Search Results (6,571)

Background and Objectives: Tobacco smoking is associated with an increased risk of depression and anxiety symptoms, but it remains unclear whether this relationship differs according to the type of nicotine product used. The increasing popularity of heated tobacco products has created a need to better understand their association with mental health, particularly in comparison with combustible cigarettes. Therefore, this study aimed to compare the prevalence of depression and anxiety symptoms among combustible cigarette (CC) users, heated tobacco product (HTP) users, and non-smokers. Materials and Methods: A cross-sectional study was conducted among 497 adults. Participants were classified into three groups according to their tobacco-use status: combustible cigarette smokers, heated tobacco users, and non-smokers. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and anxiety symptoms were assessed using the Generalized Anxiety Disorder-7 (GAD-7). Group differences were evaluated using hierarchical linear regression analyses adjusted for sociodemographic, health, and lifestyle factors. Results: Tobacco-use group significantly improved the model fit for PHQ-9 (ΔR² = 0.0575, p < 0.001) and GAD-7 (ΔR² = 0.0764, p < 0.001). In non-smokers, scores of depression were 3.48 lower than in CC users and 1.42 lower than in the HTP users’ group. In HTP users, these scores were 2.06 lower than in the CC users’ group. Anxiety scores were 3.71 lower in non-smokers than in CC users, and 1.29 lower than in the HTP users’ group. In the HTP users’ group, this score was 2.42 lower than in the CC users’ group. HC3 robust standard errors with 5000-sample BCa bootstrap confidence intervals and reduced-adjustment sensitivity analyses confirmed the primary pattern. Conclusions: Our study results showed that combustible cigarette users had the highest adjusted depression and anxiety scores, HTP users had intermediate scores, and non-smokers had the lowest. In both tobacco-using groups, greater product-specific nicotine dependence was associated with higher PHQ-9 and GAD-7 scores. Further interdisciplinary studies incorporating biomarkers of nicotine exposure, HPA axis function, inflammation, and oxidative stress are needed to clarify whether the observed differences reflect the characteristics of individuals who choose specific tobacco products or are partly attributable to product-specific effects. Full article

Background/Objectives: Periodontitis is a multifactorial chronic inflammatory disease influenced by behavioral, metabolic, and lifestyle-related factors. This study aimed to examine the associations of selected dietary habits, body mass index (BMI), physical activity, smoking, and oral hygiene behaviors with clinical periodontal parameters in a clinical sample of adults with periodontitis from northwestern Romania. Methods: This cross-sectional study included 204 adults with clinically diagnosed periodontitis. Sociodemographic characteristics, smoking status, physical activity, toothbrushing frequency, tooth mobility, and selected dietary habits were assessed using a structured questionnaire. Periodontal status was clinically evaluated using periodontal probing depth (PPD), clinical attachment loss (CAL), and bleeding on probing (BOP), while BMI was calculated from anthropometric measurements. Descriptive and inferential statistical analyses were performed to evaluate associations between the investigated factors and periodontal parameters. Multivariable linear regression models were constructed separately for PPD, CAL, and BOP, simultaneously including age, sex, BMI, smoking status, physical activity frequency, toothbrushing frequency, tooth mobility, education level, and the assessed dietary habits. Results: In the fully adjusted multivariable analyses, fish consumption 1–3 times/week was independently associated with lower PPD, whereas sweets consumption 1–3 times/week was independently associated with higher PPD. Carbonated beverage and sweets consumption 1–3 times/week were independently associated with higher BOP. Although the multivariable model for CAL was statistically significant overall, none of the individual predictors included in the model reached statistical significance. BMI and physical activity frequency were not independently associated with PPD, CAL, or BOP after simultaneous adjustment for the other variables. Age group was significantly associated with CAL category (χ²(2) = 13.28, p = 0.001, Cramér’s V = 0.255), while educational level was significantly associated with toothbrushing frequency (χ² = 62.26, p < 0.001, Cramér’s V = 0.39). Conclusions: Selected dietary habits were independently associated with PPD and BOP after adjustment for demographic, anthropometric, lifestyle, and oral hygiene factors, whereas no individual predictor was independently associated with CAL in the fully adjusted model. BMI and physical activity were not independently associated with the periodontal parameters examined. These findings emphasize the multifactorial nature of periodontal status and suggest that specific dietary habits may be associated with different clinical dimensions of periodontal disease. However, causal relationships cannot be established due to the cross-sectional design of the study. Prospective studies using validated dietary assessment methods are needed to confirm these associations. Full article

