Potential Mediators Research Articles

Skimmed milk intake reduces the risk of ER− breast cancer: a Mendelian randomization analysis

BackgroundIn prior observational investigations, it has been demonstrated that the consumption of milk is associated with the incidence of breast cancer (BC). Despite the existence of a two-sample Mendelian randomization (MR) that suggests a causal relationship between milk intake and breast cancer risk, the outcomes still lack a definitive conclusion. This ambiguity may be attributed to variables such as the variety of milk ingested, estrogen levels, the specific type of BC, and potential confounding factors. Therefore, our principal objective is to establish the causal association between the consumption of skimmed milk and full cream milk and the risk of different types of BC through the utilization of two-sample and two-step MR analyses.MethodsIn this study, we analyzed single nucleotide polymorphisms associated with skimmed and full-cream milk consumption in a cohort of 360,806 individuals from European populations through genome-wide association studies. We conducted a two-sample MR analysis using three different methods: inverse variance weighting (IVW) was used as the main analysis, and MR-Egger and Weighted median were used as supplementary analyses to IVW. We also performed sensitivity analysis, which included leave-one-out analysis, Cochran's Q test to detect heterogeneity, and MR-Egger intercept analysis to detect potential biases caused by pleiotropy. We used two-step MR analysis to evaluate potential mediators of associations.ResultsIn the two-sample MR analysis, IVW analysis suggests a potential inverse causal relationship between skimmed milk and BC [OR 0.34, 95% CI (0.12–1.00), P = 0.05]. Subgroup analysis revealed that skimmed milk reduces the risk of estrogen receptor-negative (ER−) breast cancer [OR 0.18, 95% CI (0.04–0.90), P = 0.04], but not estrogen receptor-positive (ER+) breast cancer [OR 0.42, 95% CI (0.15–1.22), P = 0.11]. MR Egger reached similar results, that is, skimmed milk reduces the risk of ER− breast cancer [OR 0.006, 95% CI (0.00–0.70), P = 0.04], but not BC [OR 0.16, 95% CI (0.01–4.66), P = 0.30] and ER+ breast cancer [OR 0.50, 95% CI (0.02–12.61), P = 0.65]. Additionally, we found no causal relationship between full cream milk and BC (P > 0.05). In two-step MR analysis, we found evidence for a mediating role of BMI in the relationship between skimmed milk intake and ER-breast cancer risk.ConclusionOur findings strengthen the evidence for a protective effect of skimmed milk consumption on ER-breast cancer risk. Further two-step MR analyses suggest that this protective effect may partly result from body mass index (BMI). There is no evidence that full cream milk consumption affects the risk of BC.

<i>Erratum</i> to: Soluble B-cell maturation antigen in lacrimal fluid as a potential biomarker and mediator of keratopathy in multiple myeloma

<i>Erratum</i> to: Soluble B-cell maturation antigen in lacrimal fluid as a potential biomarker and mediator of keratopathy in multiple myeloma

The Role of Multiple Mediation with Contextual Neighborhood Measures in Ovarian Cancer Survival..

BackgroundMediation by multiple agents can affect the relation between neighborhood deprivation and segregation indices and ovarian cancer survival. In this paper, we examine a variety of potential clinical mediators in the association between deprivation indices (DIs) and segregation indices (SIs) with all-cause survival among women with ovarian cancer in the African American Cancer Epidemiology Study (AACES). MethodsWe use novel Bayesian multiple mediation structural models to assess the joint role of mediators (stage at diagnosis, histology, diagnostic delay) combined with the DIs and SIs (Yost, ADI, Kolak’s URB, ICE-income) and a set of confounders with survival. The confounder set is selected in a preliminary step, and each DI or SI is included in separate model fits. ResultsWhen multiple mediators are included, the total impact of DIs and SIs on survival is much reduced. Unlike the single mediator examples previously reported, the Yost, ADI and ICE-income indices do not display significant direct effects. This suggests that when important clinical mediators are included, the impact of neighborhood SES indices is significantly attenuated. It is also clear that certain behavioral and demographic measures such as physical activity, smoking, or adjusted family income do not have a significant role in survival when mediated by clinical factors. ConclusionMultiple mediation via clinical and diagnostic-related measures reduces the contextual effects of neighborhood measures on ovarian cancer survival. The robust association of the Kolak URB index on survival may be due to its relevance to access to care, unlike SES-based indices whose impact was significantly reduced when important clinical mediators were included.

