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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Humans or Animals Humans Animals Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Results(1-25 of 2,338) Sort By: Publication Date Relevance Took: 0.995 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 94 1 2 3 4 > Last >> (2338 articles found) MHCPred 2.0: an updated quantitative T-cell epitope prediction server. 2006 Pingping Guan,Channa K Hattotuwagama,Irini A Doytchinova,Darren R Flower The accurate computational prediction of T-cell epitopes can greatly reduce the experimental overhead implicit in candidate epitope identification within genomic sequences. In this article we present MHCPred 2.0, an enhanced version of our online, quantitative T-cell epitope prediction server. The ... ( view more )previous version of MHCPred included mostly alleles from the human leukocyte antigen A (HLA-A) locus. In MHCPred 2.0, mouse models are added and computational constraints removed. Currently the server includes 11 human HLA class I, three human HLA class II, and three mouse class I models. Additionally, a binding model for the human transporter associated with antigen processing (TAP) is incorporated into the new MHCPred. A tool for the design of heteroclitic peptides is also included within the server. To refine the veracity of binding affinities prediction, a confidence percentage is also now calculated for each peptide predicted. AVAILABILITY: As previously, MHCPred 2.0 is freely available at the URL http://www.jenner.ac.uk/MHCPred/ CONTACT: Darren R. Flower (darren.flower@jenner.ac.uk). ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Neuropathic changes in equine laminitis pain. Dec 5, 2007 Emma Jones,Ignacio Viñuela-Fernandez,Rachel A Eager,Ada Delaney,Heather Anderson,Anisha Patel,Darren C Robertson,Andrew Allchorne,Eva C Sirinathsinghji,Elspeth M Milne,Neil MacIntyre,Darren J Shaw,Natalie K Waran,Joe Mayhew,Susan M Fleetwood-Walker Laminitis is a common debilitating disease in horses that involves painful disruption of the lamellar dermo-epidermal junction within the hoof. This condition is often refractory to conventional anti-inflammatory analgesia and results in unremitting pain, which in severe cases requires euthanasia. ... ( view more )The mechanisms underlying pain in laminitis were investigated using quantification of behavioural pain indicators in conjunction with histological studies of peripheral nerves innervating the hoof. Laminitic horses displayed consistently altered or abnormal behaviours such as increased forelimb lifting and an increased proportion of time spent at the back of the box compared to normal horses. Electron micrographic analysis of the digital nerve of laminitic horses showed peripheral nerve morphology to be abnormal, as well as having reduced numbers of unmyelinated (43.2%) and myelinated fibers (34.6%) compared to normal horses. Sensory nerve cell bodies innervating the hoof, in cervical, C8 dorsal root ganglia (DRG), showed an upregulated expression of the neuronal injury marker, activating transcription factor-3 (ATF3) in both large NF-200-immunopositive neurons and small neurons that were either peripherin- or IB4-positive. A significantly increased expression of neuropeptide Y (NPY) was also observed in myelinated afferent neurons. These changes are similar to those reported in other neuropathic pain states and were not observed in the C4 DRG of laminitic horses, which is not associated with innervation of the forelimb. This study provides novel evidence for a neuropathic component to the chronic pain state associated with equine laminitis, indicating that anti-neuropathic analgesic treatment may well have a role in the management of this condition. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Systemic plasma levels of nitrite/nitrate (NOx) reflect brachial flow-mediated dilation responses in young men and women. Dec 2007 Darren P Casey,Darren T Beck,Randy W Braith 1. The aim of the present study was to determine the relationship between plasma levels of nitrite/nitrite (NO(x)) and brachial flow-mediated dilation (FMD) in healthy young men and women. 2. Brachial artery FMD was assessed non-invasively using high-resolution ultrasound in 36 young men and women ... ( view more )(21 +/- 3 years; 18 men and 18 women). Blood samples for NO(x) assays were collected from an indwelling venous catheter in the forearm following an overnight fast and a 36 h low-nitrate diet. 3. Plasma levels of NO(x) were related to peak brachial FMD% (r = 0.53; P = 0.001). The relationship was maintained when the brachial dilation was expressed as absolute diameter change (Deltamm; r = 0.51; P = 0.002) and when it was normalized (/s) to the mean shear rate (r = 0.50; P = 0.002). 4. The present study demonstrates a relationship between peak FMD in the brachial artery and plasma levels of NO(x) in young men and women. This relationship suggests that brachial FMD and/or plasma NO(x) may be used as markers of peripheral endothelial function. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Mu opioid receptors are expressed on radial glia but not migrating neuroblasts in the late embryonic mouse brain. Oct 17, 2007 Tim J Sargeant,Darren J Day,Eli M Mrkusich,Darren F Foo,John H Miller Mu opioid receptor ligands such as morphine and met-enkephalin are known to modulate normal brain development by perturbing gliogenesis and inhibiting neuronal proliferation. Surprisingly, the distribution of the mu opioid receptor (MOR) in the embryonic brain, especially in proliferative regions, ... ( view more )is poorly defined and subject to conflicting reports. Using an immunohistochemical approach, we found that MOR protein was expressed in the neuroepithelia of the lateral ventricles, third ventricle, and aqueduct within the late embryonic (E15.5 and E18.5) mouse brain. In contrast to the ventricular neuroepithelia, the proliferative external granule layer of the embryonic cerebellum did not express MOR protein, although the Purkinje cell layer did. Within the ventricular neuroepithelium, GLAST-positive radial glia that incorporate BrdU expressed MOR, while migrating neuroblasts (doublecortin-positive) do not. BrdU labeling of proliferating cells showed an anterior to posterior gradient of proliferation (P<0.05), while an opposing posterior to anterior gradient of MOR expression (P<0.05) was found. The localization of MOR immunoreactivity within the embryonic ventricular neuroepithelia is consistent with a role for opioids in modulating neurogenesis. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Progressive resistance training without volume increases does not alter arterial stiffness and aortic wave reflection. Oct 2007 Darren P Casey,Darren T Beck,Randy W Braith Endurance exercise is efficacious in reducing arterial stiffness. However, the effect of resistance training (RT) on arterial stiffening is controversial. High-intensity, high-volume RT has been shown to increase arterial stiffness in young adults. We tested the hypothesis that an RT protocol consi... ( view more )sting of progressively higher intensity without concurrent increases in training volume would not elicit increases in either central or peripheral arterial stiffness or alter aortic pressure wave reflection in young men and women. The RT group (n = 24; 21 +/- 1 years) performed two sets of 8-12 repetitions to volitional fatigue on seven exercise machines on 3 days/week for 12 weeks, whereas the control group (n = 18; 22 +/- 1 years) did not perform RT. Central and peripheral arterial pulse wave velocity (PWV), aortic pressure wave reflection (augmentation index; AIx), brachial flow-mediated dilation (FMD), and plasma levels of nitrate/nitrite (NOx) and norepinephrine (NE) were measured before and after RT. RT increased the one-repetition maximum for the chest press and the leg extension (P < 0.001). RT also increased lean body mass (P < 0.01) and reduced body fat (%; P < 0.01). However, RT did not affect carotid-radial, carotid-femoral, and femoral-distal PWV (8.4 +/- 0.2 vs. 8.0 +/- 0.2 m/sec; 6.5 +/- 0.1 vs. 6.3 +/- 0.2 m/sec; 9.5 +/- 0.3 vs. 9.5 +/- 0.3 m/sec, respectively) or AIx (2.5% +/- 2.3% vs. 4.8% +/- 1.8 %, respectively). Additionally, no changes were observed in brachial FMD, NOx, NE, or blood pressures. These results suggest that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume does not increase central or peripheral arterial stiffness or alter aortic pressure wave characteristics in young subjects. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Effect of short-term equal-volume resistance training with different workout frequency on muscle mass and strength in untrained men and women. Feb 2007 Darren G Candow,Darren G Burke Changes in muscle mass and strength will vary, depending on the volume and frequency of training. The purpose of this study was to determine the effect of short-term equal-volume resistance training with different workout frequency on lean tissue mass and muscle strength. Twenty-nine untrained volu... ( view more )nteers (27-58 years; 23 women, 6 men) were assigned randomly to 1 of 2 groups: group 1 (n = 15; 12 women, 3 men) trained 2 times per week and performed 3 sets of 10 repetitions to fatigue for 9 exercises, group 2 (n = 14; 11 women, 3 men) trained 3 times per week and performed 2 sets of 10 repetitions to fatigue for 9 exercises. Prior to and following training, whole-body lean tissue mass (dual energy x-ray absorptiometry) and strength (1 repetition maximum squat and bench press) were measured. Both groups increased lean tissue mass (2.2%), squat strength (28%), and bench press strength (22-30%) with training (p < 0.05), with no other differences. These results suggest that the volume of resistance training may be more important than frequency in developing muscle mass and strength in men and women initiating a resistance training program. ( view less ) View Full Abstract View Article Details   Related Articles Effect of whey and soy protein supplementation combined with resistance training in young adults. Jun 2006 Darren G Candow,Natalie C Burke,T Smith-Palmer,Darren G Burke The purpose was to compare changes in lean tissue mass, strength, and myofibrillar protein catabolism