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Acute back pain with neurological symptoms is a medical emergency. Here we report a case of severe degenerative spine disease with raised inflammatory markers due to an atypical cause.

Objectives: The aim of this study was to replicate the study titled "Investigating the effects of maximal anaerobic fatigue on dynamic postural control using the Y-Balance Test" by Johnston et al. (2018) as part of a large replication project. This study aimed to determine the effects of maximal anaerobic fatigue on dynamic postural control using the Y-Balance Test, with a specific focus on anterior reach distance., Design: A single session intervention., Methods: Forty male and female university students (age: 22 ± 3 years, height: 171.88 ± 8.96 cm, mass: 76.20 ± 14.31 kg) partaking in competitive sport, completed a Y-Balance Test protocol at 20, 10, and 0 min before a modified 60 s Wingate fatiguing protocol. Post-fatigue assessments were completed at 0, 10, and 20 min after the Wingate test. Replication outcomes included significance, direction, and effect size comparison using a z-test., Results: A one-way repeated measures ANOVA showed a significant effect for maximal anaerobic fatigue on normalised anterior reach direction (F 1.82, 69.03  = 7.16, p = 0.002, η p 2  = 0.159; 95 % CI: 0.025, 0.320). Therefore, we replicated the original findings for anterior reach distance in terms of statistical significance (F = 3.818, p = 0.025, η p 2  = 0.376; 95 % CI: 0.00, 0.62). The replication and original effect size estimates for anterior reach direction were compared using a z-test and were deemed compatible (z = 1.65, p = 0.05)., Conclusions: Overall, we replicated the original study findings for the effect of maximal anaerobic fatigue on anterior reach distance in a Y-Balance Test., Competing Interests: Declaration of interest statement The authors report that there are no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate a strategy designed to optimize care and increase uptake of urate-lowering therapy (ULT) during hospitalizations for gout flares., Methods: We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment and re-hospitalization rates, were compared between patients hospitalized for flares in the 12 months post-implementation and a retrospective cohort of hospitalized patients from 12 months pre-implementation., Results: One hundred and nineteen and 108 patients, respectively, were hospitalized for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n = 94 and n = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio [aOR] 11.5; 95% CI 4.36, 30.5; P < 0.001). After implementation, more patients achieved a serum urate ≤360 μmol/l within 6 months of discharge (10.6% pre-implementation vs 26.8% post-implementation; aOR 3.04; 95% CI 1.36, 6.78; P = 0.007). The proportion of patients re-hospitalized for flares was 14.9% pre-implementation vs 9.3% post-implementation (aOR 0.53; 95% CI 0.22, 1.32; P = 0.18)., Conclusion: Over 90% of patients were initiated on ULT after implementing a strategy to optimize hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalizations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalized gout patients to achieve urate targets, closer primary-secondary care integration is still needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: To assess whether the optimal mean arterial blood pressure (MAP) target after out-of-hospital cardiac arrest (OHCA) is influenced by age and a history of arterial hypertension., Methods: Post-hoc analysis of data from the Blood Pressure and Oxygenation Targets in Post Resuscitation Care (BOX) trial. The trial included 789 comatose patients randomized to a MAP target of 63mmHg or 77mmHg. The primary outcome of this sub-study was one-year all-cause mortality. Cox proportional-hazards regression and restricted cubic splines were used to examine whether prevalent hypertension and age modified the effect of low versus high MAP target on all-cause mortality., Results: Of the 789 patients randomized, 393 were assigned to a high MAP target, and 396 to a low MAP target. Groups were well balanced for mean age (high MAP target 63±13 years versus low 62±14 years) and hypertension (45% versus 47% respectively). At one year, the primary outcome occurred in 143 patients (36%) with high MAP target and 138 (35%) with low MAP target. The risk of the primary outcome increased linearly with increasing age (P<0.001). The effect of a high versus low MAP target on the primary outcome was modified by age when tested continuously, potentially favoring low MAP target in younger patients (P for interaction=0.03). Prevalent hypertension did not modify the effect of a high versus low MAP target on the primary outcome (P for interaction=0.67)., Conclusions: Among patients resuscitated after OHCA, older patients and those with a history of hypertension did not benefit from a higher MAP target., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In January 2020, increased mortality was reported in a small broiler breeder flock in County Fermanagh, Northern Ireland. Gross pathological findings included coelomitis, oophoritis, salpingitis, visceral gout, splenomegaly, and renomegaly. Clinical presentation included inappetence, pronounced diarrhoea, and increased egg deformation. These signs, in combination with increased mortality, triggered a notifiable avian disease investigation. High pathogenicity avian influenza virus (HPAIV) was not suspected, as mortality levels and clinical signs were not consistent with HPAIV. Laboratory investigation demonstrated the causative agent to be a low-pathogenicity avian influenza virus (LPAIV), subtype H6N1, resulting in an outbreak that affected 15 premises in Northern Ireland. The H6N1 virus was also associated with infection on 13 premises in the Republic of Ireland and six in Great Britain. The close genetic relationship between the viruses in Ireland and Northern Ireland suggested a direct causal link whereas those in Great Britain were associated with exposure to a common ancestral virus. Overall, this rapidly spreading outbreak required the culling of over 2 million birds across the United Kingdom and the Republic of Ireland to stamp out the incursion. This report demonstrates the importance of investigating LPAIV outbreaks promptly, given their substantial economic impacts.

Rondaptivan pegol (previously BT200) is a PEGylated RNA aptamer that binds to the A1 domain of VWF. Recent clinical trials demonstrated that BT200 significantly increased plasma VWF-FVIII levels by attenuating VWF clearance. The biological mechanism(s) through which BT200 attenuates in vivo clearance of VWF have not been defined. We hypothesized that BT200 interaction with the VWF-A1 domain may increase plasma VWF levels by attenuating macrophage-mediated clearance. We observed that full length- and VWF-A1A2A3 binding to macrophages, and VWF-A1 domain binding to LRP1 cluster II and cluster IV, were concentration-dependently inhibited by BT200. Additionally, full length VWF binding to LRP1 expressed on HEK293T (HEK-LRP1) cells was also inhibited by BT200. Importantly, BT200 interacts with the VWF-A1 domain in proximity to a conserved cluster of four lysine residues (K1405, K1406, K1407 and K1408). Alanine mutagenesis of this K1405-K1408 cluster (VWF-4A) significantly (p<0.001) attenuated binding of VWF to both LRP1 clusters II and IV. Furthermore, in vivo clearance of VWF-4A was significantly (p<0.001) reduced compared to wild type VWF. BT200 did not significantly inhibit binding of VWF-4A to LRP1 cluster IV or HEK-LRP1 cells. Finally, BT200 interaction with the VWF-A1 domain also inhibited binding to macrophage galactose lectin (MGL) and the SR-AI scavenger receptor. Collectively, our findings demonstrate that BT200 prolongs VWF half-life by attenuating macrophage-mediated clearance and specifically the interaction of K1405-1408 in the VWF-A1 domain with macrophage LRP1. These data support the concept that targeted inhibition of VWF clearance pathways represent a novel therapeutic approach for VWD and hemophilia A., (Copyright © 2024 American Society of Hematology.)

Diabetes is the commonest cause of end stage kidney disease globally, accounting for almost 40% of new cases requiring renal replacement therapy. Management of diabetes in people with advanced kidney disease on renal replacement therapy is challenging due to some unique aspects of assessment and treatment in this group of patients. Standard glycaemic assessment using glycated haemoglobin may not be valid in such patients due to altered red blood cell turnover or iron/erythropoietin deficiency, leading to changed red blood cell longevity. Therefore, use of continuous glucose monitoring may be beneficial to enable more focussed glycaemic assessment and improved adjustment of therapy. People with advanced kidney disease may be at higher risk of hypoglycaemia due to a number of physiological mechanisms, and in addition, therapeutic options are limited in such patients due to lack of experience or license. Insulin therapy is the basis of treatment of people with diabetes with advanced kidney disease due to many other drugs classes being contraindicated. Targets for glycaemic control should be adjusted according to co-morbidity and frailty, and continuous glucose monitoring should be used in people on dialysis to ensure low risk of hypoglycaemia. Post-transplant diabetes is common amongst people undergoing solid organ transplantation and confers a greater risk of mortality and morbidity in kidney transplant recipients. It should be actively screened for and managed in the post-transplant setting., (© 2024 Diabetes UK.)

