Search

We present the first global geospace simulation to reproduce auroral giant undulations (GUs). To identify their magnetospheric drivers, we employ the MAGE (Multiscale Atmosphere‐Geospace Environment) model in a case study of a geomagnetic storm for which there were spacecraft‐ and ground‐based observations of GUs. The model reproduces the spatial and temporal scales of the GUs as well as the presence of duskside subauroral polarization streams (SAPS) and plasmapause undulations. Based on our modeling, we are able to identify the magnetospheric drivers of GUs as mesoscale ring current injections which, after drifting westward, create inverted regions of flux‐tube entropy (FTE) and subsequent interchange instability. Outward‐protruding interchange fingers disrupt shielding of the inner magnetosphere, creating longitudinally localized ripples in magnetospheric convection equatorward of the magnetospheric instability, which structure the plasmapause and duskside diffuse precipitation. While not causal, SAPS and plasmapause undulations are a consequence of the unstable magnetospheric configuration. Plain Language Summary: The visually dazzling display of the aurora during active periods is caused primarily by the precipitation of energetic electrons from the magnetosphere into the ionosphere. The auroral oval plays host to a variety of morphological features, or auroral forms, that are a reflection of magnetospheric processes and therefore a powerful tool for understanding the cross‐scale processes that bind together different geospace domains. Unlocking that power, however, requires an understanding of how magnetospheric processes are reflected in the aurora. Despite decades of study, that understanding has remained elusive, primarily due to limited in situ measurements and uncertainty in the magnetic mapping connecting them to the ionosphere. Only recently have new global geospace models emerged that can provide this understanding. In this letter we identify the magnetospheric driver of auroral giant undulations (GUs), wave‐like trains of undulations that form on the equatorward edge of the diffuse aurora with typical spatial scales of 100 km. We show that GUs are the consequence of a "buoyancy imbalance" formed during the buildup of the ring current and the subsequent disruption of the ionospheric current systems that typically shield the inner magnetosphere. Key Points: We present the first global geospace simulation to reproduce auroral giant undulations (GUs)Model shows GUs result from localized under‐shielding as a consequence of interchange instability during the buildup of the ring currentInterchange‐unstable regions drive ripples in magnetospheric convection, structuring the plasmapause and duskside diffuse precipitation [ABSTRACT FROM AUTHOR]

The electron cyclotron (EC) heating & current drive (H&CD) system on ITER provides plasma heating by generating, transmitting, and launching high-intensity, high-frequency (170 GHz) electromagnetic wave energy steerable across the plasma cross-section. The transmission line (TL) subsystem connects the Matching Optics Unit (MOU) on each of the 24 gyrotrons to the 32 feed points in the four upper launchers and the 24 feed points in the equatorial launcher. Each TL must be able to operate at up to 1.2 MW of input power for up to 1 hour pulse lengths. The TL system contains 50 mm water-cooled corrugated waveguide, 90o miter bends, 140o miter bends, polarizer miter bend pairs, switches, expansion units, pumpouts, DC breaks, MOU-TL adapters, Radio Frequency (RF) loads, and isolation shutter valves. A detailed finite element analysis has been used to verify the thermo-mechanical performance of each component. The microwave performance has been analyzed using a 2-D electromagnetic code combined with a Monte Carlo code. This approach allows the impact of manufacturing and installation tolerances to be assessed and optimized to provide a high probability of achieving the system performance requirements. Prototypes of the waveguide and TL components have been fabricated and tested at high-power. Production contracts are now being issued for fabrication and delivery of the waveguide and components to ITER.

The development of advanced spintronics materials necessitates novel characterization tools with the ability to analyze nanometer-scale spin textures. Neutrons, with their angstrom-sized wavelengths, electric neutrality, and controllable spin states, are uniquely suited for this task. Recent research has prioritized expanding the capabilities of the “neutron toolbox” to effectively characterize emerging materials. This involves the development of holographic and tomographic techniques for 3D characterization of bulk spin textures, alongside methods for creating structured neutron beams with specific spin-orbit states like helical and skyrmion configurations. Here we provide a concise overview of these advancements, exploring their potential future applications.

Sarcoglycanopathies, severe forms of autosomal recessive LGMDs, include four subtypes: LGMDR3, LGMDR4, LGMDR5, and LGMDR6. A retrospective audit at a single centre gathered motor function, respiratory, cardiac and genetic data for sarcoglycanopathy individuals diagnosed by the Highly Specialised Service for Rare Neuromuscular Disorders in Newcastle upon Tyne, UK, from 1987 to 2024. Forty-three individuals from 30 unrelated families were diagnosed with sarcoglycanopathy, 12 with LGMDR3, 11 with LGMDR4, 14 with LGMDR5, and 2 with LGMDR6. The main pathogenic variants were SCGA c.229C>T;p.(Arg77Cys), SCGB c.341C>T;p.(Ser114Phe) and SGCG c.787G>A;p.(Glu263Lys). Mean onset ages were 8.7, 7.8, 6.4, and 8.3 years for LGMDR3, LGMDR4, LGMDR5, and LGMDR6, respectively. Thirty-nine had pediatric onset (0-16), and four had young adult onset (16-40). Individuals with <3-year disease duration showed preserved motor function. Five out of six with LGMDR6 had <3 years of disease duration. The mean disease duration for loss of ambulation (LoA) occurred at ages 8.2, 12.3, and 9.5 years for LGMDR3, LGMDR4, and LGMDR5, respectively. Six out of nine non-ambulant LGMDR5 cases showed loss of ability to lift arms before LoA. This was less common in LGMDR3 and LGMDR4 cases (1/10). Four young adult-onset individuals, none with LGMDR5, remained ambulatory for an average of 21.5 years post-onset. No correlation existed between early disease onset age and time to LoA (p=0.74). The mean disease duration for losing the ability to rise from the floor and climb stairs were 6.5 and 7.6, respectively, with a strong correlation (p<0.01). Five individuals developed cardiomyopathy, with an average disease duration of 25.4 years. Forced vital capacity (FVC) was <80% in 18/43 individuals, while 11/18 developed severe restrictive pulmonary disease (FVC<50%), with an average disease duration of 19.7 years. This sarcoglycanopathy cohort may display subtype-specific patterns but lacked a correlation between disease onset age and LoA. [ABSTRACT FROM AUTHOR]

