Appetite

Background: Childhood obesity is a prevalent public health concern, particularly among children from marginalized backgrounds. Epigenomic mechanisms, including DNA methylation (DNAm), offer insight into the biological embedding of metabolic risk, yet protective family-level factors remain understudied. This study examined whether participation in a positive parenting intervention was associated with reduced epigenetic cardiometabolic risk among preschool-aged children. Methods: Participants were 74 children (n = 35 intervention; n = 39 services-as-usual; mean age = 36 months). Using a secondary analysis of a randomized controlled trial, DNAm-derived body mass index (BMI) and anthropometric BMI were assessed at baseline and 12-month follow-up, and parenting practices were observed post-treatment. Results: Children in the intervention group demonstrated significantly lower DNAm BMI at 12 months relative to controls, adjusting for child sex, race and/or ethnicity, and anthropometric BMI. No treatment effect was observed for anthropometric BMI, and DNAm BMI was not associated with anthropometric BMI at 12 months. Although parenting practices improved, they did not mediate intervention effects on DNAm-derived BMI. Conclusions: Parenting interventions may influence biological pathways related to cardiometabolic risk, even before changes in anthropometric outcomes, underscoring the potential of family-centered approaches to promote early metabolic health.

Insulin resistance, an often-untreated precursor of type 2 diabetes mellitus (T2DM), is implicated in cognitive decline in adults, yet its impact on the developing brain in youth with obesity remains poorly understood. We investigate whether insulin resistance moderates the relation between hippocampal volume and unhealthy food-seeking in overweight and depressed youth ages 9-17 who completed an oral glucose tolerance test and a cognitive task assessing unhealthy food-seeking motivation at baseline, 6-, and 24-months follow-up, and structural MRI at baseline and 6-months follow-up. Insulin sensitivity moderated this relation: smaller baseline hippocampal subfield volumes predicted increased unhealthy food-seeking over 24 months (ps<0.05). Categorical grouping revealed subfield CA2/3 and 4 volumes predicted this relation among insulin-resistant (ps<0.05), but not insulin-sensitive (ps>0.10), youth, suggesting that threshold criteria for insulin resistance are physiologically meaningful. These findings identify a neuro-metabolic risk phenotype that precedes T2DM and may accelerate unhealthy food-seeking severity in youth with obesity.

Abstract Background and Objective: To investigate the efficacy of a new, proprietary high-resistance potato starch as a prebiotic in comparison to inulin and a control. Methods: In this prospective study, an intervention of 9 g of resistant potato starch (RPS, Potatodaat), inulin, or accessible corn starch was given to participants with mild to moderate indigestion for 30 days. Short chain fatty acid (SCFA) levels, changes to the gut microbiome, and changes in clinical symptoms of indigestion were assessed as primary outcomes. Results: Subjects in the RPS (n = 22), inulin (n = 23), and accessible corn starch (n = 22) groups demonstrated similarity in age, sex, and baseline parameters. At 30 days, the groups experienced 21.1%, 6.29%, and 9.15% increases in stool butyrate, respectively. Clinical symptoms like indigestion and flatulence showed greater improvement with the use of RPS compared to the other two groups. Conclusion: Consumption of high resistance potato starch helps improve stool SCFA levels along with clinical symptoms related to digestion, showing its better prebiotic potential as compared to inulin and accessible corn starch. The new high-resistance potato starch can be considered an effective replacement for inulin.

Background Child stunting and wasting affect millions globally, with unexplained heterogeneity across LMICs. Staple foods - rice, wheat, maize, sorghum, millet and cassava - differ in protein quality (DIAAS) and zinc bioavailability. We hypothesised that these differences explain heterogeneity in undernutrition prevalence. Methods This ecological cross-sectional analysis included 127 LMICs (wasting) and 126 LMICs (stunting) using JME 2025 anthropometric data, GBD 2023 estimates and FAOSTAT 2019-2023 five-year mean food balances. Each staple was analysed individually using robust MM-estimation (primary) and quantile regression (secondary), with fixed covariates selected after circularity, correlation and multicollinearity assessment. Five sensitivity analyses tested robustness. Two secondary cross-reference analyses - WHZ, MUAC and oedema across 46 nationally representative surveys and undernutrition in infants under 6 months across 56 DHS datasets - were cross-referenced with dominant dietary staple supply. A post-hoc cross-reference analysis examined maternal short stature and low BMI by dominant dietary staple using DHS data. Findings Sorghum (beta=0.361, p<0.001) and rice (beta=0.086, p=0.004) were positively associated with wasting while Maize was negatively associated (beta=-0.139, p=0.004). Cassava showed a positive, borderline association with stunting (beta=0.975, p=0.092). HIV showed a negative wasting association reversing on exclusion of high-HIV countries. Secondary analyses confirmed MUAC-predominant wasting in cassava- and maize-dominant countries and WHZ-predominant wasting in sorghum- and millet-dominant countries. Interpretation The above findings are consistent with staple-specific growth phenotypes. Currently DHS and MICS surveys collect height and weight only - incorporating MUAC and individual staple dietary data appears imperative. Preventive measures may differ by staple context. Funding No funding was received.

