Aging

Background Cardiovascular-kidney-metabolic (CKM) syndrome integrates adiposity, metabolic risk, kidney dysfunction, and cardiovascular disease in a prevention-oriented framework. National estimates across 1999-2023 NHANES and future burden remain limited. Methods We analyzed US adults aged 20 years from 11 NHANES cycles, 1999-2000 through August 2021-August 2023. CKM stage 0-4 was assigned using harmonized examination, laboratory, medication, and questionnaire data. Prevalence was survey-weighted and standardized to the 2010 US Census adult population. Decade trends used survey-weighted logistic regression adjusted for age, sex, and race and ethnicity. Exploratory 2040 and 2050 projections combined NHANES prevalence models with US Census projections under population-aging-only, trend-continuation, and risk-improvement scenarios. Results Among 62,890 eligible adults, 62,888 had sufficient CKM data. In 2021-2023, age-standardized prevalence was 87.9% (95% CI, 86.5%-89.4%) for CKM stage 1 and 62.0% (95% CI, 60.1%-63.8%) for stages 2-4. Stage 2 accounted for 50.1% (95% CI, 48.2%-51.9%) and stages 3-4 for 11.9% (95% CI, 11.0%-12.7%). From 1999-2000 to 2021-2023, any CKM increased by 4.6 percentage points (95% CI, 2.4 to 6.9; P<0.001), whereas stages 2-4 changed by 2.1 percentage points (95% CI, 5.1 to 0.8; P=0.156). In adjusted decade models, any CKM increased (OR, 1.28; 95% CI, 1.19-1.38; P<0.001), while stages 2-4 showed no significant linear trend (OR, 0.95; 95% CI, 0.89-1.01; P=0.084). Excess adiposity and diabetes increased, dyslipidemia declined, and hypertension, chronic kidney disease, and clinical cardiovascular disease were stable. With population aging alone, projected stages 2-4 burden rose from 164.8 million adults in 2023 to 193.7 million in 2050; under risk improvement, it was 147.7 million. Conclusions CKM syndrome remained highly prevalent among US adults. Although later stages did not increase significantly, population aging may expand the absolute care burden unless broad risk improvement occurs.

Background: It is an everyday observation that people of the same chronological age differ with respect to their physical and mental capacity. However, assessing these differences in biological age remains challenging. Methods: Here, we aggregate 89 age-associated variables from the Berlin Aging Study II (BASE-II, n=1,631) to generate MultiAge, a new marker of biological age that summarizes information from ten domains reflecting organ health and global biological age. We then used methylation data obtained from an Illumina MethylationEPIC array and supervised machine learning to translate MultiAge into a DNA methylation signature, MultiAgeEpi (309 CpGs), which was subsequently validated in four independent external validation cohorts (KORA FF4, KORA Age, SHIP-TREND, BiDirect, total n=4,339). MultiAgeEpi results were compared with previously published epigenetic clocks (GrimAge, DunedinPACE, SystemsAge). Results: We report that MultiAgeEpi showed similar, and in several cases, stronger associations with age-associated outcomes such as diabetes, metabolic syndrome, multimorbidity, frailty and mortality (q < 0.05) compared to the other clocks. Conclusions: MultiAge and MultiAgeEpi thus provide a comprehensive assessment of biological age through aggregation of numerous age-associated variables and the use of the high-resolution methylomics data makes transfer of this marker to other cohorts possible.

