Does Social Support Moderate the Relationship between Frailty and Functional Ability Trajectory Among Community-Dwelling Older Adults?

BACKGROUND: Functional ability is the important prerequisite to live independently and achieve aging in place, which depends on the complex interaction of intrinsic and extrinsic factors. Identifying the trends and influencing factors of functional ability would contribute to the accurate assessment and intervention of geriatric health. This study aimed to disentangle the moderating effect of three types of social support, namely objective support, subjective support and support utilization, on the relationship between frailty and functional ability trajectories. METHODS: This was a secondary analysis using data from a prospective three-wave study with a sample of 777 Chinese community-dwelling older adults. Social support was assessed using the Social Support Rating Scale. Frailty was assessed using the FRAIL Scale. Functional ability was measured by the Lawton Instrumental Activities of Daily Living Scale. Latent growth curve models were implemented to test their relationships. RESULTS: Objective support but not subjective support or support utilization moderated on the relationship between frailty and functional ability slope. Functional ability decline over time was buffered by objective support among robust individuals but exacerbated among (pre)frail individuals. CONCLUSIONS: The moderating effect of social support on the relationship between frailty and functional ability trajectory varies by support types, which reminded that social support may be a promising intervention target to maintain functional independence for frail individuals, opening up a new perspective on social support in the field of disability prevention. Effective interventions should particularly address objective support in conjunction with empowering frail older population to optimize the trajectory of functional ability.

Joint trajectories of loneliness, social isolation and sarcopenia and associations with adverse outcomes: A prospective cohort study.

This study aimed to examine joint trajectories of loneliness, social isolation and sarcopenia and their associations with adverse outcomes. A total of 4701 participants aged ≥60 years who had a baseline and at least one follow-up assessment of loneliness, social isolation and sarcopenia across 2011, 2013 and 2015 waves in China Health and Retirement Longitudinal Study. Adverse outcomes were obtained in 2018 wave. Joint trajectories were fit using the parallel process latent class growth analysis, and their associations with adverse outcomes were evaluated using modified Poisson regression. Joint trajectory patterns for social relationship and sarcopenia did not vary by the assessment for sarcopenia, but did vary by the assessment for social relationship. Older adults exhibit distinct joint trajectories and those with persistent combination of loneliness or social isolation and sarcopenia experience greatest risk of adverse outcomes. These findings implicate integration of health care and social care for community-dwelling older adults.

Effects of cognitive reserve on cognitive frailty among older adults: A population-based prospective cohort study.

AIM: We investigated the effect of lifespan cognitive reserve and its components on cognitive frailty among older adults. METHODS: A total of 4922 participants aged ≥65 years were recruited in 2008 and were followed up in 2011 from the Chinese Longitudinal Healthy Longevity Survey. Cognitive frailty was determined through the simultaneous presence of physical frailty (pre-frailty or frailty) and mild cognitive impairment, excluding concurrent dementia. The assessment of physical frailty and mild cognitive impairment was based on the Fatigue, Resistence, Ambulation, Illness, Loss of weight (FRAIL) (Fatigue, Resistence, Ambulation, Illness, Loss) and Mini-Mental State Examination scale, respectively. The lifespan cognitive reserve consisted of education attainment, occupational complexity and later-life leisure activities. We used logistic regression models to estimate the risk of cognitive frailty associated with the lifespan cognitive reserve and its components. RESULTS: A higher level of lifespan cognitive reserve, higher educational attainment or leisure activities engagement, but not occupational complexity, were associated with lower risk of incident cognitive frailty. Furthermore, cognitive, social and physical activities were associated with lower risk of incident cognitive frailty. CONCLUSION: Cognitive reserve, particularly educational attainment and leisure activities, can protect from cognitive frailty. This implicates that individuals should accumulate cognitive reserve in their lifespan, and older adults should actively participate in leisure activities to prevent cognitive frailty. Geriatr Gerontol Int 2024; 24: 398-403.

Joint trajectories of physical frailty and social frailty and associations with adverse outcomes: A prospective cohort study.