Background: Prolonged unsupplemented spiritual fasting (USF), complete caloric abstinence motivated by spiritual practice, is undertaken by many communities worldwide, yet its physiological consequences remain poorly characterized. No prior study has documented continuous real-time monitoring during free-living fasting beyond 10 days. Methods: We conducted a self-controlled observational study of 23 experienced Jain practitioners undergoing USF. Seventeen completed at least 8 days of fasting (11 completed eight days, six continued to 30 days); six discontinued early. Continuous glucose monitoring (CGM) and blood biomarkers at baseline (Day-0), post-fasting (Day-9), and 60-day follow-up (Day-69) were obtained. Mood was assessed daily using PANAS. Within-participant comparisons used both parametric and non-parametric t-tests. Results: CGM revealed near-complete suppression of glycaemic variability within 24-48 hours of fasting onset, sustained throughout with no clinical hypoglycaemia in either cohort. Blood biomarkers showed transient perturbation during fasting -- including rises in hepatic enzymes, bilirubin, uric acid, creatinine, and lipid fractions -- broadly reversible by follow-up (Day-69). hsCRP rose during fasting then fell below baseline at follow-up (5.52{+/-}13.67 to 3.68{+/-}13.18 mg/L, p=0.034). HDL significantly rose above baseline (45.71{+/-}112.32 to 48.97{+/-}111.19, p=0.045) and LDL similarly declined below baseline (122.33{+/-}132.10 to 106.96{+/-}131.62 mg/dL, p=0.035); and then both significantly improved by follow-up. Thyroid axis suppression fully normalized by follow-up. Psychological wellbeing was maintained throughout. Conclusions: Extended USF produces a safely reversible pattern of acute physiological adaptation with net cardiometabolic benefit. Absence of clinical hypoglycaemia during 30-day water-only USF, documented here for the first time with CGM, provides empirical grounding for future controlled trials.

Background: Short-chain fatty acids (SCFAs) are microbial metabolites with immunoregulatory properties. Human milk contains SCFAs which have been proposed as potential modulators of infant immune development. We aimed to examine associations between human milk SCFA concentrations and infant allergic disease outcomes in a high-risk cohort of infants of atopic mothers. Methods: SCFAs were measured by targeted liquid chromatography-mass spectrometry in human milk samples collected at 3 and 6 months postpartum from atopic mothers enrolled in the Infant Fish Oil Supplementation (IFOS) Study (n=147). Associations between milk SCFA concentrations and early childhood allergic disease outcomes (atopic dermatitis, food allergy, allergic rhinitis, and allergen sensitisation at 1 and 2-3 years) were examined using logistic regression. Results: Human milk SCFA concentrations were broadly stable between 3 and 6 months postpartum, except for acetate which was significantly elevated at 6 months. No significant associations were observed between human milk SCFA concentrations and any allergic disease outcome after correction for multiple comparisons (all p>0.05). Conclusions: Human milk SCFA concentrations are not associated with allergic disease outcomes up to 4 years of age. These findings suggest that oral SCFA exposure via human milk is insufficient to reduce infant allergy risk, and that gut SCFA production may be a more relevant target for future allergy prevention research.