Postoperative resilience varies widely among older adults, yet the biological drivers of recovery remain unclear. We evaluated whether preoperative immune profiles, measured in plasma and through ex vivo whole blood stimulation, predict resilience to the acute stress of total knee arthroplasty. A total of 152 adults (greater or equal to 60 years) in the PRIME KNEE cohort underwent elective total knee arthroplasty and had available blood samples for measurement of 45 immune biomarkers, quantified in plasma and in whole blood stimulated ex vivo for 24 hours with lipopolysaccharide (LPS) or influenza antigen (FLU). Resilience was assessed using Expected Recovery Differential (ERD) and Resilience Trajectory (RT) across pain severity, pain interference, lower extremity physical activities of daily living (LE PADLs), and step counts. An exploratory stability selection framework using LASSO identified biomarker predictors of postoperative outcomes. Plasma and stimulated biomarkers showed broadly similar predictive performance. A shared set of biomarkers, including LBP, leptin, TNFR1, CD30, and LIF, was consistently selected across models. Immune predictors explained ~12-24% of the variance in resilience outcomes. Distinct immune signatures emerged for pain versus functional recovery: pain related predictors mapped to local inflammatory and neuroimmune pathways, whereas function related predictors reflected systemic inflammatory load and cytokine signaling. Preoperative immune biomarkers, whether measured in plasma or after ex vivo stimulation, capture meaningful variance in postoperative resilience. The divergence between pain related and function related immune signatures highlights biologically distinct pathways underlying different dimensions of recovery and supports further development of immune based perioperative risk assessment.

Background and Objectives: Arts and cultural engagement may contribute to well-being in later life. However, evidence from longitudinal studies from Asia, including Japan, remains limited. This study examined the association of arts and cultural engagement with subsequent multidimensional well-being among older adults in Japan, one of the fastest-aging countries. Research Design and Methods: This longitudinal study used panel data from 354 individuals aged 60 and older (mean age 74.0 years; 78.6% women) who completed self-administered questionnaires by mail between 2022 and 2024. The PERMA-Profiler was used to assess five multifaceted aspects of psychological well-being: positive emotion, engagement, relationships, meaning, and accomplishment. Frequencies of arts and cultural engagement at baseline were measured for active (e.g., activities by individuals and participation in groups, such as music and painting) and receptive (e.g., visiting museums, galleries, and theaters) forms. Results: Multivariable linear regression analysis, adjusted for the covariates including baseline PERMA scores, showed that higher frequencies of active engagement were positively associated with higher PERMA scores for all domains. Higher frequencies of receptive engagement were associated with the domains of positive emotion, meaning, and accomplishment, but not clearly associated with engagement and relationships. Restricted cubic spline analyses suggested clearer positive frequency-response patterns for active engagement than for receptive engagement. Discussion and Implications: Arts and cultural engagement, both active and receptive forms, was associated with subsequent multiple aspects of well-being in later life. These findings suggest the importance of ensuring access to arts and cultural opportunities for older adults to create, participate, and connect.

Background: While genetic factors strongly influence brain aging trajectories, variants conferring cognitive resilience remain poorly characterized. The neurokinin-3 receptor (NK3-R), encoded by Tachykinin Receptor 3 (TACR3), modulates cholinergic signaling in memory circuits vulnerable to aging. Previous studies linked the non-WT expression of the TACR3 variant rs2765 with cognitive decline and reduced volume of the hippocampus and basal forebrain, but systematic replication and mechanistic validation were lacking. Methods: We investigated rs2765 in the preregistered AgeGain cohort of cognitively healthy older adults (n=188) with independent validation in the ADNI cohort (n=809) which includes persons with and without Alzheimers Disease (AD) that show healthy cognition, mild cognitive impairment or dementia. Analyses integrated structural neuroimaging, longitudinal cognitive assessments, epigenetic aging (PhenoAge), genome-wide methylation profiling, and mechanistic validation through luciferase assays and cross-species protein expression studies. Results: The infrequent protective rs2765 WT variant, found in 12.8% of Europeans, conferred 49% slower cognitive decline (p = 0.002) for amyloid-positive individuals of the ADNI cohort and 3.7 years younger epigenetic age (p = 0.013, 95% CI: 0.79-6.67 years) in the cognitively healthy AgeGain cohort. WT carriers showed larger hippocampal and basal forebrain volumes across cohorts, with Allen Brain Atlas integration revealing these outcomes to occur exclusively in regions where TACR3 expression positively correlated with gray matter volume. Mechanistically, the non-WT variant ameliorated RBMX-mediated post-transcriptional regulation, reducing NK3-R protein expression by 25-40% in vitro and ex vivo murine brain slice models. Senescence-accelerated mice exhibited reduced endogenous NK3-R expression, phenocopying the predicted functional consequences of the variant. In AgeGain participants, genome-wide methylation profiling identified 2,313 differentially methylated CpGs affecting 228 pathways spanning glutamatergic signaling, acetylcholine receptor pathways, chromatin remodeling, and angiogenesis, suggesting coordinated molecular reprogramming from synaptic function to systemic aging. Conclusions: rs2765 WT confers resilience to age- and AD-related cognitive decline through RBMX-dependent regulation of NK3-R expression, with effects of remarkable size cascading from memory to systemic aging. rs2765 genotyping could stratify individuals for NK3-R modulator therapy (e.g., fezolinetant or senktides) and identify those maintaining function despite pathological burden, complementing APOE-based risk assessment in precision geromedicine.

