搜索结果：Clinical nutrition research

Micronutrient deficiencies are a major public health concern in low- and middle-income countries, where conventional supplementation and fortification programs are often limited by low bioavailability, fragile supply chains, cultural resistance, and poor long-term adherence. This research note proposes a food-based alternative model that leverages selected traditional Korean foods (K-foods)- gim (dried seaweed), kimchi (fermented vegetables), and cheonggukjang (fermented soybean paste)-as culturally adaptable and nutritionally dense components of official development assistance nutrition strategies. These foods provide functionally relevant nutrients, such as iodine, vitamin K2, probiotics, and fermentation-derived bioactive peptides, and offer benefits, including shelf stability, microbial resilience, and decentralized production. Employing a multidisciplinary clinical nutrition framework integrating food composition science, fermentation biology, public health nutrition, and development policy, this note presents a five-step research roadmap encompassing nutrient profiling, safety and stability assessment, cultural acceptability evaluation, community-based efficacy trials, and policy translation. By prioritizing food-based, multinutrient dietary interventions over single-nutrient strategies, the proposed model highlights a scalable and clinically relevant pathway for enhancing micronutrient status in resource-limited settings. This work contributes to emerging discussions on nutrition-sensitive official development assistance and highlights K-foods as potential tools for sustainable, culturally responsive global nutrition interventions.

Postgastrectomy diarrhea is often attributed to dumping syndrome or functional changes; however, exocrine pancreatic insufficiency (EPI) from anatomical and physiological alterations may be an underrecognized cause of malabsorption and nutritional decline. Because EPI symptoms are often nonspecific, it may remain undiagnosed and lead to progressive malnutrition if untreated. This case report describes severe EPI identified via nutrition-focused assessment in a patient with persistent diarrhea after Billroth II gastrectomy, and the clinical response to pancreatic enzyme replacement therapy (PERT). A patient with a history of subtotal gastrectomy with Billroth II reconstruction for gastric cancer presented with chronic diarrhea, steatorrhea, weight loss, and hypoalbuminemia. Repeated endoscopic and radiologic evaluations identified no structural cause of diarrhea. Comprehensive nutrition-focused assessment indicated fat malabsorption, and fecal pancreatic elastase was markedly reduced (23.8 µg/g), confirming severe EPI. PERT with pancreatin containing 25,000 units of lipase (Norzyme) was initiated with meals. Posttreatment, steatorrhea resolved and bowel movements normalized without dietary fat restriction. Serum albumin levels subsequently normalized, and body weight returned to the normal range, indicating improved nutritional status. This case emphasizes the clinical value of nutrition-focused assessment in identifying treatable causes of malabsorption, such as EPI, in patients with persistent postgastrectomy diarrhea.

Childhood malnutrition is linked to gut microbiome changes; however, most studies focus on faecal samples, while less is known about the small intestinal microbiome. Here, we characterized the duodenal microbiota of children in Zambia with severe acute malnutrition (SAM) and stunting and compared the microbiomes of stunted children living across the globe. To do this, duodenal aspirates from only stunted (i.e. not concurrently wasted) (n = 53) and SAM (n = 24) Zambian children were analysed by 16S rRNA gene amplicon sequencing. Associations between bacterial composition, clinical features and biomarkers of enteropathy were explored. Comparison of duodenal 16S rRNA gene datasets from malnourished children in different countries was also performed using publicly available datasets to assess the impact of age and geography on microbial diversity and composition. The duodenal microbiota in both stunted and SAM children was dominated by Streptococcus, Granulicatella, Gemella and Klebsiella. Children with SAM had lower α-diversity than stunted children. Meta-analysis revealed similarities in the bacterial composition of age-matched children in different countries, but relative abundances and their association with nutritional status differed. This study offers insight into the duodenal microbiota in children with different states of malnutrition, highlighting the potential influence of geography and age in shaping the proximal small intestine. This article is part of the theme issue 'Biological, biomedical and environmental drivers of stunting'.

