Dennis Vick (puppyland1)

As the number of infections and mortalities from the SARS-CoV-2 pandemic continues to rise, the development of an effective therapy against COVID-19 becomes ever more urgent. A few reports showing a positive correlation between BCG vaccination and reduced COVID-19 mortality have ushered in some hope. BCG has been suggested to confer a broad level of nonspecific protection against several pathogens, mainly via eliciting "trained immunity" in innate immune cells. Secondly, BCG has also been proven to provide benefits in autoimmune diseases by inducing tolerogenicity. Being an acute inflammatory disease, COVID-19 requires a therapy that induces early priming of anti-viral immune responses and regulates aberrant hyperactivity of innate-immune cells. Here, we hypothesize that BCG can offer reliable spatiotemporal protection from COVID-19 by triggering trained immunity and tolerogenesis, through multiple cellular pathways. We propose further research on BCG-mediated immunoprotection, especially in vulnerable individuals, as a strategy to halt the progress of the SARS-CoV-2 pandemic. Also see the video abstract here https//youtu.be/P2D2RXfq6Vg. Advanced fibrosis attributable to NASH is a leading cause of end-stage liver disease. In this phase 2b trial, 392 patients with bridging fibrosis or compensated cirrhosis (F3-F4) were randomized to receive placebo, selonsertib 18mg, cilofexor 30mg, or firsocostat 20mg, alone or in two-drug combinations, once-daily for 48weeks. The primary endpoint was a ≥1-stage improvement in fibrosis without worsening of NASH between baseline and 48weeks based on central pathologist review. Exploratory endpoints included changes in NAFLD Activity Score (NAS), liver histology assessed using a machine learning (ML) approach, liver biochemistry, and noninvasive markers. The majority had cirrhosis (56%) and NAS ≥5 (83%). The primary endpoint was achieved in 11% of placebo-treated patients versus cilofexor/firsocostat (21%; P=0.17), cilofexor/selonsertib (19%; P=0.26), firsocostat/selonsertib (15%; P=0.62), firsocostat (12%; P=0.94), and cilofexor (12%; P=0.96). Changes in hepatic collagen by morphometry were not significantg fibrosis and cirrhosis, 48 weeks of cilofexor/firsocostat was well tolerated, led to improvements in NASH activity, and may have an antifibrotic effect. This combination offers potential for fibrosis regression with longer-term therapy in patients with advanced fibrosis attributable to NASH.Neonicotinoid pesticides can persist in soils for extended time periods; however, they also have a high potential to contaminate ground and surface waters. Studies have reported negative effects associated with neonicotinoids and nontarget taxa, including aquatic invertebrates, pollinating insect species, and insectivorous birds. This study evaluated factors associated with clothianidin (CTN) degradation and sorption in Missouri wetland soils to assess the potential for wetland soils to mitigate potential environmental risks associated with neonicotinoids. Solid-to-solution partition coefficients (Kd ) for CTN sorption to eight wetland soils were determined via single-point sorption experiments, and sorption isotherm experiments were conducted using the two most contrasting soils. Clothianidin degradation was determined under oxic and anoxic conditions over 60 d. Degradation data were fit to zero- and first-order kinetic decay models to determine CTN half-life (t0.5 ). Sorption results indicated CTN sorption to wetland soil was relatively weak (average Kd , 3.58 L kg-1 ); thus, CTN has the potential to be mobile and bioavailable within wetland soils. However, incubation results showed anoxic conditions significantly increased CTN degradation rates in wetland soils (anoxic average t0.5 , 27.2 d; oxic average t0.5 , 149.1 d). A significant negative correlation was observed between anoxic half-life values and soil organic C content (r2 = .782; p = .046). Greater CTN degradation rates in w