bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lentiviral Nef Proteins Manipulate T Cells in a Subset-Specific Manner
Authors: Yu Hangxing , Khalid Mohammad , Heigele Anke , Schmökel Jan , M. Usmani Shariq , van der Merwe Johannes , Münch Jan , Silvestri Guido , Kirchhoff Frank 
Published: December 2014

ABSTRACT

The role of the accessory viral Nef protein as a multifunctional manipulator of the host cell that is required for effective replication of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV)
in vivo
is well established. It is unknown, however, whether Nef manipulates all or just specific subsets of CD4
+
T cells, which are the main targets of virus infection and differ substantially in their state of activation and importance for a functional immune system. Here, we analyzed the effect of Nef proteins differing in their T cell receptor (TCR)-CD3 downmodulation function in HIV-infected human lymphoid aggregate cultures and peripheral blood mononuclear cells. We found that Nef efficiently downmodulates TCR-CD3 in naive and memory CD4
+
T cells and protects the latter against apoptosis. In contrast, highly proliferative CD45RA
+
CD45RO
+
CD4
+
T cells were main producers of infectious virus but largely refractory to TCR-CD3 downmodulation. Such T cell subset-specific differences were also observed for Nef-mediated modulation of CD4 but not for enhancement of virion infectivity. Our results indicate that Nef predominantly modulates surface receptors on CD4
+
T cell subsets that are not already fully permissive for viral replication. As a consequence, Nef-mediated downmodulation of TCR-CD3, which distinguishes most primate lentiviruses from HIV type 1 (HIV-1) and its
vpu
-containing simian precursors, may promote a selective preservation of central memory CD4
+
T cells, which are critical for the maintenance of a functional immune system.

IMPORTANCE
The Nef proteins of human and simian immunodeficiency viruses manipulate infected CD4
+
T cells in multiple ways to promote viral replication and immune evasion
in vivo
. Here, we show that some effects of Nef are subset specific. Downmodulation of CD4 and TCR-CD3 is highly effective in central memory CD4
+
T cells, and the latter Nef function protects this T cell subset against apoptosis. In contrast, highly activated/proliferating CD4
+
T cells are largely refractory to receptor downmodulation but are main producers of infectious HIV-1. Nef-mediated enhancement of virion infectivity, however, was observed in all T cell subsets examined. Our results provide new insights into how primate lentiviruses manipulate their target cells and suggest that the TCR-CD3 downmodulation function of Nef may promote a selective preservation of memory CD4
+
T cells, which are critical for immune function, but has little effect on activated/proliferating CD4
+
T cells, which are the main targets for viral replication.
Improving the surgical hot clinic
Authors: Hubbard Thomas , Thomas Rhys 
Published: December 2014

AbstractAmbulatory care is an underdeveloped concept in the setting of emergency surgery, however it is recognised that many institutions will need to develop this service to cope with increased time and financial pressures.[1] There is increased emphasis on ambulatory care pathways for a variety of medical conditions.[2] Risk management is important in managing patients with acute abdominal pain in an outpatient setting and senior doctor support is essential. While the patient remains in the community, effective communication with the patient’s primary care provider improves patient safety and satisfaction.[3]This quality improvement project identified current service provision of ambulatory care for surgical patients in the hot clinic at Croydon University Hospital with subsequent consultation with the surgical department to identify problems arising from the throughput of patients. Guidelines were then updated incorporating solutions to the identified issues which were then validated by the department of general surgery. Post intervention measurement identified a decrease in patients whose principal assessment and management was made by a senior house officer level doctor through the hot clinic patient journey from 26% to 9% (64% decrease), indicating an increase in registrar and/or consultant involvement in managing the hot clinic. The number of patients attending hot clinic that had effective discharge liaison (in the form of a formal letter) to the GP increased from 18% to 68% (250% increase). In conclusion, the introduction of updated guidelines effected a safer and more effective ambulatory hot clinic to perform closer to full capacity, providing improved patient care for the local population.
EARLY CHILDHOOD IS OVERRATED—A LIFE COURSE PERSPECTIVE USING SIBLINGS AND POPULATIONS
Authors: Wall-Wieler E , Roos LL , Chateau D 
Published: December 2014

