Obesity

Preconception weight loss by metabolic-bariatric surgery (MBS) improves maternal-fetal outcomes, but little is known about its impact on offspring growth and health. The preconception bariatric surgery and child health outcomes (POSIT) study aims to estimate the effects of maternal MBS-induced preconception weight loss on infant and childhood body size, growth, and related outcomes. This report presents the methods used to construct the POSIT cohort and its baseline characteristics. This retrospective cohort study sampled members from a United States healthcare system aged 18 and older with a singleton, live birth to create three study groups: 1) a treatment group including women who underwent preconception MBS and subsequently became pregnant (n=1,374); 2) a control group matched to the MBS pre-surgery body mass index (BMI) (pre-surgery controls, n=13,740); and 3) a second control group matched to the MBS post-surgical, pre-pregnancy BMI (pre-pregnancy controls, n=13,740). MBS and pre-surgery BMI controls showed slight imbalances in that pre-surgery BMI controls were on average ~6 months younger, had 0.6 lower BMI (44.5 kg/m2) at the time of their pregnancy and were more likely to have become pregnant in earlier years than the MBS group prior to surgery. MBS and pre-pregnancy controls had comparable age (mean {+/-} SD 33 {+/-} 5 years), pre-pregnancy BMI (33 {+/-} 6 kg/m2), and year of delivery. Following matching, the MBS group had similar socioeconomic and health disparities as the pre-surgery control group, and both were worse than pre-pregnancy control group. Pregestational maternal comorbidity index improved after MBS and matched the pre-pregnancy controls. Upon extraction of offspring growth patterns and mediation analyses of maternal weight loss and metabolic responses to MBS, study findings will investigate effects of preconception weight loss by MBS on short- and long-term child health outcomes. Results will guide future studies focusing on improving maternal preconception weight and maternal-fetal outcomes.

This updated systematic review and network meta-analysis evaluated the efficacy and safety of obesity management medications (OMMs) in terms of reducing body weight and obesity related complications. Medline and Embase were searched up to 21 November 2025 for randomized controlled trials comparing OMMs versus placebo or active comparators in adults. The primary endpoint was percentage total body weight loss (TBWL%) at the end of the study. Secondary endpoints were TBWL% at 1, 2 and 3 years, anthropometric, metabolic, mental health and quality of life outcomes, cardiovascular morbidity and mortality, remission of obesity related complications, serious adverse events and all cause mortality. Sixty six RCTs (66 comparisons) were identified: orlistat (22), semaglutide (18), liraglutide (11), tirzepatide (8), naltrexone/bupropion (5) and phentermine/topiramate (2), enrolling 63,909 patients (34,861 and 29,048 with active compound and placebo, respectively). All OMMs showed significantly greater TBWL% versus placebo; tirzepatide and semaglutide exceeded 10% TBWL and showed the most favourable glycaemic effects. Semaglutide reduced major adverse cardiovascular events and all cause mortality. In dedicated complication specific trials, semaglutide and tirzepatide showed benefit on heart failure related outcomes; tirzepatide was associated with improved obstructive sleep apnoea syndrome and semaglutide with knee osteoarthritis pain remission. Tirzepatide and semaglutide were associated with improvements in metabolic dysfunction-associated steatohepatitis remission, and semaglutide with improvement in liver fibrosis. No OMMs were associated with an increased risk of serious adverse events. These updated results reinforce the need to individualize OMMs selection according to weight loss efficacy, complication profile and safety.

Background: The timing of energy intake could be important in the development of obesity. However, most observational evidence stems from adults, anthropometric defined obesity outcomes, single meal timing phenotyping, and traditional regression modeling. Objective: We aimed to describe meal timing patterns in adolescents and determine if they associated with fat mass by modeling the median and all other percentiles of the frequency distribution. Methods: We analyzed data from the Sleep and Growth Study 2 (S-Grow2, N=286, 12-13y). Participants completed 3-day 24-hour dietary recalls and time stamped eating occasions were used to define 8 meal timing traits, with aide from self-reported wake and bed timing. Principal component analysis (PCA) identified multi-dimensional meal timing patterns. Fat mass index (FMI) was estimated using dual energy X-ray absorptiometry. Quantile regression assessed if there were associations between meal timing traits and FMI across the entire FMI frequency distribution. Results: The typical first and last eating occasions were 8:00am (40 minutes after waking) and 8:00pm (2.7 hours before sleep), respectively, thus the eating period typically lasted 11.5 hours per day. The typical eating period midpoint was 2:15pm, and the timing when 50% of energy intake was consumed typically occurred at 3:15pm. PCA revealed three meal timing patterns: 1) Delayed Start, Condensed Eating Period (43% of variance; shorter eating period and delayed timing of first eating); 2) Late, Sleep Proximal Eating (30% of variance; later timing of last eating and extended eating period), and 3) Later Energy Intake (10% of variance; delayed energy intake midpoint). Higher scores for the Delayed Start, Condensed Eating Period pattern associated with higher body mass index and FMI at the upper tails of their distributions. Conclusions: Distinct multidimensional meal timing patterns emerged in early adolescence, with the delayed start, condensed eating period pattern potentially associated with higher adiposity.

