Physical activity and the prevention, reduction, and treatment of alcohol and/or substance use across the lifespan (The PHASE review): protocol for a systematic review.

Background: Alcohol and substance use results in significant human and economic cost globally and is associated with economic costs of £21 billion and £15billion within the UK, respectively, and trends for use are not improving. Pharmacological interventions are well researched, but relapse rates across interventions for substance and alcohol use disorders are as high as 60-90%. Physical activity may offer an alternative or adjunct approach to reducing rates of alcohol and substance use that is associated with few adverse side effects, is easily accessible, and is potentially cost-effective.

Effectiveness of the Healthy Lifestyles Programme (HeLP) to prevent obesity in UK primary-school children: a cluster randomised controlled trial.

Background: Although childhood overweight and obesity prevalence has increased substantially worldwide in the past three decades, scarce evidence exists for effective preventive strategies. We aimed to establish whether a school-based intervention for children aged 9-10 years would prevent excessive weight gain after 24 months.

Methods: This pragmatic cluster randomised controlled trial of the Healthy Lifestyles Programme (HeLP), a school-based obesity prevention intervention, was done in 32 schools in southwest England.

Accumulation of beta-synuclein in cortical neurons is associated with autophagy attenuation in the brains of dementia with Lewy body patients.

Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia, where an accumulation of aggregated fibrillar alpha-synuclein in neurons of limbic and forebrain regions of the brain leads to visual hallucination, cognitive impairment of a fluctuating nature and extrapyramidal motor disturbances. Beta-synuclein counteracts aggregation of alpha-synuclein in vitro and in animal models, however it is not clear whether this effect occurs in human Lewy body dementia (LBD) diseases. Here we examine expression of alpha-, beta-synuclein and autophagy markers in the frontal cortex (BA9) and occipital cortex (BA18-19) of patients with neuropathologically confirmed DLB/LBD and age-matched controls.

Factors associated with junior doctors' decisions to apply for general practice training programmes in the UK: secondary analysis of data from the UKMED project.

Background: The UK, like many high-income countries, is experiencing a worsening shortfall of general practitioners (GPs) alongside an increasing demand for their services. At the same time, factors influencing junior doctors' decisions to apply for GP training are only partially understood and research in this area has been hampered by the difficulties in connecting the datasets that map the journey from student to qualified GP. The UK Medical Education Database (UKMED) has been established to ameliorate this problem by linking institutional data across the spectrum of medical education from school to specialty training.

Outcomes of specialist discharge coordination and intermediate care schemes for patients who are homeless: analysis protocol for a population-based historical cohort.

Introduction: People who are homeless often experience poor hospital discharge arrangements, reflecting ongoing care and housing needs. Specialist integrated homeless health and care provision (SIHHC) schemes have been developed and implemented to facilitate the safe and timely discharge of homeless patients from hospital. Our study aims to investigate the health outcomes of patients who were homeless and seen by a selection of SIHHC services.

Clinical outcomes to exercise training in type 1 diabetes: A systematic review and meta-analysis.

Aims: To establish the relationship between exercise training and clinical outcomes in people with type I diabetes.

Methods: Studies were identified through a MEDLINE search strategy, Cochrane Controlled Trials Registry, CINAHL, SPORTDiscus and Science Citation Index. The search strategy included a mix of key concepts related to trials of exercise training in people with type 1 diabetes; glycaemic control.

Supplementary search methods were more effective and offered better value than bibliographic database searching: A case study from public health and environmental enhancement.

Background: We undertook a systematic review to evaluate the health benefits of environmental enhancement and conservation activities. We were concerned that a conventional process of study identification, focusing on exhaustive searches of bibliographic databases as the primary search method, would be ineffective, offering limited value. The focus of this study is comparing study identification methods.

Specific protein supplementation using soya, casein or whey differentially affects regional gut growth and luminal growth factor bioactivity in rats; implications for the treatment of gut injury and stimulating repair.

Modulation of regional growth within specific segments of the bowel may have clinical value for several gastrointestinal conditions. We therefore examined the effects of different dietary protein sources on regional gut growth and luminal growth factor bioactivity as potential therapies. Rats were fed for 14 days on isonitrogenous and isocaloric diets comprising elemental diet (ED) alone (which is known to cause gut atrophy), ED supplemented with casein or whey or a soya protein-rich feed.

The proportion of the population of England that self-identifies as lesbian, gay or bisexual: producing modelled estimates based on national social surveys.

Objectives: There is currently no widely accepted estimate of the proportion of people in England that self-identifies as lesbian, gay or bisexual (LGB), which is needed if we are to compare health inequality between different population groups. Using systematic review methods, this study identified all national social surveys with a question on sexual orientation and pooled those which represented the overall population of England. LGB proportions were synthesized into an aggregated mean estimate using weights based on sample size, response rate and missing data.

Enhanced natural killer cell activity is found in exposed uninfected recipients of hepatitis C-contaminated blood.

A minority of injecting drug users, termed exposed uninfected, are resistant to hepatitis C (HCV) infection despite repeated low-dose exposures. We identify for the first time a cohort of blood recipients who remained uninfected despite large-dose exposure to HCV-contaminated blood and characterize immune factors that may confer protection. Of 1340 blood recipients from the English Look Back database who were transfused HCV-contaminated blood, we identified 8 who remained uninfected.

Trefoil factor family peptides enhance cell migration by increasing cellular osmotic permeability and aquaporin 3 levels.

