High temperature requirement A1 serine protease (HtrA1) Losartan Osteoarthritis (OA) Temporomandibular joint (TMJ) Transforming growth factor-beta 1 (TGF-b1) s u m m a r y Objective: Transforming growth factor beta 1 (TGF-b1) is implicated in osteoarthritis (OA). The purpose of this study was to explore the ability of Losartan to inhibit the inflammatory signaling pathway of TGF-b1 observed during osteoarthritic progression in the temporomandibular joint (TMJ) and knee joint using a genetic mouse model. Methods: A murine OA model displaying the heterozygous chondrodysplasia gene (cho/þ), a col11a1 mutation, was used to test this hypothesis. Following a 7-month treatment period with Losartan, the synovial joints were analyzed for histopathological improvement comparing two experimental groups. Tissues were fixed in paraformaldehyde, processed to paraffin section, and stained with Safranin O and Fast Green to visualize proteoglycans and collagen proteins in cartilage. Using the Modified Mankin scoring system, the degree of staining and OA progression were evaluated. Results: Results show heterozygous animals receiving Losartan having diminished degeneration of TMJ condylar and knee joint articular cartilage. This was confirmed in the TMJ and knee by a statistically significant decrease in the Mankin histopathology score. Decreased expression of HtrA1, a key regulator to the TGF-b1 signaling pathway, was demonstrated in vitro as well as in vivo, via Losartan inhibition. Conclusion: Using a genetic mouse model of OA, this study demonstrated the utility of Losartan to improve treatment of human OA in the TMJ and knee joint through inhibition of the TGF-b1 signaling cascade. We further demonstrated inhibition of HtrA1, the lowering of Mankin scores to wild type control levels, and the limiting of OA progressive damage with treatment of Losartan.

Group singing and playing of wind instruments increase COVID-19 transmission risk. After a pause during the initial period of the COVID-19 pandemic, The Tabernacle Choir at Temple Square organization (hereinafter, Choir) resumed musical events in September 2021 with prevention protocols, including required vaccination and pre-event rapid antigen testing. We investigated potential SARS-CoV-2 transmission at Choir events during September 21–November 7, 2021. We interviewed COVID-19–positive members (hereinafter, case-members) and identified members exposed when a case-member attended a Choir event during his or her infectious period. We compared whole genome sequencing results to assess the genetic relatedness of available SARS-CoV-2 specimens obtained from case-members. We identified 30 case-members through pre-event testing (n = 10), self-reported positive test results (n = 18), and a review of Utah’s disease surveillance system (n = 2). All 30 case-members reported symptoms; 21 (70%) were women and 23 (77%) received a positive test result by nucleic acid amplification test. No hospitalizations or deaths were reported. We identified 176 test-eligible exposed members from 14 instances of case-members attending events during their infectious periods. All were tested at least once 2 to 14 days after exposure: 74 (42%) by rapid antigen test only (all negative) and 102 (58%) by nucleic acid amplification test (4 positive, 97 negative, and 1 equivocal). Among viral sequences available from 15 case-members, the smallest single-nucleotide polymorphism distance between 2 sequences was 2, and the next-smallest distance was 10. The lack of disease detected in most exposed members suggests that minimal, if any, transmission occurred at Choir events. When community COVID-19 incidence is high, prevention protocols might help limit SARS-CoV-2 transmission during group musical activities.