Broad-spectrum antibiotics are frequently prescribed to children. Early childhood represents a dynamic period for the intestinal microbial ecosystem, which is readily shaped by environmental cues; antibiotic-induced disruption of this sensitive community may have long-lasting host consequences. Here we demonstrate that a single pulsed macrolide antibiotic treatment (PAT) course early in life is sufficient to lead to durable alterations to the murine intestinal microbiota, ileal gene expression, specific intestinal T-cell populations, and secretory IgA expression. A PAT-perturbed microbial community is necessary for host effects and sufficient to transfer delayed secretory IgA expression. Additionally, early-life antibiotic exposure has lasting and transferable effects on microbial community network topology. Our results indicate that a single early-life macrolide course can alter the microbiota and modulate host immune phenotypes that persist long after exposure has ceased.
ObjectivesTherapies less invasive than surgery and more effective than lifestyle and pharmacotherapy are needed to contend with the obesity epidemic. Intragastric balloons (IGBs) are a minimally invasive endoscopic weight loss method recently approved for use in the US. The purpose of the study is to assess the effect of IGBs on metabolic outcomes associated with obesity.MethodsMEDLINE, Embase, and Cochrane Database were searched through July 2016. Dual extraction and quality assessment of studies using Cochrane risk of bias tool were performed independently by two authors. Primary outcomes included the change from baseline in metabolic parameters. Secondary outcomes included resolution and/or improvement in metabolic co-morbidities and association with baseline parameters.Results10 randomized controlled trials (RCT) and 30 observational studies including 5,668 subjects were analyzed. There was moderate-quality evidence for improvement in most metabolic parameters in subjects assigned to IGB therapy as compared to conventional non-surgical therapy in RCTs: mean difference (MD) in fasting glucose change: -12.7 mg/dl (95% confidence interval (CI) -21.5, -4); MD in triglycerides: -19 mg/dl (95% CI -42, 3.5); MD in waist circumference: -4.1 cm (95% CI -6.9, -1.4); MD in diastolic blood pressure: -2.9 mm Hg (95% CI -4.1, -1.8). The odds ratio for diabetes resolution after IGB therapy was 1.4 (95% CI 1.3, 1.6). The rate of serious adverse events was 1.3%.ConclusionsIGBs are more effective than diet in improving obesity-related metabolic risk factors with a low rate of adverse effects, however the strength of the evidence is limited given the small number of participants and lack of long-term follow-up.
Background and study aims There is currently no objective and validated methodology available to assess the progress of endoscopy trainees or to determine when technical competence has been achieved. The aims of the current study were to develop an endoscopic part-task simulator and to assess scoring system validity. Methods Fundamental endoscopic skills were determined via kinematic analysis, literature review, and expert interviews. Simulator prototypes and scoring systems were developed to reflect these skills. Validity evidence for content, internal structure, and response process was evaluated. Results The final training box consisted of five modules (knob control, torque, retroflexion, polypectomy, and navigation and loop reduction). A total of 5 minutes were permitted per module with extra points for early completion. Content validity index (CVI)-realism was 0.88, CVI-relevance was 1.00, and CVI-representativeness was 0.88, giving a composite CVI of 0.92. Overall, 82% of participants considered the simulator to be capable of differentiating between ability levels, and 93% thought the simulator should be used to assess ability prior to performing procedures in patients. Inter-item assessment revealed correlations from 0.67 to 0.93, suggesting that tasks were sufficiently correlated to assess the same underlying construct, with each task remaining independent. Each module represented 16.0%–26.1% of the total score, suggesting that no module contributed disproportionately to the composite score. Average box scores were 272.6 and 284.4 (P=0.94) when performed sequentially, and average score for all participants with proctor 1 was 297.6 and 308.1 with proctor 2 (P=0.94), suggesting reproducibility and minimal error associated with test administration. Conclusion A part-task training box and scoring system were developed to assess fundamental endoscopic skills, and validity evidence regarding content, internal structure, and response process was demonstrated.
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