It is unclear if adherence to healthy guidelines can modify the association between polygenic risk score (PRS) for type 2 diabetes and dementia. This study aimed to investigate interrelationships between PRS for type 2 diabetes, Life's Essential 8 (LE8) metrics, and dementia. We included 437,732 UK Biobank participants aged ≥40 years between 2006 and 2010. PRS for type 2 diabetes was calculated by summing weighted genetic variant effects. Incident all-cause and cause-specific dementias were identified using registry records up to December 2022. LE8 scores were classified as low vs. moderate-to-high levels. Cox regression and restricted cubic splines were applied. Over an average follow-up of 13.27 years (SD = 2.27), 9425 participants developed dementia. A dose-response relationship was observed between PRS and vascular dementia, with risk rising sharply beyond the 95th percentile. Individuals with low LE8 constantly showed a higher risk of all-cause dementia than those with moderate-to-high LE8 across all values of PRS for type 2 diabetes. APOE ε4 accounted for more than 35% of the population-attributable risk of dementia, whereas the PRS for type 2 diabetes contributed only 1%. The population-attributable risk of all-cause dementia could be further reduced by 5.91% to 10.46% through maintaining moderate-to-high LE8 behavioral components, even after considering APOE ε4. A dose-response relationship exists between PRS for type 2 diabetes and dementia, particularly vascular dementia. Adherence to optimal LE8 metrics, particularly behavioral components, may contribute to dementia prevention across genetic strata. These findings highlight the importance of multidomain lifestyle interventions in dementia prevention.
Background Understanding how symptomatic intracranial atherosclerotic disease (sICAD) evolves and identifying high-risk lesion characteristics could improve risk stratification. Purpose To delineate the evolution patterns of plaque morphologic features and focal hemodynamics in sICAD and identify morphologic features and hemodynamics associated with plaque progression and recurrence of stroke and/or transient ischemic attack (TIA). Materials and Methods In this prospective, longitudinal study, participants with high-grade (60%-99% stenosis) sICAD confirmed at three-dimensional rotational angiography (3DRA) between August 2007 and December 2021 received guideline-based medical treatment, with follow-up evaluations at 1, 3, 6, and 12 months and every 6 months afterward. All participants underwent follow-up 3DRA at 1 year or upon stroke recurrence if earlier. The sICAD plaque morphologic features and focal hemodynamics were assessed and compared at baseline and follow-up 3DRA and using 3DRA-based computational fluid dynamics models. The primary outcome was a composite of relevant ischemic stroke or hard TIA recurrence and/or plaque progression in 3DRA at 1 year. Results Among 97 participants (median age, 62 years [IQR, 56-68 years]; 68 male), the primary outcome occurred in 26 (27%): 17 (18%) with relevant ischemic stroke and/or TIA recurrence and nine (9%) with plaque progression. Focal pressure and wall shear stress measures also changed over 1 year. Greater plaque thickness (adjusted odds ratio, 10.49 [95% CI: 2.67, 41.20]), smaller upstream plaque shoulder angulation (adjusted odds ratio, 0.97 [95% CI: 0.95, 1.00]), and maximum stenosis located distally (adjusted odds ratio, 3.81 [95% CI: 1.19, 12.18]) at baseline were independently associated with primary outcome. Higher and lower wall shear stress measures across the upstream and downstream plaque segments, respectively, at baseline were also associated with primary outcome. Conclusion Plaque morphologic features and focal hemodynamics evolved over time in participants with sICAD under medical treatment; thicker plaque, smaller upstream shoulder angulation, and skewed distal load were associated with lesion progression and recurrence of stroke and/or TIA. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article.
Alzheimer's disease (AD) is a multifactorial disorder involving various pathological mechanisms, such as amyloidosis, immune dysfunctions, and synaptic impairments, which are important therapeutic targets. Repurposing drugs to target these mechanisms offers a promising approach to reduce the costs and duration of drug development. Genetic studies underscore the critical role of microglial clearance of amyloid-beta (Aβ) in AD pathogenesis. Specifically, soluble ST2 (sST2)-one of the two major isoforms of the ST2 protein encoded by the IL1RL1 (interleukin-1 receptor-like 1) gene-acts as a decoy receptor isoform that interferes with IL-33/ST2 signaling and has been identified as a disease-modifying factor that impairs microglial Aβ clearance functions. In this study, we investigated drug repurposing opportunities to modulate sST2 levels and alleviate AD pathologies. Unbiased screening of commonly used medications in AD patients, followed by validation in model systems, identified trazodone-an antidepressant used to treat major depressive disorder-as a leading negative regulator of sST2. Trazodone primarily suppresses sST2 expression through its antagonistic effects on adrenergic signaling. In the APP/PS1 transgenic mouse model of AD, trazodone treatment enhanced microglial interaction with Aβ and alleviated Aβ pathology. Furthermore, trazodone reduced neurodegeneration and rescued synaptic deficits in APP/PS1 mice. Comprehensive molecular profiling of APP/PS1 mouse brains showed that trazodone restored the expression of synaptic proteins critical for synaptic integrity and plasticity. Overall, these findings demonstrate that trazodone is a promising repurposing candidate for AD that targets underlying immune dysfunctions and synaptic impairment.
The study aim is to investigate whether blood biomarkers (BBMs) of Alzheimer's disease (AD) pathology are associated with postoperative cognitive dysfunction (POCD) after cardiac surgery. Cognitive performance was assessed before and 12 months postoperatively using the Montreal Cognitive Assessment (MoCA) and categorized into stages-minimal (1), notable (2), and substantial (3) decline-in the FIND DElirium RIsk factors (FINDERI) study of patients undergoing cardiac surgery. BBMs were measured preoperatively (amyloid beta [Aβ]1-42, Aβ1-40, phosphorylated tau 181 [p-tau181], p-tau217, apolipoprotein E ε4 [apoE4] and apoE). A total of 394 patients completed follow-up investigations. POCD Stage 1 was observed in 105 (26.6%), POCD Stage 2 in 52 patients (13.2%), and POCD Stage 3 in 30 patients (7.6%). The AT217term (ratio Aβ1-40/1-42 * p-tau217) was significantly associated with POCD stages in multiple logistic regression. Early Alzheimer's BBMs are associated with POCD in patients, suggesting that our exploratory findings assessing BBMs may support risk stratification, inform decision-making, and contribute to strategies aimed at preventing POCD.
Background: Frailty impacts the prognosis of respiratory diseases but lacks standardized evaluation criteria. This pilot study aimed to develop a frailty assessment method using unsupervised clustering of various physical function tests. Methods: Clinical data, handgrip strength (HS), lower limb strength (LLS), the 6 min walk test (6 min WT), the 5 m walk test (5 m WT), body composition, such as skeletal muscle mass index (SMI), whole-body phase angle (WBPhA), and pulmonary function variables were measured. Frailty status was evaluated in three groups (frail, pre-frail, and robust) using the J-CHS and Kihon Checklist. Unsupervised hierarchical clustering was performed, followed by dimensionality reduction using Principal Component Analysis. Results: Ninety-eight patients and healthy volunteers (70 males, 28 females; mean age, 57.5 years) were divided into four clusters, ranging from robust to pronounced frailty. On the 2-principal component plane, data points formed clusters across the four regions. The biplot showed variables aggregating in two directions: one including %FEV1, FEV1%, 6 min WT, and 5 m WT speed (exercise tolerance), and the other including HS, LLS, SMI, and WBPhA (physical elements). Tracking 39 participants (mean, 636 days later) showed cluster shifts that were broadly reproducible, although the small follow-up sample warrants cautious interpretation. Conclusions: As an exploratory, hypothesis-generating pilot study with a small single-center sample, this novel frailty model may offer a more granular assessment to help guide management; however, external validation in larger cohorts is required before clinical application.
