Use of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells.

This study provides an assessment of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. The system combines microfluidic technology and nanoliter-scale reactions. We sequenced 622 cells, allowing identification of 341 islet cells with high-quality gene expression profiles.

Radiographic Evidence of Hip Microinstability in Elite Ballet.

Purpose: To determine prevalence, magnitude, and predisposing radiographic features of hip subluxation in elite ballet dancers.

Methods: A cross-sectional investigation of professional male and female ballet dancers was performed using 5 plain radiographs. A "splits" anteroposterior (AP) radiograph was performed with legs abducted parallel to the trunk in the coronal plane (splits position; grand écart facial).

Effect of Health Literacy on Quality of Life amongst Patients with Ischaemic Heart Disease in Australian General Practice.

Background: Appropriate understanding of health information by patients with cardiovascular disease (CVD) is fundamental for better management of risk factors and improved morbidity, which can also benefit their quality of life.

Objectives: To assess the relationship between health literacy and health-related quality of life (HRQoL) in patients with ischaemic heart disease (IHD), and to investigate the role of sociodemographic and clinical variables as possible confounders.

Methods: Cross-sectional study of patients with IHD recruited from a stratified sample of general practices in two Australian states (Queensland and South Australia) between 2007 and 2009.

Inactivating Variants in ANGPTL4 and Risk of Coronary Artery Disease.

Background: Higher-than-normal levels of circulating triglycerides are a risk factor for ischemic cardiovascular disease. Activation of lipoprotein lipase, an enzyme that is inhibited by angiopoietin-like 4 (ANGPTL4), has been shown to reduce levels of circulating triglycerides.

Methods: We sequenced the exons of ANGPTL4 in samples obtain from 42,930 participants of predominantly European ancestry in the DiscovEHR human genetics study.

In Vivo Quantitative Microcomputed Tomographic Analysis of Vasculature and Organs in a Normal and Diseased Mouse Model.

Non-bone in vivo micro-CT imaging has many potential applications for preclinical evaluation. Specifically, the in vivo quantification of changes in the vascular network and organ morphology in small animals, associated with the emergence and progression of diseases like bone fracture, inflammation and cancer, would be critical to the development and evaluation of new therapies for the same. However, there are few published papers describing the in vivo vascular imaging in small animals, due to technical challenges, such as low image quality and low vessel contrast in surrounding tissues.

Disordered haematopoiesis and athero-thrombosis.

Atherosclerosis, the major underlying cause of cardiovascular disease, is characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries. Increased production and activation of monocytes, neutrophils, and platelets, driven by hypercholesterolaemia and defective high-density lipoproteins-mediated cholesterol efflux, tissue necrosis and cytokine production after myocardial infarction, or metabolic abnormalities associated with diabetes, contribute to atherogenesis and athero-thrombosis. This suggests that in addition to traditional approaches of low-density lipoproteins lowering and anti-platelet drugs, therapies directed at abnormal haematopoiesis, including anti-inflammatory agents, drugs that suppress myelopoiesis, and excessive platelet production, rHDL infusions and anti-obesity and anti-diabetic agents, may help to prevent athero-thrombosis.

Using qualitative insights to change practice: exploring the culture of antibiotic prescribing and consumption for urinary tract infections.

Objectives: The aim of this paper is to explore the culture of antibiotic prescribing and consumption in the community for urinary tract infections (UTI) from the perspective of the general practitioners (GPs) and community member.

Design: Indepth interviews were conducted with GPs, and focus groups were held with community members.

Setting: General practice and community setting.

Effect of Obesity on Outcomes of Forefoot Surgery.

Background: Forefoot surgery typically is elective, so it is important to define risk factors to educate patients on potential complications. The purpose of this study was to determine if obesity is an independent risk factor that contributes to increased complication rates after forefoot surgery.

Methods: Through a retrospective review of records, 633 patients were identified who had forefoot surgery at one institution between 2008 and 2010.

Native LDL promotes differentiation of human monocytes to macrophages with an inflammatory phenotype.

