The effect of β-glucan and its potential analog on the structure of Dectin-1 receptor.

Dectin-1 is a recently discovered pattern-recognition receptor that plays an important role in antifungal innate immunity, which acts a specific receptor for β-glucan (BG). The present study, aimed at clarifying effect of BG and a new analog, maltotriose (MT) on Dectin-1 receptor. We implemented molecular docking of MT on Dectin-1 along with model-independent all-atom-molecular dynamics simulations.

Associations Between Left Ventricular Dysfunction and Brain Structure and Function: Findings From the SABRE (Southall and Brent Revisited) Study.

Background: Subclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross-sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms.

Method And Results: A total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment.

Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus.

Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism.

Population trends in the 10-year incidence and prevalence of diabetic retinopathy in the UK: a cohort study in the Clinical Practice Research Datalink 2004-2014.

Objectives: To describe trends in the incidence and prevalence of diabetic retinopathy (DR) in the UK by diabetes type, age, sex, ethnicity, deprivation, region and calendar year.

Design: Cohort study using the Clinical Practice Research Datalink (CPRD).

Setting: UK primary care.

Molecular Characterization and In-Silico Analysis of the Tissue Inhibitor of Metalloproteinases-3 (TIMP-3) Gene of Canine Mammary Tumor.

Background: Mammary tumors are the second most common tumors (after skin tumors) in female dogs (Canis lupus familiaris). Tissue Inhibitor of Metlloproteinases-3 (TIMP-3) is a matrix associated endogenous inhibitor of Matrix Metalloproteinases (MMPs). Cancer metastasis occurs as a result of imbalance between MMPs and TIMPs.

Metformin and cancer in type 2 diabetes: a systematic review and comprehensive bias evaluation.

Background: Existing observational studies provide conflicting evidence for the causal effect of metformin use on cancer risk in patients with type-2 diabetes, and there are concerns about bias affecting a number of studies.

Methods: MEDLINE was used to identify observational studies investigating the association between metformin and overall or site-specific cancer in people with type-2 diabetes. A systematic data extraction and bias assessment was conducted, in which risk of eight bias domains (outcome, exposure, control selection, baseline confounding, time-dependent confounding, immortal time, missing data, censoring methods) were assessed against pre-defined criteria, and rated as unlikely, low, medium or high.

Protein Modeling and Molecular Dynamics Simulation of Cloned Regucalcin (RGN) Gene from Bubalus bubalis.

Background: Regucalcin (RGN), a calcium regulating protein having anti-prolific, antiapoptotic functions, plays important part in the biosynthesis of ascorbic acid. It is a highly conserved protein that has been reported from many tissue types of various vertebrate species. Employing its effect of regulating enzyme activities through reaction with sulfhydryl group (-SH) and calcium, structural level study believed to offer a better understanding of binding properties and regulatory mechanisms of RGN, was performed.

Recent developments in near-infrared spectroscopy (NIRS) for the assessment of local skeletal muscle microvascular function and capacity to utilise oxygen.

Purpose Of Review: Continuous wave near infrared spectroscopy (CW NIRS) provides non-invasive technology to measure relative changes in oxy- and deoxy-haemoglobin in a dynamic environment. This allows determination of local skeletal muscle O saturation, muscle oxygen consumption ([Formula: see text]) and blood flow. This article provides a brief overview of the use of CW NIRS to measure exercise-limiting factors in skeletal muscle.

Air pollution and cardiovascular mortality with over 25years follow-up: A combined analysis of two British cohorts.

Background: Adverse effects of air pollution on cardiovascular disease (CVD) mortality are well established. There are comparatively fewer studies in Europe, and in the UK particularly, than in North America. We examined associations in two British cohorts with >25years of follow-up.

Metformin in adults with type 1 diabetes: Design and methods of REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL): An international multicentre trial.

Aims: Cardiovascular (CV) disease is a major cause of reduced life expectancy in type 1 diabetes (T1D). Intensive insulin therapy prevents CV complications but is constrained by hypoglycaemia and weight gain. Adjunct metformin reduces insulin dose requirement and stabilizes weight but there are no data on its cardiovascular effects.

Exaggerated Exercise Blood Pressure is Associated with Higher Left Ventricular Mass in Adolescence. The Avon Longitudinal Study of Parents and Children.

Objective: Dynamic exercise results in an increase to systolic blood pressure (BP). Irrespective of resting BP, some individuals may experience an exaggerated rise in systolic BP with exercise, which in adulthood, is associated with greater risk of developing hypertension, cardiovascular morbidity and mortality. It is not known if exercise BP is associated with adverse cardiovascular risk during adolescence.

Hypertensive Disorders of Pregnancy and Offspring Cardiac Structure and Function in Adolescence.

Background: Fetal exposure to preeclampsia is associated with higher blood pressure and later risk of stroke. We aimed to investigate the associations of maternal preeclampsia, gestational hypertension, and maternal blood pressure change in pregnancy with offspring cardiac structure and function in adolescence.

