Potential Mediators Research Articles

Lower Educational Attainment Widens Racial/Ethnic Disparities in Alcohol Use Disorder.

Lower education is a risk factor for alcohol-related deaths, but it is unknown if the impact of education varies by race/ethnicity. We evaluated the interaction between education and race/ethnicity on the odds of alcohol use disorder (AUD) and the significance of employment and poverty as potential mediators. The 2016-19 National Survey on Drug Use and Health was used to obtain weighted prevalence of AUD in participants 26+ years. Using AUD as the outcome, multivariable logistic regression analyses were performed, stratified by four levels of education, ranging from less than high school (<HS) to 4-year college+ (4C); odds ratios (ORs) for each race/ethnicity were compared across models for interaction. The second model included employment and poverty as co-variates; changes in ORs were calculated to assess for >|10%| change implying significant mediating or confounding effect. AUD prevalence was highest among American Indian/Native Alaskans (AI/ANs) (8.06%), and similar among non-Hispanic Whites (5.37%) and Blacks (5.09%). When stratified by education, the odds of AUD among Blacks and AI/ANs increased with decreasing education [(OR 1.45, 95% CI 1.07-1.96) for Blacks v. Whites with <HS, compared to 0.55 (0.46-0.67) for Blacks v. Whites with 4C; 2.55 (1.53-4.24) for AI/ANs v. Whites with <HS v. 1.01 (0.45-2.28) for AI/ANs v. Whites with 4C). Including employment and poverty resulted in <|10%| change in ORs. Lower education significantly increased the odds of AUD among Blacks and AI/ANs. Employment and poverty did not significantly change the association, implying there are likely other mechanisms accounting for racial/ethnic disparities in AUD.

Circulating extracellular vesicles as potential biomarkers and mediators of acute respiratory distress syndrome in sepsis

The early sequence of respiratory failure events after the onset of sepsis is still unknown. We hypothesize that the lung should signal through circulating extracellular vesicles (EVs) when it is affected by a systemic inflammatory response. Blood samples were obtained from septic patients with (n = 5) and without acute respiratory distress syndrome (ARDS) (n = 13) at 24 h of intensive care unit admission and 3 days later at Sírio-Libanês Hospital. Pulmonary-originated sepsis was not considered. The characteristics of the plasma-isolated EVs were compatible with exosomes. 48 miRNAs were evaluated by real-time PCR. Comparing all samples from patients with sepsis + ARDS to sepsis only, 9 miRNAs are transported in smaller amounts: miR-766 (-35.7, p = 0.002), miR-127 (-23.8, p = 0.001), miR-340 (-13.5, p = 0.006), miR-29b (-12.8, p = 0.001), miR-744 (-7.1, p = 0.05), miR-618 (-4.0, p = 0.02), miR-598 (-3.8, p = 0.035), miR-1260 (-2.5, p = 0.035); and miR-885-5p is expressed at higher levels (9.5; p = 0.028). In paired samples, the set of altered miRNAs is generally different (p < 0.05) between sepsis + ARDS (miR-1183,-1267,-1290,-17,-192,-199a-3p,-25,-485-3p,-518d,-720) or sepsis only (miR-148a,-193a-5p,-199a-3p,-222,-25,-340,744). Bioinformatic analysis showed that when sepsis is associated with ARDS, those differentially expressed miRNAs potentially target messenger RNAs from the Glycoprotein VI/GP6 signaling pathway. Circulating EV-miRNA cargo could be potential biomarkers of lung inflammation during sepsis in patients requiring mechanical ventilation.

Association between exposure to brominated flame retardants and atherosclerosis: Evidence for inflammatory status as a potential mediator.

