Structure of the plant plastid-encoded RNA polymerase.

Chloroplast genes encoding photosynthesis-associated proteins are predominantly transcribed by the plastid-encoded RNA polymerase (PEP). PEP is a multi-subunit complex composed of plastid-encoded subunits similar to bacterial RNA polymerases (RNAPs) stably bound to a set of nuclear-encoded PEP-associated proteins (PAPs). PAPs are essential to PEP activity and chloroplast biogenesis, but their roles are poorly defined. Here, we present cryoelectron microscopy (cryo-EM) structures of native 21-subunit PEP and a PEP transcription elongation complex from white mustard (Sinapis alba). We identify that PAPs encase the core polymerase, forming extensive interactions that likely promote complex assembly and stability. During elongation, PAPs interact with DNA downstream of the transcription bubble and with the nascent mRNA. The models reveal details of the superoxide dismutase, lysine methyltransferase, thioredoxin, and amino acid ligase enzymes that are subunits of PEP. Collectively, these data provide a foundation for the mechanistic understanding of chloroplast transcription and its role in plant growth and adaptation.

Barriers and facilitators to establishing a clinical academic career in clinical education research in the UK: A focus group study.

In a rapidly changing healthcare environment, we need a robust evidence base to inform effective education and training. This study aimed to examine factors perceived to determine career progression in clinical education research in the UK. Six online focus groups were conducted, with 35 participants from a range of medical, dental, nursing, and allied health professions who identified as aspiring or early career clinical education researchers. Transcripts underwent thematic analysis. Two themes and associated subthemes were constructed to illustrate perceived factors impacting on career development: (1) A cultural challenge from clinical norms. Challenges included differences between the epistemological assumptions of biomedical and clinical research, and the underlying philosophy of education research, which is more closely aligned with the knowledge generation of the social sciences. This led to difficulty communicating the impact of education research to patient care. There were also blurred boundaries between education delivery and research, with the latter lacking a clearly defined group identity. (2) Structures, systems and relationships for career progression. Practical considerations included time and funding (or lack thereof), the opportunity to undertake formal training, networking and role models. This research highlights a number of systemic barriers and facilitators to careers in clinical education research and offers targets of intervention to enable a sustainable academic workforce in clinical education research.

Impact of COVID-19 on the management and outcomes of ureteric stones in the UK: a multicentre retrospective study.

OBJECTIVES: To determine if management of ureteric stones in the UK changed during the coronavirus disease 2019 (COVID-19) pandemic and whether this affected patient outcomes. PATIENTS AND METHODS: We conducted a multicentre retrospective study of adults with computed tomography-confirmed ureteric stone disease at 39 UK hospitals during a pre-pandemic period (23/3/2019-22/6/2019) and a period during the pandemic (the 3-month period after the first severe acute respiratory syndrome coronavirus-2 case at individual sites). The primary outcome was success of primary treatment modality, defined as no further treatment required for the index ureteric stone. Our study protocol was published prior to data collection. RESULTS: A total of 3735 patients were included (pre-pandemic 1956 patients; pandemic 1779 patients). Stone size was similar between groups (P > 0.05). During the pandemic, patients had lower hospital admission rates (pre-pandemic 54.0% vs pandemic 46.5%, P < 0.001), shorter mean length of stay (4.1 vs 3.3 days, P = 0.02), and higher rates of use of medical expulsive therapy (17.4% vs 25.4%, P < 0.001). In patients who received interventional management (pre-pandemic 787 vs pandemic 685), rates of extracorporeal shockwave lithotripsy (22.7% vs 34.1%, P < 0.001) and nephrostomy were higher (7.1% vs 10.5%, P = 0.03); and rates of ureteroscopy (57.2% vs 47.5%, P < 0.001), stent insertion (68.4% vs 54.6%, P < 0.001), and general anaesthetic (92.2% vs 76.2%, P < 0.001) were lower. There was no difference in success of primary treatment modality between patient cohorts (pre-pandemic 73.8% vs pandemic 76.1%, P = 0.11), nor when patients were stratified by treatment modality or stone size. Rates of operative complications, 30-day mortality, and re-admission and renal function at 6 months did not differ between the data collection periods. CONCLUSIONS: During the COVID-19 pandemic, there were lower admission rates and fewer invasive procedures performed. Despite this, there were no differences in treatment success or outcomes. Our findings indicate that clinicians can safely adopt management strategies developed during the pandemic to treat more patients conservatively and in the community.

