patients may result in better long-term outcomes than limb salvage. The challenge is to identify the regional injury burden for an individual that would suggest a better outcome with an amputation. The OUTLET study is a prospective, multicenter observational study comparing 18-month outcomes after limb salvage versus early amputation among patients aged 18-60 years with severe distal tibia, ankle, and foot injuries. This study aims to build upon the previous work of the Lower Extremity Assessment Project by identifying the injury and patient characteristics that help define a subgroup of salvage patients who will have better outcomes had they undergone a transtibial amputation.

  13. LIMB SALVAGE IN DIABETIC FOOT INFECTION

    OpenAIRE

    J. Ramanaiah; M. Pavani; N. Dinesh Kumar Reddy; Sai Subrahmanyam

    2017-01-01

    BACKGROUND Diabetic foot infections are a frequent clinical problem. About 50% of patients with diabetic foot infections who have foot amputations die within five years. Properly managed most can be cured, but many patients needlessly undergo amputations because of improper diagnostic and therapeutic approaches. Limb salvage procedures may prevent eventual limb loss, the need of a major limb amputation, decrease total cost and may restore full ambulation earlier. MATERIALS ...

  14. Leucocyte filtration of salvaged blood during cardiac surgery : effect on red blood cell function in concentrated blood compared with diluted blood

    NARCIS (Netherlands)

    Gu, Y. John; de Vries, Adrianus J.; Hagenaars, J. Ans M.; van Oeveren, Willem

    2009-01-01

    Objective: Leucocyte filtration of salvaged blood has been suggested to prevent patients from receiving activated leucocytes during autotransfusion in cardiac surgery. This study examines whether leucocyte filtration of salvaged blood affects the red blood cell (RBC) function and whether there is a

  15. LIMB SALVAGE IN DIABETIC FOOT INFECTION

    Directory of Open Access Journals (Sweden)

    J. Ramanaiah

    2017-02-01

    Full Text Available BACKGROUND Diabetic foot infections are a frequent clinical problem. About 50% of patients with diabetic foot infections who have foot amputations die within five years. Properly managed most can be cured, but many patients needlessly undergo amputations because of improper diagnostic and therapeutic approaches. Limb salvage procedures may prevent eventual limb loss, the need of a major limb amputation, decrease total cost and may restore full ambulation earlier. MATERIALS AND METHODS Seventy five septic diabetic feet were treated with NPWT between 2014 and 2016. Debridement with or without partial foot amputation was followed. Wound progress was measured using a digital scanner. A limb was considered salvaged if complete healing was achieved without any or with minor amputation through or below the ankle. RESULTS In this series, 33 cases were managed initially by debridement and slough excision, 11 patients underwent incision and drainage for abscess and three patients underwent fasciotomy. Seven cases who presented with gangrene of toes were treated with ray amputation. Below-knee amputation was done in 21 cases. In most of the cases, limb salvage was possible. CONCLUSION A comprehensive treatment approach incorporating surgical and nonsurgical therapies are required to avoid major limb amputations in severe diabetic foot infections.

  16. Salvage brachytherapy for locally recurrent prostate cancer after external beam radiotherapy

    Directory of Open Access Journals (Sweden)

    Yasuhiro Yamada

    2015-01-01

    Full Text Available External beam radiotherapy (EBRT is a standard treatment for prostate cancer. Despite the development of novel radiotherapy techniques such as intensity-modulated conformal radiotherapy, the risk of local recurrence after EBRT has not been obviated. Various local treatment options (including salvage prostatectomy, brachytherapy, cryotherapy, and high-intensity focused ultrasound [HIFU] have been employed in cases of local recurrence after primary EBRT. Brachytherapy is the first-line treatment for low-risk and selected intermediate-risk prostate tumors. However, few studies have examined the use of brachytherapy to treat post-EBRT recurrent prostate cancer. The purpose of this paper is to analyze the current state of our knowledge about the effects of salvage brachytherapy in patients who develop locally recurrent prostate cancer after primary EBRT. This article also introduces our novel permanent brachytherapy salvage method.

  17. Heterologous reconstruction and radiotherapy: the role of latissimus dorsi flap as a salvage.

    Science.gov (United States)

    Cagli, B; Manzo, M J; Tenna, S; Piombino, L; Poccia, I; Persichetti, P

    2012-01-01

    The versatility and effectiveness of the latissimus dorsi flap as salvage in complicated heterologous reconstructions, especially with regards to radiotherapy, is examined in this retrospective review of our 10-year experience. Twenty-eight patients with complicated heterologous reconstruction were divided into three groups: (1) 15 patients with mastectomy and immediately expander reconstruction and radiation; (2) 9 patients with previous QUART, salvage mastectomy and immediate expander reconstruction; (3) 4 patients with radical mastectomy without radiation. The most common complications were capsular contracture and radiodermitis in Group 1, cutaneous fistula in Group 2. Recipient site complications, after latissimus dorsi flap, were observed in seven patients (five smokers), five in Group 1, two in Group 2. Cosmetic result was scored excellent and good in 25 patients (89%). This study shows as a favourable and cosmetically satisfactory reconstruction can be achieved when combining an implant with a latissimus dorsi flap allowing the salvage of the entire heterologous reconstruction.

  18. An outbreak of foodborne botulism associated with food sold at a salvage store in Texas.

    Science.gov (United States)

    Kalluri, Pavani; Crowe, Colleen; Reller, Megan; Gaul, Linda; Hayslett, James; Barth, Suzanne; Eliasberg, Stacey; Ferreira, J; Holt, Kristin; Bengston, Steve; Hendricks, Kate; Sobel, Jeremy

    2003-12-01

    Foodborne botulism is caused by potent neurotoxins of Clostridium botulinum. We investigated a large outbreak of foodborne botulism among church supper attendees in Texas. We conducted a cohort study of attendees and investigated the salvage store that sold the implicated foods. We identified 15 cases of botulism (40%) among 38 church supper attendees. Nine patients (60%) had botulinum toxin type A detected in stool specimens. The diagnosis was delayed in 3 cases. Fifteen (63%) of 24 attendees who ate a chili dish developed botulism (relative risk, undefined; Pdogs. An unopened container of brand X chili yielded type A toxin. Brand X chili was purchased at a salvage store where perishable foods were inadequately refrigerated. Our investigation highlights the need to improve clinicians' awareness of botulism. More rigorous and more unannounced inspections may be necessary to detect food mishandling at salvage stores.

  19. Low success rate of salvage surgery for testicular torsion in newborns

    DEFF Research Database (Denmark)

    Jensen, Rie Overgaard; Pedersen, Mark Ellebæk; Rasmussen, Lars

    2015-01-01

    INTRODUCTION: Testicular torsion within the first 30 days of life is rare. The treatment is controversial, and the prognosis for testis viability varies from 0 to 40% in the literature. The aim of this study was to review our institutional results for surgery for testicular torsion in the neonatal...... period with a special focus on salvage surgery. METHODS: Patient records were reviewed for all children in the age up to 30 days who were operated for testicular torsion at our hospital during the past 20 years. RESULTS: A total of 13 patients were included, two with bilateral affection. Emergency...... was only salvaged in cases with urgent surgery at symptom recognition. Cases that presented within the first day of life resulted in a non-salvageable testis despite emergency surgery. The reason may be prenatal torsion. Doctor's delay was common for this rare disease. FUNDING: not relevant. TRIAL...

  20. Large-scale pathway-based analysis of bladder cancer genome-wide association data from five studies of European background.

    Directory of Open Access Journals (Sweden)

    Idan Menashe

    Full Text Available Pathway analysis of genome-wide association studies (GWAS offer a unique opportunity to collectively evaluate genetic variants with effects that are too small to be detected individually. We applied a pathway analysis to a bladder cancer GWAS containing data from 3,532 cases and 5,120 controls of European background (n = 5 studies. Thirteen hundred and ninety-nine pathways were drawn from five publicly available resources (Biocarta, Kegg, NCI-PID, HumanCyc, and Reactome, and we constructed 22 additional candidate pathways previously hypothesized to be related to bladder cancer. In total, 1421 pathways, 5647 genes and ∼90,000 SNPs were included in our study. Logistic regression model adjusting for age, sex, study, DNA source, and smoking status was used to assess the marginal trend effect of SNPs on bladder cancer risk. Two complementary pathway-based methods (gene-set enrichment analysis [GSEA], and adapted rank-truncated product [ARTP] were used to assess the enrichment of association signals within each pathway. Eighteen pathways were detected by either GSEA or ARTP at P≤0.01. To minimize false positives, we used the I(2 statistic to identify SNPs displaying heterogeneous effects across the five studies. After removing these SNPs, seven pathways ('Aromatic amine metabolism' [P(GSEA = 0.0100, P(ARTP = 0.0020], 'NAD biosynthesis' [P(GSEA = 0.0018, P(ARTP = 0.0086], 'NAD salvage' [P(ARTP = 0.0068], 'Clathrin derived vesicle budding' [P(ARTP = 0.0018], 'Lysosome vesicle biogenesis' [P(GSEA = 0.0023, P(ARTP<0.00012], 'Retrograde neurotrophin signaling' [P(GSEA = 0.00840], and 'Mitotic metaphase/anaphase transition' [P(GSEA = 0.0040] remained. These pathways seem to belong to three fundamental cellular processes (metabolic detoxification, mitosis, and clathrin-mediated vesicles. Identification of the aromatic amine metabolism pathway provides support for the ability of this approach to identify pathways

  1. The Stringent Response Induced by Phosphate Limitation Promotes Purine Salvage in Agrobacterium fabrum.

    Science.gov (United States)

    Sivapragasam, Smitha; Deochand, Dinesh K; Meariman, Jacob K; Grove, Anne

    2017-10-31

    Agrobacterium fabrum induces tumor growth in susceptible plant species. The upregulation of virulence genes that occurs when the bacterium senses plant-derived compounds is enhanced by acidic pH and limiting inorganic phosphate. Nutrient starvation may also trigger the stringent response, and purine salvage is among the pathways expected to be favored under such conditions. We show here that phosphate limitation induces the stringent response, as evidenced by production of (p)ppGpp, and that the xdhCSML operon encoding the purine salvage enzyme xanthine dehydrogenase is upregulated ∼15-fold. The xdhCSML operon is under control of the TetR family transcription factor XdhR; direct binding of ppGpp to XdhR attenuates DNA binding, and the enhanced xdhCSML expression correlates with increased cellular levels of (p)ppGpp. Xanthine dehydrogenase may also divert purines away from salvage pathways to form urate, the ligand for the transcription factor PecS, which in the plant pathogen Dickeya dadantii is a key regulator of virulence gene expression. However, urate levels remain low under conditions that produce increased levels of xdhCSML expression, and neither acidic pH nor limiting phosphate results in induction of genes under control of PecS. Instead, expression of such genes is induced only by externally supplemented urate. Taken together, our data indicate that purine salvage is favored during the stringent response induced by phosphate starvation, suggesting that control of this pathway may constitute a novel approach to modulating virulence. Because bacterial purine catabolism appears to be unaffected, as evidenced by the absence of urate accumulation, we further propose that the PecS regulon is induced by only host-derived urate.

  2. Salvage Surgery after Radiation Failure in T1/T2 Larynx Cancer: Outcomes following Total versus Conservation Surgery.

    Science.gov (United States)

    Cheraghlou, Shayan; Kuo, Phoebe; Mehra, Saral; Yarbrough, Wendell G; Judson, Benjamin L

    2017-12-01

    Objective After radiation failure for early T-stage larynx cancer, national guidelines recommend salvage surgery. Total laryngectomy and conservation laryngeal surgery with an open or endoscopic approach are both used. Beyond single-institution studies, there is a lack of evidence concerning the outcomes of these procedures. We aim to study whether treatment with conservation laryngeal surgery is associated with poorer outcomes than treatment with total laryngectomy as salvage surgery after radiation failure for T1/T2 larynx cancers. Study Design A retrospective study was conducted of adult squamous cell larynx cancer cases in the National Cancer Database diagnosed from 2004 to 2012. Setting Commission on Cancer cancer programs in the United States. Methods Demographic, facility, tumor, and survival variables were included in the analyses. Multivariate survival regressions as well as univariate Kaplan-Meier analyses were conducted. Results Slightly more than 7% of patients receiving radiotherapy for T1/T2 larynx cancers later received salvage surgery. Salvage with partial laryngectomy was not associated with diminished survival as compared with total laryngectomy. However, positive surgical margins were associated with worse outcomes (hazard ratio, 1.782; P = .001), and a larger percentage of patients receiving partial laryngectomy had positive margins than those receiving total laryngectomy. Facility characteristics were not associated with differences in salvage surgery type or outcomes. Conclusion In recognition of the inherent selection bias, patients who experienced recurrences after radiation for T1/T2 larynx cancer and underwent conservation salvage laryngeal surgery demonstrated clinical outcomes similar to those of patients undergoing salvage total laryngectomy. Increased rates of positive surgical margins were observed among patients undergoing salvage conservation surgery.

  3. Salvage surgery in recurrent head and neck squamous cell carcinoma: Oncologic outcome and predictors of disease free survival

    OpenAIRE

    Hamoir, Marc; Holvoet, Emma; Ambroise, Jérôme; Lengelé, Benoît; Schmitz, Sandra

    2017-01-01

    Objective Salvage surgery in recurrent SCCHN is associated with poor outcomes. This study aimed to better identify suitable surgical candidates and those at high risk of new recurrence. Materials and methods Single-center retrospective analysis of 109 patients undergoing salvage surgery for recurrent SCCHN. Univariate and multivariate analyses were used to identify prognostic factors affecting disease-free survival (DFS). Results The following factors showed a significant impact on DFS: Disea...

  4. Factors Influencing Rate of Testicular Salvage in Acute Testicular Torsion at a Tertiary Pediatric Center

    Directory of Open Access Journals (Sweden)

    Ramachandra, Puneeta

    2015-01-01

    Full Text Available Introduction: Studies have demonstrated that variables other than duration of symptoms can affect outcomes in children with acute testicular torsion. We examined demographic and logistical factors, including inter-hospital transfer, which may affect outcomes at a tertiary pediatric referral center. Methods: We reviewed charts of all pediatric patients with acute testicular torsion during a five-year period. Data were collected regarding age, insurance type, socioeconomic status, duration of symptoms prior to presentation, transfer status, time of day, time to surgical exploration, and testicular salvage. Results: Our study included 114 patients. Testicular salvage was possible in 55.3% of patients. Thirty-one percent of patients included in the study were transferred from another facility. Inter-hospital transfer did not affect testicular salvage rate. Time to surgery and duration of pain were higher among patients who underwent orchiectomy versus orchidopexy. Patients older than eight years of age were more likely to undergo orchidopexy than those younger than eight (61.5% vs. 30.4%, p=0.01. Ethnicity, insurance type, or time of day did not affect the testicular salvage rates. On multivariate analysis, only duration of symptoms less than six hours predicted testicular salvage (OR 22.5, p<0.001. Conclusion: Even though inter-hospital transfer delays definitive surgical management, it may not affect testicular salvage rates. Time to presentation is the most important factor in predicting outcomes in children with acute testicular torsion. [West J Emerg Med. 2015;16(1:190–194.

  5. Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

    Directory of Open Access Journals (Sweden)

    V. A. Solodkiy

    2016-01-01

    Full Text Available Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT as a method of treating local recurrence.The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

  6. Comparative study of visual pathways in owls (Aves: Strigiformes).

    Science.gov (United States)

    Gutiérrez-Ibáñez, Cristián; Iwaniuk, Andrew N; Lisney, Thomas J; Wylie, Douglas R

    2013-01-01

    Although they are usually regarded as nocturnal, owls exhibit a wide range of activity patterns, from strictly nocturnal, to crepuscular or cathemeral, to diurnal. Several studies have shown that these differences in the activity pattern are reflected in differences in eye morphology and retinal organization. Despite the evidence that differences in activity pattern among owl species are reflected in the peripheral visual system, there has been no attempt to correlate these differences with changes in the visual regions in the brain. In this study, we compare the relative size of nuclei in the main visual pathways in nine species of owl that exhibit a wide range of activity patterns. We found marked differences in the relative size of all visual structures among the species studied, both in the tectofugal and the thalamofugal pathway, as well in other retinorecipient nuclei, including the nucleus lentiformis mesencephali, the nucleus of the basal optic root and the nucleus geniculatus lateralis, pars ventralis. We show that the barn owl (Tyto alba), a species widely used in the study of the integration of visual and auditory processing, has reduced visual pathways compared to strigid owls. Our results also suggest there could be a trade-off between the relative size of visual pathways and auditory pathways, similar to that reported in mammals. Finally, our results show that although there is no relationship between activity pattern and the relative size of either the tectofugal or the thalamofugal pathway, there is a positive correlation between the relative size of both visual pathways and the relative number of cells in the retinal ganglion layer. Copyright © 2012 S. Karger AG, Basel.

  7. Reconstitution of an efficient thymidine salvage pathway in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Vernis, L.; Piskur, Jure; Diffley, J.F.X.

    2003-01-01

    as an equilibrative nucleoside transporter. By also deleting the gene encoding thymidylate synthase (CDC21) we have constructed strains that are entirely dependent upon exogenous thymidine for viability and that can grow with normal kinetics at low thymidine concentrations. Using this novel approach, we show...

  8. New function for Escherichia coli xanthosine phophorylase (xapA): genetic and biochemical evidences on its participation in NAD+ salvage from nicotinamide

    Science.gov (United States)

    2014-01-01

    Background In an effort to reconstitute the NAD+ synthetic pathway in Escherichia coli (E. coli), we produced a set of gene knockout mutants with deficiencies in previously well-defined NAD+de novo and salvage pathways. Unexpectedly, the mutant deficient in NAD+de novo and salvage pathway I could grow in M9/nicotinamide medium, which was contradictory to the proposed classic NAD+ metabolism of E. coli. Such E. coli mutagenesis assay suggested the presence of an undefined machinery to feed nicotinamide into the NAD+ biosynthesis. We wanted to verify whether xanthosine phophorylase (xapA) contributed to a new NAD+ salvage pathway from nicotinamide. Results Additional knockout of xapA further slowed down the bacterial growth in M9/nicotinamide medium, whereas the complementation of xapA restored the growth phenotype. To further validate the new function of xapA, we cloned and expressed E. coli xapA as a recombinant soluble protein. Biochemical assay confirmed that xapA was capable of using nicotinamide as a substrate for nicotinamide riboside formation. Conclusions Both the genetic and biochemical evidences indicated that xapA could convert nicotinamide to nicotinamide riboside in E. coli, albeit with relatively weak activity, indicating that xapA may contribute to a second NAD+ salvage pathway from nicotinamide. We speculate that this xapA-mediated NAD+ salvage pathway might be significant in some bacteria lacking NAD+de novo and NAD+ salvage pathway I or II, to not only use nicotinamide riboside, but also nicotinamide as precursors to synthesize NAD+. However, this speculation needs to be experimentally tested. PMID:24506841

  9. New function for Escherichia coli xanthosine phophorylase (xapA): genetic and biochemical evidences on its participation in NAD(+) salvage from nicotinamide.

    Science.gov (United States)

    Dong, Wei-Ren; Sun, Cen-Cen; Zhu, Guan; Hu, Shi-Hua; Xiang, Li-Xin; Shao, Jian-Zhong

    2014-02-08

    In an effort to reconstitute the NAD(+) synthetic pathway in Escherichia coli (E. coli), we produced a set of gene knockout mutants with deficiencies in previously well-defined NAD(+)de novo and salvage pathways. Unexpectedly, the mutant deficient in NAD(+) de novo and salvage pathway I could grow in M9/nicotinamide medium, which was contradictory to the proposed classic NAD(+) metabolism of E. coli. Such E. coli mutagenesis assay suggested the presence of an undefined machinery to feed nicotinamide into the NAD(+) biosynthesis. We wanted to verify whether xanthosine phophorylase (xapA) contributed to a new NAD(+) salvage pathway from nicotinamide. Additional knockout of xapA further slowed down the bacterial growth in M9/nicotinamide medium, whereas the complementation of xapA restored the growth phenotype. To further validate the new function of xapA, we cloned and expressed E. coli xapA as a recombinant soluble protein. Biochemical assay confirmed that xapA was capable of using nicotinamide as a substrate for nicotinamide riboside formation. Both the genetic and biochemical evidences indicated that xapA could convert nicotinamide to nicotinamide riboside in E. coli, albeit with relatively weak activity, indicating that xapA may contribute to a second NAD(+) salvage pathway from nicotinamide. We speculate that this xapA-mediated NAD(+) salvage pathway might be significant in some bacteria lacking NAD(+) de novo and NAD(+) salvage pathway I or II, to not only use nicotinamide riboside, but also nicotinamide as precursors to synthesize NAD(+). However, this speculation needs to be experimentally tested.

  10. Salvage prostate cryoablation for recurrent localized prostate cancer after radiotherapy

    Directory of Open Access Journals (Sweden)

    Justin Ji-Yuen Siu

    2016-12-01

    Full Text Available Salvage prostate cryoablation (SCA for recurrent localized prostate cancer after radiotherapy has been studied in Western countries for more than a decade. We present our experience of SCA in a Taiwanese medical center. We performed four cases of SCA for recurrent localized prostate cancer after radiotherapy. The data recorded included age, cancer stage, prostate-specific antigen (PSA level, Gleason score, prostate volume and patient outcome. The median follow-up period was 17 months. All cases were biopsy-proven to have residual cancer before cryoablation. After SCA, 25% of the patients reached undetectable PSA levels, 50% showed response but did not reach undetectable levels, and 25% showed no decrease in PSA. The median recurrence-free duration after SCA was 18 months in the patients who experienced a decrease in PSA. ADT was initiated after SCA for the patient who did not show any response, and bone metastasis was later diagnosed in that patient. Most patients experienced obstructive voiding problems after SCA, which improved over time. SCA is a safe salvage option for prostate cancer patients with local recurrence after RT. The preliminary results are encouraging. More extensive imagery to exclude extra-glandular disease is warranted before SCA. A longer follow-up period and larger sample size are necessary to delineate the benefits more conclusively.

  11. Pyrimidine Salvage Enzymes Are Essential for De Novo Biosynthesis of Deoxypyrimidine Nucleotides in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Christopher Leija

    2016-11-01

    Full Text Available The human pathogenic parasite Trypanosoma brucei possess both de novo and salvage routes for the biosynthesis of pyrimidine nucleotides. Consequently, they do not require salvageable pyrimidines for growth. Thymidine kinase (TK catalyzes the formation of dTMP and dUMP and is one of several salvage enzymes that appear redundant to the de novo pathway. Surprisingly, we show through analysis of TK conditional null and RNAi cells that TK is essential for growth and for infectivity in a mouse model, and that a catalytically active enzyme is required for its function. Unlike humans, T. brucei and all other kinetoplastids lack dCMP deaminase (DCTD, which provides an alternative route to dUMP formation. Ectopic expression of human DCTD resulted in full rescue of the RNAi growth phenotype and allowed for selection of viable TK null cells. Metabolite profiling by LC-MS/MS revealed a buildup of deoxypyrimidine nucleosides in TK depleted cells. Knockout of cytidine deaminase (CDA, which converts deoxycytidine to deoxyuridine led to thymidine/deoxyuridine auxotrophy. These unexpected results suggested that T. brucei encodes an unidentified 5'-nucleotidase that converts deoxypyrimidine nucleotides to their corresponding nucleosides, leading to their dead-end buildup in TK depleted cells at the expense of dTTP pools. Bioinformatics analysis identified several potential candidate genes that could encode 5'-nucleotidase activity including an HD-domain protein that we show catalyzes dephosphorylation of deoxyribonucleotide 5'-monophosphates. We conclude that TK is essential for synthesis of thymine nucleotides regardless of whether the nucleoside precursors originate from the de novo pathway or through salvage. Reliance on TK in the absence of DCTD may be a shared vulnerability among trypanosomatids and may provide a unique opportunity to selectively target a diverse group of pathogenic single-celled eukaryotes with a single drug.

  12. Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.

    OpenAIRE

    Mateos, F A; Puig, J G; Jiménez, M L; Fox, I H

    1987-01-01

    We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with [8-14C]adenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme-deficient patients and 6.0 +/- 0.7% (mean +/- SE) in four normal subjects. Fructose infusion increased urinary radioac...

  13. Using motion planning to study protein folding pathways.

    Science.gov (United States)

    Amato, Nancy M; Song, Guang

    2002-01-01

    We present a framework for studying protein folding pathways and potential landscapes which is based on techniques recently developed in the robotics motion planning community. Our focus in this work is to study the protein folding mechanism assuming we know the native fold. That is, instead of performing fold prediction, we aim to study issues related to the folding process, such as the formation of secondary and tertiary structure, and the dependence of the folding pathway on the initial denatured conformation. Our work uses probabilistic roadmap (PRM) motion planning techniques which have proven successful for problems involving high-dimensional configuration spaces. A strength of these methods is their efficiency in rapidly covering the planning space without becoming trapped in local minima. We have applied our PRM technique to several small proteins (~60 residues) and validated the pathways computed by comparing the secondary structure formation order on our paths to known hydrogen exchange experimental results. An advantage of the PRM framework over other simulation methods is that it enables one to easily and efficiently compute folding pathways from any denatured starting state to the (known) native fold. This aspect makes our approach ideal for studying global properties of the protein's potential landscape, most of which are difficult to simulate and study with other methods. For example, in the proteins we study, the folding pathways starting from different denatured states sometimes share common portions when they are close to the native fold, and moreover, the formation order of the secondary structure appears largely independent of the starting denatured conformation. Another feature of our technique is that the distribution of the sampled conformations is correlated with the formation of secondary structure and, in particular, appears to differentiate situations in which secondary structure clearly forms first and those in which the tertiary

  14. A study of the transition pathways of school level scholarship ...

    African Journals Online (AJOL)

    Hennie

    educational intervention two or three years post school, in order to investigate their pathways to their destinations of work and study. ...... race theory. In WR Allen, RT Teranishi & M. Bonous-Hammarth (eds). As the world turns: Implications of global shifts in higher education for theory, research and practice. Bingley, UK:.

  15. The outcome of rectal cancer after early salvage surgery following transanal endoscopic microsurgery seems promising

    DEFF Research Database (Denmark)

    Levic, Katarina; Bulut, Orhan; Hesselfeldt, Peter

    2012-01-01

    Transanal endoscopic microsurgery (TEM) allows locally complete resection of early rectal cancer as an alternative to conventional radical surgery. In patients with unfavourable post-TEM histology, salvage surgery can be performed. The aim of this study was to evaluate the results of early radical...... surgery after TEM for rectal cancer....

  16. Prognostic factors for survival after salvage total laryngectomy following radiotherapy or chemoradiation failure

    DEFF Research Database (Denmark)

    Wulff, N B; Andersen, E; Kristensen, C A

    2017-01-01

    OBJECTIVE: The primary aims were to determine the rates of and prognostic factors for overall survival, disease-specific survival and disease-free survival following salvage total laryngectomy. DESIGN: Retrospective longitudinal study. SETTING: Tertiary medical centres. PARTICIPANTS: A total of 1...

  17. Remilling of salvaged wood siding coated with lead-based paint. Part 1, Lead exposure

    Science.gov (United States)

    Robert H. Falk; John J. Janowiak; Stephen D. Cosper; Susan A. Drozdz

    2005-01-01

    It is well known that the lead contained in lead-based paint (LBP) can pose a serious human health risk if ingested. In our nation’s building infrastructure, millions of meters of high quality salvageable lumber have been coated with LBP. The study presented in this and a companion paper investigated the feasibility of producing several standardized wood product...

  18. Functional Outcome After Successful Internal Fixation Versus Salvage Arthroplasty of Patients With a Femoral Neck Fracture

    NARCIS (Netherlands)

    Zielinski, Stephanie M.; Keijsers, Noël L.; Praet, Stephan F. E.; Heetveld, Martin J.; Bhandari, Mohit; Wilssens, Jean Pierre; Patka, Peter; van Lieshout, Esther M. M.; Swiontkowski, Marc; Devereaux, Philip J.; Guyatt, Gordon; Jeray, Kyle; Liew, Susan; Schemitsch, Emil H.; Thabane, Lehana; Walter, Stephen; Sprague, Sheila; Scott, Taryn; Swinton, Marilyn; Viveiros, Helena; Heels-Ansdell, Diane; Zhou, Qi; Buckingham, Lisa; Duraikannan, Aravin; Maddock, Deborah; Agel, Julie; Rangan, Amar; Hanusch, Birgit; Della Rocca, Gregory J.; Haverlag, Robert; Slobogean, Gerard; Katz, Jeffrey; Gillespie, Brenda; Greendale, Gail A.; Guy, Pierre; Hartman, Curtis; Rubin, Craig; Waddell, James; McCormack, Robert; Apostle, Kelly; Boyer, Dory; Moola, Farhad; Perey, Bertrand; Stone, Trevor; Viskontas, Darius; Lemke, H. Michael; Zomar, Mauri; Moon, Karyn; Moon, Raely; Oatt, Amber; Buckley, Richard E.; Duffy, Paul; Korley, Robert; Puloski, Shannon; Johnston, Kelly; Powell, James; Carcary, Kimberly; Sanders, David; Lawendy, Abdel; Tiezer, Christina; Stephen, David; Kreder, Hans; Jenkinson, Richard; Nousiainene, Markku; Axelrod, Terry; Murnaghan, John; Nam, Diane; Richards, Robin; Rodriguez-Elizalde, Sebastian; Wadey, Veronica; Yee, Albert; Milner, Katrine; Kunz, Monica; Macnevin, Melanie; Cagaanan, Ria; Bicknell, Ryan; Yach, Jeff; Bardana, Davide; Wood, Gavin; Harrison, Mark; Yen, David; Lambert, Sue; Howells, Fiona; Ward, Angela; Coles, Chad; Leighton, Ross; Biddulph, Michael; Johnston, David; Glazebrook, Mark; Alexander, David; Coady, Cathy; Dunbar, Michael; Trask, Kelly; MacDonald, Shelley; Dobbin, Gwen; Ahn, Henry; Hall, Jeremy A.; McKee, Michael D.; Whelan, Daniel B.; Nauth, Aaron; Vicente, Milena; Wild, Lisa; Khan, Ryan; Hidy, Jennifer; Zalzal, Paul; Brien, Heather; Naumetz, V.; Weening, Brad; Simunovic, Nicole; Wai, Eugene K.; Papp, Steve; Gofton, Wade T.; Liew, Allen; Kingwell, Stephen P.; Roffey, Darren M.; Borsella, Vivian; Avram, Victoria; Oliver, Todd M.; Jones, Vicki; Jones, Clifford; Ringler, James; Endres, Terrence; Sietsema, Debra L.; Jeray, Kyle J.; Broderick, J. Scott; Goetz, David R.; Pace, Thomas B.; Schaller, Thomas M.; Porter, Scott E.; Tanner, Stephanie L.; Snider, Rebecca G.; Nastoff, Lauren A.; Bielby, Shea A.; Marcantonio, Andrew J.; Iorio, Richard; Garfi, John; Prayson, Michael J.; Laughlin, Richard; Rubino, Joseph; May, Jedediah; Rieser, Geoffrey Ryan; Dulaney-Cripe, Liz; Gayton, Chris; Switzer, Julie A.; Cole, Peter A.; Anderson, Sarah A.; Lafferty, Paul M.; Li, Mengnai; Ly, Thuan V.; Marston, Scott B.; Foley, Amy L.; Vang, Sandy; Wright, David M.; Vallier, Heather A.; Dolenc, Andrea; Robinson, Chalitha; Gorczyca, John T.; Gross, Jonathan M.; Humphrey, Catherine A.; Kates, Stephen; Noble, Krista; McIntyre, Allison W.; Pecorella, Kaili; Shaer, James; Schrickel, Tyson; Hileman, Barbara; Davis, Craig A.; Weinerman, Stewart; Weingarten, Peter; Stull, Philip; Lindenbaum, Stephen; Hewitt, Michael; Schwappach, John; Baker, Janell K.; Mehta, Samir; Esterhai, John; Ahn, Jaimo; Horan, Annamarie D.; McGinnis, Kelly; Kaminiski, Christine A.; Kowalski, Brynn N.; Cannada, Lisa K.; Karges, David; Hill, Leslie; Tarkin, Ivan; Siska, Peter; Gruen, Gary; Evans, Andrew; Farrell, Dana J.; Irrgang, James; Luther, Arlene; Keeve, Jonathan P.; Anderson, Christopher G.; McDonald, Michael D.; Hoffman, Jodi M.; Jenkins, Mark; Dumais, Jules; Romero, Amanda W.; Hsu, Joseph R.; Ficke, James; Charlton, Michael; Napierala, Matthew; Fan, Mary; Cross, William W.; Cass, Joseph R.; Sems, Stephen A.; Torchia, Michael E.; Scrabeck, Tyson; Sagebien, Carlos A.; Butler, Mark S.; Monica, James T.; Seuffert, Patricia; Brennan, Michael L.; Probe, Robert; Kile, Evelyn; Mills, Kelli; Clipper, Lydia; Yu, Michelle; Erwin, Katie; Tornetta, Paul; Carlisle, Hope; Silva, Heather; Archdeacon, Michael; Finnan, Ryan; Le, Toan; Wyrick, John; Hess, Shelley; McBeth, Jessica; Aurang, Kamran; Zohman, Gary; Peterson, Brett; Huff, Roger B.; Baele, Joseph; Weber, Timothy; Edison, Matt; Schmidt, Andrew H.; Westberg, Jerald R.; DePaolo, Charles J.; Alosky, Rachel; Shell, Leslie E.; Hampton, Lynne; Shepard, Stephanie; Nanney, Tracy; Cuento, Claudine; Shively, Karl; Ertl, Janos P.; Mullis, Brian; Parr, J. Andrew; Worman, Ripley; Frizzell, Valda; Moore, Molly M.; Tobias, Erin; Thomas, Emily; Cantu, Robert V.; Henderson, Eric R.; Eickhoff, Linda S.; Zamorano, David P.; Pourmand, Deeba; Lawson, Deanna; Hammerberg, E. Mark; Stahel, Philip; Hak, David; Mauffrey, Cyril; Gibula, Douglas; Gissel, Hannah; Henderson, Corey; Crist, Brett D.; Murtha, Yvonne M.; McPherson, Melinda; Anderson, Linda K.; Dohm, Michael P.; Linehan, Colleen; Pilling, Lindsey; Horwitz, Daniel; Strohecker, Kent; Lewis, Courtland G.; Caminiti, Stephanie; Sullivan, Raymond J.; Roper, Elizabeth; Obremsky, William; Kregor, Philip; Richards, Justin E.; Stringfellow, Kenya; Goslings, J. Carel; Ponsen, Jan; Bronkhorst, Maarten W. G. A.; Guicherit, Onno R.; Eversdijk, Martin G.; Peters, Rolf; den Hartog, Dennis; van Waes, Oscar J. F.; Oprel, Pim; de Rijcke, Piet A. R.; Koppert, Cees L.; Buijk, Steven E.; Groenendijk, Richard P. R.; Dawson, Imro; Tetteroo, Geert W. M.; Bruijninckx, Milko M. M.; Doornebosch, Pascal G.; de Graaf, Eelco J. R.; Visser, Gijs A.; Stockman, Heyn; Silvis, Rob; Snellen, Jaap P.; Rijbroek, Bram; Scheepers, Joris J. G.; Vermeulen, Erik G. J.; Siroen, Michel P. C.; Vuylsteke, Ronald; Brom, Hans L. F.; Rijna, Herman; Roukema, Gert R.; Josaputra, Hong; Keller, Paul; de Rooij, Peter D.; Kuiken, Hans; Boxma, Han; Clefken, Berry I.; Liem, Ronald; Rhemrev, Steven J.; Bosman, Coks H. R.; de Mol van Otterloo, Alexander; Hoogendoorn, Jochem; de Vries, Alexander C.; Meylaerts, Sven A. G.; Poolman, Rudolf W.; Simons, Maarten P.; van der Heijden, Frank H. W. M.; Willems, W. Jaap; de Meulemeester, Frank R. A. J.; van der Hart, Cor P.; Turckan, Kahn; Festen, Sebastiaan; de Nies, Frank; Out, Nico J. M.; Bosma, Jan; van der Elst, Maarten; van der Pol, Carmen C.; van't Riet, Martijne; Karsten, Tom M.; de Vries, Mark; Stassen, Laurents P. S.; Schep, Niels W. L.; Schmidt, G. Ben; Hoffman, W. H.; Segers, Michiel J. M.; Zijl, Jacco A. C.; Verhoeven, Bart; Smits, Anke B.; de Vries, Jean Paul P. M.; Fioole, Bram; Hoeven, Henk van der; Theunissen, Evert B. M.; de Vries Reilingh, Tammo S.; Govaert, Lonneke; Wittich, Philippe; de Brauw, Maurits; Wille, Jan; Go, Peter M. N. Y. M.; Ritchie, Ewan D.; Wessel, Ronald N.; Hammacher, Eric R.; Verhofstad, Michiel H. J.; Meijer, Joost; van Egmond, Teun; van der Brand, Igor; van der Vis, Harm; Campo, Martin; Verhagen, Ronald; Albers, Albert Robert; Zurcher, Arthur W.; von Kampen, Albert; Biert, Jan; van Vugt, Arie B.; Edwards, Michael J. R.; Blokhuis, Taco J.; Frölke, Jan Paul M.; Geeraedts, Leo M. G.; Gardeniers, Jean W. M.; Tan, Edward T. C. H.; Poelhekke, Lodewijk M. S. J.; de Waal Malefijt, Maarten C.; Schreurs, Bart; Simmermacher, Rogier K. J.; van Mulken, Jeroen; van Wessem, Karlijn; van Gaalen, Steven M.; Leenen, Luke P. H.; Bedi, Harvinder; Carr, Ashley; Chia, Andrew; Csongvay, Steven; Curry, Hamish; Doig, Stephen; Donohue, Craig; Edwards, Elton; Etherington, Greg; Gong, Andrew; Jain, Arvind; Li, Doug; Miller, Russell; Moaveni, Ash; Russ, Matthias; Ton, Lu; Wang, Otis; Murdoch, Zoe; Sage, Claire; Frihagen, Frede; Clarke-Jenssen, John; Hjorthaug, Geir; Ianssen, Torben; Amundsen, Asgeir; Brattgjerd, Jan Egil; Borch, Tor; Bøe, Berthe; Flatøy, Bernhard; Hasselund, Sondre; Haug, Knut Jørgen; Hemlock, Kim; Hoseth, Tor Magne; Jomaas, Geir; Kibsgård, Thomas; Kristiansen, Bjorn; Lona, Tarjei; Moatshe, Gilbert; Müller, Oliver; Molund, Marius; Nicolaisen, Tor; Nilsen, Fredrik; Rydinge, Jonas; Smedsrud, Morten; Stødle, Are; Trommer, Axel; Ugland, Stein; Vesterhus, Elise Berg; Brekke, Anne Christine; Sharma, Ateet; Sanghavi, Amir; Tetsworth, Kevin; Geoff, Donald; Weinrach, Patrick; yang, Steven; Halliday, Brett; Gervais, Trevor; Holt, Michael; Flynn, Annette; Prasad, Amal Shankar; Mishra, Vimlesh; Gupta, Ajay; Jain, Niraj; Bahatia, Mahesh; Arora, Vinod; Bhatia, Mahesh; Sundaresh, D. C.; Khanna, Angshuman; Rai, Anil; Pirpiris, Marinis; Love, David; Bucknill, Andrew; Farrugia, Richard J.; Dadi, Akhil; Palla, Naveen; Rai, B. Sachidananda; Rajakumar, Janakiraman; Cherian, Joe Joseph; Olakkengil, Davy J.; Sharma, Gaurav

    2014-01-01

    Objectives: To determine patient independency, health-related and disease-specific quality of life (QOL), gait pattern, and muscle strength in patients after salvage arthroplasty for failed internal fixation of a femoral neck fracture. Design: Secondary cohort study to a randomized controlled trial.

  19. Regeneration response to tornado and salvage harvesting in a bottomland forest

    Science.gov (United States)

    John L. Nelson; John W. Groninger; Loretta L. Battaglia; Charles M. Ruffner

    2010-01-01

    A direct hit from an F4 tornado on May 2003, followed by a partial salvage logging operation at Mermet Lake State Conservation Area on the Ohio River bottoms of southern IL have provided a rare opportunity to assess the responses of a bottomland hardwood forest to severe wind and soil disturbances. The study area encompasses 700 acres and is representative of many...

  20. Remilling of salvaged wood siding coated with lead-based paint. Part 2, Wood product yield

    Science.gov (United States)

    John J. Janowiak; Robert H. Falk; Brian W. Beakler; Richard G. Lampo; Thomas R. Napier

    2005-01-01

    Many U.S. military buildings being targeted for removal contain large quantities of potentially reusable wood materials. In this study, we evaluated approximately 2180 m (7,152 ft) of painted Douglas-fir siding salvaged from U.S. Army barracks. Utilizing a conventional woodworking molder, we evaluated the feasibility of producing several standardized wood product...

  1. Functional Outcome After Successful Internal Fixation Versus Salvage Arthroplasty of Patients With a Femoral Neck Fracture

    NARCIS (Netherlands)

    S.M. Zielinski (Stephanie); N.L. Keijsers (Noël); S.F.E. Praet (Stephan); M.J. Heetveld (Martin); M. Bhandari (Mohit); Wilssens, J.P.; P. Patka (Peter); E.M.M. van Lieshout (Esther)

    2014-01-01

    textabstractObjectives: To determine patient independency, health-related and disease-specific quality of life (QOL), gait pattern, and muscle strength in patients after salvage arthroplasty for failed internal fixation of a femoral neck fracture. Design: Secondary cohort study to a randomized

  2. External and internal hemipelvectomy for sarcomas of the pelvic girdle : consequences of limb-salvage treatment

    NARCIS (Netherlands)

    Ham, SJ; Veth, RPH; van Horn, [No Value; Eisma, WH; Hoekstra, HJ; Schraffordt Koops, H.

    1997-01-01

    The outcome of different Limb-saving treatment modalities for pelvic girdle sarcoma is controversial. The oncological and functional results after 11 external and 10 internal hemipelvectomies and the consequences of limb-salvage treatment were studied in 21 consecutive patients with primary bone (19

  3. {sup 18}F-Choline Positron Emission Tomography/Computed Tomography–Driven High-Dose Salvage Radiation Therapy in Patients With Biochemical Progression After Radical Prostatectomy: Feasibility Study in 60 Patients

    Energy Technology Data Exchange (ETDEWEB)

    D' Angelillo, Rolando M., E-mail: r.dangelillo@unicampus.it [Radiation Oncology, Campus Bio-Medico University, Rome (Italy); Sciuto, Rosa [Department of Nuclear Medicine, Regina Elena National Cancer Institute, Rome (Italy); Ramella, Sara [Radiation Oncology, Campus Bio-Medico University, Rome (Italy); Papalia, Rocco [Department of Urology, Regina Elena National Cancer Institute, Rome (Italy); Jereczek-Fossa, Barbara A. [Department of Radiation Oncology, European Institute of Oncology, Milan (Italy); Department of Health Sciences, University of Milan, Milan (Italy); Trodella, Luca E.; Fiore, Michele [Radiation Oncology, Campus Bio-Medico University, Rome (Italy); Gallucci, Michele [Department of Urology, Regina Elena National Cancer Institute, Rome (Italy); Maini, Carlo L. [Department of Nuclear Medicine, Regina Elena National Cancer Institute, Rome (Italy); Trodella, Lucio [Radiation Oncology, Campus Bio-Medico University, Rome (Italy)

    2014-10-01

    Purpose: To retrospectively review data of a cohort of patients with biochemical progression after radical prostatectomy, treated according to a uniform institutional treatment policy, to evaluate toxicity and feasibility of high-dose salvage radiation therapy (80 Gy). Methods and Materials: Data on 60 patients with biochemical progression after radical prostatectomy between January 2009 and September 2011 were reviewed. The median value of prostate-specific antigen before radiation therapy was 0.9 ng/mL. All patients at time of diagnosis of biochemical recurrence underwent dynamic {sup 18}F-choline positron emission tomography/computed tomography (PET/CT), which revealed in all cases a local recurrence. High-dose salvage radiation therapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT-positive area. Toxicity was recorded according to the Common Terminology Criteria for Adverse Events, version 3.0, scale. Results: Treatment was generally well tolerated: 54 patients (90%) completed salvage radiation therapy without any interruption. Gastrointestinal grade ≥2 acute toxicity was recorded in 6 patients (10%), whereas no patient experienced a grade ≥2 genitourinary toxicity. No grade 4 acute toxicity events were recorded. Only 1 patient (1.7%) experienced a grade 2 gastrointestinal late toxicity. With a mean follow-up of 31.2 months, 46 of 60 patients (76.6%) were free of recurrence. The 3-year biochemical progression-free survival rate was 72.5%. Conclusions: At early follow-up, {sup 18}F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity.

  4. Protection of the Environment and the International Salvage ...

    African Journals Online (AJOL)

    Eghosa O. Ekhator

    Eghosa Osa Ekhator, PhD (Hull), LL.M (Hull), LL.B (Benin); barrister and solicitor of the. Supreme Court of Nigeria. 1 The origins of salvage are ancient and existed in old legal systems such as the Roman epoch amongst ...... 114 John Willmer, (Q.C) 'Salvage and Current Legal Problems' cited in Mandaraka-. Sheppard ...

  5. Dismal salvage of testicular torsion: A call to action! | Maranya ...

    African Journals Online (AJOL)

    Background: Testicular ischaemia and infarction in cases of torsion depend on the duration and degree of twisting. Early evaluation and treatment are associated with high salvage reports. Objective: To determine the salvage rates of testicular torsion in selected hospitals at the Coast Province of Kenya Design: A ...

  6. Limb salvage: When, where, and how?

    Directory of Open Access Journals (Sweden)

    Ajay Puri

    2015-01-01

    Full Text Available From an era where amputation was the only option to the current day function preserving resections and complex reconstructions has been a major advance in the treatment of musculoskeletal sarcomas. The objectives of extremity reconstruction after oncologic resection include providing skeletal stability where necessary, adequate wound coverage to allow early subsequent adjuvant therapy, optimising the aesthetic outcome and preservation of functional capability with early return to function. This article highlights the concepts of surgical margins in oncology, discusses the principles governing safe surgical resection in these tumors and summarises the current modalities and recent developments relevant to reconstruction after limb salvage. The rationale of choice of a particular resection modality and the unique challenges of reconstruction in skeletally immature individuals are also discussed. Striking the right balance between adequate resection, while yet retaining or reconstructing tissue for acceptable function and cosmesis is a difficult task. Complications are not uncommon and patients and their families need to be counseled regarding the potential setbacks that may occur in the course of their eventual road to recovery, Limb salvage entails a well orchestrated effort involving various specialties and better outcomes are likely to be achieved with centralization of expertise at regional centers.

  7. The mangled extremity and attempt for limb salvage

    Directory of Open Access Journals (Sweden)

    Kontogeorgakos Vasileios A

    2009-02-01

    Full Text Available Abstract Background The decision, whether to amputate or reconstruct a mangled extremity remains the subject of extensive debate since multiple factors influence the decision. Methods Sixty three patients with high energy extremity trauma and attempts at limb salvage were retrospectively reviewed. We analyzed 10 cases of massive extremity trauma where there was made an attempt to salvage limbs, although there was a controversy between salvage and amputation. Results All of the patients except one had major vascular injury and ischemia requiring repair. Three patients died. All of the remaining patients were amputated within 15 days after the salvage procedure, mainly because of extremity sepsis. Seven patients required treatment at the intensive care unit. All patients had at least 2 reconstruction procedures and multiple surgical debridements. Conclusion The functional outcome should be considered realistically before a salvage decision making for extremities with indeterminate prognosis.

  8. Comparative Oncologic and Toxicity Outcomes of Salvage Radical Prostatectomy Versus Nonsurgical Therapies for Radiorecurrent Prostate Cancer: A Meta-Regression Analysis.

    Science.gov (United States)

    Philippou, Yiannis; Parker, Richard A; Volanis, Dimitrios; Gnanapragasam, Vincent J

    2016-06-01

    In the absence of randomised controlled trials comparing the oncologic, toxicity, and functional outcomes of salvage radical prostatectomy (SRP), salvage high-intensity focused ultrasound (SHIFU), salvage brachytherapy (SBT), and salvage cryotherapy (SCT), controversy exists as to the optimal salvage modality in radiorecurrent prostate cancer. We carried out a meta-regression analysis to determine whether there is a difference in oncologic, toxicity, and functional outcomes using data from original publications of salvage modalities in the postradiation setting. We performed a systematic review of PubMed/Medline citations according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. We included 63 articles in the analysis (25 on SRP, 8 on SHIFU, 16 on SCT, 14 on SBT). Median values of the following variables were extracted from each study: patient age, length of follow-up, prostate-specific antigen (PSA) before radiotherapy (RT), PSA before salvage therapy, Gleason score before RT, and time interval between RT and salvage therapy. Functional, toxicity, and oncologic outcomes were measured according to rates of impotence, incontinence, fistula formation, urethral strictures, and biochemical recurrence. Meta-regression adjusting for confounders found no significant difference in oncologic outcomes between SRP and nonsurgical salvage modalities. SBT, SCT, and SHIFU appeared to have better continence outcomes than SRP. No significant difference in toxicity outcomes between modalities was found, although limitations such as reporting, selection, and publication bias and between-study heterogeneity must also be considered with these conclusions. Oncologic outcomes are comparable for SRP and all three nonsurgical salvage modalities. We found no significant differences in toxicity outcomes among modalities; however, SRP appears to be associated with worse rates of urinary incontinence than SBT, SCT, and SHIFU. We performed a meta

  9. A Comparison of Four-Year Health Outcomes following Combat Amputation and Limb Salvage.

    Science.gov (United States)

    Melcer, Ted; Walker, Jay; Bhatnagar, Vibha; Richard, Erin; Sechriest, V Franklin; Galarneau, Michael

    2017-01-01

    Little research has described the long-term health outcomes of patients who had combat-related amputations or leg-threatening injuries. We conducted retrospective analysis of Department of Defense and Department of Veterans Affairs health data for lower extremity combat-injured patients with (1) unilateral amputation within 90 days postinjury (early amputation, n = 440), (2) unilateral amputation more than 90 days postinjury (late amputation, n = 78), or (3) leg-threatening injuries without amputation (limb salvage, n = 107). Patient medical records were analyzed for four years postinjury. After adjusting for group differences, early amputation was generally associated with a lower or similar prevalence for adverse physical and psychological diagnoses (e.g., pain, osteoarthritis, posttraumatic stress disorder) versus late amputation and/or limb salvage. By contrast, early amputation was associated with an increased likelihood of osteoporosis during the first year postinjury. The prevalence of posttraumatic stress disorder increased for all patient groups over four years postinjury, particularly in the second year. The different clinical outcomes among combat extremity injured patients treated with early amputation, late amputation, or limb salvage highlight their different healthcare requirements. These findings can inform and optimize the specific treatment pathways that address the physical and psychological healthcare needs of such patients over time.

  10. Post-fire salvage logging alters species composition and reduces cover, richness, and diversity in Mediterranean plant communities.

    Science.gov (United States)

    Leverkus, Alexandro B; Lorite, Juan; Navarro, Francisco B; Sánchez-Cañete, Enrique P; Castro, Jorge

    2014-01-15

    An intense debate exists on the effects of post-fire salvage logging on plant community regeneration, but scant data are available derived from experimental studies. We analyzed the effects of salvage logging on plant community regeneration in terms of species richness, diversity, cover, and composition by experimentally managing a burnt forest on a Mediterranean mountain (Sierra Nevada, S Spain). In each of three plots located at different elevations, three replicates of three treatments were implemented seven months after the fire, differing in the degree of intervention: "Non-Intervention" (all trees left standing), "Partial Cut plus Lopping" (felling 90% of the trees, cutting the main branches, and leaving all the biomass in situ), and "Salvage Logging" (felling and piling the logs, and masticating the woody debris). Plant composition in each treatment was monitored two years after the fire in linear point transects. Post-fire salvage logging was associated with reduced species richness, Shannon diversity, and total plant cover. Moreover, salvaged sites hosted different species assemblages and 25% lower cover of seeder species (but equal cover of resprouters) compared to the other treatments. Cover of trees and shrubs was also lowest in Salvage Logging, which could suggest a potential slow-down of forest regeneration. Most of these results were consistent among the three plots despite plots hosting different plant communities. Concluding, our study suggests that salvage logging may reduce species richness and diversity, as well as the recruitment of woody species, which could delay the natural regeneration of the ecosystem. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Salvage radiotherapy for locoregionally recurrent extrahepatic bile duct cancer after radical surgery.

    Science.gov (United States)

    Kim, Eunji; Kim, Yi-Jun; Kim, Kyubo; Song, Changhoon; Kim, Jae-Sung; Oh, Do-Youn; Nam, Eun Mi; Chie, Eui Kyu

    2017-12-01

    This study evaluated the outcome of salvage radiotherapy for locoregionally recurrent extrahepatic bile duct cancer. We performed a retrospective review of 23 extrahepatic bile duct cancer patients who underwent radiotherapy with or without concomitant chemotherapy for isolated locoregional recurrence after radical surgery between August 2001 and September 2013. The median disease-free interval was 11.8 months. Salvage radiotherapy was delivered to the recurrent tumour with or without initial operation bed up to a median dose of 54 Gy (range, 45-60). 18 patients received concomitant chemotherapy. The median follow-up period was 14.2 months for all patients, and 48.8 months for survivors. The median overall survival and progression-free survival (PFS) were 18.4 (range, 4.4-114.6) and 15.5 months (range, 1.6-114.6), respectively. On multivariate analysis, the use of concomitant chemotherapy was a favourable prognostic factor for PFS (p = 0.027), and prolonged disease-free interval (≥1 year) was associated with a significantly poor overall survival (p = 0.047). Grade 3 or higher toxicities did not occur in follow-up period. Salvage radiotherapy showed promising survival outcomes in locoregional recurrence of extrahepatic bile duct cancer. Our results indicated that concomitant chemotherapy was associated with improved PFS. Concurrent chemoradiotherapy can be a viable salvage treatment option in selected patients. Advances in knowledge: Locoregional recurrence is the most common pattern of failure after radical resection in extrahepatic bile duct cancer. In this study, salvage radiotherapy showed favourable survival outcomes without severe complications in locoregionally recurrent extrahepatic bile duct cancer patients.

  12. Limb salvage after vascular reconstruction followed by tissue transfer during the Global War on Terror.

    Science.gov (United States)

    Casey, Kevin; Sabino, Jennifer; Weiss, Jeffrey S; Kumar, Anand; Valerio, Ian

    2015-03-01

    Combat extremity wounds are complex and frequently require an immediate vascular reconstruction in the operational environment followed by delayed tissue coverage at a stateside medical treatment facility. The purpose of this study was to evaluate limb salvage outcomes after combat-related vascular reconstruction that subsequently required delayed soft tissue coverage during the Global War on Terror. Patients who incurred a war-related extremity injury necessitating an immediate vascular intervention followed by definitive limb reconstruction requiring flap coverage from combat injuries were reviewed. Patient demographics, types of vascular and extremity injuries, and surgical interventions were examined. Outcomes included limb salvage, primary and secondary graft patency, flap outcomes, and complications. Differences between upper extremities (UEs) and lower extremities (LEs) were compared. From 2003 to 2012, 27 patients were treated for combat-related extremity injuries with an immediate vascular reconstruction followed by delayed tissue coverage. Fifteen LEs and 12 UEs were treated. The mean age was 24 years. An explosion was the cause in 77% of patients, with a mean Injury Severity Score (ISS) of 19. An autogenous vein bypass was the most common reconstruction performed in 20 patients (74%). Other vascular repairs included a primary repair, a patch angioplasty with bovine pericardium, and a bypass with use of a prosthetic graft. Eight patients (30%) had a concomitant venous injury, and 23 (85%) had a bone fracture. Thirty flaps were performed at a mean of 33 days from the original injury. Pedicle flaps were used in 24 limbs and free tissue flaps in six limbs. Muscle, fasciocutaneous, bone, and composite flaps were used for tissue coverage. At a mean follow-up of 16 months, primary patency rates of all arterial reconstructions were 66% in the UE and 53% in the LE (P = .69). Secondary patency rates were 100% in the UE and 86% in the LE (P = .48). The overall limb

  13. Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases. A comparative analysis

    Energy Technology Data Exchange (ETDEWEB)

    Romagna, Alexander; Schwartz, Christoph; Tonn, Joerg-Christian; Kreth, Friedrich-Wilhelm [Ludwig-Maximilians-University, Department of Neurosurgery, Munich (Germany); Egensperger, Rupert [Ludwig-Maximilians-University, Center for Neuropathology and Prion Research, Munich (Germany); Watson, Juliana; Belka, Claus; Nachbichler, Silke Birgit [Ludwig-Maximilians-University, Department of Radiation-Oncology, Munich (Germany)

    2016-11-15

    Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk-benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT. Patients with small untreated (n = 20) or pre-irradiated (n =28) suspected metastases intended for upfront or salvage SBT, respectively, were consecutively included. Temporary iodine-125 implants were used (median reference dose: 50 Gy, median dose rate: 15 cGy/h). Cumulative biologically effective doses (BED) were calculated and used for risk assessment. Treatment toxicity was classified according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Upfront SBT was initiated in 20 patients and salvage SBT in 23. In 5 patients, salvage SBT was withheld because of proven radiation-induced lesions. Treatment groups exhibited similar epidemiologic data except for tumor size (which was slightly smaller in the salvage group). One-year local/distant tumor control rates after upfront and salvage SBT were similar (94 %/65 % vs. 87 %/57 %, p = 0.45, respectively). Grade I/II toxicity was suffered by 2 patients after salvage SBT (cumulative BED: 192.1 Gy{sub 3} and 249.6 Gy{sub 3}). No toxicity-related risk factors were identified. SBT combines diagnostic yield with effective treatment in selected patients. The low toxicity rate in the salvage group points to protective radiobiologic characteristics of continuous low-dose rate irradiation. Upfront and salvage SBT are similarly effective and safe. Histologic reevaluation should be reconsidered after previous radiotherapy to avoid under- or overtreatment. (orig.) [German] Daten zu Risiko und Effizienz ablativer

  14. [Salvage therapy for castration-refractory prostate cancer resistant to docetaxel].

