Risk factors underlying racial and ethnic disparities in tuberculosis diagnosis and treatment outcomes, 2011-19: a multiple mediation analysis of national surveillance data.

BACKGROUND: Despite an overall decline in tuberculosis incidence and mortality in the USA in the past two decades, racial and ethnic disparities in tuberculosis outcomes persist. We aimed to examine the extent to which inequalities in health and neighbourhood-level social vulnerability mediate these disparities. METHODS: We extracted data from the US National Tuberculosis Surveillance System on individuals with tuberculosis during 2011-19. Individuals with multidrug-resistant tuberculosis or missing data on race and ethnicity were excluded. We examined potential disparities in tuberculosis outcomes among US-born and non-US-born individuals and conducted a mediation analysis for groups with a higher risk of treatment incompletion (a summary outcome comprising diagnosis after death, treatment discontinuation, or death during treatment). We used sequential multiple mediation to evaluate eight potential mediators: three comorbid conditions (HIV, end-stage renal disease, and diabetes), homelessness, and four census tract-level measures (poverty, unemployment, insurance coverage, and racialised economic segregation [measured by Index of Concentration at the ExtremesRace-Income]). We estimated the marginal contribution of each mediator using Shapley values. FINDINGS: During 2011-19, 27 788 US-born individuals and 57 225 non-US-born individuals were diagnosed with active tuberculosis, of whom 27 605 and 56 253 individuals, respectively, met eligibility criteria for our analyses. We did not observe evidence of disparities in tuberculosis outcomes for non-US-born individuals by race and ethnicity. Therefore, subsequent analyses were restricted to US-born individuals. Relative to White individuals, Black and Hispanic individuals had a higher risk of not completing tuberculosis treatment (adjusted relative risk 1·27, 95% CI 1·19-1·35; 1·22, 1·11-1·33, respectively). In multiple mediator analysis, the eight measured mediators explained 67% of the disparity for Black individuals and 65% for Hispanic individuals. The biggest contributors to these disparities for Black individuals and Hispanic individuals were concomitant end-stage renal disease, concomitant HIV, census tract-level racialised economic segregation, and census tract-level poverty. INTERPRETATION: Our findings underscore the need for initiatives to reduce disparities in tuberculosis outcomes among US-born individuals, particularly in highly racially and economically polarised neighbourhoods. Mitigating the structural and environmental factors that lead to disparities in the prevalence of comorbidities and their case management should be a priority. FUNDING: US Centers for Disease Control and Prevention National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention Epidemiologic and Economic Modeling Agreement.

The Effect of Sodium Glucose Cotransporter-2 Inhibitors on Hemoglobin A1c Variability and Acute Kidney Injury: A Causal Mediation Analysis.

PURPOSE: The role of lower hemoglobin A1c (HbA1c) variability in the effect of sodium glucose cotransporter-2 inhibitors (SGLT2i) on acute kidney injury (AKI) remains unclear. We compared AKI risk between SGLT2i and dipeptidyl peptidase 4 inhibitors (DPP4i) initiators. Additionally, we aimed to explore the extent to which SGLT2i's influence on AKI risk is mediated by reducing long-term HbA1c variability. METHODS: Using 2018-2022 year data in Yinzhou Regional Health Care Database, we included adult, type 2 diabetes patients who were new users of SGLT2i or DPP4i. The effect of SGLT2i versus DPP4i on AKI, HbA1c variability, and AKI through HbA1c variability was compared using inverse probability of treatment weighted Cox proportional hazards models, median regression models, and causal mediation analysis. RESULTS: With a median follow-up of 1.76 years, 19 717 adults (for SGLT2i, n = 6008; for DPP4i, n = 13 709) with type 2 diabetes were included. The adjusted hazard ratio for SGLT2i versus DPP4i was 0.79 (95% confidence interval [CI] 0.64-0.98) for AKI. The adjusted differences in median HbA1c variability score (HVS) and HbA1c reduction were -16.67% (95% CI: -27.71% to -5.62%) and -1.98% (95% CI: -14.34% to 10.38%), respectively. Furthermore, lower AKI risk associated with SGLT2i was moderately mediated (22.77%) through HVS. The results remained consistent across various subgroups and sensitivity analyses. CONCLUSIONS: Compared to DPP4i, lower AKI risk associated with SGLT2i is moderately mediated through HbA1c variability. These findings enhance our understanding of the effect of SGLT2i on AKI and underscore the importance of considering HbA1c variability in diabetes treatment and management.

