Gadearsenault5906

SUMMARYThe substantial discrepancy between the strong effects of functional foods and various drugs, especially traditional Chinese medicines (TCMs), and the poor bioavailability of these substances remains a perplexing problem. Understanding the gut microbiota, which acts as an effective bioreactor in the human intestinal tract, provides an opportunity for the redefinition of bioavailability. Here, we discuss four different pathways associated with the role of the gut microbiota in the transformation of parent compounds to beneficial or detrimental small molecules, which can enter the body's circulatory system and be available to target cells, tissues, and organs. We further describe and propose effective strategies for improving bioavailability and alleviating side effects with the help of the gut microbiota. This review also broadens our perspectives for the discovery of new medicinal components. Copyright © 2020 American Society for Microbiology.Alpha synuclein (αsyn) is the primary component of proteinaceous aggregates termed Lewy Bodies that pathologically define synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). αSyn is hypothesized to spread through the brain in a prion-like fashion by misfolded protein forming a template for aggregation of endogenous αsyn. The cell-to-cell release and uptake of αsyn are considered important processes for its prion-like spread. Rab27b is one of several GTPases essential to the endosomal-lysosomal pathway and is implicated in protein secretion and clearance, but its role in αsyn spread has yet to be characterized. In this study, we used a paracrine αsyn in vitro neuronal model to test the impact of Rab27b on αsyn release, clearance, and toxicity. shRNA-mediated knockdown (KD) of Rab27b increased αsyn-mediated paracrine toxicity. Rab27b reduced αsyn release primarily through non-exosomal pathways, but the αsyn released after Rab27b KD was of higher molecular weight species, as determined by size exclusion chromatography. Rab27b KD increased intracellular levels of insoluble αsyn and led to an accumulation of endogenous light chain 3 (LC3)-positive puncta. Rab27b KD also decreased LC3 turnover after treatment with an autophagosome-lysosome fusion inhibitor, chloroquine, indicating that Rab27b KD induces a defect in autophagic flux. Rab27b protein levels were increased in brain lysates obtained from postmortem tissues of individuals with PD and DLB compared with healthy controls. These data indicate a role for Rab27b in the release, clearance, and toxicity of αsyn and, ultimately, in the pathogenesis of synucleinopathies. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.OBJECTIVES Standing orders are an effective way to increase vaccination rates, yet little is known about how pediatricians use this strategy for childhood immunizations. We assessed current use of, barriers to using, and factors associated with use of standing orders for vaccination among pediatricians. METHODS Internet and mail survey from June 2017 to September 2017 among a nationally representative sample of pediatricians. In the principal component analysis of barrier items, we identified 2 factors physician responsibility and concerns about office processes. A multivariable analysis that included barrier scales and physician and/or practice characteristics was used to identify factors associated with use of standing orders. RESULTS The response rate was 79% (372 of 471); 59% of respondents reported using standing orders. The most commonly identified barriers among nonusers were concern that patients may mistakenly receive the wrong vaccine (68%), concern that patients prefer to speak with the physician about a vaccine before receiving it (62%), and belief that it is important for the physician to be the person who recommends a vaccine to patients (57%). These 3 items also made up the physician responsibility barrier factor. selleck Respondents with higher physician responsibility scores were less likely to use standing orders (risk ratio 0.59 [95% confidence interval 0.53-0.66] per point increase). System-level decision-making about vaccines, suburban or rural location, and lower concerns about office processes scores were each associated with use of standing orders in the bivariate, but not the multivariable, analysis. CONCLUSIONS Among pediatricians, use of standing orders for vaccination is far from universal. Interventions to increase use of standing orders should address physicians' attitudinal barriers as well as organizational factors. Copyright © 2020 by the American Academy of Pediatrics.A 16-year-old girl presented to her primary care physician with a one-month history of decreased appetite and abdominal pain. She had normal bowel movements and no vomiting, but her periumbilical pain limited her ability to finish most meals. She had gradual weight loss over the previous 2 years, and during the previous 4 years, she intermittently received counseling for depression after the loss of her mother. Her initial physical examination and laboratory evaluation were unremarkable. She was referred to a nutritionist, adolescent medicine, and pediatric gastroenterology. Her presentation evolved over time, which ultimately led to a definitive diagnosis. Copyright © 2020 by the American Academy of Pediatrics.OBJECTIVE We analyzed data from inpatients with diabetes admitted to a large university hospital to predict the risk of hypoglycemia through the use of machine learning algorithms. RESEARCH DESIGN AND METHODS Four years of data were extracted from a hospital electronic health record system. This included laboratory and point-of-care blood glucose (BG) values to identify biochemical and clinically significant hypoglycemic episodes (BG ≤3.9 and ≤2.9 mmol/L, respectively). We used patient demographics, administered medications, vital signs, laboratory results, and procedures performed during the hospital stays to inform the model. Two iterations of the data set included the doses of insulin administered and the past history of inpatient hypoglycemia. Eighteen different prediction models were compared using the area under the receiver operating characteristic curve (AUROC) through a 10-fold cross validation. RESULTS We analyzed data obtained from 17,658 inpatients with diabetes who underwent 32,758 admissions between July 2014 and August 2018.