Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

Widening Educational Inequalities in Physical Health Due to the Obesity Trend?-A Mediation Analysis Using the German Socio-Economic Panel Study.

Objectives: This study examined the contribution of obesity to the development of educational inequalities in physical health. Methods: We used data from the German Socio-Economic Panel for the period 2002-2020. Physical health was measured with the modified SF12-questionnaire. Logistic regression analyses were applied to estimate time trends. The Relative Index of Inequality (RII) and the Slope Index of Inequality (SII) were calculated to examine educational inequalities. The role of obesity as a mediator was analyzed using the Karlson-Holm-Breen (KHB) method. Results: Over time, educational inequalities in obesity as well as impaired physical health widened in men and women, particularly among those aged 30-49 years. For individuals with a low level of education at this age, the probability of impaired physical health increased significantly by 7.7%-points in women and 9.4%-points in men. Of this increase, 25.9% for women and 14.8% for men could be attributed to the increase in obesity. Conclusion: Our findings suggest that the steeper rise in obesity among individuals with a low level of education partly explains the observed widening in educational inequalities in physical health.

Prediction and mediation analysis for treatment responses to combined cognitive and physical training for older adults.

Diminished cognitive and physical functions negatively affect the daily functions of individuals. Although combined cognitive and physical training prevents instrumental activities of daily living (IADL) disability in older adults, no predictive model or mediation analysis of IADL after combined training exists. This study aims to employ prediction and mediation analysis to identify the predictors of IADL performance and to elucidate the mediators of the association between baseline global cognition and subsequent IADL performance following combined cognitive and physical training. This study involved 177 participants aged 60 years and older who underwent combined training. Cognitive function was measured with the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Color Trails Test, Word List, and a dual task; physical function with the Timed Up and Go (TUG) test; daily function with the Lawton IADL Scale. We conducted regression analyses to identify the predictors of IADL performance, and mediation analysis to examine whether DSST and TUG mediate the relationship between MoCA and IADL. The pre-intervention DSST and TUG were significant independent predictors of post-intervention IADL. The association between the pre-intervention MoCA and post-intervention IADL was mediated by pre-intervention DSST and TUG. This study highlighted the importance of measuring and improving processing speed and functional mobility before and during interventions to enhance IADL outcomes.Trial registration: NCT03619577, 23/07/2018; NCT04689776, 29/12/2020.

Lipids as potential mediators linking body mass index to diabetes: evidence from a mediation analysis based on the NAGALA cohort.

BACKGROUND: Body mass index (BMI) and lipid disorders are both known to be strongly associated with the development of diabetes, however, the indirect effect of lipid parameters in the BMI-related diabetes risk is currently unknown. This study aimed to investigate the mediating role of lipid parameters in the association of BMI with diabetes risk. METHODS: We assessed the association of diabetes risk with BMI, as well as lipid parameters including high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-CF and LDL-CS), triglycerides(TG), total cholesterol(TC), remnant cholesterol(RC), non-HDL-C, and combined indices of lipid parameters with HDL-C (RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio, non-HDL/HDL-C ratio, LDL/HDL-C ratio) using data from 15,453 subjects in the NAGALA project. Mediation models were used to explore the mediating role of lipid parameters in the association of BMI with diabetes risk, and mediation percentages were calculated for quantifying the strength of the indirect effects. Finally, receiver operating characteristic curve (ROC) analysis was used to compare the accuracy of BMI and BMI combined with lipid parameters in predicting incident diabetes. RESULTS: Multivariate regression models, adjusted for confounding factors, demonstrated robust associations of lipid parameters, BMI, with diabetes risk, with the exception of TC, LDL-CF, LDL-CS, and non-HDL-C. Mediation analysis showed that lipid parameters except TC, LDL-CF, LDL-CS, and Non-HDL-C were involved in and mediated the association of BMI with diabetes risk, with the largest mediation percentage being the RC/HDL-C ratio, which was as high as 40%; it is worth mentioning that HDL-C and HDL-C-related lipid ratio parameters also play an important mediating role in the association between BMI and diabetes, with the mediator proportion being greater than 30%. Finally, based on the ROC results, we found that the prediction performance of all lipid parameters in the current study except TC was significantly improved when combined with BMI. CONCLUSION: Our fresh findings suggested that lipid parameters partially mediated the association of BMI with diabetes risk; this result indicated that in the context of diabetes risk screening and disease management, it is important to not only monitor BMI but also pay attention to lipid parameters, particularly HDL-C and HDL-C-related lipid ratio parameters.