Despite the broad impact of sleep in injury-related recovery, there is limited literature investigating how sleep may impact patients after anterior cruciate ligament reconstruction (ACLR). It is unclear whether patients perceive sleep changes as a result of ACLR and whether they perceive these changes to influence their health-related outcomes (eg, physical recovery, psychological functioning) in the early postoperative ACLR recovery phase. This qualitative study aimed to capture patient perceptions of sleep after ACLR as well as how they perceived the impact of sleep on their ACLR recovery within the first 3 months postoperatively. We aimed to better understand patients' subjective experiences regarding the role of sleep in recovery and to identify any barriers or facilitators to achieving optimal sleep when undergoing acute stages of ACLR rehabilitation. Qualitative study. Research university. Twelve participants aged 18 to 35 years and 1 to 3 months post-ACLR completed semistructured interviews via a videoconferencing platform. Audio and video recordings of each interview were transcribed verbatim to prepare for thematic coding. Transcriptions were anonymized with pseudonyms. Data were interpreted through thematic analysis using an inductive approach. Coding and thematic analysis was carried out by 2 independent reviewers. Three major themes were found relating to participants' perception of their sleep and ACLR experience early in the rehabilitation process: (1) sleep disturbances experienced, (2) repercussions of sleep disturbances, and (3) prior knowledge of sleep hygiene. The most important finding of this study was that patients after ACLR in this sample did perceive significant sleep disturbances leading to poor sleep quality, and these led to perceived negative impacts to health outcomes. Future researchers should focus on integrating lifestyle factors, such as sleep, into ACLR rehabilitation protocols as improving sleep may improve ACLR-specific recovery outcomes and quality of life.
Hepatopancreatobiliary (HPB) malignancies are associated with high morbidity and frequent invasive procedures near the end of life. Although palliative care improves quality of life and goal-concordant care, its relationship with procedural burden in HPB cancers at the end of life remains poorly understood. We evaluated associations between inpatient palliative care and end-of-life procedural intensity in HPB malignancies. We conducted a retrospective analysis of adult patients with HPB cancers admitted to a tertiary academic health system within 6 months of death between January 1, 2013, and December 31, 2024. Electronic health records and tumor registry data were analyzed through June 1, 2025. Patients were categorized by inpatient procedures and palliative care consultations. The primary outcome was the relationship between palliative care involvement and inpatient procedural burden. Multivariable logistic regression evaluated associations between palliative care timing and procedural characteristics. Among 2,848 patients, 1,373 (48.2%) underwent an inpatient procedure and 1,160 (40.7%) received palliative care consultation. From 2013 to 2024, palliative care utilization more than doubled, while end-of-life procedural rates remained constant. Palliative care involvement prior to any procedure was associated with lower odds of undergoing nonpalliative-intent procedures relative to palliative-intent procedures (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.51-0.98; P = 0.038). End-of-life inpatient procedures were common in HPB malignancies and persisted despite increased palliative care utilization. Early palliative care involvement was associated with a greater proportion of palliative-type procedures, suggesting an association between earlier palliative care integration and procedural decision-making that may better align with patient quality of life and end-of-life priorities.
Quantifying biological aging requires biomarkers that capture multisystem physiological decline beyond chronological age. We aimed to compare the prognostic performance of plasma proteomics, metabolomics, and conventional clinical risk factors for all-cause mortality, and to characterize molecular pathways associated with mortality risk and age-related physiological decline. Untargeted plasma proteomics and metabolomics were profiled in 848 community-dwelling adults from the I-Lan Longitudinal Aging Study (ILAS), followed for a mean of 8.5 years, during which 92 deaths occurred. Cox proportional hazards models were applied to identify mortality-associated molecular features and their enriched biological pathways. We identified 79 proteins associated with all-cause mortality (FDR < 0.1), predominantly liver-derived and immune-related. Pathway analysis revealed coordinated dysregulation across coagulation cascades, complement activation, oxidative stress responses, glucose metabolism, and bile acid metabolism. Elastic net regression was subsequently used to construct omics-based mortality risk scores, which were further evaluated in an independent validation cohort from the Longitudinal Aging Study of Taipei (LAST). A 20-protein mortality score achieved strong discrimination (C-index 0.81), outperforming metabolite-based models (C-index 0.77) and clinical risk factors (C-index 0.73) in the discovery cohort. In the external validation cohort, both proteomic- and metabolomic-derived scores showed directionally consistent associations with mortality risk. Together, these findings identify liver- and immune-enriched molecular signatures associated with mortality risk in older adults and support the utility of plasma multi-omics profiling as a scalable precision tool for biological age assessment. The identified proteomic and metabolomic pathways may help inform future interventions targeting systemic aging and age-related functional decline.