Background/Objectives: Obesity is a chronic, progressive, and relapsing disease that requires long-term, multidisciplinary management rather than episodic weight-loss treatment. Although novel incretin-based anti-obesity pharmacotherapies, including GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, have markedly improved the clinical management of obesity, weight reduction alone does not fully capture treatment success. Body composition, lean mass preservation, physical function, nutritional adequacy, psychological well-being, adherence, and long-term weight-loss maintenance are increasingly recognized as essential therapeutic outcomes. This narrative review critically examines the role of lifestyle medicine as a co-therapeutic strategy during modern anti-obesity pharmacotherapy, with particular attention to physical activity, nutrition, behavioral support, and individualized monitoring. Methods: A narrative literature search was conducted in PubMed up to June 2026. The review included studies addressing adults with overweight or obesity and evidence related to anti-obesity pharmacotherapy, physical activity, nutrition, body composition, functional outcomes, eating behavior, quality of life, treatment tolerability, adherence, weight regain, and long-term maintenance. Results: Current evidence indicates that incretin-based therapies produce substantial and clinically meaningful weight loss, but pharmacological efficacy may be limited by reductions in lean mass, gastrointestinal adverse events, inadequate nutritional intake, treatment discontinuation, and weight regain after drug withdrawal. Physical activity should be considered a therapeutic component rather than only a tool for increasing energy expenditure, as aerobic exercise supports cardiometabolic health and cardiorespiratory fitness, while resistance training helps preserve muscle strength, bone health, and functional capacity. Nutritional strategies are equally important, particularly during appetite suppression, to maintain adequate protein, fiber, fluids, micronutrients, and diet quality. Behavioral factors, including sleep, stress, mood, stigma, self-regulation, and the food environment, may influence adherence and long-term outcomes. Conclusions: Novel anti-obesity drugs should not be viewed as replacements for lifestyle medicine but as powerful tools within an integrated chronic-care model. The goal of treatment should move beyond maximal body-weight reduction to durable improvements in body composition, metabolic health, physical function, nutritional status, quality of life, and weight-loss maintenance. Full article

Glutathione is an abundant intracellular low-molecular-weight thiol that contributes importantly to cellular redox homeostasis. Besides its well-established role in the antioxidant defense of the cell, glutathione regulates mitochondrial function, metabolism of toxicants, protein thiol oxidation/reduction, redox signaling, and immunity. Disturbances in glutathione metabolism have been shown to play a role in various diseases; however, it has become clear that changes in glutathione metabolism are a part of a complex, multifactorial process. In this review, we summarize current knowledge of the molecular mechanisms governing glutathione synthesis, recycling, compartmentalization, and biological functions, with particular emphasis on redox signaling, the nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway, and reversible protein S-glutathionylation. We further examine how disturbances in glutathione homeostasis interact with mitochondrial dysfunction, chronic inflammation, metabolic stress, and impaired cellular signaling in Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, multiple sclerosis, Wilson’s disease, type 2 diabetes, and nonalcoholic fatty liver disease. We also evaluate current translational interventions targeting restoration of glutathione balance through glutathione supplementation, precursor supplementation, pharmacological modulation of endogenous antioxidant mechanisms, dietary interventions, and changes in lifestyle. Despite the fact that many interventions have been promising at the mechanistic and experimental level, there are still insufficient clinical data because of the problems associated with glutathione availability, tissue specificity, disease variability, and a lack of sufficiently powered clinical trials. The conclusion of this review is that glutathione should not be viewed as a universal therapeutic target; instead, glutathione should be perceived as an important factor contributing to cellular resilience and able to help other disease-specific interventions. Future progress in glutathione-based interventions will likely depend on integrating redox biomarkers, patient stratification, and precision medicine strategies to identify individuals most likely to benefit from targeted modulation of glutathione homeostasis. Full article