Climate change poses a major global threat to the health of current and future generations, disproportionately affecting pediatric populations. Investigating the links between climate change and pediatric diseases is crucial to inform research and prevention strategies aimed at breaking the transgenerational cycle of social inequalities. This narrative review explores the complex interactions between early-life exposures to climate change, food insecurity, and malnutrition, and their impact on infectious and non-communicable diseases (NCDs) in pediatric populations. Data reveal a concerning global scenario: half of the world's children live in areas highly vulnerable to climate change; malaria, enteric, and lower respiratory-tract infections account for approximately 60% of the global communicable disease burden and related-deaths in children and adolescents; over 2.1 billion people under-20 suffer from NCDs; almost 865 million children under-15 experience moderate to severe food insecurity; and millions of children under-5 face stunting (150.2), wasting (42.8), or obesity (35.5). The greatest burdens fall on low- and middle-income countries and the most disadvantaged households. Although the causal pathways and mechanisms linking climate change to health outcomes have not been fully elucidated, epidemiological evidence shows that exposure from conception through adolescence increases risks of acute and chronic diseases, potentially altering lifelong health trajectories. This is plausibly driven by climate-induced disruptions in eco-agrofood systems, which compromise nutrition security and worsen malnutrition. Food systems are both vulnerable to and significant contributor to climate change, and poor dietary patterns further amplify disease burdens. Addressing these intertwined challenges requires a holistic approach promoting healthy, sustainable, and equitable diets from infancy through adolescence, and employing an integrated "glocal" strategy taking into account both global and local contexts. Cross-sector collaboration and targeted pediatric research are paramount to enhance understanding of causal pathways and develop effective interventions to safeguard child health and well-being within a planetary health framework. Statement of Significance This review critically examines how early life exposure to climate-related disruptions in eco-agrofood systems exacerbates the pediatric disease burdens. It also provides actionable insights to help guide research, policy, and actions tackling these interrelated challenges, focusing on the connection between climate change and the food environments, from a "glocal" perspective, ultimately protecting child health.

Patients with head and neck cancer undergoing high-dose cisplatin chemotherapy combined with radiotherapy are particularly at risk of developing nephrotoxicity. While Acute Kidney Injury risk is well established, the role of subclinical renal impairment and its potential interplay with nutritional status remains poorly defined. We aim to evaluate how body composition pre-treatment can predict the onset of Acute Kidney Disease. We conducted a prospective, monocentric, observational study involving 110 patients with locally advanced HNC treated with concurrent cisplatin (&#x2265;200 mg/m&#xb2;) and radiotherapy. Patients were treated either in a definitive or postoperative adjuvant setting, according to institutional clinical practice. Baseline body composition was assessed by bioelectrical impedance analysis (BIA). Renal function and biochemical data were collected at three time points across 21 days. Variables associated with AKD were identified via univariate analysis (Mann-Whitney U test), followed by multivariate logistic regression for independent predictors. AKD developed in 20% of patients during treatment. Those who developed AKD exhibited a significantly higher median increase in serum creatinine compared to non-AKD patients (&#x394;creatinine: 0.48 vs. 0.04 mg/dL, p&#xa0;<&#xa0;0.001). Low body cell mass normalized for height (BCM/kg/m) emerged as a significant independent predictor of AKD (OR&#xa0;=&#xa0;1.29, p&#xa0;=&#xa0;0.04). A trend toward association was also observed for leukocyte count and platelet levels. Other nutritional indicators (BMI, phase angle, SMI) did not show a significant association. Importantly, all patients completed radiotherapy and reached the target cisplatin dose. A trend toward an association between low lymphocyte count and reduced muscle mass with AKD development suggests that pre-treatment nutritional and immunological status may influence nephrotoxicity risk. Bioimpedance-derived metrics may provide a non-invasive, reproducible method to identify high-risk patients.

We aimed to create practical recommendations to support healthcare teams starting ketogenic diet therapy (KDT) for children with super-refractory status epilepticus in intensive care settings. A literature review was conducted to extract published data on patient selection, diet prescription, diet initiation, monitoring, fine-tuning, and discontinuation of KDT for super-refractory status epilepticus. Statements were formulated within each subtopic, and an online survey was distributed to gauge the extent of international agreement with these statements to inform consensus-based recommendations for initiation and maintenance of KDT in pediatric intensive care settings, with a focus on enteral nutrition. Consensus on a statement for inclusion in the core recommendations was reached if &#x2265;75% of respondents "Agreed" or "Strongly Agreed". Recommendations from relevant published guidelines or studies were also included. Twenty-two relevant manuscripts were identified, and 25 statements were formulated. Seventy-two healthcare professionals responded to the survey, including dietitians, medics, nurses, intensivists, and a neurophysiologist. Clinical recommendations were made across the following areas, using evidence from published literature, survey agreement, or the clinical expertise of the authors: patient selection and timing of start, preparation for treatment, dietary prescription, diet initiation, monitoring adverse effects, fine tuning, and weaning of KDT. Thirty statements met the criteria for core recommendations. These are the first international multidisciplinary recommendations for use of KDT for children with super-refractory status epilepticus, intended as a sensical guide for dietitians, neurologists, intensivists, and associated healthcare professionals. The majority of the recommendations are based on survey agreement due to a paucity of published evidence. Children with very severe seizures that do not stop despite medication often need care in intensive care units. This study brings together published evidence and international expert consensus to provide clear guidance on when and how a high-fat, low-carbohydrate ketogenic diet can be started safely in this setting. The recommendations highlight early diet initiation, close monitoring, and strong teamwork between doctors, dietitians, nurses, and pharmacists while recognizing that more high-quality research is still needed.

Nutritional management is essential in caring for patients with chronic kidney disease (CKD), older adults at higher risk of malnutrition and comorbidities. However, data on actual dietary intake patterns in older adults with predialysis CKD, especially by diabetes mellitus (DM) status, remain limited. This cross-sectional study included 106 patients aged &#x2265;65 years with CKD stage G3a or higher, divided into DM (n=67) and non-DM (n=39) groups. Dietary intake was assessed using a single 24-hour recall. Nutrient and food-group intakes were compared with recommended levels. In both groups, energy intake was lower than recommended levels. More than half of the participants exceeded sodium limits, and approximately half consumed excess protein. Patients with DM had significantly higher protein intake and blood urea nitrogen (BUN) levels than those without DM. Most food groups, except protein foods, were consumed below recommended levels. Dietary patterns in older adults with predialysis CKD showed low energy intake, high sodium intake, and relatively high protein intake. Those with DM had higher protein intake and BUN levels, suggesting dietary differences by diabetes status. These findings underscore the need for age-sensitive, individualized nutritional management strategies that consider kidney function and DM status.

This study investigated the association between plant-based diet indices-overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI)-and depressive symptoms in South Korean adults. This cross-sectional study analyzed 5,846 participants (aged 19-64 years) using data from the 2014 and 2016 South Korea National Health and Nutrition Examination Survey. Dietary intake was assessed with a semiquantitative food frequency questionnaire, from which PDIs were derived. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Survey-weighted linear and logistic regression models were applied to assess associations, adjusting for sociodemographic, lifestyle, and clinical factors. In fully adjusted models, higher overall PDI and hPDI were associated with lower PHQ-9 scores (&#x3b2;=-0.23; 95% confidence interval [CI], -0.41 to -0.04 and &#x3b2;=-0.16; 95% CI, -0.30 to -0.02 per 10-unit increment, respectively), whereas higher uPDI scores were associated with higher PHQ-9 scores (&#x3b2;=0.21; 95% CI, 0.07 to 0.35 per 10-unit increment). For clinical depressive symptoms (PHQ-9 &#x2265;10), each 10-unit increase in overall PDI was associated with a 33% reduction in odds (odds ratio, 0.67; 95% CI, 0.50 to 0.89). Associations for hPDI and uPDI were attenuated and not statistically significant. Subgroup analyses revealed that these associations varied by sex, age, and obesity status. Greater adherence to healthy plant-based foods and lower intake of less healthy plant-based foods were associated with fewer depressive symptoms among South Korean adults. These findings highlight the importance of plant-based food quality, rather than quantity alone, in supporting mental health.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease in which anti-double-stranded DNA (anti-dsDNA) antibodies are closely associated with disease activity and organ involvement. However, the relationships of 25-hydroxyvitamin D [25(OH)D], CD4+/CD8+ ratio, and prognostic nutritional index (PNI) with anti-dsDNA antibody status and titer stratification remain incompletely understood. A total of 126 patients with SLE were enrolled and classified into an anti-dsDNA-negative group and an anti-dsDNA-positive group. According to anti-dsDNA titers, patients were further stratified into low-titer and high-titer groups. Clinical characteristics and laboratory parameters, including 25(OH)D, CD4+/CD8+ ratio, and PNI, were compared among groups. Receiver operating characteristic curve analysis was performed to evaluate the discriminatory performance of 25(OH)D, CD4+/CD8+ ratio, PNI, and their combined model. Compared with anti-dsDNA-negative patients, anti-dsDNA-positive patients had significantly lower levels of C3, C4, the CD4+/CD8+ ratio, 25(OH)D, and PNI, together with a higher prevalence of renal involvement (all P&#xa0;<&#xa0;0.05). Significant differences in 25(OH)D, the CD4+/CD8+ ratio, and PNI were also observed across the anti-dsDNA-negative, low-positive, and high-positive groups. In ROC analysis, 25(OH)D showed the highest AUC among the individual biomarkers for anti-dsDNA serostatus, whereas the combined assessment achieved the highest overall AUC. For stratifying low-positive from high-positive anti-dsDNA titers, the combined assessment showed better discriminatory performance than PNI and C3. Combined assessment of 25(OH)D, the CD4+/CD8+ ratio, and PNI may provide complementary value for anti-dsDNA-based stratification in SLE. Its performance was comparable to C3 for anti-dsDNA serostatus and superior to C3 for stratifying low-from high-positive anti-dsDNA titers. These findings should be considered exploratory and require validation in external cohorts.

Worldwide, approximately half of the general population is actively attempting to lose weight. However, weight loss is typically followed by substantial weight regain, often leading to repeated cycles of loss and gain of bodyweight. Weight cycling has been suggested to be metabolically harmful, in that it could lead to greater rebounds in fat mass and smaller regains in lean (muscle) mass, thereby promoting sarcopenia, lowering metabolic rate, and exacerbating obesity and its metabolic complications (eg, glucose intolerance). In this Personal view, we critically evaluate evidence from studies in humans and animals investigating whether weight cycling has adverse effects on bodyweight, body composition, energy metabolism, and metabolic function. We also briefly discuss potential strategies to mitigate weight regain and its consequences. Overall, the current evidence does not support a causal link between weight cycling per se and clinical harm in people with obesity. Most of the adverse effects reported are likely circumstantial, possibly because of ageing, unintentional weight loss, reverse causality, earlier onset of obesity, repeated obesogenic exposures, or longer cumulative exposure to obesity. Available evidence suggests that the benefits of intermittent weight reduction-such as improved metabolic markers, cardiovascular health, and quality of life-outweigh the potential risks associated with weight fluctuation.

Frailty is prevalent in older adults and affects up to half of people living with heart failure, contributing to functional decline, hospitalisation, poor quality of life, and mortality. Malnutrition manifests in frail older adults with heart failure, making nutrition a central determinant of altering the frailty trajectory. Nutritional care is commonly considered an ancillary service rather than a therapeutic component of care in multimorbid conditions. This perspective, informed by evidence, argues for repositioning "food is medicine" as a shared, preference-sensitive therapeutic strategy for frailty prevention and reduction in people with heart failure. "Food is medicine" is an intentional approach shifting beyond nutrient supplementation, positioning diet as a first-line, patient-centred intervention that supports dignity, muscle preservation, symptoms management, and functional resilience. Coordinated action across clinical practice, policy, and research is necessary to ensure nutrition is recognised and delivered as core therapy for frail individuals with heart failure.

Enteral nutrition is commonly practiced for ischemic stroke survivors with dysphagia. In Eastern Asia, nasogastric and oro-esophageal tubes are the mainstream options. However, there is a lack of rigorous clinical evidence on the effects of these two feeding methods on swallowing-related rehabilitation outcomes and clinical relevance. This study is clinically oriented and aims to assess the effect of nasogastric versus oro-esophageal tube feeding on the degree and speed of dysphagia improvement, and aspiration symptoms. This multicenter randomized controlled trial will include 422 ischemic stroke patients with dysphagia who require tube feeding. Stratified randomization will be performed to assign participants 1:1 to the oro-esophageal or nasogastric groups. All participants will receive 15-days routine rehabilitation care and nasogastric or oro-esophageal feeding, according to their group assignment. The primary outcome is the dysphagia severity assessed using the Dysphagia Outcome and Severity Scale (DOSS). The secondary outcomes include time to improvement of one level from the baseline DOSS, time to oral intake, accumulation of secretions assessed using the Murray Secretion Scale, pharyngeal residue after swallowing assessed using the Yale Pharyngeal Residual Severity Rating Scale, and airway protection assessed using the Penetration-Aspiration Scale. Aspiration symptoms will be monitored for 6&#x202f;weeks. This study aims to provide evidence-based support for the comprehensive effects of tube feeding on swallowing-related rehabilitation outcomes. ClinicalTrials.gov, identifier NCT07386834.

The lack of universal cross-species sampling and quality control methods has limited the potential of breath metabolomics to advance from clinical discovery to mechanistic validation. To address this challenge, this study developed and systematically validated an integrated cross-species breath analysis platform, with its core components comprising a high-sensitivity mouse breath sampling system (FaunaScope) and a quality control (QC) strategy incorporating behavioral monitoring. By identifying ethyl acetate and dimethyl sulfide as characteristic interference markers, the platform exhibited high detection capability and good analytical reproducibility in the analysis of 33 core volatile organic compounds (VOCs) in mouse breath, with detection rates exceeding 88.2% for 30 VOCs and coefficients of variation below 30% for more than 70% of the compounds. Using inflammatory bowel disease (IBD) as a demonstration model, the platform enabled a full-chain study from validation of breath fingerprints in clinical patients to longitudinal monitoring in mouse models, successfully capturing dynamic metabolic changes in short-chain fatty acids (SCFAs) and responses to exclusive enteral nutrition (EEN) intervention, while revealing metabolic feature divergence between humans and mice attributable to differences in pathological mechanisms. Overall, this platform exhibits high sensitivity and strong resistance to interference, providing an effective translational medicine tool for linking clinical findings with fundamental mechanistic research.

As global life expectancy rises, the focus has shifted from longevity alone to healthy aging. Although dietary models such as the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), Mediterranean-DASH Intervention for Neurodegenerative Delay, and EAT-Lancet diets show benefits for specific health outcomes, their direct application to South Korean populations is limited by differences in dietary patterns and cultural practices. This study aimed to develop nutritional criteria for a South Korean-adapted longevity diet framework. A multiphase development approach was used, including a narrative review of major dietary models and clinical nutrition guidelines to identify key components of a longevity diet. Macronutrient distribution, food group intake, and nutrient-specific recommendations were synthesized into a structured framework. The EAT-Lancet reference diet was adjusted from 2,400 to 2,000 kcal/ day to reflect energy requirements of South Korean adults. The proposed framework comprises six domain-specific recommendations, including macronutrient targets of 50%-65% carbohydrates, 10%-20% protein, and 15%-30% fat, with a 1:1 animal to plant protein ratio. Food group recommendations were tailored to South Korean dietary patterns. The framework addresses weight management, glycemic control, cardiovascular health, cognitive function, muscle function, and skin health. It emphasizes whole grains, dietary fiber, plant-based proteins, and unsaturated fats, while limiting refined carbohydrates, added sugars, and saturated fats. This study presents evidence-based nutritional criteria for a South Korean-adapted longevity diet framework that integrates disease prevention with functional health support to promote healthy aging.

Circadian rest-activity rhythms, or a person's consistency in their daily activity and rest patterns, can be quantified using various parametric and non-parametric methods. However, these methods are seldom applied to understand symptoms in cancer survivorship. This study examined associations between various rest-activity rhythm parameters and cancer-related fatigue and quality of life. Adult cancer survivors (n&#x2009;=&#x2009;31) were enrolled in a 12-week randomized clinical trial of individualized nutrition counseling with or without time-restricted eating. Participants wore actigraphy watches continuously for 3-7&#x2009;days at baseline, 6&#x2009;weeks, and 12&#x2009;weeks. Rest-activity parameters were derived using cosinor models, traditional non-parametric methods, and probabilistic hidden Markov models (HMMs). Participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, including physical, social, emotional, and functional well-being subscales; fatigue; and a quality-of-life total score. Mixed models revealed that stronger rest-activity rhythms were generally associated with lower fatigue and greater well-being in several dimensions. Specifically, intradaily variability and the HMM-derived rhythm index were positively associated with emotional well-being (p&#x2009;=&#x2009;0.040 and p&#x2009;=&#x2009;0.037, respectively, medium effect sizes). Earlier daily activity peaks, identified through both parametric and non-parametric methods, were linked to greater emotional well-being (e.g. cosinor peak time and emotional well-being, p&#x2009;=&#x2009;0.006, large effect size; start hour of the most active 10&#x2009;hours, p&#x2009;=&#x2009;0.004, large effect size). There was no effect of group (time-restricted eating vs. control) on any of the rest-activity parameters. Findings suggest that rest-activity rhythm parameters, including those derived from novel HMMs, may serve as useful biomarkers of fatigue and various dimensions of well-being, supporting further research in larger samples and potential clinical application.

Schizophrenia (SCZ) is a highly heritability psychological disorder, however the exact etiology remains unclear, and lack of the reliable and effective biomarkers for diagnosis and treatments in the management of SCZ, thus exploring the novel biomarkers in SCZ may enhance the efficacy of its predictive, preventive, and personalized medicine (PPPM/3PM) approach. Based on differentially expressed genes (DEGs) and weighted gene co-expression network (WGCNA) analyses from five brain datasets, we screened SCZ-key genes and then developed a novel machine learning (ML) framework that incorporated 12 MLs and their 84 combinations to construct a consensus diagnostic signature. Meanwhile, we constructed the nomogram with aforementioned signatures to provide a quantitative clinical practice tool for predicting SCZ. Subsequently, we performed the consensus clustering and nonnegative matrix factorization (NMF) algorithms for clustering analysis in SCZ patients. On this basis, the regulation factors of diagnostic signature, enrichment patterns and immune infiltration analysis in SCZ, and protein level among SCZ subtypes were evaluated. We identified 53 SCZ-key genes by intersecting DEGs and module genes of WGCNA, then developed a consensus diagnostic signature using a 84-combination ML framework, and established a nomogram diagnosis model with aforementioned signature for clinical practice, demonstrating promising discriminative performance and potential clinical utility benefits in predicting SCZ. Moreover, consensus clustering analysis could divide SCZ patients into two distinct clusters, and two subgroups were distinguished using NMF algorithm with DEGs of two clusters. Furthermore, we observed distinct biological functions, immune cells and protein functions between subtypes. Finally, hub genes of subgroups, which were closely associated with SCZ. Our study constructed a novel diagnostic signature and a nomogram, which all achieved higher accuracy and maybe as the potential diagnostic tools for SCZ. Meanwhile, SCZ subtypes showed distinct inflammation, immune and metabolic patterns, incorporating the subtypes into the 3PM framework will provide a unique opportunity for clinical intelligence and new management approaches.

Nutrition contributes to bone mineral density (BMD) during infancy and childhood, however, studies focusing on infant nutrition and BMD relationships in childhood are limited. To examine relationships of any breastfeeding (BF) duration (BF duration) and timing of complimentary foods and beverages (CFB) introduction with BMD outcomes in young Asian children from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Healthy term-born 6-year-old children (n=207) with available BF duration data (months), and dual-energy x-ray (DXA) absorptiometry scans of lumbar spine (LS) and whole-body (WB) were included to examine the BF duration and CFB introduction associations with DXA-derived-BMD outcomes; cohort specific Z-scores of areal BMD (aBMD, g/cm2) and bone mineral apparent density (BMAD, g/cm3) of WB and LS. Multivariable models utilized regularized regression modelling (LASSO) to leverage multiple covariates without overfitting the available data. In univariable models, longer BF duration was associated with lower ZWB-BMD (-0.013 (0.006), P=0.027) and ZLS-aBMD (-0.012 (0.006), P=0.045); in stratified analyses longer BF duration was associated with lower ZWB-BMD (-0.023 (0.008), P=0.004), ZWB-BMAD (-0.020 (0.007), P=0.006) and ZLS-aBMD (-0.018 (0.008), P=0.037) in females only. Most associations remained significant in adjusted LASSO models. Later CFB introduction was associated with lower ZWB-BMAD (-0.130 (0.065), P=0.045); in stratified analyses later CFB introduction was associated with lower ZLS-aBMD (-0.166 (0.078), P=0.037) and ZLS-BMAD (-0.205 (0.078), P=0.010) in males only. These associations were no longer apparent in adjusted LASSO models. A longer BF duration and delayed CFB introduction may reflect reduced bone accrual in early childhood, inferred from bone density at 6 years, and may vary by child's sex. Recognizing these relationships is crucial for optimizing early nutrition to support strong and healthy bone development. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE WHERE IT WAS OBTAINED: https://www. gov/study/NCT01174875.

Luteolin and fisetin are emerging lead flavonoids with significant therapeutic promise due to their wide-spectrum modulation of key molecular signalling pathways implicated in oxidative stress, inflammation, metabolic dysfunction, neurodegeneration, and cancer. However, mechanistic integration, SAR-based interpretation, and translational pharmacokinetic understanding remain fragmented. This systematic review aims to consolidate molecular targets, signalling network interactions, structure-activity relationships, pharmacokinetic limitations, and clinical advancement potential of luteolin and fisetin to define their future drug development relevance. A systematic PRISMA-based strategy was employed across PubMed, Scopus, Web of Science, and Google Scholar up to March 2025. Eligible in vitro, in vivo, and clinical studies evaluating the mechanistic activity, SAR influence, pharmacokinetics, or therapeutic efficacy of luteolin/ fisetin were included. Data were narratively synthesised due to heterogeneity in study designs. A total of 127 studies met eligibility criteria. Both flavonoids demonstrated multi-target and multi-pathway modulation involving NF-&#x3ba;B, Nrf2, MAPK, PI3K/Akt, apoptotic regulators, neuroinflammatory signals, and metabolic pathway nodes. SAR analysis identified hydroxylation patterns, O-methylation, and glycosylation as determinants of potency, membrane permeability, and ADME properties. Pharmacokinetic evidence revealed poor solubility, low oral bioavailability, and rapid metabolism, though nanoformulations, prodrugs, and targeted delivery systems significantly enhanced systemic exposure and therapeutic index. Luteolin and fisetin represent valuable flavonoid scaffolds with highly relevant druggable molecular targets. Despite promising mechanistic depth, clinical validation remains limited, and pharmacokinetic barriers warrant strategic optimisation. Future translational advancement should prioritise structure-guided analogue development, BBB penetration enhancement, and biomarker-linked clinical endpoints.

Sarcopenia is characterized by a decline in muscle mass and quality and has emerged as a life-threatening aging-related syndrome. However, the association between adult weight trajectories and muscle health remains unclear. Using data from 1,007 adults aged &#x2265;50&#x2009;years from the United States. National Health and Nutrition Examination Survey (NHANES) 2011-2014 cycles, a cross-sectional analysis of body mass index (BMI) trajectories across four adult life stages was conducted using growth mixture modeling. Dual-energy X-ray absorptiometry (DXA)-derived appendicular skeletal muscle mass index (ASMI) and muscle quality indices, including the appendicular muscle quality index (MQI.app) and total muscle quality index (MQI.total), calculated as grip strength per unit of muscle mass, were used to assess muscle health. Multivariate regression analysis was applied to evaluate the associations between BMI trajectories and muscle outcomes. Three BMI trajectories were identified: stable normal (38.5%), rapid increase (16.5%), and stable high (45.0%). The ASMI was greater, whereas the MQI was markedly lower in the rapid increase group than in the stable normal group, with odds ratios (ORs) of 11.38 (95% CI: 6.18-20.98) for the extremely low MQI.app category and 10.07 (95% CI: 5.85-17.11) for the extremely low MQI.total category. The stable high group also showed increased odds of lower MQI categories. BMI trajectory was heterogeneously associated with muscle phenotype. Static indicators such as BMI and the ASMI alone may not fully capture functional risk. These findings highlight the need for further research on muscle quality and long-term weight dynamics, and for prospective studies before any clinical screening or intervention implications can be considered.