Objectives: This study aimed to explore the relationship between circulating metabolites and postmenopausal osteoporosis (PMOP) and to assess the mediating role of inflammatory factors. Methods: Utilizing summary-level data from genome-wide association studies (GWAS) and employing a Mendelian Randomization approach, a two-sample MR analysis was conducted to assess the relationship between circulating metabolites and PMOP. Additionally, a two-step MR was used to quantify the mediating impact of inflammatory factors on the effect of circulating metabolites on PMOP. Results: The results revealed a significant association between certain metabolites and the risk of PMOP, notably the ratio of free cholesterol to total lipids in very large VLDL particles (OR: 1.399, 95% CI: 1.002-1.954, p = 0.048) and IL-16 (OR: 0.773, 95% CI: 0.608-0.983, p = 0.036). IL-16 was found to partially mediate the impact of circulating metabolites on PMOP, with a mediation effect of 10.4%. Conclusion: This study underscores the crucial role of circulating metabolites and inflammatory factors in PMOP pathogenesis. A causal relationship between circulating metabolites and PMOP was established, with IL-16 mediating some effects. These findings hold promise for clinical applications in early detection, personalized medicine, and the identification of therapeutic targets for PMOP.

BACKGROUND: The bidirectional relationship between cognitive function and depressive symptoms has been extensively reported. However, the potential mechanisms are still not clear. We aim to longitudinally investigate whether physical activity mediates the bidirectional relationships between cognitive function and specific dimensions of depressive symptoms.
METHODS: Data from 6,787 individuals aged ≥50 of 2014/15 (T1), 2016/17 (T2), and 2018/19 (T3) waves of the English Longitudinal Study of Ageing (ELSA). Cognitive function was assessed by domains of memory, orientation in time, and executive function. Physical activity was measured with the intensity and frequency of participation. Specific dimensions of depressive symptoms were assessed by the 8-item Center for Epidemiologic Studies Depression Scale, distinguishing between cognitive-affective and somatic symptoms. Cross-lagged panel models were used to investigate the mediating role of physical activity in the bidirectional relationships between cognitive function and two dimensions of depressive symptoms.
RESULTS: Poorer cognitive function was indirectly associated with worse cognitive-affective symptoms (indirect effect = -0.002, 95%CI: -0.004, -0.001) through lower physical activity levels. Poorer cognitive function was also indirectly associated with worse somatic symptoms (indirect effect = -0.003, 95%CI: -0.006, -0.002) through lower physical activity levels, and the reverse mediation was observed as well (indirect effect = -0.002, 95%CI: -0.004, -0.001).
CONCLUSIONS: There is no distinction between potential within-person and between-person effects.
CONCLUSIONS: Collaborative interventions of physical activity are beneficial in protecting cognitive function and mental health in older adults.

UNASSIGNED: A robust association between physical activity (PA) and satisfaction with life (SWL) has been established, wherein self-efficacy has been identified as a mediator across different populations. However, there is a need to further examine the relationship between PA and SWL and whether self-efficacy act a as mediator within different levels of PA among Norwegian adolescents. Thus, the objective of this study was to explore the relationship between levels of PA and SWL by testing for self-efficacy as a possible mediator.
UNASSIGNED: Cross-sectional data from the 2022 Norwegian Ungdata Survey was utilized. Data included demographics and various health data that was collected anonymously. The electronic survey took place in classrooms and was administered by the respective teacher. Permission to access and use data was approved by the Norwegian Agency for Shared Services in Education and Research (SIKT). Statistical analyses were conducted using the PROCESS macro by Andrew Hayes for SPSS software.
UNASSIGNED: Descriptive findings revealed that girls reported lower self-efficacy than boys (14.2 vs. 15.5, with a maximum of 20) and lower SWL (6.8 vs. 7.6, with a maximum of 10). About one out of five girls and one out of seven boys reported no days of weekly PA, whereas 4% of girls and 9.5% of boys adhered to the PA-recommendation of 60-min of daily exercise. Associations between PA levels and SWL was mediated by self-efficacy (all p < 0.05), with the highest indirect effect (56.3%) revealed in the association between those adhering to the PA-recommendations and SWL.
UNASSIGNED: Norwegian girls reported more sedentary behavior, less PA, lower self-efficacy, and lower SWL than boys across all grade levels. Mediation analysis revealed that up to 56.3% of the enhancement in SWL among those adhering to 60-min of PA recommendations was explained by increased self-efficacy. Norwegian government and policymakers should promote initiatives and regulations focusing on higher levels of PA to foster a resilient adolescent population with higher individual beliefs and higher subjective wellbeing.