Background. Patients on GLP-1 medications lose very different amounts of weight, and most published prediction models include only patients who complete six months. That design omits everyone who disengages earlier, which is the majority of the cohort. We built a tool that includes patients who disengage and delivers useful predictions at the week-8 visit, where the clinical decision is actually made. Methods. Beginning with 237,800 adults enrolled in a US telehealth GLP-1 program, we required a documented week-8 weight, a refill-confirmed dose, and reported ethnicity, yielding an analytic cohort of 22,538. We answered three questions: the patient's likely six-month weight loss and our confidence in it; the probability of dropout before six months; and when weight loss plateaus. For the first, we fit a cubic in week-8 percent loss plus 16 covariates, with quantile-regression bands at the 10th and 90th percentiles for the prediction interval, checking fractional-logit and isotonic recalibration as alternatives. For the second, we fit a logistic regression and compared it to gradient boosting. For the third, we fit a per-patient exponential trajectory among patients with at least four weight observations. We trained on enrollments before 2024-07-01 and tested on later ones, compared completer outcomes to published RCTs, and tested the week-8 anchor against measurements at weeks 2, 4, 6, 8, 10, 12, 16, and 20. Results. Mean six-month weight loss in completers was 11.7% on semaglutide and 14.1% on tirzepatide, in line with STEP-1 and SURMOUNT-1. Six-month disengagement was 66%. The prediction model reached test R2 = 0.65 with a mean absolute error of 2.76 percentage points. Calibration was strong: calibration-in-the-large was -0.52 pp and the calibration slope was 0.96. The 80% quantile-regression interval covered 76% of test patients; the 95% interval covered 93%. The disengagement model reached test AUC 0.79, against 0.74 for gradient boosting. Median plateau time among engaged patients was 387 days, longer in lower-BMI tertiles. The week-8 anchor gave R2 = 0.65, compared to 0.48 to 0.61 at earlier weeks and 0.67 to 0.91 at later weeks. We chose week 8 because 80% of slow responders reach their post-titration decision point at or before that visit. Two of twenty subgroup cells had reduced predictive accuracy; two more were too sparse to validate. Conclusions. Observed week-8 weight loss is the strongest predictor of six-month outcome. The model's accuracy (R2 = 0.65, MAE 2.76 pp) is appropriate for calibrating expectations and identifying patients for the post-titration decision, but not precise enough to drive that decision on its own. Disengagement is predictable at week 8 with AUC 0.79. Engaged patients plateau at a median of 387 days. Week 8 is the earliest visit at which titration is mostly complete, accuracy is in a useful range, and the post-titration decision remains actionable; later anchors predict better but inform a decision that has already been made for most patients. The model is temporally (internally) validated but not yet externally validated, and because it was developed on a single platform it should be regarded as a recalibration target rather than a drop-in deployment elsewhere. The tool is published as a public web calculator to support shared decision-making, though it is not precise enough on its own to drive an irreversible clinical decision. It is prognostic, not therapeutic; treatment-effect estimation is addressed in companion work.

This review evaluates the biological pathways linking soft drink consumption with the risk of several cancers within the framework of the Global Cancer Update Programme (CUP Global). Soft drink consumption has been associated with increased risk of multiple cancers, and glucose or insulin dysregulation has been proposed as a potential underlying mechanism. We applied a three-stage framework. In the first stage, we identified insulin sensitivity as the key biological process potentially linking soft drink consumption (sugar-sweetened or artificially sweetened) to cancer risk, with glucose-related and insulin-related biomarkers as potential intermediate phenotypes, using a combination of expert knowledge and a web-based text mining tool. In the second stage, we conducted targeted PubMed searches to identify studies examining associations between consumption of soft drinks and these intermediate phenotypes (IPs) and between these IPs and the risk of several cancers in adult humans. In the third stage, the evidence was evaluated by the Expert Committee on Cancer Mechanisms (MEC), who assessed the strength of the evidence for these associations. The MEC concluded that there was weak evidence supporting a role of glucose or insulin-related processes as a potential mechanistic pathway linking the consumption of sugar-sweetened or artificially sweetened beverages to the risk of various cancers evaluated.