We completed a video-based, four-night, in-home, level 3 sleep apnea study of healthy, low-risk pregnant participants and their bed partners in order to characterize sleep physiology in the third trimester of pregnancy. Demographic, anthropometric, and baseline sleep health characteristics were recorded, and the NightOwl home sleep apnea test device was used to measure sleep breathing, posture, and architecture parameters. Symptoms of restless legs syndrome were elicited in the exit interview. Forty-one pregnant participants and 36 bed partners completed the study. Bed partners had a significantly higher prevalence of sleep apnea than their pregnant co-sleepers (31% vs. 5.9%). Bed partners also had more severe sleep apnea than their pregnant co-sleepers, and this persisted on an adjusted analysis for baseline differences in factors known to increase risk of sleep apnea. In pregnant participants, increasing gestational age was found to be protective against mild respiratory events but not more severe events. While the correlation between STOP-Bang score and measures of sleep apnea severity was weak, an affirmative response to the witnessed apneas item on the STOP-Bang questionnaire was a strong predictor of more severe sleep apnea for all participants. Smoking history also increased sleep apnea risk. Pregnant participants had lower sleep efficiency and longer self-reported sleep onset latency. Restless legs syndrome was experienced by 39.5% of the pregnant participants but no bed partners. From a sleep breathing perspective, people with healthy, low-risk pregnancies have better sleep than their bed partners despite lower sleep efficiency and higher rates of restless legs syndrome.

STRUCTURED ABSTRACTO_ST_ABSImportanceC_ST_ABSSexual dysfunction can occur after midurethral sling (MUS) and transvaginal prolapse surgery. It remains unclear whether these procedures impact the clitoris, despite its role in sexual function and proximity to the MUS and vagina. ObjectivesTo compare postoperative sexual function and clitoral features by MUS and vaginal surgery approach after transvaginal prolapse repair with/without concomitant MUS. DesignCross-sectional ancillary study of magnetic resonance imaging (MRI) and sexual function data from the Defining Mechanisms of Anterior Vaginal Wall Descent study. SettingEight clinical sites in the US Pelvic Floor Disorders Network. Participants: 88 women with uterovaginal prolapse who underwent vaginal mesh hysteropexy or vaginal hysterectomy with uterosacral ligament suspension with/without MUS between 2013-2015. Data were analyzed between September 2021-June 2023. ExposuresBetween June 2014-May 2018, participants underwent pelvic MRI 30-42 months after surgery, or earlier if reoperation was desired. Sexual activity and function at baseline and 24-48-month follow-up were evaluated using the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR). Clitoral features were obtained from postoperative MRI-based 3-dimensional models. Main Outcomes and MeasuresPISQ-IR scores and clitoral features (size, position). ResultsEighty-two women (median [range] age, 65 [47-79] years) were analyzed: 45 MUS (22 hysteropexy, 23 hysterectomy) and 37 No-MUS (19 hysteropexy, 18 hysterectomy). Postoperatively, 25 MUS, 12 No-MUS, 20 hysteropexy, and 17 hysterectomy patients were sexually active (SA). Overall, within the MUS and vaginal surgery groups, sexual function remained unchanged or improved (most PISQ-IR change from baseline scores were [≥]0) among SA and NSA women. Among SA women after surgery, the MUS group (vs No-MUS) had a poorer PISQ-IR arousal/orgasm (SA-AO) score (median, 3.5 vs 4.3; P=.02). The hysteropexy group (vs hysterectomy) had less improvement in PISQ-IR SA-AO score (median, 0.0 vs 0.3; P=.01). Women with MUS (vs without) had a smaller clitoral glans thickness (median, 9.0 mm vs 10.0 mm; P=.008) and clitoral body volume (median, 2783.5 mm3 vs 3587.4 mm3; P=.01). Conclusions and RelevanceSA women with MUS (vs without) or hysteropexy (vs hysterectomy) experienced poorer postoperative sexual function. MUS was linked to a smaller clitoris. Future studies should explore surgery-induced changes in clitoral anatomy and sexual function. KEY POINTSO_ST_ABSQuestionC_ST_ABSHow do sexual function and clitoral anatomy differ by midurethral sling placement and vaginal surgery approach? FindingsThis cross-sectional study compared patient-reported sexual function outcomes and 30-42-month postoperative magnetic resonance imaging-based 3-dimensional clitoral models of 82 women after vaginal prolapse surgery with or without concomitant midurethral sling. Midurethral sling (vs no sling) and vaginal mesh hysteropexy (vs vaginal hysterectomy) were associated with poorer postoperative sexual function outcomes. Additionally, midurethral sling was associated with a smaller clitoral glans and body. MeaningMidurethral sling and vaginal mesh hysteropexy were associated with, and may adversely alter, postoperative sexual function and/or clitoral anatomy. VISUAL ABSTRACT/PROMOTIONAL IMAGE O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/26351291v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@904497org.highwire.dtl.DTLVardef@187514aorg.highwire.dtl.DTLVardef@e9e799org.highwire.dtl.DTLVardef@640f1a_HPS_FORMAT_FIGEXP M_FIG C_FIG

