Visual snow syndrome (VSS) is a chronic neurological disorder associated with impaired mental health. While self-efficacy and quality of life (QOL) are known to influence mental health outcomes (depression and suicidal ideation) in clinical populations, their roles in VSS remain unexplored. This study aimed to examine the associations among VSS, self-efficacy, QOL, mental health outcomes and the potential serial mediation roles of self-efficacy and QOL. A cross-sectional study compared 64 VSS patients and 67 healthy controls matched with age, sex and education level. Participants completed validated questionnaires assessing self-efficacy (GSES), QOL (WHOQOL-BREF), depression (CES-D), and suicidal ideation (BSSI, first five items). Analyses included group comparisons, correlation analyses to examine variable relationships, multimodel linear regression and serial mediation modeling to test the hypothesized sequential pathway from VSS through self-efficacy and quality of life to mental health outcomes. Compared with controls, VSS patients demonstrated significantly lower self-efficacy (VSS: 23.6 ± 6.2; Controls: 30.6 ± 6.0; p < 0.001) and QOL (VSS: 62.5 ± 9.5; Controls: 73.6 ± 8.8; p < 0.001), alongside elevated depression (median [IQR]: VSS: 28 [21,34]; Controls: 11 [7, 15]; p < 0.001) and suicidal ideation (VSS: 6 [5, 7]; Controls: 5 [5,6]; p < 0.01). Serial mediation analysis revealed that the effects of VSS on depression and suicidal ideation were mediated through self-efficacy and QOL sequentially. The total indirect effect for depression was 7.73 (95% CI [5.64-9.85]), with QOL accounting for 49.09% of the total effect. For suicidal ideation, the total indirect effect was 0.80 (95% CI [0.39-1.22]). Lower self-efficacy and QOL appear to serially mediate the associations between VSS and mental health impairments. These preliminary, cross-sectional findings indicate that self-efficacy and QOL may serve as modifiable intervention targets that mediate or moderate the risk of depression and suicidal ideation in individuals with VSS. Clinicians should prioritize routine assessments of these factors to guide early intervention strategies, although longitudinal studies are needed to confirm these causal pathways.

The rate of cognitive decline in Alzheimer's disease (AD) varies considerably from person to person. Numerous epidemiological studies point to the protective effects of cognitive, social, and physical enrichment as potential mediators of cognitive decline in AD; however, there is much debate as to the mechanism underlying these protective effects. The retrosplenial cortex (RSC) is one of the earliest brain regions with impaired functions during AD pathogenesis, and its activity is affected by cognitive, social, and physical stimulation, making it a particularly interesting region to investigate the influences of an enriched lifestyle on AD pathogenesis. In the current study, we use the 5xFAD mouse mode of AD to examine the impact of enriched housing conditions on cognitive function in AD and the viability of a particularly vulnerable cell population within the RSC - parvalbumin interneurons (PV-INs). Enriched housing conditions improved cognitive performance in female 5xFAD mice. These changes in cognitive performance coincided with restored functional connectivity of the RSC and preserved PV-IN density within this region. Along with preserved PV-IN density, there was an increase in the density of Wisteria floribunda agglutinin-positive perineuronal nets (WFA+PNNs) across the RSC of 5xFAD mice housed in enriched conditions. Direct manipulation of WFA+PNNs revealed that these extracellular matrix structures protect PV-INs from amyloid toxicity and may be the mechanisms underlying the protective effects of enrichment. Together, these results provide support for the WFA+PNN-mediated maintenance of PV-INs in the RSC as a potential mechanism mediating the protective effects of enrichment against cognitive decline in AD.Significance statement The rate of progression of Alzheimer's Disease is highly variable. The extent to which individuals engage in an enriched lifestyle is one factor that has been proposed to promote cognitive resiliency to AD pathology. Understanding how enrichment promotes resiliency is critical for promoting healthy cognitive aging. Recent work has demonstrated that the retrosplenial cortex, and especially parvalbumin interneurons in this region are highly vulnerable to AD pathology and their impairments relate to early cognitive impairments. Here, we show that environmental enrichment promotes cognitive performance and the survival of parvalbumin interneurons in the retrosplenial cortex through a mechanism dependent on perineuronal net maintenance. These results help to explain the mechanisms that mediate the influence of environmental enrichment on cognitive resiliency.

