Potential Mediators Research Articles

Causal Relationship Between Intelligence, Noncognitive Education, Cognition and Urinary Tract or Kidney Infection: A Mendelian Randomization Study.

The occurrence of urinary tract or kidney infection is correlated with intelligence, noncognitive education and cognition, but the causal relationship between them remains uncertain, and which risk factors mediate this causal relationship remains unknown. The intelligence (n=269,867), noncognitive education (n=510,795) and cognition data (n=257,700) were obtained from genome-wide association studies (GWAS) conducted in individuals of European ethnicities. The genetic associations between these factors and urinary tract or kidney infection (UK Biobank, n=397,867) were analyzed using linkage disequilibrium score regression. We employed a two-sample univariate and multivariate Mendelian randomization to evaluate the causal relationship, and utilized a two-step Mendelian randomization to examine the involvement of 28 potential mediators and their respective mediating proportions. The genetic correlation coefficients of intelligence, noncognitive education, cognition, and urinary tract or kidney infection were -0.338, -0.218, and -0.330. The Mendelian randomization using the inverse variance weighted method revealed each 1-SD increase in intelligence, the risk of infection decreased by 15.9%, while after adjusting for noncognitive education, the risk decreased by 20%. For each 1-SD increase in noncognitive education, the risk of infection decreased by 8%, which further reduced to 7.1% after adjusting for intelligence and to 6.7% after adjusting for cognition. For each 1-SD increase in cognition, the risk of infection decreased by 10.8%, increasing to 11.9% after adjusting for noncognitive education. The effects of intelligence and cognition are interdependent. 2 out of 28 potential mediating factors exhibited significant mediation effects in the causal relationship between noncognitive education and urinary tract or kidney infection, with body mass index accounting for 12.1% of the mediation effect and smoking initiation accounting for 14.7%. Enhancing intelligence, noncognitive education, and cognition can mitigate the susceptibility to urinary tract or kidney infection. Noncognitive education exhibited independent effect, while body mass index and smoking initiation assuming a mediating role.

Correlation Among Psoriasis, Iridocyclitis, and Non-alcoholic Fatty Liver Disease: Insights from Mendelian Randomization and Mediation Analysis.

Purpose: The aim of this study is to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship among psoriasis, iridocyclitis, and non-alcoholic fatty liver disease (NAFLD), and to explore any potential mediation effects. Methods: Pooled data were derived from the public genome-wide association study (GWAS) in NAFLD (finn-b-NAFLD), iridocyclitis (finn-b-H7_IRIDOCYCLITIS) and psoriasis (finn-b-L12_PSORI_VULG). Univariable MR (UVMR) analysis was implemented to explore the causal relationship among psoriasis, iridocyclitis, and NAFLD, and inverse variance weighting (IVW) was used as the primary analytical method. Additionally, Cochran's Q and MR-Egger tests were utilized to evaluate the heterogeneity and horizontal pleiotropy, respectively. Simultaneously, the reliability of MR results was evaluated by leave-one-out (LOO) method. Finally, multivariable MR (MVMR) analysis and mediation analysis were performed to further reveal the mechanism of mediation effect among the three diseases. Results: With regard to the results of IVW method, both iridocyclitis (P=0.0185, OR=1.0757) and psoriasis (P=0.0115, OR=1.1246) had significant causal relationships with the occurrence of NAFLD, and both were risk factors for NAFLD. Besides, it was observed that there was significant causal effect of iridocyclitis (P= 0.0181, OR=1.1729) on psoriasis and iridocyclitis was a risk factor. Additionally, there was a lack of heterogeneity (P>0.05) among the selected SNPs when MR analysis was conducted with NAFLD as the outcome. Horizontal pleiotropy was not detected by the MR-Egger test. The LOO analysis demonstrated that the instrumental variables were appropriately chosen, suggesting the reliability of the MR results. Ultimately, MVMR and mediation analysis revealed iridocyclitis affected the development of NAFLD, 20.81% of which was caused by the pathway of iridocyclitis induced psoriasis leading to NAFLD. Conclusion: This study highlighted that iridocyclitis was significantly associated with an increased risk of NAFLD and that psoriasis was involved in the mechanism by which iridocyclitis triggered NAFLD, which might offer potential preventive strategies for NAFLD.