Brominated flame retardants (BFRs) are a widely used category of environmentally persistent, bioaccumulative chemicals. However, research focusing on the potential adverse effects of these chemicals on human health, particularly on cardiovascular issues, remains limited. This study aimed to investigate the association between BFR exposure and the development of atherosclerosis with a particular focus on the potential role of inflammatory indicators as mediators. Six typical BFRs (BB-153, BDE-28, BDE-47, BDE-99, BDE-100, and BDE-153) and six inflammatory indicators (white blood cells [WBC], neutrophils, mononuclear cells, lymphocytes, blood platelet [PLT], and C-reactive protein) were examined using data from 1654 participants in the National Health and Nutrition Examination Survey 2003-2004. Statistical analysis revealed that the levels of serum BFR, including BB-153, BDE-28, BDE-47, BDE-99, and BDE-100, were markedly elevated in the atherosclerosis group compared with those in the non-atherosclerosis group (all P<0.05). Restricted cubic splines demonstrated a nonlinear relationship between BB-153 and BDE-100 and atherosclerosis, with BB-153 exhibiting a significant correlation with atherosclerosis in an inverted U-shape (P=0.001). In the Binary logistic regression model, BB-153, BDE-28, BDE-47, and BDE-100 were significantly correlated with atherosclerosis, with BB-153 exhibiting the strongest association [OR=2.059, 95% CI: (1.540-2.754), P=0.001]. BFRs were re-analyzed after being divided into four quartiles, revealing a dose-response relationship in which the risk of atherosclerosis increased with higher serum BFRs levels. Bayesian kernel machine regression model and quantile-based G-computation model analyses also demonstrated consistent correlations with mixed BFR exposures, with BB-153 having the greatest contribution. Moreover, mediation analysis demonstrated that WBC count and PLT levels were the primary mediators (proportion mediated: 5.10% and 4.20%, respectively) in the link between of BDE-153, BDE-100, and atherosclerosis. Thus, the inflammatory status may serve as a mediating factor in the relationship between BFR exposure and atherosclerosis.

Inter- and Intraindividual Relations Between Agentic, Communal Self-Enhancement and Hedonic, Eudaimonic Well-Being: Feedback and Mediation Mechanisms.

Researchers seldom consider the interplay between self-enhancement (SE) and well-being at both inter- and intraindividual levels. Previous studies have primarily focused on agentic SE and hedonic well-being, often neglecting communal SE and eudaimonic well-being. This study aims to address these gaps by examining the reciprocal relationship between both agentic and communal SE and both hedonic and eudaimonic well-being. Self-esteem is identified as a potential mediator in these relationships at both inter- and intraindividual levels. Using experience sampling, 172 participants (Mage = 24.25, 75% female) responded to smartphone prompts four times daily for 10 days, yielding 5925 observations. Data were analyzed with Dynamic Structural Equation Modeling. At the intraindividual level, stronger SE predicted increased hedonic and eudaimonic well-being within a short period (about 4 h). This enhanced well-being, in turn, was related to stronger SE, creating a positive feedback loop. At the interindividual level, higher agentic and communal SE correlated with greater well-being. Self-esteem mediated the reciprocal associations between SE and well-being at both levels. These findings offer new insights into the dynamics of SE and well-being, supporting the positive link between SE and well-being in everyday life, emphasizing the mediating role of self-esteem across different analysis levels.

The Interaction and Mediation of Physical Activity of Body Mass Index with Cardiovascular Disease: evidence from NHANES and MR Analysis.

Both insufficient physical activity (PA) and excess body weight are important risk factors for cardiovascular disease (CVD), and PA is closely related to body weight. However, it remains unclear whether PA modifies or mediates the association of body mass index (BMI) with CVD. We conducted a cross-sectional study of 35,406 adults participating in the National Health and Nutrition Examination Survey (NHANES). The mediation and interaction effects of PA were assessed using a four-way decomposition approach. An additional two-step Mendelian randomization (MR) analysis was performed to verify the potential causal mediation effect. A strong association was observed between PA and lower odds of CVD after adjusting for all confounders [Odds Ratio (OR): 0.84; 95% Confidence Interval (CI): 0.74-0.95]. Increased BMI was associated with higher odds of CVD (OR: 1.04; 95% CI: 1.03-1.04). PA showed interaction and mediation effects on the association of BMI with CVD. The overall proportion attributable to interaction was -37.5%, while the overall proportion attributable to mediation was 22.2%. MR analysis further confirmed that PA causally mediated the pathway from BMI to CVD. PA modified the association of BMI with CVD, suggesting that sufficient PA is needed to lower the impact of high BMI on CVD risk. Moreover, we found that PA served as a causal influence on the association of BMI with CVD, indicating that higher BMI led to a lower level of PA, which in turn increased the risk of CVD.

