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Objective: To describe coronavirus disease 2019 (COVID‐19) mitigation measures in workplaces of employed US blood donors by industry and work arrangement. Methods: During May–December 2021, blood donors responded to a survey; we describe the distribution of reported workplace mitigation measures by industry and work arrangement, organized using the hierarchy of controls. Results.: Of 53,433 respondents representing 21 industries, ventilation upgrades were reported by 4%–38% of respondents (overall: 20%); telework access ranged from 14%–80% (53% overall). Requiring masks (overall: 84%; range: 40%–94%), physical distancing (77%; 51%–86%), paid leave for illness (70%; 38%–87%), and encouraging vaccination (61%; 33%–80%) were common. Independent workers reported fewer mitigation measures than those in traditional employment settings. Conclusions: Mitigation measures varied by industry and work arrangement. Some mitigation measures may be challenging to implement or irrelevant in certain industries, supporting the idea that mitigation is not a one‐size‐fits‐all strategy. Policy Implications: Tailored strategies to mitigate workplace risks of disease transmission are vital. Strategies should rely on effective methods for identifying workplace controls (e.g., through the hierarchy of controls) and account for industry‐specific characteristics and workplace environments. [ABSTRACT FROM AUTHOR]

Background: Work is a social determinant of health that is often overlooked. There are major work‐related differences in the risk of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection and death, but there have been few analyses of infection rates across industry groups. To date, only one national assessment of SARS‐CoV‐2 infection prevalence by industry based on self‐report has been completed. No study has looked at seroprevalence of COVID‐19 by industry. Methods: During May–December 2021, blood donors with SARS‐CoV‐2 antinucleocapsid testing were sent an electronic survey about their work. Free‐text industry responses were classified using the North American Industry Classification System. We estimated seroprevalence and 95% confidence intervals (CIs) of SARS‐CoV‐2 infection by industry. Results: Of 57,726 donors, 7040 (12%, 95% CI: 11.9%−12.5%) had prior SARS‐CoV‐2 infection. Seroprevalence was highest among Accommodation & Food Services (19.3%, 95% CI: 17.1%−21.6%), Mining, Quarrying, and Oil and Gas Extraction (19.2%, 95% CI: 12.8%−27.8%), Healthcare & Social Assistance (15.6%, 95% CI: 14.9%−16.4%), and Construction (14.7%, 95% CI: 13.1%−16.3%). Seroprevalence was lowest among Management of Companies & Enterprises (6.5%, 95% CI: 3.5%−11.5%), Professional Scientific & Technical Services (8.4%, 95% CI: 7.7%−9.0%), and Information (9.9%, 95% CI: 8.5%−11.5%). Conclusions: While workers in all industries had serologic evidence of SARS‐CoV‐2 infection, certain sectors were disproportionately impacted. Disease surveillance systems should routinely collect work characteristics so public health and industry leaders can address health disparities using sector‐specific policies. [ABSTRACT FROM AUTHOR]

The devastating sequelae of diabetes mellitus include microvascular permeability, which results in retinopathy. Despite clinical and scientific advances, there remains a need for new approaches to treat retinopathy. Here, we have presented a possible treatment strategy, whereby targeting the small GTPase ARF6 alters VEGFR2 trafficking and reverses signs of pathology in 4 animal models that represent features of diabetic retinopathy and in a fifth model of ocular pathological angiogenesis. Specifically, we determined that the same signaling pathway utilizes distinct GEFs to sequentially activate ARF6, and these GEFs exert distinct but complementary effects on VEGFR2 trafficking and signal transduction. ARF6 activation was independently regulated by 2 different ARF GEFs - ARNO and GEP100. Interaction between VEGFR2 and ARNO activated ARF6 and stimulated VEGFR2 internalization, whereas a VEGFR2 interaction with GEP100 activated ARF6 to promote VEGFR2 recycling via coreceptor binding. Intervening in either pathway inhibited VEGFR2 signal output. Finally, using a combination of in vitro, cellular, genetic, and pharmacologic techniques, we demonstrated that ARF6 is pivotal in VEGFR2 trafficking and that targeting ARF6-mediated VEGFR2 trafficking has potential as a therapeutic approach for retinal vascular diseases such as diabetic retinopathy., Introduction Over 25 million people in the United States have diabetes mellitus (1) and are prone to suffer from its devastating sequelae. The metabolic derangements seen in diabetes lead to [...]