    Science.gov (United States)

    Takayama, Tatsuya; Sugiyama, Takayuki; Furuse, Hiroshi; Yajima, Takashi; Suzuki, Takahisa; Kai, Fumitake; Nagata, Masao; Otsuka, Atsushi; Ishii, Yasuo; Ozono, Seiichiro

    2013-11-01

    To evaluate the treatment for castration-refractory prostate cancer (CRPC) resistant to docetaxel Among 45 patients with CRPC treated with docetaxel (70-75 mg/m2) every 3 to 4 weeks at Hamamatsu University Hospital from January 2004 to July 2012, 19 patients underwent salvage treatments. We retrospectively analyzed the medical records of 14 patients except for 5 patients who were enrolled in clinical trials. The median age and serum prostate-specific antigen (PSA) level at starting salvage treatments was 71 years (range 45 to 79) and 241.1 ng/mL (range 3.06 to 1,643.0), respectively. All patients maintained castration status. Salvage treatments include DTX (30 mg/m2) + cisplatin (CDDP) (70 mg/m2)/carboplatin (Area under the curve = 4), etoposide + CDDP, paclitaxel + CDDP, cyclophosphamide, S-l, tegaful-uracil. The reasons why 14 patients moved to salvage treatments after DTX were progressive disease in 12 patients and adverse events in 2. Eight patients had a PSA response, 3 patients>50% and 5 patients<50%. Six patients had a PSA progression. The median overall survival was 10.4 months (range 4.1 to 27.3). All patients died of cancer, 13 patients with prostate cancer and one patient with lung adenocarcinoma. Most adverse events were mild. Transitory grade 3 leukopenia was observed in 2 patients, and grade 3 anemia in 2. No grade 4 toxicities were noted. All salvage treatments without grade 4 toxicities described in this study may be acceptable in the patients with CRPC progressing after docetaxel although the effect would be limited.

  15. Salvage cryotherapy with third-generation technology for locally recurrent prostate cancer after radiation therapy.

    Science.gov (United States)

    Lian, Huibo; Yang, Rong; Lin, Tingsheng; Wang, Wei; Zhang, Gutian; Guo, Hongqian

    2016-09-01

    To present the intermediate results of the use of third-generation cryotherapy as salvage treatment for locally recurrent prostate cancer after radiation therapy. From January 2006 to July 2010, 32 patients with locally recurrent prostate cancer after radiotherapy underwent salvage cryoablation using third-generation technology. Biochemical recurrence-free survival (BRFS) was defined as the time period from salvage treatment to the date of biochemical recurrence (Phoenix definition of nadir +2 ng/ml). Complications were classified as grades 1-5 according to the modified Clavien system. Multivariate logistic regression analysis was performed to identify potential risk factors associated with recurrence after salvage cryotherapy. The median follow-up was 63 months (range 38-92). Mild complications (grades 1 and 2) included mild incontinence (9.4 %), acute rectal pain (31.3 %), hematuria (6.3 %), scrotal edema (9.4 %), urinary tract infection (3.1 %), lower urinary tract symptoms (15.6 %) and erectile dysfunction (57.1 %). Severe events (grade 3) included severe incontinence (3.1 %) and urethral sloughing (3.1 %). The rate of rectourethral fistula and urinary retention was absent. The 5-year overall survival was 92.3 %. The 5-year cancer-specific survival was 100 %. The 5-year BRFS rate using the Phoenix definition was 43.5 %. A multivariate analysis disclosed that PSA at cryoablation was the only predictive factor for biochemical recurrence. Salvage cryotherapy using third-generation technology offers a safe and effective alternative for locally recurrent prostate cancer after radiation therapy. Additional studies with longer follow-up are necessary to determine the sustained efficacy of this procedure.

  16. In vitro analysis of cell salvage blood collection with a laparoscopic suction device.

    Science.gov (United States)

    Nagarsheth, Nimesh P; Fenske, Suzanne Silverman; Shah, Apurva; Moshier, Erin; Stahl, Rosalyn; Shander, Aryeh

    2013-01-01

    To determine whether cell salvage blood collection with a laparoscopic suction device is inferior to use of a traditional Yankauer suction device. Prospective, in vitro study. Academic teaching hospital. Individual units of donated packed red blood cells were diluted with normal saline solution to a hematocrit level of 21%. The blood was divided into 2 equal parts and then suctioned with either a laparoscopic suction device or a Yankauer plastic suction catheter tip connected to double-lumen cell salvage tubing with a diluted heparin drip and a vacuum pressure of 100 mm Hg. Collected blood was processed with a cell salvage device. Red blood cell volume was calculated by multiplying the hematocrit level by the total volume of blood product at the time of testing. Mean hemolysis indexes were compared between the laparoscopic and Yankauer method of blood collection by use of a 2-sample t test. Assuming a clinically acceptable limit of loss to be 7%, percent loss in red blood cell volume was tested with a 95% one-sided confidence limit to assess noninferiority. The mean hemolysis index was 43.33 with laparoscopic suction method and 34.67 with the Yankauer suction method. The mean difference was 8.67 and was not considered significant (p = .074). The percent loss in red blood cell volume after collection and cell salvage processing was 33.2% with the laparoscopic suction method and 29.57% with the Yankauer method. The mean difference was 3.63% and was within the acceptable 7% loss limit for noninferiority (p = .0278). Laparoscopic blood collection is not inferior to the standard Yankauer method for cell salvage collection. Published by Elsevier Inc.

  17. Use of mass spectrometry to study signaling pathways

    DEFF Research Database (Denmark)

    Pandey, A; Andersen, Jens S.; Mann, M

    2000-01-01

    Activation of cells by extracellular stimuli, such as growth factors, initiates a cascade of events involving posttranslational modifications, including phosphorylation, formation of protein complexes, and induction or repression of gene expression. Traditionally, genetic methods or specific...... biochemical assays have been used to identify molecules involved in signaling pathways. Lately, mass spectrometry, combined with elegant biochemical approaches, has become a powerful tool for identifying proteins and posttranslational modifications. With this protocol, we hope to bridge the gap between...... the biochemical and molecular aspects of signal transduction pathways and the mass spectrometric tools and techniques that are available to study them. We provide methods for large-scale cell culture and immunoprecipitation of tyrosine-phosphorylated proteins, silver staining of gels, trypsin digests, and protein...

  18. INDONESIAN SALVAGE LAW WITHIN THE FRAMEWORK OF CONTEMPORARY MARITIME LAW

    Directory of Open Access Journals (Sweden)

    Dhiana Puspitawati

    2015-12-01

    Full Text Available Located in a strategic position, that is between two great oceans and two land masses have made Indonesia a centre of international trade and shipping. In fact, 90% of international trades are carried out through the ocean. It is therefore crucial to assure that the activities in carrying goods across the ocean are incident free. However, if accident happens, assistance from professionals to preserve items of property is desirable. In such, salvage law emerged. This paper discusses comprehensively Indonesian salvage law within the framework of contemporary maritime law. While Indonesian maritime law is mostly based on its national law on the carriage of goods by the sea, in fact, the development of maritime law is highly affected by international practices which are largely based on international conventions and regulations. This research finds that while Indonesian salvage law can be found in Book II Chapter VII article 545-568k Wetboek Van Koophandel or known as Kitab Undang-undang Hukum Dagang (KUHD, which focused narrowly on the value of salved property as the primary measures of success, yet Indonesian salvage law has not been developed in accordance with current international salvage law, which adopted a broader and more balanced approached in both commercial and environmental aspects. Although it is believed that such approached is “culturally unrecognized” in Indonesia, this research argued that since Indonesian waters are part of international waters, all process by waters including salvage should confirm the relevant international practices and regulations. While Indonesia has taken out salvage law from KUHD and regulates it within Act Number 17/2008 on navigation, however, such act only provides one article for salvage stating that salvage will be regulates further by Ministry Regulation. Untill this paper was written no such government regulation produced yet by Indonesia. Since Indonesian waters is the centre of international

  19. Predictors of biochemical failure in patients undergoing prostate whole-gland salvage cryotherapy: a novel risk stratification model.

    Science.gov (United States)

    Spiess, Philippe E; Levy, David A; Mouraviev, Vladimir; Pisters, Louis L; Jones, J Stephen

    2013-08-01

    What's known on the subject? and what does the study add?: Previous studies have identified the most important prognostic factors of the likely outcomes of salvage prostate whole-gland ablation, including initial clinical stage, biopsy Gleason score, and PSA (total and doubling time). There is potential for further optimization of candidate selection for salvage cryoablation with curative intent and nadir PSA achieved after whole-gland cryotherapy may provide additional prognostic value. The study shows that the most important prognostic factors of biochemical progression-free survival for patients who have undergone whole-gland salvage prostate cryotherapy are nadir PSA achieved after therapy and pre-therapy biopsy Gleason score. Based on these two prognostic variables, we have identified risk stratification groups (low, intermediate and high) which help predict the expected outcomes of salvage whole-gland prostate cryotherapy in a given patient. This risk stratification constitutes a useful clinical tool in defining which patients maybe best suited for this local salvage treatment method. To assess the prognostic variables predicting the risk of biochemical progression-free survival (bPFS) after salvage prostate whole-gland cryotherapy using the Phoenix definition of bPFS. A total of 132 patients underwent prostate whole-gland salvage cryotherapy with curative intent. No patient underwent neoadjuvant/adjuvant hormonal ablative therapy, and all had extended post-salvage prostate-specific antigen (PSA) follow-up data. Cox univariate and multivariate logistic regression analyses of potential predictors of bPFS were conducted. Kaplan-Meier analyses of bPFS was also performed. At a mean (range) follow-up of 4.3 (0.9-12.7) years, the median (range) post-cryotherapy nadir PSA achieved was 0.17 (0-33.9) ng/mL. On multivariate analysis, predictors of bPFS were nadir PSA post-cryotherapy and pre-salvage biopsy Gleason score (P 2.5 ng/mL or biopsy Gleason score ≥ 7, with

  20. Salvage cryotherapy for local recurrence after radiotherapy for prostate cancer.

    Science.gov (United States)

    Kvorning Ternov, Klara; Krag Jakobsen, Ane; Bratt, Ola; Ahlgren, Göran

    2015-04-01

    The aim of this study was to present the outcome of patients treated with salvage cryotherapy after radiotherapy for prostate cancer at one institution. Consecutive patients treated between 2007 and 2013 with transperineal cryotherapy for biopsy-verified local recurrence after radiotherapy were investigated. An external reviewer retrieved outcome data retrospectively from medical records. Complications were graded according to the Clavien classification. One patient with less than 1 year of follow-up was excluded from the analysis of side-effects. Thirty patients were included, 29 of whom had a follow-up of at least 1 year. The median follow-up was 2.7 years (range 1-6.5 years). Eleven of the 23 patients without hormonal treatment at the time of cryotherapy reached a prostate-specific antigen (PSA) nadir of less than 0.5 ng/ml. At the end of follow-up five of these 23 patients still had a PSA below 0.5 ng/ml and 10 were free from recurrence according to the Phoenix definition. Clinical recurrence (verified with imaging or biopsies) was detected in 13 patients, six of which were local. One patient died from prostate cancer. Eleven patients had urinary incontinence grade 1-2 and three had grade 3-4, seven had pelvic pain, three had severe but transitory tissue sloughing, three developed a urethral stricture or had prolonged urinary retention, and one developed a urinary fistula 4.5 years after cryotherapy. Salvage cryotherapy should be considered as an alternative to hormonal treatment and surgery for local recurrence after radiotherapy for prostate cancer. The results compare well to those reported from centres with longer experience.

  1. Salvage surgery for residual primary and locally recurrent anal squamous cell carcinoma after chemoradiotherapy in HIV-positive individuals.

    Science.gov (United States)

    Cunin, Laila; Alfa-Wali, M; Turner, J; Bower, M; Ion, L; Allen-Mersh, T

    2014-02-01

    The treatment of anal cancer in human immunodeficiency virus (HIV) patients-as in the general population-is primarily with chemoradiotherapy (CRT), and abdominoperineal resection of residual or recurrent primary disease. The aim of this study was to evaluate the extent of residual primary disease and local recurrence as well as the outcome of salvage surgery after CRT for anal carcinoma in HIV-positive individuals. We retrospectively studied HIV-positive anal carcinoma patients treated between February 1989 and November 2012 in a specialist London unit. Extent of residual primary disease, local recurrence after CRT, postoperative complications, and survival after salvage surgery were evaluated. Complete response was experienced in 44 of 53 (83%) of HIV patients treated with CRT for anal carcinoma. One patient (2.3%) developed local recurrence. Nine patients (eight residual primary disease after CRT and one local recurrence) underwent salvage surgery after CRT. There were no perioperative deaths, and perioperative CD4 counts were sustained. Complications occurred in five patients (55%). Median interval to complete perineal healing was 4 months (range 2-11 months), and median hospital stay was 29 days. Survival (median 16 months) was 25% at 2 years from salvage surgery. Results in HIV-positive patients receiving highly active antiretroviral therapy (HAART) suggest that loss of HIV sensitivity to HAART can be avoided, but that there is increased postoperative morbidity that may be related to HIV disease. Survival was comparable to that for salvage therapy after optimal CRT in non-HIV anal carcinoma patients.

  2. Psychosocial and Functional Outcomes in Long-Term Survivors of Osteosarcoma: A Comparison of Limb-Salvage Surgery and Amputation

    Science.gov (United States)

    Robert, Rhonda S.; Ottaviani, Giulia; Huh, Winston W.; Palla, Shana; Jaffe, Norman

    2009-01-01

    Background Traditionally, physicians have believed that limb-salvage surgery has functional and cosmetic advantages over amputation, yet the literature is equivocal. Therefore, we sought to compare the psychosocial and functional outcomes in osteosarcoma survivors after limb-salvage surgery and amputation. We hypothesized there to be neither psychosocial nor functional outcome differences between groups. Procedure Participants received treatment of extremity osteosarcoma, had received their cancer diagnosis at least 2 years prior, and were at least 16 years old. A comprehensive set of validated psychosocial and functional measures was used to assess outcome. Results Fifty-seven patients participated in this study (33 who underwent limb-salvage surgery and 24 who underwent amputation). Participants had gone 12–24 years since diagnosis and were 16–52 years old at study participation. We used multiple linear regression models to examine differences in quality of life, body image, self-esteem, and social support between the two groups and found no differences. Lower limb function was a significant predictor of quality of life (p amputation, amputation after failed limb salvage, than by those who did not. Conclusions Participants with more functional lower limbs had better quality of life than did those with less functional lower limbs regardless of whether they underwent amputation or limb-salvage surgery. PMID:20135700

  3. Algebraic Systems Biology: A Case Study for the Wnt Pathway.

    Science.gov (United States)

    Gross, Elizabeth; Harrington, Heather A; Rosen, Zvi; Sturmfels, Bernd

    2016-01-01

    Steady-state analysis of dynamical systems for biological networks gives rise to algebraic varieties in high-dimensional spaces whose study is of interest in their own right. We demonstrate this for the shuttle model of the Wnt signaling pathway. Here, the variety is described by a polynomial system in 19 unknowns and 36 parameters. It has degree 9 over the parameter space. This case study explores multistationarity, model comparison, dynamics within regions of the state space, identifiability, and parameter estimation, from a geometric point of view. We employ current methods from computational algebraic geometry, polyhedral geometry, and combinatorics.

  4. Reaction pathways of the dissociation of methylal: A DFT study

    Energy Technology Data Exchange (ETDEWEB)

    Frey, H.-M.; Beaud, P.; Gerber, T.; Mischler, B.; Radi, P.P.; Tzannis, A.-P. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Schemata for modelling combustion processes do not yet include reaction rates for oxygenated fuels like methylal (DMM) which is considered as an additive or replacement for diesel due to its low sooting propensity. Density functional theory (DFT) studies of the possible reaction pathways for different dissociation steps of methylal are presented. Cleavage of a hydrogen bond to the methoxy group or the central carbon atom were simulated at the BLYP/6-311++G{sup **} level of theory. The results are compared to the experiment when dissociating and/or ionising DMM with femtosecond pulses. (author) 1 fig., 1 tab., 1 ref.

  5. [Neuro-ophthalmological conditions: Study of the clinical care pathway].

    Science.gov (United States)

    Layat, I; Challe, G; LeHoang, P; Bodaghi, B; Touitou, V

    2017-09-01

    Neuro-ophthalmologic conditions require specialized multidisciplinary management, both medical and surgical, for patients affected by visual loss due to nervous system disease. The primary goal of this study is to define the specificity of neuro-ophthalmology within the realm of visual health. The secondary goal is to review clinical care pathways by studying the organization of management, in terms of accessibility to care and personalization of the care pathway. A field study was carried out from February to June 2015, within the ophthalmology service of the Pitié-Salpêtrière University Medical Center in Paris. A 30-minute interview with the patient before or after his or her neuro-ophthalmology consultation was performed, so as to describe the clinical care pathway. The medical records of interviewed patients were also analyzed. Seventeen care pathways (10 women and 7 men) were reviewed. The mean age at appearance of visual involvement was 44.5 years (±8.4 years). If we exclude 3 patients over 66 years and retired, 35.71% were active, 35.71% were disabled, and 28.57% were on sick leave. Ten patients (58.82%) met the criteria for admission to long-term care. The first step had been carried out by local private practitioners. The first physician seen was the general medicine physician (59%), then the private ophthalmologist on an emergency basis (17%). On average, patients went through 8 steps during their care pathway (from 6 to 10 steps) and 14 medical departments were involved. The study showed collaboration with the other services of the University Hospital Department of Vision and Disabilities (notably with the Fondation Rothschild, the Quinze-Vingts National Ophthalmology Hospital and the Fondation Sainte-Marie). In addition to rehabilitation services, health care professionals participating in the outpatient care of the patients included an orthoptist (11.7%), a psychologist (11.7%), and an optician specializing in low vision for visual aids

  6. Effects of postfire salvage logging on deadwood-associated beetles.

    Science.gov (United States)

    Cobb, T P; Morissette, J L; Jacobs, J M; Koivula, M J; Spence, J R; Langor, D W

    2011-02-01

    In Canada and the United States pressure to recoup financial costs of wildfire by harvesting burned timber is increasing, despite insufficient understanding of the ecological consequences of postfire salvage logging. We compared the species richness and composition of deadwood-associated beetle assemblages among undisturbed, recently burned, logged, and salvage-logged, boreal, mixed-wood stands. Species richness was lowest in salvage-logged stands, largely due to a negative effect of harvesting on the occurrence of wood- and bark-boring species. In comparison with undisturbed stands, the combination of wildfire and logging in salvage-logged stands had a greater effect on species composition than either disturbance alone. Strong differences in species composition among stand treatments were linked to differences in quantity and quality (e.g., decay stage) of coarse woody debris. We found that the effects of wildfire and logging on deadwood-associated beetles were synergistic, such that the effects of postfire salvage logging could not be predicted reliably on the basis of data on either disturbance alone. Thus, increases in salvage logging of burned forests may have serious negative consequences for deadwood-associated beetles and their ecological functions in early postfire successional forests. ©2010 Society for Conservation Biology.

  7. Electrolyte and acid/base changes in dogs undergoing autologous blood transfusion via a cell salvage device.

    Science.gov (United States)

    Lamb, Jodie L; Thieman Mankin, Kelley M; Levine, Gwendolyn J; Thompson, James

    2015-09-01

    This study reports electrolyte and acid/base disturbances observed in clinical cases receiving autologous transfusion of blood processed by a cell salvage device. The records of 12 client-owned dogs that received an autologous transfusion via a cell salvage device with pre- and post-autologous transfusion blood work available were reviewed. Blood work from the 12 case dogs was compared to blood work from 12 control dogs with similar diseases. Control dogs received similar surgical treatment and were administered a similar volume per kg of packed red blood cells as case dogs, but did not undergo autologous transfusion. Case dogs that received autologous transfusion via a cell salvage device were significantly more likely to experience a decrease in ionized calcium and magnesium levels post-transfusion than were control dogs. Calcium and magnesium levels should be closely monitored during and after autologous transfusion. Calcium and/or magnesium supplementation may be required.

  8. Long-Term Outcomes After High-Dose Postprostatectomy Salvage Radiation Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Goenka, Anuj; Magsanoc, Juan Martin; Pei Xin; Schechter, Michael; Kollmeier, Marisa; Cox, Brett [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Scardino, Peter T.; Eastham, James A. [Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-09-01

    patients with greater burden of disease at time of SRT as reflected by either radiographic imaging or a greater PSA level. Salvage radiation doses {>=}70 Gy may ultimately be most beneficial in these patients, but this needs to be further studied.

  9. Limb salvage treatment vs. amputation in sarcoma

    Directory of Open Access Journals (Sweden)

    Motamedi M

    1993-05-01

    Full Text Available Many years ago the treatment of sarcoma was radiotherapy up to 2000-4000 rad. This treatment was very complicated, due to producing neoplasm after radiotherapy. By this method of treatment of osteosarcoma, the rate of survival became about 20% (two years. The second method of treatment was chemotherapy for a period of 2-5 weeks that amputation was performed afterwards. By chemotherapy, the rate of being alive reached up to 25-27% (five years. Right now, the best treatment for sarcoma is limb salvage. In our report, the chance of being alive in chondrosarcoma was about four years. This was nearly the same as that of the other institutes in the world especially in America, Europe, and Japan. The rate of recurrence was also more than that from different parts of the world. The survival rate in osteosarcomatic patients was about two years less for males the females, and it was more in tall people than short ones. The survival rate of the patients with giant cell tumor was more than osteosarcoma up to five years, and it has no recurrence or metastasis

  10. Salvage pulmonary resection after stereotactic body radiotherapy: A feasible and safe option for local failure in selected patients.

    Science.gov (United States)

    Antonoff, Mara B; Correa, Arlene M; Sepesi, Boris; Nguyen, Quynh-Nhu; Walsh, Garrett L; Swisher, Stephen G; Vaporciyan, Ara A; Mehran, Reza J; Hofstetter, Wayne L; Rice, David C

    2017-08-01

    For inoperable patients with pulmonary malignancy, stereotactic body radiotherapy is a reasonable therapeutic option. Despite good early tumor control, local failure occurs in up to 10% of patients by 3 years. Because management of local recurrence after stereotactic body radiotherapy is unclear, we evaluated use of surgery as a salvage option. A retrospective review was conducted of consecutive patients from a single institution who underwent salvage resection of primary and metastatic pulmonary malignancies previously treated with stereotactic body radiotherapy. In addition, a literature search was conducted to identify previous reports of pulmonary resection for local stereotactic body radiotherapy failures, to allow cumulative analyses with previously published cases. A total of 21 patients met inclusion criteria. The median time between stereotactic body radiotherapy and salvage surgery was 16.2 months (range, 6.4-71.5). Postoperative complications occurred in 7 patients (18.9%), in whom atrial arrhythmias and prolonged air leaks (>5 days) were most frequent (n = 2 each, 5.4%). There was no local recurrence after salvage surgery. Distant failure occurred in 5 of 21 patients (23.8%) at a median of 36.2 months, and median disease-free survival was 19.2 months. The 30- and 90-day mortality was 4.8% (1 patient). Cumulative analysis included 37 patients from 4 institutions and comprised 26 (78.8%) primary non-small cell lung cancers and 11 (29.7%) lung metastases. Median overall survival after salvage surgery was 46.9 months, and 3-year survival was 71.8%. After local failure of stereotactic body radiotherapy, salvage resection remains a viable option for operable patients, with acceptable morbidity and survival. As use of stereotactic body radiotherapy continues to expand, further studies to evaluate the optimal management for local failure are needed. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights

  11. Designing a Care Pathway Model – A Case Study of the Outpatient Total Hip Arthroplasty Care Pathway

    Directory of Open Access Journals (Sweden)

    Robin I. Oosterholt

    2017-03-01

    Full Text Available Introduction: Although the clinical attributes of total hip arthroplasty (THA care pathways have been thoroughly researched, a detailed understanding of the equally important organisational attributes is still lacking. The aim of this article is to contribute with a model of the outpatient THA care pathway that depicts how the care team should be organised to enable patient discharge on the day of surgery. Theory: The outpatient THA care pathway enables patients to be discharged on the day of surgery, short- ening the length of stay and intensifying the provision and organisation of care. We utilise visual care modelling to construct a visual design of the organisation of the care pathway. Methods: An embedded case study was conducted of the outpatient THA care pathway at a teaching hospital in the Netherlands. The data were collected using a visual care modelling toolkit in 16 semi- structured interviews. Problems and inefficiencies in the care pathway were identified and addressed in the iterative design process. Results: The results are two visual models of the most critical phases of the outpatient THA care pathway: diagnosis & preparation (1 and mobilisation & discharge (4. The results show the care team composition, critical value exchanges, and sequence that enable patient discharge on the day of surgery. Conclusion: The design addressed existing problems and is an optimisation of the case hospital’s pathway. The network of actors consists of the patient (1, radiologist (1, anaesthetist (1, nurse specialist (1, pharmacist (1, orthopaedic surgeon (1,4, physiotherapist (1,4, nurse (4, doctor (4 and patient applica- tion (1,4. The critical value exchanges include patient preparation (mental and practical, patient education, aligned care team, efficient sequence of value exchanges, early patient mobilisation, flexible availability of the physiotherapist, functional discharge criteria, joint decision making and availability of the care team.

  12. Genotypic and phenotypic nevirapine resistance correlates with virological failure during salvage therapy including abacavir and nevirapine

    DEFF Research Database (Denmark)

    Jørgensen, L B; Katzenstein, T L; Gerstoft, J

    2000-01-01

    OBJECTIVE: To study the development of resistance during 8 weeks of salvage therapy with abacavir and nevirapine in combination with other reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). METHODS: Samples obtained at baseline and after 8 weeks of therapy from 16 heavily...... pretreated patients were analysed for genotypic and phenotypic resistance. Genotypic resistance was analysed in cell-associated DNA and plasma HIV-RNA using direct sequencing. Phenotypic resistance was analysed in a PBMC-based assay and in a recombinant virus assay. Plasma viral load was measured at baseline...... and after 2, 4 and 8 weeks of therapy. RESULTS: The majority of patients was genotypically and phenotypically resistant to lamivudine, abacavir, zidovudine and PIs, whereas 50% of the patients showed resistance to nevirapine at baseline in at least one of the methods used. After 8 weeks of salvage therapy...

  13. Recurrent oral cavity cancer: Patterns of failure after salvage multimodality therapy.

    Science.gov (United States)

    Quinlan-Davidson, Sean R; Morrison, William H; Myers, Jeffrey N; Gunn, Gary B; William, William N; Beadle, Beth M; Skinner, Heath D; Gillenwater, Ann M; Frank, Steven J; Phan, Jack; Johnson, Faye M; Fuller, Clifton D; Zafereo, Mark E; Rosenthal, David I; Garden, Adam S

    2017-04-01

    We focused on a cohort of radiation naïve patients who had recurrent oral cavity cancer (recurrent OCC) to assess their outcomes with salvage multimodal therapy. A retrospective single institutional study was performed of patients with recurrent OCC. Disease recurrence and survival outcomes were assessed. Seventy-eight patients were analyzed. All patients had salvage surgery and intensity-modulated radiotherapy (IMRT) and 74% had chemotherapy. Five-year overall survival, recurrence-free survival, and locoregional control rates were 59%, 60%, and 74%, respectively. Outcomes of radiation naïve patients with recurrent OCC are fair, and seem similar with patients with locally advanced nonrecurrent OCC treated with multimodal therapy. © 2016 Wiley Periodicals, Inc. Head Neck 39: 633-638, 2017. © 2016 Wiley Periodicals, Inc.

  14. Rotationplasty as a salvage of failed primary limb reconstruction: up to date review and case report.

    Science.gov (United States)

    Canavese, Federico; Samba, Antoine; Khan, Ahmad; Dechelotte, Pierre; Krajbich, Joseph I

    2014-05-01

    We report a case of a 15-year-old girl who is a known case for proximal focal femoral deficiency. She underwent several surgical lengthening procedures. Her course was complicated by femur nonunion, knee joint dislocation, stiff knee, and final lower limb discrepancy of over 15 cm. Rotationplasty was performed to salvage her previous surgical failures and restore her function. Surgery was uneventful and the patient was able to walk with the prosthesis in a few months after index surgery. Although the outcome of rotationplasty is visually unusual, for some children restored function and physical capabilities outweigh cosmetic concerns. The aim of the present study was to report a case of rotationplasty in salvaging a failed primary limb reconstruction in a patient with proximal femur focal deficiency.

  15. Experimental test of postfire management in pine forests: impact of salvage logging versus partial cutting and nonintervention on bird-species assemblages.

    Science.gov (United States)

    Castro, Jorge; Moreno-Rueda, Gregorio; Hódar, José A

    2010-06-01

    There is an intense debate about the effects of postfire salvage logging versus nonintervention policies on regeneration of forest communities, but scant information from experimental studies is available. We manipulated a burned forest area on a Mediterranean mountain to experimentally analyze the effect of salvage logging on bird-species abundance, diversity, and assemblage composition. We used a randomized block design with three plots of approximately 25 ha each, established along an elevational gradient in a recently burned area in Sierra Nevada Natural and National Park (southeastern Spain). Three replicates of three treatments differing in postfire burned wood management were established per plot: salvage logging, nonintervention, and an intermediate degree of intervention (felling and lopping most of the trees but leaving all the biomass). Starting 1 year after the fire, we used point sampling to monitor bird abundance in each treatment for 2 consecutive years during the breeding and winter seasons (720 censuses total). Postfire burned-wood management altered species assemblages. Salvage logged areas had species typical of open- and early-successional habitats. Bird species that inhabit forests were still present in the unsalvaged treatments even though trees were burned, but were almost absent in salvage-logged areas. Indeed, the main dispersers of mid- and late-successional shrubs and trees, such as thrushes (Turdus spp.) and the European Jay (Garrulus glandarius) were almost restricted to unsalvaged treatments. Salvage logging might thus hamper the natural regeneration of the forest through its impact on assemblages of bird species. Moreover, salvage logging reduced species abundance by 50% and richness by 40%, approximately. The highest diversity at the landscape level (gamma diversity) resulted from a combination of all treatments. Salvage logging may be positive for bird conservation if combined in a mosaic with other, less-aggressive postfire

  16. Transsulfuration pathway thiols and methylated arginines: the Hunter Community Study.

    Directory of Open Access Journals (Sweden)

    Arduino A Mangoni

    Full Text Available Serum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH activity] and with symmetric dimethylarginine (SDMA. We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level.Data on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS, and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR = 64 (60-70 years].REGRESSION ANALYSIS SHOWED THAT: a age (P = 0.001, gender (P = 0.03, lower estimated glomerular filtration rate (eGFR, P = 0.08, body mass index (P = 0.008, treatment with beta-blockers (P = 0.03, homocysteine (P = 0.02, and glutamylcysteine (P = 0.003 were independently associated with higher ADMA concentrations; and b age (P = 0.001, absence of diabetes (P = 0.001, lower body mass index (P = 0.01, lower eGFR (P<0.001, cysteine (P = 0.007, and glutamylcysteine (P < 0.001 were independently associated with higher SDMA concentrations. No significant associations were observed between methylated arginines and either glutathione or taurine concentrations.After adjusting for clinical, demographic, biochemical, and pharmacological confounders the combined assessment of transsulfuration pathway thiols shows that glutamylcysteine has the strongest and positive independent associations with ADMA and SDMA. Whether this reflects a direct effect of glutamylcysteine on DDAH activity (for ADMA and/or cationic amino acid transport requires further investigations.

  17. Deoxynucleoside salvage in fission yeast allows rescue of ribonucleotide reductase deficiency but not Spd1-mediated inhibition of replication

    DEFF Research Database (Denmark)

    Fleck, Oliver; Fahnøe, Ulrik; Løvschal, Katrine Vyff

    2017-01-01

    In fission yeast, the small, intrinsically disordered protein S-phase delaying protein 1 (Spd1) blocks DNA replication and causes checkpoint activation at least in part, by inhibiting the enzyme ribonucleotide reductase, which is responsible for the synthesis of DNA. The CRL4(Cdt2) E3 ubiquitin...... triphosphate (dNTP) pools; yet we find that Spd1 and Spd2 together inhibit DNA replication upon Cdt2 depletion. To directly test whether this block of replication was solely due to insufficient dNTP levels, we established a deoxy-nucleotide salvage pathway in fission yeast by expressing the human nucleoside...... ribonucleotide reductase. However, salvage completely failed to rescue S phase delay, checkpoint activation, and damage sensitivity, which was caused by CRL4(Cdt2) inactivation, suggesting that Spd1-in addition to repressing dNTP synthesis-together with Spd2, can inhibit other replication functions. We propose...

  18. Anastomotic salvage after rectal cancer resection using the Turnbull-Cutait delayed anastomosis.

    Science.gov (United States)

    Hallet, Julie; Bouchard, Alexandre; Drolet, Sébastien; Milot, Hélène; Desrosiers, Emilie; Lebrun, Aude; Grégoire, Roger Charles

    2014-12-01

    Turnbull-Cutait abdominoperineal pull-through followed by delayed coloanal anastomosis (DCA) was first described in 1961. Studies have described its use for challenging colorectal conditions. We reviewed our experience with Turnbull-Cutait DCA as a salvage procedure for complex failure of colorectal anastomosis. We performed a retrospective cohort study from October 2010 to September 2011, with analysis of postoperative morbidity and mortality. Seven DCAs were performed for anastomotic complications (3 chronic leaks, 2 rectovaginal fistulas, 1 colovesical fistula, 1 colonic ischemia) following surgery for rectal cancer. Six patients had a diverting ileostomy constructed as part of previous treatment for anastomotic complications before the salvage procedure. No anastomotic leaks were observed. All procedures but 1 were completed successfully. One patient who underwent DCA subsequently required an abdominoperineal resection and a permanent colostomy for postoperative extensive colonic ischemia. No 30-day mortality occurred. Salvage Turnbull-Cutait DCA appears to be a safe procedure and could be offered to patients with complex anastomotic complications. This procedure could be added to the surgeon's armamentarium as an alternative to the creation of a permanent stoma.

  19. Effectiveness of salvage selective and modified radical neck dissection for regional pathologic lymphadenopathy after chemoradiation.

    Science.gov (United States)

    van der Putten, Lisa; van den Broek, Guido B; de Bree, Remco; van den Brekel, Michiel W M; Balm, Alfons J M; Hoebers, Frank J P; Doornaert, Patricia; Leemans, C René; Rasch, Coen R N

    2009-05-01

    The objective of this study was to evaluate the effectiveness and safety of our careful observational strategy and neck dissections and the accuracy of ultrasound-guided fine-needle aspiration cytology, and to determine the prognostic factors for outcome and regional control after primary chemoradiation. Diagnostic evaluation of the regional status after concurrent chemoradiation for advanced head and neck cancer remains difficult, and the indications for a salvage neck dissection and its extent are not clearly defined. In a series of 540 patients, there was suspicion of regional residual or recurrent disease after chemoradiation in 61 patients who underwent 68 salvage neck dissections and 68 patients who were considered unresectable. For the patients with salvage neck dissection, the accuracy of ultrasound-guided fine-needle aspiration cytology was determined. Disease control in the neck, disease-specific and overall survival, and parameters that may have prognostic value for the outcome were evaluated. Neck dissection specimens contained viable tumor in 26 (43%) patients. Of these, 13 had selective neck dissections and 13 modified radical neck dissections. Ultrasound-guided fine-needle aspiration cytology had a sensitivity of 80% and specificity of 42%. Nine patients developed a regional recurrence after salvage neck dissection (5 located in contralateral neck). Five-year regional control and overall survival rates were 79% and 36%, respectively. Significant prognostic factors for overall survival were surgical margins and "residual versus recurrent disease" in multivariate analysis. Considering the good regional control rate and the high rate of unnecessary neck dissections with a theoretical planned neck dissection strategy, we conclude that a careful observational strategy is worthwhile and safe. For the evaluation of radiation treatment response, ultrasound-guided fine-needle aspiration cytology has a low specificity.

  20. Salvage chemotherapy with taxane and platinum for women with recurrent uterine carcinosarcoma.

    Science.gov (United States)

    Matsuo, Koji; Ross, Malcolm S; Yunokawa, Mayu; Johnson, Marian S; Machida, Hiroko; Omatsu, Kohei; Klobocista, Merieme M; Im, Dwight D; Satoh, Shinya; Baba, Tsukasa; Ikeda, Yuji; Bush, Stephen H; Hasegawa, Kosei; Blake, Erin A; Takekuma, Munetaka; Shida, Masako; Nishimura, Masato; Adachi, Sosuke; Pejovic, Tanja; Takeuchi, Satoshi; Yokoyama, Takuhei; Ueda, Yutaka; Iwasaki, Keita; Miyake, Takahito M; Yanai, Shiori; Nagano, Tadayoshi; Takano, Tadao; Shahzad, Mian M K; Ueland, Frederick R; Kelley, Joseph L; Roman, Lynda D

    2017-12-01

    To examine survival after recurrence (SAR) among women with recurrent uterine carcinosarcoma who received a taxane/platinum doublet as the first-line salvage chemotherapy. We retrospectively examined 148 women with recurrent uterine carcinosarcoma who received salvage chemotherapy within a cohort of 906 uterine carcinosarcomas. An independent association of salvage chemotherapy type and SAR was examined with multivariate analysis. There were 71 (48.0%) women who received a taxane/platinum regimen. On univariate analysis, women who received a taxane/platinum doublet had a higher 2-year SAR rate compared to women who received non-taxane/platinum regimens (55.5% versus 34.8%, Pimproved SAR compared to the non-taxane/platinum regimens (adjusted-hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35 to 0.91, P=0.02). When stratified by disease-free interval, women with a disease-free interval ≥6months who received a taxane/platinum doublet had a higher 2-year SAR rate compared to those who received non-taxane/platinum regimens (61.9% versus 40.0%, HR 0.46, 95% CI 0.28 to 0.75, P=0.002); conversely, in women with a disease-free interval chemotherapy, re-treatment with taxane/platinum doublet as salvage chemotherapy remained beneficial (2-year SAR rate, 62.1% versus 39.7%, HR 0.40, 95% CI 0.18 to 0.86, P=0.019). Our study suggests that taxane/platinum doublet may be a more effective chemotherapy regimen compared to other regimens among women with recurrent uterine carcinosarcoma, especially for those who had a disease-free interval of ≥6months. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Evaluation of canine red blood cell quality after processing with an automated cell salvage device.

    Science.gov (United States)

    Hofbauer, Nina; Windberger, Ursula; Schwendenwein, Ilse; Tichy, Alexander; Eberspächer, Eva

    2016-05-01

    To evaluate the properties of RBC concentrate harvested after processing fresh whole blood units from healthy dogs with an automated cell salvage device. Prospective, in vitro, experimental study. University teaching hospital. Sixteen healthy, privately owned dogs of various breeds. Fresh canine whole blood collected in bags with citrate phosphate dextrose adenine solution was processed with an automated cell salvage device and analyzed in vitro. Laboratory values determined before (baseline, from a catheter sample) and after processing RBCs (procRBCs) included a complete blood count, selected blood chemistry analytes, erythrocyte osmotic resistance, whole blood viscosity, RBC aggregation, and RBC deformability. Total recovery of RBCs was 80% ± 12%. Hematocrit of the procRBCs yielded by the device was 77% ± 3.7% (mean ± standard deviation). Gross morphology of the RBCs remained unchanged. The mean corpuscular volume, erythrocyte osmotic resistance, RBC deformability, RBC aggregation, and the activity of lactate dehydrogenase showed minor but statistically significant changes from baseline. No differences in the concentrations of free hemoglobin were observed. Whole blood viscosity was less in the procRBCs. Seventy-seven percent (mean) of the platelets were washed out, while a mean of 57% of the leukocytes remained in the procRBCs. Although processing canine blood with this automated cell salvage device leads to slight changes in some properties of RBCs, most of these changes are comparable to changes seen in human blood after processing. Present data indicate that the use of this cell salvage device does not induce changes in canine RBC concentrate that would preclude its use for transfusion. © Veterinary Emergency and Critical Care Society 2016.

  2. Natural recovery and leaf water potential after fire influenced by salvage logging and induced drought stress

    Directory of Open Access Journals (Sweden)

    D. Moya

    2013-01-01

    Full Text Available Salvage logging is one of the most common emergency actions in the short-term management after a fire. Several studies have been carried out and some obtained positive results which incite to carry it out but other, found negative effects on seedling establishment and regeneration. In addition, climatic changes will have large impacts on vegetation productivity and resilience since the regional models for south-eastern Spain predicts a rainfall decrease of about 20% and temperature increase of 4.5 ºC. Our aim was to determine how short-term forest management and induced drought affect the ecosystem recovery in Aleppo pine stands naturally recovered after a fire.In summer 2009, a mid-high severity fire burned 968 ha of Aleppo pine (Pinus halepensis Mill. forest in south-eastern Spain. Six months later, a salvage logging was carried out. The Aleppo pine recruitment was negligible. During summer 2010, twelve square plots (2m x 2m were set in the three scenarios: control, salvaged and drought induced. The surface cover and soil water availability for three dominant understory species were recorded in four field campaigns: Spring-2010, Fall-2010, Spring-2011 and Fall-2011.The season, management and the target species showed significant differences in growing and water stress. In general, Esparto grass showed lower water stress, mainly in Fall, a higher increase of total coverage. Both effects were showing their highest values in non-salvaged areas and no drought. Changes in leaf water potential and soil water content after the drought season influence the survival and development of individuals.Our results indicate that soil water content and ecosystem response can be modified by short-term silvicultural treatments. Therefore, management after fire could cause opposite effects to those initially foreseen, since they depend on fire severity, and type of ecosystem management response. So, their application must be evaluated and assessed before

  3. The outcome of rectal cancer after early salvage surgery following transanal endoscopic microsurgery seems promising.

    Science.gov (United States)

    Levic, Katarina; Bulut, Orhan; Hesselfeldt, Peter; Bülow, Steffen

    2012-09-01

    Transanal endoscopic microsurgery (TEM) allows locally complete resection of early rectal cancer as an alternative to conventional radical surgery. In patients with unfavourable post-TEM histology, salvage surgery can be performed. The aim of this study was to evaluate the results of early radical surgery after TEM for rectal cancer. From 1997 to 2010, 86 TEM procedures were performed in 79 patients due to rectal cancer. Early salvage surgery was performed in 25 patients. Data were obtained from the patients' charts and reviewed retrospectively. Perioperative data and oncological outcome were analysed. No patients received preoperative chemotherapy. The median time to salvage surgery was 37 days. Five patients underwent laparoscopic surgery. The median operative time was 165 min (range: 101-341 min, 95% confidence interval (CI): 156-214 min) and the median blood loss 275 ml (range: 0-1,275 ml, 95% CI: 232-530 ml). The 30-day mortality was 8% (95% CI: 1-19%, n = 2). Intraoperative perforation occurred in 20% (95% CI: 3-37%, n = 5). The median number of harvested lymph nodes was 12 (range: 3-25, 95% CI: 9-14) and the median circumferential resection margin (CRM) was 10 mm (range: 0-20 mm, 95% CI: 5-12 mm). Only one patient (4%, 95%CI: 1-12%) had a positive CRM. The median follow-up time was 25 months (range: 3-80 months). There was no local recurrence. Distant metastasis occurred in 4% (95% CI: 1-12%, n = 1). Early salvage surgery after TEM seems to be safe despite a high risk of specimen perforation during the operation. not relevant. not relevant.

  4. Extended Salvage Pelvic Lymph Node Dissection in Patients with Recurrent Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Daniar K. Osmonov

    2014-01-01

    Full Text Available Background. Treatment of patients with a biochemical recurrence (BCR of prostate cancer (PCa is generally difficult and without valid treatment options. Since 2004 we have been developing therapeutic possibilities for these patients. Methods. We retrospectively analyzed a cohort of 41 patients with a BCR of PCa and a mean followup of 40.3±20.8 months. Group 1 (n=10: salvage radical prostatectomy (sRP with SePLND (salvage extended pelvic lymph nodes dissection (initial treatment: combined brachytherapy. Group 2 (n=22: SePLND (initial treatment: radical prostatectomy (RP. Group 3 (n=9: SePLND (initial treatment: RP and adjuvant radiation therapy (RT. We observed PSA, PSA-velocity, localization of LNs and LNs+, BCR-free period, and BR (biochemical response. Results. Group 1: 60% with BCR-freedom (mean 27.2 months. Group 2: 63.6% with BCR-freedom (mean 17.5 months. Group 3: 33.3% with BCR-freedom (mean 17.6 months. In total, BCR-freedom was observed in 23 of 41 patients (56.1% after salvage surgery. 75.6% of all patients showed a BR. 765 LNs were removed and 14.8% of these were LN+. Conclusions. The BCR-free period and BR are comparable in all three groups. Sensibility to ADT can be reestablished and prolonged as a result of SePLND. Multicenter studies are needed for a reliable output.

  5. Comparative study on gene set and pathway topology-based enrichment methods.

    Science.gov (United States)

    Bayerlová, Michaela; Jung, Klaus; Kramer, Frank; Klemm, Florian; Bleckmann, Annalen; Beißbarth, Tim

    2015-10-22

    Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis. We comparatively investigated gene set and pathway topology-based enrichment approaches, considering three gene set and four topological methods. These methods were compared in two extensive simulation studies and on a benchmark of 36 real datasets, providing the same pathway input data for all methods. In the benchmark data analysis both types of methods showed a comparable ability to detect enriched pathways. The first simulation study was conducted with KEGG pathways, which showed considerable gene overlaps between each other. In this study with original KEGG pathways, none of the topology-based methods outperformed the gene set approach. Therefore, a second simulation study was performed on non-overlapping pathways created by unique gene IDs. Here, methods accounting for pathway topology reached higher accuracy than the gene set methods, however their sensitivity was lower. We conducted one of the first comprehensive comparative works on evaluating gene set against pathway topology-based enrichment methods. The topological methods showed better performance in the simulation scenarios with non-overlapping pathways, however, they were not conclusively better in the other scenarios. This suggests that simple gene set approach might be sufficient to detect an enriched pathway under realistic circumstances. Nevertheless, more extensive studies and further benchmark data are needed to systematically evaluate these methods and to assess what gain and cost pathway topology information introduces into enrichment analysis. Both

  6. Gynecologic examination and cervical biopsies after (chemo) radiation for cervical cancer to identify patients eligible for salvage surgery

    NARCIS (Netherlands)

    Nijhuis, Esther R.; van der Zee, Ate G. J.; In 't Hout, Bertha A.; Boomgaard, Jantine J.; de Hullu, Joanne A.; Pras, Elisabeth; Hollema, Harry; Aalders, Jan G.; Jijman, Hans W.; Willemse, Pax H. B.; Mourits, Marian J. E.

    2006-01-01

    Purpose: The aim of this study was to evaluate efficacy of gynecologic examination under general anesthesia with cervical biopsies after (chemo) radiation for cervical cancer to identify patients with residual disease who may benefit from salvage surgery. Methods and Materials: In a retrospective

  7. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review

    DEFF Research Database (Denmark)

    Benfield, Thomas; Atzori, Chiara; Miller, Robert F

    2008-01-01

    BACKGROUND: Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP). METHODS: We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007 and inc...

  8. Pathways through which health influences early retirement: a qualitative study.

    Science.gov (United States)

    de Wind, Astrid; Geuskens, Goedele A; Reeuwijk, Kerstin G; Westerman, Marjan J; Ybema, Jan Fekke; Burdorf, Alex; Bongers, Paulien M; van der Beek, Allard J

    2013-04-03

    Due to the aging of the population, there is a societal need for workers to prolong their working lives. In the Netherlands, many employees still leave the workforce before the official retirement age of 65. Previous quantitative research showed that poor self-perceived health is a risk factor of (non-disability) early retirement. However, little is known on how poor health may lead to early retirement, and why poor health leads to early retirement in some employees, but not in others. Therefore, the present qualitative study aims to identify in which ways health influences early retirement. Face-to-face semi-structured interviews were conducted with 30 employees (60-64 years) who retired before the official retirement age of 65. Participants were selected from the Study on Transitions in Employment, Ability and Motivation. The interviews were transcribed verbatim, a summary was made including a timeline, and the interviews were open coded. In 15 of the 30 persons, health played a role in early retirement. Both poor and good health influenced early retirement. For poor health, four pathways were identified. First, employees felt unable to work at all due to health problems. Second, health problems resulted in a self-perceived (future) decline in the ability to work, and employees chose to retire early. Third, employees with health problems were afraid of a further decline in health, and chose to retire early. Fourth, employees with poor health retired early because they felt pushed out by their employer, although they themselves did not experience a reduced work ability. A good health influenced early retirement, since persons wanted to enjoy life while their health still allowed to do so. The financial opportunity to retire sometimes triggered the influence of poor health on early retirement, and often triggered the influence of good health. Employees and employers barely discussed opportunities to prolong working life. Poor and good health influence early

  9. A Newsvendor Model with Initial Inventory and Two Salvage Opportunities

    Directory of Open Access Journals (Sweden)

    Ali Cheaitou

    2011-06-01

    Full Text Available In this paper, we develop an extension of the newsvendor model with initial inventory. In addition to the usual quantity ordered at the beginning of the horizon and the usual quantity salvaged at the end of the horizon, we introduce a new decision variable: a salvage opportunity at the beginning of the horizon, which might be used in the case of high initial inventory level. We develop the expression of the optimal policy for this extended model, for a general demand distribution. The structure of this optimal policy is particular and is characterized by two threshold levels. Some managerial insights are given via numerical examples.

  10. Preliminar results of paleontological salvage at Belo Monte Powerplant construction.

    Science.gov (United States)

    Tomassi, H Z; Almeida, C M; Ferreira, B C; Brito, M B; Barberi, M; Rodrigues, G C; Teixeira, S P; Capuzzo, J P; Gama-Júnior, J M; Santos, M G K G

    2015-08-01

    In this paper some preliminary fossil specimens are presented. They represent a collection sampled by Belo Monte's Programa de Salvamento do Patrimônio Paleontológico (PSPP), which includes unprecedented invertebrate fauna and fossil vertebrates from Pitinga, Jatapu, Manacapuru, Maecuru e Alter do Chão formations from Amazonas basin, Brazil. The Belo Monte paleontological salvage was able to recover 495 microfossil samples and 1744 macrofossil samples on 30 months of sampling activities, and it is still ongoing. The macrofossils identified are possible plant remains, ichnofossils, graptolites, brachiopods, molluscs, athropods, Agnatha, palynomorphs (miosphores, acritarchs, algae cysts, fungi spores and unidentified types) and unidentified fossils. However, deep scientific research is not part of the scope of the program, and this collection must be further studied by researchers who visit Museu Paraense Emilio Goeldi, where the fossils will be housed. More material will be collected until the end of the program. The collection sampled allows a mosaic composition with the necessary elements to assign, in later papers, taxonomic features which may lead to accurate species identification and palaeoenvironmental interpretations.

  11. Preliminar results of paleontological salvage at Belo Monte Powerplant construction

    Directory of Open Access Journals (Sweden)

    HZ. Tomassi

    Full Text Available Abstract In this paper some preliminary fossil specimens are presented. They represent a collection sampled by Belo Monte’s Programa de Salvamento do Patrimônio Paleontológico (PSPP, which includes unprecedented invertebrate fauna and fossil vertebrates from Pitinga, Jatapu, Manacapuru, Maecuru e Alter do Chão formations from Amazonas basin, Brazil. The Belo Monte paleontological salvage was able to recover 495 microfossil samples and 1744 macrofossil samples on 30 months of sampling activities, and it is still ongoing. The macrofossils identified are possible plant remains, ichnofossils, graptolites, brachiopods, molluscs, athropods, Agnatha, palynomorphs (miosphores, acritarchs, algae cysts, fungi spores and unidentified types and unidentified fossils. However, deep scientific research is not part of the scope of the program, and this collection must be further studied by researchers who visit Museu Paraense Emilio Goeldi, where the fossils will be housed. More material will be collected until the end of the program. The collection sampled allows a mosaic composition with the necessary elements to assign, in later papers, taxonomic features which may lead to accurate species identification and palaeoenvironmental interpretations.

  12. Influential factors in the response to salvage radiotherapy after radical prostatectomy.

    Science.gov (United States)

    Algarra, R; Tienza, A; Hevia, M; Zudaire, J; Rosell, D; Robles, J E; Pascual, I

    2014-12-01

    To analyze the influential factors in the response in prostatectomized patients with subsequent biochemical relapse (BCR) and treated with salvage radiotherapy (RTP). We analyzed 313 patients with pT2/pT3 prostate cancer who were receiving salvage therapy due to biochemical relapse (from a series of 1,310 radical prostatectomies between 1989-2012). Of the 313 patients; 159 (50.8%) only received androgen deprivation (AD), 63 (20.1%) Radiotherapy (RTP) plus concomitant AD and 91 (29.1%) only RTP. Of these, 57 (62.6%) have maintained complete response and 34 (37.4%) had failure response with post-RTP BCR. Study of the group treated exclusively with salvage RTP. Ninety-one patients were treated with salvage RTP. Median follow-up was 6.4 years and median to recurrence 11 months. Post-RTP biochemical relapse-free survival (PRBRFS) was 68 ± 7% and 30 ± 10% in 5 to 10 years. Median PRBRFS was 7.3 years (6.3-8.3). Initial PSA (HR: 1.08; 95% CI: 1.01-1.1 P=.02) with best PSA cut-off point PSA>20 ng/ml (HR: 13.6; 95% CI: 2.1-86 P=.005) and PSA pre-RTP (HR: 1.9; 95% CI: 1.2-3.3; P=.009), best PSA cut-off point PSA preRTP 0.92 ng/ml (HR: 4.5; 95% CI: 1.3-15.6; P=.01) showed independent influence in the response in the multivariate study. PRBRFS at 5 years, 81 ± 9% versus 58 ± 9% with initial PSA 20 ng/ml (P=.03). PRBRFS at 5 years, 93 ± 5% versus 53 ± 10% according to PSA pre-RTP 0.9 ng/ml (P=.02). In patients treated with salvage RTP after radical prostatectomy, the preoperative PSA>20 ng/ml and PSA preRTP>0.92 ng/ml shows an independent influence on the response. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  13. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-12-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  14. Study of Arachidonic Acid Pathway in Human Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama

    2009-01-01

    Full Text Available Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of tumorigenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of tumorigenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and tumorigenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human bladder tumor tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.

  15. Woody plant regeneration after blowdown, salvage logging, and prescribed fire in a northern Minnesota forest

    Science.gov (United States)

    Brian J. Palik; Doug. Kastendick

    2009-01-01

    Salvage logging after natural disturbance has received increased scrutiny in recent years because of concerns over detrimental effects on tree regeneration and increased fine fuel levels. Most research on tree regeneration after salvage logging comes from fire-prone systems and is short-term in scope. Limited information is available on longer term responses to salvage...

  16. Utility of remotely sensed imagery for assessing the impact of salvage logging after forest fires

    Science.gov (United States)

    Sarah A. Lewis; Peter R. Robichaud; Andrew T. Hudak; Brian Austin; Robert J. Liebermann

    2012-01-01

    Remotely sensed imagery provides a useful tool for land managers to assess the extent and severity of post-wildfire salvage logging disturbance. This investigation uses high resolution QuickBird and National Agricultural Imagery Program (NAIP) imagery to map soil exposure after ground-based salvage operations. Three wildfires with varying post-fire salvage activities...

  17. Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure

    Energy Technology Data Exchange (ETDEWEB)

    Kukielka, A.M.; Hetnal, M.; Dabrowski, T.; Walasek, T.; Brandys, P.; Reinfuss, M. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Radiotherapy, Krakow (Poland); Nahajowski, D.; Kudzia, R.; Dybek, D. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Medical Physics, Department of Radiotherapy, Krakow (Poland)

    2014-02-15

    The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy. Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83 %). The aim of the hyperthermia treatment was to heat the prostate to 41-43 C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir + 2 ng/ml). The median age was 71 years (range 62-83 years), the median initial PSA level was 16.3 ng/ml (range 6.37-64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044-25.346 ng/ml). The median follow-up was 13 months (range 4-48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan-Meier estimate of biochemical control after salvage treatment was 74 %. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir < 0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients. IHT in combination

  18. Pemetrexed Alone versus Pemetrexed Combined with Oxaliplatin as Salvage Therapy 
in Stage IV Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Youru LIU

    2011-09-01

    Full Text Available Background and objective At present, there is no standard salvage treatment strategies for lung cancer. The aim of this study is to compare the efficacies and safeties of pemetrexed alone with pemetrexed combined with oxaliplatin as salvage therapy in stage IV lung adenocarcinoma to provide evidences for combination therapy. Methods From January 2009 to February 2011, 83 patients with stage IV lung adenocarcinoma received pemetrexed alone (single agent arm, n=47 or pemetrexed combined with oxaliplatin (combination arm, n=36 as salvage therapy. All 83 patients had performance status (PS scores of 0-2. Results Eighty-one patients were included in the final analysis. The median progression-free survival (PFS in the single agent arm was 3.6 months versus 4.1 months in the combination arm (P=0.268. The objective response rate (ORR was 6.5% versus 20% (P=0.092, and the disease control rate (DCR was 56.5% versus 65.7% (P=0.493, respectively. The response rates of the hematological and gastrointestinal toxicities in the single agent and combination arms were 33.9% versus 47.2% (P=0.460 and 21.2% versus 25.0% (P=0.213, respectively. Conclusion For salvage therapy, pemetrexed combined with oxaliplatin is tolerable in stage IV lung adenocarcinoma patients with good PS scores. Compared with pemetrexed alone, pemetrexed combined with oxaliplatin therapy showed higher response rate, but did not significantly prolong the PFS.

  19. Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab).

    Science.gov (United States)

    Tam, Constantine S; O'Brien, Susan; Plunkett, William; Wierda, William; Ferrajoli, Alessandra; Wang, Xuemei; Do, Kim-Anh; Cortes, Jorge; Khouri, Issa; Kantarjian, Hagop; Lerner, Susan; Keating, Michael J

    2014-11-13

    Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment. To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR. After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression. The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage. Patients with a short REM1 (<3 years) had a short survival period, irrespective of salvage therapy received; these patients have high unmet medical needs and are good candidates for investigation of novel therapies. In patients with a long REM1 (≥3 years), salvage treatment with either repeat FCR or lenalidomide-based therapy results in subsequent median survival exceeding 5 years; for these patients, FCR rechallenge represents a reasonable standard of care. © 2014 by The American Society of Hematology.