Xenohormesis proposes that phytochemicals produced to combat stressors in the host plant exert biochemical effects in animal cells lacking cognate receptors. Xenohormetic phytochemicals such as flavonoids and phytoalexins modulate a range of human cell signaling mechanisms but functional correlations with human pathophysiology are lacking. Here, potent inhibitory effects of grapefruit-derived Naringenin (Nar) and soybean-derived Glyceollins (Gly) in human microphysiological models of bulk tissue vasculogenesis and tumor angiogenesis are reported. Despite this interference of vascular morphogenesis, Nar and Gly are not cytotoxic to endothelial cells and do not prevent cell cycle entry. The anti-vasculogenic effects of Glyceollin are significantly more potent in sex-matched female (XX) models. Nar and Gly do not decrease viability or expression of proangiogenic genes in triple negative breast cancer (TNBC) cell spheroids, suggesting that inhibition of sprouting angiogenesis by Nar and Gly in a MPS model of the (TNBC) microenvironment are mediated via direct effects in endothelial cells. The study supports further research of Naringenin and Glyceollin as health-promoting agents with special attention to mechanisms of action in vascular endothelial cells and the role of biological sex, which can improve the understanding of dietary nutrition and the pharmacology of phytochemical preparations., (© 2024 The Author(s). Advanced Biology published by Wiley‐VCH GmbH.)

Locally advanced or recurrent prostate cancer which invades adjacent pelvic organs, bone or other soft tissue structures is a rare situation. This study aimed to report the outcomes of ten consecutive patients who underwent total pelvic exenteration for prostate cancer at a high-volume specialist centre. Two patients had locally advanced primary tumours, while eight had locally recurrent prostate cancer. Median operating time, blood loss, ICU stay, and hospital stay was 12.2 h (range 9.6-13.8), 2500 ml (500-3000), 4.5 days (2-7) and 36 days (21-78), respectively. There was no inpatient, 30-day, or 90-day mortality. Six patients developed a Clavien-Dindo III complication. R0 resection was achieved in eight patients. Median follow up was 16 months (range 2-77). At last follow up, five patients were alive without disease. These findings suggest that pelvic exenteration for locally advanced and recurrent prostate cancer is safe and represents a potentially curative treatment option for highly selected patients., Competing Interests: Declaration of competing interest All the authors have made a significant contribution to this manuscript, have seen and approved the final manuscript, and have agreed to its submission to the EJSO. There are no conflicts of interest to declare., (© 2024 Published by Elsevier Ltd.)

Background: von Willebrand factor (VWF)-R1205H variant (Vicenza) results in markedly enhanced VWF clearance in humans that has been shown to be largely macrophage-mediated. However, the biological mechanisms underlying this enhanced clearance remain poorly understood., Objectives: This study aimed to investigate the roles of (i) specific VWF domains and (ii) different macrophage receptors in regulating enhanced VWF-R1205H clearance., Methods: In vivo clearance of full-length and truncated wild-type (WT)-VWF and VWF with R1205 substitutions was investigated in VWF -/- mice. Plate-binding assays were employed to characterize VWF binding to purified scavenger receptor class A member 1 (SR-AI), low-density lipoprotein receptor-related protein-1 (LRP1) cluster II or cluster IV receptors, and macrophage galactose-type lectin., Results: In full-length VWF missing the A1 domain, introduction of R1205H led to significantly enhanced clearance in VWF -/- mice compared with WT-VWF missing the A1 domain. Importantly, R1205H in a truncated VWF-D'D3 fragment also triggered increased clearance compared with WT-VWF-D'D3. Additional in vivo studies demonstrated that VWF-R1205K (which preserves the positive charge at 1205) exhibited normal clearance, whereas VWF-R1205E (which results in loss of the positive charge) caused significantly enhanced clearance, pinpointing the importance of the positive charge at VWF-R1205. In vitro plate-binding studies confirmed increased VWF-R1205H interaction with SR-AI compared with WT-VWF. Furthermore, significantly enhanced VWF-R1205H binding to LRP1 cluster IV (P < .001) and less marked enhanced binding to LRP1 cluster II (P = .034) was observed. In contrast, VWF-R1205H and WT-VWF demonstrated no difference in binding affinity to macrophage galactose-type lectin., Conclusion: Disruption of the positive charge at amino acid R1205 causes conformational changes in the VWF-D'D3 domains and triggers enhanced LRP1-mediated and SR-AI-mediated clearance., Competing Interests: Declaration of competing interests J.S.O.D. has served on the speaker’s bureau for Baxter, Bayer, Novo Nordisk, Sobi, Boehringer Ingelheim, Leo Pharma, Takeda, and Octapharma. He has also served on the advisory boards of Baxter, Sobi, Bayer, OctapharmaCSL Behring, Daiichi Sankyo, Boehringer Ingelheim, Takeda, and Pfizer. J.S.O.D. has also received research grant funding awards from 3M, Baxter, Bayer, Pfizer, Shire, Takeda, and Novo Nordisk. F.A. received research support from CSL Behring, Takeda, Octapharma, and Sobi. D.L. has received research support from BioMarin, CSL Behring, and Sanofi; he has acted in an advisory role for BioMarin, CSL Behring, Novo Nordisk, Pfizer, Sanofi, and Takeda. The remaining authors declare no competing financial interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Post-COVID conditions (PCC) are difficult to characterize, diagnose, predict, and treat due to overlapping symptoms and poorly understood pathology. Identifying inflammatory profiles may improve clinical prognostication and trial endpoints., Methods: 1,988 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative post-COVID symptom scores were included in this analysis. Among participants who reported moderate-to-severe symptoms on surveys collected 6-months post-SARS-CoV-2 infection, principal component analysis (PCA) followed by K-means clustering identified distinct clusters of symptoms., Results: Three symptom-based clusters were identified: a sensory cluster (loss of smell and/or taste), a fatigue/difficulty thinking cluster, and a difficulty breathing/exercise intolerance cluster. Individuals within the sensory cluster were all outpatients during their initial COVID-19 presentation. The difficulty breathing cluster had a higher likelihood of obesity and COVID-19 hospitalization compared to those with no/mild symptoms at 6-months post-infection. Multinomial regression linked early post-infection D-dimer and IL-1RA elevation to fatigue/difficulty thinking, and elevated ICAM-1 concentrations to sensory symptoms., Conclusions: We identified three distinct symptom-based PCC phenotypes with specific clinical risk factors and early post-infection inflammatory predictors. With further validation and characterization, this framework may allow more precise classification of PCC cases and potentially improve the diagnosis, prognostication, and treatment of PCC., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

The human ileum contains a high density of enteroendocrine L-cells, which release the appetite-suppressing hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release, but the link between food structures, ileal metabolites, and appetite hormone release remains unclear owing to limited access to intact human ileum. In a randomized crossover trial (ISRCTN11327221; isrctn.com), we investigated the role of human ileum in GLP-1 and PYY release by giving healthy volunteers diets differing in fiber and food structure: high-fiber (intact or disrupted food structures) or low-fiber disrupted food structures. We used nasoenteric tubes to sample chyme from the intact distal ileum lumina of humans in the fasted state and every 60 min for 480 min postprandially. We demonstrate the highly dynamic, wide-ranging molecular environment of the ileum over time, with a substantial decrease in ileum bacterial numbers and bacterial metabolites after food intake. We also show that high-fiber diets, independent of food structure, increased PYY release compared with a low-fiber diet during 0 to 240 min postprandially. High-fiber diets also increased ileal stachyose, and a disrupted high-fiber diet increased certain ileal amino acids. Treatment of human ileal organoids with ileal fluids or an amino acid and stachyose mixture stimulated PYY expression in a similar profile to blood PYY concentrations, confirming the role of ileal metabolites in PYY release. Our study demonstrates the diet-induced changes over time in the metabolite environment of intact human ileum, which play a role in PYY release.