Background: Depressive symptoms have become a significant public health issue faced by middle-aged and older adults in China. Although previous studies have primarily focused on demographic and socioeconomic factors, the association between modifiable lifestyle behaviors and depressive symptoms still requires further investigation. Objective: To examine the associations between sleep duration, physical activity, digital participation, social participation, and depressive symptoms as well as life satisfaction among middle-aged and older adults in China. Methods: A cross-sectional analysis was conducted using data from the 2020 China Health and Retirement Longitudinal Survey (CHARLS). Depressive symptoms were defined as CES-D-10 scores ≥10, with 13,576 individuals included in the analysis sample. Adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression, while ordinal logistic regression was employed to analyze life satisfaction. The analysis controlled for covariates such as demographics, socioeconomic status, and health status, and accounted for the complex sampling design. Results: The weighted prevalence of depressive symptoms was 44.5%. Sleep deprivation (<7 h/day) was significantly associated with elevated depressive symptoms (aPR = 1.49, 95% CI: 1.33–1.68); participation in recreational activities was significantly associated with reduced depressive symptoms (aPR = 0.86, 95% CI: 0.77–0.96); adequate physical activity was associated with a higher prevalence of elevated depressive symptoms (aPR = 1.17, 95% CI: 1.04–1.32); watching videos (aPR = 0.87, 95% CI: 0.76–0.99) and playing online games (aPR = 0.65, 95% CI: 0.50–0.83) were significantly associated with reduced depressive symptoms; and overall internet use was correlated with lower life satisfaction (OR = 0.90, 95% CI: 0.81–1.00). Women, rural residents, and low-income groups exhibited higher prevalence of elevated depressive symptoms. Conclusion: Sleep deprivation, as well as different types of social engagement, physical activity, and digital behavior, exhibit distinct associations with depressive symptoms in middle-aged and older adults. Behavioral intervention strategies targeting sleep hygiene, leisure activities, and tailored digital behaviors warrant further attention. Full article

Background: Medical students are vulnerable to sleep disturbance and nocturnal eating behaviors that may jointly increase psychiatric and metabolic morbidity. Comprehensive sleep-eating evaluations in Turkish medical students remain limited. To determine the prevalence of poor sleep quality and night eating syndrome (NES) risk and to examine their cross-sectional associations with insomnia, anxiety, emotional eating, restless legs symptoms, chronotype, and lifestyle factors. Methods: This cross-sectional study, conducted from March to December 2023, included 265 medical students who completed validated instruments assessing sleep quality (Pittsburgh Sleep Quality Index [PSQI]), night eating syndrome (NES) risk (a score of ≥25 indicating high risk), insomnia severity, daytime sleepiness (Epworth Sleepiness Scale [ESS]), anxiety, emotional eating, Restless Legs Syndrome (RLS) symptoms, and chronotype. Group comparisons, Spearman’s correlation analyses, and multiple linear regression were conducted. Results: Poor sleep quality (PSQI > 5) affected 50.2% of participants, and high NES risk affected 14.7%. PSQI correlated with NEQ (r = 0.301; p < 0.001), insomnia severity (r = 0.538), anxiety, and emotional eating. Mean NEQ was higher in the poor-sleep group (18.67 ± 8.00 vs. 15.38 ± 6.36; p < 0.001; Cohen’s d = 0.455). Females had higher PSQI and ESS scores, anxiety, and emotional eating scores; high NES risk was numerically more frequent in males (18.6% vs. 11.8%; p = 0.175). RLS symptoms (score > 0) were present in 34.7% (mild 22.6%; moderate 7.9%; severe 4.2%). In the primary multivariable model (PSQI and sex), PSQI was the strongest independent correlate of NEQ (standardized β = 0.325; p < 0.001); sensitivity analyses showed stable PSQI estimates after additional covariate adjustment, whereas sex coefficients were non-significant and unstable across models. A secondary model excluding PSQI identified alcohol use as a significant lifestyle correlate (standardized β = 0.167; p = 0.014). R² = 0.148 for the full covariate model and R² = 0.108 for the primary model. Conclusions: Sleep disturbance and NES risk are prevalent and cross-sectionally associated in Turkish medical students. Poor sleep quality was the strongest independent correlate of night eating scores. Integrated campus screening targeting sleep, eating behavior, anxiety, and comorbid sleep symptoms may facilitate prevention and referral. Full article