Older adults with osteosarcopenia, defined as the coexistence of osteopenia/osteoporosis and sarcopenia, have been associated with an increased risk of fractures compared with those with normal bone mineral density (BMD) and without sarcopenia. However, the conventional definition of osteosarcopenia has led to mixed results on its predictive accuracy for hip fractures. We aimed to define osteosarcopenia by identifying sex-specific cut-offs for low BMD according to different sarcopenia statuses and compare its predictive performance with osteosarcopenia defined conventionally and osteoporosis alone. A cohort of 4000 community-dwelling older adults (2000 females, mean age 72.5 ± 5.2 years) was recruited. Body composition and BMD of hip, lumbar spine and femoral neck were measured using dual energy X-ray absorptiometry at baseline. According to the Asian Working Group for Sarcopenia 2019 consensus, all participants were classified as non-sarcopenia, possible sarcopenia and sarcopenia. Incidence of hip fractures was documented during the follow-up period from 2001 to 2013. The classification and regression tree (CART) analysis was performed to identify the optimal cut-off values of T-scores for participants with possible sarcopenia and those with sarcopenia, respectively. Cox proportional hazards regression models were used to estimate the associations between osteosarcopenia and hip fractures. The discrimination and predictive ability of osteosarcopenia were evaluated by Uno's concordance index (C-index), time-dependent net reclassification improvement (NRI) and integrated discrimination improvement (IDI). During an average of 9.2 years of follow-up, 63 (3.2%) men and 69 (3.5%) women had at least one hip fracture. Sex- and sarcopenia-specific cut-offs of T-scores were identified (men with possible sarcopenia: T-score < -2.2; men with sarcopenia: T-score < -2.0; women with possible sarcopenia: T-score < -2.1; women with sarcopenia: T-score ≤ -2.5). Osteosarcopenia defined with these specific cut-offs was associated with an increased risk of hip fractures independent of clinical risk factors in both men and women (HR = 5.232, 95% CI = 3.172-8.631, and HR = 3.574, 95% CI = 2.01-6.355, respectively). It had the highest Uno's C-index (men: 0.774 and women: 0.750, respectively) and outperformed osteosarcopenia using conventional definition and osteoporosis alone in predicting hip fractures by using NRI and IDI approaches. Our findings suggested that including possible sarcopenia and adopting sex- and sarcopenia-specific cut-offs to define osteosarcopenia could improve hip fracture prediction. Further studies are warranted to validate the cut-offs of T-score identified in our cohort.
End-stage chronic kidney disease (CKD) requires hemodialysis, which carries significant biopsychosocial impact. This study aimed to investigate the relationship between family functionality and social support among older individuals undergoing hemodialysis. This cross-sectional and correlational study was conducted at a renal replacement therapy unit located in São Paulo State. A total of 118 participants aged ≥ 60 years undergoing hemodialysis were interviewed individually using the Family adaptability, partnership, growth, affection, and resolve (APGAR), and the Medical Outcomes Study Social Support Scale. All ethical principles were duly respected. Majority of participants were male (69.5%), aged between 60-69 years (50.8%), white ethnicity (63.6%), with a stable partner (54.2%), and had an income of one to three times the minimum wage (55.9%). Regarding the domains of social support, affective support (AS) had the highest mean score (93.44 ± 12.97), whereas informational support (IS) had the lowest (81.69 ± 24.60). Overall, 83.9% reported good family functioning, 9.3% moderate family dysfunction, and 6.8% severe dysfunction. A statistically significant positive correlation with a moderate magnitude was confirmed between APGAR with all support domains. Material support (MS, r = 0.327), AS (r = 0.425), emotional support (ES, r = 0.518), positive social interaction support (PSIS, r = 0.466), and IS (r = 0.421). Social support was positively associated with family functioning, indicating that patients with CKD undergoing hemodialysis who reported better family functioning also perceived higher levels of social support.
