Occupational Risks during a Monkeypox Outbreak, Wisconsin, 2003

Veterinary staff were at high risk; standard veterinary infection-control guidelines should be followed

Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription

AbstractBackground: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3.Results: SB-216763 and SB-415286 are structurally distinct maleimides that inhibit GSK-3α in vitro, with Kis of 9 nM and 31 nM respectively, in an ATP competitive manner. These compounds inhibited GSK-3β with similar potency. However, neither compound significantly inhibited any member of a panel of 24 other protein kinases. Furthermore, treatment of cells with either compound stimulated responses characteristic of extracellular stimuli that are known to inhibit GSK-3 activity. Thus, SB-216763 and SB-415286 stimulated glycogen synthesis in human liver cells and induced expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. In both cases, compound treatment was demonstrated to inhibit cellular GSK-3 activity as assessed by activation of glycogen synthase, which is a direct target of this kinase.Conclusions: SB-216763 and SB-415286 are novel, potent and selective cell permeable inhibitors of GSK-3. Therefore, these compounds represent valuable pharmacological tools with which the role of GSK-3 in cellular signalling can be further elucidated. Furthermore, development of similar compounds may be of use therapeutically in disease states associated with elevated GSK-3 activity such as non-insulin dependent diabetes mellitus and neurodegenerative disease

The Relationships Between Socioeconomic Status, COVID-19 Risk Perceptions, and the Adoption of Protective Measures in a Mid-Western City in the United States

An individual\u27s perception of risk plays an influential role in the behaviors they engage in, which could reduce or increase exposure or transmission of a certain disease. Since risk perceptions vary by social identities (e.g., gender, race/ethnicity, age) they are believed to influence the interpretation and likelihood of following guidance from risk-communication efforts. This study aims to understand how COVID-19 risk perceptions vary by social identity (with an emphasis upon socioeconomic factors), how such identities influence behavior adoption through risk-communication pathways, and how findings can be practically applied in messaging. Previous studies have investigated the role of social factors on risk perceptions, but SES has not been modeled as the main factor. Guided by the Health Belief Model and Social Determinant of Health Frameworks, findings from our 326 participants suggest those with high-risk COVID-19 perceptions identified as higher income and held more advanced educational degrees, suggesting a positive relationship between risk perceptions and SES. Individuals with high-risk perceptions more frequently reported practicing protective behaviors against COVID-19 and reported greater severity, susceptibility, barriers, benefits, trust, confidence, and health literacy in adopting behavior changes against the virus. When applying such findings to create a local risk-communication plan (logic model), it was found that messaging should be culturally relevant, in-plain language, and consistent to improve health literacy. In addition to using the most trusted and frequently used communication sources self-identified by residents, we recommend uniting trusted formal and informal community leaders to provide information in diverse pathways and formats

At Least Seven Distinct Rotavirus Genotype Constellations in Bats with Evidence of Reassortment and Zoonotic Transmissions

International audienceBats host many viruses pathogenic to humans, and increasing evidence suggests that rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many mammals and birds, and their segmented genomes allow them to reassort and increase their genetic diversity. Eighteen out of 2,142 bat fecal samples (0.8%) collected from Europe, Central America, and Africa were PCR-positive for RVA, and 11 of those were fully characterized using viral metagenomics. Upon contrasting their genomes with publicly available data, at least 7 distinct bat RVA genotype constellations (GCs) were identified, which included evidence of reassortments and 6 novel genotypes. Some of these constellations are spread across the world, whereas others appear to be geographically restricted. Our analyses also suggest that several unusual human and equine RVA strains might be of bat RVA origin, based on their phylogenetic clustering, despite various levels of nucleotide sequence identities between them. Although SA11 is one of the most widely used reference strains for RVA research and forms the backbone of a reverse genetics system, its origin remained enigmatic. Remarkably, the majority of the genotypes of SA11-like strains were shared with Gabonese bat RVAs, suggesting a potential common origin. Overall, our findings suggest an underexplored genetic diversity of RVAs in bats, which is likely only the tip of the iceberg. Increasing contact between humans and bat wildlife will further increase the zoonosis risk, which warrants closer attention to these viruses