Social network, fair payment, subjective well-being, and general health: a moderation mediation analysis.

Objective: This research aimed to investigate whether subjective general health mediated the relationship between social networks and subjective well-being and whether the perception of fair payment moderated the mediating effect of subjective general health on subjective well-being. Methods: Data were drawn from round 9 of the European Social Survey (ESS), involving 3,843 respondents from 19 countries, with ages ranging from 65 to 90 years (Meanage = 73.88 ± 6.61 years). The participants completed self-reported measures assessing subjective well-being, social networks, subjective general health, and perception of fair payment. Results: Subjective general health played a mediating role in the relationship between social networks and subjective well-being. The perception of fair payment emerged as a moderator in the mediating effect of subjective general health on the association between social networks and subjective well-being. Conclusion: This study suggests that the impact of social networks on both subjective general health and subjective well-being is contingent upon individuals' perceptions of fair payment. These results highlight the significance of social networks in fostering social connections and promoting overall subjective well-being.

Effects of perceived stress on college students' sleep quality: a moderated chain mediation model.

BACKGROUND: Perceived Stress has been shown as a key contributor to sleep quality, but the underlying mechanism between perceived stress and sleep quality remains unknown. This study aimed to investigate the impact of perceived stress on sleep quality of college students and the chain mediating roles of presence of meaning in life (PML) and depression, as well as the moderating role of search for meaning in life (SML). METHODS: Participants were 8178 college students (4599 boys and 3579 girls; Mage = 19.10 years, SD = 1.08) who completed self-report questionnaire, including the Perceived Stress Scale (PSS), the Pittsburgh Sleep Quality Index (PSQI), the Meaning in Life Questionnaire (MLQ), and the Patient Health Questionnaire-9 (PHQ-9). RESULTS: The results showed that higher perceived stress was directly related to poorer sleep quality. This negative impact on sleep quality was mediated through the chained roles of PML and depression. Additionally, the study found that SML moderates the influence of perceived stress, PML and depression on sleep quality. Specifically, for individuals actively search for meaning, the adverse effects of perceived stress and depression on sleep quality are diminished. Concurrently, the positive influence of PML on sleep quality is enhanced. CONCLUSION: This study revealed that the PML and depression mediate the effect of perceived stress on sleep quality, with SML playing a significant protective role. These results emphasize the necessity of integrating strategies to enhance PML and SML into interventions designed to improve emotion management and sleep quality among college students.

The role of parenting stress on parenting self-efficacy and parental burnout among Turkish parents: a moderated mediation model.

OBJECTIVE: Parental burnout is a significant problem that negatively effects parent-child interaction, parenting skills, and child well-being. Research has identified parenting stress as one of the leading factors in parent burnout. Although crucial connections have been explained between parenting stress and parental burnout, not much is known about how parenting self-efficacy operates in these relationships. This study aims to investigate the roles of parenting self-efficacy and number of children in the relationship between parenting stress and parental burnout. METHODS: The participants consist of a total of 456 parents (Mage = 35.64 ± 9.28, Range = 25-65 years). The data were collected using a personal information form, the Parenting Stress Scale, the Parental Burnout Scale and the Parenting Self-Efficacy Scale. Relationships among variables were examined using Pearson's correlation, while moderated mediation analysis was carried out using Hayes's bootstrapping. RESULTS: The correlation analyses reveal a negative relationship between parenting self-efficacy and parenting stress, between parenting self-efficacy and parental burnout, and between parenting self-efficacy and number of children, while a positive significant relationship was found between parenting stress and parental burnout. The mediation analyses show parenting self-efficacy to mediate the correlation between parenting stress and parental burnout. The mediating effect of parenting self-efficacy is also moderated by number of children. CONCLUSIONS: This study provides empirical evidence for the effect of parenting stress and parenting self-efficacy on parental burnout, with fewer children in the household alleviating parental burnout.

The association between physical activity and delayed neurocognitive recovery in elderly patients: a mediation analysis of pro-inflammatory cytokines.

