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Results for “Modifiable factors”

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PubMed2026

Lifestyle Combination Patterns as Key Modifiable Factors for Type 2 Diabetes Mellitus Risk among Middle-Aged Korean Men.

BACKGRUOUND: The increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide highlights the need to understand risk factors and effective prevention strategies. Although individual lifestyle factors associated with diabetes risk have been identified, research on their collective interactions is limited. This study aimed to identify lifestyle combination patterns in middle-aged Korean men and evaluate their impact on T2DM risk. METHODS: A total of 2,332 middle-aged men without T2DM at baseline (2001-2002) from the Korean Genome and Epidemiology Study (KoGES) cohort were included. T2DM incidence was tracked through the 8th follow-up survey (2017-2018). Lifestyle combination patterns were identified using factor analysis based on sociodemographic, lifestyle, and dietary data. Cox regression was used to assess T2DM incidence across patterns. RESULTS: Four lifestyle combination patterns were identified: 'Healthy Lifestyle,' 'Low Carb & High Protein,' 'High SES & Irregular Lifestyle,' and 'Bad Eating Habits.' The risk of developing T2DM varied across patterns. The 'Healthy Lifestyle' and 'Low Carb & High Protein' patterns showed a slight decrease in risk in T3, but the differences were not significant. The 'High SES & Irregular Lifestyle' pattern was associated with a higher T2DM risk in T3 than in T1 (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.05 to 1.55), but the association was attenuated after adjustment for family history. The 'Bad Eating Habits' pattern showed a 1.21-fold higher risk in T3 (HR, 1.21; 95% CI, 1.01 to 1.47). CONCLUSION: This study underscores the existence of distinct lifestyle combination patterns and their differential implications for T2DM risk. These findings support the need for tailored preventive strategies based on lifestyle patterns.

Humans↗

PubMed2025

Causal relationships between modifiable risk factors and heart failure: A comprehensive Mendelian randomization study.

Heart failure threatens human health across the globe. Comprehensively identifying its risk factors has public health importance. This work utilized the Mendelian randomization (MR) method to evaluate the effects of over 200 modifiable factors on heart failure. The data from genome-wide association studies (GWAS) was used, with the sample size ranging from 711 to 1232,091. Two distinct GWAS datasets for heart failure were employed for results validation. The inverse variance weighted (IVW) method was used and other supplementary models were employed for comparison. Sensitivity analysis was conducted to verify the results. After integrating the MR estimates derived from heart failure GWAS datasets from integrative epidemiology unit (IEU) and Finngen, we found that body measurement indices like body mass index, whole body fat mass, trunk fat mass, basal metabolic rate, body fat percentage, waist circumference, and waist-hip ratio, were associated with a higher risk of heart failure. Similarly, smoking behavior, sedentary behavior, overall health rating, and type 2 diabetes were determined to increase the risk of heart failure. In contrast, college or university degree showed a protective effect on heart failure. Among these significant findings, body mass index, whole body fat mass, trunk fat mass, basal metabolic rate, body fat percentage, overall health rating, smoking initiation, waist circumference, lifetime smoking index, college or university degree, sedentary behavior, waist-hip ratio, and type 2 diabetes were replicated validated. This MR work figured out that obesity, socioeconomic factors, lifestyle factors, and metabolic features showed broad relations with heart failure. The findings would provide evidence for future policy development for the management of heart failure.

Humans↗

PubMed2026

Machine learning-based clinical tool for identifying factors associated with symptomatic knee osteoarthritis: the Nagahama study.

BACKGROUND: A clinical tool that evaluates factors associated with symptomatic knee osteoarthritis (OA) based on modifiable factors is lacking. This study aimed to develop a machine learning-based clinical assessment tool using modifiable factors to identify factors associated with symptomatic knee OA and to determine its accuracy. METHODS: This study included 429 participants (81.8% women; age, 69.0 ± 5.3 years) from the Nagahama Study who were ≥60 years old and had radiographically confirmed knee OA. A Knee Society Knee Scoring System 2011 symptom score of <23 points defined symptomatic knee OA. Participants were randomly assigned to training (70%) and test (30%) datasets. A machine learning model was developed using Extreme Gradient Boosting with 27 variables, and the SHapley Additive exPlanation (SHAP) values were used to assess feature importance. The top 8 features were translated into a 100-point clinical scoring tool weighted by their SHAP contributions. The cutoff value indicating symptomatic knee OA in the clinical assessment tool was determined using receiver operating characteristic analysis, and model performance was evaluated in both datasets. RESULTS: The clinical assessment tool consisted of low back pain, OA severity, depressive tendencies, knee flexion/extension range of motion, knee extension and hip abduction strength, and lower limb muscle quality. The model showed moderate discriminative performance (AUC 0.771 and 0.773 in the training and test datasets, respectively), with a cutoff point of 47. CONCLUSION: The proposed clinical assessment tool may provide a structured framework for assessing modifiable factors associated with symptomatic knee OA, reflecting their contribution to current symptom status.