Neurotrophin-3 as a mediator in the link between PM2.5 exposure and psychiatric disorders: A Mendelian randomization study.

Neurotrophin-3 as a mediator in the link between PM2.5 exposure and psychiatric disorders: A Mendelian randomization study.

Effect of serum uric acid to creatinine ratio on cognitive function decline in middle-aged adults: Longitudinal evidence from CHARLS.

Serum uric acid (SUA) was a predictor of cognitive function. The association of SUA/serum creatinine ratio (Scr), which represents renal function-normalized SUA and cognitive function is unknown. This study investigated the association of the SUA/Scr with cognitive function and the potential mediation effect of inflammation in the above relationship. This study used 1-5 waves of data from the China Health and Retirement Longitudinal Study. 3302 participants aged 45-60 years at baseline were included. Among them, 1129 who attended subsequent 2-3 waves were further included for cumulative exposure calculation to the SUA/Scr ratio. The Cox models were used to evaluate the impact of baseline SUA/Scr ratio and its cumulative exposure on cognitive function decline. During a median follow-up of 8.6 years, there were 1512 (45.8%) cognitive function declined. After adjustment, the highest quartile of the SUA/SCr ratio was associated with the highest risk of cognitive function decline (Hazard ratio, 1.175; 95% confidence interval, 1.015-1.360). Restricted cubic spline showed a linear association between the SUA/Scr ratio and the risk of cognitive function decline (pnon-linear = 0.514). There were a stronger association of cumulative SUA/Scr ratio and its exposure burden with cognitive function decline [the highest versus lowest quartile: 1.635 (1.006-2.656), the high versus low group: 1.729 (1.212-2.466), respectively]. No significant mediating effect through white blood cell count or C-reactive protein in SUA/Scr ratio-cognitive function decline was found. The SUA/Scr ratio was associated with a higher risk of cognitive decline, whereas the mechanism mediated by inflammation indicators was not found.

Migraine and its major subtypes - with and without aura are associated with polygenic scores for autism.

Individuals with autism spectrum disorder (ASD) experience a wide array of neurological, psychiatric and medical comorbidities, yet little attention has been given to the potential link between ASD and migraine, one of the most prevalent neurological disorders worldwide. This study aimed to investigate whether a genetic predisposition for ASD is linked to migraine and its major subtypes, with and without aura. Additionally, potential moderator and mediators of the association between ASD and migraine were explored. Polygenic scores (PGS) for ASD were constructed based on the genome-wide association study by the Psychiatric Genomics Consortium, on the UK Biobank cohort dataset comprising 337,386 participants using PRSice-2. Regression analyses were performed to investigate the association of ASD PGS with migraine and its major subtypes, with and without aura. Sex was explored as a potential moderating factor. The mediation analyses took into consideration variables such as education, personality trait neuroticism, body mass index (BMI) and four categories of comorbidities (psychiatric, vascular, neurologic and others). ASD PGS were significantly and positively associated with migraine (odds ratio (OR) = 1.04, 95% confidence interval (CI) = 1.02-1.05, p < 0.002), migraine without aura (OR = 1.05, 95% CI = 1.02-1.07, p < 0.002) and migraine with aura (OR = 1.05, 95% CI = 1.02-1.07, p < 0.002). No moderating effect of sex on the association between ASD PGS and migraine was observed. As for potential mediators, only the personality trait neuroticism significantly mediated the association between ASD PGS and migraine, with the proportion of effect mediated 8.75% (95% CI = 4-18%). Our study suggests that individuals genetically predisposed to autism are at higher risk of experiencing migraine, including the two major subtypes, with and without aura. While emphasizing the complex shared genetic and pathophysiological interactions of these conditions, the role of personality trait neuroticism as a mediator of this relationship is highlighted.

