Real-World Clinical Experience of Oral Semaglutide in a Secondary Diabetes Clinic in the UK: A Retrospective Observational Study.

INTRODUCTION: Oral semaglutide improves cardiovascular risk factors in people with type 2 diabetes (T2D) in clinical trials, though real-world evidence is limited. We aimed to determine the real-world impact of oral semaglutide on routinely collected clinical data in our practice. METHODS: People with T2D initiated on oral semaglutide in secondary care diabetes clinics at two hospital sites in Wales (United Kingdom) were included. Data were collected on reasons for oral semaglutide initiation and changes in bodyweight, blood pressure, glycemic control, and lipid profiles over follow-up at 3-6 months, and at 6-12 months. Data were collected to determine the safety of oral semaglutide. RESULTS: Seventy-six patients were included, with a median age 59.3 [51.4-67.6] years, and 38 (50.0%) patients were female. The most common reasons for oral semaglutide were need for weight loss and improved glycemia (69.8%), and improved glycemia alone (25.0%). Oral semaglutide associated with significantly reduced bodyweight (- 3.3 kg), body mass index (BMI) (- 0.9 kg/m2), glycated hemoglobin (HbA1c) (- 11 mmol/mol), and total cholesterol (- 0.4 mmol/l) by 3-6 months follow-up. At 6-12 months, there was a significant reduction in systolic blood pressure (- 7.0 mmHg), in addition to sustained reductions in other metabolic parameters. By 12 months, 18 (23.6%) patients had discontinued the drug, largely resulting from gastrointestinal disturbance, but there were no serious events in this cohort. CONCLUSIONS: Oral semaglutide was effective in improving cardiovascular risk factors in this real-world population living with T2D, and no serious events were identified related to oral semaglutide in this patient group.

Correlation Between the Glycemia Risk Index and Longitudinal Hemoglobin A1c in Children and Young Adults With Type 1 Diabetes.

BACKGROUND: The glycemia risk index (GRI) is a composite metric developed and used to estimate quality of glycemia in adults with diabetes who use continuous glucose monitor (CGM) devices. In a cohort of youth with type 1 diabetes (T1D), we examined the utility of the GRI for evaluating quality of glycemia between clinic visits by analyzing correlations between the GRI and longitudinal glycated hemoglobin A1c (HbA1c) measures. METHOD: Using electronic health records and CGM data, we conducted a retrospective cohort study to analyze the relationship between the GRI and longitudinal HbA1c measures in youth (T1D duration ≥1 year; ≥50% CGM wear time) receiving care from a Midwest pediatric diabetes clinic network (March 2016 to May 2022). Furthermore, we analyzed correlations between HbA1c and the GRI high and low components, which reflect time spent with high/very high and low/very low glucose, respectively. RESULTS: In this cohort of 719 youth (aged = 2.5-18.0 years [median = 13.4; interquartile range [IQR] = 5.2]; 50.5% male; 83.7% non-Hispanic White; 68.0% commercial insurance), baseline GRI scores positively correlated with HbA1c measures at baseline and 3, 6, 9, and 12 months later (r = 0.68, 0.65, 0.60, 0.57, and 0.52, respectively). At all time points, strong positive correlations existed between HbA1c and time spent in hyperglycemia. Substantially weaker, negative correlations existed between HbA1c and time spent in hypoglycemia. CONCLUSIONS: In youth with T1D, the GRI may be useful for evaluating quality of glycemia between scheduled clinic visits. Additional CGM-derived metrics are needed to quantify risk for hypoglycemia in this population.

Post-Acute Cardiovascular Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Project.