Background: Research in behavioral genetics has demonstrated that genetic factors significantly contribute to individual differences in behavior, while environmental exposures shape gene expression through epigenetic mechanisms. This interaction is also relevant to the development of antisocial behavior and psychopathic traits. One of the first evidence of gene–environment interaction was the association between low-activity variants of the MAOA gene, childhood maltreatment, and increased risk of antisocial behavior [¹]. Similarly, our research in incarcerated populations showed that adverse paternal parenting is associated with higher levels of psychopathy and the HTR1B rs13212041 TT genotype appears to modulate the individual susceptibility to negative experiences [²]. Single genetic variants, however, exert only modest effects and current evidence supports a polygenic model in which multiple genetic factors interact with environmental adversity to influence neurodevelopment and behavioral outcomes. Using a genome-wide/endophenotype informed analysis, for example, we identified novel gene–environment interactions as risk factors for psychopathy, involving three independent genetic loci in interaction with paternal maltreatment, which were previously associated with disruptive behavior, temperament, and neuroticism [³]. More recently, we also evaluated whether machine-learning models, integrating behavioral, environmental, and genetic variables, could be helpful to predict psychopathic traits. Methods: We compared logistic regression, random forest, support vector machine, XGBoost, and multilayer perceptron. Results: Support vector machine showed the highest accuracy for predicting Psychopathy Check List-Revised (PCL-R) Factor 2 (antisocial lifestyle). Feature-importance analyses identified impulsivity (BIS-11), empathy (IRI), childhood maltreatment (MOPS), and 12 SNPs as the most informative predictors. Notably, removing genetic variables or MOPS scores substantially reduced the model accuracy, indicating that both genetic and environmental information meaningfully contributed to prediction of antisocial behavior. Conclusions: These findings confirm that genetic influences are neither deterministic nor sufficient to explain criminal behavior but may contribute to interindividual differences in vulnerability, particularly through their interaction with environmental and psychosocial factors. In forensic psychiatry, the integration of genetic and environmental information into behavioral assessment may provide additional objective correlates that complement, rather than replace, traditional clinical and psychosocial evaluations. Such an integrated approach could potentially contribute to a more comprehensive understanding of individual vulnerability and behavioral trajectories. However, the use of genetic information in assessments of criminal responsibility should be approached with caution and proven expertise, given the complex, multifactorial nature of antisocial and criminal behavior. Full article

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide, driven by complex interactions among dyslipidemia, chronic inflammation, insulin resistance, endothelial dysfunction, and gut microbiome-derived metabolites. This review synthesizes mechanistic and clinical evidence on non-pharmacological strategies that modulate these pathways and contribute to ASCVD risk reduction. Dietary patterns such as Mediterranean, DASH, and plant-based diets improve lipid metabolism, attenuate inflammation, and enhance endothelial function. Chrononutrition approaches, including time-restricted feeding and structured fasting protocols, influence circadian regulation of glucose and lipid homeostasis. Circadian misalignment—including irregular sleep timing, shift work, and disrupted feeding–fasting cycles—independently contributes to ASCVD through impaired glucose tolerance, dyslipidemia, endothelial dysfunction, and systemic inflammation. Modulation of the gut microbiome, particularly through increased short-chain fatty acid production and reduced TMAO formation, provides additional cardiometabolic benefits. Key nutraceuticals—phytosterols, omega-3 fatty acids, and berberine—demonstrate clinically meaningful effects through micellar competition, inflammation-resolving lipid mediators, and AMPK activation, respectively. When combined with evidence-based pharmacotherapy, these interventions exert synergistic effects on cardiometabolic risk factors. This integrative biomedical framework highlights the importance of combining lifestyle, metabolic, microbiome-targeted, and nutraceutical strategies for comprehensive ASCVD prevention. Full article