Purpose/Rationale for the projectHow important are early childhood predictors in the presence of later childhood and early adolescent predictors when examining several late adolescent health and education outcomes? How well do the models work? A sibling design examines a set of time-varying predictors on two health outcomes (ADHD/Conduct Disorders, asthma) between ages 14 and 18 and one education outcome (failure to graduate high school), controlling for a variety measures.MethodsMulti-level modeling of a sample of randomly selected consecutive siblings and twins (n=29,444) born in Manitoba, Canada between 1984 and 1989 allowed comparing family and individual level characteristics. Extensive sensitivity testing involved comparison with a population sample (n=62,820). This analysis uses files from the Population Health Research Data Repository at the Manitoba Centre for Health Policy (MCHP), linked across ministries, which include information on individual level health and education. Census data on neighborhood household income, education and so forth, were also incorporated.Results/Next stepsAlthough several 0–3 variables were significant for the education outcome, very few were significant for the health outcomes indicating that early childhood variables are not particularly important in predicting late adolescent health and education outcomes. Time-varying predictors in early childhood were markedly less important when including later childhood (4–8) and early adolescent (9–13) health predictor; however, events in early childhood might be important in embedding specific outcomes in later life. Using a life course approach provided an excellent fit for the externalizing mental conditions model (c-statistic=0.826) and a reasonable fit for failure to graduate high school (c-statistic=0.793) and asthma (c-statistic=0.798) models. This paper adds to the growing literature that suggests a stronger focus be put on adolescence as a “second sensitive developmental period” when examining late adolescent and adult outcomes. Future research should be less concerned with birth and early childhood predictors and put a stronger focus on the late childhood and early adolescent time periods, as they bring with them a period of rapid brain maturation that can significantly modify childhood trajectories.
DEVELOPING A SHELTER EVALUATION INSTRUMENT THAT PROMOTES POST-DISASTER POPULATION HEALTH
Authors: Nath R , Shannon H , Kabali C , Oremus M 
Published: December 2014

IntroductionAbsence of shelter may adversely affect the health of post-disaster populations. When shelters are inadequate or not provided, overcrowded ad hoc communities may form and encourage the spread of infectious disease. Shelter evaluation is therefore necessary to promote post-disaster population health. Even in cases where evaluations are carried out, standardized evaluation indicators do not exist.ObjectivesTo determine what indicators are being used and which should be used to evaluate shelter assistance following natural disasters.Methodology 1. Review: Using systematic review methods, electronic databases and the grey literature were searched for publications that evaluated shelter assistance following natural disasters in developing countries. Indicators used to evaluate shelter assistance were extracted and the most common indicators were identified. 2. Interviews: Based on the indicators extracted, a preliminary evaluation instrument was designed to evaluate shelter assistance. Six shelter experts were interviewed to establish validity of the indicators and evaluation questions. The transcripts from the interviews were analyzed using rigorous qualitative research methodology.Results 1. Review: A total of 1480 indicators were extracted from 181 publications. Indicators most commonly evaluated in the field were: community involvement in shelter planning (n=108), quality and labour of construction (n=107), and scale of assistance provided (n=99). 2. Interviews: Shelter experts felt that the correct indicators had been extracted; however, they expressed the need for more health related indicators. They also felt that the questions evaluating the indicators measured output and should be rephrased to evaluate outcome and impact.ConclusionsThis evaluation instrument, directly based on the most important indicators in the literature and validated by shelter experts, will enable aid agencies to better assess and meet the shelter and health needs of populations impacted by disasters.
THE EFFECTIVENESS OF PHARMACOLOGICAL AND NON-PHARMACOLOGICAL INTERVENTIONS IN IMPROVING RESTLESS LEGS SYNDROME SEVERITY AMONG PATIENTS ON DIALYSIS: A SYSTEMATIC REVIEW
Authors: Quach K , Gandhi M , Brimble KS , Walsh M 
Published: December 2014