Trefoil factor family (TFF) peptides are produced rapidly at sites of injury, stimulating epithelial migration, a process involving rapid changes in cell shape and volume, requiring rapid flow of water into and out of the cell. We examined the effect of TFFs on fluidity of cells by measuring their sensitivity to osmotic challenges and cell migration, and determined whether those results were mediated through altering the levels of aquaporins (AQPs), a family of transmembrane water channels involved in cellular water homeostasis. Gastric (AGS) and colonic (Caco-2) cell lines had intrinsic TFF levels determined and the predominant TFF peptide knocked down (RNA interference).

StemMapper: a curated gene expression database for stem cell lineage analysis.

Transcriptomic data have become a fundamental resource for stem cell (SC) biologists as well as for a wider research audience studying SC-related processes such as aging, embryonic development and prevalent diseases including cancer, diabetes and neurodegenerative diseases. Access and analysis of the growing amount of freely available transcriptomics datasets for SCs, however, are not trivial tasks. Here, we present StemMapper, a manually curated gene expression database and comprehensive resource for SC research, built on integrated data for different lineages of human and mouse SCs.

An experimental model to measure the ability of headphones with active noise control to reduce patient's exposure to noise in an intensive care unit.

Background: Defining the association between excessive noise in intensive care units, sleep disturbance and morbidity, including delirium, is confounded by the difficulty of implementing successful strategies to reduce patient's exposure to noise. Active noise control devices may prove to be useful adjuncts but there is currently little to quantify their ability to reduce noise in this complex environment.

Methods: Sound meters were embedded in the auditory meatus of three polystyrene model heads with no headphones (control), with headphones alone and with headphones using active noise control and placed in patient bays in a cardiac ICU.

Simvastatin as a Potential Disease-Modifying Therapy for Patients with Parkinson's Disease: Rationale for Clinical Trial, and Current Progress.

Many now believe the holy grail for the next stage of therapeutic advance surrounds the development of disease-modifying approaches aimed at intercepting the year-on-year neurodegenerative decline experienced by most patients with Parkinson's disease (PD). Based on recommendations of an international committee of experts who are currently bringing multiple, potentially disease-modifying, PD therapeutics into long-term neuroprotective PD trials, a clinical trial involving 198 patients is underway to determine whether Simvastatin provides protection against chronic neurodegeneration. Statins are widely used to reduce cardiovascular risk, and act as competitive inhibitors of HMG-CoA reductase.

Nutrient-extraction blender preparation reduces postprandial glucose responses from fruit juice consumption.

Although whole-fruit consumption is regarded as protective against type 2 diabetes (T2DM), conventionally prepared fruit juice is associated with increased T2DM risk, and current public health advice recommends its restriction. 'Nutrient extractor' style blenders are increasing in popularity worldwide as an alternative means of juicing fruit, but little is known about their effect on postprandial glucose levels. The current study investigated the effect of nutrient extraction on postprandial blood glucose response and glycemic index (GI) compared with a glucose control for both mixed fruit and a high GI fruit (mango).

Kinetic Measurements of Di- and Tripeptide and Peptidomimetic Drug Transport in Different Kidney Regions Using the Fluorescent Membrane Potential-Sensitive Dye, DiS-C-(3).

Tri- and dipeptides are transported in the kidney by PEPT1 and PEPT2 isoforms. The aim of this study was to investigate differences in transport kinetics between renal brush border (BBMV) and outer medulla (OMMV) membrane vesicles (where PEPT1 and PEPT2 are sequentially available) for a range of di- and tripeptides and peptidomimetic drugs. This was accomplished through the use of the potential-sensitive fluorescent dye 3,3'-dipropylthiacarbocyanine iodide [DiS-C-(3)].

Testing patient-reported outcome measurement equivalence in multinational clinical trials: An exemplar using the 12-item Multiple Sclerosis Walking Scale.

Background: Although multinational clinical trials frequently use patient-reported outcomes to measure efficacy, measurement equivalence across cultures and languages, a scientific requirement, is rarely tested. Clinically accessible accounts are rare; exemplars are needed.

Objective: To develop and test a Turkish version of the Multiple Sclerosis Walking Scale (MSWS-12v2) as a clinical exemplar for examining measurement equivalence.

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial.

Background: Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population.

Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy.

How do national specialty groups develop undergraduate guidelines for medical schools, and which are successful? A systematic review.

Purpose: To better understand the steps undertaken by medical specialties to develop and implement undergraduate national, and international, educational guidelines for use in medical schools, and to find what makes them successful in terms of uptake and knowledge.

Methods: Systematic review of databases to find inter- and nationally-created undergraduate medical specialty guidelines, and descriptions of development and analysis, from 1998 to January 2015.

Results: Ninety six eligible papers were found, covering 59 different guidelines in 32 specialties.

Genome-wide significant locus for Research Diagnostic Criteria Schizoaffective Disorder Bipolar type.

Studies have suggested that Research Diagnostic Criteria for Schizoaffective Disorder Bipolar type (RDC-SABP) might identify a more genetically homogenous subgroup of bipolar disorder. Aiming to identify loci associated with RDC-SABP, we have performed a replication study using independent RDC-SABP cases (n = 144) and controls (n = 6,559), focusing on the 10 loci that reached a p-value <10 for RDC-SABP in the Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder sample. Combining the WTCCC and replication datasets by meta-analysis (combined RDC-SABP, n = 423, controls, n = 9,494), we observed genome-wide significant association at one SNP, rs2352974, located within the intron of the gene TRAIP on chromosome 3p21.