Mccartycates8432

Moreover, the therapeutic effect lasts for up to 12 months and no off-target effects were shown. Conclusions Our study strongly demonstrates that gene editing therapy is a promising therapeutic strategy to treat inherited retinal degeneration.Purpose Meibomian glands are essential in maintaining the integrity and health of the ocular surface. Meibomian gland dysfunction (MGD), mainly induced by ductal occlusion, is considered as the major cause of dry eye disease. In this study, a novel in vitro model was established for investigating the role of inflammation in the process of MGD. Methods Mouse tarsal plates were removed from eyelids after dissection and explants were cultured during various time ranging from 24 to 120 hours. Meibomian gland epithelial cells were further enzymatically digested and dissociated from tarsal plates before culturing. Both explants and cells were incubated in different media with or without serum or azithromycin (AZM). Furthermore, explants were treated with IL-1β or vehicle for 48 hours. Analyses for tissue viability, histology, biomarker expression, and lipid accumulation were performed with hematoxylin and eosin (H&E) staining, immunofluorescence staining, and Western blot. Results Higher viability was preserved when explants were cultured on Matrigel with immediate addition of culture medium. The viability, morphology, biomarker expression, and function of meibomian glands were preserved in explants cultured for up to 72 hours. Lipid accumulation and peroxisome proliferator-activated receptor γ (PPARγ) expression increased in both explants and cells cultured in media containing serum or AZM. Rottlerin mw Treatment with IL-1β induced overexpression of Keratin (Krt) 1 in meibomian gland ducts. Conclusions Intervention with pro-inflammatory cytokine IL-1β induces hyperkeratinization in meibomian gland ducts in vitro. This novel organotypic culture model can be used for investigating the mechanism of MGD.Iron and zinc deficiencies are some of the most widespread micronutrient deficiencies in low- and middle-income countries (LMIC). Dietary diversification, food fortification, nutrition education, and supplementation can be used to control micronutrient deficiencies. Legumes are important staple foods in most households in LMIC. Legumes are highly nutritious (good sources of essential minerals, fiber, and low glycemic index) and offer potential benefits in addressing nutrition insecurity in LMIC. Several efforts have been made to increase micronutrient intake by use of improved legumes. Improved legumes have a higher nutrient bioavailability, lower phytate, or reduced hard-to-cook (HTC) defect. We hypothesize that consumption of improved legumes leads to optimization of zinc and iron status and associated health outcomes. Therefore, the objective of this review is to examine the evidence on the efficacy of interventions using improved legumes. Nine relevant studies are included in the review. Consumption of imes suggesting them to be a sustainable solution to improve iron status. Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.Interpreting genetic variants of unknown significance (VUS) is essential in clinical applications of genome sequencing for diagnosis and personalized care. Noncoding variants remain particularly difficult to interpret, despite making up a large majority of trait associations identified in GWAS analyses. Predicting the regulatory effects of noncoding variants on candidate genes is a key step in evaluating their clinical significance. Here we develop a machine learning algorithm, ICE (Inference of Connected eQTLs), to predict the regulatory targets of noncoding variants identified in studies of expression quantitative trait loci (eQTLs). We assemble datasets using eQTL results from the Genotype-Tissue Expression (GTEx) project and learn to separate positive and negative pairs based on annotations characterizing the variant, gene and the intermediate sequence. ICE achieves an area under the receiver operating characteristic curve (ROC-AUC) of 0.799 using random cross-validation, and 0.700 for a more stringent poermissions@oup.com.Background The coronavirus disease 2019 pandemic has or threatens to overwhelm health care systems. Many institutions are developing ventilator triage policies. Objective To characterize the development of ventilator triage policies and compare policy content. Design Survey and mixed-methods content analysis. Setting North American hospitals associated with members of the Association of Bioethics Program Directors. Participants Program directors. Measurements Characteristics of institutions and policies, including triage criteria and triage committee membership. Results Sixty-seven program directors responded (response rate, 91.8%); 36 (53.7%) hospitals did not yet have a policy, and 7 (10.4%) hospitals' policies could not be shared. The 29 institutions providing policies were relatively evenly distributed among the 4 U.S. geographic regions (range, 5 to 9 policies per region). Among the 26 unique policies analyzed, 3 (11.3%) were produced by state health departments. The most frequently cited triage criteria were benefit (25 policies [96.2%]), need (14 [53.8%]), age (13 [50.0%]), conservation of resources (10 [38.5%]), and lottery (9 [34.6%]). Twenty-one (80.8%) policies use scoring systems, and 20 of these (95.2%) use a version of the Sequential Organ Failure Assessment score. Among the policies that specify the triage team's composition (23 [88.5%]), all require or recommend a physician member, 20 (87.0%) a nurse, 16 (69.6%) an ethicist, 8 (34.8%) a chaplain, and 8 (34.8%) a respiratory therapist. Thirteen (50.0% of all policies) require or recommend those making triage decisions not be involved in direct patient care, but only 2 (7.7%) require that their decisions be blinded to ethically irrelevant considerations. Limitation The results may not be generalizable to institutions without academic bioethics programs. Conclusion Over one half of respondents did not have ventilator triage policies. Policies have substantial heterogeneity, and many omit guidance on fair implementation.