Background and objectivesRestless legs syndrome (RLS) is common amongst patients receiving dialysis. It is unclear how to optimally treat RLS in dialysis patients. We conducted a systematic review to identify therapies to reduce the severity of RLS.MethodsWe systematically searched MEDLINE and EMBASE and hand searched narrative reviews for randomized controlled trials that assessed the use of pharmacological or non-pharmacological interventions to reduce the severity of RLS among patients receiving dialysis. The primary outcome was RLS symptoms.ResultsOf 621 abstracts identified, 12 studies that included 13 interventions met the inclusion and exclusion criteria. All trials reported interventions that significantly improved RLS severity. The interventions included dopamine agonists (n=6), gabapentin (n=2), intradialytic exercise (n=2) intravenous iron (n=1), vitamins C and E (n=1), and clonidine (n=1). In studies that compared two interventions, ropinirole gabapentin, and intradialytic exercise with resistance were all more effective than L-dopa in comparisons. However, all studies were at high risk of bias with the most common causes due to lack of allocation concealment, high losses to follow-up, and missing data. Further, follow-up for these studies was short-term ranging from 3 days to 24 weeks.ConclusionsRopinirole, gabapentin, and intradialytic exercise appear promising to reduce RLS in dialysis patients. However, methodologically rigorous, appropriately powered, longer term RCTs are required to determine the optimal treatment strategy for RLS among dialysis patients.
ASSOCIATIONS BETWEEN EXPOSURE TO AIR POLLUTION AND GESTATIONAL HYPERTENSION IN URBAN HALIFAX
Authors: Poirier A , Dodds L , Johnson M , Dummer T , Rainham D 
Published: December 2014

IntroductionExposure to air pollution has been linked with an increased risk for cardiovascular morbidity and mortality. Few studies have examined possible associations between air pollution and gestational hypertension (GH). The prevalence of GH in Canada is approximately 6%, translating into roughly 300 women developing GH in Halifax annually. GH disorders account for 2–8% of pregnancy complications worldwide.ObjectiveThe current study examined the relationship between exposure to air pollution during pregnancy and GH.MethodsA retrospective cohort study including women residing in urban Halifax, Nova Scotia who delivered a singleton infant between 2008 and 2012. The Nova Scotia Atlee Perinatal Database was used to determine socio-demographic characteristics and pregnancy conditions. Spatial estimates of air pollution were determined from land-use regression (LUR) models and were linked to women in the Perinatal Database based on their six-digit postal code. Residential concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter (PM1, PM2.5,PM10), toluene, and benzene were averaged over three seasons and categorized into quartiles. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression, adjusting for potential confounders.ResultsOf the 11,724 singleton births analyzed, 7.7% of the cohort developed GH. When adjusted for smoking, pre-pregnancy weight, maternal age and parity a significant inverse relationship was observed for exposure to all pollutants (top quartile of exposure relative to lowest quartile); SO2(OR: 0.75; 95% CI: 0.62, 0.92), NO2(0.66; 0.54, 0.81), PM1(0.71; 0.57, 0.87), PM2.5(0.68, 0.56, 0.83), PM10(0.71; 0.58, 0.87) toluene (0.68; 0.56, 0.83) and benzene (0.62; 0.51, 0.75).ConclusionThe inverse relationships observed were contrary to what has been observed in past research. These results stress the importance of conducting more research in this field to better understand the characteristics that influence the relationship between air pollution and GH.
ADIPOSITY SIGNIFICANTLY MODIFIES GENETIC RISK FOR DYSLIPIDEMIA
Authors: Cole CC , Nikpay M , Lau P , Stewart AFR , Davies RW , Wells GA , Dent R , McPherson R 
Published: December 2014