  20. Graduate Pathways: A Longitudinal Study of Graduates in Outdoor Studies in the U.K.

    Science.gov (United States)

    Prince, Heather

    2005-01-01

    A longitudinal study provides a more detailed analysis of the career pathways of graduates than the First Destination Survey can achieve. This survey of 41% of graduates from a BSc (Honours) Outdoor Studies degree also examines the importance of named skills to their careers and the success of the degree in developing each skill. Two thirds of…

  1. Vitamins and aging: pathways to NAD+ synthesis.

    Science.gov (United States)

    Denu, John M

    2007-05-04

    Recent genetic evidence reveals additional salvage pathways for NAD(+) synthesis. In this issue, Belenky et al. (2007) report that nicotinamide riboside, a new NAD(+) precursor, regulates Sir2 deacetylase activity and life span in yeast. The ability of nicotinamide riboside to enhance life span does not depend on calorie restriction.

  2. Ankle Arthrodesis Following Trauma, a Useful Salvage Procedure ...

    African Journals Online (AJOL)

    Open musculoskeletal injuries remain a difficult problem to manage especially in resource-poor regions. They are complicated by prolonged morbidity and chronic osseous infections and sometimes gangrene. Our objective was to look at ankle arthrodesis as a primary and useful salvage procedure through simple ...

  3. Salvageability of renal function following renal revascularisation in ...

    African Journals Online (AJOL)

    tion for the aortic arch and its branches.[1,2] It is ... Renal artery revascularisation procedures are usually carried out on children with renal artery stenosis from varied causes, including ... Salvageability of renal function in children who underwent renal revascularisation for Takayasu's arteritisinduced renal artery stenosis ...

  4. Recombinant alpha-interferon as salvage therapy in multiple myeloma

    African Journals Online (AJOL)

    1989-08-05

    Aug 5, 1989 ... optimal supportive care aimed at reversal of metabolic abnor- malities and relief of pain using local radiotherapy. However, loss of disease control usually occurs within 2 - 3 years and salvage therapy is then of limited benefit, although a number of alternative options exist. The latter include newer drug.

  5. Radiolabeling as a tool to study uptake pathways in plants

    Energy Technology Data Exchange (ETDEWEB)

    Schymura, Stefan; Hildebrand, Heike; Franke, Karsten [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Reactive Transport; Fricke, T. [Vita34 BioPlanta, Leipzig (Germany)

    2017-06-01

    The identification of major uptake pathways in plants is an important factor when evaluation the fate of manufactured nanoparticles in the environment and the associated risks. Using different radiolabeling techniques we were able to show a predominantly particulate uptake for CeO{sub 2} nanoparticles (NPs) in contrast to a possible uptake in the form of ionic cerium.

  6. [Progress in studies on TLR4 signaling pathway and major depressive disorder].

    Science.gov (United States)

    Wang, Lu; Chen, Jindong

    2017-06-28

    TLR4 signaling pathway plays an important role in regulation of the innate immune response and the adaptive immune response. Studies have shown that TLR4 signaling pathway is closely associated with the immune inflammatory process in major depressive disorder, but the underlying mechanisms are not clear. The pathophysiological process of depression involves multiple molecule mechanisms and signal pathways. The change of TLR4 signaling pathways exists in the peripheral circulation system or the central nervous system of depressive patients and depression animal models. The activation of TLR4 signaling pathways is associated with "stress-inflammation-depression" approach and "leaky gut" hypothesis, however, the relationship of peripheral and central TLR4 signaling pathways is not clear yet. TLR4 signaling pathway may be potential targets for the anti-inflammatory treatment of depression.

  7. Involvement of reperfusion injury salvage kinases in preconditioning depends critically on the preconditioning stimulus.

    Science.gov (United States)

    Manintveld, Olivier C; Sluiter, Wim; Dekkers, Dick H W; te Lintel Hekkert, Maaike; Lamers, Jos M J; Verdouw, Pieter D; Duncker, Dirk J

    2011-07-01

    Different preconditioning stimuli can activate divergent signaling pathways. In rats, adenosine-independent pathways (triple 3-min coronary artery occlusion [3CAO3]) and adenosine-dependent pathways (one 15-min coronary artery occlusion [ICAO15]) exist, both ultimately converging at the level of the mitochondrial respiratory chain. Furthermore, while 3CAO3, 1CAO15 and exogenous adenosine (ADO) are equally cardioprotective, only 1CAO15 increases interstitial myocardial adenosine levels. Reperfusion Injury Salvage Kinase (RISK) pathway kinases have been implicated in ischemic preconditioning, but not all preconditioning stimuli activate this pathway. Consequently, we evaluated in anesthetized rats the effects of three distinctly different preconditioning stimuli (3CAO3, 1CAO15 or ADO) on infarct size (IS), signaling pathways with a special emphasis on kinases belonging to the RISK pathway (phosphatidylinositol 3-kinase-Akt-nitric oxide synthase and extracellular signal-related kinase [ERK]) and mitochondrial respiration. All three stimuli increased state-2 respiration (using succinate as complex-II substrate), thereby decreasing the respiratory control index, which was accompanied by a limitation of IS produced by a 60-min coronary artery occlusion (CAO). Nitric oxide synthase inhibition abolished the mitochondrial effects and the cardioprotection by 3CAO3, 1CAO15 or ADO. In contrast, the PI3 kinase inhibitor, wortmannin, blocked protection by 1CAO15, but did not affect protection by 3CAO3 or ADO. Western blotting confirmed that phosphorylation of Akt and ERK were increased by 1CAO15 (which was inhibited by wortmannin), but not by 3CAO3 or ADO. In conclusion, while the three cardioprotective stimuli 3CAO3, 1CAO15 and ADO afford cardioprotection via nitric oxide-mediated modulation of mitochondrial respiration, only the 1CAO15 exerts its protection via activation of kinases belonging to the RISK pathway.

  8. A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy.

    Directory of Open Access Journals (Sweden)

    Erica Hlavin Bell

    Full Text Available To develop a microRNA (miRNA-based predictive model for prostate cancer patients of 1 time to biochemical recurrence after radical prostatectomy and 2 biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy.Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%. Eight hundred miRNAs were analyzed simultaneously using the nCounter human miRNA v2 assay (NanoString Technologies; Seattle, WA. Univariate and multivariate Cox proportion hazards regression models as well as receiver operating characteristics were used to identify statistically significant miRNAs that were predictive of biochemical recurrence.Eighty eight miRNAs were identified to be significantly (p36 months. Nine miRNAs were identified to be significantly (p<0.05 associated by multivariate analysis with biochemical failure after salvage radiation therapy. A new predictive model for biochemical recurrence after salvage radiation therapy was developed; this model consisted of miR-4516 and miR-601 together with, Gleason score, and lymph node status. The area under the ROC curve (AUC was improved to 0.83 compared to that of 0.66 for Gleason score and lymph node status alone.miRNA signatures can distinguish patients who fail soon after radical prostatectomy versus late failures, giving insight into which patients may need adjuvant therapy. Notably, two novel miRNAs (miR-4516 and miR-601 were identified that significantly improve prediction of biochemical failure post-salvage radiation therapy compared to clinico-histopathological factors, supporting the use of miRNAs within clinically used predictive models. Both findings warrant further

  9. Clinical experience of the use of voriconazole, caspofungin or the combination in primary and salvage therapy of invasive aspergillosis in haematological malignancies.

    Science.gov (United States)

    Raad, Issam I; Zakhem, Aline El; Helou, Gilbert El; Jiang, Ying; Kontoyiannis, Dimitrios P; Hachem, Ray

    2015-03-01

    Invasive aspergillosis (IA) is a life-threatening infection in severely immunocompromised haematological malignancy patients. In this study, the efficacy and safety of caspofungin, voriconazole or the combination as primary and salvage therapy in patients with IA were compared. The study included 181 patients with haematological malignancies and IA who received primary or salvage therapy with caspofungin, voriconazole or the combination. In total, 138 patients who received treatment for ≥7 days were analysed; 86 underwent primary antifungal therapy (15 with caspofungin, 38 with voriconazole and 33 with both). Among the salvage therapy patients, 17 received caspofungin, 24 received voriconazole and 35 received both. In the primary therapy group, no difference in therapy response was found, but caspofungin was associated with higher IA mortality rates. A multivariate competing risk analysis of primary antifungal therapy revealed that voriconazole was independently associated with lower IA-associated mortality rates than caspofungin (hazard ratio=0.2, 95% confidence interval 0.06-0.96; P=0.04). In the salvage therapy group, the three treatment groups had similar responses and IA-associated mortality rates. The combination of voriconazole and caspofungin did not result in better outcomes compared with voriconazole alone, as primary or salvage therapy, in haematological malignancy patients. However, voriconazole was associated with a lower Aspergillus-associated mortality rate compared with caspofungin monotherapy. Copyright © 2014. Published by Elsevier B.V.

  10. INFLUENCE OF INTRAOPERATIVE BLOOD SALVAGE ON SURGERY FOR SCOLIOSIS

    Directory of Open Access Journals (Sweden)

    JOSÉ ALBERTO ALVES OLIVEIRA

    Full Text Available ABSTRACT Objective: To evaluate the effectiveness of intraoperative blood salvage (IBS in reducing allogeneic transfusion in patients undergoing surgery for scoliosis. Methods: Retrospective case-control study with 69 patients who underwent surgical treatment for scoliosis correction from August 2008 to December 2014 in a teaching hospital. We used the IBS in 43 patients and it was not used in 26. The groups were compared according to the medical records, and the data were processed on SPSS 20.0. For the associations between the variable IBS and non-IBS and the independent variables we applied the χ 2 and the likelihood ratio tests, and the strength of which was calculated by their 95% CI. The means were compared by Student's t and Mann-Whitney tests. The confidence level was 0.05. Results: There were no significant differences between groups with the variables age, sex, preoperative weight, postoperative blood drainage and surgical time. There was a significant reduction of intraoperative allogeneic transfusion in the IBS group submitted to posterior arthrodesis compared with the control group, with no difference in the transfusion of red blood cells between the two groups postoperatively. In the 24 patients who underwent combined arthrodesis, there was no significant difference in allogeneic transfusion in the intra- and postoperative periods between the groups. Conclusion: The system proved to be effective in reducing allogeneic transfusion during surgery in patients undergoing posterior arthrodesis for scoliosis, but it was not effective in reducing allogeneic transfusion in the intra- and postoperative periods of those undergoing combined arthrodesis.

  11. Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study

    OpenAIRE

    Zhiwei Cao; Huiliang Li; Ruixin Zhu; Qi Liu; Jian Tang

    2011-01-01

    The hedgehog signal pathway is an essential agent in developmental patterning, wherein the local concentration of the Hedgehog morphogens directs cellular differentiation and expansion. Furthermore, the Hedgehog pathway has been implicated in tumor/stromal interaction and cancer stem cell. Nowadays searching novel inhibitors for Hedgehog Signal Pathway is drawing much more attention by biological, chemical and pharmological scientists. In our study, a solid computational model is proposed whi...

  12. Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

    Energy Technology Data Exchange (ETDEWEB)

    Ovacik, Meric A. [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Sen, Banalata [National Center for Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709 (United States); Euling, Susan Y. [National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC 20460 (United States); Gaido, Kevin W. [U.S. Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Division of Human Food Safety, Rockville, MD 20855 (United States); Ierapetritou, Marianthi G. [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Androulakis, Ioannis P., E-mail: yannis@rci.rutgers.edu [Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ 08854 (United States); Biomedical Engineering Department, Rutgers University, NJ 08854 (United States)

    2013-09-15

    Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data.

  13. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

    DEFF Research Database (Denmark)

    Sarwar, Nadeem; Sandhu, Manjinder S; Ricketts, Sally L

    2010-01-01

    Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality.......Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality....

  14. Salvage high-intensity focused ultrasound ablation for prostate cancer local recurrence after external-beam radiation therapy: prognostic value of prostate MRI.

    Science.gov (United States)

    Rouvière, O; Sbihi, L; Gelet, A; Chapelon, J-Y

    2013-07-01

    To assess the prognostic value of magnetic resonance imaging (MRI) before salvage high-intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after external-beam radiotherapy (EBRT). Forty-six patients who underwent prostate MRI before salvage HIFU for locally recurrent prostate cancer after EBRT were retrospectively studied. HIFU failure was defined as a prostate-specific antigen (PSA) value >nadir + 2 ng/ml (Phoenix criteria) or positive follow-up biopsy or initiation of any other salvage therapy. The following prognostic parameters were assessed: neoadjuvant hormone therapy, clinical stage and Gleason score of recurrence, PSA level and velocity at HIFU treatment, and six MRI-derived parameters (prostate volume, tumour volume, extracapsular extension, seminal vesicle invasion, tumour extension into the apex or anterior to the urethra). Two factors were significant independent predictors of salvage HIFU failure: the PSA level at HIFU treatment (p HIFU failure for locally recurrent prostate cancer after EBRT. Therefore, MRI may be useful for patient selection before post-EBRT salvage HIFU ablation. Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  15. Salvage of the PWI/DWI mismatch up to 48 h from stroke onset leads to favorable clinical outcome.

    Science.gov (United States)

    Ma, H; Wright, P; Allport, L; Phan, T G; Churilov, L; Ly, J; Zavala, J A; Arakawa, S; Campbell, B; Davis, S M; Donnan, G A

    2015-06-01

    In acute ischemic stroke perfusion/diffusion-weighted image, mismatch using magnetic resonance imaging approximates the ischemic penumbra. For early time windows, mismatch salvage improves clinical outcomes, but uncertainty exists at later time epochs. We hypothesized that (a) mismatch may exist up to 48 h; (b) the proportion of mismatch salvage is time independent; and (c) when salvaged, it improves clinical outcomes. Magnetic resonance imaging was performed within 48 h of ischemic stroke. Perfusion-weighted image was defined by relative Tmax two-second delay. Perfusion/diffusion-weighted image mismatch was the perfusion-weighted image not overlapped by the diffusion-weighted image when coregistered. Infarct volume and disability (modified Rankin Score) were assessed at three-months. Mismatch salvage was the region not overlapped by final infarction. Favorable outcome was defined as modified Rankin Score 0-1. Sixty-six patients were studied [mean age 69.9 years (standard deviation 13.1), initial median National Institute of Health Stroke Scale 9.0 (interquartile range 6.0, 18.3)]. There was no relationship between time of stroke onset and the proportion of mismatch salvaged (P = 0.73). Age (adjusted odds ratio = 0.92, 95% confidence interval 0.86-0.98, P = 0.01), initial National Institute of Health Stroke Scale (adjusted odds ratio = 0.80, 95% confidence interval 0.70-0.92, P < 0.01), mismatch volume (adjusted odds ratio = 0.98, 95% confidence interval 0.968-0.1, P = 0.05), and percentage of mismatch salvage (adjusted odds ratio = 1.04, 95% confidence interval 0.99-1.07, P = 0.05) were independently associated with favorable outcome. Using coregistered perfusion/diffusion-weighted image criteria, mismatch persists up to 48 h post stroke. For the whole group, the proportion of mismatch salvage remains independent of time and, although the effect is small, its salvage is independently associated with improved clinical

  16. Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only

    Energy Technology Data Exchange (ETDEWEB)

    Rischke, Hans Christian [University of Freiburg, Department of Radiation Oncology, Freiburg (Germany); University of Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Schultze-Seemann, Wolfgang; Kroenig, Malte; Schlager, Daniel; Jilg, Cordula Annette [University of Freiburg, Department of Urology, Freiburg (Germany); Wieser, Gesche [University of Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Drendel, Vanessa [University of Freiburg, Department of Pathology, Freiburg (Germany); Stegmaier, Petra; Henne, Karl; Volegova-Neher, Natalia; Grosu, Anca-Ligia [University of Freiburg, Department of Radiation Oncology, Freiburg (Germany); Krauss, Tobias; Kirste, Simon [University of Freiburg, Department of Radiology, Freiburg (Germany)

    2015-04-01

    Nodal pelvic/retroperitoneal recurrent prostate cancer (PCa) after primary therapy can be treated with salvage lymph node dissection (salvage-LND) in order to delay disease progression and offer cure for a subset of patients. Whether adjuvant radiotherapy (ART) in affected regions improves the outcome by elimination of residual tumour burden remains unclear. A total of 93 patients with exclusively nodal PCa relapse underwent choline-positron-emission tomography-computed-tomography-directed pelvic/retroperitoneal salvage-LND; 46 patients had surgery only and 47 patients received ART in regions with proven lymph node metastases. In case of subsequent prostate specific antigen (PSA) progression, different imaging modalities were performed to confirm next relapse within or outside the treated region (TR). Mean follow-up was 3.2 years. Lymphatic tumour burden was balanced between the two groups. Additional ART resulted in delayed relapse within TR (5-year relapse-free rate 70.7 %) versus surgery only (5-year relapse-free rate 26.3 %, p < 0.0001). In both treatment arms, time to next relapse outside the TR was almost equal (median 27 months versus 29.6 months, p = 0.359). With respect to the detection of the first new lesion, regardless if present within or outside the TR, 5 years after the treatment 34.3 % of patients in the group with additional ART were free of relapse, versus 15.4 % in the surgery only group (p = 0.0122). ART had no influence on the extent of PSA reduction at latest follow-up compared to treatment with surgery only. ART after salvage-LND provides stable local control in TR and results in overall significant improved next-relapse-free survival, compared to patients who received surgery only in case of nodal PCa-relapse. (orig.) [German] Das nodal positive Prostatakarzinom(PCa)-Rezidiv nach Primaertherapie kann durch eine Salvage-Lymphadenektomie (Salvage-LND) therapiert werden. Der Krankheitsprogress wird aufgehalten und selektionierte Patienten

  17. Metabolic signature of sun exposed skin suggests catabolic pathway overweighs anabolic pathway.

    Directory of Open Access Journals (Sweden)

    Manpreet Randhawa

    Full Text Available Skin chronically exposed to sun results in phenotypic changes referred as photoaging. This aspect of aging has been studied extensively through genomic and proteomic tools. Metabolites, the end product are generated as a result of biochemical reactions are often studied as a culmination of complex interplay of gene and protein expression. In this study, we focused exclusively on the metabolome to study effects from sun-exposed and sun-protected skin sites from 25 human subjects. We generated a highly accurate metabolomic signature for the skin that is exposed to sun. Biochemical pathway analysis from this data set showed that sun-exposed skin resides under high oxidative stress and the chains of reactions to produce these metabolites are inclined toward catabolism rather than anabolism. These catabolic activities persuade the skin cells to generate metabolites through the salvage pathway instead of de novo synthesis pathways. Metabolomic profile suggests catabolic pathways and reactive oxygen species operate in a feed forward fashion to alter the biology of sun exposed skin.

  18. WRIST SALVAGE PROCEDURES ALTER MOMENT ARMS OF THE PRIMARY WRIST MUSCLES

    Science.gov (United States)

    Nichols, Jennifer A.; Bednar, Michael S.; Havey, Robert M.; Murray, Wendy M.

    2015-01-01

    Background Proximal row carpectomy and scaphoid-excision four-corner fusion are salvage procedures that relieve pain by removing arthritic joint surfaces. While numerous studies have examined how these procedures affect joint motion, few have examined how they influence muscle mechanical actions. This study examines whether muscle moment arms change after these procedures. Methods Moment arms of primary wrist muscles were measured in 8 cadaveric specimens using the tendon excursion method. In each specimen, moment arms were measured for two degrees of freedom (flexion-extension and radial-ulnar deviation) and three conditions (nonimpaired, scaphoid-excision four-corner fusion, and proximal row carpectomy). For each muscle and degree of freedom, moment arm versus joint angle curves for the three conditions were statistically compared. Findings Wrist salvage procedures significantly alter moment arms of the primary wrist muscles. Proximal row carpectomy primarily alters flexion-extension moment arms, while scaphoid-excision four-corner fusion primarily alters radial-ulnar deviation moment arms. Both procedures also alter the balance between agonist and antagonist wrist muscles. Following proximal row carpectomy, wrist extensors have smaller moment arms in extended postures. Following scaphoid-excision four-corner fusion, radial deviators have larger moment arms throughout radial-ulnar deviation. Interpretation Different moment arms indicate that different forces are required to complete the same tasks in nonimpaired and surgically altered wrists. The altered muscle moment arms likely contribute to post-operative impairments. Understanding how salvage procedures alter muscle mechanical actions is a critical first step toward identifying the cause of post-operative impairments and is necessary to develop effective interventions to augment deficient muscles and improve overall function. PMID:25843482

  19. Osteocutaneous pedicle flap transfer for salvage of transtibial amputation after severe lower-extremity injury.

    Science.gov (United States)

    Vallier, Heather A; Fitzgerald, Steven J; Beddow, Meghan E; Sontich, John K; Patterson, Brendan M

    2012-03-07

    A conventional transtibial amputation may not be possible when the zone of injury involves the proximal part of the tibia, or in cases of massive tibial bone and/or soft-tissue loss. The purpose of this study was to examine the outcomes of salvage of a transtibial amputation level with a rotational osteocutaneous pedicle flap from the ipsilateral hindfoot. Fourteen patients who had an osteocutaneous pedicle flap from the ipsilateral foot were included in the study. Twelve patients were followed for more than twenty-four months (mean, 60.2 months) and were evaluated with use of the Sickness Impact Profile (SIP), Musculoskeletal Function Assessment (MFA), and a 100-ft (30.48-m) timed walking test. There were ten men and four women with mean age of 43.2 years. Thirteen patients had a type-IIIB open tibial fracture, and one had extensive soft-tissue loss secondary to a burn. Four patients were treated for infection after the index procedure. There were no nonunions of the tibia to the calcaneus. Three patients underwent late reconstructive procedures to improve prosthetic fit. No patient required subsequent revision to a more proximal amputation level. Mean knee flexion was 139°. A novel technique has been developed to salvage a transtibial amputation level with use of a rotational osteocutaneous flap from the hindfoot. In the absence of adequate tibial length and/or soft-tissue coverage to salvage the entire limb or to perform a conventional-length transtibial amputation, this technique is a highly functional alternative that does not require microvascular free tissue transfer.

  20. Salvage of extensively burned upper limbs by a pedicled latissimus dorsi flap.

    Science.gov (United States)

    Delay, E; Foyatier, J L; el Kollali, R; Comparin, J P; Weil, E; Latarjet, J

    1995-09-01

    Very deep burns of the arm and elbow lead to soft tissue necrosis and infection with exposure of important structures. Aggressive debridement should be performed as early as possible to cut the vicious circle, and the defect, which may be extensive, should be covered by well-vascularized tissues. The reliability and versatility of the pedicled latissimus dorsi muscle or musculocutaneous flap make it our first choice in the management of this problem. A retrospective study of three patients for whom salvage of the upper limb has been achieved by the use of a pedicled latissimus dorsi flap is presented, illustrating the advantages of this technique.

  1. Deoxynucleoside Salvage in Fission Yeast Allows Rescue of Ribonucleotide Reductase Deficiency but Not Spd1-Mediated Inhibition of Replication

    Directory of Open Access Journals (Sweden)

    Oliver Fleck

    2017-04-01

    Full Text Available In fission yeast, the small, intrinsically disordered protein S-phase delaying protein 1 (Spd1 blocks DNA replication and causes checkpoint activation at least in part, by inhibiting the enzyme ribonucleotide reductase, which is responsible for the synthesis of DNA. The CRL4Cdt2 E3 ubiquitin ligase mediates degradation of Spd1 and the related protein Spd2 at S phase of the cell cycle. We have generated a conditional allele of CRL4Cdt2, by expressing the highly unstable substrate-recruiting protein Cdt2 from a repressible promoter. Unlike Spd1, Spd2 does not regulate deoxynucleotide triphosphate (dNTP pools; yet we find that Spd1 and Spd2 together inhibit DNA replication upon Cdt2 depletion. To directly test whether this block of replication was solely due to insufficient dNTP levels, we established a deoxy-nucleotide salvage pathway in fission yeast by expressing the human nucleoside transporter human equilibrative nucleoside transporter 1 (hENT1 and the Drosophila deoxynucleoside kinase. We present evidence that this salvage pathway is functional, as 2 µM of deoxynucleosides in the culture medium is able to rescue the growth of two different temperature-sensitive alleles controlling ribonucleotide reductase. However, salvage completely failed to rescue S phase delay, checkpoint activation, and damage sensitivity, which was caused by CRL4Cdt2 inactivation, suggesting that Spd1—in addition to repressing dNTP synthesis—together with Spd2, can inhibit other replication functions. We propose that this inhibition works at the point of the replication clamp proliferating cell nuclear antigen, a co-factor for DNA replication.

  2. Theoretical studies on the reaction pathways of electronically excited DAAF

    Energy Technology Data Exchange (ETDEWEB)

    Quenneville, Jason M [Los Alamos National Laboratory; Moore, David S [Los Alamos National Laboratory

    2009-01-01

    The use of temporally and spectrally shaped ultrafast laser pulses to initiate, as well as detect, high explosives is being explored at Los Alamos. High level ab initio calculations, presented here, are employed to help guide and interpret the experiments. The ground and first excited electronic states of 3,3{prime}-diamino-4,4{prime}-azoxyfurazan (DAAF) are investigated using complete active space self-consistent field (CASSCF) and time-dependent density functional theory (TD-DFT). The geometrical and energetic character of the excited state minima, conical intersections and reaction pathways of DAAF are described. Two radiative and two non-radiative excited state population quenching mechanisms are outlined, and possible pathways for photochemical and spectroscopic control are discussed. The use of laser light to control chemical reactions has many applications. The initiation and the detection of explosives are two such applications currently under development at Los Alamos. Though inherently experimental, the project can be aided by theory through both prediction and interpretation. When the laser light is in the UV/visible region of the electromagnetic spectrum, the absorbing molecule is excited electronically and excitation decay may occur either radiatively (fluorescence or phosphorescence) or non-radiatively (through internal conversion). In many cases decay of the excitation occurs through a mixture of processes, and maximizing the desired result requires sophisticated laser pulses whose amplitude has been optimally modulated in time and/or frequency space. Control of cis-stilbene photochemistry was recently demonstrated in our group, and we aim to extend this work to high explosive compounds. Maximizing radiative decay leads to increased fluorescence quantum yields and enhances the possibility of spectral detection of the absorbing molecule. Maximizing non-radiative decay can lead to chemistry, heating of the sample and possibly detonation initiation in

  3. Physiological and morphological responses of pine and willow saplings to post-fire salvage logging

    Science.gov (United States)

    Millions, E. L.; Letts, M. G.; Harvey, T.; Rood, S. B.

    2015-12-01

    With global warming, forest fires may be increasing in frequency, and post-fire salvage logging may become more common. The ecophysiological impacts of this practice on tree saplings remain poorly understood. In this study, we examined the physiological and morphological impacts of increased light intensity, due to post-fire salvage logging, on the conifer Pinus contorta (pine) and deciduous broadleaf Salix lucida (willow) tree and shrub species in the Crowsnest Pass region of southern Alberta. Photosynthetic gas-exchange and plant morphological measurements were taken throughout the summer of 2013 on approximately ten year-old saplings of both species. Neither species exhibited photoinhibition, but different strategies were observed to acclimate to increased light availability. Willow saplings were able to slightly elevate their light-saturated rate of net photosynthesis (Amax) when exposed to higher photosynthetic photon flux density (PPFD), thus increasing their growth rate. Willow also exhibited increased leaf inclination angles and leaf mass per unit area (LMA), to decrease light interception in the salvage-logged plot. By contrast, pine, which exhibited lower Amax and transpiration (E), but higher water-use efficiency (WUE = Amax/E) than willow, increased the rate at which electrons were moved through and away from the photosynthetic apparatus in order to avoid photoinhibition. Acclimation indices were higher in willow saplings, consistent with the hypothesis that species with short-lived foliage exhibit greater acclimation. LMA was higher in pine saplings growing in the logged plot, but whole-plant and branch-level morphological acclimation was limited and more consistent with a response to decreased competition in the logged plot, which had much lower stand density.

  4. Robotic Salvage Lymph Node Dissection After Radical Prostatectomy

    Directory of Open Access Journals (Sweden)

    Fabio C. M. Torricelli

    2015-08-01

    Full Text Available ABSTRACTIntroduction and objective:Radical prostatectomy is a first-line treatment for localized prostate cancer. However, in some cases, biochemical recurrence associated with imaging-detected nodal metastases may happen. Herein, we aim to present the surgical technique for salvage lymph node dissection after radical prostatectomy.Materials and Methods:A 70 year-old asymptomatic man presented with a prostate-specific antigen (PSA of 7.45ng/ mL. Digital rectal examination was normal and trans-rectal prostate biopsy revealed a prostate adenocarcinoma Gleason 7 (3+4. Pre-operative computed tomography scan and bone scintigraphy showed no metastatic disease. In other service, the patient underwent a robotic-assisted radical prostatectomy plus obturador lymphadenectomy. Pathologic examination showed a pT3aN0 tumor. After 6 months of follow-up, serum PSA was 1.45ng/mL. Further investigation with 11C–Choline PET/CT revealed only a 2-cm lymph node close to the left internal iliac artery. The patient was counseled for salvage lymph node dissection.Results:Salvage lymph node dissection was uneventfully performed. Operative time was 1.5 hour, blood loss was minimal, and there were no intra- or postoperative complications. The patient was discharged from hospital in the 1st postoperative day. After 12 months of follow-up, his PSA was undetectable with no other adjuvant therapy.Conclusion:Robotic salvage pelvic lymph node dissection is an effective option for treatment of patients with biochemical recurrence after radical prostatectomy and only pelvic lymph node metastasis detected by C11-Choline PET/CT.

  5. Salvage chemotherapy for gestational trophoblastic neoplasia: Utility or futility?

    Science.gov (United States)

    Essel, Kathleen G; Bruegl, Amanda; Gershenson, David M; Ramondetta, Lois M; Naumann, R Wendel; Brown, Jubilee

    2017-07-01

    To determine the efficacy of chemotherapy after failed initial treatment in patients with high risk gestational trophoblastic neoplasia (GTN). We performed a retrospective IRB-approved chart review of all patients with GTN seen at a single institution from 1985 to 2015, including all patients who failed initial treatment. We summarized clinical characteristics with descriptive statistics and estimated progression-free survival (PFS) and overall survival (OS) with the Kaplan-Meier method. Of 68 identified patients, 38 required >2 chemotherapy regimens. Patients were treated for GTN (n=53), including choriocarcinoma, persistent GTN, and invasive mole; for placental site trophoblastic tumor (PSTT) (n=5); and for intermediate trophoblastic tumor (ITT) (n=10). Patients with GTN had a median of 2 salvage regimens, median PFS of 4.0months, and median OS was not reached at median follow-up of 71.2months. Active regimens included EMACO, MAC, BEP, platinum- and etoposide-based combination therapies, and ICE; 8 of 53 patients died of disease (DOD). Patients with PSTT had a median of 3 salvage regimens, median PFS of 2.8months, and median OS of 38.8months. Active regimens included ICE and EMA-EP; 4 of 5 patients DOD. Patients with ITT had a median of 3 salvage regimens, median PFS of 4.1months, and median OS of 38.2months. Active regimens included liposomal doxorubicin, platinum-containing regimens, EMA-CO, and EMA-EP; 7 of 10 patients DOD. Several salvage chemotherapy regimens demonstrate activity in high risk GTN. Multiple regimens may be required and cure is not universal. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Malawer limb salvage surgery for the treatment of scapular chondrosarcoma.

    Science.gov (United States)

    Chang, Fei; Liu, Guang-Yao; Zhang, Qiao; Lin, Gang; Huang, Hong; Duan, De-Sheng; Wang, Jin-Cheng

    2014-06-30

    Chondrosarcoma is a common malignant bone tumor, which accounts for 20% of all malignant bone tumors. It often occurs in the long bones, but the incidence of scapular chondrosarcoma is rare. Here, we describe a case of a large chondrosarcoma occurring in the scapula which was treated with Malawer limb salvage surgery. The patient retained considerable limb function after complete removal of the tumor tissue as assessed at the follow-up visit two years and ten months following surgery.

  7. Effects of Post-Fire Salvage Logging on Infiltration, Soil Compaction, and Erosion in Central California.

    Science.gov (United States)

    Demirtas, I.; Wagenbrenner, J. W.; Olsen, W.; Robichaud, P. R.

    2016-12-01

    Post-fire salvage logging can be an economic concern for forest managers in recently burned areas. Previous studies have shown that logging activities in burned areas can affect soil compaction, runoff, and erosion. Our objectives were to: (1) determine the effects of specific salvage logging activities on field-saturated hydraulic conductivity (Kfs), (2) determine the relationship between soil compaction and Kfs, and (3) compare the sediment yields among different levels of salvage logging disturbances. We established study plots at two spatial scales and multiple levels of logging impact in three sites severely burned by the 2013 Rim Fire after salvage logging occurred in 2014-2015. At the hillslope scale ( 75 m2), plots represented a uniform disturbance including burned and unlogged controls, logged areas with no mechanical disturbance, few pass skid trails (1-3 passes), and many pass skid trails (4 or more passes). The small catchment scale ( 0.09-0.74 ha) reflected spatially distributed impacts of 5 levels of disturbance: burned, non-trafficked areas; feller-buncher tracks; few and many pass skid trails; and a combination of multiple disturbances. Across the three sites we installed 27 hillslope plots (9 controls and 6 of each type of uniform logging disturbance) and 14 small catchments (5 controls and 9 logged). Kfs was measured using a DualHead infiltrometer in each hillslope plot and in an area representative of each disturbance class in each catchment in summer 2015 and summer 2016. Compaction was measured using a bulk density core sampler at 0-5 and 5-10 cm adjacent to each Kfs measurement. Sediment yields were measured by silt fences through fall 2016. Few and many pass skid trails reduced Kfs, and these areas had 76% to 82% lower Kfs than the controls, respectively. Few and many pass skid trails also increased the soil compaction relative to undisturbed controls. Control plots produced a mean annual sediment yield of 23 Mg ha-1, and the logged plots

  8. "I Am-We Are": Personal and Social Pathways to Further Study, Work and Family Life

    Science.gov (United States)

    Bornholt, L. J.; Maras, P. M.; Robinson, R. A.

    2009-01-01

    This project explores the apparent layers in motivation for young people's plans in order to extend Pathways Theory. We bring together personal, relational and group motivation to explain the planned pathways to study, work and family life. Location was an Australian town, close to the national socio-economic average, to control broad social…

  9. Radial Artery Approach to Salvage Nonmaturing Radiocephalic Arteriovenous Fistulas

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Mu-Yang; Lin, Lin; Tsai, Kuei-Chin; Wu, Chih-Cheng, E-mail: chihchengwumd@gmail.com [National Taiwan University Hospital, Department of Cardiology (China)

    2013-08-01

    PurposeTo evaluate the usefulness of an approach through the radial artery distal to the arteriovenous anastomosis for salvaging nonmaturing radiocephalic arteriovenous fistulas.MethodsProcedures that fulfilled the following criteria were retrospectively reviewed: (1) autogenous radiocephalic fistulas, (2) fistulas less than 3 months old, (3) distal radial artery approach for salvage. From 2005 to 2011, a total of 51 patients fulfilling the above criteria were enrolled. Outcome variables were obtained from angiographic, clinical and hemodialysis records, including the success, complication, and primary and secondary patency rates.ResultsThe overall anatomical and clinical success rates for the distal radial artery approach were 96 and 94 %, respectively. The average procedure time was 36 {+-} 19 min. Six patients (12 %) experienced minor complications as a result of extravasations. No arterial complication or puncture site complication was noted. The postinterventional 6-month primary patency rate was 51 %, and the 6-month secondary patency rate was 90 %. When the patients were divided into a stenosed group (20 patients) and an occluded group (31 patients), there were no differences in the success rate, complication rate, or primary and secondary patency rates.ConclusionAn approach through the radial artery distal to the arteriovenous anastomosis is an effective and safe alternative for the salvage of nonmaturing radiocephalic arteriovenous fistulas, even for occluded fistulas.

  10. Integrative pathway-based approach for genome-wide association studies: identification of new pathways for rheumatoid arthritis and type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Finja Büchel

    Full Text Available Genome-wide association studies (GWAS led to the identification of numerous novel loci for a number of complex diseases. Pathway-based approaches using genotypic data provide tangible leads which cannot be identified by single marker approaches as implemented in GWAS. The available pathway analysis approaches mainly differ in the employed databases and in the applied statistics for determining the significance of the associated disease markers. So far, pathway-based approaches using GWAS data failed to consider the overlapping of genes among different pathways or the influence of protein-interactions. We performed a multistage integrative pathway (MIP analysis on three common diseases--Crohn's disease (CD, rheumatoid arthritis (RA and type 1 diabetes (T1D--incorporating genotypic, pathway, protein- and domain-interaction data to identify novel associations between these diseases and pathways. Additionally, we assessed the sensitivity of our method by studying the influence of the most significant SNPs on the pathway analysis by removing those and comparing the corresponding pathway analysis results. Apart from confirming many previously published associations between pathways and RA, CD and T1D, our MIP approach was able to identify three new associations between disease phenotypes and pathways. This includes a relation between the influenza-A pathway and RA, as well as a relation between T1D and the phagosome and toxoplasmosis pathways. These results provide new leads to understand the molecular underpinnings of these diseases. The developed software herein used is available at http://www.cogsys.cs.uni-tuebingen.de/software/GWASPathwayIdentifier/index.htm.

  11. Impact of Heart Rate on Myocardial Salvage in Timely Reperfused Patients with ST-Segment Elevation Myocardial Infarction: New Insights from Cardiovascular Magnetic Resonance.

    Directory of Open Access Journals (Sweden)

    Luca Arcari

    Full Text Available Previous studies evaluating the progression of the necrotic wave in relation to heart rate were carried out only in animal models of ST-elevated myocardial infarction (STEMI. Aim of the study was to investigate changes of myocardial salvage in relation to different heart rates at hospital admission in timely reperfused patients with STEMI by using cardiovascular magnetic resonance (CMR.One hundred-eighty-seven patients with STEMI successfully and timely treated with primary coronary angioplasty underwent CMR five days after hospital admission. According to the heart rate at presentation, patients were subcategorized into 5 quintiles: <55 bpm (group I, n = 44, 55-64 bpm (group II, n = 35, 65-74 bpm (group III, n = 35, 75-84 bpm (group IV, n = 37, ≥85 bpm (group V, n = 36. Area at risk, infarct size, microvascular obstruction (MVO and myocardium salvaged index (MSI were assessed by CMR using standard sequences.Lower heart rates at presentation were associated with a bigger amount of myocardial salvage after reperfusion. MSI progressively decreased as the heart rates increased (0.54 group I, 0.46 group II, 0.38 group III, 0.34 group IV, 0.32 group V, p<0.001. Stepwise multivariable analysis showed heart rate, peak troponin and the presence of MVO were independent predictor of myocardial salvage. No changes related to heart rate were observed in relation to area at risk and infarct size.High heart rates registered before performing coronary angioplasty in timely reperfused patients with STEMI are associated with a reduction in salvaged myocardium. In particular, salvaged myocardium significantly reduced when heart rate at presentation is ≥85 bpm.

  12. Salvage treatments for prostatic radiation failure; Traitements de rattrapage apres radiotherapie prostatique

    Energy Technology Data Exchange (ETDEWEB)

    Baumert, H. [Service d' urologie, groupe hospitalier Paris Saint-Joseph, 75 - Paris (France)

    2010-10-15

    Local recurrence after external radiotherapy or brachytherapy occurs in 30% of patients treated for prostate cancer. These recurrences can be localised to the prostate and controlled by salvage treatment. Salvage prostatectomy is the gold standard treatment, however, it is associated with a high morbidity rate. Minimally invasive treatments such as cryo-therapy and high intensity focused ultrasound (HIFU) can be proposed to treat local recurrences. Indications, complications and oncological results of these salvage treatments are discussed in this article. (author)

  13. The Initial Case Report: Salvage Robotic Assisted Radical Prostatectomy After Heavy Ion Radiotherapy

    Directory of Open Access Journals (Sweden)

    Choichiro Ozu

    2016-07-01

    Full Text Available Salvage radical prostatectomy is one of treatments after radiation therapy to patients with prostate cancer. To date, no case of the salvage robotic assisted radical prostatectomy (RARP following heavy ion radiotherapy (HIRT has been published. We report on a 70-year-old man with a history of HIRT for prostate cancer in 2011. For 3 years after. HIRT, his serum PSA levels were permissible range. However, his PSA levels were increased. We had diagnosis localized prostate cancer after HIRT. We had carried out salvage RARP. Until 10 months after salvage RARP, his PSA level was not detectable.

  14. Early individual experience with distal venous arterialization as a lower limb salvage procedure.

    Science.gov (United States)

    Djoric, Predrag

    2011-06-01

    This prospective randomized study reported early results of the treatment of 36 unreconstructable patients with critical lower limb ischemia. The patients were divided into two groups: 12 were treated with distal venous arterialization (DVA) and 24 were conservatively (CT) using antiplatelet drugs. There were seven men and five women with an average age 64.3 ± 9.9 in DVA and 13 men and 11 women with a average age 67.1 ± 10.8 in CT groups of patients. The aim of this study was to estimate the validity of DVA as the limb salvage procedure. During the period of monitoring, morbidity and mortality rates were 50 and 0 per cent at DVA versus a mortality rate in the CT group of 33.3 per cent (P DVA was 4.8 ± 3.9 months (range, 1 to 14 months) versus 4.9 ± 2.4 months (range, 1 to 9 months) for the CT group (P > 0.05). Graft patency was 83.3 per cent with two early graft thromboses. There were significant differences between the two groups in limb salvage (91.7% DVA vs 12.5% CT, P DVA vs 8.3% CT, P DVA vs 0% CT, P DVA may improve the outcome of the treatment of the patients for whom the conventional bypass procedure mainly was not possible.

  15. The Role of High Dose Intratympanic Dexamethasone as Salvage Therapy for Idiopathic Sudden Sensorineural Hearing Loss.

    Science.gov (United States)

    Kordiš, Špela; Battelino, Saba

    2017-11-21

    The aim of this study was to assess the efficacy of a single high dose intratympanic (IT) dexamethasone (DEX) as salvage therapy for idiopathic sudden sensorineural hearing loss (ISSNHL) after unsuccessful treatment with oral corticosteroid (CS). This was a prospective open-label study of 59 patients treated with IT DEX after systemic CS therapy has failed. All patients received high dose (24 mg/mL) IT DEX in a single injection through myringotomy. Of the 59 patients, 40.7% showed improvement in their mean pure tone average (PTA) with IT DEX (p=0.005). The difference in the mean PTA after oral CS treatment only from baseline was not statistically significant (p=0.074). The time from onset of hearing loss to the start of therapy was significantly associated with the outcome (p=0.03). We determined that high dose IT DEX as salvage therapy was beneficial when the primary treatment with oral CS had failed. An early start of the treatment significantly influenced the improvement of hearing.

  16. Percutaneous Creation of Bare Intervascular Tunnels for Salvage of Thrombosed Hemodialysis Fistulas Without Recanalizable Outflow

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Matt Chiung-Yu, E-mail: jjychen@gmail.com [Yuan’s General Hospital, Department of Interventional Radiology (China); Wang, Yen-Chi [E-Da Hospital, Department of Radiology (China); Weng, Mei-Jui [Kaohsiung Veterans General Hospital, Department of Radiology (China)

    2015-08-15

    PurposeThis study aimed to retrospectively assess the efficacy of a bare intervascular tunnel for salvage of a thrombosed hemodialysis fistula. We examined the clinical outcomes and provided follow-up images of the bare intervascular tunnel.Materials and MethodsEight thrombosed fistulas lacked available recanalizable outflow veins were included in this study. These fistulas were salvaged by re-directing access site flow to a new outflow vein through a percutaneously created intervascular tunnel without stent graft placement. The post-intervention primary and secondary access patency rates were calculated using the Kaplan–Meier method.ResultsThe procedural and clinical success rates were 100 %. Post-intervention primary and secondary access patency at 300 days were 18.7 ± 15.8 and 87.5 ± 11.7 %, respectively. The mean follow-up period was 218.7 days (range 10–368 days). One patient died of acute myocardial infarction 10 days after the procedure. No other major complications were observed. Minor complications, such as swelling, ecchymosis, and pain around the tunnel, occurred in all of the patients.ConclusionsPercutaneous creation of a bare intervascular tunnel is a treatment option for thrombosed hemodialysis fistulas without recanalizable outflow in selected patients.

  17. Botrytis cinerea can import and utilize nucleosides in salvage and catabolism and BcENT functions as high affinity nucleoside transporter.

    Science.gov (United States)

    Daumann, Manuel; Golfier, Philippe; Knüppel, Nathalie; Hahn, Matthias; Möhlmann, Torsten

    2016-08-01

    Nucleotide de novo synthesis is an essential pathway in nearly all organisms. Transport processes as well as salvage and catabolism of nucleotides and pathway intermediates are required to balance nucleotide pools. We have analysed the genome of the fungal plant pathogen Botrytis cinerea for genes involved in nucleotide metabolism and found a complete set of genes necessary for purine and pyrimidine uptake and salvage based on homology of the gene products to corresponding proteins from Aspergillus nidulans. Candidate genes required for a complete purine catabolic sequence were identified in addition. These analyses were complemented by growth tests showing functional transport and salvage activity for pyrimidines. Growth of B. cinerea mycelium in nitrogen free medium could be restored by addition of purines, indicating the presence of a functional purine catabolism, whereas pyrimidines did not support growth. Bcin07g05490 (BcENT) was identified as sole member of the equilibrative nucleoside transporter (ENT) family. The protein synthesized in Saccharomyces cerevisiae revealed high affinity transport of adenosine (KM = 6.81 μM) and uridine (KM=9.04 μM). Furthermore, a BcENT knockout mutant was generated and tested in a range of growth and infection assays. These results provide detailed insight in the use of externally supplied nucleobases and nucleosides by B. cinerea. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  18. Incorporating biological pathways via a Markov random field model in genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Min Chen

    2011-04-01

    Full Text Available Genome-wide association studies (GWAS examine a large number of markers across the genome to identify associations between genetic variants and disease. Most published studies examine only single markers, which may be less informative than considering multiple markers and multiple genes jointly because genes may interact with each other to affect disease risk. Much knowledge has been accumulated in the literature on biological pathways and interactions. It is conceivable that appropriate incorporation of such prior knowledge may improve the likelihood of making genuine discoveries. Although a number of methods have been developed recently to prioritize genes using prior biological knowledge, such as pathways, most methods treat genes in a specific pathway as an exchangeable set without considering the topological structure of a pathway. However, how genes are related with each other in a pathway may be very informative to identify association signals. To make use of the connectivity information among genes in a pathway in GWAS analysis, we propose a Markov Random Field (MRF model to incorporate pathway topology for association analysis. We show that the conditional distribution of our MRF model takes on a simple logistic regression form, and we propose an iterated conditional modes algorithm as well as a decision theoretic approach for statistical inference of each gene's association with disease. Simulation studies show that our proposed framework is more effective to identify genes associated with disease than a single gene-based method. We also illustrate the usefulness of our approach through its applications to a real data example.

  19. Genome-wide pathway association studies of multiple correlated quantitative phenotypes using principle component analyses.

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    Full Text Available Genome-wide pathway association studies provide novel insight into the biological mechanism underlying complex diseases. Current pathway association studies primarily focus on single important disease phenotype, which is sometimes insufficient to characterize the clinical manifestations of complex diseases. We present a multi-phenotypes pathway association study(MPPAS approach using principle component analysis(PCA. In our approach, PCA is first applied to multiple correlated quantitative phenotypes for extracting a set of orthogonal phenotypic components. The extracted phenotypic components are then used for pathway association analysis instead of original quantitative phenotypes. Four statistics were proposed for PCA-based MPPAS in this study. Simulations using the real data from the HapMap project were conducted to evaluate the power and type I error rates of PCA-based MPPAS under various scenarios considering sample sizes, additive and interactive genetic effects. A real genome-wide association study data set of bone mineral density (BMD at hip and spine were also analyzed by PCA-based MPPAS. Simulation studies illustrated the performance of PCA-based MPPAS for identifying the causal pathways underlying complex diseases. Genome-wide MPPAS of BMD detected associations between BMD and KENNY_CTNNB1_TARGETS_UP as well as LONGEVITYPATHWAY pathways in this study. We aim to provide a applicable MPPAS approach, which may help to gain deep understanding the potential biological mechanism of association results for complex diseases.

  20. High PSA anxiety and low health literacy skills: drivers of early use of salvage ADT among men with biochemically recurrent prostate cancer after radiotherapy?

    Science.gov (United States)

    Mahal, B A; Chen, M-H; Bennett, C L; Kattan, M W; Sartor, O; Stein, K; D'Amico, A V; Nguyen, P L

    2015-07-01

    Although commonly used, early initiation of salvage androgen deprivation therapy (ADT) has not been proven to enhance survival. We evaluated whether prostate-specific antigen (PSA) anxiety or health literacy are associated with use of early salvage ADT among men with recurrent prostate cancer after radiotherapy. The prospective Comprehensive, Observational, Multicenter, Prostate Adenocarcinoma Registry was used to study 375 men with biochemically recurrent prostate cancer after external beam radiation or brachytherapy. Multivariable logistic regression was used to determine whether PSA anxiety and health literacy are associated with salvage ADT as initial management after biochemical recurrence. Sixty-eight men (18.1%) received salvage ADT as initial management for PSA recurrence. Men with high PSA anxiety were twice as likely to receive salvage ADT compared with men who did not have high PSA anxiety on both univariable [28.8% versus 13.1%; odds ratio (OR) 2.15; 95% confidence interval (CI) 1.16-4.00; P = 0.015] and multivariable analysis [adjusted OR (AOR) 2.36; 95% CI 1.21-4.62; P = 0.012]. Furthermore, men who had higher levels of health literacy were nearly half as likely to undergo salvage ADT compared with men who had lower levels of health literacy on univariable analysis (15.2% versus 26.3%; OR 0.50; 95% CI 0.29-0.88; P = 0.016), with a trend toward this association on multivariable analysis (AOR 0.58; 95% CI 0.32-1.05; P = 0.07). Among men with PSA recurrence after radiotherapy, odds of use of salvage ADT were nearly twice as great among men with high PSA anxiety or low health literacy, suggesting that these men are receiving higher rates of unproven treatment. Given that early salvage ADT is costly, worsens quality of life, and has not been shown to improve survival, quality improvement strategies are needed for these individuals. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights

  1. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  2. Target definition in salvage radiotherapy for recurrent prostate cancer: the role of advanced molecular imaging

    Directory of Open Access Journals (Sweden)

    Gaël eAmzalag

    2016-03-01

    Full Text Available Salvage radiotherapy (SRT represents the main treatment option for relapsing prostate cancer patients after radical prostatectomy (RP. Several open questions remain unanswered in terms of target volumes definition and delivered doses for SRT: the effective dose necessary to achieve biochemical control in the SRT setting may be different if the tumor recurrence is micro- or macroscopic. At the same time, irradiation of the prostatic bed only or of the whole pelvis will depend on the localization of the recurrence, local or loco-regional. In the theragnostic imaging era, molecular imaging using Positron Emission Tomography (PET constitutes a useful tool for clinicians to define the site of the recurrence, the extent of disease and individualize salvage treatments. The best option currently available in clinical routine is the combination of radiolabelled choline PET imaging and multiparametric magnetic resonance imaging (MRI, associating the nodal and distant metastases identification based on PET and the local assessment by MRI. A new generation of targeted tracers, namely prostate specific membrane antigen (PSMA, show promising results, with a contrast superior to choline imaging and a higher detection rate even for low prostate specific antigen levels; validation studies are ongoing. Finally, imaging targeting bone remodeling using whole body SPECT-CT is a relevant complement to molecular/metabolic PET imaging when bone involvement is suspected.

  3. Pathway-based analysis using reduced gene subsets in genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Liu Jianjun

    2011-01-01

    Full Text Available Abstract Background Single Nucleotide Polymorphism (SNP analysis only captures a small proportion of associated genetic variants in Genome-Wide Association Studies (GWAS partly due to small marginal effects. Pathway level analysis incorporating prior biological information offers another way to analyze GWAS's of complex diseases, and promises to reveal the mechanisms leading to complex diseases. Biologically defined pathways are typically comprised of numerous genes. If only a subset of genes in the pathways is associated with disease then a joint analysis including all individual genes would result in a loss of power. To address this issue, we propose a pathway-based method that allows us to test for joint effects by using a pre-selected gene subset. In the proposed approach, each gene is considered as the basic unit, which reduces the number of genetic variants considered and hence reduces the degrees of freedom in the joint analysis. The proposed approach also can be used to investigate the joint effect of several genes in a candidate gene study. Results We applied this new method to a published GWAS of psoriasis and identified 6 biologically plausible pathways, after adjustment for multiple testing. The pathways identified in our analysis overlap with those reported in previous studies. Further, using simulations across a range of gene numbers and effect sizes, we demonstrate that the proposed approach enjoys higher power than several other approaches to detect associated pathways. Conclusions The proposed method could increase the power to discover susceptibility pathways and to identify associated genes using GWAS. In our analysis of genome-wide psoriasis data, we have identified a number of relevant pathways for psoriasis.

  4. Theoretical study of the decomposition pathways and products of C5- perfluorinated ketone (C5 PFK

    Directory of Open Access Journals (Sweden)

    Yuwei Fu

    2016-08-01

    Full Text Available Due to the high global warming potential (GWP and increasing environmental concerns, efforts on searching the alternative gases to SF6, which is predominantly used as insulating and interrupting medium in high-voltage equipment, have become a hot topic in recent decades. Overcoming the drawbacks of the existing candidate gases, C5- perfluorinated ketone (C5 PFK was reported as a promising gas with remarkable insulation capacity and the low GWP of approximately 1. Experimental measurements of the dielectric strength of this novel gas and its mixtures have been carried out, but the chemical decomposition pathways and products of C5 PFK during breakdown are still unknown, which are the essential factors in evaluating the electric strength of this gas in high-voltage equipment. Therefore, this paper is devoted to exploring all the possible decomposition pathways and species of C5 PFK by density functional theory (DFT. The structural optimizations, vibrational frequency calculations and energy calculations of the species involved in a considered pathway were carried out with DFT-(UB3LYP/6-311G(d,p method. Detailed potential energy surface was then investigated thoroughly by the same method. Lastly, six decomposition pathways of C5 PFK decomposition involving fission reactions and the reactions with a transition states were obtained. Important intermediate products were also determined. Among all the pathways studied, the favorable decomposition reactions of C5 PFK were found, involving C-C bond ruptures producing Ia and Ib in pathway I, followed by subsequent C-C bond ruptures and internal F atom transfers in the decomposition of Ia and Ib presented in pathways II + III and IV + V, respectively. Possible routes were pointed out in pathway III and lead to the decomposition of IIa, which is the main intermediate product found in pathway II of Ia decomposition. We also investigated the decomposition of Ib, which can undergo unimolecular reactions to

  5. Nicotinamide Riboside and Nicotinic Acid Riboside Salvage in Fungi and Mammals

    Science.gov (United States)

    Belenky, Peter; Christensen, Kathryn C.; Gazzaniga, Francesca; Pletnev, Alexandre A.; Brenner, Charles

    2009-01-01

    NAD+ is a co-enzyme for hydride transfer enzymes and an essential substrate of ADP-ribose transfer enzymes and sirtuins, the type III protein lysine deacetylases related to yeast Sir2. Supplementation of yeast cells with nicotinamide riboside extends replicative lifespan and increases Sir2-dependent gene silencing by virtue of increasing net NAD+ synthesis. Nicotinamide riboside elevates NAD+ levels via the nicotinamide riboside kinase pathway and by a pathway initiated by splitting the nucleoside into a nicotinamide base followed by nicotinamide salvage. Genetic evidence has established that uridine hydrolase, purine nucleoside phosphorylase, and methylthioadenosine phosphorylase are required for Nrk-independent utilization of nicotinamide riboside in yeast. Here we show that mammalian purine nucleoside phosphorylase but not methylthioadenosine phosphorylase is responsible for mammalian nicotinamide riboside kinase-independent nicotinamide riboside utilization. We demonstrate that so-called uridine hydrolase is 100-fold more active as a nicotinamide riboside hydrolase than as a uridine hydrolase and that uridine hydrolase and mammalian purine nucleoside phosphorylase cleave nicotinic acid riboside, whereas the yeast phosphorylase has little activity on nicotinic acid riboside. Finally, we show that yeast nicotinic acid riboside utilization largely depends on uridine hydrolase and nicotinamide riboside kinase and that nicotinic acid riboside bioavailability is increased by ester modification. PMID:19001417

  6. Pathway for inpatients with depressive episode in Flemish psychiatric hospitals: a qualitative study

    Directory of Open Access Journals (Sweden)

    Simoens Steven R

    2009-10-01

    Full Text Available Abstract Background Within the context of a biopsychosocial model of the treatment of depressive episodes, a multidisciplinary approach is needed. Clinical pathways have been developed and implemented in hospitals to support multidisciplinary teamwork. The aim of this study is to explore current practice for the treatment of depressive episodes in Flemish psychiatric hospitals. Current practice in different hospitals is studied to get an idea of the similarities (outlined as a pathway and the differences in the treatment of depressive episodes. Methods A convenience sample of 11 Flemish psychiatric hospitals participated in this qualitative study. Semi-structured interviews were conducted with different types of health care professionals (n = 43. The websites of the hospitals were searched for information on their approach to treating depressive episodes. Results A flow chart was made including the identified stages of the pathway: pre-admission, admission (observation and treatment, discharge and follow-up care. The characteristics of each stage are described. Although the stages are identified in all hospitals, differences between hospitals on various levels of the pathway exist. Hospitals emphasized the individual approach of each patient. The results point to a biopsychosocial approach to treating depressive episodes. Conclusion This study outlined current practice as a pathway for Flemish inpatients with depressive episodes. Within the context of surveillance of quality and quantity of care, this study may encourage hospitals to consider developing clinical pathways.