resulting from combining whey protein or soy protein with resistance training. Twenty-seven untrained healthy subjects (18 female, 9 male) age 18 to 35 y were randomly assigned (double blind) to su... ( view more )pplement with whey protein (W; 1.2 g/kg body mass whey protein + 0.3 g/kg body mass sucrose power, N = 9: 6 female, 3 male), soy protein (S; 1.2 g/kg body mass soy protein + 0.3 g/kg body mass sucrose powder, N= 9: 6 female, 3 male) or placebo (P; 1.2 g/kg body mass maltodextrine + 0.3 g/kg body mass sucrose powder, N = 9: 6 female, 3 male) for 6 wk. Before and after training, measurements were taken for lean tissue mass (dual energy X-ray absorptiometry), strength (1-RM for bench press and hack squat), and an indicator of myofibrillar protein catabolism (urinary 3-methylhistidine). Results showed that protein supplementation during resistance training, independent of source, increased lean tissue mass and strength over isocaloric placebo and resistance training (P < 0.05). We conclude that young adults who supplement with protein during a structured resistance training program experience minimal beneficial effects in lean tissue mass and strength. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Streamlined system for purifying and quantifying a diverse library of compounds and the effect of compound concentration measurements on the accurate interpretation of biological assay results. Dec 15, 2004 Ioana G Popa-Burke,Olga Issakova,James D Arroway,Paul Bernasconi,Min Chen,Louis Coudurier,Scott Galasinski,Ajit P Jadhav,William P Janzen,Dennis Lagasca,Darren Liu,Roderic S Lewis,Robert P Mohney,Nikolai Sepetov,Darren A Sparkman,C Nicholas Hodge As part of an overall systems approach to generating highly accurate screening data across large numbers of compounds and biological targets, we have developed and implemented streamlined methods for purifying and quantitating compounds at various stages of the screening process, coupled with autom... ( view more )ated "traditional" storage methods (DMSO, -20 degrees C). Specifically, all of the compounds in our druglike library are purified by LC/MS/UV and are then controlled for identity and concentration in their respective DMSO stock solutions by chemiluminescent nitrogen detection (CLND)/evaporative light scattering detection (ELSD) and MS/UV. In addition, the compound-buffer solutions used in the various biological assays are quantitated by LC/UV/CLND to determine the concentration of compound actually present during screening. Our results show that LC/UV/CLND/ELSD/MS is a widely applicable method that can be used to purify, quantitate, and identify most small organic molecules from compound libraries. The LC/UV/CLND technique is a simple and sensitive method that can be easily and cost-effectively employed to rapidly determine the concentrations of even small amounts of any N-containing compound in aqueous solution. We present data to establish error limits for concentration determination that are well within the overall variability of the screening process. This study demonstrates that there is a significant difference between the predicted amount of soluble compound from stock DMSO solutions following dilution into assay buffer and the actual amount present in assay buffer solutions, even at the low concentrations employed for the assays. We also demonstrate that knowledge of the concentrations of compounds to which the biological target is exposed is critical for accurate potency determinations. Accurate potency values are in turn particularly important for drug discovery, for understanding structure-activity relationships, and for building useful empirical models of protein-ligand interactions. Our new understanding of relative solubility demonstrates that most, if not all, decisions that are made in early discovery are based upon missing or inaccurate information. Finally, we demonstrate that careful control of compound handling and concentration, coupled with accurate assay methods, allows the use of both positive and negative data in analyzing screening data sets for structure-activity relationships that determine potency and selectivity. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Effect of ceasing creatine supplementation while maintaining resistance training in older men. Jul 2004 Darren G Candow,Phillip D Chilibeck,Karen E Chad,Murray J Chrusch,K Shawn Davison,Darren G Burke The authors previously found that creatine (Cr) combined with 12 weeks of resistance training enhanced muscle strength and endurance and lean tissue mass (LTM) in older men. Their purpose in this study was to assess these variables with cessation of Cr combined with 12 weeks of reduced training (33... ( view more )% lower volume) in a subgroup of these men (n = 8, 73 years old) compared with 5 men (69 years old) who did not receive Cr. Strength (1-repetition maximum [1-RM]), endurance (maximum number of repetitions over 3 sets at 70-80% 1-RM), and LTM (dual-energy X-ray absorptiometry) were assessed before and after 12 weeks of Cr cessation combined with reduced-volume training. No changes in strength or LTM occurred. Muscle endurance was significantly reduced (7-21%; p <.05), with the rate of change similar between groups. Withdrawal from Cr had no effect on the rate of strength, endurance, and loss of lean tissue mass with 12 weeks of reduced-volume training. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Effect of creatine and weight training on muscle creatine and performance in vegetarians. Nov 2003 Darren G Burke,Philip D Chilibeck,Gianni Parise,Darren G Candow,Douglas Mahoney,Mark Tarnopolsky PURPOSE: To compare the change in muscle creatine, fiber morphology, body composition, hydration status, and exercise performance between vegetarians and nonvegetarians with 8 wk of creatine supplementation and resistance training. METHODS: Eighteen VG and 24 NV subjects (19-55 yr) were randomly as... ( view more )signed (double blind) to four groups: VG + creatine (VGCr, N=10), VG + placebo (VGPl, N=8), NV + creatine (NVCr, N=12), and NV + placebo (NVPl, N=12). Before and at the end of the study, muscle biopsies were taken from the vastus lateralis m, body composition was assessed by DXA, and strength was assessed using 1-RM bench press and leg press. Subjects participated in the same 8-wk resistance-training program. Creatine dosage was based on lean tissue mass (0.25 g.kg(-1) LTM.d(-1) x 7 d; 0.0625 g.kg(-1) LTM.d(-1) x 49 d). RESULTS: Biopsy samples indicated that total creatine (TCr=free Cr + PCr) was significantly lower in VG compared with NV at baseline (VG=117 mmol.kg(-1); NV=130 mmol.kg(-1); P<0.05). For Cr subjects, there was a greater increase in PCr, TCr, bench-press strength, isokinetic work, Type II fiber area, and whole-body lean tissue compared with subjects on placebo (P<0.05). Vegetarians who took Cr had a greater increase in TCr, PCr, lean tissue, and total work performance than nonvegetarians who took Cr (P<0.05). The change in muscle TCr was significantly correlated with initial muscle TCr, and the change in lean tissue mass and exercise performance. These findings confirm an ergogenic effect of Cr during resistance training and suggest that subjects with initially low levels of intramuscular Cr (vegetarians) are more responsive to supplementation. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Effect of alpha-lipoic acid combined with creatine monohydrate on human skeletal muscle creatine and phosphagen concentration. Sep 2003 Darren G Burke,Philip D Chilibeck,Gianni Parise,Mark A Tarnopolsky,Darren G Candow Alpha-lipoic acid has been found to enhance glucose uptake into skeletal muscle in animal models. Studies have also found that the co-ingestion of carbohydrate along with creatine increases muscle creatine uptake by a process related to insulin-stimulated glucose disposal. The purpose of this study... ( view more ) was to determine the effect of alpha-lipoic acid on human skeletal muscle creatine uptake by directly measuring intramuscular concentrations of creatine, phosphocreatine, and adenosine triphosphate when creatine monohydrate was co-ingested with alpha-lipoic acid. Muscle biopsies were acquired from the vastus lateralis m. of 16 male subjects (18-32 y) before and after the experimental intervention. After the initial biopsy, subjects ingested 20 g x d(-1) of creatine monohydrate, 20 g x d(-1) of creatine monohydrate + 100 g x d(-1) of sucrose, or 20 g x d(-1) of creatine monohydrate + 100 g x d(-1) of sucrose + 1000 mg x d(-1) of alpha-lipoic acid for 5 days. Subjects refrained from exercise and consumed the same balanced diet for 7 days. Body weight increased by 2.1% following the nutritional intervention, with no differences between the groups. There was a significant increase in total creatine concentration following creatine supplementation, with the group ingesting alpha-lipoic acid showing a significantly greater increase (p < .05) in phosphocreatine (87.6 --> 106.2 mmol x kg(-1) dry mass [dm]) and total creatine (137.8 --> 156.8 mmol x kg(-1) dm). These findings indicate that co-ingestion of alpha-lipoic acid with creatine and a small amount of sucrose can enhance muscle total creatine content as compared to the ingestion of creatine and sucrose or creatine alone. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Functional significance of protein kinase A activation by endothelin-1 and ATP: negative regulation of SRF-dependent gene expression by PKA. Jun 2003 Amanda Davis,Kyle Hogarth,Darren Fernandes,Julian Solway,Jiaxin Niu,Vladimir Kolenko,Darren Browning,Joseph M Miano,Sergei N Orlov,Nickolai O Dulin Endothelin-1 (ET1) and ATP stimulate contraction and hypertrophy of vascular smooth muscle cells (VSMC) by activating diverse signalling pathways. In this study, we show that in VSMC, ET1 and ATP stimulate transient and sustained activation of protein kinase A (PKA), respectively. Using a dominant ... ( view more )negative PKA mutant (PKA-DN), we examined the functional significance of PKA activation in the signalling of ET1 and ATP. Overexpression of PKA-DN did not alter the ET1- or ATP-induced phosphorylation of the extracellular signal-regulated protein kinase, Erk2. ATP stimulated a profound, PKA-dependent activation of cAMP-response element (CRE), whereas the effect of ET1 was negligible. Both ET1 and ATP stimulated serum response factor (SRF)-dependent gene expression. Overexpression of PKA-DN potentiated the effects of ET1 and ATP on SRF activity, whereas stimulation of PKA by isoproterenol, forskolin or by overexpression of the PKA catalytic subunit decreased SRF activity. These data demonstrate that (i) PKA negatively regulates SRF activity and (ii) ET1 and ATP stimulate opposing pathways, whose balance determines the net activity of SRF. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Screening of human primary melanocytes of defined melanocortin-1 receptor genotype: pigmentation marker, ultrastructural and UV-survival studies. Jun 2003 J Helen Leonard,Lisa H Marks,Wei Chen,Anthony L Cook,Glen M Boyle,Darren J Smit,Darren L Brown,Jennifer L Stow,Peter G Parsons,Richard A Sturm Recent population studies have demonstrated an association with the red-hair and fair-skin phenotype with variant alleles of the melanocortin-1 receptor (MC1R) which result in amino acid substitutions within the coding region leading to an altered receptor activity. In particular, Arg151Cys, Arg160... ( view more )Trp and Asp294His were the most commonly associated variants seen in the south-east Queensland population with at least one of these alleles found in 93% of those with red hair. In order to study the individual effects of these variants on melanocyte biology and melanocytic pigmentation, we established a series of human melanocyte strains genotyped for the MC1R receptor which included wild-type consensus, variant heterozygotes, compound heterozygotes and homozygotes for Arg151Cys, Arg160Trp, Val60Leu and Val92Met alleles. These strains ranged from darkly pigmented to amelanotic, with all strains of consensus sequence having dark pigmentation. UV sensitivity was found not to be associated with either MC1R genotype or the level of pigmentation with a range of sensitivities seen across all genotypes. Ultrastructural analysis demonstrated that while consensus strains contained stage IV melanosomes in their terminal dendrites, Arg151Cys and Arg160Trp homozygote strains contained only stage II melanosomes. This was despite being able to show expression of tyrosinase and tyrosinase-related protein-1 markers, although at reduced levels and an ability to convert exogenous 3,4-dihydroxyphenyl-alanine (DOPA) to melanin in these strains. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes. Jun 2003 Richard A Sturm,David L Duffy,Neil F Box,Wei Chen,Darren J Smit,Darren L Brown,Jennifer L Stow,J Helen Leonard,Nicholas G Martin We have examined melanocortin-1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color,... ( view more ) freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32-140) or weak r (OR = 5; 95% CI 3-11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild-type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Neural correlates of successful encoding identified using functional magnetic resonance imaging. Nov 1, 2002 Paul J Reber,Robert M Siwiec,Darren R Gitelman,Todd B Parrish,M-Marsel Mesulam,Ken A Paller,Darren R Gitleman Neural activity that occurs during the creation of a new memory trace can be observed using functional magnetic resonance imaging (fMRI). Event-related designs have been used to demonstrate that activity in prefrontal and medial temporal lobe areas is associated with successful memory storage. Here... ( view more ) we contrasted activity associated with encoding success and encoding effort. Participants viewed a series of 150 words but attempted to remember only half of them. Encoding effort was manipulated using a cue in the form of a letter (R or F) presented after each word to instruct participants either to remember or to forget that word. Increased activity in left inferior prefrontal cortex was observed when words were followed by the cue to remember. In contrast, increased left medial temporal lobe activity was observed for words that were successfully recalled later. These results show that fMRI correlates of the intention to encode a word are different from fMRI correlates of whether that encoding is successful. Prefrontal activation was strongly associated with intentional verbal encoding, whereas left medial temporal activation was crucial for the encoding that actually led to successful memory on the subsequent test. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Changes in head and neck position have a greater effect on elbow joint position sense in people with whiplash-associated disorders. 