Loss of interferon regulatory factor-1 prevents lung fibrosis by upregulation of pon1 expression

BackgroundInterferon regulatory factor-1 (IRF1) is a transcription factor that plays a significant role in various biological processes, including inflammatory injury, viral infection, cell death, and immune responses, and it has been extensively studied in the context of different lung diseases. However, the mechanism underlying its involvement in lung fibrosis remains largely unknown.MethodsWild type (WT) mice, IRF1 global-null mice (Irf1−/−) were subjected to a bleomycin-induced lung fibrosis model to enable examination of the role of IRF1 in lung fibrosis. Proteomic analysis of lung tissue from WT and Irf1−/− mice treated with saline or bleomycin was performed to explore the mechanism of IRF1 in regulating lung fibrosis.ResultsIn the bleomycin-induced fibrosis mouse model, increased expression of IRF1 was observed. Irf1 knockout mice displayed decreased lung fibrosis relative to WT mice following treatment with bleomycin. The protein expression of fibronectin, as assessed by the Western blot analysis of lung tissues, was downregulated in Irf1−/− mice. We observed a similar reduction in collagen content using hydroxyproline detection. Histologically, there was less collagen deposition in the lungs of Irf1−/− mice compared with WT mice. Proteomics data revealed that IRF1 may be involved in lung fibrosis via the regulation of ferroptosis. We determined that paraoxonase 1(PON1), a poorly characterized protein in lung fibrosis, was upregulated in Irf1−/− mice following exposure to bleomycin. In vitro experiments revealed that IRF1 could regulate the level of GSH and MDA through PON1. We also determined that PON1 levels were lower in the plasma of IPF patients compared with healthy controls.ConclusionOur data highlight the importance of IRF1 in the fibrotic process, and PON1 may be a potential mediator of IRF1 in the progression of lung fibrosis.

Sex-dependent interplay of phosphate and inflammation on muscle strength irrespective of muscle mass in middle-aged and older adults

BackgroundElevated circulatory phosphate levels are linked to age-related muscle dysfunction, yet the mechanisms remain unclear. This study investigated the hypothesis that inflammation plays a role in connecting elevated phosphate levels to muscular dysfunction in middle-aged and older individuals and explored potential sex-based differences in these associations. MethodsThe study, based on the I-Lan Longitudinal Aging Study Cohort, analyzed individuals' serum phosphate and hsCRP levels. Sex-specific analyses explored links between circulatory phosphate, inflammation, and muscle profiles (mass, handgrip strength, and walking speed). The study also examined potential mediation or synergistic effects of inflammation in the circulatory phosphate-muscle relationship. ResultsThe study included 2006 participants (mean age: 65.5 ± 6.5 years; 49.8 % men). Women exhibited higher circulatory phosphate levels than men. Linear analyses revealed that higher phosphate levels were significantly associated with weaker handgrip strength but not with reduced muscle mass in both men and women. In women, circulatory phosphate was not associated with inflammation (hsCRP levels), while in men, higher phosphate levels were significantly associated with higher hsCRP levels. In men, a synergistic effect was observed, where the combination of high hsCRP and elevated phosphate levels had a more pronounced impact on reducing handgrip strength than either factor alone. ConclusionsThis study highlights a sex-specific association of inflammation in the mechanisms of hyperphosphatemia-related muscle weakness. The findings emphasize the importance of managing both hyperphosphatemia and chronic inflammation to mitigate their collective impact on muscle function, particularly in older men. Addressing these factors is crucial for promoting muscle health in later life.