Background: The risk of cardiovascular outcomes in the post-acute phase of SARS-CoV-2 infection has been quantified among adults and children. This paper aimed to assess a multitude of cardiac signs, symptoms, and conditions, as well as focused on patients with and without congenital heart defects (CHDs), to provide a more comprehensive assessment of the post-acute cardiovascular outcomes among children and adolescents after COVID-19. Methods: This retrospective cohort study used data from the RECOVER consortium comprising 19 US children's hospitals and health institutions between March 2020 and September 2023. Every participant had at least a six-month follow-up after cohort entry. Absolute risks of incident post-acute COVID-19 sequelae were reported. Relative risks (RRs) were calculated by contrasting COVID-19-positive with COVID-19-negative groups using a Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through propensity scoring stratification. Results: A total of 1,213,322 individuals under 21 years old (mean[SD] age, 7.75[6.11] years; 623,806 male [51.4%]) were included. The absolute rate of any post-acute cardiovascular outcome in this study was 2.32% in COVID-19 positive and 1.38% in negative groups. Patients with CHD post-SARS-CoV-2 infection showed increased risks of any cardiovascular outcome (RR, 1.63; 95% confidence interval (CI), 1.47-1.80), including increased risks of 11 of 18 post-acute sequelae in hypertension, arrhythmias (atrial fibrillation and ventricular arrhythmias), myocarditis, other cardiac disorders (heart failure, cardiomyopathy, and cardiac arrest), thrombotic disorders (thrombophlebitis and thromboembolism), and cardiovascular-related symptoms (chest pain and palpitations). Those without CHDs also experienced heightened cardiovascular risks after SARS-CoV-2 infection (RR, 1.63; 95% CI, 1.57-1.69), covering 14 of 18 conditions in hypertension, arrhythmias (ventricular arrhythmias and premature atrial or ventricular contractions), inflammatory heart disease (pericarditis and myocarditis), other cardiac disorders (heart failure, cardiomyopathy, cardiac arrest, and cardiogenic shock), thrombotic disorders (pulmonary embolism and thromboembolism), and cardiovascular-related symptoms (chest pain, palpitations, and syncope). Conclusions: Both children with and without CHDs showed increased risks for a variety of cardiovascular outcomes after SARS-CoV-2 infection, underscoring the need for targeted monitoring and management in the post-acute phase. Clinical Perspective section: What is new?: We investigated the risks of 18 post-acute COVID-19 cardiovascular outcomes in the pediatric population without Multisystem Inflammatory Syndrome in Children (MIS-C) in over 1 million patients, stratified by congenital heart defects (CHD) status.We extended the follow-up period beyond previous pediatric studies, ensuring every participant had at least a six-month follow-up after cohort entry.We included a comprehensive cross-section of the US pediatric population across various healthcare settings including primary, specialty, and emergency care, as well as testing and inpatient facilities.What are the clinical implications?: Within the post-acute phase, children and adolescents previously infected with SARS-CoV-2 are at statistically significant increased risk of incident cardiovascular outcomes, including hypertension, ventricular arrhythmias, myocarditis, heart failure, cardiomyopathy, cardiac arrest, thromboembolism, chest pain, and palpitations. These findings are consistent among patients with and without CHDs.Awareness of the heightened risk of cardiovascular disorders after COVID-19 can lead to a timely referral, investigations, and management of these conditions in children and adolescents.

Ehf controls mammary alveolar lineage differentiation and is a putative suppressor of breast tumorigenesis.

The transcription factor EHF is highly expressed in the lactating mammary gland, but its role in mammary development and tumorigenesis is not fully understood. Utilizing a mouse model of Ehf deletion, herein, we demonstrate that loss of Ehf impairs mammary lobuloalveolar differentiation at late pregnancy, indicated by significantly reduced levels of milk genes and milk lipids, fewer differentiated alveolar cells, and an accumulation of alveolar progenitor cells. Further, deletion of Ehf increased proliferative capacity and attenuated prolactin-induced alveolar differentiation in mammary organoids. Ehf deletion also increased tumor incidence in the MMTV-PyMT mammary tumor model and increased the proliferative capacity of mammary tumor organoids, while low EHF expression was associated with higher tumor grade and poorer outcome in luminal A and basal human breast cancers. Collectively, these findings establish EHF as a non-redundant regulator of mammary alveolar differentiation and a putative suppressor of mammary tumorigenesis.

Chemistry domain of applicability evaluation against existing estrogen receptor high-throughput assay-based activity models.

