9 research outputs found

    Divergent pathogenetic outcomes in BALB/c mice following Omicron subvariant infection

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    Following the emergence of B.1.1.529 Omicron, the SARS-CoV-2 virus evolved into a significant number of sublineage variants that possessed numerous mutations throughout the genome, but particularly within the spike glycoprotein (S) gene. For example, the BQ.1.1 and the XBB.1 and XBB.1.5 subvariants contained 34 and 41 mutations in S, respectively. However, these variants elicited largely replication only or mild disease phenotypes in mice. To better model pathogenic outcomes and measure countermeasure performance, we developed mouse adapted versions (BQ.1.1 MA; XBB.1 MA; XBB.1.5 MA) that reflect more pathogenic acute phase pulmonary disease symptoms of SARS-CoV-2, as well as derivative strains expressing nano-luciferase (nLuc) in place of ORF7 (BQ.1.1 nLuc; XBB.1 nLuc; XBB.1.5 nLuc). Amongst the mouse adapted (MA) viruses, a wide range of disease outcomes were observed including mortality, weight loss, lung dysfunction, and tissue viral loads in the lung and nasal turbinates. Intriguingly, XBB.1 MA and XBB.1.5 MA strains, which contained identical mutations throughout except at position F486S/P in S, exhibited divergent disease outcomes in mice (Ao et al., 2023). XBB.1.5 MA infection was associated with significant weight loss and ∼45 % mortality across two independent studies, while XBB.1 MA infected animals suffered from mild weight loss and only 10 % mortality across the same two independent studies. Additionally, the development and use of nanoluciferase expressing strains provided moderate throughput for live virus neutralization assays. The availability of small animal models for the assessment of Omicron VOC disease potential will enable refined capacity to evaluate the efficacy of on market and pre-clinical therapeutics and interventions

    Violence in childhood, attitudes about partner violence, and partner violence perpetration among men in Vietnam

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    Purpose: We assess the association of men’s exposure to violence in childhood—witnessing physical violence against one’s mother and being hit or beaten by a parent or adult relative—with their attitudes about intimate partner violence (IPV) against women. We explore whether men’s perpetration of IPV mediates this relationship and whether men’s attitudes about IPV mediate any relationship of exposure to violence in childhood with perpetration of IPV. Methods: Five hundred twenty-two married men 18-51 years in Vietnam were interviewed. Multivariate regressions for ordinal and binary responses were estimated to assess these relationships. Results: Compared with men experiencing neither form of violence in childhood, men experiencing either or both had higher adjusted odds of reporting more reasons to hit a wife (aOR, 1.43; 95% CI, 1.03-2.00 and aOR, 1.66; 95% CI, 1.05-2.64, respectively). Men’s lifetime perpetration of IPV accounted fully for these associations. Compared with men experiencing neither form of violence in childhood, men experiencing either or both had higher adjusted odds of ever perpetrating IPV (aOR, 3.28; 95% CI, 2.15-4.99 and aOR, 4.56; 95% CI, 2.90-7.17, respectively). Attitudes about IPV modestly attenuated these associations. Conclusions: Addressing violence in childhood is needed to change men’s risk of perpetrating IPV and greater subsequent justification of it

    Paneth Cell α-Defensin Synthesis and Function

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