Genetic Insights Into Lipid Traits and Lipid-Modifying Drug Targets in Pregnancy Complications: A Two-Sample Mendelian Randomization Study.

Dyslipidemia is linked to pregnancy complications, but its causal role remains uncertain. This two-sample Mendelian Randomization (MR) study investigated the causal relationship between lipid traits and pregnancy complications and evaluated the impact of lipid-modifying drug targets. Genetic instruments for lipid traits and targets for lipid-modifying drugs were obtained from the Global Lipids Genetics Consortium. Three pregnancy complications' summary statistics came from the FinnGen R9 database. Significant drug targets underwent further analysis using Expression Quantitative Trait Loci data, and mediation analysis identified potential mediators. Increased high-density lipoprotein cholesterol (HDL-C) reduced the incidence of preeclampsia (OR: 0.755, 95% CI: 0.639-0.891, p=0.001, FDR=0.012) and gestational diabetes mellitus (GDM) (OR: 0.835, 95% CI: 0.741-0.942, p=0.003, FDR=0.018). Genetic proxies for cholesteryl ester transfer protein (CETP) inhibition correlated with a decreased risk of preeclampsia (OR: 0.863, 95% CI: 0.786-0.947, p=0.002, FDR=0.027), while genetic inhibition of HMG-CoA reductase (HMGCR) increased preeclampsia risk (OR: 1.700, 95% CI: 1.189-2.431, p=0.004, FDR=0.036). Genetically mimicking the enhancement of lipoprotein lipase (LPL) related to a reduced risk of GDM (OR: 0.681, 95% CI: 0.560-0.829, p=1.29×10-4, FDR=0.004). Higher LPL expression in subcutaneous adipose tissue also reduced GDM risk (OR: 0.642, 95% CI: 0.454-0.909, p=0.013). Waist circumference (4.2%) and waist-to-hip ratio adjusted by BMI (5.7%) partially mediated LPL's effect on GDM risk. Elevated HDL-C levels help prevent preeclampsia and GDM. CETP and LPL could be therapeutic targets for preeclampsia and GDM, respectively. However, caution is advised with HMGCR-targeting drugs, as they may increase the preeclampsia risk.

Associations between brominated flame retardants exposure and non-alcoholic fatty liver disease: Mediation analysis in the NHANES.

Exposure to brominated flame retardants (BFRs) may negatively impact human health. The association of BFRs with nonalcoholic fatty liver disease (NAFLD) in the general population is unclear. Meanwhile, limited studies have investigated the potential role of oxidative stress and inflammation in this link. We included 4110 adults from the 2009-2014 National Health and Nutrition Examination Survey (NHANES). NAFLD was diagnosed by serum alanine aminotransferase (ALT), hepatic steatosis index (HSI), and United States fatty liver index (USFLI). The link between a single BFR exposure and NAFLD was estimated using weighted logistic regression and restricted cubic splines (RCS). The quantile-based g-computation (QGC), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were applied to evaluate the overall correlation of BFRs mixtures with NAFLD and identify significant compounds. Furthermore, we investigated the potential mediation function of oxidative stress and inflammation. Our study demonstrated that specific concentrations of BFRs are related to an increased risk of NAFLD, both individually and when combined. PBB153, PBDE28, PBDE209, and PBDE153 exhibited the highest importance for NAFLD and were potential risk factors worthy of concern. Additionally, mediation analysis showed that absolute neutrophil cell count (ANC) and lymphocyte count (LC) (inflammation markers) have significantly mediated influences on the correlations of PBB153, PBDE85, and PBDE28 with N AFLD risk. Albumin (ALB) (oxidative stress marker) has notably mediated influences on the correlations of PBDE99, PBDE154, and PBDE85 with NAFLD risk. Men had higher serum BFRs concentrations than women, and the association between BFRs and NAFLD was also more prominent in men, which may be related to physiological differences between the sexes. Our findings offer evidence for single and mixed associations of BFRs and NAFLD in ordinary US adults. Furthermore, oxidative stress and chronic inflammation may mediate the effects of BFR exposure on NAFLD development.