Objectives: To examine the pattern, magnitude, and demographic distribution of measurable improvements across five outcome parameters following three monthly pharmacist-led nutritional counselling sessions delivered to community-dwelling participants in semi-urban India. Design: Secondary analysis of interventional follow-up data from a prospective community-based study. Setting: Schools and colleges in Narasaraopeta, Andhra Pradesh, India, from September 2021 to March 2022. Participants: Of 1,200 participants assessed at baseline, 1,135 (94.6%) completed at least one counselling session and formed the analysis cohort. The age range was 10 to 60 years. The majority of participants, 92.4%, were aged between 11 and 20 years. All 1,135 were anaemic at baseline. Interventions: Three structured monthly counselling sessions were delivered by pharmacy students under qualified faculty pharmacist supervision. Each session included individualised dietary guidance, lifestyle modification advice, and culturally adapted written health education materials. Primary and secondary outcome measures: Cumulative proportion of participants achieving measurable improvement in body mass index (BMI), waist circumference (WC), hip circumference (HC), waist to hip ratio (WHR), and haemoglobin (Hb) concentration at each session, stratified by age group and sex. Results: All five parameters showed progressive cumulative improvement across sessions. By session three, 44 participants (3.6%) showed improved BMI, 39 (3.25%) achieved reduced WC, 34 (2.8%) reduced HC, 33 (2.75%) improved WHR, and 115 (9.5%) demonstrated improved Hb. Adolescents aged 11 to 20 years were consistently the most responsive subgroup. Haemoglobin showed the steepest improvement trajectory, rising from 1.75% at session one to 9.5% at session three, representing a 5.4 fold increase achieved through dietary counselling alone without pharmacological supplementation. Conclusions: Three monthly pharmacist led nutritional counselling sessions produce measurable and progressive improvements in both anthropometric and haematological outcomes in community settings. Adolescents are the most responsive population. These findings support the integration of pharmacists into community non communicable disease prevention programmes in India and provide a replicable low resource model applicable to comparable global settings.

BackgroundHypertension is the leading modifiable risk factor for ischemic stroke, yet the adequacy of preventative hypertension care in routine clinical practice remains suboptimal. Whether gaps in hypertension management represent missed opportunities for stroke prevention remains unclear. ObjectiveTo evaluate the association between hypertension care delivery and the risk of incident ischemic stroke. MethodsWe conducted a retrospective, matched, nested case-control study among adults with hypertension using electronic health record data from a large regional health system (2010-2024). Patients with a first-ever ischemic stroke were matched 1:2 to controls on age, sex, race and ethnicity, and calendar time. Three care metrics were assessed during follow-up: (1) outpatient visits with blood pressure (BP) measurement per year; (2) number of antihypertensive medication ingredients; and (3) medication intensification score. Conditional logistic regression estimated adjusted odds ratios (aORs). ResultsThe study included 13,476 cases and 26,952 matched controls (N = 40,428). Mean (SD) age was 64.8 (12.2) years, 54.1% were female, and mean follow-up was 2,497 (1,308) days. Cases had fewer BP visits per year (median, 2.50 vs. 3.01; p < 0.001), similar number of medication ingredients (2.00 vs 2.00), and lower treatment intensification scores (-0.211 vs - 0.125). In adjusted models, >5 BP visits per year was associated with lower stroke odds (aOR, 0.55; 95% CI, 0.51-0.59) compared with [&le;]1 visit. Use of 2-3 medication ingredients (vs 0) was also associated with reduced stroke odds (aOR, 0.80; 95% CI, 0.75-0.86), whereas >3 ingredients was not significant. The highest quartile of treatment intensification showed the strongest association (aOR, 0.47; 95% CI, 0.44-0.51). Findings were consistent across subgroup and sensitivity analyses, including strata defined by baseline SBP and follow-up SBP. ConclusionsGreater engagement in hypertension care was associated with lower odds of ischemic stroke, suggesting that gaps in routine management may represent missed opportunities for prevention.

