Valsartan Improves Adipose Tissue Function in Humans with Impaired Glucose Metabolism: A Randomized Placebo-Controlled Double-Blind Trial

<div><h3>Background</h3><p>Blockade of the renin-angiotensin system (RAS) reduces the incidence of type 2 diabetes mellitus. In rodents, it has been demonstrated that RAS blockade improved adipose tissue (AT) function and glucose homeostasis. However, the effects of long-term RAS blockade on AT function have not been investigated in humans. Therefore, we examined whether 26-wks treatment with the angiotensin II type 1 receptor blocker valsartan affects AT function in humans with impaired glucose metabolism (IGM).</p> <h3>Methodology/Principal Findings</h3><p>We performed a randomized, double-blind, placebo-controlled parallel-group study, in which 38 subjects with IGM were treated with valsartan (VAL, 320 mg/d) or placebo (PLB) for 26 weeks. Before and after treatment, an abdominal subcutaneous AT biopsy was collected for measurement of adipocyte size and AT gene/protein expression of angiogenesis/capillarization, adipogenesis, lipolytic and inflammatory cell markers. Furthermore, we evaluated fasting and postprandial AT blood flow (ATBF) (¹³³Xe wash-out), systemic inflammation and insulin sensitivity (hyperinsulinemic-euglycemic clamp). VAL treatment markedly reduced adipocyte size (<em>P</em><0.001), with a shift toward a higher proportion of small adipocytes. In addition, fasting (<em>P</em> = 0.043) and postprandial ATBF (<em>P</em> = 0.049) were increased, whereas gene expression of angiogenesis/capillarization, adipogenesis and macrophage infiltration markers in AT was significantly decreased after VAL compared with PLB treatment. Interestingly, the change in adipocyte size was associated with alterations in insulin sensitivity and reduced AT gene expression of macrophage infiltration markers. VAL did not alter plasma monocyte-chemoattractant protein (MCP)-1, TNF-α, adiponectin and leptin concentrations.</p> <h3>Conclusions/Significance</h3><p>26-wks VAL treatment markedly reduced abdominal subcutaneous adipocyte size and AT macrophage infiltration markers, and increased ATBF in IGM subjects. The VAL-induced decrease in adipocyte size was associated with reduced expression of macrophage infiltration markers in AT. Our findings suggest that interventions targeting the RAS may improve AT function, thereby contributing to a reduced risk of developing cardiovascular disease and type 2 diabetes.</p> <h3>Trial Registration</h3><p>Trialregister.nl NTR721 (ISRCTN Registry: ISRCTN<a href="http://www.controlled-trials.com/isrctn/pf/42786336">42786336</a>)</p> </div

The association between mental health nursing and hospital admissions for people with serious mental illness: a protocol for a systematic review

Background: Relapse in individuals with severe mental illness (SMI) is a frequent occurrence and can add considerably to the burden of disease. As such, relapse prevention is an essential therapeutic outcome for people with SMI. Mental health nurses (MHNs) are well placed to support individuals with SMI and to prevent relapse; notwithstanding, there has been no synthesis of the evidence to date to determine whether MHNs prevent relapse in this population. Methods: Electronic databases will be systemically searched for observational studies and clinical trials that report the association between mental health nursing and the hospitalisation of persons living with an SMI. The search will be supplemented by reference checking and a search of the grey literature. The primary outcome of interest will be hospital admission rate. Screening of articles, data extraction and critical appraisal will be undertaken by two reviewers, independently, with a third reviewer consulted should disagreement occur between reviewers. The quality of studies will be assessed using the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tool and the Cochrane Collaboration risk of bias tool. Depending on the number of studies and level of heterogeneity, the evidence may be synthesised using meta-analysis or narrative synthesis. Discussion: This review will explore for the first time the clinical potential of mental health nursing in preventing relapse in persons with SMI. The findings of this review will serve to inform future research and education in this area. The evidence may also help inform future policy, including decisions regarding future mental health workforce development and planning

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

Search for high-mass resonances decaying to dilepton final states in pp collisions at s√=7 TeV with the ATLAS detector

The ATLAS detector at the Large Hadron Collider is used to search for high-mass resonances decaying to an electron-positron pair or a muon-antimuon pair. The search is sensitive to heavy neutral Z′ gauge bosons, Randall-Sundrum gravitons, Z * bosons, techni-mesons, Kaluza-Klein Z/γ bosons, and bosons predicted by Torsion models. Results are presented based on an analysis of pp collisions at a center-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.9 fb−1 in the e + e − channel and 5.0 fb−1 in the μ + μ −channel. A Z ′ boson with Standard Model-like couplings is excluded at 95 % confidence level for masses below 2.22 TeV. A Randall-Sundrum graviton with coupling k/MPl=0.1 is excluded at 95 % confidence level for masses below 2.16 TeV. Limits on the other models are also presented, including Technicolor and Minimal Z′ Models

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level