Hematocrit predicts long-term mortality in a nonlinear and sex-specific manner in hypertensive adults.

Hematocrit has been inconsistently reported to be a risk marker of cardiovascular morbidity and mortality. The Glasgow Blood Pressure Clinic Study cohort included 10951 hypertensive patients, who had hematocrit measured at their initial clinic visit and followed for ≤35 years. Cox proportional hazards models were used to estimate hazard ratios for all-cause, cardiovascular, ischemic heart disease, stroke, and noncardiovascular mortality.

The effect of menstrual cycle on periodontal health - a clinical and microbiological study.

Purpose: Fluctuations in female sex hormones result in changes in the gingival and periodontal tissues. The purpose of this study was to compare the periodontal status of premenopausal women at different time points during their menstrual cycle and to find the associated subgingival microbiota.

Materials And Methods: One hundred premenopausal women participated in the study and were divided into two groups: group I consisted of 50 subjects with clinically healthy gingival, and group II consisted of 50 subjects with chronic gingivitis.

Impact of comprehensive cardiovascular risk reduction programme on risk factor clustering associated with elevated blood pressure in an Indian industrial population.

Background & Objectives: Cardiovascular risk factors clustering associated with blood pressure (BP) has not been studied in the Indian population. This study was aimed at assessing the clustering effect of cardiovascular risk factors with suboptimal BP in Indian population as also the impact of risk reduction interventions.

Methods: Data from 10543 individuals collected in a nation-wide surveillance programme in India were analysed.

Genetic basis of blood pressure and hypertension.

Blood pressure (BP) is a complex trait regulated by an intricate network of physiological pathways involving extracellular fluid volume homeostasis, cardiac contractility and vascular tone through renal, neural or endocrine systems. Untreated high BP, or hypertension (HTN), is associated with increased mortality, and thus a better understanding of the pathophysiological and genetic underpinnings of BP regulation will have a major impact on public health. However, identifying genes that contribute to BP and HTN has proved challenging.

Distributed medical image analysis and diagnosis through crowd-sourced games: a malaria case study.

In this work we investigate whether the innate visual recognition and learning capabilities of untrained humans can be used in conducting reliable microscopic analysis of biomedical samples toward diagnosis. For this purpose, we designed entertaining digital games that are interfaced with artificial learning and processing back-ends to demonstrate that in the case of binary medical diagnostics decisions (e.g.

Integrated rapid-diagnostic-test reader platform on a cellphone.

We demonstrate a cellphone-based rapid-diagnostic-test (RDT) reader platform that can work with various lateral flow immuno-chromatographic assays and similar tests to sense the presence of a target analyte in a sample. This compact and cost-effective digital RDT reader, weighing only ~65 g, mechanically attaches to the existing camera unit of a cellphone, where various types of RDTs can be inserted to be imaged in reflection or transmission modes under light-emitting diode (LED)-based illumination. Captured raw images of these tests are then digitally processed (within less than 0.

Association between genetic variants on chromosome 15q25 locus and objective measures of tobacco exposure.

Background: Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure.

Methods: We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730-rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers.

Targeting Aurora A kinase activity with the investigational agent alisertib increases the efficacy of cytarabine through a FOXO-dependent mechanism.

Novel therapies are urgently needed to improve clinical outcomes for patients with acute myeloid leukemia (AML). The investigational drug alisertib (MLN8237) is a novel Aurora A kinase inhibitor being studied in multiple Phase I and II studies. We investigated the preclinical efficacy and pharmacodynamics of alisertib in AML cell lines, primary AML cells and mouse models of AML.

Genetics and hypertension: is it time to change my practice?

Recent advances in genotyping technology and in particular a number of large-scale genome-wide association studies have helped to unravel the genetic basis of hypertension. Although our knowledge is still far from being complete it is important to ask how genetic findings could be translated to clinical practice. In a first step we summarize the strategies to dissect the genetics of hypertension from candidate gene studies to genome-wide association studies and recent sequencing experiments.

(1)H, (13)C and (15)N assignments of CdnL, an essential protein in Myxococcus xanthus.

CdnL, an essential protein in Myxococcus xanthus and several other bacteria, is a member of the large CarD_TRCF family of bacterial proteins that interact with RNA polymerase. Structural analyses of the 164-residue M. xanthus CdnL by NMR is complicated because of broadening, and hence overlap, of the signals due to the self-association and the monomer-dimer equilibrium that occurs in solution.

Metabolism, pharmacokinetics, tissue distribution, and stability studies of the prodrug analog of an anti-hepatitis B virus dinucleoside phosphorothioate.