Medical Error Prevalence, Nursing Power, and Structural Empowerment: A Serial Mediation Analysis.

Aim: To investigate how structural empowerment and power may contribute to and predict the reduction of medical errors. Background: Medical errors threaten patient well-being, leading to adverse outcomes. Improving work conditions holds promise for reducing medical errors among nurses. Methods: A multisite correlational cross-sectional design was utilized. Data were completed by 375 nurses from four hospitals in Jordan. Data collection occurred between September and November 2023 using sociodemographic, structural empowerment, and medical error questionnaires. The study employed descriptive statistics, Pearson r correlation, and serial mediation analysis. Informed consent was obtained from each participant. Results: Pearson r correlation revealed significant negative correlations between medical error and structural empowerment, formal power, and informal power. The conceptual framework was significant and predicted 16% of the variance in medical errors. The mediation analysis confirmed that formal power and informal power mediate the relationship between structural empowerment and medical error. Conclusions and Implications. This study sheds light on the intricate connection of structural empowerment, formal and informal power, and their collective impact on reducing medical errors. Understanding and addressing these dynamics allows nurses and administrators to achieve a culture of patient safety. Reduction of medical errors is paramount to a safe healthcare environment that prioritizes patient outcomes. Strategies should be fostered to enhance structural empowerment, refine formal power structures, and leverage the positive aspects of informal networks.

Mendelian randomisation and mediation analysis of self-reported walking pace and coronary artery disease.

The aim of this study was to assess the causal relationship between habitual walking pace and cardiovascular disease risk using a Mendelian randomisation approach. We performed both one- and two-sample Mendelian randomisation analyses in a sample of 340,000 European ancestry participants from UK Biobank, applying a range of sensitivity analyses to assess pleiotropy and reverse causality. We used a latent variable framework throughout to model walking pace as a continuous exposure, despite being measured in discrete categories, which provided more robust and interpretable causal effect estimates. Using one-sample Mendelian randomisation, we estimated that a 1 mph (i.e., 1.6 kph) increase in self-reported habitual walking pace corresponds to a 63% (hazard ratio (HR) = 0.37, 95% confidence interval (CI), 0.25-0.55, P = 2.0 × 10-6) reduction in coronary artery disease risk. Using conditional analyses, we also estimated that the proportion of the total effect on coronary artery disease mediated through BMI was 45% (95% CI 16-70%). We further validated findings from UK Biobank using two-sample Mendelian randomisation with outcome data from the CARDIoGRAMplusC4D consortium. Our findings suggest that interventions that seek to encourage individuals to walk more briskly should lead to protective effects on cardiovascular disease risk.

Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis.

BACKGROUND: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. METHODS: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. RESULTS: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. CONCLUSIONS: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

Instrumental activities of daily living function and cognitive status among Chinese older adults: a serial multiple mediation model.