Sex steroid hormones mediate the association between neonicotinoids and obesity among children and adolescents.

Sex steroid hormones mediate the association between neonicotinoids and obesity among children and adolescents.

Universal parent-focused child sexual abuse prevention: A quasi-experimental protocol.

Child sexual abuse (CSA) is a significant public health concern, and there is a lack of universal, evidence-based primary prevention interventions that extend beyond a focus solely on children. Parents remain a consistently underutilized target for primary prevention efforts aimed at mitigating CSA despite their unique relationship and close proximity to their children. CSA risk is not confined to any specific demographic, and its effects on affected children are well-documented, significantly impacting numerous dimensions of their wellbeing. Thus, there is a clear and urgent need to address this gap in prevention strategies. This study will use a quasi-experimental design (target N = 412) to examine potential gains in CSA-related awareness and intentions to use protective behaviors among parents who participate in a universal parent-focused CSA prevention workshop, Smarter Parents. Safer Kids., compared to those who do not. Participants in both the control (n = 206) and experimental group (n = 206) will complete 3 survey assessments: Survey 0 (baseline), Survey 1 (1-month), and Survey 2 (3-month follow-up). The experimental group will participate in a Smarter Parents. Safer Kids. workshop between the Surveys 0 and 1. We will use data collected from the baseline to measure potential mediators of CSA-related awareness and intention to use protective and preventive behaviors. In adjacent efforts to enhance the curriculum's reach with future dissemination and implementation, we will also explore the impact of recruitment materials and strategies on parental engagement. Results of this study will advance efforts to implement parent-focused CSA prevention with a universal audience.

Heart Rate Variability: A Psychophysiological Factor Related to Both Regular Physical Activity and Eudaimonic Well‐Being Among Young Adults

ABSTRACTIntroductionEudaimonic well‐being (EWB), which refers to optimal human functioning, is associated with psychophysiological outcomes, such as reduced inflammation and a lower risk of depression. Although physical activity (PA) and mindfulness have been shown to be predictive factors for EWB, potential mediators of the relationships of PA or mindfulness with EWB have yet to be identified. PA, mindfulness‐related psychophysiological factors (including serotonin [5‐HT], oxytocin [OXT]), and dopamine [DA] levels), and heart rate variability (HRV) have been shown to be associated with mental disorders or emotion regulation capacity.PurposeThe purpose of this study is to explore the potential psychophysiological factors associated with PA, mindfulness and EWB.MethodsA total of 49 young adults (25 males, 24 females) were included with an average age of 25 years (± 5). Plasma 5‐HT, OXT, and DA levels were obtained via blood samples from the brachial vein and were analyzed with enzyme‐linked immunosorbent assays (ELISAs), and HRV was obtained via 5‐min electrocardiograms (ECGs), with participants in the supine position. Spearman's correlation analyses were performed, followed by partial correlation analyses controlling for age, sex, and social status (i.e., student or working professional).ResultsHRV was found to be positively correlated with both moderate‐intensity PA (r = 0.47, p = 0.04) and EWB (purpose in life; r = 0.50, p = 0.03), even after controlling for relevant variables. On the other hand, neither 5‐HT, OXT, nor DA was correlated with PA, mindfulness, and EWB.ConclusionThese results suggest that HRV may mediate the relationship between PA and EWB. Additional intervention studies are needed to elucidate the causal relationships among PA, HRV, and EWB.