The protective effects of cheese intake on joint pain and underlying biomarkers: Insights from the Mendelian randomization.

This study aimed to investigate the relationship between cheese consumption and the risk of joint pain, as well as to assess the mediating role of biomarkers. Utilizing Mendelian randomization methods, we analyzed data from the UK Biobank and the FinnGen Biobank to evaluate the link between cheese intake and joint pain, examining 44 biomarkers as potential mediators. The findings revealed a significant inverse association between cheese intake and the risk of joint pain, mediated by various biomarkers, including neutrophil count, apolipoprotein A, peak expiratory flow, cystatin C, IGF-1, sex hormone-binding globulin, urate, and automated diastolic blood pressure. These results suggest that cheese intake may reduce the risk of joint pain by affecting specific biomarkers, providing a scientific basis for dietary interventions to decrease the incidence of joint pain. However, the study's limitations include the ethnic homogeneity of the sample population and incomplete analysis of biomarkers, indicating the need for further research to confirm and expand upon these initial findings.

Hopelessness as a Mediator of the Association Between Parenting Factors and Adolescent Suicidality and Substance Use Among Juvenile Justice‐Referred Youth

ABSTRACTYouth involved in the juvenile justice system are more likely to have a substance use disorder and/or suicidality (e.g., suicidal thoughts and behavior) compared to other youth. Although parental support and monitoring may play an important role in youth substance use and suicidality outcomes, the potential mechanisms have not been elucidated. Our purpose was to evaluate the extent to which parental support and monitoring were associated with latent, continuous construct scores of suicidality and substance use and to determine whether youths’ hopelessness may indirectly affect these relationships among a sample of youth referred to the juvenile justice system. The sample included juvenile justice‐referred youth aged 14–17 (N = 77; 69% White, 58% male, 74% non‐Hispanic). The primary predictors of interest were parental support and monitoring, measured by the Parent Support Scale and Parental Monitoring Scale. The primary potential mediator of interest was hopelessness. Linear regression was used to model continuous suicidality and substance use severity scores, measured via a computer adaptive test, on parental support and monitoring. We tested hopelessness as a potential mediator. All analyses controlled for age, sex assigned at birth, race, ethnicity, and family income. After adjustment, parental support was associated with decreased suicidality severity (β = −0.30, p = 0.002). Parent support and monitoring were associated with youth‐reported hopelessness. The indirect mediation effects of hopelessness in the relationship between parental support (β = −0.18 [SE, 1.73]), as well as parental monitoring (β = −0.17 [SE, 0.20]), and suicidality severity were statistically significant. Parental support and youth hopelessness may be important intervention targets for improving and addressing disparities in substance use and suicidality among juvenile justice‐referred youth. Hope‐based interventions may be effectively integrated into existing juvenile justice programs, and their potential to improve both mental health and behavioral outcomes among justice‐involved youth should be examined.

Association among cognitive emotion regulation strategies, psychological flexibility and subjective well-being in patients with breast cancer: a cross-sectional latent profile and mediation analysis.

To explore the relationship among cognitive emotion regulation strategies, psychological flexibility, and subjective well-being, analyze the latent profiles of cognitive emotion regulation strategies, and examine the mediating role of psychological flexibility between cognitive emotion regulation strategies and subjective well-being in patients with breast cancer. The cross-sectional study was conducted from April to December 2023, involving 313 patients with breast cancer. The Cognitive Emotion Regulation Questionnaire-short, the Acceptance and Action Questionnaire-II, and the Index of Well-Being were utilized for data collection. Descriptive statistics, Pearson's correlation coefficient, latent profile, Bayesian factor, and mediation effect were used for data analysis. There was a small to strong correlation among the variables. Latent profile analysis revealed three potential profiles of cognitive emotion regulation strategies, named "low copers", "high copers", and "flexible copers", respectively. Compared with the "flexible copers" group, psychological flexibility might potentially mediate the relationship between the "low copers" profile and subjective well-being, as well as between the "high copers" profile and subjective well-being, with relative indirect effects of -0.720 (95%CI: -1.104, -0.387) and -1.216 (95%CI: -1.732, -0.711), respectively. The results examined the relationship among variables, identified three distinct profiles of cognitive emotion regulation strategies, and indicated that psychological flexibility might serve as a potential mediator between cognitive emotion regulation strategies and subjective well-being.