Objective: This study aimed to develop and validate a serial multiple mediation model to investigate the association between instrumental activities of daily living (IADL) function and cognitive status among older adults while exploring the underlying mechanisms. Methods: This cross-sectional study involved 3,665 individuals aged 60 years and older who participated in the China Health and Retirement Longitudinal Survey (CHARLS). A serial multiple mediation model was utilized to explore the direct and indirect relationship between IADL function and cognitive status and whether sleep duration, social engagement, and depressive symptoms mediated this relationship. Results: Decreased IADL function was associated with worse cognitive status [effect = -0.620, 95% CI: (-0.692, -0.540)]. Sleep duration, social participation (SP), and depressive symptoms all acted as mediators in the relationship between IADL function and cognitive status. Conclusion: This study found both direct and indirect associations between IADL function and cognitive status, providing new insights into the effective prevention and intervention of cognitive decline among older adults.

Direct and indirect treatment effects in the presence of semicompeting risks.

Semicompeting risks refer to the phenomenon that the terminal event (such as death) can censor the nonterminal event (such as disease progression) but not vice versa. The treatment effect on the terminal event can be delivered either directly following the treatment or indirectly through the nonterminal event. We consider 2 strategies to decompose the total effect into a direct effect and an indirect effect under the framework of mediation analysis in completely randomized experiments by adjusting the prevalence and hazard of nonterminal events, respectively. They require slightly different assumptions on cross-world quantities to achieve identifiability. We establish asymptotic properties for the estimated counterfactual cumulative incidences and decomposed treatment effects. We illustrate the subtle difference between these 2 decompositions through simulation studies and two real-data applications in the Supplementary Materials.

Relationships of gaming disorder, ADHD, and academic performance in university students: A mediation analysis.

This study investigates the intersection of Gaming Disorder (GD) and Attention-Deficit/Hyperactivity Disorder (ADHD), and Grade Point Average (GPA), among university students, a critical demographic often overlooked in research on these disorders. A sample of 348 university students was analyzed using the IGD-20 Test for risk of GD, the Adult ADHD Self-Report Scale (ASRS-v1.1) for ADHD symptoms, and GPA as a metric of academic performance. The findings indicate that 4.3% of the surveyed sample scored within the range for GD. The prevalence was higher in males, with 5.3% of the male cohort affected, compared to 1.2% of the female cohort. Significantly, the prevalence of ADHD was substantially higher in the GD group (35.7%) than in the non-GD group (24.2%). Further, ADHD symptoms were found to be a stronger predictor of GD in females than in males. Incorporating the mediating role of Gaming Disorder, this study also probes into how GD may serve as an intermediary in the impact of ADHD on academic performance. By examining the intricate relationship between these disorders, our findings suggest that GD exacerbates the negative effects of ADHD on academic performance, thereby underscoring the potential for Gaming Disorder to act as a bridge in this dynamic. This mediation analysis clarifies how ADHD may indirectly impact academic performance through GD. The study reveals a positive correlation between ADHD symptoms and GD severity, which in turn correlates negatively with academic achievement. In addition, the findings underscore the need for gender-sensitive interventions and highlight the importance of considering the comorbidity of ADHD and GD in academic settings, advocating for systematic screening for GD among students with ADHD, and vice versa. The dual challenges posed by ADHD and GD should be addressed to prevent their escalation into pervasive academic and psychosocial adversities.

Association and mediation analyses among multiple metal exposure, mineralocorticoid levels, and serum ion balance in residents of northwest China.

Toxic metals are vital risk factors affecting serum ion balance; however, the effect of their co-exposure on serum ions and the underlying mechanism remain unclear. We assessed the correlations of single metal and mixed metals with serum ion levels, and the mediating effects of mineralocorticoids by investigating toxic metal concentrations in the blood, as well as the levels of representative mineralocorticoids, such as deoxycorticosterone (DOC), and serum ions in 471 participants from the Dongdagou-Xinglong cohort. In the single-exposure model, sodium and chloride levels were positively correlated with arsenic, selenium, cadmium, and lead levels and negatively correlated with zinc levels, whereas potassium and iron levels and the anion gap were positively correlated with zinc levels and negatively correlated with selenium, cadmium and lead levels (all P < 0.05). Similar results were obtained in the mixed exposure models considering all metals, and the major contributions of cadmium, lead, arsenic, and selenium were highlighted. Significant dose-response relationships were detected between levels of serum DOC and toxic metals and serum ions. Mediation analysis showed that serum DOC partially mediated the relationship of metals (especially mixed metals) with serum iron and anion gap by 8.3% and 8.6%, respectively. These findings suggest that single and mixed metal exposure interferes with the homeostasis of serum mineralocorticoids, which is also related to altered serum ion levels. Furthermore, serum DOC may remarkably affect toxic metal-related serum ion disturbances, providing clues for further study of health risks associated with these toxic metals.