BACKGROUND: Delayed neurocognitive recovery (dNCR) can result in unfavorable outcomes in elderly surgical patients. Physical activity (PA) has been shown to improve cognitive function, potentially by reducing systemic inflammatory responses. However, there is a lack of supportive data indicating whether PA has a protective effect against dNCR. AIMS: To examine the correlation between dNCR and PA, and to further analyze if pro-inflammatory cytokines mediate this relationship. METHODS: This study is a prospective nested case-control investigation of elderly patients who had knee replacement surgery. dNCR was defined as a decline in cognitive function compared with baseline by using a battery of neuropsychological tests. PA was assessed with the Physical Activity Scale for the Elderly (PASE). Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of IL-6, IL-1ß, and TNF-α. Multivariable logistic regression analysis was conducted to assess the association between PA and dNCR. Mediation analysis was employed to evaluate whether pro-inflammatory cytokines mediate the relationship between them. RESULTS: A cohort of 152 patients was included, resulting in an incidence rate of dNCR of 23.68%. PA was associated with dNCR after full adjustment [OR = 0.199, (95% CI, 0.061; 0.649), P = 0.007]. Mediation analysis showed that the IL-6 mediated the statistical association between PA and dNCR, with mediation proportions (%) of 77.68 (postoperative concentration of IL-6) or 27.58 (the absolute change in IL-6 before and after surgery). CONCLUSIONS: PA serves as a protective factor against dNCR, possibly through the reduction of pro-inflammatory cytokine concentrations. THE CHINESE CLINICAL TRAIL REGISTRY: : www.http://chictr.org.cn , Registration No. ChiCTR2300070834, Registration date: April 24, 2023.

Proactive Personality and Caring Behavior of Clinical Nurses: A Moderated Mediation Model of Emotional Intelligence and Disgust Sensitivity.

The aims of the research were to investigate the mediating effect of emotional intelligence and the moderating effect of disgust sensitivity on the relationship between proactive personality and caring behavior among clinical nurses. A cross-sectional design while adhering to STROBE guidelines was used for this study. Three hundred ninety-three purposely selected nurses from three tertiary general hospitals completed an online survey. Measures included proactive personality, emotional intelligence, disgust sensitivity, and caring behavior. The findings showed that proactive personality positively predicted nurses' caring behavior, and that emotional intelligence played a mediating role in the relationship between proactive personality and caring behavior. Disgust sensitivity indirectly and negatively moderated the impact of proactive personality on nurses' caring behavior mainly in the second half of this moderated relationship. The findings underscore that the nursing managers may consider incorporating emotional intelligence topic in practical nursing skills training and improving nurses' ability to control their disgust sensitivity can improve their professional behavior, thus to provide patients with high-quality nursing services.

The mediating role of adolescent psychopathology in the association between frequent or severe childhood abuse and labor market inactivity in young adulthood: A causal mediation approach.

BACKGROUND: Labor market inactivity is common among young adults with a history of childhood abuse, which might be attributable to elevated psychopathology in adolescence. OBJECTIVE: We examined and decomposed the effect of adolescent psychopathology in the association between frequent or severe childhood abuse and labor market inactivity in young adulthood. PARTICIPANTS AND SETTING: This study used data from the population and high-risk samples of the Dutch prospective TRacking Adolescents' Individual Lives Survey (N = 2172). METHODS: Childhood abuse included measures of emotional, physical and sexual abuse. We operationalized adolescent psychopathology using the broadband emotional and behavioral problem scales. Labor market inactivity in young adulthood was defined as being neither in education, employment nor training or receiving benefits. We applied causal mediation analysis combined with a four-way decomposition approach to estimate our effects of interest. RESULTS: Individuals who reported frequent or severe childhood abuse were 1.51 (95 % CI: 1.13 to 2.22) times more likely to report labor market inactivity, constituting an excess relative risk (ERR) of 0.51. Most of this excess relative risk is due to mediation by psychopathology at 64.7 % (ERR: 0.33, 95 % CI: 0.16 to 0.50). We found no evidence for a mediated interactive effect (ERR: -0.04, 95 % CI: -0.24 to 0.24). CONCLUSIONS: Adolescent psychopathology largely explains the association between frequent and severe childhood abuse and labor market inactivity in young adulthood. Intervening in the occurrence of adolescent psychopathology following frequent and severe childhood abuse may reduce the risk of subsequent labor market inactivity.

Causal definitions versus casual estimation: Reply to Valente et al. (2022).