Diabetic nephropathy (DN) remains a major cause of end-stage kidney disease. Stem cell-derived exosomes have emerged as a promising therapeutic strategy due to their ability to deliver bioactive molecules to damaged tissues. This narrative review, conducted in accordance with PRISMA guidelines, aims to evaluate the therapeutic potential of exosomes derived from various stem cell sources, including mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), in the context of DN. A comprehensive literature search was performed using relevant databases (e.g., PubMed, Web of Science, Scopus) to identify preclinical and clinical studies investigating the effects of stem cell-derived exosomes on DN. The identified studies were assessed for quality and methodological rigor. Priority was given to high-impact studies and those with robust experimental evidence. The selected literature was synthesized thematically to provide a coherent overview of the current state of research on exosome-based therapies for DN, highlighting current findings, and future directions. Results from preclinical studies suggest that exosomes derived from different stem cell sources can exert reno-protective effects, including reducing inflammation, fibrosis, and oxidative stress. However, comparisons between different exosome types indicate that MSCs-derived exosomes (MSC-Exos) may offer superior therapeutic benefits. While clinical trials are ongoing to evaluate the safety and efficacy of stem cell-derived exosomes in DN patients, further research is needed to optimize exosome production, delivery, and therapeutic efficacy.
Interprofessional collaboration is proposed as an appropriate strategy to meet the increasingly complex care demands for older adults. The electronic health record (EHR) can support interprofessional teams in their daily work and quality improvement efforts. While various studies have reported on care professionals' perspectives on the EHR, to date, no study has compared the views of different care professionals on EHR use. This study aimed to investigate how different disciplines of care professionals in nursing homes view the use of EHRs. A qualitative design was adopted. Six homogeneous focus groups were organized, with certified nurse assistants, registered nurses, elderly care physicians, and students in these three professions. Conventional content analysis was used to analyze the focus groups. Forty-three (student) care professionals in the care for older adults participated in the focus groups. Analysis revealed three main themes. First, the EHR is mainly used as a communication tool, and further purposes, such as data-informed care, were pointed out as goals to be realized in the future. Second, better navigation of the EHR system necessitates skill development among EHR users and improvements in the technical functions of the EHR system. Finally, the EHR can support interprofessional collaboration in the care for older people. Yet, care professionals recognized that there is still room for improvement in such a collaboration. Different interpretations of what is considered good EHR reporting hindered effective collaboration. Proper collaboration with the EHR in the care for older adults requires increased digital literacy of care professionals, and EHR systems that are easier to use. Future studies should investigate what interprofessional teams need to better work together towards quality improvement in the care for older adults.
Recent advances in biotechnology and personalized medicine have driven the development of efficient clinical trial methodologies for assessing treatment efficacy across multiple populations defined by treatment effect modifiers. Within-patient comparison of different treatments is a promising approach for improving study efficiency across multiple populations by eliminating between-patient variability in treatment evaluation. This study provides a framework for evaluating treatment efficacy in multiple populations for 2 × 2 $$ 2\times 2 $$ crossover trials and evaluates the efficacy gain in comparison with the standard parallel-group analysis. Simulation experiments confirm that the crossover analysis consistently outperforms the parallel-group analysis in statistical power, especially when carryover effects are small. An application to a clinical trial in Type 2 diabetes demonstrates the efficiency advantages of the crossover analysis. These numerical results emphasize the potential of the crossover analysis for enhancing the efficiency of clinical development of personalized medicine.