Psychological maltreatment, meaning-centered coping, psychological flexibility, and suicide cognitions: A moderated mediation model.

BACKGROUND: Mental health problems are currently diversifying, increasing the possibility of suicide. Exposure to psychological maltreatment is one of the factors that increases suicidal cognitions. In addition, psychological flexibility and meaning-centered approaches may be effective in coping with suicidal cognitions. OBJECTIVE: A hypothesized model was tested to examine the relationships among psychological maltreatment, suicidal cognitions, psychological flexibility, and meaning-centered coping. METHOD: Data were collected from a sample of 652 participants. Mediation and moderation analyses were conducted to examine the mediating and moderating role of psychological flexibility and meaning-centered coping in the relationship between childhood psychological maltreatment and suicide cognitions among Turkish adults. RESULTS: The results of the study indicated significant negative and positive relationships between psychological maltreatment, suicide cognitions, psychological flexibility, and meaning-centered coping. The findings suggest that psychological flexibility and meaning-centered coping have a serial mediating effect on the relationship between psychological maltreatment and suicide cognitions. Furthermore, according to the study results, psychological flexibility plays a moderating role both between psychological maltreatment and suicidal cognitions and between meaning-centered coping and suicidal cognitions. CONCLUSIONS: The study suggests that psychological maltreatment can be considered as a risk factor and meaning-centered coping and psychological flexibility as protective factors in suicide prevention studies.

Explaining how childhood physical abuse and physical neglect influence adult depression: An analysis with multiple sequential mediators.

BACKGROUND: Substantial evidence indicates that experiencing physical abuse and neglect during childhood significantly elevates the likelihood of developing depression in adulthood. Nevertheless, there remains a dearth of understanding regarding the mechanisms underpinning this correlation. OBJECTIVE: In this study, we aimed to examine the associations of childhood physical abuse and physical neglect with depression using follow-up data from UK Biobank and quantified the contribution of smoking, insomnia, and BMI in these associations. PARTICIPANTS AND SETTINGS: This study included 144,704 participants (64,168 men and 80,536 women) from UK Biobank, most of whom were white (97 %). METHODS: Physical abuse and physical neglect were measured using two items of Childhood Trauma Screener (CTS). Data on the incidence of depression were obtained from primary care, hospital inpatient records, self-reported medical conditions, and death registries. We used a sequential mediation analysis based on the "g-formula" approach to explore the individual and joint effects of potential mediators. RESULTS: The depression incidence rate was 1.85 per 1000 person-years for men and 2.83 per 1000 person-years for women, respectively. Results of Cox proportional risk regression showed that physical abuse (HRs: 1.39-1.53, P < 0.001) and physical neglect (HRs: 1.43-1.60, P < 0.001) are associated with depression. Smoking, insomnia, and BMI together mediated 3 %-26 % of the associations. CONCLUSIONS: These findings contribute to our understanding of how physical abuse and physical neglect influence depression. Furthermore, a more effective reduction in the burden of depression can be achieved by managing modifiable mediators.

Causal mediation analysis with mediator values below an assay limit.