In this response to Valente et al. (2022), I am discussing the plausibility and applicability of the proposed mediation model and its causal effects estimation for single case experimental designs (SCEDs). I will focus on the underlying assumptions that the authors use to identify the causal effects. These assumptions include the particularly problematic assumption of sequential ignorability or no-unmeasured confounders. First, I will discuss the plausibility of the assumption in general and then particularly for SCEDs by providing an analytic argument and a reanalysis of the empirical example in Valente et al. (2022). Second, I will provide a simulation that reproduces the design by Valente et al. (2022) with the exception that, for a more realistic depiction of empirical data, an unmeasured confounder affects the mediator and outcome variables. The results of this simulation study indicate that even minor violations will lead to Type I error rates up to 100% and coverage rates as low as 0% for the defined causal direct and indirect effects. Third, using historical data on the effect of birth control on stork population and birth rates, I will show that mediation models like the proposed method can lead to surprising artifacts. These artifacts can hardly be identified with statistically means including methods such as sensitivity analyses. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways.

BACKGROUND: Neurocognitive dysfunction is observationally associated with the risk of psychiatric disorders. Blood metabolites, which are readily accessible, may become highly promising biomarkers for brain disorders. However, the causal role of blood metabolites in neurocognitive function, and the biological pathways underlying their association with psychiatric disorders remain unclear. METHODS: To explore their putative causalities, we conducted bidirectional two-sample Mendelian randomization (MR) using genetic variants associated with 317 human blood metabolites (nmax = 215,551), g-Factor (an integrated index of multiple neurocognitive tests with nmax = 332,050), and 10 different psychiatric disorders (n = 9,725 to 807,553) from the large-scale genome-wide association studies of European ancestry. Mediation analysis was used to assess the potential causal pathway among the candidate metabolite, neurocognitive trait and corresponding psychiatric disorder. RESULTS: MR evidence indicated that genetically predicted acetylornithine was positively associated with g-Factor (0.035 standard deviation units increase in g-Factor per one standard deviation increase in acetylornithine level; 95% confidence interval, 0.021 to 0.049; P = 1.15 × 10-6). Genetically predicted butyrylcarnitine was negatively associated with g-Factor (0.028 standard deviation units decrease in g-Factor per one standard deviation increase in genetically proxied butyrylcarnitine; 95% confidence interval, -0.041 to -0.015; P = 1.31 × 10-5). There was no evidence of associations between genetically proxied g-Factor and metabolites. Furthermore, the mediation analysis via two-step MR revealed that the causal pathway from acetylornithine to bipolar disorder was partly mediated by g-Factor, with a mediated proportion of 37.1%. Besides, g-Factor mediated the causal pathway from butyrylcarnitine to schizophrenia, with a mediated proportion of 37.5%. Other neurocognitive traits from different sources provided consistent findings. CONCLUSION: Our results provide genetic evidence that acetylornithine protects against bipolar disorder through neurocognitive abilities, while butyrylcarnitine has an adverse effect on schizophrenia through neurocognition. These findings may provide insight into interventions at the metabolic level for risk of neurocognitive and related disorders.

Behavioral risk factors and socioeconomic inequalities in ischemic heart disease mortality in the United States: A causal mediation analysis using record linkage data.