Alpha-band default mode network (DMN) connectivity declines with aging and Alzheimer's disease (AD), yet most electroencephalography (EEG) connectivity studies used pairwise (two-order) measures, such as mutual information rate (MIR). We leveraged O-information rate (OIR) to quantify three-order interactions and to separate redundant from synergistic information processing across frontal, temporal, and parietal DMN regions. We hypothesized that, extending established findings of reduced pairwise connectivity, (i) OIR (and its components) would be reduced in older versus younger adults and in AD versus healthy controls (HC); (ii) combining MIR with OIR would improve classification compared with MIR alone; and (iii) OIR measures would correlate positively with global cognition (as assessed by the Montreal Cognitive Assessment (MoCA)). Resting-state EEG from two samples-healthy adult lifespan aging (95 younger; 93 older) and AD spectrum (44 HC; 84 amnestic mild cognitive impairment [aMCI]; 41 AD)-was source-localized using eLORETA to DMN regions. Alpha band (8-13 Hz) MIR and OIR were computed through multivariate spectral analysis. Group differences were tested using t-tests or analysis of covariance (ANCOVA) with multiple comparison correction. Classification (OIR, MIR, demographic, and combined feature sets) used cross-validated logistic-regression, linear-SVM, and random-forest models, with bootstrap 95% confidence intervals and DeLong tests for AUC comparisons. OIR and its redundancy component were significantly reduced in older versus younger adults and in AD versus HC/aMCI, with no HC-aMCI differences. The synergy component showed no group differences. MIR decreased broadly with aging and fronto-parietally in AD. Regarding classification (AD spectrum dataset, cross-validated AUC), OIR-based metrics outperformed MIR (AD vs. HC: 0.93 vs. 0.73; AD vs. aMCI: 0.93 vs. 0.71; aMCI vs. HC: 0.48 vs. 0.46). Combining demographics with all information-theoretic features improved AD vs. HC (0.98; DeLong p = 0.023) but not AD vs. aMCI (0.93), where OIR alone was already at ceiling; no feature set exceeded chance for aMCI vs. HC. After correction, OIR and its redundancy component correlated positively with MoCA scores; MIR and the synergy component did not. Alpha-band three-order DMN interactions-particularly redundant information processing-decline with aging and AD and provide additional information beyond two-order connectivity for diagnostic classification. OIR offers complementary measures to traditional metrics, and future studies should examine its value when combined with more established AD biomarkers.
Informal caregivers (ICs) of people living with dementia (PwD) are often referred to as invisible second patients, as they frequently experience chronic stress and related health issues. Identifying factors that contribute to or buffer caregiver stress is therefore of critical importance. This study aimed to explore how caregiver burden and resilience jointly are associated with stress among ICs of PwD - a rarely adopted approach. The sample consists of n = 172 ICs. To examine the associations between our dependent variable, stress (PSS), and caregiver burden (BIZA-D-PV), caregiver resilience (BRS), the quality of life of the PwD (QoL-AD), as well as the IC's sociodemographic characteristics, we conducted a hierarchical multivariate regression analysis. Resilience was included as a second block to assess changes in model fit and variable effects. Furthermore, an interaction model was calculated to investigate potential moderating effect of resilience. In Block 1, without considering resilience, personal constraints of the IC (p < 0.001), the QoL of the PwD (p < 0.001), and cohabitation of the IC and PwD (p = 0.006) were significantly associated with stress. In Block 2, only personal constraints (p < 0.001) and the QoL of the PwD (p = 0.001) remained significant, and, additionally, the explained variance (R²) increased significantly (p < 0.001). In the interaction model, only the main effects of resilience (p = 0.004), personal constraints (p = 0.002), and QoL of the PwD (p = 0.002) were significant. These findings might highlight important considerations for future interventions aimed at supporting ICs and PwD. Special attention could be given to cohabiting IC-PwD dyads, as these relationships often involve unique challenges and stressors that could be mitigated through tailored support strategies. German Register of Clinical Trials (Deutsches Register Klinischer Studien, DRKS), DRKS00023560. Registered 13 November 2020 Retrospectively registered, https//www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00023560.