Background: Bidirectional next-day associations between sleep disturbances and affective symptoms have been shown in previous research, yet the consecutive day effects between these factors remains poorly understood. Methods: We analysed longitudinal ecological momentary assessment (EMA) data obtained from a subsample of young persons in the Brazilian High-Risk Cohort (BHRC) study collected in 2020-2021. Participants reported sleep quality each morning and rated affective symptoms relating to mood, anxiety, and energy four times daily for 28 days. We selected 88 individuals (17.83{+/-}1.74 years, 56 [63.6%] female gender) with at least one instance where individuals were observed three-days in a row. Within-person bidirectional next-day effects between sleep quality and affective symptoms were estimated using mixed-effects regression analysis adjusting. We then applied g-estimation approaches to estimate the effect that lagged sleep quality and consecutive improvements in sleep quality had on affective symptoms. Results: Sleep quality and affective symptoms had bidirectional next-day effects, with sleep quality tending to have greater influence on affective symptoms than the reverse. Improved lagged sleep quality had positive effects on affective symptoms incrementally above the prior night's sleep quality. Also, improvement of sleep quality across consecutive days had incremental and approximately equal effects on affective symptoms. Conclusions: Sleep quality and affective symptoms exhibit a feedback loop, whereby poor sleep quality influences affective symptoms over consecutive days. Breaking these feedback loops, by improving sleep quality across several consecutive nights should improve affective symptoms. This supports interventions that target sustained improvement in sleep and possibly circadian regulation to improve affective symptoms.

Stress-related psychiatric disorders and inflammatory bowel diseases share high co-morbidity and contribute to the symptom severity of one another. In mice, ten days of Chronic Social Defeat Stress (CSDS) is sufficient to reduce gut microbiome diversity and the relative abundance of Firmicutes, which are hallmarks of inflammatory bowel diseases. However, mechanisms by which stress causes gut microbiome dysbiosis are largely unknown. Here, we demonstrate that pharmacologically inhibiting {beta}-adrenergic receptors (ARs), which are activated by (nor)adrenaline during stress, mitigates gut dysbiosis otherwise caused by CSDS. Compared to vehicle-treated mice following CSDS, propranolol-treated mice displayed a modest increase in sociability, increased alpha diversity, and increased abundance of anaerobic commensal Clostridia. Abundance of short-chain fatty acid-producing anaerobic Firmicutes abundance correlated with sociability following CSDS across all treatments. Pharmacologically blocking -ARs during stress increased subsequent sociability, but had little effect on gut microbiome composition. Together, our findings support the hypothesis that {beta}-AR activation contributes to stress-induced changes of the gut microbiome. One Sentence SummaryPharmacologically inhibiting beta-adrenergic receptors during chronic stress mitigates reductions in anaerobic, short-chain fatty acid-producing bacteria in the gut.

Efficiently summarizing dietary records at scale remains a persistent bottleneck in nutritional epidemiology. We present FoodScribe, which translates free-text meal descriptions into quantitative nutrient profiles by combining ingredient parsing with nutrient retrieval by querying the USDA FoodData Central (FDC) database. Benchmarked using three LLM providers using Nutribench dataset, FoodScribe completed annotation of 3,807 meal descriptions in 2.5 hours, a task otherwise requiring substantial manual effort from trained nutritionists. FoodScribe achieved accuracy across macronutrient estimation (F1=0.79-0.89), with models performing better for protein than fat estimation. Application to a Mediterranean diet intervention cohort indicated dietary shifts consistent with the intervention pattern based on model-derived estimates. Integration with metabolomics data suggested that fiber and vegetable intake were positively associated with a fecal metabolite cluster.

Consumer-grade bioelectrical impedance analyzers have become widely used for body composition assessment, yet their accuracy varies considerably across devices. The Hume Pod is a popular consumer-grade analyzer marketed as being highly accurate, but independent validation is lacking. The purpose of this study was to evaluate the reliability and validity of the Hume Pod relative to both a four-compartment (4C) model and dual-energy X-ray absorptiometry (DXA). Sixty-seven adults (42 females, 25 males; age 37.2 +/- 13.5 years, body mass index: 24.6 +/- 4.9 kg/m2, body fat percentage [BF%]: 26.4 +/- 10.2%) completed duplicate Hume Pod assessments alongside DXA and 4C evaluations. Reliability was evaluated using the technical error of measurement (TEM) and intraclass correlation coefficients (ICC). Validity was assessed using equivalence testing, Lin's concordance correlation coefficient (CCC), standard error of the estimate (SEE), Bland-Altman analysis, and additional tests. The Hume Pod demonstrated strong reliability, with ICCs >/= 0.993 and TEMs of 0.8% for BF% and 0.6 kg for fat mass (FM) and fat-free mass (FFM). Relative to the 4C model, BF%, FM, and FFM estimates were statistically equivalent (all p<0.05), with strong agreement (CCC=0.95-0.98), low SEE values (3.1%, 2.3 kg, and 2.2 kg, respectively), moderate limits of agreement (+/-6.1%, +/-4.5 kg, and +/-4.5 kg), and no proportional bias. Compared with DXA, generally strong agreement was also observed. These findings indicate that the Hume Pod demonstrates strong reliability and validity compared with laboratory reference methods for body composition estimation, supporting its potential use as a consumer body composition assessment.