ABSTRACT Background Medical students face demanding academic schedules and elevated stress levels, predisposing them to poor sleep quality. Sleep hygiene, a set of behavioural and environmental practices aimed at optimising sleep, has been identified as a modifiable determinant of sleep quality, yet its role among medical students in Sudan remains unstudied. Objectives To assess current sleep hygiene practices among medical students at UMST and determine their association with sleep quality outcomes. Methods A facility based cross-sectional study was conducted at UMST among 240 medical students from three academic batches (3rd, 4th, and 5th year), selected via stratified random sampling. Data were collected using two validated self administered instruments: the Pittsburgh Sleep Quality Index (PSQI) and the Sleep Hygiene Index (SHI). Descriptive statistics, independent sample t tests, one way ANOVA, chi-square tests, Pearson correlation, and binary logistic regression were performed using SPSS version 23. Results Poor sleep quality (PSQI >5) was prevalent in 72.1% of participants (mean PSQI 7.25 +/- 2.66), and poor sleep hygiene (SHI >16) in 92.5% (mean SHI 27.1 +/- 7.9). SHI score (continuous) was the only significant independent predictor of sleep quality on logistic regression (OR = 1.13 per unit increase; 95% CI: 1.08-1.19; p < 0.001), equivalent to a 3.4-fold increase in odds per 10-unit rise in SHI score. Female sex was additionally identified as a significant predictor (OR = 1.88; 95% CI: 1.00-3.53; p = 0.049). A significant positive correlation was observed between PSQI and SHI scores (r = 0.359, p < 0.001). Conclusion Poor sleep hygiene is highly prevalent among UMST medical students and is the most significant modifiable predictor of poor sleep quality, with each unit increase in SHI score increasing the odds of poor sleep quality by 13%. These findings highlight a gap in sleep health education within Sudanese medical institutions and support the integration of targeted sleep hygiene interventions into the medical curriculum. Keywords: sleep hygiene; sleep quality; medical students; Sudan; PSQI; SHI; cross-sectional study

Background: Few studies have examined racioethnic disparities in cardiovascular disease (CVD) in women after breast cancer treatment, who are at higher risk due to cardiotoxic cancer treatment. Methods: Based on the Pathways Heart Study of women with a history of breast cancer, this analysis examines the association between cardiometabolic risk factors (hypertension, diabetes, and dyslipidemia) and CVD events with self-reported race and ethnicity, as well as genetic similarity. Multivariable logistic and Cox proportional hazards regression models were used to test race and ethnicity and genetic similarity with prevalent and incident cardiometabolic risk factors and CVD events. Results: Of the 4,071 patients in this analysis, non-Hispanic Black (NHB), Asian, and Hispanic women were more likely to have prevalent and incident diabetes than non-Hispanic White (NHW) women. Analysis of genetic similarity revealed results consistent with self-reported race and ethnicity. For CVD risk, NHB women were more likely to develop heart failure and cardiomyopathy than NHW women. In contrast, Hispanic women were at lower risk of any incident CVD, serious CVD, arrhythmia, heart failure or cardiomyopathy, and ischemic heart disease, which was consistent with the associations found with Native American ancestry. Conclusions: This is the largest multi-ethnic study of disparities in CVD health in breast cancer survivors, demonstrating corroborating findings between self-reported race and ethnicity and genetic similarity. The results highlight disparities in cardiometabolic risk factors and CVD among breast cancer survivors that warrant more research and clinical attention in these distinct, high-risk populations.

