This study assessed the risk of cardiovascular diseases (CVD) at various stages in women with gestational diabetes mellitus (GDM) and aimed to identify critical time points when the risk increases. Fifteen cohort studies including a total of 7,515,168 pregnant women were analyzed, among whom 429,564 had GDM and 13,773 developed CVD. Participants were grouped based on follow-up periods of approximately 5, 10, 15, and 25 years. Using random effects models, pooled hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Within five years of diagnosis, women with GDM had a 19% higher risk of CVD (HR 1.19, 95% CI 1.11-1.27) compared to those without GDM, rising to 78% by the tenth year (HR 1.78, 95% CI 1.67-1.89). Long-term follow-up showed risk increases of 31% at 15 years (HR 1.31, 95% CI 1.28-1.35) and 26% at 25 years (HR 1.26, 95% CI 1.16-1.38). Overall, women with GDM had a 35% higher risk of developing CVD than those without (HR 1.35, 95% CI 1.32-1.38). These findings highlight that GDM significantly elevates the risk of cardiovascular diseases, particularly within ten years after diagnosis, emphasizing the need for timely intervention and ongoing monitoring to reduce cardiovascular risk in affected women.

BackgroundIndividuals with type 2 diabetes (T2D) experience epigenetic age acceleration (EAA), as described by DNA methylation based epigenetic clocks. It is critical to examine relationships between social determinants of health (SDOH) and EAA in people living with T2D to understand mechanisms interconnecting social and biologic drivers of health disparities. The purpose of this systematic review was to describe the role of SDOH as factors influencing EAA in T2D.MethodsPubMed, CINAHL, and Embase were comprehensively searched. Research reports were independently screened and abstracted; quality was assessed using JBI checklists. The Healthy People 2030 SDOH Framework guided this study. Domains of SDOH were benchmarked against the framework to identify roles and gaps.ResultsOf 25 included research reports which evaluated epigenetic aging in T2D, 64% describe at least one SDOH. SDOHs within education access and quality (44%), neighborhood and built environment (40%), and economic stability (36%) domains are the most well represented; however, the depth and breadth of conceptual understanding were limited. Concepts representative of SDOH including childhood low socioeconomic status and victimization, trauma, and lower education and income were positively associated with EAA in T2D.DiscussionWhile SDOH are increasingly included in studies of EAA in people with T2D, critical gaps in understanding the roles and relationships between SDOH and EAA were revealed. Findings support the need to move further than socioeconomic status to comprehensively explore SDOH domains influencing EAA in individuals living with T2D, which will provide a framework for identifying health inequities.

: Chemotherapy-induced nausea and vomiting (CINV) represent prevalent and distressing adverse effects among cancer patients, substantially compromising treatment compliance and quality of life. This systematic review and meta-analysis evaluate the therapeutic efficacy of aromatherapy in managing CINV, with the objective of informing evidence-based clinical decision-making in supportive cancer care. : We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) assessing aromatherapy's effects on CINV. Two reviewers independently screened studies, extracted data, and evaluated bias risk. Meta-analysis was performed using RevMan 5.4, with outcomes expressed as odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs). : Twelve RCTs (n = 1,572) were included. Aromatherapy significantly reduced acute nausea (OR = 0.46, 95% CI 0.29-0.73), acute vomiting (OR = 0.56, 95% CI 0.40-0.79), and delayed nausea (OR = 0.64, 95% CI 0.47-0.88). However, no significant effects were observed for delayed vomiting (OR = 0.72, 95% CI 0.39-1.34), VAS scores (MD = -1.30, 95% CI -2.76-0.16), or INVR scores (MD = -1.67, 95% CI -3.67-0.32). No publication bias was detected ( > 0.05). : The existing body of evidence suggests that aromatherapy may function as a valuable adjunctive therapy in mitigating chemotherapy-induced nausea, especially during the acute phase. Nevertheless, its efficacy in managing vomiting and symptoms in the delayed phase remains uncertain. Future research efforts should focus on conducting large-scale, methodologically robust RCTs that employ standardized aromatherapy protocols and incorporate longitudinal assessments of outcomes and understanding the biological mechanisms associated with aromatherapy therapeutic effects.