All medical degrees are equal, but some are more equal than others: An analysis of medical degree classifications.

BACKGROUND: Inequity in assessment can lead to differential attainment. Degree classifications, such as 'Honours', are an assessment outcome used to differentiate students after graduation. However, there are no standardised criteria used to determine what constitutes these awards. METHODS: We contacted all medical schools in the UK and collected data relating to classifications awarded, criteria used and percentage of students receiving classifications across the 5-year period prior to the 2019/2020 academic year. RESULTS: All 42 UK medical schools responded, and 36 universities provided usable data. Of these 36 universities, 30 (83%) awarded classifications above a 'Pass'. We identified four classifications above a 'Pass', and these were 'Commendation', 'Merit', 'Distinction' and 'Honours'. Sixteen (44%) universities awarded a single additional classification, and 14 (39%) universities awarded two or more. There was considerable variation in the criteria used by each university to award classifications. For example, 30 (67%) out of 45 classifications were dependent on all examined years, 9 (20%) for a combination of years and 6 (13%) for final year alone. Twenty-five of 30 universities that awarded classifications provided data on the percentage of students awarded a classification, and a median of 15% of students received any type of classification from their university (range 5.3% to 38%). There was a wide range in the percentage of students awarded each classification type across the universities (e.g. Honours, range = 3.1%-24%). CONCLUSIONS: We demonstrate considerable variation in the way UK medical degree classifications are awarded-regarding terminology, criteria and percentage of students awarded classifications. We highlight that classifications are another form of inequity in medical education. There is a need to fully evaluate the value of hierarchical degree awards internationally as the consequential validity of these awards is understudied.

Use of Glycoprotein IIb-IIIa Inhibitors in Patients Undergoing Carotid Artery Stenting in the Vascular Quality Initiative.

BACKGROUND: Antiplatelet therapies with thromboxane inhibitors and adenosine 5'-diphosphate antagonists have been widely used following carotid artery stenting (CAS). However, these therapies may not apply to patients who are intolerant or present acutely. Glycoprotein IIb/IIIa inhibitors (GPI) are a proposed alternative therapy in these patients; however, their use has been limited due to concerns of increased risk for intracranial bleeding. Thus, this study aims to assess the safety profile of GPI in patients undergoing CAS. METHODS: All patients undergoing CAS in the Society of Vascular Surgery - Vascular Quality Initiative database from 2012 to 2021 was included and grouped into GPI versus non-GPI therapy (control). The primary outcome was in-hospital stroke or death, and secondary outcomes included in-hospital stroke/transient ischemic attack (TIA), death, myocardial infarction, and intracranial hemorrhage (ICH)/seizure. Patients were stratified by surgical approach (Transcarotid artery revascularization using flow reversal (TCAR) and transfemoral carotid artery stenting), and stepwise backward logistic regression analysis was conducted to evaluate major primary and secondary outcomes. RESULTS: A total of 50,628 patients underwent carotid revascularization. Of these, 4.4% of the patients received GPI. Mean age was similar between control versus GPI (71.35(9.67) vs. 71.36(10.20) years). Compared to the control group, patients who receive GPI are less likely to be on optimal medical therapy, including aspirin (83.0% vs. 88.1%), P2Y12 inhibitor (73.0% vs. 82.7%), and statin (82.3% vs. 86.0%) (All P < 0.05). In addition, patients in the GPI group were more likely to undergo TCAR for carotid revascularization (52.2% vs. 48.4%) for emergent/urgent (29.4% vs. 16.8%) and symptomatic indications (55.5% vs. 49.7%) (All P < 0.001). After stratifying by surgical approach, if patients underwent TFCAS and received a GPI, they were at increased odds of developing stroke/death (1.77(1.25-2.51)), death (odds ratio (OR) (95% CI): 1.67(1.07-2.61)), stroke/TIA (OR (95% confidence interval (CI)): 1.65(1.09-2.51)), and ICH/seizure (OR (95% CI): 2.13(1.23-3.68)) (All P < 0.05). No difference was seen in outcomes between the 2 groups if undergoing TCAR. CONCLUSIONS: Patients who receive GPI were more likely to be symptomatic at presentation and less likely to be medically optimized before their carotid revascularization. Transfemoral access in patients receiving GPI was associated with increased odds of morbidity and mortality. However, this was not observed if undergoing TCAR. TCAR can be considered for its overall favorable results in high-risk patients who are not medically optimized.