Background Low-level systemic inflammation has been associated with late-life depressive symptoms. Whether individuals with higher inflammation derive preventive benefit from low-dose aspirin therapy is unknown. Methods We performed a post-hoc analysis of the ASPiring in Reducing Events in the Elderly (ASPREE) randomised, double-blind, placebo-controlled trial. Baseline C-reactive protein (hsCRP) was measured in plasma and depressive symptoms were assessed annually using the Center for Epidemiologic Studies Depression 10 Scale with elevated symptoms defined as CES-D-10 >= 8. Participants with elevated depressive symptoms at baseline were excluded. We fitted population-averaged logistic generalised estimating equation models adjusted for baseline sociodemographic and lifestyle covariates, including an hsCRP x treatment interaction to test effect modification by aspirin. Results Higher baseline hsCRP was associated with increased odds of elevated depressive symptoms during follow-up (OR 1.07 per SD increase in hsCRP, 95% CI 1.03-1.11). Low-dose aspirin allocation did not modify the hsCRP-depressive symptoms association (interaction OR 1.02, 95% CI 0.94-1.10). Findings were similar after additional adjustment for comorbidity and other covariates. Conclusions In community-dwelling older adults during the ASPREE randomised trial period, higher baseline hsCRP was modestly associated with elevated depressive symptoms. There was no evidence that low-dose aspirin was associated with reduced risk of depressive symptoms among participants with higher baseline inflammation.

Background Slow walking in older adults with mild parkinsonian signs (MPS) is a complex, multifactorial phenomenon arising from the cumulative burden of subclinical age-associated pathologies. This decline reflects age-associated neuronal loss in the dopaminergic system. A recent study suggests that levodopa treatment may enhance gait parameters. The goal of this small pilot study is to explore the effect of levodopa treatment on slow walking gait in older adults with MPS. Method This study was a randomized, placebo-controlled clinical pilot trial. Slow walking older adults without clinical evidence of PD were recruited and randomized into 2 groups (active treatment group or placebo control group). Participants in the active group were pre-treated with carbidopa for three days, followed by carbidopa-levodopa for seven days. Spatiotemporal gait parameters were evaluated at baseline and post-intervention. Results Gait factor analysis identified three main factors explaining gait characteristics at baseline, which included gait efficiency, gait rhythmicity, and gait turning.No effect of treatment was observed in the placebo group (p=0.111, p=0.616), no group difference was observed between the placebo and active group at baseline ({beta}=0.310, p=0.547), but a strong trend for a treatment-related increase was observed in the active treatment group ({beta}=0.506, p=0.076). Conclusion Our preliminary data suggest that sustained levodopa treatment (one week) in conjunction with carbidopa pre-treatment and concomitant carbidopa supplementation is feasible in slow walking older adults with MPS. Moreover, the data indicate potential efficacy, showing improvements in cadence, and step durations.