Significant association between methyl mercury level and latent tuberculosis infection risk: a cross-sectional study.

OBJECTIVES: This cross-sectional study aimed to explore the association between methyl mercury (MeHg) level and latent tuberculosis infection (LTBI) risk based on the data from National Health and Nutrition Examination Survey (NHANES 2011-2012). METHODS: A total of 5243 participants with 20 variables were enrolled. The importance of these variables on TB infection was first ranked by XGBoost and Random Forest methods. Then the association between MeHg level and infection risk was evaluated by restricted cubic spline, threshold effect, and generalized linear regression analyses. We also explored the factors correlated with the difference in MeHg level and finally conducted a mediation analysis to assess the mediating effect of MeHg in LTBI. RESULTS: 521 participants were experiencing the LTBI, and 12 variables showed the differences between infection and non-infection groups (all P < 0.05). Of them, MeHg presented the highest importance on the LTBI. Restricted cubic spline (RCS) next revealed a significant non-linear correlation of MeHg with LTBI (all P < 0.05). Adjusted regression models further indicated their independent association (all P < 0.05), and infection risk increased with the increase of MeHg (P for trend < 0.05). We also found a significant turning point, and their association was significantly observed when MeHg > 5.75 µg/L (P < 0.05). In addition, asthma history was related to the difference in MeHg levels between LTBI and non-LTBI groups. Mediation analysis found that MeHg level partially mediated the association of asthma and LTBI risk (all P < 0.05). CONCLUSIONS: Our study identified MeHg as an independent risk factor for LTBI risk. Their causal relationship needs more investigation to verify.

Mediating effect of diabetes on the relationship between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease: a prospective cohort study.

OBJECTIVE: This study explored the mediating effect of diabetes on the relationship between nonalcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD). METHODS: In this prospective community cohort study, 82 975 participants were enrolled, with the primary outcome being the incidence of new-onset ASCVD. Using the Cox proportional hazards model, the hazard ratio (HR) and 95% confidence interval (CI) for ASCVD occurrence were computed between NAFLD and non-NAFLD groups. The correlation between NAFLD and diabetes was assessed using a binary logistic regression model, and that between NAFLD, diabetes and ASCVD using a mediation model. RESULTS: During follow-up, 9471 ASCVD cases were observed. Compared with individuals without NAFLD, those with NAFLD showed an increased ASCVD risk (HR: 1.424; 95% CI: 1.363-1.488; P < 0.001). Stratifying NAFLD based on metabolic subphenotypes revealed a higher ASCVD risk in the NAFLD combined with diabetes subgroup than in the non-NAFLD subgroup (HR: 1.960; 95% CI: 1.817-2.115; P < 0.001). NAFLD was positively associated with baseline diabetes (odds ratio: 2.983; 95% CI: 2.813-3.163; P < 0.001). Furthermore, NAFLD severity was positively correlated with diabetes risk. Mediation analysis indicated that diabetes partially mediated the effect of NAFLD on ASCVD incidence, accounting for 20.33% of the total effect. CONCLUSION: NAFLD is an independent predictor of increased ASCVD risk, which may be slightly mediated by diabetes in patients with NAFLD. Evaluating NAFLD and diabetes may be crucial in the early screening and prevention of ASCVD.

Interleukin-33 links asthma to alopecia areata: Mendelian randomization and mediation analysis.