Background/Objectives: Recent pediatric sleep research has increasingly adopted an integrated lifestyle perspective, examining sleep together with diet, physical activity, sedentary behavior, and family environments. However, bowel habits remain comparatively underrepresented despite their potential importance for child health. This conceptual narrative review revisits the Four Kai framework, which brings together sleep, eating, bowel habits, and physical activity as four fundamental daily physiological behaviors and explores their potential relationships with adaptive pleasure, self-regulation, and daytime functioning. Methods: This conceptual narrative review incorporated a descriptive PubMed literature-mapping exercise conducted on 16 July 2026. The search covered publications from January through June of each year from 2022 to 2026 and focused on studies in which sleep was a principal research topic together with terms related to diet, bowel function, physical activity, and lifestyle. Publications clearly outside pediatric or adolescent populations were excluded. Titles and abstracts were reviewed, with full texts consulted when necessary, and eligible studies were classified thematically according to their principal research objective. This exercise was intended to provide descriptive context for the conceptual review and was not conducted as a systematic or scoping review. Results: The descriptive mapping and narrative synthesis indicate that pediatric sleep research frequently examines sleep in relation to diet, physical activity, sedentary behavior, family environments, and other lifestyle factors, whereas everyday bowel habits remain comparatively underrepresented. The reviewed literature supports multiple individual and pairwise associations among sleep, eating, physical activity, bowel function, and daytime functioning but does not establish that these four behaviors operate as a single integrated physiological system. Direct empirical evidence for a pathway linking the Four Kai through adaptive pleasure and positive self-regulation to daytime functioning is currently lacking. Conclusions: The Four Kai framework is best regarded as a hypothesis-generating conceptual framework rather than an established biological or causal model. Its potential value lies in bringing sleep, eating, bowel habits, and physical activity into a common perspective and generating testable questions about their possible functional integration. Future longitudinal and intervention studies should evaluate these behaviors together with adaptive pleasure, self-regulation, and daytime functioning to determine which proposed relationships can be empirically supported. Full article

Background/Objectives: Recurrent pregnancy loss (RPL) has traditionally been investigated predominantly through maternal factors, while the clinical role of paternal assessment remains inconsistently defined. Current guidelines differ substantially regarding semen analysis, sperm DNA fragmentation (SDF), genetic testing, and referral for andrological evaluation. This review aimed to compare contemporary guideline recommendations, critically appraise the directness, prognostic value, and clinical utility of the supporting evidence, and classify paternal assessment strategies as routine, selective, or investigational. Methods: A structured narrative review was conducted using PubMed and Scopus searches through June 2026. International RPL, obstetric, reproductive medicine, and andrology guidelines were compared. Evidence from systematic reviews, meta-analyses, clinical studies, and clinically relevant molecular investigations was evaluated according to its directness to RPL populations, diagnostic and prognostic value, and evidence that test-guided interventions improve miscarriage or live-birth outcomes. Results: Routine paternal assessment should include age, reproductive and medical history, body weight, lifestyle, medication exposure, and relevant environmental or occupational risks. Conventional semen analysis is appropriate primarily when RPL coexists with infertility or suspected male reproductive disease. SDF is the most extensively studied advanced paternal biomarker and is frequently elevated in RPL cohorts, but findings vary by assay and comparator population, while prospective prediction of subsequent live birth and benefit from SDF-directed treatment remain unproven. Parental karyotyping has established counselling value but should be risk-stratified. Sperm aneuploidy testing, oxidative stress assays, seminal microbiome profiling, epigenetic biomarkers, and biomarker-directed interventions remain investigational. Conclusions: Paternal assessment in RPL should be couple-based, clinically targeted, and evidence-informed. Current evidence supports routine clinical evaluation, selective use of semen analysis, SDF testing, genetic assessment, and reproductive urology referral, and restriction of unvalidated biomarkers and treatments to research settings. Full article

