Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells

COVID-19, caused by the novel coronavirus SARS-CoV-2, is a global health issue with more than 2 million fatalities to date. Viral replication is shaped by the cellular microenvironment, and one important factor to consider is oxygen tension, in which hypoxia inducible factor (HIF) regulates transcriptional responses to hypoxia. SARS-CoV-2 primarily infects cells of the respiratory tract, entering via its spike glycoprotein binding to angiotensin-converting enzyme 2 (ACE2). We demonstrate that hypoxia and the HIF prolyl hydroxylase inhibitor Roxadustat reduce ACE2 expression and inhibit SARS-CoV-2 entry and replication in lung epithelial cells via an HIF-1α-dependent pathway. Hypoxia and Roxadustat inhibit SARS-CoV-2 RNA replication, showing that post-entry steps in the viral life cycle are oxygen sensitive. This study highlights the importance of HIF signaling in regulating multiple aspects of SARS-CoV-2 infection and raises the potential use of HIF prolyl hydroxylase inhibitors in the prevention or treatment of COVID-19

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Discourses of blame: accounting for aggression and violence on an acute mental health inpatient unit

The English National Service Framework for Mental Health stipulates that the highest quality of health care should be provided for mental health service users in the most efficient and effective manner. Incidents of aggression and violence militate against achieving that goal, yet such incidents are frequently reported in inpatient settings. Traditionally, research in this area has focused on the extent of the phenomenon, the individual characteristics of those involved and precursors to the incident. For the most part the literature reflects a dualistic, perpetrator/victim conceptualisation of incidents. This study aimed to address the lack of research undertaken from a more systemic perspective by examining how all those involved understood and attributed meaning to violent or aggressive situations and how these attributions justified individual perceptions, reactions and actions. Working from the position that all behaviour, including violent behaviour, has meaning to those involved and can be understood, 16 semi-structured interviews were carried out in one mental health unit. Because only one client was both willing and able to give a full account of an incident, we focus here on two incidents in which that client was involved. Discourse analytic techniques were used to examine her account of the two incidents and those of the staff members involved. Participants discussed key themes from the interviews in terms of several dilemmas: whether the violent or aggressive behaviour was 'mad' or 'bad'; predictable or unpredictable; and had resulted from 'personality' or ' mental illness'. The client and staff discourses were strikingly similar and in each case the central concern was with the attribution of blame. The findings have implications for the professional discourse of mental health care, including the discourse of the current policy agenda, a discourse itself constructed with the primary function of exoneration from and attribution of blame.Mental health services Violence Psychiatric inpatients UK