Humans↗

PubMed2026

Causal Relationships Between Modifiable Risk Factors and Gastroesophageal Reflux Disease: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a prevalent digestive disorder, yet the causal roles of modifiable risk factors remain unclear. This study aims to investigate the causal relationships between 28 modifiable risk factors (including obesity traits, mental health disorders, sleep traits, metabolic comorbidities, and serum parameters) and GERD using two-sample Mendelian randomization (MR). Gastroesophageal reflux disease (GERD). Our findings aim to inform targeted prevention and treatment strategies for GERD. METHODS: This study obtained data from extensive genome-wide association studies (GWAS). Pooled data associated with gastroesophageal reflux associations were obtained from the 23andMe Research team's research, which included a total of 129,080 cases of gastroesophageal reflux and 473,524 controls of European ancestry. We conducted a univariable Mendelian randomization (MR) analysis to ascertain whether genetic evidence of exposure demonstrated a statistically significant association with the risk of GERD. Subsequently, a multivariable MR analysis was carried out to estimate the independent effects of the exposures on GERD. RESULTS: Univariable MR analysis utilizing extensive GWAS data suggested that genetic factors such as BMI, Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), Attention Deficit and Hyperactivity Disorder (ADHD), Major Depressive Disorder (MDD), Schizophrenia, Negative emotions (including nervousness, anxiety, tension, or depression), Insomnia, Sleep apnea syndrome, Sleep duration, and Snoring, as well as Total cholesterol levels and Apolipoprotein B levels, are associated with the development of GERD. Multivariate Mendelian randomization of BMI and Negative emotion as correction factors showed that Waist circumference, Arm fat mass (left and right), Leg fat mass (left and right), ADHD, Insomnia, Sleep apnea syndrome, and Snoring were associated with an increased risk of GERD (p< 0.05). Conversely, longer sleep duration was associated with a reduced risk of GERD (p< 0.05). DISCUSSION: This MR study reveals novel causal mechanisms in GERD pathogenesis: (1) Peripheral adiposity (arm/leg fat mass) exerts independent effects beyond central obesity, indicating site-specific fat distribution significance; (2) ADHD emerges as a distinct psychiatric risk factor independent of mental disorders; (3) Sleep apnea operates through BMI-independent pathways. Collectively, these findings redefine GERD pathophysiology, highlighting fat depot specificity and brain-gut interactions as critical mechanistic drivers. CONCLUSION: Overall, our findings suggest that multiple risk factors are associated with the risk of GERD. These results provide a theoretical basis for controlling body weight and plasticity, improving sleep habits, and preventing and timely seeking medical attention to reduce the occurrence of psychiatric disorders, which will be important strategies to prevent and alleviate GERD.

Humans↗

PubMed2025

Modifiable risk factors associated with the risk of developing Parkinson's disease: a critical review.

The etiology of Parkinson's disease (PD) is complex and multifactorial, depending on interactions involving environmental/lifestyle and genetic factors. The genetic aspects of the disease are becoming well characterized, while the environmental factors still need further investigation. In the present narrative review, we have described the most concrete evidence of associations between environmental factors and the risk of developing PD. Physical activity, healthy dietary patterns, smoking, and caffeine intake are protective factors against PD. Head trauma, consumption of milk and dairy products, and pesticide exposure were associated with a higher risk of developing PD. The associations of alcohol consumption, living in rural areas, farming, and consumption of well water with PD are still controversial. Results of several studies strongly suggest that diabetes mellitus is a risk factor for the development of PD, as well as the pre-diabetic state. Lower serum levels of uric acid were associated with an increased risk of developing PD and with worse clinical features and faster progression of symptoms. The protective effects of nonsteroidal antiinflammatory drugs use are controversial. Several other factors were potentially associated with the risk of developing PD: environmental pollutants such as organic solvents, exposure to sunlight, vitamin D deficiency, bullous pemphigoid, bipolar disorder, inflammatory bowel disease, irritable bowel syndrome, certain infections and agents, and essential tremor. Environmental factors are important risk markers for the development of PD. Understanding these risks and protective factors could lead to the implementation of risk-modifying actions for PD.