The alkoxycarbonyloxy dinucleotide prodrug R(p), S(p)-2 is an orally bioavailable anti-hepatitis B virus agent. The compound is efficiently metabolized to the active dinucleoside phosphorothioate R(p), S(p)-1 by human liver microsomes and S9 fraction without cytochrome P450-mediated oxidation or conjugation. The conversion of R(p), S(p)-2 to R(p), S(p)-1 appears to be mediated by liver esterases, occurs in a stereospecific manner, and is consistent with our earlier reported studies of serum-mediated hydrolytic conversion of R(p), S(p)-2 to R(p), S(p)-1.

Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.

Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy.

Purpose: Romidepsin is a structurally unique, potent class 1 selective histone deacetylase inhibitor. The primary objective of this international, pivotal, single-arm, phase II trial was to confirm the efficacy of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

Patients And Methods: Patients who were refractory to at least one prior systemic therapy or for whom at least one prior systemic therapy failed received romidepsin at 14 mg/m(2) as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days.

CarF mediates signaling by singlet oxygen, generated via photoexcited protoporphyrin IX, in Myxococcus xanthus light-induced carotenogenesis.

Blue light triggers carotenogenesis in the nonphototrophic bacterium Myxococcus xanthus by inducing inactivation of an anti-σ factor, CarR, and the consequent liberation of the cognate extracytoplasmic function (ECF) σ factor, CarQ. CarF, the protein implicated earliest in the response to light, does not resemble any known photoreceptor. It interacts physically with CarR and is required for its light-driven inactivation, but the mechanism is unknown.

A bayesian dose-finding design adapting to efficacy and tolerability response.

We propose a new adaptive Bayesian design, explicitly modeling the trade-off between efficacy and tolerability in dose-finding studies. This design incorporates a continuous efficacy variable and a dichotomous tolerability variable. This adaptive design was developed in the context of a drug under development for treatment of major depression, but is easily extended to any setting with a continuous efficacy and a dichotomous tolerability or safety variable.

Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.

Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions.

Blood pressure loci identified with a gene-centric array.

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples.

A comparison of races and leukemia subtypes among patients in different cancer survivorship phases.

Background: The three phases of cancer survivorship include the acute survival phase (ASP), the extended survival phase (ESP), and the permanent survival phase (PSP). This Institutional Review Board-approved retrospective pilot project compared races and leukemia subtypes among patients in the ASP, ESP, and PSP.

Methods: Fifty-five adult patients from our National Cancer Institute-designated cancer center were individually interviewed.

A novel bacteriophage Tail-Associated Muralytic Enzyme (TAME) from Phage K and its development into a potent antistaphylococcal protein.

Background: Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. However, the rapid emergence of antibiotic resistance limits the choice of therapeutic options for treating infections caused by this organism. Muralytic enzymes from bacteriophages have recently gained attention for their potential as antibacterial agents against antibiotic-resistant gram-positive organisms.

A 10-month, open-label evaluation of desvenlafaxine in outpatients with major depressive disorder.

Background: The primary objective was to evaluate the long-term safety of desvenlafaxine (administered as desvenlafaxine succinate) during open-label treatment in adult outpatients with a primary DSM-IV diagnosis of major depressive disorder (MDD).

Method: Depressed adult outpatients (≥ 18 years) who had completed 8-week, double-blind therapy (desvenlafaxine, venlafaxine extended release, or placebo) in a phase 3 study of desvenlafaxine for MDD received up to 10 months of open-label treatment with flexible-dose desvenlafaxine (200 to 400 mg/d). Safety assessments included physical examination, measurement of weight and vital signs, laboratory determinations, and 12-lead electrocardiogram recordings.

Four genetic loci influencing electrocardiographic indices of left ventricular hypertrophy.

Background: Presence of left ventricular hypertrophy on an ECG (ECG-LVH) is widely assessed clinically and provides prognostic information in some settings. There is evidence for significant heritability of ECG-LVH. We conducted a large-scale gene-centric association analysis of 4 commonly measured indices of ECG-LVH.

Evaluation of the genotoxic effects of fixed appliances on oral mucosal cells and the relationship to nickel and chromium concentrations: an in-vivo study.

Introduction: The release of metal ions from fixed orthodontic appliances is a source of concern. The aim of this study was to evaluate genotoxic damage in the oral mucosal cells of patients wearing fixed appliance, and the nickel and chromium ion contents in these cells.

Methods: Twenty patients undergoing orthodontic treatment formed the experimental group, and 20 untreated subjects comprised the control group.

In-vivo evaluation of salivary nickel and chromium levels in conventional and self-ligating brackets.

Introduction: Our objective was to evaluate and compare the salivary levels of nickel and chromium before and 1, 7, and 30 days after placement of conventional and self-ligating appliance systems.

Methods: Twenty women were randomly divided into 2 groups. Patients in group 1 had conventional brackets bonded to their teeth; in group 2, self-ligating brackets were bonded.