Polydactyl zinc finger (ZF) proteins have prominent roles in gene regulation and often execute multiple regulatory functions. To understand how these proteins perform varied regulation, we studiedDrosophila Suppressor of Hairy-wing [Su(Hw)], an exemplar multifunctional polydactyl ZF protein. We identified separation-of-function (SOF) alleles that encode proteins disrupted in a single ZF that retain one of the Su(Hw) regulatory activities. Through extended in vitro analyses of the Su(Hw) ZF domain, we show that clusters of ZFs bind individual modules within a compound DNA consensus sequence. Through in vivo analysis of SOF mutants, we find that Su(Hw) genomic sites separate into sequence subclasses comprised of combinations of modules, with subclasses enriched for different chromatin features. These data suggest a Su(Hw) code, wherein DNA binding dictates its cofactor recruitment and regulatory output. We propose that similar DNA codes might be used to confer multiple regulatory functions of other polydactyl ZF proteins.
Health care personnel (HCP) are at increased risk for infection with SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), as a result of their exposure to patients or community contacts with COVID-19 (1,2). Since the first confirmed case of COVID-19 in Minnesota was reported on March 6, 2020, the Minnesota Department of Health (MDH) has required health care facilities* to report HCP † exposures to persons with confirmed COVID-19 for exposure risk assessment and to enroll HCP with higher-risk exposures into quarantine and symptom monitoring. During March 6-July 11, MDH and 1,217 partnering health care facilities assessed 21,406 HCP exposures; among these, 5,374 (25%) were classified as higher-risk § (3). Higher-risk exposures involved direct patient care (66%) and nonpatient care interactions (e.g., with coworkers and social and household contacts) (34%). Within 14 days following a higher-risk exposure, nearly one third (31%) of HCP who were enrolled in monitoring reported COVID-19-like symptoms, ¶ and more than one half (52%) of enrolled HCP with symptoms received positive * Health care facilities as defined by MDH include acute care hospitals, critical access hospitals, long-term acute care hospitals, skilled nursing facilities, assisted living facilities, group homes, adult foster care, treatment facilities, dialysis centers, outpatient clinics, dental clinics, home health care, and hospice. † HCP as defined by MDH include, but are not limited to, emergency medical service personnel, nurses, nursing assistants, physicians, technicians, therapists, phlebotomists, pharmacists, students and trainees, contractual staff members not employed by the health care facility, and persons not directly involved in patient care, but who could be exposed to infectious agents that can be transmitted in the health care setting (e.g., clerical, dietary, environmental services, laundry, security, engineering and facilities management, administrative, billing, and volunteer personnel). HCP does not include clinical laboratory personnel. § During February 8-May 18, 2020, CDC exposure risk assessment guidance included medium-and high-risk categories, with risk level based on PPE worn and type of potential contact with a person with confirmed COVID-19. On May 19, CDC's risk assessment was updated to include a single higher-risk exposure category to include close (within 6 feet), prolonged (≥15 minutes or of any duration during an aerosol-generating procedure) contact with a person with confirmed COVID
To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case–control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living.
Objective: To characterize residential social vulnerability among healthcare personnel (HCP) and evaluate its association with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection. Design: Case–control study. Setting: This study analyzed data collected in May–December 2020 through sentinel and population-based surveillance in healthcare facilities in Colorado, Minnesota, New Mexico, New York, and Oregon. Participants: Data from 2,168 HCP (1,571 cases and 597 controls from the same facilities) were analyzed. Methods: HCP residential addresses were linked to the social vulnerability index (SVI) at the census tract level, which represents a ranking of community vulnerability to emergencies based on 15 US Census variables. The primary outcome was SARS-CoV-2 infection, confirmed by positive antigen or real-time reverse-transcriptase– polymerase chain reaction (RT-PCR) test on nasopharyngeal swab. Significant differences by SVI in participant characteristics were assessed using the Fisher exact test. Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) for associations between case status and SVI, controlling for HCP role and patient care activities, were estimated using logistic regression. Results: Significantly higher proportions of certified nursing assistants (48.0%) and medical assistants (44.1%) resided in high SVI census tracts, compared to registered nurses (15.9%) and physicians (11.6%). HCP cases were more likely than controls to live in high SVI census tracts (aOR, 1.76; 95% CI, 1.37–2.26). Conclusions: These findings suggest that residing in more socially vulnerable census tracts may be associated with SARS-CoV-2 infection risk among HCP and that residential vulnerability differs by HCP role. Efforts to safeguard the US healthcare workforce and advance health equity should address the social determinants that drive racial, ethnic, and socioeconomic health disparities.
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