Humans↗

PubMed2022

Epigenome-wide meta-analysis of PTSD symptom severity in three military cohorts implicates DNA methylation changes in genes involved in immune system and oxidative stress.

Epigenetic factors modify the effects of environmental factors on biological outcomes. Identification of epigenetic changes that associate with PTSD is therefore a crucial step in deciphering mechanisms of risk and resilience. In this study, our goal is to identify epigenetic signatures associated with PTSD symptom severity (PTSS) and changes in PTSS over time, using whole blood DNA methylation (DNAm) data (MethylationEPIC BeadChip) of military personnel prior to and following combat deployment. A total of 429 subjects (858 samples across 2 time points) from three male military cohorts were included in the analyses. We conducted two different meta-analyses to answer two different scientific questions: one to identify a DNAm profile of PTSS using a random effects model including both time points for each subject, and the other to identify a DNAm profile of change in PTSS conditioned on pre-deployment DNAm. Four CpGs near four genes (F2R, CNPY2, BAIAP2L1, and TBXAS1) and 88 differentially methylated regions (DMRs) were associated with PTSS. Change in PTSS after deployment was associated with 15 DMRs, of those 2 DMRs near OTUD5 and ELF4 were also associated with PTSS. Notably, three PTSS-associated CpGs near F2R, BAIAP2L1 and TBXAS1 also showed nominal evidence of association with change in PTSS. This study, which identifies PTSD-associated changes in genes involved in oxidative stress and immune system, provides novel evidence that epigenetic differences are associated with PTSS.

Adaptor Proteins, Signal Transducing↗

PubMed2024

The associations between functional dyspepsia and potential risk factors: A comprehensive Mendelian randomization study.

BACKGROUND: Previous cross-sectional studies have identified multiple potential risk factors for functional dyspepsia (FD). However, the causal associations between these factors and FD remain elusive. Here we aimed to fully examine the causal relationships between these factors and FD utilizing a two-sample MR framework. METHODS: A total of 53 potential FD-related modifiable factors, including those associated with hormones, metabolism, disease, medication, sociology, psychology, lifestyle and others were obtained through a comprehensive literature review. Independent genetic variants closely linked to these factors were screened as instrumental variables from genome-wide association studies (GWASs). A total of 8875 FD cases and 320387 controls were available for the analysis. The inverse variance weighted (IVW) method was employed as the primary analytical approach to assess the relationship between genetic variants of risk factors and the FD risk. Sensitivity analyses were performed to evaluate the consistency of the findings using the weighted median model, MR-Egger and MR-PRESSO methods. RESULTS: Genetically predicted depression (OR 1.515, 95% confidence interval (CI) 1.231 to 1.865, p = 0.000088), gastroesophageal reflux disease (OR 1.320, 95%CI 1.153 to 1.511, p = 0.000057) and years of education (OR 0.926, 95%CI 0.894 to 0.958, p = 0.00001) were associated with risk for FD in univariate MR analyses. Multiple medications, alcohol consumption, poultry intake, bipolar disorder, mood swings, type 1 diabetes, elevated systolic blood pressure and lower overall health rating showed to be suggestive risk factors for FD (all p<0.05 while ≥0.00167). The positive causal relationship between depression, years of education and FD was still significant in multivariate MR analyses. CONCLUSIONS: Our comprehensive MR study demonstrated that depression and lower educational attainment were causal factors for FD at the genetic level.

Humans↗

PubMed2026

Analysis of the Relationship between Early Clinical Factors and Glasgow Outcome Scale in Patients With Traumatic Brain Injury.