Background: Youth obesity and depression are public health concerns. Although meta-analyses suggest a positive association between those conditions in adults and adolescents, evidence remains unclear in prepubertal children. We examined the bidirectional associations between levels of depressive symptoms and weight status in 8-10-year-old children with a parental history of obesity, over two years, and whether they differ by sex., Methods: Data were drawn from the QUebec Adipose and Lifestyle InvesTigation in Youth Cohort Study's baseline and first follow-up evaluations (n = 558). Depressive symptoms were assessed using the 12-item Center for Epidemiological Studies Depression scale and weight status using body mass index z-scores based on World Health Organization standards. Linear and logistic regression models were used to test the directionality and magnitude of the associations, adjusting for age, sex, physical activity, screen time, parental education, alcohol and cigarette use, and baseline outcome measure., Results: Children with higher levels of depressive symptoms at baseline were not more likely to have overweight/obesity at follow-up (odds ratio [95 % Coefficient Interval] = 0.95[0.88;1.02]). Baseline overweight/obesity was not associated with subsequent higher levels of depressive symptoms (beta coefficient [95 % Coefficient Interval] = 0.20 [-0.47;0.87]). No sex differences emerged., Limitations: Selection bias may have occurred due to loss at follow-up (10 % attrition) and exclusion of 6 participants taking mood disorder medication., Conclusions: Unlike in adults and adolescents, no association between weight status and depressive symptoms was observed in childhood over two years. Underlying mechanisms linking both conditions later in life may not apply as early as prepubertal childhood., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mélanie Henderson reports financial support was provided by Canadian Institutes of Health Research. Mélanie Henderson reports financial support was provided by Heart and Stroke Foundation of Canada. Mélanie Henderson reports financial support was provided by the Fonds de recherche du Québec - Santé. Soren Harnois-Leblanc reports financial support was provided by the Fonds de recherche du Québec- Santé. Marie-Eve Mathieu reports financial support was provided by Canada research chair (Tier 2) on physical activity and juvenile obesity. Marie-Eve Mathieu reports financial support was provided by Junior 1 Fonds de recherche du Québec- Santé researcher award. Tracie A. Barnett reports financial support was provided by Fonds de recherche du Québec- Santé senior researcher award. Catherine M. Sabiston reports financial support was provided by Canada Research Chairs Program. Melanie Henderson reports financial support was provided by Senior salary award from the Fonds de recherche du Québec. Mélanie Henderson reports financial support was provided by Canadian Society of Endocrinology and Metabolism. Mélanie Henderson reports a relationship with Canadian Society of Endocrinology and Metabolism that includes: funding grants (recipient of 2019 the Canadian Society of Endocrinology and Metabolism's Young Investigator Award). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Data on associations between adiposity and heart rate variability (HRV) in prepubertal children are limited. We examined the associations between adiposity indices and HRV, independent of lifestyle behaviors, comparing multiple indicators of adiposity, and explored differences between boys and girls., Methods: Data stem from 469 participants of the QUALITY cohort (630 children aged 8-10 years with a parental history of obesity). Adiposity indices included waist-to-height ratio, body mass index (BMI) percentiles and categories (overweight, obesity), dual-energy x-ray absorptiometry (DEXA) defined fat mass percentage and android/gynoid ratio. HRV indices in the frequency and the spectral domain were derived from a daytime 3-h Holter recording. Multivariable linear regression models were adjusted for age, sex, Tanner stage, physical activity, screen time, and fitness. Interactions between sex and adiposity were tested., Results: Greater adiposity was associated with decreased parasympathetic modulation and increased sympathetic dominance. Waist-to-height ratio was associated with lower parasympathetic activity: root mean square of the successive differences (RMSSD) [B =  -23.32, 95% confidence interval (CI) -42.42, -4.22], pNN50 (B =  -16.93, 95% CI - 28.58, - 5.27), LF/HF ratio (B = 1.83, 95% CI 0.97-2.70). Patterns of association were similar for android/gynoid ratio. Overweight was not associated with altered HRV. Obesity was negatively associated with RMSSD and pNN50 and positively with LF/HF ratio. Greater fat mass percentage was associated with lower RMSSD, pNN50, and HF, and increased LF/HF ratio. There were no differences between boys and girls., Conclusions: Specific markers of adiposity relate to altered HRV in childhood, with waist-to-height ratio being potentially a more relevant marker of HRV than BMI and more pragmatic than percent body fat., Trial Registration: NCT03356262, 11 November 2017., (© 2024. Springer-Verlag GmbH Germany.)

Background: Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates the efficacy and tolerability of B vs D in a UK test-and-treat setting., Setting: BIC-T&T was a randomised, open-label, multi-centre, study in which participants initiated ART within 14 days after confirmed HIV-1 diagnosis before baseline laboratory., Methods: The primary endpoint is the virological response (HIV RNA < 50copies/mL) at week 12 by time-weighted average change in log 10 HIV RNA recorded in viral load assays from treatment initiation to week 12, using two-sample Wilcoxon rank-sum test., Results: 36 participants were randomised: 94% were male, 53% white; mean (SD) age was 35 years (11.8). Baseline mean (±SD) log 10 HIV-RNA was 4.79 (± 0.87) log 10 copies/mL and CD4 505 (±253) cells/mm 3 . The mean (±SD) time from confirmed HIV diagnosis to ART initiation was 7.9 (± 3.7) days. The time-weighted mean decrease in log 10 HIV RNA from treatment initiation to week 12 was significantly greater in B in comparison to D (3.1 vs. 2.6 log 10 copies/mL, p  < 0.001). Both regimens demonstrated good tolerability with infrequent laboratory abnormalities and no grade 3 or 4 adverse events., Conclusion: In this first head-to-head study in the context of ART initiation, HIV RNA decline from baseline to week 12 was significantly more rapid for BIC/F/TAF compared with DRV/c/F/TAF.

Objective: To estimate associations between physical activity and sedentary behaviors and early markers of cardiovascular diseases in adolescents with and without type 1 diabetes., Study Design: Cross-sectional data stem from the CARdiovascular Disease risk in pEdiatric type 1 diAbetes (CARDEA) study, a study investigating early cardiovascular disease development in 100 adolescents with type 1 diabetes recruited at Sainte-Justine University Hospital Diabetes Clinic and 97 healthy adolescents without diabetes (14-18 years), in Montreal, Canada. Outcomes included arterial stiffness by pulse-wave velocity, endothelial function (velocity time integral) by flow-mediated dilation test, and cardiac magnetic resonance imaging markers. Moderate-to-vigorous physical activity (MVPA) and sedentary time were estimated by accelerometry and leisure screen time by questionnaire. We estimated multivariable linear regression models stratified by group., Results: In adolescents with type 1 diabetes, 10-minutes daily increase in MVPA was associated with 3.69 g/m (95% CI: -1.16; 8.54) higher left ventricular (LV) mass/height and 1-hour increase in device-measured sedentary time with 0.68 mm (0.20; 1.16) higher wall thickness but only in those with glycated hemoglobin ≤7.5%. In healthy adolescents, a 10-minute increase in MVPA was associated with 1.32 g/m (-0.03; 2.66) higher LV mass/height. Every 1-hour increase in sedentary time was associated with -1.82 cm (-3.25; -0.39) lower velocity time integral, -2.99 g/m (-5.03; -0.95) lower LV mass/height, and -0.47 mm (-0.82; -0.12) lower wall thickness., Conclusions: Being active and limiting sedentary time appears beneficial for cardiac structure and endothelial function in healthy adolescents; however, adequate glycemic control combined with higher levels of MVPA may be required for adolescents with type 1 diabetes to overcome the impact of diabetes., Competing Interests: Declaration of Competing Interest The CARDEA study was supported by the Canadian Institutes of Health Research (CIHR) (#366194), the Heart and Stroke Foundation of Canada (#G-16-00012590), and the Fonds de recherche du Québec - Santé. S.H.L. was supported by a doctoral bursary for health professionals from the Fonds de Recherche du Québec – Santé. V.M.N. was supported by a Natural Sciences and Engineering Research Council of Canada doctoral bursary. M.G.F. is funded by the McGill University Health Centre Foundation. A.V.H. holds a Junior 1 salary award from the Fonds de recherche du Québec – Santé. A.M.N. is funded by CIHR, the Heart and Stroke Foundation of Canada, and the Cercle de Sainte-Justine DOHaD Research Chair. T.A.B. was supported by a Fonds de Recherche du Québec - Santé senior salary award. A.B. is funded by Fonds de Recherche du Québec – Santé salary award. M.-E.M. was supported by the Canadian Institutes of Health Research and holds a Canada research chair (Tier 2) on physical activity and juvenile obesity. M.-P.S. holds a Junior 2 salary award from the Fonds de recherche du Québec – Santé. M.H. was funded by a Diabetes Junior Investigator Award from the Canadian Society of Endocrinology and Metabolism/AstraZeneca and a Fonds de Recherche du Québec - Santé senior salary award and is the recipient of the 2019 Canadian Society for Endocrinology and Metabolism Young Investigator Award and reports financial support was provided by Heart and Stroke Foundation of Canada. Funders played no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. M.G.F. reports a relationship with Circle Cardiovascular Imaging Inc that includes the following: board membership, consulting or advisory, and equity or stocks. The other authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether race- and sex-based biases are present in a predictive model of avoidable hospital (AH) events., Study Setting and Design: We examined whether Medicare fee-for-service (FFS) beneficiaries in Maryland with similar risk scores differed in true AH event risk on the basis of race or sex (n = 324,834). This was operationalized as a logistic regression of true AH events on race or sex with fixed effects for risk score percentile., Data Sources and Analytic Sample: Beneficiary-level risk scores were derived from 36 months of Medicare FFS claims (April 2019-March 2022) and generated in May 2022. True AH events were observed in claims from June 2022., Principal Findings: Black patients had higher average risk scores than White patients; however, the likelihood of experiencing an AH event did not differ by race when controlling for predicted risk (Marginal Effect [ME] = 0.0003, 95%CI -0.0003 to 0.0009). AH event likelihood was lower in males when controlling for risk level; however, the effect was small (ME = -0.0008, 95% CI -0.0013 to -0.0003) and it did not differ by sex for the target group for intervention (ME = 0.0002, 95% CI -0.0031 to 0.0036)., Conclusions: We implemented a simple bias assessment methodology and found no evidence of meaningful race- or sex-based bias in this model. We encourage the incorporation of bias checks into predictive model development and monitoring processes., (© 2024 Health Research and Educational Trust.)