Hypertension, diabetes, and cardiovascular disease nexus: investigating the role of urbanization and lifestyle in Cabo Verde

ABSTRACT Background Although hypertension and diabetes are known to increase cardiovascular disease risk, the influencing and underlying factors remain unclear. Objective To examine the mediating effect of location of residence and the moderating effects of recommended lifestyle practices in the hypertension/diabetes and cardiovascular disease nexus. Material and methods Data were drawn from 4,563 participants in Steps 1 and 2 of the 2020 World Health Organization’s STEPS survey in Cabo Verde, with a subsample of 2,436 individuals completing Step 3. A logit regression model was employed to examine the correlations of cardiovascular disease, while structural equation modeling and interaction analysis were used to identify mediators and moderators within the explored relationships. Results Living with hypertension and diabetes were both observed to increase the likelihood of having a cardiovascular disease [Coeff. (RSE), 0.46, (0.12), p < 0.001; 1.26, (0.14), p < 0.001, respectively]. We identify urbanicity as a potential mediator through which hypertension/diabetes leads to a cardiovascular disease and waist circumference as a moderator of hypertension/diabetes-cardiovascular nexus. Conclusion These findings add to the toolset of public health practitioners and policymakers in formulating policies and interventions aimed at managing cardiovascular diseases, particularly in developing nations.

Association between sleep disorder and anhedonia in adolescence with major depressive disorder: the mediating effect of stress

BackgroundMajor depressive disorder (MDD) is a highly prevalent mental disorder with devastating consequences that often first manifest during adolescence. Anhedonia has emerged as one of the most promising symptoms of adolescent MDD, which means a longer time to remission， fewer depression-free days, and also increased risk of suicide ideas or actions. Research has shown that at least two-thirds of depressed adolescents have significant sleep-onset or sleep-maintenance problems. However, the association between sleep disorder and anhedonia, and the potential mediators are less understood.MethodsThis is a cross-sectional study that includes 200 adolescents suffered from MDD between the ages of 12–17. We use Spearman’s test to explore the relationship among main variables. To evaluate the mediating effects of stress, we applied regression models and used bootstrap method to validate the significance of effects.ResultsSignificant correlation exists among sleep disorder, stress, and anhedonia (P<0.05).The direct effect of sleep disorder on anhedonia was 0.214 (95% CI: 1.5235, 6.2073), while the total effect was 0.295 (95% CI: 2.9683, 7.6924). The indirect effect of sleep disorder on anhedonia mediated by stress was 0.081 (95% CI: 0.5842, 2.5268). Robustness of the regression analysis results has been verified by bootstrap test.ConclusionsOur finding suggested a positive correlation between sleep disturbance and anhedonia in adMDD. Stress partially mediated the relationship between sleep disorder and anhedonia. Due to the deleterious effects of anhedonia on depressed adolescents, these findings provide impetus to investigate further the causal relationship between sleep problems and anhedonia.Trial registrationChiCTR2200060176(Registration Date: 21/05/2022).

