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Background: Myocarditis is an inflammation of the heart muscle most often caused by viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood., Methods: Male and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis. We performed enrichment analysis and functional validation to understand sex differences in the transcriptional landscape of myocarditis and identify factors that might drive sex differences in myocarditis., Results: As expected, the hearts of male and female mice with myocarditis were significantly enriched for pathways related to an innate and adaptive immune response compared to uninfected controls. Unique to this study, we found that males were enriched for inflammatory pathways and gene changes that suggested worse mitochondrial electron transport function while females were enriched for pathways related to mitochondrial homeostasis. Mitochondria isolated from the heart of males were confirmed to have worse mitochondrial respiration than females during myocarditis. Unbiased TRANSFAC analysis identified estrogen-related receptor alpha (ERRα) as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis. Transcript and protein levels of ERRα were confirmed as elevated in females with myocarditis compared to males. Differential binding analysis from chromatin immunoprecipitation (ChIP) sequencing confirmed that ERRα bound highly to select predicted respiratory chain genes in females more than males during myocarditis., Conclusions: Females with viral myocarditis regulate mitochondrial homeostasis by upregulating master regulators of mitochondrial transcription including ERRα., Competing Interests: Declarations. Ethics approval and consent to participate: Mice were used in accordance with the recommendations in the Guide for the Care and Use the Laboratory Animals of the National Institutes of Health (NIH) and approval obtained from the Animal Care and Use Committee at Mayo Clinic Florida for all procedures (IACUC# A00003984). Mice were maintained under pathogen-free conditions in the animal facility at Mayo Clinic Florida and mice were sacrificed according to the Guide for the Care and Use of Laboratory Animals of the NIH. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Myocarditis is typically caused by viral infections, but most cases are thought to be subclinical. Echocardiography is often used for initial assessment of myocarditis patients but is poor at detecting subtle changes in cardiac dysfunction. Cardiac strain, such as global longitudinal strain (GLS) and global circumferential strain (GCS), represents an increasingly used set of measurements which can detect these subtle changes. Using a murine model of coxsackievirus B3 myocarditis, we characterized functional changes in the heart using echocardiography during myocarditis and by sex. We found that 2D GLS, 4D mode, and 4D strains detected a significant reduction in ejection fraction and GLS during myocarditis compared to baseline and in males compared to females. Furthermore, worse GLS correlated to increased levels of CD45 + , CD11b+, and CD3 + immune cells. Our findings closely resemble published reports of GLS in patients with myocarditis indicating the usefulness of this animal model for translational studies of myocarditis., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Reduced exercise capacity has been suggested as a cardinal sequela of COVID-19. However, only cross-sectional approaches that either do not consider individuals with concomitant cardiorespiratory disease or account for exercise capacity before infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) support this assumption. Is reduced exercise capacity a sequela of SARS-CoV-2 infection in patients with concomitant cardiorespiratory disease? We retrospectively reviewed cardiopulmonary exercise testing (CPET) data collected across three hospitals between October 2018 and March 2022. Forty-two patients who completed a CPET before and after COVID-19 and 25 patients who performed two separate CPETs but did not contract COVID-19 (CTL) were included. Within each patient, the same test protocol was performed at the first and second CPETs. The time between CPETs was similar between the groups (COVID-19 489 ± 534 vs. CTL 534 ± 257 days, P = 0.662). The COVID-19 group performed the CPETs 312 ± 232 days before and 176 ± 110 days after infection. Exercise time, peak heart rate, peak systolic pressure, oxygen uptake (V̇o 2 ) at anaerobic threshold, peak ventilation, and ventilatory efficiency were not different between the CPETs in both groups. Peak V̇o 2 was reduced from before to after SARS-CoV-2 infection. However, the change in V̇o 2peak from the first to the second CPET was not different between COVID-19 vs. CTL. Accounting for V̇o 2peak before COVID-19 and including a group of control patients, we find limited evidence for reduced exercise capacity as a sequela of SARS-CoV-2 infection in patients with concomitant cardiorespiratory disease. NEW & NOTEWORTHY There is accumulating evidence that reduced exercise capacity is, or can be, an outcome following COVID-19. However, evidence to date relies upon cross-sectional approaches that either do not consider patients with concomitant cardiorespiratory disease or account for pre-infection exercise capacity data. Accounting for V̇o 2peak before COVID-19 and including a group of control patients, we find limited evidence for reduced exercise capacity as a sequela of SARS-CoV-2 infection in patients with concomitant cardiorespiratory disease.

