Background: To longitudinally investigate the impact of best-corrected visual acuity (BCVA), non-modifiable risk factors, modifiable habits, and disease course on the vision-related quality of life (VRQOL) of patients with central serous chorioretinopathy (CSCR). Methods: We longitudinally enrolled 109 CSCR patients and 42 non-diseased control participants from our clinic. In addition to clinical examination, the National Eye Institute Visual Function Questionnaire (NEI-VFQ-39) was employed for assessments, along with questions pertaining to various aspects of lifestyle habits. Alongside the cross-sectional analyses, the VRQOL of CSCR patients was tracked longitudinally over one year. Results: Consistent with prior studies, CSCR patients reported a lower VRQOL compared to non-diseased participants (79.3 ± 14.1 for CSCR and 92.6 ± 7.6 for CTRL; p < 0.0001), but fared better than those with other ocular conditions. No significant associations were observed between BCVA, any non-modifiable risk factors, or interventions, and VRQOL, both in cross-sectional and longitudinal contexts (cross-sectional BCVA with VRQOL: Pearson r correlation 0.173, p = 0.072). Among modifiable habits, sleep duration (p = 0.036), perceived quality of sleep rhythm (p = 0.006), hours of physical activity (p = 0.036), and the presence of non-ocular conditions (p = 0.001) were significantly correlated with VRQOL. Notably, enhanced sleep duration (+4.232 vs. -0.041 non-enhanced at 3 months, p = 0.033) and higher perceived quality of sleep rhythm (+6.248 vs. +0.094 non-higher, p = 0.009) showed a positive correlation with improved VRQOL over time. Conclusions: The study reveals that VRQOL has minimal dependence on BCVA or other clinical factors, suggesting that patient-reported outcome measures (PROMs) could serve as alternative endpoints in clinical studies for more holistic patient welfare assessment. Furthermore, the strong correlations between VRQOL and modifiable lifestyle habits indicate potential therapeutic value in targeting these areas for intervention.

BACKGROUND: Alzheimer\'s disease (AD) is a progressive neurodegenerative disorder characterized by intricate genetic and environmental etiology. The objective of this study was to identify robust non-genetic risk factors for AD through an updated umbrella review.
METHODS: We conducted a comprehensive search of meta-analyses and systematic reviews on non-genetic risk factors associated with AD in PubMed, Cochrane, Embase, and Ovid Medline up to June 30, 2023. After collecting data, we estimated the summary effect size and their 95% confidence intervals. The degree of heterogeneity between studies was assessed using I2 statistics and a 95% prediction interval was determined. Additionally, we evaluated potential excess significant bias and small study effects within the selected candidate studies.
RESULTS: The umbrella review encompassed a total of 53 eligible papers, which included 84 meta-analyses covering various factors such as lifestyle, diet, environmental exposures, comorbidity or infections, drugs, and biomarkers. Based on the evidence classification criteria employed in this study, two factors as convincing evidence (Class I), including rheumatoid arthritis (RA), potentially reduced the risk of AD, but diabetes significantly increased the risk of AD. Furthermore, three factors as highly suggestive evidence (Class II), namely depression, high homocysteine, and low folic acid level, potentially increased the risk of AD.
CONCLUSIONS: Our findings highlight several risk factors associated with AD that warrant consideration as potential targets for intervention. However, it is crucial to prioritize the identified modifiable risk factors, namely rheumatoid arthritis, diabetes, depression, elevated homocysteine levels, and low folic acid levels to effectively address this complex neurodegenerative disorder.

BACKGROUND: This study investigates the relationship between cognitive functioning and 59 modifiable and intrinsic factors at the cusp of midlife.
METHODS: We analyzed data from 1221 participants in the Colorado Adoption/Twin Study of Lifespan behavioral development and cognitive aging (CATSLife; Mage = 33.20, %Female = 52.74). We assessed the impact of 59 factors on cognitive functioning using regularized regression and co-twin control models, controlling for earlier-life cognitive functioning and gray matter volume.
RESULTS: Eight robust factors were identified, including education attainment, cognitive complexity, purpose-in-life, and smoking status. Twins reporting higher levels of cognitive complexity and purpose-in-life showed better cognitive performance than their cotwin, while smoking was negatively associated. Using meta-analytically derived effect size threshold, we additionally identified that twins experiencing more financial difficulty tend to perform less well compared with their cotwin.
CONCLUSIONS: The findings highlight the early midlife link between cognitive functioning and lifestyle/psychological factors, beyond prior cognitive performance, brain status, genetic and familial confounders. Our results further highlight the potential of established adulthood as a crucial window for dementia prevention interventions targeting lifestyle and psychosocial factors.
UNASSIGNED: Cog complexity(+), purpose-in-life(+) were associated with cognition in early midlife.Smoking(-) was also associated with cognition in early midlife.Results were consistent controlling for genetic and environmental confounds.Association between EA and cognition might be mostly genetic and familial confounded.