  7. Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease

    Science.gov (United States)

    Wang, Kai; Zhang, Haitao; Kugathasan, Subra; Annese, Vito; Bradfield, Jonathan P.; Russell, Richard K.; Sleiman, Patrick M.A.; Imielinski, Marcin; Glessner, Joseph; Hou, Cuiping; Wilson, David C.; Walters, Thomas; Kim, Cecilia; Frackelton, Edward C.; Lionetti, Paolo; Barabino, Arrigo; Van Limbergen, Johan; Guthery, Stephen; Denson, Lee; Piccoli, David; Li, Mingyao; Dubinsky, Marla; Silverberg, Mark; Griffiths, Anne; Grant, Struan F.A.; Satsangi, Jack; Baldassano, Robert; Hakonarson, Hakon

    2009-01-01

    Previous genome-wide association (GWA) studies typically focus on single-locus analysis, which may not have the power to detect the majority of genuinely associated loci. Here, we applied pathway analysis using Affymetrix SNP genotype data from the Wellcome Trust Case Control Consortium (WTCCC) and uncovered significant association between Crohn Disease (CD) and the IL12/IL23 pathway, harboring 20 genes (p = 8 × 10−5). Interestingly, the pathway contains multiple genes (IL12B and JAK2) or homologs of genes (STAT3 and CCR6) that were recently identified as genuine susceptibility genes only through meta-analysis of several GWA studies. In addition, the pathway contains other susceptibility genes for CD, including IL18R1, JUN, IL12RB1, and TYK2, which do not reach genome-wide significance by single-marker association tests. The observed pathway-specific association signal was subsequently replicated in three additional GWA studies of European and African American ancestry generated on the Illumina HumanHap550 platform. Our study suggests that examination beyond individual SNP hits, by focusing on genetic networks and pathways, is important to unleashing the true power of GWA studies. PMID:19249008

  8. Exploring Student and Advisor Experiences in a College-University Pathway Program: A Study of the Bachelor of Commerce Pathway

    Science.gov (United States)

    Percival, Jennifer; DiGiuseppe, Maurice; Goodman, Bill; LeSage, Ann; Hinch, Ron; Samis, John; Sanchez, Otto; Rodrigues, Anna; Raby, Phil; Longo, Fabiola; De La Rocha, Arlene

    2015-01-01

    Currently, there is great interest across Ontario in the expansion of pathway programs between colleges and universities. Through strategic partnerships, two Ontario-based postsecondary institutions (a college and a university) have developed innovative and effective pathway programs that facilitate the transition of students between institutions…

  9. Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline.

    Science.gov (United States)

    Thompson, Ian M; Valicenti, Richard K; Albertsen, Peter; Davis, Brian J; Goldenberg, S Larry; Hahn, Carol; Klein, Eric; Michalski, Jeff; Roach, Mack; Sartor, Oliver; Wolf, J Stuart; Faraday, Martha M

    2013-08-01

    The purpose of this guideline is to provide a clinical framework for the use of radiotherapy after radical prostatectomy as adjuvant or salvage therapy. A systematic literature review using the PubMed®, Embase, and Cochrane databases was conducted to identify peer-reviewed publications relevant to the use of radiotherapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Guideline statements are provided for patient counseling, the use of radiotherapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a re-staging evaluation. Physicians should offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy (i.e., seminal vesicle invasion, positive surgical margins, extraprostatic extension) and should offer salvage radiotherapy to patients with prostatic specific antigen or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiotherapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiotherapy as well as the potential benefits of preventing recurrence. The decision to administer radiotherapy should be made by the patient and the multi-disciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. Please visit the ASTRO and AUA websites (http://www.redjournal.org/webfiles/images/journals/rob/RAP%20Guideline.pdf and http://www.auanet.org/education/guidelines/radiation-after-prostatectomy.cfm) to view this guideline in its entirety, including the full literature review. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Salvage of Ear Framework Exposure in Total Auricular Reconstruction.

    Science.gov (United States)

    Kim, Young Soo; Yun, In Sik; Chung, Seum

    2017-02-01

    One of the most common complications of total auricular reconstruction is delayed wound healing, which results in skin necrosis and exposure of the ear framework. Various options exist for salvage of the exposed ear framework. From January 2009 to May 2014, 149 patients underwent total auricular reconstruction using an autogenous cartilage framework or porous polyethylene framework (Medpor; Stryker, USA). An autogenous cartilage framework was used in 48 patients, and a Medpor framework was used in 101 cases. Three cases of framework exposure (3/48, 6.3%) were observed among the patients treated with an autogenous cartilage framework. In contrast, framework exposure took place in 11 patients who were treated with a Medpor framework (11/101, 10.9%). Depending on the method of total ear reconstruction and the location of exposure, the authors used local skin flaps, temporoparietal fascia flaps, deep temporal fascia (DTF) flaps, or mastoid fascia (MF) flaps with skin grafting. Among the 11 patients who experienced framework exposure after being treated with a Medpor framework, a DTF flap with skin grafting was used in 6 patients and an MF flap with skin grafting in 6 patients; 1 patient was treated with both a DTF flap and an MF flap. All 3 cases of cartilage framework exposure were salvaged using a temporoparietal fascia flap with skin grafting, and a local skin flap was used in 1 case. In all 3 cases, the exposed framework was completely covered with the flap, and the reconstructed ears showed well-defined convolutions. Salvage of framework exposure remains a challenging issue in total auricular reconstruction. However, appropriate wound management using various flaps allows the reconstructed ear to be safely preserved.

  11. Gastric peroral endoscopic pyloromyotomy (G-POEM) as a salvage therapy for refractory gastroparesis: a case series of different subtypes.

    Science.gov (United States)

    Mekaroonkamol, P; Li, L Y; Dacha, S; Xu, Y; Keilin, S D; Willingham, F F; Cai, Q

    2016-08-01

    Gastroparesis is a poorly understood, chronic, debilitating motility disorder with very limited medical therapeutic options. Gastric peroral endoscopic pyloromyotomy (G-POEM) is an emerging novel endoscopic technique as an incisionless pyloroplasty for refractory cases. Effective information of G-POEM on different types of gastroparesis is sparse. Cases of G-POEM using selective circular myotomy as a salvage therapy for refractory symptoms were retrospective studied. The G-POEM procedures were performed by a single expert endoscopist under a certain protocol. Gastroparesis Cardinal Symptoms Index (GCSI) and gastric emptying scintigraphy (GES) were evaluated before and after the procedure. Procedures related adverse event were also recorded. All procedures were successfully completed without complications. Each case in this series was different in demography and etiology of gastroparesis, namely postsurgical, postinfectious, and idiopathic gastroparesis in an elderly male and two young female adults. All cases were refractory to conventional treatment but demonstrated obvious success after G-POEM as a salvage therapy both clinically and on GES. G-POEM as a salvage therapy improves symptoms and gastric emptying in patients with different types of refractory gastroparesis. Our cases are also the firsts to show success of G-POEM in postinfectious gastroparesis and in elderly male patient. More data are needed to determine which subgroup of patients would benefit most from this novel procedure. © 2016 John Wiley & Sons Ltd.

  12. Acute myocardial infarction: estimation of at-risk and salvaged myocardium at myocardial perfusion SPECT 1 month after infarction.

    Science.gov (United States)

    Romero-Farina, Guillermo; Aguadé-Bruix, Santiago; Candell-Riera, Jaume; Pizzi, M Nazarena; Pineda, Victor; Figueras, Jaume; Cuberas, Gemma; de León, Gustavo; Castell-Conesa, Joan; García-Dorado, David

    2013-11-01

    To estimate at-risk and salvaged myocardium by using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging after acute myocardial infarction (AMI). The study was approved by the hospital's Ethical Committee on Clinical Trials (trial register number, PR(HG)36/2000), and all patients gave informed consent. Forty patients (mean age, 61.78 years; eight women) with a first AMI underwent two gated SPECT examinations--one before percutaneous coronary intervention (PCI) and one 4-5 weeks after PCI. Myocardium at risk was estimated by assessing the perfusion defect at the first gated SPECT examination, and salvaged myocardium was estimated by assessing the risk area minus necrosis at the second examination. Myocardium at risk was estimated by determining the discordance between the areas of left ventricular (LV) wall motion and perfusion at the second examination. Concordance between tests was analyzed by means of linear regression analysis, the Pearson correlation, the intraclass correlation coefficient, and Bland-Altman analysis. An improvement in perfusion, wall motion, wall thickening, and LV ejection fraction (P Myocardial perfusion gated SPECT performed 1 month after early PCI in a first AMI provides potentially useful information on at-risk and salvaged myocardium. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13122324/-/DC1. RSNA, 2013

  13. Association study of the oestrogen signalling pathway genes in ...

    Indian Academy of Sciences (India)

    Yamamoto T. 2004 Association study using single nucleotide polymorphisms in the estrogen receptor beta (ESR2) gene for preeclampsia. Hypertens Res. 27, 903–909. Murabito J. M., Yang Q., Fox C., Wilson P. W. and Cupples L. A.. 2005a Heritability of age at natural menopause in the Framing- ham Heart Study. J. Clin.

  14. A study of the transition pathways of school level scholarship ...

    African Journals Online (AJOL)

    Hennie

    School-level educational interventions targeting learners from low socioeconomic backgrounds often have the long-term goal of enabling access to, and successful completion of tertiary studies. This study tracked the progress of alumni of an educational intervention two or three years post school, in order to investigate their ...

  15. Limb salvage procedures in osteosarcomas around the knee joint

    Directory of Open Access Journals (Sweden)

    Emérito Carlos Rodriguez Merchán

    Full Text Available Surgical techniques developed for restoring skeletal continuity after a local resection of a bone tumor (limb salvage procedures revolutionized the management of the patient suffering from osteosarcomas around the knee. In this article the authors review the current status of various reconstruction procedures; they include osteoarticular allograft arthrodesis, rotation plasty, expandable prosthesis and knee arthroplasty. In summary they suggest that the knee arthrodesis is the preferred procedure for young and active patients, the rotation plasty should be recommended as the alternative to amputation for very young patients, and the customized prostheses are preferred for patients with limited longevity.

  16. Impact of a Solution for the Study of Neural Pathways in Morphophysiology III

    OpenAIRE

    José Manuel Ruiz Medina; Alicia Ríos Carbonell; Gisela Trevín Fernández; Elnis Quiala Ballester; Vivian Santoya Varela

    2013-01-01

    Background: current conditions for teaching Morphophysiology subject and awareness of the historical difficulties that students face in understanding the morphological and functional characteristics of neural pathways require a solution. Objective: to create a set of means in order to provide a practical resource for the study of the morphological and functional characteristics of the neural pathways and to assess the impact of its implementation in Morphophysiology III teaching. Methods: we ...

  17. Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy

    NARCIS (Netherlands)

    Peters, Max; van der Voort van Zyp, Jochem R N; Moerland, Marinus A; Hoekstra, Carel J; van de Pol, Sandrine; Westendorp, Hendrik; Maenhout, Metha; Kattevilder, Rob; Verkooijen, Helena M; van Rossum, Peter S N; Ahmed, Hashim U; Shah, Taimur T; Emberton, Mark; van Vulpen, Marco

    BACKGROUND: Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to

  18. Absolute lymphocyte count predicts response to rituximab-containing salvage treatment for relapsed/refractory B-cell non-Hodgkin's lymphoma with prior rituximab exposure

    Directory of Open Access Journals (Sweden)

    Man-Hsin Hung

    2013-04-01

    Conclusion: Our study results show that for patients with relapsed/refractory B-cell NHL, rituximab-containing salvage treatment is feasible and generally tolerable. A high ALC-R value was significantly associated with a better response to this treatment.

  19. Building Data-Driven Pathways From Routinely Collected Hospital Data: A Case Study on Prostate Cancer.

    Science.gov (United States)

    Bettencourt-Silva, Joao H; Clark, Jeremy; Cooper, Colin S; Mills, Robert; Rayward-Smith, Victor J; de la Iglesia, Beatriz

    2015-07-10

    Routinely collected data in hospitals is complex, typically heterogeneous, and scattered across multiple Hospital Information Systems (HIS). This big data, created as a byproduct of health care activities, has the potential to provide a better understanding of diseases, unearth hidden patterns, and improve services and cost. The extent and uses of such data rely on its quality, which is not consistently checked, nor fully understood. Nevertheless, using routine data for the construction of data-driven clinical pathways, describing processes and trends, is a key topic receiving increasing attention in the literature. Traditional algorithms do not cope well with unstructured processes or data, and do not produce clinically meaningful visualizations. Supporting systems that provide additional information, context, and quality assurance inspection are needed. The objective of the study is to explore how routine hospital data can be used to develop data-driven pathways that describe the journeys that patients take through care, and their potential uses in biomedical research; it proposes a framework for the construction, quality assessment, and visualization of patient pathways for clinical studies and decision support using a case study on prostate cancer. Data pertaining to prostate cancer patients were extracted from a large UK hospital from eight different HIS, validated, and complemented with information from the local cancer registry. Data-driven pathways were built for each of the 1904 patients and an expert knowledge base, containing rules on the prostate cancer biomarker, was used to assess the completeness and utility of the pathways for a specific clinical study. Software components were built to provide meaningful visualizations for the constructed pathways. The proposed framework and pathway formalism enable the summarization, visualization, and querying of complex patient-centric clinical information, as well as the computation of quality indicators and

  20. Insights into pancreatic cancer etiology from pathway analysis of genome-wide association study data.

    Directory of Open Access Journals (Sweden)

    Peng Wei

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death in the U.S. and the etiology of this highly lethal disease has not been well defined. To identify genetic susceptibility factors for pancreatic cancer, we conducted pathway analysis of genome-wide association study (GWAS data in 3,141 pancreatic cancer patients and 3,367 controls with European ancestry.Using the gene set ridge regression in association studies (GRASS method, we analyzed 197 pathways identified from the Kyoto Encyclopedia of Genes and Genomes database. We used the logistic kernel machine (LKM test to identify major contributing genes to each pathway. We conducted functional enrichment analysis of the most significant genes (P<0.01 using the Database for Annotation, Visualization, and Integrated Discovery (DAVID.Two pathways were significantly associated with risk of pancreatic cancer after adjusting for multiple comparisons (P<0.00025 and in replication testing: neuroactive ligand-receptor interaction, (Ps<0.00002, and the olfactory transduction pathway (P = 0.0001. LKM test identified four genes that were significantly associated with risk of pancreatic cancer after Bonferroni correction (P<1×10(-5: ABO, HNF1A, OR13C4, and SHH. Functional enrichment analysis using DAVID consistently found the G protein-coupled receptor signaling pathway (including both neuroactive ligand-receptor interaction and olfactory transduction pathways to be the most significant pathway for pancreatic cancer risk in this study population.These novel findings provide new perspectives on genetic susceptibility to and molecular mechanisms of pancreatic cancer.

  1. Penalized differential pathway analysis of integrative oncogenomics studies

    NARCIS (Netherlands)

    van Wieringen, W.N.; van de Wiel, M.A.

    2014-01-01

    Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving

  2. A study of the transition pathways of school level scholarship ...

    African Journals Online (AJOL)

    ... of the school-level intervention. The benefits reported included a sound preparation for life and academic studies, and other benefits that the researchers categorised as developing resilience and grit. Keywords: grit; resilience; secondary-tertiary interface; socioeconomic status (SES); transitional paths; university success ...

  3. Forest structure following tornado damage and salvage logging in northern Maine, USA

    Science.gov (United States)

    Shawn Fraver; Kevin J. Dodds; Laura S. Kenefic; Rick Morrill; Robert S. Seymour; Eben Sypitkowski

    2017-01-01

    Understanding forest structural changes resulting from postdisturbance management practices such as salvage logging is critical for predicting forest recovery and developing appropriate management strategies. In 2013, a tornado and subsequent salvage operations in northern Maine, USA, created three conditions (i.e., treatments) with contrasting forest structure:...

  4. 33 CFR 155.4030 - Required salvage and marine firefighting services to list in response plans.

    Science.gov (United States)

    2010-07-01

    ... of your VRP, the salvage and marine firefighting services listed in Table 155.4030(b)—Salvage and... your VRP, adjacent to the name of the resource provider. (b) Table 155.4030(b) lists the required... as found in § 155.1030(h). (e) Ensuring the proper emergency towing vessels are listed in your VRP...

  5. 28 CFR 25.56 - Responsibilities of junk yards and salvage yards and auto recyclers.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Responsibilities of junk yards and salvage yards and auto recyclers. 25.56 Section 25.56 Judicial Administration DEPARTMENT OF JUSTICE... Responsibilities of junk yards and salvage yards and auto recyclers. (a) By no later than March 31, 2009, and...

  6. Elucidating novel dysfunctional pathways in Alzheimer's disease by integrating loci identified in genetic and epigenetic studies

    Directory of Open Access Journals (Sweden)

    Adam R. Smith

    2016-06-01

    Full Text Available Alzheimer's disease is a complex neurodegenerative disorder. A large number of genome-wide association studies have been performed, which have been supplemented more recently by the first epigenome-wide association studies, leading to the identification of a number of novel loci altered in disease. Twin studies have shown monozygotic twin discordance for Alzheimer's disease (Gatz et al., 2006, leading to the conclusion that a combination of genetic and epigenetic mechanisms is likely to be involved in disease etiology (Lunnon & Mill, 2013. This review focuses on identifying overlapping pathways between published genome-wide association studies and epigenome-wide association studies, highlighting dysfunctional synaptic, lipid metabolism, plasma membrane/cytoskeleton, mitochondrial, and immune cell activation pathways. Identifying common pathways altered in genetic and epigenetic studies will aid our understanding of disease mechanisms and identify potential novel targets for pharmacological intervention.

  7. Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

    Directory of Open Access Journals (Sweden)

    Stefanie Friedrichs

    2017-01-01

    Full Text Available The analysis of genome-wide association studies (GWAS benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways. We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

  8. Toe salvage procedure for the recurrent chondromyxoid fibroma

    Directory of Open Access Journals (Sweden)

    Peruvaje Ramakrishna Krishnaprasad

    2017-03-01

    Full Text Available The treatment options for recurrent chondromyxoid fibroma of the toe range from total amputation to salvaging a functional toe. There is no globally accepted treatment protocol available for this tumour because of its rarer incidence and lack of population based data. Here we suggest performing a staged approach, which involves en block resection initially and maintenance of metatarsophalangeal space by using a kirshner wire with the bone cement. If there is no sign of malignancy in the histopathology, we recommend performing interposition arthroplasty at the metatarsophalangeal joint with the tricortical iliac crest graft. The kirshner wire should be kept which incorporates the iliac graft and the soft tissue, which is being interposed at the metatarsal head. This will cause pseudoarthrosis and also decreases the chances of having chronic pain. We believe that this staged approach which leads to toe salvage is the best suitable treatment option for the recurrent chondromyxoid fibroma. This will prevent amputation of the toe and will give cosmetic success to the patient

  9. Salvage cryosurgery for locally recurrent prostate cancer after primary cryotherapy.

    Science.gov (United States)

    Chang, Xiaofeng; Liu, Tieshi; Zhang, Fan; Zhao, Xiaozhi; Ji, Changwei; Yang, Rong; Gan, Weidong; Zhang, Gutian; Li, Xiaogong; Guo, Hongqian

    2015-02-01

    To report our preliminary experience of salvage cryosurgery (SCS) for locally recurrent prostate cancer (PCa) after primary cryotherapy and determine the efficacy of cryoablation of the prostate in the salvage setting. We conducted a retrospective review of the records of all patients who underwent SCS for locally recurrent PCa after primary cryotherapy between February 2008 and March 2012. Patients were assessed after treatment by prostate-specific antigen (PSA) testing, transrectal ultrasonography, radiologic imaging, and biopsy. Biochemical failure was defined using the Phoenix criteria. Data from 12 patients who had undergone SCS were entered. Median age at SCS was 77.5 year. Before SCS, patients had a median PSA level of 2.5 ng/ml and median Gleason sum of 7. Patients underwent SCS at a median of 7.8 months after primary CS. Median PSA nadir after SCS was 1.32 ng/ml. The mean (range) follow-up was 33.5 months. Three patients were started on hormonal therapy for disease progression at a median post-SCS period of 12 months. Two patients underwent repeat cryoablation. Only one patient developed mild incontinence after SCS. Urethral sloughing occurred in one patient. Only two patients suffered from transient impotence. It is feasible for patients with PCa to adopt SCS when primary cryotherapy has failed. The application of SCS also allows hormonal therapy to be deferred for a sufficient period of time.

  10. [Study on pollutant pathway of norovirus contamination in oysters].

    Science.gov (United States)

    Saito, Koichi; Sato, Naoto; Takahashi, Akemi; Tsutsumi, Reiko; Sato, Shigehiro

    2006-07-01

    Noroviruses (NVs) cause human gastroenteritis through person-to-person transmission and via contaminated foods. In food poisoning, a major suspected cause is the consumption of raw oysters. We detected NVs from environmental water and oysters around a closed gulf where oysters are cultivated. We collected oyster and water samples once or twice a month for 30 months from October 2001 to March 2004. We then studied monthly changes in virus occurrence and in genetic relationships among 208 NVs isolated from water and oyster samples and from the feces of children suffering from acute gastroenteritis during the same period in the same region. In the analysis of untreated water flowing into farm sewage, NVs were detected year round. In other water samples -processed sewage, river water, and seawater-, oysters, and children's feces, NVs were detected mainly in winter. A comparison of NV nucleotide sequences showed genetic diversity, but some strains predominated in certain winter seasons. These predominant strains were detected across sample materials. In 2002/03, an identical strain was detected in sewage, river water, seawater, oysters, and feces. We also found that NV genetic types changed at the beginning of the season, in November or December, in both 2001/02 and 2002/03. This study showed a clear relationship between NVs detected in children's feces and those in environmental water and oysters. These results support the idea that NVs are transmitted from the feces of infected persons to oysters by the flow of water through farm sewage, rivers, and the sea, finally accumulating in the mid-gut gland of oysters.

  11. A method for utilizing biocytin to study retinofugal pathways at the light and electron microscopic levels.

    Science.gov (United States)

    Helm, G A; Palmer, P E; Simmons, N E; diPierro, C G; Ebbesson, S O

    1993-08-01

    Numerous methods have been utilized in the past to study the retinofugal pathway at both the light and electron microscopic levels. However, many of these techniques have technical drawbacks that make them difficult to use in electron microscopic studies. We present herein a method for utilizing the anterograde tracer biocytin to study the retinal pathways at both the light and electron microscopic levels. Biocytin is an especially useful tracer since it clearly labels very small axons and boutons in addition to the larger fibers. In addition, the synaptic ultrastructure is left intact and the technique can be utilized in numerous double-labeling neuroanatomical studies.

  12. Effects of salvage logging and pile-and-burn on fuel loading, potential fire behaviour, fuel consumption and emissions

    Science.gov (United States)

    Morris C. Johnson; Jessica E. Halofsky; David L. Peterson

    2013-01-01

    We used a combination of field measurements and simulation modelling to quantify the effects of salvage logging, and a combination of salvage logging and pile-and-burn fuel surface fuel treatment (treatment combination), on fuel loadings, fire behaviour, fuel consumption and pollutant emissions at three points in time: post-windstorm (before salvage logging), post-...

  13. Care Pathways in Persistent Orofacial Pain: Qualitative Evidence from the DEEP Study.

    Science.gov (United States)

    Breckons, M; Bissett, S M; Exley, C; Araujo-Soares, V; Durham, J

    2017-01-01

    Persistent orofacial pain is relatively common and known to have an adverse effect on quality of life. Previous studies suggest that the current care pathway may be problematic, but it is not well understood which health services patients access and what their experience is. The aim of this study was to explore care pathways and their impact from the perspective of patients. Qualitative interviews were conducted with a maximum variation sample of patients recruited from primary (community based) and secondary (specialist hospital based) care in the United Kingdom. Questions focused on the stages in their pathway and the impact of the care that they had received. Interviews were digitally recorded and transcribed verbatim, and analysis followed principles of the constant comparative method. NVivo 10 was used to help organize and analyze data. Twenty-two patients were interviewed at baseline, and 18 took part in a second interview at 12 mo. Three main themes emerged from the data: the "fluidity of the care pathway," in which patients described moving among health care providers in attempts to have their pain diagnosed and managed, occurring alongside a "failure to progress," where despite multiple appointments, patients described frustration at delays in obtaining a diagnosis and effective treatment for their pain. Throughout their care pathways, patients described the "effects of unmanaged pain," where the longer the pain went unmanaged, the greater its potential to negatively affect their lives. Findings of this study suggest that the current care pathway is inefficient and fails to meet patient needs. Future work needs to focus on working with stakeholder groups to redesign patient-centered care pathways. Knowledge Transfer Statement: Data from qualitative interviews conducted with patients with persistent orofacial pain suggest significant problems with the existing care pathway, consisting of delays to diagnosis, treatment, and referral. Patients describing

  14. Male and Female Pathways to Psychopathology: Findings from a Preventive Intervention Study

    NARCIS (Netherlands)

    P. Vuijk (Patricia)

    2006-01-01

    textabstractThe objective of the present study was to extent the knowledge on the pathways to male and female psychopathology from childhood into early adolescence. In Chapter 1, the background of the Good Behavior Game (GBG) study was presented. The GBG study is a randomized controlled

  15. SNP-based pathway enrichment analysis for genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Potkin Steven G

    2011-04-01

    Full Text Available Abstract Background Recently we have witnessed a surge of interest in using genome-wide association studies (GWAS to discover the genetic basis of complex diseases. Many genetic variations, mostly in the form of single nucleotide polymorphisms (SNPs, have been identified in a wide spectrum of diseases, including diabetes, cancer, and psychiatric diseases. A common theme arising from these studies is that the genetic variations discovered by GWAS can only explain a small fraction of the genetic risks associated with the complex diseases. New strategies and statistical approaches are needed to address this lack of explanation. One such approach is the pathway analysis, which considers the genetic variations underlying a biological pathway, rather than separately as in the traditional GWAS studies. A critical challenge in the pathway analysis is how to combine evidences of association over multiple SNPs within a gene and multiple genes within a pathway. Most current methods choose the most significant SNP from each gene as a representative, ignoring the joint action of multiple SNPs within a gene. This approach leads to preferential identification of genes with a greater number of SNPs. Results We describe a SNP-based pathway enrichment method for GWAS studies. The method consists of the following two main steps: 1 for a given pathway, using an adaptive truncated product statistic to identify all representative (potentially more than one SNPs of each gene, calculating the average number of representative SNPs for the genes, then re-selecting the representative SNPs of genes in the pathway based on this number; and 2 ranking all selected SNPs by the significance of their statistical association with a trait of interest, and testing if the set of SNPs from a particular pathway is significantly enriched with high ranks using a weighted Kolmogorov-Smirnov test. We applied our method to two large genetically distinct GWAS data sets of schizophrenia, one

  16. Comparison of methicillin-resistant Staphylococcus pseudintermedius adherence to 2 canine limb salvage endoprosthesis implants.

    Science.gov (United States)

    Nazarali, Alim; Singh, Ameet; Morrison, Shauna; Gibson, Thomas W G; Rousseau, Joyce; Weese, J Scott; Boston, Sarah E

    2017-09-01

    The objective of our study was to compare adhesion of methicillin-resistant Staphylococcus pseudintermedius (MRSP) to stainless steel (SS) and to tantalum (TA) canine limb salvage endoprosthesis implants in an in vitro experimental study. The median of the mean log10 colony forming units/mL for adherent MRSP was 4.96 (range: 4.63 to 6.33) for the TA endoprosthesis and 4.31 (range: 3.86 to 5.05) for the SS endoprosthesis (P = 0.009). Although the trabecular and porous design of the TA endoprosthesis provides mechanical benefits over the SS endoprosthesis, it may increase the risk of developing infection due to higher levels of bacterial adherence.

  17. Beyond induced mutants: using worms to study natural variation in genetic pathways

    NARCIS (Netherlands)

    Kammenga, J.E.; Philips, P.C.; Bono, de M.; Doroszuk, A.

    2008-01-01

    Induced mutants in the nematode Caenorhabditis elegans are used to study genetic pathways of processes ranging from aging to behavior. The effects of such mutations are usually analyzed in a single wildtype background: N2. However, studies in other species demonstrate that the phenotype(s) of

  18. Intra-operative cell salvage in South Africa: feasible, beneficial and economical.

    Science.gov (United States)

    Solomon, Leigh; von Rahden, Richard P; Allorto, Nikki L

    2013-08-26

    Healthcare services in KwaZulu-Natal (KZN) frequently experience shortages of blood products. Alternatives to traditional blood sources are needed. One possibility is cell salvage and autologous blood transfusion. Few data exist relating to their use in the South African context. To ascertain whether cell salvage (CS) is beneficial, feasible and economical in our setting, with the anticipation that results would excite further studies and potentially change current practice and improve existing protocols. Methods. This study reviewed current intraoperative Cell Saver use at Grey's and Edendale hospitals in Pietermaritzburg, KZN. Current practices were observed and compared with the costs of the equivalent amount of red cell concentrate (RCC) purchased from the South African National Blood Service (SANBS). All cases of Cell Saver usage over a 1-year period from July 2012 to June 2013 were analysed. The total volume of blood transfused from CS was 55 735 ml, approximately equivalent to 186 RCC units. The comparative cost of equivalent units of RCC from SANBS was R258 445. The total cost of Cell Saver disposables during the study period was R206 047, or R263 478 when Cell Saver machine depreciation costs were included. More than one CS blood unit was available for transfusion in 66% of cases. No additional staff were required to operate the Cell Saver, which was successfully used by medical officers. This study showed that intraoperative CS use is feasible, has potential patient benefit by reducing blood bank blood transfusion, and is financially comparable to purchasing the equivalent number of SANBS RCC.

  19. Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+.

    Science.gov (United States)

    Belenky, Peter; Racette, Frances G; Bogan, Katrina L; McClure, Julie M; Smith, Jeffrey S; Brenner, Charles

    2007-05-04

    Although NAD(+) biosynthesis is required for Sir2 functions and replicative lifespan in yeast, alterations in NAD(+) precursors have been reported to accelerate aging but not to extend lifespan. In eukaryotes, nicotinamide riboside is a newly discovered NAD(+) precursor that is converted to nicotinamide mononucleotide by specific nicotinamide riboside kinases, Nrk1 and Nrk2. In this study, we discovered that exogenous nicotinamide riboside promotes Sir2-dependent repression of recombination, improves gene silencing, and extends lifespan without calorie restriction. The mechanism of action of nicotinamide riboside is totally dependent on increased net NAD(+) synthesis through two pathways, the Nrk1 pathway and the Urh1/Pnp1/Meu1 pathway, which is Nrk1 independent. Additionally, the two nicotinamide riboside salvage pathways contribute to NAD(+) metabolism in the absence of nicotinamide-riboside supplementation. Thus, like calorie restriction in the mouse, nicotinamide riboside elevates NAD(+) and increases Sir2 function.

  20. Male and Female Pathways to Psychopathology: Findings from a Preventive Intervention Study

    OpenAIRE

    Vuijk, Patricia

    2006-01-01

    textabstractThe objective of the present study was to extent the knowledge on the pathways to male and female psychopathology from childhood into early adolescence. In Chapter 1, the background of the Good Behavior Game (GBG) study was presented. The GBG study is a randomized controlled intervention study that started in 1998 when 666 children from 13 elementary schools in the metropolitan area of Rotterdam and Amsterdam were enrolled in the study at age 6. The GBG intervention is a universal...

  1. A developing world experience with distal foot amputations for diabetic limb salvage

    Directory of Open Access Journals (Sweden)

    Omer Salahuddin

    2013-10-01

    Full Text Available Objectives: To evaluate the functional outcome, morbidity, and viability of foot salvage in diabetic patients. Materials and methods: This prospective case series was conducted from March 2007 to December 2012 at the department of surgery Pakistan Ordnance Factories Hospital, Wah Cantt, Pakistan. 123 males and 26 female patients were included in the study. All the patients were treated after getting admitted in the hospital and wounds were managed with daily dressings, nursing care and debridement of necrotic tissue with adequate antibiotic coverage. Results: In total, 149 patients (mean age: 56±7.52 years with 171 amputations were included in the study. The mean duration of diabetes mellitus (DM was 9±4.43 years. Ninety-seven percent of the patients were diagnosed with type 2 DM. Wound debridement was performed under general anesthesia in 48 (33.2% patients, whereas local anesthesia was used for the rest of the patients after having good glycemic control and improvement in general health. The most common pathogen isolated from the infected wounds was Staphylococcus aureus in approximately 46% cases. Regarding the types of amputation, partial toe amputation was performed in 21 (12.2% cases, second-toe amputation in 60 (35% cases, hallux amputation in 41 (24% cases, multiple toe amputations in 29 (17% cases, bilateral feet involvement was observed in 16 (9.3% cases, and transmetatarsal amputation was performed in 4 (2.3% cases. The wounds healed well except in 19 cases where amputation had to be revised to a more proximal level. Thirty-nine patients died during the study period: 3 died of wound-related complications and 36 died of systemic complications. Conclusion: With the ever-increasing epidemic of DM, the number of patients with diabetic foot ulcers has also significantly risen. Early surgical management with good glycemic control and foot care with close monitoring can decrease amputations and thus foot salvage can be successfully

  2. Late urinary morbidity and quality of life after radical prostatectomy and salvage radiotherapy for prostate cancer

    DEFF Research Database (Denmark)

    Ervandian, Maria; Hoyer, Morten; Petersen, Stine Elleberg

    2017-01-01

    OBJECTIVE: There is a paucity of knowledge of long-term urinary morbidity in patients treated for prostate cancer (PCa) with radical prostatectomy (RP) and salvage radiotherapy (SRT). Improved long-term survival calls for heightened awareness of late effects from radiotherapy after RP. The purpose...... of this study was to assess late urinary morbidity and its potential impact on quality of life (QoL) in patients treated with RP plus SRT compared with patients treated with RP alone. MATERIALS AND METHODS: Long-term morbidity and QoL were evaluated using a cross-sectional design with validated questionnaires...... in urinary morbidity [Danish Prostatic Symptom Score (DAN-PSS)] and QoL [European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)]. Included were a total of 227 patients treated with SRT and 192 treated with RP in the periods 2006-2010 and 2005...

  3. What is a clinical pathway? Refinement of an operational definition to identify clinical pathway studies for a Cochrane systematic review

    NARCIS (Netherlands)

    A.K. Lawal (Adegboyega K.); T. Rotter (Thomas); L. Kinsman (Leigh); A. Machotta (Andreas); U. Ronellenfitsch (Ulrich); S.D. Scott (Shannon D.); D. Goodridge (Donna); C. Plishka (Christopher); G. Groot (Gary)

    2016-01-01

    textabstractClinical pathways (CPWs) are a common component in the quest to improve the quality of health. CPWs are used to reduce variation, improve quality of care, and maximize the outcomes for specific groups of patients. An ongoing challenge is the operationalization of a definition of CPW in

  4. [F-18]2-fluoro-2-deoxyglucose (FDG) positron emission tomography after limb salvage surgery: post-surgical appearance, attenuation correction and local complications

    Energy Technology Data Exchange (ETDEWEB)

    Gelfand, Michael J.; Sharp, Susan E. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Nuclear Medicine Division, Cincinnati, OH (United States)

    2015-08-15

    Metal endoprostheses and internal fixation devices cause significant artifacts on CT after limb salvage surgery; positron emission tomography (PET) images should be evaluated for artifacts. (1) To describe [F-18]2-fluoro-2-deoxyglucose (FDG) PET uptake patterns after limb salvage surgery. (2) To determine whether metal endoprostheses and fixation hardware cause significant artifacts on CT attenuation-corrected PET that interfere with diagnostic use of PET/CT after limb salvage surgery. We reviewed 92 studies from 18 patients ages 5-21 years. Diagnoses were osteogenic sarcoma in 14, Ewing sarcoma in 3, and malignant peripheral nerve sheath tumor originating in bone in 1. Nine patients had distal femur/knee endoprostheses, five had lower-extremity bone allografts secured by large metal plates and four had upper-extremity limb salvage procedures. Maximum standardized uptake value was calculated at lower-extremity soft-tissue-endoprosthesis interfaces. In 15 patients with PET/CT imaging, the first PET/CT scan after limb salvage surgery was reviewed for metal artifacts on CT images and for artifacts at locations on PET corresponding to the CT metal artifacts. Increased FDG uptake was consistently present at soft-tissue interfaces with endoprostheses, allografts and internal fixation devices, with little or no FDG uptake at cemented endoprosthesis-bone interfaces. Maximum standardized uptake value at margins of femur/knee endoprostheses ranged from 1.4 to 5.7. In four patients with distal femur/knee endoprostheses, minimal artifact was noted on attenuation-corrected PET images, but image interpretation was not affected. In the other 11 patients who had CT attenuation correction, we detected no artifacts caused by the attenuation correction. CT attenuation correction did not cause artifacts that affected interpretation of attenuation-corrected PET images. (orig.)

  5. Limb salvage treatment for congenital deficiency of the tibia.

    Science.gov (United States)

    Wada, Akifusa; Fujii, Toshio; Takamura, Kazuyuki; Yanagida, Haruhisa; Urano, Noriko; Yamaguchi, Toru

    2006-01-01

    Nine limb salvage treatments were performed in 7 patients with congenital deficiency of the tibia. All feet showed equinovarus deformity and were centralized in a slightly equinus position by placing the distal end of the fibula into the posterior facet of the calcaneus. Tibiofibular fusion was performed in 4 patients with partial deficiency, and fibular transfer (fibular centralization; Brown procedure) in 5 with complete deficiency of the tibia. Callus distraction lengthening was performed repeatedly for leg-length discrepancy on either the femur or the centralized fibula. Satisfactory functional and cosmetic results were obtained in all limbs with partial deficiency, whereas in limbs with completely deficiency, none of the 5 knees treated by fibular transfer achieved a satisfactory functional result because of insufficient quadriceps strength, progressive knee flexion contracture, and persistent ligamentous instability. Nevertheless, in these 5 cases, all patients were ultimately able to withstand weight-bearing.

  6. Theoretical study of the decomposition pathways and products of C5- perfluorinated ketone (C5 PFK)

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Yuwei; Wang, Xiaohua, E-mail: xhw@mail.xjtu.edu.cn, E-mail: mzrong@mail.xjtu.edu.cn; Li, Xi; Yang, Aijun; Wu, Yi; Rong, Mingzhe, E-mail: xhw@mail.xjtu.edu.cn, E-mail: mzrong@mail.xjtu.edu.cn [State Key Laboratory of Electrical Insulation and Power Equipment, Xi’an Jiaotong University, No. 28 XianNing West Road, Xi’an, Shaanxi Province 710049 (China); Han, Guohui; Lu, Yanhui [Pinggao Group Co. Ltd., Pingdingshan, Henan Province 467001 (China)

    2016-08-15

    Due to the high global warming potential (GWP) and increasing environmental concerns, efforts on searching the alternative gases to SF{sub 6}, which is predominantly used as insulating and interrupting medium in high-voltage equipment, have become a hot topic in recent decades. Overcoming the drawbacks of the existing candidate gases, C5- perfluorinated ketone (C5 PFK) was reported as a promising gas with remarkable insulation capacity and the low GWP of approximately 1. Experimental measurements of the dielectric strength of this novel gas and its mixtures have been carried out, but the chemical decomposition pathways and products of C5 PFK during breakdown are still unknown, which are the essential factors in evaluating the electric strength of this gas in high-voltage equipment. Therefore, this paper is devoted to exploring all the possible decomposition pathways and species of C5 PFK by density functional theory (DFT). The structural optimizations, vibrational frequency calculations and energy calculations of the species involved in a considered pathway were carried out with DFT-(U)B3LYP/6-311G(d,p) method. Detailed potential energy surface was then investigated thoroughly by the same method. Lastly, six decomposition pathways of C5 PFK decomposition involving fission reactions and the reactions with a transition states were obtained. Important intermediate products were also determined. Among all the pathways studied, the favorable decomposition reactions of C5 PFK were found, involving C-C bond ruptures producing Ia and Ib in pathway I, followed by subsequent C-C bond ruptures and internal F atom transfers in the decomposition of Ia and Ib presented in pathways II + III and IV + V, respectively. Possible routes were pointed out in pathway III and lead to the decomposition of IIa, which is the main intermediate product found in pathway II of Ia decomposition. We also investigated the decomposition of Ib, which can undergo unimolecular reactions to give the

  7. Rotationplasty--surgical treatment modality after failed limb salvage procedure.

    Science.gov (United States)

    Hillmann, A; Gosheger, G; Hoffmann, C; Ozaki, T; Winkelmann, W

    2000-01-01

    Twelve patients aged between 10.9 and 64.7 (mean 28.5) years with a malignant tumour of the knee region underwent a rotationplasty after failed primary limb salvage procedure. The reasons for failure which finally lead to surgery were recurrent infection in 10 patients and local recurrence of the tumour in 2. The number of operations before the rotationplasty was performed was between 2 and 23 (mean 6.7). According to the primary tumour site, 9 patients underwent a rotationplasty type A1, 3 patients type A2, and 1 patient type BII. In 9 patients the rotationplasty was successful, but 3 patients finally had to undergo amputation. Intraoperative preservation of the vessels was difficult in these 3 patients due to infection and oedema of the arteries or massive fibrous tissues after the previous surgery. After rotationplasty, 3 of 9 patients had to undergo additional surgery because of thrombosis, pseudarthrosis and infection (n = 5, range 1-2). The mean follow-up after rotationplasty was 34.9 (range 13-65) months. The mean functional status according to the MSTS criteria in patients after rotationplasty scored 21.3 of 30 points. In the group of amputees, the score was 19 (range 16-22). Concerning the health-related quality-of-life, the mean score in physical functioning was 76.3 in the group with a rotationplasty versus 50.0 in the group of amputees. Patients with a rotationplasty reached a higher score of global health status (77.1 vs 58.3). Based on the present results we are convinced that rotationplasty can be recommended as a treatment option after a failed limb salvage procedure.

  8. Anatomical study of the final common pathway for vocalization in the cat

    Science.gov (United States)

    Holstege, Gert

    1989-01-01

    Results are presented of an anatomical study of the neuronal pathways in the cat, via which the periaqueductal gray (PAG) produces excitation of motoneurons involved in vocalization. It is shown that a specific cell group in the lateral part of the caudal PAG and in the tegmentum just lateral to it projects bilaterally to the nucleus retroambiguus (NRA) in the caudal medulla oblongata. Neurons in the NRA in turn project, via a contralateral pathway through the ventral funiculus of the spinal cord, to the motoneuronal cell groups innervating intercostal and abdominal muscles. In the brainstem, the NRA neurons project to the motoneuronal cell groups innervating mouth-opening and perioral muscles as well as to motoneurons innervating the pharynx, soft palate, and tongue. These results indicate that the projections from PAG via NRA to vocalization motoneurons form the final common pathway in vocalization.

  9. PAPA: a flexible tool for identifying pleiotropic pathways using genome-wide association study summaries.

    Science.gov (United States)

    Wen, Yan; Wang, Wenyu; Guo, Xiong; Zhang, Feng

    2016-03-15

    : Pleiotropy is common in the genetic architectures of complex diseases. To the best of our knowledge, no analysis tool has been developed for identifying pleiotropic pathways using multiple genome-wide association study (GWAS) summaries by now. Here, we present PAPA, a flexible tool for pleiotropic pathway analysis utilizing GWAS summary results. The performance of PAPA was validated using publicly available GWAS summaries of body mass index and waist-hip ratio of the GIANT datasets. PAPA identified a set of pleiotropic pathways, which have been demonstrated to be involved in the development of obesity. PAPA program, document and illustrative example are available at http://sourceforge.net/projects/papav1/files/ : fzhxjtu@mail.xjtu.edu.cn Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Rotationplasty for Limb Salvage in the Treatment of Malignant Tumors: A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Hsien-Chung Wang

    2003-12-01

    Full Text Available Limb salvage is now more common than amputation after radical excision to treat malignant tumors. In a skeletally immature patient who has malignant tumors in a lower extremity, rotationplasty offers a more reliable and durable option than other limb salvage procedures. It is an excellent method of resolving the problem of unequal leg lengths, and preserves best limb function with few complications. Here, we present our experience with rotationplasty for limb salvage in the treatment of malignant tumors, with good functional results seen in follow-up examination 11 years after surgery.

  11. Rotationplasty for limb salvage in the treatment of malignant tumors: a report of two cases.

    Science.gov (United States)

    Wang, Hsien-Chung; Lu, Yen-Mou; Chien, Song-Hsiung; Lin, Gau-Tyan; Lu, Cheng-Chang

    2003-12-01

    Limb salvage is now more common than amputation after radical excision to treat malignant tumors. In a skeletally immature patient who has malignant tumors in a lower extremity, rotationplasty offers a more reliable and durable option than other limb salvage procedures. It is an excellent method of resolving the problem of unequal leg lengths, and preserves best limb function with few complications. Here, we present our experience with rotationplasty for limb salvage in the treatment of malignant tumors, with good functional results seen in follow-up examination 11 years after surgery.

  12. Switching addictions between HER2 and FGFR2 in HER2-positive breast tumor cells: FGFR2 as a potential target for salvage after lapatinib failure

    Energy Technology Data Exchange (ETDEWEB)

    Azuma, Koichi [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Tsurutani, Junji, E-mail: tsurutani_j@dotd.med.kindai.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Sakai, Kazuko; Kaneda, Hiroyasu [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Fujisaka, Yasuhito; Takeda, Masayuki [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Watatani, Masahiro [Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Arao, Tokuzo [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Satoh, Taroh; Okamoto, Isamu; Kurata, Takayasu [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511 (Japan)

    2011-04-01

    Highlights: {yields} A lapatinib-resistant breast cancer cell line, UACC812 (UACC812/LR), was found to harbor amplification of the FGFR2 gene. {yields} Inhibition of the molecule by a specific inhibitor of FGFR dramatically induced growth inhibition accompanied by cell death. {yields} Immunohistochemical analysis of patients with HER2-positive breast cancer demonstrated an association between FGFR2 expression and poor outcome for lapatinib-containing chemotherapy. -- Abstract: Agents that target HER2 have improved the prognosis of patients with HER2-amplified breast cancers. However, patients who initially respond to such targeted therapy eventually develop resistance to the treatment. We have established a line of lapatinib-resistant breast cancer cells (UACC812/LR) by chronic exposure of HER2-amplified and lapatinib-sensitive UACC812 cells to the drug. The mechanism by which UACC812/LR acquired resistance to lapatinib was explored using comprehensive gene hybridization. The FGFR2 gene in UACC812/LR was highly amplified, accompanied by overexpression of FGFR2 and reduced expression of HER2, and a cell proliferation assay showed that the IC{sub 50} of PD173074, a small-molecule inhibitor of FGFR tyrosine kinase, was 10,000 times lower in UACC812/LR than in the parent cells. PD173074 decreased the phosphorylation of FGFR2 and substantially induced apoptosis in UACC812/LR, but not in the parent cells. FGFR2 appeared to be a pivotal molecule for the survival of UACC812/LR as they became independent of the HER2 pathway, suggesting that a switch of addiction from the HER2 to the FGFR2 pathway enabled cancer cells to become resistant to HER2-targeted therapy. The present study is the first to implicate FGFR in the development of resistance to lapatinib in cancer, and suggests that FGFR-targeted therapy might become a promising salvage strategy after lapatinib failure in patients with HER2-positive breast cancer.

  13. Effectiveness of Previous Initiatives Similar to Programs of Study: Tech Prep, Career Pathways, and Youth Apprenticeships

    Science.gov (United States)

    Lewis, Morgan V.

    2008-01-01

    The federal career and technical legislation reauthorized in 2006 required the recipients of its funding to offer at least one Program of Study (POS). All states have developed some components of POS through earlier initiatives, primarily Tech Prep, career pathways, and youth apprenticeship, that attempted to ease the transition of students from…

  14. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    DEFF Research Database (Denmark)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from ...

  15. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

    NARCIS (Netherlands)

    Kromhout, D.

    2010-01-01

    Background -Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. Methods - We assessed the -1131T>C (rs662799) promoter polymorphism of the

  16. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

    NARCIS (Netherlands)

    Sarwar, Nadeem; Sandhu, Manjinder S.; Ricketts, Sally L.; Butterworth, Adam S.; Di Angelantonio, Emanuele; Boekholdt, S. Matthijs; Ouwehand, Willem; Watkins, Hugh; Samani, Nilesh J.; Saleheen, Danish; Lawlor, Debbie; Reilly, Muredach P.; Hingorani, Aroon D.; Talmud, Philippa J.; Danesh, John; Braund, P. S.; Hall, A. S.; Samani, N. J.; Thompson, J.; März, W.; Ouwehand, W.; Sivapalaratnam, S.; Soranzo, N.; Trip, M.; Lawlor, D. A.; Casas, J. P.; Ebrahim, S.; Arsenault, B. J.; Khaw, K. T.; Ricketts, S. L.; Sandhu, M. S.; Wareham, N. J.; Grallert, H.; Illig, T.; Humphries, S. E.; Talmud, Talmud; Rader, D. J.; He, J.; Reilly, M. P.; Clarke, R.; Hamsten, A.; Hopewell, J. C.; Watkins, H.; Saleheen, D.; Frossard, P.; Deloukas, P.; Danesh, J.; Ye, S.; Simpson, I. A.; Onat, A.; Kömürcü-Bayrak, E.; Martinelli, N.; Olivieri, O.; Girelli, D.; Hingorani, A. D.; Kivimäki, M.; Kumari, M.; Aouizerat, B. E.; Baum, L.; Campos, H.; Chaaba, R.; Chen, B. S.; Cho, E. Y.; Evans, D.; Hill, J.; Hsu, L. A.; Hubacek, J. A.; Lai, C. Q.; Lee, J. H.; Klos, K.; Liu, H.; Masana, L.; Melegh, B.; Nabika, T.; Ribalta, J.; Ruiz-Narvaez, E.; Thomas, G. N.; Tomlinson, B.; Szalai, C.; Vaverkova, H.; Yamada, Y.; Yang, Y.; Kastelein, J. J.; Tipping, R. W.; Ford, C. E.; Pressel, S. L.; Ballantyne, C.; Brautbar, A.; Knuiman, M.; Whincup, P. H.; Wannamethee, S. G.; Morris, R. W.; Kiechl, S.; Willeit, J.; Santer, P.; Mayr, A.; Wald, N.; Yarnell, J. W. G.; Gallacher, J.; Casiglia, E.; Tikhonoff, V.; Cushman, M.; Psaty, B. M.; Tracy, R. P.; Tybjaerg-Hansen, A.; Nordestgaard, B. G.; Benn, M.; Frikke-Schmidt, R.; Giampaoli, S.; Palmieri, L.; Panico, S.; Vanuzzo, D.; Pilotto, L.; de la Cámara, A. Gómez; Gómez-Gerique, J. A.; Simons, L.; McCallum, J.; Friedlander, Y.; Fowkes, F. G. R.; Lee, A. J.; Taylor, J.; Guralnik, J. M.; Phillips, C. L.; Wallace, R.; Blazer, D. G.; Khaw, K.-T.; Brenner, H.; Raum, E.; Müller, H.; Rothenbacher, D.; Jansson, J. H.; Wennberg, P.; Nissinen, A.; Donfrancesco, C.; Salomaa, V.; Harald, K.; Jousilahti, P.; Vartiainen, E.; D'Agostino, R. B.; Vasan, R. S.; Pencina, M. J.; Bladbjerg, E. M.; Jørgensen, T.; Møller, L.; Jespersen, J.; Dankner, R.; Chetrit, A.; Lubin, F.; Björkelund, C.; Lissner, L.; Bengtsson, C.; Cremer, P.; Nagel, D.; Rodriguez, B.; Dekker, J. M.; Nijpels, G.; Stehouwer, C. D. A.; Sato, S.; Iso, H.; Kitamura, A.; Noda, H.; Salonen, J. T.; Nyyssönen, K.; Tuomainen, T.-P.; Voutilainen, S.; Meade, T. W.; Cooper, J. A.; Kuller, L. H.; Grandits, G.; Gillum, R.; Mussolino, M.; Rimm, E.; Hankinson, S.; Manson, J. A. E.; Pai, J. K.; Bauer, K. A.; Naito, Y.; Amouyel, P.; Arveiler, D.; Evans, A.; Ferrières, J.; Schulte, H.; Assmann, G.; Packard, C. J.; Sattar, N.; Westendorp, R. G.; Buckley, B. M.; Cantin, B.; Lamarche, B.; Després, J.-P.; Dagenais, G. R.; Barrett-Connor, E.; Wingard, D. L.; Bettencourt, R.; Gudnason, V.; Aspelund, T.; Sigurdsson, G.; Thorsson, B.; Trevisan, M.; Tunstall-Pedoe, H.; Tavendale, R.; Lowe, G. D. O.; Woodward, M.; Howard, B. V.; Zhang, Y.; Best, L.; Umans, J.; Ben-Shlomo, Y.; Davey-Smith, G.; Njølstad, I.; Mathiesen, E. B.; Løchen, M. L.; Wilsgaard, T.; Ingelsson, E.; Lind, L.; Giedraitis, V.; Michaëlsson, K.; Brunner, E.; Shipley, M.; Ridker, P.; Buring, J.; Shepherd, J.; Cobbe, S. M.; Ford, I.; Robertson, M.; Ibañez, A. Marin; Feskens, E. J. M.; Kromhout, D.; Walker, M.; Watson, S.; Collins, R.; Di Angelantonio, E.; Kaptoge, S.; Perry, P. L.; Sarwar, N.; Thompson, A.; Thompson, S. G.; White, I. R.; Wood, A. M.

    2010-01-01

    BACKGROUND: Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality. METHODS: We assessed the -1131T>C (rs662799) promoter polymorphism of the

  17. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayés, Mònica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, René; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; de Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flickinger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisén, Louise; Gallagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; de Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andrés; Ising, Marcus; Jamain, Stéphane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kähler, Anna K.; Kahn, René S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landén, Mikael; Längström, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-de-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Mühleisen, Thomas W.; Muir, Walter J.; Müller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Nöthen, Markus M.; Nwulia, Evaristus A.; Nyholt, Dale R.; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnström, Karola; Reif, Andreas; Ribasés, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; St Clair, David; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutcliffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, J. C. G.; van Grootheest, Gerard; van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zöllner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Kendler, Kenneth S.; Weiss, Lauren A.; Wray, Naomi R.; Zhao, Zhaoming; Geschwind, Daniel H.; Sullivan, Patrick F.; Smoller, Jordan W.; Holmans, Peter A.; Breen, Gerome

    2015-01-01

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  18. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

    NARCIS (Netherlands)

    O'Dushlaine, Colm; Rossin, Lizzy; Lee, Phil H.; Duncan, Laramie; Parikshak, Neelroop N.; Newhouse, Stephen; Ripke, Stephan; Neale, Benjamin M.; Purcell, Shaun M.; Posthuma, Danielle; Nurnberger, John I.; Lee, S. Hong; Faraone, Stephen V.; Perlis, Roy H.; Mowry, Bryan J.; Thapar, Anita; Goddard, Michael E.; Witte, John S.; Absher, Devin; Agartz, Ingrid; Akil, Huda; Amin, Farooq; Andreassen, Ole A.; Anjorin, Adebayo; Anney, Richard; Anttila, Verneri; Arking, Dan E.; Asherson, Philip; Azevedo, Maria H.; Backlund, Lena; Badner, Judith A.; Bailey, Anthony J.; Banaschewski, Tobias; Barchas, Jack D.; Barnes, Michael R.; Barrett, Thomas B.; Bass, Nicholas; Battaglia, Agatino; Bauer, Michael; Bayes, Monica; Bellivier, Frank; Bergen, Sarah E.; Berrettini, Wade; Betancur, Catalina; Bettecken, Thomas; Biederman, Joseph; Binder, Elisabeth B.; Black, Donald W.; Blackwood, Douglas H. R.; Bloss, Cinnamon S.; Boehnke, Michael; Boomsma, Dorret I.; Breuer, Rene; Bruggeman, Richard; Cormican, Paul; Buccola, Nancy G.; Buitelaar, Jan K.; Bunney, William E.; Buxbaum, Joseph D.; Byerley, William F.; Byrne, Enda M.; Caesar, Sian; Cahn, Wiepke; Cantor, Rita M.; Casas, Miguel; Chakravarti, Aravinda; Chambert, Kimberly; Choudhury, Khalid; Cichon, Sven; Mattheisen, Manuel; Cloninger, C. Robert; Collier, David A.; Cook, Edwin H.; Coon, Hilary; Cormand, Bru; Corvin, Aiden; Coryell, William H.; Craig, David W.; Craig, Ian W.; Crosbie, Jennifer; Cuccaro, Michael L.; Curtis, David; Czamara, Darina; Datta, Susmita; Dawson, Geraldine; Day, Richard; De Geus, Eco J.; Degenhardt, Franziska; Djurovic, Srdjan; Donohoe, Gary J.; Doyle, Alysa E.; Duan, Jubao; Dudbridge, Frank; Duketis, Eftichia; Ebstein, Richard P.; Edenberg, Howard J.; Elia, Josephine; Ennis, Sean; Etain, Bruno; Fanous, Ayman; Farmer, Anne E.; Ferrier, I. Nicol; Flicldnger, Matthew; Fombonne, Eric; Foroud, Tatiana; Frank, Josef; Franke, Barbara; Fraser, Christine; Freedman, Robert; Freimer, Nelson B.; Freitag, Christine M.; Friedl, Marion; Frisen, Louise; Gailagher, Louise; Gejman, Pablo V.; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Gill, Michael; Gordon, Scott D.; Gordon-Smith, Katherine; Green, Elaine K.; Greenwood, Tiffany A.; Grice, Dorothy E.; Gross, Magdalena; Grozeva, Detelina; Guan, Weihua; Gurling, Hugh; De Haan, Lieuwe; Haines, Jonathan L.; Hakonarson, Hakon; Hallmayer, Joachim; Hamilton, Steven P.; Hamshere, Marian L.; Hansen, Thomas F.; Hartmann, Annette M.; Hautzinger, Martin; Heath, Andrew C.; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hipolito, Maria; Hoefels, Susanne; Holsboer, Florian; Hoogendijk, Witte J.; Hottenga, Jouke-Jan; Hultman, Christina M.; Hus, Vanessa; Ingason, Andres; Ising, Marcus; Jamain, Stephane; Jones, Edward G.; Jones, Ian; Jones, Lisa; Tzeng, Jung-Ying; Kaehler, Anna K.; Kahn, Rene S.; Kandaswamy, Radhika; Keller, Matthew C.; Kennedy, James L.; Kenny, Elaine; Kent, Lindsey; Kim, Yunjung; Kirov, George K.; Klauck, Sabine M.; Klei, Lambertus; Knowles, James A.; Kohli, Martin A.; Koller, Daniel L.; Konte, Bettina; Korszun, Ania; Krabbendam, Lydia; Krasucki, Robert; Kuntsi, Jonna; Kwan, Phoenix; Landen, Mikael; Laengstroem, Niklas; Lathrop, Mark; Lawrence, Jacob; Lawson, William B.; Leboyer, Marion; Ledbetter, David H.; Lencz, Todd; Lesch, Klaus-Peter; Levinson, Douglas F.; Lewis, Cathryn M.; Li, Jun; Lichtenstein, Paul; Lieberman, Jeffrey A.; Lin, Dan-Yu; Linszen, Don H.; Liu, Chunyu; Lohoff, Falk W.; Loo, Sandra K.; Lord, Catherine; Lowe, Jennifer K.; Lucae, Susanne; MacIntyre, Donald J.; Madden, Pamela A. F.; Maestrini, Elena; Magnusson, Patrik K. E.; Mahon, Pamela B.; Maier, Wolfgang; Malhotra, Anil K.; Mane, Shrikant M.; Martin, Christa L.; Martin, Nicholas G.; Matthews, Keith; Mattingsdal, Morten; McCarroll, Steven A.; McGhee, Kevin A.; McGough, James J.; McGrath, Patrick J.; McGuffin, Peter; McInnis, Melvin G.; McIntosh, Andrew; McKinney, Rebecca; McLean, Alan W.; McMahon, Francis J.; McMahon, William M.; McQuillin, Andrew; Medeiros, Helena; Medland, Sarah E.; Meier, Sandra; Melle, Ingrid; Meng, Fan; Meyer, Jobst; Middeldorp, Christel M.; Middleton, Lefkos; Milanova, Vihra; Miranda, Ana; Monaco, Anthony P.; Montgomery, Grant W.; Moran, Jennifer L.; Moreno-De-Luca, Daniel; Morken, Gunnar; Morris, Derek W.; Morrow, Eric M.; Moskvina, Valentina; Muglia, Pierandrea; Muehleisen, Thomas W.; Muir, Walter J.; Mueller-Myhsok, Bertram; Murtha, Michael; Myers, Richard M.; Myin-Germeys, Inez; Neale, Michael C.; Nelson, Stan F.; Nievergelt, Caroline M.; Nikolov, Ivan; Nimgaonkar, Vishwajit; Nolen, Willem A.; Noethen, Markus M.; Nwulia, Evaristus A.; Nyholt, Dale R.; Oades, Robert D.; Olincy, Ann; Oliveira, Guiomar; Olsen, Line; Ophoff, Roel A.; Osby, Urban; Owen, Michael J.; Palotie, Aarno; Parr, Jeremy R.; Paterson, Andrew D.; Pato, Carlos N.; Pato, Michele T.; Penninx, Brenda W.; Pergadia, Michele L.; Pericak-Vance, Margaret A.; Pickard, Benjamin S.; Pimm, Jonathan; Piven, Joseph; Potash, James B.; Poustka, Fritz; Propping, Peter; Puri, Vinay; Quested, Digby J.; Quinn, Emma M.; Ramos-Quiroga, Josep Antoni; Rasmussen, Henrik B.; Raychaudhuri, Soumya; Rehnstroem, Karola; Reif, Andreas; Ribases, Marta; Rice, John P.; Rietschel, Marcella; Roeder, Kathryn; Roeyers, Herbert; Rothenberger, Aribert; Rouleau, Guy; Ruderfer, Douglas; Rujescu, Dan; Sanders, Alan R.; Sanders, Stephan J.; Santangelo, Susan L.; Sergeant, Joseph A.; Schachar, Russell; Schalling, Martin; Schatzberg, Alan F.; Scheftner, William A.; Schellenberg, Gerard D.; Scherer, Stephen W.; Schork, Nicholas J.; Schulze, Thomas G.; Schumacher, Johannes; Schwarz, Markus; Scolnick, Edward; Scott, Laura J.; Shi, Jianxin; Shilling, Paul D.; Shyn, Stanley I.; Silverman, Jeremy M.; Slager, Susan L.; Smalley, Susan L.; Smit, Johannes H.; Smith, Erin N.; Sonuga-Barke, Edmund J. S.; Cair, David St.; State, Matthew; Steffens, Michael; Steinhausen, Hans-Christoph; Strauss, John S.; Strohmaier, Jana; Stroup, T. Scott; Sutdiffe, James S.; Szatmari, Peter; Szelinger, Szabocls; Thirumalai, Srinivasa; Thompson, Robert C.; Todorov, Alexandre A.; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; Van den Oord, Edwin J. C. G.; Van Grootheest, Gerard; Van Os, Jim; Vicente, Astrid M.; Vieland, Veronica J.; Vincent, John B.; Visscher, Peter M.; Walsh, Christopher A.; Wassink, Thomas H.; Watson, Stanley J.; Weissman, Myrna M.; Werge, Thomas; Wienker, Thomas F.; Wijsman, Ellen M.; Willemsen, Gonneke; Williams, Nigel; Willsey, A. Jeremy; Witt, Stephanie H.; Xu, Wei; Young, Allan H.; Yu, Timothy W.; Zammit, Stanley; Zandi, Peter P.; Zhang, Peng; Zitman, Frans G.; Zoellner, Sebastian; Devlin, Bernie; Kelsoe, John R.; Sklar, Pamela; Daly, Mark J.; O'Donovan, Michael C.; Craddock, Nicholas; Kendler, Kenneth S.; Weiss, Lauren A.; Wray, Naomi R.; Zhao, Zhaoming; Geschwind, Daniel H.; Sullivan, Patrick F.; Smoller, Jordan W.; Holmans, Peter A.; Breen, Gerome

    Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from

  19. Limb salvage with microvascular free fibula following primary bone sarcoma resection

    Directory of Open Access Journals (Sweden)

    Sahasrabudhe Parag

    2016-01-01

    Full Text Available Background: Extremity sarcomas are challenging to manage. Total eradication of tumour has to be balanced with restoration of limb function to prevent mortality and morbidity. Disease-free survival with maximum limb function is the ultimate goal in these patients. Materials and Methods: We present a series of ten cases of extremity malignancies, where limb salvage was attempted with microvascular free fibula for limb reconstruction from the period of 2008 to 2015. Results: Of the ten cases in the study, there were two females and eight males. There were nine patients with lower limb malignancies and one patient with upper limb malignancy. There were four patients with Ewing's sarcoma of femur, five patients with osteosarcoma of femur and one patient with chondrosarcoma of the humerus. The follow-up period ranged from 1.2 to 6.2 years with mean follow-up of 3.1 years. There were two deaths during follow-up, both were due to distant metastasis. The assessment of the function was done on the basis of Musculoskeletal Tumour Society functional score. Maximum score was 30 and minimum score was 24, the average score being 26. Of the eight surviving patients, three patients had full weightbearing, four patients had partial weightbearing at end of 2 years and one patient of upper limb reconstruction had complete upper limb function. None of the patients had to undergo limb amputation. Conclusion: Limb salvage with vascularised fibula graft offers good functional outcome along with good disease-free survival rates.