OBJECTIVE: Bladder cancer (BC) is predominantly a disease of older, comorbid adults, and radical cystectomy (RC), which is the gold standard treatment, carries considerable morbidity. We sought to determine the impact of baseline dementia and frailty on the care trajectory beyond the immediate postoperative period. We hypothesized that frail patients and those with dementia undergoing RC for BC will have poorer care trajectories. METHODS AND MATERIALS: We identified Medicare beneficiaries [&ge;] 66 years old who underwent RC for BC in 2017 with 12 months of pre- and post-RC enrollment. Frailty and dementia were characterized using validated, claims-based measures. Associations between baseline frailty and dementia with postoperative care trajectory outcomes were determined using Fine-Gray competing risk models. RESULTS: We identified 3,600 beneficiaries of whom 11.6% were frail and 3.4% met criteria for dementia. Patients with dementia were more likely to be frail, comorbid, and not receive standard-of-care neoadjuvant chemotherapy. Frailty was independently associated with [&ge;] 2 transitions in care level after index discharge from RC and skilled nursing facility (SNF) admissions within 1 year of RC, exposure to intensive post-RC interventions, including dialysis and feeding tube placement, and poorer survival. Dementia remained associated with SNF admissions regardless of frailty level. CONCLUSIONS: Among a contemporary cohort of older adults undergoing RC for BC, preoperative dementia and frailty were independently associated with poorer care trajectory beyond the immediate postoperative period after RC. Our work highlights a role for preoperative geriatric assessment in identifying and optimizing patients at greatest risk.

Introduction Menopause is a central marker of reproductive ageing, but national evidence on menstrual cessation among Nigerian women in the late reproductive ages remains limited. This study examined the prevalence and socio-demographic correlates of prolonged amenorrhea/possible menopausal transition among Nigerian women aged 30-49 years. Methods The study used the women's individual recode file from the 2024 Nigeria Demographic and Health Survey. The analytic sample was restricted to women aged 30-49 years, excluding women who were currently pregnant, currently or postpartum amenorrheic, and those with invalid or special responses on time since last menstrual period. The final sample comprised 14,223 women. The outcome combined women whose last menstrual period occurred 12 or more months before the survey, and women reported as being in menopause. Weighted descriptive statistics, design-adjusted bivariate tests and survey-weighted binary logistic regression were used. Results The weighted prevalence of prolonged amenorrhea/possible menopausal transition was 7.6%. Prevalence rose from 1.2% among women aged 30-34 years to 23.6% among women aged 45-49 years. In the adjusted model, women aged 35-39 years (OR=1.64; p=0.030), 40-44 years (OR=6.20; p<0.001) and 45-49 years (OR=24.51; p<0.001) had higher odds than women aged 30-34 years. Primary education (OR=1.65; p=0.004), middle wealth status (OR=1.37; p=0.043) and poorest wealth status (OR=1.60; p=0.024) were associated with higher odds. Muslim affiliation (OR=0.72; p=0.024) and traditional contraceptive use (OR=0.24; p<0.001) were associated with lower odds. Conclusion Prolonged amenorrhea/possible menopausal transition among Nigerian women aged 30-49 is strongly age-patterned and socially differentiated. The findings support the need to make midlife menstrual health more visible within reproductive, family planning and primary healthcare services. Because the measure is based on survey-reported menstrual recency, it should not be interpreted as clinically confirmed natural menopause.

Background. Nascent findings suggest that people with attention-deficit/hyperactivity disorder (ADHD) experience higher rates of mortality. To date, study samples have been insufficiently well-characterized to examine the mechanisms via which this neurodevelopmental condition elevates mortality risk. Methods. We used data from the 2007 and 2011 waves of the US National Health Interview Survey, a general population-based cohort study comprising 52097 adults (28675 women) aged 18 years or older at baseline. ADHD diagnosis and an array of demographic, socioeconomic, lifestyle, and co-morbidity (somatic and psychiatric) covariates were self-reported. Findings. At baseline, compared with unaffected individuals, participants with ADHD were more likely to be socioeconomically disadvantaged, smoke cigarettes, consume alcohol, and report symptoms of psychological distress. A median 7.75 years of mortality surveillance (range: 7.25-12.25) gave rise to 6597 deaths from all-causes. After adjustment for age, sex, ethnicity, and survey year, ADHD was associated with a markedly elevated risk of death (hazard ratio [95% confidence interval]: 1.58 [1.20-2.09]). Statistical adjustment for socioeconomic circumstances (11% attenuation), physical co-morbidities (15%), and lifestyle factors (17%) had only a modest impact on the ADHD-death gradient, with the greatest explanatory power apparent for symptoms of depression and anxiety (58%). The magnitude of the association of ADHD with mortality was commensurate to that for several well-established risk factors such as poverty (1.66 [1.55-1.78]), hypertension (1.41 [1.32-1.51]), and diabetes (1.71 [1.59-1.85]) but somewhat lower than cigarette smoking (2.51 [2.29-2.76]) after controlling for age, sex, ethnicity, and survey year. Associations between ADHD and cause-specific mortality from cardiovascular disease, cancer, and chronic respiratory disease were inconclusive. Interpretation. In the present study, the influence of ADHD on total mortality appears to be largely embodied via a series of malleable characteristics, particularly mental illness. If confirmed elsewhere, these results raise the possibility that risk factor modification via standard pharmacological and behavioral interventions could help reduce rates of premature mortality in this patient group. Funding. This paper received no direct funding. GDB is supported by the UK Medical Research Council (MR/P023444/1) and the US National Institute on Aging (1R56AG052519-01, 1R01AG052519-01A1).