OBJECTIVE: The objective of this study is to elucidate the causal association between asthma and alopecia areata (AA) through the application of Mendelian randomization (MR) analysis, leveraging summary data from genome-wide association studies (GWAS). Additionally, it explores potential mediating factors. MATERIALS AND METHODS: Mendelian randomization (MR) analysis was employed to investigate the causal relationship between asthma and AA using genetic instrumental variables (IVs) for asthma, 91 circulating inflammatory proteins, and AA extracted from large-scale GWAS. The primary analytical approach utilized the inverse-variance weighted (IVW) method, supplemented by weighted median and MR-Egger methods to assess robustness. Tests for heterogeneity and pleiotropy were conducted to ensure result reliability. Furthermore, the study examined the mediating role of circulating inflammatory proteins in the asthma-AA relationship. RESULTS: The findings revealed an increased risk of AA among asthma patients (odds ratio (OR) = 14.070; 95% confidence interval (CI) = 1.410-140.435; P = 0.024). Interleukin-33 (IL-33) emerged as a significant mediator in the asthma-AA relationship, explaining 13.1% of the mediation effect. Bidirectional Mendelian randomization analyses did not establish a causal effect of AA on asthma occurrence. CONCLUSION: This study, utilizing Mendelian Randomization, elucidates the causal link between asthma and AA, highlighting the mediating role of IL-33. These findings underscore the importance of considering AA risk in asthma management and offer insights for potential therapeutic strategies targeting IL-33. Future research should explore additional biomarkers and mediating mechanisms between asthma and AA to enhance treatment approaches and patient quality of life.

Association of parent-child discrepancies in educational aspirations with physical fitness, quality of life and school adaptation among adolescents: a multiple mediation model.

BACKGROUND: The global public health issue of diminishing physical fitness among adolescents has gained increasing attention. The impact of parents' negative emotions or pressure regarding adolescents' educational aspirations may have a passive impact on the quality of life and adaptation of adolescents in and out of school, and ultimately harm their physical health. This study aims to explore whether parent-child discrepancies in educational aspirations influence physical fitness in adolescents through school adaptation and quality of life. METHODS: Participants consisted of 9,768 students, males 4,753(48.7%), females 5,015(51.3%), aged 11-19 years, males 14.3 ± 1.92, females 14.4 ± 1.93. The educational aspirations were gauged using a six-point scale for expectation scores. Physical fitness assessments were based on criteria from the National Student Physical Fitness and Health Survey. School adaptation was evaluated using the School Social Behaviors Scale-2. Quality of life for adolescents was measured using Chinese version of the Quality of Life Scale for Children and Adolescents. To analyze the multiple mediating effects, structural equation models were used, and 95% confidence intervals were determined through bootstrap methods. RESULTS: The results illustrated that school adaptation and quality of life played a significant mediating role in the effect of parent-child discrepancies in educational aspirations and physical fitness. There were three intermediary paths were confirmed: (1) discrepancies in educational aspirations → school adaptation → physical fitness (ß=-0.088 SE = 0.021; p<0.01; 95% CI: -0.135, -0.05); (2) discrepancies in educational aspirations → quality of life → physical fitness (ß=-0.025; SE = 0.011; p = 0.010; 95% CI: -0.050, -0.006); (3) discrepancies in educational aspirations → school adaptation→ quality of life → physical fitness (ß=-0.032; SE = 0.014; p = 0.011; 95% CI: -0.061, -0.007). CONCLUSION: This study suggests that parents should reduce negative emotions and pressure regarding adolescents' academic aspirations may help their children get better physical fitness.

Clinical trials with mechanism evaluation of intervention(s): mind the power and sample size calculation.