Methods And Results: Using data from a prospective birth cohort study, we included offspring who underwent echocardiography (mean age, 17.

Association of Retinopathy and Retinal Microvascular Abnormalities With Stroke and Cerebrovascular Disease.

Background And Purpose: Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and (1) strokes and subclinical cerebral infarcts and (2) cerebral white matter lesions in a UK-based triethnic population-based cohort.

Methods: A total of 1185 participants (age, 68.

Strategies & recent development of transmission-blocking vaccines against .

Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity.

Associations of night-time road traffic noise with carotid intima-media thickness and blood pressure: The Whitehall II and SABRE study cohorts.

Background: Road traffic noise has been linked to increased risk of stroke, for which hypertension and carotid intima-media thickness (cIMT) are risk factors. A link between traffic noise and hypertension has been established, but there are few studies on blood pressure and no studies on cIMT.

Objectives: To examine cross-sectional associations for long-term exposure to night-time noise with cIMT, systolic blood pressure (SBP), diastolic blood pressure (DBP) and hypertension.

MicroRNA-126 and micro-/macrovascular complications of type 1 diabetes in the EURODIAB Prospective Complications Study.

Aims: Increasing evidence suggests a potential role of circulating miRNAs as clinical biomarkers, and loss of miRNA-126 has been proposed as a predictor of type 2 diabetes onset. However, a systematic analysis of circulating miRNAs in type 1 diabetic patients with micro-/macrovascular complications has not yet been performed.

Methods: A cross-sectional nested case-control study from the EURODIAB Prospective Complications Study of 455 type 1 diabetic patients was performed.

Algorithms for the Capture and Adjudication of Prevalent and Incident Diabetes in UK Biobank.

Objectives: UK Biobank is a UK-wide cohort of 502,655 people aged 40-69, recruited from National Health Service registrants between 2006-10, with healthcare data linkage. Type 2 diabetes is a key exposure and outcome. We developed algorithms to define prevalent and incident diabetes for UK Biobank.

The effect of regulating molecules on the structure of the PPAR-RXR complex.

The PPAR-RXR complex is one of the most significant and prevalent regulatory systems, controlling lipid metabolism by gene expression. Both proteins are members of the nuclear hormone receptor family, consisting of a ligand-binding domain (LBD), a hinge and a DNA binding domain (DBD). The two proteins form a heterodimer in the nucleus.

Urinary proteomics predict onset of microalbuminuria in normoalbuminuric type 2 diabetic patients, a sub-study of the DIRECT-Protect 2 study.

Background: Early prevention of diabetic nephropathy is not successful as early interventions have shown conflicting results, partly because of a lack of early and precise indicators of disease development. Urinary proteomics has shown promise in this regard and could identify those at high risk who might benefit from treatment. In this study we investigate its utility in a large type 2 diabetic cohort with normoalbuminuria.

A global × global test for testing associations between two large sets of variables.

In high-dimensional omics studies where multiple molecular profiles are obtained for each set of patients, there is often interest in identifying complex multivariate associations, for example, copy number regulated expression levels in a certain pathway or in a genomic region. To detect such associations, we present a novel approach to test for association between two sets of variables. Our approach generalizes the global test, which tests for association between a group of covariates and a single univariate response, to allow high-dimensional multivariate response.

Health Education and General Practitioner Training in Hypertension Management: Long-Term Effects on Kidney Function.

Background And Objectives: In the Control of Blood Pressure and Risk Attenuation trial, a 2×2 factorial design study (2004-2007), the combined home health education and trained general practitioner intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. We aimed to assess the effectiveness of the interventions on kidney function.

Design, Participants, Settings, & Methods: In 2012-2013, we conducted extended follow-up of a total of 1271 individuals aged ≥40 years with hypertension (systolic BP ≥140 mmHg, diastolic BP ≥90 mmHg, or receipt of antihypertensive treatment) and serum creatinine measurements with 2 years in-trial and 5 years of post-trial period in 12 randomly selected low-income communities in Karachi, Pakistan.

Modulation of p73 isoforms expression induces anti-proliferative and pro-apoptotic activity in mantle cell lymphoma independent of p53 status.

Mantle cell lymphoma (MCL) is characterized by a clinically aggressive course with frequent relapse and poor survival. The p53 pathway is frequently dysregulated and p53 status predicts clinical outcome. In this report, we investigated whether modulation of p73 isoforms by diclofenac inhibits cell growth, induces apoptosis and/or cell cycle arrest in MCL relative to p53 status.

Midlife blood pressure predicts future diastolic dysfunction independently of blood pressure.

Objectives: High blood pressure (BP) is associated with diastolic dysfunction, but the consequence of elevated BP over the adult life course on diastolic function is unknown. We hypothesised that high BP in earlier adulthood would be associated with impaired diastolic function independent of current BP.

Methods: Participants in the Medical Research Council National Survey of Health and Development birth cohort (n=1653) underwent investigations including echocardiography at age 60-64 years.