The role of the liver, a vital metabolic organ, in ocular health and the corresponding mechanisms remains unclear. This study aimed to examine the association between liver function and retinal thickness, and whether metabolic signatures (MS) of liver function mediate these associations. We used data from 31019 participants in UK Biobank. Liver function was measured using seven serum-based circulating biomarkers: alanine transaminase, aspartate transaminase, gamma-glutamyltransferase, alkaline phosphatase, total bilirubin, total protein, and albumin levels. Retinal thickness was measured using optical coherence tomography, including the retinal nerve fiber layer, ganglion cell-inner plexiform layer, inner nuclear layer, inner nuclear layer-external limiting membrane, external limiting membrane-inner and outer photoreceptor segments, inner and outer photoreceptor segments-retinal pigment epithelium (ISOSRPE), and retinal pigment epithelium (RPE). The circulating metabolome was quantified using nuclear magnetic resonance spectroscopy. A linear regression model and formal mediation analyses were performed. We find that abnormal liver function is significantly associated with increased RPE thickness (β [SE]: 0.094(0.034); P = 0.021) and decreased ISOSRPE thickness (β [SE]: -0.172 (0.048); P < 0.001), after adjusting for demographic, lifestyle factors, best-corrected visual acuity, and intraocular pressures. Among the 249 metabolites, 23 are selected using lasso regression to construct MS for liver function. The mediation proportion of MS in association between liver function and ISOSRPE thickness is 28.6% (P = 0.004). Among the 23 metabolites, six play a significant mediating role in the association between liver function and ISOSRPE thickness, with mediation proportions ranging from 3.20% to 16.4%. This study demonstrates significant associations of liver function with retinal thickness and reveals potential underlying metabolomic mechanisms, providing insights into the liver-eye axis. Whether the liver, as a vital metabolic organ, may have direct impact on eye health - as well as the corresponding mechanisms - remains unclear. In this study, we focused on over 31,000 participants from the UK Biobank, using various methods to measure liver function, eye health, and compounds in the blood. We found that poorer liver function was associated with decreased health of the retina. Crucially, about 28.6% of this association was explained by a pattern in the blood, with six specific compounds playing key roles. This evidence reveals a “liver–eye axis” mediated through the bloodstream, suggesting that improving liver function may also benefit long-term eye health.
Parkinson's disease (PD) remains challenging to diagnose at early stages owing to subtle and heterogeneous clinical manifestations and the lack of reliable biomarkers. Metabolomics offers a powerful approach to capture disease-related biochemical alterations that reflect underlying pathophysiology. This study aimed to identify robust plasma metabolic signatures for PD diagnosis and to elucidate metabolic alterations associated with clinical severity. We performed untargeted plasma metabolomic profiling using ultra-high performance liquid chromatography-tandem mass spectrometry in a large Chinese population comprising two independent early-stage PD groups, one of which consisted of drug-naïve, de novo patients. Integrative statistical analyses, pathway enrichment, and machine learning-based diagnostic modelling were applied to identify discriminative metabolites and characterise disease- and treatment-related metabolic changes. In the two case-control datasets, 111 metabolites were consistently altered in early-stage PD, among which 12-hydroxyeicosatetraenoic acid, spermine, and niacinamide emerged as key differential metabolites. Pathway enrichment analysis highlighted sphingolipid metabolism as a major dysregulated pathway in early-stage PD. Using machine learning-based models, a classification model based on six metabolites achieved strong performance (area under the receiver operating characteristic curve [AUC] = 0.976), while individual metabolites also demonstrated good discriminative ability, with the highest AUC reaching 0.916. We further observed that antiparkinsonian medication was significantly associated with metabolic alterations in tyrosine, tryptophan, and polyamine pathways. In addition, gut microbiota-derived metabolites, particularly phenylacetylglutamine and p-Cresol glucuronide, were markedly elevated in PD and associated with both motor and non-motor symptom severity, suggesting a potential contribution to clinical heterogeneity. These findings indicate reproducible plasma metabolic differences associated with early PD and suggest the potential diagnostic value of internally validated classifiers for disease diagnosis. Alterations in gut microbiota-derived metabolites correlate with clinical severity, highlighting the need for further mechanistic and translational research. This study was supported by the National Natural Science Foundation of China (82271281 and 82471267), the Science and Technology Major Project of Hunan Provincial Science and Technology Department (2021SK1010), and the National Key Research and Development Program of China (2021YFC2501204).