Background: College-attending young adults frequently experience declines in diet quality, physical activity, and psychological well-being during the transition to independent living, contributing to weight gain during the first year of college. Although multicomponent lifestyle interventions have been developed to address these behaviors, the responsiveness to such programs could differ across demographic factors associated with health behaviors, such as sex, race, and ethnicity. Hence, this secondary analysis of large-scale college health trials evaluated whether the effectiveness of such interventions differed by these demographic factors. Methods: Data were combined from two multi-site randomized controlled trials: Young Adults Eating and Active for Health (YEAH) trial and the Get FRUVED trial. Both interventions used theory-based approaches to promote healthy weight management through improvements in diet quality, physical activity, and stress management. Baseline-adjusted linear regression models evaluated the effects of group (intervention, control) and its interactions with sex, race (White, Black, Other), or Hispanic ethnicity. Models were adjusted for baseline outcome values, baseline BMI, study (YEAH vs. FRUVED), and state of data collection. Results: Intervention participants reported higher fruit and vegetable intake, lower processed meat intake, and longer sleep duration compared with controls. However, there was significant heterogeneity in these dietary outcomes by ethnicity, race, and sex. Non-Hispanic participants in the intervention group had higher fruit and vegetable intake compared to controls (p < 0.05). And, within the intervention group, Hispanic females had lower bacon/sausage intake than Hispanic males and non-Hispanic females (p < 0.05). With respect to race, Black participants reported higher total processed meat intake than White and Other race participants (p <0.05). These demographic factors did not moderate the intervention's impact on physical activity, sleep duration, and perceived stress. Overall, the intervention appeared to be the least effective for Hispanic males who exhibited higher body weight and waist circumference compared with Hispanic females and non-Hispanic males (p < 0.05). Conclusions: Multicomponent lifestyle interventions can improve selected dietary outcomes among college students, but effectiveness may differ across demographic subgroups. Culturally and sex-tailored strategies that consider the intersecting influences of sex, race, and ethnicity may enhance intervention effectiveness during the transition to college.

Objective. Menopause is a significant physiological transition with implications for health outcomes (e.g., cardiometabolic), yet gaps remain in understanding the menopause transition, including how menopause timing and type influence health outcomes. Large-scale cohort studies in midlife (age~40-60) females, including the All of Us Research Program (AoURP), provide opportunities to study menopause across diverse populations and data modalities. We characterized menopause-related data in AoURP, focusing on age distributions and concordance between EHR diagnosis codes and self-reported survey responses. Methods. We analyzed menopause-related survey, EHR diagnostic code, and genomic data among ~396,000 participants in AoURP with female sex. We summarized menopause data across modalities, overlap between survey, EHR, and genomic data, and age distributions overall and across sociodemographic characteristics. Results. Among ~396,000 females, surveys captured ~193,000 menopause observations, nearly seven times more than structured EHR diagnoses (~28,000), suggesting under- ascertainement in EHR data. Nearly all females (~99%) with an EHR menopause diagnosis also reported menopause in the survey. Approximately 22,000 participants had intersected EHR, survey, and genomic menopause-related data. Survey-based age patterns matched expectations, with participants <40 years predominantly reporting pre-menopausal status and those >60 years predominantly reporting post-menopausal status. A small subset (N{approx}1,700; 4%) (age>70 years) reported no menopause, suggesting response or recall bias. EHR menopause codes were concentrated after age>45 years, with a notable spike at age 65. Modest differences in survey-based menopause age distributions were observed by sociodemographic characteristics (e.g., race, ancestry). Conclusions. These findings inform sampling strategies, power calculations, phenotype definition, and study design for menopause research using AoURP.

ObjectiveStudies of nutritional status and host responses during severe and critical illness have focused predominantly on obesity; in contrast, the relationship between undernutrition, host responses, and clinical outcomes in adults hospitalized with severe infection remains poorly defined. We sought to determine whether severe undernutrition is associated with distinct host responses and clinical outcomes in adults hospitalized with severe infection. DesignProspective cohort study. SettingTwo public referral hospitals in Uganda. PatientsNon-pregnant adults ([&ge;]18 yr) hospitalized with severe, undifferentiated infection. InterventionsNone. Measurements and Main ResultsWe analyzed clinical data and serum Olink proteomic data from 432 participants (median age, 45 yr [IQR, 31-57 yr]; 44% male). Overall, 213 participants (49%) met prespecified criteria for undernutrition, including 52 (12%) with severe undernutrition. Clinically, severe undernutrition was associated with HIV coinfection, microbiologically diagnosed tuberculosis, greater physiological instability, and higher mortality. After adjustment for age, sex, illness duration, study site, and HIV, malaria, and tuberculosis coinfection, severe undernutrition was associated with higher expression of proteins involved in pro-inflammatory immune signaling, endothelial and vascular remodeling, hypoxia and oxidative stress responses, and extracellular matrix remodeling, together with lower expression of proteins linked to growth signaling, anticoagulant regulation, and lipid homeostasis. ConclusionsSevere undernutrition is associated with a distinct high-risk clinical phenotype and biologic signature in adults hospitalized with severe infection. These findings suggest that undernutrition may potentiate key domains of sepsis pathobiology, with implications for strengthening nutritional support and informing host-directed treatment strategies in low- and middle-income countries where malnutrition is common. Key PointsO_ST_ABSQuestionC_ST_ABSHow does undernutrition influence immune, metabolic, and endothelial responses to severe infection in adults? FindingsIn this multicenter cohort study of 432 adults hospitalized with severe infection in Uganda, severe undernutrition was associated with greater physiologic instability, higher mortality, and a distinct proteomic host-response profile. Adults with severe undernutrition exhibited a proteomic signature characterized by pro-inflammatory immune signaling, endothelial and extracellular matrix remodeling, and hypoxia and oxidative stress responses, together with lower expression of proteins involved in growth signaling, anticoagulant regulation, and lipid homeostasis. MeaningSevere undernutrition is associated with a distinct high-risk clinical and biologic phenotype during severe infection, with implications for nutritional support, risk stratification, and host-directed therapeutic strategies, particularly in low- and middle-income countries.