Background: Healthy lifestyle guidance is an important component of outpatient preventive care, yet evidence is limited on whether outpatients receive satisfactory guidance across multiple lifestyle domains. This study examined receipt of satisfactory healthy lifestyle guidance and its associated factors among outpatients in China. Methods: This national multicenter cross-sectional study used data from the outpatient component of the fifth National Third-Party Evaluation of the Action Plan for Further Improving Healthcare Services. A total of 31,599 outpatients from 143 tertiary public hospitals across all 31 provincial-level administrative regions of mainland China were included. The primary outcome was receipt of satisfactory healthy lifestyle guidance, defined as receiving at least one type of guidance and reporting satisfaction or high satisfaction. Mixed-effects logistic regression models with hospital-level random intercepts were used to identify associated factors. Results: Dietary guidance was the most frequently reported domain, followed by physical activity, weight management, and smoking cessation and alcohol reduction guidance. Overall, most outpatients were classified as having received satisfactory healthy lifestyle guidance. In the fully adjusted model, male sex and hypertension were associated with higher odds of satisfactory guidance, whereas a greater number of chronic conditions and unclear physician type were associated with lower odds. Satisfaction with history taking and disease communication and perceived respect and comfort from healthcare professionals were strongly associated with satisfactory healthy lifestyle guidance. However, these contemporaneously measured patient-reported indicators may reflect overlapping dimensions of patients’ overall outpatient care experience. Sensitivity analyses yielded broadly consistent findings. Conclusions: Satisfactory healthy lifestyle guidance was common among outpatients in China’s tertiary public hospitals, but guidance was unevenly distributed across lifestyle domains. Patients’ evaluations of satisfactory healthy lifestyle guidance were closely associated with their broader communication and interpersonal care experiences. However, because these measures were self-reported and assessed contemporaneously, the observed associations should not be interpreted causally. 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: Life satisfaction and psychological distress are associated with multiple lifestyle, sleep-related, psychosocial, and sociodemographic factors. However, multinational evidence simultaneously examining these positive and negative psychological dimensions within a comprehensive Mediterranean lifestyle framework remains limited. This study examined correlates of life satisfaction and psychological distress among adults from Mediterranean and neighbouring countries participating in the MEDIET4ALL survey. Methods: Data were collected from 4010 adults (59.5% female) across 10 Mediterranean and neighbouring countries using a standardized multilingual e-survey. Life satisfaction was assessed as the primary outcome using the Short Life Satisfaction Questionnaire (SLSQ), whereas psychological distress (depression, anxiety, and stress) was assessed as the secondary outcomes using the Depression Anxiety Stress Scales (DASS-21). Mediterranean lifestyle adherence was assessed using the validated MEDLIFE index, integrating dietary habits with brief indicators of physical activity, rest, and social/convivial habits, while complementary validated measures provided more detailed assessments of physical activity, sedentarily, sleep, insomnia and social participation. Hierarchical multiple linear regression analyses were conducted to identify correlates of the primary and secondary outcomes. Bootstrapped exploratory cross-sectional indirect-association analyses were conducted to examine selected indirect statistical associations involving Mediterranean lifestyle adherence, physical activity, social participation, insomnia severity, life satisfaction, and psychological outcomes. Results: Higher life satisfaction was associated with greater Mediterranean lifestyle adherence, better subjective sleep quality, higher social participation, higher education, marital or cohabiting status, and better self-reported health status (β ≈ 0.06–0.18). Conversely, lower life satisfaction was associated with higher body mass index, greater physical activity expenditure, higher insomnia severity, and regional differences between Mediterranean and neighbouring/non-Mediterranean countries (β ≈ −0.05 to −0.19). Insomnia severity showed the strongest negative association with life satisfaction (β = −0.19). Across psychological distress outcomes, insomnia severity emerged as the strongest positive correlate of depression, anxiety, and stress (β ≈ 0.43–0.47), followed by alcohol consumption (β ≈ 0.12–0.15) and residence in Mediterranean countries (β ≈ 0.05–0.08). Older age, analysed as a continuous variable, better self-reported health status, and higher physical activity levels were consistently associated with lower distress levels (β ≈ −0.03 to −0.14). Exploratory cross-sectional indirect-association analyses identified statistically significant indirect associations involving insomnia severity among Mediterranean lifestyle adherence, life satisfaction, and psychological distress. Additional indirect statistical associations involving life satisfaction were observed among physical activity, social participation, and psychological distress outcomes, although their magnitudes were small. Conclusions: Mediterranean lifestyle adherence, social participation, physical activity, sleep-related characteristics, and sociodemographic and health-related factors were associated with life satisfaction and psychological distress. Sleep-related variables, particularly insomnia severity and subjective sleep quality, emerged as the most consistent correlates across the psychological outcomes. These cross-sectional findings, including the exploratory indirect statistical associations, should be interpreted as hypothesis-generating and not as evidence of temporal ordering, causal mediation, or behavioural mechanisms. Full article