Introduction: Cancer and its associated side effects can cause changes in dietary intakes of people with cancer due to a variety of nutrition impact symptoms. These symptoms can lead to suboptimal dietary intakes which negatively affect muscle mass and therefore survivorship. The aim of this qualitative study was to assess the nutrition needs and dietary changes made by cancer patients in Ireland., Methods: Online focus groups were completed with cancer patients and caregivers, and demographic information was collected via an online questionnaire. An inductive thematic analysis approach was utilised to derive themes and subthemes from the data., Results: Four online focus groups were held with cancer patients and caregivers (n = 15) which reflected 18 total cancer experiences. Novel themes identified from this research included that symptoms were varied and transient-coming and going rapidly-and that patients were not satisfied with dietetic and broader nutrition services provided by hospitals. Themes that aligned with previous research were the severity and variety of nutrition impact symptoms and the variety of both evidence-based and non-evidence-based nutrition strategies used by patients to overcome nutrition impact symptoms, as general coping strategies, and potentially due to the belief that nutrition can be curative., Conclusion: Treatment of nutrition impact symptoms must be rapid and responsive. The development of responsive self-management resources such as booklets and apps for patients is likely to be valuable to ensure that patients can access support for their nutrition impact symptoms as-and when-they occur. Nutrition support must be integrated across the multi-disciplinary team to optimise trust in nutrition strategies., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objective: Loneliness, when prolonged, is associated with many deleterious effects and has been shown to be highly prevalent in those with a history of stroke, yet the cognitive mechanisms underpinning this phenomenon remain unclear. Therefore, the current study aims to investigate the extent to which cognitive factors, with specific focus on processing speed, are associated with loneliness in those with a history of stroke., Method: Utilizing data from the British Cohort Study, a nationally representative dataset, we conducted secondary data analysis. A total of 7,752 participants completed relevant questions related to health, social interactions, demographics, loneliness, and cognitive assessments. Among them, 47 had experienced a stroke ("stroke," n = 47), 5,545 reported other health conditions ("ill," n = 5,545), and 2,857 were deemed healthy ("healthy," n = 2,857)., Results: Consistent with previous research, our findings confirmed a positive correlation between stroke history and heightened loneliness. However, inferential analysis revealed that processing speed, alongside other cognitive factors, had a minimal impact on loneliness, with correlations too small to draw definitive conclusions., Conclusion: This study suggests that cognitive processing speed alone is not a robust predictor of loneliness in stroke survivors. Consequently, when developing interventions to combat loneliness in this population, it is crucial to consider a broader spectrum of factors, such as social engagement, emotional wellbeing, and interpersonal relationships. This underscores the imperative need for comprehensive assessments to better comprehend the multifaceted nature of loneliness and inform more effective intervention strategies., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of 177 Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of 177 Lu-DOTATATE therapy in patients with progressive NETs. Methods: This was a retrospective chart review of adults with advanced NETs. The patients had undergone initial treatment with up to 4 cycles of 177 Lu-DOTATATE and, after disease progression and a period of at least 6 mo since the end of the initial treatment, were retreated with at least 1 additional cycle at a single center (2010-2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using criteria from Common Terminology Criteria for Adverse Events, version 5.0. Kaplan-Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177 Lu-DOTATATE retreatment, 61% were male and 94% were White. Overall, patients received a median of 6 cycles (4 initial cycles and 2 retreatment cycles), and the mean administered activity was 41.9 GBq. Two patients also went on to receive additional retreatment (1 and 2 cycles, individually) after a second period of at least 6 mo and progression after retreatment. Best responses of partial response and stable disease were observed in 35% and 65% of patients after the initial treatment and 23% and 45% of patients after retreatment, respectively. The median PFS after the initial treatment was 20.2 mo and after retreatment was 9.6 mo. The median OS after the initial treatment was 42.6 mo and after retreatment was 12.6 mo. Hematologic parameters decreased significantly during both the initial treatment and retreatment but recovered such that there was little difference between the values before the initial treatment and before the retreatment. Clinically significant hematotoxicity occurred in 1 and 3 patients after the initial treatment and retreatment, respectively. No grade 3 or 4 nephrotoxicity was observed. Conclusion: Retreatment with 177 Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial 177 Lu-DOTATATE treatment., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Chronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neuropsychological impairment, it is important to characterize the frequency and predictors of this post-infection phenotype., Methods: The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal study assessing the impact of SARS-CoV-2 infection in U.S. Military Healthcare System (MHS) beneficiaries, i.e. those eligible for care in the MHS including active duty servicemembers, dependents, and retirees. Four broad areas of neuropsychological symptoms were assessed cross-sectionally among subjects 1-6 months post-infection/enrollment, including: depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), fatigue (PROMIS® Fatigue 7a), and cognitive function (PROMIS® Cognitive Function 8a and PROMIS® Cognitive Function abilities 8a). Multivariable Poisson regression models compared participants with and without SARS-CoV-2 infection history on these measures, adjusting for sex, ethnicity, active-duty status, age, and months post-first positive or enrollment of questionnaire completion (MPFP/E); models for fatigue and cognitive function were also adjusted for depression and anxiety scores., Results: The study population included 2383 participants who completed all five instruments within six MPFP/E, of whom 687 (28.8%) had at least one positive SARS-CoV-2 test. Compared to those who had never tested positive for SARS-CoV-2, the positive group was more likely to meet instrument-based criteria for depression (15.4% vs 10.3%, p<0.001), fatigue (20.1% vs 8.0%, p<0.001), impaired cognitive function (15.7% vs 8.6%, p<0.001), and impaired cognitive function abilities (24.3% vs 16.3%, p<0.001). In multivariable models, SARS-CoV-2 positive participants, assessed at an average of 2.7 months after infection, had increased risk of moderate to severe depression (RR: 1.44, 95% CI 1.12-1.84), fatigue (RR: 2.07, 95% CI 1.62-2.65), impaired cognitive function (RR: 1.64, 95% CI 1.27-2.11), and impaired cognitive function abilities (RR: 1.41, 95% CI 1.15-1.71); MPFP/E was not significant., Conclusions: Participants with a history of SARS-CoV-2 infection were up to twice as likely to report cognitive impairment and fatigue as the group without prior SARS-CoV-2 infection. These findings underscore the continued importance of preventing SARS-CoV-2 infection and while time since infection/enrollment was not significant through 6 months of follow-up, this highlights the need for additional research into the long-term impacts of COVID-19 to mitigate and reverse these neuropsychological outcomes., Competing Interests: Potential conflicts of interest. S. D. P., T. H. B., J.S.R., and M.P.S. report that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and the Henry M. Jackson Foundation (HJF) were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both of these trials were part of the US Government COVID-19 response. Neither is related to the work presented here. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Aims: It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS)., Methods and Results: Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%)., Conclusion: Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements., Competing Interests: Conflict of interest: M.P. discloses the following relationships—advisory board: AstraZeneca, Janssen-Cilag, and Novo Nordisk; grant support: Danish Cardiovascular Academy funded by the Novo Nordisk Foundation and the Danish Heart Foundation (grant number CPD5Y-2022004-HF); and speaker honorarium: AstraZeneca, Bayer, Boehringer Ingelheim, and Janssen-Cilag. M.V. has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Relypsa, and Roche Diagnostics; speaker engagements with Novartis and Roche Diagnostics; and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis. C.B. discloses the following relationships—speaker honorarium: Bayer. T.B.-S. discloses the following relationships—steering committee member of the Amgen-financed GALACTIC-HF trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘NUDGE-FLU’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-1’ trial, chief investigator and steering committee chair of the Sanofi Pasteur–financed ‘DANFLU-2’ trial, and steering committee member of ‘LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific’s Investigational ICM System’ trial; advisory board: Sanofi Pasteur, Amgen, and GSK; speaker honorarium: Novartis, Sanofi Pasteur, and GSK; and research grants: GE Healthcare and Sanofi Pasteur. M.M. is supported by a grant from the Novo Nordisk Foundation (grant number NNFOC0074083) and has received lecture and advisory board fees from Novo Nordisk. C.P.M. is supported by a grant from the National Institutes of Health (K23HL167659) and has received consulting fees/honorarium from Roche Diagnostics and Abbott Laboratories. L.K. discloses the following relationships—speaker honorarium from Novo Nordisk, Novartis, AstraZeneca, Boehringer, and Bayer. N.T.O. discloses the following relationships—research funding: Abbott and Shockwave. D.L.B. discloses the following relationships—advisory board: Angiowave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures and Hims; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT Trial); honoraria: American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and US national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site co-investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo and Takeda. The other authors report no relevant disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The term athlete does not currently have an agreed definition or standardized use across the literature. We analyzed the use of the term "athlete" amongst review studies specific to Anterior Cruciate Ligament (ACL) rehabilitation to investigate if the term was justified in its use. A comprehensive review of a database was performed to identify review papers which used the term "athlete" in the title, and which were related to ACL rehabilitation and surveillance. These papers were analyzed and their source papers were extracted for review. Twenty-eight review papers were identified. Source studies were extracted and analyzed. After removal of duplicates 223 source papers were identified. Despite using the term "athlete" in the review study titles only 5/17 (10.7%) sufficiently justified the use of this term. The term athlete was used in 117/223 (52.5%) of the source studies. Of those, 78/117 source studies (66.7%) justified the term athlete. The remaining 39/117 (33.3%) papers where participants were stated to be athletes, gave no justification. The ambiguous use of the term athlete amongst published studies highlights the need for a definition or justification of the term to be used in studies. The lack of a standard definition leads to the potential for studies to dilute high quality data by the potentially differing rehabilitation requirements and access to resources available to those with varying exercise levels. The indiscriminate use of the term athlete could lead to participants with widely ranging physical activity levels being included in the same study, and being used to create clinical advice for all. Advice could potentially vary across those of differing physical activity levels., (© 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Background: Most studies evaluating robotic-assisted total knee arthroplasty (RA TKA) analyzed the advantages offered to high-volume surgeons. This study aims to determine if RA TKA improves radiographic or clinical outcomes for low-volume, non-arthroplasty-trained surgeons., Methods: Radiographic and early clinical outcomes of 19 RA TKAs and 41 conventional TKAs, all performed by a single, non-arthroplasty-trained orthopaedic surgeon, were compared. Radiographic outliers were based on surgeon targets and defined as tibial posterior slope outside of 0°-5°, tibial tray varus outside of 0°-3°, and the presence of notching. Clinical outcomes included inpatient narcotic usage, length of stay, range of motion, and Patient-Reported Outcome Measurement Information System scores., Results: There was a significant decrease in tibial slope outliers (RA TKA 0% vs non-RA TKA 22%, P  = .024) and notching incidence (RA TKA 0% vs non-RA TKA 19.5%, P  = .044) in the RA group. Tibial tray varus/valgus outliers trended lower in the RA TKA group (10.0% vs 26.8%, P  = .189). Length of stay was significantly shorter in RA patients (48.0 hours [standard deviation: 25.5] vs 67.7 hours [34.3], P  = .038). RA patients trended toward lower in postoperative inpatient total mean morphine equivalents usage (79.9 [89.2] vs 140.1 [169.3], P  = .142) and inpatient mean morphine equivalents usage per day (30.36 [26.9] vs 45.6 [36.7], P  = .105). There was no significant difference in Patient-Reported Outcome Measurement Information System scores or range of motion at first and second postoperative follow-up within 3 months., Conclusions: RA TKA reduced the incidence of radiographic outliers when compared to conventional TKA for a low-volume arthroplasty surgeon., (© 2023 The Authors.)