Background: We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biologics for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life (QoL)., Methods: International expert healthcare professionals (HCPs) and patients with severe asthma were invited to: 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA; 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of HCPs evaluated CONFiRM's external validity., Results: Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroids use were rated as most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between HCPs and patients, although patients assigned greater importance to QoL. The CONFiRM score quantified response to a biological from -31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (AUC≥0.92) and a substantial (AUC≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult respectively (p<0.0001))., Conclusions: We have developed novel patient-centred paediatric and adult CONFiRMs which include QoL measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores., (Copyright ©The authors 2024.)

Objective: To summarize the literature on bariatric surgery for managing pediatric obesity, including intervention effects to improve patient-reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry, and assess adverse events (AEs)., Methods: Eligible studies were published between January 2012 and January 2022 and included randomized controlled trials (RCTs) and observational (controlled and uncontrolled) studies before and after surgery with a mean age <18 years old. Outcomes and subgroups were selected a priori by stakeholders; estimates of effect for outcomes were presented relative to minimal important differences (MIDs) and GRADE certainty of evidence. We examined data on PROMs, cardiometabolic risk factors, anthropometry, and AEs. Subgroup analyses examined outcomes by follow-up duration and surgical technique, when possible., Results: Overall, 63 publications (43 original studies) met our inclusion criteria (n = 6128 participants; 66% female). Studies reported six different surgical techniques that were evaluated using uncontrolled single arm observational (n = 49), controlled observational (n = 13), and RCT (n = 1) designs. Most studies included short-term follow-up (<18 months) only. PROMs were measured in 12 (28%) studies. Surgery led to large improvements in health-related quality of life compared to baseline and control groups, and moderate to very large improvements in cardiometabolic risk factors compared to baseline. Large to very large improvements in BMIz were noted compared to baseline across all follow-up periods. There was limited evidence of AEs with most reporting mild or non-specific AEs; serious AEs were uncommon., Conclusion: Bariatric surgery demonstrated primarily moderate to very large improvements across diverse outcomes with limited evidence of AEs, albeit with low to moderate certainty of evidence., (© 2024 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Objective: To summarize the literature on pharmacotherapy for managing paediatric obesity., Methods: A systematic review and meta-analysis were conducted of randomized controlled trials (RCTs) with <18-year-olds of pharmacotherapeutic agents published up to November 2022. Estimates of effect for outcomes were presented relative to minimal important differences and GRADE certainty of evidence. We examined data on patient/proxy-reported outcome measures (PROMs), cardiometabolic risk factors, anthropometry and adverse events (AEs)., Results: Overall, 35 RCTs were included. Trials examined metformin (n = 26), glucagon-like peptide-1 receptor agonists (GLP1RAs) (n = 7) and a lipase inhibitor (orlistat; n = 2). Intervention duration varied (3-24 months). Metformin had little to no benefit on PROMs (e.g., health-related quality of life [HRQoL]; 6 RCTs), moderate reductions in triglycerides, a moderate decline in insulin resistance, a small to moderate decline in BMI z-score (BMIz) and a moderate increase in mild to moderate gastrointestinal AEs. Response to GLP1RAs was heterogeneous and results of subgroup analysis demonstrated variability of impact. Liraglutide (2 RCTs) resulted in a small reduction in HOMA-IR and BMIz, but little to no benefit on other outcomes. Exenatide (4 RCTs) had a moderate reduction on blood pressure and a small decrease in BMIz with little to no benefit on other outcomes. Semaglutide (1 RCT) had a small benefit on HRQoL, a small reduction on SBP, a moderate reduction on total cholesterol and LDL-cholesterol, a large reduction on triglyceride, and a very large decline in BMIz accompanied by a small increase in mild to moderate gastrointestinal AEs. Orlistat had a moderate reduction in DBP and little to no benefit in other outcomes measured, but had a very large increased risk of mild to moderate gastrointestinal AEs. Serious AEs were rare and for interventions with sufficent AE reporting, were considered not likely attributable to the interventions., Conclusion: Few studies examined the impact of pharmacotherapy on PROMs. There is evidence that metformin and GLP1RAs lead to important improvements in cardiometabolic and anthropometric outcomes while accompanied by mild to moderate AEs. Long-term effectiveness and safety of GLP1RAs remain to be evaluated., (© 2024 The Author(s). Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Purpose of Review: HIV-associated cardiac disease was well recognized in the preantiretroviral (ART) era among children with perinatally-acquired HIV infection (PHIV). While ART has dramatically improved survival, it has become increasingly apparent that individuals with PHIV continue to experience multisystem co-morbidities. We review the cardiac and vascular manifestations in people growing up with PHIV in the ART era., Recent Findings: ART has resulted in a drop in incidence of serious cardiac morbidity. However, there is a substantial body of evidence that demonstrates that cardiac and vascular structural and functional abnormalities, mostly subclinical, are common in people with PHIV taking ART. Studies have considerable heterogeneity with respect to types of cardiovascular assessments used. HIV-mediated chronic inflammation and potentially effects of ART contribute to these abnormalities. The long-term clinical significance of these abnormalities remains unknown as studies have mainly been cross-sectional, but it is likely that the burden of cardiovascular disease will grow as individuals with PHIV age and the prevalence of traditional risk factors increases., Summary: Understanding the pathogenesis of cardiovascular disease in PHIV, is critical to inform screening and interventional strategies. Longitudinal studies are also needed to understand the natural history of cardiovascular abnormalities and incidence of clinical outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Fibromyalgia (FMS) is a chronic condition that encompasses widespread pain associated with cognitive impairment and significant emotional distress related to functional disability. This study aimed to obtain evidence of the role of pain in the effect of time since FMS diagnosis and cognitive performance using a novel online protocol of neuropsychological evaluation since the COVID-19 pandemic has challenged traditional neuropsychology testing leading to the need for novel procedures transitioning to tele-neuropsychology. A sample of 70 adult women was evaluated (50 with FMS and 19 controls) using online questionnaires that evaluated pain and executive functioning (impulsivity, inhibition control, monitoring, and planning). Afterward, participants were evaluated by trained neuropsychologists in a 30 min online session using virtually adapted cognitive tests: the Hopkins Verbal Learning Test (memory), the Symbol-Digit Modalities Test (attention and speed processing), the F-A-S test (verbal fluency), and Digit Span tests (working memory). We found that the time of FMS diagnosis has an effect on cognitive functioning predominantly mediated by pain. Our results point out the role of pain as a mediator on cognitive performance, specifically in executive functions which are directly affected by the cumulative effect of the time of diagnosis. Furthermore, the importance of considering a broader perspective for assessment and treatment including novel procedures via tele-neuropsychology.