: Middle-aged adults experience degenerative aging-related changes, often differing by sex. Research identifying sex-specific factors contributing to biological aging among middle-aged adults remains limited. This study aimed to identify sex-specific factors influencing GrimAge acceleration (GrimAA), a DNA methylation-based estimator of biological aging, among middle-aged Korean adults. : Data were derived from the Korean Genome and Epidemiology Study (KoGES) cohort involving 686 middle-aged adults (422 men and 264 women). GrimAA was calculated from DNA methylation data using the GrimAge epigenetic clock. Demographic, lifestyle, clinical, and psychosocial stress variables were assessed, and sex-specific factors influencing GrimAA were identified through hierarchical multiple regression models. : In men, higher GrimAA was significantly associated with current smoking, current drinking, physical inactivity, and elevated Hs-CRP or HbA1C levels, whereas among women, early menopause (<50 years) emerged as a notable factor related to increased GrimAA. Hierarchical regression analyses revealed that chronological age, current smoking, and Hs-CRP were robust predictors of GrimAA in men, whereas GrimAA in women was significantly predicted by current smoking and Hs-CRP. : Sex differences in GrimAA may result from the interplay of lifestyle behaviors, inflammatory biomarkers, and hormonal factors. Targeted interventions addressing these sex-specific determinants could be effective strategies to mitigate biological aging acceleration among middle-aged adults.

Biomarkers may complement patient-reported outcomes by providing objective insight into the multidimensional nature of chronic pain. The urine metabolite pain indicator (UMPI), a composite of four urine metabolites, has previously demonstrated cross-sectional associations with pain-related symptoms; however, it is unclear whether these associations are consistent over time. This study evaluated whether the UMPI and its individual metabolites remain associated with chronic pain outcomes following intervention, which would support its potential as a monitoring biomarker. A secondary analysis of a pragmatic clinical trial, where 148 active-duty service members with chronic pain provided urine samples and completed 11 self-reported outcome measures at baseline and 6-week follow-up after either a complementary and integrative health or a standard rehabilitative care pain intervention. Associations were examined using linear regression and mixed models. The UMPI remained significantly associated with physical function and overall pain impact post-intervention. Ethylmalonic acid showed associations with fatigue, anger, and physical function. Notably, methylmalonate, while not significant at baseline, had the most robust association with pain post-intervention, including significant correlations with both physical function and pain impact. Kynurenic acid was associated with sleep-related impairment. Pyroglutamic acid showed no significant adjusted associations. No statistically significant differences in metabolite and symptom correlations were found between time points, suggesting that these associations remained consistent over the short term. The UMPI may serve as a reliable, noninvasive index biomarker for tracking chronic pain burden, particularly physical outcomes. Findings support integrating the UMPI into biologically informed chronic pain assessment.

Perimenopausal and postmenopausal women commonly experience vasomotor symptoms, bone loss, and mental health challenges that diminish quality of life (QoL). Although Traditional Chinese Exercise (TCE) has shown benefits in alleviating certain menopausal symptoms, its overall effects on health-related outcomes remain controversial. This study aimed to systematically analyze the effects of TCE on menopausal symptoms, bone health, and mental health in perimenopausal and postmenopausal women. A systematic search was conducted across 7 databases through April 2025 for randomized controlled trials (RCTs) investigating the effects of TCE in perimenopausal and postmenopausal women. Risk of bias was assessed using the Cochrane Risk of Bias Tool 2 (RoB 2). Stata 17.0 was used for meta-analysis, with pooled outcomes reported as standardized or mean differences (SMD/MD) with 95% confidence intervals (CIs). Twelve RCTs involving 1,023 participants were included. Meta-analysis showed that TCE significantly reduced menopausal symptoms (SMD = -0.82, 95% CI: -1.41 to -0.22), and depression (SMD = -1.73, 95% CI: -2.49 to -0.98). TCE also improved spine BMD (MD = 0.05, 95% CI: 0.02 to 0.08). For upper limb, thigh, pelvis, trunk, and whole-body BMD, effects remained uncertain due to the limited number of studies. Three studies assessed QoL, and pooled results showed no significant improvement in physical (MD = 4.52, 95% CI: -2.93 to 11.97) or mental component scores (MD = 3.28, 95% CI: -3.67 to 10.23). TCE appears to be an effective intervention for menopausal symptoms, spine BMD, and depression. However, its effects on QoL and other skeletal sites remain inconclusive. Larger, high-quality RCTs are warranted to clarify optimal protocols and long-term benefits.