IntroductionOver one billion people worldwide have hypertension. In Zimbabwe, prevalence is an estimated 38%, surpassing the global average of 34%, and >50% of hypertensives are undiagnosed. The Community BP groups (Com-BP) study examined whether community groups of people living with hypertension, provided with BP machines and led by trained Facilitators could improve awareness, screening and support for those diagnosed with hypertension, to help blood pressure (BP) control. We present findings from the quantitative evaluation of the Com-BP pilot intervention. MethodsThe acceptability of the Com-BP intervention, its potential effectiveness in improving knowledge, attitudes and practices (KAP) and in reducing BP among hypertensive adults in Zimbabwe, was evaluated. Cross-sectional surveys using standardised questionnaires, and BP and Body Mass Index (BMI) assessments, were done at the start and end of the pilot intervention. Statistical evidence of difference between baseline and follow-up was examined using Wilcoxon signed-rank test for continuous data and McNemars test for categorical data. ResultsFourteen groups (seven urban and seven rural) were formed and 151 participants joined over a median of 5months. Retention in the groups was 97.9% (137/140 recruited at baseline), with approximately equal numbers from the urban and rural sites. Median age at baseline was 54 years (IQR 45-66y; min-max 30-92y) and the majority (79%, n=108) were female. Most participants (82.5%, n=113) rated their experience of the group sessions as excellent. The proportions of participants with changes in KAP from baseline to endline were as follows: 45.3% (n=62) to 81.0% (n=111) (p=0.004) able to identify at least two pre-disposing factors for hypertension; 65.0% (n=89) to 77.4% (n=106) (p=0.02) reporting [&ge;]1day of vigorous physical activity/week; 28.5% (n=39) to 13.9% (n=19) (p=0.001) reporting salt added to meals at the table. There was no statistical evidence of any difference in medication adherence, p=0.06. The proportion of participants with uncontrolled hypertension was 58.1% (n=79) at baseline and reduced to 31.8% (n=43) at follow-up (p<0.001). DiscussionCommunity groups for improving awareness, detection and support are acceptable and led to improvements in self-reported KAP and prevalence of uncontrolled BP. Further research on the sustainability and impact of the intervention is required.

Excess body weight has been associated with increased cancer risk, but the role of weight change across adulthood remains unclear. We examined body weight trajectories from ages 17 to 60 and their associations with site-specific cancer incidence. Data were based on the ODDS study, a pooled, nationwide cohort study in Sweden, with data on weight spanning 1911 to 2020, and cancer follow-up through 2023. Weight trajectories were estimated with linear mixed effects models in individuals with at least three weight measurements. Cox regressions estimated hazard ratios for associations between weight trajectories and established and potentially obesity-related cancers. Fifth versus first quintile of weight change was associated with many cancers, most strongly with esophageal adenocarcinoma in men (HR 2.25; 95% CI 1.66-3.04), liver cancer in men (HR 2.67; 95% CI 2.15-3.33), endometrial cancer in women (HR 3.78; 95% CI 3.09-4.61), and pituitary tumors in both sexes (men: HR 3.13 [95% CI 2.13-4.61]; women: HR 2.13 [95% CI 1.41-3.22]). Associations varied by sex and age. Heavier weight at age 17 years and earlier obesity onset were also associated with higher cancer incidence. These findings highlight the importance of a life-course approach to weight management and support sex- and age-targeted cancer prevention strategies.