Aims: Patients with cardiac disease living in rural areas may face significant challenges in accessing care and studies suggest that living in rural areas may be associated with worse outcomes. However, it is unclear whether rural-urban disparities have an impact on mortality in patients presenting with acute myocardial infarction (AMI) and heart failure (HF). This meta-analysis aimed to assess differences in mortality between rural and urban patients presenting with AMI and HF., Methods: A systematic search of the literature was performed using PubMed, Embase, MEDLINE and CENTRAL for all studies published until January 16, 2024. A grey literature search was also performed using a manual web search. The following inclusion criteria were applied: (i) studies must compare rural patients to urban patients presenting to hospital with AMI or HF; and (ii) studies must report on mortality. The primary outcome was all-cause mortality. Comprehensive data were extracted including study design, patient characteristics (sex, age and comorbidities), sample size, follow-up period and outcomes. Odds ratios (ORs) were pooled with random-effects model. A subgroup analysis was performed to investigate causes for heterogeneity in which studies were separated based on in-hospital mortality, post-discharge mortality, and region of origin including North America, Europe, Asia and Australia., Results: In total, 37 studies were included (29 retrospective studies, 4 cross-sectional studies and 4 prospective cohort studies) in our meta-analysis; 24 studies for AMI, 11 studies for HF and 2 studies for both AMI and HF. This included a total of 21,107,886 patients with AMI (2,230,264 of which were in rural regions) and 18,434,270 patients with HF (2,655,469 of which were in rural regions). Rural patients with AMI had similar age (mean age 69.8 +/- 5.7; vs 67.5 +/- 5.1) and were more likely to be female (43.2% vs 38.5%) compared to urban patients. Rural patients with HF had similar age (mean age 77.1 +/- 4.4 vs 76.5 +/- 4.2) and were more likely to be female (56.4% vs 49.5%) compared to urban patients. The range of follow-up for the AMI cohort was 0 days to 24 months and the range of follow-up for the HF cohort was 0 days to 24 months. Compared with urban patients, rural patients with AMI had higher mortality rate at follow-up (15.5% vs 13.4%; OR 1.18, 95% CI, 1.13-1.24; I2 = 97%). Compared with urban patients, rural patients with HF had higher mortality rate at follow-up (12.3% vs 11.6%; OR 1.11, 95% CI, 1.11-1.12; I2 = 98%)., Conclusions: To our knowledge, this is the first systematic review and meta-analysis assessing mortality differences between rural and urban patients presenting with AMI and HF. We found that patients living in rural areas had an increased risk of mortality when compared to patients in urban areas. Clinical and policy efforts are required to reduce these disparities., (© 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.)

Axon guidance molecules are frequently altered in pancreatic ductal adenocarcinoma (PDA) and influence PDA progression. However, the molecular mechanism remained unclear. Using genetically engineered mouse models to examine semaphorin 3D (SEMA3D), we identified a dual role for tumor- and nerve-derived SEMA3D in the malignant transformation of pancreatic epithelial cells and invasive PDA development. Pancreatic-specific knockout of the SEMA3D gene from the KRAS G12D and TP53 R172H mutation knock-in, PDX1-Cre(KPC) mouse model demonstrated delayed tumor initiation, prolonged survival, absence of metastasis, and reduced M2 macrophage expression. Mechanistically, tumor- and nerve-derived SEMA3D indirectly reprograms macrophages through KRAS MUT -dependent ARF6 signaling in PDA cells, resulting in increased lactate production, which is sensed by GPCR132 on macrophages to stimulate protumorigenic M2 polarization. Multiplex immunohistochemistry demonstrated increased M2-polarized macrophages proximal to nerves in SEMA3D-expressing human PDA tissue. This study suggests that altered SEMA3D expression leads to an acquisition of cancer-promoting functions, and nerve-derived SEMA3D is "hijacked" by PDA cells to support growth and metastasis in a KRAS MUT -dependent manner.

Background: The inflammatory response to cardiopulmonary bypass (CPB) in pediatric patients remains an unresolved challenge. Sanguineous CPB prime, composed of allogenic blood products, is one potentially important stimulus. This study aims to identify specific inflammatory mediators active in sanguineous CPB prime and their impact on the inflammatory response at CPB initiation., Methods: In a post-hoc analysis of a prospective observational cohort study (NCT05154864), where pediatric patients undergoing cardiac surgery with CPB were enrolled after informed consent, patients were grouped by CPB prime type ( sanguineous vs crystalloid ). Arterial samples were collected post-sternotomy as a baseline and again at CPB initiation from all patients. In the sanguineous group, CPB prime samples were also collected after buffered ultrafiltration but before CPB initiation. Luminex® measured concentrations of 24 inflammatory mediators for comparison between groups. Statistical analyses were by Mann-Whitney test and Wilcoxon signed-rank test. Data are presented as median [IQR]., Results: Forty consecutive pediatric patients participated. The sanguineous group ( n = 26) was younger (4.0 [0.2 - 6.0] vs 48.5 [39.0 - 69.5] months; p = 2.6 × 10 -7 ) and smaller (4.9 [34 - 6.6] vs 17.2 [14.9 - 19.6] kg; p = 2.6 × 10 -7 ) than the crystalloid group ( n = 14). Despite this, baseline concentrations of 20 complement and cytokine concentrations were comparable between groups ( p > 0.05) while four showed differences between groups ( p < 0.05). The sanguineous prime contained supraphysiologic concentrations of complement mediators: C2, C3, C3a, C3b, and C5a. Correspondingly, upon CPB initiation, patients receiving sanguineous prime exhibited a significantly larger burden of C2, C3, C3b, C5, and C5a ( p < 0.001) relative to the crystalloid group. Cytokine and chemokine mediators were present at trace levels in the sanguineous prime., Conclusions: Sanguineous prime contains activated complement that accelerates the inflammatory response at CPB initiation in neonates and infants. Immunomodulatory interventions targeting complement during CPB prime preparation could offer substantial benefits for these vulnerable patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: There is limited evidence on how the physical health of children and young people (CYP) who are care experienced (eg, in foster or out-of-home care) compares to the general population. UK research suggests that the prevalence of some chronic conditions may be similar for these groups., Design: We undertook longitudinal population-wide data linkage of social care, prescription and hospitalisation records for care experienced and general population CYP born 1990-2004, followed from birth to August 2016. We compared prevalence estimates for asthma, diabetes (type 1) and epilepsy between the cohorts and used Poisson and survival models to estimate the association between social care and hospitalisations for these conditions., Results: Care experience was not associated with a higher prevalence of asthma and diabetes, but epilepsy was more prevalent. Care was associated with increased hospitalisation rates for all three conditions, particularly for males. HRs for hospitalisations were highest before and after care and lower while the child was in care, for diabetes these were, respectively 1.88 (95% CI 1.28 to 2.77), 2.40 (95% CI 1.55 to 3.71) and 1.31 (95% CI 0.91 to 1.88) for care experienced CYP compared with general population., Conclusions: Hospitalisations for chronic conditions are higher among care experienced CYP, particularly for males, and outside care episodes. Families with children with chronic conditions should be offered support to manage these conditions and help keep families together. Higher hospitalisations after care suggest that care leavers should be provided more support to help manage their health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Importance: Depression and eating disorders are heightened for adolescents with obesity. Clinical reviews alongside self-report questionnaires are important to ensure appropriate intervention., Objective: To evaluate changes in self-report symptoms of depression, eating disorders, and binge eating in adolescents with obesity during the Fast Track to Health trial., Design, Setting, and Participants: This was a randomized clinical trial conducted from 2018 to 2023. It was a multisite trial conducted at children's hospitals in Sydney, New South Wales, and Melbourne, Victoria, Australia, and included adolescents (13-17 years) with obesity (defined as adult equivalent body mass index ≥30; calculated as weight in kilograms divided by height in meters squared) and 1 or more related complications., Interventions: Duration was 52 weeks including a very low energy diet for 4 weeks followed by intermittent energy restriction (IER) or continuous energy restriction (CER)., Main Outcomes and Measures: Self-report symptoms of depression (Center for Epidemiologic Studies Depression Scale-Revised 10-Item Version for Adolescents [CESDR-10]; scores 0-30), eating disorders (Eating Disorder Examination Questionnaire [EDE-Q]; scores 0-6), and binge eating (Binge Eating Scale [BES]; scores 0-46) were assessed. Adolescents were screened for depression and eating disorders (weeks 0, 4, 16, and 52) and monitored for the onset of new symptoms of disordered eating during dietetic consults., Results: Of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) enrolled, median baseline EDE-Q score was 2.28 (IQR, 1.43-3.14), median baseline CESDR-10 score was 9.00 (IQR, 4.00-14.50), and median baseline BES score was 11.00 (IQR, 5.00-17.00). There were no differences between groups for change in CESDR-10 (mean difference at week 52, 0.75; 95% CI, -1.86 to 3.37), EDE-Q (mean difference at week 52, 0.02; 95% CI, -0.41 to 0.45), or BES (mean difference at week 52, -2.91; 95% CI, -5.87 to 0.05). The within-group reductions at week 4 were maintained at week 52, for CESDR-10 and EDE-Q, indicating reduced symptoms of depression and eating disorders. Within-group reductions on the BES were maintained in the IER group only. Seventeen adolescents (12.1%) required support or referral for depression and/or disordered eating, including 7 (5%; 5 IER, 2 CER) adolescents who experienced the onset or reemergence of symptoms during the intervention., Conclusions and Relevance: Results suggest that many treatment-seeking adolescents with obesity self-reported symptoms of depression and eating disorders. Although symptoms reduced for most, some required additional support. Obesity treatment is an opportune time to screen and monitor for depression and disordered eating., Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001630303.

