The World Health Organization recommends the use of balanced energy protein (BEP) supplements during pregnancy in settings with a ≥ 20% prevalence of underweight women of reproductive age to reduce the risk of adverse health outcomes. Several countries are implementing BEP supplementation in varied formats. However, the implementation and monitoring of outcomes remain poor across countries. This qualitative study explores the experiences, opportunities, and challenges related to implementing national and sub-national BEP supplementation programs in nine countries (12 countries originally invited) to inform best practices. Methods: Semi-structured interviews were conducted with 15 personnel involved in its implementation in Haiti, India, Malawi, Mexico, Nigeria, Pakistan, Rwanda, Senegal, and Sri Lanka between October 2024 and March 2025. The interviewees in each country were predominantly implementation experts but also government officials involved in the provision of BEP supplementation. The transcripts were analyzed thematically, focusing on acceptability, adoption, appropriateness, cost, feasibility, and sustainability of outcomes. Results: In non-humanitarian settings (five countries), BEP supplementation was commonly integrated into the governmental health system or social protection programs. However, humanitarian contexts (four countries) often relied on partner-led (e.g., UN organizations) implementation. Clear operational protocols, including behavioral change communication strategies, facilitated the implementation. Community-based organization partnerships strengthened adherence; however, implementation costs, stock shortages, and geographic inequities in coverage varied and were limiting factors in scale-up, primarily in humanitarian contexts. Conclusion: In sum, two distinct implementation pathways emerged: government-led models characterized by policy integration, national ownership, and more stable systems, and humanitarian or donor-led models shaped by crisis response, external dependency, and non-committal challenges. Successful implementation of BEP supplements depends on the presence of effective policies, context-adapted design, integration into health systems, consistent funding, and effective monitoring. There is a need for implementation research to generate evidence on best practices when implementing BEP supplementation programs.

Introduction: Alterations of the microbiota–gut–brain axis, including increased intestinal permeability (IP), changes in microbial activity, and immune activation, are central to the pathophysiology of irritable bowel syndrome with diarrhea (IBS-D). The low-fermentable oligo-di-monosaccharides and polyols (FODMAP) diet (LFD) is an established therapy for IBS, yet its systemic effects, particularly in patients with elevated depressive symptoms, remain incompletely characterized. Methods: This single-arm pre–post study investigated associations between depressive symptom severity and markers of small IP (s-IP), endotoxin exposure, inflammation, and erythrocyte membrane polyunsaturated fatty acid (PUFA) composition in 43 IBS-D patients undergoing a 12-week personalized LFD. Patients were classified using the Symptom Checklist-90-Revised depression subscale into those with (d+, n = 23) and without (d−, n = 20) clinically elevated depressive symptoms. Results: At baseline, d+ patients exhibited higher s-IP, circulating lipopolysaccharide levels, inflammatory markers, and a more pro-inflammatory PUFA profile. Following LFD, significant improvements in symptoms and several biological parameters were observed in the overall cohort. Greater absolute changes in d+ patients were consistent with their higher baseline values rather than indicating differential responsiveness. Baseline depressive symptoms were not significantly associated with the magnitude of post-intervention changes in IP or inflammatory markers. Conclusions: These findings suggest that elevated depressive symptoms identify an IBS-D subgroup characterized by greater baseline biological burden. Results should be interpreted as associative given the single-arm design, absence of a control group, and the concurrent reduction in body weight, which may have influenced the observed changes. Randomized controlled studies are needed to clarify the role of dietary interventions in modulating gut–brain axis-related pathways in IBS-D.