Background: Current diabetic ketoacidosis (DKA) treatment guidelines recommend using normal saline (NS); however, NS may delay DKA resolution by causing more hyperchloremic metabolic acidosis compared with balanced crystalloids. This study's objective was to determine the feasibility of a future multicentred randomised controlled trial (RCT) comparing intravenous Ringer's lactate (RL) with NS in managing ED patients with DKA., Methods: We conducted a parallel-arm, triple-blind, pilot RCT of adults (≥18 years) with DKA at a Canadian academic tertiary care ED. The primary feasibility outcome was recruitment rate (target ≥41.3% of eligible participants over the 1-year study period); the primary efficacy outcome was time elapsed from ED presentation to DKA resolution. The superiority margin for a clinically significant difference was chosen to be a 40% time reduction to DKA resolution. We also assessed the need to break allocation concealment and loss to follow-up. Patients with clinical suspicion for DKA were screened for inclusion and enrolled patients were randomised 1:1 to receive RL or NS. Patients, clinicians and outcome assessors were blinded to allocation., Results: We enrolled 52 (25 RL, 27 NS) of 60 eligible patients (86.7%), exceeding our target recruitment rate. There were more patients in the NS group with type 1 diabetes, and more patients in the RL group had an admission co-diagnosis in addition to DKA. For the 44 participants with confirmed laboratory evidence of resolution, median (IQR) time to DKA resolution for RL versus NS was 15.7 (10.4-18.8) and 12.7 (7.9-19.2) hours, respectively. There were no cases where blinding was broken, and there was no loss to follow-up., Conclusions: This pilot trial demonstrated our protocol's feasibility by exceeding our target recruitment rate. Our results may be used to inform future multicentre trials to compare the safety and efficacy of RL and NS in managing DKA in the ED., Trial Registration Number: NCT04926740., Competing Interests: Competing interests: Outside of this study, KKC has received a research award sponsored in part by AstraZeneca. She has attended conferences sponsored by Merck. She has received honoraria for delivering certified medical education from Sutherland Global Services Canada ULC, the Canadian Medical and Surgical Knowledge Translation Group and the CPD Network. There are no other conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The sophistication and accessibility of modern-day imaging result in frequent detection of small or equivocal lesions of the testes. Traditionally, diagnosis of a testicular lesion with any possibility of malignancy would usually prompt radical orchidectomy. However, awareness is growing that a substantial proportion of these lesions might be benign and that universal application of radical orchidectomy risks frequent overtreatment. Given the potentially profound effects of radical orchidectomy on fertility, endocrine function and psychosexual well-being, particularly in scenarios of an abnormal contralateral testis or bilateral lesions, organ-preserving strategies for equivocal lesions should be considered. Image-based active surveillance can be applied for indeterminate lesions measuring ≤15 mm with a low conversion rate to surgical treatment. However, these outcomes are early and from relatively small, selected cohorts, and concerns prevail regarding the metastatic potential of even small undiagnosed germ cell tumours. No consensus exists on optimal surveillance (short interval (<3 months) ultrasonography is generally adopted); histological sampling is a widespread alternative, involving inguinal delivery of the testis and excisional biopsy of the lesion, with preoperative marking or intraoperative ultrasonographic localization when necessary. Frozen section analysis in this context demonstrates excellent diagnostic accuracy. Histological results support that approximately two-thirds of marker-negative indeterminate solitary testicular lesions measuring ≤25 mm overall are benign. In summary, modern imaging detects many small indeterminate testicular lesions, of which the majority are benign. Awareness is growing of surveillance and organ-sparing diagnostic and treatment strategies with the aim of minimizing rates of overtreatment with radical orchidectomy., (© 2023. Springer Nature Limited.)

Effective therapies for obesity require invasive surgical and endoscopic interventions or high patient adherence, making it challenging for patients with obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. We designed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill, an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release and yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (~40%, P < 0.0001) and minimized the weight gain rate ( P < 0.05) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.

A woman in her 40s presented to the emergency department with epistaxis. Anterior nasal packing was unsuccessful in achieving haemostasis. After the exchange of devices and insertion of a posterior nasal pack, the patient developed a junctional rhythm and progressively unstable bradycardia. The rhythm and bradycardia immediately improved following the removal of the posterior nasal pack. This case describes a rare occurrence of Trigeminocardiac reflex (TCR), following an insertion of a posterior nasal pack. Only one other such case has been reported and published. This case highlights the importance of raising awareness of this rare reflex and the need for prompt removal of the triggering cause in such scenarios. TCR can induce a junctional rhythm, which progresses to unstable bradycardia and may lead to asystole in susceptible individuals. The removal of the stimulus resolves the reflex and can result in prompt resolution of the bradycardia and hypotension induced via the TCR., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aimed to assess the feasibility of estimating the pulmonary blood volume noninvasively using standard Rubidium-82 myocardial perfusion imaging (MPI) and characterize the changes during adenosine-induced hyperemia., Methods: This study comprised 33 healthy volunteers (15 female, median age = 23 years), of which 25 underwent serial rest/adenosine stress Rubidium-82 MPI sessions. Mean bolus transit times (MBTT) were obtained by calculating the time delay from the Rubidium-82 bolus arrival in the pulmonary trunk to the arrival in the left myocardial atrium. Using the MBTT, in combination with stroke volume (SV) and heart rate (HR), we estimated pulmonary blood volume (PBV = (SV × HR) × MBTT). We report the empirically measured MBTT, HR, SV, and PBV, all stratified by sex [male (M) vs female (F)] as mean (SD). In addition, we report grouped repeatability measures using the within-subject repeatability coefficient., Results: Mean bolus transit times was shortened during adenosine stressing with sex-specific differences [(seconds); Rest: Female (F) = 12.4 (1.5), Male (M) = 14.8 (2.8); stress: F = 8.8 (1.7), M = 11.2 (3.0), all P ≤ 0.01]. HR and SV increased during stress MPI, with a concomitant increase in the PBV [mL]; Rest: F = 544 (98), M = 926 (105); Stress: F = 914 (182), M = 1458 (338), all P < 0.001. The following test-retest repeatability measures were observed for MBTT (Rest = 17.2%, Stress = 17.9%), HR (Rest = 9.1%, Stress = 7.5%), SV (Rest = 8.9%, Stress = 5.6%), and for PBV measures (Rest = 20.7%, Stress = 19.5%) CONCLUSION: Pulmonary blood volume can be extracted by cardiac rubidium-82 MPI with excellent test-retest reliability, both at rest and during adenosine-induced hyperemia., (© 2023. The Author(s).)