ILLNESS INTRUSIVENESS AND PERCEIVED CONTROL ON QUALITY OF LIFE IN OLDER ADULTS WITH ARTHRITIS AND MULTIMORBIDITY

Abstract Arthritis is independently associated with diminished quality of life (QOL) among older adults; and QOL is even worse among those with arthritis and multimorbidity (MM). Illness intrusiveness—i.e., the perception that diseases and their treatments interfere with valued roles and activities—leads to poor QOL among those with chronic illnesses. Further, the perceived control individuals have over their illnesses has been proposed as a mechanism underlying the relationship between illness intrusiveness and QOL. While illness intrusiveness and perceived control are amenable to change, they are understudied among older adults with arthritis and MM. We investigated the role of perceived control as a potential mediator or moderator in the relationship between illness intrusiveness and QOL among older adults with arthritis and MM. We conducted a secondary analysis on a cross-sectional sample of older adults with MM (N=228) using PROCESS macro for SPSS. Participants were on average 72.0 years (SD=5.5), largely women (66.1%), with 2.8 chronic illnesses (SD=0.4), and high levels of pain intensity (M =7.92, SD=2.29) and illness intrusiveness (M=38.86, SD=16.55). Perceived control was a significant mediator in the relationship between illness intrusiveness and QOL, even after adjustment for pain intensity [β = -0.16, 95% CI (-0.13, -0.06)]. Perceived control did not moderate the relationship. In this sample of older adults with arthritis and MM, with high levels of illness intrusiveness and pain intensity, perceived control mediated the relationship between illness intrusiveness and QOL. Perceived control may be a target for future behavioral interventions to improve QOL in this population.

RELATIONAL RELIGIOSITY, FORGIVENESS, AND FAMILY FUNCTIONING IN OLDER AFRICAN AMERICAN COUPLES

Abstract Despite recent advances in studies on positive psychology, relatively little is known about the factors that influence the romantic relationships of older African Americans. Existing literature does note that older African Americans are among the most religious racial/ethnic groups in the United States. In addition, forgiveness is recognized as a common mediator between relational religiosity and other positive outcomes, such as psychological well-being and successful aging. Given the need for more strength-focused studies on minority-based romantic relationships, this study examined forgiveness as a potential mediator between relational religiosity and family functioning among older, romantically involved African American couples. This study utilized the dyadic data of 194 African American couples with partners between the ages of 50 and 86 years. Data were captured with the Revised Sanctification of Marriage scale, six items assessing interpersonal forgiveness, and the McMaster Family Assessment Device. Indirect effects were verified with 95% confidence intervals within 10,000 bias-corrected bootstrap iterations. The relations between men’s relational religiosity and men’s reports of family functioning were partially mediated by men’s self-reported ability to forgive their partner (B =.053 (95% CI [.001,.187])), as well as the sum of all men’s and women’s reported abilities to forgive and perceive forgiveness (B =.132 (95% CI [.012,.260])). These findings highlight the growing, yet underrecognized, need to understand the religiosity of older African American men relative to positive relational outcomes. Further, this data helps to counter the deficit-narratives that often paint African American family functioning as poor and flawed.

THE RELATIONSHIP BETWEEN RETIREMENT AND CARDIOVASCULAR DISEASE: A MEDIATION ANALYSIS IN THE U.S. AND SOUTH KOREA

Abstract Retirement has been linked to increased risk for cardiovascular disease (CVD), but little is known about the pathways underlying the association. Moreover, most studies have been conducted in Western countries, and their findings might be less generalizable to Eastern countries due to different social contexts and labor and employment environment. We examined 1) whether retirement status is associated with a higher risk of CVD in South Korea and the U.S., and 2) whether health (e.g., hypertension, diabetes, and obesity), behavioral (e.g., physical activity, alcohol consumption, and smoking), and psychological factors (e.g., loneliness, depressive symptoms, and quality of life) mediate these associations. Data were drawn from the Health and Retirement Study (HRS, 2002–2014; n=11,855) and the Korean Longitudinal Study of Aging (KLoSA, 2006–2018; n=4,908). We analyzed the data using cox proportional hazard model, controlling for socio-demographic factors, health conditions, health behavior, and social isolation. We also performed causal mediation analyses based on counterfactual framework. After adjusting for all covariates, retirement (vs. employment) was associated with an increased likelihood of developing CVD (Hazard Ratio (HR): 1.22, 95% CI: 1.00-1.49) in Korea but not in the U.S. Regarding potential mediators, several physical health factors accounted for a proportion of the association in KLoSA: hypertension (17.7%, p&amp;lt; 0.01), diabetes (12.1%, p&amp;lt; 0.05), and obesity (3.7%, p=0.01). The psychological pathway, specifically quality of life, also mediated the association (4.8%, p&amp;lt; 0.05). Our findings highlight that public health interventions targeting physical and mental health could be an important strategy for preventing CVD among retirees, especially in Korea.