BACKGROUND: We examined joint trajectories of physical frailty and social frailty as well as their associations with adverse outcomes. METHODS: We conducted a prospective cohort study by using five waves of national data from China Health and Retirement Longitudinal Study (CHARLS 2011-2020), involving 4531 participants aged ≥60 years. We identified 4-year trajectories at three examinations from 2011 to 2015 using parallel process latent class growth analysis. Adverse outcomes were obtained from 2015 to 2020 across two subsequent waves. We calculated hazard ratios (HR) using Cox proportional hazard models. We also conducted analyses by gender. RESULTS: Three joint trajectories were identified, including persistent absence of physical and social frailty (58.5 %), no physical frailty but social frailty (28.1 %), and persistent combination of physical and social frailty (13.4 %). Compared with persistent absence of physical and social frailty, no physical frailty but social frailty and persistent combination of physical and social frailty were associated with higher risk of instrumental activities of daily living (IADL) disability (HR = 1.182-2.020, 95 % CI: 1.014-2.416) and all-cause mortality (HR = 1.440-2.486, 95 % CI: 1.211-3.009). The persistent combination of physical and social frailty was also associated with ADL disability (HR = 2.412, 95 % CI: 1.999-2.911) and falls (HR = 1.410, 95 % CI: 1.196-1.662). Gender differences were observed in relationships between joint trajectories and adverse outcomes. CONCLUSION: Community-dwelling older adults exhibit distinct joint trajectories and those with persistent combination of physical and social frailty experience greatest risk of incident adverse outcomes. Clinical and public health measures targeting physical or social frailty should account for both and be gender-specific.

Urinary C4d and progression of kidney disease in IgA vasculitis.

BACKGROUND: IgA vasculitis nephritis is the most common secondary IgA nephropathy. Urinary C4d have been identified associated with the development and progression in primary IgA nephropathy. However, its role in kidney disease progression of IgA vasculitis nephritis is still unclear. METHODS: This study enrolled 139 patients with IgA vasculitis nephritis (IgAVN), 18 healthy subjects, 23 Focal segmental glomerulosclerosis patients and 38 IgA nephropathy (IgAN) patients. Urinary C4d levels at kidney biopsy were measured using enzyme-linked immunosorbent assay. The association between urinary C4d/creatinine and kidney disease progression event, defined as 40% eGFR decline or ESKD, was assessed using Cox proportional hazards models and restricted cubic splines. RESULTS: The levels of urinary C4d/creatinine in IgAVN and IgAN patients were higher than in healthy controls. Higher levels of urinary C4d/creatinine were associated with higher proteinuria and severe Oxford C lesions and glomerular C4d deposition. After a median follow-up of 52.79 months, 18 (12.95%) participants reached composite kidney disease progression event. The risk of kidney disease progression event was higher with higher levels of ln (urinary C4d/creatinine). After adjustment for clinical data, higher levels of urinary C4d/creatinine were associated with kidney disease progression in IgA vasculitis nephritis (per ln transformed urinary C4d/creatinine, hazard ratio (HR) =1.573, 95% confidence interval (CI) 1.101-2.245; P = 0.013). Compared to the lower C4d/creatinine group, hazard ratio was 5.539(95%CI, 1.135-27.035; P = 0.034) for the higher levels group. CONCLUSIONS: Higher levels of urinary C4d/creatinine were associated with kidney disease progression event in patients IgAVN.

A promising natural killer cell-based model and a nomogram for the prognostic prediction of clear-cell renal cell carcinoma.

BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) is one of prevalent kidney malignancies with an unfavorable prognosis. There is a need for a robust model to predict ccRCC patient survival and guide treatment decisions. METHODS: RNA-seq data and clinical information of ccRCC were obtained from the TCGA and ICGC databases. Expression profiles of genes related to natural killer (NK) cells were collected from the Immunology Database and Analysis Portal database. Key NK cell-related genes were identified using consensus clustering algorithms to classify patients into distinct clusters. A NK cell-related risk model was then developed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to predict ccRCC patient prognosis. The relationship between the NK cell-related risk score and overall survival, clinical features, tumor immune characteristics, as well as response to commonly used immunotherapies and chemotherapy, was explored. Finally, the NK cell-related risk score was validated using decision tree and nomogram analyses. RESULTS: ccRCC patients were stratified into 3 molecular clusters based on expression of NK cell-related genes. Significant differences were observed among the clusters in terms of prognosis, clinical characteristics, immune infiltration, and therapeutic response. Furthermore, six NK cell-related genes (DPYSL3, SLPI, SLC44A4, ZNF521, LIMCH1, and AHR) were identified to construct a prognostic model for ccRCC prediction. The high-risk group exhibited poor survival outcomes, lower immune cell infiltration, and decreased sensitivity to conventional chemotherapies and immunotherapies. Importantly, the quantitative real-time polymerase chain reaction (qRT-PCR) confirmed significantly high DPYSL3 expression and low SLC44A4 expression in ACHN cells. Finally, the decision tree and nomogram consistently show the dramatic prediction performance of the risk score on the survival outcome of the ccRCC patients. CONCLUSIONS: The six-gene model based on NK cell-related gene expression was validated and found to accurately mirror immune microenvironment and predict clinical outcomes, contributing to enhanced risk stratification and therapy response for ccRCC patients.

