Vapor swellable colloidal photonic crystals with pressure tunability

Polyferrocenylsilane gel photonic crystals have been reversibly swollen using solvent vapors, and exhibit precise pressure tunability over a wavelength range of greater than 100 nmGeneralitat Valenciana CTDIA/2002/2

Nanometer-Scale Precision Tuning of 3D Photonic Crystals Made Possible Using Polyelectrolytes with Controlled Short Chain Length and Narrow Polydispersity

Nanometer‐scale tuning of the optical properties of prefabricated photonic crystals is achieved via layer‐by‐layer assembly of polyelectrolytes in the interstitial spaces of the photonic lattice. The key to the approach is using polyelectrolytes with controlled short chain lengths. This ensures they do not block the air voids, thereby maintaining uniform coating and thus precise and reproducible optical tuning.Ministerio de Economía y Competitividad MAT2011-23593, CSD2007-00007Junta de Andalucía FQM3579, FQM5247European Union 30708

The research on endothelial function in women and men at risk for cardiovascular disease (REWARD) study: methodology

Background Endothelial function has been shown to be a highly sensitive marker for the overall cardiovascular risk of an individual. Furthermore, there is evidence of important sex differences in endothelial function that may underlie the differential presentation of cardiovascular disease (CVD) in women relative to men. As such, measuring endothelial function may have sex-specific prognostic value for the prediction of CVD events, thus improving risk stratification for the overall prediction of CVD in both men and women. The primary objective of this study is to assess the clinical utility of the forearm hyperaemic reactivity (FHR) test (a proxy measure of endothelial function) for the prediction of CVD events in men vs. women using a novel, noninvasive nuclear medicine -based approach. It is hypothesised that: 1) endothelial dysfunction will be a significant predictor of 5-year CVD events independent of baseline stress test results, clinical, demographic, and psychological variables in both men and women; and 2) endothelial dysfunction will be a better predictor of 5-year CVD events in women compared to men. Methods/Design A total of 1972 patients (812 men and 1160 women) undergoing a dipyridamole stress testing were recruited. Medical history, CVD risk factors, health behaviours, psychological status, and gender identity were assessed via structured interview or self-report questionnaires at baseline. In addition, FHR was assessed, as well as levels of sex hormones via blood draw. Patients will be followed for 5 years to assess major CVD events (cardiac mortality, non-fatal MI, revascularization procedures, and cerebrovascular events). Discussion This is the first study to determine the extent and nature of any sex differences in the ability of endothelial function to predict CVD events. We believe the results of this study will provide data that will better inform the choice of diagnostic tests in men and women and bring the quality of risk stratification in women on par with that of men

Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains

Ruiz JC, D'Afonseca V, Silva A, et al. Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains. PLoS ONE. 2011;6(4): e18551.Background: Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity. Methodology and Findings: We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer. Conclusions: These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers CP001809 and CP001829

Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p&lt;1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p&lt;5×10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.</p

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response

Randomized feasibility trial of the Scleroderma patient-centered intervention network hand exercise program (SPIN-HAND): Study protocol

BACKGOUND: Significant functional impairment of the hands is nearly universal in systemic sclerosis (SSc, scleroderma). Hand exercises may improve hand function, but developing, testing and disseminating rehabilitation interventions in SSc is challenging. The Scleroderma Patient-centered Intervention Network (SPIN) was established to address this issue and has developed an online hand exercise program to improve hand function for SSc patients (SPIN-HAND). The aim of the proposed feasibility trial is to evaluate the feasibility of conducting a full-scale randomized controlled trial (RCT) of the SPIN-HAND intervention. DESIGN AND METHODS: The SPIN-HAND feasibility trial will be conducted via the SPIN Cohort. The SPIN Cohort was developed as a framework for embedded pragmatic trials using the cohort multiple RCT design. In total, 40 English-speaking SPIN Cohort participants with at least mild hand function limitations (Cochin Hand Function Scale ≥3) and an indicated interest in using an online hand-exercise intervention will be randomized with a 1:1 ratio to be offered to use the SPIN-HAND program or usual care for 3 months. The primary aim is to evaluate the trial implementation processes, required resources and management, scientific aspects, and participant acceptability and usage of the SPIN-HAND program. DISCUSSION: The SPIN-HAND exercise program is a self-help tool that may improve hand function in patients with SSc. The SPIN-HAND feasibility trial will ensure that trial methodology is robust, feasible, and consistent with trial participant expectations. The results will guide adjustments that need to be implemented before undertaking a full-scale RCT of the SPIN-HAND program. TRIAL REGISTRATION: ClinicalTrials.gov IDENTIFIER: NCT03092024

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe