Search Results (3,399)

Heart failure (HF) is a systemic syndrome in which prognosis depends on cardiac dysfunction, congestion, cardiorenal and cardiohepatic interactions, inflammation, and metabolic dysregulation. The liver is exposed to elevated systemic venous pressure and reduced forward flow, and contributes to albumin and coagulation factor synthesis, bile acid metabolism, iron homeostasis, and the acute-phase response. Cardiohepatic injury involves hemodynamic stress, sinusoidal endothelial dysfunction, oxidative stress, inflammatory signaling, fibrogenesis, and altered metabolic regulation. Congestive hepatopathy is associated with right-sided HF, tricuspid regurgitation (TR), pulmonary hypertension, and elevated central venous pressure, whereas hypoxic hepatitis develops during low-output states, shock, or acute circulatory deterioration. These mechanisms may coexist, producing congestive/cholestatic, hypoperfusive/ischemic and mixed/systemic reserve profiles. Composite liver-related scores, including Model for End-Stage Liver Disease (MELD), MELD excluding International Normalized Ratio (MELD-XI), MELD with sodium (MELD-Na), MELD-Albumin and albumin–bilirubin (ALBI) score, may reflect congestion, hepatorenal dysfunction, nutritional status and reduced systemic reserve. This review summarizes hemodynamic and molecular mechanisms of cardiohepatic injury, liver-related biomarkers and composite scores, with emphases on advanced HF, left ventricular assist device (LVAD) therapy and heart transplantation. Liver-related abnormalities remain underrecognized in HF. Their serial interpretation may support risk stratification, but composite scores should complement rather than replace comprehensive clinical assessment. Full article

Vitamin D is a fat-soluble vitamin, considered a prohormone, that plays a fundamental role in calcium absorption and reabsorption, as well as the modulation of inflammatory response in infectious conditions such as COVID-19. A literature search was conducted in scientific databases and official sources, selecting studies published in the last 10 years in Spanish and English related to vitamin D and COVID-19; studies unrelated to the nutritional approach were excluded to reduce bias and ensure a rigorous and reproducible analysis. It was observed that the probability of contracting COVID-19 increases as the D3 hypovitaminosis prevalence increases. In Mexico, the relevance of vitamin D deficiency or supplementation in this disease has been controversial. Some studies claim that vitamin D supplementation could be a protective factor. According to the National Health Survey in Mexico (Ensanut), the Mexican population has significant deficiencies in this vitamin, contributing to an unfavorable diagnosis, particularly for children and pregnant women, as it is considered a deficiency in the blood when it is below 30 ng/mL and insufficiency when below 20 ng/mL, making these deficiencies important risk factors in the development of COVID-19 severe cases. Nevertheless, the use of vitamin D as an adjuvant agent in the treatment of COVID-19 can represent one of the main options for public health, providing therapeutic properties and health benefits. Full article

Background/Objectives: Social determinants of health are implicated in metabolic dysfunction–associated steatotic liver disease (MASLD), yet longitudinal evidence on incident disease is scarce, and whether individual- and community-level determinants act independently remains unclear. The objective of this study was to examine whether individual food insecurity and neighborhood deprivation are independently associated with incident MASLD. Methods: In this retrospective cohort of 40,693 U.S. adults without baseline MASLD in the diverse NIH All of Us Research Program, food insecurity (two-item Hunger Vital Sign) and neighborhood deprivation (validated five-domain composite) were co-primary exposures, with incident MASLD ascertained from validated diagnostic codes. Proportional hazards models were adjusted for demographic, socioeconomic, and metabolic factors, including obesity. Results: Over 116,220 person-years, 1240 (3.0%) participants developed MASLD. Both associations remained significant after adjustment for demographic, socioeconomic, and major metabolic risk factors, including obesity (food insecurity adjusted hazard ratio [aHR] 1.32, 95% CI 1.13–1.53; neighborhood deprivation aHR 1.20, 95% CI 1.05–1.37). Unadjusted cumulative incidence was highest among participants with both exposures and lowest among those with neither. Findings were consistent across sensitivity analyses; the food-insecurity association remained when neighborhood disadvantage was specified with a census-based index. Conclusions: Food insecurity and neighborhood deprivation were independently associated with higher incidence of MASLD. Nutrition-focused, equity-oriented interventions warrant evaluation to reduce MASLD burden and advance health equity. Full article

Early-life calf mortality is a significant barrier to herd growth and overall productivity in yak husbandry. This retrospective study investigated the survival pattern and potential risk factors linked to yak calf mortality during the first 90 days of life. Analysis was performed on existing farm records from 428 yak calves born between 2013 and 2025 at a semi-intensive yak farm. The Kaplan–Meier method was used to estimate survival probability, and the log-rank test was used to compare survival probabilities; additionally, a multivariate Cox proportional hazards model was employed to identify independent risk factors. Overall, 70 (16.4%) calves died within the first 90 days after birth. The Kaplan–Meier analysis indicated significantly lower survival probability among low-birth-weight calves (≤12 kg; p = 0.0005) and calves born to primiparous dams (p = 0.0003). In contrast, survival did not differ according to calf sex (p = 0.620) and birth season (p = 0.658). In the multivariate Cox proportional hazards model, low birth weight (HR = 2.27, 95% CI: 1.24–4.16; p = 0.008) and primiparous dams (HR = 2.08, 95% CI: 1.28–3.38; p = 0.003) were independently associated with higher mortality risk. As a result, calf sex and birth season were not significant predictors. Diarrhea and respiratory disease were the predominant causes of calf deaths. The current study’s results indicate that maternal and neonatal factors are the major determinants of early-life calf survival. This highlights the need for special care with optimum nutrition and regular monitoring of primiparous dams and low-birth-weight calves in order to lower pre-weaning mortality and improve overall herd productivity. Full article

Background/Objectives: Aluminium is a widespread environmental element and food contaminant to which the general population is continuously exposed, primarily through diet and drinking water. Although gastrointestinal absorption is generally low, bioavailability varies according to chemical form, food matrix, and interactions with dietary components. Prolonged exposure can nevertheless result in gradual tissue accumulation. This review summarises current evidence on dietary aluminium exposure, factors influencing its bioavailability, toxicokinetics, biological effects, gut microbiota interactions, and population-level health risk. Methods: A comprehensive narrative literature review was conducted using publications retrieved from PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Original research articles, review papers, and reports issued by international organisations were critically evaluated with particular emphasis on dietary sources, drinking water, food additives, food contact materials, gastrointestinal absorption, toxicokinetics, biological mechanisms, gut microbiota, and health risk assessment. Results: Food represents the principal source of aluminium exposure in the general population, while drinking water usually contributes a smaller but continuous fraction of total oral intake. Dietary exposure varies substantially between populations and is influenced by food composition, processing practices, the use of aluminium-containing additives, and migration from food contact materials. Aluminium bioavailability is modified by chemical speciation and dietary constituents, including citrate, phosphates, silicates, phytates, polyphenols, and essential minerals. Despite limited absorption, prolonged exposure can lead to gradual aluminium accumulation, particularly in bone tissue and the central nervous system. Proposed biological mechanisms include oxidative stress, mitochondrial dysfunction, disruption of mineral homeostasis, and inflammatory signalling. Emerging evidence also indicates that aluminium may alter the gut microbiota, impair intestinal barrier integrity, and influence the gut–brain axis. Population exposure assessments show considerable regional variation, with some groups approaching or exceeding established tolerable weekly intake values. Conclusions: Dietary aluminium exposure represents a relevant issue in nutritional toxicology and food safety. Although current evidence does not establish that typical dietary exposure directly causes chronic disease, long-term exposure, differences in bioavailability, and the possibility of elevated intake in selected population groups justify continued monitoring and further prospective human studies. Future research should integrate dietary intake, aluminium speciation, nutritional status, biomarkers of internal exposure, and long-term health outcomes to improve risk assessment and support effective exposure-reduction strategies. Full article

Background: Alcohol use disorder (AUD) is generally regarded as a relative contraindication to pancreas transplantation. Yet the effect of documented AUD before transplantation on long-term results after pancreas transplantation is still poorly understood. Therefore, we used a large real-world electronic health records database to compare the three-year outcomes among pancreas transplant recipients who had and who had not had documented AUD before transplantation. Methods: We carried out a retrospective cohort study involving propensity score matching using the TriNetX US Collaborative Network. Each adult patient who had a documented case of alcohol use disorder (ICD-10-CM codes F10.1/F10.2) before transplantation was paired one to one with a patient who did not have such a disorder, matching them on demographic characteristics, comorbidities, transplant-related factors, medications, body mass index, and glycated hemoglobin. The outcomes were evaluated from one day after transplantation up to three years later and comprised all-cause mortality, emergency visits, transplant complications, cachexia, severe protein–calorie malnutrition, pain, vitamin deficiencies, iron deficiency anaemia, diarrhea, and adult failure to thrive. Results: Out of 14,367 eligible recipients, propensity score matching resulted in 439 patients in each group. Pretransplant AUD was linked to a significantly higher rate of all-cause mortality (15.1% compared with 8.5%; risk ratio [RR] 1.78, 95% CI 1.22–2.60; hazard ratio [HR] 1.86, 95% CI 1.25–2.78; p = 0.002). Cachexia affected 5.2% rather than 2.5% (RR 2.09, 95% CI 1.03–4.24; HR 2.16, 95% CI 1.06–4.44; p = 0.036), while diarrhea occurred in 39.6% compared with 28.2% (RR 1.40, 95% CI 1.16–1.69; HR 1.54, 95% CI 1.22–1.94; p < 0.001). There were no significant differences in the case of emergency visits (49.0% versus 44.6%; p = 0.199), transplant complications (11.1% versus 14.4%; p = 0.163), severe protein–calorie malnutrition (12.1% versus 8.9%; p = 0.123), pain (59.0% versus 54.7%; p = 0.195), vitamin deficiencies (31.4% versus 29.4%; p = 0.509), iron deficiency anemia (21.2% versus 21.9%; p = 0.805), or adult failure to thrive (7.3% versus 4.3%; p = 0.061). Conclusions: The presence of a history of alcohol use disorder (AUD) before transplantation was found to be independently linked to a higher three-year mortality rate, as well as the occurrence of cachexia and diarrhea after pancreas transplantation, but it was not associated with an increased number of coded transplant complications or most of the other adverse outcomes following the procedure. These results indicate that pancreas transplant recipients with a history of AUD should have enhanced monitoring in the areas of nutrition, the gastrointestinal system, and addiction. Full article

Background: Population aging is driving a convergent rise in three disorders historically managed in isolation: cardiovascular disease, neurocognitive decline, and osteoporotic bone loss. Mechanistic data indicate that these systems are coupled through shared regulators of calcium trafficking, inflammation resolution, vascular integrity, and inflammaging. On this basis, a “Heart–Brain–Bone” axis has been proposed; it should be understood as an integrative conceptual framework that organizes evidence drawn from three separate studies, not as a validated physiological entity with agreed diagnostic criteria or demonstrated modifiability. Three lipid-soluble nutrients—long-chain omega-3 polyunsaturated fatty acids (EPA/DHA), vitamin D3 (cholecalciferol), and vitamin K2 (menaquinone-7 [MK-7])—act on overlapping nodes of this network. Methods: We performed a structured narrative review. PubMed/MEDLINE, Embase, the Cochrane Library, and Web of Science were searched from database inception to 25 June 2026 using predefined term blocks for each nutrient, each organ domain, and each candidate mechanism, and the search was updated on 7 August 2026. Records were screened against prespecified inclusion and exclusion criteria by two authors independently, with disagreements resolved by a third. The strength of evidence for each nutrient–organ relationship was graded with an explicitly defined four-level scheme ((−) to (+++)) applied separately to preclinical, observational, randomized and meta-analytic evidence. Results: Vitamin K2-dependent gamma-carboxylation of matrix Gla protein (MGP) and osteocalcin has been proposed to influence whether calcium is incorporated into the bone matrix or deposited in the arterial wall, offering a candidate mechanistic account of the “calcium paradox” associated with isolated vitamin D3 supplementation; EPA/DHA-derived specialized pro-resolving mediators may support resolution of endothelial and neuronal inflammation; and bone-, vascular- and brain-derived signals (osteocalcin, FGF23, the neurovascular unit) interconnect the three organs. These mechanisms are biologically plausible but remain insufficiently confirmed in humans. The clinical evidence is heterogeneous, formulation- and population-dependent, and comprises positive, neutral and null results: cardiovascular omega-3 trials are discordant (REDUCE-IT, which used icosapent ethyl [an EPA ethyl ester], positive; VITAL/STRENGTH/ASCEND null, predominantly in lower-risk or replete cohorts); cognitive trials are largely null or subgroup-dependent (MAPT, DO-HEALTH, VITAL); and MK-7 improves surrogate bone and calcification biomarkers and slowed coronary artery calcification in one recent randomized imaging trial (VitaK-CAC), whereas combined MK-7 plus vitamin D3 did not slow aortic valve or coronary calcification in AVADEC and MK-7 did not reduce bone loss in early menopausal women. Recognized safety signals include a dose-dependent increase in atrial fibrillation with high-dose omega-3, adverse skeletal effects of high-dose or bolus vitamin D, and clinically relevant interference of even low-dose MK-7 with vitamin K antagonist therapy. Conclusions: No adequately powered randomized trial has demonstrated that the combination of long-chain omega-3, vitamin D3 and MK-7 is superior to its individual components or to placebo for any clinical endpoint. The combined regimen is therefore mechanistically rational and hypothesis-generating rather than clinically established; benefit appears most plausible in individuals with elevated risk or demonstrable nutritional insufficiency, and least in replete, low-risk populations. Findings should be interpreted within a broader healthy-aging context that includes lifestyle and psychosocial factors. Adequately powered factorial randomized controlled trials stratified by baseline Omega-3 index, 25(OH)D and vitamin K status, with prespecified mechanistic biomarkers and hard endpoints, are required. Full article

Background: Focal involvement in brucellosis complicates clinical management and increases treatment failure risk. This study evaluated the predictive value of routine inflammatory markers and, for the first time, the C-reactive protein-albumin-lymphocyte (CALLY) index for predicting focal complications. Methods: A retrospective cohort study conducted between February 2016 and January 2026 included 203 brucellosis patients, categorized into “no focal involvement” (n = 114) and “focal involvement” (n = 89) groups. Admission blood count parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and CALLY index were compared using Receiver Operating Characteristic (ROC) curves, DeLong tests, and multivariate logistic regression models incorporating CRP, albumin, CALLY index, ESR, hemoglobin, MPV, age, and gender. Results: Patients with focal involvement were older (p = 0.029) and exhibited higher ESR, CRP, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios but lower hemoglobin, mean platelet volume, albumin, and CALLY index (p < 0.001). ROC analysis showed ESR had the highest predictive value (AUC: 0.839), followed by albumin (AUC: 0.751) and the CALLY index (AUC: 0.728). DeLong tests confirmed ESR’s statistical superiority over the CALLY index (p = 0.002) and albumin (p = 0.016). In multivariate regression, ESR remained a robust independent prognostic factor (OR: 1.042, p < 0.001), whereas the CALLY index lacked independent significance. Conclusions: Despite its theoretical appeal as a novel immuno-nutritional biomarker, the CALLY index does not outperform traditional markers in predicting focal complications of brucellosis at initial presentation. ESR remains a robust, inexpensive, and statistically superior independent predictor. These findings emphasize that clinicians should continue to rely on widely accessible traditional markers like ESR for early diagnostic risk stratification, while the potential utility of composite scores like the CALLY index may be better reserved for monitoring dynamic therapeutic responses and managing chronic cases. Full article

Background/Objectives: Conflict-driven displacement can disrupt food environments, health services, and caregiver practices, increasing the risk of unhealthy feeding behaviors among young children. Evidence from ethnic internally displaced populations (IDPs) in Myanmar remains scarce. This study examined the prevalence and determinants of unhealthy feeding practices among IDP mothers of children aged 6–23 months. Methods: A sequential explanatory mixed-method study was conducted among 617 mothers in Karen ethnic IDP camps in Myanmar. Structured interviews were used to assess mother-reported zero vegetable or fruit consumption (ZVF) and unhealthy food consumption (UFC) among children, and multivariable logistic regression identified associated factors. Subsequently, six focus group discussions explored contextual influences on feeding practices and were analyzed via thematic analysis. The findings were integrated using a joint display approach. Results: A total of 29.2% of children experienced ZVF, while 57.5% consumed unhealthy foods. Mothers who attended fewer than the recommended antenatal care (ANC) visits were more likely to report both ZVF (AOR = 1.968, 95% CI: 1.297–2.988) and UFC (AOR = 1.830, 95% CI: 1.265–2.649). Higher maternal decision-making autonomy was also associated with increased odds of ZVF (AOR = 1.757, 95% CI: 1.031–2.995) and UFC (AOR = 1.606, 95% CI: 1.040–2.481). Other associated factors included child age, household income, family structure, paternal employment, and household dietary practices. Qualitative findings identified six themes influencing feeding practices: “familiarity breeds acceptance”, “traditional beliefs and food restrictions”, “constrained local food environments”, “time constraints and convenience feeding”, “preference for sweet foods”, and “disrupted access to health and nutrition services”. Conclusions: Unhealthy feeding practices were common in this displaced population. Greater maternal decision-making autonomy was not necessarily associated with healthier feeding practices, highlighting the importance of nutrition literacy and supportive food environments. Community-based nutrition interventions may help improve complementary feeding practices in conflict-affected settings. Full article

Selenium (Se) is an essential trace element for humans and animals, with nutritional functions and abiotic stress regulation capacity, and has been confirmed to alleviate heavy metal toxicity and inhibit its accumulation in crops. Soil lead contamination has become a prominent environmental safety problem in agricultural production, particularly in South China, and lead over-standard in edible crops poses irreversible threats to the human nervous system and blood circulation through food chain transmission. As an efficient exogenous antagonist, Se can comprehensively regulate the absorption, translocation, and compartmentalization of lead in soil–plant systems. This review systematically summarizes the interactive effects of soil physicochemical properties, crop genotypes, and Se speciation on plant lead uptake, and focuses on phytochelatin synthase (PCS), the core rate-limiting enzyme for intracellular heavy metal chelation, to elucidate the molecular cascade of Se-mediated PCS-dependent lead detoxification. We further outline multi-pathway agronomic Se applications for lead reduction; analyze key limiting factors, including Se concentration, application method, and rhizosphere microbial community; and discuss contradictory results and unresolved questions in existing studies. Current evidence confirms that appropriate Se treatment increases glutathione (GSH) content via antioxidant system regulation, upregulates PCS gene transcription and activity, promotes phytochelatins (PCs) polymerization, and forms stable PC-Pb complexes sequestered in vacuoles to reduce cytoplasmic lead mobility. Additionally, Se reshapes rhizosphere microbial community composition to lower soil Pb²⁺ bioavailability and enhances lignin and pectin biosynthesis in root cell walls to physically block root Pb²⁺ influx. Nevertheless, critical knowledge gaps remain unaddressed: (1) upstream signal transduction cascades triggering Se-induced differential PCS expression; (2) precise Pb²⁺ binding sites and affinity of PC oligomers; (3) valence-dependent disparities in selenate, selenite, and nano-Se (SeNPs) modulating PCS activity; and (4) standardized field Se fertilization protocols tailored to staple and tropical tuber crops such as cassava. This review provides systematic theoretical reference and technical foundations for dissecting Se-Pb antagonistic molecular networks, developing Se-enriched low Pb²⁺ functional fertilizers, and mitigating Pb²⁺ contamination risk in agricultural commodities. Full article

Background/Objectives: Dietary inflammation may influence cardiometabolic health, yet the gut mycobiome and bacterial–fungal interactions remain unclear. Building upon our earlier findings and data from the TALENTs trial (Targeting Aging and Longevity with Exogenous Nucleotides) baseline data, we explored gut fungal profiles and bacterial–fungal co-occurrence patterns in relation to the Dietary Inflammatory Index (DII) and Life’s Essential 8 (LE8) in older adults. Methods: We enrolled 301 community residents aged 60–70 years, with 285 providing qualified fungal internal transcribed spacer (ITS) sequencing data. DII scores were derived from 3-day dietary records to reflect dietary inflammatory risk, and LE8 (integrating health behaviors including physical activity and metabolic health factors including BMI, blood lipids, blood pressure, and blood glucose) was used to assess cardiovascular health; LE8_non-diet was applied as a sensitivity measure. Fungal diversity, genus-level taxa, ecological guilds, and bacterial–fungal associations were analyzed using diversity indices, ZINB/Hurdle models, bootstrap, E-values, DIABLO analysis, and network construction. Results: DII showed an inverse correlation with LE8_non-diet (r = −0.130, p = 0.024). Fungal alpha and beta diversity did not differ significantly across DII-defined groups. Conversely, better cardiovascular status was linked to higher fungal richness, with significantly elevated Chao1 and ACE indices in the high-CVH group (both p < 0.05). Additionally, integrated ZINB, Hurdle, and stability analyses jointly pinpointed four candidate fungal genera that correlated with both DII and LE8. Both ZINB and DIABLO analyses consistently indicated that antagonistic interactions dominated gut bacterial–fungal associations (89.9% vs. 63.8% of negative associations, respectively), with DIABLO further revealing synchronized community-level co-variation between the two kingdoms (r = 0.325, p < 0.01). FUNGuild prediction further revealed saprotrophic guilds enriched in the high-CVH group and host-associated guilds in the low-CVH group, with similar patterns across DII-defined groups. Conclusions: This cross-sectional study reveals gut mycobiome profiles and potential bacterial–fungal co-occurrence patterns among older adults stratified by dietary inflammatory potential and cardiovascular health status, generating testable hypotheses for subsequent nutritional and metabolic research integrating lifestyle behaviors and functional health outcomes. Full article

Background/Objectives: Disordered eating behaviours are increasingly common among young adults, yet nutrition-focused, region-specific data from Romania and Central and Eastern Europe (CEE) remain scarce. We characterised nutritional patterns, weight-control practices, disordered-eating indicators, body image, and psychosocial factors among Romanian young adults and tested how these differed across body mass index (BMI) categories. Methods: In a cross-sectional online survey (March–April 2026), 753 Romanian adults aged 18–30 years (93.5% female) completed a 30-item questionnaire. Self-reported anthropometric measurements were classified using WHO BMI cutoffs. Prevalences (with Wilson 95% confidence intervals [CIs]) were compared across BMI categories using the chi-square test, and multivariable logistic regression, adjusted for age and sex, estimated odds ratios (ORs). Results: Most participants were normal weight (59.1%); 11.6% were underweight, 29.3% were overweight or obese, and 86.3% were omnivorous. Dietary restriction (57.4%) and physical exercise (46.7%) were the leading weight-control methods; self-induced vomiting (6.4%) and medication (4.5%) were less frequent. Lifetime compulsive/emotional eating was reported by 50.1%, current stress-related eating by 49.1%, and guilt after eating by 66.1%. Lifetime night eating reached 31.9% (current, 12.9%). Body dissatisfaction (36.1% “not at all satisfied”), difficulty looking in the mirror (66.7%) and self-reported stress (82.2%) were widespread. In adjusted models, dietary restriction, emotional eating and guilt after eating rose steeply and monotonically with BMI (overweight/obesity vs. normal weight: aOR 2.34, 2.49 and 2.73, respectively; all p < 0.001), whereas current night eating and frequent self-weighing did not differ across BMI categories (p = 0.92 and p = 0.82). Dietary restriction increased from 24.1% in underweight to 55.5% in normal-weight and 74.2% in overweight/obesity participants; corresponding gradients were also observed for emotional eating and food-related guilt. Conclusions: In this predominantly female, largely urban online convenience sample of Romanian young adults, self-reported behavioural risk indicators related to disordered eating were common. Restriction, emotional eating and food-related guilt increased with BMI, whereas night eating and self-weighing showed no clear BMI gradient. These findings should be interpreted cautiously and should not be generalised to Romanian young men or rural populations without confirmation in more representative samples. Full article

The intrauterine environment plays a critical role in shaping lifelong health, forming the foundation of the Developmental Origins of Health and Disease (DOHaD) paradigm. Increasing evidence suggests that maternal lifestyle factors, particularly physical activity and nutrition, can actively influence embryonic development; however, how exercise and dietary signals interact to regulate developmental programming remains insufficiently understood. In this review, we summarize emerging evidence that maternal exercise and nutrition function as interconnected regulators of embryonic organogenesis through coordinated maternal–placental–fetal communication. Exercise-induced metabolic, endocrine, and immunological adaptations are highly dependent on maternal nutritional status, while dietary composition provides essential substrates and signaling molecules that modulate exercise-mediated benefits. Through regulation of placental function, exerkines, microbiota-derived metabolites, epigenetic modifications, and nutrient-sensing pathways, the integrated exercise–nutrition axis shapes the development of multiple embryonic organ systems and influences offspring health trajectories. We further discuss current challenges in defining optimal combinations of maternal exercise patterns and nutritional strategies, highlighting the need to move beyond isolated interventions toward precision lifestyle approaches during pregnancy. This perspective establishes maternal exercise and nutrition as synergistic modulators of developmental programming and provides a conceptual framework for understanding how combined lifestyle interventions may enhance offspring developmental resilience and reduce the risk of chronic disease across generations. Full article

Persistent racial and ethnic disparities in type 2 diabetes mellitus (T2DM) are incompletely explained by genetic susceptibility, obesity, lifestyle, and socioeconomic factors, suggesting that additional biological mechanisms may link environmental exposures to metabolic disease risk. Increasing evidence indicates that the exposome, encompassing environmental exposures across the life course, may influence long-term metabolic health through molecular mechanisms that integrate environmental signals with host biology. This Review synthesizes epidemiological, experimental, and mechanistic evidence on the gut microbiota–host epigenetic axis and its potential role in linking environmental exposures to population differences in T2DM susceptibility. Gut microbial dysbiosis alters the production and metabolism of short-chain fatty acids, bile acids, and tryptophan-derived metabolites. These microbial metabolites can modulate host signaling and epigenetic processes, including DNA methylation, histone modifications, and non-coding RNA activity, which may influence the expression of genes involved in glucose homeostasis, inflammation, and insulin sensitivity. Conversely, host epigenetic programs may influence intestinal barrier integrity and immune responses, thereby potentially affecting the gut microbial ecosystem, highlighting the reciprocal nature of host–microbiota interactions. We further examine how diet, psychosocial stress, environmental pollutants, and socioeconomic conditions may shape the microbiota–epigenetic axis across diverse populations, providing a framework for understanding differences in metabolic susceptibility without attributing disparities to intrinsic biological variation. However, direct human evidence linking the gut microbiota–host epigenetic axis to racial and ethnic disparities in T2DM risk remains limited, and much of the current framework is based on mechanistic studies, animal models, and associative human data rather than direct causal evidence. Further research in diverse human populations is needed to validate these pathways and establish their contribution to T2DM disparities. This framework may inform biomarker discovery, stratification, precision nutrition, and microbiome-targeted interventions and generate hypotheses for equitable prevention and personalized management of T2DM across diverse populations. Full article

Background/Objectives: Outcomes after perioperative FLOT for gastric and gastroesophageal junction adenocarcinoma remain variable, even among patients treated with curative intent. Although postoperative pathological findings are central to risk assessment, they do not fully capture patient-related factors that may influence recovery, treatment completion, and survival. This multicenter study evaluated routinely available clinical, laboratory, and pathological variables and assessed whether integrating these variables could improve postoperative prognostic stratification. Methods: We retrospectively analyzed 173 patients with locally advanced gastric or gastroesophageal junction adenocarcinoma treated with perioperative FLOT across seven oncology centers in Türkiye. Overall survival (OS) was the primary endpoint. Baseline inflammatory/nutritional status, pretreatment carcinoembryonic antigen (CEA), postoperative nodal status, and comorbidity burden were assessed. An exploratory modified FLOT Prognostic Score (mFPS) was constructed by assigning one point each for high inflammatory/nutritional risk, elevated CEA, ypN-positive disease, and age-adjusted Charlson Comorbidity Index ≥ 5. Results: At a median follow-up of 39.7 months, median OS was 41.4 months, with estimated 2-year and 5-year OS rates of 69% and 44%, respectively. Surgery was performed in 164 patients, and 83 patients completed planned adjuvant chemotherapy. In multivariable analysis, ypN-positive disease, higher comorbidity burden, and high inflammatory/nutritional risk were independently associated with shorter OS. Among the 126 patients with complete data available for all score components, the mFPS stratified patients into groups with significantly different outcomes: median overall survival was not reached in the low-risk group, compared with 56.1 months in the intermediate-risk group and 18.7 months in the high-risk group. Conclusions: Survival after perioperative FLOT was not determined by residual disease burden alone. Integrating postoperative nodal status with baseline host-related factors may help identify patients at increased risk of adverse outcomes following curative-intent treatment. The proposed score should be considered exploratory and requires external validation before clinical application. Full article