Researchers often use terminology to define their participant groups that is rooted in a clinical understanding of the group's shared identity(ies). Such naming often ignores the ways that the individuals who comprise these populations identify themselves. One oft-cited benefit of patient-oriented or community-engaged research is that language is local and relevant to impacted communities. This paper aims to contribute to the literature on how this local and relevant language can best be established. We ask how researchers can identify and implement accurate terminology, even when divergent perspectives exist within the communities involved. We draw from our experience with the Expanding Plasma Donation in Canada study, a community-engaged research study, which explored the views of people impacted by the "men who have sex with men" (MSM) blood donation policies in Canada. We describe the collaborative process through which we came to a consensual naming of this population, the challenges we faced, and a set of guiding principles we used to address them. We did not find an all-encompassing term or acronym that worked for all stages of research. Instead, we offer a set of guiding principles that can aid researchers engaging in a similar process: harm reduction, consent and transparency, collaboration and community involvement, recognition of missing voices, and resisting and/or restructuring oppressive standards., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: In 2021, Canada implemented a pilot plasma program allowing some sexually active men who have sex with men (including but not limited to gay and bisexual men; gbMSM) to donate plasma. Changes to plasma donation policy could help address inequities in access to plasma donation and increase Canada's domestically collected plasma supply if more gbMSM donate as a result. We aimed to (1) examine views regarding plasma donation and the pilot program prior to implementation and (2) identify modifiable theory-informed predictors of gbMSM's intention to donate plasma., Methods: We developed, piloted, and disseminated a questionnaire informed by the Theoretical Domains Framework (TDF). We recruited gbMSM in London (ON) and Calgary (AB) to an anonymous, online cross-sectional survey., Results: A total of 246 gbMSM completed the survey. On scales from 1 (strongly disagree) to 5 (strongly agree), general intention to donate was high (mean = 4.24; SD = 0.94). The pilot program itself was mostly acceptable (mean = 3.71, SD = 1.16), but the intention to donate under the unique requirements of the pilot program was lower than general intention (mean = 3.58; SD = 1.26). Two domains from the theoretical domains framework (TDF) (beliefs about consequences of donating plasma and social influences) were independently associated with general intention to donate., Discussion: The pilot plasma program as an incremental step toward more inclusive policies was mostly viewed as acceptable by the impacted communities. Historical and ongoing exclusions create unique barriers to donation. There are clear opportunities for developing theory-informed interventions to support gbMSM to donate plasma as policies continue to become more inclusive and more become eligible to donate., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Canada has incrementally reduced restrictions to blood and plasma donation that impact men who have sex with men, gay, bisexual, and queer men, and some Two Spirit, transgender and non-binary individuals (MSM/2SGBTQ+). Prior to the launch of a pilot program in 2021 enabling some MSM/2SGBTQ + to donate source plasma, we explored the acceptability of the program among individuals who could become eligible to donate in the program., Methods: We invited men identifying as MSM/2SGBTQ + to participate in two consecutive semi-structured interviews to explore their views on blood and plasma donation policy, plasma donation, and the proposed Canadian plasma donation program. Interview transcripts were analyzed thematically and acceptability-related themes were mapped onto the Theoretical Framework of Acceptability., Results: Twenty-seven men identifying as having sex with men participated in 53 interviews. Eighteen themes were mapped onto the seven construct domains of the Theoretical Framework of Acceptability. Underlying all aspects of acceptability was a tension between four primary values influencing participants' views: altruism, equity, supply sufficiency, and evidence-based policy. The program was viewed as welcome progress on a discriminatory policy, with many excited to participate, yet tension with inequitable aspects of the program undermined support for the program and interest to contribute to it. The high demands of the program are unique for MSM/2SGBTQ + and are only tolerable as part of a program that is an incremental and instrumental step to more equitable donation policies., Conclusion: Findings highlight past experiences of exclusion in Canada as a unique and critical part of the context of the donation experience among MSM/2SGBTQ+. Despite the program's goals of greater inclusivity of MSM/2SGBTQ + individuals, the anticipated experience of the program included continued stigmatization and inequities. Future research should seek to understand the experienced views of MSM/2SGBTQ + donors to ensure that as policies change, policies are implemented equitably., (© 2023. The Author(s).)

Long distance and open water swimming have increased in popularity over recent years. Swimming a long distance in lakes, rivers and the sea present numerous challenges, including cold water exposure and maintaining adequate nutritional intake to fuel exercising muscles. Guidelines exist outlining issues to consider and potential solutions to overcome the difficulties in feeding athletes. Exercising with type 1 diabetes adds further complexity, mostly around matching insulin to the recommended high carbohydrate intake, but also because of the way in which higher circulating insulin levels affect glucose utilisation and fat oxidation. This paper describes the nutritional considerations for people with type 1 diabetes intending to undertake long distance open water events, and insulin management suggestions to trial alongside. In addition, we include personal testimony from a swimmer with type 1 diabetes describing the challenges and considerations he faced when undertaking marathon swimming., Competing Interests: Author NO has received honoraria for advisory board participation and for speaking from Roche Diabetes and Dexcom, and has received research funding from Dexcom and Roche Diabetes. Author NH has received continuous glucose monitoring equipment and study funding from Dexcom San Diego, California for research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rilstone, Spurway, Oliver and Hill.)