BACKGROUND: Mediation analysis, often completed as secondary analysis to estimating the main treatment effect, investigates situations where an exposure may affect an outcome both directly and indirectly through intervening mediator variables. Although there has been much research on power in mediation analyses, most of this has focused on the power to detect indirect effects. Little consideration has been given to the extent to which the strength of the mediation pathways, i.e., the intervention-mediator path and the mediator-outcome path respectively, may affect the power to detect the total effect, which would correspond to the intention-to-treat effect in a randomized trial. METHODS: We conduct a simulation study to evaluate the relation between the mediation pathways and the power of testing the total treatment effect, i.e., the intention-to-treat effect. Consider a sample size that is computed based on the usual formula for testing the total effect in a two-arm trial. We generate data for a continuous mediator and a normal outcome using the conventional mediation models. We estimate the total effect using simple linear regression and evaluate the power of a two-sided test. We explore multiple data generating scenarios by varying the magnitude of the mediation paths whilst keeping the total effect constant. RESULTS: Simulations show the estimated total effect is unbiased across the considered scenarios as expected, but the mean of its standard error increases with the magnitude of the mediator-outcome path and the variability in the residual error of the mediator, respectively. Consequently, this affects the power of testing the total effect, which is always lower than planned when the mediator-outcome path is non-trivial and a naive sample size was employed. Analytical explanation confirms that the intervention-mediator path does not affect the power of testing the total effect but the mediator-outcome path. The usual effect size consideration can be adjusted to account for the magnitude of the mediator-outcome path and its residual error. CONCLUSIONS: The sample size calculation for studies with efficacy and mechanism evaluation should account for the mediator-outcome association or risk the power to detect the total effect/intention-to-treat effect being lower than planned.

Psychometric properties and moderated mediation analysis of the ICIQ-NQOL in Chinese primary care patients with nocturia.

BACKGROUND: Many individuals consider nocturia a significant nuisance, leading to a reduced health-related quality of life (HRQOL). However, there has been a lack of psychometrically sound patient-reported outcome measures to assess the impact of nocturia on patients in Chinese contexts. This study aimed to translate, culturally adapt, and validate the International Consultation on Incontinence Questionnaire Nocturia Quality of Life Module (ICIQ-NQOL) for use among primary care patients in Hong Kong, China. Additionally, it sought to investigate the mechanisms that link nocturia and sleep quality with HRQOL by employing moderated mediation analysis. METHODS: The traditional Chinese version of the ICIQ-NQOL was developed through iterative translations, cognitive debriefing interviews, and panel reviews. The psychometric evaluation included assessments of factor structure, convergent validity, concurrent validity, known-group validity, internal consistency, test-retest reliability and responsiveness. Study instruments included the ICIQ-NQOL, International Prostate Symptom Score (IPSS), Pittsburgh Sleep Quality Index (PSQI), and a modified Incontinence Impact Questionnaire-Short Form (IIQ-7). RESULTS: A total of 419 primary care patients were recruited from general outpatient clinics, among whom 228 experiencing an average of two or more nocturia episodes per night over the past four weeks. Confirmatory factor analysis supported the two-factor structure of the ICIQ-NQOL. Concurrent validity was confirmed by moderate correlations between the IIQ-7 total score and the total score as well as two domain scores of the ICIQ-NQOL (r ranging from 0.43 to 0.49, all p < 0.001). The ICIQ-NQOL also had moderate correlations with the IPSS total symptom score (r ranging from 0.40 to 0.48, all p < 0.001). Convergent validity was supported by moderate correlations between the global PSQI score and the total score as well as two domain scores of the ICIQ-NQOL (r ranging from 0.42 to 0.52, all p < 0.001). Known-group comparisons showed that the ICIQ-NQOL could differentiate between patients with and without nocturia in terms of sleep/energy domain score (p < 0.001), bother/concern domain score (p < 0.001), and total score (p < 0.001), each demonstrating a moderate Cohen's d effect size. Item-total correlations corrected for overlap exceeded 0.4, and Cronbach's alpha coefficients were greater than 0.7. Test-retest reliability was confirmed with intraclass correlation coefficients exceeding 0.7 among patients reporting no change in their nocturia symptoms at a 2-week follow-up. Regarding responsiveness, the Cohen's d effect sizes for differences in domain and total scores between the baseline and 2-week follow-up assessments were greater than 0.3 among patients showing improvement in nocturia. Our moderated mediation analysis indicated that sleep quality significantly moderated the impact of nocturia on HRQOL, with a notably stronger indirect effect among females compared to males. CONCLUSIONS: The ICIQ-NQOL is a reliable and valid instrument for assessing the HRQOL in primary care patients suffering from nocturia. The findings advocate for gender-specific approaches in the management and treatment of nocturia to optimize HRQOL.