  20. Implementation of an obstetric cell salvage service in a tertiary women's hospital.

    Science.gov (United States)

    Lew, Eileen; Tagore, Shephali

    2015-08-01

    Intraoperative cell salvage (ICS) is an important aspect of patient blood management programmes. An ICS service was introduced at KK Women's and Children's Hospital, Singapore, from 2 May 2011 to 30 April 2013 to aid in the management of massive obstetric haemorrhage. With support from the Ministry of Health's Healthcare Quality Improvement and Innovation Fund, a workgroup comprising obstetricians, anaesthetists and nursing staff was formed to develop training requirements, clinical guidelines and protocols for implementing ICS using the Haemonetics Cell Saver 5. Pregnant women with an anticipated blood loss of > 1,000 mL during Caesarean delivery, a baseline haemoglobin level of < 10 g/dL, rare blood types and who had refused donor blood were recruited to the service after obtaining informed consent. A total of 11 women were recruited to the ICS service; the primary indications were placenta praevia and placenta accreta. Median blood loss in these 11 patients was 1,500 (range 400-3,000) mL. In four patients, adequate autologous blood was collected to initiate processing and salvaged, processed blood was successfully reinfused (mean 381.3 [range 223.0-700.0] mL). Median blood loss among these four patients was 2,000 (range 2,000-3,000) mL. No adverse event occurred following autologous transfusion. Mean immediate postoperative haemoglobin level was 8.0 (range 7.1-9.4) g/dL. The implementation of an obstetric ICS service in our institution was successful. Future studies should seek to address the cost-effectiveness of ICS in reducing allogeneic blood utilisation.

  1. Limb-salvage angioplasty in poor surgical chronic liver disease and diabetic patients.

    Science.gov (United States)

    Hamdy, Hussam; El-Kolly, M; Ezzat, H; Abbas, M; Farouk, Y; Naser, M; Magdy, M; Elraouf, A

    2013-08-01

    Critical limb ischemia (CLI) in high surgical risk patients with chronic liver diseases has a grave prognosis with a one-year mortality rate of 20% and a one-year amputation rate of 25% after the initial diagnosis. According to Trans-Atlantic Inter-Society Consensus (TASC)-II Guidelines, revascularization (surgical & endovascular) is the treatment of choice for patients with critical limb ischemia (CLI). The primary goal of revascularization is to relieve ischemic rest pain, heal ulcers, prevent amputation, improve patient's quality of life (limb salvage) and secondary goal was the periprocedural complications. Endovascular techniques include balloon angioplasty, stents, stent-grafts, and plaque debulking procedures. Surgical options, identification of patients at risk of postoperative complications could have an impact on the indications for a procedure as well as permitting modifications of treatment to reduce the surgical risk This study evaluated the treatment out comas after limb salvage angioplasty for patients who otherwise would be candidates for primary amputation due to poor co-morbid conditions as chronic liver disease and diabetes. The clinical evaluation, laboratory investigations and abdominal ultrasonography were performed to all patients to evaluate their liver status. Patients were classified according to Child-pugh classification into child A, B & C. All patients were subjected to either detailed arterial duplex or C.T. angiography to assess their arterial lesions from January 2008- January 2010. 95 patients with critical limb ischemia (Rutherford categories 4, 5, 6) were treated by primary percutaneous transluminal angioplasty (PTA). No patient was excluded on the basis of the extent of arterial occlusive disease. The primary end points were immediate technical success, clinical improvement and limb salvages rates. Secondary end points were periprocedural complications and mortality. Most of the patients were male (54.7%) with mean age 62 (48

  2. Comparative study of Hippo pathway genes in cellular conveyor belts of a ctenophore and a cnidarian

    Directory of Open Access Journals (Sweden)

    Alicia Coste

    2016-02-01

    Full Text Available Abstract Background The Hippo pathway regulates growth rate and organ size in fly and mouse, notably through control of cell proliferation. Molecular interactions at the heart of this pathway are known to have originated in the unicellular ancestry of metazoans. They notably involve a cascade of phosphorylations triggered by the kinase Hippo, with subsequent nuclear to cytoplasmic shift of Yorkie localisation, preventing its binding to the transcription factor Scalloped, thereby silencing proliferation genes. There are few comparative expression data of Hippo pathway genes in non-model animal species and notably none in non-bilaterian phyla. Results All core Hippo pathway genes could be retrieved from the ctenophore Pleurobrachia pileus and the hydrozoan cnidarian Clytia hemisphaerica, with the important exception of Yorkie in ctenophore. Expression study of the Hippo, Salvador and Scalloped genes in tentacle “cellular conveyor belts” of these two organisms revealed striking differences. In P. pileus, their transcripts were detected in areas where undifferentiated progenitors intensely proliferate and where expression of cyclins B and D was also seen. In C. hemisphaerica, these three genes and Yorkie are expressed not only in the proliferating but also in the differentiation zone of the tentacle bulb and in mature tentacle cells. However, using an antibody designed against the C. hemiphaerica Yorkie protein, we show in two distinct cell lineages of the medusa that Yorkie localisation is predominantly nuclear in areas of active cell proliferation and mainly cytoplasmic elsewhere. Conclusions This is the first evidence of nucleocytoplasmic Yorkie shift in association with the arrest of cell proliferation in a cnidarian, strongly evoking the cell division-promoting role of this protein and its inhibition by the activated Hippo pathway in bilaterian models. Our results furthermore highlight important differences in terms of deployment and

  3. Comparative study of Hippo pathway genes in cellular conveyor belts of a ctenophore and a cnidarian.

    Science.gov (United States)

    Coste, Alicia; Jager, Muriel; Chambon, Jean-Philippe; Manuel, Michaël

    2016-01-01

    The Hippo pathway regulates growth rate and organ size in fly and mouse, notably through control of cell proliferation. Molecular interactions at the heart of this pathway are known to have originated in the unicellular ancestry of metazoans. They notably involve a cascade of phosphorylations triggered by the kinase Hippo, with subsequent nuclear to cytoplasmic shift of Yorkie localisation, preventing its binding to the transcription factor Scalloped, thereby silencing proliferation genes. There are few comparative expression data of Hippo pathway genes in non-model animal species and notably none in non-bilaterian phyla. All core Hippo pathway genes could be retrieved from the ctenophore Pleurobrachia pileus and the hydrozoan cnidarian Clytia hemisphaerica, with the important exception of Yorkie in ctenophore. Expression study of the Hippo, Salvador and Scalloped genes in tentacle "cellular conveyor belts" of these two organisms revealed striking differences. In P. pileus, their transcripts were detected in areas where undifferentiated progenitors intensely proliferate and where expression of cyclins B and D was also seen. In C. hemisphaerica, these three genes and Yorkie are expressed not only in the proliferating but also in the differentiation zone of the tentacle bulb and in mature tentacle cells. However, using an antibody designed against the C. hemiphaerica Yorkie protein, we show in two distinct cell lineages of the medusa that Yorkie localisation is predominantly nuclear in areas of active cell proliferation and mainly cytoplasmic elsewhere. This is the first evidence of nucleocytoplasmic Yorkie shift in association with the arrest of cell proliferation in a cnidarian, strongly evoking the cell division-promoting role of this protein and its inhibition by the activated Hippo pathway in bilaterian models. Our results furthermore highlight important differences in terms of deployment and regulation of Hippo pathway genes between cnidarians and ctenophores.

  4. Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study

    Directory of Open Access Journals (Sweden)

    Zhiwei Cao

    2011-05-01

    Full Text Available The hedgehog signal pathway is an essential agent in developmental patterning, wherein the local concentration of the Hedgehog morphogens directs cellular differentiation and expansion. Furthermore, the Hedgehog pathway has been implicated in tumor/stromal interaction and cancer stem cell. Nowadays searching novel inhibitors for Hedgehog Signal Pathway is drawing much more attention by biological, chemical and pharmological scientists. In our study, a solid computational model is proposed which incorporates various statistical analysis methods to perform a Quantitative Structure-Activity Relationship (QSAR study on the inhibitors of Hedgehog signaling. The whole QSAR data contain 93 cyclopamine derivatives as well as their activities against four different cell lines (NCI-H446, BxPC-3, SW1990 and NCI-H157. Our extensive testing indicated that the binary classification model is a better choice for building the QSAR model of inhibitors of Hedgehog signaling compared with other statistical methods and the corresponding in silico analysis provides three possible ways to improve the activity of inhibitors by demethylation, methylation and hydroxylation at specific positions of the compound scaffold respectively. From these, demethylation is the best choice for inhibitor structure modifications. Our investigation also revealed that NCI-H466 served as the best cell line for testing the activities of inhibitors of Hedgehog signal pathway among others.

  5. Signalling pathways in trophic skeletal development and morphogenesis: Insights from studies on teleost fish.

    Science.gov (United States)

    Ahi, Ehsan Pashay

    2016-12-01

    During the development of the vertebrate feeding apparatus, a variety of complicated cellular and molecular processes participate in the formation and integration of individual skeletal elements. The molecular mechanisms regulating the formation of skeletal primordia and their development into specific morphological structures are tightly controlled by a set of interconnected signalling pathways. Some of these pathways, such as Bmp, Hedgehog, Notch and Wnt, are long known for their pivotal roles in craniofacial skeletogenesis. Studies addressing the functional details of their components and downstream targets, the mechanisms of their interactions with other signals as well as their potential roles in adaptive morphological divergence, are currently attracting considerable attention. An increasing number of signalling pathways that had previously been described in different biological contexts have been shown to be important in the regulation of jaw skeletal development and morphogenesis. In this review, I provide an overview of signalling pathways involved in trophic skeletogenesis emphasizing studies of the most species-rich group of vertebrates, the teleost fish, which through their evolutionary history have undergone repeated episodes of spectacular trophic diversification. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. [Effects of acute hypervolemic hemodilution and intraoperative blood salvage on erythrocyte morphology and biomechanics].

    Science.gov (United States)

    Zhang, Yiwen; Xinh, Zumin; Guo, Qiang; He, Zhongcheng

    2015-07-01

    To investigate the effects of acute hypervolemic hemodilution (AHH) and intraoperative blood salvage (IOBS) on the morphology and biomechanics of erythrocytes using atomic force microscopy (AFM). Blood samples were collected from 20 patients undergoing orthopedic surgery before operation (T1), immediately after AHH (T2), and after blood salvage (T3). AFM at nanometer resolution was used to examine the morphology and biomechanics of the collected erythrocytes. The blood samples collected at T1 showed a significantly lower ratio of heteromorphous erythrocytes than those collected at T2 and T3 [(2.6∓1.3)% vs (19.3∓1.6)% and (17.6∓1.4)%, Pbiomechanics of the single erythrocyte in salvaged blood and blood after AHH compared with those of venous blood. AHH and IOBS may cause significant changes in the morphology and biomechanics of erythrocytes in the salvaged blood.

  7. Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Safdieh, Joseph; Schwartz, David; Weiner, Joseph; Weiss, Jeffrey P.; Madeb, Isaac; Rotman, Marvin; Schreiber, David [Dept.of Veteran Affairs, New York Harbor Healthcare System, Brooklyn (United States); Rineer, Justin [University of Florida Health Cancer Center, Orlando (United States)

    2014-09-15

    To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

  8. Blood PGC-1α Concentration Predicts Myocardial Salvage and Ventricular Remodeling After ST-segment Elevation Acute Myocardial Infarction.

    Science.gov (United States)

    Fabregat-Andrés, Óscar; Ridocci-Soriano, Francisco; Estornell-Erill, Jordi; Corbí-Pascual, Miguel; Valle-Muñoz, Alfonso; Berenguer-Jofresa, Alberto; Barrabés, José A; Mata, Manuel; Monsalve, María

    2015-05-01

    Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) is a metabolic regulator induced during ischemia that prevents cardiac remodeling in animal models. The activity of PGC-1α can be estimated in patients with ST-segment elevation acute myocardial infarction. The aim of the present study was to evaluate the value of blood PGC-1α levels in predicting the extent of necrosis and ventricular remodeling after infarction. In this prospective study of 31 patients with a first myocardial infarction in an anterior location and successful reperfusion, PGC-1α expression in peripheral blood on admission and at 72 hours was correlated with myocardial injury, ventricular volume, and systolic function at 6 months. Edema and myocardial necrosis were estimated using cardiac magnetic resonance imaging during the first week. At 6 months, infarct size and ventricular remodeling, defined as an increase > 10% of the left ventricular end-diastolic volume, was evaluated by follow-up magnetic resonance imaging. Myocardial salvage was defined as the difference between the edema and necrosis areas. Greater myocardial salvage was seen in patients with detectable PGC-1α levels at admission (mean [standard deviation (SD)], 18.3% [5.3%] vs 4.5% [3.9%]; P = .04). Induction of PGC-1α at 72 hours correlated with greater ventricular remodeling (change in left ventricular end-diastolic volume at 6 months, 29.7% [11.2%] vs 1.2% [5.8%]; P = .04). Baseline PGC-1α expression and an attenuated systemic response after acute myocardial infarction are associated with greater myocardial salvage and predict less ventricular remodeling. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  9. Defining the Salvage Time Window for the Use of Ischemic Postconditioning in Skeletal Muscle Ischemia Reperfusion Injury.

    Science.gov (United States)

    Schmucker, Ryan W; Mendenhall, Shaun D; Reichensperger, Joel D; Yang, Mei; Neumeister, Michael W

    2015-10-01

    The aim of this study was to determine the optimal salvage time window within which ischemic postconditioning can be used to ameliorate ischemia/reperfusion (I/R) injury in skeletal muscle. A total of 48 Sprague-Dawley rats were divided into two groups: I/R only (control) and I/R with postconditioning. Subgroups were divided by duration of ischemia (2, 4, 6, and 8 hours). A pedicled gracilis muscle model was used. The postconditioning protocol consisted of six cycles of 15 seconds of reperfusion followed by 15 seconds of ischemia (total time = 3 minutes). Muscles were harvested 24 hours after I/R injury to examine tissue viability, histology, myeloperoxidase activity, and protective gene expression. Postconditioning groups showed improved muscle viability after 4 and 6 hours of ischemia time as compared with controls (p < 0.05). Higher expression of mitochondrial complexes I, II, III, endothelial nitric oxide synthase, inducible nitric oxide synthase, and Bcl-2 were observed in the postconditioning group after 4 and 6 hours of ischemia (p < 0.05). Lower expression of tumor necrosis factor-α and caspase 3 was observed in the postconditioning group at 4 hours (p < 0.05). Myeloperoxidase activity was similar in both groups at all-time points except 8 hours ischemia, where the control group had higher activity (p < 0.05). Results of this study demonstrate that the effective time window within which postconditioning is most effective for the salvage of skeletal muscle is between 4 and 6 hours of ischemia. Postconditioning offered improved mitochondrial and vascular function with decreased inflammation and cell death. This may be clinically useful as a postinjury salvage technique to attenuate I/R injury after 4 to 6 hours of ischemia. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  10. Salvage felling in the Slovak forests in the period 2004–2013

    Directory of Open Access Journals (Sweden)

    Kunca Andrej

    2015-09-01

    Full Text Available Salvage felling is one of the indicators of the forest health quality and stability. Most of the European Union countries monitor forest harmful agents, which account for salvage felling, in order to see trends or functionality between factors and to be able to predict their development. The systematic evidence of forest harmful agents and volume of salvage felling in Slovakia started at the Forest Research Institute in Zvolen in 1960. The paper focuses on the occurrence of the most relevant harmful agents and volume of salvage felling in the Slovak forests over the last decade. Within the 10 years period (2004–2013 salvage felling in Slovakia reached 42.31 mil. m3 of wood, which was 53.2% of the total felling. Wind and European spruce bark beetle Ips typographus damaged 78.4% of salvage wood, i.e. they were the most important pest agents. Norway spruce (Picea abies was the most frequently damaged tree species that represented the amount of 35.6 mil. m3 of wood (81.2% of total volume of salvage felling. As Norway spruce grows mostly in mountains, these regions of Central and Northern Slovakia were most affected. At the damaged localities new forests were prevailingly established with regard to suitable ecological conditions for trees, climate change scenarios and if possible, natural regeneration has been preferred. These approaches in forest stand regeneration together with silvicultural and control measures are assumed to gradually decrease the amount of salvage felling over long term perspective.

  11. Obstacles to continuity of care in young mental health service users’ pathways - an explorative study

    Directory of Open Access Journals (Sweden)

    Marian Ådnanes

    2013-08-01

    Full Text Available Background: Users of mental health services often move between different primary and specialised health and care services, depending on their current condition, and this often leads to fragmentation of care. The aim of this study was to map care pathways in the case of young adult mental health service users and to identify key obstacles to continuity of care.Method: Quarterly semi-structured interviews were performed with nine young adults with mental health difficulties, following their pathways in and out of different services in the course of a year.Results: Key obstacles to continuity of care included the mental health system's lack of access to treatment, lack of integration between different specialist services, lack of progress in care and inadequate coordination tools such as ‘Individual Plan’ and case conferences that did not prevent fragmented care pathways.Conclusions: Continuity of care should be more explicitly linked to aspirations for development and progress in the users' care pathways, and how service providers can cooperate with users to actually develop and make progress. Coordination tools such as case conferences and ‘individual plans’ should be upgraded to this end and utilised to the utmost. This may be the most effective way to counteract the system obstacles.

  12. Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial

    DEFF Research Database (Denmark)

    Gimsing, P; Hjertner, Ø; Abildgaard, N

    2015-01-01

    Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib...... included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT...... with the initial ASCT. Bortezomib-HDM conditioning combo was feasible, and toxicity was as expected for patients treated with bortezomib and ASCT. In conclusion, in bortezomib-naïve patients treated at first relapse with salvage ASCT including bortezomib, PSF and TNT did not differ significantly from initial ASCT...

  13. Pathway collages: personalized multi-pathway diagrams.

    Science.gov (United States)

    Paley, Suzanne; O'Maille, Paul E; Weaver, Daniel; Karp, Peter D

    2016-12-13

    Metabolic pathway diagrams are a classical way of visualizing a linked cascade of biochemical reactions. However, to understand some biochemical situations, viewing a single pathway is insufficient, whereas viewing the entire metabolic network results in information overload. How do we enable scientists to rapidly construct personalized multi-pathway diagrams that depict a desired collection of interacting pathways that emphasize particular pathway interactions? We define software for constructing personalized multi-pathway diagrams called pathway-collages using a combination of manual and automatic layouts. The user specifies a set of pathways of interest for the collage from a Pathway/Genome Database. Layouts for the individual pathways are generated by the Pathway Tools software, and are sent to a Javascript Pathway Collage application implemented using Cytoscape.js. That application allows the user to re-position pathways; define connections between pathways; change visual style parameters; and paint metabolomics, gene expression, and reaction flux data onto the collage to obtain a desired multi-pathway diagram. We demonstrate the use of pathway collages in two application areas: a metabolomics study of pathogen drug response, and an Escherichia coli metabolic model. Pathway collages enable facile construction of personalized multi-pathway diagrams.

  14. Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Narayan, Vivek [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vapiwala, Neha [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Mick, Rosemarie [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Subramanian, Pearl [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P.; Bekelman, Justin E.; Deville, Curtiland; Rajendran, Ramji [Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Haas, Naomi B., E-mail: naomi.haas@uphs.upenn.edu [Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2017-02-01

    Purpose: In up to half of patients treated with salvage radiation therapy (SRT) for rising prostate-specific antigen levels, a second biochemical recurrence ultimately develops. Phosphatase and tensin homolog inactivation is implicated in prostate cancer progression, and upregulation of the mammalian target of rapamycin pathway can lead to tumor hypoxia and radioresistance. Everolimus is a mammalian target of rapamycin inhibitor with both antitumor and radiosensitizing effects. Methods and Materials: We performed a phase 1 study using a modified 3 + 3 dose-escalation design to evaluate the safety and tolerability of everolimus in combination with standard SRT for the treatment of biochemical recurrence following prostatectomy. After a 2-week run-in period of everolimus daily therapy, patients received prostate bed irradiation with daily cone beam computed tomography localization in 37 fractions of 1.8 Gy each (total dose, 66.6 Gy). Patients were monitored for both acute (≤90 days) and chronic (>90 days) treatment-related toxicities. Results: Eighteen patients received everolimus at dose levels of 5 mg (n=6), 7.5 mg (n=6), or 10 mg (n=6) daily in conjunction with SRT. No dose-limiting toxicities were observed. Common acute treatment-related toxicities included grade 1 or 2 mucositis (55.6%), grade 1 or 2 fatigue (38.9%), grade 1 or 2 rash (61.1%), and grade 1 urinary symptoms (61.1%). A grade 3 acute toxicity occurred in 4 patients (22.2%) (n=1 for rash, anemia, lymphopenia, and neutropenia), and no patients had a chronic toxicity of grade 3 or greater. After a median follow-up time of 17.8 months (range, 1.2-46.0 months), an undetectable prostate-specific antigen nadir was achieved in 9 patients (56.3%) and a second biochemical recurrence developed in 5 patients (31.3%). Conclusions: Everolimus at a dose of ≤10 mg daily appears to be safe and tolerable in combination with fractionated post-prostatectomy radiation therapy.

  15. Late amputation may not reduce complications or improve mental health in combat-related, lower extremity limb salvage patients.

    Science.gov (United States)

    Krueger, Chad A; Rivera, Jessica C; Tennent, David J; Sheean, Andrew J; Stinner, Daniel J; Wenke, Joseph C

    2015-08-01

    Following severe lower extremity trauma, patients who undergo limb reconstruction and amputations both endure frequent complications and mental health sequelae. The purpose of this study is to assess the extent to which late amputation following a period of limb salvage impacts the evolution of the clinical variables that can affect the patient's perception of his or her limb: ongoing limb associated complications and mental health conditions. A case series of US service members who sustained a late major extremity amputation from September 2001 through July 2011 were analysed. Pre- and post-amputation complications, mental health conditions, and reason(s) for desiring amputation were recorded. Forty-four amputees with detailed demographic, injury and treatment data were identified. The most common reasons for desiring a late amputation were pain and being dissatisfied with the function of the salvage limb. An average of 3.2 (range 1-10) complications were reported per amputee prior to undergoing late amputation and an average of 1.8 (range 0-5) complications reported afterwards. The most common complication prior to and after late amputation was soft tissue infection (24 (17%) and 9 (22%), respectively). Twenty-nine (64%) late amputees were diagnosed with a mental health condition prior to undergoing their amputation and 27 (61%) late amputees were diagnosed with mental conditions after late amputation. Only three of the 15 patients who did not have a mental health condition documented prior to their late amputation remained free of a documented mental health condition after the amputation. Ongoing complications and mental health conditions can affect how a patient perceives and copes with his or her limb following severe trauma. Patient dissatisfaction following limb reconstruction can influence the decision to undergo a late amputation. Patients with a severe, combat related lower extremity injury that are undergoing limb salvage may not have a reduction in

  16. A Salvage Operation for Total Penis Amputation Due to Circumcision

    Directory of Open Access Journals (Sweden)

    Bilsev Ince

    2013-05-01

    Full Text Available Circumcision is one of the most common rituals in Jewish and Islamic cultures. It may also be performed for phimosis correction or the treatment of recurrent balanitis. Although circumcision is considered to be a technically easy and safe surgical procedure with no significant risk, it may lead to severe complications such as necrotizing fasciitis or total penis amputation. In this report, we present a case of penis amputation at two levels occurring with third-degree burns due to electrocautery during circumcision. Although penile replantation was attempted, it was unsuccessful due to burn damage to the veins. After restoration of the functional structures, the penis was buried in the inguinal area by reepithelization to maintain blood circulation. The recovery of the penis was successful. This case is presented as a novel example of groin flap surgery to achieve a functionally and aesthetically acceptable outcome in a salvage operation for a penis with significant traumatic injury, which has not been previously reported in the literature.

  17. Developing Effective and Efficient care pathways in chronic Pain: DEEP study protocol.

    Science.gov (United States)

    Durham, Justin; Breckons, Matthew; Araujo-Soares, Vera; Exley, Catherine; Steele, Jimmy; Vale, Luke

    2014-01-21

    Pain affecting the face or mouth and lasting longer than three months ("chronic orofacial pain", COFP) is relatively common in the UK. This study aims to describe and model current care pathways for COFP patients, identify areas where current pathways could be modified, and model whether these changes would improve outcomes for patients and use resources more efficiently. The study takes a prospective operations research approach. A cohort of primary and secondary care COFP patients (n = 240) will be recruited at differing stages of their care in order to follow and analyse their journey through care. The cohort will be followed for two years with data collected at baseline 6, 12, 18, and 24 months on: 1) experiences of the care pathway and its impacts; 2) quality of life; 3) pain; 4) use of health services and costs incurred; 5) illness perceptions. Qualitative in-depth interviews will be used to collect data on patient experiences from a purposive sub-sample of the total cohort (n = 30) at baseline, 12 and 24 months. Four separate appraisal groups (public, patient, clincian, service manager/commissioning) will then be given data from the pathway analysis and asked to determine their priority areas for change. The proposals from appraisal groups will inform an economic modelling exercise. Findings from the economic modelling will be presented as incremental costs, Quality Adjusted Life Years (QALYs), and the incremental cost per QALY gained. At the end of the modelling a series of recommendations for service change will be available for implementation or further trial if necessary. The recent white paper on health and the report from the NHS Forum identified chronic conditions as priority areas and whilst technology can improve outcomes, so can simple, appropriate and well-defined clinical care pathways. Understanding the opportunity cost related to care pathways benefits the wider NHS. This research develops a method to help design efficient systems built

  18. Kinetic studies of the folding of heterodimeric monellin: evidence for switching between alternative parallel pathways.

    Science.gov (United States)

    Aghera, Nilesh; Udgaonkar, Jayant B

    2012-07-13

    Determining whether or not a protein uses multiple pathways to fold is an important goal in protein folding studies. When multiple pathways are present, defined by transition states that differ in their compactness and structure but not significantly in energy, they may manifest themselves by causing the dependence on denaturant concentration of the logarithm of the observed rate constant of folding to have an upward curvature. In this study, the folding mechanism of heterodimeric monellin [double-chain monellin (dcMN)] has been studied over a range of protein and guanidine hydrochloride (GdnHCl) concentrations, using the intrinsic tryptophan fluorescence of the protein as the probe for the folding reaction. Refolding is shown to occur in multiple kinetic phases. In the first stage of refolding, which is silent to any change in intrinsic fluorescence, the two chains of monellin bind to one another to form an encounter complex. Interrupted folding experiments show that the initial encounter complex folds to native dcMN via two folding routes. A productive folding intermediate population is identified on one route but not on both of these routes. Two intermediate subpopulations appear to form in a fast kinetic phase, and native dcMN forms in a slow kinetic phase. The chevron arms for both the fast and slow phases of refolding are shown to have upward curvatures, suggesting that at least two pathways each defined by a different intermediate are operational during these kinetic phases of structure formation. Refolding switches from one pathway to the other as the GdnHCl concentration is increased. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

    Directory of Open Access Journals (Sweden)

    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  20. Streptomyces coelicolor XdhR is a direct target of (p)ppGpp that controls expression of genes encoding xanthine dehydrogenase to promote purine salvage.

    Science.gov (United States)

    Sivapragasam, Smitha; Grove, Anne

    2016-05-01

    The gene encoding Streptomyces coelicolor xanthine dehydrogenase regulator (XdhR) is divergently oriented from xdhABC, which encodes xanthine dehydrogenase (Xdh). Xdh is required for purine salvage pathways. XdhR was previously shown to repress xdhABC expression. We show that XdhR binds the xdhABC-xdhR intergenic region with high affinity (Kd ∼ 0.5 nM). DNaseI footprinting reveals that this complex formation corresponds to XdhR binding the xdhR gene promoter at two adjacent sites; at higher protein concentrations, protection expands to a region that overlaps the transcriptional and translational start sites of xdhABC. While substrates for Xdh have little effect on DNA binding, GTP and ppGpp dissociate the DNA-XdhR complex. Progression of cells to stationary phase, a condition associated with increased (p)ppGpp production, leads to elevated xdhB expression; in contrast, inhibition of Xdh by allopurinol results in xdhB repression. We propose that XdhR is a direct target of (p)ppGpp, and that expression of xdhABC is upregulated during the stringent response to promote purine salvage pathways, maintain GTP homeostasis and ensure continued (p)ppGpp synthesis. During exponential phase growth, basal levels of xdhABC expression may be achieved by GTP serving as a lower-affinity XdhR ligand. © 2016 John Wiley & Sons Ltd.

  1. Pharmacogenetic study focused on fluoxetine pharmacodynamics in children and adolescent patients: impact of the serotonin pathway.

    Science.gov (United States)

    Mas, Sergi; Blázquez, Ana; Rodríguez, Natalia; Boloc, Daniel; Lafuente, Amalia; Arnaiz, Joan A; Lázaro, Luisa; Gassó, Patricia

    2016-11-01

    Pharmacogenetic studies of fluoxetine in children and adolescents are scarce. After reporting the effect of genetic variants in genes related to the fluoxetine pharmacokinetics on clinical response in a pediatric population, we now evaluate the impact of genetic markers involved in its pharmacodynamics. The assessment was performed in 83 patients after 12 weeks of fluoxetine treatment. The genetic association analysis included a total of 316 validated single nucleotide polymorphisms in 45 candidate genes involved in six different pathways. Clinical improvement after treatment with fluoxetine in our pediatric population was associated significantly with two polymorphisms located in genes related to the serotonergic system: the 5-hydroxytryptamine receptor 1B (HTR1B) and the tryptophan 5-hydroxylase 2 (TPH2). Although a wide range of candidate genes related to different pathways were assessed, the results show that genetic markers directly related to serotonin have an important effect on fluoxetine response.

  2. PET probes for distinct metabolic pathways have different cell specificities during immune responses in mice.

    Science.gov (United States)

    Nair-Gill, Evan; Wiltzius, Stephanie M; Wei, Xiao X; Cheng, Donghui; Riedinger, Mireille; Radu, Caius G; Witte, Owen N

    2010-06-01

    Clinical tools that measure changes in immune cell metabolism would improve the diagnosis and treatment of immune dysfunction. PET, utilizing probes for specific metabolic processes, detects regions of immune activation in vivo. In this study we investigated the immune cell specificity of PET probes for two different metabolic pathways: [18F]-2-fluorodeoxyglucose ([18F]-FDG) for glycolysis and [18F]-2-fluoro-D-(arabinofuranosyl)cytosine ([18F]-FAC) for deoxycytidine salvage. We isolated innate and adaptive immune cells from tissues of mice challenged with a retrovirus-induced sarcoma and measured their ability to accumulate FDG and FAC. We determined that the two probes had distinct patterns of accumulation: FDG accumulated to the highest levels in innate immune cells, while FAC accumulated predominantly in CD8+ T cells in a manner that correlated with cellular proliferation. This study demonstrates that innate and adaptive cell types differ in glycolytic and deoxycytidine salvage demands during an immune response and that these differential metabolic requirements can be detected with specific PET probes. Our findings have implications for the interpretation of clinical PET scans that use [18F]-FDG or [18F]-FAC to assess immune function in vivo and suggest potential applications of metabolic PET to monitor the effects of targeted immune modulation.

  3. Squamous Cancers of the Rectum Demonstrate Poorer Survival and Increased Need for Salvage Surgery Compared With Squamous Cancers of the Anus.

    Science.gov (United States)

    Kulaylat, Audrey S; Hollenbeak, Christopher S; Stewart, David B

    2017-09-01

    Squamous cell cancers of the anus are rare GI malignancies for which neoadjuvant chemoradiation is the first-line treatment for nonmetastatic disease. Squamous cancers of the rectum are far less common, and it is unclear to what degree chemoradiotherapy improves their outcomes. The purpose of this study was to compare stage-specific survival for anal and rectal squamous cancers stratified by treatment approach. This was a retrospective cohort study. The study was conducted at Commission on Cancer designated hospitals. Patients (2006-2012) identified in the National Cancer Database with pretreatment clinical stage I to III cancers who underwent chemoradiotherapy, with and without subsequent salvage surgical resection (low anterior resection or abdominoperineal resection), ≥12 weeks after chemoradiotherapy were included in the study. Overall survival and the need for salvage surgery were measured. Anal cancers (n = 11,224) typically presented with stage II (45.7%) or III (36.3%) disease, whereas rectal cancer stages (n = 1049) were more evenly distributed (p cancer underwent low anterior or abdominoperineal resections 12 weeks or later after chemoradiotherapy versus those undergoing abdominoperineal resection for anal cancer (3.8% versus 1.2%; p cancer was associated with poorer survival compared with anal cancer (stage I, p = 0.017; stage II, p cancer was associated with worse survival for stage I to III cancers; salvage surgery did not significantly affect survival for rectal cancer. This was a retrospective study without cancer-specific survival measures. Squamous rectal cancers are associated with significantly worse survival than squamous cancers of the anus for clinical stage I and II disease. Despite both cancers exhibiting squamous histology, rectal cancers may be less radiosensitive than anal cancers, as suggested by the greater incidence of salvage surgery that does not appear to significantly improve overall survival. See Video Abstract at http

  4. Neuroimmune Pathways in Alcohol Consumption: Evidence from Behavioral and Genetic Studies in Rodents and Humans

    Science.gov (United States)

    Robinson, Gizelle; Most, Dana; Ferguson, Laura B.; Mayfield, Jody; Harris, R. Adron; Blednov, Yuri A.

    2014-01-01

    Immune or brain proinflammatory signaling has been linked to some of the behavioral effects of alcohol. Immune signaling appears to regulate voluntary ethanol intake in rodent models, and ethanol intake activates the immune system in multiple models. This bidirectional link raises the possibility that consumption increases immune signaling, which in turn further increases consumption in a feed-forward cycle. Data from animal and human studies provide overlapping support for the involvement of immune-related genes and proteins in alcohol action, and combining animal and human data is a promising approach to systematically evaluate and nominate relevant pathways. Based on rodent models, neuroimmune pathways may represent unexplored, nontraditional targets for medication development to reduce alcohol consumption and prevent relapse. Peroxisome proliferator-activated receptor agonists are one class of anti-inflammatory medications that demonstrate antiaddictive properties for alcohol and other drugs of abuse. Expression of immune-related genes is altered in animals and humans following chronic alcohol exposure, and the regulatory influences of specific mRNAs, microRNAs, and activated cell types are areas of intense study. Ultimately, the use of multiple datasets combined with behavioral validation will be needed to link specific neuroimmune pathways to addiction vulnerability. PMID:25175860

  5. Best strategies to implement clinical pathways in an emergency department setting: study protocol for a cluster randomized controlled trial.

    Science.gov (United States)

    Jabbour, Mona; Curran, Janet; Scott, Shannon D; Guttman, Astrid; Rotter, Thomas; Ducharme, Francine M; Lougheed, M Diane; McNaughton-Filion, M Louise; Newton, Amanda; Shafir, Mark; Paprica, Alison; Klassen, Terry; Taljaard, Monica; Grimshaw, Jeremy; Johnson, David W

    2013-05-22

    The clinical pathway is a tool that operationalizes best evidence recommendations and clinical practice guidelines in an accessible format for 'point of care' management by multidisciplinary health teams in hospital settings. While high-quality, expert-developed clinical pathways have many potential benefits, their impact has been limited by variable implementation strategies and suboptimal research designs. Best strategies for implementing pathways into hospital settings remain unknown. This study will seek to develop and comprehensively evaluate best strategies for effective local implementation of externally developed expert clinical pathways. We will develop a theory-based and knowledge user-informed intervention strategy to implement two pediatric clinical pathways: asthma and gastroenteritis. Using a balanced incomplete block design, we will randomize 16 community emergency departments to receive the intervention for one clinical pathway and serve as control for the alternate clinical pathway, thus conducting two cluster randomized controlled trials to evaluate this implementation intervention. A minimization procedure will be used to randomize sites. Intervention sites will receive a tailored strategy to support full clinical pathway implementation. We will evaluate implementation strategy effectiveness through measurement of relevant process and clinical outcomes. The primary process outcome will be the presence of an appropriately completed clinical pathway on the chart for relevant patients. Primary clinical outcomes for each clinical pathway include the following: Asthma--the proportion of asthmatic patients treated appropriately with corticosteroids in the emergency department and at discharge; and Gastroenteritis--the proportion of relevant patients appropriately treated with oral rehydration therapy. Data sources include chart audits, administrative databases, environmental scans, and qualitative interviews. We will also conduct an overall process

  6. Study on roles of anaplerotic pathways in glutamate overproduction of Corynebacterium glutamicum by metabolic flux analysis

    Directory of Open Access Journals (Sweden)

    Shioya Suteaki

    2007-06-01

    Full Text Available Abstract Background Corynebacterium glutamicum has several anaplerotic pathways (anaplerosis, which are essential for the productions of amino acids, such as lysine and glutamate. It is still not clear how flux changes in anaplerotic pathways happen when glutamate production is induced by triggers, such as biotin depletion and the addition of the detergent material, Tween 40. In this study, we quantitatively analyzed which anaplerotic pathway flux most markedly changes the glutamate overproduction induced by Tween 40 addition. Results We performed a metabolic flux analysis (MFA with [1-13C]- and [U-13C]-labeled glucose in the glutamate production phase of C. glutamicum, based on the analysis of the time courses of 13C incorporation into proteinogenic amino acids by gas chromatography-mass spectrometry (GC-MS. The flux from phosphoenolpyruvate (PEP to oxaloacetate (Oxa catalyzed by phosphoenolpyruvate carboxylase (PEPc was active in the growth phase not producing glutamate, whereas that from pyruvate to Oxa catalyzed by pyruvate carboxylase (Pc was inactive. In the glutamate overproduction phase induced by the addition of the detergent material Tween 40, the reaction catalyzed by Pc also became active in addition to the reaction catalyzed by PEPc. Conclusion It was clarified by a quantitative 13C MFA that the reaction catalyzed by Pc is most markedly increased, whereas other fluxes of PEPc and PEPck remain constant in the glutamate overproduction induced by Tween 40. This result is consistent with the previous results obtained in a comparative study on the glutamate productions of genetically recombinant Pc- and PEPc-overexpressing strains. The importance of a specific reaction in an anaplerotic pathway was elucidated at a metabolic level by MFA.

  7. Predictability of salvage and outcome of Gustilo and Anderson type-IIIA and type-IIIB open tibial fractures using Ganga Hospital Scoring system.

    Science.gov (United States)

    Madhuchandra, P; Rafi, Mohammed; Devadoss, Sathish; Devadoss, A

    2015-02-01

    Although numerous scoring systems are designed for lower limb open injuries, most of them are based on orthopaedic and vascular injuries and can define only an amputation score. These scoring system lack specificity and sensitivity in predicting the salvage and outcome. Ganga Hospital Scoring system was found to have good specificity in predicting the outcome in Gustilo type-IIIA and type-IIIB injuries. We have validated in our study the Ganga Hospital Scoring system which grades the open injuries based on severity of injury to covering structures, functional and the skeletal units. The score was validated in 40 open injuries of tibia, 11 type-IIIA and 29 type-IIIB. Predictability of salvage and outcome was measured based on this scoring system. Results of our study correlated well with outcome of Ganga hospital study. 38 of 40 limbs with score below 14 and 1 with score above 14 were salvaged. The sensitivity and specificity for the threshold score of 14 was 100% and 95% respectively. Requirement of flaps, number of surgical procedures, time to bony union and infection rates in different groups were similar to original study. The Ganga scoring system was found to have good specificity and sensitivity and reliable in prognosticating the outcome in open injuries of the tibia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Effectiveness of Second through Sixth Line Salvage Helicobacter pylori Treatment: Bismuth Quadruple Therapy is Almost Always a Reasonable Choice.

    Science.gov (United States)

    Shaikh, Tahir; Fallone, Carlo A

    2016-01-01

    Aim. There is a paucity of data on the efficacy of empiric H. pylori treatment after multiple treatment failures. The aim of this study is to examine the efficacy of empiric salvage therapy as a second through sixth line treatment. Methods. In this single gastroenterology center prospective study in Montreal, Canada, patients with failed H. pylori treatment were offered empiric salvage therapy based on the patients' previous antibiotic exposure. Enrollment occurred after 1-5 previous failed attempts and eradication determined at least 4 weeks after completion of treatment. Results. 205 treatments were attempted in 175 patients using 7 different regimens. Eradication was achieved in 154 attempts (PP = 81% (154/191), ITT = 75% (154/205)). Bismuth quadruple therapy (BQT) had higher eradication success (PP = 91% (102/112), ITT = 84% (102/121)) when compared to all PPI triple therapies combined (PP = 66% (49/74), absolute risk reduction (ARR): 25% (95% CI: 13-37), ITT = 62% (49/79), ARR: 22% (95% CI: 10-35), and p bismuth and tetracycline exposure had a lower proportion of eradication compared to patients without such an exposure (PP: 60% (6/10) versus 95% (94/99), ARR: 35% (95% CI: 11-64), and p bismuth quadruple regimen is superior to triple therapies and is effective for second through fifth line empirical treatment (≥85% PP, ≥70% ITT). Successful eradication is significantly lower with BQT if a similar bismuth based regimen was used in the past.

  9. Short-time effect of salvage harvesting on microbial soil properties in a Mediterranean area affected by a wildfire: preliminary results

    Science.gov (United States)

    Moltó, Jorge; Mataix-Solera, Jorge; Arcenegui, Victoria; Morugan, Alicia; Girona, Antonio; Garcia-orenes, Fuensanta

    2014-05-01

    In the Mediterranean region, wildfires are considered one of the main ecological factors, which, in addition to and in relation to changes in soil use, may cause soil loss and degradation, one of the most important environmental problems that humanity must face up to. As is well known, the soil-plant system is one of the key factors determining ecological recovery after the occurrence of a wildfire. Traditionally, a variety of forestry practices have been implemented on spanish sites after the incidence of a wildfire. Among them stands out the complete extraction of the burned wood, which consist in getting rid of the branches and other wooden debris using small controlled bonfires, splintering or mechanical extraction. This set of post-fire management practices is known as salvage logging or salvage harvesting. Despite the remarkable relevance and influence that this conjunction of techniques has on land management after a wildfire, very little experimental research focused on assessing the impact of salvage logging on the vegetal community has been done. Furthermore, even less research inquiring into the mode and grade of incidence that the salvage logging produces on soil properties has taken place. The aim of this research is to assess the effects that the salvage harvesting has on different soil microbial properties and other related properties. The study area is located in the Natural Park of the "Sierra de Mariola" in the province of Alicante, southeastern Spain. This location was affected by a wildfire whose extension reached more than 500 Ha in July 2012. Different post-fire treatments were proposed by the authorities, including salvage harvesting in some areas. Two different treatments were distinguished for the study, "control" (without any kind of burned wood removal) and "harvest" (where salvage logging was carried out), in each area three 4 m2 sampling plots were set up. These two treatments were established on the same slope with the same orography

  10. Interaction pathways between soft lipid nanodiscs and plasma membranes: A molecular modeling study.

    Science.gov (United States)

    Li, Shixin; Luo, Zhen; Xu, Yan; Ren, Hao; Deng, Li; Zhang, Xianren; Huang, Fang; Yue, Tongtao

    2017-10-01

    Lipid nanodisc, a model membrane platform originally synthesized for study of membrane proteins, has recently been used as the carrier to deliver amphiphilic drugs into target tumor cells. However, the central question of how cells interact with such emerging nanomaterials remains unclear and deserves our research for both improving the delivery efficiency and reducing the side effect. In this work, a binary lipid nanodisc is designed as the minimum model to investigate its interactions with plasma membranes by using the dissipative particle dynamics method. Three typical interaction pathways, including the membrane attachment with lipid domain exchange of nanodiscs, the partial membrane wrapping with nanodisc vesiculation, and the receptor-mediated endocytosis, are discovered. For the first pathway, the boundary normal lipids acting as ligands diffuse along the nanodisc rim to gather at the membrane interface, repelling the central bola lipids to reach a stable membrane attachment. If bola lipids are positioned at the periphery and act as ligands, they diffuse to form a large aggregate being wrapped by the membrane, leaving the normal lipids exposed on the membrane exterior by assembling into a vesicle. Finally, by setting both central normal lipids and boundary bola lipids as ligands, the receptor-mediated endocytosis occurs via both deformation and self-rotation of the nanodiscs. All above pathways for soft lipid nanodiscs are quite different from those for rigid nanoparticles, which may provide useful guidelines for design of soft lipid nanodiscs in widespread biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Mathematical and Statistical Techniques for Systems Medicine: The Wnt Signaling Pathway as a Case Study

    KAUST Repository

    MacLean, Adam L.

    2015-12-16

    The last decade has seen an explosion in models that describe phenomena in systems medicine. Such models are especially useful for studying signaling pathways, such as the Wnt pathway. In this chapter we use the Wnt pathway to showcase current mathematical and statistical techniques that enable modelers to gain insight into (models of) gene regulation and generate testable predictions. We introduce a range of modeling frameworks, but focus on ordinary differential equation (ODE) models since they remain the most widely used approach in systems biology and medicine and continue to offer great potential. We present methods for the analysis of a single model, comprising applications of standard dynamical systems approaches such as nondimensionalization, steady state, asymptotic and sensitivity analysis, and more recent statistical and algebraic approaches to compare models with data. We present parameter estimation and model comparison techniques, focusing on Bayesian analysis and coplanarity via algebraic geometry. Our intention is that this (non-exhaustive) review may serve as a useful starting point for the analysis of models in systems medicine.

  12. Metabolic pathway analysis and kinetic studies for production of nattokinase in Bacillus subtilis.

    Science.gov (United States)

    Unrean, Pornkamol; Nguyen, Nhung H A

    2013-01-01

    We have constructed a reaction network model of Bacillus subtilis. The model was analyzed using a pathway analysis tool called elementary mode analysis (EMA). The analysis tool was used to study the network capabilities and the possible effects of altered culturing conditions on the production of a fibrinolytic enzyme, nattokinase (NK) by B. subtilis. Based on all existing metabolic pathways, the maximum theoretical yield for NK synthesis in B. subtilis under different substrates and oxygen availability was predicted and the optimal culturing condition for NK production was identified. To confirm model predictions, experiments were conducted by testing these culture conditions for their influence on NK activity. The optimal culturing conditions were then applied to batch fermentation, resulting in high NK activity. The EMA approach was also applied for engineering B. subtilis metabolism towards the most efficient pathway for NK synthesis by identifying target genes for deletion and overexpression that enable the cell to produce NK at the maximum theoretical yield. The consistency between experiments and model predictions proves the feasibility of EMA being used to rationally design culture conditions and genetic manipulations for the efficient production of desired products.

  13. Total Femur Replacement After Tumor Resection: Limb Salvage Usually Achieved But Complications and Failures are Common.

    Science.gov (United States)

    Sevelda, Florian; Schuh, Reinhard; Hofstaetter, Jochen Gerhard; Schinhan, Martina; Windhager, Reinhard; Funovics, Philipp Theodor

    2015-06-01

    Primary bone or soft tissue tumors of the femur sometimes present with severe and extensive bone destruction, leaving few limb-salvage options other than total femur replacement. However, there are few data available regarding total femur replacement and, in particular, regarding implant failures. We asked: (1) What are the revision-free and overall implant survival rates of conventional total femur replacements in patients treated for sarcoma of the femur or soft tissues? (2) What are the revision-free and overall implant survival rates of expandable total femur replacements in skeletally immature patients? (3) Using the comprehensive International Society of Limb Salvage failure-mode classification, what types of complications occur with conventional and expandable total femur replacements? Our retrospective, single-center cohort study was based on data prospectively collected for 50 patients who received a total femur replacement after tumor resection for indications other than carcinoma or metastatic disease. Of the 50 patients, six (12%) were lost to followup before 6 months. Ten of the remaining 44 patients received expandable implants. The mean followup was 57 months (range, 1-280 months) and 172 months (range, 43-289 months) for patients who underwent conventional and expandable total femur replacements, respectively. For implant survival, competing risk analyses were used. At 5 years, revision-free implant survival of conventional total femur replacements was 48% (95% CI, 0.37-0.73), and overall implant survival was 97% (95% CI, 0.004-0.20). Five-year revision-free implant survival of expandable total femur replacements was 30% (95% CI, 0.47-1.00) and overall implant survival was 100%. With conventional total femur replacements soft tissue failures occurred in 13 of 34 patients, structural failures in three, infection in six, and local tumor progression in one. No patient had aseptic loosening with conventional total femur replacements, but hip

  14. Influence of Immediate and Delayed Lower-Limb Amputation Compared with Lower-Limb Salvage on Functional and Mental Health Outcomes Post-Rehabilitation in the U.K. Military.

    Science.gov (United States)

    Ladlow, Peter; Phillip, Rhodri; Coppack, Russell; Etherington, John; Bilzon, James; McGuigan, M Polly; Bennett, Alexander N

    2016-12-07

    Medical practitioners face difficult decisions over whether to amputate or to salvage a lower limb that has undergone trauma. To our knowledge, there has been little evidence reporting the impact of different surgical decisions on functional and mental health outcomes following intensive rehabilitation that might inform decision-making. This study is a retrospective, independent-group comparison of rehabilitation outcomes from a U.K. military complex trauma rehabilitation center. There were 100 procedures examined: 36 unilateral amputations (11 immediate-below-the-knee amputations, 15 delayed below-the-knee amputations, and 10 immediate above-the-knee amputations), 43 bilateral amputations, and 21 single-limb salvages (including 13 below-the-knee limb salvages); the patients had a mean age (and standard deviation) of 29 ± 6 years and a mean New Injury Severity Score of 34 ± 15 points. The outcome measures at completion of rehabilitation included a 6-minute walk test (6MWT), Defence Medical Rehabilitation Centre mobility and activities of daily living scores, screening for depression (Patient Health Questionnaire [PHQ-9]) and general anxiety disorder (General Anxiety Disorder 7-item scale [GAD-7]), mental health support, and pain scores. On completion of their rehabilitation, the unilateral amputation group walked significantly farther in 6 minutes (564 ± 92 m) than the limb-salvage group (483 ± 108 m; p 0.05). The limb-salvage group was less capable of running independently compared with all amputee groups. No significant differences (p > 0.05) were reported in mean mental health outcomes between the below-the-knee injury groups, and depression and anxiety scores were comparable with population norms. At discharge, 97% of all patients were able to control their pain. After completing a U.K. military interdisciplinary rehabilitation program, the unilateral amputation group demonstrated a significant functional advantage over the limb-salvage and bilateral

  15. PROGNOSTIC FACTORS OF BIOCHEMICAL RELAPSE FREE SURVIVAL FOLLOWING SALVAGE RADIOTHERAPY IN MEN WITH BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY

    Directory of Open Access Journals (Sweden)

    P. D. Demeshko

    2014-07-01

    Full Text Available Purpose. To evaluate influence of clinical, biochemical and histological factors to biochemical relapse free survival (BRFS following salvage radiotherapy (RT in men with biochemical recurrence after radical prostatectomy.Material and methods. 77 patients with newly diagnosed biochemical recurrence (BR after RPE were included into retrospective study. All of them underwent local salvage RT. Сlinical variables (age, serum prostate-specific antigen [PSA] level and PSA kinetics, time RPE-BR, Gleason grade, stage after RPE and clinical findings were evaluated using Cox proportional hazards regression analysis.Results. The median, 1- and 3-year BRFS were 19,9 months, 63,8 ± 6,5 % and 24,7 ± 8,5 % respectively. Significant variables in the multivariable model were age, PSA level before RT, prostatectomy T3b stage, PSA doubling time and positive digital rectal examination findings (p < 0,05. Several clinical parameters help predict the outcomes of men with PSA elevation after radical prostatectomy. These data may be useful in counseling men regarding the timing of administration of adjuvant therapies.

  16. Salvage treatment experience in advanced synovial sarcoma: a multicenter retrospective analysis of the Anatolian society of medical oncology.

    Science.gov (United States)

    Yetisyigit, Tarkan; Arpaci, Erkan; Seber, Erdogan Selcuk; Kucukoner, Mehmet; Kos, Fatma Tugba; Sonmez, Ozlem Uysal; Alici, Suleyman; Akman, Tulay; Aktas, Bilge; Yildiz, Ramazan; Gunaydin, Yusuf; Inanc, Mevlude; Demirci, Umut; Alkis, Necati; Gumus, Mahmut

    2013-01-01

    We aimed to evaluate prognostic factors and response rates to various treatment approaches to patients with synovial sarcoma in an advanced setting. We retrospectively reviewed the medical records of 55 patients (18 pts; 32.7% women) diagnosed with synovial sarcomas. Twenty had metastatic disease at the time of diagnosis while the remainder of the study group consisted of patients who developed metastatic or inoperable locally advanced disease during follow up. The median follow up time was 15 months (range: 1-53). Regarding outcomes for the 55 patients, 3 and 5 year overall survival rates were 26% and 14%, respectively. In univariate analyses among demographic factors female gender was associated with a better outcome (p=0.030). Patients with early progressing disease (difference did not reach statistical significance (p=0.056). According to multivariate Cox regression analysis patients who had undergone metastasectomy had a significant survival advantage (p=0.044). The overall response rate to different salvage chemotherapy regimens given as second line treatment was around 42.9-53.9% for all regimes. There were no statistically significant differences between chemotherapy regimens given in either second or third line settings in terms of overall survival. We observed no major differences in terms of response rate and survival between different salvage chemotherapy regimens. Although metastatic disease still carries a poor prognosis, metastasectomy was found to be associated with improved survival.