Background: Lifestyle habits are critical determinants of psychological health. This study aimed to determine the association between lifestyle factors and perceived stress levels, examining the potential mediating role of Mediterranean diet adherence (MDA). Methods: A cross-sectional study was conducted with 1229 participants (50.04% female, mean age of 13.45 ± 1.97 years). Lifestyle factors, including MDA, screen time (ST), sleep duration, active commuting and physical activity, were assessed. A multiple linear regression and mediation analysis were performed, adjusting for age and sex. Results: Significant sex differences were found, with females reporting higher stress and lower MDA (p < 0.001). Regression models revealed that higher MDA (p = 0.001) and lower ST (b = 0.22, p = 0.014) were significantly related to reduced stress. Mediation analysis showed that MDA statistically (partially) mediated the association between ST and stress (Indirect effect = 0.025, 95%CI; 0.005, 0.054). Specifically, MDA accounted for 10.12% of the total effect of ST on stress, representing a modest indirect contribution. Conclusions: Elevated ST routines are positively associated with adolescent perceived stress, whereas higher MDA displays an inverse relationship with stress. Additionally, this association is structurally modulated by MDA, highlighting that the unfavorable correlates of excessive television viewing and video-game use are modestly linked to concurrent variations in dietary quality within school environments. Given the cross-sectional design, these findings should be interpreted as indirect associations rather than causal pathways, and reverse or bidirectional relationships cannot be ruled out. Full article

As global aging accelerates, identifying age- and lifestyle-associated gut microbiota alterations has become critical for understanding healthy aging and microbiota-targeted interventions. To explore the associations of age and lifestyle factors with gut microbiota profiles in community-dwelling adults, 159 Chongqing residents were divided into young (18–39, n = 44), middle-aged (40–59, n = 71) and elderly (60–89, n = 44) groups. Fecal samples were analyzed by 16S rRNA gene sequencing, and lifestyle factors were assessed using a study-specific structured questionnaire. The Shannon index differed significantly between the young and middle-aged groups (p < 0.05), whereas other α-diversity and β-diversity analyses showed no significant differences. Age-related shift trends included decreased Bacillota and increased abundance of Bacteroidota. Young adults were enriched in Parasutterella, the [Eubacterium] ventriosum group and Anaerostipes; middle-aged adults were enriched in Clostridium sensu stricto 4, Clostridium sensu stricto 1 and Holdemanella; and elderly adults were enriched in Prevotellaceae UCG-004, Helicobacter, Lactobacillus, Streptococcus and Fusobacterium. Lifestyle factors were independently associated with specific microbial signatures, including tea-related enrichment of Catenibacterium and Escherichia–Shigella, exercise-related enrichment of Dialister and Bavariicoccus, and milk-related enrichment of Bacillus and Klebsiella (formerly Raoultella). Overall, these findings provide population-based evidence linking age and lifestyle factors with gut microbial profiles and may inform microbiota-targeted strategies for healthy aging. Full article