Recruitment of monocytes in atherosclerosis is dependent upon increased levels of plasma lipoproteins which accumulate in the blood vessel wall. The extracellular milieu can influence the phenotype of monocyte subsets (classical: CD14++CD16-, intermediate: CD14+CD16+ and non-classical: CD14dimCD16++) and macrophages (M1 or M2) and consequently the initiation, progression and/or regression of atherosclerosis. However, it is not known what effect lipoproteins, in particular native low-density lipoproteins (nLDL), have on the polarisation of monocyte-derived macrophages.

A Qualitative Study of Prescription Contraception Use: The Perspectives of Users, General Practitioners and Pharmacists.

Background: The oral contraceptive pill (OCP) remains the most popular form of prescription contraception in many countries, despite adherence difficulties for many. Uptake of long acting reversible contraceptives (LARCs), which are less reliant on user adherence, remains low. The aim of this study was to explore the experiences of, and attitudes towards, prescription contraception amongst samples of contraception users, general practitioners (GPs) and pharmacists.

IL-18 Production from the NLRP1 Inflammasome Prevents Obesity and Metabolic Syndrome.

Interleukin-18 (IL-18) is activated by Caspase-1 in inflammasome complexes and has anti-obesity effects; however, it is not known which inflammasome regulates this process. We found that mice lacking the NLRP1 inflammasome phenocopy mice lacking IL-18, with spontaneous obesity due to intrinsic lipid accumulation. This is exacerbated when the mice are fed a high-fat diet (HFD) or a high-protein diet, but not when mice are fed a HFD with low energy density (high fiber).

Intervention to improve the quality of antimicrobial prescribing for urinary tract infection: a cluster randomized trial.

Background: Overuse of antimicrobial therapy in the community adds to the global spread of antimicrobial resistance, which is jeopardizing the treatment of common infections.

Methods: We designed a cluster randomized complex intervention to improve antimicrobial prescribing for urinary tract infection in Irish general practice. During a 3-month baseline period, all practices received a workshop to promote consultation coding for urinary tract infections.

Myostatin blockade with a fully human monoclonal antibody induces muscle hypertrophy and reverses muscle atrophy in young and aged mice.

Background: Loss of skeletal muscle mass and function in humans is associated with significant morbidity and mortality. The role of myostatin as a key negative regulator of skeletal muscle mass and function has supported the concept that inactivation of myostatin could be a useful approach for treating muscle wasting diseases.

Methods: We generated a myostatin monoclonal blocking antibody (REGN1033) and characterized its effects in vitro using surface plasmon resonance biacore and cell-based Smad2/3 signaling assays.

Loss of SFRP4 Alters Body Size, Food Intake, and Energy Expenditure in Diet-Induced Obese Male Mice.

Secreted frizzled-related protein 4 (SFRP4) is an extracellular regulator of the wingless-type mouse mammary tumor virus integration site family (WNT) pathway. SFRP4 has been implicated in adipocyte dysfunction, obesity, insulin resistance, and impaired insulin secretion in patients with type 2 diabetes. However, the exact role of SFRP4 in regulating whole-body metabolism and glucose homeostasis is unknown.

Laparoscopic Gastrojejunostomy Tube Placement in Infants with Congenital Cardiac Disease.

Introduction: Gastrojejunostomy (GJ) tubes are an option for durable enteral access for critically ill infants with congenital cardiac disease who struggle with obtaining adequate nutrition.

Materials And Methods: Infants weighing less than 10 kg with cardiac disease who received placement of a laparoscopic GJ tube from November 2011 to January 2015 were reviewed. The operative technique used an umbilical port for the camera and a single stab incision for the gastric access site.

ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by episodically exuberant heterotopic ossification (HO), whereby skeletal muscle is abnormally converted into misplaced, but histologically normal bone. This HO leads to progressive immobility with catastrophic consequences, including death by asphyxiation. FOP results from mutations in the intracellular domain of the type I BMP (bone morphogenetic protein) receptor ACVR1; the most common mutation alters arginine 206 to histidine (ACVR1(R206H)) and has been thought to drive inappropriate bone formation as a result of receptor hyperactivity.

