Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

Introduction: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor.

Toward a molecular microbial blood test for tuberculosis infection.

The World Health Organization's aim to end the global tuberculosis (TB) epidemic by 2050 cannot be achieved without taking measures to identify people with asymptomatic Mycobacterium tuberculosis (Mtb) infection and offer them an intervention to reduce the risk of disease progression, such as preventive antimicrobial therapy. Implementation of this strategy is limited by the fact that existing tests for Mtb infection, which use immunosensitization to Mtb-specific antigens as a proxy for infection, have low positive predictive value for progression to TB. A blood test that detects Mtb deoxyribonucleic acid (DNA) could allow preventive therapy to be targeted at individuals with microbiological evidence of persistent infection.

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

Background: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result.

A Spectroscopic Reflectance-Based Low-Cost Thickness Measurement System for Thin Films: Development and Testing.

The requirement for alternatives in roll-to-roll (R2R) processing to expand thin film inspection in wider substrates at lower costs and reduced dimensions, and the need to enable newer control feedback options for these types of processes, represents an opportunity to explore the applicability of newer reduced-size spectrometers sensors. This paper presents the hardware and software development of a novel low-cost spectroscopic reflectance system using two state-of-the-art sensors for thin film thickness measurements. The parameters to enable the thin film measurements using the proposed system are the light intensity for two LEDs, the microprocessor integration time for both sensors and the distance from the thin film standard to the device light channel slit for reflectance calculations.

Effectiveness of Fortified Mid-Day Meal in Reducing Anemia Among School Children in Dhenkanal, Odisha: A Quasi-Experimental Study.

Background: Iron-deficiency anemia among school-aged children is widespread in India. The efficacy of micronutrient and iron fortified school-served meals in reducing iron deficiency anemia has been demonstrated in randomized controlled trials in other parts of the globe. The current study evaluates its effectiveness in real-world Indian settings.

Inspection of Enamel Removal Using Infrared Thermal Imaging and Machine Learning Techniques.

Within aerospace and automotive manufacturing, the majority of quality assurance is through inspection or tests at various steps during manufacturing and assembly. Such tests do not tend to capture or make use of process data for in-process inspection and certification at the point of manufacture. Inspection of the product during manufacturing can potentially detect defects, thus allowing consistent product quality and reducing scrappage.

Determinants of QuantiFERON Plus-diagnosed tuberculosis infection in adult Ugandan TB contacts: A cross-sectional study.

Background: The tuberculin skin test is commonly used to diagnose latent tuberculosis infection (LTBI) in resource-limited settings, but its specificity is limited by factors including cross-reactivity with BCG vaccine and environmental mycobacteria. Interferon-gamma release assays (IGRA) overcome this problem by detecting M. tuberculosis complex-specific responses, but studies to determine risk factors for IGRA-positivity in high TB burden settings are lacking.

Inflammation-mediated tissue damage in pulmonary tuberculosis and host-directed therapeutic strategies.

Treatment of tuberculosis (TB) involves the administration of anti-mycobacterial drugs for several months. The emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb, the causative agent) together with increased disease severity in people with co-morbidities such as diabetes mellitus and HIV have hampered efforts to reduce case fatality. In severe disease, TB pathology is largely attributable to over-exuberant host immune responses targeted at controlling bacterial replication.

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial.

Background: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia.

Methods: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.

Genetic models of latent tuberculosis in mice reveal differential influence of adaptive immunity.

Studying latent Mycobacterium tuberculosis (Mtb) infection has been limited by the lack of a suitable mouse model. We discovered that transient depletion of biotin protein ligase (BPL) and thioredoxin reductase (TrxB2) results in latent infections during which Mtb cannot be detected but that relapse in a subset of mice. The immune requirements for Mtb control during latency, and the frequency of relapse, were strikingly different depending on how latency was established.

Strategic Supplementation of Antioxidant Micronutrients in Peri-parturient Murrah Buffaloes Helps Augment the Udder Health and Milk Production.

The experiment was conducted to study the effect of supplementation of designer dietary antioxidant micronutrients on udder health, milk yield, and its quality in buffaloes under field conditions. Sixteen healthy multiparous advanced pregnant graded Murrah buffaloes (around the last 3 months of gestation), identical in body weights, parity, and feeding conditions, were selected for the study. Feed offered and residues left of an individual animal were measured and recorded for 7 consecutive days with the sampling of feeds being offered to buffaloes and analyzed for dry matter and trace minerals Zn, Cu, and Se.