OBJECTIVE: This study aimed to evaluate the association between early clinical factors and the Glasgow outcome scale (GOS) in patients with traumatic brain injury (TBI). METHODS: We conducted a retrospective analysis of 98 TBI patients who underwent emergency surgery between January 2021 and January 2024. Based on GOS scores at 6 months post-surgery, patients were classified into a favorable outcome group (GOS ≥ 4, defined as moderate disability or good recovery, n = 58) and an unfavorable outcome group (GOS < 4, i.e., death, persistent vegetative state, or severe disability, n = 40). Baseline and early clinical parameters were compared between groups. Statistically significant variables from univariate analysis were entered into a multivariate logistic regression model to identify independent prognostic factors. RESULTS: Significant intergroup differences were observed in age, time from injury to surgery, bleeding site, midline shift, Glasgow coma scale (GCS) score at admission, blood glucose level, and D-dimer level (all p < 0.05). Multivariate analysis confirmed that age, time from injury to surgery, GCS score, blood glucose, and D-dimer level were independent predictors of GOS (all p < 0.05). CONCLUSION: Early clinical factors, including age, time to surgery, GCS score, blood glucose, and D-dimer level, independently influence GOS in TBI patients. Time from injury to surgery emerged as a potentially modifiable factor in this cohort, suggesting that minimizing delays may improve outcomes.

Humans↗

PubMed2026

Factors associated with periprosthetic joint infection following total knee arthroplasty: an updated systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically evaluate factors associated with periprosthetic joint infection (PJI) following total knee arthroplasty (TKA), and thereby to provide evidence-based references for clinical prevention and perioperative risk stratification. METHODS: Computerized searches were conducted in the following databases from their inception until May 26, 2025: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database. Two researchers independently screened the literature, extracted data, and assessed study quality. The methodological quality was assessed using the Newcastle-Ottawa Scale. Quantitative synthesis was performed when at least two studies reported comparable exposure definitions and sufficient comparator information; otherwise, narrative synthesis was used. Review Manager 5.4 software was used for the primary analysis. This study is registered on PROSPERO (CRD420251079339). RESULTS: A total of 25 observational studies were included in the qualitative synthesis, of which 24 contributed to the primary quantitative synthesis. Quantitatively pooled factors associated with PJI included male sex (OR = 1.39, 95% CI 1.27-1.51), BMI ≥30 kg/m2 (OR = 5.72, 95% CI 2.65-12.36), prolonged operative time, type 2 diabetes mellitus (OR = 2.09, 95% CI 1.45-3.01), rheumatoid arthritis (OR = 2.64, 95% CI 1.38-5.02), smoking (OR = 1.65, 95% CI 1.34-2.04), blood transfusion (OR = 2.27, 95% CI 1.59-3.25), American Society of Anesthesiologists score ≥3 (OR = 2.73, 95% CI 1.02-7.32), history of hormone therapy (OR = 4.88, 95% CI 2.90-8.22), postoperative urinary tract infection (OR = 3.59, 95% CI 1.15-11.21), intraoperative blood loss >200 ml (OR = 1.51, 95% CI 1.03-2.22), postoperative drainage tube placement duration ≥24 h (OR = 2.23, 95% CI 1.50-3.32), preoperative anemia (OR = 1.82, 95% CI 1.67-1.99), and combined pulmonary disease (OR = 5.54, 95% CI 1.93-15.96). Age was narratively summarized because its classification differed substantially across studies. CONCLUSION: Multiple demographic, comorbidity-related, and perioperative factors were associated with PJI after TKA. However, because the included studies were observational and clinically heterogeneous, these findings should be interpreted as associations rather than causal effects. Optimization of modifiable factors may help reduce the burden of PJI, but further prospective studies using standardized PJI definitions and adjusted effect estimates are required.

Humans↗

PubMed2026

Genetic architecture of endometriosis: risk factors, comorbidities and clinical implications.