Being moved, also known as kama muta, is an emotion associated with warmth and social connectedness. Although theoretical accounts posit that it may contribute to the development and maintenance of romantic relationships by fostering intimacy, affirming commitment, and reinforcing shared values, empirical research remains limited. To address this gap, we conducted three studies. Study I explored the situational effects of recalling touching events on relationship satisfaction. Building on this, Study II examined whether proneness to being moved is associated with relationship satisfaction, and additionally tested intimacy and closeness as potential mediators, and attachment styles as potential moderators of this link. Study III refined this approach by employing a relationship-specific measure of being moved to assess whether the observed effects generalize when measured within the romantic domain. Study I demonstrated that recalling touching events enhanced satisfaction, particularly among less satisfied individuals. Study II revealed that dispositional being moved was positively associated with satisfaction via intimacy and closeness, and that avoidant attachment attenuated these effects. Study III confirmed these results using the refined measure. Across three studies, being moved emerged as a relational emotion that promotes intimacy and closeness, thereby contributing to relationship satisfaction. By linking situational experiences, dispositional tendencies, and relationship-specific measurement, this research provided preliminary indications of the potential role of kama muta in sustaining romantic bonds.

There are few effective treatments for acute whiplash-associated disorder (WAD) following a road traffic crash. Early clinical features of central sensitisation, for example widespread hyperalgesia, predict poor recovery. Pregabalin's effects on central sensitisation suggest the potential to prevent or modulate these processes after whiplash injury and prevent later chronic pain. Preliminary evidence indicates that pregabalin provided in the Emergency Department and within 96hours of injury shows promise to prevent chronic pain. This trial aims to definitively evaluate, in patients at risk for poor recovery following whiplash injury, the effectiveness of early (within 96hours of injury) pregabalin, compared to placebo, to reduce pain severity. The PReventing chronic pain after whiplash Road Traffic Injury (PRioRTI) study is a 12-month randomised, placebo-controlled, triple-blind trial. Individuals with acute WAD (aged 18-70years) and at risk of poor recovery (pain ≥ 5/10) will be recruited from hospital Emergency Departments in Australia. Participants will be randomly assigned 1:1 to receive pregabalin or placebo. All participants will additionally receive an evidence-based advice booklet. Pregabalin will be commenced at 75mg bd and titrated to 300mg bd over 4weeks, then weaned for 2weeks. Participants will complete online questionnaires at 6weeks and 3, 6 and 12months post-randomisation. The primary outcome will be average pain intensity over 24hours (0-10 numerical rating scale) at 3months post-randomisation. Secondary outcomes include disability, patient global impression of recovery, psychological distress, quality of life and the number of adverse events. A cost-effectiveness analysis will be conducted. Potential mediators of treatment effects will be explored. A process evaluation will be conducted to explore barriers and facilitators for future implementation. There are few effective treatments for acute WAD. To address this gap, the PRioRTI trial aims to improve health outcomes by targeting central nociceptive processes very soon after whiplash injury using a readily available medication, pregabalin. If successful, the results of this trial will address an urgent unmet need to reduce pain severity after injury and will have clear implications for the early treatment of patients with whiplash injury. TRIAL REGISTRATION {2A AND 2B}: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12624001359527. Registered 13th November 2024.