The proteasome inhibiter bortezomib has been successfully used to treat patients with relapsed multiple myeloma; however, many of these patients become thrombocytopenic, and it is not clear how the proteasome influences platelet production. Here we determined that pharmacologic inhibition of proteasome activity blocks proplatelet formation in human and mouse megakaryocytes. We also found that megakaryocytes isolated from mice deficient for PSMC1, an essential subunit of the 26S proteasome, fail to produce proplatelets. Consistent with decreased proplatelet formation, mice lacking PSMC1 in platelets ([Psmc1.sup.fl/fl] Pf4-Cre mice) exhibited severe thrombocytopenia and died shortly after birth. The failure to produce proplatelets in proteasome-inhibited megakaryocytes was due to upregulation and hyperactivation of the small GTPase, RhoA, rather than NF-κB, as has been previously suggested. Inhibition of RhoA or its downstream target, Rho-associated protein kinase (ROCK), restored megakaryocyte proplatelet formation in the setting of proteasome inhibition in vitro. Similarly, fasudil, a ROCK inhibitor used clinically to treat cerebral vasospasm, restored platelet counts in adult mice that were made thrombocytopenic by tamoxifen-induced suppression of proteasome activity in megakaryocytes and platelets ([Psmc1.sup.fl/fl] PdgfCre-ER mice). These results indicate that proteasome function is critical for thrombopoiesis, and suggest inhibition of RhoA signaling as a potential strategy to treat thrombocytopenia in bortezomib-treated multiple myeloma patients., Introduction Thrombocytopenia (low platelet count) is observed in numerous diseases and can be life threatening due to bleeding complications. Bortezomib, a reversible chemotherapeutic inhibitor used to treat patients with relapsed [...]

The innate immune response is essential for combating infectious disease. Macrophages and other cells respond to infection by releasing cytokines, such as interleukin-1β (IL-1β), which in turn activate a well-described, [...]

Objectives: To characterise heat-related acute kidney injury (HR-AKI) among US workers in a range of industries.Methods: Two data sources were analysed: archived case files of the Occupational Safety and Health Administration's (OSHA) Office of Occupational Medicine and Nursing from 2010 through 2020; and a Severe Injury Reports (SIR) database of work-related hospitalisations that employers reported to federal OSHA from 2015 to 2020. Confirmed, probable and possible cases of HR-AKI were ascertained by serum creatinine measurements and narrative incident descriptions. Industry-specific incidence rates of HR-AKI were computed. A capture-recapture analysis assessed under-reporting in SIR.Results: There were 608 HR-AKI cases, including 22 confirmed cases and 586 probable or possible cases. HR-AKI occurred in indoor and outdoor industries including manufacturing, construction, mail and package delivery, and solid waste collection. Among confirmed cases, 95.2% were male, 50.0% had hypertension and 40.9% were newly hired workers. Incidence rates of AKI hospitalisations from 1.0 to 2.5 hours per 100 000 workers per year were observed in high-risk industries. Analysis of overlap between the data sources found that employers reported only 70.6% of eligible HR-AKI hospitalisations to OSHA, and only 41.2% of reports contained a consistent diagnosis.Conclusions: Workers were hospitalised with HR-AKI in diverse industries, including indoor facilities. Because of under-reporting and underascertainment, national surveillance databases underestimate the true burden of occupational HR-AKI. Clinicians should consider kidney risk from recurrent heat stress. Employers should provide interventions, such as comprehensive heat stress prevention programmes, that include acclimatisation protocols for new workers, to prevent HR-AKI. [ABSTRACT FROM AUTHOR]