This paper provides an overview of methods for measuring genetic ancestry, specifically focusing on applications for nurses engaged in research. We describe methods and current tools widely implemented by the research community to introduce nurses who conduct research in the landscape of measuring genetic admixture for individuals and genetic substructure for populations. The intended impact of this paper is to enhance awareness and understanding of the importance of measuring genetic ancestry to control for latent confounding in genetic association studies. Measurement of genetic ancestry can prevent confounding in genetic association studies. Nurses approach health from a holistic perspective that includes information about individual, environmental, and social factors. This framework necessitates consideration of individual genetic characteristics and social identity and position. This paper serves as a primer on concepts related to genetic ancestry, including ancestry informative markers, reference populations, and statistical approaches, that nurses engaged in research may incorporate into their study design and implementation.

To evaluate the effects of aerobic, resistance, and combined training on cardiorespiratory fitness in healthy older adults, with a focus on improvements in maximal/peak oxygen uptake (VOmax/peak) and the 6-min walk distance (6-MWD). A systematic review and meta-analysis were conducted through July 2024, searching six databases: PubMed, CINAHL, Medline, Embase, Web of Science, and Scopus. Analyses were performed using Review Manager 5.3. Fifty-one studies involving 3152 participants met the inclusion criteria. Exercise interventions significantly improved VOmax/peak (standardized mean difference (SMD): 0.51; 95% confidence interval (CI), 0.38 to 0.65; < .001) and 6-MWD (MD: 36.18 m; 95% CI, 26.52 to 45.84; < .001) compared to control groups. Subgroup analyses showed consistent benefits across aerobic, resistance, and combined training modalities. Significant improvements were also observed across both medium-term (≤24 weeks) and long-term (>24 weeks) interventions, and in both male and female participants. Structured exercise interventions, regardless of type, are effective for improving cardiorespiratory fitness in older adults. The consistency of these effects across modalities, durations, and sexes underscores the adaptability and value of exercise as a central component of healthy aging strategies. Future research should aim to standardize intervention protocols and extend follow-up periods to clarify long-term outcomes and inform clinical guidelines.

There is growing evidence that psychological (e.g., optimism, pessimism, depressive symptoms) and biological factors play an essential role in the experience of chronic low back pain (CLBP). This study aimed to examine the nature of the relationship between optimism or pessimism, depressive symptoms, the pace of biological aging, CLBP severity, and interference. Using mediation analysis, we tested the hypothesis that depressive symptoms and pace of biological aging measured using the Dunedin Pace of Aging from the Epigenome (DunedinPACE) serially mediate the relationship between optimism or pessimism and CLBP severity and interference. Our sample included non-Hispanic Black and non-Hispanic White adults aged 18-82 years: 74 without pain, 56 with low-impact pain, and 77 with high-impact pain. On average, individuals with high-impact pain reported lower levels of optimism, greater pessimism, and faster DunedinPACE than those in the low-impact or no-pain group ( < .05). Mediation analyses revealed indirect associations between both optimism and pessimism with pain severity and interference serially via depressive symptoms and the pace of biological aging ( < .05). These indirect effects were not statistically significant after controlling for chronological age, sex, race, and BMI. The results suggest that psychological interventions that increase optimism and reduce pessimism may slow the biological aging process, which may improve nonspecific CLBP outcomes in non-Hispanic Black and non-Hispanic White adults.