Changes in economic deprivation and parental self-efficacy: Unemployment, poverty, and the mediating effect of psychological distress

Objective: The article investigates the influence of three aspects of economic deprivation on parental self-efficacy, and whether, or to what extent, these effects are mediated by psychological distress. Background: Scholarship shows that psychological resources such as parental self-efficacy can attenuate the negative repercussions of poverty for families. The article builds on the family stress model that higlights the role of economic deprivation for family functioning by Conger and colleagues. It focuses on the consequences of transitioning into unemployment, objective poverty, and subjective poverty for parental self-efficacy, and the potential mediating effect of psychological distress. Method: Using data from the German Family Panel (pairfam) Waves 4 to 12 (2011–2020), Baron and Kenny mediation analyses are conducted based on fixed effects regressions with standard errors based on clustered bootstrap procedure. Results: The results show that transitioning into subjective poverty significantly decreases parental self-efficacy, and that only a marginal part of this effect is mediated by psychological distress. A transition into objective poverty, by contrast, has no effect on parental self-efficacy. Likewise, unemployment has no direct effect on parental self-efficacy. However, transitioning into short-term unemployment reduces psychological distress and thereby buffers parent’s self-efficacy. This does by contrast not apply for long-term unemployment. Conclusion: The findings demonstrate the importance of differentiating between specific aspects of economic deprivation when investigating its consequences for parental self-efficacy and considering psychological distress as a potential mediator. Moreover, the findings provide longitudinal evidence for the consequences of a transition into economic deprivation for parental self-efficacy and point to the presence of gender effects with regard to unemployment.

DNA methylation and non-coding RNAs in metabolic disorders: Epigenetic Roles of Nutrients, Dietary Patterns and Weight Loss Interventions for Precision Nutrition.

Dysregulation of epigenetic processes and abnormal epigenetic profiles are associated with various metabolic disorders. Nutrition, as an environmental factor, can induce epigenetic changes through both direct exposure and transgenerational inheritance, continuously altering gene expression and shaping the phenotype. Nutrients consumed through food or supplementation, such as vitamin B12, folate, vitamin B6, and choline, play a pivotal role in DNA methylation, a critical process for gene regulation. Additionally, there is mounting evidence that the expression of non-coding RNAs (ncRNAs) can be modulated by the intake of specific nutrients and natural compounds, thereby influencing processes involved in the onset and progression of metabolic diseases. Evidence suggests that dietary patterns, weight-loss interventions, nutrients and nutritional bioactive compounds can modulate the expression of various miRNAs and DNA methylation levels, contributing to development of metabolic disorders such as obesity and type 2 diabetes. Furthermore, several studies have proposed that DNA methylation and microRNA (miRNA) expression could serve as biomarkers for the effects of weight-loss programs. Despite ongoing debate regarding the effects of nutrient supplementation on DNA methylation levels and the expression of ncRNAs, certain DNA methylation marks and ncRNA expressions might predict the risk of metabolic disorders and act as biomarkers for forecasting the success of therapies within the framework of precision medicine and nutrition. The role of DNA methylation and miRNA expression as potential mediators of the effects of weight loss underscores their potential as biomarkers for the outcomes of weight loss programs. This highlights the influence of dietary patterns and weight-loss interventions on the regulation of miRNA expression and DNA methylation levels, suggesting an interaction between these epigenetic factors and the body's response to weight loss.