Background: University students experience substantial psychological well-being and body-image concerns, while scalable, personalized digital support remains underexamined in Malaysia. Artificial intelligence chatbots may deliver repeated lifestyle guidance, but the incremental value of personalization over structured chatbot support is uncertain. Objectives: This study evaluated changes in psychological well-being and body appreciation following a 12 week personalized AI-powered lifestyle intervention, NExGEN, among Malaysian university students. Methods: A two-arm, controlled, quasi-experimental pre-post study allocated 140 students aged 18 to 35 years by matched blocks to NExGEN (n = 70) or a structured-prompt ChatGPT control (n = 70). NExGEN generated adaptive weekly lifestyle actions from a 47-item onboarding assessment, whereas control participants received standardized weekly prompts covering the same lifestyle domains. Psychological well-being and body appreciation were assessed at baseline and week 12 using the World Health Organization-Five Well-Being Index and Body Appreciation Scale-2. Intention-to-treat linear mixed models estimated adjusted within-group changes and between-group differences in change, with Holm adjustment for the co-primary outcomes. Results: Week-12 assessments were completed by 121 participants (86.43%). In NExGEN, psychological well-being improved by an adjusted 8.68 points (95% CI, 6.22 to 11.14), z = 6.91, p < .001, and body appreciation improved by 0.17 points (95% CI, 0.10 to 0.24), z = 4.82, p < .001. However, between-group differences in change were not statistically significant for psychological well-being (2.87 points; 95% CI, -0.48 to 6.23; z = 1.68; Holm-adjusted p = .093) or body appreciation (0.10 points; 95% CI, 0.00 to 0.19; z = 1.99; Holm-adjusted p = .093). Median platform logins were 68.00 in NExGEN and 58.50 in control; mean acceptability scores were 3.92 and 3.59, respectively. Conclusions: NExGEN participation was associated with significant within-group improvements in psychological well-being and body appreciation, but personalized guidance did not demonstrate superiority over structured chatbot guidance. Because allocation was quasi-experimental, causal attribution remains limited. Randomized component-level trials are needed to determine whether personalization provides incremental benefit.

Background Functional neurological disorder (FND), one of the most common neurological conditions, affects women almost twice as frequently as men. The reasons for this are unknown, and there has been minimal research into how physiological and pathological features of women's health interact with symptoms of FND. Methods We conducted an online survey assessing the effect of several aspects of women's health with the severity of symptoms of FND. Results 484 people completed the survey. Among the 223 who had regular or fairly regular menstrual cycles, a strong difference across the menstrual cycle was seen, with symptoms at their best in the follicular phase, worsening in the luteal phase, and worst in the pre-menstrual period and the menses. This effect was not moderated by a proxy measure of pre-menstrual dysphoric disorder (PMDD). Participants who were taking the combined oral contraceptive (COC, n=43) and progesterone-based contraception (n=80) were more likely to report symptom improvement from starting the medication than worsening. When compared to menstruating participants who were not taking the COC, participants taking the COC reported less worsening in their symptoms of FND in the luteal, pre-menstrual, and menstrual phases. Of the 99 women who had passed menopause since developing FND, 76% reported worsening of their FND symptoms after menopause. Discussion This study demonstrates interactions between several aspects of women's health and symptoms of FND. The observed pattern of symptom fluctuation across hormonal states suggests a potential modulatory role of oestrogen, warranting further targeted investigation.