Purpose: A case of loperamide-induced recurrent torsades de pointes is reported to raise awareness of an increasingly common phenomenon that could be encountered by medical providers during the current opioid epidemic., Summary: A 40 year-old-man with a prior history of opioid abuse who presented to the emergency department after taking up to 100 tablets of loperamide 2 mg daily for 5 years to blunt opioid withdrawal symptoms and was subsequently admitted to the intensive care unit for altered mental status and hyperthermia. The patient had prolonged QTc and 2 episodes of torsades de pointes (TdP) that resulted in cardiac arrest with return of spontaneous circulation. He was managed with isoproterenol, overdrive pacing, and methylnatrexone with no other events of TdP or cardiac arrest., Conclusion: A 40-year-old male who developed torsades de pointes from loperamide overdose effectively treated with overdrive pacing, isoproterenol, and methylnatrexone.

Background: Canadian Blood Services introduced new eligibility criteria that allows some sexually active gay, bisexual, and other men who have sex with men (gbMSM) to donate source plasma, marking a significant change from time-based deferral criteria. We aimed to identify potential barriers and enablers to implementing the new criteria from the perspective of donor center staff., Study Design and Methods: We conducted Theoretical Domains Framework-informed interviews with staff from two source plasma donation centers in Canada., Results: We completed 28 interviews between June 2020 and April 2021. Three themes representing eight domains captured key tensions. Valuing inclusive eligibility criteria: staff support inclusive criteria; many were concerned the new criteria remained discriminatory. Investing in positive donor experiences: staff wished to foster positive donor experiences; however, they worried gbMSM donors would express anger and disappointment regarding the new criteria, staff would experience unease over using stigmatizing criteria and convey nonverbal cues of discomfort, and recurring plasma donors may behave inappropriately. Supporting education, training, and transparency of eligibility criteria: participants believed providing in-person training (i.e., to explain criteria rationale, address discomfort, practice responding to donor questions) and ensuring donors and the public were well-informed of the upcoming changes would improve implementation., Discussion: Participant views emphasize the importance of supporting staff through training and transparent communication to optimize the delivery of world-class equitable care for a new cohort of donors who have previously been excluded from plasma donation. Findings inform which staff supports to consider to improve implementation as policies continue to shift internationally., (© 2022 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Background: Rugby union player size has increased since the game turned professional in 1995. Changes in physical and performance capability over this period have yet to be fully described., Hypothesis: Increases in player momentum would result from changes in body mass., Methods: Within-player rates of change in anthropometric and kinetic variables with season played were sampled in three successively studied professional rugby union club cohorts playing at the highest level of European competition between 1999 and 2019. Data comprised 910 seasons of observation for 291 elite male players. Most players had 2, 3 or 4 seasons of observation. Mixed-effects modelling distinguished changes independent of position played, club and international status., Results: With each season played, player body mass, fat-free mass and maximum speed increased significantly, while per cent fat decreased. The mean maximal velocity of a rugby player in 1999 was 8.2 (±0.18) m/s, which in 2019 had risen to 9.1 (±0.10) m/s. Player's momentum in 2019 was 14% more than those playing in 1999. In the Front Five, momentum increased in this period by >25%, mainly driven by greater running speed, disproving our hypothesis., Conclusions: The momentum of players, particularly forwards, increased markedly over 20 seasons of professional rugby. The resulting forces generated in collisions are thus significantly greater, although these may be mitigated by better player conditioning. Proactive regulation to address player safety may be required to address the changing nature of anthropometric measures and physical performance, minimising injury rates and potential long-term sequelae., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Medical personnel may find it challenging to distinguish severe Exertional Heat Illness (EHI), with attendant risks of organ-injury and longer-term sequalae, from lesser forms of incapacity associated with strenuous physical exertion. Early evidence for injury at point-of-incapacity could aid the development and application of targeted interventions to improve outcomes. We aimed to investigate whether biomarker surrogates for end-organ damage sampled at point-of-care (POC) could discriminate EHI versus successful marathon performance., Methods: Eight runners diagnosed as EHI cases upon reception to medical treatment facilities and 30 successful finishers of the same cool weather marathon (ambient temperature 8 rising to 12 ºC) were recruited. Emerging clinical markers associated with injury affecting the brain (neuron specific enolase, NSE; S100 calcium-binding protein B, S100β) and renal system (cystatin C, cysC; kidney-injury molecule-1, KIM-1; neutrophil gelatinase-associated lipocalin, NGAL), plus copeptin as a surrogate for fluid-regulatory stress, were sampled in blood upon marathon collapse/completion, as well as beforehand at rest (successful finishers only)., Results: Versus successful finishers, EHI showed significantly higher NSE (10.33 [6.37, 20.00] vs. 3.17 [2.71, 3.92] ug.L-1, P<0.0001), cysC (1.48 [1.10, 1.67] vs. 1.10 [0.95, 1.21] mg.L-1, P = 0.0092) and copeptin (339.4 [77.0, 943] vs. 18.7 [7.1, 67.9] pmol.L-1, P = 0.0050). Discrimination of EHI by ROC (Area-Under-the-Curve) showed performance that was outstanding for NSE (0.97, P<0.0001) and excellent for copeptin (AUC = 0.83, P = 0.0066)., Conclusions: As novel biomarker candidates for EHI outcomes in cool-weather endurance exercise, early elevations in NSE and copeptin provided sufficient discrimination to suggest utility at point-of-incapacity. Further investigation is warranted in patients exposed to greater thermal insult, followed up over a more extended period., Competing Interests: The authors have declared that no competing interests exist.

