Targeting StarD3 may increase circulating levels of HDL and protect the liver against lipotoxicity; loss of hepatic expression of this protein, induced by genetic obesity, may contribute to the pathogenesis of dyslipidaemia and steatosis.

Background: Accurate, affordable, and rapid point-of-care (PoC) diagnostics are critical to the global control and management of the COVID-19 pandemic. The current standard for accurate diagnosis of SARS-CoV-2 is laboratory-based reverse transcription polymerase chain reaction (RT-PCR). Here, we report a preliminary prospective performance evaluation of the QuantuMDx Q-POC SARS CoV-2 RT-PCR assay. Methods: Between November 2020 and March 2021, we obtained 49 longitudinal nose and throat swabs from 29 individuals hospitalised with RT-PCR confirmed COVID-19 at St Georges' NHS Foundation Trust, London (UK). In addition, we obtained 101 mid nasal swabs from healthy volunteers in June 2021. We then used these samples to evaluate the Q-POC SARS-CoV-2 RT-PCR assay. The primary analysis was to compare the sensitivity and specificity of the Q-POC test against a reference laboratory-based RT-PCR assay. Results: The overall sensitivity of the Q-POC test compared with the reference test was 96.88% (83.78%- 99.92% CI) for a cycle threshold (Ct) cut-off value for the reference test of 35 and 80.00% (64.35% to 90.95% CI) without altering the reference test's Ct cut-off value of 40. Conclusions: The Q-POC test is a sensitive, specific and rapid point-of-care test for SARS-CoV-2 at a reference Ct cut-off value of 35. The Q-POC test provides an accurate and afforda-ble option for RT-PCR at point-of-care without the need for sample pre-processing and laboratory handling. The Q-POC test would enable rapid diagnosis and clinical triage in acute care and other settings.

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Pancreatic β-cells are sensitive to fluctuations in cholesterol content, which can damage the insulin secretion pathway, contributing to the aetiology of type 2 diabetes mellitus. Cholesterol efflux to (apo)lipoproteins, via ATP-binding cassette (ABC) transporter A1 (ABCA1), can prevent intracellular cholesterol accumulation; in some peripheral cells, ABCA1-dependent efflux is enhanced by promotion of cholesterol trafficking to, and generation of Liver X receptor (LXR) ligands by, mitochondrial sterol 27-hydroxylase (Cyp27A1 (cytochrome P450 27 A1/sterol 27-hydroxylase)) and its redox partners, adrenodoxin (ADX) and ADX reductase (ADXR). Despite this, the roles of mitochondrial cholesterol trafficking (steroidogenic acute regulatory protein [StAR] and 18-kDa translocator protein [TSPO]) and metabolising proteins in insulin-secreting cells remain wholly uncharacterised. Here, we demonstrate an increase in pancreatic expression of Cyp27A1, ADXR, TSPO and LXRα, but not ADX or StAR, in obese (fa/fa) rodents compared with lean (Fa/?) controls. Overexpression of Cyp27A1 alone in BRIN-BD11 cells increased INS2 expression, without affecting lipid metabolism; however, after exposure to low-density lipoprotein (LDL), cholesterol efflux to (apo)lipoprotein acceptors was enhanced in Cyp27A1-overexpressing cells. Co-transfection of Cyp27A1, ADX and ADXR, at a ratio approximating that in pancreatic tissue, stimulated cholesterol efflux to apolipoprotein A-I (apoA-I) in both basal and cholesterol-loaded cells; insulin release was stimulated equally by all acceptors in cholesterol-loaded cells. Thus, genetic obesity increases pancreatic expression of Cyp27A1, ADXR, TSPO and LXRα, while modulation of Cyp27A1 and its redox partners promotes cholesterol efflux from insulin-secreting cells to acceptor (apo)lipoproteins; this response may help guard against loss of insulin secretion caused by accumulation of excess intracellular cholesterol.

No abstract

Accurate and rapid point-of-care (PoC) diagnostics are critical to the control of the COVID-19 pandemic. The current standard for accurate diagnosis of SARS-CoV-2 is laboratory-based reverse transcription polymerase chain reaction (RT-PCR) assays. Here, a preliminary prospective performance evaluation of the QuantuMDx Q-POC SARS-CoV-2 RT-PCR assay is reported. Between November 2020 and March 2021, 49 longitudinal combined nose/throat (NT) swabs from 29 individuals hospitalised with RT-PCR confirmed COVID-19 were obtained at St George’s Hospital, London. In addition, 101 mid-nasal (MN) swabs were obtained from healthy volunteers in June 2021. These samples were used to evaluate the Q-POC SARS-CoV-2 RT-PCR assay. The primary analysis was to compare the sensitivity and specificity of the Q-POC test against a reference laboratory-based RT-PCR assay. The overall sensitivity of the Q-POC test compared with the reference test was 96.88% (83.78– 99.92% CI) for a cycle threshold (Ct) cut-off value for the reference test of 35 and 80.00% (64.35–90.95% CI) without altering the reference test’s Ct cut-off value of 40. The Q-POC test is a sensitive, specific and rapid PoC test for SARS-CoV-2 at a reference Ct cut-off value of 35. The Q-POC test provides an accurate option for RT-PCR at PoC without the need for sample pre-processing and laboratory handling, enabling rapid diagnosis and clinical triage in acute care and other settings.