  17. CT-Guided 125I Seed Interstitial Brachytherapy as a Salvage Treatment for Recurrent Spinal Metastases after External Beam Radiotherapy

    Directory of Open Access Journals (Sweden)

    Lihong Yao

    2016-01-01

    Full Text Available The aim of this study is to evaluate the feasibility, safety, and clinical efficacy of CT-guided 125I seed interstitial brachytherapy in patients with recurrent spinal metastases after external beam radiotherapy (EBRT. Between August 2003 and September 2015, 26 spinal metastatic lesions (24 patients were reirradiated by this salvage therapy modality. Treatment for all patients was preplanned using a three-dimensional treatment planning system 3–5 days before 125I seed interstitial brachytherapy; dosimetry verification was performed immediately after seed implantation. Median actual D90 was 99 Gy (range, 90–176, and spinal cord median Dmax was 39 Gy (range, 6–110. Median local control (LC was 12 months (95% CI: 7.0–17.0. The 6- and 12-month LC rates were 52% and 40%, respectively. Median overall survival (OS was 11 months (95% CI: 7.7–14.3; 6-month and 1-, 2-, and 3-year OS rates were 65%, 37%, 14%, and 9%, respectively. Pain-free survival ranged from 2 to 42 months (median, 6; 95% CI: 4.6–7.4. Treatment was well-tolerated, with no radiation-induced vertebral compression fractures or myelopathy reported. Reirradiation with CT-guided 125I seed interstitial brachytherapy appears to be feasible, safe, and effective as pain relief or salvage treatment for patients with recurrent spinal metastases after EBRT.

  18. [Salvage radiotherapy for patients with PSA relapse after radical prostatectomy: comparisons among ASTRO and Phoenix biochemical failure definitions].

    Science.gov (United States)

    Quero, L; Mongiat-Artus, P; Ravery, V; Hennequin, V; Maylin, C; Desgrandchamps, F; Hennequin, C

    2009-07-01

    Study about the efficacy of salvage radiotherapy (RT), in terms of biochemical disease free survival (bDFS), according to ASTRO and Phoenix (nadir+2) definitions, for persistent or rising PSA after radical prostatectomy. Retrospective analysis of 59 patients who underwent RT between 1990 and 2003 for PSA recurrence after radical prostatectomy. Patients received a median of 66Gy to the prostate bed with 3D or 2D RT. The main end point was bDFS according to ASTRO and Phoenix (nadir+2) definitions. Different criterion sets were analysed to calculate bDFS and pretreatment factors that might predict biochemical relapse were sought for each. After a 38-month median follow-up, the 3-year bDFS rates were: 60 and 72% for ASTRO and Phoenix (nadir+2 ng/ml) definitions respectively. According to univariate analysis, pre-RT PSA> or =1 ng/ml and seminal vesicle involvement were associated with biochemical relapse. Multivariate analysis retained only pre-RT PSA> or =1 ng/ml as an independent predictor of biochemical relapse for the two definitions. Salvage RT is an effective treatment after radical prostatectomy according to ASTRO or Phoenix definitions. Only pre-RT PSA> or =1 ng/ml predicted relapse.

  19. Paclitaxel with Cisplatin as Salvage Treatment for Patients with Previously Treated Advanced Transitional Cell Carcinoma of the Urothelial Tract

    Directory of Open Access Journals (Sweden)

    Ji Eun Uhm

    2007-01-01

    Full Text Available BACKGROUND: This study was performed to evaluate the safety and efficacy of paclitaxel with cisplatin as salvage therapy in patients previously treated with gemcitabine and cisplatin (G/C for advanced transitional cell carcinoma (TCC of the urothelial tract. METHODS: Twenty-eight patients with metastatic or locally advanced TCC who had received prior G/C chemotherapy were enrolled. All patients received paclitaxel (175 mg/m2 and cisplatin (60 mg/m2 every 3 weeks for eight cycles or until disease progression. RESULTS: The median age was 61 years (range, 43–83 years, and the median Eastern Cooperative Oncology Group performance status was 1 (range, 0–2. The overall response rate was 36% [95% confidence interval (95% CI = 18–54], with three complete responses and seven partial responses. The median time to progression was 6.2 months (95% CI = 3.9–8.5, and the median overall survival was 10.3 months (95% CI = 6.1–14.1. The most common Grade 3/4 nonhematologic and hematologic toxicities were emesis (10 of 28 patients; 36% and neutropenia (5 of 110 cycles; 5%. CONCLUSIONS: Salvage chemotherapy with paclitaxel and cisplatin displayed promising results with tolerable toxicity profiles in patients with metastatic or locally advanced TCC who had been pretreated with G/C.

  20. High Dose Involved Field Radiation Therapy as Salvage for Loco-Regional Recurrence of Non-Small Cell Lung Cancer

    Science.gov (United States)

    Bae, Sun Hyun; Nam, Heerim; Park, Hee Chul; Pyo, Hong Ryull; Shim, Young Mog; Kim, Jhingook; Kim, Kwhanmien; Ahn, Jin Seok; Ahn, Myung-Ju; Park, Keunchil

    2012-01-01

    Purpose To determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals. Materials and Methods Between 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only. Results The median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS. Conclusion The current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery. PMID:23074111

  1. Salvage brachytherapy in prostate local recurrence after radiation therapy: predicting factors for control and toxicity

    Science.gov (United States)

    2014-01-01

    Purpose To evaluate efficacy and toxicity after salvage brachytherapy (BT) in prostate local recurrence after radiation therapy. Methods and materials Between 1993 and 2007, we retrospectively analyzed 56 consecutively patients (pts) undergoing salvage brachytherapy. After local biopsy-proven recurrence, pts received 145 Gy LDR-BT (37 pts, 66%) or HDR-BT (19 pts, 34%) in different dose levels according to biological equivalent doses (BED2 Gy). By the time of salvage BT, only 15 pts (27%) received ADT. Univariate and multivariate analyses were performed to identify predictors of biochemical control and toxicities. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded using Common Terminology Criteria for Adverse Events (CTCv3.0). Results Median follow-up after salvage BT was 48 months. The 5-year FFbF was 77%. HDR and LDR late grade 3 GU toxicities were observed in 21% and 24%. Late grade 3 GI toxicities were observed in 2% (HDR) and 2.7% (LDR). On univariate analysis, pre-salvage prostate-specific antigen (PSA) > 10 ng/ml (p = 0.004), interval to relapse after initial treatment < 24 months (p = 0.004) and salvage HDR-BT doses BED2 Gy level < 227 Gy (p = 0.012) were significant in predicting biochemical failure. On Cox multivariate analysis, pre-salvage PSA, and time to relapse were significant in predicting biochemical failure. HDR-BT BED2 Gy (α/β 1.5 Gy) levels ≥ 227 (p = 0.013), and ADT (p = 0.049) were significant in predicting grade ≥ 2 urinary toxicity. Conclusions Prostate BT is an effective salvage modality in some selected prostate local recurrence patients after radiation therapy. Even, we provide some potential predictors of biochemical control and toxicity for prostate salvage BT, further investigation is recommended. PMID:24885287

  2. Adjuvant and salvage radiotherapy after prostatectomy: a systematic review and meta-analysis.

    Science.gov (United States)

    Chen, Changhao; Lin, Tianxin; Zhou, Yu; Li, Doudou; Xu, Kewei; Li, Zhihua; Fan, Xinxiang; Zhong, Guangzheng; He, Wang; Chen, Xu; He, Xianyin; Huang, Jian

    2014-01-01

    In men with adverse prognostic factors (APFs) after radical prostatectomy (RP), the most appropriate timing to administer radiotherapy remains a subject for debate. We conducted a systemic review and meta-analysis to evaluate the therapeutic strategies: adjuvant radiotherapy (ART) and salvage radiotherapy (SRT). We comprehensively searched PubMed, EMBASE, Web of Science and the Cochrane Library and performed the meta-analysis of all randomized controlled trials (RCTs) and retrospective comparative studies assessing the prognostic factors of ART and SRT. Between May 1998 and July 2012, 2 matched control studies and 16 retrospective studies including a total of 2629 cases were identified (1404 cases for ART and 1185 cases for SRT). 5-year biochemical failure free survival (BFFS) for ART was longer than that for SRT (Hazard Ratio [HR]: 0.37; 95% CI, 0.30-0.46; pAPFs and may reduce the need for SRT. Given the inherent limitations of the included studies, future well-designed RCTs are awaited to confirm and update this analysis.

  3. Imaging of limb salvage surgery and pelvic reconstruction following resection of malignant bone tumours

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Tien Jin, E-mail: tien_jin_tan@cgh.com.sg [Department of Radiology, Vancouver General Hospital, Vancouver, BC (Canada); Aljefri, Ahmad M. [Department of Radiology, Vancouver General Hospital, Vancouver, BC (Canada); Clarkson, Paul W.; Masri, Bassam A. [Department of Orthopaedics, University of British Columbia, Vancouver, BC (Canada); Ouellette, Hugue A.; Munk, Peter L.; Mallinson, Paul I. [Department of Radiology, Vancouver General Hospital, Vancouver, BC (Canada)

    2015-09-15

    Highlights: • Advances in reconstructive orthopaedic techniques now allow for limb salvage and prosthetic reconstruction procedures to be performed on patients who would otherwise be required to undergo debilitating limb amputations for malignant bone tumours. • The resulting post-operative imaging of such cases can be daunting for the radiologist to interpret, particularly in the presence of distorted anatomy and unfamiliar hardware. • This article reviews the indications for limb salvage surgery, prosthetic reconstruction devices involved, expected post-operative imaging findings, as well as the potential hardware related complications that may be encountered in the management of such cases. • By being aware of the various types of reconstructive techniques used in limb salvage surgery as well as the potential complications, the reporting radiologist should possess greater confidence in making an accurate assessment of the expected post-operative imaging findings in the management of such cases. - Abstract: Advances in reconstructive orthopaedic techniques now allow for limb salvage and prosthetic reconstruction procedures to be performed on patients who would otherwise be required to undergo debilitating limb amputations for malignant bone tumours. The resulting post-operative imaging of such cases can be daunting for the radiologist to interpret, particularly in the presence of distorted anatomy and unfamiliar hardware. This article reviews the indications for limb salvage surgery, prosthetic reconstruction devices involved, expected post-operative imaging findings, as well as the potential hardware related complications that may be encountered in the management of such cases.

  4. [Perioperative management and prevention of complication for salvage esophagectomy after definitive chemoradiotherapy].

    Science.gov (United States)

    Kamei, Takashi; Miyazaki, S

    2008-07-01

    Salvage esophagectomy has been increasing as a second-line treatment after failure of definitive chemoradiotherapy (CRT) for esophageal cancer. A number of patients who have received CRT, especially those who have residual tumors and shorter waiting times until operation, have developed malnutrition and problems in their immunologic condition because of decreasing oral intake and bone marrow suppression. Because high-dose radiation causes inflammation, fibrosis and peripheral circulatory disturbance of various tissues in the treatment fields, salvage surgery can be a technically difficult operation. In our previous experience, postoperative complications of salvage esophagectomy are more frequent and more serious than that of planned esophagectomy. For example, we have experienced necrosis of the reconstructed gastric tube, esophago-tracheal fistula, mediastinal abscess, hard-to-treat acute respiratory distress syndrome (ARDS) and so on. In particular, respiratory tract necrosis or perforation is the most critical complication and frequently becomes lethal. Patients who undergo a salvage esophagectomy have a significantly higher risk of pulmonary and cardiac complication, and have high rates of repeated surgery. Rapid diagnosis and appropriate treatment of complications are necessary to reduce postoperative mortality. To improve the overall outcome, it is very important to better understand the condition of patients after CRT, so appropriate surgery can be carefully planned. Furthermore, it is absolutely essential to perform the operation with great care and to meticulously manage the perioperative care for salvage esophagectomy.

  5. Success Stories of Undergraduate Retention: A Pathways Study of Graduate Students in Solar and Space Physics

    Science.gov (United States)

    Morrow, C. A.; Stoll, W.; Moldwin, M.; Gross, N. A.

    2012-12-01

    This presentation describes results from an NSF-funded study of the pathways students in solar and space physics have taken to arrive in graduate school. Our Pathways study has documented results from structured interviews conducted with graduate students attending two, week-long, NSF-sponsored scientific workshops during the summer of 2011. Our research team interviewed 48 solar and space physics students (29 males and 19 females currently in graduate programs at US institutions,) in small group settings regarding what attracted and retained them along their pathways leading to grad school. This presentation addresses what these students revealed about the attributes and influences that supported completion of their undergraduate experience and focused their aspirations toward graduate school. In advance of the interview process, we collected 125 on-line survey responses from students at the two workshops. This 20-item survey included questions about high school and undergraduate education, as well as about research and graduate experience. A subset of the 125 students who completed this on-line survey volunteered to be interviewed. Two types of interview data were collected from the 48 interviewees: 1) written answers to a pre-interview questionnaire; and 2) detailed notes taken by researchers during group interviews. On the pre-interview questionnaire, we posed the question: "How did you come to be a graduate student in your field?" Our findings to date are based on an analysis of responses to this question, cross correlated with the corresponding on-line survey data. Our analysis reveals the importance of early research experiences. About 80% of the students participating in the Pathways study cited formative undergraduate research experiences. Moreover, about 50% of participants reported undergraduate research experiences that were in the field of their current graduate studies. Graduate students interviewed frequently cited a childhood interest in science

  6. Exploring the Causal Pathway From Telomere Length to Coronary Heart Disease: A Network Mendelian Randomization Study.

    Science.gov (United States)

    Zhan, Yiqiang; Karlsson, Ida K; Karlsson, Robert; Tillander, Annika; Reynolds, Chandra A; Pedersen, Nancy L; Hägg, Sara

    2017-07-21

    Observational studies have found shorter leukocyte telomere length (TL) to be a risk factor for coronary heart disease (CHD), and recently the association was suggested to be causal. However, the relationship between TL and common metabolic risk factors for CHD is not well understood. Whether these risk factors could explain pathways from TL to CHD warrants further attention. To examine whether metabolic risk factors for CHD mediate the causal pathway from short TL to increased risk of CHD using a network Mendelian randomization design. Summary statistics from several genome-wide association studies were used in a 2-sample Mendelian randomization study design. Network Mendelian randomization analysis-an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality-was performed to examine the causal association between telomeres and CHD and metabolic risk factors. Summary statistics from the ENGAGE Telomere Consortium were used (n=37 684) as a TL genetic instrument, CARDIoGRAMplusC4D Consortium data were used (case=22 233 and control=64 762) for CHD, and other consortia data were used for metabolic traits (fasting insulin, triglyceride, total cholesterol, low-density lipoprotein cholesterol, fasting glucose, diabetes mellitus, glycohemoglobin, body mass index, waist circumference, and waist:hip ratio). One-unit increase of genetically determined TL was associated with -0.07 (95% confidence interval, -0.01 to -0.12; P=0.01) lower log-transformed fasting insulin (pmol/L) and 21% lower odds (95% confidence interval, 3-35; P=0.02) of CHD. Higher genetically determined log-transformed fasting insulin level was associated with higher CHD risk (odds ratio, 1.86; 95% confidence interval, 1.01-3.41; P=0.04). Overall, our findings support a role of insulin as a mediator on the causal pathway from shorter telomeres to CHD pathogenesis. © 2017 American Heart Association, Inc.

  7. High-dose-rate brachytherapy with or without intensity modulated radiation therapy as salvage treatment for an isolated, gross local recurrence of prostate cancer post-prostatectomy.

    Science.gov (United States)

    Strom, Tobin J; Wilder, Richard B; Fernandez, Daniel C; Mellon, Eric A; Saini, Amarjit S; Hunt, Dylan C; Biagioli, Matthew C

    2014-01-01

    To evaluate the use of high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) as salvage therapy for patients with an isolated, gross local recurrence of prostate cancer after radical prostatectomy. Between October 2009 and May 2013, the authors treated six patients with salvage iridium-192 HDR brachytherapy ± IMRT for biopsy-proven, recurrent prostate cancer post-prostatectomy. In each patient, a pelvic MRI scan or CT scan demonstrated a nodule (range 1.6, 4.7 cm) in the prostate bed. Although prostate-specific antigen values were 0.2-9.5 ng/mL at the time of salvage brachytherapy, there was no pelvic adenopathy on CT or MRI scan, and a bone scan was negative in all cases. Five patients were treated with IMRT to 4500-5040 cGy in 25-28 fractions to the prostate bed followed by two 950 cGy HDR brachytherapy fractions separated by 1-2 weeks. A sixth patient underwent HDR brachytherapy monotherapy consisting of 3800 cGy in four fractions over 3 days. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median followup was 9 months (range 3, 40 months). All six patients have been free of androgen deprivation therapy and have an undetectable prostate-specific antigen. One patient developed late Grade 2 urinary incontinence. There was no late grade ≥2 gastrointestinal toxicity. HDR brachytherapy ± IMRT is a safe and effective salvage therapy option for an isolated, gross local recurrence of prostate cancer after radical prostatectomy and merits further study. Copyright © 2014. Published by Elsevier Inc.

  8. Tissue-Selective Salvage of the White Matter by Successful Endovascular Stroke Therapy.

    Science.gov (United States)

    Kleine, Justus F; Kaesmacher, Mirjam; Wiestler, Benedikt; Kaesmacher, Johannes

    2017-10-01

    White matter (WM) is less vulnerable to ischemia than gray matter. In ischemic stroke caused by acute large-vessel occlusion, successful recanalization might therefore sometimes selectively salvage the WM, leading to infarct patterns confined to gray matter. This study examines occurrence, determinants, and clinical significance of such effects. Three hundred twenty-two patients with acute middle cerebral artery occlusion subjected to mechanical thrombectomy were included. Infarct patterns were categorized into WM - (sparing the WM) and WM + (involving WM). National Institutes of Health Stroke Scale-based measures of neurological outcome, including National Institutes of Health Stroke Scale improvement or National Institutes of Health Stroke Scale worsening, good functional midterm outcome (day 90-modified Rankin Scale score of ≤2), the occurrence of malignant swelling, and in-hospital mortality were predefined outcome measures. WM - infarcts occurred in 118 of 322 patients and were associated with successful recanalization and better collateral grades ( P <0.05). Shorter symptom-onset to recanalization times were also associated with WM - infarcts in univariate analysis, but not when adjusted for collateral grades. WM - infarcts were independently associated with good neurological outcome (adjusted odds ratio, 3.003; 95% confidence interval, 1.186-7.607; P =0.020) and good functional midterm outcome (adjusted odds ratio, 8.618; 95% confidence interval, 2.409-30.828; P =0.001) after correcting for potential confounders, including final infarct volume. Only 2.6% of WM - patients, but 20.5% of WM + patients exhibited neurological worsening, and none versus 12.8% developed malignant swelling ( P <0.001), contributing to lower mortality in this group (2.5% versus 10.3%; P =0.014). WM infarction commonly commences later than gray matter infarction after acute middle cerebral artery occlusion. Successful recanalization can therefore salvage completely the WM at risk in

  9. Preoperative Counseling in Salvage Total Laryngectomy: Content Analysis of Electronic Medical Records.

    Science.gov (United States)

    Raol, Nikhila; Lilley, Elizabeth; Cooper, Zara; Dowdall, Jayme; Morris, Megan A

    2017-10-01

    Objective To study preoperative counseling in patients undergoing salvage total laryngectomy (STL). Study Design Case series with chart review. Setting Tertiary care academic hospital. Subjects and Methods We reviewed charts of patients ≥18 years undergoing STL between 2005 and 2015. Fifty-eight patients were identified. Notes written within 2 months prior to surgery by head and neck surgical oncologists, radiation oncologists, medical oncologists, speech-language pathologists, social workers, and nurse practitioners were extracted and coded into 4 categories. Coded content was then analyzed using a simple tally within content areas. Results Nonphysicians documented patient values and priorities, exclusive of treatment desires, more frequently. These topics included apprehension about family obligations, fear about communication, questions regarding quality of life, and anxiety regarding job continuation. Physician notes documented priorities regarding preferences for surgical treatment. No patients were seen by palliative care preoperatively, and only 14% (n = 8) patients had documentation of an end-of-life discussion. Conclusions Preoperative counseling for STL patients that included nonphysicians had a higher frequency of discussion of patients' priorities. This suggests including these types of providers may lead to more patient-centered care. A prospective study evaluating patient and physician perceptions of preoperative counseling can better identify where discrepancies exists and help conceptualize a framework for preoperative counseling in STL patients and other patients undergoing high-risk surgery.

  10. Sustainable production of afforestation and reforestation to salvage land degradation in Asunafo District, Ghana

    Directory of Open Access Journals (Sweden)

    Kenneth Peprah

    2017-10-01

    Full Text Available Savannazation and marshy areas are common features of once evergreen and deciduous forest of Ghana. Attempts to salvage such degraded lands have considered replacement with closed tree canopy. This study aims at examining efforts at Asunafo forest area to use tree planting of different species to remedy land degradation in a swamp area colonized by shrubs and grasses. Study methods include the use of field visits and transect walk, photography, archival data, key informant interview, community meeting and socio-economic survey for sourcing primary data for analysis. The results indicate that where the swamp is vegetated by shrubs of different kinds, afforestation shows rapid success. And, where the swamp is dominated by grass species, afforestation success is slow. Terminalia ivorensis, Triplochiton scleroxylon and Ceiba pentandra registered quick impacts in height growth, stem development, canopy formation where the degraded land was originally covered with shrubs. Trees grow well when weed competition for essential resources is reduced through weed control. The study concludes that tree planting in swamp area is sustainable land management practice to redeem land degradation. Also, environmental benefits are imperatives but host communities derived near to zero social and economic benefits because such projects happen outside clean development mechanisms’ arrangement.

  11. Outcomes of primary refractory diffuse large B-cell lymphoma (DLBCL) treated with salvage chemotherapy and intention to transplant in the rituximab era.

    Science.gov (United States)

    Vardhana, Santosha A; Sauter, Craig S; Matasar, Matthew J; Zelenetz, Andrew D; Galasso, Natasha; Woo, Kaitlin M; Zhang, Zhigang; Moskowitz, Craig H

    2017-02-01

    Rituximab-containing salvage chemotherapy followed by high-dose therapy and autologous stem cell transplant (ASCT) in chemosensitive patients remains the standard of care for patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, its role in those patients achieving less than a complete response to first-line therapy (primary refractory disease) in the rituximab era is not well defined. We reviewed the outcomes of 82 transplant-eligible patients with primary refractory DLBCL who underwent salvage therapy with the intent of administering high-dose therapy and ASCT to patients achieving chemosensitive remission. The estimated 3-year overall and progression-free survival for all patients was 38% and 29%, respectively, and 65% and 60% respectively for patients proceeding to stem cell transplant. Long-term remission was achieved in 45% of patients achieving a partial response (PR) to initial induction therapy and DLBCL, particularly for those achieving a PR to frontline therapy. The primary barrier to curative therapy in patients with primary refractory disease is resistance to salvage therapy, and future studies should be aimed towards increasing the response rate in this population. © 2016 John Wiley & Sons Ltd.

  12. Diabetes effect on Quality of Life in the long-term after Limb salvage with Infrageniculate Bypasses accompanied with minor amputations.

    Science.gov (United States)

    Peker, Kivanc Derya; Aksoy, Murat

    2014-09-01

    Objective : To evaluate the quality of life in patients, who had their limbs salvaged with an infrageniculate bypass and minor amputation in the long term and to see if diabetics are prone to worse results. The patients with limb salvage following an infrageniculate bypass and minor amputation were asked to complete Short Form 36 at the last follow-up visit. The mean scores in diabetic and non-diabetic population were compared to each other .The mean follow-up period was 58±8 months. Results : Of 142 patients, 40 patients were eligible to be included in the study. 33 (82.5%) patients were male and 7 (17.5%) patients were female. The mean age at the time of intervention was 57±14 (33-83) years. The mean scores for eight domains of SF-36 evaluation ranged from 44 to 67 out of 100. There were no significant differences concerning the mean scores of any dimension between the diabetic and non-diabetic group. Conclusion : Despite a minor amputation, the functional outcome of limb salvage with an infrageniculate bypass is favorable and diabetes does not seem to have negative effect on the functional outcome and Quality of Life.

  13. Salvage radiotherapy for biochemical relapse after complete PSA response following radical prostatectomy: outcome and prognostic factors for patients who have never received hormonal therapy

    Directory of Open Access Journals (Sweden)

    Novaes Paulo ERS

    2007-02-01

    Full Text Available Abstract Objectives To evaluate the results of salvage conformal radiation therapy (3DC-EBRT for patients submitted to radical prostatectomy (RP who have achieved complete PSA response and who have never been treated with hormonal therapy (HT. To present the results of biochemical control, a period free from hormonal therapy and factors related to its prognosis. Materials and methods from August 2002 to December 2004, 43 prostate cancer patients submitted to RP presented biochemical failure after achieving a PSA Results 3-year biochemical non-evidence of disease (BNED was 71%. PSA doubling time lower than 4 months (p = 0.01 and time from recurrence to salvage EBRT (p = 0.04 were associated with worse chance of biochemical control. Biochemical control of 76% was achieved when RT had been introduced with a PSA lower than 1 ng/ml vs. 48% with a PSA higher than 1 (p = 0.19. Late toxicity was acceptable. Conclusion 70% of biochemical control in 3 years can be achieved with salvage radiotherapy in selected patients. The importance of PSADT was confirmed in this study and radiotherapy should be started as early as possible. Longer follow up is necessary, but it is possible to conclude that a long interval free from hormonal therapy was achieved with low rate of toxicity avoiding or at least delaying several important adverse effects related to hormonal treatment.

  14. Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium.

    Science.gov (United States)

    Bennis, Anna; Ten Brink, Jacoline B; Moerland, Perry D; Heine, Vivi M; Bergen, Arthur A

    2017-01-01

    The retinal pigment epithelium (RPE) is a neural monolayer lining the back of the eye. Degeneration of the RPE leads to severe vision loss in, so far incurable, diseases such as age-related macular degeneration and some forms of retinitis pigmentosa. A promising future replacement therapy may be autologous iris epithelial cell transdifferentiation into RPE in vitro and, subsequently, transplantation. In this study we compared the gene expression profiles of the iris epithelium (IE) and the RPE. We collected both primary RPE- and IE cells from 5 freshly frozen human donor eyes, using respectively laser dissection microscopy and excision. We performed whole-genome expression profiling using 44k Agilent human microarrays. We investigated the gene expression profiles on both gene and functional network level, using R and the knowledge database Ingenuity. The major molecular pathways related to the RPE and IE were quite similar and yielded basic neuro-epithelial cell functions. Nonetheless, we also found major specific differences: For example, genes and molecular pathways, related to the visual cycle and retinol biosynthesis are significantly higher expressed in the RPE than in the IE. Interestingly, Wnt and aryl hydrocarbon receptor (AhR-) signaling pathways are much higher expressed in the IE than in the RPE, suggesting, respectively, a possible pluripotent and high detoxification state of the IE. This study provides a valuation of the similarities and differences between the expression profiles of the RPE and IE. Our data combined with that of the literature, represent a most comprehensive perspective on transcriptional variation, which may support future research in the development of therapeutic transplantation of IE.

  15. Comparative gene expression study and pathway analysis of the human iris- and the retinal pigment epithelium.

    Directory of Open Access Journals (Sweden)

    Anna Bennis

    Full Text Available The retinal pigment epithelium (RPE is a neural monolayer lining the back of the eye. Degeneration of the RPE leads to severe vision loss in, so far incurable, diseases such as age-related macular degeneration and some forms of retinitis pigmentosa. A promising future replacement therapy may be autologous iris epithelial cell transdifferentiation into RPE in vitro and, subsequently, transplantation. In this study we compared the gene expression profiles of the iris epithelium (IE and the RPE.We collected both primary RPE- and IE cells from 5 freshly frozen human donor eyes, using respectively laser dissection microscopy and excision. We performed whole-genome expression profiling using 44k Agilent human microarrays. We investigated the gene expression profiles on both gene and functional network level, using R and the knowledge database Ingenuity.The major molecular pathways related to the RPE and IE were quite similar and yielded basic neuro-epithelial cell functions. Nonetheless, we also found major specific differences: For example, genes and molecular pathways, related to the visual cycle and retinol biosynthesis are significantly higher expressed in the RPE than in the IE. Interestingly, Wnt and aryl hydrocarbon receptor (AhR- signaling pathways are much higher expressed in the IE than in the RPE, suggesting, respectively, a possible pluripotent and high detoxification state of the IE.This study provides a valuation of the similarities and differences between the expression profiles of the RPE and IE. Our data combined with that of the literature, represent a most comprehensive perspective on transcriptional variation, which may support future research in the development of therapeutic transplantation of IE.

  16. Clinical study of central taste disorders and discussion of the central gustatory pathway.

    Science.gov (United States)

    Onoda, Keiko; Ikeda, Minoru; Sekine, Hiroki; Ogawa, Hisashi

    2012-02-01

    The aim of this work is to examine the clinical findings of patients with taste disorders due to central lesions and also to study the central gustatory pathway in humans. We conducted a retrospective review of 13 patients with central taste disorders that visited Nihon University Itabashi Hospital. An additional 25 cases with central taste disorders previously reported in the literature were assessed in the study. We examined 38 patients with taste disorders due to central lesions. The sites of the central lesions and their frequencies, the laterality of taste disorders relative to the central lesions, and prognosis of taste disorders were studied. We identified the following taste-related regions in the central nervous system: the medulla, pons, midbrain, thalamus, internal capsule, putamen, corona radiata, and cerebral cortex. As for the laterality of the taste disorders, we observed more ipsilateral cases for lesions located from the medulla to the pons. We observed ipsilateral, contralateral, and bilateral cases for lesions located above the midbrain, but bilateral cases were more frequently detected. Taste disorders of 80% of the patients improved by 24 weeks. The prognoses of central taste disorders appeared to be good. We identified eight central regions supposed to be relate to taste disorders. From the laterality of the taste disorders relative to the central lesions, it was suggested that the central gustatory pathway ascends ipsilaterally from the medulla to the pons, branches at the upper pons, and then ascends bilaterally from the midbrain to the cerebral cortex.

  17. A second pathway to degrade pyrimidine nucleic acid precursors in eukaryotes

    DEFF Research Database (Denmark)

    Andersen, Gorm; Bjornberg, Olof; Polakova, Silvia

    2008-01-01

    Pyrimidine bases are the central precursors for RNA and DNA, and their intracellular pools are determined by de novo, salvage and catabolic pathways. In eukaryotes, degradation of uracil has been believed to proceed only via the reduction to dihydrouracil. Using a yeast model, Saccharomyces kluyv...... of the eukaryotic or prokaryotic genes involved in pyrimidine degradation described to date....

  18. Vascularized tissue to reduce fistula following salvage total laryngectomy: a systematic review.

    Science.gov (United States)

    Paleri, Vinidh; Drinnan, Mike; van den Brekel, Michiel W M; Hinni, Michael L; Bradley, Patrick J; Wolf, Gregory T; de Bree, Remco; Fagan, Johannes J; Hamoir, Marc; Strojan, Primož; Rodrigo, Juan P; Olsen, Kerry D; Pellitteri, Phillip K; Shaha, Ashok R; Genden, Eric M; Silver, Carl E; Suárez, Carlos; Takes, Robert P; Rinaldo, Alessandra; Ferlito, Alfio

    2014-08-01

    Pharyngocutaneous fistulae (PCF) are known to occur in nearly one-third of patients after salvage total laryngectomy (STL). PCF has severe impact on duration of admission and costs and quality of life and can even cause severe complications such as bleeding, infection and death. Many patients need further surgical procedures. The implications for functional outcome and survival are less clear. Several studies have shown that using vascularized tissue from outside the radiation field reduces the risk of PCFs following STL. This review and meta-analysis aims to identify the evidence base to support this hypothesis. English language literature from 2004 to 2013 REVIEW METHODS: We searched the English language literature for articles published on the subject from 2004 to 2013. Adequate data was available to identify pooled incidence rates from seven articles. The pooled relative risk derived from 591 patients was 0.63 (95% CI: 0.47 to 0.85), indicating that patients who have flap reconstruction/reinforcement reduced their risk of PCF by one-third. This pooled analysis suggests that there is a clear advantage in using vascularized tissue from outside the radiation field in the laryngectomy defect. While some studies show a clear reduction in PCF rates, others suggest that the fistulae that occur are smaller and rarely need repair. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  19. A biosynthetic pathway for anandamide.

    Science.gov (United States)

    Liu, Jie; Wang, Lei; Harvey-White, Judith; Osei-Hyiaman, Douglas; Razdan, Raj; Gong, Qian; Chan, Andrew C; Zhou, Zhifeng; Huang, Bill X; Kim, Hee-Yong; Kunos, George

    2006-09-05

    The endocannabinoid arachidonoyl ethanolamine (anandamide) is a lipid transmitter synthesized and released "on demand" by neurons in the brain. Anandamide is also generated by macrophages where its endotoxin (LPS)-induced synthesis has been implicated in the hypotension of septic shock and advanced liver cirrhosis. Anandamide can be generated from its membrane precursor, N-arachidonoyl phosphatidylethanolamine (NAPE) through cleavage by a phospholipase D (NAPE-PLD). Here we document a biosynthetic pathway for anandamide in mouse brain and RAW264.7 macrophages that involves the phospholipase C (PLC)-catalyzed cleavage of NAPE to generate a lipid, phosphoanandamide, which is subsequently dephosphorylated by phosphatases, including PTPN22, previously described as a protein tyrosine phosphatase. Bacterial endotoxin (LPS)-induced synthesis of anandamide in macrophages is mediated exclusively by the PLC/phosphatase pathway, which is up-regulated by LPS, whereas NAPE-PLD is down-regulated by LPS and functions as a salvage pathway of anandamide synthesis when the PLC/phosphatase pathway is compromised. Both PTPN22 and endocannabinoids have been implicated in autoimmune diseases, suggesting that the PLC/phosphatase pathway of anandamide synthesis may be a pharmacotherapeutic target.

  20. Middle longitudinal fasciculus delineation within language pathways: A diffusion tensor imaging study in human

    Energy Technology Data Exchange (ETDEWEB)

    Menjot de Champfleur, Nicolas, E-mail: nicolasdechampfleur@orange.fr [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Team “Plasticity of Central Nervous System, Stem Cells and Glial Tumors,” Institut National de la Santé et de la Recherche Médicale Unité 1051, Institut of Neurosciences of Montpellier, Saint Eloi Hospital, Montpellier (France); Lima Maldonado, Igor [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Team “Plasticity of Central Nervous System, Stem Cells and Glial Tumors,” Institut National de la Santé et de la Recherche Médicale Unité 1051, Institut of Neurosciences of Montpellier, Saint Eloi Hospital, Montpellier (France); Divisão de Neurologia e Epidemiologia (CPPHO), Complexo Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador-Bahia (Brazil); Moritz-Gasser, Sylvie [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Department of Neurology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Machi, Paolo [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); and others

    2013-01-15

    Introduction: The existence in the human brain of the middle longitudinal fasciculus (MdLF), initially described in the macaque monkey, is supported by diffusion tensor imaging studies. In the present work, we aim (1) to confirm that this fascicle is found constantly in control subjects with the use of DTI techniques and (2) to delineate the MdLF from the other fiber bundles that constitute the language pathways. Materials and methods: Tractography was realized in four right-handed healthy volunteers for the arcuate fascicle, uncinate fascicle, inferior fronto-occipital fascicle, inferior longitudinal fascicle and the middle longitudinal fascicle. The fiber tracts were characterized for their size, mean fractional anisotropy (FA), for their length, number of streamlines, and lateralization indices were calculated. Results: The MdLF is found constantly and it is clearly delineated from the other fascicles that constitute the language pathways, especially the ventral pathway. It runs within the superior temporal gyrus white matter from the temporal pole, then it extends caudally in the upper part of the sagittal stratum and the posterior part of the corona radiata, to reach the inferior parietal lobule (angular gyrus). We found a leftward asymmetry for all fiber tracts when considering the mean FA. Discussion: Using DTI methods, we confirm that the MdLF connects the angular gyrus and the superior temporal gyrus. On the basis of these findings, the role of the MdLF is discussed. Conclusion: The middle longitudinal fasciculus, connects the angular gyrus and the superior temporal gyrus and its course can be systematically differenciated from those of other fascicles composing both ventral and dorsal routes (IFOF, IFL, AF and UF)

  1. The anatomy of extended limbic pathways in Asperger syndrome: a preliminary diffusion tensor imaging tractography study.

    Science.gov (United States)

    Pugliese, Luca; Catani, Marco; Ameis, Stephanie; Dell'Acqua, Flavio; Thiebaut de Schotten, Michel; Murphy, Clodagh; Robertson, Dene; Deeley, Quinton; Daly, Eileen; Murphy, Declan G M

    2009-08-15

    It has been suggested that people with autistic spectrum disorder (ASD) have altered development (and connectivity) of limbic circuits. However, direct evidence of anatomical differences specific to white matter pathways underlying social behaviour and emotions in ASD is lacking. We used Diffusion Tensor Imaging Tractography to compare, in vivo, the microstructural integrity and age-related differences in the extended limbic pathways between subjects with Asperger syndrome and healthy controls. Twenty-four males with Asperger syndrome (mean age 23+/-12 years, age range: 9-54 years) and 42 age-matched male controls (mean age 25+/-10 years, age range: 9-54 years) were studied. We quantified tract-specific diffusivity measurements as indirect indexes of microstructural integrity (e.g. fractional anisotropy, FA; mean diffusivity, MD) and tract volume (e.g. number of streamlines) of the main limbic tracts. The dissected limbic pathways included the inferior longitudinal fasciculus, inferior frontal occipital fasciculus, uncinate, cingulum and fornix. There were no significant between-group differences in FA and MD. However, compared to healthy controls, individuals with Asperger syndrome had a significantly higher number of streamlines in the right (p=.003) and left (p=.03) cingulum, and in the right (p=.03) and left (p=.04) inferior longitudinal fasciculus. In contrast, people with Asperger syndrome had a significantly lower number of streamlines in the right uncinate (p=.02). Within each group there were significant age-related differences in MD and number of streamlines, but not FA. However, the only significant age-related between-group difference was in mean diffusivity of the left uncinate fasciculus (Z(obs)=2.05) (p=.02). Our preliminary findings suggest that people with Asperger syndrome have significant differences in the anatomy, and maturation, of some (but not all) limbic tracts.

  2. Norovirus contamination and the glycosphingolipid biosynthesis pathway in Pacific oyster: A transcriptomics study.

    Science.gov (United States)

    Ma, Liping; Su, Laijin; Liu, Hui; Zhao, Feng; Zhou, Deqing; Duan, Delin

    2017-07-01

    Noroviruses are the primary pathogens associated with shellfish-borne gastroenteritis outbreaks. These viruses remain stable in oysters, suggesting an active mechanism for virus concentration. In this study, a deep RNA sequencing technique was used to analyze the transcriptome profiles of Pacific oysters at different time points after inoculation with norovirus (GII.4). We obtained a maximum of 65, 294, 698 clean sample reads. When aligned to the reference genome, the average mapping ratio of clean data was approximately 65%. In the samples harvested at 12, 24, and 48 h after contamination, 2,223, 2,990, and 2020 genes, respectively, were differentially expressed in contaminated and non-contaminated oyster digestive tissues, including 500, 1748, and 1039 up-regulated and 1723, 1242, and 981 down-regulated genes, respectively. In particular, FUT2 and B3GNT4, genes encoding the signaling components of glycosphingolipid biosynthesis, were significantly up-regulated in contaminated samples. In addition, we found up-regulation of some immune- and disease-related genes in the MHC I pathway (PA28, HSP 70, HSP90, CANX, BRp57, and CALR) and MHC II pathway (GILT, CTSBLS, RFX, and NFY), although NoVs did not cause diseases in the oysters. We detected two types of HBGA-like molecules with positive-to-negative ratios similar to type A and H1 HBGA-like molecules in digestive tissues that were significantly higher in norovirus-contaminated than in non-contaminated oysters. Thus, our transcriptome data analysis indicated that a human pathogen (GII.4 Norovirus) was likely concentrated in the digestive tissues of oysters via HBGA-like molecules that were synthesized by the glycosphingolipid biosynthesis pathway. The identified differentially expressed genes also provide potential candidates for functional analysis to identify genes involved in the accumulation of noroviruses in oysters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

    Energy Technology Data Exchange (ETDEWEB)

    Bolo, N.R.

    1991-11-01

    The goal of this work is to investigate the potential for and limitations of in vivo nuclear magnetic resonance (NMR) spectroscopy for quantitation of glucose flux through the pentose phosphate pathway (shunt). Interest in the shunt is motivated by the possibility that its activity may be greatly increased in cancer and in the pathological states of cardiac and cerebral ischemia. The ability to dynamically monitor flux through the pentose shunt can give new knowledge about metabolism in pathological states. {sup 13}C NMR spectroscopy was used to monitor shunt activity by determination of the ratios of ({sup 13}C-4) to ({sup 13}C-5)-glutamate, ({sup 13}C-3) to ({sup 13}C-2)-alanine or ({sup 13}C-3) to ({sup 13}C-2)-lactate produced when ({sup 13}C-2)-glucose is infused. These methods provide measures of the effect of oxidative stresses on shunt activity in systems ranging from cell free enzyme-substrate preparations to cell suspensions and whole animals. In anaerobic cell free preparations, the fraction of glucose flux through the shunt was monitored with a time resolution of 3 minutes. This work predicts the potential for in vivo human studies of pentose phosphate pathway activity based on the mathematical simulation of the {sup 13}C fractional enrichments of C4 and C5-glutamate as a function of shunt activity and on the signal-to- noise ratio acquired in {sup 13}C NMR human studies from the current literature.

  4. Enantiomerization pathway and atropochiral stability of the BINAP ligand: a density functional theory study.

    Science.gov (United States)

    García, Juan Sanz ; Lepetit, Christine; Canac, Yves; Chauvin, Remi; Boggio-Pasqua, Martial

    2014-02-01

    A theoretical study of the enantiomerization pathway of BINAP, the paradigm of atropochiral ligands in asymmetric organometallic catalysis, is reported. Density functional theory was used with the B3PW91 functional and the 6-31G(d,p) basis set. The calculation level was validated through the study of the syn and anti enantiomerization pathways of the 1,1′-binaphthyl reference for which the enantiomerization barrier was calculated to be in good agreement with experimental data. Calculations were then performed on BINAP itself using the same level of theory, and showed that its enantiomerization mechanism follows the syn route through a concerted, yet highly asynchronous, all-chiral process. The enantiomerization barrier was computed at 213 kJ mol(−1) and proved little sensitive to the functional or to the basis set used, with values always larger than 200 kJ mol(−1). The configurational stability of BINAP was finally characterized by a computed Oki’s racemization temperature of 491 °C.

  5. Neutrophils cross the BBB primarily on transcellular pathways: an in vitro study.

    Science.gov (United States)

    von Wedel-Parlow, Magdalena; Schrot, Sebastian; Lemmen, Julia; Treeratanapiboon, Lertyot; Wegener, Joachim; Galla, Hans-Joachim

    2011-01-07

    The cerebral microcapillary endothelium forms a highly important barrier between the blood and the interstitial fluid of the brain (blood-brain barrier) that controls the passage of molecules and cells in and out of the CNS. Several CNS diseases include leukocyte extravasation through the endothelium via two mechanistically distinct routes, the paracellular and the transcellular pathway. We established a new in vitro model of the inflamed blood-brain barrier consisting of primary cultured porcine brain capillary endothelial cells which express a tight endothelial barrier even under inflammatory conditions. By means of this specialized blood-brain barrier model we extensively studied the transmigration of neutrophils. Electron and scanning force microscopy as well as immunofluorescence imaging captured the penetrating neutrophil on the endothelial cellular body in between the junctions clearly suggesting a transcellular migration pathway. Electric cell-substrate impedance sensing and transendothelial electrical resistance measurements in combination with expression analysis of tight junction proteins demonstrate that the neutrophil-endothelial interaction does not disrupt the barrier. In conclusion, this study, based on an in vitro model of the blood-brain barrier under inflammatory conditions, evidently implicates that neutrophils preferentially migrate across the BBB via the transcellular route without impairing endothelial barrier function whereas paracellular transmigration plays only a minor role if the barrier is strongly expressed. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Pouch Salvage Surgery for Treatment of Colitis and Familial Adenomatous Polyposis: Report of Five Cases

    Directory of Open Access Journals (Sweden)

    Derakhshani

    2016-08-01

    Full Text Available Introduction The restorative proctocolectomy (RPC with ileal pouch-anal anastomosis (IPAA is currently the preferred surgical method for most patients with ulcerative colitis and familial adenomatous polyposis and sometimes, functional bowel diseases. Infection around the pouch, remaining rectal stump, stricture at anastomosis site, pouch dysfunction and refractory pouchitis can lead to pouch failure. Pouch salvage surgery could prevent pouch failure in some cases. Case Presentation In this report, five patients were introduced, who underwent pouch salvage surgery after RPC/IPAA surgery failure. Two of the patients were male and three were female and the relevant age range was 16 to 41. Initially, RPC/IPAA surgery was performed on these five patients. Four of the patients underwent RPC/IPAA surgery as a result of ulcerative colitis and, one of the patients as a result of familial adenomatous polyposis. However, due to pouch failure from the RPC/IPAA surgery, pouch-salvage surgery was performed on each of these five patients. Two of the patients underwent pouch-salvage surgery due to infection and pouch fistula, and the other three underwent this surgery due to the remaining rectal stump, anastomosis stenosis and pouch dysfunction. The average time for when pouch-salvage surgery was performed was 3.5 years (three months to five years after the initial operation and the patients were under follow-up care for two to seven years. Conclusions After performing pouch salvage operation, pouch function was acceptable in all patients and we could close ileostomies of all of them.

  7. Short-term understory plant community responses to salvage logging in beetle-affected lodgepole pine forests

    Science.gov (United States)

    Paula J. Fornwalt; Charles C. Rhoades; Robert M. Hubbard; Rebecca L. Harris; Akasha M. Faist; William D. Bowman

    2018-01-01

    Recent bark beetle outbreaks in western North American subalpine forests have prompted managers to salvage log some beetle-affected stands. We examined the short-term (i.e., two to three years post-treatment) consequences of such salvage logging on vascular understory plant (i.e., graminoid, forb, and shrub) communities. At 24 lodgepole pine (Pinus contorta) sites in...

  8. Pathway-based analysis using genome-wide association data from a Korean non-small cell lung cancer study.

    Directory of Open Access Journals (Sweden)

    Donghoon Lee

    Full Text Available Pathway-based analysis, used in conjunction with genome-wide association study (GWAS techniques, is a powerful tool to detect subtle but systematic patterns in genome that can help elucidate complex diseases, like cancers. Here, we stepped back from genetic polymorphisms at a single locus and examined how multiple association signals can be orchestrated to find pathways related to lung cancer susceptibility. We used single-nucleotide polymorphism (SNP array data from 869 non-small cell lung cancer (NSCLC cases from a previous GWAS at the National Cancer Center and 1,533 controls from the Korean Association Resource project for the pathway-based analysis. After mapping single-nucleotide polymorphisms to genes, considering their coding region and regulatory elements (±20 kbp, multivariate logistic regression of additive and dominant genetic models were fitted against disease status, with adjustments for age, gender, and smoking status. Pathway statistics were evaluated using Gene Set Enrichment Analysis (GSEA and Adaptive Rank Truncated Product (ARTP methods. Among 880 pathways, 11 showed relatively significant statistics compared to our positive controls (PGSEA≤0.025, false discovery rate≤0.25. Candidate pathways were validated using the ARTP method and similarities between pathways were computed against each other. The top-ranked pathways were ABC Transporters (PGSEA<0.001, PARTP = 0.001, VEGF Signaling Pathway (PGSEA<0.001, PARTP = 0.008, G1/S Check Point (PGSEA = 0.004, PARTP = 0.013, and NRAGE Signals Death through JNK (PGSEA = 0.006, PARTP = 0.001. Our results demonstrate that pathway analysis can shed light on post-GWAS research and help identify potential targets for cancer susceptibility.

  9. Salvage of distal radius nonunion with a dorsal spanning distraction plate.

    Science.gov (United States)

    Mithani, Suhail K; Srinivasan, Ramesh C; Kamal, Robin; Richard, Marc J; Leversedge, Fraser J; Ruch, David S

    2014-05-01

    Treatment of nonunion after previous instrumentation of distal radius fractures represents a reconstructive challenge. Resultant osteopenia provides a poor substrate for fixation, often necessitating wrist fusion for salvage. A spanning dorsal distraction plate (bridge plate) can be a useful adjunct to neutralize forces across the wrist, alone or in combination with nonspanning plates to achieve union, salvage wrist function, and avoid wrist arthrodesis in distal radius nonunion. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  10. TA-60 Warehouse and Salvage SWPPP Rev 2 Jan 2017-Final

    Energy Technology Data Exchange (ETDEWEB)

    Burgin, Jillian Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-02-07

    The Stormwater Pollution Prevention Team (PPT) for the TA-60-0002 Salvage and Warehouse Area consists of operations and management personnel from the facility, Multi-Sector General Permitting (MSGP) stormwater personnel from Environmental Compliance Programs (EPC-CP) organization, and Deployed Environmental Professionals. The EPC-CP representative is responsible for Laboratory compliance under the National Pollutant Discharge Elimination System (NPDES) permit regulations. The team members are selected on the basis of their familiarity with the activities at the facility and the potential impacts of those activities on stormwater runoff. The Warehouse and Salvage Yard are a single shift operation; therefore, a member of the PPT is always present during operations.

  11. Infliximab Salvage Therapy after Cyclosporine in an Acute Flare of Chronic Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    ECS Lam

    2003-01-01

    Full Text Available Although infliximab (Remicade, Schering Canada Inc, Quebec therapy has been well studied in steroid refractory Crohn’s disease, its use remains controversial in chronic ulcerative colitis. A 24-year-old woman with a 14-year history of well controlled left sided ulcerative colitis presented with an acute flare. Clinical, endoscopic and biopsy evidence of an acute flare of ulcerative pancolitis were present. There was no response to intravenous steroids but improvement was seen after receiving 14 days of intravenous cyclosporine (4 mg/kg/day continuous infusion. The patient was discharged from hospital with azathioprine (2.5 mg/kg/day and low dose oral cyclosporine (4 mg/kg/day. She presented with worsening symptoms seven days after discharge. Because of the patient’s unwillingness for surgery, she instead received two injections of infliximab 5 mg/kg at week 0 and week 2. An initial response occurred, but her clinical improvement was not durable. Colectomy was performed four weeks later. This is the first report of infliximab as a salvage therapy in an acute flare of chronic ulcerative colitis following failure of cyclosporine.

  12. Stage IE Primary Bone Lymphoma:Limb Salvage for Local Recurrence

    Directory of Open Access Journals (Sweden)

    Khodamorad Jamshidi

    2015-01-01

    Full Text Available Background:   Primary bone lymphoma or non-Hodgkin lymphoma of bone is a rare disease. There are only a few case series of stage IE of this condition in medical literature. The aim of this study is to determine the rate of survival   for stage IE after combined modality treatment, the rate of local recurrence, and the results of limb salvage in cases   of local recurrence.     Methods:   We collected data from 61 patients with histologically confirmed PBL treated at the Musculoskeletal   Oncology Department of our hospital from 2000 to 2010. Retrospective evaluation included demographics, symptoms, tumor locations, outcomes of surgical treatment for local recurrence and survival rates. Results:   All patients received Combined Modality Therapy. Overall,five year survival was 89% and five year disease free survival rate was 78%. Local recurrence occurred in 6 patients during follow up period, which was treated surgically     by wide excision and reconstruction. The mean follow-up for the local recurrence group was 36(24-54 months and mortality rate in this group was 17%. Conclusions:   Combined Modality Therapy for stage IE primary bone lymphomaresults in good survival rate. In case   of local recurrence, wide excision and reconstruction improves the outcomes.

  13. A preliminary evaluation of limb salvage surgery for osteosarcoma around knee joint.

    Directory of Open Access Journals (Sweden)

    Xing Wu

    Full Text Available OBJECTIVE: To evaluate the effectiveness and drawbacks of diversified procedures of limb salvage surgery (LSS, providing a reference of rational surgical criterion of LSS. METHODS: Fifty eight patients with stage IIB extremity osteosarcoma around knee joint area between 1992 and 2002 were studied retrospectively. Among them, 43 patients were treated by LSS followed by reconstruction. Reconstruction approaches included re-implantation of irradiation-devitalized tumor bone (n = 12, autoclaving-devitalized tumor bone (n = 8, prosthetic replacement (n = 11, allograft transplantation (n = 8 and vascularized fibula autograft implantation (n = 4. Amputations were performed in 15 patients. Patients were followed up for 6-16 years. RESULTS: There were no significant difference between LSS and amputation groups regarding disease free survival and local recurrence rates. The actuarial 5-year continuous disease free survival and local recurrence rate were 30.0% and 25.0% in patients of devitalized LSS group, whereas those were 56.5% and 8.7% in patients of non-devitalized reconstruction group. The complication rate was significantly higher in LSS group compared to amputation group (P = 0.003. CONCLUSION: LSS with non-devitalized procedures is the optimal treatment for osteosarcoma around knee joint area. Prosthesis implantation is the preferred option for bone reconstruction following LSS. Prevention and treatment of post-operative complications should be paid more attention to get good long-term outcomes of surgery.

  14. Salvage/Adjuvant Brachytherapy After Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Francis, Jasmine H., E-mail: francij1@mskcc.org [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Barker, Christopher A.; Wolden, Suzanne L.; McCormick, Beryl; Segal, Kira; Cohen, Gil [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Gobin, Y. Pierre; Marr, Brian P. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York-Presbyterian Hospital, New York, New York (United States); Brodie, Scott E. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Mount Sinai School of Medicine, New York, New York (United States); Dunkel, Ira J.; Abramson, David H. [Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Weill-Cornell Medical College, New York-Presbyterian Hospital, New York, New York (United States)

    2013-11-01

    Purpose: To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. Methods and Materials: This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). Results: Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P=.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes. Conclusions: Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG.

  15. Direct vs. indirect pathway for nitrobenzene reduction reaction on a Ni catalyst surface: a density functional study.

    Science.gov (United States)

    Mahata, Arup; Rai, Rohit K; Choudhuri, Indrani; Singh, Sanjay K; Pathak, Biswarup

    2014-12-21

    Density functional theory (DFT) calculations are performed to understand and address the previous experimental results that showed the reduction of nitrobenzene to aniline prefers direct over indirect reaction pathways irrespective of the catalyst surface. Nitrobenzene to aniline conversion occurs via the hydroxyl amine intermediate (direct pathway) or via the azoxybenzene intermediate (indirect pathway). Through our computational study we calculated the spin polarized and dispersion corrected reaction energies and activation barriers corresponding to various reaction pathways for the reduction of nitrobenzene to aniline over a Ni catalyst surface. The adsorption behaviour of the substrate, nitrobenzene, on the catalyst surface was also considered and the energetically most preferable structural orientation was elucidated. Our study indicates that the parallel adsorption behaviour of the molecules over a catalyst surface is preferable over vertical adsorption behaviour. Based on the reaction energies and activation barrier of the various elementary steps involved in direct or indirect reaction pathways, we find that the direct reduction pathway of nitrobenzene over the Ni(111) catalyst surface is more favourable than the indirect reaction pathway.

  16. Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE Cohorts

    Directory of Open Access Journals (Sweden)

    Unjin Shim

    2014-12-01

    Full Text Available Metabolic syndrome (MetS is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs, important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs, explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE was used for analysis, which include 8,842 individuals (age, 52.2 ± 8.9 years; body mass index, 24.6 ± 3.2 kg/m2. A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 × 10-6, and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 × 10-7, Bonferroni-adjusted p < 0.05. Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF, the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

  17. Cortico-striatal language pathways dynamically adjust for syntactic complexity: A computational study.

    Science.gov (United States)

    Szalisznyó, Krisztina; Silverstein, David; Teichmann, Marc; Duffau, Hugues; Smits, Anja

    2017-01-01

    A growing body of literature supports a key role of fronto-striatal circuits in language perception. It is now known that the striatum plays a role in engaging attentional resources and linguistic rule computation while also serving phonological short-term memory capabilities. The ventral semantic and the dorsal phonological stream dichotomy assumed for spoken language processing also seems to play a role in cortico-striatal perception. Based on recent studies that correlate deep Broca-striatal pathways with complex syntax performance, we used a previously developed computational model of frontal-striatal syntax circuits and hypothesized that different parallel language pathways may contribute to canonical and non-canonical sentence comprehension separately. We modified and further analyzed a thematic role assignment task and corresponding reservoir computing model of language circuits, as previously developed by Dominey and coworkers. We examined the models performance under various parameter regimes, by influencing how fast the presented language input decays and altering the temporal dynamics of activated word representations. This enabled us to quantify canonical and non-canonical sentence comprehension abilities. The modeling results suggest that separate cortico-cortical and cortico-striatal circuits may be recruited differently for processing syntactically more difficult and less complicated sentences. Alternatively, a single circuit would need to dynamically and adaptively adjust to syntactic complexity. Copyright © 2016. Published by Elsevier Inc.

  18. Allosteric communication pathways and thermal rectification in PDZ-2 protein: a computational study.

    Science.gov (United States)

    Miño-Galaz, Germán A

    2015-05-21

    Allosteric communication in proteins is a fundamental and yet unresolved problem of structural biochemistry. Previous findings, from computational biology ( Ota, N.; Agard, D. A. J. Mol. Biol. 2005 , 351 , 345 - 354 ), have proposed that heat diffuses in a protein through cognate protein allosteric pathways. This work studied heat diffusion in the well-known PDZ-2 protein, and confirmed that this protein has two cognate allosteric pathways and that heat flows preferentially through these. Also, a new property was also observed for protein structures: heat diffuses asymmetrically through the structures. The underling structure of this asymmetrical heat flow was a normal length hydrogen bond (∼2.85 Å) that acted as a thermal rectifier. In contrast, thermal rectification was compromised in short hydrogen bonds (∼2.60 Å), giving rise to symmetrical thermal diffusion. Asymmetrical heat diffusion was due, on a higher scale, to the local, structural organization of residues that, in turn, was also mediated by hydrogen bonds. This asymmetrical/symmetrical energy flow may be relevant for allosteric signal communication directionality in proteins and for the control of heat flow in materials science.