Background: Children born prematurely (before 37 weeks) or admitted to the neonatal unit (NNU) are at increased risk of adverse long-term physical health outcomes. It is also recognised that there is an association with later academic performance and special educational needs, however it is not clear whether these broad risk factors could be used as stand-alone heuristics to identify children who may benefit from additional support in educational settings. We aimed to examine the associations between neonatal unit (NNU) admission and educational attainment in mid-childhood. Methods and Findings: Pregnancy data from a prospective birth cohort (Pregnancy Outcome Prediction Study, Cambridge, United Kingdom, 2008-2012) were linked to national educational outcomes (Department for Education, United Kingdom). Multivariable regression models adjusted for maternal, child, and socioeconomic factors were used to evaluate associations between (i) all NNU admissions, (ii) at term NNU admissions >48 hours, (iii) preterm birth without ongoing physical health needs, and educational outcomes at ages 5-11 years. Children who required any NNU care were more likely not to meet expected educational standards across multiple ages and domains in early and mid-childhood: age 5 early year foundation (aOR 1.64, 95% CI 1.19-2.27, p=0.003), phonics at age 6 (aOR 2.43, 95% CI 1.72-3.57, p<0.001), and at age 7 (here assessments were divided into multiple domains): reading (aOR 1.67, 95% CI 1.18-2.38, p=0.004), writing (aOR 1.72, 95% CI 1.25-2.38, p<0.001), mathematics (aOR 1.56, 95% CI 1.09-2.22, p=0.020), and science (aOR 1.85, 95% CI 1.22-2.78, p=0.003). Similar patterns were observed among both at term-born infants who stayed >48hrs in NNU (phonics assessment at age 6 aOR 2.26, 95% CI 1.51-3.36, p<0.001) and in children born preterm without long-term physical health sequelae (phonics assessment at age 6 aOR 3.07, 95% CI 1.96-4.81, p<0.001). These associations were robust to adjustment for demographic, perinatal, and socio-economic factors. By age 11, differences in academic attainment were attenuated and no longer clearly distinguishable across all exposure groups. However, there was an increased likelihood of special educational needs (SEN) at age 11 associated with any NNU admission (aOR 1.78, 95% CI 1.15-2.73, p=0.009), at term NNU admission for >48hrs (aOR 1.88, 95% CI 1.19-3.00, p=0.007), and children born preterm without long-term physical health sequelae (aOR 1.50, 95% CI 1.00-2.25, p=0.049). Predictive performance of any NNU admission for SEN at age 11 was moderate (AUC 0.70, 95% CI: 1.14-2.65, p=0.010), with balanced sensitivity and specificity and high negative predictive value. Conclusions: NNU admission, for both term and preterm infants, is associated with poorer educational outcomes and an increased likelihood of special educational needs in mid-childhood.

Prenatal alcohol exposure (PAE) is a major cause of neurodevelopmental disorders, yet most children are diagnosed late or misdiagnosed. Neuroplacentology suggest that placental factors released into maternal and/or umbilical cord blood contribute to fetal brain development. Consistently, a preclinical inter-organ transcriptomic database revealed that PAE disrupts the expression ratio of angiogenic and inflammatory factors suggesting an angio-inflammatory response. This study aimed i) to assay, by multiplex immunoassay, angiogenic and inflammatory factors in maternal and umbilical cord blood from alcohol-consuming women and ii) to perform a maternofetal analysis according to neonatal sex. Afterwards, dysregulated factors from mothers who gave birth to females or males were submitted to STRING and ShinyGO analyses. Results showed that PAE differently altered the distribution profiles of dysregulated angiogenic and inflammatory factors in maternal and umbilical cord blood. Moreover, sex-specific differences were observed, with 36% of dysregulated proteins specific to males, 48% to females, and 16% common to both. STRING analysis revealed robust functional protein-protein interactions linking together inflammatory and angiogenic clusters while the ShinyGO analysis identified enriched pathways related to vascular shear stress. These findings provide the first maternofetal analysis of combined angiogenic and inflammatory factors from alcohol-consuming mothers.