Importance: Adolescent obesity requires effective and accessible treatment. Intensive dietary interventions have the potential to be used as adjunctive therapy for behavioral weight management., Objective: To examine the effectiveness of 2 diet therapies, delivered as part of an intensive behavioral weight management intervention, in adolescents with metabolic complications associated with obesity., Design, Setting, and Participants: This multisite, 52-week randomized clinical trial was conducted from January 31, 2018, to March 31, 2023, at 2 tertiary pediatric centers in Australia. Adolescents (aged 13-17 years) with obesity and 1 or more associated complications were included., Interventions: Intensive behavioral interventions, delivered by a multidisciplinary team, comparing intermittent energy restriction (IER) or continuous energy restriction (CER), with 3 phases: very low-energy diet (weeks 0-4), intensive intervention (weeks 5-16), and continued intervention and/or maintenance (weeks 17-52)., Main Outcomes and Measures: The primary outcome was body mass index (BMI) z score at 52 weeks in the IER vs CER group. Anthropometry, body composition, and cardiometabolic health were assessed at baseline and 52 weeks. The BMI z score and percentiles were determined using Centers for Disease Control and Prevention growth charts. Insulin resistance, dyslipidemia, and elevated hepatic function were assessed., Results: A total of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) were enrolled, 71 in the IER group and 70 in the CER group, and 97 (68.8%) completed the intervention, 43 in the IER group and 54 in the CER group. At week 52, both groups had reduced BMI z scores (estimated marginal mean change, -0.28 [95% CI, -0.37 to -0.20] for IER and -0.28 [95% CI, -0.36 to -0.20] for CER) and reduced BMI expressed as a percentage of the 95th percentile (estimated marginal mean change, -9.56 [95% CI, -12.36 to -6.83] for IER and -9.23 [95% CI, -11.82 to -6.64] for CER). No differences were found in body composition or cardiometabolic outcomes between the groups. Both groups had a reduction in the occurrence of insulin resistance (from 52 of 68 [76.5%] to 32 of 56 [57.1%] in the IER group and from 59 of 68 [86.8%] to 31 of 60 [57.1%] in the CER group) at week 16; however, at week 52, this effect was observed in the CER group only (from 59 of 68 [86.7%] to 30 of 49 [61.2%]). The occurrence of dyslipidemia was unchanged between baseline and week 52 (60 of 137 [42.6%] and 37 of 87 [42.5%], respectively), with a small improvement in occurrence of impaired hepatic function tests (37 of 139 [27.0%] and 15 of 87 [17.2%], respectively). No differences were found in dyslipidemia or hepatic function between groups., Conclusions and Relevance: These findings suggest that for adolescents with obesity-associated complications, IER can be incorporated into a behavioral weight management program, providing an option in addition to CER and offering participants more choice., Trial Registration: http://anzctr.org.au Identifier: ACTRN12617001630303.

Objectives: Early prevention strategies are needed to mitigate the high risk of cardiovascular disease in adolescents with type 1 diabetes (T1D). Residential neighbourhood features can promote healthy lifestyle behaviours and reduce cardiovascular risk, but less is known about their role in lifestyle behaviours in adolescents with T1D, and no studies used comparisons to healthy controls., Methods: We examined associations between residential neighbourhood features and lifestyle behaviours in adolescents with T1D and healthy controls. Data were analyzed from the CARdiovascular Disease risk factors in pEdiatric type 1 diAbetes (CARDEA) study, a cross-sectional investigation of 100 adolescents with T1D (14 to 18 years) from a pediatric diabetes clinic in Montréal, Canada, and 97 healthy controls. Outcomes included physical activity and sedentary behaviour (accelerometry), screen time and sleep duration (questionnaires), and dietary habits (24-hour recalls). Cluster analysis of selected neighbourhood indicators computed for participants' postal codes resulted in 2 neighbourhood types: central urban and peri-urban. Central urban neighbourhoods were characterized by very high population density, high active living index, numerous points of interest, higher social deprivation, higher residential mobility, and lower median household income compared with peri-urban neighbourhoods. Associations of neighbourhood type with lifestyle behaviours were estimated with multiple linear regressions and interactions by T1D status were tested., Results: Living in central urban neighbourhoods was associated with greater daily minutes of moderate-to-vigorous physical activity (beta = 8.61, 95% confidence interval 1.79 to 15.44) compared with living in peri-urban neighbourhoods. No associations were observed for other lifestyle behaviours, and no statistically significant interactions were found between neighbourhood type and T1D status., Conclusion: Features that characterize central urban built environments appear to promote physical activity in adolescents, regardless of T1D status., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: With high disease and disability burden in rural and remote regions, student-assisted clinics can be an effective workforce development tool to meet community health needs and workforce shortages. This research sought to identify the conditions under which student-assisted clinics can be successfully utilised as a workforce development strategy, with specific application to remote Queensland, Australia., Methods: A rapid review of the international literature in English was conducted. This was the most appropriate type of review because the results of the review were time-sensitive, with the student-assisted clinic model being trialled in Queensland soon. A mixed methods design was applied, with the search strategy piloted with one database., Results: Eleven studies met the inclusion criteria. Seven reported data on participant experiences, including consumers, students, services/clinics, and educators/supervisors/health professionals. Each of the studies operationalised student-assisted clinics through practice models (university-driven learning need), service delivery models (service driven need addressed through a student workforce), community need models (student delivered services primarily addressing a community health need), and blended models (practice need and community need). Some studies reported concerns about fragmentation of services, referral pathways and issues with follow-up, while others reported concerns about sustainable funding. All models reported successful outcomes when focused on service or consumer health outcomes, or student learning outcomes., Conclusions: Student-assisted clinics make an important contribution to the development of the rural and remote health workforce. Student-assisted clinics can complement and extend existing services, supporting workforce development in an overstretched health system impacted by an ongoing pandemic., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Repeat hospitalizations adversely impact the well-being of adults dually eligible for Medicare and Medicaid in the United States. This study aimed to identify behavioral, cognitive, and functional characteristics associated with the risk of a repeat hospital episode (HE) among the statewide population of dually eligible adults in Maryland receiving long-term services and supports prior to an HE between July 2018 and May 2020. The odds of experiencing a repeat HE within 30 days after an initial HE were positively associated with reporting difficulty with hearing (adjusted odds ratio, AOR: 1.10 [95% confidence interval: 1.02-1.19]), being easily distractible (AOR: 1.09 [1.00-1.18]), being self-injurious (AOR: 1.33 [1.09-1.63]), and exhibiting verbal abuse (AOR: 1.15 [1.02-1.30]). Conversely, displaying inappropriate public behavior (AOR: 0.62 [0.42-0.92]) and being dependent for eating (AOR: 0.91 [0.83-0.99]) or bathing (AOR: 0.79 [0.67-0.92]) were associated with reduced odds of a repeat HE. We also observed differences in the magnitude and direction of these associations among adults 65 years of age or older relative to younger counterparts., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Stockwell is co-founder of PreSquared, a health care analytics company. All other authors have no conflict of interest to declare. Technical advisors from CRISP, the HSCRC, and hMetrix provided feedback on the execution of this study. CRISP and the Maryland Department of Health reviewed and approved the manuscript for publication. The statements contained in this manuscript are solely those of the authors and do not necessarily reflect the views or policies of the sponsors.