Introduction: The U. S. Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP) Tier 1 assays are used to screen for potential endocrine system-disrupting chemicals. A model integrating data from 16 high-throughput screening assays to predict estrogen receptor (ER) agonism has been proposed as an alternative to some low-throughput Tier 1 assays. Later work demonstrated that as few as four assays could replicate the ER agonism predictions from the full model with 98% sensitivity and 92% specificity. The current study utilized chemical clustering to illustrate the coverage of the EDSP Universe of Chemicals (UoC) tested in the existing ER pathway models and to investigate the utility of chemical clustering to evaluate the screening approach using an existing 4-assay model as a test case. Although the full original assay battery is no longer available, the demonstrated contribution of chemical clustering is broadly applicable to assay sets, chemical inventories, and models, and the data analysis used can also be applied to future evaluation of minimal assay models for consideration in screening. Methods: Chemical structures were collected for 6,947 substances via the CompTox Chemicals Dashboard from the over 10,000 UoC and grouped based on structural similarity, generating 826 chemical clusters. Of the 1,812 substances run in the original ER model, 1,730 substances had a single, clearly defined structure. The ER model chemicals with a clearly defined structure that were not present in the EDSP UoC were assigned to chemical clusters using a k-nearest neighbors approach, resulting in 557 EDSP UoC clusters containing at least one ER model chemical. Results and Discussion: Performance of an existing 4-assay model in comparison with the existing full ER agonist model was analyzed as related to chemical clustering. This was a case study, and a similar analysis can be performed with any subset model in which the same chemicals (or subset of chemicals) are screened. Of the 365 clusters containing >1 ER model chemical, 321 did not have any chemicals predicted to be agonists by the full ER agonist model. The best 4-assay subset ER agonist model disagreed with the full ER agonist model by predicting agonist activity for 122 chemicals from 91 of the 321 clusters. There were 44 clusters with at least two chemicals and at least one agonist based upon the full ER agonist model, which allowed accuracy predictions on a per-cluster basis. The accuracy of the best 4-assay subset ER agonist model ranged from 50% to 100% across these 44 clusters, with 32 clusters having accuracy ≥90%. Overall, the best 4-assay subset ER agonist model resulted in 122 false-positive and only 2 false-negative predictions compared with the full ER agonist model. Most false positives (89) were active in only two of the four assays, whereas all but 11 true positive chemicals were active in at least three assays. False positive chemicals also tended to have lower area under the curve (AUC) values, with 110 out of 122 false positives having an AUC value below 0.214, which is lower than 75% of the positives as predicted by the full ER agonist model. Many false positives demonstrated borderline activity. The median AUC value for the 122 false positives from the best 4-assay subset ER agonist model was 0.138, whereas the threshold for an active prediction is 0.1. Conclusion: Our results show that the existing 4-assay model performs well across a range of structurally diverse chemicals. Although this is a descriptive analysis of previous results, several concepts can be applied to any screening model used in the future. First, the clustering of the chemicals provides a means of ensuring that future screening evaluations consider the broad chemical space represented by the EDSP UoC. The clusters can also assist in prioritizing future chemicals for screening in specific clusters based on the activity of known chemicals in those clusters. The clustering approach can be useful in providing a framework to evaluate which portions of the EDSP UoC chemical space are reliably covered by in silico and in vitro approaches and where predictions from either method alone or both methods combined are most reliable. The lessons learned from this case study can be easily applied to future evaluations of model applicability and screening to evaluate future datasets.

A novel high-titer, bifunctional lentiviral vector for autologous hematopoietic stem cell gene therapy of sickle cell disease.