Comprehensive analysis of a tryptophan metabolism-related model in the prognostic prediction and immune status for clear cell renal carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized as one of the most common types of urological cancer with high degrees of malignancy and mortality. Due to the limited effectiveness of existing traditional therapeutic methods and poor prognosis, the treatment and therapy of advanced ccRCC patients remain challenging. Tryptophan metabolism has been widely investigated because it significantly participates in the malignant traits of multiple cancers. The functions and prognostic values of tryptophan metabolism-related genes (TMR) in ccRCC remain virtually obscure. METHODS: We employed the expression levels of 40 TMR genes to identify the subtypes of ccRCC and explored the clinical characteristics, prognosis, immune features, and immunotherapy response in the subtypes. Then, a model was constructed for the prediction of prognosis based on the differentially expressed genes (DEGs) in the subtypes from the TCGA database and verified using the ICGC database. The prediction performance of this model was confirmed by the receiver operating characteristic (ROC) curves. The relationship of Risk Score with the infiltration of distinct tumor microenvironment cells, the expression profiles of immune checkpoint genes, and the treatment benefits of immunotherapy and chemotherapy drugs were also investigated. RESULTS: The two subtypes revealed dramatic differences in terms of clinical characteristics, prognosis, immune features, and immunotherapy response. The constructed 6-gene-based model showed that the high Risk Score was significantly connected to poor overall survival (OS) and advanced tumor stages. Furthermore, increased expression of CYP1B1, KMO, and TDO2 was observed in ccRCC tissues at the translation levels, and an unfavorable prognosis for these patients was also found. CONCLUSION: We identified 2 molecular subtypes of ccRCC based on the expression of TMR genes and constructed a prognosis-related model that may be used as a powerful tool to guide the prediction of ccRCC prognosis and personalized therapy. In addition, CYP1B1, KMO, and TDO2 can be regarded as the risk prognostic genes for ccRCC.

MAPK1 Mediates MAM Disruption and Mitochondrial Dysfunction in Diabetic Kidney Disease via the PACS-2-Dependent Mechanism.

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). Mitochondrial dysfunction in renal tubules, occurring early in the disease, is linked to the development of DKD, although the underlying pathways remain unclear. Here, we examine diabetic human and mouse kidneys, and HK-2 cells exposed to high glucose, to show that high glucose disrupts mitochondria-associated endoplasmic reticulum membrane (MAM) and causes mitochondrial fragmentation. We find that high glucose conditions increase mitogen-activated protein kinase 1(MAPK1), a member of the MAP kinase signal transduction pathway, which in turn lowers the level of phosphofurin acidic cluster sorting protein 2 (PACS-2), a key component of MAM that tethers mitochondria to the ER. MAPK1-induced disruption of MAM leads to mitochondrial fragmentation but this can be rescued in HK-2 cells by increasing PACS-2 levels. Functional studies in diabetic mice show that inhibition of MAPK1 increases PACS-2 and protects against the loss of MAM and the mitochondrial fragmentation. Taken together, these results identify the MAPK1-PACS-2 axis as a key pathway to therapeutically target as well as provide new insights into the pathogenesis of DKD.

Effectiveness of subjective support-focused cognitive behavioral therapy on depressive symptoms among (pre)frail community-dwelling older adults: A randomized controlled trial.