The Association Between Adult Attachment Patterns, Attachment to Group and Mental Health in Israel Following the October 7th Attack: The Role of Emotion Regulation Strategies

We examined the associations between attachment anxiety, attachment avoidance, and attachment to group (to Israel) and mental health scores. The study used a community sample of 434 participants in response to the October 7th attack on Israel. Additionally, we explored the potential mechanisms linking these attachment patterns to mental health scores. We focused on emotion regulation strategies, such as task-focused, emotion-focused, and distance-focused strategies, as potential mediators. The results indicated that the negative direct association between attachment anxiety and mental health is fully mediated by a high emotion-focused strategy and a low task-focused strategy. Attachment avoidance did not have a significant direct association with mental health scores. However, it had significant negative indirect associations through a high emotion-focused strategy and a low task-focused strategy. Attachment to the group (to Israel) showed both direct and indirect positive associations with mental health through a low emotion-focused strategy and a high task-focused strategy. The discussion highlights the role of internal representations of insecure attachment, group attachment, and emotion regulation strategies (especially emotion- and task-focused strategies) in how highly stressful external situations affect mental health.

The Multiple Challenges of Nutritional Microbiome Research During COVID-19—A Perspective and Results of a Single-Case Study

The global coronavirus disease 2019 (COVID-19) pandemic has affected multiple aspects of people’s lives, which may also influence the results of studies conducted during this period across diverse research domains. This particularly includes the field of nutritional science, investigating the gut microbiota as a potential mediator in the association between dietary intake and health-related outcomes. This article identifies the challenges currently facing this area of research, points out potential solutions, and highlights the necessity to consider a range of issues when interpreting trials conducted during this period. Some of these issues have arisen specifically because of the measures implemented to interrupt the spread of small acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while others remain relevant beyond the pandemic.

The Impact of SGLT1 Inhibition on Frailty and Sarcopenia: A Mediation Mendelian Randomization Study.

Although pharmacological effects of SGLT2 inhibitors on the development of frailty and sarcopenia were known, the role of SGLT1 remained less clear. The present study investigated the possible effect of SGLT1 inhibition on these conditions and explored potential mediators. A two-sample Mendelian randomization (MR) analysis was performed to assess the effect of SGLT1 inhibition on frailty index (FI) and low grip strength in individuals aged 60 years and older using both the FNIH and EWGSOP criteria. Subsequently, a two-step MR analysis was conducted to investigate the mediating role of insulin resistance phenotype and identify potential mediators of the effect of SGLT1 inhibition on the FI and low grip strength from 1558 plasma proteins and 1352 metabolites. Genetically predicted SGLT1 inhibition was associated with decreased FI (β: -0.290 [95% CI: -0.399, -0.181]) and reduced risk of low grip strength in individuals aged 60 years and older under both FNIH (β: -0.796 [95% CI: -1.216, -0.376]) and EWGSOP criteria (β: -0.287 [95% CI: -0.532, -0.041]). The two-step MR analysis demonstrated the role of insulin resistance phenotype in mediating SGTL1 inhibition on alleviating frailty (mediation proportion = 19.56% [95% CI: 8.42%, 30.70%]). After screening, 24 proteins and 16 metabolites were identified as mediators of the impact of SGLT1 inhibition on FI. Additionally, 13 proteins and 16 metabolites were found to mediate the effect of SGLT1 inhibition on low grip strength according to FNIH criteria while 22 proteins and 6 metabolites were shown to mediate the impact of SGLT1 inhibition on low grip strength under EWGSOP criteria. SGLT1 inhibition potentially mitigated frailty and sarcopenia through several biological mediators, shedding new light for therapeutic intervention.

Mediators of the association between physical activity and executive functions in primary school children

ABSTRACT There is growing interest in identifying the mechanisms underpinning the effects of physical activity on executive functions (e.g. inhibitory control, cognitive flexibility) in children. Our study examined cardiorespiratory fitness, muscular fitness, and motor competence as potential mediators of this relationship. The study used baseline data from the Learning to Lead (L2L) cluster randomised controlled trial. In total, 675 children (7–11 years, 49.5% girls) completed measures of moderate-to-vigorous physical activity (MVPA), cardiorespiratory fitness, muscular fitness, motor competence, and executive functions. Structural equation modelling was used to examine the potential mediating roles of cardiorespiratory fitness, muscular fitness, and motor competence in the cross-sectional association between MVPA and executive functions. Cardiorespiratory fitness (β = 0.06, SE = 0.021, p = 0.004) partially mediated the association between MVPA and cognitive flexibility. Muscular fitness was a significant mediator of the association between MVPA and both inhibitory control (β = 0.03, SE = 0.014, p = 0.027) and cognitive flexibility (β = 0.06, SE = 0.021, p = 0.005). No significant mediated effects were found for motor competence. Our findings suggest cardiorespiratory and muscular fitness (but not motor competence) mediate the association between physical activity and executive functions in children.