Causal indirect and direct effects provide an interpretable method for decomposing the total effect of an exposure on an outcome into the indirect effect through a mediator and the direct effect through all other pathways. A natural choice for a mediator in a randomized clinical trial is the treatment's targeted biomarker. However, when the mediator is a biomarker, values can be subject to an assay lower limit. The mediator is affected by the treatment and is a putative cause of the outcome, so the assay lower limit presents a compounded problem in mediation analysis. We propose two approaches to estimate indirect and direct effects with a mediator subject to an assay limit: (1) extrapolation and (2) numerical optimization and integration of the observed likelihood. Since these estimation methods solely rely on the so-called Mediation Formula, they apply to most approaches to causal mediation analysis: natural, separable, and organic indirect, and direct effects. A simulation study compares the two estimation approaches to imputing with half the assay limit. Using HIV interruption study data from the AIDS Clinical Trials Group described in Li et al 2016, AIDS; Lok and Bosch 2021, Epidemiology, we illustrate our methods by estimating the organic/pure indirect effect of a hypothetical HIV curative treatment on viral suppression mediated by two HIV persistence measures: cell-associated HIV-RNA and single-copy plasma HIV-RNA.

Influence of Green Human Resource Management on firm's environmental performance: Green Employee Empowerment as a mediating factor.

This research aimed to investigate the mediating function of Green Employee Empowerment (GEE) in the relationship between Green Human Resource Management practices (GHRM) and the environmental performance of small and medium-sized enterprises (SMEs) in Ghana, drawing on the Ability-Motivation-Opportunity (AMO) theory. This study assessed the hypotheses in the established research model using structural equation modeling based on data collected from 320 participants from small and medium-sized firms in Ghana. The study's results revealed that GHRM practices were significantly correlated with the firm's environmental performance. The study found significant GHRM's indirect consequences on environmental performance through GEE in all models examined. These findings suggest that GEE plays a crucial role in translating the impact of GHRM practices into improved environmental performance. The study overlooked other potential mediators or moderators in the relationship between GHRM practices and environmental performance, focusing on GEE. To better understand the complex dynamics behind GHRM techniques' environmental performance, future research might examine business culture, leadership style, and employee sustainability attitudes.

The role of lifestyle factors in the association between education and self-reported fibromyalgia: a mediation analysis.

BACKGROUND: Socioeconomic status as measured by education, income, or occupation, has been associated with fibromyalgia but the underlying mechanism and the role of lifestyle factors are unclear. Thus, we examine the role of modifiable lifestyle factors (body mass index, physical activity, alcohol consumption and smoking) in the association between education and self-reported fibromyalgia. METHODS: We used data from 74,157 participants in the population-based prospective Norwegian Women and Cancer (NOWAC) study. Socioeconomic position, operationalized as years of educational attainment, and lifestyle factors were assessed via self-reported questionnaires. Multiple mediation analysis was used to decompose total effects into direct and indirect effects. Estimates were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The cumulative incidence of fibromyalgia was 3.2% after a median follow up time of 13 years. Fibromyalgia was inversely associated with years of educational attainment for ≤ 9 years (HR = 2.56; 95% CI 2.32-2.91) and for 10-12 years (HR = 1.84; 95% CI 1.72-2.02), compared with ≥ 13 years of education. Overall, all lifestyle factors together jointly mediated 17.3% (95% CI 14.3-21.6) and 14.1% (95% CI 11.3-18.9) of the total effect for ≤ 9 years and 10-12 years of education, respectively. Smoking and alcohol consumption contributed the most to the proportion mediated, for ≤ 9 years (5.0% and 7.0%) and 10-12 years (5.6% and 4.5%) of education. CONCLUSION: The association between education and self-reported fibromyalgia was partly explained through lifestyle factors, mainly smoking and alcohol consumption.

The influence of Life's Essential 8 on the link between socioeconomic status and depression in adults: a mediation analysis.

