Glucose Depletion in the Airway Surface Liquid Is Essential for Sterility of the Airways

Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL) and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources –including glucose– in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

BACKGROUND: Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. METHODS: The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. DISCUSSION: The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. TRIAL REGISTRATION: Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.MRC Funding: MC_UP_1302/3 NIHR Funding: RP-PG-0610-1006

Sequencing technologies and genome sequencing

The high-throughput - next generation sequencing (HT-NGS) technologies are currently the hottest topic in the field of human and animals genomics researches, which can produce over 100 times more data compared to the most sophisticated capillary sequencers based on the Sanger method. With the ongoing developments of high throughput sequencing machines and advancement of modern bioinformatics tools at unprecedented pace, the target goal of sequencing individual genomes of living organism at a cost of $1,000 each is seemed to be realistically feasible in the near future. In the relatively short time frame since 2005, the HT-NGS technologies are revolutionizing the human and animal genome researches by analysis of chromatin immunoprecipitation coupled to DNA microarray (ChIP-chip) or sequencing (ChIP-seq), RNA sequencing (RNA-seq), whole genome genotyping, genome wide structural variation, de novo assembling and re-assembling of genome, mutation detection and carrier screening, detection of inherited disorders and complex human diseases, DNA library preparation, paired ends and genomic captures, sequencing of mitochondrial genome and personal genomics. In this review, we addressed the important features of HT-NGS like, first generation DNA sequencers, birth of HT-NGS, second generation HT-NGS platforms, third generation HT-NGS platforms: including single molecule Heliscope™, SMRT™ and RNAP sequencers, Nanopore, Archon Genomics X PRIZE foundation, comparison of second and third HT-NGS platforms, applications, advances and future perspectives of sequencing technologies on human and animal genome research

Regional differences in portion size consumption behaviour: Insights for the global food industry

Abstract: Given the influence of globalization on consumer food behaviour across the world, the purpose of this paper is to contribute to the theoretical discourse around food portion size as a global consumption-related symbol and its underlying socio-economic drivers for food industry strategy. Overall, 25,000 global food consumers were surveyed across 24 countries to elicit insight on portion size consumption behaviour as well as consumer perception on eating and drinking small portion size within selected socio-economic classes. The data was quantitatively analysed to answer the pertinent research objectives. In 20 out of the 24 global markets surveyed, large food portion size was statistically established as a prevalent consumption-related symbol. The paper found that there are regional differences in portion size food consumption behaviour, and further disparities exist across age, gender and income status in 24 countries covering all regions, including Australia, China, Mexico, South Africa, United Kingdom and United States of America. The outlined food industry implications reveal that adaptation and standardisation strategies are still relevant in global food and nutrition strategy as revealed by the variations in the preference for food portion sizes across various countries of the world

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

S

BMC Psychol

Background Preschoolers regularly display disruptive behaviors in child care settings because they have not yet developed the social skills necessary to interact prosocially with others. Disruptive behaviors interfere with daily routines and can lead to conflict with peers and educators. We investigated the impact of a social skills training program led by childcare educators on children’s social behaviors and tested whether the impact varied according to the child’s sex and family socio-economic status. Methods Nineteen public Child Care Centers (CCC, n = 361 children) located in low socio-economic neighborhoods of Montreal, Canada, were randomized into one of two conditions: 1) intervention (n = 10 CCC; 185 children) or 2) wait list control (n = 9 CCC; 176 children). Educators rated children’s behaviors (i.e., disruptive and prosocial behaviors) before and after the intervention. Hierarchical linear mixed models were used to account for the nested structure of the data. Results At pre-intervention, no differences in disruptive and prosocial behaviors were observed between the experimental conditions. At post-intervention, we found a significant sex by intervention interaction (β intervention by sex = − 1.19, p = 0.04) indicating that girls in the intervention condition exhibited lower levels of disruptive behaviors compared to girls in the control condition (f2 effect size = − 0.15). There was no effect of the intervention for boys. Conclusions Girls may benefit more than boys from social skills training offered in the child care context. Studies with larger sample sizes and greater intervention intensity are needed to confirm the results