People with HIV (PWH) are at risk of developing HIV-related comorbidities, such as cardiovascular disease (CVD), which appears independent of combination antiretroviral therapy (cART). Angiopoietin (ANG) has been associated with vascular augmentation (i.e., arterial stiffness) in response to both human immunodeficiency virus (HIV) and alcohol use, but their combined health effects are not well understood. This study assessed data from the WiseApp study, examining ANG-1/ANG-2 blood serum levels and alcohol consumption in 109 adults with HIV at baseline. Alcohol consumption was measured using the Alcohol Use Disorders Identification Test - Concise (AUDIT-C) measure, and ANG-1 and ANG-2 levels were measured using high sensitivity Enzyme-Linked Immunoassay (ELISA) kits. Generalized linear mixed model analysis was used to explore the effect of alcohol consumption on angiopoietin levels in PWH, adjusting for demographic variables. Alcohol consumption was not significantly associated with either ANG-1 or ANG-2 serum levels in our sample. However, CD4 serum levels were significantly correlated with both ANG-1 and 2, with a positive association for ANG-1 and negative associations for ANG-2. Additionally, demographic factors, including gender identity, sexual identity, and race, were significantly associated with ANG-2 levels but not ANG-1 levels. These findings underscore the complex interplay between immune function, vascular regulation, and demographic characteristics in persons with HIV. Future research should explore these relationships in larger and more diverse cohorts, incorporating longitudinal analyses to better understand the temporal dynamics of alcohol use, immune status, and endothelial function.

Adults of childbearing age have the highest rate of electronic cigarette (e-cigarette) use in the United States. Users perceive passive e-cigarette vapor exposure to be less harmful than passive conventional cigarette smoke exposure. We conducted a systematic review to understand the risks of passive e-cigarette vapor exposure in children. Data sources included PubMed, CINAHL, Web of Science, and Scopus. Eligibility criteria included studies published between 2010 and 2024 with (1) children ages 0-18 or animal models representing children and in vitro studies, (2) descriptive, experimental, and qualitative designs, and (3) a focus on passive e-cigarette vapor exposure. Two independent reviewers screened studies, with a third for arbitration. Thirty-three studies were included in this review. Emerging evidence, primarily from animal studies, suggests that passive e-cigarette vapor exposure is associated with poor respiratory, immunological, physical growth, and neurological effects. Air assessments noted increased particulate matter and concentrations of nicotine, metals, and volatile organic compounds. Parents were more likely to use e-cigarettes than non-parents, and a majority reported use in the home and car. Risk of bias assessment indicated that 23 of the 33 studies were rated as weak, highlighting methodological limitations in the current evidence base. More rigorously designed studies are needed to strengthen the evidence base. Passive e-cigarette vapor exposure may be harmful to children, and many parents seem unaware of this potential threat. Parents should be cautioned to minimize exposure until more is known.

To identify single nucleotide polymorphisms (SNPs) associated with cardiovascular disease (CVD) and examine the association of genetic and lifestyle factors using data from the Korean Genome and Epidemiology Study (KoGES). A secondary analysis was conducted using Phase 1 data from the Health Examinee (HEXA) cohort, including 26,546 participants (1,919 with CVD and 24,627 controls). Sex-stratified analyses were performed on 17,390 females and 9,156 males. SNPs associated with CVD were identified using PLINK 1.9, and logistic regression models were used to assess associations between CVD and genetic, demographic, and lifestyle factors in IBM SPSS Statistics 27.0. Three SNPs (rs8086325, rs34233878, rs218463) were significantly associated with CVD in the overall sample. In males, rs79682491, rs2540719, and rs2576541 showed significant associations, while in females, rs76830381, rs6496602, rs8086325, and rs34233878 were identified. In multivariate analyses, age ≥60 (OR = 15.56), BMI ≥30 (OR = 4.74), male sex, smoking, low protein intake, low income, and selected SNPs were significantly associated with CVD risk. This study underscores the multifactorial nature of CVD risk, highlighting the joint association of genetic, behavioral, and demographic factors. The observed sex-specific genetic associations reinforce the need for personalized prevention strategies. Nurses are well-positioned to lead efforts in implementing sex-sensitive, genomics-informed approaches to reduce CVD risk and promote cardiovascular health.