BACKGROUND: Ischemic heart disease (IHD) is a major cause of death in the United States (US), with marked mortality inequalities. Previous studies have reported inconsistent findings regarding the contributions of behavioral risk factors (BRFs) to socioeconomic inequalities in IHD mortality. To our knowledge, no nationwide study has been conducted on this topic in the US. METHODS AND FINDINGS: In this cohort study, we obtained data from the 1997 to 2018 National Health Interview Survey with mortality follow-up until December 31, 2019 from the National Death Index. A total of 524,035 people aged 25 years and older were followed up for 10.3 years on average (SD: 6.1 years), during which 13,256 IHD deaths occurred. Counterfactual-based causal mediation analyses with Cox proportional hazards models were performed to quantify the contributions of 4 BRFs (smoking, alcohol use, physical inactivity, and BMI) to socioeconomic inequalities in IHD mortality. Education was used as the primary indicator for socioeconomic status (SES). Analyses were performed stratified by sex and adjusted for marital status, race and ethnicity, and survey year. In both males and females, clear socioeconomic gradients in IHD mortality were observed, with low- and middle-education people bearing statistically significantly higher risks compared to high-education people. We found statistically significant natural direct effects of SES (HR = 1.16, 95% CI: 1.06, 1.27 in males; HR = 1.28, 95% CI: 1.10, 1.49 in females) on IHD mortality and natural indirect effects through the causal pathways of smoking (HR = 1.18, 95% CI: 1.15, 1.20 in males; HR = 1.11, 95% CI: 1.08, 1.13 in females), physical inactivity (HR = 1.16, 95% CI: 1.14, 1.19 in males; HR = 1.18, 95% CI: 1.15, 1.20 in females), alcohol use (HR = 1.07, 95% CI: 1.06, 1.09 in males; HR = 1.09, 95% CI: 1.08, 1.11 in females), and BMI (HR = 1.03, 95% CI: 1.02, 1.04 in males; HR = 1.03, 95% CI: 1.02, 1.04 in females). Smoking, physical inactivity, alcohol use, and BMI mediated 29% (95% CI, 24%, 35%), 27% (95% CI, 22%, 33%), 12% (95% CI, 10%, 16%), and 5% (95% CI, 4%, 7%) of the inequalities in IHD mortality between low- and high-education males, respectively; the corresponding proportions mediated were 16% (95% CI, 11%, 23%), 26% (95% CI, 20%, 34%), 14% (95% CI, 11%, 19%), and 5% (95% CI, 3%, 7%) in females. Proportions mediated were slightly lower with family income used as the secondary indicator for SES. The main limitation of the methodology is that we could not rule out residual exposure-mediator, exposure-outcome, and mediator-outcome confounding. CONCLUSIONS: In this study, BRFs explained more than half of the educational differences in IHD mortality, with some variations by sex. Public health interventions to reduce intermediate risk factors are crucial to reduce the socioeconomic disparities and burden of IHD mortality in the general US population.

Suggested guidelines in reporting results from mediation analysis, standardized or unstandardized?

Mediation analysis is commonly implemented in psychological, epidemiological, and social behavior studies to identify potential factors that mediate associations between exposures and physical or psychological outcomes. Various analytical tools are available to perform mediation analyses, among which Mplus is widely used due to its user-friendly interface. In practice, sumptuous results provided by Mplus, such as the estimated standardized and unstandardized effect sizes, can be difficult for researchers to choose to match their studies. Through a comprehensive review and utilizing findings from a proven study, we proposed guidelines and recommendations to help users select between standardized or unstandardized results based on data attributes and users' hypotheses. We also provided guidelines to choose from several types of standardized values based on the types of variables, including exposures, mediators, and outcomes.

Interaction mechanism of discharge readiness between discharge teaching and post-discharge outcomes in gynecological inpatients: a mediation analysis.

BACKGROUND: With the rapid implementation of enhanced recovery after surgery, most gynecological patients are discharged without full recovery. Discharge planning is necessary for patients and their families to transition from hospital to home. Discharge teaching and discharge readiness are two core indicators used to evaluate the quality of discharge planning, which impacts the post-discharge outcomes. To improve post-discharge outcomes, the interaction mechanism of the three variables needs to be determined, but few studies have focused on it. OBJECTIVES: Explore the mediating effect of discharge readiness between discharge teaching and post-discharge outcomes of gynecological inpatients. METHODS: Discharge teaching and discharge readiness were measured by the Quality of Discharge Teaching Scale (QDTS) and Readiness for Hospital Discharge Scale (RHDS). Post-discharge outcomes on postoperative Day 7 (POF-D7) and postoperative Day 28 (POF-D28) were measured by a self-designed tool. Spearman correlations, Kruskal‒Wallis tests and Mann‒Whitney U tests were conducted to explore the correlation between post-discharge outcomes and other variables. Mediation analysis was used to explore the mediating effect of discharge readiness between discharge teaching and post-discharge outcomes. RESULTS: QDTS and RHDS showed strong positive correlations with post-discharge outcomes. The mediation analyses verified that RHDS was a full mediator between QDTS and POF-D7, and the indirect effect accounted for 95.6% of the total direct effect. RHDS was a partial mediator between QDTS and POF-D28, and the indirect effect accounted for 50.0% of the total direct effect. RHDS was a full mediator between QDTS and total scores of post-discharge outcomes, and the indirect effect accounted for 88.9% of the total direct effect. CONCLUSIONS: Discharge teaching can improve the post-discharge outcomes of gynecological inpatients through the intermediary role of discharge readiness. Doctors and nurses should value the quality of discharge teaching and the discharge readiness improving of gynecological inpatients. Future studies should note the interaction mechanism of the three variables to explore more efficient ways of improving post-discharge outcomes of gynecological inpatients.