Causal Mediation Analysis for Integrating Exposure, Genomic, and Phenotype Data

Causal mediation analysis provides an attractive framework for integrating diverse types of exposure, genomic, and phenotype data. Recently, this field has seen a surge of interest, largely driven by the increasing need for causal mediation analyses in health and social sciences. This article aims to provide a review of recent developments in mediation analysis, encompassing mediation analysis of a single mediator and a large number of mediators, as well as mediation analysis with multiple exposures and mediators. Our review focuses on the recent advancements in statistical inference for causal mediation analysis, especially in the context of high-dimensional mediation analysis. We delve into the complexities of testing mediation effects, especially addressing the challenge of testing a large number of composite null hypotheses. Through extensive simulation studies, we compare the existing methods across a range of scenarios. We also include an analysis of data from the Normative Aging Study, which examines DNA methylation CpG sites as potential mediators of the effect of smoking status on lung function. We discuss the pros and cons of these methods and future research directions.

Hikikomori in the Middle East: The role of problematic gaming, social media use, and loneliness

Hikikomori, a form of severe social withdrawal has been found to be associated with behavioral addictions such as gaming addiction and problematic social media use (PSMU). Since literature related to hikikomori is lacking in the Middle East, this study aimed to determine whether there are significant differences in hikikomori-like traits between two different types of social media users and gamers and investigate loneliness as a potential mediator between hikikomori and the two types of problematic behaviors. A cross-sectional, correlational design was employed, collecting a final sample of 220 participants residing in Middle Eastern countries using a mixture of convenience and snowball sampling. Results showed that passive social media users demonstrated significantly greater hikikomori-like traits compared to active users. Furthermore, hikikomori-like traits exhibited significant positive associations with problematic gaming, PSMU, and loneliness. Two separate mediation analyses, the first with PSMU and a second with problematic gaming as predictors, revealed that loneliness acted as a significant mediator between both these problematic behaviors and hikikomori-like traits.

Lymphopenia Predicts Poor Outcomes in Newly Diagnosed Multiple Myeloma

Bone marrow microenvironment plays an important role in promoting growth and survival of multiple myeloma (MM) cells. The tumor-promoting immune microenvironment is augmented while anti-tumor immune responses are inhibited. Although clinical and genomic markers of high-risk MM have been described, the immune status is just being recognized as a potential mediator of disease behavior. This is even more important with the development of a number of immune-based therapies. Based on these considerations, we evaluated peripheral blood absolute lymphocyte count (ALC) as an easily accessible marker representing immune microenvironment at diagnosis and following treatment of MM. We retrospectively evaluated 11,427 patients diagnosed with MM between 2000 and 2019 at Veteran's Administration hospitals using ALC obtained closest to diagnosis and up to 2.5 years thereafter. Patients were stratified into 3 ALC categories: severely low, low, and normal (<1, 1-1.5, and >1.5 x 103/mm3, respectively). Lymphopenia (including severely low and low ALC) was present in 53% of patients at MM diagnosis and was associated with inferior overall survival (OS). Median OS of patients with severely low, low, and normal ALC at diagnosis was 2.7, 3.3, and 4.2 years (P < .001), respectively. Moreover, persistent or new development of lymphopenia during treatment and follow-up was also associated with inferior OS. Our findings support the use of ALC as a biomarker for risk stratification in MM.