BACKGROUND: In 1999, Dr Susan Treloar and colleagues conducted a landmark twin study in Australia and reported their estimate of 51% for the heritability of endometriosis. This important result led several groups to begin mapping genetic factors contributing to increased endometriosis risk. Despite early challenges, advances in genome-wide association studies (GWAS) have identified multiple genetic risk factors and some target genes implicated in follow-up studies on genetic regulation of transcription. Access to large publicly available genetic datasets and analysis with endometriosis GWAS results is also providing new opportunities to answer important questions about comorbid conditions associated with endometriosis and their implications for clinical practice. OBJECTIVE AND RATIONALE: The objective of the review is to summarize the last 25 years of genetic studies in endometriosis, outline contributions to our understanding of the disease, and suggest future directions to accelerate biological insights from genetic studies to improve clinical outcomes. SEARCH METHODS: A comprehensive review of scientific literature on the genetics of endometriosis was conducted through searches in PubMed and Google Scholar up to June 2026. Search terms included "endometriosis AND (genetics OR GWAS OR genetic risk factors)", For studies addressing the functional characterization of genetic risk loci, additional searches employed the terms "endometriosis AND (genotype-phenotype associations OR colocalization OR eQTL OR mQTL OR multi omics methods)". To identify studies examining shared genetic risk between endometriosis and comorbid conditions, the search strategy included "endometriosis AND (genetic correlation OR colocalization OR Mendelian randomisation)". Publications reporting discoveries related to genetic risk factors for endometriosis and studies interpreting their biological and clinical significance were critically evaluated, and 144 publications were discussed in the review. OUTCOMES: Discovery of genetic risk factors started slowly and has accelerated in recent years with developments in technology and international collaborations to combine data and increase statistical power. GWAS have mapped 80 genetic risk factors that implicate gene regulation of hormonal targets, development of the reproductive tract, regulation of cell proliferation, and regulation of epithelial cell differentiation. In common with most other complex diseases, effects of individual common genetic risk factors are small. However, several examples demonstrate that small effect sizes are not a good predictor for the impact of drugs developed against genetically validated targets. Genetic risk factors implicate five genes regulating gonadotrophin release and oestrogen action, the major target pathway of current drugs for treatment of endometriosis demonstrating proof-of-principal for biologically meaningful results. Genetic correlation and Mendelian Randomization studies highlight important causal relationships between endometriosis and comorbid conditions including a possible role for testosterone during development and shared genetic risk factors for gynaecological, gastrointestinal, pain, psychiatric, and inflammatory conditions. Understanding causal relationships between endometriosis and related conditions will aid clinical management and more personalized treatments. WIDER IMPLICATIONS: Genetic studies provide novel insights into endometriosis pathogenesis and associations with related comorbid conditions. Genetic factors modifying gene regulation and disease risk likely act in specific cell types, and access to datasets from genetically informed cell-based models, single-cell and spatial omics data are needed to accelerate progress. Future studies should address critical questions of heterogeneity and disease subtypes, expand the search for genetic risk factors to non-European populations, evaluate the role of rare and structural variants, and better integrate data from functional, genomics, genetics, and clinical studies to reduce diagnostic delay, develop novel treatment strategies, and translate discoveries into personalized management strategies for affected individuals. REGISTRATION NUMBER: N/A.

comorbid conditions↗

PubMed2026

The presence or absence of standard modifiable cardiovascular risk factors in patients with myocardial infarction impacts long-term but not 30-day mortality: a UK Biobank prospective cohort study.

AIMS: Prior studies reported higher early mortality after acute myocardial infarction (MI) in patients without standard modifiable cardiovascular risk factors (SMuRFs), warranting further validation. We aimed to evaluate whether SMuRF-absence is associated with increased 30-day cardiovascular mortality following MI. METHODS AND RESULTS: We conducted a population-based cohort study using UK Biobank data (n = 487 177). Incident MI cases occurring between 2006 and 2022 were identified through linkage to hospital and death registries. Standard modifiable cardiovascular risk factors (diabetes, hypertension, hypercholesterolaemia, current smoker) were defined at baseline and continuously assessed until MI onset. Thirty-day mortality following MI was estimated using Cox proportional hazards models, adjusted for sociodemographic, clinical, and cardiogenomic variables, were used to estimate 30-day mortality risks. Logistic regression model was used to estimate mortality risk at 10 years post-MI. Among 15 463 patients experiencing an MI (1034 without SMuRFs), SMuRF-absence was not significantly associated with 30-day mortality (HR: 0.82, 95% CI: 0.65-1.04, P = 0.103). Propensity score-matched analyses supported these findings (HR: 0.95, 95% CI: 0.69-1.29, P = 0.729). Further analyses stratified by distinct time intervals (2006-2022) revealed no significant modification of this association by advancements in acute MI management. Interaction analyses indicated no significant effect modification by sex, age, socioeconomic status, or period of MI occurrence. However, extended analysis to 10 years revealed that SMuRF absence was significantly associated with lower long-term mortality (OR: 0.61, 95% CI: 0.49-0.75, P < 0.01). CONCLUSION: In this population-based cohort, SMuRF status significantly impacted long-term but not short-term mortality following MI, indicating early survival is predominantly driven by acute-phase factors rather than baseline cardiovascular risk profiles.