A Bayesian nonparametric approach for causal mediation with a post-treatment confounder.

We propose a new Bayesian nonparametric method for estimating the causal effects of mediation in the presence of a post-treatment confounder. The methodology is motivated by the Rural Lifestyle Intervention Treatment Effectiveness Trial (Rural LITE) for which there is interest in estimating causal mediation effects but is complicated by the presence of a post-treatment confounder. We specify an enriched Dirichlet process mixture (EDPM) to model the joint distribution of the observed data (outcome, mediator, post-treatment confounder, treatment, and baseline confounders). For identifiability, we use the extended version of the standard sequential ignorability (SI) as introduced in Hong et al. along with a Gaussian copula model assumption. The observed data model and causal identification assumptions enable us to estimate and identify the causal effects of mediation, that is, the natural direct effects (NDE) and natural indirect effects (NIE). Our method enables easy computation of NIE and NDE for a subset of confounding variables and addresses missing data through data augmentation under the assumption of ignorable missingness. We conduct simulation studies to assess the performance of our proposed method. Furthermore, we apply this approach to evaluate the causal mediation effect in the Rural LITE trial, finding that there was not strong evidence for the potential mediator.

Personality and Health-Related Quality of Life of Older Chinese Adults: Cross-Sectional Study and Moderated Mediation Model Analysis.

Background: Personality has an impact on the health-related quality of life (HRQoL) of older adults. However, the relationship and mechanisms of the 2 variables are controversial, and few studies have been conducted on older adults. Objective: The aim of this study was to explore the relationship between personality and HRQoL and the mediating and moderating roles of sleep quality and place of residence in this relationship. Methods: A total of 4123 adults 60 years and older were from the Psychology and Behavior Investigation of Chinese Residents survey. Participants were asked to complete the Big Five Inventory, the Brief version of the Pittsburgh Sleep Quality Index, and EQ-5D-5L. A backpropagation neural network was used to explore the order of factors contributing to HRQoL. Path analysis was performed to evaluate the mediation hypothesis. Results: As of August 31, 2022, we enrolled 4123 older adults 60 years and older. Neuroticism and extraversion were strong influencing factors of HRQoL (normalized importance >50%). The results of the mediation analysis suggested that neuroticism and extraversion may enhance and diminish, respectively, HRQoL (index: ß=-.262, P<.001; visual analog scale: ß=-.193, P<.001) by increasing and decreasing brief version of the Pittsburgh Sleep Quality Index scores (neuroticism: ß=.17, P<.001; extraversion: ß=-.069, P<.001). The multigroup analysis suggested a significant moderating effect of the place of residence (EQ-5D-5L index: P<.001; EQ-5D-5L visual analog scale: P<.001). No significant direct effect was observed between extraversion and EQ-5D-5L index in urban older residents (ß=.037, P=.73). Conclusions: This study sheds light on the potential mechanisms of personality and HRQoL among older Chinese adults and can help health care providers and relevant departments take reasonable measures to promote healthy aging.

Mediation analysis for TNF-α as a mediator between multiple metal exposure and kidney function.

The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause. This study aimed to determine the association between of kidney function and metals, such as arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), lead (Pb), selenium (Se), and zinc (Zn), and to explore the possible mediating role of tumor necrosis factor alpha (TNF-α) between metal toxicity and kidney function. In this study, we recruited 421 adults from a health examination. The concentration of blood metals was analyzed using inductively coupled plasma mass spectrometry. We used linear regression models to assess the association between metals and TNF-α. Then, mediation analysis was applied to investigate the relationship between metal exposure, TNF-α, and kidney function. In univariate linear regression, blood As, Cd, Co, Cu, Pb, and Zn levels significantly increased TNF-α and decreased kidney function. Higher blood As and Pb levels significantly increased TNF-α in multivariable linear regressions after adjusting for covariates. We found that blood levels of As (coefficients = -0.021, p = 0.011), Pb (coefficients = -0.060, p < 0.001), and Zn (coefficients = -0.230, p < 0.001) showed a significant negative association with eGFR in the multiple-metal model. Furthermore, mediation analysis showed that TNF-α mediated 41.7 %, 38.8 %, and 20.8 % of blood Cd, As and Pb, respectively. Among the essential elements, TNF-α mediated 24.5 %, 21.5 % and 19.9 % in the effects of blood Co, Cu, and Zn on kidney function, respectively. TNF-α, acting as a mediator, accounted for 20.1 % of the contribution between the WQS score of metal mixtures and the eGFR (p < 0.001). This study suggested that TNF-α may be a persuasive pathway mediating the association between metals and kidney function. Inflammation and kidney injury could be the underlying mechanisms of metal exposure. However, there is still a need to clarify the biochemical mechanism in follow-up studies.