Exploratory mediation analysis of the effect of semaglutide on cardiovascular outcomes in people with overweight or obesity in the SELECT randomised trial

Abstract Background Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to reduce major adverse cardiovascular (CV) events (MACE) in people with diabetes. The SELECT trial investigated weekly subcutaneous semaglutide 2.4 mg versus placebo in people with pre-existing CV disease and body mass index ≥27kg/m², but without diabetes at randomisation. Over a mean duration of follow-up of 39.8 months, risk of MACE was lower in patients treated with semaglutide vs placebo (6.5% vs 8.0%, hazard ratio, 0.80; 95% CI, 0.72, 0.90; P<0.001). There were improvements in several CV risk factors; however, mechanisms underlying the MACE reduction are unclear. Purpose This prespecified analysis explored whether the effects on measured CV risk factors may mediate the 20% reduction in MACE in SELECT. Methods CV risk factors measured during the trial and included as potential mediators in the analysis were: body weight, waist circumference, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA1c), lipids, blood pressure, estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Mediation analyses were performed using the Vansteelandt repeated regression approach. First, the observed difference in MACE-free survival between semaglutide and placebo at 36 months was estimated as the total effect. The direct effect of semaglutide was then estimated as the difference in MACE-free survival, had the semaglutide arm experienced the values of the mediator observed in the placebo arm during follow-up. The % mediation was then calculated as 100 × (1 – [direct effect] / [total effect]). A reversed counterfactual approach estimating the direct effect as the difference between arms in MACE-free survival, had the placebo arm experienced the mediator values observed in the semaglutide arm, was also conducted. A large disparity between the % mediation from the two approaches can indicate potential treatment–mediator interaction or hidden confounding. Results Statistically significant (P<0.05) improvements in all potential mediators were observed with semaglutide. Table 1 shows the estimated mediation of each potential mediator when evaluated separately. Point estimates for the % mediation were largest for waist circumference (64.0%), hsCRP (42.1%), HbA1c (29.0%) and body weight (19.5%), but with wide 95% CIs. For waist circumference, the estimated mediation was markedly lower using the reversed counterfactual approach, suggesting potential hidden confounding or treatment–mediator interaction (Figure 1). In a multivariable analysis, the estimated joint mediation was 31.4% (−30.1%, 143.6%). Conclusions The results suggest that neither change in body weight nor other measured CV risk factors fully explain the effect of semaglutide on MACE in SELECT. Substantial unmeasured pleiotropic effects of semaglutide on MACE not mediated through these risk factors remain possible.

Race/Ethnicity, Education, and All-Cause Mortality in US Adults: Mediation by Telomere Length

Abstract Background Racial/ethnic inequities in mortality risk are pervasive in the United States even after controlling for socioeconomic status indicators such as educational attainment. Although the mechanisms underlying these inequities remain unclear, telomere length (TL) has emerged as a potential mediator. We aimed to investigate the joint association of race/ethnicity and education with all-cause mortality risk, and the contribution of TL to this relationship. Methods We used data from the U.S. National Health and Nutrition Examination Survey, 1999 to 2002, and 2019 Linked Mortality File (n = 6,526 non-institutionalized adults aged 25 years or older, including 2,166 deaths), a retrospective cohort study with a follow-up period to December 31, 2019. Cox proportional hazards regression and causal mediation analysis were used to address these aims. We reported hazard ratios (HR) and 95 % confidence intervals (CI). Furthermore, for the mediation analysis, we reported the total, direct, and indirect effects measured as HR and 95 % CI. Results After adjusting for age and sex, among White individuals, those with less than a high school education had a 2.26 times higher (95% CI: 1.93, 2.65) rate of all-cause mortality compared to those with some college or higher education. When compared with White adults with at least a college degree, Black adults with at least a college degree had a 1.38 higher rate of dying (95% CI: 1.04, 1.84). There was no significant joint association of race/ethnicity and education on all-cause mortality in Mexican Americans. In the mediation analysis, TL did not significantly contribute to the joint association of race/ethnicity and education with all-cause mortality risk. Discussion These findings underscore the need for a better understanding of the joint relationship of race/ethnicity and education on mortality risk inequities and their potential mechanisms to improve population health ultimately. Key messages • Lower educational attainment was associated with higher mortality rates among White individuals, disparities persisted among the Black population, despite higher education levels. • Our analysis did not find a significant mediation effect of telomere length on the joint effect of race/ethnicity and education-mortality relationship.

