Staff testing for COVID-19 via an online pre-registration form.

BACKGROUND: Healthcare workers are at increased risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potentially causing institutional outbreaks. Staff testing is critical in identifying and isolating infected individuals, whilst also reducing unnecessary workforce depletion. Tygerberg Hospital implemented an online pre-registration system to expedite staff and cluster testing. We aimed to identify specific presentations associated with a positive or negative result for SARS-CoV-2. METHODS: A retrospective descriptive study design involving all clients making use of the hospital's pre-registration system during May 2020. RESULTS: Of 799 clients, most were young and females with few comorbidities. Nurses formed the largest staff contingent in the study, followed by administrative staff, doctors and general assistants. Doctors tested earlier compared with other staff (median: 1.5 vs. 4 days). The most frequent presenting symptoms included headache, sore throat, cough and myalgia. Amongst those testing positive (n = 105), fever, altered smell, altered taste sensation, and chills were the most common symptoms. Three or more symptoms were more predictive of a positive test, but 12/145 asymptomatic clients also tested positive. CONCLUSION: Staff coronavirus testing using an online pre-registration form is a viable and acceptable strategy. Whilst some presentations are less likely to be associated with SARS-CoV-2 infection, no symptom can completely exclude it. Staff testing should form part of a bundle of strategies to protect staff, including wearing masks, regular handwashing, buddy screening, physical distancing, availability of personal protective equipment and special dispensation for coronavirus disease 2019 (COVID-19)-related leave.

Role of desumoylation in the development of prostate cancer.

SUMO is a novel ubiquitin-like protein that can covalently modify a large number of nuclear proteins. SUMO modification has emerged as an important regulatory mechanism for protein function and localization. Sumoylation is a dynamic process that is mediated by activating (E1), conjugating (E2), and ligating (E3) enzymes and is readily reversed by a family of SUMO-specific proteases (SENPs). Since SUMO was discovered 10 years ago, the biologic contribution of this posttranslational modification has remained unclear. In this review, we report that SENP1, a member of the SENP family, is overexpressed in human prostate cancer specimens. The induction of SENP1 is observed with the chronic exposure of prostate cancer cells to androgen and/or interleukin (IL) 6. SENP1 upregulation modulates the transcriptional activity of androgen receptors (ARs) and c-Jun, as well as cyclin D1 expression. Initial in vivo data from transgenic mice indicate that overexpression of SENP1 in the prostate leads to the development of prostatic intraepithelial neoplasia at an early age. Collectively, these studies indicate that overexpression of SENP1 is associated with prostate cancer development.

Desensitization of alpha 2A-adrenoceptor signalling by modest levels of adrenaline is facilitated by beta 2-adrenoceptor-dependent GRK3 up-regulation.

(1) Adrenaline (ADR) and noradrenaline (NA) can simultaneously activate inhibitory alpha(2)- and stimulatory beta-adrenoceptors (AR). However, ADR and NA differ significantly in that ADR is a potent beta(2)-AR agonist while NA is not. Only recently has the interaction resulting from the simultaneous activation of alpha(2)- and beta(2)-AR been examined at the cellular level to determine the mechanisms of alpha(2)-AR regulation following concomitant activation of both alpha(2)- and beta(2)-ARs by chronic ADR. (2) This study evaluates beta(2)-AR regulation of alpha(2A)-AR signalling following chronic ADR (300 nM) and NA (1 and 30 micro M) treatments of BE(2)-C human neuroblastoma cells that natively express both beta(2)- and alpha(2A)-ARs. (3) Chronic (24 h) treatment with ADR (300 nM) desensitized the response to the alpha(2A)-AR agonist, brimonidine, in BE(2)-C cells. Addition of the beta-AR antagonist, propranolol, blocked the ADR-induced alpha(2A)-AR desensitization. Unlike ADR, chronic NA (1 micro M) treatment had no effect on the alpha(2A)-AR response. However if NA was increased to 30 micro M for 24 h, alpha(2A)-AR desensitization was observed; this desensitization was partially reversed by propranolol. (4) Chronic ADR (300 nM) treatment reduced alpha(2A)-AR binding levels, contributing to the alpha(2A)-AR desensitization. This decrease was prevented by addition of propranolol during ADR treatment. Chronic NA (30 micro M), like ADR, treatment lowered specific binding, whereas 1 micro M NA treatment was without effect. (5) Chronic ADR treatment produced a significant increase in GRK3 levels and this was blocked by propranolol or GRK2/3 antisense DNA treatment. This antisense DNA, common to both GRK2 and GRK3, also blocked chronic ADR-induced alpha(2A)-AR desensitization and down-regulation. (6) Acute (1 h) ADR (300 nM) or NA treatment (1 micro M) produced alpha(2A)-AR desensitization. The desensitization produced by acute treatment was beta-AR independent, as it was not blocked by propranolol. (7) We conclude that chronic treatment with modest levels of ADR produces alpha(2A)-AR desensitization by mechanisms that involve up-regulation of GRK3 and down-regulation of alpha(2A)-AR levels through interactions with the beta(2)-AR.