Insulin signalling contributes to neurodevelopment and brain function, and insulin resistance (IR)-related traits are associated with cognitive performance. However, the genetic architecture shared across specific cognitive domains and IR-related phenotypes remains insufficiently defined. We analysed large-scale genome-wide association study summary statistics for 11 IR-related traits (N=53,334-933,970) and 10 cognitive measures (N=28,156-436,853) to quantify global and local genetic correlations, fine-map shared association signals, and annotate implicated genes and drug-gene interactions. Pairwise global and local genetic correlations were estimated, and shared high-confidence variants were prioritised using the multivariate Sum of Single Effects model. Positional and expression quantitative trait locus mapping was performed, and implicated genes were examined through functional annotation, tissue enrichment, and drug-gene interaction analyses. Low-to-moderate genetic correlations were observed between six IR-related traits and seven cognitive measures (|rg|=0.08-0.34), with predominantly opposite directions, except for correlations involving visual declarative short-term memory. Local genetic correlations showed mixed effect directions across most trait pairs, and multivariate fine-mapping prioritised 696 shared likely causal variants with high posterior support. Gene annotation indicated enrichment in several pathways, including immune-related, signal transduction, neurogenesis, neurotransmitter metabolism, receptor regulation, and lipid and cholesterol metabolism regulation. Implicated genes were expressed across various brain regions and showed prior associations with neuropsychiatric and cardiometabolic conditions. Several drug-gene interactions were identified, involving immunomodulatory and anti-inflammatory compounds. These findings indicate widespread heterogeneous genetic overlap between IR-related traits, particularly body mass index and waist-to-hip ratio, and cognitive measures of general intelligence, processing speed, and short-term visual declarative memory. The findings prioritise apolipoprotein-related lipid transport and inflammatory and oxidative stress pathways as candidate mechanisms linking cognitive, cardiometabolic, and neuropsychiatric phenotypes.

Introduction Auto-Induced Cognitive Trance (AICT) is a non-ordinary state of consciousness (NOSC) that can be accessed by will alone once a standardised self-induction procedure has been learnt. The first research publication on AICT dates back only ten years, meaning that research on this phenomenon is still in its infancy. Previous reports concerning the phenomenology and neurophysiology of AICT revealed similarities with more extensively described NOSCs, as well as unusual features, raising questions about the potential benefits of AICT practice for well-being. Objective This study aimed to gather quantitative descriptive data on features associated with well-being in a large comparative sample of AICT practitioners and non-practitioners. Method This research followed a web-based survey study design which enquired AICT-trained and yet-to-be trained participants to self-report through validated standardised questionnaires on vitality, self-esteem, mental well-being, trait anxiety, life satisfaction, happiness, positive and negative affect, nature-relatedness and connectedness. Data on NOSCs practices, life history events that could have led to spontaneous NOSCs, and demographic data were collected for further inclusion as control variables in statistical models. Results The online questionnaire yielded 607 valid responses, (171 yet-to-be trained participants and 436 AICT-trained participants). AICT practice was found to be associated with increased self-esteem (RSE), overall connectedness (WCS) as well as all subdimensions of connectedness (WCS Self, WCS Others, WCS World). AICT practice Duration exhibited significant effects on global connectedness and all subdimensions of connectedness, self-esteem, trait anxiety (STAIT-5), and positive affect (PANAS+). Conclusions AICT seems to benefit to practitioners well-being shortly after training through increases in self-esteem and in the sense of connectedness. Prolonged AICT practice is associated with added decreased trait anxiety and increased positive affect. Further research is needed to confirm these findings with a sample including AICT-uninterested participants, and to clarify the underlying mechanisms of AICT.

Background: Stunting affects approximately 32% of children under five years in Benin. While birth intervals shorter than 33 months are a recognized risk factor for childhood malnutrition, the optimal birth interval for preventing stunting in the Beninese context is still unclear. Objective: This study examined the association between preceding birth interval (PBI) and stunting among children aged 6 to 59 months in Benin. Methods: This study used a cross sectional design to analyze data from the 2017 to 2018 Benin Demographic and Health Survey. We included 10,153 children aged 6 to 59 months. Stunting was defined as height for age z score below 2 standard deviations from World Health Organization standards. Preceding birth interval was categorized as <24, 24 to 32, 33 to 44, 45 to 56, and >56 months. Survey adjusted multivariable logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals for the association between PBI and stunting, controlling for child, maternal, and household level covariates. Potential effect modification by child age group (6 to 23 vs. 24 to 59 months) was assessed through a multiplicative interaction term and evaluated using information criteria, a likelihood ratio test, and the statistical significance of individual interaction terms. Results: Compared with children born after an interval of <24 months, those born after 45 to 56 months (AOR: 0.63; 95% CI: 0.51 to 0.78) and >56 months (AOR: 0.67; 95% CI: 0.54 to 0.82) had significantly lower odds of stunting (both p<0.001). Intervals of 24 to 32 months and 33 to 44 months were not significantly associated with stunting, nor was firstborn status. No evidence of effect modification by child age group was found (likelihood ratio test p=0.336), and stratified analyses conducted separately for children aged 6 to 23 months and 24 to 59 months yielded results consistent with those from the pooled model. Conclusion: The lack of protective effect for intervals shorter than 45 months indicates a threshold specific to this context above which nutritional benefits become manifest. Integrating family planning messages emphasizing birth intervals longer than 45 months into child nutrition programs, coupled with strengthened access to modern contraception, could contribute to stunting reduction in Benin among other factors. Alongside this, nutritional support for pregnant and breastfeeding women, including adequate dietary supplementation and counselling, may further contribute to improved child growth outcomes. Keywords: Birth interval; stunting; family planning; Benin; childhood morbidity; nutrition