BACKGROUND: Subjective support could ameliorate the adverse effect of (pre)frailty on depressive symptoms. However, there is scarce evidence regarding subjective support-focused intervention in preventing depression among (pre)frail community-dwelling older adults. This study aims to explore the effectiveness of subjective support-focused cognitive behavioral therapy (SS-CBT) in preventing depression among this group of population. METHODS: A total of 100 community-dwelling (pre)frail older adults were recruited from six communities in a Chinese city and were randomized to an 8-week SS-CBT group or a wait-list control group. Depressive symptoms and subjective support were assessed at baseline (T0), and at 8 week (T1), 12 week (T2), 16 week (T3) after randomization. Generalized estimating equation was used to examine the effectiveness of SS-CBT on depressive symptoms and subjective support. Hierarchical linear regression models and Bootstrapping method were used to examine whether subjective support mediated the effectiveness of SS-CBT on depressive symptoms. RESULTS: Participants in SS-CBT group reported significant reduction in depressive symptoms (Wald χ2 = 20.800, p < 0.001) and improvement in subjective support (Wald χ2 = 92.855, p < 0.001) compared to those in wait-list control group. Changes in subjective support mediated the effectiveness of SS-CBT on changes in depressive symptoms. LIMITATIONS: Restricted regions to recruit participants, inclusion of the most motivated participants, lack of diagnosis of depression, potential experimenter bias and contamination, short follow-up period, and lack of an active control group. CONCLUSIONS: The findings support the benefits of SS-CBT in preventing depression among (pre)frail community-dwelling older adults, and provide insight into possible mechanisms.

Relationship between intrinsic capacity and health-related quality of life among community-dwelling older adults: the moderating role of social support.

PURPOSE: To examine how social support might moderate the relationship between intrinsic capacity and health-related quality of life (HRQoL) based on the buffering model of social support. METHODS: This was a cross-sectional study with a sample of 1181 Chinese community-dwelling older adults aged ≥ 60 years in 2016. Social support was assessed using the Social Support Rating Scale. Intrinsic capacity was assessed using the revised integrated care for older people screening tool. HRQoL was measured by the 12-item Short Form Health Survey. Hierarchical linear regression analysis was implemented to test the moderating effect of social support. RESULTS: Support utilization attenuated the relationship between lower intrinsic capacity and poor physical HRQoL while subjective support attenuated the relationship between lower intrinsic capacity and poor mental HRQoL. However, objective support had no significant moderating effect on the relationship between intrinsic capacity and specific domains of HRQoL. CONCLUSION: The moderating effects of social support on the association between intrinsic capacity and HRQoL vary by support types. Effective interventions should target the perception and utilization of available support among older adults with lower intrinsic capacity to maintain their physical and mental HRQoL.

Prognostic biomarkers for sepsis mortality based on the literature and LC-MS-based metabolomics of sepsis patients.

OBJECTIVES: The management of sepsis, a potentially lethal overreaction to infection, is limited by the lack of prognostic tools to guide its treatment. Our aim is to identify a novel metabolic biomarker panel for predicting sepsis mortality based on a literature review and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. METHODS: In the literature, we found metabolomics biomarkers reported to predict sepsis mortality. We determined the classifications, reported frequency, and KEGG pathway enrichment of these markers. Using serum samples from 20 sepsis survivors and 20 non-survivors within 28 days after admission to the intensive care unit (ICU), we performed LC-MS-based metabolomics. Based on the literature review and metabolomics, a prognostic biomarker panel for sepsis was identified and its area under the curve (AUC) values was assessed. RESULTS: Kynurenate, caffeine, and lysoPC 22:4 were selected as a prognostic biomarker panel for sepsis. The panel had an area under the curve (AUC) of 0.885 (95% CI, 0.694-1) evaluated by linear support vector machine (SVM) and 0.849 (0.699-1) by random forest (RF), which was higher than that of the Sequential Organ Failure Assessment (SOFA). A combination of kynurenate, caffeine, and lysoPC 22:4 and SOFA provided the best discriminating performance, with AUCs of 0.961 (0.878-1) for SVM and 0.916 (0.774-1) for RF. CONCLUSIONS: The prognostic biomarker panel consisting of kynurenate, caffeine, and lysoPC 22:4 may aid in the identification of sepsis patients at a high risk of death, leading to personalized therapy in clinical practice that will improve sepsis survival.

The multifaceted role of placental growth factor in the pathogenesis and progression of bronchial asthma and pulmonary fibrosis: Therapeutic implications.