Psychosocial stressors are linked with declined physical and psychological health, and short telomere length (TL). While positive social interactions have been linked to improved postpartum physical and mental health, little research has explored the longitudinal effects of psychosocial stressors and telomere dynamics in the sensitive postpartum period. This study aimed to examine the effect of positive and negative social interactions on TL among first-time mothers during the first year postpartum. A cohort of 103 first-time mothers from Northern Israel completed validated measures assessing social support, marital satisfaction, and depressive symptoms, and provided blood samples for leukocyte TL analysis. Hierarchical linear and logistic regressions, adjusting for covariates, examined the association between social interactions and change in TL. We observed three patterns of telomere dynamics over the year: telomere shortening, moderate telomere lengthening, and relatively high telomere lengthening in the lower, medium, and upper tertiles of change in TL, respectively, used as our categorical outcome. Hierarchical logistic regressions analyses revealed that mothers with higher marital satisfaction had a 4-fold greater likelihood of substantial telomere lengthening (OR = 3.997, 95%CI [1.345, 11.876] .013), remaining significant after correction for multiple comparisons. Negative social interactions showed initial associations (OR = 0.332, 95%CI [0.114, 0.971] .044) but did not maintain significance after multiple comparison adjustment. Marital satisfaction showed a robust association with telomere lengthening postpartum, representing the most consistent finding. Social relationships, particularly intimate partnership quality, may be important in the postpartum period, not just for mental health but for biological aging indices.

The hemoglobin-albumin-lymphocyte-platelet (HALP) index, a composite marker reflecting nutritional, inflammatory, and immune status, has been linked to various health outcomes. However, its role in predicting deep vein thrombosis (DVT) occurrence in stroke patients and its potential influence on coagulation biomarkers, particularly D-dimer, remain poorly understood. This study aims to investigate the association between the HALP index and the occurrence of DVT in stroke patients, exploring the potential moderating role of HALP in regulating D-dimer levels and DVT formation. A retrospective study was conducted with 611 stroke patients, categorized into quartiles based on HALP scores. Multivariate logistic regression, restricted cubic spline (RCS) analysis, and subgroup analyses stratified by age, gender, body mass index (BMI), and D-dimer levels were performed to assess the relationship between HALP and DVT. Moderation analysis was used to explore the regulatory effect of HALP on D-dimer levels. HALP levels were inversely associated with DVT occurrence. Patients in higher HALP quartiles (Q3: 33.40-47.93, Q4: 47.93-152.58) exhibited significantly lower odds of DVT ( .001). RCS modeling identified a threshold effect, with a sharp increase in DVT occurrence below a HALP level of 33.5. Subgroup analyses revealed that the protective association of higher HALP scores with reduced DVT incidence was consistent across all age groups and was significant in patients with both low and high D-dimer levels. This protective association was particularly strong in males (OR = 0.148) and overweight patients (OR = 0.089). The interaction between HALP and D-dimer was significant ( .001), with HALP moderating the association between D-dimer and DVT occurrence. HALP is a strong, independent predictor of post-stroke DVT and moderates the prothrombotic impact of D-dimer. As a low-cost, integrative marker, HALP offers clinical value for early DVT occurrence stratification and individualized prevention strategies in stroke patients.

This research intends to provide a comprehensive review of existing literature on sleep within the nursing field, employing bibliometric methods. A comprehensive analysis of the available literature concerning sleep in nursing was carried out through the Web of Science Core Collection (WoSCC) on October 20, 2025. The search terms "sleep" and "nursing" played a crucial role in identifying relevant research studies. VOSviewer was applied for bibliometric analysis and visualization to identify authors, journals, countries and display the keyword co-occurrence networks. A total of 2.456 publications focused on the topic of sleep were identified from 1991 to 2025. The dataset comprised predominantly research articles (2.296, 93.5%). These publications appeared in a total of 191 distinct academic journals and collectively received 103,025 citations over the analyzed period. The number of publications increased by an average of 6.83 units per year during the observed period (R = 0.9622; p < 0.001). In the keyword co-occurrence network, "sleep," "sleep quality," and "nursing" keywords the highest frequency. The Journal of Clinical Nursing exhibited the highest publication output with 109 articles. The United States accounted for the largest share of publications. Development and Adaptation of Sleep Instruments in Nursing was performed on 14 measurement tools. This bibliometric study revealed the research points and trends in the field of sleep in nursing research. Future research should aim to strengthen international collaboration among nurse researchers, leveraging artificial intelligence tools and wearable technologies to effectively address sleep-related issues and enhance sleep quality.