Introduction: Brain-predicted age, estimated from structural MRI data, is a machine-learning biomarker of biological brain aging. Greater brain age gap (BAG) indicates advanced brain aging and is associated with cognitive decline and mortality. Cardiometabolic risk factors, including elevated blood glucose, body mass index (BMI), blood pressure, and cholesterol, increase risk of cognitive impairment and dementia in aging. Their relationship with BAG in severe obesity remains poorly characterized despite increased prevalence of cardiometabolic risk factors among this population. Methods: T1-weighted MRI data from 97 adults (BMI 35-73) were used to calculate BAG using ENIGMA and Pyment brain age models. Associations between BAG and HbA1c, BMI, hypertension, and hyperlipidemia were examined using multiple linear regression and MM-estimation robust regression, adjusting for age, sex, and race. Post hoc analyses stratified models by clinical HbA1c cutoffs (normoglycemic, prediabetic, diabetic). Results: Higher HbA1c was associated with greater BAGENIGMA (B = 1.58, p = .014) and BAGPyment (B = 0.93, p = .013) in linear regression models. In robust models, HbA1c remained significantly associated with BAGENIGMA (B = 1.70, p = .002) but not BAGPyment (B = 0.71, p = .13). BMI, hypertension, and hyperlipidemia were not associated with BAG in either linear or robust models. HbA1c was associated with greater BAGENIGMA (B = 2.15, p = .01) and BAGPyment (B =1.21, p = .04) in those at or above prediabetic levels and with BAGENIGMA (B = 2.49, p = .047) in those with diabetes. Conclusions: Elevated HbA1c is associated with accelerated brain aging in individuals with severe obesity. BAG was not associated with BMI, hypertension, and hyperlipidemia, which may reflect the restricted BMI range inherent to the sample with severe obesity.

Background: Wheeled walkers can improve safety during walking, but improper use may increase fall risk among frail older adults. No suitable tool exists to assess safe indoor wheeled walker use in this population. This study aimed to develop and validate a video-based expert assessment tool. Methods: Based on the literature and expert consensus, seven problematic indoor situations were identified, and an assessment tool with five safety criteria per situation was developed (maximum score = 35). Fifty participants (mean age 83.9 years, 64% women) from a geriatric rehabilitation clinic and a nursing home were video-recorded while using a rollator. Expert ratings were compared with nursing staff ratings, self-ratings, and the Timed Up and Go test to evaluate validity. Intra- and inter-rater reliability were determined from independent ratings by two physiotherapists and a repeated expert rating after seven days. Sensitivity to change was assessed after two weeks of rehabilitation, and feasibility by the time required for assessment. Results: The expert score of rater 1 at baseline was 28.5 points, and assessment required a mean of 17.5 minutes. Intra-rater reliability was excellent (ICC = 0.98) and inter-rater reliability was good (ICC = 0.80). Validity analyses showed the strongest association with nursing staff assessments (r = 0.74) and a moderate association with the Timed Up and Go test (r = -0.45). After two weeks, patients improved by an average of 2.38 points (8.4% of baseline score). Conclusions: The new instrument demonstrated high reliability, acceptable validity, sensitivity to change, and good feasibility for assessing safe wheeled walker use in frail older adults. Trial registration number and date of registration: DRKS00038358, 07/11/2025