Nocturnal Artificial Light Exposure in Expectant Mothers and Risk of Congenital Glaucoma

Abstract Background While the impact of light pollution on human health is gaining recognition, its role in transmitting the effects of maternal exposure to the fetus remains unclear. This study is to investigate the association between exposure to artificial light at night (ALAN) during pregnancy and risk of congenital glaucoma. Methods All birth cohorts spanning from 2008 to 2011 in urban areas of South Korea, comprising over 90% of the total population, were identified in the Korean National Health Insurance database. Average levels of ALAN at the residential addresses of mothers during pregnancy were estimated using time-varying satellite data for a composite view of persistent night-time illumination at ∼1 km2 scale.The odd ratios (ORs) and 95% confidence intervals (CIs) of the association between residential ALAN and risk of congenital glaucoma - was computed using logistic regression. These calculations were adjusted for socio-demographic factors and area-level risk factors (night-time traffic noise and particulate matter with an aerodynamic diameter ≤ 10 μm). Results A total of 745,458 mother-father-child trios (mean [SD] age of the mothers, 32.4 [3.8] years; 387,275 [52.0%] boy) were included in the study. In fully adjusted models, an IQR (21.8 nW/cm2/sr) increase in ALAN level was associated with an OR of 1.12 (95% CI: 1.05, 1.19) for incident congenital glaucoma. The exposure-response curve demonstrated an upward slope with a threshold at approximately 62 nW/cm2/sr. Conclusions In this nationwide population-based case-control study, higher levels of residential ALAN during pregnancy were associated with increased risk of congenital glaucoma. Future studies with more detailed information on exposure, individual adaptive behaviors and potential mediators are warranted. Key messages • This study indicates an association between elevated levels of ALAN exposure in pregnant women and a heightened risk of congenital glaucoma in their offspring. • These results are consistent with a growing body of evidence underscoring the detrimental effects of ALAN on health, reinforcing its potential role as a risk factor for congenital glaucoma.

Assessing cyberchondria and eHealth literacy differences in urban and rural China

Abstract Background and Objectives This study aimed to explore the association between cyberchondria and eHealth literacy in the general Chinese population, and to assess how this relationship changes between urban and rural residents. Methods Data obtained from a web-based, cross-sectional survey that evaluate cyberchondria and its impact on health in February 2024. The Cyberchondria Severity Scale - 12 item was used to measure the cyberchondria, while the eHealth Literacy Scale was used to evaluate eHealth literacy. Descriptive analysis was used to describe the background characteristics of the participants. Then, a multivariable linear regression model was then performed for urban and rural subsample to examine the relationship between cyberchondria and eHealth literacy, respectively, providing a comparative analysis between the urban and rural populations. Results A total of 634 individuals completed the questionnaire. The average age was 33.2 years (SD = 7.4), with approximately 50.3% (n = 319) being female. Urban residents made up 71.4% (n = 451) of the participants. The mean eHEALS scores for urban and rural residents were 31.9 (SD = 4.3) and 30.4 (SD = 4.2), respectively. The CSS-12 scores for urban residents were 40.3 (SD = 7.58) and for rural residents were 39.1 (SD = 7.2). Linear regression analyses showed a significant association between eHealth literacy and cyberchondria for urban residents (Beta = 0.30, p < 0.001), but age and education level had no significant impact. For rural residents, a statistically significant association between eHealth literacy and cyberchondria was also observed (Beta = 0.40, p = 0.002). Conclusions Overall, eHealth literacy consistently predicts cyberchondria severity in both urban and rural samples. Higher eHealth literacy is linked to greater cyberchondria, especially in rural areas. Future research should explore other potential mediators, including psychological factors, internet usage patterns, and access to healthcare services. Key messages • eHealth literacy strongly predicts cyberchondria severity in both urban and rural populations, with a notably stronger impact observed in rural settings. • Urban and rural differences highlight the need for customized digital health literacy programs to effectively address region-specific challenges and behaviors.