  19. The European quality of care pathways (EQCP study on the impact of care pathways on interprofessional teamwork in an acute hospital setting: study protocol: for a cluster randomised controlled trial and evaluation of implementation processes

    Directory of Open Access Journals (Sweden)

    Deneckere Svin

    2012-05-01

    Full Text Available Abstract Background Although care pathways are often said to promote teamwork, high-level evidence that supports this statement is lacking. Furthermore, knowledge on conditions and facilitators for successful pathway implementation is scarce. The objective of the European Quality of Care Pathway (EQCP study is therefore to study the impact of care pathways on interprofessional teamwork and to build up understanding on the implementation process. Methods/design An international post-test-only cluster Randomised Controlled Trial (cRCT, combined with process evaluations, will be performed in Belgium, Ireland, Italy, and Portugal. Teams caring for proximal femur fracture (PFF patients and patients hospitalized with an exacerbation of chronic obstructive pulmonary disease (COPD will be randomised into an intervention and control group. The intervention group will implement a care pathway for PFF or COPD containing three active components: a formative evaluation of the actual teams’ performance, a set of evidence-based key interventions, and a training in care pathway-development. The control group will provide usual care. A set of team input, process and output indicators will be used as effect measures. The main outcome indicator will be relational coordination. Next to these, process measures during and after pathway development will be used to evaluate the implementation processes. In total, 132 teams have agreed to participate, of which 68 were randomly assigned to the intervention group and 64 to the control group. Based on power analysis, a sample of 475 team members per arm is required. To analyze results, multilevel analysis will be performed. Discussion Results from our study will enhance understanding on the active components of care pathways. Through this, preferred implementation strategies can be defined. Trail registration NCT01435538

  20. Second-line salvage treatment of AIDS-associated Pneumocystis jirovecii pneumonia: a case series and systematic review

    DEFF Research Database (Denmark)

    Benfield, T.; Atzori, C.; Miller, R.F.

    2008-01-01

    BACKGROUND: Limited clinical data exist to guide the choice of second-line salvage treatment for AIDS-associated Pneumocystis jirovecii pneumonia (PCP). METHODS: We did a systematic search of MEDLINE for all randomized and observational studies of PCP treatment published up to August 2007...... and included individual treatment data of AIDS-associated PCP from a tricenter study. We calculated pooled estimates of reported outcome of second-line treatment using averaged odds ratios (ORs). RESULTS: Twenty-nine studies with sufficient detail of second-line treatment and outcome, including data from 82......-SMX should be used as a second-line treatment for those failing first-line treatments with regimens other than TMP-SMX Udgivelsesdato: 2008/5/1...

  1. Multivariable model development and internal validation for prostate cancer specific survival and overall survival after whole-gland salvage Iodine-125 prostate brachytherapy.

    Science.gov (United States)

    Peters, Max; van der Voort van Zyp, Jochem R N; Moerland, Marinus A; Hoekstra, Carel J; van de Pol, Sandrine; Westendorp, Hendrik; Maenhout, Metha; Kattevilder, Rob; Verkooijen, Helena M; van Rossum, Peter S N; Ahmed, Hashim U; Shah, Taimur T; Emberton, Mark; van Vulpen, Marco

    2016-04-01

    Whole-gland salvage Iodine-125-brachytherapy is a potentially curative treatment strategy for localised prostate cancer (PCa) recurrences after radiotherapy. Prognostic factors influencing PCa-specific and overall survival (PCaSS & OS) are not known. The objective of this study was to develop a multivariable, internally validated prognostic model for survival after whole-gland salvage I-125-brachytherapy. Whole-gland salvage I-125-brachytherapy patients treated in the Netherlands from 1993-2010 were included. Eligible patients had a transrectal ultrasound-guided biopsy-confirmed localised recurrence after biochemical failure (clinical judgement, ASTRO or Phoenix-definition). Recurrences were assessed clinically and with CT and/or MRI. Metastases were excluded using CT/MRI and technetium-99m scintigraphy. Multivariable Cox-regression was used to assess the predictive value of clinical characteristics in relation to PCa-specific and overall mortality. PCa-specific mortality was defined as patients dying with distant metastases present. Missing data were handled using multiple imputation (20 imputed sets). Internal validation was performed and the C-statistic calculated. Calibration plots were created to visually assess the goodness-of-fit of the final model. Optimism-corrected survival proportions were calculated. All analyses were performed according to the TRIPOD statement. Median total follow-up was 78months (range 5-139). A total of 62 patients were treated, of which 28 (45%) died from PCa after mean (±SD) 82 (±36) months. Overall, 36 patients (58%) patients died after mean 84 (±40) months. PSA doubling time (PSADT) remained a predictive factor for both types of mortality (PCa-specific and overall): corrected hazard ratio's (HR's) 0.92 (95% CI: 0.86-0.98, p=0.02) and 0.94 (95% CI: 0.90-0.99, p=0.01), respectively (C-statistics 0.71 and 0.69, respectively). Calibration was accurate up to 96month follow-up. Over 80% of patients can survive 8years if PSADT>24

  2. Differential recovery of water quality parameters eight years after severe wildfire and salvage logging in Alberta's southern Rocky Mountains

    Science.gov (United States)

    Silins, U.; Bladon, K. D.; Stone, M.; Emelko, M. B.; Collins, A.; Boon, S.; Williams, C.; Wagner, M. J.; Martens, A. M.; Anderson, A.

    2012-12-01

    Broad regions of western North America rely on water supplies that originate from forested regions of the Rocky Mountain cordillera where landuse pressures, and stresses including changing natural disturbance regimes associated with shifting climates has been impacting critical source water supplies from this region. Increases in magnitude and severity of wildfires along with impacts on downstream water supplies has been observed along the length of the North American Rocky Mountain chain, however, the longevity of these impacts (including impacts to important water quality parameters) remain highly uncertain because processes regulating recovery from such disturbances can span a range of timescales from a few years to decades depending on both the hydro-climatic regime, and which water quality parameters are important. Studies document such long-term changes are few. The Southern Rockies Watershed Project (SRWP) was established to document the magnitude and recovery from the severe 2003 Lost Creek wildfire in the Crowsnest Pass region of southwest Alberta, Canada. Hydrology, water quality (physical & chemical) have been studies in 9 instrumented catchments (4-14 km2) encompassing burned, burned and salvage logged, prescribed burned, and unburned (reference) conditions since late winter 2004. While most important water quality parameters were strongly elevated in burned and burned-salvage logged catchments after the fire, strongly differential rates of recovery were observed for contaminant concentration, export, and yield across a range of water quality parameters (2004-2011). For example, while various nitrogen (N) species (total nitrogen, dissolved nitrogen, NO3-, NH4+) showed 2-7 fold increases in concentration the first 1-2 years after the wildfire, N recovered back to baseline concentrations 4-5 years after the wildfire. In contrast, eight full years after the wildfire (2011), no recovery of sediment or phosphorus (P) production (soluble reactive, total

  3. Dopamine pathway gene variants may modulate cognitive performance in the DHS - Mind Study.

    Science.gov (United States)

    Martelle, Susan E; Raffield, Laura M; Palmer, Nichole D; Cox, Amanda J; Freedman, Barry I; Hugenschmidt, Christina E; Williamson, Jeff D; Bowden, Don W

    2016-04-01

    There is an established association between type 2 diabetes and accelerated cognitive decline. The exact mechanism linking type 2 diabetes and reduced cognitive function is less clear. The monoamine system, which is extensively involved in cognition, can be altered by type 2 diabetes status. Thus, this study hypothesized that sequence variants in genes linked to dopamine metabolism and associated pathways are associated with cognitive function as assessed by the Digit Symbol Substitution Task, the Modified Mini-Mental State Examination, the Stroop Task, the Rey Auditory-Verbal Learning Task, and the Controlled Oral Word Association Task for Phonemic and Semantic Fluency in the Diabetes Heart Study, a type 2 diabetes-enriched familial cohort (n = 893). To determine the effects of candidate variants on cognitive performance, genetic association analyses were performed on the well-documented variable number tandem repeat located in the 3' untranslated region of the dopamine transporter, as well as on single-nucleotide polymorphisms covering genes in the dopaminergic pathway, the insulin signaling pathway, and the convergence of both. Next, polymorphisms in loci of interest with strong evidence for involvement in dopamine processing were extracted from genetic datasets available in a subset of the cohort (n = 572) derived from Affymetrix(®) Genome-Wide Human SNP Array 5.0 and 1000 Genomes imputation from this array. The candidate gene analysis revealed one variant from the DOPA decarboxylase gene, rs10499695, to be associated with poorer performance on a subset of Rey Auditory-Verbal Learning Task measuring retroactive interference (P = 0.001, β = -0.45). Secondary analysis of genome-wide and imputed data uncovered another DOPA decarboxylase variant, rs62445903, also associated with retroactive interference (P = 7.21 × 10(-7), β = 0.3). These data suggest a role for dopaminergic genes, specifically a gene involved in regulation of dopamine synthesis

  4. Diffusion tensor studies dissociated two fronto-temporal pathways in the human memory system.

    Science.gov (United States)

    Takahashi, Emi; Ohki, Kenichi; Kim, Dae-Shik

    2007-01-15

    Recent functional neuroimaging studies have shown that multiple cortical areas are involved in memory encoding and retrieval. However, the underlying anatomical connections among these memory-related areas in humans remain elusive due to methodological limitations. Diffusion tensor imaging (DTI) is a technique based on detecting the diffusion of water molecules from magnetic resonance images. DTI allows non-invasive mapping of anatomical connections and gives a comprehensive picture of connectivity throughout the entire brain. By combining functional magnetic resonance imaging (fMRI) and DTI, we show that memory-related areas in the left dorsolateral prefrontal cortex (DLPFC) and the left ventrolateral prefrontal cortex (VLPFC) each connect with memory-related areas in the left temporal cortex. This result suggests there are two pathways between prefrontal cortex and temporal cortex related to the human memory system.

  5. Life after the Liverpool Care Pathway (LCP): a qualitative study of critical care practitioners delivering end-of-life care.

    Science.gov (United States)

    Ramasamy Venkatasalu, Munikumar; Whiting, Dean; Cairnduff, Karen

    2015-09-01

    To explore the experiences, challenges and practices of critical care practitioners since the discontinuation of the Liverpool Care Pathway in critical care settings. The Liverpool Care Pathway was widely used with an aim to improve communication and care for dying individuals and their relatives. However, widespread media criticism prompted a review, which resulted in the discontinuation of the Liverpool Care Pathway across all UK clinical settings. A qualitative study. The study was carried out in two large acute hospitals in England. Semi-structured interviews were conducted with 14 critical care practitioners, 6 months after discontinuation of the Liverpool Care Pathway. Transcribed verbatim data were analysed using framework analysis. Three key themes emerged: 'lessons learned', 'uncertainties and ambivalences' and 'the future'. Critical care practitioners reported that life after the Liverpool Care Pathway in critical care settings often involved various clinical ambivalences, uncertainties and inconsistencies in the delivery of end-of-life care, especially for less experienced practitioners. Critical care practitioners had 'become accustomed' to the components of the Liverpool Care Pathway, which still guide them in principle to ensure quality end-of-life care. The Liverpool Care Pathway's structured format was perceived to be a useful clinical tool, but was also criticized as a 'tick-box exercise' and for lacking in family involvement. This study posits two key conclusions. Despite experienced critical care practitioners being able to deliver quality end-of-life care without using the Liverpool Care Pathway, junior nursing and medical staff need clear guidelines and support from experienced mentors in practice. Evidence-based guidelines related to family involvement in end-of-life care planning in critical care settings are also needed to avoid future controversies. © 2015 John Wiley & Sons Ltd.

  6. Nuclear magnetic resonance studies of the regulation of the pentose phosphate pathway

    Energy Technology Data Exchange (ETDEWEB)

    Bolo, Nicolas Robin [Univ. of California, Berkeley, CA (United States)

    1991-11-01

    The goal of this work is to investigate the potential for and limitations of in vivo nuclear magnetic resonance (NMR) spectroscopy for quantitation of glucose flux through the pentose phosphate pathway (shunt). Interest in the shunt is motivated by the possibility that its activity may be greatly increased in cancer and in the pathological states of cardiac and cerebral ischemia. The ability to dynamically monitor flux through the pentose shunt can give new knowledge about metabolism in pathological states. 13C NMR spectroscopy was used to monitor shunt activity by determination of the ratios of [13C-4] to [13C-5]-glutamate, [13C-3] to [13C-2]-alanine or [13C-3] to [13C-2]-lactate produced when [13C-2]-glucose is infused. These methods provide measures of the effect of oxidative stresses on shunt activity in systems ranging from cell free enzyme-substrate preparations to cell suspensions and whole animals. In anaerobic cell free preparations, the fraction of glucose flux through the shunt was monitored with a time resolution of 3 minutes. This work predicts the potential for in vivo human studies of pentose phosphate pathway activity based on the mathematical simulation of the 13C fractional enrichments of C4 and C5-glutamate as a function of shunt activity and on the signal-to- noise ratio acquired in 13C NMR human studies from the current literature.

  7. Prevalence of anti-retroviral treatment failure and salvage therapy in ...

    African Journals Online (AJOL)

    With long term therapy with ARVs however, problems arise due to poor adherence. The concept of “salvage therapy” was conceived subsequent to experiencing multiple treatment failures to ARV combinations. It implies a final attempt, in the battle against HIV/AIDS. Objective: To determine the prevalence of treatment ...

  8. Intraoperative cell salvage during cardiac surgery is associated with reduced postoperative lung injury

    NARCIS (Netherlands)

    Engels, Gerwin E; van Klarenbosch, Jan; Gu, Y John; van Oeveren, Willem; de Vries, Adrianus J

    2016-01-01

    OBJECTIVES: In addition to its blood-sparing effects, intraoperative cell salvage may reduce lung injury following cardiac surgery by removing cytokines, neutrophilic proteases and lipids that are present in cardiotomy suction blood. To test this hypothesis, we performed serial measurements of

  9. Intraoperative cell salvage during cardiac surgery is associated with reduced postoperative lung injury

    NARCIS (Netherlands)

    Engels, Gerwin E.; van Klarenbosch, Jan; Gu, Y. John; van Oeveren, Willem; de Vries, Adrianus J.

    OBJECTIVES: In addition to its blood-sparing effects, intraoperative cell salvage may reduce lung injury following cardiac surgery by removing cytokines, neutrophilic proteases and lipids that are present in cardiotomy suction blood. To test this hypothesis, we performed serial measurements of

  10. Vegetation response to large scale disturbance in a southern Appalachian forest: Hurricane Opal and salvage logging

    Science.gov (United States)

    Katherine J. Elliott; Stephanie L. Hitchcock; Lisa Krueger

    2002-01-01

    Disturbance such as catastrophic windthrow can play a major role in the structure and composition of southern Appalachian forests. We report effects of Hurricane Opal followed by salvage logging on vegetation dynamics (regeneration, composition, and diversity) the first three years after disturbance at the Coweeta Hydrologic Laboratory in western North Carolina. The...

  11. Dictyostelium discoideum salvages purine deoxyribonucleosides by highly specific bacterial-like deoxyribonucleoside kinases

    DEFF Research Database (Denmark)

    Sandrini, Michael; Soderbom, F.; Mikkelsen, N.E.

    2007-01-01

    The salvage of deoxyribonucleosides in the social amoeba Dictyostelium discoideum, which has an extremely A + T-rich genome, was investigated. All native deoxyribonucleosides were phosphorylated by D. discoideum cell extracts and we subcloned three deoxyribonucleoside kinase (dNK) encoding genes....

  12. Current ideas to reduce or salvage radiation damage to salivary glands

    NARCIS (Netherlands)

    Vissink, A; van Luijk, P; Langendijk, J A; Coppes, R P

    Radiation-induced hyposalivation is still a major problem after radiotherapy for head and neck cancer. Current and promising new thoughts to reduce or salvage radiation damage to salivary gland tissue are explored. The main cause underlying radiation-induced hyposalivation is a lack of functional

  13. Salvage high-dose-rate brachytherapy for esophageal cancer in previously irradiated patients: A retrospective analysis.

    Science.gov (United States)

    Wong Hee Kam, Stéphanie; Rivera, Sofia; Hennequin, Christophe; Lourenço, Nelson; Chirica, Mircea; Munoz-Bongrand, Nicolas; Gornet, Jean-Marc; Quéro, Laurent

    2015-01-01

    To evaluate outcomes after exclusive salvage high-dose-rate (HDR) intraluminal esophageal brachytherapy given to previously irradiated patients with recurrent esophageal cancer. We reviewed medical records of 30 patients who were treated by salvage HDR brachytherapy for local esophageal cancer. Brachytherapy delivered four to six fractions of 5-7 Gy at 5 mm from the applicator surface and 20 mm above and below the macroscopic tumor volume. Eighty percentage of patients received treatment as initially planned. Complete response rate, evaluated 1 month after brachytherapy by endoscopy and biopsy, was 53%. Squamous histology and complete endoscopic tumor response at 1 month were significantly associated with better local tumor control. Median local progression-free survival was 9.8 months. Overall survival was 31.5% and 17.5% at 1 and 2 years, respectively. On univariate analysis, preserved performance status and limited weight loss (brachytherapy were associated with better overall survival. Severe toxicity (Grade ≥3) occurred in 7 patients (23%). Although esophageal cancer in previously irradiated patients is associated with poor outcomes, HDR brachytherapy may be a valuable salvage treatment for inoperable patients with locally limited esophageal cancer, particularly in the subset of patients with preserved performance status and limited weight loss (≤10%) before salvage brachytherapy. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  14. 32 CFR 644.478 - Demolition of buildings and other improvements for utilization of salvage material.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Demolition of buildings and other improvements for utilization of salvage material. 644.478 Section 644.478 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Disposal of Buildings and Other Improvements (without the...

  15. The outcome of rectal cancer after early salvage TME following TEM compared with primary TME

    DEFF Research Database (Denmark)

    Bulut, O; Levic, K; Hesselfeldt, P

    2014-01-01

    difference between two groups of patients in the median number of harvested lymph nodes (P = 0.34), median circumferential resection margin (CRM) (P = 0.99) or the completeness of the mesorectal fascia plane. No local recurrences occurred among the patients with salvage TME, and there were 2 patients (8...

  16. The outcome of rectal cancer after early salvage TME following TEM compared with primary TME

    DEFF Research Database (Denmark)

    Levic, K; Bulut, O; Hesselfeldt, P

    2012-01-01

    difference between two groups of patients in the median number of harvested lymph nodes (P = 0.34), median circumferential resection margin (CRM) (P = 0.99) or the completeness of the mesorectal fascia plane. No local recurrences occurred among the patients with salvage TME, and there were 2 patients (8...

  17. Management of complex diabetic foot wound by external fixation: An effective way for limb salvage

    Directory of Open Access Journals (Sweden)

    Biswaranjan Nayak

    2016-01-01

    Conclusion: External fixation provides limb off-loading, immobilization, skeletal fixation, wound care, preservation of vascular structures and simultaneously allow the soft tissue healing in complex diabetic wound. So it is a better method of limb salvaging than the traditional methods with encouraging results.

  18. Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound

    Energy Technology Data Exchange (ETDEWEB)

    Holtzman, Adam L. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Letter, Haley P.; Bryant, Curtis; Nichols, Romaine C.; Henderson, Randal H.; Mendenhall, William M.; Morris, Christopher G. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States); Williams, Christopher R. [Department of Surgery, University of Florida College of Medicine, Jacksonville, Florida (United States); Li, Zuofeng; Mendenhall, Nancy P. [University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida (United States)

    2016-05-01

    Purpose: Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS. Methods and Materials: We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually. Results: Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold. Conclusions: PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.

  19. Cellulose production is coupled to sensing of the pyrimidine biosynthetic pathway via c-di-GMP production by the DgcQ protein of Escherichia coli.

    Science.gov (United States)

    Rossi, Elio; Motta, Sara; Aliverti, Alessandro; Cossu, Federica; Gourlay, Louise; Mauri, Pierluigi; Landini, Paolo

    2017-09-11

    Production of cellulose, a stress response-mediated process in enterobacteria, is modulated in Escherichia coli by the activity of the two pyrimidine nucleotide biosynthetic pathways, namely, the de novo biosynthetic pathway and the salvage pathway, which relies on the environmental availability of pyrimidine nitrogenous bases. We had previously reported that prevalence of the salvage over the de novo pathway triggers cellulose production via synthesis of the second messenger c-di-GMP by the DgcQ (YedQ) diguanylate cyclase. In this work, we show that DgcQ enzymatic activity is enhanced by UTP, whilst being inhibited by N-carbamoyl-aspartate, an intermediate of the de novo pathway. Thus, direct allosteric control by these ligands allows full DgcQ activity exclusively in cells actively synthesizing pyrimidine nucleotides via the salvage pathway. Inhibition of DgcQ activity by N-carbamoyl-aspartate appears to be favoured by protein-protein interaction between DgcQ and PyrB, a subunit of aspartate transcarbamylase, which synthesizes N-carbamoyl-aspartate. Our results suggest that availability of pyrimidine bases might be sensed, somehow paradoxically, as an environmental stress by E. coli. We hypothesize that this link might have evolved since stress events, leading to extensive DNA/RNA degradation or lysis of neighbouring cells, can result in increased pyrimidine concentrations and activation of the salvage pathway. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  20. ICSNPathway: identify candidate causal SNPs and pathways from genome-wide association study by one analytical framework

    Science.gov (United States)

    Zhang, Kunlin; Chang, Suhua; Cui, Sijia; Guo, Liyuan; Zhang, Liuyan; Wang, Jing

    2011-01-01

    Genome-wide association study (GWAS) is widely utilized to identify genes involved in human complex disease or some other trait. One key challenge for GWAS data interpretation is to identify causal SNPs and provide profound evidence on how they affect the trait. Currently, researches are focusing on identification of candidate causal variants from the most significant SNPs of GWAS, while there is lack of support on biological mechanisms as represented by pathways. Although pathway-based analysis (PBA) has been designed to identify disease-related pathways by analyzing the full list of SNPs from GWAS, it does not emphasize on interpreting causal SNPs. To our knowledge, so far there is no web server available to solve the challenge for GWAS data interpretation within one analytical framework. ICSNPathway is developed to identify candidate causal SNPs and their corresponding candidate causal pathways from GWAS by integrating linkage disequilibrium (LD) analysis, functional SNP annotation and PBA. ICSNPathway provides a feasible solution to bridge the gap between GWAS and disease mechanism study by generating hypothesis of SNP → gene → pathway(s). The ICSNPathway server is freely available at http://icsnpathway.psych.ac.cn/. PMID:21622953

  1. Glycolytic pathway and hydrogen yield studies of the extreme thermophile Caldicellulosiruptor saccharolyticus

    NARCIS (Netherlands)

    Vrije, de G.J.; Mars, A.E.; Budde, M.A.W.; Lai, M.H.; Dijkema, C.; Waard, de P.; Claassen, P.A.M.

    2007-01-01

    NMR analysis of 13C-labelling patterns showed that the Embden¿Meyerhof (EM) pathway is the main route for glycolysis in the extreme thermophile Caldicellulosiruptor saccharolyticus. Glucose fermentation via the EM pathway to acetate results in a theoretical yield of 4 mol of hydrogen and 2 mol of

  2. Defining and Modeling Known Adverse Outcome Pathways: Domoic Acid and Neuronal Signaling as a Case Study

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Karen H.; Andersen, Melvin E.; Basu, Nil; Carvan, Michael J.; Crofton, Kevin M.; King, Kerensa A.; Sunol, Cristina; Tiffany-Castiglioni, Evelyn; Schultz, Irvin R.

    2011-01-01

    An adverse outcome pathway (AOP) is a sequence of key events from a molecular-level initiating event and an ensuing cascade of steps to an adverse outcome with population level significance. To implement a predictive strategy for ecotoxicology, the multiscale nature of an AOP requires computational models to link salient processes (e.g., in chemical uptake, toxicokinetics, toxicodynamics, and population dynamics). A case study with domoic acid was used to demonstrate strategies and enable generic recommendations for developing computational models in an effort to move toward a toxicity testing paradigm focused on toxicity pathway perturbations applicable to ecological risk assessment. Domoic acid, an algal toxin with adverse effects on both wildlife and humans, is a potent agonist for kainate receptors (ionotropic glutamate receptors whose activation leads to the influx of Na+ and Ca2+). Increased Ca2+ concentrations result in neuronal excitotoxicity and cell death primarily in the hippocampus, which produces seizures, impairs learning and memory, and alters behavior in some species. Altered neuronal Ca2+ is a key process in domoic acid toxicity which can be evaluated in vitro. Further, results of these assays would be amenable to mechanistic modeling for identifying domoic acid concentrations and Ca2+ perturbations that are normal, adaptive, or clearly toxic. In vitro assays with outputs amenable to measurement in exposed populations can link in vitro to in vivo conditions, and toxicokinetic information will aid in linking in vitro results to the individual organism. Development of an AOP required an iterative process with three important outcomes: (1) a critically reviewed, stressor-specific AOP; (2) identification of key processes suitable for evaluation with in vitro assays; and (3) strategies for model development.

  3. Pathways in coal thermolysis: a theoretical and experimental study with model compounds

    Energy Technology Data Exchange (ETDEWEB)

    Ekpenyong, I.A.; Virk, P.S.

    1982-01-01

    Fundamental aspects of coal thermolysis were investigated, including how the chemical structures of aromatics, hydroaromatics, and alcohols affect their reactivities as hydrogen donors and acceptors in coal processing. The susceptibilities of substructural entities in coals to fragmentation via a number of thermal pericyclic and free radical mechanisms were probed, as were the factors governing relative reactivities within series of such coal model compounds. The theoretical part of the work applied perturbation molecular orbital (PMO) and frontier orbital theories, in conjunction with ..pi..- and pseudo-..pi.. MO's, to the study of model compound reactivity. This enabled prediction of reactivity patterns of H-donors, H-acceptors and coal-like structures as functions of their ..pi..- and sigma-bond configurations, including heteroatomic effects. Experimentally, the liquid phase reactions of the coal model compound PhOCH/sub 2/Ph (Benzyl phenyl ether, BPE) were detailed for the first time in each of four hydronaphthalene H-donor solvents in the temperature range 220/sup 0/ to 300/sup 0/C. The thermolysis of BPE exhibited a pronounced dependence on solvent structure, both with respect to product selectivities and reaction kinetics. BPE thermolysis pathways were delineated as involving (a) rearrangement, leading to isomerization, (b) hydrogenations, leading ultimately to PhOH and PhCH/sub 3/ products, and (c) addition reactions, engendering heavy products. Pathways (b) and (c) are competitive and, in each, self-reactions of BPE-derivatives vie against reactions between these and the donor solvent. Of the detailed free radical and pericyclic reaction mechanisms postulated, the latter rationalized many more facets of the BPE results than the former. The theoretical and experimental results were appraised against previous coal thermolysis literature.

  4. Predictability and epidemic pathways in global outbreaks of infectious diseases: the SARS case study

    Directory of Open Access Journals (Sweden)

    Barthélemy Marc

    2007-11-01

    Full Text Available Abstract Background The global spread of the severe acute respiratory syndrome (SARS epidemic has clearly shown the importance of considering the long-range transportation networks in the understanding of emerging diseases outbreaks. The introduction of extensive transportation data sets is therefore an important step in order to develop epidemic models endowed with realism. Methods We develop a general stochastic meta-population model that incorporates actual travel and census data among 3 100 urban areas in 220 countries. The model allows probabilistic predictions on the likelihood of country outbreaks and their magnitude. The level of predictability offered by the model can be quantitatively analyzed and related to the appearance of robust epidemic pathways that represent the most probable routes for the spread of the disease. Results In order to assess the predictive power of the model, the case study of the global spread of SARS is considered. The disease parameter values and initial conditions used in the model are evaluated from empirical data for Hong Kong. The outbreak likelihood for specific countries is evaluated along with the emerging epidemic pathways. Simulation results are in agreement with the empirical data of the SARS worldwide epidemic. Conclusion The presented computational approach shows that the integration of long-range mobility and demographic data provides epidemic models with a predictive power that can be consistently tested and theoretically motivated. This computational strategy can be therefore considered as a general tool in the analysis and forecast of the global spreading of emerging diseases and in the definition of containment policies aimed at reducing the effects of potentially catastrophic outbreaks.

  5. Motor pathway degeneration in young ataxia telangiectasia patients: A diffusion tractography study.

    Science.gov (United States)

    Sahama, Ishani; Sinclair, Kate; Fiori, Simona; Doecke, James; Pannek, Kerstin; Reid, Lee; Lavin, Martin; Rose, Stephen

    2015-01-01

    Our understanding of the effect of ataxia-telangiectasia mutated gene mutations on brain structure and function is limited. In this study, white matter motor pathway integrity was investigated in ataxia telangiectasia patients using diffusion MRI and probabilistic tractography. Diffusion MRI were obtained from 12 patients (age range: 7-22 years, mean: 12 years) and 12 typically developing age matched participants (age range 8-23 years, mean: 13 years). White matter fiber tracking and whole tract statistical analyses were used to assess quantitative fractional anisotropy and mean diffusivity differences along the cortico-ponto-cerebellar, cerebellar-thalamo-cortical, somatosensory and lateral corticospinal tract length in patients using a linear mixed effects model. White matter tract streamline number and apparent fiber density in patient and control tracts were also assessed. Reduced fractional anisotropy along all analyzed patient tracts were observed (p < 0.001). Mean diffusivity was significantly elevated in anterior tract locations but was reduced within cerebellar peduncle regions of all patient tracts (p < 0.001). Reduced tract streamline number and tract volume in the left and right corticospinal and somatosensory tracts were observed in patients (p < 0.006). In addition, reduced apparent fiber density in the left and right corticospinal and right somatosensory tracts (p < 0.006) occurred in patients. Whole tract analysis of the corticomotor, corticospinal and somatosensory pathways in ataxia telangiectasia showed significant white matter degeneration along the entire length of motor circuits, highlighting that ataxia-telangiectasia gene mutation impacts the cerebellum and multiple other motor circuits in young patients.

  6. Intervention pathways towards improving the resilience of pastoralists: A study from Borana communities, southern Ethiopia

    Directory of Open Access Journals (Sweden)

    Argaw Ambelu

    2017-09-01

    Full Text Available Building resilient communities towards recurrent droughts is increasingly becoming an important element in development endeavours, particularly among communities vulnerable to shocks and stresses. Despite decades of remarkable efforts made by governmental and non-governmental organization, the resilience capacity of pastoralists in Ethiopia remains poor. The aim of this study is to test the statistical relationships among the resilience dimensions that emerged through community consultations, and to identify the intervention pathways for effective resilience building efforts. Data were collected from 1058 randomly sampled households in Arero and Dhas districts of Borana Zone, Southern Ethiopia. The data were collected through interviewer administered structured questionnaire and observational checklist. Principal component analyses were done to develop composite scores of the different resilience dimensions. Structural equation model (SEM verified the theoretical model. The SEM also revealed that resilience towards impact of recurrent droughts was multi-dimensional and showed statistically significant (p < 0.05 relationships. Consequently, household food insecurity manifested as ultimate outcome of poor resilience. Infrastructure and social services (β = −0.24, livestock dimension (β = −0.21, human capital (β = −0.12, psychosocial distress (β = −0.1 dimensions significantly (p < 0.05 affected the status of household food insecurity. Furthermore, livestock and wealth (β = 0.16, wealth and infrastructure (β = 0.06, infrastructure and human capital (β = 0.18, livestock and psychosocial distress (β = −0.09 dimensions have structural relationships and significantly influence each other. Environment, and peace and security are found to be major underlying resilience factors and significantly associated with pastoralists’ resilience which affect other resilience dimensions. The intervention pathway indicated that

  7. Early postnatal development of the rat corticostriatal pathway: an anterograde axonal tracing study using biocytin pellets.

    Science.gov (United States)

    Christensen, J; Sørensen, J C; Ostergaard, K; Zimmer, J

    1999-07-01

    The ontogenetic development of the neocortical projections to the striatum was studied in postnatal rats by sensitive anterograde tracing with biocytin. The developmental status of this mainly glutamatergic pathway is important as it plays a major role in regulation of striatal maturation and induction of excitotoxic striatal neurodegeneration resembling the type found in Huntington's disease. Biocytin pelletts were injected into the motorcortex caudal forelimb area of newborn rats and of rats aged 3, 6, 13, 27 and 61 days followed by sacrifice and visualisation of the tracer 24 h later, at P1, P7, P14, P28 and P62, respectively. Biocytin pellets were also injected into the motorcortex jaw-lip-tongue area and into the cingulate cortex of newborn and 6-day-old rats. The biocytin pellets produced intense anterograde labelling of corticofugal projection fibres from the injection sites, as well as a local Golgi-like labelling of neurons. From postnatal day 1 into adult age efferent fibres from the motorcortex caudal forelimb area displayed a progressively denser innervation of the ipsilateral and contralateral, dorsolateral striatum. The terminating fibres were most dense in the ipsilateral striatum. In the dorsolateral striatum the corticostriatal fibres displayed a patch/matrix-like arrangement from postnatal day 14 onwards. Injections into the motorcortex jaw-lip-tongue area at postnatal days 0 and 6 displayed a progressive, denser innervation of the ipsilateral and contralateral ventrolateral striatum. The cingulate corticostriatal fibre projection, was more developed at birth than the projection from the motorcortex and increased its fibre density in the ipsilateral dorsomedial striatum up to at least day 7. the ipsilateral corticostriatal projections from the rat motorcortex and cingulate areas are present in newborn rats. During postnatal life the pathway develops further and specialisation of the terminating fibres into a patch/matrix like arrangement can be

  8. Adjuvant and salvage radiotherapy after prostatectomy: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Changhao Chen

    Full Text Available In men with adverse prognostic factors (APFs after radical prostatectomy (RP, the most appropriate timing to administer radiotherapy remains a subject for debate. We conducted a systemic review and meta-analysis to evaluate the therapeutic strategies: adjuvant radiotherapy (ART and salvage radiotherapy (SRT.We comprehensively searched PubMed, EMBASE, Web of Science and the Cochrane Library and performed the meta-analysis of all randomized controlled trials (RCTs and retrospective comparative studies assessing the prognostic factors of ART and SRT.Between May 1998 and July 2012, 2 matched control studies and 16 retrospective studies including a total of 2629 cases were identified (1404 cases for ART and 1185 cases for SRT. 5-year biochemical failure free survival (BFFS for ART was longer than that for SRT (Hazard Ratio [HR]: 0.37; 95% CI, 0.30-0.46; p<0.00001, I(2 = 0%. 3-year BFFS was significantly longer in the ART (HR: 0.38; 95% CI, 0.28-0.52; p<0.00001, I(2 = 0%. Overall survival (OS was also better in the ART (RR: 0.53; 95% CI, 0.41-0.68; p<0.00001, I(2 = 0%, as did disease free survival (DFS (RR: 0.53; 95% CI, 0.43-0.66; p<0.00001, I(2  = 0%. Exploratory subgroup analysis and sensitivity analysis revealed the similar results with original analysis.ART therapy offers a safe and efficient alternative to SRT with longer 3-year and 5-year BFFS, better OS and DFS. Our recommendation is to suggest ART for patients with APFs and may reduce the need for SRT. Given the inherent limitations of the included studies, future well-designed RCTs are awaited to confirm and update this analysis.

  9. Oncological and functional outcomes of salvage renal surgery following failed primary intervention for renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Fernando G. Abarzua-Cabezas

    2015-02-01

    Full Text Available Purpose To assess the oncologic and functional outcomes of salvage renal surgery following failed primary intervention for RCC. Materials and Methods We performed a retrospective review of patients who underwent surgery for suspected RCC during 2004-2012. We identified 839 patients, 13 of whom required salvage renal surgery. Demographic data was collected for all patients. Intraoperative and postoperative data included ischemic duration, blood loss and perioperative complications. Preoperative and postoperative assessments included abdominal CT or magnetic resonance imaging, chest CT and routine laboratory work. Estimated glomerular filtration rate (eGFR was calculated according to the Modification of Diet in Renal Disease equation. Results The majority (85% of the patients were male, with an average age of 64 years. Ten patients underwent salvage partial nephrectomy while 3 underwent salvage radical nephrectomy. Cryotherapy was the predominant primary failed treatment modality, with 31% of patients undergoing primary open surgery. Pre-operatively, three patients were projected to require permanent post-operative dialysis. In the remaining 10 patients, mean pre- and postoperative serum creatinine and eGFR levels were 1.35 mg/dL and 53.8 mL/min/1.73 m2 compared to 1.43 mg/dL and 46.6 mL/min/1.73 m2, respectively. Mean warm ischemia time in 10 patients was 17.4 min and for all patients, the mean blood loss was 647 mL. The predominant pathological stage was pT1a (8/13; 62%. Negative surgical margins were achieved in all cases. The mean follow-up was 32.9 months (3.5-88 months. Conclusion While salvage renal surgery can be challenging, it is feasible and has adequate surgical, functional and oncological outcomes.

  10. Microvascular Resistance Predicts Myocardial Salvage and Infarct Characteristics in ST‐Elevation Myocardial Infarction

    Science.gov (United States)

    Payne, Alexander R.; Berry, Colin; Doolin, Orla; McEntegart, Margaret; Petrie, Mark C.; Lindsay, M. Mitchell; Hood, Stuart; Carrick, David; Tzemos, Niko; Weale, Peter; McComb, Christie; Foster, John; Ford, Ian; Oldroyd, Keith G.

    2012-01-01

    Background The pathophysiology of myocardial injury and repair in patients with ST‐elevation myocardial infarction is incompletely understood. We investigated the relationships among culprit artery microvascular resistance, myocardial salvage, and ventricular function. Methods and Results The index of microvascular resistance (IMR) was measured by means of a pressure‐ and temperature‐sensitive coronary guidewire in 108 patients with ST‐elevation myocardial infarction (83% male) at the end of primary percutaneous coronary intervention. Paired cardiac MRI (cardiac magnetic resonance) scans were performed early (2 days; n=108) and late (3 months; n=96) after myocardial infarction. T2‐weighted‐ and late gadolinium–enhanced cardiac magnetic resonance delineated the ischemic area at risk and infarct size, respectively. Myocardial salvage was calculated by subtracting infarct size from area at risk. Univariable and multivariable models were constructed to determine the impact of IMR on cardiac magnetic resonance–derived surrogate outcomes. The median (interquartile range) IMR was 28 (17–42) mm Hg/s. The median (interquartile range) area at risk was 32% (24%–41%) of left ventricular mass, and the myocardial salvage index was 21% (11%–43%). IMR was a significant multivariable predictor of early myocardial salvage, with a multiplicative effect of 0.87 (95% confidence interval 0.82 to 0.92) per 20% increase in IMR; Pmicrovascular obstruction and myocardial hemorrhage. Conclusion Microvascular resistance measured during primary percutaneous coronary intervention significantly predicts myocardial salvage, infarct characteristics, and left ventricular ejection fraction in patients with ST‐elevation myocardial infarction. (J Am Heart Assoc. 2012;1:e002246 doi: 10.1161/JAHA.112.002246) PMID:23130166

  11. Adjuvant Versus Salvage Radiotherapy for Patients With Adverse Pathological Findings Following Radical Prostatectomy: A Decision Analysis

    Directory of Open Access Journals (Sweden)

    Christopher J. D. Wallis MD

    2017-05-01

    Full Text Available Background: Patients undergoing surgery for prostate cancer who have adverse pathological findings experience high rates of recurrence. While there are data supporting adjuvant radiotherapy compared to a wait-and-watch strategy to reduce recurrence rates, there are no randomized controlled trials comparing adjuvant radiotherapy with the other standard of care, salvage radiotherapy (radiotherapy administered at the time of recurrence. Methods: We constructed a health state transition (Markov model employing two-dimensional Monte Carlo simulation using a lifetime horizon to compare the quality-adjusted survival associated with postoperative strategies using adjuvant or salvage radiotherapy. Prior to analysis, we calibrated and validated our model using the results of previous randomized controlled trials. We considered clinically important oncological health states from immediately postoperative to prostate cancer–specific death, commonly described complications from prostate cancer treatment, and other causes of mortality. Transition probabilities and utilities for disease states were derived from a literature search of MEDLINE and expert consensus. Results: Salvage radiotherapy was associated with an increased quality-adjusted life expectancy (QALE (58.3 months as compared with adjuvant radiotherapy (53.7 months, a difference of 4.6 months (standard deviation 8.8. Salvage radiotherapy had higher QALE in 53% of hypothetical cohorts. There was a minimal difference in overall life expectancy (-0.1 months. Examining recurrence rates, our model showed validity when compared with available randomized controlled data. Conclusions: A salvage radiotherapy strategy appears to provide improved QALE for patients with adverse pathological findings following radical prostatectomy, compared with adjuvant radiotherapy. As these findings reflect, population averages, specific patient and tumor factors, and patient preferences remain central for individualized

  12. Second salvage high-dose-rate brachytherapy for radiorecurrent prostate cancer

    Directory of Open Access Journals (Sweden)

    Metha Maenhout

    2017-04-01

    Full Text Available Purpose : Salvage treatments for localized radiorecurrent prostate cancer can be performed safely when a focal and image guided approach is used. Due to the low toxicity, the opportunity exists to investigate a second salvage treatment when a second locally recurrent prostate cancer occurs. Here, we describe a second salvage treatment procedure of 4 patients. Material and methods : Four patients with a pathologically proven second local recurrence were treated in an outpatient magnetic resonance imaging (MRI-guided setting with a single fraction of 19 Gy focal high-dose-rate brachytherapy (HDR-BT. Delineation was performed using choline-PET-CT or a 68Ga-PSMA PET in combination with multiparametric 3 Tesla MRI in all four patients. Toxicity was measured using common toxicity criteria for adverse events (CTCAE version 4.0. Results : With a median follow-up of 12 months (range, 6-15, there were 2 patients with biochemical recurrence as defined by the Phoenix-definition. There were no patients with grade 3 or more toxicity. In all second salvage HDR-BT treatments, the constraints for rectum, bladder, and urethra were met. Median treatment volume (GTV was 4.8 cc (range, 1.9-6.6 cc. A median of 8 catheters (range, 6-9 were used, and the median dose to the treatment volume (GTV was a D95: 19.3 Gy (SD 15.5-19.4 Gy. Conclusions : Second focal salvage MRI-guided HDR-BT for a select group of patients with a second locally recurrent prostate cancer is feasible. There was no grade 3 or more acute toxicity for these four patients.

  13. Anhydride formation is not a valid mechanism for peptide cleavage by carboxypeptidase-A: a semiempirical reaction pathway study

    Science.gov (United States)

    Vardi-Kilshtain, Alexandra; Shoham, Gil; Goldblum, Amiram

    The mechanism of action of zinc metalloproteinases has been studied by following the direct nucleophilic pathway, which has been frequently suggested but not yet examined by computational methods, and comparing it to other pathways. We computed the reaction enthalpies for the direct nucleophilic attack by Glu270 in the active site model of carboxypeptidase-A on a model substrate's peptide carbonyl and followed this pathway through mixed anhydride formation and subsequent anhydride cleavage by water. The starting molecular coordinates originate in our own high-resolution crystal structure and the computations have been conducted with the minimal neglect of differential overlap (MNDO) Hamiltonian, modified to include the d-orbitals of zinc and the effects of multiple hydrogen bonding, thus labelled MNDO/d/H. Compared to our recent results for two other candidate pathways for this mechanism, both of the General-Acid-General-Base type, we conclude that the direct nucleophilic or 'anhydride' pathway has a much higher energy barrier at the rate determining step, which is a proton transfer, than previously calculated paths. We argue that the 'anhydride' pathway is thus not a valid one for the cleavage of peptides by carboxypeptidase-A.

  14. Salvage logging effect on soil properties in a fire-affected Mediterranean forest: a two years monitoring research

    Science.gov (United States)

    Mataix-Solera, Jorge; Moltó, Jorge; Arcenegui, Vicky; García-Orenes, Fuensanta; Chrenkovà, Katerina; Torres, Pilar; Jara-Navarro, Ana B.; Díaz, Gisela; Izquierdo, Ezequiel

    2015-04-01

    In the Mediterranean countries, forest fires are common and must be considered as an ecological factor, but changes in land use, especially in the last five decades have provoked a modification in their natural regime. Moreover, post-fire management can have an additional impact on the ecosystem; in some cases, even more severe than the fire. Salvage logging is a traditional management in most fire-affected areas. In some cases, the way of doing it, using heavy machinery, and the vulnerability of soils to erosion and degradation make this management potentially very agresive to soil, and therefore to the ecosystem. Very little research has been done to study how this treatment could affect soil health. In this research we show 2 years of monitoring of some soil properties in an area affected by a forest fire, where some months later this treatment was applied. The study area is located in 'Sierra de Mariola Natural Park' in Alcoi, Alicante (E Spain). A big forest fire (>500 has) occurred in July 2012. The forest is composed mainly of Pinus halepensis trees with an understory of typical Mediterranean shrubs species such as Quercus coccifera, Rosmarinus officinalis, Thymus vulgaris, Brachypodium retusum, etc. Soil is classified as a Typic Xerorthent (Soil Survey Staff, 2014) developed over marls. In February 2013, salvage logging (SL) treatment consisting in a complete extraction of the burned wood using heavy machinery was applied in a part of the affected forest. Plots for monitoring this effect were installed in this area and in a similar nearby area where no treatment was done, and then used as control (C) for comparison. Soil samplings were done immediately after treatment and every 6 months. Some soil properties were analysed, including soil organic matter (SOM) content, basal soil respiration (BSR), microbial biomass carbon (MBC), bulk density (BD), soil water repellency (SWR), aggregate stability (AS), field capacity, nitrogen, etc. After two years of

  15. Can salvage logging affect seed dispersal by birds into burned forests?

    Science.gov (United States)

    Rost, J.; Pons, P.; Bas, J. M.

    2009-09-01

    The recovery of vegetation in Mediterranean ecosystems after wildfire is mostly a result of direct regeneration, since the same species existing before the fire regenerate on-site by seeding or resprouting. However, the possibility of plant colonization by dispersal of seeds from unburned areas remains poorly studied. We addressed the role of the frugivorous, bird-dependent seed dispersal (seed rain) of fleshy-fruited plants in a burned and managed forest in the second winter after a fire, before on-site fruit production had begun. We also assessed the effect on seed rain of different microhabitats resulting from salvage logging (erosion barriers, standing snags, open areas), as well as the microhabitats of unlogged patches and an unburned control forest, taking account of the importance of perches as seed rain sites. We found considerable seed rain by birds in the burned area. Seeds, mostly from Olive trees Olea europaea and Evergreen pistaches Pistacia lentiscus, belonged to plants fruiting only in surrounding unburned areas. Seed rain was heterogeneous, and depended on microhabitat, with the highest seed density in the unburned control forest but closely followed by the wood piles of erosion barriers. In contrast, very low densities were found under perches of standing snags. Furthermore, frugivorous bird richness seemed to be higher in the erosion barriers than elsewhere. Our results highlight the importance of this specific post-fire management in bird-dependent seed rain and also may suggest a consequent heterogeneous distribution of fleshy-fruited plants in burned and managed areas. However, there needs to be more study of the establishment success of dispersed seeds before an accurate assessment can be made of the role of bird-mediated seed dispersal in post-fire regeneration.

  16. Salvamento de acesso vascular para hemodiálise: relato de caso Hemodialysis vascular access salvage: case report

    Directory of Open Access Journals (Sweden)

    Milton Alves das Neves Junior

    2010-09-01

    Full Text Available A insuficiência renal crônica (IRC tem alta prevalência e a maior parte dos pacientes acometidos está em programa de hemodiálise necessitando, portanto, de acesso vascular. As fístulas arteriovenosas (FAV são os acessos mais indicados e duradouros. Mesmo em casos de complicações, deve-se tentar o salvamento desses acessos. Trabalhos da literatura mostram a possibilidade de salvamento das FAV's, mesmo de maneira tardia. Deve-se tentar sempre a reparação do acesso atual, evitando o esgotamento do sistema venoso. Este trabalho relata o caso de uma paciente de 69 anos com IRC apresentando uma trombose de FAV braquiocefálica com drenagem para veia basílica por ramos colaterais, o que a tornou maturada. Essa veia foi utilizada no reparo do acesso, evitando o uso de cateteres.Chronic renal insufficiency (CRI has high prevalence and the majority of the patients are in hemodialysis program and, then, they need a vascular access. Arteriovenous fistulas (AVF are the more indicated accesses and have a long term use. Even in cases of complications, the salvage of theses accesses must be tried. Researches of literature show the possibility of access salvage of AFV's, even in a long time after the complication. The repair of thepresent access must always be tried, avoiding the depletion of the venous system. This study is a case report of a 69 years-old female patient with CRI presenting thrombosis of a brachial-cefalic AFV with drainage to basilic vein by collateral branches, which maturated that vein. Basilic vein was used on the access repair, avoiding catheter use.

  17. Vascularised fibular grafts as a salvage procedure in failed intercalary reconstructions after bone tumour resection of the femur.

    Science.gov (United States)

    Campanacci, Domenico Andrea; Puccini, Serena; Caff, Giuseppe; Beltrami, Giovanni; Piccioli, Andrea; Innocenti, Marco; Capanna, Rodolfo

    2014-02-01

    Vascularised fibular grafts (VFGs) are widely used for primary reconstruction of long bones after bone tumour resections. The biological properties of VFGs are such that they can be a useful option even in failed intercalary reconstructions. The purpose of the current study was to investigate the results and the morbidity of VFGs as a salvage procedure in failed previous reconstructions after intercalary bone tumour resection of the femur. Our series included 12 patients, treated from April 1989 to March 2005, with an average age of 23 years (range 10-43 years) at presentation. The initial diagnosis was osteosarcoma in 10 cases and Ewing's sarcoma in two cases. All patients received chemotherapy and none received radiation therapy. Seven patients received VFG as biologic augmentation in intercalary allograft non-union and in the other five patients, a combination of allograft and VFG was used to replace a cement spacer with hardware failure (four patients) and a failed intercalary prosthesis (one patient). Three patients died during follow-up, in all cases because of metastatic disease. At an average follow-up of 147 months (range 11-260 months), the remaining nine patients were continuously disease-free. Complete healing of the osteotomy of both allograft and VFG was observed in 10 patients at final follow-up. Two major complications were observed that required surgical revision, eventually healing in one case and leading to a poor functional outcome in one case. Significant hypertrophy of the VFG was detected in seven of nine evaluable patients. At final follow-up the mean Musculoskeletal Tumour Society (MSTS)'93 functional score of the nine evaluable patients was 90% (range 66-100%). These results indicate that VFG is a valid salvage procedure in failed intercalary reconstructions of the femur after bone resection. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Induced Pluripotent Stem Cell Neuronal Models for the Study of Autophagy Pathways in Human Neurodegenerative Disease.

    Science.gov (United States)

    Jiménez-Moreno, Natalia; Stathakos, Petros; Caldwell, Maeve A; Lane, Jon D

    2017-08-11

    Human induced pluripotent stem cells (hiPSCs) are invaluable tools for research into the causes of diverse human diseases, and have enormous potential in the emerging field of regenerative medicine. Our ability to reprogramme patient cells to become hiPSCs, and to subsequently direct their differentiation towards those classes of neurons that are vulnerable to stress, is revealing how genetic mutations cause changes at the molecular level that drive the complex pathogeneses of human neurodegenerative diseases. Autophagy dysregulation is considered to be a major contributor in neural decline during the onset and progression of many human neurodegenerative diseases, meaning that a better understanding of the control of non-selective and selective autophagy pathways (including mitophagy) in disease-affected classes of neurons is needed. To achieve this, it is essential that the methodologies commonly used to study autophagy regulation under basal and stressed conditions in standard cell-line models are accurately applied when using hiPSC-derived neuronal cultures. Here, we discuss the roles and control of autophagy in human stem cells, and how autophagy contributes to neural differentiation in vitro. We also describe how autophagy-monitoring tools can be applied to hiPSC-derived neurons for the study of human neurodegenerative disease in vitro.

  19. Phytochemicals as multi-target inhibitors of the inflammatory pathway- A modeling and experimental study.

    Science.gov (United States)

    Devi, Nisha S; Ramanan, Meera; Paragi-Vedanthi, Padmapriya; Doble, Mukesh

    2017-03-11

    The arachidonic acid pathway consists of several enzymes and targeting them is favored for developing anti-inflammatory drugs. However, till date the current drugs are generally active against a single target, leading to undesirable side-effects. Phytochemicals are known to inhibit multiple targets simultaneously and hence, an attempt is made here to investigate their suitability. A pharmacophore based study is performed with three sets of reported phytochemicals namely, dual 5-LOX/mPGES1, alkaloids and FLAP inhibitors. The analysis indicated that phenylpropanoids (including ferulic acid) and benzoic acids derivatives, and berberine mapped onto these pharmacophores with three hydrophobic centroids and an acceptor feature. 2,4,5-trimethoxy (7) and 3,4-dimethoxy cinnamic acids (8) mapped onto all the three pharmacophores. Experimental studies indicated that berberine inhibited 5-LOX (100 μM) and PGE 2 (50 μM) production by 72.2 and 72.0% and ferulic acid by 74.3 and 54.4% respectively. This approach offers a promising theoretical combined with experimental strategy for designing novel molecules against inflammatory enzymes. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Immune characteristics study of AG490, a signal pathway inhibitor, in EAE model mice

    Directory of Open Access Journals (Sweden)

    Zhihua Zhao

    2017-02-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by demyelination, axonal damage and progressive neurologic dysfunction in central nervous system (CNS. Many evidences show that B cells play an important role in the pathogenesis of MS. Follicular helper T cells (Tfh secrete IL-21 to prompt the proliferation and differentiation of B cells in germinal center (GC through clonal proliferation, somatic hypermutation, antibody class switching, antibody affinity maturation process. AG490 is a synthetic inhibitor to JAK-STAT signal pathway, which has been studied in inflammatory, tumor and autoimmune diseases. In the present study, the experimental mice were divided into 3 groups, vehicle group and AG490 group were given MOG35-55 to induce EAE model, from the third day after immunization, the mice were given vehicle or AG490 by intraperitoneal injection every other day. All mice were assessed clinical scores after immunization. On twentieth day, all mice were sacrificed, HE staining and solochrome cyanine staining were performed to evaluate inflammatory cells infiltration and demyelination, spleen sections were stained with PNA-FITC to analyze the difference in germinal center. Compared with vehicle group, the incidence of AG490 group was deceased, onset time was delayed, the severity was significantly reduced. The inflammatory cells and demyelination in AG490 group were lower than those in vehicle group. Immunofluorescence showed the fluorescence intensity of AG490 group was significantly lower than in the vehicle group, but higher than that of control group.

  1. Preparing for the Educational Black Hole? Teachers' Learning in Two Pathways into Middle School Social Studies Teaching

    Science.gov (United States)

    Conklin, Hilary G.

    2010-01-01

    The author presents findings from the first phase of a longitudinal, comparative case study that investigates what teachers learn about intellectually demanding social studies teaching at the middle school level from two distinctive teacher education pathways: a specialized middle school teacher education program and a secondary social studies…

  2. Exploration of Counsellors' Perceptions of the Redesigned Service Pathways: A Qualitative Study of a UK University Student Counselling Service

    Science.gov (United States)

    Randall, Eve M.; Bewick, Bridgette M.

    2016-01-01

    To address the mental health needs of students, UK universities offer bespoke student counselling services. Economic pressures have led services to find innovative ways of redesigning their service pathway. Few studies have investigated staff perceptions of these changes. The aim of this study was to investigate perceptions of staff employed as…

  3. Pyrolysis of methyl tert-butyl ether (MTBE). 2. Theoretical study of decomposition pathways.

    Science.gov (United States)

    Zhang, Taichang; Zhang, Lidong; Wang, Jing; Yuan, Tao; Hong, Xin; Qi, Fei

    2008-10-23

    The thermal decomposition pathways of MTBE have been investigated using the G3B3 method. On the basis of the experimental observation and theoretical calculation, the pyrolysis channels are provided, especially for primary pyrolysis reactions. The primary decomposition pathways include formation of methanol and isobutene, CH4 elimination, H2 elimination and C-H, C-C, C-O bond cleavage reactions. Among them, the formation channel of methanol and isobutene is the lowest energy pathway, which is in accordance with experimental observation. Furthermore, the secondary pyrolysis pathways have been calculated as well, including decomposition of tert-butyl radical, isobutene, methanol and acetone. The radicals play an important role in the formation of pyrolysis products, for example, tert-butyl radical and allyl radical are major precursors for the formation of allene and propyne. Although some isomers (isobutene and 1-butene, allene and propyne, acetone and propanal) are identified in our experiment, these isomerization reaction pathways occur merely at the high temperature due to their high activation energies. The theoretical calculation can explain the experimental results reported in part 1 and shed further light on the thermal decomposition pathways.

  4. Use of spatiotemporal templates for pathway discrimination in peripheral nerve recordings: a simulation study

    Science.gov (United States)

    Koh, Ryan G. L.; Nachman, Adrian I.; Zariffa, José

    2017-02-01

    Objective. Extraction of information from the peripheral nervous system can provide control signals in neuroprosthetic applications. However, the ability to selectively record from different pathways within peripheral nerves is limited. We investigated the integration of spatial and temporal information for pathway discrimination in peripheral nerves using measurements from a multi-contact nerve cuff electrode. Approach. Spatiotemporal templates were established for different neural pathways of interest, and used to obtain tailored matched filters for each of these pathways. Simulated measurements of compound action potentials propagating through the nerve in different test cases were used to evaluate classification accuracy, percentage of missed spikes, and ability to reconstruct the original firing rates of the neural pathways. Main results. The mean Pearson correlation coefficients between the original firing rates and estimated firing rates over all tests cases was found to be 0.832  ±  0.161, 0.421  ±  0.145, 0.481  ±  0.340 for our algorithm, Bayesian spatial filters, and velocity selective recordings respectively. Significance. The proposed method shows that the spatiotemporal templates were able to provide more robust spike detection and reliable pathway discrimination than these existing algorithms.