BACKGROUND: Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear.
METHODS: We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations.
RESULTS: In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P < 0.05/22). Among European population, alanine transaminase, AST, MASLD, percent liver fat, and liver iron content were significantly associated with a higher risk of HCC (P < 0.05/33). The replication dataset and meta-analysis further confirmed these results.
CONCLUSIONS: Although East Asian and European populations have different factors for HCC, their common modifiable risk factors AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC.

BACKGROUND: Lynch syndrome is the most common cause of hereditary colorectal and endometrial cancer. Lifestyle modification may provide an opportunity for adjunctive cancer prevention. In this study, we aimed to characterise modifiable risk factors in people with Lynch syndrome and compare this with international guidelines for cancer prevention.
METHODS: A cross-sectional study was carried out utilizing survey methodology. Following public and patient involvement, the survey was disseminated through patient advocacy groups and by social media. Self-reported demographic and health behaviours were collected in April 2023. Guidelines from the World Cancer Research Fund (WCRF) were used to compare percentage adherence to 9 lifestyle recommendations, including diet, physical activity, weight, and alcohol intake. Median adherence scores, as a surrogate for lifestyle risk, were calculated and compared between groups.
RESULTS: 156 individuals with Lynch syndrome participated from 13 countries. The median age was 51, and 54% were cancer survivors. The mean BMI was 26.7 and the mean weekly duration of moderate to vigorous physical activity was 90 min. Median weekly consumption of ethanol was 60 g, and 3% reported current smoking. Adherence to WCRF recommendations for cancer prevention ranged from 9 to 73%, with all but one recommendation having < 50% adherence. The median adherence score was 2.5 out of 7. There was no significant association between median adherence scores and age (p = 0.27), sex (p = 0.31), or cancer history (p = 0.75).
CONCLUSIONS: We have characterised the modifiable risk profile of people living with Lynch syndrome, outlining targets for intervention based on lifestyle guidelines for the general population. As evidence supporting the relevance of modifiable factors in Lynch syndrome emerges, behavioural modification may prove an impactful means of cancer prevention.

BACKGROUND: Pedometer-based walking programs hold promise as a health promotion strategy for stroke prevention in community-dwelling older adults, particularly when targeted at physical activity-related modifiable risk factors. The question arises: What is the effectiveness of pedometer-based walking program interventions in improving modifiable stroke risk factors among community-dwelling older adults?
METHODS: Eight databases were searched up to December 2nd, 2023, following the Preferred Reporting Items for Systematic Review and Meta-Analysis protocol. Inclusion criteria focused on randomized controlled trials (RCTS) involving community-dwelling older adults and reported in English. Two independent reviewers utilized Physiotherapy Evidence Database (PEDro) tool to extract data, assess eligibility, evaluate study quality, and identify potential bias. Standardized mean difference (SMD) was employed as summary statistics for primary -physical activity level -and secondary outcomes related to cardiovascular function (blood pressure) and metabolic syndrome, including obesity (measured by body mass index and waist circumference), fasting blood sugar, glycated hemoglobin, high-density lipoprotein cholesterol (HDL-C), and triglycerides. A random-effects model was used to generate summary estimates of effects.
RESULTS: The review analyzed eight studies involving 1546 participants aged 60-85 years, with 1348 successfully completing the studies. Across these studies, pedometer-based walking programs were implemented 2-3 times per week, with sessions lasting 40-60 minutes, over a duration of 4-26 weeks. The risk of bias varied from high to moderate. Our narrative synthesis revealed positive trends in HDL-C levels, fasting blood sugar, and glycated hemoglobin, suggesting improved glycemic control and long-term blood sugar management. However, the impact on triglycerides was only marginal. Primary meta-analysis demonstrated significantly improved physical activity behavior (SMD=0.44,95%CI:0.26, 0.61,p=<0.00001;I2=0%;4 studies; 532 participants) and systolic blood pressure (SMD=-0.34,95%CI:-0.59,-0.09;p=<0.008;I2=65%,2 studies;249 participants), unlike diastolic blood pressure (SMD=0.13,95%CI:-0.13,-0.38,p=0.33; I2=91%; 2 studies; 237 participants). Interventions based on social cognitive, self-efficacy, and self-efficiency theory(ies), and social cognitive theory applied in an ecological framework, were linked to successful physical activity behavior outcomes.
CONCLUSIONS: Pedometer-based walking programs, utilizing interpersonal health behavior theory/ecological framework, enhance physical activity behavior and have antihypertensive effects in community-dwelling older adults. While they do not significantly affect diastolic blood pressure, these programs potentially serve as a primary stroke prevention strategy aligning with global health goals.
BACKGROUND: Registration Number: INPLASY202230118.