Reducing hospital mortality: Incremental change informed by structured mortality review is effective.

Hospital mortality rates have frequently been improved by identifying diagnostic groups with high mortality and targeting interventions to those specific groups. We found that high residual inpatient mortality persisted after targeted measures had achieved an initial reduction, and that the causes were spread across a wide range of diagnostic groups. Further interventions were put in place consisting of a structured electronic mortality form and systematised mortality scrutiny and reporting (primary intervention) accompanied by a number of quality improvement interventions arising from the mortality analysis (secondary interventions).

Effect of caste on health, independent of economic disparity: evidence from school children of two rural districts of India.

Caste, a stratifying axis of the Indian society, is associated with wealth and health. However, to what extent caste-based health inequality is explained by wealth disparities, is not clear. Therefore, we aimed to examine the caste-based differences in anaemia (haemoglobin < 11 gm/dl) and self-reported sickness absenteeism in schoolchildren and the mediating role of economic disparity.

Plasticity of the Mycobacterium tuberculosis respiratory chain and its impact on tuberculosis drug development.

The viability of Mycobacterium tuberculosis (Mtb) depends on energy generated by its respiratory chain. Cytochrome bc1-aa3 oxidase and type-2 NADH dehydrogenase (NDH-2) are respiratory chain components predicted to be essential, and are currently targeted for drug development. Here we demonstrate that an Mtb cytochrome bc1-aa3 oxidase deletion mutant is viable and only partially attenuated in mice.

Targeting protein biotinylation enhances tuberculosis chemotherapy.

Successful drug treatment for tuberculosis (TB) depends on the unique contributions of its component drugs. Drug resistance poses a threat to the efficacy of individual drugs and the regimens to which they contribute. Biologically and chemically validated targets capable of replacing individual components of current TB chemotherapy are a major unmet need in TB drug development.

Discovery of Novel Muscarinic Receptor Modulators by Integrating a Natural Product Framework and a Bioactive Molecule.

Muscarinic acetylcholine receptors (mAChRs) are important therapeutic targets for several diseases of the central nervous system and periphery. However, the lack of subtype-selective ligands for these receptors is a major challenge. A novel approach involving the integration of a natural product framework with a bioactive molecule (iNPBM) by using gephyrotoxin and the isoindoline framework is demonstrated for the discovery of new and selective mAChR modulators.

Reasons for non-recruitment of eligible patients to a randomised controlled trial of secondary prevention after intracerebral haemorrhage: observational study.

Background: Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH.

Method: By the end of May 2015, 158 participants had been recruited at 108 active sites in RESTART.

Managing older medical patients in hospital: a study of the outcomes from a shift of resources to the 'front door'.

We performed a retrospective cohort comparison study to look at the processes for concentrating geriatric resources in the acute admissions area in a general hospital in the UK and compare key outcomes. The number of consultant geriatricians and other staff working at the 'front door' - acute medical unit (AMU) and short stay ward (SSW) - was increased. We compared 'front door' outcomes with whole department outcomes in 2013 and 2014, looking at the proportion of patients discharged within 3 and 5 days of admission, the proportion discharged from the 'front door', mean lengths of stay (LOS) and readmissions within 28 days of discharge.

Targeting Mycobacterium tuberculosis Biotin Protein Ligase (MtBPL) with Nucleoside-Based Bisubstrate Adenylation Inhibitors.

Mycobacterium tuberculosis (Mtb), responsible for both latent and symptomatic tuberculosis (TB), remains the second leading cause of mortality among infectious diseases worldwide. Mycobacterial biotin protein ligase (MtBPL) is an essential enzyme in Mtb and regulates lipid metabolism through the post-translational biotinylation of acyl coenzyme A carboxylases. We report the synthesis and evaluation of a systematic series of potent nucleoside-based inhibitors of MtBPL that contain modifications to the ribofuranosyl ring of the nucleoside.

Efficient access to enantiopure 1,3-disubstituted isoindolines from selective catalytic fragmentation of an original desymmetrized rigid overbred template.

An efficient and scalable synthesis of various enantiopure 1,3- disubstituted isoindolines is reported. The base catalyzed nucleophilic fragmentation of a rigid overbred template is established with various substrates to afford the corresponding 1,3-disubstituted isoindoline ester, amide, thioate, 1,3-amino alcohol and isoindolylcarboxylic acid. The crucial rigid overbred template is synthesized in an optically pure form in multigram scale by asymmetric desymmetrization of the corresponding meso compound.