The trailmaking test (TMT) has an educational bias that makes it inapplicable to people with low levels of education due to its dependence on the alphabet. The TMT standardization is the only one available in Chile, and there is a need for alternative ways of using the TMT that do not depend on the level of education for its applicability. To determine the normative scores of the TMT - black & white (TMT B&W), considering sociodemographic factors in adult and elderly Chilean population. A total sample of 227 participants (133 healthy, 94 cognitively impaired) from the Ageing Mets cohort were recruited from three areas in Chile (Antofagasta, Santiago, and Puerto Montt). The TMT B&W was administered to all participants. A multiple regression model was used to generate normative data only in the cognitively healthy group, considering the effect of age, education and sex. A significant effect of age was found in the score of the TMT B&W Parts A and B. The level of education influenced the part B of the test; however, the completion rate of the TMT B&W parts A and B was over 90% in cognitively healthy people. Norms for the number of errors were obtained, and differences between groups were found after controlling for the effect of age and education. This study is the first to provide normative data for the Chilean version of the TMT B&W and will benefit clinical neuropsychologists by improving the procedures for more accurately assessing executive functions and its impairments., (© 2024 The British Psychological Society.)

Background: Few longitudinal studies have investigated the role of weight-loss attempts or weight-related stress on body image during childhood. We examined whether weight-loss attempts and weight-related stress are associated with weight misperception and body dissatisfaction across childhood and adolescence. Methods: Data were drawn from the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort of Canadian children with parental obesity (8-10 years: n  = 630; 10-12 years: n  = 564; 15-17 years: n  = 377). We assessed weight-loss attempts and weight-related stress at baseline and first follow-up, and perceived and desired silhouettes at first and second follow-up with questionnaires. Weight misperception consisted of the difference in BMI z-score (zBMI) from the perceived silhouette and the measured zBMI. Body dissatisfaction consisted of the discordance between perceived and desired silhouettes. We estimated multivariable mixed-effects regression models adjusting for age, sex, pubertal stage, parental BMI and education, and sport-based teasing. Results: Weight loss attempts were associated with a higher weight misperception score (ever tried, beta [95% confidence intervals; CI]: 0.13 [0.01-0.24]) and with 2.13 times higher desire to be thinner (95% CI: 1.39-3.26) at the subsequent follow-up. Similarly, children stressed by their weight had a higher misperception score (beta [95% CI]: 0.15 [0.02-0.27]) and greater desire to be thinner at the next follow-up (odds ratio [95% CI]: 1.73 [0.999-3.00]). Conclusions: Weight-loss attempts and weight-related stress in children and adolescents are associated with weight misperception and body dissatisfaction, supporting empowerment and counseling focusing on healthy eating behaviors and a positive body image. Clinical Trial Registration Number: NCT03356262.

Introduction: Surgical repair is the standard of care for most infants and children with congenital heart disease. Cardiopulmonary bypass (CPB) is required to facilitate these operations but elicits a systemic inflammatory response, leading to postoperative organ dysfunction, morbidity and prolonged recovery after the surgery. Subzero-balance ultrafiltration (SBUF) has been shown to extract proinflammatory cytokines continuously throughout the CPB exposure. We hypothesize that a high-exchange SBUF (H-SBUF) will have a clinically relevant anti-inflammatory effect compared with a low-exchange SBUF (L-SBUF)., Methods and Analysis: The ULTrafiltration to enhance Recovery After paediatric cardiac surgery (ULTRA) trial is a randomised, double-blind, parallel-group randomised trial conducted in a single paediatric cardiac surgery centre. Ninety-six patients less than 15 kg undergoing cardiac surgery with CPB will be randomly assigned to H-SBUF during CPB or L-SBUF during CPB in a 1:1 ratio with stratification by The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) score 1 and STAT score 2-5. The primary outcome is peak postoperative vasoactive-ventilation-renal score. Time series and peak values of vasoactive-ventilation renal score, vasoactive-inotrope score, ventilation index and oxygenation index will be collected. Secondary clinical outcomes include acute kidney injury, ventilator-free days, inotrope-free days, low cardiac output syndrome, mechanical circulatory support, intensive care unit length of stay and operative mortality. Secondary biomarker data include cytokine, chemokine and complement factor concentrations at baseline before CPB, at the end of CPB exposure and 24 hours following CPB. Analyses will be conducted on an intention-to-treat principle., Ethics and Dissemination: The study has ethics approval (#1024932 dated August 31, 2021) and enrolment commenced in September 2021. The primary manuscript and any subsequent analyses will be submitted for peer-reviewed publication., Trial Registration Number: NCT04920643., Competing Interests: Competing interests: None declared., (© 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.)

Objective: To describe associations between cardiac abnormalities and Trypanosoma cruzi serostatus by use of a simplified diagnostic evaluation in dogs at risk for T cruzi infection., Methods: A prospective, cross-sectional study was performed using a simplified diagnostic evaluation including high-sensitivity cardiac troponin I, 30-second ECG, and echocardiogram with 7 variables in 46 client-owned dogs from high-risk environments. Dogs were categorized as serologically positive (SP), negative (SN), or discordant (SD) by use of 2 antibody tests. Functional evaluation of cardiac health scores and blood PCR were obtained., Results: Dogs were SP (n = 19), SN (17), and SD (10), with 9 PCR positive (7 SP, 1 SN, 1 SD). Troponin was above reference range in 6 of 46 (4 SP, 1 SN, 1 SD), and functional evaluation of cardiac health scores were 0 in all dogs. Conduction system abnormalities (prolonged interval durations, second-degree atrioventricular block, splintered QRS complex) and ventricular arrhythmias were documented in 8 (7 SP, 0 SN, 1 SD). Twenty-six (12 SP, 8 SN, 6 SD) had echocardiographic abnormalities, most often myxomatous mitral valve disease (MMVD) and left ventricular enlargement. Seropositive dogs were significantly older and had a higher likelihood of MMVD. Conduction system abnormalities were associated with positive serostatus., Conclusions: Echocardiographic abnormalities were complicated by MMVD and did not distinguish between serostatus. An ECG with assessment and detailed measurement of complexes and cardiac troponin I are simple tests to perform with abnormalities detected in seroreactive dogs., Clinical Relevance: Electrocardiographic abnormalities in high-risk or seroreactive dogs should prompt further evaluation and monitoring of T cruzi infection.