Numerous studies have demonstrated a negative relationship between community violence and youth academic achievement, but they have varied in their geographic definition of "community," especially as it relates to proximity to students' residences. We extend this by considering the independent relationships between academic achievement and violent events (from 911 dispatches; e.g., gun shots) at the neighborhood (i.e., census tract) and street-block levels. We use data from standardized Math and English Language Arts (ELA) tests from Boston, MA for 2011-2013. Exposure to community violence was partially independent between streets and tracts, with some students living on low-crime streets in high-crime neighborhoods or high-crime streets in low-crime neighborhoods. Initial regression models found that differences in a neighborhood's violent crime predicted up to a 3% difference in test scores on both Math and ELA tests. Students living on high-crime streets scored an additional 1% lower than neighbors on safer streets. Subsequent models with student-level fixed effects, however, eliminated these relationships, except for the effect of neighborhood-level violence on Math scores. These findings suggest that future work should consider community violence at both geographic scales, but that in this case the impacts were only consistent at the neighborhood level and associations at the street level were seemingly due to spatial segregation of households., Competing Interests: No authors have competing interests.

Introduction: Diseases and non-battle injuries (DNBIs) are common on UK military deployments, but the collection and analysis of clinically useful data on these remain a challenge. Standard medical returns do not provide adequate clinical information, and clinician-led approaches have been laudable, but not integrated nor standardised nor used long-term. Op TRENTON is a novel UK military humanitarian operation in support of the United Nations Mission in South Sudan, which included the deployment of UK military level 1 and level 2 medical treatment facilities at Bentiu to provide healthcare for UK and United Nations (UN) personnel., Methods: A service evaluation of patient consultations and admissions at the UK military level 2 hospital was performed using two data sets collected by the emergency department (ED) and medicine (MED) teams., Results: Over a three-month (13-week) period, 286 cases were seen, of which 51% were UK troops, 29% were UN civilians and 20% were UN troops. The ED team saw 175 cases (61%) and provided definitive care for 113 (40%), whereas the MED team saw and provided definitive care for 128 cases (45%). Overall, there were 75% with diseases and 25% with non-battle injuries. The most common diagnoses seen by the ED team were musculoskeletal injuries (17%), unidentified non-malarial undifferentiated febrile illness (UNMUFI) (17%), malaria (13%), chemical pneumonitis (13%) and wounds (8%). The most common diagnoses seen by the MED team were acute gastroenteritis (AGE) (56%), UNMUFI (12%) and malaria (9%). AGE was due to viruses (31%), diarrhoeagenic Escherichia coli (32%), other bacteria (6%) and protozoa (12%)., Conclusion: Data collection on DNBIs during the initial phase of this deployment was clinically useful and integrated between different departments. However, a standardised, long-term solution that is embedded into deployed healthcare is required. The clinical activity recorded here should be used for planning, training, service development and targeted research., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The majority of studies report that the Covid-19 pandemic lockdown did not have a detrimental effect on glycaemia. We sought to explore the impact of lockdown on glycaemia and whether this is sustained following easing of restrictions., Methods: Retrospective, observational analysis in adults and children with type 1 diabetes attending a UK specialist centre, using real-time or intermittently scanned continuous glucose monitoring. Data from the following 28-day time periods were collected: (i) pre-lockdown; (ii) during lockdown; (iii) immediately after lockdown; and (iv) a month following relaxation of restrictions (coinciding with Government-subsidised restaurant food). Data were analysed for times in glycaemic ranges and are expressed as median (IQR)., Results: 145 adults aged 35.5 (25.8-51.3) years with diabetes duration of 19.0 (7.0-29.0) years on multiple daily injections of insulin (60%) and continuous insulin infusion (40%) were included. In adults, % time