Glycemic variability and its management hold significant prognostic implications in clinical practice for patient outcomes. The aim of this study is to analyze the correlation between glycemic variability and the deterioration of neurological function in patients with intracerebral hemorrhage (ICH), to provide evidence-based support for the treatment and care of clinical ICH patients. Patients with ICH admitted to our hospital between January 2022 and August 2024 were subjected to the National Institutes of Health Stroke Scale (NIHSS) scoring upon admission and discharge. A comparative analysis of baseline characteristics and glycemic variability parameters was conducted. A total of 156 patients with ICH were included. The incidence of neurological deterioration in ICH patients was 30.8%. Correlation analysis revealed significant associations between age (r = 0.602), mean glucose levels (r = 0.623), Time in Range (TIR) (r = 0.589), Mean Amplitude of Glycemic Excursions (MAGE) (r = 0.608), and Large Amplitude of Glycemic Excursions (LAGE) (r = 0.634) with the occurrence of neurological deterioration. Logistic regression analysis identified age (OR = 2.512, 95%CI: 1.924-3.006), mean glucose (OR = 2.743, 95%CI: 2.101-3.286), TIR (OR = 3.204, 95%CI: 2.985-3.607), MAGE (OR = 3.029, 95%CI: 2.601-3.748), and LAGE (OR = 2.768, 95%CI: 2.245-3.103) as significant predictors of neurological deterioration in ICH patients. This finding underscores the critical importance of considering both chronological age and glycemic control metrics in the prognostic evaluation of ICH patients. Integrating these factors into clinical assessments may enhance the accuracy of predicting patient outcomes and guide tailored therapeutic strategies.

DNA methylation (DNAm) is an epigenetic process of addition or reduction of methyl groups to genes that modify gene expression and can alter the physiological response to psychological stress. DNAm associated with psychological stress is malleable, making it a prime target for psychobehavioral interventions. Research is beginning to examine changes in DNAm in response to psychobehavioral interventions, such as mindfulness-based stress reduction, cognitive behavioral therapy, and yoga. A better understanding of the current evidence may provide direction for future research. The purpose of this scoping review is to summarize current studies, identify knowledge gaps, and make recommendations for further research related to examining alterations in DNAm in response to psychobehavioral interventions. A scoping review was conducted based on the methods recommended by Arksey and O'Malley (2005). Studies examining response of blood or saliva DNAm to psychobehavioral interventions in adult humans were reviewed. Twenty-one studies met the inclusion criteria. Although many studies were inadequately powered, several reported differences in DNAm in response to a psychobehavioral intervention across a variety of genes, including genes related to stress and inflammation. However, the studies varied with respect to participant health status, type and duration of psychobehavioral interventions evaluated, biospecimens examined, and method of DNA analysis. The evaluation of DNAm in response to psychobehavioral interventions is a growing area of research. Future research is needed to address design limitations of existing investigations, evaluate the biological importance of observations, and link the DNAm response to physiological and psychological outcomes of the interventions.

Most infants are diagnosed with hyperbilirubinemia in the first day of life. Although phototherapy is the most common treatment used in hyperbilirubinemia, different alternative therapies such as massage are also used. This systematic review and meta-analysis was designed to evaluate the effect of massage on serum bilirubin levels, defecation frequency, and length of hospital stay in neonates with hyperbilirubinemia receiving phototherapy. A review of randomized controlled trials published in English from 2008 to November 2023 was conducted using PubMed-Medline, Academic Search Ultimate-EBSCOhost, Web of Science, and Scopus databases. From 217 identified trials, six randomized controlled studies were included, with a total sample of 394 term infants. Infant massage was effective in increasing defecation frequency (MD: 0.52, 95% CI: Min: 0.29- Max: 0.76, 0.0001), reducing serum bilirubin levels on the 3rd and 4th days (MD: -1.19, 95% CI: Min: -1.50- Max: -0.89, 0.0001) (MD:-2.33, 95% CI: Min: -2.88- Max: -1.79, 0.0001), and shortening hospital stay (MD:-13.66, 95% CI: Min: -16.74- Max: -10.59, 0.0001). This systematic review and meta-analysis suggest that infant massage is a safe and effective intervention for term neonates with hyperbilirubinemia, contributing to a shorter hospital stay by lowering serum bilirubin levels and increasing defecation frequency.