Examining medical student volunteering during the COVID-19 pandemic as a prosocial behaviour during an emergency.

PURPOSE: Understanding the factors that influence prosocial behaviour during the COVID-19 pandemic is essential due to the disruption to healthcare provision. METHODS: We conducted an in-depth, mixed-methods cross-sectional survey, from 2 May 2020 to 15 June 2020, of medical students at medical schools in the United Kingdom. Data analysis was informed by Latané and Darley's theory of prosocial behaviour during an emergency. RESULTS: A total of 1145 medical students from 36 medical schools responded. Although 947 (82.7%) of students were willing to volunteer, only 391 (34.3%) had volunteered. Of the students, 92.7% understood they may be asked to volunteer; however, we found deciding one's responsibility to volunteer was mitigated by a complex interaction between the interests of others and self-interest. Further, concerns revolving around professional role boundaries influenced students' decisions over whether they had the required skills and knowledge. CONCLUSION: We propose two additional domains to Latané and Darley's theory that medical students consider before making their final decision to volunteer: 'logistics' and 'safety'. We highlight modifiable barriers to prosocial behaviour and provide suggestions regarding how the conceptual framework can be operationalized within educational strategies to address these barriers. Optimizing the process of volunteering can aid healthcare provision and may facilitate a safer volunteering process. Key messages  What is already known on this topic: There is a discrepancy between the number of students willing to volunteer during pandemics and disasters, and those who actually volunteer. Understanding the factors that influence prosocial behaviour during the current COVID-19 pandemic and future pandemics and disasters is essential. What this study adds: We expanded on Latané and Darley's theory of prosocial behaviour in an emergency and used this to conceptualize students' motivations to volunteer, highlighting a number of modifiable barriers to prosocial behaviour during the COVID-19 pandemic. How this study might affect research, practice, or policy: We provide suggestions regarding how the conceptual framework can be operationalized to support prosocial behaviours during emergencies for the ongoing COVID-19 pandemic and future crises.

Clinical support during COVID-19: An opportunity for service and learning? A cross-sectional survey of UK medical students.

PURPOSE: Medical students providing support to clinical teams during Covid-19 may have been an opportunity for service and learning. We aimed to understand why the reported educational impact has been mixed to inform future placements. METHODS: We conducted a cross-sectional survey of medical students at UK medical schools during the first Covid-19 'lockdown' period in the UK (March-July 2020). Analysis was informed by the conceptual framework of service and learning. RESULTS: 1245 medical students from 37 UK medical schools responded. 57% of respondents provided clinical support across a variety of roles and reported benefits including increased preparedness for foundation year one compared to those who did not (p < 0.0001). However, not every individual's experience was equal. For some, roles complemented the curriculum and provided opportunities for clinical skill development, reflection, and meaningful contribution to the health service. For others, the relevance of their role to their education was limited; these roles typically focused on service provision, with few opportunities to develop. CONCLUSION: The conceptual framework of service and learning can help explain why student experiences have been heterogeneous. We highlight how this conceptual framework can be used to inform clinical placements in the future, in particular the risks, benefits, and structures.[Box: see text].

Analysis of Inclusive Gender, Sexuality and Sexual Orientation Data Elements in Academic Electronic Health Records.

Findings from an analysis of three vended academic electronic health records used in health science education are presented in this article. The quality assurance project examined the lexical and semantic fit and content coverage of gender, sexuality, and sexual orientation data elements within the academic electronic health records. A semantic comparative content analysis using a cognitive walkthrough was conducted as a means of comparing the ideal set of gender, sexuality, and sexual orientation data elements with those found in the three vended academic electronic health records. The results indicated a need for alignment to the research literature, expert consensus, and technical standards similar to what is expected for electronic health records used in clinical practice because of a lack of ideal state data elements. The findings align with ongoing issues with bias and disparities seen in the care of the lesbian, gay, bisexual, and transgender population and a lack of diverse, inclusive media and teaching technologies in health science education. The quality project and findings can inform academic electronic health record vendors on how they can create more inclusive systems and bring awareness to healthcare educators about the potential for implicit and explicit bias in their teaching technologies.

Assessing the impact of MRI based diagnostics on pre-treatment disease classification and prognostic model performance in men diagnosed with new prostate cancer from an unscreened population.