BackgroundThe Global Lipids Genetics Consortium identified 95 common loci that explained 12.2% (LDL-C), 12.1% (HDL-C) and 9.6% (triglycerides [TG]) of total variance in plasma lipid traits in the Framingham Heart Study. Since adiposity is associated with plasma levels of TG and HDL-C, we hypothesized that the predictive value of common risk variants for these lipid traits would differ for obese versus lean subjects.MethodsThe study population consisted of two independent cohorts of subjects of European de-scent, genotyped on the Affymetrix 6.0 array with 1000G imputation. 1) OBLE: 959 obese/869 lean. 2) CC (healthy elderly subjects recruited as con-trols for a CAD study) 830 obese/1,044 lean. A genetic predisposition score was calculated for each individual as a sum across SNPs of the number of risk alleles at that SNP multiplied by the effect size of the SNP.ResultsIn the OBLE cohort, a genetic risk score explained a greater percentage of the total TG variance in obese vs lean (beta GRS=0.154 mmol/L (p<2e-16) vs 0.094 mmol/L (p=5.8e-10); adjusted R2=0.090 vs 0.042), a finding that was replicated in the CC cohort for obese vs lean (beta GRS=0.153 mmol/L (p=1.5e-7) vs 0.102 mmol/L (p=4.2e-6); adjusted R2=0.044 vs 0.024). A similar but less significant trend was noted for LDL-C. In addition, the genetic risk score predicted variability in TG better than sex/age for obese subjects. In contrast a genetic risk score for HDL-C was a better predictor of this trait in lean versus obese subjects in both the OBLE and CC cohorts. Genetic risk scores for each lipid trait showed no association with BMI (P>0.2) indicating that the above findings are not due to possible overlap between genetic loci for BMI and lipid traits.ConclusionsGenetic predisposition to elevated plasma triglycerides and LDL-C and low HDL-C is highly sensitive to extremes of BMI.
VALIDITY AND RELIABILITY OF A FOOD FREQUENCY QUESTIONNAIRE AMONG LEBANESE CHILDREN FOR THE ASSESSMENT OF ENERGY AND NUTRIENT INTAKE
Authors: Hammami N , Moghames P , Shoaib H , Nasreddine L , Hwalla N , Naja F 
Published: December 2014

IntroductionIn order to evaluate the diet-disease association, valid dietary assessment tools that accurately assess nutritional intake are critical. Childhood is a critical window for intervention to delineate the risk of many nutrition-related diseases later in life. Limited validated tools exist to assess dietary intake in children aged less than 10 years in the Middle East and North Africa Region and in Lebanon.ObjectivesThe main objectives of this study were to develop and validate a Food Frequency Questionnaire (FFQ) to assess dietary intake among Lebanese children aged 5–10 years.MethodsChildren were recruited from public and private schools in the Lebanese capital Beirut. Mothers (used as proxy) completed the FFQ (FFQ-1) in the first visit. During the following 4 weeks, 4 Multiple Pass 24 hour recalls (MPRs) were collected. At Week 4, the FFQ (FFQ-2) was completed a second time. Validity tested the developed FFQ against the mean of the MPRs. It was assessed by spearman correlation coefficients and Bland Altman plots. The Intraclass Correlation Coefficient (ICC) and kappa statistic were used to test reliability between FFQ-1 and FFQ-2.Results120 children completed the study. Spearman correlation coefficients for energy, protein and total fat intakes were 0.60, 0.40 and 0.60, respectively. Other nutrients' coefficients ranged between 0.20–0.65. Bland-Altman's Limits of Agreement showed acceptable agreement.ICCs for energy, protein and total fat intakes were 0.87, 0.85 and 0.85, respectively. Other nutrients' ICC ranged between 0.18–0.90. The kappa coefficients between FFQ-1 and FFQ-2 ranged between substantial and moderate agreement.ConclusionsThis study's findings indicated that the developed FFQ is valid and reliable among Lebanese children aged 5–10 years. This validated questionnaire will be a useful tool for assessing Lebanese children's dietary intakes. It will also be an asset that other researchers in the region can use or adapt to suit their study populations.
Understanding dynamic changes in live cell adhesion with neutron reflectometry
Authors: Junghans Ann , Waltman Mary Jo , Smith Hillary L. , Pocivavsek Luka , Zebda Noureddine , Birukov Konstantin , Viapiano Mariano , Majewski Jaroslaw 
Published: December 2014