High-density lipoprotein inhibits human M1 macrophage polarization through redistribution of caveolin-1.

Background And Purpose: Monocyte-derived macrophages are critical in the development of atherosclerosis and can adopt a wide range of functional phenotypes depending on their surrounding milieu. High-density lipoproteins (HDLs) have many cardio-protective properties including potent anti-inflammatory effects. We investigated the effects of HDL on human macrophage phenotype and the mechanisms by which these occur.

Prescription contraception use: a cross-sectional population study of psychosocial determinants.

Objective: Many forms of contraception are available on prescription only for example, the oral contraceptive pill (OCP) and long-acting reversible contraceptives (LARCs). In this analysis we aim to identify key determinants of prescription contraceptive use.

Design: Cross-sectional population survey.

The variability and seasonality of the environmental reservoir of Mycobacterium bovis shed by wild European badgers.

The incidence of Mycobacterium bovis, the causative agent of bovine tuberculosis, has been increasing in UK cattle herds resulting in substantial economic losses. The European badger (Meles meles) is implicated as a wildlife reservoir of infection. One likely route of transmission to cattle is through exposure to infected badger urine and faeces.

Improving antimicrobial prescribing in Irish primary care through electronic data collection and surveillance: a feasibility study.

Background: The increase in the spread of antimicrobial resistance (AMR) in bacterial pathogens and limited availability of new antimicrobials places immense pressure on general practitioners (GPs) to prescribe appropriately. Currently, electronic antimicrobial prescribing data is not routinely collected from GPs in Ireland for surveillance purposes to assess regional specific fluctuations or trends in antimicrobial prescribing. The current study aimed to address this issue by assessing the feasibility of remotely extracting antimicrobial prescribing data from primary care practices in Ireland, for the purpose of assessing prescribing quality using the European Surveillance of Antimicrobial Consumption (ESAC) drug specific quality indicators.

Primary care organisational interventions for secondary prevention of ischaemic heart disease: a systematic review and meta-analysis.

Background: Ischaemic heart disease (IHD) is the most common cause of death worldwide.

Aim: To determine the long-term impact of organisational interventions for secondary prevention of IHD.

Design And Setting: Systematic review and meta-analysis of studies from CENTRAL, MEDLINE(®), Embase, and CINAHL published January 2007 to January 2013.

Performance of a Noninvasive Test for Detecting Mycobacterium bovis Shedding in European Badger (Meles meles) Populations.

The incidence of Mycobacterium bovis, the causative agent of bovine tuberculosis, in cattle herds in the United Kingdom is increasing, resulting in substantial economic losses. The European badger (Meles meles) is implicated as a wildlife reservoir and is the subject of control measures aimed at reducing the incidence of infection in cattle populations. Understanding the epidemiology of M.

Glucagon Receptor Blockade With a Human Antibody Normalizes Blood Glucose in Diabetic Mice and Monkeys.

Antagonizing glucagon action represents an attractive therapeutic option for reducing hepatic glucose production in settings of hyperglycemia where glucagon excess plays a key pathophysiological role. We therefore generated REGN1193, a fully human monoclonal antibody that binds and inhibits glucagon receptor (GCGR) signaling in vitro. REGN1193 administration to diabetic ob/ob and diet-induced obese mice lowered blood glucose to levels observed in GCGR-deficient mice.

Three temperature regimes in superconducting photon detectors: quantum, thermal and multiple phase-slips as generators of dark counts.

We perform measurements of the switching current distributions of three w ≈ 120 nm wide, 4 nm thick NbN superconducting strips which are used for single-photon detectors. These strips are much wider than the diameter of the vortex cores, so they are classified as quasi-two-dimensional (quasi-2D). We discover evidence of macroscopic quantum tunneling by observing the saturation of the standard deviation of the switching distributions at temperatures around 2 K.