Impact of a change from A­F grading to honors/pass/fail grading on academic performance at Yonsei University College of Medicine in Korea: a cross-sectional serial mediation analysis.

PURPOSE: This study aimed to explore how the grading system affected medical students' academic performance based on their perceptions of the learning environment and intrinsic motivation in the context of changing from norm-referenced A­F grading to criterion-referenced honors/pass/fail grading. METHODS: The study involved 238 second-year medical students from 2014 (n=127, A­F grading) and 2015 (n=111, honors/pass/fail grading) at Yonsei University College of Medicine in Korea. Scores on the Dundee Ready Education Environment Measure, the Academic Motivation Scale, and the Basic Medical Science Examination were used to measure overall learning environment perceptions, intrinsic motivation, and academic performance, respectively. Serial mediation analysis was conducted to examine the pathways between the grading system and academic performance, focusing on the mediating roles of student perceptions and intrinsic motivation. RESULTS: The honors/pass/fail grading class students reported more positive perceptions of the learning environment, higher intrinsic motivation, and better academic performance than the A­F grading class students. Mediation analysis demonstrated a serial mediation effect between the grading system and academic performance through learning environment perceptions and intrinsic motivation. Student perceptions and intrinsic motivation did not independently mediate the relationship between the grading system and performance. CONCLUSION: Reducing the number of grades and eliminating rank-based grading might have created an affirming learning environment that fulfills basic psychological needs and reinforces the intrinsic motivation linked to academic performance. The cumulative effect of these 2 mediators suggests that a comprehensive approach should be used to understand student performance.

Self-Critical Perfectionism and Anxious and Depressive Symptoms Over 2 Years: Moderated Mediation Models of Anxiety Sensitivity and Experiential Avoidance.

This three-wave longitudinal study of 297 community adults (mean age = 38.66 years, 67% female) examined how anxiety sensitivity and experiential avoidance work together to explain the relation between perfectionism and anxious and depressive symptoms over 2 years. Participants completed measures of self-critical (SC) and personal standards (PS) higher-order dimensions of perfectionism, anxiety sensitivity, experiential avoidance, and anxious and depressive symptoms at Time 1. Participants completed measures of anxiety sensitivity, experiential avoidance, and symptoms again at Time 2 one year later, and symptoms measures again at Time 3 two years after baseline. Moderated mediation analyses showed that for those with higher Time 1 experiential avoidance, Time 1 SC perfectionism was indirectly related to Time 3 anxious arousal symptoms through Time 2 anxiety sensitivity. For those with moderate to higher Time 1 anxiety sensitivity, Time 1 SC perfectionism was indirectly associated with Time 3 general distress and anxious arousal symptoms through Time 2 experiential avoidance. These moderated mediation effects were not found for PS perfectionism. These results support anxiety sensitivity and experiential avoidance as moderating and mediating processes that may be important treatment targets for reducing vulnerability to anxious and depressive symptoms over the longer-term in SC perfectionistic individuals.

Blood coagulation in Prediabetes clusters-impact on all-cause mortality in individuals undergoing coronary angiography.

BACKGROUND: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. METHODS: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. RESULTS: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. CONCLUSIONS: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies.

Coronary artery calcification burden, atherogenic index of plasma, and risk of adverse cardiovascular events in the general population: evidence from a mediation analysis.