Adverse childhood experiences, mental distress, and autoimmune disease in adult women: findings from two large cohort studies.

Adverse childhood experiences (ACEs) have been associated with increased risks of autoimmune diseases. However, data are scarce on the role of specific ACEs as well as the potential mediating role of adverse mental health symptoms in this association. A cohort study using the nationwide Icelandic Stress-And-Gene-Analysis (SAGA, 22,423 women) cohort and the UK Biobank (UKB, 86,492 women) was conducted. Participants self-reported on five ACEs. Twelve autoimmune diseases were self-reported in SAGA and identified via hospital records in UKB. Poisson regression was used to assess the cross-sectional association between ACEs and autoimmune diseases in both cohorts. Using longitudinal data on self-reported mental health symptoms in the UKB, we used causal mediation analyses to study potential mediation by depressive, anxiety, and PTSD symptoms in the association between ACEs and autoimmune diseases. The prevalence of ACEs was 50% in SAGA and 35% in UKB, while the prevalence of autoimmune diseases was 29% (self-reported) and 14% (clinically confirmed), respectively. In both cohorts, ACEs were associated with an increased prevalence ratio (PR) of any studied autoimmune disease in a dose-response manner (PR=1.10 (95%CI=1.08-1.12) per ACE), particularly for Sjögrens (PR=1.34), polymyalgia rheumatica (PR=1.20), rheumatoid arthritis (PR=1.14), systemic lupus erythematosus (PR=1.13), and thyroid disease (PR=1.11). Sexual abuse and physical and emotional neglect were consistently associated with an elevated prevalence of autoimmune diseases when including all ACEs in the model. Approximately one fourth of the association was mediated through depression, anxiety, and PTSD. These findings based on two large cohorts indicate a role of ACEs and corresponding mental health distress in autoimmune diseases among adult women.

A156 FECAL PROTEOLYTIC ACTIVITY IS ASSOCIATED WITH SYMPTOMATIC STATUS IN CROHN’S DISEASE

Abstract Background An imbalance in host proteolytic activity (PA) has been reported in patients with inflammatory bowel disease (IBD) versus healthy controls (HCs). Fecal PA increases before the diagnosis of ulcerative colitis (UC) which is proinflammatory and has a microbial component. High microbial PA is also present in Crohn’s disease (CD), and when transferred to germ-free mice, induces inflammation through protease receptor-2 signaling. However, whether high PA associates with symptoms in IBD is unknown. Aims To investigate whether patients with IBD and high PA have higher symptoms as assessed by Symptom IBD Short Index (SIBDSI). Methods Patients with IBD and HCs were recruited and followed for &amp;gt;4 years in the MAGIC study via the IMAGINESPOR network (www.imaginespor.com). Ethnicity, sex, and age information were collected at the initial visit and stool donations were collected at baseline and at each yearly visit. IBD patients completed the SIBDSI survey at each fecal donation and were classified as asymptomatic (UC &amp;lt;13, CD &amp;lt;14) or symptomatic (UC &amp;gt;13, CD &amp;gt;14). From the larger cohort, 60 HC, 60 CD patients, and 60 UC patients were selected and fecal samples from baseline and 1-year follow up visits were used for proteolytic activity assays. Total proteolytic (trypsin), elastase-like (N-Suc-Ala3-pNA), and mucolytic (bioassay) activities were measured in the feces at baseline and follow up from IBD patients and HCs. Results Demographic information, SIBDSI scores, and fecal donations from 60 HCs (39F/22M), 60 CD (33F/24M), and 60 UC (33F/25M) patients were analyzed from baseline and 1-year follow up. The average age for HCs, CD patients, and UC patients was 55, 51, and 45, respectively, and most patients were Caucasian. Overall proteolytic activity and mucolytic activities were (p=0.0001) in IBD patients compared with HCs. From baseline to follow up, 27 CD and 24 UC patients had a change in their symptom status classification. In symptomatic CD patients compared with asymptomatic CD patients, total fecal PA was higher (p=0.04). Conclusions Dysregulated PA is emerging as a potential mediator of inflammation in some patients with IBD. Our data suggest that high overall proteolytic activity may be linked with symptomatic status in a subset of CD patients. PA activity may constitute a novel non-invasive biomarker for monitoring CD disease activity that could therapeutically be targeted in patients with proteolytic-driven disease. Funding Agencies CCC, CIHR