Neutron reflectometry (NR) was used to examine various live cells' adhesion to quartz substrates under different environmental conditions, including flow stress. To the best of our knowledge, these measurements represent the first successful visualization and quantization of the interface between live cells and a substrate with sub-nanometer resolution.In our first experiments, we examined live mouse fibroblast cells as opposed to past experiments using supported lipids, proteins, or peptide layers with no associated cells. We continued the NR studies of cell adhesion by investigating endothelial monolayers and glioblastoma cells under dynamic flow conditions. We demonstrated that neutron reflectometry is a powerful tool to study the strength of cellular layer adhesion in living tissues, which is a key factor in understanding the physiology of cell interactions and conditions leading to abnormal or disease circumstances. Continuative measurements, such as investigating changes in tumor cell — surface contact of various glioblastomas, could impact advancements in tumor treatments. In principle, this can help us to identify changes that correlate with tumor invasiveness. Pursuit of these studies can have significant medical impact on the understanding of complex biological problems and their effective treatment, e.g. for the development of targeted anti-invasive therapies.
Mechanism and consequences of the shift in cardiac arginine metabolism following ischaemia and reperfusion in rats
Authors: Cabrera-Fuentes Hector , Steinert Isabel , Preissner Klaus , Bencsik Péter , Sárközy Márta , Csonka Csaba , Ferdinandy Péter , Schulz Rainer , Schlüter Klaus-Dieter , Schreckenberg Rolf , Weber Pia 
Published: December 2014

SummaryCardiac ischaemia and reperfusion leads to irreversible injury and subsequent tissue remodelling. Initial reperfusion seems to shift arginine metabolism from nitric oxide (NO) to polyamine formation. This may limit functional recovery at reperfusion. The hypothesis was tested whether ischaemia/reperfusion translates such a shift in arginine metabolism in a tumour necrosis factor (TNF)-α-dependent way and renin-angiotensin system (RAS)-dependent way into a sustained effect. Both, the early post-ischaemic recovery and molecular adaptation to ischaemia/reperfusion were analysed in saline perfused rat hearts undergoing global no-flow ischaemia and reperfusion. Local TNF-α activation was blocked by inhibition of TNF-α sheddase ADAM17. To interfere with RAS captopril was administered. Arginase was inhibited by administration of Nor-NOHA. Long-term effects of ischemia/reperfusion on arginine metabolism were analysed in vivo in rats receiving an established ischaemia/reperfusion protocol in the closed chest mode. mRNA expression analysis indicated a shift in the arginine metabolism from NO formation to polyamine metabolism starting within 2 hours (h) of reperfusion and translated into protein expression within 24 h. Inhibition of the TNF-α pathway and captopril attenuated these delayed effects on post-ischaemic recovery. This shift in arginine metabolism was associated with functional impairment of hearts within 24 h. Inhibition of arginase but not that of TNF-α and RAS pathways improved functional recovery immediately. However, no benefit was observed after four months. In conclusion, this study identified TNF-α and RAS to be responsible for depressed cardiac function that occurred a few hours after reperfusion.
VWF excess and ADAMTS13 deficiency: a unifying pathomechanism linking inflammation to thrombosis in DIC, malaria, and TTP
Authors: Schwameis Michael , Schörgenhofer Christian , Assinger Alice , Steiner Margarete M. , Jilma Bernd 
Published: December 2014

SummaryAbsent or severely diminished activity of ADAMTS13 (A Disintegrin And Metalloprotease with a ThromboSpondin type 1 motif, member 13) resulting in the intravascular persistence and accumulation of highly thrombogenic ultra large von Willebrand factor (UL-VWF) multimers is the pathophysiological mechanism underlying thrombotic thrombocytopenic purpura. Reduced VWF-cleaving protease levels, however, are not uniquely restricted to primary thrombotic microangiopathy (TMA), e. g. thrombotic thrombocytopenic purpura, but also occur in other life-threatening thrombocytopenic conditions: severely decreased ADAMTS13 activity is seen in severe sepsis, disseminated intravascular coagulation (DIC) and complicated malarial infection. The clinical relevance of these secondary thrombotic microangiopathies is increasingly recognised, but its therapeutic implications have not yet been determined. The presence of a secondary TMA in certain diseases may define patient groups which possibly could benefit from ADAMTS13 replacement or a VWF-targeting therapy. This short-review focuses on the role of UL-VWF multimers in secondary TMA and discusses the potential of investigational therapies as candidates for the treatment of TTP. In conclusion, prospective clinical trials on the effectiveness of protease replacement in vivo seem reasonable. Carefully selected patients with secondary TMA may benefit from therapies primarily intended for the use in patients with TTP.