Background: Performing an episiotomy where clinically indicated is a key intervention in the Obstetric Anal Sphincter Injury Care Bundle (OASI-CB) implemented across England and Wales to reduce the risk and increase the detection of severe perineal trauma after birth. Standards of consent provided to people in maternity care generally and for episiotomy specifically have been reported as suboptimal. Compromising birthing people's personal autonomy or sense of control has been linked to a dissatisfying birth experience, negative psychological sequelae, and litigation., Methods: This study explored experienced midwives' practice of informed consent for episiotomy during a midwife-led birth. We sampled 43 midwives across eight NHS Trusts in England and Wales using online focus groups and telephone interviews about their experience of consent in episiotomy. Using qualitative content analysis and art-based co-analysis methods with eight midwives from across the research sites, we co-analyzed and co-constructed three themes and four practice recommendations from the data., Results: Three themes were constructed from the data: Assent rather than consent, Change in culture to support best practice, and Standardized information. These themes informed the shaping of four recommendations for best practice in episiotomy informed consent., Conclusion: This study has shown how variations in midwifery practice and culture may impact birthing people's experience of informed consent in episiotomy. Midwives may not have the knowledge or skills to conduct a detailed consent conversation, leading to variation in practice and messages for birthing people. The use of antenatal discussion aids can offer women the opportunity to become informed and fully participate in the decision-making process., (© 2023 The Authors. Birth published by Wiley Periodicals LLC.)

Aim: To evaluate the feasibility of retrospectively detecting and correcting periodical (cardiac and respiratory motion) and non-periodical shifts of the myocardial position (myocardial creep) using only the acquired Rubidium-82 positron emission tomography raw (listmode) data., Methods: This study comprised 25 healthy participants (median age = 23 years) who underwent repeat rest/adenosine stress Rubidium-82 myocardial perfusion imaging (MPI) and 53 patients (median age = 64 years) considered for revascularization who underwent a single MPI session. All subjects were evaluated for myocardial creep during MPI by assessing the myocardial position every 200 ms. A proposed motion correction protocol, including corrections for cardiorespiratory and creep motion (3xMC), was compared to a guideline-recommended protocol (Standard Recon ). For the volunteers, we report test-retest repeatability using standard error of measurements (SEM). For the patient cohort, we evaluated the area under the receiver operating curve (AUC) for both stress and ischemic total perfusion deficits (sTPD and iTPD, respectively) using myocardial ischemia defined as fractional flow reserve values < 0.8 in the relevant coronary segment as the gold standard., Results: Test-retest repeatability was significantly improved following corrections for myocardial creep (SEM; sTPD: Standard Recon  = 2.2, 3xMC = 1.8; iTPD: Standard Recon  = 1.6, 3xMC = 1.2). AUC analysis of the ROC curves revealed significant improvements for iTPD measurements following 3xMC [sTPD: Standard Recon  = 0.88, 3xMC = 0.92 (P = .21); iTPD: Standard Recon  = 0.88, 3xMC = 0.95 (P = .039)]., Conclusion: 3xMC has the potential to improve the diagnostic accuracy of myocardial MPI obtained from positron emission tomography. Therefore, its use should be considered both in clinical routine and large-scale multicenter studies., (© 2023. The Author(s).)

Objective: Anterior cruciate ligament (ACL) tears are exceedingly common among the athletic population and are seen with higher incidence in females. Observational studies have noted peak ACL tear rates in the luteal phase of the menstrual cycle, a time in which the hormone relaxin peaks in serum concentration., Methods: A systematic review of the literature was performed. Inclusion criteria specified all prospective and retrospective studies which included the role of relaxin in the pathogenesis of ACL tears., Results: Six studies met inclusion criteria yielding 189 subjects from clinical studies and 51 in vitro samples. Included studies found that ACL samples exhibit selective relaxin binding. When pre-treated with estrogen prior to relaxin exposure, female ACL tissue samples exhibit increased expression of collagen degrading receptors., Conclusion: Relaxin displays binding specificity to the female ACL and increased serum concentrations are correlated with increased ACL tear rates in female athletes. Further research is needed in this area., Level of Evidence: V., (© 2023. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Previous studies have reported elevated von Willebrand factor (VWF) levels in patients with sickle cell disease (SCD) and demonstrated a key role for the VWF-ADAMTS13 axis in the pathobiology of SCD vaso-occlusion. Although blood transfusion is the gold standard for stroke prevention in SCD, the biological mechanisms underpinning its improved efficacy compared with hydroxycarbamide are not fully understood. We hypothesized that the improved efficacy of blood transfusion might relate to differences in VWF-ADAMTS13 axis dysfunction. In total, 180 children with a confirmed diagnosis of SCD (hemoglobin SS) on hydroxycarbamide (n = 96) or blood transfusion (n = 84) were included. Despite disease-modifying treatment, plasma VWF and VWF propeptide were elevated in a significant proportion of children with SCD (33% and 47%, respectively). Crucially, all VWF parameters were significantly higher in the hydroxycarbamide compared with the blood transfusion cohort (P < .05). Additionally, increased levels of other Weibel-Palade body-stored proteins, including factor VIII (FVIII), angiopoietin-2, and osteoprotegerin were observed, indicated ongoing endothelial cell activation. Children treated with hydroxycarbamide also had higher FVIII activity and enhanced thrombin generation compared with those in the blood transfusion cohort (P < .001). Finally, hemolysis markers strongly correlated with VWF levels (P < .001) and were significantly reduced in the blood transfusion cohort (P < .001). Cumulatively, to our knowledge, our findings demonstrate for the first time that despite treatment, ongoing dysfunction of the VWF-ADAMTS13 axis is present in a significant subgroup of pediatric patients with SCD, especially those treated with hydroxycarbamide., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: The long-term effects of coronavirus disease 2019 (COVID-19) on physical fitness are unclear, and the impact of vaccination on that relationship is uncertain., Methods: We compared survey responses in a 1-year study of US military service members with (n = 1923) and without (n = 1591) a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We fit Poisson regression models to estimate the association between history of SARS-CoV-2 infection and fitness impairment, adjusting for time since infection, demographics, and baseline health., Results: The participants in this analysis were primarily young adults aged 18-39 years (75%), and 71.5% were male. Participants with a history of SARS-CoV-2 infection were more likely to report difficulty exercising (38.7% vs 18.4%; P < .01), difficulty performing daily activities (30.4% vs 12.7%; P < .01), and decreased fitness test (FT) scores (42.7% vs 26.2%; P < .01) than those without a history of infection. SARS-CoV-2-infected participants were at higher risk of these outcomes after adjusting for other factors (unvaccinated: exercising: adjusted risk ratio [aRR], 3.99; 95% CI, 3.36-4.73; activities: aRR, 5.02; 95% CI, 4.09-6.16; FT affected: aRR, 2.55; 95% CI, 2.19-2.98). Among SARS-CoV-2-positive participants, full vaccination before infection was associated with a lower risk of post-COVID-19 fitness impairment (fully vaccinated: exercise: aRR, 0.81; 95% CI, 0.70-0.95; activities: aRR, 0.76; 95% CI, 0.64-0.91; FT: aRR, 0.87; 95% CI, 0.76-1.00; boosted: exercise: aRR, 0.62; 95% CI, 0.51-0.74; activities: aRR, 0.52; 95% CI, 0.41-0.65; FT: aRR, 0.59; 95% CI, 0.49-0.70)., Conclusions: In this study of generally young, healthy military service members, SARS-CoV-2 infection was associated with lower self-reported fitness and exercise capacity; vaccination and boosting were associated with lower risk of self-reported fitness loss., Competing Interests: Potential conflicts of interest. 1045 S.D.P., T.H.B., J.S.R., and M.P.S. report that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and the HJF were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both trials were part of the US Government COVID-19 response. Neither is related to the work presented here. R.C.M. receives research support paid to his institution from Sound Pharmaceuticals for an investigational COVID-19 therapeutic unrelated to the work presented here. M.J.M. is a paid speaker for Xarelto (Janssen Pharmaceuticals). All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective., Objectives: The objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers., Design and Methods: This study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked primary-secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals., Result: Systematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing ( p < 0.01); the CPRD-HES data set indicated that 70% did not achieve target treatment levels, and demonstrated increased cardiovascular disease risk among these individuals, compared with controls (hazard ratio 9.14, 95% CI 8.55 to 9.76). The specialist familial hypercholesterolaemia register confirmed excessive cardiovascular morbidity (standardised morbidity ratio 7.17, 95% CI 6.79 to 7.56). Cost-effectiveness modelling found a net health gain from diagnosis of -0.27 to 2.51 quality-adjusted life-years at the willingness-to-pay threshold of £15,000 per quality-adjusted life-year gained. The cost-effective protocols cascaded from genetically confirmed index cases by contacting first- and second-degree relatives simultaneously and directly. Interviews found a service-led direct-contact approach was more reliable, but combining direct and indirect approaches, guided by index patients and family relationships, may be more acceptable., Limitations: Systematic reviews were not used in the economic analysis, as relevant studies were lacking or of poor quality. As only a proportion of those with primary care-coded familial hypercholesterolaemia are likely to actually have familial hypercholesterolaemia, CPRD analyses are likely to underestimate the true effect. The cost-effectiveness analysis required assumptions related to the long-term cardiovascular disease risk, the effect of treatment on cholesterol and the generalisability of estimates from the data sets. Interview recruitment was limited to white English-speaking participants., Conclusions: Based on limited evidence, most cost-effective cascade-testing protocols, diagnosing most relatives, select index cases by genetic testing, with services directly contacting relatives, and contacting second-degree relatives even if first-degree relatives have not been tested. Combined approaches to contact relatives may be more suitable for some families., Future Work: Establish a long-term familial hypercholesterolaemia cohort, measuring cholesterol levels, treatment and cardiovascular outcomes. Conduct a randomised study comparing different approaches to contact relatives., Study Registration: This study is registered as PROSPERO CRD42018117445 and CRD42019125775., Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 27, No. 16. See the NIHR Journals Library website for further project information.