Background. GLP-1 receptor agonist trials are tightly controlled: standardized titration, intensive dietary counseling, frequent in-person follow-up, and rigorous exclusion criteria. The real world is none of those things. In a U.S. telehealth GLP-1 program, diet engagement, exercise, medication choice, dose timing, and out-of-pocket cost vary substantially from patient to patient. Whether trial-level efficacy translates into the outcomes a patient and clinician will actually see is an open question, and the answer matters, because telehealth is now where most GLP-1 prescribing happens. Methods. We conducted a retrospective cohort study of 13,507 adults who used a single GLP-1 agent (tirzepatide or semaglutide) through the Mochi Health telehealth obesity program and had a documented six-month weight observation. The primary outcome was achievement of >=10% total body weight loss at six months. To address selection bias in the tirzepatide-semaglutide comparison, we used 1:1 nearest-neighbor propensity-score matching on age, sex, baseline BMI, baseline weight, and comorbid diabetes, hypertension, dyslipidemia, and prior bariatric surgery (recorded at intake), with a 0.25 SD caliper on the propensity logit. We drew a directed acyclic graph (DAG) with a clinical co-author to make the identifying assumptions explicit and to mark where unobserved variables (insurance, socioeconomic status, concomitant medications such as metformin) limit causal interpretation. We report multivariable predictors via logistic regression, compute an E-value for the matched contrast, and benchmark our point estimates against landmark RCT outcomes. Results. Overall, 59.1% of patients achieved >=10% loss at six months, with mean loss of 11.5% (median 11.3%). Threshold attainment was 86.6% at >=5%, 59.1% at >=10%, 27.5% at >=15%, and 9.1% at >=20%. The unadjusted tirzepatide-semaglutide response gap was +16.0 percentage points (68.8% vs 52.8%); after 1:1 propensity-score matching (3,480 pairs, all post-match |SMD| < 0.05) the gap was +18.1 percentage points (69.6% vs 51.6%, 95% CI +15.9 to +20.3). Matching on the measured covariates did not attenuate the advantage, indicating that selection on those characteristics does not explain it; the matched risk ratio was 1.35 (E-value 2.04). The gap was unchanged when a self-reported insurance indicator was added to the matching (+18.4 pp) and remained large (+14.2 pp) within patients who reached a therapeutic dose. Multivariable predictors of response were tirzepatide (OR 2.10, 1.95-2.26), female sex (OR 1.37, 1.20-1.56), and prior bariatric surgery (OR 1.36, 1.18-1.57); response was lower with comorbid diabetes (OR 0.84, 0.77-0.92) and, modestly, with higher baseline BMI per unit (OR 0.98, 0.97-0.99). Response varied by baseline BMI, from 58.0% in overweight patients (BMI <30) and a peak of 63.5% in Obese I to 52.4% in Obese III. Conclusions. Real-world response to GLP-1 therapy in a telehealth setting is meaningfully attenuated from RCT benchmarks but remains clinically substantial: roughly three in five patients reach the 10% threshold. The tirzepatide advantage over semaglutide is large and, notably, does not shrink under propensity-score matching on measured confounders, so it is not an artifact of the observed selection variables; an unmeasured confounder would need a risk-ratio association of about 2.0 with both drug choice and response to explain it away (E-value 2.04). The findings are observational, conditional on the DAG's identifying assumptions, and unmeasured confounders (insurance, socioeconomic status, concomitant medications) remain possible.