In this study, we aimed to investigate if the pace of biological aging serves as a critical mediator in the relationship between chronic pain resilience and chronic low back pain intensity and disability. Two hundred seven community-dwelling non-Hispanic Black (NHB) and non-Hispanic White (NHW) adults completed the Pain Resilience Scale (PRS) and Graded Chronic Pain Scale (GCPS). Blood genomic DNA was sequenced using Illumina's MethylationEPIC, and the pace of biological aging estimated using the DunedinPACE (the Dunedin Pace of Aging Calculated from the Epigenome) algorithm. In bivariate correlations, DunedinPACE significantly correlated with pain intensity (r = 0.40), and disability (r = 0.39), at .05. Pain resilience negatively correlated with pain intensity (rs = -0.22), pain disability (rs = -0.30), and DunedinPACE (r = -0.11). After controlling for chronological age, sex, race, and BMI, mediation analyses revealed a significant indirect association of pain resilience on pain intensity through the pace of biological aging (β = -0.66 (SE); Boot 95% CI [-1.06, -0.25]). Similarly, DunedinPACE partially mediated the relationship between resilience and pain disability (β = -0.82; 95% CI, [-1.20 to -0.44]). We found that higher levels of resilience correlate with a slower pace of biological aging, which in turn correlates with better pain outcomes. The pace of biological aging emerged as an important potential target for future interventions studies for pain management.

Frailty and chronic pain are closely related, but the causal relationship between them needs to be further explored with high-level evidence. Mendelian randomization (MR) was used to analyse the bidirectional causal relationship between nine chronic pain disorders and two frailty indicators in this study. We used Causal Analysis Using Summary Effect Estimates (CAUSE) as the primary method of analysis. The inverse-variance-weighted, simple model, weighted model, penalized weighted median and MR‒Egger regression methods were used to evaluate the robustness of the results. The frailty index (FI) was significantly associated with the number of chronic pain sites (multisite chronic pain, MCP, < .001) and the risk of chronic widespread pain (CWP, < .001). The Fried frailty score (FFS) was significantly associated with MCP ( < .001), the risk of CWP ( < .001) and chronic back pain ( = .031). In the reverse analysis, both MCP and CWP were significantly positively associated with the FI ( < .001; = .003) and FFS ( < .001; = .009). This study revealed a bidirectional causal relationship between frailty and chronic pain, with the number of pain sites playing a key role. This finding has significant implications for effectively managing frailty and chronic pain in older adults.

DNA methylation affects gene expression. While the Apolipoprotein E () genotype impacts cardiovascular risk, methylation impact remains unknown, particularly in women with breast cancer (BC). This study explored associations of methylation with hypertension history and cardiovascular fitness (CVF) and whether genotype and methylation moderate exercise effects over 6 months. This study leveraged data from a 6-month exercise randomized clinical trial in postmenopausal women with BC. Using peripheral blood, methylation M-values (Illumina Infinium Methylation EPIC Beadchip) and 13 CpG sites within and 2kb 5' and 3' to were abstracted post data quality checks. Outcome variables: self-reported hypertension and CVF (peak oxygen consumed per kilogram per minute [VOmax/kg/min] and peak metabolic equivalents [METs] through graded exercise testing). Participants completed 150 min/week of aerobic exercise or usual care for 6 months. Logistic and linear regression examined associations between CpG M-values and hypertension, VOmax/kg/min and METs. Baseline M-value and genotype were interaction terms for longitudinal analyses. This study included 102 women (Mean = 62 yrs). ε4 carriers had increased methylation of cg06750524 ( 0.04) and cg19514613 ( 0.03), but lower methylation of cg21879725 ( 0.04). Increased cg06750524 methylation was associated with higher hypertension odds ( 0.022, OR = 2.813) and lower VOmax/kg/min and METs ( 0.005). Increased cg05501958 methylation (M = 4.539, SD = 0.17) was associated with lower hypertension odds ( 0.02, OR = 0.035) and higher VOmax/kg/min and METs ( 0.022). Neither nor baseline methylation moderated exercise effects. methylation, differentially by ε4 carriage, may impact cardiovascular outcomes and serve as a biomarker of risk in women with BC.