Potential mechanisms of gut microbiota influence on different types of vertigo: a bidirectional Mendelian randomization and mediation analysis.

BACKGROUND: The relationship between gut microbiota and vertigo, specifically Benign Paroxysmal Vertigo (BPV) and Vertigo of Central (VC), remains underexplored. AIM AND HYPOTHESES: This study aims to investigate the causal relationships between gut microbiota and two types of vertigo, BPV and VC. Additionally, the study seeks to explore the mediation effects of metabolic, inflammatory, and psychological factors on these relationships. We hypothesize that specific taxa of gut microbiota have a causal effect on the risk of developing BPV and VC. The mediation effects of HbA1c, obesity, major depression, and interleukin-18 levels significantly influence the relationships between gut microbiota and vertigo. METHOD: Utilizing a bidirectional two-sample Mendelian randomization approach, this study investigated causal associations between gut microbiota and the two types of vertigo. A network MR assessed mediation effects of HbA1c, major depression, obesity, and interleukin-18 levels, with data sourced from several consortia, including MiBioGen. RESULTS: Distinct gut microbiota displayed varying influences on BPV and VC risks. A total of ten taxa affect BPV. Among these, two taxa have an odds ratio (OR) greater than 1, including one class, one order. Conversely, eight taxa have an OR less than 1, encompassing four families, three genera, and one order. The OR for these taxa ranges from 0.693 to 0.930, with p-values between 0.006 and 0.048. For VC, eight taxa were found to have an impact. Five of these taxa exhibit an OR greater than 1, including four genera and one phylum. The OR for these taxa ranges from 1.229 to 2.179, with p-values from 0.000 to 0.046. The remaining three taxa have an OR less than 1, comprising one family and two genera, with an OR range of 0.445 to 0.792 and p-values ranging from 0.013 to 0.050. The mediation analysis for BPV shows that major depression, obesity, and HbA1c are key mediators between specific taxa and BPV. Major depression mediates 28.77% of the effect of family Rhodospirillaceae on BPV. Obesity mediates 13.90% of the effect of class Lentisphaeria/order Victivallales. HbA1c mediates 11.79% of the effect of genus Bifidobacterium, 11.36% of family Bifidobacteriaceae/order Bifidobacteriales. For VC, interleukin-18 levels and major depression are significant mediators. Interleukin-18 levels mediate 6.56% of the effect of phylum Actinobacteria. Major depression mediates 6.51% of the effect of genus Alloprevotella. CONCLUSION: The study highlights potential causal links between gut microbiota and vertigo, emphasizing metabolic and psychological mediators. These insights underscore the therapeutic potential of targeting gut health in vertigo management.

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.

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.

Co-exposure effects of urinary polycyclic aromatic hydrocarbons and metals on lung function: mediating role of systematic inflammation.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and metals were associated with decreased lung function, but co-exposure effects and underlying mechanism remained unknown. METHODS: Among 1,123 adults from National Health and Nutrition Examination Survey 2011-2012, 10 urinary PAHs, 11 urinary metals, and peripheral white blood cell (WBC) count were determined, and 5 lung function indices were measured. Least absolute shrinkage and selection operator, Bayesian kernel machine regression, and quantile-based g-computation were used to estimate co-exposure effects on lung function. Mediation analysis was used to explore mediating role of WBC. RESULTS: These models demonstrated that PAHs and metals were significantly associated with lung function impairment. Bayesian kernel machine regression models showed that comparing to all chemicals fixed at median level, forced expiratory volume in 1 s (FEV1)/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25 and 75% decreased by 1.31% (95% CI: 0.72%, 1.91%), 231.62 (43.45, 419.78) mL/s, and 131.64 (37.54, 225.74) mL/s respectively, when all chemicals were at 75th percentile. In the quantile-based g-computation, each quartile increase in mixture was associated with 104.35 (95% CI: 40.67, 168.02) mL, 1.16% (2.11%, 22.40%), 294.90 (78.37, 511.43) mL/s, 168.44 (41.66, 295.22) mL/s decrease in the FEV1, FEV1/forced vital capacity, peak expiratory flow, and forced expiratory flow between 25% and 75%, respectively. 2-Hydroxyphenanthrene, 3-Hydroxyfluorene, and cadmium were leading contributors to the above associations. WBC mediated 8.22%-23.90% of association between PAHs and lung function. CONCLUSIONS: Co-exposure of PAHs and metals impairs lung function, and WBC could partially mediate this relationship. Our findings elucidate co-exposure effects of environmental mixtures on respiratory health and underlying mechanisms, suggesting that focusing on highly prioritized toxicants would effectively attenuate adverse effects.