Background Observational studies link lifestyle factors to diabetes, but confounding limits causal inference. This study employed Mendelian randomization (MR) to investigate the potential causal effects of major dietary, obesity, smoking, and physical activity exposures on diabetes risk. Methods A two-sample MR framework integrated FinnGen and United Kingdom Biobank (UKB) data. Genetic instruments for diet (fruits, vegetables, cheese), smoking (initiation, intensity, maternal), body mass index (BMI), and physical activity came from various consortia (n=64, 949-632, 802). Associations with diabetes odds were assessed using inverse-variance weighted analysis. Results Fruit and cheese intake and physical activity per standard deviation increase causally reduced diabetes risk in both cohorts. Conversely, smoking initiation, maternal smoking around birth, and BMI per standard deviation increase causally increased diabetes risk in both cohorts. Coffee increased diabetes risk only in FinnGen, whereas smoking intensity increased diabetes risk only in UKB. Conclusion This study provides robust evidence that modifiable lifestyle factors may have causal effects on diabetes risk. Fruit, cheese, and physical activity may protect against diabetes, whereas smoking, maternal smoking, and higher BMI appear to increase risk. Findings support public health interventions targeting diet, physical activity, smoking cessation, and healthy weight to combat the global diabetes epidemic.

UNASSIGNED: Polycystic Ovary Syndrome (PCOS) is a heritable condition with an as yet unclear etiology. Various factors, such as genetics, lifestyle, environment, inflammation, insulin resistance, hyperandrogenism, iron metabolism, and gut microbiota, have been proposed as potential contributors to PCOS. Nevertheless, a systematic assessment of modifiable risk factors and their causal effects on PCOS is lacking. This study aims to establish a comprehensive profile of modifiable risk factors for PCOS by utilizing a two-sample Mendelian Randomization (MR) framework.
UNASSIGNED: After identifying over 400 modifiable risk factors, we employed a two-sample MR approach, including the Inverse Variance Weighted (IVW) method, Weighted Median method, and MR-Egger, to investigate their causal associations with PCOS. The reliability of our estimates underwent rigorous examination through sensitivity analyses, encompassing Cochran\'s Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plots.
UNASSIGNED: We discovered that factors such as smoking per day, smoking initiation, body mass index, basal metabolic rate, waist-to-hip ratio, whole body fat mass, trunk fat mass, overall health rating, docosahexaenoic acid (DHA) (22:6n-3) in blood, monounsaturated fatty acids, other polyunsaturated fatty acids apart from 18:2 in blood, omega-3 fatty acids, ratio of bisallylic groups to double bonds, omega-9 and saturated fatty acids, total lipids in medium VLDL, phospholipids in medium VLDL, phospholipids in very large HDL, triglycerides in very large HDL, the genus Oscillibacter, the genus Alistipes, the genus Ruminiclostridium 9, the class Mollicutes, and the phylum Tenericutes, showed a significant effect on heightening genetic susceptibility of PCOS. In contrast, factors including fasting insulin interaction with body mass index, sex hormone-binding globulin, iron, ferritin, SDF1a, college or university degree, years of schooling, household income, the genus Enterorhabdus, the family Bifidobacteriaceae, the order Bifidobacteriales, the class Actinobacteria, and the phylum Actinobacteria were determined to reduce risk of PCOS.
UNASSIGNED: This study innovatively employs the MR method to assess causal relationships between 400 modifiable risk factors and the susceptibility of PCOS risk. It supports causal links between factors like smoking, BMI, and various blood lipid levels and PCOS. These findings offer novel insights into potential strategies for the management and treatment of PCOS.

Evaluating whether genetic susceptibility modifies the impact of lifestyle-related factors on dementia is critical for prevention.
We studied 5170 participants from a French cohort of older persons free of dementia at baseline and followed for up to 17 years. The LIfestyle for BRAin health risk score (LIBRA) including 12 modifiable factors was constructed at baseline (higher score indicating greater risk) and was related to both subsequent cognitive decline and dementia incidence, according to genetic susceptibility to dementia (reflected by the apolipoprotein E [APOE] ε4 allele and a genetic risk score [GRS]).
The LIBRA was associated with higher dementia incidence, with no significant effect modification by genetics (hazard ratio for one point score = 1.09 [95% confidence interval, 1.05; 1.13]) in APOE ε4 non-carriers and = 1.15 [1.08; 1.22] in carriers; P = 0.15 for interaction). Similar findings were obtained with the GRS and with cognitive decline.
Lifestyle-based prevention may be effective whatever the genetic susceptibility to dementia.

Aging and cancer exhibit apparent links that we will examine in this review. The null hypothesis that aging and cancer coincide because both are driven by time, irrespective of the precise causes, can be confronted with the idea that aging and cancer share common mechanistic grounds that are referred to as \'hallmarks\'. Indeed, several hallmarks of aging also contribute to carcinogenesis and tumor progression, but some of the molecular and cellular characteristics of aging may also reduce the probability of developing lethal cancer, perhaps explaining why very old age (> 90 years) is accompanied by a reduced incidence of neoplastic diseases. We will also discuss the possibility that the aging process itself causes cancer, meaning that the time-dependent degradation of cellular and supracellular functions that accompanies aging produces cancer as a byproduct or \'age-associated disease\'. Conversely, cancer and its treatment may erode health and drive the aging process, as this has dramatically been documented for cancer survivors diagnosed during childhood, adolescence, and young adulthood. We conclude that aging and cancer are connected by common superior causes including endogenous and lifestyle factors, as well as by a bidirectional crosstalk, that together render old age not only a risk factor of cancer but also an important parameter that must be considered for therapeutic decisions.