Placental growth factor (PlGF) is a glycosylated dimeric protein that is homologous to vascular endothelial growth factor (VEGF). PlGF expression is upregulated in patients with bronchial asthma, suggesting that it plays a role in the pathogenesis of asthma. Bronchial asthma is characterized by chronic airway inflammation and airway hyperresponsiveness (AHR). After recurrent asthma attacks, pulmonary fibrosis develops and leads to airway remodeling and a further decline in lung function. In this review, we focused on the pivotal role of PlGF in chronic airway inflammation, AHR, and airway remodeling during bronchial asthma. Furthermore, we summarized data showing that PlGF may be a potential therapeutic target in bronchial asthma.

Development and validation of a preliminary clinical support system for measuring the probability of incident 2-year (pre)frailty among community-dwelling older adults: A prospective cohort study.

OBJECTIVE: To develop the wed-based system for predicting risk of (pre)frailty among community-dwelling older adults. MATERIALS AND METHODS: (Pre)frailty was determined by physical frailty phenotype scale. A total of 2802 robust older adults aged ≥60 years from the China Health and Retirement Longitudinal Study (CHARLS) 2013-2015 survey were randomly assigned to derivation or internal validation cohort at a ratio of 8:2. Logistic regression, Random Forest, Support Vector Machine and eXtreme Gradient Boosting (XGBoost) were used to construct (pre)frailty prediction models. The Grid search and 5-fold cross validation were combined to find the optimal parameters. All models were evaluated externally using the temporal validation method via the CHARLS 2011-2013 survey. The (pre)frailty predictive system was web-based and built upon representational state transfer application program interfaces. RESULTS: The incidence of (pre)frailty was 34.2 % in derivation cohort, 34.8 % in internal validation cohort, and 32.4 % in external validation cohort. The XGBoost model achieved better prediction performance in derivation and internal validation cohorts, and all models had similar performance in external validation cohort. For internal validation cohort, XGBoost model showed acceptable discrimination (AUC: 0.701, 95 % CI: [0.655-0.746]), calibration (p-value of Hosmer-Lemeshow test > 0.05; good agreement on calibration plot), overall performance (Brier score: 0.200), and clinical usefulness (decision curve analysis: more net benefit than default strategies within the threshold of 0.15-0.80). The top 3 of 14 important predictors generally available in community were age, waist circumference and cognitive function. We embedded XGBoost model into the server and this (pre)frailty predictive system is accessible at http://www.frailtyprediction.com.cn. A nomogram was also conducted to enhance the practical use. CONCLUSIONS: A user-friendly web-based system was developed with good performance to assist healthcare providers to measure the probability of being (pre)frail among community-dwelling older adults in the next two years, facilitating the early identification of high-risk population of (pre)frailty. Further research is needed to validate this preliminary system across more controlled cohorts.

Clinical practice guidelines for frailty vary in quality but guide primary health care: a systematic review.

OBJECTIVES: To appraise the methodological quality, clinical applicability, and reporting quality of clinical practice guidelines (CPGs) for frailty in primary care and identify research gaps using evidence mapping. STUDY DESIGN AND SETTING: We conducted a systematic literature search in PubMed, Web of Science, Embase, CINAHL, guideline databases, and frailty or geriatric society websites. Appraisal of Guidelines Research and Evaluation II, AGREE-Recommendations Excellence, and Reporting Items for Practice Guidelines in Healthcare checklist were used to evaluate overall quality for frailty CPGs as "high", "medium", or "low" quality. We used bubble plots to show recommendations in CPGs. RESULTS: Twelve CPGs were identified. According to the overall quality evaluation, five CPGs were considered as high quality, six as medium quality, and one as low quality. The recommendations in CPGs were generally consistent and mainly focused on frailty prevention, identification, multidisciplinary, nonpharmacological, and other treatments. However, evidence was lacking in some areas, such as effective prevention strategies and implementation of recommendations. CONCLUSION: The frailty CPGs vary in quality but have consistent recommendations that can guide clinical practice in primary care. This could point the way for future research to address existing gaps and facilitate the development of trustworthy CPGs for frailty.

Elevated Urinary IL-6 Predicts the Progression of IgA Nephropathy.