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.

Causal effect of obesity and adiposity distribution on the risk of pressure ulcers and potential mediation by type 2 diabetes mellitus: insights from multivariable mendelian randomization and mediation analysis.

Previous observational studies have identified a link between obesity, adiposity distribution, type 1 Diabetes Mellitus (T1DM), type 2 Diabetes Mellitus (T2DM), and the risk of pressure ulcers (PUs). However, the definitive causality between obesity and PUs, and potential DM mediators remains unclear. Univariable, multivariable, and mediation Mendelian randomization (MR) analyses were conducted to explore the mediating role of T1DM or T2DM in the association between obesity, adiposity distribution, and PUs. Instrumental variables for obesity and adiposity distribution, including Body Mass Index (BMI), waist circumference, hip circumference, trunk fat mass, whole body fat mass, trunk fat percentage, and body fat percentage, were selected from two genome-wide association studies (GWAS). In univariable MR analysis, BMI, hip circumference, and obesity were associated with PUs using inverse variance weighted (IVW) regression. These findings were further corroborated by the replication cohorts and meta-analysis (BMI: OR = 1.537, 95% CI = 1.294-1.824, p < 0.001; Hip circumference: OR = 1.369, 95% CI = 1.147-1.635, p < 0.001; Obesity: OR = 1.235, 95% CI = 1.067-1.431, p = 0.005), respectively. Even after adjusting for confounding factors such as T1DM and T2DM, BMI and hip circumference remained statistically significant in multivariable MR analyses. T2DM may mediate the pathogenesis of BMI-related (OR = 1.106, 95% CI = 1.054-1.160, p = 0.037) and obesity-related PUs (OR = 1.053, 95% CI = 1.034-1.973, p = 0.004). These findings provide insights for the prevention and treatment of PUs, particularly in patients with obesity or DM.

Investigating the causal relationship between wealth index and ICT skills: a mediation analysis approach.

This study examines the relationship between the wealth index (WI) and Information and Communication Technology (ICT) skills among women aged 15-49 in Bangladesh. The research aims to establish a cause-and-effect relationship between WI and ICT skills, while also examining how education mediates this relationship. Using the data from the Bangladesh Multiple Indicator Cluster Survey (MICS) Program 2019, a two-stage stratified clustered sampling method yielded a sample of 64,378 women. The analysis employed inverse probability weighting (IPW) to assess the causal effect of WI on ICT skills while investigating the mediating role of education in this cause-and-effect relationship through causal mediation analysis. The findings demonstrate a significant relationship between higher economic status and increased ICT proficiency among women aged 15-49 in Bangladesh. Mediation analysis reveals education status as a significant mediator, indicating that educational attainment plays a vital role in linking wealth and ICT skills among women. Sensitivity analysis indicates the observed effect estimates are robust to unmeasured confounding. This research underscores the importance of economic empowerment and educational interventions in narrowing the digital divide and fostering ICT skills development among women, particularly in rural and economically disadvantaged communities.

Multiple mediation analysis of a task-shared psychosocial intervention for perinatal anxiety: Exploratory findings from a randomized controlled trial in Pakistan.

