No abstract

this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr).COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) have been shown to be highly protective against COVID-19associated hospitalizations (1-3). Data are limited on the level of protection against hospitalization among disproportionately affected populations in the United States, particularly during periods in which the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, predominates (2). U.S. veterans are older, more racially diverse, and have higher prevalences of underlying medical conditions than persons in the general U.S. population (2,4). CDC assessed the effectiveness of mRNA vaccines against COVID-19associated hospitalization among 1,175 U.S. veterans aged ≥18 years hospitalized at five Veterans Affairs Medical Centers (VAMCs) during February 1-August 6, 2021. Among these hospitalized persons, 1,093 (93.0%) were men, the median age was 68 years, 574 (48.9%) were non-Hispanic Black (Black), 475 were non-Hispanic White (White), and 522 (44.4%) had a Charlson comorbidity index score of ≥3 (5). Overall adjusted vaccine effectiveness against COVID-19-associated hospitalization was 86.8% (95% confidence interval [CI] = 80.4%-91.1%) and was similar before (February 1-June 30) and during (July 1-August 6) SARS-CoV-2 Delta variant predominance (84.1% versus 89.3%, respectively). Vaccine effectiveness was 79.8% (95% CI = 67.7%-87.4%) among adults aged ≥65 years and 95.1% (95% CI = 89.1%-97.8%) among those aged 18-64 years. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated hospitalization in this older, racially diverse population of predominately male U.S. veterans. Additional evaluations of vaccine effectiveness among various age groups are warranted. To prevent COVID-19-related hospitalizations, all eligible persons should receive COVID-19 vaccination.

this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr).Monovalent COVID-19 mRNA vaccines, designed against the ancestral strain of SARS-CoV-2, successfully reduced COVID-19related morbidity and mortality in the United States and globally (1,2). However, vaccine effectiveness (VE) against COVID-19associated hospitalization has declined over time, likely related to a combination of factors, including waning immunity and, with the emergence of the Omicron variant and its sublineages, immune evasion (3). To address these factors, on September 1, 2022, the Advisory Committee on Immunization Practices recommended a bivalent COVID-19 mRNA booster (bivalent booster) dose, developed against the spike protein from ancestral SARS-CoV-2 and Omicron BA.4/BA.5 sublineages, for persons who had completed at least a primary COVID-19 vaccination series (with or without monovalent booster doses) ≥2 months earlier (4). Data on the effectiveness of a bivalent booster dose against COVID-19 hospitalization in the United States are lacking, including among older adults, who are at highest risk for severe COVID-19-associated illness. During September 8-November 30, 2022, the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network § assessed

Purpose: The purpose of this study was to assess whether troglitazone (TRO) would induce cellular acidosis by inhibiting Na ؉ /H ؉ exchanger (NHE) 1 in breast carcinoma-derived cell lines and, if so, whether cellular acidosis would be associated with a reduction in proliferation.Experimental Design: Intracellular pH (pH i ) and acid extrusion capacity after an exogenous acid load were assayed using (2, 7)-biscarboxyethyl-5(6)-carboxyfluorescein in MCF-7 and MDA-MB-231 cells treated with TRO. Radiolabeled thymidine incorporation was used to assess DNA synthesis. Peroxisome proliferator-activated receptor (PPAR) ␥ involvement was assessed using an antagonist and PPAR␥ ؊/؊ NIH3T3 cells. Results: TRO induced a prompt (<4 minute) and severe cellular acidosis in both MCF-7 (7.54 ؎ 0.23 to 6.77 ؎ 0.06; P < 0.001) and MDA-MB-231 cells (7.38 ؎ 0.18 to 6.89 ؎ 0.25; P < 0.05) after 12 minutes, without increasing acid production. Acid extrusion as assessed by the response to an exogenous acid load (NH 4 Cl pulse) was markedly blunted (MDA-MB-231, P < 0.01) or eliminated (MCF-7, P < 0.001). Chronic exposure to TRO resulted in NHE1 activity reduction (P < 0.05) and a dose-dependent decrease in DNA synthesis (<75% inhibition at 100 mol/L; P < 0.001 and P < 0.01 for MCF-7 and MDA-MB-231, respectively) associated with a decreased number of viable cells. TROmediated inhibition of proliferation was not reversed by the presence of the PPAR␥ inhibitor GW9662 and was demonstrable in PPAR␥ ؊/؊ NIH3T3 cells, consistent with a PPAR␥-independent mechanism.Conclusions: TRO induces marked cellular acidosis in MCF-7 and MDA-MD-231 cells. Sustained acidosis is consonant with decreased proliferation and growth that is not reversed by a PPAR␥ antagonist. Our results support a NHE-mediated action of TRO that exerts its effect independent of PPAR␥.

No abstract