A major limitation of gene therapy for sickle cell disease (SCD) is the availability and access to a potentially curative one-time treatment, due to high treatment costs. We have developed a high-titer bifunctional lentiviral vector (LVV) in a vector backbone that has reduced size, high vector yields, and efficient gene transfer to human CD34+ hematopoietic stem and progenitor cells (HSPCs). This LVV contains locus control region cores expressing an anti-sickling ßAS3-globin gene and two microRNA-adapted short hairpin RNA simultaneously targeting BCL11A and ZNF410 transcripts to maximally induce fetal hemoglobin (HbF) expression. This LVV induces high levels of anti-sickling hemoglobins (HbAAS3 + HbF), while concurrently decreasing sickle hemoglobin (HbS). The decrease in HbS and increased anti-sickling hemoglobin impedes deoxygenated HbS polymerization and red blood cell sickling at low vector copy per cell in transduced SCD patient CD34+ cells differentiated into erythrocytes. The dual alterations in red cell hemoglobins ameliorated the SCD phenotype in the SCD Berkeley mouse model in vivo. With high titer and enhanced transduction of HSPC at a low multiplicity of infection, this LVV will increase the number of patient doses of vector from production lots to decrease costs and help improve accessibility to gene therapy for SCD.

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

BACKGROUND AND OBJECTIVES: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. METHODS: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. RESULTS: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. DISCUSSION: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Effect of interventions to improve safety culture on healthcare workers in hospital settings: a systematic review of the international literature.

BACKGROUND: In an era of safety systems, hospital interventions to build a culture of safety deliver organisational learning methodologies for staff. Their benefits to hospital staff are unknown. We examined the literature for evidence of staff outcomes. Research questions were: (1) how is safety culture defined in studies with interventions that aim to enhance it?; (2) what effects do interventions to improve safety culture have on hospital staff?; (3) what intervention features explain these effects? and (4) what staff outcomes and experiences are identified? METHODS AND ANALYSIS: We conducted a mixed-methods systematic review of published literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was conducted in MEDLINE, EMBASE, CINAHL, Health Business Elite and Scopus. We adopted a convergent approach to synthesis and integration. Identified intervention and staff outcomes were categorised thematically and combined with available data on measures and effects. RESULTS: We identified 42 articles for inclusion. Safety culture outcomes were most prominent under the themes of leadership and teamwork. Specific benefits for staff included increased stress recognition and job satisfaction, reduced emotional exhaustion, burnout and turnover, and improvements to working conditions. Effects were documented for interventions with longer time scales, strong institutional support and comprehensive theory-informed designs situated within specific units. DISCUSSION: This review contributes to international evidence on how interventions to improve safety culture may benefit hospital staff and how they can be designed and implemented. A focus on staff outcomes includes staff perceptions and behaviours as part of a safety culture and staff experiences resulting from a safety culture. The results generated by a small number of articles varied in quality and effect, and the review focused only on hospital staff. There is merit in using the concept of safety culture as a lens to understand staff experience in a complex healthcare system.

The Glycemia Risk Index Predicts Performance of Diabetes Self-Management Habits in Youth With Type 1 Diabetes Mellitus.

BACKGROUND: The Glycemia Risk Index (GRI) was developed in adults with diabetes and is a validated metric of quality of glycemia. Little is known about the relationship between GRI and type 1 diabetes (T1D) self-management habits, a validated assessment of youths' engagement in habits associated with glycemic outcomes. METHOD: We retrospectively examined the relationship between GRI and T1D self-management habits in youth with T1D who received care from a Midwest pediatric diabetes clinic network. The GRI was calculated using seven days of continuous glucose monitor (CGM) data, and T1D self-management habits were assessed ±seven days from the GRI score. A mixed-effects Poisson regression model was used to evaluate the total number of habits youth engaged in with GRI, glycated hemoglobin A1c (HbA1c), age, race, ethnicity, and insurance type as fixed effects and participant ID as a random effect to account for multiple clinic visits per individual. RESULTS: The cohort included 1182 youth aged 2.5 to 18.0 years (mean = 13.8, SD = 3.5) comprising 50.8% male, 84.6% non-Hispanic White, and 64.8% commercial insurance users across a total of 6029 clinic visits. Glycemia Risk Index scores decreased as total number of habits performed increased, suggesting youth who performed more self-management habits achieved a higher quality of glycemia. CONCLUSIONS: In youth using CGMs, GRI may serve as an easily obtainable metric to help identify youth with above target glycemia, and engagement/disengagement in the T1D self-management habits may inform clinicians with suitable interventions for improving glycemic outcomes.