A negative relationship between mindful eating and eating disorder risk has been suggested in previous research. However, the potential mediating roles of depression and body mass index (BMI) in the relationship between the four facets of mindful eating and eating disorders remain understudied. Therefore, this study aimed to examine the associations between the four facets of mindful eating and the risk of eating disorders in adults, and to explore possible mediators of this relationship. This cross-sectional study was conducted online with 239 participants. Data were collected using the Four Facet Mindful Eating Scale (FFaMES), the Eating Disorder Examination-Questionnaire-13 (EDE-Q-13), and the Depression-Anxiety-Stress Scale-21 (DASS-21). To identify potential mediating factors, multiple mediation analyses were performed to examine the relationship between mindful eating and eating disorder risk. Higher levels of mindful eating were inversely correlated with eating disorder risk (r = -0.569, p < 0.001), depression (r = -0.321, p < 0.001), and BMI (r = -0.314, p < 0.001). Conversely, eating disorder risk was positively correlated with both depression (r = 0.268, p < 0.001) and BMI (r = 0.341, p < 0.001). Mediation analyses revealed that depression (β = -0.012, 95% CI [-0.025, -0.002]) and BMI (β = -0.018, 95% CI [-0.033, -0.007]) were potential mediators of the association between non-reactance and eating disorder risk. A similar pattern was observed for non-judgment, with depression (β = -0.016, 95% CI [-0.032, -0.004]) and BMI (β = -0.021, 95% CI [-0.041, -0.007]) identified as potential mediators. Eating with internal awareness was associated with higher eating disorder risk, with depression partially mediating this relationship (β = 0.030, 95% CI [0.008, 0.060]), whereas no mediation effect was found for eating with external awareness (β = 0.021, 95% CI [-0.016, 0.051]). Overall, higher depression (β = -0.012, 95% CI [-0.025, -0.002]) and higher BMI (β = -0.018, 95% CI [-0.064, -0.032]) were identified as potential mediators in the association between lower mindful eating and higher eating disorder risk. This study indicated that mindful eating in adults is associated with lower eating disorder risk, and that BMI and depression scores are potential mediators of this relationship.

Genome-wide cross-trait analyses reveal shared genetic architecture and causal links between attention-deficit/hyperactivity disorder and cardiovascular diseases.

Thrombospondin-1 (THBS1) is dysregulated in preeclampsia.

Intersectional stigma, health behaviors, and allostatic load among sexual and gender diverse people.

Blood glucose and systemic inflammation mediate the association between lifestyle factors and serum Klotho levels in US adults.

Offspring innate immunity varies with parental age in a long-lived seabird.

ABSTRACT Local food consumption offers numerous health, economic, and community benefits, yet consumers’ motivations to purchase local foods vary widely. While prior research has emphasized egotistic (self-benefit) and altruistic (other-benefit) values, far less attention has been directed toward biospheric values, the concern for environmental well-being, as a driver of local food purchase intentions. This study tests whether exposure to a biospheric advertising appeal influences intentions to buy local foods. The study manipulated message framing (biospheric appeal vs. control) and measured four potential mediators: internal values, external values, fun/excitement values, and biospheric values. Although the serial mediation analysis did not reveal a significant indirect effect, internal values positively shaped external, biospheric, and fun/excitement values; external. Biospheric values further influenced fun/excitement values; and biospheric values uniquely increased purchase intention. Consumers who score higher on biospheric values demonstrate stronger intentions to purchase local foods. These findings contribute to the literature by isolating the influence of biospheric values and offer practical implications for marketers seeking to promote local food through environmentally-focused appeals.

Maternal consumption of a high-fructose (HF) diet or exposure to microplastics (MPs) can each independently affect kidney development and increase the risk of hypertension in adult offspring, yet their combined impact remains poorly understood. Dysregulation of hydrogen sulfide (H2S) signaling and alterations in gut microbiota are potential mediators of this programming. Pregnant rats received either standard chow or a 60% HF diet, with half of each group additionally exposed to sulfate-modified MPs (1 mg/L) with a 5 μm diameter throughout pregnancy and lactation. Male offspring were divided into four groups (n = 7–8 per group): control, HF, MP, and HF+MP. Maternal HF or MP exposure raised offspring blood pressure (BP), with additive effects when combined, and MP exposure caused renal injury. MP treatment also suppressed renal H2S-generating enzymes and reduced H2S production. Both HF and MP exposures altered gut microbial composition linked to BP regulation and induced metabolic changes in taurine/hypotaurine and sulfur pathways, suggesting impaired H2S production. These results indicate that maternal HF and MP exposures interfere with H2S signaling, gut microbiota, and metabolic programming, highlighting the H2S signaling as a potential target to reduce long-term kidney and cardiometabolic risks.