UNASSIGNED: Sleep complaints were reported to be associated with stroke, however, the evidence on the association between healthy sleep pattern and stroke risk in Chinese is limited.
UNASSIGNED: The aim of this study was to investigate the association between healthy sleep pattern and stroke in Chinese, and the influence of metabolic diseases on the association.
UNASSIGNED: A total of 11,851 participants from the Kailuan study in China without stroke at baseline were included. We calculated a healthy sleep score according to four sleep factors, and defined the low-risk groups as follows: no insomnia, no excessive daytime sleepiness, no frequent snoring, and sleep 7-8h/d. Each low-risk sleep factor was assigned a score of 1. Cox proportional hazard models were used to assess the association between healthy sleep score and stroke. Mediation analysis was used to estimate the role of metabolic diseases (obesity, diabetes, and hypertension) in the healthy sleep score-stroke association.
UNASSIGNED: During a mean follow-up period of 7.7 years, 504 cases of stroke were identified. A higher healthy sleep score was associated with a lower risk of stroke in a dose-response manner (P-trend=0.03). The adjusted hazard ratio (HR) for participants with a healthy sleep score of 4 versus ≤2 was 0.75 (95% confidence interval [CI]: 0.56, 0.96). In addition, obesity, diabetes, and hypertension collectively explained 21.9% (95% CI: 17.2, 26.5) of the association between healthy sleep score and stroke.
UNASSIGNED: Adherence to healthy sleep pattern was associated with a lower risk of stroke, and the favorable association was partially mediated by metabolic diseases.

BACKGROUND: The causal relationship between childhood adiposity and adult risk of heart diseases has not been clearly demonstrated. This study aims to ascertain whether genetically predicted childhood body mass index (BMI) and childhood obesity are causally associated with adult coronary heart disease, myocardial infarction, heart failure, atrial fibrillation, hypertrophic cardiomyopathy, and pulmonary heart disease.
RESULTS: To investigate the causative relationships and underlying mechanisms between childhood adiposity and adult heart diseases, 3 main methods of Mendelian randomization were used: 2-sample Mendelian randomization, multivariable Mendelian randomization with controlling for several cardiometabolic risk variables, and mediation analysis. Every 1-SD rise in genetically predicted childhood body mass index was associated with 24% (odds ratio [OR], 1.24 [95% CI, 1.12-1.37]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), 28% (OR, 1.28 [95% CI, 1.14-1.42]), and 27% (OR, 1.27 [95% CI, 1.04-1.49]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. Every 1-unit increase in log-odds in childhood obesity was associated with 11% (OR, 1.11 [95% CI, 1.06-1.16]), 14% (OR, 1.14 [95% CI, 1.04-1.23]), 10% (OR, 1.10 [95% CI, 1.03-1.18]), and 20% (OR, 1.20 [95% CI, 1.08-1.32]) higher risk of coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation, respectively. The link between childhood adiposity and adult heart diseases was found to be mediated by high-density lipoprotein cholesterol, triglyceride, hypertension, and type 2 diabetes.
CONCLUSIONS: Our findings support the causal relationships between childhood adiposity and risk of adult coronary heart disease, myocardial infarction, heart failure, and atrial fibrillation. Blood lipids, hypertension, and type 2 diabetes are factors that mediate the aforementioned associations.

BACKGROUND: Systemic inflammation and endothelial dysfunction are potentially modifiable factors implicated in Alzheimer\'s disease (AD), which offer potential therapeutic targets to slow disease progression.
METHODS: We investigated the relationship between baseline circulating levels of inflammatory (TNF-α, IL-1ß) and endothelial cell markers (VCAM-1, ICAM-1, E-selectin) and 18-month cognitive decline (ADAS-cog12) in 266 mild-to-moderate AD patients from the NILVAD study. We employed individual growth models to examine associations, potential mediation, and interaction effects while adjusting for confounders.
RESULTS: The average increase in ADAS-cog12 scores over all patients was 8.1 points in 18 months. No significant association was found between the markers and the rate of cognitive decline. Mediation analysis revealed no mediating role for endothelial cell markers, and interaction effects were not observed.
CONCLUSIONS: Our results do not support the role of systemic inflammation or endothelial dysfunction in progression in persons with AD.

BACKGROUND: The family environment has a significant influence on the personality development of young people and their assessment of life satisfaction. Perceived stress is related to life satisfaction, but this relationship is also influenced by the family context. The present study analysed the impact of perceived stress on life satisfaction and the mediating role of family climate in university students.
METHODS: A sample of 920 university students was recruited for this study. The instruments used included the Perceived Stress Scale, the Satisfaction with Life Scale, and the Family Social Climate Scale, and socioeducational information was collected.
RESULTS: The results indicate that perceived stress had a significant and positive effect on both conflictive and violent family climates, while life satisfaction was negatively impacted by these negative family climates. Additionally, supportive and cohesive family climates, along with difficulty expressing feelings and opinions, were found to have significant positive effects on life satisfaction.
CONCLUSIONS: These findings highlight the importance of the family system in shaping individual conditions and how it can regulate the relationship between stress and life satisfaction.

Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results. Our results showed that genetically predicted T2D was associated with increased CAVS risk (OR 1.153, 95% CI 1.096-1.214, p < 0.001), and this association persisted even after adjusting for adiposity traits in multivariable MR analysis. Furthermore, the two-step MR analysis identified 69 of 251 candidate mediators that partially mediated the effect of T2D on CAVS, including total branched-chain amino acids (proportion mediated: 23.29%), valine (17.78%), tyrosine (9.68%), systolic blood pressure (8.72%), the triglyceride group (6.07-11.99%), the fatty acid group (4.78-12.82%), and the cholesterol group (3.64-11.56%). This MR study elucidated the causal impact of T2D on CAVS risk independently of adiposity and identified potential mediators in this association pathways. Our findings shed light on the pathogenesis of CAVS and suggest additional targets for the prevention and intervention of CAVS attributed to T2D.

BACKGROUND: The relationships between BUNCr (blood urea nitrogen and creatinine ratio) and cognitive function, as well as depressive symptoms, remain unclear. We aim to investigate the association between BUNCr and cognition, as well as depressive symptoms, and to identify the mechanisms underlying these relationships.
METHODS: We utilized data from the China Health and Retirement Longitudinal Study (CHARLS) from 2015 to 2020. Cognitive function was assessed using the Telephone Interview of Cognitive Status (TICS) scale, while depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10). We employed multivariate linear regression models to examine the association between BUNCr and cognitive function, as well as depressive symptoms. Additionally, causal mediation analysis was conducted to identify potential mediation effects of depressive symptoms between BUNCr and cognition.
RESULTS: We observed a negative association between BUNCr and cognitive function (coefficient: -0.192; 95% confidence interval [CI]: -0.326 ∼ -0.059) and a positive relationship between BUNCr and depressive symptoms (coefficient: 0.145; 95% CI: 0.006 ∼ 0.285). In addition, the causal mediation analysis revealed that depressive symptoms (proportion mediated: 7.0%) significantly mediated the association between BUNCr and cognition.
CONCLUSIONS: Our study has unveiled that BUNCr is inversely associated with cognitive function and positively linked to depressive symptoms. Moreover, we found that depressive symptoms significantly mediated the association between BUNCr and cognition. These findings provide new evidence and insights for the prevention and management of cognitive function and dementia.

UNASSIGNED: There are positive and negative correlations in different directions between smoking, personality traits, and health-related quality of life (HRQOL), where smoking may mask the pathway between personality traits and HRQOL. Understanding the masking pathway of smoking between personality traits and HRQOL can elucidate the mechanisms of smoking\'s psychosocial effects and provide new ideas for developing tobacco control strategies.
UNASSIGNED: The purpose of this study was to investigate the correlation between Big Five personality traits and HRQOL and whether smoking mediates the relationship between them.
UNASSIGNED: This was a cross-sectional study using data from 21,916 respondents from the 2022 Psychology and Behavior Investigation of Chinese Residents survey. Linear regression models were used to analyze the correlations between smoking, Big Five personality traits, and HRQOL while controlling for potential confounders. The mediating role of smoking on the association between Big Five Personality traits and HRQOL was analyzed using the Sobel-Goodman mediation test.
UNASSIGNED: Extraversion (β=.001; P=.04), agreeableness (β=.003; P<.001), and neuroticism (β=.003; P<.001) were positively correlated with HRQOL, whereas openness was negatively correlated with HRQOL (β=-.001; P=.003). Smoking was associated with a decrease in HRQOL and mediated the positive effect of HRQOL on extraversion (z=-2.482; P=.004), agreeableness (z=-2.264; P=.02), and neuroticism (z=-3.230; P=.001). Subgroup analyses further showed that smoking mediated the effect of neuroticism on HRQOL in the population with chronic illnesses (z=-2.724; P=.006), and in the population without chronic illnesses, smoking contributed to the effect of HRQOL on extraversion (z=-2.299; P=.02), agreeableness (z=-2.382; P=.02), and neuroticism (z=-2.213; P=.03).
UNASSIGNED: This study provided evidence that there is a correlation between personality traits and HRQOL. It also found that smoking plays a role in mediating the connection between personality traits and HRQOL. The development of future tobacco control strategies should consider the unique traits of each individual\'s personality, highlighting the significance of extraversion, agreeableness, and neuroticism.