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Random population-based surveys to estimate prevalence of SARS-CoV2 infection causing coronavirus disease (COVID-19) are useful to understand distributions and predictors of the infection. In April 2020, the first-ever nationally representative survey in Canada polled 4,240 adults age 18 years and older about self-reported COVID experience in March, early in the epidemic. We examined the levels and predictors of COVID symptoms, defined as fever plus difficulty breathing/shortness of breath, dry cough so severe that it disrupts sleep, and/or loss of sense of smell; and testing for SARS-CoV-2 by respondents and/or household members. About 8% of Canadians reported that they and/or one or more household members experienced COVID symptoms. Symptoms were more common in younger than in older adults, and among visible minorities. Overall, only 3% of respondents and/or household members reported testing for SARS-CoV-2. Being tested was associated with having COVID symptoms, Indigenous identity, and living in Quebec. Periodic nationally representative surveys of symptoms, as well as SARS-CoV-2 antibodies, are required in many countries to understand the pandemic and prepare for the future. [ABSTRACT FROM AUTHOR]

Intracellular sulfhydryls, both protein and non-protein, are potential targets of nitric oxide-related species. S-Nitrosation of proteins can occur in vivo and can affect their activity. Metabolic pathways that regulate protein S-nitrosation are therefore likely to be biologically important. We now report that formaldehyde dehydrogenase, an enzyme that decomposes S-nitrosoglutathione, can indirectly regulate the level of cellular protein S-nitrosation. Nitrogen oxide donors induced high levels of protein S-nitrosation in HeLa cells and lower levels in Mutatect fibrosarcoma cells, as determined by Saville–Griess assay and Western-dot-blot analysis. Depletion of glutathione by treatment with buthionine sulfoximine markedly increased protein S-nitrosation in both cell lines. Glutathione depletion also increased cytokine-induced S-nitrosation in brain endothelial cells. Formaldehyde dehydrogenase activity was 2-fold higher in Mutatect than in HeLa cells. We downregulated formaldehyde dehydrogenase activity in Mutatect cells by stably expressing antisense RNA and short-interfering RNA. In these cells, both protein S-nitrosation and S-nitrosoglutathione levels were significantly enhanced after exposure to nitrogen oxide donors as compared to parental cells. Overall, a strong inverse correlation between total S-nitrosothiols and formaldehyde dehydrogenase activity was seen. Inhibition of glutathione reductase, the enzyme that converts oxidized to reduced glutathione, by dehydroepiandrosterone similarly increased protein S-nitrosation and S-nitrosoglutathione levels in both cell lines. Our results provide the first evidence that formaldehyde dehydrogenase-dependent decomposition of S-nitrosoglutathione plays a role in protecting against nitrogen oxide-mediated protein S-nitrosation. We propose that formaldehyde dehydrogenase and glutathione reductase participate in a glutathione-dependent metabolic cycle that decreases protein S-nitrosation following exposure of cells to nitric oxide. [Copyright &y& Elsevier]

While SARS-CoV-2 infection appears to have spread widely throughout Africa, documentation of associated mortality is limited. We implemented a representative serosurvey in one city of Sierra Leone in Western Africa, paired with nationally representative mortality and selected death registration data. Cumulative seroincidence using high quality SARS-CoV-2 serological assays was 69% by July 2021, rising to 84% by April 2022, mostly preceding SARS-CoV-2 vaccination. About half of infections showed evidence of neutralizing antibodies. However, excess death rates were low, and were concentrated at older ages. During the peak weeks of viral activity, excess mortality rates were 22% for individuals aged 30-69 years and 70% for those over 70. Based on electronic verbal autopsy with dual independent physician assignment of causes, excess deaths during viral peaks from respiratory infections were notable. Excess deaths differed little across specific causes that, a priori, are associated with COVID, and the pattern was consistent among adults with or without chronic disease risk factors. The overall 6% excess of deaths at ages ≥30 from 2020-2022 in Sierra Leone is markedly lower than reported from South Africa, India, and Latin America. Thus, while SARS-CoV-2 infection was widespread, our study highlights as yet unidentified mechanisms of heterogeneity in susceptibility to severe disease in parts of Africa., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Osman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: 5-Fluorouracil (5-FU) is an antineoplastic drug that targets thymidylate synthase (TS). Tumour cells can develop resistance to anti-TS drugs by a variety of mechanisms including up-regulation of TS protein and alterations in drug uptake and degradation. The possible mechanisms of the observed rapid development of resistance to the pyrimidine analogs 5-FUdR and 5-FU in cultured HCT116 colon cancer cells were investigated., Materials and Methods: Cell survival was determined in resistant and control HCT116 cells treated with 5-FUdR and 5-FU for 7 days. The ability of the cells to take up and metabolize these drugs was determined by Western blotting and [3H]thymidine incorporation., Results and Conclusion: Resistant HCT116 cells were 5- and 100-fold more resistant to killing by 5-FU and 5-FUdR, respectively, than the parental cells and exhibited impaired uptake. Although the HCT116R cells were initially Mycoplasma free, a low level of Mycoplasma contamination was found in these cells after several weeks in culture. Sensitivity to 5-FUdR was restored by treatment with an anti-Mycoplasma antibiotic. Our observations emphasize the need for frequent testing for Mycoplasma contamination in any cell line under investigation for resistance to anti-TS drugs.

Objective: Because nitric oxide related species have been found in the inflamed joints of patients with arthritis, we investigated whether protein nitrotyrosine (a marker of tissue exposure to peroxynitrite) is present in their synovial tissues., Methods: Protein nitrotyrosine was detected immunohistochemically and by Western blot analysis. Synovial tissues removed surgically from 12 patients with rheumatoid arthritis (RA) (mean age 63.7 yrs) and 20 with osteoarthritis (OA) (mean age 66.6 yrs) were studied., Results: Nitrated proteins were detected immunohistochemically in all of 18 tissues examined. Diffuse staining of the stroma was seen in all patients, with more extensive staining in RA than OA (p = 0.008). Intense staining was detected in some lymphocytes, but not in others, even within a single lymphoid aggregate. Neutrophils did not stain for nitrotyrosine. Vascular endothelial cells stained for nitrotyrosine but adjoining smooth muscle cells did not. Both cytoplasmic and nuclear staining was seen in macrophages, endothelial cells, and lymphocytes. Numerous bands of nitrated proteins were detected by Western blot analysis of 15 synovial tissue extracts. Inducible nitric oxide synthase (iNOS) was detected immunohistochemically in endothelial cells, macrophages, vascular smooth muscle cells, and synoviocytes., Conclusion: Nitrotyrosine-containing proteins were found in essentially all synovia from RA and OA patients. The most prominent site of nitration in all cases was the stroma. iNOS, the likely source of the nitrating species, was found in a variety of cell types.