Humans↗

PubMed2026

Integrative Analysis Uncover the Effects and Multi-Omics Features of Thigh Muscle Fat Infiltration.

The health impacts and underlying biological pathways of thigh muscle fat infiltration (TMFI) remain incompletely understood. In this study, we analyzed TMFI measured by magnetic resonance imaging in 55,120 UK Biobank participants and found that higher TMFI was significantly associated with all-cause mortality as well as with all major system-specific diseases examined (p values ranged from 2.50 × 10-88 to 9.97 × 10-04). TMFI also mediated the effects of lifestyle factors on health-related outcomes, with mediation proportions ranging from 6.7% to 71.7%. A genome-wide association study (GWAS) identified 79 lead single nucleotide polymorphisms (SNPs) linked to TMFI, and the polygenic risk score for TMFI was significantly associated with mortality and all incident diseases across examined organ systems in an independent subset of UK Biobank participants of European ancestry who were not included in the TMFI GWAS (n = 362,286, all p < 0.05). Gene-drug interactions identified multiple drugs that could potentially modulate TMFI. Analysis of single-cell transcriptomic data indicated that myogenic cells were strongly linked to TMFI (p = 7.08 × 10-08). Summary-data-based Mendelian randomization and Transcriptome-Wide Association Study analyses revealed numerous genes whose expression in specific tissues was associated with TMFI. Proteomic and metabolomic profiling uncovered a broad array of circulating biomarkers associated with TMFI, many of which mediated the effects of modifiable factors and genetic risk on TMFI. Overall, our results highlight the biological relevance of TMFI to human health and provide insights into the multi-omics mechanisms underlying TMFI, identifying potential targets for interventions.

Humans↗

PubMed2026

Life-course influence of birthweight and subsequent pathways on healthy aging: a Mendelian randomization study.

BACKGROUND: Birthweight readily measurable marker of fetal growth that may influence health across the lifespan. We aimed to investigate the potential causal association between birthweight and healthy aging and to identify the mediating roles of subsequent socioeconomic, behavioral, functional, and disease-related factors to inform life-course strategies to promote healthy aging and reduce health inequities. METHODS: We performed two-sample Mendelian randomization analyses in European-ancestry participants to estimate the effect of birthweight (n = 298,142-423,683) on two robust, composite healthy aging phenotypes (genetically independent phenotype of aging (aging-GIP) and multivariate aging-related genetic factor (mvAge)) and six individual aging phenotypes, including healthspan, resilience, parental lifespan, self-rated health, phenotypic age deceleration, and 90th percentile self-longevity (n = 34,710-1,958,774), and screened for 100 candidate mediators (n = 14,267-1,812,017) using a two-step mediation analysis. RESULTS: Genetically determined each 1-SD higher birthweight was associated with higher aging-GIP (β [95% CI] in different models ranging from 0.131 [0.066-0.196] to 0.162 [0.089-0.235] SDs) and mvAge (0.036 [0.010-0.063] to 0.045 [0.024-0.067]), independent of later-life obesity indicators; also with more interpretable benefits, including 12%-16% higher odds of longer healthspan, a 0.079-0.089 SD improvement in resilience, and a 1.22-1.74 year increase in parental lifespan. Of 100 candidates, 26 and 25 mediated the effect of birthweight on aging-GIP and mvAge, respectively, including socioeconomic indicators (education, household income, occupational attainment; individual mediation proportion: 12.72%-27.79%); behaviors (e.g., cheese intake, age at first sex; 10.38%-29.56%); physical functions (e.g., blood pressure, grip strength; 7.57%-42.65%); and cardiometabolic diseases (e.g., type 2 diabetes, cardiovascular diseases; 25.02%-70.11%). CONCLUSIONS: Higher birthweight within the normal range directly promotes healthy aging, mediated by multifaceted modifiable factors. Our findings advocate adopting a life-course approach to foster healthy aging, starting with optimal birthweight and extending to interventions that enhance socioeconomic status, promote healthy behaviors, strengthen physical functions, and prevent cardiometabolic diseases.

Mendelian Randomization Analysis↗

PubMed2026

Perceptions of Pharmacogenomic Testing Among People With Treatment Resistant Depression: Legitimization as a Facilitator of Acceptance.