Background: Chlorophyll (Chl), widespread in fruits and vegetables, has been shown to have numerous nutritional functions, including beneficial effects on obesity. However, whether Chl has an anti-aging effect remains unclear. Methods: Here, we studied the beneficial effects and mechanism of Chl on delaying aging using a Drosophila model. Results: The results showed that dietary supplementation of Chl in an appropriate dose (3.925 mg/L) significantly extended the lifespan (7.66–13.94%), improved climbing ability, increased CAT activity, reduced MDA content, enhanced stress resistance to starvation, heat stress, and cold shock in Drosophila. Notably, lifespan extension was not associated with dietary restriction, reproductive sacrifice, or circadian rhythm regulation. RNA-Seq analysis showed that Chl supplementation led to differential expression of 723 genes in female flies and 435 genes in male flies. KEGG analysis revealed that these differentially expressed genes were significantly enriched in the xenobiotic metabolism (XM) pathway. Within this pathway, phase II detoxifying enzyme genes associated with the CncC (Nrf2) signaling pathway (GstD10, GstE7, Ugt37A3, and AOX2) were significantly downregulated in both sexes. In contrast, protective target genes from the same pathway (cat, Mrp4, Hsp68) were significantly upregulated, as confirmed by qPCR. Conclusions: Taken together, our data indicate that Chl supplementation delays aging in Drosophila melanogaster via enhanced stress resistance and remodeling of the detoxification network.

Background: Obesity is a heterogeneous chronic disease in which eating behavior phenotypes may influence treatment response. Yet, anti-obesity medication (AOM) selection is still largely guided by anthropometric and metabolic parameters, with limited use of behavioral phenotyping in routine practice. We evaluated whether multidimensional eating behavior changes, measured by the Brazilian Eating Behavior Phenotype Scale (Escala de Fenótipos do Comportamento Alimentar, EFCA), differ across commonly used AOMs in a real-world cohort. Methods: We conducted a retrospective, observational, real-world study in obesity outpatient care settings in São Paulo, Brazil. Adults with obesity (18–65 years) treated with a single principal AOM for 6 months and paired baseline/6-month follow-up EFCA and anthropometric data were included. Analyses focused on early responders (≥5% total body weight loss at 3 months). Five AOM groups available in Brazil were analyzed: semaglutide (oral or subcutaneous), naltrexone/bupropion, sibutramine, topiramate, and tirzepatide. Outcomes included percent weight loss, EFCA total score, and five EFCA subscales (hedonic, emotional, compulsive, hyperphagic, disorganized). Within-medication behavioral changes were assessed using paired tests and standardized effect sizes (Cohen’s dz, 95% CI), summarized in heatmap form. Results: The analytical cohort comprised 66 early responders with paired EFCA assessments at baseline and 6 months. EFCA profiling revealed distinct behavioral response fingerprints across AOMs. Effect size mapping showed predominantly large behavioral effects (many dz ≥ 0.8) in hedonic, emotional, hyperphagic, and compulsive domains. Strongest signals included emotional eating reductions with naltrexone/bupropion (dz 2.04), tirzepatide (dz 1.77), semaglutide (dz 1.52), and topiramate (dz 1.54); hedonic reductions with tirzepatide (dz 2.06), semaglutide (dz 1.55), and naltrexone/bupropion (dz 1.52); hyperphagic reductions with tirzepatide (dz 1.50) and semaglutide (dz 1.34); and compulsive reductions with topiramate (dz 1.41) and consistent effects across tirzepatide, semaglutide, and sibutramine (≈dz 0.95–0.96). Disorganized eating showed heterogeneous/attenuated responsiveness, from near-null with tirzepatide (dz 0.03) to large but imprecise effects in smaller groups (e.g., topiramate dz 1.24, wide CI). Conclusions: In this responder-enriched real-world cohort, AOMs showed distinct and reproducible EFCA behavioral signatures, supporting a clinically actionable phenotype-informed framework to prioritize, sequence, and monitor obesity pharmacotherapy beyond nonspecific weight reduction, while highlighting disorganization as a potential target for adjunctive behavioral strategies.

Background/Objectives: Low milk production is more prevalent after preterm birth and may be associated with infrequent milk expression, delayed secretory activation and elevated milk biomarkers including sodium (Na) and sodium–potassium ratio (Na:K). This study aimed to describe milk production, expression frequency, and milk biomarkers (Na and Na:K) in the first 4 weeks and explore associations in the first 2 weeks after preterm birth. Methods: Women who birthed at 28–34 weeks of gestation provided milk expression data and milk samples every second day from birth to Day 10, then every third day until infant transfer/discharge from the neonatal unit. Lactation characteristics and milk Na and Na:K across the first 4 weeks were described, and associations between milk production, expression frequency and milk biomarkers were examined. Results: In a sample of N = 44 women that maintained a median expression frequency of 6–7 × 24 h, temporal patterns in milk Na and Na:K were similar to those observed after birth at term, and a milk production ≥ 600 mL/24 h was achieved by 61.5% on Day 13. One third of women experienced delayed secretory activation. Expression volumes on Day 4 were associated with milk production on Day 13 and Day 16 (both p < 0.001). Conclusions: Our findings suggest that low expression volumes in the days after preterm birth may indicate women at risk of low milk production. Further research is needed to determine the predictive value of early expression frequency and milk composition on subsequent milk production.

