SARS-CoV-2 spike protein-ACE2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK.

Immunostaining in lungs of patients who died with COVID-19 infection showed increased intensity and distribution of chondroitin sulfate and decline in N-acetylgalactostamine-4-sulfatase (Arylsulfatase B; ARSB). To explain these findings, human small airway epithelial cells were exposed to the SARS-CoV-2 spike protein receptor binding domain (SPRBD) and transcriptional mechanisms were investigated. Phospho-p38 MAPK and phospho-SMAD3 increased following exposure to the SPRBD, and their inhibition suppressed the promoter activation of the carbohydrate sulfotransferases CHST15 and CHST11, which contributed to chondroitin sulfate biosynthesis.

Veterans' Use of Veterans Health Administration Primary Care in an Era of Expanding Choice.

Background: The Veterans Choice Program (VCP), aimed at improving access to care, included expanded options for Veterans to receive primary care through community providers.

Objectives: The objective of this study was to characterize and compare Veterans use of Veterans Health Administration (VA) primary care services at VA facilities and through a VA community care network (VA-CCN) provider.

Research Design: This was a retrospective, observational over fiscal years (FY) 2015-2018.

Sleep Apnea in Type 2 Diabetes.

IN BRIEF Obstructive sleep apnea (OSA) alters glucose metabolism, promotes insulin resistance, and is associated with development of type 2 diabetes. Obesity is a key moderator of the effect of OSA on type 2 diabetes. However, chronic exposure to intermittent hypoxia and other pathophysiological effects of OSA affect glucose metabolism directly, and treatment of OSA can improve glucose homeostasis.

Identification of a Novel Toll-like Receptor 7 Endogenous Ligand in Rheumatoid Arthritis Synovial Fluid That Can Provoke Arthritic Joint Inflammation.

Objective: Levels of Toll-like receptor 7 (TLR-7) are elevated in rheumatoid arthritis (RA), but the impact on RA is unknown because the endogenous ligand for TLR-7 has not been identified. The aim of this study was to identify a TLR-7 endogenous ligand and to determine its role in the pathogenesis of RA.

Methods: The presence of an endogenous TLR-7 ligand, microRNA let-7b (miR-let-7b), was examined by real-time polymerase chain reaction (PCR) analysis.