Background: Cervical cancer is the fourth most common cancer in women worldwide and remains a major public health challenge. In Ethiopia, it is the second leading cause of cancer deaths, with around 8,000 new cases and 6,000 deaths each year. Region?specific data on the prevalence and predictors of precancerous lesions remain scarce, yet such information is vital for guiding targeted reproductive health strategies. This study therefore examined the prevalence and predictors of cervical precancerous lesions among women aged 21-60 years undergoing Pap smear screening in public hospitals in Hawassa City, Sidama Region. Methods: An institution-based cross-sectional study was conducted among 241 women attending Pap smear screening at public hospitals in Hawassa City from March to August 2025. Sociodemographic and clinical data were collected via interviews and medical records. Lesions were classified based on the standardized international framework for reporting cervical cytology results from Pap smears per the Bethesda system. Multivariable logistic regression identified predictors p<0.05). Result: Of 241 women screened (mean age 35.3 years), cervical epithelial abnormalities were detected in 52 (prevalence 21.6%). Atypical squamous cells of undetermined significance was the most common abnormality (16.6%). Multivariable analysis showed HIV infection was significantly associated with precancerous lesions (AOR = 3.7, 95% CI: 1.69-8.12, p<0.05), while hormonal contraceptive use was protective (AOR = 0.27, 95% CI: 0.11-0.67, p<0.05). Conclusion: These results underscore the urgent need to strengthen cervical cancer prevention through targeted screening and early intervention. Integrating routine HIV testing with Pap smear programs would be especially valuable. Health authorities should expand accessible screening for women aged 21-60, with particular attention to those living with HIV, to help reduce the burden of precancerous lesions.

As genetic testing becomes increasingly integrated into Parkinson disease (PD) research, including targeted testing for variants in LRRK2 and GBA1, the return of individual research results is becoming more common. However, limited qualitative data exists regarding how research participants experience genetic results disclosure and post-test genetic counseling in PD research settings. We conducted semi-structured qualitative interviews with participants (n=13) enrolled in the Parkinson Precision Medicine Initiative (formerly Parkinson Progression Markers Initiative; PPMI) who had received PD-related genetic test results and post-test genetic counseling. Interviews were conducted 1 to 3 weeks following result disclosure and analyzed using thematic analysis with a primarily deductive coding approach informed by study aims and inductive identification of emergent themes. Four primary themes were identified: (1) personal connection and motivations for participation, (2) centrality of result disclosure and information preferences, (3) emotional experiences and support needs, and (4) communication quality and alignment with participant needs. Overall, our findings underscore the importance of person-centered genetic counseling within PD research. As return of genetic and biomarker results in research and clinical trial contexts expand, thoughtful integration of relational, informational, and communication-focused practices will be essential to support participant engagement and trust.

Background and Aims: Fatigue is a prevalent and disabling symptom in inflammatory bowel disease (IBD), yet its underlying biological mechanisms remain poorly understood. We aimed to characterize fatigue-associated molecular signatures in IBD patients by integrating DNA methylation and mRNA expression analyses. Methods: Peripheral blood was collected from 40 patients with Crohn's disease (CD), 29 with ulcerative colitis (UC), and 10 healthy controls. Fatigue severity was assessed continuously using the Multidimensional Fatigue Inventory (MFI). Epigenome-wide DNA methylation profiling and mRNA sequencing were performed, identifying differentially methylated regions (DMRs) and differentially expressed genes (DEGs) for active and quiescent CD and UC, adjusting for age, sex, and smoking status. Pathway enrichment analysis was performed on genes with differential methylation and expression. Results: In active CD, more severe fatigue was associated with transcriptional suppression of immune and metabolic pathways (246 DMRs; 1,090 DEGs), versus upregulation of mitochondrial and metabolic processes in quiescent CD (200 DMRs; 1,619 DEGs). In active UC, fatigue was associated with anabolic pathway upregulation and epigenetic silencing of neuroactive pathways (6,927 DMRs; 343 DEGs; 56 concordant genes). Quiescent UC showed transcriptional changes without significant epigenetic pathway enrichment (1,710 DMRs; 3,224 DEGs). Healthy controls exhibited a distinct profile spanning metabolic, immune, and neuronal pathways (8,621 DMRs; 395 DEGs). Fatigue-associated signatures were largely non-overlapping across all five groups. Conclusions: Fatigue-associated molecular profiles differed substantially by disease subtype and activity state, highlighting the biological heterogeneity of IBD-related fatigue and laying the foundation for multi-omics approaches to identify biomarkers and potential therapeutic targets.