BACKGROUND: Individuals with low socioeconomic status (SES) are at a higher risk of developing depression. However, evidence on the role of cardiovascular health (CVH) in this chain is sparse and limited. The purpose of this research was to assess the mediating role of Life's Essential 8 (LE8), a recently updated measurement of CVH, in the association between SES and depression according to a nationally representative sample of adults. METHODS: Data was drawn from the National Health and Nutrition Examination Survey (NHANES) in 2013-2018. Multivariate logistic regression analysis was applied to analyze the association of SES (measured via the ratio of family income to poverty (FIPR), occupation, educational level, and health insurance) and LE8 with clinically relevant depression (CRD) (evaluated using the Patient Health Questionnaire (PHQ-9)). Multiple linear regression analysis was performed to analyze the correlation between SES and LE8. Mediation analysis was carried out to explore the mediating effect of LE8 on the association between SES and CRD. Moreover, these associations were still analyzed by sex, age, and race. RESULTS: A total of 4745 participants with complete PHQ-9 surveys and values to calculated LE8 and SES were included. In the fully adjusted model, individuals with high SES had a significantly higher risk of CRD (odds ratio = 0.21; 95% confidence interval: 0.136 to 0.325, P < 0.01) compared with those with low SES. Moreover, LE8 was estimated to mediate 22.13% of the total association between SES and CRD, and the mediating effect of LE8 varied in different sex and age groups. However, the mediating effect of LE8 in this chain was significant in different sex, age, and racial subgroups except for Mexican American (MA) individuals. CONCLUSION: The results of our study suggest that LE8 could mediate the association between SES and CRD. Additionally, the mediating effect of LE8 in this chain could be influenced by the race of participants.

Sleep disturbance and internalizing symptoms in adolescents: a moderated mediation model of self-control and mindfulness.

OBJECTIVES: Despite accumulating evidence regarding the impact of sleep disturbance on internalizing symptoms among adolescents, the underlying psychological mechanisms remain inadequately explored. This study aimed to investigate a conceptual framework elucidating how sleep disturbance influences internalizing symptoms in adolescents through the mediating role of self-control, with mindfulness as a moderator. METHODS: In this cross-sectional study, 1876 Chinese adolescents (Mage = 14.88 years, SD = 1.47 years, range = 12-19 years, 44.7% boys) completed the Youth Self-Rating Insomnia Scale (YSIS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Brief Self-control Scale (BSCS), and Mindful Attention Awareness Scale-Children (MAAS-C) to provide data on sleep-related variables, internalizing symptoms (anxiety and depression), self-control, and mindfulness, respectively. The PROCESS macro for SPSS was applied to perform moderated mediation analysis. RESULTS: Sleep disturbance demonstrated a significant positive correlation with internalizing symptoms in adolescents, including anxiety (ß = 0.481, p < 0.001) and depression (ß = 0.543, p < 0.001). Self-control served as a mediator between sleep disturbance and two forms of internalizing symptoms. Moreover, mindfulness moderated the pathways from self-control to internalizing symptoms (for anxiety symptoms: ß = 0.007, p < 0.001; for depression symptoms: ß = 0.006, p < 0.001), and the mediating relationships were weaker for adolescents exhibiting higher levels of mindfulness. CONCLUSIONS: Our findings enhance understanding of the impact, pathways, and influencing factors of sleep disturbance on adolescent internalizing symptoms, suggesting the importance of enhancing mindfulness levels in addressing self-control deficits and subsequently reducing internalizing symptoms among adolescents.

Effects of multiple metals exposure on abnormal liver function: The mediating role of low-density lipoprotein cholesterol.