Gut microbiota, inflammatory cytokines, and Kawasaki disease: a Mendelian randomization study and mediation analysis.

This study investigates the causal relationship between gut microbiota, inflammatory cytokines, and Kawasaki disease (KD), and whether cytokines mediate the effect of gut microbiota on KD. A Mendelian randomization analysis using the inverse-variance weighted method assessed the causal effects of gut microbiota and inflammatory cytokines on KD and explored potential mediation. The study found causal links between 20 types of gut microbiota and KD. Ten types increased KD risk, notably Francisellales (OR = 27.82, P = 0.0309). Ten types provided protection, with Fusobacteriaceae showing the strongest effect (OR = 0.0424, P = 0.002). Five inflammatory cytokines were significantly associated with KD; adenosine deaminase was most protective (OR = 0.7447, P = 0.0037), while Fractalkine indicated higher risk (OR = 2.0448, P = 0.0315). Mediation analysis revealed that the Interleukin-10 receptor subunit beta mediates the effect of Bifidobacterium adolescentis on KD, with a mediation effect of -0.0237 (4.75% ratio). Interleukin-20 mediates the effect of Faecalicatena lactaris on KD, with a mediation effect of -0.1168 (15.30% ratio). The findings indicate a causal relationship among gut microbiota, inflammatory cytokines, and KD, suggesting that the gut microbiome influences KD through specific cytokines. The study confirmed a causal relationship between 20 types of gut microbiota and Kawasaki disease, finding that 10 types increase the risk of Kawasaki disease, particularly Francisellales. Five inflammatory cytokines were significantly associated with Kawasaki disease, with adenosine deaminase showing a protective effect, while Fractalkine increased the risk. Mediation analysis indicated that specific inflammatory cytokines (such as Interleukin-10 receptor subunit beta and Interleukin-20) play a significant mediating role between gut microbiota and Kawasaki disease.

Maternal per- and polyfluoroalkyl substance concentrations and placental DNA methylation of thyroid hormone-related genes.

Studies suggested that per- and polyfluoroalkyl substances (PFAS) may have adverse effects on fetus by altering placental DNA methylation. In the study, we explored associations of maternal PFAS concentrations with placental DNA methylation of thyroid hormone (TH)-related genes and the potential mediating role of DNA methylation levels in PFAS-fetal TH associations. We measured PFAS concentrations in maternal plasma in early pregnancy and levels of total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) in cord plasma. We assessed DNA methylation in 345 placental samples for five TH-related genes, i.e., iodothyronine deiodinase 3 (DIO3), solute carrier family 16 member 2 (SLC16A2), solute carrier organic anion transporter family member 1C1 (SLCO1C1), thyrotropin-releasing hormone (TRH), and transthyretin (TTR). We found the associations of PFDA with increased SLC16A2 methylation, PFOA with decreased SLCO1C1 methylation, PFOS with increased TRH methylation, and PFDoA with decreased TRH methylation, and these associations showed sex-specific patterns. Mediation analyses suggested placental SLCO1C1 and SLC16A2 methylation as potential mediators in the associations of PFOA with FT3 and PFUdA with TT4, respectively. These findings provided evidence for associations between prenatal PFAS exposure and epigenetic changes in placental TH-related genes.

Mediating effect of X-26109 on the causal relationship between CD14+ CD16- monocyte activation complex and rheumatoid arthritis in Europe.