in range (70-180mg/dL) increased during lockdown (60.2 (45.2-69.3)%) compared to pre-lockdown (56.7 (43.5-65.3)%; p<0.001). This was maintained in the post-lockdown time periods. Similarly, % time above range (>180mg/dL) reduced in lockdown compared to pre-lockdown (p = 0.01), which was sustained thereafter. In children, no significant changes to glycaemia were observed during lockdown. In multivariable analysis, a greater increase in %TIR 3.9-10mmol/L (70-180mg/dL) during lockdown was associated with higher levels of deprivation (coefficient: 4.208, 95% CI 0.588 to 7.828; p = 0.02)., Conclusions: Glycaemia in adults improved during lockdown, with people from more deprived areas most likely to benefit. This effect was sustained after easing of restrictions, with government-subsidised restaurant eating having no adverse impact on glycaemia., Competing Interests: M.R. has received honoraria for advisory board participation from Dexcom and Roche Diabetes. N.O. has received honoraria for speaking and advisory board participation from Abbott Diabetes, Dexcom, Medtronic Diabetes, and Roche Diabetes. N.E.H. received study grants from Dexcom. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Introduction: Patients with diabetes mellitus admitted to hospital with COVID-19 have poorer outcomes. However, the drivers of poorer outcomes are not fully elucidated. We performed detailed characterization of patients with COVID-19 to determine the clinical and biochemical factors that may be drivers of poorer outcomes., Research Design and Methods: This is a retrospective cohort study of 889 consecutive inpatients diagnosed with COVID-19 between March 9 and April 22, 2020 in a large London National Health Service Trust. Unbiased multivariate logistic regression analysis was performed to determine variables that were independently and significantly associated with increased risk of death and/or intensive care unit (ICU) admission within 30 days of COVID-19 diagnosis., Results: 62% of patients in our cohort were of non-white ethnic background and the prevalence of diabetes was 38%. 323 (36%) patients met the primary outcome of death/admission to the ICU within 30 days of COVID-19 diagnosis. Male gender, lower platelet count, advancing age and higher Clinical Frailty Scale (CFS) score (but not diabetes) independently predicted poor outcomes on multivariate analysis. Antiplatelet medication was associated with a lower risk of death/ICU admission. Factors that were significantly and independently associated with poorer outcomes in patients with diabetes were coexisting ischemic heart disease, increasing age and lower platelet count., Conclusions: In this large study of a diverse patient population, comorbidity (ie, diabetes with ischemic heart disease; increasing CFS score in older patients) was a major determinant of poor outcomes with COVID-19. Antiplatelet medication should be evaluated in randomized clinical trials among high-risk patient groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Exercise training is associated with positive health outcomes in people with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). However, fear of hypoglycaemia is a potential barrier to participants attending a cardiac exercise class. Therefore, we assessed the capillary blood glucose (CBG) responses to the Imperial NHS Trust cardiac exercise class. Forty patients (median age 66 years, interquartile range [IQR] 57-74 years) with CVD and T2DM treated with insulin and/or sulfonylureas completed a cardiac exercise class. CBG was measured immediately before and after the exercise class. Subgroup analysis assessed CBG levels in patients who had consumed food <2 and ≥2 hours and had taken their insulin and/or sulfonylureas <4 and ≥4 hours before the exercise class. Overall, post-exercise CBG had significantly decreased (-3.0 mmol/L, p≤0.0001). Subgroup analyses demonstrated significant reductions in CBG in both food consumption groups (<2 hours -2.9 mmol/L, p≤0.0001, and ≥2 hours -3.1 mmol/L, p≤0.0001) and medication groups (<4 hours -3.4 mmol/L, p≤0.0002, and ≥4 hours -2.7 mmol/L, p≤0.0001). However, there were no significant differences in CBG between the food consumption groups and the medication groups, respectively (p=0.7 and p=0.3). Cardiac exercise classes resulted in significant reductions in CBG levels. However, the timing of food consumption or medication intake did not influence the magnitude of CBG decline after the cardiac exercise class., Competing Interests: None declared., (Copyright © 2020 Medinews (Cardiology) Limited.)