2006 Jul-Aug Joanna Joy Knox,Darren Jay Beilstein,Scott Darren Charles,Geir Arne Aarseth,Shivanthi Rayar,Julia Treleaven,Paul William Hodges BACKGROUND: It has been shown that perception of elbow joint position is affected by changes in head and neck position. Further, people with whiplash-associated disorders (WAD) present with deficits in upper limb coordination and movement. OBJECTIVES: This study is aimed to determine whether the ef... ( view more )fect of changes in head position on elbow joint position error (JPE) is more pronounced in people with WAD, and to determine whether this is related to the participant's pain and anxiety levels. METHODS: Nine people with chronic and disabling WAD and 11 healthy people participated in this experiment. The ability to reproduce a position at the elbow joint was assessed after changes in the position of the head and neck to 30 degrees , and with the head in the midline. Pain was monitored in WAD participants. RESULTS: Absolute elbow JPE with the head in neutral was not different between WAD and control participants (P=0.5). Changes in the head and neck position increased absolute elbow JPE in the WAD group (P<0.05), but did not affect elbow JPE in the control group (P=0.4). There was a connection between pain during testing and the effect of changes in head position on elbow JPE (P<0.05). DISCUSSION: Elbow JPE is affected by movement of the head and neck, with smaller angles of neck rotation in people with WAD than in healthy individuals. This observation may explain deficits in upper limb coordination in people with WAD, which may be due to the presence of pain or reduced range of motion in this population. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Combination iminium, enamine and copper(i) cascade catalysis: a carboannulation for the synthesis of cyclopentenes. Jul 7, 2008 Ting Yang,Alessandro Ferrali,Leonie Campbell,Darren J Dixon A one-pot, multistep reaction cascade to cyclopentenes from alpha,beta-unsaturated ketones and propargylated carbon acids through a combination of organocatalysis and transition metal ion catalysis is reported; the reaction cascade is simple to perform, occurs under mild conditions and is broad in ... ( view more )scope. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The effect of network mixing patterns on epidemic dynamics and the efficacy of disease contact tracing. Jul 6, 2008 Istvan Z Kiss,Darren M Green,Rowland R Kao In networks, nodes may preferentially contact other nodes with similar (assortatively mixed) or dissimilar (disassortatively mixed) numbers of contacts. Different patterns of contact support different epidemic dynamics, potentially affecting the efficacy of control measures such as contact tracing,... ( view more ) which aims to identify and isolate nodes with infectious contacts. We used stochastic simulations to investigate the effects of mixing patterns on epidemic dynamics and contact-tracing efficacy. For uncontrolled epidemics, outbreaks occur at lower infection rates for more assortatively mixed networks, with faster initial epidemic growth rate and shorter epidemic duration than for disassortatively mixed networks. Contact tracing performs better for assortative mixing where epidemic size is large and tracing rate low, but it performs better for disassortative mixing at higher contact rates. For assortatively mixed networks, disease spreads first to highly connected nodes, but this is balanced by contact tracing quickly identifying these same nodes. The converse is true for disassortative mixing, where both disease and tracing are less likely to target highly connected nodes. For small epidemics, contact tracing is more effective on disassortative networks due to the greater resilience of assortative networks to link removal. Multi-step contact tracing is more effective than single-step tracing for assortative mixing, but this effect is smaller for disassortatively mixed networks. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles DNA-based vaccines protect against zoonotic schistosomiasis in water buffalo. Jul 4, 2008 Akram A Da'dara,Yuesheng S Li,Tie Xiong,Jie Zhou,Gail M Williams,Donald P McManus,Zheng Feng,Xin L Yu,Darren J Gray,Donald A Harn Schistosomiasis japonica is an endemic, zoonotic disease of major public health importance in China where water buffaloes account for approximately 75% of disease transmission. Interventions that reduce schistosome infection in water buffaloes will enhance their health simultaneously reducing disea... ( view more )se transmission to humans. While chemotherapy has proved successful, it requires continued time consuming and expensive mass treatments. A more sustainable option would be development of vaccines that reduce transmission of S. japonicum from bovines to replace bovine chemotherapy. We performed two randomized double blind trials in water buffaloes to determine if DNA vaccines encoding triose-phosphate isomerase (SjCTPI), or the tetraspanin 23kDa integral membrane protein (SjC23), alone or fused to bovine heat shock protein 70 (Hsp70) could induce a level of immunity conducive to long-term sustainable control. Groups of water buffaloes (15/group) received three intramuscular injections, 4 weeks apart. Booster immunizations were co-administered with a plasmid DNA encoding IL-12. Four weeks after the last injection, water buffaloes were challenged with 1000 cercariae, and vaccine efficacy analyzed 8 weeks later. Water buffaloes vaccinated with SjCTPI-Hsp70 or SjCTPI plasmids had worm burdens reduced by 51.2% and 41.5%, respectively. Importantly, fecal miracidial hatching was reduced by 52.1% and 33.2% respectively compared to control vaccinated water buffaloes. Vaccination with SjC23-Hsp70 and SjC23 plasmids reduced worm burdens by 50.9% and 45.5%, respectively, and fecal miracidial hatching by 52.0% and 47.4%. A mathematical model of schistosome transmission predicts that schistosome vaccines capable of reducing water buffaloes' fecal egg output by 45%, alone or in conjunction with praziquantel treatment, will lead to a significant reduction in transmission of schistosomiasis. Both DNA vaccines tested here exceed this hypothetical level. Indeed, mathematical modeling of SjCTPI-Hsp70 and SjC23-Hsp70 alone and in conjunction with human chemotherapy showed a significant reduction in transmission almost to the point of elimination. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles cGMP-dependent protein kinase anchoring by IRAG regulates its nuclear translocation and transcriptional activity. Jul 2008 Darren E Casteel,Tong Zhang,Shunhui Zhuang,Renate B Pilz Type I cGMP-dependent protein kinases (PKGs) translocate to the nucleus to regulate gene expression in some, but not all cell types; we hypothesized that nuclear translocation of PKG may be regulated by extra-nuclear anchoring proteins. The inositol 1,4,5-triphosphate (IP(3)) receptor-associated cG... ( view more )MP kinase substrate (IRAG) binds to the N-terminus of PKG Ibeta, but not PKG Ialpha, and in smooth muscle cells, IRAG and PKG Ibeta are in a complex with the IP(3) receptor at endoplasmatic reticulum membranes, where the complex regulates calcium release [Schlossmann et al., Nature, 404 (2000) 197]. We found that co-expression of IRAG and PKG Ibeta in baby hamster kidney cells prevented cGMP-induced PKG Ibeta translocation to the nucleus, and decreased cGMP/PKG Ibeta transactivation of a cAMP-response element-dependent reporter gene. These effects required the PKG Ibeta/IRAG association, as demonstrated by a binding-incompetent IRAG mutant, and were specific for PKG Ibeta, as nuclear translocation and reporter gene activation by PKG Ialpha was not affected by IRAG. A phosphorylation-deficient IRAG mutant that is no longer functionally regulated by PKG phosphorylation suppressed cGMP/PKG Ibeta transcriptional activity, indicating that IRAG's effect was not explained by changes in intracellular calcium, and was not related to competition of IRAG with other PKG substrates. These results demonstrate that PKG anchoring to a specific binding protein is sufficient to dictate subcellular localization of the kinase and affect cGMP signaling in the nucleus, and may explain why nuclear translocation of PKG I does not occur in all cell types. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Changes in central artery blood pressure and wave reflection during a cold pressor test in young adults. Jul 2008 Darren P Casey,Randy W Braith,Gary L Pierce The relative contribution of sympathetic nervous system (SNS)-induced increase in peripheral vascular resistance on central artery blood pressure (BP) and aortic wave reflection (augmentation index; AIx) is not completely understood. Central BP and wave reflection characteristics were measured usin... ( view more )g radial artery applanation tonometry before, during a 3-min cold pressor test (CPT), and 90 and 180-s post-CPT in 15 young, healthy adults (25 +/- 1 years). The CPT resulted in a greater magnitude of change in the estimated aortic systolic (31 vs. 23%, P < 0.05) and pulse (31 vs. 13%, P < 0.05) BP compared with the change in brachial artery BP. Additionally, the CPT resulted in an increased mean arterial pressure (MAP) (P < 0.05) and AIx (10 +/- 2 vs. 26 +/- 2%, P < 0.05). The change in MAP during the CPT was correlated to the change in AIx (r = 0.73, P < 0.01) and inversely related to roundtrip duration of the reflected wave to the periphery and back (r = -0.57, P < 0.05). The present study suggests that cold pressor testing results in a significant increase in arterial wave reflection intensity, possibly due to an increased MAP. However, the greater increase in systolic and pulse BP in the central compared with the peripheral circulation suggests that increased central artery wave reflection intensity contributes to increased left ventricular myocardial oxygen demand during CPT-induced hypertension. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles (2R)-[(4-Biphenylylsulfonyl)amino]-N-hydroxy-3-phenylpropionamide (BiPS), a matrix metalloprotease inhibitor, is a novel and potent activator of hypoxia-inducible factors. Jul 2008 Marie-Claude Lauzier,Geneviève A Robitaille,Denise A Chan,Amato J Giaccia,Darren E Richard Hypoxia-inducible factors (HIFs) are unstable heterodimeric transcription factors and decisive elements for the transcriptional regulation of genes important in the adaptation to low-oxygen conditions. Hypoxia is the ubiquitous inducer of HIFs, stabilizing the alpha-subunit and permitting the forma... ( view more )tion of a functional HIF complex. Here, we identify (2R)-[(4-biphenylylsulfonyl)amino]-N-hydroxy-3-phenylpropionamide (BiPS), a commercially available metalloprotease-2 and -9 inhibitor, as a rapid and potent inducer of HIFs. We show that in different cell lines, BiPS induces the HIF-alpha subunit by inhibiting its degradation through stabilization of its labile oxygen-dependent degradation domain. This is achieved through the inhibition of HIF-1alpha hydroxylation. The HIF-1 complex, formed after BiPS treatment, is capable of DNA binding and activation of HIF target genes, including the expression of vascular endothelial growth factor. Because novel HIF activators have generated considerable interest in the possible treatment of different ischemic diseases, we believe that BiPS and derivative molecules could have strong therapeutic potential. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Sleep deprivation alters functioning within the neural network underlying the covert orienting of attention. Jun 27, 2008 Bryce A Mander,Kathryn J Reid,Vijay K Davuluri,Dana M Small,Todd B Parrish,M-Marsel Mesulam,Phyllis C Zee,Darren R Gitelman One function of spatial attention is to enable goal-directed interactions with the environment through the allocation of neural resources to motivationally relevant parts of space. Studies have shown that responses are enhanced when spatial attention is predictively biased towards locations where s... ( view more )ignificant events are expected to occur. Previous studies suggest that the ability to bias attention predictively is related to posterior cingulate cortex (PCC) activation [Small, D.M., et al., 2003. The posterior cingulate and medial prefrontal cortex mediate the anticipatory allocation of spatial attention. Neuroimage 18, 633-41]. Sleep deprivation (SD) impairs selective attention and reduces PCC activity [Thomas, M., et al., 2000. Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity. J. Sleep Res. 9, 335-352]. Based on these findings, we hypothesized that SD would affect PCC function and alter the ability to predictively allocate spatial attention. Seven healthy, young adults underwent functional magnetic resonance imaging (fMRI) following normal rest and 34-36 h of SD while performing a task in which attention was shifted in response to peripheral targets preceded by spatially informative (valid), misleading (invalid), or uninformative (neutral) cues. When rested, but not when sleep-deprived, subjects responded more quickly to targets that followed valid cues than those after neutral or invalid cues. Brain activity during validly cued trials with a reaction time benefit was compared to activity in trials with no benefit. PCC activation was greater during trials with a reaction time benefit following normal rest. In contrast, following SD, reaction time benefits were associated with activation in the left intraparietal sulcus, a region associated with receptivity to stimuli at unexpected locations. These changes may render sleep-deprived individuals less able to anticipate the locations of upcoming events, and more susceptible to distraction by stimuli at irrelevant locations. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Paradoxical imaging findings in cerebral gliomas. Jun 15, 2008 Marie Atkinson,Csaba Juhász,Jagdish Shah,Xi Guo,William Kupsky,Darren Fuerst,Robert Johnson,Craig Watson Gliomas represent approximately one-third of all intracranial tumors in adults and commonly present clinically with seizures. We report two seizure patients with paradoxical imaging findings on preoperative grading of their cerebral gliomas. A 53-year-old man with a history of temporal lobe epileps... ( view more )y originating from a mass in the right medial temporal region (patient 1) and a 44-year-old man with a history of predominantly left sided sensory seizures with a mass in the right posterior parietal region (patient 2) underwent presurgical evaluation including MRI and glucose PET, followed by surgery to remove cerebral tumors associated with seizure onset. Preoperatively, patient 1 had a homogenous non-enhancing lesion on MRI and hypometabolism on PET imaging, suggesting a low-grade tumor. Postoperative histopathology was consistent with a glioblastoma multiforme (grade IV). Patient 2 had a heterogeneous lesion with cyst formation, edema, and contrast enhancement on preoperative MRI imaging, and interictal hypermetabolism on PET scan, thus suggesting a high-grade tumor. Postoperative histopathology was consistent with an oligodendroglioma (grade II) without anaplastic features. We conclude preoperative grading of cerebral gliomas may be inaccurate occasionally even in cases with concordant structural and functional imaging findings. This should be considered when counseling patients. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Efficient base catalyzed alkylation reactions with aziridine electrophiles. Jun 7, 2008 Thomas A Moss,Aurelie Alba,David Hepworth,Darren J Dixon N-Mesitylene sulfonyl and N-tosyl aziridines have been identified as effective electrophiles in alkylation reactions of carbon acids catalyzed by the organic phosphorine base BEMP; yields of up to 99% for a range of pro-nucleophiles under mild reaction conditions are reported. View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 94 1 2 3 4 > Last >> (2338 articles found)

      
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