BACKGROUND: Dyslipidemia and abnormal cholesterol metabolism are closely related to coronary artery calcification (CAC) and are also critical factors in cardiovascular disease death. In recent years, the atherogenic index of plasma (AIP) has been widely used to evaluate vascular sclerosis. This study aimed to investigate the potential association of AIP between CAC and major adverse cardiovascular events (MACEs). METHODS: This study included 1,121 participants whose CACs were measured by multislice spiral CT. Participants' CAC Agatston score, CAC mass, CAC volume, and number of vessels with CACs were assessed. AIP is defined as the base 10 logarithm of the ratio of triglyceride (TG) concentration to high-density lipoprotein-cholesterol (HDL-C) concentration. We investigated the multivariate-adjusted associations between AIP, CAC, and MACEs. The mediating role of the AIP in CAC and MACEs was subsequently discussed. RESULTS: During a median follow-up of 31 months, 74 MACEs were identified. For each additional unit of log-converted CAC, the MACE risk increased by 48% (HR 1.48 [95% CI 1.32-1.65]). For each additional unit of the AIP (multiplied by 10), the MACEs risk increased by 19%. Causal mediation analysis revealed that the AIP played a partial mediating role between CAC (CAC Agatston score, CAC mass) and MACEs, and the mediating proportions were 8.16% and 16.5%, respectively. However, the mediating effect of CAC volume tended to be nonsignificant (P = 0.137). CONCLUSIONS: An increased AIP can be a risk factor for CAC and MACEs. Biomarkers based on lipid ratios are a readily available and low-cost strategy for identifying MACEs and mediating the association between CAC and MACEs. These findings provide a new perspective on CAC treatment, early diagnosis, and prevention of MACEs.

The gut-facial aging axis: A two-sample Mendelian randomization and mediation analysis of gut microbiota, gut microbiota metabolic pathways, and blood metabolites.

BACKGROUND: Facial aging (FA) is a complex process influenced by both genetic and environmental factors. Gut microbiota (GM), gut microbiota metabolic pathways (GMMPs), and blood metabolites (BMs) have been implicated in the regulation of FA, but the causal and mediating effects of these factors remain unclear. METHODS: We used summary-level data from genome-wide association studies (GWAS) of 16S rRNA gene sequencing data for GM (n = 18 340), GWAS of GMMPs (n = 7738), BMs (n = 24 925), and GWAS of FA (n = 423 999). We applied Mendelian randomization (MR) methods to estimate the causal effects of GM, GMMPs, and BMs on FA. We performed mediation analysis to quantify the proportion of the effects mediated by blood metabolites. RESULTS: We identified nine genus, two phylum, two families of GM, nine GM metabolic pathways, and 73 BMs that showed potential causal effects on FA. After Bonferroni correction, three BMs remained causally associated with FA, including average number of methylene groups per double bond (ß, -0.023; 95% CI, -0.032∼-0.014; p = 3.120×10-7) and average number of methylene groups in a fatty acid chain (ß, -0.031; 95% CI, -0.045∼-0.016; p = 2.062×10-5), which had strong negative causal effects on FA, and ratio of bisallylic groups to total fatty acids (ß, 0.023; 95% CI, 0.017∼-0.029; p = 8.441×10-15), which had a strong positive causal effect on FA. Mediation analysis revealed that histidine, average number of methylene groups in a fatty acid chain, and triglycerides in chylomicrons and largest VLDL particles mediated the effects of anaerofilum and/ or superpathway of Laspartate and Lasparagine biosynthesis on FA. CONCLUSION: Our study provides novel insights into the causal and mediating effects of GM, GMMPs, and BMs on FA. These findings may have implications for the development of new strategies for preventing or delaying FA.

The relationship between neuroticism and social aggression: a moderated mediation model.

Neuroticism appears to be a factor that triggers social aggression, but the relationship between neuroticism and social aggression and its underlying mechanisms is unclear. Questionnaire data from 942 college students ranging in age from 17 to 24 (Mage = 20.33, SD = 1.03) were analysed to assess whether depression symptoms mediated the relationship between neuroticism and social aggression, and to test a moderating effect of perceived social support. Results showed that neuroticism positively predicted social aggression and this association was mediated by depression symptoms. Moderation was found for the association between neuroticism and depression symptoms, as well as between neuroticism and social aggression, and that neuroticism had a stronger predictive effect on depression symptoms and social aggression under low compared to high perceived social support. These findings may inform prevention and intervention efforts to reduce social aggression.