What does this study add to the field?Using latent class analysis (LCA), we identified two subgroups among a cohort of 483 patients with COVID-19-related ARDS. Class 2 patients had higher inflammatory markers and lactate and corresponded with the previously identified hyperinflammatory subphenotype, whereas Class 1 corresponded with the hypoinflammatory subphenotype. Class 2 had significantly higher 90-day mortality compared with Class 1 (75% vs 48%; p<0•0001). Differential response to corticosteroid treatment was observed, with decreased mortality in steroid-treated patients in Class 2 but not Class 1. SARS-CoV-2 polymerase chain reaction cycle threshold was a predictor of mortality in Class 1, but not Class 2, suggesting distinct drivers of mortality among classes.
Nanosized titanium dioxide (TiO) is a common additive in food and cosmetic products. The goal of this study was to investigate if TiO nanoparticles affect intestinal epithelial tissues, normal intestinal function, or metabolic homeostasis using in vitro and in vivo methods. An in vitro model of intestinal epithelial tissue was created by seeding co-cultures of Caco-2 and HT29-MTX cells on a Transwell permeable support. These experiments were repeated with monolayers that had been cultured with the beneficial commensal bacteria Lactobacillus rhamnosus GG (L. rhamnosus). Glucose uptake and transport in the presence of TiO nanoparticles was assessed using fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG). When the cell monolayers were exposed to physiologically relevant doses of TiO, a statistically significant reduction in glucose transport was observed. These differences in glucose absorption were eliminated in the presence of beneficial bacteria. The decrease in glucose absorption was caused by damage to intestinal microvilli, which decreased the surface area available for absorption. Damage to microvilli was ameliorated in the presence of L. rhamnosus. Complimentary studies in Drosophila melanogaster showed that TiO ingestion resulted in decreased body size and glucose content. The results suggest that TiO nanoparticles alter glucose transport across the intestinal epithelium, and that TiO nanoparticle ingestion may have physiological consequences.
Prevention of the development of recalcitrance is the logical beginning of practical management of tuberculous patients who fail to follow medical recommendations. Several steps can be taken to assist in lessening the uncooperative behavior of these patients.
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