Halitosis, commonly known as bad breath, is a highly prevalent condition often associated with volatile sulfur compounds (VSCs) produced by oral anaerobic bacteria. While intraoral halitosis is the most frequent type, its psychosocial impact remains underexplored in terms of its correlation with objective diagnostic markers. This study investigated the association between VSC concentrations and halitosis-related quality of life using the Halitosis Associated Life-Quality Test (HALT). In this cross-sectional study, 40 adults self-reporting halitosis were assessed using OralChroma™, a portable gas chromatograph that quantifies hydrogen sulfide, methyl mercaptan, and dimethyl sulfide. Breath samples were collected at baseline and after an L-cysteine oral rinse challenge. Participants completed the HALT questionnaire to assess emotional, social, and functional impacts. Statistical analyses included descriptive metrics, Pearson's correlation, and multiple linear regression. Model assumptions were tested for validity. At baseline, 25% of participants had VSC levels above diagnostic thresholds; after L-cysteine administration, this proportion increased to 87.5%, indicating the presence of latent halitosis. Methyl mercaptan concentration before the challenge showed a significant correlation with HALT scores (r = 0.353; p = 0.025) and was the only significant predictor in the final regression model (β = 1.03; p = 0.025; R² = 0.125). Elevated HALT scores were also observed in participants without clinically confirmed halitosis, suggesting that self-perception and emotional distress play a central role in patient experience. These findings highlight the relevance of combining objective VSC measurements with validated, condition-specific quality-of-life instruments to better understand and manage halitosis. Methyl mercaptan may serve as a biochemical marker of halitosis severity and also as a potential mediator of its psychosocial consequences.

The triglyceride-glucose (TyG) index has been recognized as a surrogate marker for insulin resistance (IR) and an independent risk factor for cardiovascular disease (CVD). However, the combined effect of the TyG index and visceral obesity on CVD incidence remains unclear. We aimed to investigate the interaction, joint association, and potential mediators between the TyG index and comprehensive anthropometric indices with CVD risk in middle-aged and older adults. We analyzed 7046 participants aged ≥ 45years without baseline CVD from the China Health and Retirement Longitudinal Study (CHARLS) over a 9-year follow-up period. Retrospective collection included sociodemographic details, health status, physical examination results, and blood biomarkers. Adjusted Cox proportional hazards models were used to examine the interaction between TyG levels and anthropometric indices and their joint associations with CVD incidence. Subgroup analyses were conducted to evaluate the associations across different populations, and mediation analysis was performed to identify potential mediating pathways. The predictive value was determined using the area under the curve (AUC) of receiver operating characteristic curves. In addition, we validated the findings in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. In the CHARLS study, 1768 (25.1%) participants developed CVD. All TyG-anthropometric indices exhibited significant positive associations with the incidence of CVD. TyG-waist-to-height ratio (WHtR) showed the strongest association, with each 1-SD increase correlating with a 25% increase in CVD risk. Elevated systolic and diastolic blood pressure (BP) levels partially mediated these associations. TyG-weight-adjusted waist index (WWI) indicated the highest predictive performance in CHARLS, while TyG-conicity index (ConI) was the most predictive in the MESA cohort. Across both cohorts, TyG-WHtR provided the most substantial incremental improvement to the baseline model. Models combining TyG-anthropometric indices showed higher prediction accuracy and goodness of fit than the basic model combining TyG or anthropometric indices alone. Decision curve analysis showed that TyG-WC and TyG-ConI yielded the superior net clinical benefits for CVD prediction. Subgroup analyses demonstrated consistent associations between TyG-anthropometric indices and CVD incidence across different clinical characteristics and sociodemographic groups. The integration of TyG with anthropometric indices strengthened its association with CVD incidence. While TyG-WWI and TyG-ConI exhibited the highest predictive ability in the CHARLS and MESA cohorts, respectively, TyG-WHtR consistently yielded the greatest improvement to traditional risk models. Elevated BP levels partially mediated this association. Early intervention targeting visceral adiposity and impaired insulin sensitivity is crucial for mitigating CVD incidence in middle-aged and older adults.