INTRODUCTION: Pre-treatment risk and prognostic groups are the cornerstone for deciding management in non-metastatic prostate cancer. All however, were developed in the pre-MRI era. Here we compared categorisation of cancers using either only clinical parameters or with MRI enhanced information in men referred for suspected prostate cancer from an unscreened population. PATIENT AND METHODS: Data from men referred from primary care to our diagnostic service and with both clinical (digital rectal examination [DRE] and systematic biopsies) and MRI enhanced attributes (MRI stage and combined systematic/targeted biopsies) were used for this study. Clinical vs MRI data were contrasted for clinico-pathological and risk group re-distribution using the European Association of Urology (EAU), American Urological Association (AUA) and UK National Institute for Health Care Excellence (NICE) Cambridge Prognostic Group (CPG) models. Differences were retrofitted to a population cohort with long-term prostate cancer mortality (PCM) outcomes to simulate impact on model performance. We further contrasted individualised overall survival (OS) predictions using the Predict Prostate algorithm. RESULTS: Data from 370 men were included (median age 66y). Pre-biopsy MRI stage reassignments occurred in 7.8% (versus DRE). Image-guided biopsies increased Grade Group 2 and ≥ Grade Group 3 assignments in 2.7% and 2.9% respectively. The main change in risk groups was more high-risk cancers (6.2% increase in the EAU and AUA system, 4.3% increase in CPG4 and 1.9% CPG5). When extrapolated to a historical population-based cohort (n = 10,139) the redistribution resulted in generally lower concordance indices for PCM. The 5-tier NICE-CPG system outperformed the 4-tier AUA and 3-tier EAU models (C Index 0.70 versus 0.65 and 0.64). Using an individualised prognostic model, changes in predicted OS were small (median difference 1% and 2% at 10- and 15-years' respectively). Similarly, estimated treatment survival benefit changes were minimal (1% at both 10- and 15-years' time frame). CONCLUSION: MRI guided diagnostics does change pre-treatment risk groups assignments but the overall prognostic impact appears modest in men referred from unscreened populations. Particularly, when using more granular tiers or individualised prognostic models. Existing risk and prognostic models can continue to be used to counsel men about treatment option until long term survival outcomes are available.

COVID-19 Infection Enhances Susceptibility to Oxidative Stress-Induced Parkinsonism.

BACKGROUND: Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with those observed after pandemic influenza, there is a question whether a similar syndrome of postencephalic parkinsonism could follow coronavirus disease 2019 infection. OBJECTIVE: The goal of this study was to determine whether prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. METHODS: K18-hACE2 mice were infected with SARS-CoV-2 to induce mild-to-moderate disease. After 38 days of recovery, mice were administered a non-lesion-inducing dose of the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and euthanized 7 days later. Subsequent neuroinflammation and substantia nigra pars compacta (SNpc) dopaminergic (DA) neuron loss were determined and compared with SARS-CoV-2 or MPTP alone. RESULTS: K18-hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss after MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc DA neurons than SARS-CoV-2 or MPTP, respectively (P < 0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in both the SNpc and striatum of the SARS-CoV-2 + MPTP group compared with SARS-CoV-2 or MPTP alone. CONCLUSIONS: Our observations have important implications for long-term public health, given the number of people who have survived SARS-CoV-2 infection, as well as for future public policy regarding infection mitigation. However, it will be critical to determine whether other agents known to increase risk for PD also have synergistic effects with SARS-CoV-2 and are abrogated by vaccination. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Pediatric single large-scale mtDNA deletion syndromes: The power of patient reported outcomes.

There is a limited understanding of system-level clinical outcomes and interventions associated with single large-scale mitochondrial DNA deletion syndromes (SLSMDS). Additionally, no research exists that describes patient reported outcomes (PROs) of children with SLSMDS. A global and observational registry was established to understand the multi-systemic course of SLSMDS and track clinical outcomes. The development and design of the registry is described. Demographic characteristics, history and diagnoses, and system level prevalence of problems and interventions are reported for 42 children. System level problems and interventions include information on the following body systems: audiology, cardiac, endocrine, gastrointestinal (including pancreatic and hepatobiliary system), hematological, metabolic, neurological (including autonomic, mobility, & learning), ophthalmic, psychiatric, renal, and respiratory. Results emphasize the need of patient registries and suggest that the diagnostic odyssey and burden of disease for children with SLSMDS is significant. System-level findings may help families and clinical providers with diagnosis, prognostication, and treatment. A multidisciplinary team of clinical experts with a central coordinating specialist for children with SLSMDS is recommended.