Pharmacogenomic testing for psychiatric medications has been proposed as both an early intervention to optimize treatment response, and for use among patients who have tried multiple medications without symptom remission. Therefore, this testing may be particularly salient to the subset of individuals with major depressive disorder for whom depression has been labeled as "treatment resistant". Understanding the impact of this diagnostic label on illness identity and attitudes towards new therapies is important as genomic technology expands and rates of depression increase. We sought to explore perceptions and attitudes towards pharmacogenomic testing among individuals who had received a diagnosis of treatment resistant depression. We conducted a qualitative study with a constructivist orientation. Participants were recruited from a larger genomic research study and interviewed by phone or video call. We took an inductive approach to coding guided by reflexive thematic analysis. Themes were then organized into a relational framework following principles of interpretive description. Twelve individuals were interviewed. Key themes included internalized acceptance/hopelessness, and external validation/frustration, which were cyclically interconnected. These themes were situated within a larger framework illustrating the ways that illness identity and modifying factors such as relief of guilt, social support, pharmacogenomic testing and depressive symptoms can either facilitate acceptance and validation or contribute to feelings of hopelessness and frustration. Though participants expressed some skepticism around its effectiveness, pharmacogenomic testing may contribute to the shift towards acceptance and validation by legitimizing individuals' experiences with lack of treatment response. Genetic counselors and other healthcare providers should be aware of the complex balance between hope and frustration underlying conversations around pharmacogenomic testing, and factors that are more likely to foster self-acceptance.

Humans↗

PubMed2025

Healthcare transition readiness in an adolescent and young adult urologic population: The ADHERENT study.

INTRODUCTION: There is a paucity of research regarding transition to adult services within pediatric and adolescent urology. Several recent articles have discussed the barriers in transitioning urologic patients from pediatric to adult health care, but empiric data that may drive intervention are lacking. This study proposes to begin to address this gap in literature and to provide information that may lead to improved understanding of how best to support transition in urologic care. OBJECTIVES: 1) to identify modifiable and non-modifiable factors related to transition readiness as measured by Transition Readiness Assessment Questionnaire (TRAQ) scores in a congenital urologic population and 2) to evaluate the relationships between TRAQ scores (a validated questionnaire measuring transition readiness) and scores measuring anxiety levels related to transition (using an adapted, non-validated questionnaire). STUDY DESIGN: This is a cross-sectional study of adolescent and young adult patients with complex congenital urologic diagnoses. Subjects were electronically administered the validated TRAQ and a study-developed ADHERENT survey, which assesses anxiety and worry surrounding transition. Regression models for the outcomes of the TRAQ and ADHERENT scales were developed to assess multivariable associations with variables of clinical importance. RESULTS: The youngest subgroup (14-17 years of age) compared to the oldest subgroup (21-25 years of age) had significantly lower TRAQ scores [regression estimate = 12.3 (95 % CI: 2.9, 21.7), p = 0.010]. Additionally, single participants versus those in a stable relationship had significantly lower TRAQ scores [estimate = 8.7 (95 % CI: 1.9, 15.4), p = 0.012]. The Spearman correlation coefficient between TRAQ and ADHERENT scores was 0.52 (p = <0.001), indicating a positive, moderate relationship between the two measures, suggesting more readiness correlated with less anxiety. DISCUSSION: This study found that age, higher education, and stable relationship status were associated with higher measures of transition readiness. There was a correlation found between more transition readiness and less anxiety surrounding transition. This finding can be used to inform future research and emphasizes the need for multidisciplinary support throughout the transition process. CONCLUSION: Early discussion of transition of care and education around transition readiness are not the only solution to improving transition success. The second phase of ADHERENT seeks to understand the patient experience and to include adolescents and young adults in shaping effective healthcare transition strategies.

Humans↗

PubMed2026

Cleavage region organizes the structural architecture of the SINE-derived B2 repressive ribozyme.