The devastating sequelae of diabetes mellitus include microvascular permeability, which results in retinopathy. Despite clinical and scientific advances, there remains a need for new approaches to treat retinopathy. Here, we have presented a possible treatment strategy, whereby targeting the small GTPase ARF6 alters VEGFR2 trafficking and reverses signs of pathology in 4 animal models that represent features of diabetic retinopathy and in a fifth model of ocular pathological angiogenesis. Specifically, we determined that the same signaling pathway utilizes distinct GEFs to sequentially activate ARF6, and these GEFs exert distinct but complementary effects on VEGFR2 trafficking and signal transduction. ARF6 activation was independently regulated by 2 different ARF GEFs - ARNO and GEP100. Interaction between VEGFR2 and ARNO activated ARF6 and stimulated VEGFR2 internalization, whereas a VEGFR2 interaction with GEP100 activated ARF6 to promote VEGFR2 recycling via coreceptor binding. Intervening in either pathway inhibited VEGFR2 signal output. Finally, using a combination of in vitro, cellular, genetic, and pharmacologic techniques, we demonstrated that ARF6 is pivotal in VEGFR2 trafficking and that targeting ARF6-mediated VEGFR2 trafficking has potential as a therapeutic approach for retinal vascular diseases such as diabetic retinopathy. [ABSTRACT FROM AUTHOR]

On October 29, 2021, the Food and Drug Administration expanded the Emergency Use Authorization for Pfizer-BioNTech COVID-19 vaccine to children aged 5-11 years; CDC's Advisory Committee on Immunization Practices' recommendation followed on November 2, 2021.* In late December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant strain in the United States, † coinciding with a rapid increase in COVID-19-associated hospitalizations among all age groups, including children aged 5-11 years (1). COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) § data were analyzed to describe characteristics of COVID-19-associated hospitalizations among 1,475 U.S. children aged 5-11 years throughout the pandemic, focusing on the period of early Omicron predominance (December 19, 2021-February 28, 2022). Among 397 children hospitalized during the Omicron-predominant period, 87% were unvaccinated, 30% had no underlying medical conditions, and 19% were admitted to an intensive care unit (ICU). The cumulative hospitalization rate during the Omicron-predominant period was 2.1 times as high among unvaccinated children (19.1 per 100,000 population) as among vaccinated ¶ children (9.2).** Non-Hispanic Black (Black) children accounted for the largest proportion of unvaccinated children (34%) and represented approximately one third of COVID-19-associated hospitalizations in this age group. Children with diabetes and obesity were more likely to experience severe COVID-19. The potential for serious illness among children aged 5-11 years, including those with no underlying health conditions, highlights the importance of vaccination among this age group. Increasing vaccination coverage among children, particularly among racial and ethnic minority groups disproportionately affected by COVID-19, is critical to preventing COVID-19-associated hospitalization and severe outcomes., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Evan J. Anderson reports grants from Pfizer, Merck, PaxVax, Micron, Sanofi-Pasteur, Janssen, MedImmune, and GlaxoSmithKline; personal fees from Pfizer, Medscape, Kentucky Bioprocessing, Inc., Sanofi-Pasteur, Janssen, and GlaxoSmithKline outside the submitted work; and institutional funding from the National Institutes of Health to conduct clinical trials of Moderna and Janssen COVID-19 vaccines. Laurie M. Billing, Andy Weigel, Justin Henderson, and Andrea Price report grants from the Council of State and Territorial Epidemiologists during the conduct of the study. Ruth Lynfield reports editorial payments from the American Academy of Pediatrics Red Book (Committee on Infectious Diseases), which were donated to the Minnesota Department of Health. No other potential conflicts of interest were disclosed.