The regulation of the immune system is crucial in the pathogenesis of various diseases. The direct involvement of immune cells in the development of rheumatoid arthritis (RA) and the potential mediation by metabolites remains to be elucidated. This study utilized a two-step, two-sample Mendelian randomization (MR) approach employing the inverse variance weighted (IVW) method to investigate the causal role of immune cells in RA and to assess the mediation effect of metabolites on the association between immune cells and RA. MR analyses identified 44 immune cell traits that were suggestively associated with RA. Additionally, five metabolites demonstrated protective effects against RA. Notably, mediation MR indicated that the causal role of CD14+ CD16- monocyte activation complex (AC) on RA (total effect IVW: OR = 0.978, 95% CI [0.959, 0.998], P = 0.028) was significantly mediated by X-26109 levels, accounting for 7.32% of the total effect. This study provides evidence of a causal relationship between immune cells and RA, with metabolites potentially mediating this relationship. Key Points • Mendelian randomization (MR) analysis was used to investigate the causal impact of immune cells on RA progression and the potential mediating role of metabolites, identifying 44 immune cell traits and several metabolites associated with RA risk • The study found that CD14 + CD16 - monocyte activation complex (AC) is associated with a reduced RA risk, with this effect largely mediated by metabolite X-26109 levels, suggesting a potential therapeutic target for RA prevention and treatment.

Physical activity associated with age at menopause: A Mendelian randomization study.

In previous observational studies, physical activity may have an impact on the age at menopause (ANM), potentially delaying or advancing the onset of menopause. However, the causal relationship between physical activity and age at menopause remains unclear. Therefore, we designed a 2-sample Mendelian randomization (MR) and mediation MR study to explore the causal relationship between physical activity and ANM and to identify potential mediating factors such as BMI, insomnia, hypertension and hyperglycemia. We investigated the causal link between physical activity and age at menopause using 2-sample Mendelian randomization (MR) and tested for potential mediators using 2-step MR. Our approach includes IVW and other MR methods and uses a variety of sensitivity tests to verify the robustness of the results. In 2-sample MR analysis, moderate physical activity was associated with delayed age at menopause (β = 0.64, 95% CI = [0.02-1.26], P = .04), but there was no evidence of a causal relationship between vigorous physical activity and age at menopause (P = .68).In contrast, a 2-step MR method showed that body mass index (BMI) mediated the effects of physical activity and delayed age at menopause (proportion mediated, 4.9%, 95% CI = 0.8 to 8%; P = .02), whereas the mediating effects of insomnia, hypertension and hyperglycemia were not significant. Our study shows that moderate physical activity can delay the age of menopause and is informative for the prevention of ovarian failure and the maintenance of women's reproductive health.

Obesity, sarcopenia, sarcopenic obesity and hypertension: mediating role of inflammation and insulin resistance.

This study aimed to assess the association between obesity, sarcopenia, and sarcopenic obesity with hypertension and to explore the potential mediation of inflammation indicators and insulin resistance. Data from the UK Biobank, a large-scale prospective cohort, were utilized. Obesity was defined using percentage of fat mass, while sarcopenia was defined as low muscle mass and low muscle strength. The primary outcome assessed was new-onset hypertension within a 5-year follow-up period. The association analysis was examined using a Cox regression model. A total of 183,091 participants were enrolled in this study. During 5 years of follow-up, 3812 (2.08%) developed hypertension. In the fully adjusted model, compared to men without these conditions, those with obesity, sarcopenia, and sarcopenic obesity had 2.32 times (95% CI, 2.12-2.55), 3.10 times (95% CI, 2.35-4.08), and 3.66 times (95% CI, 2.98-4.50) higher risks of developing hypertension, respectively. Women with obesity, sarcopenia, and sarcopenic obesity had 2.27 times (95% CI, 2.03-2.54), 2.93 times (95% CI, 1.95-4.39), and 4.04 times (95% CI, 3.32-4.91) higher risks of hypertension, respectively. Significant mediating effects of C-reactive protein, neutrophils, white blood cells, triglyceride-glucose index, and triglyceride to high-density lipoprotein cholesterol ratio were found, with mediations ranging from 6% to 13% for men and 2% to 21% for women in the association between sarcopenic obesity and hypertension. Obesity, sarcopenia, and sarcopenic obesity significantly increased the risk of hypertension. Inflammation and insulin resistance appeared to mediate the association between sarcopenic obesity and hypertension.