Abstract Objective: The onset of hypertension occurs at a younger age in China, and the relationship between health literacy and quality of life among middle-aged and older hypertensive patients remains unclear. This study explored whether perceived social support and self-efficacy mediate the association between health literacy and quality of life in middle-aged and older hypertensive patients. Methods: A questionnaire was administered to 1,015 middle-aged and older hypertensive adults from communities in six central provinces of China. The EQ-5D scale, Perceived Social Support (PSS) scale, Self-Efficacy Scale (SES), and Health Literacy Scale (HLS) were used to assess quality of life, social support, self-efficacy, and health literacy, respectively. Mplus 8.3 software was used to construct a structural equation model for path analysis. Results: The mean PSS, SES, HLS, EQ-5D, and EQ-VAS scores were 15.57{+/-}3.45, 10.61{+/-}2.41, 9.49{+/-}2.86, 0.88{+/-}0.18, and 71.06{+/-}17.49, respectively. Health literacy and quality of life scores significantly differed among middle-aged and older hypertensive patients, and both showed positive correlations with perceived social support and self-efficacy (both P<0.001). Perceived social support and self-efficacy exhibited a chain mediated effect on the relationship between health literacy and quality of life (EQ-5D utility index and EQ-VAS), accounting for 28.57% of the total effect of the EQ-5D utility index and 27.26% of that of the EQ-VAS. This study is the first to elucidate the mechanism by which health literacy influences quality of life in middle-aged and older hypertensive patients through the chain-mediated effect of perceived social support and self-efficacy. Conclusion : Health literacy is significantly correlated with quality of life in middle-aged and older hypertensive patients. This correlation can directly or indirectly explain the impact on quality of life through mediating pathways involving perceived social support and self-efficacy. Keywords: hypertensive patients, perceived social support, self-efficacy, health literacy, quality of life, mediating effect

Introduction: While growing evidence suggests that music training supports child development, few long-term randomized controlled trials (RCTs) have rigorously tested these claims. Moreover, it remains unclear whether the benefits are confined to music-specific domains or extend to higher-order cognitive functions such as inhibitory control (IC), a core executive function associated with long-term outcomes in academic achievement, career success, socio-emotional health, and physical well-being. This paper presents the protocol for the Extracurricular Activity and Child Early Learning and Development (EXCEL) trial, an RCT designed to assess the feasibility of a long-term music training program focusing on the brain and behavioral correlates of IC. Methods: A total of 126 children, aged 6 to 8 years and residing in neighborhoods with limited resources in Los Angeles, were individually randomized to either a music (intervention) or theatre (active control) after-school program. Both programs were delivered over 24 months by established community arts organizations. Eligibility criteria included: average intellectual functioning, no major medical or psychiatric conditions, and MRI eligibility. Children with prior formal music training exceeding six months or severe hearing impairment were excluded. Before the intervention began, all participants completed baseline behavioral and neuroimaging assessments. The primary trial aim was to assess the effects of extended music training, relative to theatre training, on changes in measures of IC (i.e., Go/No-Go task and delayed gratification) and related neural functional activation. A secondary interim aim of the trial was to evaluate the feasibility of conducting a long-term RCT of music education in a first cohort, measured by participant retention, adherence to the program, willingness to continue at the 12-month mark, and fidelity. Progress: Recruitment, screening, baseline testing, randomization, and program enrollment began in August 2022, and after-school programming began in October 2022. The randomized interventions and all data for the first cohort (N = 42) have been collected. Intervention and active control programs for a second cohort are ongoing and will end in Fall 2026. Discussion: This paper reports the EXCEL trial protocol and provides feasibility estimates for implementing a long-term randomized controlled trial of music training in real-world, community-based settings with children. While similar neuroimaging RCTs are currently underway in Europe, the EXCEL trial is among the first in the United States to integrate longitudinal neuroimaging with arts intervention. Findings will inform the viability of scaling such programs and contribute to our understanding of how sustained music engagement may influence the development of inhibitory control circuitry in childhood.