A fear conditioned cue orchestrates a suite of behaviors in rats.

Pavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, a cue is paired with foot shock, and subsequent cue presentation elicits freezing, a behavior theoretically linked to predator detection. Studies have since shown a fear conditioned cue can elicit locomotion, a behavior that - in addition to jumping, and rearing - is theoretically linked to imminent or occurring predation. A criticism of studies observing fear conditioned cue-elicited locomotion is that responding is non-associative. We gave rats Pavlovian fear discrimination over a baseline of reward seeking. TTL-triggered cameras captured 5 behavior frames/s around cue presentation. Experiment 1 examined the emergence of danger-specific behaviors over fear acquisition. Experiment 2 examined the expression of danger-specific behaviors in fear extinction. In total, we scored 112,000 frames for nine discrete behavior categories. Temporal ethograms show that during acquisition, a fear conditioned cue suppresses reward seeking and elicits freezing, but also elicits locomotion, jumping, and rearing - all of which are maximal when foot shock is imminent. During extinction, a fear conditioned cue most prominently suppresses reward seeking, and elicits locomotion that is timed to shock delivery. The independent expression of these behaviors in both experiments reveal a fear conditioned cue to orchestrate a temporally organized suite of behaviors.

Lab on a bead with oscillatory centrifugal microfluidics for fast and complete mixing enables fast and accurate biomedical assays.

Rapid mixing and precise timing are key for accurate biomedical assay measurement, particularly when the result is determined as the rate of a reaction: for example rapid immunoassay in which the amount of captured target is kinetically determined; determination of the concentration of an enzyme or enzyme substrate; or as the final stage in any procedure that involves a capture reagent when an enzyme reaction is used as the indicator. Rapid mixing and precise timing are however difficult to achieve in point-of-care devices designed for small sample volumes and fast time to result. By using centrifugal microfluidics and transposing the reaction surface from a chamber to a single mm-scale bead we demonstrate an elegant and easily manufacturable solution. Reagents (which may be, for example, an enzyme, enzyme substrate, antibody or antigen) are immobilised on the surface of a single small bead (typically 1-2 mm in diameter) contained in a cylindrical reaction chamber subjected to periodically changing rotational accelerations which promote both mixing and uniform mass-transfer to the bead surface. The gradient of Euler force across the chamber resulting from rotational acceleration of the disc, dΩdisc/dt, drives circulation of fluid in the chamber. Oscillation of Euler force by oscillation of rotational acceleration with period, T, less than that of the hydrodynamic relaxation time of the fluid, folds the fluid streamlines. Movement of the bead in response to the fluid and the changing rotational acceleration provides a dynamically changing chamber shape, further folding and expanding the fluid. Bead rotation and translation driven by fluid flow and disc motion give uniformity of reaction over the surface. Critical parameters for mixing and reaction uniformity are the ratio of chamber radius to bead radius, rchamber/rbead, and the product Trchamber(dΩdisc/dt), of oscillation period and Euler force gradient across the fluid. We illustrate application of the concept using the reaction of horse radish peroxidase (HRP) immobilised on the bead surface with its substrate tetramethylbenzidine (TMB) in solution. Acceleration from rest to break a hydrophobic valve provided precise timing for TMB contact with the bead. Solution uniformity from reaction on the surface of the bead in volumes 20-50 uL was obtained in times of 2.5 s or less. Accurate measurement of the amount of surface-bound HRP by model fitting to the measured kinetics of colour development at 10 s intervals is demonstrated.

Comparing pregnancy outcomes in patients with Systemic Lupus Erythematosus (SLE) and Undifferentiated Connective Tissue Disease (UCTD): a descriptive cohort study.