Rural communities face disproportionate burdens of chronic disease, mental illness, workforce shortages, and fragmented services despite historic national health spending. The Whole Health, Whole Communities: Dialogues to Reduce Rural Health Disparities symposium in Roanoke, Virginia, convened cross-sector leaders to identify reforms necessary to embed person-centered care into rural systems. Participants outlined staged reforms across governance, financing, workforce development, and data infrastructure. Priority actions include trauma-informed care expansion, payment redesign, sustainable community health worker funding, participatory research, and cross-sector coordination - advancing scalable, community-embedded Whole Health models to reduce rural disparities.
This study aimed to develop a pen-based, audio-assisted health education tool and evaluate its feasibility in a pilot study. In this single-arm pilot study, a literature review and guideline analysis were conducted to identify the health education needs of older adults following percutaneous coronary intervention (PCI). Guided by geragogy principles, a health education tool comprising three modules was developed: (1) a manual integrating text, images, audio, and video for educational delivery; (2) a poster placed in visible locations to reinforce instructions related to emergency management and follow-up care; and (3) a medication box providing pen-activated audio instructions for medication administration. Following prototype development, a 4-week pilot study was conducted using convenience sampling in 20 patients after PCI. Usability, satisfaction, perceived usefulness, engagement, and applicability were assessed using questionnaires and interviews. Descriptive statistics were used for quantitative data. A pen-based, audio-assisted health education tool characterized by operational simplicity and alignment with the cognitive and physiological characteristics of older adults was developed. The 20 participants had a mean age of 71.30±5.03 years. The overall mean item score on the 5-point questionnaire was 4.82±0.26, with dimension scores ranging from 4.53±0.23 (applicability) to 4.96±0.17 (satisfaction). All patients (100%) demonstrated high applicability. Interview data indicated that audiovisual components reduced anxiety associated with memory impairment, and the medication box with audio-enabled instructions was reported to improve medication adherence. The pen-based, audio-assisted health education tool demonstrated preliminary feasibility and good acceptability among patients. It has the potential to address limitations of conventional education approaches and to enhance the learning experience of older adults, providing a basis for further evaluation of clinical effectiveness. Limitations include the absence of a control group and the small sample size, which preclude definitive conclusions on efficacy and needs to be further tested in a RCT format.
Aging is accompanied by widespread transcriptional remodeling across tissues, yet how aging impacts different categories of tissue-resident macrophages is not well understood. Macrophages are highly specialized innate immune cells shaped by their local microenvironments, suggesting that aging may elicit both shared and niche-specific transcriptional responses. Here, we performed a meta-analysis of publicly available bulk and single-cell RNA-seq datasets to characterize age-associated transcriptional changes in murine macrophages across tissues and sexes. We curated and uniformly processed 33 macrophage transcriptomic datasets, derived from 10 distinct tissue niches, in male and female C57BL/6 mice, examining transcriptional changes as a function of age. The similarity of differentially expressed aging genes was compared across niches and pathway-level analysis uncovered conserved age-associated signatures, including upregulation of gene sets related to antigen presentation, antioxidant responses, and negative regulation of ferroptosis, alongside downregulation of gene sets related to Wnt, GTPase, and extracellular matrix organization signaling. Transcription factor activity inference identified consistent age-associated activation of AP-1 (Fos, Jun), C/EBPβ, PU.1, and Egr1 across niches. Meta-analysis defined 593 consistently age-altered genes in > 3/4 of analyzed datasets, converging on dysregulation of small GTPase signaling. Focused analysis of alveolar macrophages and microglia, made possible by the larger number of available datasets, revealed sex-specific transcriptional programs altered with age in these macrophage subtypes. These findings demonstrate that macrophage aging is shaped by both tissue niche and sex and provides a framework for understanding the transcriptomic signatures of macrophage aging across tissues.