Background: Increasing numbers of older patients are presenting to the ED following trauma. These patients require multidisciplinary care that the traditional trauma model fails to provide. A Silver Trauma Review Clinic (STRC) was developed in conjunction with the geriatric ED and multidisciplinary services to improve the post-discharge care of patients with non-operative traumatic injuries.We aimed to assess the STRC by reviewing the journey and outcomes of patients who attended the clinic., Methods: A retrospective review of electronic chart data was performed on all patients who attended the clinic over the initial 1-year period. Data were collected on patient demographics, medical history, medications, timelines, trauma assessments and further investigations, fracture types, occult injuries, geriatric assessments (Comprehensive Geriatric Assessment, Clinical Frailty Scale, bone health, falls, Orthostatic Hypotension (OH), cognitive screening, mobility), number of reviews and discharge destination., Results: 137 patients were reviewed with a median age of 80 years (IQR 74-86) and 69% were female. The median Clinical Frailty Scale was 3 with a median time from the patient's initial ED presentation to clinic of 15 days (IQR 9.75-21) and median time from initial review to discharge 20 days (IQR 1-35). 71% of presentations were as a result of falls under 2 m. Tertiary survey in the STRC identified previously unrecognised injuries in 24 patients (18%). In total, 56 patients were reviewed with vertebral fractures. 87% of these patients (n=49) were further investigated with a CT or MRI and 95% of patients (n=53) were referred for physiotherapy. Patients attending the STRC had a comprehensive geriatric assessment with abnormal Mini-Cog assessments found in 29%, a new diagnosis of osteoporosis in 43% and orthostatic hypotension diagnosed in 13% of patients. 61% were discharged to primary care and 19% linked into a specialist geriatric clinic., Conclusion: The STRC is a novel approach allowing timely, patient-focused, comprehensive and collaborative trauma care of older patients following non-operative injuries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Attention-Deficit / Hyperactivity Disorder (ADHD) is prevalent at a higher rate in correctional settings than in the general population. Treatment of ADHD in this environment is challenging as stimulants, the most common treatment for ADHD, require cautious prescribing in the context of frequent substance use disorders (SUD) and diversion in the institutional setting. In addition, both pharmacological and non-pharmacological treatment approaches require significant staff resources. The aim of this scoping review is to map and summarize all literature addressing treatment of ADHD specifically in correctional settings, synthesize the evidence supporting various approaches, and highlight areas for future research. Due to the limited number of primary research studies addressing this question directly, we chose a scoping review methodology that would allow us to explore what kinds of studies and literature exist and include all types of articles directly related to our question., Results: Five-hundred sixty-five relevant articles were screened. Thirty-two articles were included in the final review. Eleven of the articles reported primary research. Five of these articles were based on three randomized controlled trials. Among randomized controlled trials on the effect of stimulants, inclusion criteria, outcome measures and effectiveness varied widely. Non-male and non-white populations were under-represented. Among review articles and recommendations opinion was inconsistent, with some recommending stimulants as first-line treatment and others recommending they be avoided altogether. The effect of non-stimulant medications was examined in 2 small studies. The only non-pharmacological treatment examined was dialectical behavior therapy, and only feasibility was reported. Four articles provided practice recommendations from consensus or expert opinion. Two of these recommended stimulants as first-line treatment, and two recommended stimulants as treatment of last resort., Conclusions: We found a diverse but shallow literature addressing our research question. Primary research in the corrections setting is limited and varies in inclusion criteria, outcomes studied, and effectiveness. Recommendations on treatment are inconsistent. Future research should address methods of diagnosis, the role of non-stimulants, non-pharmacological interventions, non-male and non-white people who are incarcerated (PWAI), and effects of treatment method on patients, staff and other PWAI. Better research and guidance on treating ADHD has potential to improve health of PWAI, the institutional environment, and resource utilization., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Heteroatom doping of graphene is a promising approach for tailoring its chemical and electronic properties-a prerequisite for many applications such as sensing, catalysis, and energy storage. Doping chemical vapour deposition (CVD) graphene with nitrogen during growth ( in situ doping) is a common strategy, but it produces a distribution of inequivalent dopant sites and requires substantial modifications to the CVD growth process. In this study, we demonstrate a novel and simple oxide-mediated approach to introduce nitrogen dopants into pre-existing CVD graphene ( ex situ doping) which achieves comparable doping densities to in situ doping methodologies. Furthermore, we demonstrate that thermal annealing of N-doped graphene can selectively remove pyridinic, retaining graphitic and pyrrolic nitrogen dopants, offering an attractive route to further modify graphene functionality. The methodologies we present are simple and scalable to precisely tailor graphene properties without the need to alter CVD growth protocols., (Creative Commons Attribution license.)

