Prevalence of SARS-CoV-2 Antibodies in a Multistate Academic Medical Center.

OBJECTIVE: To estimate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in health care personnel. METHODS: The Mayo Clinic Serology Screening Program was created to provide a voluntary, two-stage testing program for SARS-CoV-2 antibodies to health care personnel. The first stage used a dried blood spot screening test initiated on June 15, 2020. Those participants identified as reactive were advised to have confirmatory testing via a venipuncture. Venipuncture results through August 8, 2020, were considered. Consent and authorization for testing was required to participate in the screening program. This report, which was conducted under an institutional review board-approved protocol, only includes employees who have further authorized their records for use in research. RESULTS: A total of 81,113 health care personnel were eligible for the program, and of these 29,606 participated in the screening program. A total of 4284 (14.5%) of the dried blood spot test results were "reactive" and warranted confirmatory testing. Confirmatory testing was completed on 4094 (95.6%) of the screen reactive with an overall seroprevalence rate of 0.60% (95% CI, 0.52% to 0.69%). Significant variation in seroprevalence was observed by region of the country and age group. CONCLUSION: The seroprevalence for SARS-CoV-2 antibodies through August 8, 2020, was found to be lower than previously reported in other health care organizations. There was an observation that seroprevalence may be associated with community disease burden.

Safely Returning America to Work: Part I: General Guidance for Employers.

: Businesses are struggling to re-open as the world continues to deal with the coronavirus 2019 (COVID-19) pandemic. The reopening of businesses will require employers to implement safe return-to-work strategies through evaluation, testing, work modifications, and development of appropriate workplace policies. There will be unique challenges along the way as no one approach will be ideal for all workplaces and industries. This document is intended to provide return-to-work guidance for both employers and the occupational and environmental medicine physicians who will be supporting businesses in implementing safe return-to-work strategies.

Overexpression of the transcription factor Hand1 causes predisposition towards arrhythmia in mice.

Elevated levels of the cardiac transcription factor Hand1 have been reported in several adult cardiac diseases but it is unclear whether this change is itself maladaptive with respect to heart function. To test this possibility, we have developed a novel, inducible transgenic system, and used it to overexpress Hand1 in adult mouse hearts. Overexpression of Hand1 in the adult mouse heart leads to mild cardiac hypertrophy and a reduction in life expectancy. Treated mice show no significant fibrosis, myocyte disarray or congestive heart failure, but have a greatly reduced threshold for induced ventricular tachycardia, indicating a predisposition to cardiac arrhythmia. Within 48 h, they show a significant loss of connexin43 protein from cardiac intercalated discs, with increased intercalated disc beta-catenin expression at protein and RNA levels. These changes are sustained during prolonged Hand1 overexpression. We propose that cardiac overexpression of Hand1 offers a useful mouse model of arrhythmogenesis and elevated HAND1 may provide one of the molecular links between the failing heart and arrhythmia.

The haphazard approach to the early detection of asymptomatic renal cancer: results from a contemporary executive health programme.

OBJECTIVE To compare the detection of asymptomatic renal cell carcinoma (RCC) in an executive health programme (EHP) that uses traditional methods of screening (history, physical examination and urine analysis) to programmes that screen by renal imaging. PATIENTS AND METHODS We retrospectively reviewed case records from patients undergoing executive health examinations at Mayo Clinic between 1 January 2002 and 30 September 2007. Results Of 32 310 patients, 18 RCCs were detected; of these, 13 (72%) were detected by the EHP and five (28%) were missed by the initial EHP screening process but subsequently discovered within 4-24 months. Of the 13 detected through the EHP, eight were discovered incidentally, two because of symptoms, and three because of asymptomatic microscopic haematuria (AMH). Of the 13, 12 were classified as early-stage cancers (Stage I). By contrast, of the five cancers missed by the EHP screening process, two were diagnosed because of the development of symptoms and only one was classified as Stage I. To date, two of these patients whose cancers were undetected by the EHP developed metastasis and one of them has died. Both had been followed in the EHP for years and neither had MH in multiple specimens. CONCLUSION Our EHP follows standard policy and relies on a history, physical examination and urine analysis to decide who to evaluate for asymptomatic RCC. This practice missed >70% of the potentially diagnosable cancers. The patients with RCCs that were discovered initially by the EHP fared better than those whose diagnosis was delayed. Our detection rate of four per 10 000 was only a fraction of those reported by programmes using imaging as a screening tool. The logic behind our current approach to the early detection of asymptomatic RCC needs to be reassessed. AMH is coincidental in most cases and patients could forego imaging if they are unsuitable candidates for screening. However, AMH will miss most treatable cancers and is not an appropriate screening test for an early detection programme. In the absence of reliable biomarkers, renal imaging should be the primary screening tool for detecting asymptomatic RCC in informed, clinically suitable individuals enrolled in an early detection programme.

Intact RNA-binding domains are necessary for structure-specific DNA binding and transcription control by CBTF122 during Xenopus development.

CBTF122 is a subunit of the Xenopus CCAAT box transcription factor complex and a member of a family of double-stranded RNA-binding proteins that function in both transcriptional and post-transcriptional control. Here we identify a region of CBTF122 containing the double-stranded RNA-binding domains that is capable of binding either RNA or DNA. We show that these domains bind A-form DNA in preference to B-form DNA and that the -59 to -31 region of the GATA-2 promoter (an in vivo target of CCAAT box transcription factor) adopts a partial A-form structure. Mutations in the RNA-binding domains that inhibit RNA binding also affect DNA binding in vitro. In addition, these mutations alter the ability of CBTF122 fusions with engrailed transcription repressor and VP16 transcription activator domains to regulate transcription of the GATA-2 gene in vivo. These data support the hypothesis that the double-stranded RNA-binding domains of this family of proteins are important for their DNA binding both in vitro and in vivo.

The origins of cardiac tissue in the amphibian, Xenopus laevis.

Understanding the mechanisms that regulate cardiogenesis is of fundamental importance if we are to determine the origins of congenital heart disease or devise effective new therapies for the regeneration of healthy cardiac tissue. Amphibian embryos provide a useful model for such studies because embryos are relatively large, available in large numbers, and robust enough to survive simple microsurgery. Because eggs are shed from the adult prior to fertilization, all stages of embryo development are readily accessible. Furthermore, until swimming tadpole stages, development occurs without growth, using nutrients stored in each cell. These features have three significant experimental consequences: all stages of heart development are readily accessible, explants of embryonic tissue will continue to differentiate in simple salts solution, and the function of individual gene products can be studied by microinjection into embryonic cells. Additionally, because heart function is entirely unnecessary until tadpoles begin feeding, even treatments that cause severe disruption of cardiogenesis are readily amenable to study. This article reviews how the combination of simple embryologic manipulation and direct assays of gene function have been used to investigate the cell interactions necessary for heart formation in Xenopus embryos.