BACKGROUND: Females diagnosed with systemic lupus erythematosus (SLE) face an elevated risk of adverse pregnancy outcomes (APOs). However, the evidence regarding whether a similar association exists in patients with undifferentiated connective tissue disease (UCTD) is inconclusive. METHODS: We conducted a retrospective review (2006-2019) of pregnancy outcomes among patients with SLE (n = 51) and UCTD (n = 20) within our institution. We examined the occurrence of various APOs, encompassing miscarriage, stillbirth, termination, preterm birth, pre-eclampsia, eclampsia, HELLP syndrome, intrauterine growth restriction, abruption placentae, congenital heart block, or other cardiac abnormalities. RESULTS: The mean age at pregnancy was 35 ±â€¯7.0 years for patients with SLE and 35 ±â€¯6.8 years for those with UCTD (p = 0.349). The proportion of Caucasian women was 47% in SLE and 80% in UCTD. Pregnancies in both groups were planned (81% in SLE and 77% in UCTD), and patients presented with inactive disease at conception (96% in SLE and 89% in UCTD). Hydroxychloroquine at conception was utilized by 86% of women with SLE, in contrast to 36% in the UCTD group. Both, SLE and UCTD cohorts exhibited low rates of disease flares during pregnancy and/or puerperium (14% vs. 10%). The incidence of APOs was 15.6% in SLE patients compared to 5% in those with UCTD (Risk difference 19.5%; 95% confidence interval: -3.9 to 43.1; p = 0.4237). CONCLUSION: Our study underscores the importance of strategic pregnancy planning and the maintenance of appropriate treatment throughout pregnancy to ensure optimal disease management and minimize adverse outcomes in both SLE and UCTD pregnancies.

Uterine Fibroids.

This JAMA Insights in the Women's Health series discusses the incidence, diagnosis, and treatment of uterine fibroids.

Machine learning-based 3D segmentation of mitochondria in polarized epithelial cells.

Mitochondria are dynamic organelles that alter their morphological characteristics in response to functional needs. Therefore, mitochondrial morphology is an important indicator of mitochondrial function and cellular health. Reliable segmentation of mitochondrial networks in microscopy images is a crucial initial step for further quantitative evaluation of their morphology. However, 3D mitochondrial segmentation, especially in cells with complex network morphology, such as in highly polarized cells, remains challenging. To improve the quality of 3D segmentation of mitochondria in super-resolution microscopy images, we took a machine learning approach, using 3D Trainable Weka, an ImageJ plugin. We demonstrated that, compared with other commonly used methods, our approach segmented mitochondrial networks effectively, with improved accuracy in different polarized epithelial cell models, including differentiated human retinal pigment epithelial (RPE) cells. Furthermore, using several tools for quantitative analysis following segmentation, we revealed mitochondrial fragmentation in bafilomycin-treated RPE cells.

Leveraging wastewater surveillance to detect viral diseases in livestock settings.

Wastewater surveillance has evolved into a powerful tool for monitoring public health-relevant analytes. Recent applications in tracking severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection highlight its potential. Beyond humans, it can be extended to livestock settings where there is increasing demand for livestock products, posing risks of disease emergence. Wastewater surveillance may offer non-invasive, cost-effective means to detect potential outbreaks among animals. This approach aligns with the "One Health" paradigm, emphasizing the interconnectedness of animal, human, and ecosystem health. By monitoring viruses in livestock wastewater, early detection, prevention, and control strategies can be employed, safeguarding both animal and human health, economic stability, and international trade. This integrated "One Health" approach enhances collaboration and a comprehensive understanding of disease dynamics, supporting proactive measures in the Anthropocene era where animal and human diseases are on the rise.

Changes in Cognitive Function Following Bariatric Surgery: An Updated Systematic Review.

Since a previous systematic review published in 2016, there have been further studies investigating the association of changes in cognitive function following bariatric surgery. All studies since the original review that reported at least one element of cognitive function before and after bariatric surgery were eligible. A total of 137 additional studies were identified; 13 were included in addition to the 18 studies previously. Almost all studies reported improvements in at least one domain. Most revealed improvements were limited to a few domains and were not universal. Further findings investigated cognitive function improvement in relation to procedure choice, and mental health or quality of life post-surgery. Further high-powered studies are still necessary, but these findings support the impact of bariatric surgery on cognitive function in obesity.