NEIGHBORHOOD DISORDER AND COGNITIVE HEATH: THE CAUSAL MEDIATING EFFECTS OF ALLOSTATIC LOAD AND PHYSICAL ACTIVITIES

Abstract Numerous studies have attempted to establish a link between neighborhood disorder and later life cognitive decline, with stress accumulation and reduced physical activity hypothesized as potential mediators. However, there remains a significant gap in our understanding of the causal mechanisms underlying this link. This research utilizes data from the Health and Retirement Study (2006-2008 and 2010-2012) to investigate whether stress accumulation, as measured by allostatic load, and physical activity mediate the association between perceived neighborhood disorder and cognitive health. Older Americans aged 65 years and older without dementia at baseline were selected (n=4,346). Cognitive function was measured using the Telephone Interview for Cognitive Status (TICS). Employing propensity score matching followed by causal mediation analyses, we find that higher levels of perceived neighborhood disorder at baseline are associated with poorer cognitive health at a subsequent wave. Under a counterfactual framework, if every respondent had experienced one standard deviation above the mean level of neighborhood disorder, the cognitive score would be 0.68 lower than the score if everyone had experienced one standard deviation below the mean (total effect: -0.68, 95% CI: -0.94, -0.42). Approximately three percent (natural indirect effect = -0.02, 95% CI: -0.04, -0.01) of this effect is attributable to physical activity. Notably, we find no significant mediating effect of allostatic load (natural indirect effect = -0.005, 95% CI: -0.02, 0.004) after adjusting for individual-level characteristics. Our findings underscore the significant role of the behavioral factor in mediating the relationship between disadvantaged neighborhoods and cognitive health among older adults.

PHYSICAL ACTIVITY, PURPOSE, AND COGNITION: TESTING POSSIBLE MEDIATION PATHWAYS WITH CROSS-LAGGED PANEL ANALYSIS

Abstract Numerous studies have emphasized the cognitive benefits older adults experience from engaging in regular physical activity. Previous research has largely highlighted the physiological mechanisms of this relationship, like improvements in cardiovascular health and brain structure, but recent work has begun investigating possible psychological pathways. Prior work from the authors supported the hypothesis that purpose in life acts as a mediator between physical activity and cognitive function, though research suggests a bidirectional relationship between physical activity and purpose in life. Given the bidirectional nature of the relationship between these two variables, the current work tests the possibility that physical activity could also act as the mediator in a single model using a structural equation modeling framework. In a sample of 2960 adults aged 33 to 92 collected through two waves of the Midlife in the United States (MIDUS) study, we examined two potential mediation pathways in a cross-lagged panel model where purpose in life mediates the effect of physical activity on cognition and vice versa. Two separate models test mediation pathways on executive functioning and episodic memory. Results show that purpose in life acted as a significant mediator between physical activity and both cognitive abilities (p &amp;lt;.021), while the indirect effects of physical activity between purpose in life and both cognitive abilities were not significant (p &amp;gt;.67). Findings from this study suggest that among physical activities with similar cardiovascular benefits, the one that also nurtures individuals’ purpose in life and boosts psychological well-being should be prioritized.

ANRIL upregulates TGFBR1 to promote idiopathic pulmonary fibrosis in TGF-β1-treated lung fibroblasts via sequestering let-7d-5p