Ultra-processed food (UPF) may contribute to increased energy intake and weight gain, but evidence synthesis from randomised controlled trials (RCT) is lacking. A pre-registered systematic review and meta-analysis of RCTs was conducted comparing UPF with less processed food (LPF) on energy intake and/or body weight in humans. Secondary analyses (meta-regression and sub-group) examined effects of UPF on appetite sensations, eating rate, palatability and considered the role of nutrient profile in explaining results. Ten eligible studies were included. UPF trial arms tended to have higher energy intake (standardised mean differences [SMDs]=0.18-0.44), but statistical significance varied between analytic models. Weight gain (SMD=0.65) and eating rate (SMD=0.96) were significantly greater in UPF trial arms. No significant differences in palatability, appetite sensations or energy intake later in the day were observed. Diets (UPF vs. LPF) used in trials were not matched for nutrient profile. Effects on energy intake varied if UPFs were higher (SMD=0.71) or similar (SMD=0.02) in energy density. Current RCTs are suggestive that UPFs may increase energy intake and body weight; however, results may be explained by energy density of foods used. Further research is needed to understand whether the level of processing impacts health outcomes independent to nutrient profile.

Background: Childhood and adolescent hearing loss affects not only communication and cognitive development but also motor skills and school participation. Consequently, it generates inequalities in learning and educational inclusion. Nevertheless, no systematic review has yet analyzed these differences from an inclusive education perspective. Methods: A systematic review with meta-analysis was conducted following PRISMA guidelines and registered in PROSPERO. Observational studies comparing physical fitness between children and adolescents with hearing loss and their hearing peers were included. Methodological quality was assessed using the Newcastle--Ottawa Scale, and standardized effect sizes were calculated with a random-effects model. Results: Five studies (n=404) were analyzed. Findings revealed significant differences in strength, agility, speed, and balance. Moreover, the meta-analysis showed a large standardized effect favoring hearing children (ES=-2.35; 95% CI: -3.34 to -1.37). Conclusions: Children and adolescents with hearing loss present significantly lower physical fitness, which may affect the planning of physical education activities if their capacities are misinterpreted. Implementing inclusive and adapted strategies within the school curriculum is essential to ensure equal opportunities, improve physical fitness, and promote educational equity.

Introduction: To investigate the epidemiological characteristics of chronic kidney diseases (CKD) in China in 2021 and its trends between 1990 and 2021, in the context of significant population growth and lifestyle changes over the past 30 years that have likely influenced the CKD spectrum. Methods: Data on CKD prevalence, mortality, disability-adjusted life-years (DALY), and risk factors were obtained from the Global Burden of Disease Study 2021. The estimated decadal percentage changes were calculated to evaluate changes in trends in prevalence, mortality and disease burden. Results: In 2021, an estimated 118.4 (95% UI 109.4 to 127.5) million people in China were affected by CKD, contributing to 204 230 (95% UI 164 736 to 246 372) deaths and 6.13 (95% UI 5.18 to 7.21) million DALY. Although CKD due to diabetes mellitus and hypertension accounted for less than a quarter of all cases, they were responsible for over 90% of CKD-related deaths. Over the past three decades, CKD mortality and DALY rates have steadily increased, although the prevalence has stabilized in the last decade. Diabetes mellitus type 2 and hypertension have emerged as key drivers of CKD burden in China. Conclusions: The CKD burden in China shows a dual pattern of rising incidence and high mortality from diabetes and hypertension-related chronic kidney disease, alongside persistently high years lived with disability from glomerulonephritis and other causes.