Objectives: People who use or would benefit from pre-exposure prophylaxis (PrEP) for HIV infection are disproportionately affected by sexually transmitted infections (STIs). Integrating STI services when offering PrEP fosters synergies and efficiencies in response to HIV/STI and promotes people-centred care. Including guidance on STI interventions for people on PrEP may facilitate implementation and uptake. We conducted a global review of national PrEP guidance documents and analysed the inclusion of recommendations for the provision of STI services by country level of income., Methods: We searched national PrEP guidance documents published by WHO Member States through the WHO, the Joint United Nations Programme on HIV/AIDS (UNAIDS) databases, the PrEPWatch repository and Google. Information on a range of STI-related interventions was extracted from documents available by October 2023., Results: Of the 113 national PrEP guidance documents retrieved, STIs were mentioned in 77% (90/117). Viral hepatitis B testing and vaccination were recommended by most high-income countries (HICs) and low-income and middle-income countries (LMICs). Recommendation for syphilis testing was prominent in HICs (91%) and moderately noted in LMICs (68%). Gonorrhoea and chlamydia testing was recommended frequently in HICs (88%) and 42% in LMICs. However, the review noted that, to a much lesser extent, specific type of testing for these pathogens was mentioned. Recommendation for quarterly STI testing for syphilis, gonorrhoea and chlamydia was ubiquitous, while the need to offer STI partner services was rarely mentioned., Conclusions: PrEP services offer an opportunity for improved and expanded STI services, increasing person-centred care and addressing STI epidemics alongside HIV. Our review highlights the strengths and gaps in incorporating critical STI interventions into national PrEP normative guidance. Addressing these gaps through a stepwise approach and increasing targeted testing and partner services can help improve quality of care and support an effective response to HIV and other STIs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Context: Surrogate measures of childhood and adolescent obesity have impaired the understanding of the relationship of body composition with insulin resistance in the young population., Objective: We aim to examine the longitudinal associations of directly measured total fat mass, trunk fat mass, and lean mass with the risk of hyperglycemia, hyperinsulinemia, and insulin resistance from ages 15 to 24 years, the mediation path through which lipids and inflammation influence insulin resistance, and whether increased fat mass temporally precede insulin resistance., Methods: We studied 3160 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, who had complete dual-energy x-ray absorptiometry measure and fasting blood samples at age 15 years and repeated measures at ages 17- and 24-years clinic visit. Fasting glucose greater than 6.1 mmol/L, insulin greater than 11.78 mU/L, and homeostatic model assessment for insulin resistance (HOMA-IR) greater than or equal to the 75th percentile were categorized as hyperglycemia, hyperinsulinemia, and high insulin resistance, respectively. Longitudinal associations were examined with generalized logit-mixed-effect models, while mediation and temporal path analyses were examined using structural equation models, adjusting for cardiometabolic and lifestyle factors., Results: Among 3160 participants (51% female), fat mass and lean mass increased linearly both in males and females, while glucose, insulin, and HOMA-IR had a U-shaped course from age 15 through 24 years. After full adjustment, each 1-kg cumulative increase in total fat mass (odds ratio 1.12 [95% CI, 1.11-1.13]) and trunk fat mass (1.21 [1.19-1.23]) from ages 15 through 24 years were associated with a progressively worsening risk of high insulin resistance as well as hyperglycemia and hyperinsulinemia. The association of increased total fat mass with increased insulin resistance was partly mediated by triglycerides (9% mediation). In the temporal path analysis, higher total fat mass at age 15 years was associated with higher insulin resistance at age 17 years, but not vice versa. Higher total fat mass at age 17 years was bidirectionally associated with higher insulin resistance at 24 years., Conclusion: Mid-adolescence may be an optimal time for interrupting the worsening fat mass-insulin resistance pathologic cycle and attenuating the risk of progressively worsening metabolic dysfunction before young adulthood., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: Predictive models have proliferated in the health system in recent years and have been used to predict both health services utilization and medical outcomes. Less is known, however, on how these models function and how they might adapt to different contexts. The purpose of the current study is to shed light on the inner workings of a large-scale predictive model deployed in 2 distinct populations, with a particular emphasis on adaptability issues., Methods: We compared the performance and functioning of a predictive model of avoidable hospitalization in 2 very different populations: Medicaid and Medicare enrollees in Maryland. Specifically, we assessed characteristics of the risk scores from March 2022 for the 2 populations, the predictive ability of the scores, and the driving risk factors behind the scores. In addition, we created and assessed the performance of an "unadapted" model by applying coefficients from the Medicare model to the Medicaid population., Results: The model adapted to, and performed well in, both populations, despite demographic differences in these 2 groups. However, the most salient risk factors and their relative weightings differed, sometimes dramatically, across the 2 populations. The unadapted Medicaid model displayed poor performance relative to the adapted model., Conclusions: Our findings speak to the need to "peek behind the curtain" of predictive models that may be applied to different populations, and we caution that risk prediction is not "one size fits all": for optimal performance, models should be adapted to, and trained on, the target population., Competing Interests: M.H. has 1 patent pending through his institution (US20220013238A1). F.H. has 1 patent pending through his institution (US20220013238A1). I.S. has 2 patents pending through his institution (US20220013238A1 and US20210407685A1). The remaining authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Executive functions (EFs) are a set of cognitive processes that enable individuals to manage and coordinate their thoughts and actions toward achieving specific goals. EFs include planning, organizing, initiating, and monitoring actions, and have been found to improve with age due to the maturation of the brain, especially during childhood. Therefore, our correlational study sought to determine the relationship between the performance in executive functions and age in 79 children (36 girls, 45.6%) throughout development, between the ages of 6 and 12 (mean = 9.25; SD  = 2.05), using a battery designed in Chile: BEFE ( Batería de Evaluación de las Funciones Ejecutivas : Executive Function Assessment Battery) based on traditional neuropsychological tests to evaluate Working Memory, Inhibitory Control, Cognitive Flexibility, and Planning skills. Our results showed various correlations between the variables age and performance in various behavioral parameters, demonstrating an increase in the number of correct responses (positive correlation) and/or a decrease in errors (negative correlation) with age (6-12) in the subtests that correspond to dimensions of Cognitive Flexibility (Semantic and Phonological Fluency, Card Sorting Game, and Tracing Tasks), Inhibitory Control (ENA-F and Sentence Completion), Working Memory (Audio-verbal WM Forward and Ordering, and Visuospatial WM Forward and Backward), and Planning (La Portada de Antofagasta and FISA Maps). These results are consistent with previous empirical evidence and support the notion of a developmental relationship between EF performance and age. Additionally, this study contributes to understanding EF development in culturally specific contexts, highlighting the importance of contextually relevant assessment tools in evaluating cognitive development.