A systematic review of living kidney donor enhanced recovery after surgery.

Enhanced recovery after surgery (ERAS) reduces complications and shortens hospital stay without increasing readmission or mortality. However, its role in living donor nephrectomy (LDN) has not yet been defined. Medline, Embase, CINAHL, PsycINFO, and Cochrane Central were searched prior to 08/01/21 for all randomized controlled and cohort studies comparing ERAS to standard of care in LDN. The study was registered on PROSPERO (CRD: CRD42019141706). One thousand, three hundred seventy-seven patients were identified from 14 studies (698 patients with ERAS and 679 patients without). There were considerable differences in the protocols used, and compliance with general ERAS recommendations was poor. Meta-analysis of laparoscopic procedures (including hand- and robot-assisted) revealed that duration of stay was significantly reduced by 0.98 days with ERAS (95% CI = 0.36-1.60, P = .002) and opiate requirement by 32.4 mg (95% CI = 1.1-63.7, P = .04). There was no significant difference n readmission rates or complications. Quality of evidence was low to moderate assessed using the GRADE tool. This review suggests there is a positive benefit of ERAS in laparoscopic LDN. However, there was considerable variation in ERAS protocols used, and the quality of evidence was low; as such, a guideline for ERAS in LDN should be developed and validated.

Early protocol computer tomography and endovascular interventions in pancreas transplantation.

BACKGROUND: Early vascular complications following pancreatic transplantation are not uncommon (3%-8%). Typically, cross-sectional imaging is requested in response to clinical change. We instituted a change in protocol to request imaging pre-emptively to identify patients with thrombotic complications. METHODS: In 2013, protocol computer tomography angiography (CTA) at days 3-5 and day 10 following pancreas transplantation was introduced. A retrospective analysis of all pancreas transplants performed at our institution from January 2001 to May 2019 was undertaken. RESULTS: A total of 115 patients received pancreas transplants during this time period. A total of 78 received pancreas transplant without routine CTA and 37 patients with the new protocol. Following the change in protocol, we detected a high number of subclinical thromboses (41.7%). There was a significant decrease in invasive intervention for thrombosis (78.6% before vs 30.8% after, p = .02), and graft survival was significantly higher (61.5% before vs 86.1% after, p = .04). There was also a significant reduction in the number of graft failures (all-cause) where thrombosis was present (23.4% before vs 5.6% after, p = .02). Patient survival was unaffected (p = .48). CONCLUSIONS: Implementation of early protocol CTA identifies a large number of patients with subclinical graft thromboses that are more amenable to conservative management and significantly reduces the requirement for invasive intervention.

Opioid Dependence After Lung Cancer Resection: Institutional Analysis of State Prescription Drug Database.

BACKGROUND: The national opioid epidemic is a public health crisis. Thoracic surgery has also been associated with high incidence of new persistent opioid use. Our purpose was to describe the incidence and predictors of opioid use after lung cancer resection. METHODS: Retrospective review of lung cancer resections from 2015 to 2018 was performed using the Ohio Automated Rx Reporting System. Opioid dosing was recorded as milligram morphine equivalents (MME). Patients were stratified by preoperative opioid use. Chronic preoperative opioid users (opioid dependent) filled > 120 days supply of opioid pain medication in the 12 months prior to surgery; intermittent opioid users filled < 120 days. Chronic postoperative opioid users continued monthly use after 180 days postoperatively. RESULTS: 137 patients underwent resection. 16.1% (n = 22) were opioid dependent preoperatively, 29.2% (n = 40) were intermittent opioid users, and 54.7% (n = 75) were opioid naïve. Opioid dependent patients had higher daily inpatient opioid use compared to intermittent users and opioid naïve (43[30.0-118.1] MME vs 17.9[3.5-48.8] MME vs 8.8[2.1-25.0] MME, p < 0.001). Twenty-six percent (n = 35) of all patients were opioid users beyond 180 days postoperatively. Variables associated with opioid use > 180 days were: chronic preoperative opioid use (OR 23.8, p < 0.01), daily inpatient opioid requirement (1.02, p < 0.01), and neoadjuvant chemotherapy (28.2, p < 0.01). CONCLUSIONS: A quarter of patients are opioid dependent after lung cancer resection. This is due to both preexisting and new persistent opioid use. Improved strategies are needed to prevent chronic pain and opioid dependence after lung cancer resection.