Projected future climatic forcing on the global distribution of vegetation types.

Most emissions scenarios suggest temperature and precipitation regimes will change dramatically across the globe over the next 500 years. These changes will have large impacts on the biosphere, with species forced to migrate to follow their preferred environmental conditions, therefore moving and fragmenting ecosystems. However, most projections of the impacts of climate change only reach 2100, limiting our understanding of the temporal scope of climate impacts, and potentially impeding suitable adaptive action. To address this data gap, we model future climate change every 20 years from 2000 to 2500 CE, under different CO2 emissions scenarios, using a general circulation model. We then apply a biome model to these modelled climate futures, to investigate shifts in climatic forcing on vegetation worldwide, the feasibility of the migration required to enact these modelled vegetation changes, and potential overlap with human land use based on modern-day anthromes. Under a business-as-usual scenario, up to 40% of terrestrial area is expected to be suited to a different biome by 2500. Cold-adapted biomes, particularly boreal forest and dry tundra, are predicted to experience the greatest losses of suitable area. Without mitigation, these changes could have severe consequences both for global biodiversity and the provision of ecosystem services. This article is part of the theme issue 'Ecological novelty and planetary stewardship: biodiversity dynamics in a transforming biosphere'.

"I'm more than my sport": Exploring the dynamic processes of identity change in athletic retirement.

Retirement is one of the most impactful career transitions athletes face. Researchers recognise the role that athletic identity plays in this, but analysis of identity content and change processes is limited. Addressing this gap, we conducted a qualitative study exploring the experience of identity change in 21 competitive and successful elite athletes who had retired from sport. All participated in a one-session psychoeducational program that explored the challenges of transitioning out of sport before being interviewed about their understanding of identity in sport, and their experiences negotiating identity loss and change in retirement. Using reflexive thematic analysis, we identified three themes: (i) the role of identity and self-categorizations in shaping sport performance, (ii) adjusting to identity loss (with subthemes indicating that this experience varied depending on the extent to which a person had multiple or exclusive identities), and (iii) attempts to remoor identity in the transition (with subthemes of searching for a new identity and actively repurposing identity). We interpret these themes through the lens of the Social Identity Model of Identity Change and show that this provides a framework for extending our understanding the complexities of identity change associated with retirement from elite sport.

Identifying potential cases of eating disorders in an acute medical hospital.

OBJECTIVE: To identify patients presenting to an acute medical hospital with common signs and symptoms that occur in people with eating disorders (EDs), and determine by retrospective file audit if these are diagnosed cases of an ED. METHOD: The investigators screened electronic medical records of people 16 years and older for common signs and symptoms of an ED such as hypokalemia, in patients presenting to an acute hospital in Sydney, Australia from 2018 to 2020. Cases where the clinical finding was unexplained had their file audited. Cases with a known ED diagnosis or coded with an ED were also retrieved to audit. RESULTS: Investigators identified 192 definite ED cases with a total of 598 episodes of care from 2018 to 2020 presenting to the hospital. Eighty-three cases were identified as possible EDs due to unexplained clinical signs consistent with an ED, but were not confirmed cases due to lack of clinical history in the file. Only 19.1% of presentations were diagnostically coded with an ED in the electronic medical record. DISCUSSION: Our study revealed a large number of definite ED cases presenting to an acute medical hospital via the emergency department, who were not recognized as having an ED. Greater awareness of clinical signs and symptoms of an ED, such as unexplained low body mass index and hypokalemia, is necessary among acute care clinicians. Correctly identifying EDs in those seeking somatic care should be a public health priority, to facilitate timely and equitable access to diagnostic assessment and evidence based treatment. PUBLIC SIGNIFICANCE: People with eating disorders (EDs) present to acute care settings and have a relatively high utilization of generalist health services with nonspecific problems such as abdominal pain. An enhanced understanding of healthcare utilization by people with EDs, who may not disclose their symptoms, is crucial for improving access to treatment.