Objective: This study investigated whether exposure to suboptimal gestational factors (SGFs) alters mechanical efficiency (ME) and substrate oxidation during rest and exercise in children as a mechanism contributing to obesity., Methods: Data from the Quebec Adiposity and Lifestyle Investigation in Youth cohort were used. Children aged 8 to 10 years performed an incremental maximal cycling test with indirect calorimetry. Their ME was measured during submaximal and maximal effort. The substrate oxidation during rest and submaximal effort was also computed. ME and substrate oxidation results between children exposed to each SGF during pregnancy (gestational diabetes mellitus: n = 68; hypertensive disorders: n = 49; maternal smoking: n = 77) and nonexposed children (n = 370) were compared., Results: No difference was observed for ME during submaximal (F [3,540]  = 0.46, p = 0.713) and maximal effort (F [3,545]  = 0.86, p = 0.463) between exposed and nonexposed children. The percentage contributions of lipids and carbohydrates did not differ during rest (F [3,545] =1.68, p = 0.169) or submaximal exercise (F [3,544]  = 0.31, p = 0.534) between exposed and nonexposed children., Conclusions: Children exposed to investigated SGFs display a similar physiological response regarding ME and substrate oxidation during rest and exercise compared to nonexposed children. Future studies should confirm these novel results and continue investigating other research avenues to explain the higher risk of obesity in this population., (© 2024 The Obesity Society.)

Background: The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively., Methods: By multiplex long-distance PCR or next-generation sequencing technology we characterized the BCR::ABL1 genomic fusion in 971 patients (adults and children, with CML and ALL: pediatric ALL: n = 353; pediatric CML: n = 197; adult ALL: n = 166; adult CML: n = 255 patients) and designed "Break-App" web tool to allow visualization and various analyses of the breakpoints. Pearson's Chi-Squared test, Kolmogorov-Smirnov test and logistic regression were used for statistical analyses., Results: Detailed analysis showed a non-random distribution of breaks in both BCR regions, whereas ABL1 breaks were distributed more evenly. However, we found a significant difference in the distribution of breaks between CML and ALL. We found no association of breakpoints with any type of interspersed repeats or DNA motifs. With a few exceptions, the primary structure of the fusions suggests non-homologous end joining being responsible for the BCR and ABL1 gene fusions. Analysis of reciprocal ABL1::BCR fusions in 453 patients showed mostly balanced translocations without major deletions or duplications., Conclusions: Taken together, our data suggest that physical colocalization and chromatin accessibility, which change with the developmental stage of the cell (hence the difference between ALL and CML), are more critical factors influencing breakpoint localization than presence of specific DNA motifs., (© 2024. The Author(s).)

Numerous pharmaceutical and industrial chemicals are classified as endocrine-disrupting chemicals (EDCs) that interfere with hormonal homeostasis, leading to developmental disorders and other pathologies. The synthetic estrogen 17α-ethynylestradiol (EE2) is used in oral contraceptives and other hormone therapies. EE2 and other estrogens are inadvertently introduced into aquatic environments through municipal wastewater and agricultural effluents. Exposure of male fish to estrogens increases expression of the egg yolk precursor protein vitellogenin (Vtg), which is used as a molecular marker of exposure to estrogenic EDCs. The mechanisms behind Vtg induction are not fully known, and we hypothesized that it is regulated via DNA methylation. Adult zebrafish were exposed to either dimethyl sulfoxide or 20 ng/L EE2 for 14 days. Messenger RNA (mRNA) expression and DNA methylation were assessed in male zebrafish livers at 0, 0.25, 0.5, 1, 4, 7, and 14 days of exposure; and those of females were assessed at 13 days (n ≥ 4/group/time point). To test the persistence of any changes, we included a recovery group that received EE2 for 7 days and did not receive any for the following 7 days, in the total 14-day study. Methylation of DNA at the vtg1 promoter was assessed with targeted gene bisulfite sequencing in livers of adult male and female zebrafish. A significant increase in vtg1 mRNA was observed in the EE2-exposed male fish as early as 6 h. Interestingly, DNA methylation changes were observed at 4 days. Decreases in the overall methylation of the vtg1 promoter in exposed males resulted in levels comparable to those in female controls, suggesting feminization. Importantly, DNA methylation levels in males remained significantly impacted after 7 days post-EE2 removal, unlike mRNA levels. These data identify an epigenetic mark of feminization that may serve as an indicator of not only estrogenic exposure but also previous exposure to EE2. Environ Toxicol Chem 2024;43:1547-1556. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA., (© 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: The aim of this study was to examine associations of childhood physical activity, sedentary behavior, and dietary intake with adiposity trajectories from childhood to adolescence. Methods: Quebec Adipose and Lifestyle Investigation in Youth (QUALITY) cohort ( n  = 630) data from 3 time points (8-10, 10-12, and 15-17 years) for 377 Caucasian children with parental obesity were analyzed. Height and weight, physical activity and sedentary behavior (7-day accelerometry), screen time (self-reported), and dietary intake (three 24-hour diet recalls) were measured. Group-based trajectory modeling identified longitudinal trajectories of body-mass index z-scores (zBMIs). Inverse probability of exposure-weighted multinomial logistic regressions examined associations between baseline lifestyles and zBMI trajectory groups. Results: Six trajectory groups were identified: Stable-Low-Normal-Weight (two groups, 5.7% and 33.0%, which were combined), Stable-High-Normal-Weight (24.8%), Stable-Overweight (19.8%), Stable-Obesity (8.8%), and Overweight-Decreasers (7.9%). For every additional portion of fruits and vegetables, the likelihood of being in the group of Overweight-Decreasers increased by 29% (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.09-1.55) compared with the reference group (Stable-Low-Normal-Weight). For every additional hour of sedentary behavior, the likelihood of belonging to the group of Overweight-Decreasers increased 2-fold (OR: 1.99, 95% CI: 1.28-3.21) and Stable-Obesity increased 1.5-fold (OR: 1.56, 95% CI: 1.08-2.23), compared with the reference. Every additional 10 minutes of moderate-to-vigorous physical activity was associated with a lower likelihood of belonging to the Stable-Obesity group (OR: 0.75, 95% CI: 0.61-0.89) and to the group of Overweight-Decreasers (OR: 0.79, 95% CI: 0.64-0.95) compared with the reference. Finally, children were more likely to belong to the Stable-Obesity group with each additional hour/day of screen time (OR: 1.23, 95% CI: 1.01-1.58). Conclusions: Trajectories of zBMIs from childhood to late adolescence were stable, except for one group which decreased from overweight in childhood to normal weight in adolescence. The latter had more favorable baseline dietary intake of fruits and vegetables. ClinicalTrials.org no. NCT03356262.

Cognitive decline, particularly in dementia, presents complex challenges in early detection and diagnosis. While Item Response Theory (IRT) has been instrumental in identifying patterns of cognitive impairment through psychometric tests, its parametric models often require large sample sizes and strict assumptions. This creates a need for more adaptable, less demanding analytical methods. This study aimed to evaluate the effectiveness of Mokken scale analysis (MSA), a nonparametric IRT model, in identifying hierarchical patterns of cognitive impairment from psychometric tests. Using data from 1164 adults over 60 years old, we applied MSA to the orientation subscale of ACE-III. Our analysis involved calculating scalability, monotone homogeneity, invariant item ordering (IIO) and response functions. The MSA effectively retrieved the hierarchical order of cognitive impairment patterns. Most items showed strong scalability and consistent patterns of cognitive performance. However, challenges with IIO were observed, particularly with items having adjacent difficulty parameters. The findings highlight MSA's potential as a practical alternative to parametric IRT models in cognitive impairment research. Its ability to provide valuable insights into patterns of cognitive deterioration, coupled with less stringent requirements, makes it a useful tool for clinicians and researchers., (© 2024 The British Psychological Society.)