Background: Food security systems are central to nutritional health and Sustainable Development Goal 2 (SDG 2), yet existing assessments have paid limited attention to cross-dimensional coordination within food security systems. This study assessed both system performance and coordination in low- and middle-income countries (LMICs) during 2019–2021. Methods: Based on a multidimensional 25-indicator framework, the entropy-weighted Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) approach was used to evaluate system performance. Spearman’s rank correlation and Bland–Altman agreement analyses against the SDG 2 Index and the Under-Five Mortality Rate (U5MR) were used to examine the validity. The coupling coordination degree (CCD) model was used to assess coordination across the four dimensions of food security: availability, access, utilization, and stability. Results: Among all included LMICs, composite scores ranged from 0.103 to 0.698. Regionally, Europe and Central Asia showed the strongest overall performance (mean = 0.54), whereas Sub-Saharan Africa exhibited the lowest levels (mean = 0.27). The dimensions of access and stability were identified as the principal global bottlenecks of overall food security system development. The proposed index correlated positively with the SDG 2 Index (R = 0.662, p < 0.001) and inversely with the U5MR (R = −0.769, p < 0.001). The coupling degrees were consistently high but exceeded coordination levels across regions, indicating that strong interdependence among dimensions did not necessarily translate into balanced or synergistic system development. Conclusions: Food security systems in LMICs are constrained by weaknesses in the access and stability dimensions, as well as by insufficient cross-dimensional coordination. Strengthening them requires integrated, cross-sectoral strategies that enhance both system performance and interdimensional coordination.

Background/Objectives: Camellia bee pollen refers to pollen pellets collected by bees from plant stamens and mixed with salivary secretions. Alcoholic fatty liver disease (AFLD), as the initial phase within the spectrum of alcohol-induced liver diseases, has resulted in a rising global incidence rate and treatment burden of such liver ailments. Methods: This study employs acute zebrafish juvenile and adult zebrafish chronic alcoholic liver models to explore the protective effects of camellia bee pollen as well as its ethanol and water extracts on zebrafish alcoholic fatty liver. Results: The research findings indicate that the intervention group treated with camellia bee pollen significantly mitigated the accumulation of lipid droplets in zebrafish larvae and notably improved the liver lobule structure of adult zebrafish, bringing it close to normal conditions. The camellia pollen intervention group could significantly decrease the levels of triglyceride (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA), while increasing the levels of glutathione (GSH) and total superoxide dismutase (T-SOD). Conclusions: This experiment indicates that the pollen of tea flowers has a significant protective effect against alcoholic liver damage.

Background/Objective: Intermittent fasting (IF) shows promise for metabolic and mental health benefits, but evidence in older adults remains limited. This study systematically evaluated the safety and effectiveness of IF in adults aged ≥60 years, comparing different protocols using network meta-analysis. Methods: Systematic review and network meta-analysis following Cochrane and PRISMA guidelines were conducted, producing a literature search until June 2025 across PubMed, Scopus, and ScienceDirect databases, with inclusion criteria comprising randomized controlled trials, clinical trials, and observational studies evaluating IF in adults ≥60 years. Network meta-analysis compared time-restricted eating (TRE), IF 5:2 method, Islamic Sunnah fasting (ISF), Healthy Living Diet and usual diet. The NMA was conducted exclusively using randomized controlled trials (RCTs; n = 7); pre–post trials and observational studies were included solely in the narrative systematic review component and did not contribute to any pooled NMA estimates. Observational data contributed exclusively to the narrative synthesis. Results: Thirty-one studies were included; seven RCTs were eligible for network meta-analysis. ISF and TRE 16:8 were most effective for weight (ISF: −2.36 kg; TRE 16:8: −1.92 kg) and BMI reduction (−0.81 and −1.01 kg/m2) without lean mass loss. Findings on cardiometabolic parameters, mental health, and cognitive function are based on the narrative synthesis of individual studies. Long-term structured IF was associated with improvements in standardized cognitive performance assessed via validated instruments. However, very restrictive eating windows (≤10 h) and prolonged fasting (>12.38 h) were associated with adverse outcomes, including lower cognitive scores and 58% increased cardiovascular mortality. Conclusions: TRE 16:8 and ISF showed the strongest comparative evidence for weight reduction in the RCT-based NMA, with acceptable short-term safety profiles in the included trials. In the narrative review, these protocols were associated with clinically meaningful improvements in body weight, metabolic markers, and blood pressure while generally preserving lean muscle mass in older adults. The cardiovascular mortality risk associated with very restrictive eating windows may emphasize the importance of moderate fasting approaches in this vulnerable population. Further long-term research is needed to confirm optimal protocols and identify at-risk subgroups.