Equilibration of metal metabolism is critical for normal liver function. Most epidemiological studies have only concentrated on the influence of limited metals. However, the single and synergistic impact of multiple-metal exposures on abnormal liver function (ALF) are still unknown. A cross-sectional study involving 1493 Chinese adults residing in Shenzhen was conducted. Plasma concentrations of 13 metals, including essential metals (calcium, copper, cobalt, iron, magnesium, manganese, molybdenum, zinc, and selenium) and toxic metals (aluminum, cadmium, arsenic, and thallium) were detected by the inductively coupled plasma spectrometry (ICP-MS). ALF was ascertained as any observed abnormality from albumin, alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase, and direct bilirubin. Diverse statistical methods were used to evaluate the single and mixture effect of metals, as well as the dose-response relationships with ALF risk, respectively. Mediation analysis was conducted to evaluate the role of blood lipids in the relation of metal exposure with ALF. The average age of subjects was 59.7 years, and 56.7 % were females. Logistic regression and the least absolute shrinkage and selection operator (LASSO) penalized regression model consistently suggested that increased levels of arsenic, aluminum, manganese, and cadmium were related to elevated risk of ALF; while magnesium and zinc showed protective effects on ALF (all p-trend < 0.05). The grouped weighted quantile sum (GWQS) regression revealed that the WQS index of essential metals and toxic metals showed significantly negative or positive relationship with ALF, respectively. Aluminum, arsenic, cadmium, and manganese showed linear whilst magnesium and zinc showed non-linear dose-response relationships with ALF risk. Mediation analysis showed that LDL-c mediated 4.41 % and 14.74 % of the relationship of plasma cadmium and manganese with ALF, respectively. In summary, plasma aluminum, arsenic, manganese, cadmium, magnesium, and zinc related with ALF, and LDL-c might underlie the pathogenesis of ALF associated with cadmium and manganese exposure. This study may provide critical public health significances in liver injury prevention and scientific evidence for the establishment of environmental standard.

Effect of the gut microbiome, plasma metabolome, peripheral cells, and inflammatory cytokines on obesity: a bidirectional two-sample Mendelian randomization study and mediation analysis.

Background: Obesity is a metabolic and chronic inflammatory disease involving genetic and environmental factors. This study aimed to investigate the causal relationship among gut microbiota abundance, plasma metabolomics, peripheral cell (blood and immune cell) counts, inflammatory cytokines, and obesity. Methods: Summary statistics of 191 gut microbiota traits (N = 18,340), 1,400 plasma metabolite traits (N = 8,299), 128 peripheral cell counts (blood cells, N = 408,112; immune cells, N = 3,757), 41 inflammatory cytokine traits (N = 8,293), and 6 obesity traits were obtained from publicly available genome-wide association studies. Two-sample Mendelian randomization (MR) analysis was applied to infer the causal links using inverse variance-weighted, maximum likelihood, MR-Egger, weighted median, weighted mode, and Wald ratio methods. Several sensitivity analyses were also utilized to ensure reliable MR results. Finally, we used mediation analysis to identify the pathway from gut microbiota to obesity mediated by plasma metabolites, peripheral cells, and inflammatory cytokines. Results: MR revealed a causal effect of 44 gut microbiota taxa, 281 plasma metabolites, 27 peripheral cells, and 8 inflammatory cytokines on obesity. Among them, five shared causal gut microbiota taxa belonged to the phylum Actinobacteria, order Bifidobacteriales, family Bifidobacteriaceae, genus Lachnospiraceae UCG008, and species Eubacterium nodatum group. Furthermore, we screened 42 shared causal metabolites, 7 shared causal peripheral cells, and 1 shared causal inflammatory cytokine. Based on known causal metabolites, we observed that the metabolic pathways of D-arginine, D-ornithine, linoleic acid, and glycerophospholipid metabolism were closely related to obesity. Finally, mediation analysis revealed 20 mediation relationships, including the causal pathway from gut microbiota to obesity, mediated by 17 metabolites, 2 peripheral cells, and 1 inflammatory cytokine. Sensitivity analysis represented no heterogeneity or pleiotropy in this study. Conclusion: Our findings support a causal relationship among gut microbiota, plasma metabolites, peripheral cells, inflammatory cytokines, and obesity. These biomarkers provide new insights into the mechanisms underlying obesity and contribute to its prevention, diagnosis, and treatment.