BackgroundPractical alcohol risk-reduction strategies are widely recommended in public-facing alcohol guidance, but randomized evidence from socially interactive drinking episodes remains limited. We conducted a pilot cluster randomized trial to evaluate the feasibility and preliminary effects of a package intervention comprising practical drinking-strategy information, participant self-selection of same-day strategies, and a brief commitment declaration in a social drinking laboratory. MethodsThis single-center, parallel-group pilot trial was conducted in Japan. Pre-existing social groups participated. One or two groups scheduled in the same session slot were combined into a time-slot allocation unit, which was randomized 1:1 either to the package intervention or to alcohol-related knowledge only. The primary outcome was total pure alcohol intake during the first 120 min. Session satisfaction on a Visual Analog Scale (VAS) was a prespecified secondary participant-experience outcome. ResultsOf 83 interested individuals, 63 were randomized and 59 participants in 17 social groups and 12 allocation units were included in the modified intention-to-treat analysis. The mean paired intervention-control difference for 120-min alcohol intake was-8.84 g (95% confidence interval [CI]-27.92 to 10.23; exact sign-flip p = 0.281). The corresponding exploratory 0-30 min difference was-4.90 g (95% CI-10.48 to 0.68; exact sign-flip p = 0.094). In a genotype-adjusted participant-level sensitivity analysis, the intervention coefficient for 120-min intake was-16.0 g (95% CI-30.9 to-1.1; p = 0.036). Session satisfaction was high in both arms with no clear between-arm difference. Next-day follow-up was 100%, and no adverse-event-related discontinuations occurred. ConclusionsThe intervention was feasible to deliver in a socially interactive drinking setting, and session satisfaction was high in both arms. Primary allocation-unit estimates favored lower alcohol intake but were imprecise. Larger trials are needed to estimate effects more precisely, while considering the potential influence of genotype imbalance on effect estimation in East Asian samples. Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000060685. Registered 17 February 2026.

Background: Narcolepsy is a debilitating sleep disorder caused by hypocretin deficiency. Aside from its role to induce wakefulness, hypocretin is linked to modulated appetite and metabolism, often resulting in weight gain. Study objectives: We aimed to unravel the comprehensive epidemiological connection between narcolepsy and major cardiometabolic outcomes. Methods: We analyzed cardiovascular and metabolic disease distribution in the FinnGen study. Using longitudinal electronic health records, we assessed associations between narcolepsy, cardiac/metabolic markers, and prescriptions for relevant drugs. Results: Our findings demonstrate significant associations between narcolepsy and metabolic traits (OR [95% CI] = 2.65 [1.81, 3.89]) as well as stroke (OR = 2.36 [1.38, 4.04]). Narcolepsy patients exhibit a less favourable metabolic profile, including higher glucose levels (OR = 1.1143 [1.0599, 1.1715]) and dyslipidaemia. This is supported by increased prescriptions of insulin (OR = 2.269 [1.46, 3.53]), simvastatin (OR = 2.292 [1.59, 3.31]), and metformin (OR = 2.327 [1.66, 3.25]), reflecting high metabolic disturbances. Furthermore, positive associations with antihypertensive and antiplatelet medications were observed, consistent with elevated cardiovascular risk. Conclusion: Taken together, our findings highlight the cardiometabolic burden in narcolepsy. This study enhances understanding of the metabolic and cardiovascular consequences of narcolepsy and offers timely guidance for effective disease control.

Childhood obesity remains a pressing global health challenge, yet the impact of dynamic adiposity changes during active developmental window retains poorly understood. Leveraging longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study (N=8519 at baseline; N=1873 at 4-year follow-up), our study reveals distinct neurodevelopmental implications of central fat dynamics during adolescence. At baseline, central fat indices (body roundness index, BRI / waist-to-height ratio, WHtR) outperformed BMI in predicting cognitive deficits, showing robust associations with impaired inhibitory control and episodic memory. The prediction effect was partially mediated by cortical changes in prefrontal and temporal regions. Longitudinally, the rate of fat accumulation ({Delta}) emerged as a critical predictor: faster adiposity accrual predicted attenuated cortical thinning (i.e., slower development) in parietal lobes and poorer executive function at follow-up, while baseline adiposity showed no significant effects on the follow-up brain morphology or cognitive development. Notably, subgroup analyses uncovered that obese adolescents with central fat reduction exhibited accelerated cortical thinning in posterior cingulate (change difference p=0.006-0.029) alongside rapid improvement in inhibitory control (Flanker slope difference p<0.05), whereas those with persistent adiposity showed delayed thinning in the postcentral gyrus. The study reveals that central fat (BRI/WHtR) is closely linked to neurocognitive risks, and longitudinal fat accumulation?rather than baseline adiposity?drives cortical alteration. Notably, fat reduction activated adaptive neural change in obese adolescents, underscoring the importance of weigh regulation during neurodevelopment.