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. However, biomarkers for predicting the progression or regression of IgAN remain a clinical challenge. In the present study, we aim to identify promising prognostic markers of IgAN. Methods: Using the cytokine antibody array, we detected serum and urinary levels of 9 common cytokines selected from 23 IgAN-related biomarkers in 32 patients with IgAN and 16 healthy controls. The best biomarkers for distinguishing IgAN patients from healthy controls were identified and confirmed in a multicenter cohort with 222 patients with IgAN and 159 age- and sex-matched healthy controls. Their associations with IgAN progression were further explored in 762 patients with IgAN with a median follow-up of 65 months. Results: Among the 9 candidate markers, urinary interleukin-6 (IL-6) and transforming growth factor-ß1 (TGF-ß1) levels were the best for distinguishing patients with IgAN from healthy controls. In the diagnostic cohort, both urinary IL-6 and TGF-ß1 levels were elevated in patients with IgAN and showed good discriminatory power, with an area under curve (AUC) of 0.9725 (95% confidence interval: 0.9593-0.9858). Elevated urinary IL-6 level was independently and significantly correlated with the high risk of composite renal outcome (hazard ratio per log-transformed IL-6:1.420 [1.139-1.769]), but no statistical significance was observed between urinary TGF-ß1 level and IgAN progression after adjusting for multiple confounders. Conclusions: Elevated urinary IL-6 and TGF-ß1 levels predict the progression of IgAN. Urinary IL-6 is an independent risk factor and a promising noninvasive predictor for IgAN progression.

How does social support interact with intrinsic capacity to affect the trajectory of functional ability among older adults? Findings of a population-based longitudinal study.

BACKGROUND: The ecological model of health and ageing has proposed that functional ability (FA) is determined by the interaction between intrinsic capacity (IC) and environmental characteristics. This study empirically examined how social support, as an important social environmental resource, interacts with IC to affect FA trajectories among older adults. METHODS: This was a prospective three-wave cohort study with a sample of 775 community-dwelling older adults. Social support, IC and FA were assessed using the Social Support Rating Scale, the revised Integrated Care for Older People screening tool and the Lawton Instrumental Activities of Daily Living Scale, respectively. Latent growth curve models (LGCM) were implemented to test their relationships. RESULTS: FA significantly declined over 3 years, and the detrimental effect of impaired IC on the deterioration rate of FA was buffered by subjective support but was aggravated by support utilization and was not changed by objective support. FA decline among older adults with impaired IC was observed in those with low subjective support or with high support utilization but not in those with high subjective support or with low support utilization. Among older adults with intact IC, FA decline was observed in those with low support utilization but not in those with high support utilization or with low or high subjective support. CONCLUSIONS: Subjective support may prevent FA decline among older adults with impaired IC, while support utilization may benefit older adults with intact IC but may be detrimental for those with impaired IC. Social support interventions to optimize FA trajectories should improve older adults' perceptions of support and bridge the gap in support utilization among older adults with impaired IC.

Executive function and attentional bias as serial mediators in the relationship between frailty and depressive symptoms among older inpatients: A cross-sectional study.

AIMS AND OBJECTIVES: To examine the serial mediating effect of executive function and attentional bias in the relationship between frailty and depressive symptoms. BACKGROUND: Although the role of frailty in predicting depression has been well documented, the underlying mechanisms remain unclear. DESIGN: A cross-sectional study was conducted with 667 older inpatients aged 60-90 years in the internal medicine wards of a hospital in China. METHODS: Attentional bias, frailty and depressive symptoms were assessed using the Attention to Positive and Negative Information Scale, the Physical Frailty Phenotype and the 5-item Geriatric Depression Scale. Executive function was measured using 3 tests, including digital backward, category Verbal Fluency Test and Trail Making Test. The study followed the STROBE guideline. RESULTS: The latent profile analysis (LPA) identified four patterns of attentional bias, namely "no positive bias & no negative bias" (class 1, 9.3%), "minor positive bias & no negative bias" (class 2, 48.0%), "major positive bias & minor negative bias" (class 3, 25.6%) and "major positive bias & no negative bias" (class 4, 17.1%). Regression analysis found that frailty was associated with depressive symptoms. Frailty was also negatively associated with executive function, which was a protective factor for attentional bias class 1, 2 and 3 with reference to class 4. Attentional bias class 1 and 2 but not class 3 was associated with depressive symptoms with reference to class 4. The joint significance test confirmed executive function and attentional bias as serial mediators linking frailty to depressive symptoms. DISCUSSION: Unlike robust older adults who have the age-related positivity effect, frail older adults have attentional bias deficits due to executive dysfunction, and consequently experience clinically relevant depressive symptoms. RELEVANCE TO CLINICAL PRACTICE: Healthcare providers should take executive function training and attentional bias regulation into consideration to reduce the detrimental effects of frailty on emotional well-being.