Nek7 conformational flexibility and inhibitor binding probed through protein engineering of the R-spine.

Nek7 is a serine/threonine-protein kinase required for proper spindle formation and cytokinesis. Elevated Nek7 levels have been observed in several cancers, and inhibition of Nek7 might provide a route to the development of cancer therapeutics. To date, no selective and potent Nek7 inhibitors have been identified. Nek7 crystal structures exhibit an improperly formed regulatory-spine (R-spine), characteristic of an inactive kinase. We reasoned that the preference of Nek7 to crystallise in this inactive conformation might hinder attempts to capture Nek7 in complex with Type I inhibitors. Here, we have introduced aromatic residues into the R-spine of Nek7 with the aim to stabilise the active conformation of the kinase through R-spine stacking. The strong R-spine mutant Nek7SRS retained catalytic activity and was crystallised in complex with compound 51, an ATP-competitive inhibitor of Nek2 and Nek7. Subsequently, we obtained the same crystal form for wild-type Nek7WT in apo form and bound to compound 51. The R-spines of the three well-ordered Nek7WT molecules exhibit variable conformations while the R-spines of the Nek7SRS molecules all have the same, partially stacked configuration. Compound 51 bound to Nek2 and Nek7 in similar modes, but differences in the precise orientation of a substituent highlights features that could be exploited in designing inhibitors that are selective for particular Nek family members. Although the SRS mutations are not required to obtain a Nek7-inhibitor structure, we conclude that it is a useful strategy for restraining the conformation of a kinase in order to promote crystallogenesis.

Preparing medical students for a pandemic: a systematic review of student disaster training programmes.

OBJECTIVE: To identify pandemic and disaster medicine-themed training programmes aimed at medical students and to assess whether these interventions had an effect on objective measures of disaster preparedness and clinical outcomes. To suggest a training approach that can be used to train medical students for the current COVID-19 pandemic. RESULTS: 23 studies met inclusion criteria assessing knowledge (n=18, 78.3%), attitude (n=14, 60.9%) or skill (n=10, 43.5%) following medical student disaster training. No studies assessed clinical improvement. The length of studies ranged from 1 day to 28 days, and the median length of training was 2 days (IQR=1-14). Overall, medical student disaster training programmes improved student disaster and pandemic preparedness and resulted in improved attitude, knowledge and skills. 18 studies used pretest and post-test measures which demonstrated an improvement in all outcomes from all studies. CONCLUSIONS: Implementing disaster training programmes for medical students improves preparedness, knowledge and skills that are important for medical students during times of pandemic. If medical students are recruited to assist in the COVID-19 pandemic, there needs to be a specific training programme for them. This review demonstrates that medical students undergoing appropriate training could play an essential role in pandemic management and suggests a course and assessment structure for medical student COVID-19 training. REGISTRATION: The search strategy was not registered on PROSPERO-the international prospective register of systematic reviews-to prevent unnecessary delay.

COVIDReady2 study protocol: cross-sectional survey of medical student volunteering and education during the COVID-19 pandemic in the United Kingdom.

BACKGROUND: The coronavirus disease 2019 pandemic has led to global disruption of healthcare. Many students volunteered to provide clinical support. Volunteering to work in a clinical capacity was a unique medical education opportunity; however, it is unknown whether this was a positive learning experience or which volunteering roles were of most benefit to students. METHODS: The COVIDReady2 study is a national cross-sectional study of all medical students at medical schools in the United Kingdom. The primary outcome is to explore the experiences of medical students who volunteered during the pandemic in comparison to those who did not. We will compare responses to determine the educational benefit and issues they faced. In addition to quantitative analysis, thematic analysis will be used to identify themes in qualitative responses. DISCUSSION: There is a growing body of evidence to suggest that service roles have potential to enhance medical education; yet, there is a shortage of studies able to offer practical advice for how these roles may be incorporated in future medical education. We anticipate that this study will help to identify volunteer structures that have been beneficial for students, so that similar infrastructures can be used in the future, and help inform medical education in a non-pandemic setting. TRIAL REGISTRATION: Not Applicable.

Systematic review of medical student willingness to volunteer and preparedness for pandemics and disasters.

