National Eye Research Centre, Above and Beyond, and Moorfields Eye Charity.

ORP2 is implicated in cholesterol transport, triglyceride metabolism, and adrenocortical steroid hormone production. We addressed ORP2 function in hepatocytes by generating ORP2-knockout (KO) HuH7 cells by CRISPR-Cas9 gene editing, followed by analyses of transcriptome, F-actin morphology, migration, adhesion, and proliferation. RNA sequencing of ORP2-KO cells revealed >2-fold changes in 579 mRNAs. The Ingenuity Pathway Analysis (IPA) uncovered alterations in the following functional categories: cellular movement, cell-cell signaling and interaction, cellular development, cellular function and maintenance, cellular growth and proliferation, and cell morphology. Many pathways in these categories involved actin cytoskeleton, cell migration, adhesion, or proliferation. Analysis of the ORP2 interactome uncovered 109 putative new partners. Their IPA analysis revealed Ras homolog A (RhoA) signaling as the most significant pathway. Interactions of ORP2 with SEPT9, MLC12, and ARHGAP12 were validated by independent assays. ORP2-KO resulted in abnormal F-actin morphology characterized by impaired capacity to form lamellipodia, migration defect, and impaired adhesion and proliferation. Rescue of the migration phenotype and generation of typical cell surface morphology required an intact ORP2 phosphoinositide binding site, suggesting that ORP2 function involves phosphoinositide binding and transport. The results point at a novel function of ORP2 as a lipid-sensing regulator of the actin cytoskeleton, with impacts on hepatocellular migration, adhesion, and proliferation.-Kentala, H., Koponen, A., Kivelä, A. M., Andrews, R., Li, C., Zhou, Y., Olkkonen, V. M. Analysis of ORP2-knockout hepatocytes uncovers a novel function in actin cytoskeletal regulation.

Background The COVID-19 pandemic has created a hiatus in in-person clinical assessments due to safety and logistical concerns. We aimed to evaluate student perception and utility of an online Integrated Structured Clinical Examinations (ISCEs) during the pandemic. Methods Final-year medical students from a single institution were offered an online mock ISCE through a student-to-student (“near-peer”) teaching-programme. A questionnaire-based cross-sectional study was conducted pre- and post-online mock ISCE. Results Sixty-four students completed the study. Pre- and post-data showed an increase in confidence (p<0.0001), less worry regarding the online format (p<0.0001) and less anxiety about excelling in ISCEs (p<0.001). Students felt that having done the mock, an online format would more positively affect their overall performance (p=0.007). Conclusion This study demonstrates a positive change in student perception and confidence in online ISCEs. Online ISCEs are thus feasible, though sole reliance on this format may provide an incomplete assessment of student’s overall clinical competency.

Background: The COVID-19 pandemic has changed the delivery of primary care in the NHS. Consultations have largely moved from face-to-face to remote, forcing practitioners to modify the ways in which they deliver care to patients. Aim: In this study, we aim to investigate the appropriateness of antibiotic prescribing in tonsillitis during the COVID-19 pandemic. Design and Setting: An observational quantitative analysis in the North Wales primary care setting. Method: Retrospective review of computer records across 5 GP centers from March 2020 until the end of October 2020. Data was extracted and analyzed using chi-square or fisher exact rank and Mann–Whitney test. Results: Our results have shown no significant difference in antibiotic prescribing behavior comparing face-to-face and remote consultations. Conclusion: Remote consultation is as effective as face-to-face consultation with regards to the assessment of tonsillitis and the appropriateness of antibiotic prescription in primary care.

BackgroundGraves' orbitopathy has a profound negative impact on quality of life. Surgery is undertaken to preserve vision, correct diplopia and improve aesthetics. We sought to quantify the effect of different surgical approaches on quality of life. MethodsElectronic databases Ovid-MEDLINE, EMBASE were used from inception until 22 nd March, 2021 to identify studies assessing quality of life pre-and post-surgical intervention for Graves' orbitopathy. Two reviewers independently extracted data and performed quality assessments.Random-effects and Bayesian models for meta-analyses were utilised. Results10 articles comprising 632 patients with a mean age of 48.4 years (range 16-85 years) were included. All used the Graves' Ophthalmopathy Quality of Life questionnaire (GO-QOL). For GO-QOL appearance, the pooled standardised mean improvement for patients after surgery was +0.72 (95% CI 0.50-0.94) I 2 69% (95% CI 52-80%). For GO-QOL visual functioning, the pooled SMD for patients after surgery was +0.41 (95% CI 0.25-0.58) I 2 60% (95% CI 36-74%).For visual appearance, orbital decompression yielded the greatest improvement (SMD +0.84, 95% CI 0.54-1.13) followed by eyelid surgery (SMD +0.38, 95% CI 0.05-0.70), while strabismus correction had no significant effect (SMD +0.94, 95% CI -0.10-1.99). Conversely strabismus correction was associated with the greatest improvement (SMD +1.25, 95% CI 0.29-2.

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BackgroundRecent reports show that about 10% of UK-graduate doctors leave the country to pursue specialty training elsewhere. Our article aims to evaluate the motivating factors for UK graduates to leave the National Health Service (NHS), especially during the COVID-19 pandemic and Brexit.Study designCross-sectional study.MethodA novel 22-item questionnaire was disseminated at a webinar series regarding the application process to pursue residency training in six different countries/regions from 2 August 2020 to 13 September 2020. The data was analysed using Kruskal-Wallis rank-sum with post-hoc Wilcoxon test to compare the difference in significance among the motivating factors.Results1118 responses from the UK medical students and doctors were collected; of which, 1001 (89.5%) were medical students, and 88 (7.9%) were junior doctors. There was a higher propensity for leaving after the Foundation Programme compared with other periods (p<0.0001 for all comparisons). There was no difference between desire for leaving after core surgical/medical training and specialty training (p=0.549). However, both were significantly higher than leaving the NHS after medical school (p<0.0001). Quality of life and financial prospects (both p<0.0001) were the most agreed reasons to leave the NHS, followed by clinical and academic opportunities and, subsequently, family reasons.ConclusionFuture work on the quality of life for doctors in the UK should be explored, especially among those considering leaving the NHS. Policymakers should focus on assessing the difference in working hours, on-call hours and wages that may differ among healthcare systems.

P < .001), and saw patients more frequently (mean [SE] visits per patient in the last 12 months, 10.3 [0.7] vs 20.4 [2.2]; P < .001) (Table ).Conclusions | Despite the small sample of psychiatrists in the NAMCS and the associational design of this study, this study appears to find that many patients continue to self-pay for psychiatrist visits and many psychiatrists continue to only care for patients that can self-pay. Psychiatrists may be more likely to rely on self-payment models than other specialties because of low insurance reimbursement rates, particularly for psychotherapy, as well as a demand for psychiatric services that outstrips supply. Our findings begin to highlight a 2-tiered system for outpatient psychiatrist care, which presents potential issues of health equity. Patients who choose to or must rely on third-party payment for psychiatrist appointments may be receiving only psychopharmacology, while those who can selfpay may be able to receive psychotherapy as well.