The SINE-encoded B2 retrotransposon is an RNA Polymerase III (POL-III)-derived transcript whose expression is substantially upregulated during various cellular stress responses. Beyond retrotransposition, the B2 non-coding RNA can directly bind and repress the activity of RNA Polymerase II (POL-II), leading to a significant downregulation of transcripts during stress. Notably, our recent findings have shown that B2 is a self-cleaving ribozyme whose activity can be induced by interactions with chromatin-modifying factors through non-canonical epigenetic mechanisms that co-regulate its function across distinct chromatin-binding target loci. Here, by integrating RNA chemical probing, small-angle X-ray scattering, and 3D motif modeling, we determine structural ensemble-to-function relations for the B2 SINE ribozyme RNA. Genetic perturbations of the RNA suggest that the B2 SINE ribozyme has a well-defined secondary and dynamic tertiary structure that depends on the integrity of the critical region, which confers ribozymatic activity and repressive extent by POL-II. Using an RNA engineering approach, we examine the effects of point mutations, deletions of the main cleavage site, and deletions of the cleavage domain on the structural ensemble of the RNA. Combining this approach with in vitro and in vivo functional perturbation methods highlights the relationships between structural ensembles and various biologically relevant functional outcomes.

RNA, Catalytic↗

PubMed2025

A randomized controlled trial to unveil the influence of an exercise intervention on brain integrity and gut microbiome structure in individuals with HIV.

OBJECTIVE: Exercise intervention programs enhance physical fitness, cognition, neuroimaging measures, and alter the structure of the gut microbiome in individuals without HIV. However, interventional studies exploring the effects of exercise in persons with HIV (PWH) have not included neuroimaging or gut microbiome analyses. DESIGN: A randomized controlled trial conducted at Washington University in St. Louis, MO, USA. METHODS: 65 PWH (aged ≥40 years, self-reported sedentary lifestyle) were randomly assigned to a 6-month cardiorespiratory and resistance training (EXS) or stretching control (SIS) intervention in a 2 : 1 ratio. Longitudinal change in cognition, cerebral blood flow (CBF), physical and cardiorespiratory fitness, and gut microbiome diversity and composition were examined among participants ( n  = 62) who completed any portion of the intervention (ClinicalTrials.gov: NCT02663934). RESULTS: Better fitness and better cognitive performance were associated with greater phylogenetic diversity in gut microbiome composition at baseline. Longitudinal findings indicated slight but significant improvements in psychomotor speed and executive function, reductions in body mass index, improvements in physical fitness, and increased gut microbiome diversity. These changes were observed regardless of assigned intervention group. There were no observed changes in CBF for either group. CONCLUSIONS: These findings highlight physical fitness as a modifiable factor in PWH that may improve cognitive performance and change gut microbiome composition. Both interventions were beneficial, suggesting light stretching exercise or study participation alone could have been sufficient to introduce positive cognitive shifts in previously sedentary PWH. Longer interventions with more participants are needed to identify changes in neuroimaging metrics related to brain integrity.

Humans↗

PubMed2026

The effect of antiretroviral therapy adherence on viral load suppression rate among people living with HIV in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: Antiretroviral therapy (ART) adherence is a key determinant of viral load suppression among people living with HIV (PLHIV). In Ethiopia, evidence on the magnitude of ART adherence and its effect on virological outcomes remains fragmented. This systematic review and meta-analysis aimed to estimate the pooled prevalence of ART adherence and viral load suppression, and to measure the association between adherence and viral suppression among PLHIV in Ethiopia. METHODS: This systematic review and meta-analysis used the PRISMA checklist for systematic reviews and meta-analyses. The review protocol has been registered onPROSPERO:(CRD420251125899). PubMed, ScienceDirect, Scopus, Epistemonikos, and Google Scholar were searched. The quality of included articles has been evaluated with a Newcastle-Ottawa Scale (NOS), adapted for observational studies. A random-effects model using restricted maximum likelihood (REML) with Knapp-Hartung adjustment was used to estimate pooled prevalence and odds ratio. Heterogeneity was assessed using I2, τ2, and Cochran's Q test. RESULTS: A total of 39 studies were included in the final analysis. The pooled prevalence of good ART adherence was 79.4% (95% CI: 74.8%-83.4%), while the pooled viral load suppression rate was 77.5% (95% CI: 72.5%-81.8%). The pooled odds ratio showed that good ART adherence was strongly associated with viral load suppression (OR = 6.30, 95% CI: 4.84-8.19). Substantial heterogeneity was observed across studies for both adherence and viral suppression outcomes (I2 > 90%). CONCLUSIONS: ART adherence and viral load suppression among PLHIV in Ethiopia are relatively high but remain below global targets. Good adherence was significantly associated with virologic suppression, highlighting adherence as a critical modifiable factor for achieving optimal treatment outcomes. Strengthening adherence support interventions is essential to improve virological success and advance progress toward HIV epidemic control.

Humans↗