Cumulative disaster exposure and hypertension among mothers who survived Hurricane Katrina

Abstract Background: As climate change intensifies, hurricanes and weather-related disasters have been increasingly frequent and severe, impacting regions like the U.S. Gulf Coast with repeated hurricanes. While acute and short-term health impacts are well-described, impacts on longer-term and chronic conditions such as hypertension remain underexplored. This study examines the association between repeated hurricane exposure and hypertension risk in survivors.&amp;#xD;Methods: We used data from the Resilience in Survivors of Katrina (RISK) project, a longitudinal (2003-2018) cohort of predominantly Black, low-income mothers affected by Hurricane Katrina. A sample of 505 women who were not hypertensive pre-Katrina was analyzed. Cumulative exposure was defined as the number of hurricanes experienced post-Katrina, assessed at several survey waves over 12 years. Logistic regression estimated associations between hurricane exposure and hypertension in 2016-18, with mediation analyses exploring the indirect effect via psychological distress.&amp;#xD;Results: In adjusted models, exposure to two hurricanes was associated with a 61% increase in hypertension odds (OR = 1.61, 95% CI: 1.00, 2.63) and exposure to three or more with 87% increased odds (OR = 1.87, 95% CI: 1.01, 3.47), relative to exposure to only one hurricane. The indirect effect from hurricane exposure to hypertension via psychological distress was statically significant (95% CI: 1.01, 1.09).&amp;#xD;Conclusions: Findings highlight a novel link between cumulative disaster exposure and hypertension, with psychological distress as a potential mediator. This suggests that repeated exposure to hurricanes not only impacts mental health but may also contribute to adverse physical health outcomes. Addressing both mental and physical health in disaster response, especially for vulnerable populations, is crucial.&amp;#xD;

Causal Effect Between Gut Microbiota, Gut Bacterial Pathway, and Chronic Spontaneous Urticaria: A Large-Scale Bidirectional Mendelian Randomization Analysis.

To analyze causality between gut microbiota and chronic spontaneous urticaria (CSU) and to investigate the mediating effect of metabolic pathways. We extracted genome-wide association study summary statistics for 211 microbiota taxa from the MiBioGen consortium (N=18 340), 205 microbiota metabolic pathways from the Dutch Microbiome Project (N=7738), and CSU from the FinnGen genomics initiative (N=450). Bidirectional Mendelian randomization (MR) was performed to detect genetic causality between gut microbiota, gut bacterial pathways, and CSU. Sensitivity analyses were performed to validate the robustness of the results. Mediation MR investigated mediators in the association between gut microbiota and CSU. MR analysis suggested that the family Peptococcaceae and its child taxon, the genus Peptococcus, were risk factors for CSU. In addition, the genera Collinsella, Lachnospiraceae UCG004, Ruminococcaceae UCG004, and Sellimonas were also risk factors for CSU, whereas Family XIII UCG001, Lachnospiraceae UCG010, and Methanobrevibacter had protective effects on CSU. As for metabolic pathways, NONMEVIPP-PWY, PWY-5022, and PWY-7221 were positively associated with CSU, although others, such as KDO-NAGLIPASYN-PWY, PWY- 6353, and PWY-7400 presented a suggestive association with CSU. Moreover, PWY-7400 was a mediator in causality between the family Peptococcaceae and CSU. These results were based on nominal significance (P<.05). None of the Bonferroni corrected P values were <.05. Our study confirmed a causal association between gut microbiota and CSU, with the metabolic pathway being a potential mediator. Our findings provide new insights for further mechanistic and clinical studies in CSU.

Longitudinal associations of dietary intake with fatigue in colorectal cancer survivors up to 1 year post-treatment, and the potential mediating role of the kynurenine pathway.