Background: Breathing pattern disorders (BPDs) and inducible laryngeal obstruction (ILO) cause similar symptoms to asthma, including dyspnea and chest tightness, with an estimated prevalence of up to one-fifth of patients with asthma. Both conditions can be comorbid with asthma, and there is evidence that they are misdiagnosed and mistreated as asthma., Objective: This study aims to explore whether the symptoms of ILO and BPD were topics of discussion in a UK asthma online health community and patient experiences of diagnosis and treatment, in particular their use of reliever inhalers., Methods: A qualitative thematic analysis was performed with posts from an asthma community between 2018 and 2022. A list of key ILO or BPD symptoms was created from the literature. Posts were identified using the search terms "blue inhaler" and "breath" and included if describing key symptoms. Discussion threads of included posts were also analyzed., Results: The search retrieved a total of 1127 relevant posts: 1069 written by 302 users and 58 posted anonymously. All participants were adults, except 2 who were parents writing about their children. Sex and age were only available for 1.66% (5/302; 3 females and 2 males) and 9.93% (30/302) of participants (27 to 73 years old), respectively. The average number of posts written by each participant was 3.54 (range 1-63). Seven participants wrote >20 posts each. Participants experiencing undiagnosed ILO or BPD symptoms, whether or not comorbid with asthma, expressed frustration with the "one-size-fits-all" approach to diagnosis, as many felt that their asthma diagnosis did not fully explain symptoms. Some suspected or were formally diagnosed with BPD or ILO, the latter reporting relief on receiving a diagnosis and appropriate management. Participants showed awareness of their inappropriate salbutamol use or overuse due to lack of effect on symptoms. BPD and ILO symptoms were frequently comorbid with asthma. The asthma online community was a valuable resource: engagement with peers not only brought comfort but also prompted action with some going back to their clinicians and reaching a diagnosis and appropriate management., Conclusions: Undiagnosed ILO and BPD symptoms and lack of effects of asthma treatment were topics of discussion in an asthma online community, caused distress and frustration in participants, and affected their relationship with health care professionals, showing that patients experiencing BPD and ILO have unmet needs. Clinicians' education on BPD and ILO diagnosis and management, as well as increased access to appropriate management options, such as respiratory physiotherapy and speech and language therapy, are warranted particularly in primary care. Qualitative evidence that engagement with the online community resulted in patients taking action going back to their clinicians and reaching a diagnosis of ILO and BPD prompts future research on online peer support from an established online health community as a self-management resource for patients., (©Catrin Byrne, Paul E Pfeffer, Anna De Simoni. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 14.08.2023.)

Bottom-up production of semiconductor nanomaterials is often accompanied by inhomogeneity resulting in a spread in electronic properties which may be influenced by the nanoparticle geometry, crystal quality, stoichiometry, or doping. Using photoluminescence spectroscopy of a population of more than 11 000 individual zinc-doped gallium arsenide nanowires, inhomogeneity is revealed in, and correlation between doping and nanowire diameter by use of a Bayesian statistical approach. Recombination of hot-carriers is shown to be responsible for the photoluminescence lineshape; by exploiting lifetime variation across the population, hot-carrier dynamics is revealed at the sub-picosecond timescale showing interband electronic dynamics. High-throughput spectroscopy together with a Bayesian approach are shown to provide unique insight in an inhomogeneous nanomaterial population, and can reveal electronic dynamics otherwise requiring complex pump-probe experiments in highly non-equilibrium conditions., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Background: Current imaging guidelines recommend using at least 16 ECG gates when performing MUGA and cardiac SPECT to assess left ventricular ejection fraction (LVEF). However, for Rubidium-82 ( 82 Rb) PET, 8 ECG-gated reconstructions have been a mainstay. This study investigated the implications of quantitative assessments when employing 16 gate, instead of 8 gate, reconstructions for 82 Rb myocardial perfusion imaging (MPI)., Methods: The study comprised 25 healthy volunteers (median age 23 years) who underwent repeat MPI sessions employing 82 Rb PET/CT. We report LVEF, its reserve (stress LVEF - rest LVEF), and their repeatability measures (RMS method) obtained for 8- and 16 ECG-gated reconstructions., Results: Similar LVEF and LVEF reserve estimates were found for the 8- and 16-gated reconstructions ([%] LVEF (8/16 gates): rest = 61 ± 6/64 ± 6, stress = 68 ± 7/71 ± 6, LVEF reserve (8/16 gates): 8 ± 3/6 ± 4, and all P ≥ 0.13). Similar test-retest repeatability measures were observed for rest and stress LVEF and their reserves [LVEF (8/16 gates); Rest = 4.5/4.6 (P = 0.81), Stress = 3.5/3.2 (P = 0.33), LVEF reserve = 46.7/49.3 (P = 0.13)]., Conclusion: In healthy subjects, 8 and 16 ECG gates can be used interchangeably if only volumetric assessments are desired. However, if filling and emptying rates are of interest, a minimum of 16 ECG gates should be employed., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Current guidelines for diabetic ketoacidosis (DKA) recommend treatment with normal saline (NS). However, NS, with its high chloride concentrations, may worsen acidosis and contribute to a hyperchloremic metabolic acidosis. Alternatives to NS are balanced crystalloids (e.g. Ringer's Lactate [RL]) which have chloride concentrations similar to human plasma; therefore, treatment with balanced crystalloids may lead to faster DKA resolution. A recent systematic review and meta-analysis by Catahay et al. (2022) demonstrated the need for more blinded, high-quality trials comparing NS versus RL in the treatment of DKA., Methods: We describe a protocol for BRISK-ED (Balanced crystalloids [RInger's lactate] versus normal Saline in adults with diabetic Ketoacidosis in the Emergency Department). Our study is a single-centre, triple-blind, pilot randomized controlled trial (RCT) of adults (≥ 18 years) with DKA presenting to an academic tertiary care ED in London, Canada. Patients with clinical suspicion for DKA will be screened and those found to not meet DKA criteria or have euglycemic DKA will be excluded. We will aim to recruit 52 patients with DKA and will randomize them 1:1 to receive intravenous RL or NS. The primary feasibility outcome will be recruitment rate, and the primary efficacy outcome will be time elapsed from ED presentation to DKA resolution. Secondary outcomes include time to insulin infusion discontinuation, intensive care unit admission, in-hospital death, and major adverse kidney events within 30 days, defined as a composite of: i) death, ii) new renal replacement therapy, or iii) final serum creatinine ≥ 200% baseline at the earliest of hospital discharge or 30 days after ED presentation. Patients, clinicians, and outcome assessors will be blinded to allocation group. We will follow an intention-to-treat analysis. Gehan-Wilcoxon, Mann-Whitney U, or chi-square tests will be used to compare groups as appropriate., Discussion: The results of this pilot study will inform the design and feasibility of a full-scale, multicentre RCT to assess fluid choice in adult ED patients with DKA. If proven to demonstrate faster resolution of DKA, administration of balanced crystalloids may replace NS in diabetes treatment guidelines and improve patient and health systems outcomes., Trial Registration: ClinicalTrials.gov, Registration # NCT04926740; Registered June 15, 2021., (© 2023. The Author(s).)

Background: Per- and polyfluoroalkyl substances (PFAS) are a component of firefighting foams used at military installations. Although high PFAS exposures have been related to cancer risks among civilian populations, the effects for military personnel are unclear., Objectives: We investigated associations between serum PFAS concentrations and testicular germ cell tumors (TGCT) among U.S. Air Force servicemen., Methods: This nested case-control study involved active-duty Air Force servicemen with sera from the Department of Defense Serum Repository. We selected 530 cases and 530 controls individually matched on birth date, race and ethnicity, year entered the service, and year of sample collection, with prediagnostic serum samples collected between 1988 and 2017. A second prediagnostic sample, collected a median of 4 y after the first, was selected for 187 case-control pairs. Seven PFAS were quantified using isotope-dilution tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression adjusting for military grade, number of deployments, and, in some models, other PFAS, estimated associations between PFAS concentrations (categorized using quartiles among controls) and TGCT., Results: Elevated concentrations of some PFAS were observed for military employment in firefighting [perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid] and service at a base with high PFAS concentrations in drinking water (PFHxS). Elevated PFOS concentrations in the second sample were positively associated with TGCT [OR for fourth vs. first quartile ( OR Q 4 ) = 2.6 , 95% CI: 1.1, 6.4; p trend = 0.02 ], including after adjustment for other PFAS ( OR Q 4 = 4.6 , 95% CI: 1.4, 15.1; p trend = 0.009 ). Associations with PFOS in the first/only samples were weak and not statistically significant. Elevated concentrations of perfluorononanoic acid were inversely associated with TGCT, whereas results were null for other PFAS., Discussion: We identified service-related predictors of PFAS concentrations and increased TGCT relative risks with elevated PFOS concentrations among Air Force servicemen. These findings warrant further investigation in other populations and military service branches. https://doi.org/10.1289/EHP12603.