This cross-sectional derivation and internal validation study aimed to develop and internally validate a clinical triage scoring system (CTSS) for field-based identification of collegiate athletes requiring priority intervention for lumbopelvic-hip (LPH) dysfunction. A total of 864 collegiate athletes (mean age 21.3 {+/-} 2.4 years; 80.8% male) were recruited from 10 universities. Participants underwent standardized assessments including demographic characteristics, clinical history, and LPH functional testing. Using an expert-adjudicated binary reference standard (priority intervention vs self-management), a multivariable logistic regression model was developed to derive the weighted CTSS. Model performance was evaluated using discrimination, calibration, and decision curve analysis (DCA), and internal validation was performed using 1,000 bootstrap resamples. Of the 864 participants, 463 athletes (53.6%) were classified as requiring priority intervention. The final 14-factor CTSS comprised 12 positive-weight predictors, such as localized LPH pain, muscle weakness, and higher body mass index, and 2 negative-weight predictors, positive Lasegues sign and hamstring weakness, which functioned served as safety-related modifiers. The model demonstrated acceptable discrimination (AUROC = 0.851, 95% CI: 0.824-0.876), with minimal optimism (optimism-corrected AUROC = 0.842) and excellent calibration (calibration slope = 1.000; calibration intercept = 0.000). A total score of [&ge;]9 was identified as the optimal threshold, yielding a sensitivity of 84.4% and specificity of 71.8%. DCA showed greater net benefit than treat-all and treat-none strategies across clinically relevant threshold probabilities (20%-50%), with a net benefit of 0.319 at a 50% threshold probability. The CTSS may provide a pragmatic field-based triage tool to support early identification of athletes who may require priority intervention, although external validation is needed before broader implementation in sports medicine settings.

Non-invasive glucose monitoring (NIGM) has been pursued for decades, yet no device has achieved regulatory approval despite numerous studies reporting high accuracy. This systematic review and meta-analysis of 32 studies (38 cohorts: 20 NIGM, 18 iCGM; N = 1,693) investigated methodological factors underlying this accuracy-regulatory gap. The pooled Mean Absolute Relative Difference (MARD) for NIGM (10.21%; 95% CI: 8.73-11.69%) showed no significant difference from iCGM (11.82%; 95% CI: 10.36-13.29%; p = 0.13), with extreme heterogeneity (I^2 = 95.2%). Meta-regression revealed that study duration was the strongest predictor of NIGM accuracy ({beta} = 3.94, p < 0.001), with MARD degrading from 8.7% in short-term to 15.2% in long-term studies, while iCGM accuracy remained stable. Only 15% of NIGM cohorts validated in the hypoglycemia range, compared to 89% of iCGM studies (p < 0.001). These findings suggest that reported NIGM accuracy is substantially influenced by methodological asymmetries.

Obesity affects one in three adults and is complicated by adipose inflammation, lipotoxicity and cell death. We previously identified RIPK1 as a genetic determinant of human obesity risk and adipose inflammation. Because RIPK1 is the apical kinase in the necroptosis pathway upstream of RIPK3 and the executioner protein MLKL, and emerging evidence links MLKL to lipid metabolism, MLKL has surfaced as a potential metabolic regulator. However, conflicting findings in Mlkl knockout mice fed a high fat diet have left its therapeutic relevance unresolved. MLKL has not been previously targeted through therapeutic knockdown in vivo in the context of diet-induced obesity. Here, we evaluated two independent MLKL antisense oligonucleotides (ASOs) in high fat diet (HFD)-fed C57BL/6J mice. In a 24-week progression model, MLKL ASO markedly reduced body weight, fat mass and hepatic steatosis compared with controls, while preserving lean mass. MLKL knockdown also lowered the respiratory exchange ratio, indicating a shift toward increased fat oxidation. In the intervention model, once obesity was established after 12 weeks of HFD feeding, both MLKL ASOs, and similarly, two independent RIPK1 ASOs, reversed weight gain and improved systemic glucose control. In vitro, MLKL-CRISPR/Cas9 knockout blocked 3T3-L1 adipogenesis, indicating a requirement for MLKL during adipocyte differentiation. However, in mature adipocytes, MLKL siRNA reduced palmitic acid-induced lipid accumulation, increased isoprenaline-stimulated lipolysis, and prevented TNF-mediated suppression of insulin-mediated AKT signalling and glucose uptake. Collectively, these findings demonstrate that partial MLKL suppression reprograms whole-body energy metabolism, enhances insulin sensitivity and limits diet-induced adiposity. MLKL, therefore, represents a promising and mechanistically novel therapeutic target for obesity and insulin resistance.