OBJECTIVE: This systematic review aimed to estimate the willingness of students to volunteer during a disaster, and how well-prepared medical students are for volunteering by assessing their knowledge and medical school curriculum of disaster and pandemic medicine. RESULTS: A total of 37 studies met inclusion criteria including 11 168 medical students and 91 medical schools. 24 studies evaluated knowledge (64.9%), 16 evaluated volunteering (43.2%) and 5 evaluated medical school curricula (13.5%). Weighted mean willingness to volunteer during a disaster was 68.4% (SD=21.7%, range=26.7%-87.8%, n=2911), and there was a significant difference between those planning to volunteer and those who actually volunteered (p<0.0001). We identified a number of modifiable barriers which may contribute to this heterogeneity. Overall, knowledge of disasters was poor with a weighted mean of 48.9% (SD=15.1%, range=37.1%-87.0%, n=2985). 36.8% of 76 medical schools curricula included teaching on disasters. However, students only received minimal teaching (2-6 hours). CONCLUSIONS: This study demonstrates that there is a large number of students who are willing to volunteer during pandemics. However, they are unlikely to be prepared for these roles as overall knowledge is poor, and this is likely due to minimal teaching on disasters at medical school. During the current COVID-19 pandemic and in future disasters, medical students may be required to volunteer as auxiliary staff. There is a need to develop infrastructure to facilitate this process as well as providing education and training to ensure students are adequately prepared to perform these roles safely.

Bladder-Drained Pancreas Transplantation: Urothelial Innate Defenses and Urinary Track Infection Susceptibility.

BACKGROUND: Pancreas transplantation restores insulin secretion in type 1 diabetes mellitus. The graft also produces exocrine secretions that can be drained enterically (enteric drainage [ED]) or via the bladder (bladder drainage [BD]). We suggest that in BD transplants, such secretions destroy bladder innate immunity, specifically host defense peptides/proteins (HDPs), which increases patient susceptibility to recurrent urinary tract infections (rUTIs). MATERIALS AND METHODS: BD and ED patient records were reviewed retrospectively for UTIs. Urine samples from ED and BD transplant recipients were analyzed for pH, the HDPs ß-defensin 2 (HBD2) and lipocalin-2, and amylase concentrations. In vitro, bacterial growth curves and antimicrobial assays were used to evaluate the effects of pH, HBD2, and HBD2 + pancreatic digestive enzymes (pancreatin) on uropathogenic Escherichia coli (UPEC) survival and growth. RESULTS: Urinalysis revealed a significant difference in pH between the BD and ED cohorts (7.2 ± 0.8 versus 6.7 ± 0.8; P = 0.012). Urinary HDPs were measured and BD, but not ED, lipocalin-2 concentrations were significantly decreased compared with those of diabetics awaiting transplant (P < 0.05). In vitro, an alkaline environment, pH 8.0, concomitant with the urine of the patient who underwent BD transplantation, significantly reduced UPEC growth (P < 0.05); addition of pancreatin to the growth medium was associated with a significant increase (P < 0.001) in growth rate. Antimicrobial data suggested significant UPEC killing in the presence of HBD2 (P < 0.01), but not in the presence of HBD2 + pancreatin (>12,500 amylase units). CONCLUSIONS: These in vivo and in vitro data suggest that BD pancreatic exocrine secretions inactivate the bladder innate defenses, which facilitate UPEC growth and underpins the increased susceptibility of patients who underwent BD pancreas transplantation to rUTIs.

School education to increase organ donation and awareness of issues in transplantation in the UK.

BACKGROUND: Over 6000 people are on the United Kingdom organ transplant waiting list, and approximately three people die each day due to a lack of donors. Social deprivation status has been shown to affect registration. The aim of this study was to evaluate the effectiveness of school level education at increasing awareness of the issues surrounding organ donation and organ donor registration, and the effect of socioeconomic deprivation and age has on these outcomes. METHODS: A 15-minute presentation about organ donation and the issues in transplantation was given to secondary school students from the United Kingdom. An optional questionnaire was then distributed. RESULTS: 1155 paper questionnaires were completed from nine schools. The average age was 15.5 (SD = 0.5) years. Before the presentation, 10% of students were on the ODR. Following the presentation, the number of students who were on the ODR or planned to join significantly increased to 56%, independent of age (P < 0.0001). Similarly, there was a significant increase in Likert scores for awareness of the issues in transplantation, independent of age (P < 0.0001). CONCLUSIONS: This early educational presentation significantly increased awareness of the issues in transplantation and planned organ donor registration, independent of age and deprivation.