A healthy diet may help to reduce cancer-related fatigue, but evidence is limited and mechanisms remain unclear. Both diet and fatigue following colorectal cancer (CRC) have been linked to metabolites (kynurenines) of the kynurenine pathway (KP). We investigated longitudinal associations between dietary intake and fatigue, and the potential mediating role of the KP, in CRC survivors up to 1 year post-treatment. Measurements at 6 weeks, 6 months, and 1 year post-treatment were performed in 209 stage I-III CRC survivors. Diet was assessed by 7-day food records. Plasma kynurenines were analyzed using LC-MS/MS. Fatigue, including subjective fatigue, was assessed using validated questionnaires. To analyse longitudinal associations between diet and fatigue and to explore potential mediation by the KP, we used confounder-adjusted multilevel parallel-multiple mediator models with all kynurenines included simultaneously, and simple mediator models with established KP ratios to estimate total (c: diet-fatigue), direct (c': diet-fatigue, while controlling for mediators), metabolite-specific indirect (ab: diet-metabolite-fatigue), and total indirect (ab: diet-metabolites-fatigue) effects. Higher intake of total carbohydrates and mono- and disaccharides was longitudinally associated with more subjective fatigue, while higher intake of plant protein, total fat, and unsaturated fats was associated with less subjective fatigue (c). Most associations remained statistically significant after controlling for KP metabolites, except for mono- and disaccharides (c'). All kynurenines simultaneously did not mediate longitudinal associations between diet and subjective fatigue (ab). The kynurenic acid-to-quinolinic acid (KA/QA) ratio significantly mediated associations of intakes of carbohydrate, mono- and disaccharides, alcohol, magnesium, and zinc, whereas the HKr significantly mediated the association between polysaccharide intake and subjective fatigue (ab). Our findings suggest that carbohydrate intake is associated with greater fatigue, while protein and fat intake are associated with lower fatigue in CRC survivors up to 1 year post-treatment. While all KP metabolites simultaneously did not significantly mediate associations between diet and fatigue in our population, the KA/QA ratio and HKr were significant mediators in several diet-fatigue associations. These results should be repeated in larger observational studies.

Anxiety disorder, depression and coronary artery disease: associations and modification by genetic susceptibility

BackgroundAssociations of anxiety disorder and depression with coronary artery disease (CAD) are heterogeneous between populations. This study investigated how genetic susceptibility to CAD alters these associations with incident CAD, comparing and combining anxiety disorder and depression.MethodsThis is a prospective cohort study using UK Biobank. Diagnoses of anxiety disorder and depression were ascertained through linked hospital admission data. Incident CAD was ascertained through hospital admission and death certificate data after baseline. CAD polygenic risk score (PRSCAD) was obtained from CARDIoGRAMplus4 and categorised into low, intermediate, and high. Cox proportional hazard models were used to examine associations between anxiety disorder and depression and CAD.ResultsBoth anxiety disorder (HR 2.31, 95% CI 1.92–2.78) and depression (HR 2.15, 95% CI 1.90–2.24) were associated with CAD after adjusting for sociodemographic confounders. There was an addictive interaction between depression and PRSCAD (RERI 0.97, 95% CI 0.12–1.81) such that the association between depression and CAD was strongest among those with a high PRSCAD whilst there was no such evidence for anxiety disorder. Anxiety disorder only (HR 1.68, 95% 1.16–2.44), depression only (HR 2.13, 95% CI 1.72–2.64), and concomitant anxiety disorder and depression (HR 3.85, 95% CI 2.48–5.98) were associated with CAD even among people with a low PRSCAD. Adjusting for potential mediators attenuated all these associations across PRS categories.ConclusionsCAD genetic susceptibility might partly contribute to the clustering of depression and CAD but does not provide a full explanation, nor does it explain the association between anxiety disorder and CAD. Therefore, other mechanisms should be explored.

Biological embodiment of educational attainment and future risk of breast cancer: findings from a French prospective cohort

BackgroundWomen with higher educational attainment have a higher risk of developing breast cancer (BC). Despite the acknowledged impact of reproductive and lifestyle factors, some excess risks remain unexplained. Many studies...