BACKGROUND: The "Healthy Mother Healthy Baby" (HMHB) study is a phase three, single-blind randomized clinical trial conducted at Holy Family Hospital (HFH) in association with Rawalpindi Medical University (RMU). We aimed to examine the mediators of a specialized psychosocial approach based on Cognitive Behavioural Therapy principles, targeting pregnant women experiencing anxiety. The HMHB intervention was effective in treating perinatal anxiety symptoms and preventing future depressive episodes. METHODS: The trial randomized participants into two arms: the HMHB intervention or Enhanced Usual Care (EUC), following World Health Organization guidelines. The HMHB intervention comprised strategies to strengthen social support networks, improving mother-baby bonding and strategies to deal with interpersonal conflicts, economic challenges, and societal gender preferences using cognitive and behavioural techniques and culturally resonant illustrations. Participants underwent rigorous data collection at three pivotal timepoints: baseline, third trimester, and 6-weeks postnatal. The primary outcome was anxiety symptom severity scores using the Hospital Anxiety and Depression Scale (HADS) at 6-weeks post-childbirth. Four potential mediators - social support, behavioural activation, perceived stress, and pregnancy experience - were assessed in the third trimester of pregnancy. RESULTS: A total of 1200 participants were randomized to the HMHB and EUC arms. In the six-week follow-up time point, 379 participants remained in the EUC group, and 387 continued in the HMHB group. Post-intervention, HMHB participants displayed significant improvements in postnatal anxiety and depression scores. Mediation analyses revealed social support and pregnancy hassles as significant mediators of the intervention's effect on postnatal anxiety outcomes, while only social support emerged as a significant mediator for depression outcomes. CONCLUSION: The HMHB intervention showed promising results in improving anxiety and depression scores among pregnant women. Significant mediation effects suggest the importance of targeting social support and managing pregnancy-related hassles for optimal intervention effectiveness.

Effects of aircraft noise exposure on self-reported health through aircraft noise annoyance: Causal mediation analysis in the DEBATS longitudinal study in France.

BACKGROUND: Previous studies reported an association between transportation noise and self-reported health status (SRHS). They also suggested a mediating role of noise annoyance using conventional statistical methods. These methods are subject to bias in longitudinal studies with time-dependent exposure, mediator and confounding factors. This study aims to investigate the mediating role of aircraft noise annoyance in the effect of aircraft noise on SRHS using a causal inference approach to address time-dependent variables issues. METHODS: We used data from 881 participants in all three visits in the DEBATS longitudinal study conducted around three French airports. Participants over 18 years of age reported their self-perceived health status, aircraft noise annoyance, and noise sensitivity by completing a questionnaire at three visits in 2013, 2015 and 2017. Noise maps were used to estimate aircraft noise levels outside their homes. Marginal structural models with inverse probability weighting were used to estimate the total effect of aircraft noise levels on SRHS and its decomposition into direct and indirect effect through aircraft noise annoyance. RESULTS: This study showed a deleterious effect of aircraft noise on SRHS. The odds ratio (OR) corresponding to the total effect and comparing the highest aircraft noise category (≥60 dBA) to the reference category (<50 dBA) was significant (ORpoor/fair_SHRS = 1.25 (95%CI: 1.06 to 2.08)). It also showed no direct effect of aircraft noise levels on SRHS, but an indirect effect through annoyance. This indirect effect increased as aircraft noise levels increased, with a statistically significant OR when comparing the highest noise category (≥60 dBA) to the lowest (<50 dBA) (ORpoor/fair_SHRS = 1.16 (95%CI: 1.03 to 1.52)). Nearly 66% of aircraft noise's effect on SRHS was mediated by aircraft noise annoyance. CONCLUSION: This study supports the deleterious causal effect of aircraft noise on SRHS. The results highlight the important mediating role of aircraft noise annoyance in the causal pathway from exposure to aircraft noise to poor/fair SRHS.

Impact of a change from A-F 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 A-F grading to criterion-referenced honors/pass/fail grading. METHODS: The study involved 238 second-year medical students from 2014 (n=127, A-F grading) and 2015 (n=111, honors/pass/fail grading) at Yonsei University College of Medicine in Korea. Scores on the Dundee Ready Educational 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 A-F 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.

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.