Sex differences in association between dietary sodium intake and white matter hyperintensity volume

Abstract Background There is limited evidence on the relationship between dietary sodium intake (dNa) and brain health, and very little on sex differences in associations. Purpose To study the relationship between dNa and imaging measures of brain health in men and women from the INSIGHT 46 substudy of the MRC National Survey of Health and Development (British 1946 birth cohort). Methods Participants had measurements (dNa using 5-day food diary, anthropometrics, blood pressure (BP) body mass index (BMI)) at 60-64years. Whole-brain and hippocampal volumes, white matter hyperintensity volume (WMHV) and florbetapir amyloid-β positivity were measured using MRI-PET imaging at 69-71years. Associations (β (95% confidence intervals)) were estimated separately in men and women using generalized linear models with robust standard errors adjusted for potential confounders (age, diet quality, energy intake, socioeconomic status) or potential mediators (BMI, BP). Results Participants’ characteristics are shown in Table 1. In women but not men dNa was positively associated with higher WMHV (β[women]=32(1, 72) %/g; p=0.043; β[men]=-10(-27, 11)%/g; p=0.342); this relationship in women was independent of BMI (β = 32(1, 72)%/g; p = 0.043) or systolic BP (β = 31(1, 70)%/g; p=0.041). dNa was not associated with total brain volume, hippocampal volume or amyloid-β positivity in either sex. Conclusions Elevated sodium consumption in the diet is associated with cerebral small vessel disease in older age women but not men. This association was independent of BMI or BP.Table 1

Innovative Approaches for Personalized Cardiovascular Prevention: the INNOPREV multicentric trial

Abstract Background Cardiovascular diseases (CVD) represent a major global health concern, requiring innovative primary prevention strategies. Personalized prevention, through the use of digital technologies and genetic risk scores (PRS), holds promise but requires further investigation to assess clinical efficacy. Consequently, the INNOPREV trial aims to investigate the efficacy of PRS and/or digital technologies in the uptake of CV preventive behaviors uptakes. Methods The INNOPREV trial is a multicenter randomized controlled trial conducted in Italy across three hospital centers in Rome, Catania, and Palermo. It aims to recruit 1020 participants aged 40-69 with a high 10-year CVD risk. Participants are allocated to traditional CVD risk assessment, or genetic testing, or digital interventions, or a combination of both. The study involves comprehensive CV risk assessments at baseline and follow-up visits at one, five, and twelve months. Data analysis will utilize mixed-effects models to analyze longitudinally collected data and explore potential moderators and mediators of behavior change. Results Preliminary results indicate good progress in recruitment, which currently stands at 250 participants (25% of expected). Recruited females have a mean age of 59 ± 6 years, while males have a mean age of 58 ± 6 years. Currently, PRS analyses indicate that 77% of participants have intermediate scores, and 23% have low scores. Follow-up will be essential to evaluate the efficacy of the proposed interventions. Conclusions We expect that the INNOPREV trial will provide evidence towards integration of innovative approaches based on PRS and digital devices, in the traditional preventive approaches for CVDs. Expectations are high based on the limited effectiveness of the current approaches in CV risk reduction based on lifestyle advice. Key messages • INNOPREV trial examines PRS and digital technology for CVD prevention, aiming to enhance preventive efficacy. Initial findings suggest promising potential for innovative CVD prevention strategies. • The INNOPREV trial aims to investigate the efficacy of personalized prevention strategies, including PRS and digital technologies, in improving cardiovascular preventive behaviors.