The addition of excess glucose to the diet drives a coordinated response of lipid metabolism pathways to tune the membrane composition to the altered diet. Here, we have employed targeted lipidomic approaches to quantify the specific changes in the phospholipid and sphingolipid populations that occur in elevated glucose conditions. The lipids within wild-type Caenorhabditis elegans are strikingly stable with no significant changes identified in our global mass spectrometry-based analysis. Previous work has identified ELO-5, an elongase that is critical for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs), as essential for surviving elevated glucose conditions. Therefore, we performed targeted lipidomics on elo-5 RNAi-fed animals and identified several significant changes in these animals in lipid species that contain mmBCFAs as well as in species that do not contain mmBCFAs. Of particular note, we identified a specific glucosylceramide (GlcCer 17:1;O2/22:0;O) that is also significantly upregulated with glucose in wild-type animals. Furthermore, compromising the production of the glucosylceramide pool with elo-3 or cgt-3 RNAi leads to premature death in glucose-fed animals. Taken together, our lipid analysis has expanded the mechanistic understanding of metabolic rewiring with glucose feeding and has identified a new role for the GlcCer 17:1;O2/22:0;O., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Testicular germ cell tumours (TGCTs) are the most commonly diagnosed malignancy among active duty US military servicemen. Occupational risk factors may play a role in TGCT aetiology, although the evidence is inconclusive. The objective of our study was to investigate associations between military occupations and TGCT risk among US Air Force (USAF) servicemen., Methods: This nested case-control study among active duty USAF servicemen obtained information on military occupations for 530 histologically confirmed TGCT cases diagnosed during 1990-2018 and 530 individually matched controls. We determined military occupations using Air Force Specialty Codes ascertained at two time points: at case diagnosis and at a time point on average 6 years earlier. We computed adjusted ORs and 95% CIs from conditional logistic regression models to evaluate associations between occupations and TGCT risk., Results: The mean age at TGCT diagnosis was 30 years. Increased TGCT risk was observed for pilots (OR=2.84, 95% CI: 1.20-6.74) and servicemen with aircraft maintenance jobs (OR=1.85, 95% CI: 1.03-3.31) who held those jobs at both time points. Fighter pilots (n=18) and servicemen with firefighting jobs (n=18) at the time of case diagnosis had suggestively elevated TGCT odds (OR=2.73, 95% CI: 0.96-7.72 and OR=1.94, 95% CI: 0.72-5.20, respectively)., Conclusions: In this matched, nested case-control study of young active duty USAF servicemen, we found that pilots and men with aircraft maintenance jobs had elevated TGCT risk. Further research is needed to elucidate specific occupational exposures underlying these associations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Upon entry-to-practice, graduate nurses must be able to effectively manage oncologic emergencies to ensure best patient and family outcomes. Thus, nurse educators must develop active teaching strategies to prepare prelicensure nursing students with appropriate nursing oncology knowledge and skills. The purposes of this study were to determine the effect of simulation-based experiences (SBEs) with standardized participants (SPs) involving a patient and family member on baccalaureate nursing students' confidence and competence, anxiety and self-confidence with clinical decision-making, and satisfaction and self-confidence in learning using SBEs related to management of oncologic emergencies within a seminar-style course. A longitudinal, one-group, convergent mixed-methods design was used. Baccalaureate nursing students enrolled in a senior seminar participated in two SBEs. Study data were collected pre-seminar, pre-SBE, and post-SBE. Twenty-five senior nursing students participated in this study. There was a significant increase in students' confidence and self-perceived competence, and a significant decrease in anxiety and increase in self-confidence with clinical decision-making related to the nursing management of oncologic emergencies over time. All seven student groups in the hypercalcemia SBE, and five student groups in the hypersensitivity reaction SBE demonstrated objective competence. Qualitative themes identified included: realism, critical thinking, and benefits for professional practice. Study findings support the use of SBEs with SPs to enhance nursing students' confidence and competence, and to increase self-confidence and reduce anxiety with clinical decision-making related to the management of oncologic emergencies in a seminar-style course. The inclusion of a family member enhanced the realism of complex SBEs., (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

The availability of high-quality semen from genetically elite bulls is essential to support continued genetic gain and the sustainability of cattle production worldwide. While reducing the age at which usable semen is available also reduces the generation interval, it is dependent on timely onset of puberty in young bulls. There is now good evidence that hastened sexual development in bulls is achieved through enhancing nutrition in early life. This review will cover the physiological and molecular-based response to prevailing diet in key organs that orchestrate the ontogeny of sexual development in the bull calf. Given the central importance of the interaction between metabolic status and neuronal function to the progression of sexual development, we will discuss how communication between metabolic organs, reproductive organs and the brain are mediated via molecular and physiological processes. The availability of high-throughput nucleic acid and protein sequencing technologies and innovative data analytics have allowed us to improve our understanding of molecular regulation of puberty and sexual development. Analysing data from a number of organs, simultaneously, allows for a better understanding of the underlying biology and biochemical interactions that are influencing sexual development. Specifically, we can determine how early life nutritional interventions augment changes in potential key molecules regulating sexual development. Ultimately, a greater understanding of the inherent regulation of postnatal sexual development in the bull calf and how strategically targeted nutritional management can advance the ontogeny of this process, will facilitate the timely availability of high-quality semen from genetically elite animals, thus supporting more economically and environmentally sustainable beef and dairy production systems., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: To determine surgical, survival and quality of life outcomes across different tumour streams and lessons learned over 28 years., Methods: Consecutive patients undergoing pelvic exenteration at a single, high volume, referral hospital, between 1994 and 2022 were included. Patients were grouped according to their tumour type at presentation as follows, advanced primary rectal cancer, other advanced primary malignancy, locally recurrent rectal cancer, other locally recurrent malignancy and non-malignant indications. The main outcomes included, resection margins, postoperative morbidity, long-term overall survival, and quality of life outcomes. Non-parametric statistics and survival analyses were performed to compare outcomes between groups., Results: Of the 1023 pelvic exenterations performed, 981 (95.9%) unique patients were included. Most patients underwent pelvic exenteration due to locally recurrent rectal cancer (N = 321, 32.7%) or advanced primary rectal cancer (N = 286, 29.2%). The rates of clear surgical margins (89.2%; P < 0.001) and 30-days mortality were higher in the advanced primary rectal cancer group (3.2%; P = 0.025). The 5-year overall survival rates were 66.3% in advanced primary rectal cancer and 44.6% in locally recurrent rectal cancer. Quality of life outcomes differed across groups at baseline, but generally had good trajectories thereafter. International benchmarking revelled excellent comparative outcomes., Conclusions: The results of this study demonstrate excellent outcomes overall, but significant differences in surgical, survival and quality of life outcomes across patients undergoing pelvic exenteration due to different tumour streams. The data reported in this manuscript can be utilized by other centres as benchmarking as well as proving both subjective and objective outcome details to support informed decision-making for patients., (© 2023 Royal Australasian College of Surgeons.)

Aims: To explore healthcare professionals' views about the training and support needed to rollout closed-loop technology to pregnant women with type 1 diabetes. Methods: We interviewed ( n  = 19) healthcare professionals who supported pregnant women using CamAPS FX closed-loop during the Automated insulin Delivery Amongst Pregnant women with Type 1 diabetes (AiDAPT) trial. Data were analyzed descriptively. An online workshop involving ( n  = 15) trial team members was used to inform recommendations. Ethics approvals were obtained in conjunction with those for the wider trial. Results: Interviewees expressed enthusiasm for a national rollout of closed-loop, but anticipated various challenges, some specific to use during pregnancy. These included variations in insulin pump and continuous glucose monitoring expertise and difficulties embedding and retaining key skills, due to the relatively small numbers of pregnant women using closed-loop. Inexperienced staff also highlighted difficulties interpreting data downloads. To support rollout, interviewees recommended providing expert initial advice training, delivered by device manufacturers together with online training resources and specific checklists for different systems. They also highlighted a need for 24 h technical support, especially when supporting technology naive women after first transitioning onto closed-loop in early pregnancy. They further recommended providing case-based meetings and mentorship for inexperienced colleagues, including support interpreting data downloads. Interviewees were optimistic that if healthcare professionals received training and support, their long-term workloads could be reduced because closed-loop lessened women's need for glycemic management input, especially in later pregnancy. Conclusions: Interviewees identified challenges and opportunities to rolling-out closed-loop and provided practical suggestions to upskill inexperienced staff supporting pregnant women using closed-loop. A key priority will be to determine how best to develop mentorship services to support inexperienced staff delivering closed-loop. Clinical Trials Registration: NCT04938557.