Association between self-efficacy and self-management behaviours among individuals at high risk for stroke: Social support acting as a mediator.

AIMS AND OBJECTIVES: To explore the association between self-efficacy and self-management by modelling three types of social support as mediators among stroke high-risk populations. BACKGROUND: Self-efficacy and social support (i.e. objective support, subjective support and support utilisation) are important for self-management among stroke high-risk populations. Self-efficacy activates three types of social support, and the effect of social support on self-management varies by types among chronic patients. Therefore, social support may act as a mediator between self-efficacy and self-management, and the mediating role may vary by types of social support. Disentangling the role of these different types of social support can guide tailored interventions. DESIGN: A cross-sectional study. METHODS: This study was conducted among 448 Chinese adults at high risk for stroke. Self-efficacy, self-management and social support were assessed using the Self-Efficacy Scale, the Stroke Self-management Scale and the Social Support Rating Scale respectively. The PROCESS SPSS Macro version 3.3, model 4 was used to explore the mediating role of different types of social support in the relationship between self-efficacy and self-management. This study followed STROBE checklist for cross-sectional studies (Appendix S1). RESULTS: Self-efficacy improved three types of social support, and subjective support and support utilisation promoted self-management, but objective support hindered self-management. The specific indirect effect of objective support and subjective support was significant but not that of support utilisation. Objective support, subjective support and support utilisation attenuated the total effect of self-efficacy on self-management by -23.8%, 23.8% and 7.7% respectively. CONCLUSIONS: Mediating effect of social support in the relationship between self-efficacy and self-management varies by type, and the positive effect of subjective support is offset by the detrimental effect of objective support. RELEVANCE TO CLINICAL PRACTICE: Among stroke high-risk populations, interventions should target objective support and subjective support as well as self-efficacy to efficiently improve their self-management.

STXBP3 and GOT2 predict immunological activity in acute allograft rejection.

Background: Acute allograft rejection (AR) following renal transplantation contributes to chronic rejection and allograft dysfunction. The current diagnosis of AR remains dependent on renal allograft biopsy which cannot immediately detect renal allograft injury in the presence of AR. In this study, sensitive biomarkers for AR diagnosis were investigated and developed to protect renal function. Methods: We analyzed pre- and postoperative data from five databases combined with our own data to identify the key differently expressed genes (DEGs). Furthermore, we performed a bioinformatics analysis to determine the immune characteristics of DEGs. The expression of key DEGs was further confirmed using the real-time quantitative PCR (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemical (IHC) staining in patients with AR. ROC curves analysis was used to estimate the performance of key DEGs in the early diagnosis of AR. Results: We identified glutamic-oxaloacetic transaminase 2 (GOT2) and syntaxin binding protein 3 (STXBP3) as key DEGs. The higher expression of STXBP3 and GOT2 in patients with AR was confirmed using RT-qPCR, ELISA, and IHC staining. ROC curve analysis also showed favorable values of STXBP3 and GOT2 for the diagnosis of early stage AR. Conclusions: STXBP3 and GOT2 could reflect the immunological status of patients with AR and have strong potential for the diagnosis of early-stage AR.

The integrated comprehension of lncRNA HOXA-AS3 implication on human diseases

Long non-coding RNA (lncRNA) is a non-protein-coding RNA with a length of more than 200 nucleotides. Studies have shown that lncRNAs have vital impacts on various pathological processes and participate in the development of human diseases, usually through acting as competing endogenous RNAs to modulate miRNA expression and biological functions. lncRNA HOXA Cluster Antisense RNA 3 (HOXA-AS3) was a newly discovered lncRNA and has been demonstrated to be abnormally expressed in many diseases. Moreover, HOXA-AS3 expression was closely correlated with the clinicopathologic characteristics in cancer patients. In addition, HOXA-AS3 exhibited significant properties in regulating several biological processes, including cell proliferation, invasion, and migration. Furthermore, HOXA-AS3 has provided promising values in the diagnosis, prognosis, and therapeutic strategies of several diseases such as liver cancer, glioma, lung cancer, oral cancer, gastric cancer, and even atherosclerosis. In this review, we discuss the abnormal expression of HOXA-AS3 in several human disorders and some pathobiological processes and its clinical characteristics, followed by a summary of HOXA-AS3 functions, regulatory mechanisms, and clinical application potential (AU)