Background: Blood donation policy in Canada for gay, bisexual and other men who have had sex with men (gbMSM) has changed progressively in the last decade from indefinite deferral to 3-month deferral from last male-to-male sex. Driven by safety data and overseen by the national regulator, more inclusive policies continue to redress the disparity in donation for gbMSM. At the same time, the need for source plasma to prepare fractionated blood products is growing worldwide. The collection and processing of source plasma ensures greater safety compared to whole blood donation with respect to transfusion-transmitted infection. This greater safety offers an opportunity to evolve policies for gbMSM from time-based to behaviour-based deferral using revised eligibility criteria. However, changing policies does not in itself necessarily guarantee that gbMSM will donate or that staff in donor clinics are ready to support them to do so. In anticipation of a move to behaviour-based donation screening for gbMSM in Canada, we aim to assess the acceptability of and perceived barriers and enablers to source plasma donation using revised screening criteria for gbMSM among key stakeholders to inform policy implementation strategies., Methods: This mixed-methods feasibility study will involve gbMSM and donor centre staff to understand modifiable barriers to implementing more inclusive eligibility criteria. Key informant interviews and surveys will be rooted in the Theoretical Domains Framework to identify modifiable factors associated with source plasma donation motives in gbMSM and training needs in donation centre staff. We will use an integrated knowledge translation approach involving a partnership between researchers, the national blood operator and gbMSM, situating knowledge users as key research team members to ensure their perspectives inform all aspects of the research., Discussion: Our integrated knowledge translation approach will provide a more comprehensive and collaborative understanding of blood operator and gbMSM needs while accelerating the implementation of study findings. Given the historical backdrop of the decades of exclusion of sexually active gbMSM from blood donation, this study has the potential not only to inform a process and policy for gbMSM to donate source plasma, a blood product, but also offers opportunities for new relationships between these knowledge users.

Aims: Robust evidence supports intensive glucose control in those with recently diagnosed type 1 diabetes to reduce the risk of developing micro- and macrovascular complications. Data to support longitudinal glycaemic targets is lacking. We aimed to explore if longer duration of diabetes and greater age might reduce the impact of glycaemia on the risk of vascular complications., Research and Design Methods: Data for adults age 20 years or more, was extracted from a clinical database of people with type 1 diabetes cared for at a London teaching hospital. The presence or absence of micro- and macro-vascular complications was recorded. Multivariable logistic regression analysis was performed using HbA1c as independent variable, diabetes duration and age as continuous variable and obesity, hypertension, hypercholesterolaemia, low HDL cholesterol and hypertriglyceridaemia as categorical variables., Results: Data from 495 patients was used. HbA1c above 60 mmol/mol (7.6%) was associated with increased microvascular complications in patients aged 20-44 years, independent of age and duration of diabetes. In older people with T1DM duration of diabetes was the major risk factor., Conclusions: Our study suggests that increased age and greater duration of diabetes reduce the impact of glycaemia on the risk of vascular complications. Intensive blood glucose management in patients aged ≥45 years may have limited benefits in terms of reducing the risk of complications although this does not dismiss the benefits of good glycaemic control in older people with T1DM., Competing Interests: The authors have declared that no competing interests exist.

Context: Survival rates after severe injury are improving, but complication rates and outcomes are variable., Objective: This cohort study addressed the lack of longitudinal data on the steroid response to major trauma and during recovery., Design: We undertook a prospective, observational cohort study from time of injury to 6 months postinjury at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) > 15)., Main Outcome Measures: We measured adrenal and gonadal steroids in serum and 24-hour urine by mass spectrometry, assessed muscle loss by ultrasound and nitrogen excretion, and recorded clinical outcomes (ventilator days, length of hospital stay, opioid use, incidence of organ dysfunction, and sepsis); results were analyzed by generalized mixed-effect linear models., Findings: We screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed all male survivors <50 years not treated with steroids (N = 60; median age 27 [interquartile range 24-31] years; median NISS 34 [29-44]). Urinary nitrogen excretion and muscle loss peaked after 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 months, respectively, to recover; opioid treatment delayed dehydroepiandrosterone recovery in a dose-dependent fashion. Androgens and precursors correlated with SOFA score and probability of sepsis., Conclusion: The catabolic response to severe injury was accompanied by acute and sustained androgen suppression. Whether androgen supplementation improves health outcomes after major trauma requires further investigation., (© Endocrine Society 2020.)

School context serves as a testing ground for exploring social relationships and satisfying needs for connection and affirmation, but often includes feelings of rejection. With a diverse high school sample (n = 645; 55% female; 61% White, 18% African American, 10% Latino, 10% Asian American, 1% Multiracial), patterns of experiences with marginalization and connection were identified and their associations with achievement and mental health examined. Using two-step cluster analysis, three clusters were identified: above the fray, exposed and protected, and targeted and unsupported. Ethnic/racial background was not related to cluster membership. Except for gender and well-being, associations between cluster membership and outcomes were similar across demographic background. The above the fray and the exposed and protected clusters were associated with better outcomes., (© 2018 Society for Research on Adolescence.)