ABSTRACT Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening respiratory disease characterized by worsening lung function due to excessive scarring. The objective of this study was to investigate the role of the long non-coding RNA ANRIL (antisense non-coding RNA in the INK4 locus) in the development of IPF. Our research revealed a significant increase in ANRIL expression in pulmonary fibrosis, consistent with prior studies indicating elevated ANRIL levels in fibrotic tissues. In vitro experiments demonstrated that elevated ANRIL expression promoted fibroblast activation, as evidenced by the upregulation of fibrosis-related markers. Mechanistically, we found that ANRIL interacts with let-7d-5p, a microRNA involved in gene regulation, acting as a sponge for let-7d-5p. Functional experiments confirmed a potential influence of let-7d-5p on fibroblast activation through direct interaction with ANRIL. Furthermore, our investigation identified TGFBR1 as a potential mediator of ANRIL’s fibrogenic effects. Silence of TGFBR1 mitigated the fibrotic phenotype induced by ANRIL overexpression. Collectively, these results suggest that ANRIL promotes fibroblast activation and fibrosis development, possibly through the let-7d-5p/TGFBR1 axis, indicating that ANRIL could be a potential therapeutic target for pulmonary fibrosis.

MENTAL AND PHYSICAL HEALTH PATHWAYS LINKING EXPOSURE TO HIGHWAYS AND COGNITIVE HEALTH AMONG OLDER MEXICAN AMERICANS

Abstract Residing in an area with more major roadways is associated with worse cognitive function, yet few studies examine this relationship among older Mexican Americans. Our objective is to explore mental and physical health pathways linking exposure to highways to cognitive performance/function among Mexican Americans aged 75 and older. We used data from the Hispanic Established Population for the Epidemiological Study of the Elderly (2004/2005). Our exposure was the number of primary and secondary roads in a participant’s census tract. Our outcome was the Mini-Mental State Examination (MMSE) score. We examined depressive symptoms (Center for Epidemiologic Studies Depression Scale), neighborhood satisfaction (very satisfied/satisfied vs. neutral/dissatisfied/very dissatisfied), basic activity of daily living (ADL) limitations (7-item modified Katz ADL scale), and physical function (Short Physical Performance Battery) as separate potential mediators, using path analysis. Covariates included age, sex, education, marital status, nativity, language of interview, length of time in residence, and census tract characteristics (urbanicity, affluence, disadvantage, and proportion of Hispanic residents). Our analytic sample (n=1,723) had an average age of 81.5 years (standard deviation: 4.9) and was 61.2% female. Residing in census tracts with more highways was associated with lower MMSE scores. Depressive symptoms, neighborhood satisfaction, and physical function were not mediators while ADL limitations mediated 40% of the relationship between living in census tracts with more highways and MMSE scores. Future work is needed to understand the direct and indirect mechanisms underlying the association between exposure to highways and ADL limitations, as well as between ADL limitations and cognitive health.

RECOLLECTING AND REFLECTING: STORY ASIDES IN YOUNG AND OLDER ADULTS’ AUTOBIOGRAPHICAL STORIES

Abstract The ways people tell autobiographical stories changes with age. One change is the amount of tangentially-related information included in these stories. These pieces of information–story asides–add context (e.g. knowledge about the world or storyteller). Story asides are expressed more frequently in the autobiographical stories of older adults compared to young adults, but the underlying mechanism is unclear. One potential mechanism is how people remember the story. The current study tested two potential mediators of this expression in young and older adults’ autobiographical stories. As part of a larger study, 61 young (M = 19.9 years) and 35 older (M = 73.8 years) adults shared an autobiographical story about the same event, a positive vacation. Participants then completed a modified version of the Autobiographical Memory Questionnaire, including 5 items about recollection (e.g., feeling the emotions they felt then) and 3 items about reflection (e.g., how significant this event is) on their autobiographical story. Mediation regression analyses indicated that story aside expression, recollecting about events, and reflecting on events all increased with increasing age. However, recollection and reflection did not predict story asides, nor were there any mediating effects of these variables between age and story aside expression in autobiographical stories. These findings suggest the way people remember and reflect on their stories is perhaps not an underlying mechanism for age group differences in story aside expression. If not the subjective indicators of memory quality and experience (recollection, reflection), then other cognitive and goal-oriented variables might explain these changes.