Autism spectrum disorder (ASD) is highly heterogeneous in symptom onset and severity, comorbidities, and treatment responsiveness, challenging the notion of a single pathogenic mechanism. Increasing evidence indicates that some individuals with ASD exhibit prominent peripheral physiological alterations, including gastrointestinal (GI) dysfunction, gut microbial dysbiosis, immune imbalance, oxidative stress, and mitochondrial/energy metabolic vulnerability. In this context, gut-derived metabolites—particularly short-chain fatty acids (SCFAs)—have emerged as plausible modulators of the neurodevelopmental milieu through the expanded gut–immune–metabolic–brain axis. This review synthesizes: (i) SCFAs’ biogenesis and physiological roles, (ii) context- and developmental stage-dependent effects, (iii) the clinical heterogeneity of reported microbiome and SCFA alterations in ASD, and (iv) propionate as a frequently discussed candidate signal and the interpretive boundaries of preclinical evidence. Human studies show substantial inter-study variability in SCFA alterations (increases, decreases, or no differences), influenced by factors such as sample type (stool vs. blood), GI symptoms, diet, medication exposure, and analytical variability. Accordingly, SCFAs should not be treated as universal ASD biomarkers but rather as context-dependent metabolic signals relevant under specific clinical and biological conditions. Building on this premise, we propose the conceptual framework of “metabolic ASD” representing a metabolically informed dimension of biological variability in which peripheral metabolic–immune perturbations may contribute to neurodevelopmental vulnerability. To avoid premature causal claims, we outline design requirements for future research, including stratified study designs, longitudinal cohorts, and integrative multi-layer analyses. Ultimately, metabolic ASD should be positioned as a testable precision medicine research framework rather than a universal etiological model.

Background: Body mass index (BMI) is a common nutritional marker, but admission-only measurements present limitations. Early dynamic BMI changes may better reflect metabolic stress and fluid balance. However, the clinical significance of early BMI trajectory during critical illness remains poorly understood. This study evaluated the impact of early BMI trajectory on mortality and ventilator weaning in critically ill patients. Methods: This retrospective cohort study included 1355 adult patients (ICU stay ≥ 7 days) admitted to the medical ICU between 2019 and 2025. BMI trajectory was defined as the percentage change from admission to day 7 and was categorized into three groups: decrease (>5% reduction), stable (±5%), and increase (>5% gain). Multivariable Cox proportional hazard and logistic regression analyses were performed to evaluate the association between BMI trajectory and clinical outcomes. Results: Of the 1355 patients, 15.9%, 57.7%, and 26.4% were in the decrease, stable, and increase groups, respectively. The increase group demonstrated significantly higher hospital mortality (52.5%) than the decrease (41.9%) and stable (40.0%) groups (p = 0.001). Multivariable analysis revealed that an increasing BMI trajectory was independently associated with higher hospital mortality (HR 1.25, 95% CI 1.05–1.48). A decreasing BMI trajectory strongly predicted successful ventilator weaning (OR 2.76, 95% CI 1.81–4.21). Conclusions: Early BMI trajectory significantly predicted ICU outcomes. Increasing and decreasing BMI were associated with higher mortality and improved ventilator weaning, respectively. These findings suggest that BMI trajectory may be a simple surrogate marker of metabolic stress, nutritional status, and fluid balance during early critical illness.