ABSTRACTDepressive disorders often show recurrent courses that cannot be sufficiently prevented by existing therapeutic protocols. In other affective disorders, recurrence has been linked to three mechanisms –spontaneous recovery, accelerated new/relearning, and reinstatement– which are related to the preservation of disorder‐related memory traces even through successful extinction‐based interventions. Reconsolidation‐interference protocols aim to directly alter such traces by reactivating and destabilizing them before intervention. While this approach has shown benefits in fear, craving, and trauma‐related symptoms, its application to depression remains untested. To our knowledge, this study provides the first experimental evidence of its utility in depression‐like states. Sixty participants took part in a three‐day, three‐group, double‐blind randomized controlled trial. On day one, helplessness was induced using a modified unsolvable anagram task. On day two, participants were randomized into three groups undergoing different interventions while completing another cognitive demanding task: (1) extinction, where participants experienced success from start to finish; (2) reconsolidation, where participants briefly reexperienced failure before succeeding; or (3) reactivation, where failure repeated. On day three, the helplessness task was presented again to evaluate susceptibility for recurrence across conditions. Behavioral, self‐report, and EEG data were collected. Across test days, participants showed reduced motivation and performance, attributing failure to personal ability, confirming successful helplessness induction. However, interventions at day two produced no robust group differences on behavioral, self‐report, or EEG measures. Exploratory analyses suggested that brain‐derived neurotrophic factor (BDNF) levels may have mediated outcomes. Findings do not confirm reconsolidation‐based behavioral interference as effective for depression‐like helplessness. Nonetheless, exploratory results highlight BDNF as a potential mediator, warranting further study on its role in postretrieval extinction effects in depression.

Mental health issues, such as depression, are increasingly recognized as critical comorbidities in chronic obstructive pulmonary disease (COPD). While analyses of individual domains or pairwise relationships among airflow obstruction severity, brain morphological features, and mental health conditions in COPD have provided valuable insights into their direct associations, a more integrative approach may offer additional mechanistic understanding. This study aimed to clarify potential mediators in multiple brain regions between airflow obstruction and depressive tendencies in patients with COPD. We analyzed 19 patients with COPD and 23 age-matched healthy controls. Path analysis was used to evaluate the relationships among respiratory indices, regional brain volumes, and depressive symptoms. The path analysis revealed two potential pathways to depressive symptoms in the COPD group. One was a pulmonary pathway, involving forced expiratory volume in one second (%FEV1) and the genu of the corpus callosum (β = 0.503, p < 0.05) leading to depressive symptoms (β = 0.532, p < 0.05). The other was a behavioral pathway, in which physical activity (β = 0.444, p < 0.05) affected the right postcentral gyrus (β = −0.286, p < 0.05) and, in turn, depressive symptoms. No significant group differences were observed in other examined regions, including the posterior cingulate, hippocampus, hypothalamus, insula, or other corpus callosum subregions, nor in depression or anxiety scores. The model demonstrated a good fit in the COPD group (GFI = 0.876), whereas in controls, the model showed poor fit and no significant relationships (GFI = 0.784). These preliminary findings suggest potential brain pathways linking airflow obstruction, physical activity, and depressive symptoms in COPD, which warrant confirmation in larger, longitudinal studies.

College closures and psychological distress during COVID-19: The role of loneliness, social media use, and physical activity.