We describe a 67-year-old man admitted from a mental health unit with an incidental finding of hyponatraemia on routine blood tests. Laboratory investigations were in keeping with syndrome of inappropriate antidiuretic hormone secretion (SIADH). He had been recently commenced on mirtazapine. During his inpatient stay, he became increasingly confused. Review of a previous admission with hyponatraemia raised the possibility of voltage-gated potassium channel antibody-associated limbic encephalitis, although subsequent investigations deemed this unlikely as a cause of hyponatraemia. Although his sodium levels improved with fluid restriction, serial point-of-care testing proved misleading in monitoring the efficacy of treatment as inconsistencies were seen in comparison with laboratory testing. The cause of hyponatraemia may have been medication-induced SIADH and/or polydipsia. This case highlights the importance of collating detailed histories and laboratory blood testing to guide management in cases of hyponatraemia of unknown aetiology., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Growing evidence indicates that identity-based victimization (IBV; e.g., discrimination) is traumatic, and associated with mental health and academic concerns. Youth with multiple stigmatized identities face a higher risk of both victimization and poor mental health. The current study enhances a growing research base on intersectional IBV by examining 1) identity, rather than attribution, 2) a range of IBV experiences, 3) both mental health and academic achievement, 4) the mediating role of discrimination across multiple social identities, and 5) including gender expansive youth within a diverse sample representative of a high school population in the U.S., Methods: A cluster analysis was conducted to provide a nuanced depiction of intersectionality in a diverse sample of high school students (N = 946; ages 14-20, 44% cisgender boys, 53% cisgender girls, 3% gender expansive youth). Outcome and IBV differences across clusters were examined, in addition to the mediation of cluster membership and outcomes by discrimination., Results: Three distinct profiles of identity emerged: LGBTQ Youth (24%), Heterosexual Youth of Color (37%), and Heterosexual White Youth (39%). LGBTQ Youth and Heterosexual Youth of Color experienced the most IBV, and had higher levels of depression, lower wellbeing, and lower GPAs. Finally, discrimination partially mediated the association between identity and outcomes for LGBTQ youth, and fully mediated this association for Heterosexual Youth of Color., Conclusions: The disproportionately of IBV, poor mental health, and lower academic achievement faced by LGBTQ youth and youth with intersecting stigmatized identities suggests that they may benefit from tailored and targeted treatments., (Copyright © 2019 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Objectives: To investigate changes in renal status from exercise in the heat with acclimatisation and to evaluate surrogates markers of Acute Kidney Injury., Design: Prospective observational cohort study., Methods: 20 male volunteers performed 60 min standardised exercise in the heat, at baseline and on four subsequent occasions during a 23-day acclimatisation regimen. Blood was sampled before and after exercise for serum creatinine, copeptin, interleukin-6, normetanephrine and cortisol. Fractional excretion of sodium was calculated for corresponding urine samples. Ratings of Perceived Exertion were reported every 5 min during exercise. Acute Kidney Injury was defined as serum creatinine rise ≥26.5 μmol L -1 or fall in estimated glomerular filtration rate >25%. Predictive values of each candidate marker for developing Acute Kidney Injury were determined by ROC analysis., Results: From baseline to Day 23, serum creatinine did not vary at rest, but showed a significant (P<0.05) reduction post-exercise (120 [102, 139] versus 102 [91, 112] μmol L -1 ). Acute Kidney Injury was common (26/100 exposures) and occurred most frequently in the unacclimatised state. Log-normalised fractional excretion of sodium showed a significant interaction (exercise by acclimatization day), with post-exercise values tending to rise with acclimatisation. Ratings of Perceived Exertion predicted AKI (AUC 0.76, 95% confidence interval 0.65-0.88), performing at least as well as biochemical markers., Conclusions: Heat acclimatization is associated with reduced markers of renal stress and AKI incidence, perhaps due to improved regional perfusion. Acclimatisation and monitoring Ratings of Perceived Exertion are practical, non-invasive measures that could help to reduce renal injury from exercise in the heat., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Joint problems commonly occur in people with diabetes. Cheiroarthropathy affects the hands and results in painless limited finger joint extension, appearing to be associated with longer diabetes duration and the presence of microvascular complications. The prevalence of cheiroarthropathy seems to be falling, perhaps as a result of improvements in glycaemic management. Non-enzymatic glycation of collagen results in abnormally crosslinked protein resistant to degradation with subsequent increased build-up of collagen in joints. The management of cheiroarthropathy is predominantly conservative, with occupational and hand therapy at the forefront. Tendinopathy is more common in people with diabetes than those without, and is associated with obesity and insulin resistance. As with cheiroarthropathy, the exact causative mechanism of tendinopathy in diabetes is not known, but may be linked to inflammation, apoptosis and increased vascularity of affected tendons, driven by hyperinsulinaemia. Local fat pads have also been suggested to play a role in the pathogenesis of tendinopathy., (© 2019 Diabetes UK.)