  5. Intensity-Modulated Radiation Therapy in the Salvage of Locally Recurrent Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Qiu Sufang [Department of Radiation Oncology, Cancer Hospital of Fujian Medical University, Fuzhou, Fujian (China); Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore (Singapore); Lin Shaojun [Department of Radiation Oncology, Cancer Hospital of Fujian Medical University, Fuzhou, Fujian (China); Tham, Ivan W.K. [Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore (Singapore); Pan Jianji; Lu Jun [Department of Radiation Oncology, Cancer Hospital of Fujian Medical University, Fuzhou, Fujian (China); Lu, Jiade J., E-mail: mdcljj@nus.edu.sg [Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore (Singapore)

    2012-06-01

    Purpose: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. Methods and Materials: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. Results: The median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. Conclusion: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

  6. Direct evaluation of myocardial viability and stem cell engraftment demonstrates salvage of the injured myocardium.

    Science.gov (United States)

    Kim, Paul J; Mahmoudi, Morteza; Ge, Xiaohu; Matsuura, Yuka; Toma, Ildiko; Metzler, Scott; Kooreman, Nigel G; Ramunas, John; Holbrook, Colin; McConnell, Michael V; Blau, Helen; Harnish, Phillip; Rulifson, Eric; Yang, Phillip C

    2015-03-27

    The mechanism of functional restoration by stem cell therapy remains poorly understood. Novel manganese-enhanced MRI and bioluminescence reporter gene imaging were applied to follow myocardial viability and cell engraftment, respectively. Human-placenta-derived amniotic mesenchymal stem cells (AMCs) demonstrate unique immunoregulatory and precardiac properties. In this study, the restorative effects of 3 AMC-derived subpopulations were examined in a murine myocardial injury model: (1) unselected AMCs, (2) ckit(+)AMCs, and (3) AMC-derived induced pluripotent stem cells (MiPSCs). To determine the differential restorative effects of the AMC-derived subpopulations in the murine myocardial injury model using multimodality imaging. SCID (severe combined immunodeficiency) mice underwent left anterior descending artery ligation and were divided into 4 treatment arms: (1) normal saline control (n=14), (2) unselected AMCs (n=10), (3) ckit(+)AMCs (n=13), and (4) MiPSCs (n=11). Cardiac MRI assessed myocardial viability and left ventricular function, whereas bioluminescence imaging assessed stem cell engraftment during a 4-week period. Immunohistological labeling and reverse transcriptase polymerase chain reaction of the explanted myocardium were performed. The unselected AMC and ckit(+)AMC-treated mice demonstrated transient left ventricular functional improvement. However, the MiPSCs exhibited a significantly greater increase in left ventricular function compared with all the other groups during the entire 4-week period. Left ventricular functional improvement correlated with increased myocardial viability and sustained stem cell engraftment. The MiPSC-treated animals lacked any evidence of de novo cardiac differentiation. The functional restoration seen in MiPSCs was characterized by increased myocardial viability and sustained engraftment without de novo cardiac differentiation, indicating salvage of the injured myocardium. © 2015 American Heart Association, Inc.

  7. Host lipid droplets: An important source of lipids salvaged by the intracellular parasite Toxoplasma gondii.

    Science.gov (United States)

    Nolan, Sabrina J; Romano, Julia D; Coppens, Isabelle

    2017-06-01

    Toxoplasma is an obligate intracellular parasite that replicates in mammalian cells within a parasitophorous vacuole (PV) that does not fuse with any host organelles. One mechanism developed by the parasite for nutrient acquisition is the attraction of host organelles to the PV. Here, we examined the exploitation of host lipid droplets (LD), ubiquitous fat storage organelles, by Toxoplasma. We show that Toxoplasma replication is reduced in host cells that are depleted of LD, or impaired in TAG lipolysis or fatty acid catabolism. In infected cells, the number of host LD and the expression of host LD-associated genes (ADRP, DGAT2), progressively increase until the onset of parasite replication. Throughout infection, the PV are surrounded by host LD. Toxoplasma is capable of accessing lipids stored in host LD and incorporates these lipids into its own membranes and LD. Exogenous addition of oleic acid stimulates LD biogenesis in the host cell and results in the overaccumulation of neutral lipids in very large LD inside the parasite. To access LD-derived lipids, Toxoplasma intercepts and internalizes within the PV host LD, some of which remaining associated with Rab7, which become wrapped by an intravacuolar network of membranes (IVN). Mutant parasites impaired in IVN formation display diminished capacity of lipid uptake from host LD. Moreover, parasites lacking an IVN-localized phospholipase A2 are less proficient in salvaging lipids from host LD in the PV, suggesting a major contribution of the IVN for host LD processing in the PV and, thus lipid content release. Interestingly, gavage of parasites with lipids unveils, for the first time, the presence in Toxoplasma of endocytic-like structures containing lipidic material originating from the PV lumen. This study highlights the reliance of Toxoplasma on host LD for its intracellular development and the parasite's capability in scavenging neutral lipids from host LD.

  8. Characteristics and quality of intra-operative cell salvage in paediatric scoliosis surgery.

    Science.gov (United States)

    Perez-Ferrer, A; Gredilla-Díaz, E; de Vicente-Sánchez, J; Navarro-Suay, R; Gilsanz-Rodríguez, F

    2016-02-01

    To determine the haematological and microbiological characteristics of blood recovered by using a cell saver with a rigid centrifuge bowl (100ml) in paediatric scoliosis surgery and to determine whether it conforms to the standard expected in adult patients. A cross-sectional, descriptive cohort study was performed on 24 consecutive red blood cell (RBC) units recovered from the surgical field and processed by a Haemolite® 2+ (Haemonetics Corp., Braintree, MA, EE. UU.) cell saver. Data were collected regarding age, weight, surgical approach (anterior or posterior), processed shed volume and volume of autologous RBC recovered, full blood count, and blood culture obtained from the RBC concentrate, and incidence of fever after reinfusion. The processed shed volume was very low (939±569ml) with high variability (coefficient of variation=0.6), unlike the recovered volume 129±50ml (coefficient of variation=0.38). A statistically significant correlation between the processed shed volume and recovered RBC concentrate haematocrit was found (Pearson, r=.659, P=.001). Haematological parameters in the recovered concentrate were: Hb 11±5.3g dl(-1); haematocrit: 32.1±15.4% (lower than expected); white cells 5.34±4.22×103 ul(-)1; platelets 37.88±23.5×103 ul(-1) (mean±SD). Blood culture was positive in the RBC concentrate recovered in 13 cases (54.2%) in which Staphylococcus coagulase (-) was isolated. Cell salvage machines with rigid centrifuge bowls (including paediatric small volume) do not obtain the expected haematocrit if low volumes are processed, and therefore they are not the best choice in paediatric surgery. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Cardiac MRI of myocardial salvage at the peri-infarct border zones after primary coronary intervention.

    Science.gov (United States)

    O'Regan, Declan P; Ahmed, Rizwan; Neuwirth, Clare; Tan, Yvonne; Durighel, Giuliana; Hajnal, Joseph V; Nadra, Imad; Corbett, Simon J; Cook, Stuart A

    2009-07-01

    The purpose of this study was to use cardiac MRI to define the morphology of the reversibly injured peri-infarct border zone in patients treated with primary percutaneous coronary intervention (PPCI) for acute ST elevation myocardial infarction. In 15 patients, T2-weighted myocardial edema imaging was used to identify the ischemic bed or area at risk (AAR), and late gadolinium enhancement imaging was used to measure infarct size. Images were coregistered, and the boundaries of edema and necrosis were defined using an edge-detection methodology. We observed that infarction always involved the subendocardium but showed variable transmural extension within the AAR. The mean infarct size was 22 +/- 19% (range: 8-48%), and the mean AAR was 34 +/- 12% (range: 20-57%). The infarcted myocardium was always smaller than the ischemic AAR and involved between 34% and 99% (mean 72 +/- 21%) of the ischemic bed primarily due to variation in transmural infarct extension. Although a lateral border zone of potentially viable myocardium was often present, its extent was limited (range: 0-11 mm, mean: 5 +/- 4 mm). As a result of this, infarcts occupied the majority (range: 70-100%, mean: 82 +/- 13%) of the width of the AAR. The mean fractional wall thickening in the infarcted, peri-infarcted, and remote myocardium was 3.6 +/- 16.0%, 40.5 +/- 26.4%, and 88.2 +/- 39.3%, respectively. These findings demonstrate that myocardial salvage is largely determined by epicardial limitation of the infarct within the ischemic AAR after PPCI. The lateral boundaries of necrosis approximate to the lateral extent of the ischemic bed and systolic wall motion abnormalities extend well beyond the infarct border zone.

  10. Paracrine Effects of the Pluripotent Stem Cell-Derived Cardiac Myocytes Salvage the Injured Myocardium.

    Science.gov (United States)

    Tachibana, Atsushi; Santoso, Michelle R; Mahmoudi, Morteza; Shukla, Praveen; Wang, Lei; Bennett, Mihoko; Goldstone, Andrew B; Wang, Mouer; Fukushi, Masahiro; Ebert, Antje D; Woo, Y Joseph; Rulifson, Eric; Yang, Phillip C

    2017-09-01

    Cardiac myocytes derived from pluripotent stem cells have demonstrated the potential to mitigate damage of the infarcted myocardium and improve left ventricular ejection fraction. However, the mechanism underlying the functional benefit is unclear. To evaluate whether the transplantation of cardiac-lineage differentiated derivatives enhance myocardial viability and restore left ventricular ejection fraction more effectively than undifferentiated pluripotent stem cells after a myocardial injury. Herein, we utilize novel multimodality evaluation of human embryonic stem cells (hESCs), hESC-derived cardiac myocytes (hCMs), human induced pluripotent stem cells (iPSCs), and iPSC-derived cardiac myocytes (iCMs) in a murine myocardial injury model. Permanent ligation of the left anterior descending coronary artery was induced in immunosuppressed mice. Intramyocardial injection was performed with (1) hESCs (n=9), (2) iPSCs (n=8), (3) hCMs (n=9), (4) iCMs (n=14), and (5) PBS control (n=10). Left ventricular ejection fraction and myocardial viability, measured by cardiac magnetic resonance imaging and manganese-enhanced magnetic resonance imaging, respectively, was significantly improved in hCM- and iCM-treated mice compared with pluripotent stem cell- or control-treated mice. Bioluminescence imaging revealed limited cell engraftment in all treated groups, suggesting that the cell secretions may underlie the repair mechanism. To determine the paracrine effects of the transplanted cells, cytokines from supernatants from all groups were assessed in vitro. Gene expression and immunohistochemistry analyses of the murine myocardium demonstrated significant upregulation of the promigratory, proangiogenic, and antiapoptotic targets in groups treated with cardiac lineage cells compared with pluripotent stem cell and control groups. This study demonstrates that the cardiac phenotype of hCMs and iCMs salvages the injured myocardium effectively than undifferentiated stem cells through

  11. Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Sun Hyun [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Hee Chul, E-mail: rophc@skku.edu [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lim, Do Hoon; Lee, Jung Ae [Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul [Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-03-15

    Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

  12. Genes Involved in the Endoplasmic Reticulum N-Glycosylation Pathway of the Red Microalga Porphyridium sp.: A Bioinformatic Study

    Directory of Open Access Journals (Sweden)

    Oshrat Levy-Ontman

    2014-02-01

    Full Text Available N-glycosylation is one of the most important post-translational modifications that influence protein polymorphism, including protein structures and their functions. Although this important biological process has been extensively studied in mammals, only limited knowledge exists regarding glycosylation in algae. The current research is focused on the red microalga Porphyridium sp., which is a potentially valuable source for various applications, such as skin therapy, food, and pharmaceuticals. The enzymes involved in the biosynthesis and processing of N-glycans remain undefined in this species, and the mechanism(s of their genetic regulation is completely unknown. In this study, we describe our pioneering attempt to understand the endoplasmic reticulum N-Glycosylation pathway in Porphyridium sp., using a bioinformatic approach. Homology searches, based on sequence similarities with genes encoding proteins involved in the ER N-glycosylation pathway (including their conserved parts were conducted using the TBLASTN function on the algae DNA scaffold contigs database. This approach led to the identification of 24 encoded-genes implicated with the ER N-glycosylation pathway in Porphyridium sp. Homologs were found for almost all known N-glycosylation protein sequences in the ER pathway of Porphyridium sp.; thus, suggesting that the ER-pathway is conserved; as it is in other organisms (animals, plants, yeasts, etc..

  13. Genes Involved in the Endoplasmic Reticulum N-Glycosylation Pathway of the Red Microalga Porphyridium sp.: A Bioinformatic Study

    Science.gov (United States)

    Levy-Ontman, Oshrat; Fisher, Merav; Shotland, Yoram; Weinstein, Yacob; Tekoah, Yoram; Arad, Shoshana Malis

    2014-01-01

    N-glycosylation is one of the most important post-translational modifications that influence protein polymorphism, including protein structures and their functions. Although this important biological process has been extensively studied in mammals, only limited knowledge exists regarding glycosylation in algae. The current research is focused on the red microalga Porphyridium sp., which is a potentially valuable source for various applications, such as skin therapy, food, and pharmaceuticals. The enzymes involved in the biosynthesis and processing of N-glycans remain undefined in this species, and the mechanism(s) of their genetic regulation is completely unknown. In this study, we describe our pioneering attempt to understand the endoplasmic reticulum N-Glycosylation pathway in Porphyridium sp., using a bioinformatic approach. Homology searches, based on sequence similarities with genes encoding proteins involved in the ER N-glycosylation pathway (including their conserved parts) were conducted using the TBLASTN function on the algae DNA scaffold contigs database. This approach led to the identification of 24 encoded-genes implicated with the ER N-glycosylation pathway in Porphyridium sp. Homologs were found for almost all known N-glycosylation protein sequences in the ER pathway of Porphyridium sp.; thus, suggesting that the ER-pathway is conserved; as it is in other organisms (animals, plants, yeasts, etc.). PMID:24514561

  14. Lateral medullary syndrome following injury of the vestibular pathway to the core vestibular cortex: Diffusion tensor imaging study.

    Science.gov (United States)

    Yeo, Sang Seok; Jang, Sung Ho; Kwon, Jung Won

    2017-12-05

    The parieto-insular vestibular cortex (PIVC) is a core region of vestibular input into regions of the cortex. The vestibular nuclei have reciprocal connections with the PIVC. However, little is known about injury of the core vestibular pathway to the PIVC in patients with dorsolateral medullary infarctions. In this study, using diffusion tensor tractography (DTT), we investigated injury of the neural connections between the vestibular nuclei and the PIVC in patients with typical central vestibular disorder. Eight consecutive patients with lateral medullary syndrome and 10 control subjects were recruited for this study. To reconstruct the core vestibular pathway to the PIVC, we defined the seed region of interest (ROI) as the vestibular nuclei of the pons and the target ROI as the PIVC. Fractional anisotropy (FA), mean diffusivity (MD), and tract volume were measured. The core vestibular pathway to the PIVC showed significantly lower tract volume in patients compared with the control group (p0.05). In conclusion, injury of the core vestibular pathway to the PIVC was demonstrated in patients with lateral vestibular syndrome following dorsolateral medullary infarcts. We believe that analysis of the core vestibular pathway to the PIVC using DTT would be helpful in evaluating patients with lateral medullary syndrome. Copyright © 2017. Published by Elsevier B.V.

  15. Commercial production and distribution of fresh fruits and vegetables: A scoping study on the importance of produce pathways to dose

    Energy Technology Data Exchange (ETDEWEB)

    Marsh, T.L.; Anderson, D.M.; Farris, W.T.; Ikenberry, T.A.; Napier, B.A.; Wilfert, G.L.

    1992-09-01

    This letter report summarizes a scoping study that examined the potential importance of fresh fruit and vegetable pathways to dose. A simple production index was constructed with data collected from the Washington State Department of Agriculture (WSDA), the United States Bureau of the Census, and the United States Department of Agriculture (USDA). Hanford Environmental Dose Reconstruction (HEDR) Project staff from Battelle, Pacific Northwest Laboratories, in cooperation with members of the Technical Steering Panel (TSP), selected lettuce and spinach as the produce pathways most likely to impact dose. County agricultural reports published in 1956 provided historical descriptions of the predominant distribution patterns of fresh lettuce and spinach from production regions to local population centers. Pathway rankings and screening dose estimates were calculated for specific populations living in selected locations within the HEDR study area.

  16. Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO.

    Directory of Open Access Journals (Sweden)

    Khalid S Khan

    2017-12-01

    Full Text Available Excessive haemorrhage at cesarean section requires donor (allogeneic blood transfusion. Cell salvage may reduce this requirement.We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016 of routine cell salvage use (intervention versus current standard of care without routine salvage use (control in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome between groups. Among 3,028 women randomised (2,990 analysed, 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06. In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99, whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83 (interaction p = 0.46. No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013. We are unable to comment on long-term antibody sensitisation effects.The overall reduction observed in donor blood transfusion associated with the

  17. Homelessness Pathways for Australian Single Mothers and Their Children: An Exploratory Study

    Directory of Open Access Journals (Sweden)

    Wayne Warburton

    2018-03-01

    Full Text Available There is increasing concern about family homelessness. Homeless mothers and their children are one of society’s most disadvantaged and at-risk populations. However, very little Australian research exploring mothers’ views on their homelessness experiences exists. Using semi-structured interviews with 14 mothers and four agency staff, this study explored homeless Australian mothers’ pathways into and out of homelessness, their specific needs and the services and supports that were (or would have been most helpful. In this sample of single mothers and their children, early experiences of homelessness and domestic violence contributed most commonly to homelessness episodes. Almost immediate engagement with welfare agencies seemed to be protective against re-experiencing homelessness, however Australian restrictions on length of program involvement and limited housing options for mothers exiting homelessness programs, may place such mothers and their children at high risk of re-entering homelessness. Younger mothers had greater needs and benefited most from personalised one-on-one support that addressed key parenting and life skills. The implications of these findings are considered in relation to service delivery to this vulnerable group and avenues for future research are noted.

  18. Strengthening the Community College Pathway to Medical School: A Study of Latino Students in California.

    Science.gov (United States)

    Talamantes, Efrain; Gonzalez, Karla; Mangione, Carol M; Ryan, Gery; Jimenez, Alejandro; Gonzalez, Fabio; Greenwood, Seira Santizo; Hayes-Bautista, David E; Moreno, Gerardo

    2016-10-01

    One third of Latino medical students begin their premedical undergraduate education at a community college (CC) or 2-year college, compared to a 4-year university. This study explored the academic and personal experiences Latino premedical students commonly encounter at the CC. In 2013, five focus groups with Latino premedical and medical students (n=45) were conducted in Los Angeles and San Jose, CA. All students were enrolled or attended a CC. In addition, 20 CC key informants participated in semi-structured interviews to further describe the Latino CC premedical experience. The focus group and key informant transcripts were transcribed and analyzed for common themes using qualitative methods. Content analysis of 2,826 distinct comments identified major themes: (1) Personal health-related experiences in underserved communities, (2) CC relevant premedical guidance, (3) Limited preparation in navigating the pathways to medical school, and (4) Competing demands and college affordability. Early CC enrichment programs with direct ties to health professions advising programs, 4-year universities, medical schools, and physician mentors are needed to support Latino pre-medical students.

  19. Functional studies of signaling pathways in peri-implantation development of the mouse embryo by RNAi

    Directory of Open Access Journals (Sweden)

    Bell Graham

    2005-12-01

    Full Text Available Abstract Background Studies of gene function in the mouse have relied mainly on gene targeting via homologous recombination. However, this approach is difficult to apply in specific windows of time, and to simultaneously knock-down multiple genes. Here we report an efficient method for dsRNA-mediated gene silencing in late cleavage-stage mouse embryos that permits examination of phenotypes at post-implantation stages. Results We show that introduction of Bmp4 dsRNA into intact blastocysts by electroporation recapitulates the genetic Bmp4 null phenotype at gastrulation. It also reveals a novel role for Bmp4 in the regulation the anterior visceral endoderm specific gene expression and its positioning. We also show that RNAi can be used to simultaneously target several genes. When applied to the three murine isoforms of Dishevelled, it leads to earlier defects than previously observed in double knock-outs. These include severe delays in post-implantation development and defects in the anterior midline and neural folds at headfold stages. Conclusion Our results indicate that the BMP4 signalling pathway contributes to the development of the anterior visceral endoderm, and reveal an early functional redundancy between the products of the murine Dishevelled genes. The proposed approach constitutes a powerful tool to screen the functions of genes that govern the development of the mouse embryo.

  20. Interaction studies between periplasmic cytochromes provide insights into extracellular electron transfer pathways of Geobacter sulfurreducens.

    Science.gov (United States)

    Fernandes, Ana P; Nunes, Tiago C; Paquete, Catarina M; Salgueiro, Carlos A

    2017-02-20

    Geobacter bacteria usually prevail among other microorganisms in soils and sediments where Fe(III) reduction has a central role. This reduction is achieved by extracellular electron transfer (EET), where the electrons are exported from the interior of the cell to the surrounding environment. Periplasmic cytochromes play an important role in establishing an interface between inner and outer membrane electron transfer components. In addition, periplasmic cytochromes, in particular nanowire cytochromes that contain at least 12 haem groups, have been proposed to play a role in electron storage in conditions of an environmental lack of electron acceptors. Up to date, no redox partners have been identified in Geobacter sulfurreducens, and concomitantly, the EET and electron storage mechanisms remain unclear. In this work, NMR chemical shift perturbation measurements were used to probe for an interaction between the most abundant periplasmic cytochrome PpcA and the dodecahaem cytochrome GSU1996, one of the proposed nanowire cytochromes in G. sulfurreducens The perturbations on the haem methyl signals of GSU1996 and PpcA showed that the proteins form a transient redox complex in an interface that involves haem groups from two different domains located at the C-terminal of GSU1996. Overall, the present study provides for the first time a clear evidence for an interaction between periplasmic cytochromes that might be relevant for the EET and electron storage pathways in G. sulfurreducens. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  1. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

    Directory of Open Access Journals (Sweden)

    Norbert W Lutz

    Full Text Available Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE and adjuvant arthritis (AA in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA and spinal-cord homogenate (SC-H, whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group. Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE or extra-cerebral (AA inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and

  2. Application of the proximity-dependent assay and fluorescence imaging approaches to study viral entry pathways.

    Science.gov (United States)

    Lipovsky, Alex; Zhang, Wei; Iwasaki, Akiko; DiMaio, Daniel

    2015-01-01

    Virus entry into cells is a complex, multistep process that requires the coordinated activities of a large number of cellular factors and multiple membrane compartments. Because viruses can enter cells via one or more of a large number of preexisting pathways, understanding the mechanism of virus entry and transport between various intracellular compartments is a challenging task. The arrival of "omics" technologies such as genome-wide RNA interference screens has greatly advanced our ability to study the molecular intricacies of viral entry. Bioinformatics analyses of high-throughput screen data can identify enriched gene categories and specific individual genes required for infection, which can yield important insights into the cellular compartments that viruses traverse during infection. Although there are a variety of well-established genetic and biochemical approaches to validate genome-wide screen findings, confirmation of phenotypes obtained from RNA interference studies remains an important challenge. Imaging techniques commonly used to visualize virus localization to cellular organelles are often prone to artifacts that result from the necessity of using a high multiplicity of infection. Fortunately, recent advances in microscopy-based methods for studying protein location have improved our ability to accurately pinpoint virus localization within its host cell. Here we describe in detail one such technique-the proximity ligation assay (PLA)-as a tool to validate findings from a genome-wide loss-of-function genetic screen. In addition, we discuss a number of important considerations for the utilization of immunofluorescence microscopy and RNA interference to investigate the molecular mechanisms of virus entry.

  3. Distinction of salvaged and infarcted myocardium within the ischaemic area-at-risk with T2 mapping

    DEFF Research Database (Denmark)

    Hammer-Hansen, Sophia; Ugander, Martin; Hsu, Li-Yueh

    2014-01-01

    values from T2 maps and signal intensities on T2-weighted images were measured in the corresponding areas. RESULTS: At both imaging time points, the T2 of the salvaged myocardium was longer than of remote (66.0 ± 6.9 vs. 51.4 ± 3.5 ms, P ...AIM: Area-at-risk (AAR) measurements often rely on T2-weighted images, but subtle differences in T2 may be overlooked with this method. To determine the differences in oedema between salvaged and infarcted myocardium, we performed quantitative T2 mapping of the AAR. We also aimed to determine...... (14.7 ± 5.6 vs. 8.7 ± 5.1 ms, P = 0.02). CONCLUSIONS: T2 relaxation parameters are different in the infarcted and salvaged myocardium, and both are significantly longer than remote. Furthermore, the magnitude of increase in T2 was less in the salvaged myocardium after longer reperfusion, indicating...

  4. 1980 Volvo award winner in basic science. Nutritional pathways of the intervertebral disc. An experimental study using hydrogen washout technique.

    Science.gov (United States)

    Ogata, K; Whiteside, L A

    1981-01-01

    The pathways of material transfer to the intervertebral disc were studied in adult dogs by measuring diffusion of hydrogen molecules in the nucleus pulposus before and after disruption of the route through the annulus fibrosus and before and after disruption of the end-plate route. The interfaces was only in the central two-thirds of one side, caused significantly greater decrease in the rate of hydrogen washout than the disruption of the annulus route. Histologically, the bone-cartilage interface was frequently perforated by marrow cavity and vascular buds. These findings suggest that the end-plate route is a major pathway for material transfer to the intervertebral disc.

  5. Experimental Studies of the Molecular Pathways Regulated by Exercise and Resveratrol in Heart, Skeletal Muscle and the Vasculature

    Directory of Open Access Journals (Sweden)

    Vernon W. Dolinsky

    2014-09-01

    Full Text Available Regular exercise contributes to healthy aging and the prevention of chronic disease. Recent research has focused on the development of molecules, such as resveratrol, that activate similar metabolic and stress response pathways as exercise training. In this review, we describe the effects of exercise training and resveratrol on some of the organs and tissues that act in concert to transport oxygen throughout the body. In particular, we focus on animal studies that investigate the molecular signaling pathways induced by these interventions. We also compare and contrast the effects of exercise and resveratrol in diseased states.

  6. Neuroinflammatory pathways as treatment targets and biomarker candidates in epilepsy: emerging evidence from preclinical and clinical studies.

    Science.gov (United States)

    van Vliet, Erwin A; Aronica, Eleonora; Vezzani, Annamaria; Ravizza, Teresa

    2017-10-04

    Accumulating evidence indicates an important pathophysiological role of brain inflammation in epilepsy. In this review, we will provide an update of specific inflammatory pathways that have been proposed to be crucial in the underlying molecular mechanisms of epilepsy, including the interleukin-1 receptor/toll-like receptor signaling, cyclooxygenase-2, tumor necrosis factor-alpha, complement signaling and chemokines. Furthermore, by drawing on evidence from preclinical and clinical studies we will discuss the potential of these signaling pathways targets for novel therapeutic interventions that control drug-resistant seizures or have disease-modifying effects. Finally, we will assess the use of these inflammatory pathways as potential biomarkers for the development of epilepsy or to measure the effectiveness of therapeutic interventions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. A genome-wide association study of the Protein C anticoagulant pathway.

    Directory of Open Access Journals (Sweden)

    Georgios Athanasiadis

    Full Text Available The Protein C anticoagulant pathway regulates blood coagulation by preventing the inadequate formation of thrombi. It has two main plasma components: protein C and protein S. Individuals with protein C or protein S deficiency present a dramatically increased incidence of thromboembolic disorders. Here, we present the results of a genome-wide association study (GWAS for protein C and protein S plasma levels in a set of extended pedigrees from the Genetic Analysis of Idiopathic Thrombophilia (GAIT Project. A total number of 397 individuals from 21 families were typed for 307,984 SNPs using the Infinium® 317 k Beadchip (Illumina. Protein C and protein S (free, functional and total plasma levels were determined with biochemical assays for all participants. Association with phenotypes was investigated through variance component analysis. After correcting for multiple testing, two SNPs for protein C plasma levels (rs867186 and rs8119351 and another two for free protein S plasma levels (rs1413885 and rs1570868 remained significant on a genome-wide level, located in and around the PROCR and the DNAJC6 genomic regions respectively. No SNPs were significantly associated with functional or total protein S plasma levels, although rs1413885 from DNAJC6 showed suggestive association with the functional protein S phenotype, possibly indicating that this locus plays an important role in protein S metabolism. Our results provide evidence that PROCR and DNAJC6 might play a role in protein C and free protein S plasma levels in the population studied, warranting further investigation on the role of these loci in the etiology of venous thromboembolism and other thrombotic diseases.

  8. A genome-wide association study of the Protein C anticoagulant pathway.

    Science.gov (United States)

    Athanasiadis, Georgios; Buil, Alfonso; Souto, Juan Carlos; Borrell, Montserrat; López, Sonia; Martinez-Perez, Angel; Lathrop, Mark; Fontcuberta, Jordi; Almasy, Laura; Soria, José Manuel

    2011-01-01

    The Protein C anticoagulant pathway regulates blood coagulation by preventing the inadequate formation of thrombi. It has two main plasma components: protein C and protein S. Individuals with protein C or protein S deficiency present a dramatically increased incidence of thromboembolic disorders. Here, we present the results of a genome-wide association study (GWAS) for protein C and protein S plasma levels in a set of extended pedigrees from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project. A total number of 397 individuals from 21 families were typed for 307,984 SNPs using the Infinium® 317 k Beadchip (Illumina). Protein C and protein S (free, functional and total) plasma levels were determined with biochemical assays for all participants. Association with phenotypes was investigated through variance component analysis. After correcting for multiple testing, two SNPs for protein C plasma levels (rs867186 and rs8119351) and another two for free protein S plasma levels (rs1413885 and rs1570868) remained significant on a genome-wide level, located in and around the PROCR and the DNAJC6 genomic regions respectively. No SNPs were significantly associated with functional or total protein S plasma levels, although rs1413885 from DNAJC6 showed suggestive association with the functional protein S phenotype, possibly indicating that this locus plays an important role in protein S metabolism. Our results provide evidence that PROCR and DNAJC6 might play a role in protein C and free protein S plasma levels in the population studied, warranting further investigation on the role of these loci in the etiology of venous thromboembolism and other thrombotic diseases. © 2011 Athanasiadis et al.

  9. Evaluation of magnocellular pathway abnormalities in schizophrenia: a frequency doubling technology study and clinical implications

    Directory of Open Access Journals (Sweden)

    Fabiana Benites Vaz de Lima

    2013-04-01

    Full Text Available BACKGROUND: Visual processing deficits have been reported for patients with schizophrenia. Previous studies demonstrated differences in early-stage processing of schizophrenics, although the nature, extent, and localization of the disturbance are unknown. The magnocellular and parvocellular visual pathways are associated with transient and sustained channels, but their respective contributions to schizophrenia-related visual deficits remains controversial. PURPOSE: The aim of this study was to evaluate magnocellular dysfunction in schizophrenia using frequency doubling technology. METHODS: Thirty-one patients with schizophrenia and 34 healthy volunteers were examined. Frequency doubling technology testing was performed in one session, consisting of a 15-minute screening strategy followed by the C-20 program for frequency doubling technology. RESULTS: Schizophrenic patients showed lower global mean sensitivity (30,97 ± 2,25 dB compared with controls (32,17 ± 3,08 dB, p<0.009. Although there was no difference in the delta sensitivity of hemispheres, there was a difference in sensitivity analysis of the fibers crossing the optic chiasm, with lower mean sensitivity in the patient group (28,80 dB versus controls (30,66 dB. The difference was higher in fibers that do not cross the optic chiasm, with lower mean sensitivity in patients (27,61 dB versus controls (30,26 dB, p<0.005. CONCLUSIONS: Our results suggest that there are differences between global sensitivity and fiber sensitivity measured by frequency doubling technology. The different sensitivity of fibers that do not cross the optic chiasm is consistent with most current etiological hypotheses for schizophrenia. The decreased sensitivity responses in the optic radiations may significantly contribute to research assessing early-stage visual processing deficits for patients with schizophrenia.

  10. Port retrieval for salvage of tissue expansion in case of lost or malfunctioning port

    Directory of Open Access Journals (Sweden)

    Makhija Lalit

    2010-01-01

    Full Text Available Tissue expansion though a promising modality of reconstructive surgery is fraught with many complications. In addition to expander-related complications, subcutaneous port-related mishaps during tissue expansion, though infrequent, can result in procedure failures. We are reporting two patients with port-related complications. In one patient, there was failure to localise the port and the other had a leaking port. Both the expanders were salvaged by retrieving the ports. In the former, as the port was competent, it was simply exteriorised. But in the later case, the connecting tube was retrieved and the incompetent port was replaced with a Luer lock external port. Both the cases were successfully salvaged without any further complications. Expansions were completed and requisite reconstructive end points were achieved.

  11. Foetal salvage by Caesarean section in a case of maternal burn injury.

    Science.gov (United States)

    Banerjee, Tibar; Karmakar, Anirvan; Adhikari, Souvik

    2012-11-01

    Burn injury sustained during pregnancy is a serious clinical complication that requires individualisation of management. We describe the case of a 30-week pregnant woman who presented to the hospital in a state of shock with approximately 90% burn injuries. Resuscitation was carried out, and the patient's family consented to an emergency Caesarean section in view of the grave prognosis of such burn injuries. A live male infant was delivered via emergency Caesarean section. However, the mother succumbed to her injuries two days after the operation, while the baby was successfully resuscitated and discharged after ten days. This case highlights the importance of timely decision-making and coordination, which are required to salvage a near-term foetus. It also underscores that emergent resuscitation and timely operative procedures might be able to salvage a living foetus, particularly in patients with burns covering more than 60% of total body surface area.

  12. Developmental Pathways to Depressive Symptoms in Adolescence: A Multi-Wave Prospective Study of Negative Emotionality, Stressors, and Anxiety

    Science.gov (United States)

    Barrocas, Andrea L.; Hankin, Benjamin L.

    2011-01-01

    This study examined two potential developmental pathways through which the temperament risk factor of negative emotionality (NE) leads to prospective increases in depressive symptoms through the mediating role of stressors and anxious symptoms in a sample of early to middle adolescents (N = 350, 6th-10th graders). The primary hypothesized model…

  13. Diverse pathways of phosphatidylcholine biosynthesis in algae as estimated by labeling studies and genomic sequence analysis.

    Science.gov (United States)

    Sato, Naoki; Mori, Natsumi; Hirashima, Takashi; Moriyama, Takashi

    2016-08-01

    Phosphatidylcholine (PC) is an almost ubiquitous phospholipid in eukaryotic algae and plants but is not found in a few species, for example Chlamydomonas reinhardtii. We recently found that some species of the genus Chlamydomonas possess PC. In the universal pathway, PC is synthesized de novo by methylation of phosphatidylethanolamine (PE) or transfer of phosphocholine from cytidine diphosphate (CDP)-choline to diacylglycerol. Phosphocholine, the direct precursor to CDP-choline, is synthesized either by methylation of phosphoethanolamine or phosphorylation of choline. Here we analyzed the mechanism of PC biosynthesis in two species of Chlamydomonas (asymmetrica and sphaeroides) as well as in a red alga, Cyanidioschyzon merolae. Comparative genomic analysis of enzymes involved in PC biosynthesis indicated that C. merolae possesses only the PE methylation pathway. Radioactive tracer experiments using [(32) P]phosphate showed delayed labeling of PC with respect to PE, which was consistent with the PE methylation pathway. In Chlamydomonas asymmetrica, labeling of PC was detected from the early time of incubation with [(32) P]phosphate, suggesting the operation of phosphoethanolamine methylation pathway. Genomic analysis indeed detected the genes for the phosphoethanolamine methylation pathway. In contrast, the labeling of PC in C. sphaeroides was slow, suggesting that the PE methylation pathway was at work. These results as well as biochemical and computational results uncover an unexpected diversity of the mechanisms for PC biosynthesis in algae. Based on these results, we will discuss plausible mechanisms for the scattered distribution of the ability to biosynthesize PC in the genus Chlamydomonas. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  14. 15years of progress in gestational trophoblastic disease: Scoring, standardization, and salvage.

    Science.gov (United States)

    Brown, Jubilee; Naumann, R Wendel; Seckl, Michael J; Schink, Julian

    2017-01-01

    Significant improvements in treatment and the understanding of gestational trophoblastic neoplasia have occurred in the last 15years. These diseases are almost always curable, and refractory patients have more options for salvage therapy. Recent improvements in the understanding of epidemiology, diagnosis, and cell biology have resulted in changes in staging, advances in treatment options, and opportunities for fertility preservation. Copyright © 2016. Published by Elsevier Inc.

  15. Salvage of a Below Knee Amputation Utilizing Rotationplasty Principles in a Patient with Chronic Tibial Osteomyelitis

    OpenAIRE

    Moralle, Matthew R.; Stekas, Nicholas D.; Reilly, Mark C.; Sirkin, Michael S.; Adams, Mark R.

    2016-01-01

    Introduction: Chronic osteomyelitis is a disease that requires fastidious treatment to eliminate. However, when eradication is unable to be achieved through exhaustive modalities of antibiotic therapy and multiple debridements, significant resection of the infected bone and soft tissue must be considered, including amputation. Here we report of a salvage procedure for chronic osteomyelitis of the left tibia by employing a rotationplasty to avoid an above knee amputation and instead provide th...

  16. A Comparison of Four Year Health Outcomes following Combat Amputation and Limb Salvage

    Science.gov (United States)

    2017-01-25

    the overall four-year model. Diagnoses of deep vein thrombosis/ pulmonary embolism (DVT/PE) and non-healing wounds were not significantly associated...deep vessel thrombosis/ pulmonary embolism . doi:10.1371/journal.pone.0170569.t002 Four-Year Health Outcomes following Combat Amputation and Limb...1.46 [95% CI, 1.2–1.76]) relative to limb salvage. CI = confidence interval, DVT/PE = deep vessel thrombosis/ pulmonary embolism , ISS = Injury

  17. Recanalisation of Chronically Occluded Remote Superficial Femoral Artery Endarterectomy Through Angioplasty for Limb Salvage

    Energy Technology Data Exchange (ETDEWEB)

    Husainy, Mohammad Ali, E-mail: m.husainy@nhs.net [King’s College Hospital, Department of Radiology (United Kingdom); Slim, Hani; Rashid, Hisham [King’s College Hospital, Department of Vascular Surgery (United Kingdom); Huang, Dean Y. [King’s College Hospital, Department of Radiology (United Kingdom)

    2017-02-15

    We report a novel application of balloon angioplasty to recanalise a chronically occluded remote endarterectomy superficial femoral artery. This patient previously had two occluded surgical bypass grafts in an attempt to revascularise the limb and presented with critical limb ischaemia and necrotic foot ulcerations. Following the angioplasty, the patient showed significant improvement in rest pain and healing of the ulcerations. This technique may be useful for limb salvage in patients where surgical options have been exhausted.

  18. Functional salvage of a mangled lower limb using custom-made endoprosthetic replacement

    OpenAIRE

    Mohammed, Riazuddin; Baloch, Khalid; Peart, Francis; Abudu, Adesegun

    2009-01-01

    Functional salvage of a severely injured extremity is a challenge for the patient and the treating surgeon. We report a case of a woman presenting with severely injured lower limb and bone loss, which was managed using a custom-made endoprosthetic replacement for successful functional outcome. Despite being complicated by bone loss, nerve injury and infection; a planned staged surgical treatment and rehabilitation have resulted in satisfactory outcome. At 3-year follow-up, the functional scor...

  19. Outcome in recurrent head neck cancer treated with salvage-IMRT

    Directory of Open Access Journals (Sweden)

    Graetz Klaus W

    2008-12-01

    Full Text Available Abstract Background Recurrent head neck cancer (rHNC is a known unfavourable prognostic condition. The purpose of this work was to analyse our rHNC subgroup treated with salvage-intensity modulated radiation therapy (IMRT for curable recurrence after initial surgery alone. Patients Between 4/2003–9/2008, 44 patients with squamous cell rHNC were referred for IMRT, mean/median 33/21 (3–144 months after initial surgery. None had prior head neck radiation. 41% underwent definitive, 59% postoperative IMRT (66–72.6 Gy. 70% had simultaneous chemotherapy. Methods Retrospective analysis of the outcome following salvage IMRT in rHNC patients was performed. Results After mean/median 25/21 months (3–67, 22/44 (50% patients were alive with no disease; 4 (9% were alive with disease. 18 patients (41% died of disease. Kaplan Meier 2-year disease specific survival (DSS, disease free survival (DFS, local and nodal control rates of the cohort were 59/49/56 and 68%, respectively. Known risk factors (advanced initial pTN, marginal initial resection, multiple recurrences showed no significant outcome differences. Risk factors and the presence of macroscopic recurrence gross tumor volume (rGTV in oral cavity patients vs others resulted in statistically significantly lower DSS (30 vs 70% at 2 years, p = 0.03. With respect to the assessed unfavourable outcome following salvage treatment, numbers needed to treat to avoid one recurrence with initial postoperative IMRT have, in addition, been calculated. Conclusion A low salvage rate of only ~50% at 2 years was found. Calculated numbers of patients needed to treat with postoperative radiation after initial surgery, in order to avoid recurrence and tumor-specific death, suggest a rather generous use of adjuvant irradiation, usually with simultaneous chemotherapy.

  20. Combined targeting of EGFR-dependent and VEGF-dependent pathways: rationale, preclinical studies and clinical applications.

    Science.gov (United States)

    Tortora, Giampaolo; Ciardiello, Fortunato; Gasparini, Giampietro

    2008-09-01

    Cellular heterogeneity, redundancy of molecular pathways and effects of the microenvironment contribute to the survival, motility and metastasis of cells in solid tumors. It is unlikely that tumors are entirely dependent on only one abnormally activated signaling pathway; consequently, treatment with an agent that interferes with a single target may be insufficient. Combined blockade of functionally linked and relevant multiple targets has become an attractive therapeutic strategy. The EGFR and ERBB2 (HER2) pathways and VEGF-dependent angiogenesis have a pivotal role in cancer pathogenesis and progression. Robust experimental evidence has shown that these pathways are functionally linked and has demonstrated a suggested role for VEGF in the acquired resistance to anti-ERBB drugs when these receptors are pharmacologically blocked. Combined inhibition of ERBB and VEGF signaling interferes with a molecular feedback loop responsible for acquired resistance to anti-ERBB agents and promotes apoptosis while ablating tumor-induced angiogenesis. To this aim, either two agents highly selective against VEGF and ERBB respectively, or, alternatively, a single multitargeted agent, can be used. Preclinical studies have proven the efficacy of both these approaches and early clinical studies have provided encouraging results. This Review discusses the experimental rationale for, preclinical studies of and clinical trials on combined blockade of ERBB and VEGF signaling.

  1. Outdoor thermal physiology along human pathways: a study using a wearable measurement system

    Science.gov (United States)

    Nakayoshi, Makoto; Kanda, Manabu; Shi, Rui; de Dear, Richard

    2015-05-01

    An outdoor summer study on thermal physiology along subjects' pathways was conducted in a Japanese city using a unique wearable measurement system that measures all the relevant thermal variables: ambient temperature, humidity, wind speed ( U) and short/long-wave radiation ( S and L), along with some physio-psychological parameters: skin temperature ( T skin), pulse rate, subjective thermal sensation and state of body motion. U, S and L were measured using a globe anemo-radiometer adapted use with pedestrian subjects. The subjects were 26 healthy Japanese adults (14 males, 12 females) ranging from 23 to 74 years in age. Each subject wore a set of instruments that recorded individual microclimate and physiological responses along a designated pedestrian route that traversed various urban textures. The subjects experienced varying thermal environments that could not be represented by fixed-point routine observational data. S fluctuated significantly reflecting the mixture of sunlit/shade distributions within complex urban morphology. U was generally low within urban canyons due to drag by urban obstacles such as buildings but the subjects' movements enhanced convective heat exchanges with the atmosphere, leading to a drop in T skin. The amount of sweating increased as standard effective temperature (SET*) increased. A clear dependence of sweating on gender and body size was found; males sweated more than females; overweight subjects sweated more than standard/underweight subjects. T skin had a linear relationship with SET* and a similarly clear dependence on gender and body size differences. T skin of the higher-sweating groups was lower than that of the lower-sweating groups, reflecting differences in evaporative cooling by perspiration.

  2. Outdoor thermal physiology along human pathways: a study using a wearable measurement system.

    Science.gov (United States)

    Nakayoshi, Makoto; Kanda, Manabu; Shi, Rui; de Dear, Richard

    2015-05-01

    An outdoor summer study on thermal physiology along subjects' pathways was conducted in a Japanese city using a unique wearable measurement system that measures all the relevant thermal variables: ambient temperature, humidity, wind speed (U) and short/long-wave radiation (S and L), along with some physio-psychological parameters: skin temperature (T skin), pulse rate, subjective thermal sensation and state of body motion. U, S and L were measured using a globe anemo-radiometer adapted use with pedestrian subjects. The subjects were 26 healthy Japanese adults (14 males, 12 females) ranging from 23 to 74 years in age. Each subject wore a set of instruments that recorded individual microclimate and physiological responses along a designated pedestrian route that traversed various urban textures. The subjects experienced varying thermal environments that could not be represented by fixed-point routine observational data. S fluctuated significantly reflecting the mixture of sunlit/shade distributions within complex urban morphology. U was generally low within urban canyons due to drag by urban obstacles such as buildings but the subjects' movements enhanced convective heat exchanges with the atmosphere, leading to a drop in T skin. The amount of sweating increased as standard effective temperature (SET*) increased. A clear dependence of sweating on gender and body size was found; males sweated more than females; overweight subjects sweated more than standard/underweight subjects. T skin had a linear relationship with SET* and a similarly clear dependence on gender and body size differences. T skin of the higher-sweating groups was lower than that of the lower-sweating groups, reflecting differences in evaporative cooling by perspiration.

  3. Evaluation of the effect of a comprehensive multidisciplinary care pathway for hip fractures: design of a controlled study.

    Science.gov (United States)

    Flikweert, Elvira R; Izaks, Gerbrand J; Reininga, Inge H F; Wendt, Klaus W; Stevens, Martin

    2013-10-12

    Hip fractures constitute an economic burden on healthcare resources. Most persons with a hip fracture undergo surgery. As morbidity and mortality rates are high, perioperative care leaves room for improvement. Improvement can be achieved if it is organized in comprehensive care pathways, but the effectiveness of these pathways is not yet clear. Hence the objective of this study is to compare the clinical effectiveness of a comprehensive care pathway with care as usual on self-reported limitations in Activities of Daily Living. A controlled trial will be conducted in which the comprehensive care pathway of University Medical Center Groningen will be compared with care as usual in two other, nonacademic, hospitals. In this trial, propensity scores will be used to adjust for differences at baseline between the intervention and control group. Propensity scores can be used in intervention studies where a classical randomized controlled trial is not feasible. Patients aged 60 years and older will be included. The hypothesis is that 15% more patients at University Medical Center Groningen compared with patients in the care-as-usual condition will have recovered at least as well at 6 months follow-up to pre-fracture levels for Activities of Daily Living. This study will yield new knowledge with respect to the clinical effectiveness of a comprehensive care pathway for the treatment of hip fractures. This is relevant because of the growing incidence of hip fractures and the consequent massive burden on the healthcare system. Additionally, this study will contribute to the growing knowledge of the application of propensity scores, a relatively novel statistical technique to simulate a randomized controlled trial in studies where it is not possible or difficult to execute this kind of design. Nederlands Trial Register NTR3171.

  4. The combined use of the Ilizarov method and microsurgical techniques for limb salvage.

    Science.gov (United States)

    Hollenbeck, Scott T; Woo, Shoshana; Ong, Siang; Fitch, Robert D; Erdmann, Detlev; Levin, L Scott

    2009-05-01

    The purpose of this article is to review clinical outcomes and propose a new classification scheme for combined use of Ilizarov Method with free tissue transfer for limb salvage. This is an Institutional Review Board-approved retrospective review of 62 patients treated with free tissue transfer and Ilizarov method over the past 15 years at a single institution. The surgical management of these patients is classified into 4 distinct approaches. The mean age was 37 years with the most common injury being Gustillo IIIB tibial fractures (61%). Eighty-seven percent of patients had failed prior fixation and 63% had osteomyelitis with a draining wound. The overall flap survival rate was 97%. The mean duration of Ilizarov fixation was 6.9 months with a mean limb length correction of 3 cm. The overall rate of primary bony union was 74%. With a mean follow-up of 42 months, the combined techniques resulted in limb salvage for 84% of cases. Failure of primary bony union was the only predictor of limb amputation. This multidisciplinary approach to limb salvage combines reconstructive microsurgery and the Ilizarov method.

  5. An ecosystem services approach to the ecological effects of salvage logging: valuation of seed dispersal.

    Science.gov (United States)

    Leverkus, Alexandro B; Castro, Jorge

    2017-06-01

    Forest disturbances diminish ecosystem services and boost disservices. Because post-disturbance management intends to recover the greatest possible value, selling timber often prevails over other considerations. Ecological research has shown diverse effects of salvage logging, yet such research has focused on the biophysical component of post-disturbance ecosystems and lacks the link with human well-being. Here we bridge that gap under the ecosystem services framework by assessing the impact of post-fire management on a non-timber value. By employing the replacement cost method, we calculated the value of the post-fire natural regeneration of Holm oaks in southern Spain under three post-fire management options by considering the cost of planting instead. The value of this ecosystem service in non-intervention areas doubled that of salvage-logged stands due to the preference for standing dead trees by the main seed disperser. Still, most of the value resulted from the resprouting capacity of oaks. The value of this and other ecosystem services should be added to traditional cost/benefit analyses of post-disturbance management. We thus call for a more holistic approach to salvage logging research, one that explicitly links ecological processes with human well-being through ecosystem services, to better inform decision-makers on the outcomes of post-disturbance management. © 2017 by the Ecological Society of America.

  6. Septic Shock following Prostate Biopsy: Aggressive Limb Salvage for Extremities after Pressor-Induced Ischemic Gangrene

    Directory of Open Access Journals (Sweden)

    Jocelyn Lu, BS

    2017-09-01

    Full Text Available Summary:. Vasopressors used to treat patients with septic shock can cause ischemic necrosis of appendages such as the ears and nose, as well as the extremities. Cases of quadruple-extremity necrosis have high morbidity and mortality, and a profound negative impact on quality of life. This case report details the successful limb salvage and return to function using free tissue transfer as a means to salvage bilateral lower extremities in a patient who suffered vasopressor-induced ischemia of upper and lower extremities after prostate biopsy–induced septic shock. Septic shock following transrectal ultrasound–guided prostate biopsy is a rare, yet life-threatening complication. Successful treatment included thorough planning and staging of therapies such as awaiting tissue demarcation and serial surgical debridement to adequately prepare the tissue bed for free tissue transfer. Adjunctive treatments such as hyperbaric oxygen therapy, negative-pressure wound therapy, and meticulous wound care played a crucial role in wound healing. This vigilant planning and coordinated care resulted in the successful lower extremity salvage, consisting of bilateral transmetatarsal amputations and free tissue transfer to both limbs. We present our long-term follow-up of a functional ambulatory patient after catastrophic, life-threatening infection and appropriate multidisciplinary care.

  7. Low-dose-rate brachytherapy as salvage treatment of local prostate cancer recurrence after radical prostatectomy.

    Science.gov (United States)

    Traudt, Krystyna; Ciezki, Jay; Klein, Eric A

    2011-06-01

    To present our initial experience with brachytherapy used as a salvage procedure for local recurrence of prostate cancer in the prostatic fossa after radical prostatectomy. The patients included 5 consecutive men who underwent brachytherapy as a salvage procedure after radical prostatectomy from December 2006 to March 2008. We used a technique of implanting the local recurrences similar to the American Brachytherapy Society Guidelines for implanting an intact prostate as definitive therapy. Two modifications were made related to the recurrence location: a rare need to manage urethral doses because the recurrence was typically perirectal, and more aggressive management of the dose to the rectum because of this proximity. All patients tolerated the brachytherapy procedure well and showed a decline in the prostate-specific antigen level, with a median nadir of 0.72 ng/mL at a median follow-up of 13 months. The postprocedural symptoms were minor and included limited new-onset urgency. At the last follow-up visit, all patients had prostate-specific antigen doubling times, which have been associated with long median survival times. Salvage brachytherapy for biopsy-proven local recurrence of prostate cancer is a technically feasible alternative to external beam radiotherapy for local control of recurrences in the prostatic fossa in selected patients after radical prostatectomy. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies

    NARCIS (Netherlands)

    Sarwar, Nadeem; Butterworth, Adam S.; Freitag, Daniel F.; Gregson, John; Willeit, Peter; Gorman, Donal N.; Gao, Pei; Saleheen, Danish; Rendon, Augusto; Nelson, Christopher P.; Braund, Peter S.; Hall, Alistair S.; Chasman, Daniel I.; Tybjærg-Hansen, Anne; Chambers, John C.; Benjamin, Emelia J.; Franks, Paul W.; Clarke, Robert; Wilde, Arthur A. M.; Trip, Mieke D.; Steri, Maristella; Witteman, Jacqueline C. M.; Qi, Lu; van der Schoot, C. Ellen; de Faire, Ulf; Erdmann, Jeanette; Stringham, Heather M.; Koenig, Wolfgang; Rader, Daniel J.; Melzer, David; Reich, David; Psaty, Bruce M.; Kleber, Marcus E.; Panagiotakos, Demosthenes B.; Willeit, Johann; Wennberg, Patrik; Woodward, Mark; Adamovic, Svetlana; Rimm, Eric B.; Meade, Tom W.; Gillum, Richard F.; Shaffer, Jonathan A.; Hofman, Albert; Onat, Altan; Sundström, Johan; Wassertheil-Smoller, Sylvia; Mellström, Dan; Gallacher, John; Cushman, Mary; Tracy, Russell P.; Kauhanen, Jussi; Karlsson, Magnus; Salonen, Jukka T.; Wilhelmsen, Lars; Amouyel, Philippe; Cantin, Bernard; Best, Lyle G.; Ben-Shlomo, Yoav; Manson, JoAnn E.; Davey-Smith, George; de Bakker, Paul I. W.; O'Donnell, Christopher J.; Wilson, James F.; Wilson, Anthony G.; Assimes, Themistocles L.; Jansson, John-Olov; Ohlsson, Claes; Tivesten, Åsa; Ljunggren, Östen; Reilly, Muredach P.; Hamsten, Anders; Ingelsson, Erik; Cambien, Francois; Hung, Joseph; Thomas, G. Neil; Boehnke, Michael; Schunkert, Heribert; Asselbergs, Folkert W.; Kastelein, John J. P.; Gudnason, Vilmundur; Salomaa, Veikko; Harris, Tamara B.; Kooner, Jaspal S.; Allin, Kristine H.; Nordestgaard, Børge G.; Hopewell, Jemma C.; Goodall, Alison H.; Ridker, Paul M.; Hólm, Hilma; Watkins, Hugh; Ouwehand, Willem H.; Samani, Nilesh J.; Kaptoge, Stephen; Di Angelantonio, Emanuele; Harari, Olivier; Danesh, John; Quertermous, Thomas; Go, Alan S.; Hlatky, Mark A.; Knowles, Joshua W.; Smith, Albert V.; Chrysohoou, Christina; Pitsavos, Christos; Stefanadis, Christodoulos; Balmforth, Anthony J.; Thompson, John R.; Sivapalaratnam, Suthesh; Maiwald, Stephani; Basart, Hanneke; Motazacker, Mahdi; de Jong, Jonas S. S. G.; Dekker, Lucas R. C.; Tanck, Michael; Bezzina, Connie R.; Whincup, Peter H.; Morris, Richard W.; Wannamethee, S. Goya; Kiechl, Stefan; Yarnell, John W. G.; Lowe, Gordon; Rumley, Ann; Mukamal, Kenneth J.; Havulinna, Aki S.; Lokki, Marja-Liisa; Nieminen, Markku S.; Ripatti, Samuli; Sinisalo, Juha; McQuillan, Brendan M.; Beilby, John P.; Thompson, Peter L.; Thorleifsson, Guðmar; Thorgeirsson, Guðmundur; Thorsteinsdóttir, Unnur; Stefansson, Kari; Jula, Antti; Männistö, Satu; Perola, Markus; Tikkanen, Emmi; Boer, Jolanda M. A.; Onland-Moret, N. Charlott; van der Schouw, Yvonne T.; Verschuren, W. M. Monique; Jansson, Jan-Håkan; Dupuis, Josée; Fontes, João D.; Yin, Xiaoyan; Tuomilehto, Jaakko; Koenig, Inke R.; Nahrstaedt, Janja; Loley, Christina; Stark, Klaus; Willenborg, Christina; Hengstenberg, Christian; Schreiber, Stefan; Preuss, Michael; Barroso, Inês; Hallmans, Göran; Shungin, Dmitry; Cheng, Kar Keung; Lam, Tai Hing; Jiang, Chao Chiang; Pai, Jennifer; Collins, Rory; Parish, Sarah; Armitage, Jane; Jackson, Anne; Hveem, Kristian; Wiggins, Kerri L.; Heckbert, Susan R.; Smith, Nicholas L.; Bis, Joshua C.; Ferrucci, Luigi; Guralnik, Jack M.; Bandinelli, Stefania; Singleton, Andrew B.; Tuomainen, Tomi-Pekka; Kurl, Sudhir; Zhang, Weihua; Kooner, Angad S.; Das, Debashis; März, Winfried; Scharnagl, Hubert; Böhm, Bernhard O.; Winkelmann, Bernhard R.; Folsom, Aaron R.; Shea, Steven J.; Laakso, Markku; Kuusisto, Johanna; Baumert, Jens; Thorand, Barbara; Illig, Thomas; Meisinger, Christa; Rosengren, Annika; Karlsson, Magnus K.; Hu, Frank B.; Hankinson, Susan E.; Davidson, Karina W.; Fraser, Ross; Wild, Sarah; Campbell, Harry; Qasim, Atif; Qu, Liming; Li, Mingyao; Lind, Lars; Syvänen, Ann-Christine; Arveiler, Dominique; Farrall, Martin; Peden, John F.; Deloukas, Panos; Sheikh, Nasir; Rasheed, Asif; Dagenais, Gilles R.; Dehghan, Abbas; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Abecasis, Goncalo R.; Cucca, Francesco; Sanna, Serena; Uda, Manuela; Schlessinger, David; Sabater-Lleal, Maria; Silveira, Angela; Gigante, Bruna; Howard, Barbara V.; Basu, Samar; Rose, Lynda M.; Buring, Julie

    2012-01-01

    Background Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we