Mental disorders pose a growing threat to young adults globally. While ozone exposure has been linked to anxiety and depression, reliance on ambient measurements may misrepresent personal exposure. This study examined associations between ozone exposure at ambient, indoor, and personal levels and anxiety symptoms, depressive symptoms, and sleep disturbance among young adults, and assessed sleep quality as a potential mediator. A nationwide cross-sectional survey (2023-2024) was conducted across 261 Chinese municipalities. Annual maximum 8-h ozone concentrations over the preceding year were estimated at outdoor, indoor, and personal exposure levels. Validated scales were used to assess anxiety symptoms (GAD-7), depressive symptoms (PHQ-9), and sleep quality (PSQI). Multivariable logistic regression and mediation analysis within a logistic framework were applied, adjusting for sociodemographic, behavioral, and health condition covariates. Among 13,028 participants, the prevalence of anxiety symptoms, depressive symptoms, and sleep disturbance was 14%, 19%, and 39%, respectively. Associations with anxiety and depressive symptoms varied modestly across outdoor, indoor, and personal ozone exposure. Per interquartile range increase in outdoor, indoor, and personal ozone concentrations, odds ratios for anxiety were 1.17, 1.19, and 1.14; corresponding estimates for depression were 1.14, 1.13, and 1.10. Sleep quality mediated 10-30% and 16-49% of the ozone-anxiety and ozone-depression associations, respectively. These findings suggest that incorporating indoor and personal exposure metrics may provide additional insight into ozone-related mental health risks, with sleep quality serving as a mediator.

Changes in well-being, personality, and personal values have been documented post-psilocybin; however, evidence from placebo-controlled trials is limited. To examine the effects of psilocybin versus placebo on psychiatric symptoms, personality, and personal values in healthy participants. Potential mediators were also explored. This secondary analysis used data from a phase I, double-blind, randomised, placebo-controlled trial testing a single dose of 10 mg (n = 30) or 25 mg psilocybin (n = 30) versus an inert placebo (n = 29) in 89 healthy participants. Effects of psilocybin on personality (Neo Five-Factor Inventory; NEO-FFI), psychiatric symptoms (Symptom Checklist-90; SCL-90), and values (Life Changes Inventory; LCI) at short- (day 8) and long-term follow-up (day 85) were analysed using mixed-effects models. Group differences in cognitive flexibility (Intra-Extra Dimensional Set Shift task; IED) at day 8 were analysed using a Kruskal-Wallis test. Potential mediating effects of the acute psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire; 5D-ASC) were explored. No between-group differences were found on the NEO-FFI, SCL-90, or IED. Both psilocybin groups showed greater LCI absolute change scores at both follow-up points compared to placebo. The 5D-ASC oceanic boundlessness subscale partially mediated these changes. Oceanic boundlessness also fully or partially mediated differences across several LCI subscales, and auditory alterations mediated differences on one subscale. The acute psychedelic experience, namely oceanic boundlessness and, to a lesser extent, auditory alterations, mediates self-reported changes in values in healthy volunteers. Findings from this exploratory study are tentative and should be replicated in larger samples.

Matrix metalloproteinases (MMPs) have been increasingly recognized as potential contributors or mediators in the pathogenesis of diabetic retinopathy (DR). Nevertheless, the relationships among MMPs and the risk of DR have not been definitively elucidated and still require further investigation. The bidirectional two-sample Mendelian randomization (MR) analyses were implemented to evaluate the causal effect of MMPs (specifically, MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13, MMP-14, MMP-16, and MMP-17) on DR. The inverse variance weighted (IVW) served as the primary MR method, accompanied by sensitivity analyses to verify the result stability. In the forward MR analyses, genetically predicted MMP-7 was associated with an increased risk of DR (IVW: odds ratio = 1.15; 95% confidence interval: 1.05–1.25; P = 2.759 × 10⁻³]. In contrast, higher MMP-8 were robustly associated with a reduced risk of DR (IVW: odds ratio = 0.86; 95% confidence interval: 0.82–0.91; P = 5.506 × 10⁻⁸). No significant causal associations were observed between DR and the remaining MMPs. Sensitivity analyses revealed that the causal estimate for MMP-7 was sensitive to the threshold used for instrumental variables, whereas the association for MMP-8 was largely driven by 1 single nucleotide polymorphism (rs12614). In the reverse MR analyses, no significant causal effects of DR on any of the MMPs were detected after correction for multiple testing. This study provides preliminary and exploratory evidence supporting a causal association between MMPs and DR risk in European population. Specifically, MMP-7 may be associated with an increased risk of DR, while MMP-8 may be protective against DR. These findings suggest distinct pathophysiological roles for specific MMPs in DR development. However, given the exploratory nature of the analysis, further validation in mechanistic and longitudinal studies is warranted. not applicable.