Competing Interests: Competing interests: None declared.

An impaired capacity of muscle to regenerate after critical illness results in long-term functional disability. We previously described in a long-term rat peritonitis model that gastrocnemius displays near-normal histology whereas soleus demonstrates a necrotizing phenotype. We thus investigated the link between the necrotizing phenotype of critical illness myopathy and proteasome activity in these two limb muscles. We studied male Wistar rats that underwent an intraperitoneal injection of the fungal cell wall constituent zymosan or n-saline as a sham-treated control. Rats ( n = 74) were killed at 2, 7, and 14 days postintervention with gastrocnemius and soleus muscle removed and studied ex vivo. Zymosan-treated animals displayed an initial reduction of body weight but a persistent decrease in mass of both lower hindlimb muscles. Zymosan increased chymotrypsin- and trypsin-like proteasome activities in gastrocnemius at days 2 and 7 but in soleus at day 2 only. Activated caspases-3 and -9, polyubiquitin proteins, and 14-kDa fragments of myofibrillar actin (proteasome substrates) remained persistently increased from day 2 to day 14 in soleus but not in gastrocnemius. These results suggest that a relative proteasome deficiency in soleus is associated with a necrotizing phenotype during long-term critical illness. Rescuing proteasome clearance may offer a potential therapeutic option to prevent long-term functional disability in critically ill patients.

Background: . Diarrhea is a well-established problem in travellers, with military personnel at especially high risk. This study aimed to characterise the spectrum of pathogens causing diarrhea in UK military personnel in South Sudan, and assess the utility of culture-independent testing for etiology and antimicrobial resistance in a logistically challenging and austere environment., Methods: . All military personnel presenting with diarrhea were admitted to the UK Level 2 Medical Treatment Facility in Bentiu, South Sudan. Samples were tested for etiology utilising multiplex PCR-based diagnostics (BioFire FilmArray). In addition, the presence of carbapenemase resistance genes was determined using the geneXpert Carba-R platform., Results: . Over 5 months, 127 samples were tested. The vast majority of pathogens detected were diarrheagenic Escherichia coli. The presence of either enterotoxigenic (ETEC) or enteropathogenic (EPEC) E. coli was a significant predictor of the other being present. In this study patients presenting with vomiting were 32 times more likely to have norovirus than not (p < 0.001). No carbapenem resistance was detected., Conclusions: . Diarrhea in UK military personnel in South Sudan was determined to be predominantly bacterial, with norovirus presenting a distinct clinical and epidemiological pattern. Multiplex PCR and molecular resistance point of care testing were robust and effective in this environment., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Soldier operational performance is determined by their fitness, nutritional status, quality of rest/recovery, and remaining injury/illness free. Understanding large fluctuations in nutritional status during operations is critical to safeguarding health and well-being. There are limited data world-wide describing the effect of extreme climate change on nutrient profiles. This study investigated the effect of hot-dry deployments on vitamin D status (assessed from 25-hydroxyvitamin D (25(OH)D) concentration) of young, male, military volunteers. Two data sets are presented (pilot study, n 37; main study, n 98), examining serum 25(OH)D concentrations before and during 6-month summer operational deployments to Afghanistan (March to October/November). Body mass, percentage of body fat, dietary intake and serum 25(OH)D concentrations were measured. In addition, parathyroid hormone (PTH), adjusted Ca and albumin concentrations were measured in the main study to better understand 25(OH)D fluctuations. Body mass and fat mass (FM) losses were greater for early (pre- to mid-) deployment compared with late (mid- to post-) deployment (P&lt;0·05). Dietary intake was well-maintained despite high rates of energy expenditure. A pronounced increase in 25(OH)D was observed between pre- (March) and mid-deployment (June) (pilot study: 51 (sd 20) v. 212 (sd 85) nmol/l, P&lt;0·05; main study: 55 (sd 22) v. 167 (sd 71) nmol/l, P&lt;0·05) and remained elevated post-deployment (October/November). In contrast, PTH was highest pre-deployment, decreasing thereafter (main study: 4·45 (sd 2·20) v. 3·79 (sd 1·50) pmol/l, P&lt;0·05). The typical seasonal cycling of vitamin D appeared exaggerated in this active male population undertaking an arduous summer deployment. Further research is warranted, where such large seasonal vitamin D fluctuations may be detrimental to bone health in the longer-term.