Association between domain-specific physical activity and mental health status after embryo transfer in IVF-ET-assisted pregnancy patients.

Physical activity has been shown to impact mental health in in vitro fertilization-embryo transfer (IVF-ET) patients, but the relationship between domain-specific physical activity and mental health in this population remains unclear. In a cross-sectional observational study, 208 patients undergoing IVF-ET with long-term ovulation induction cycles were recruited from a reproductive center. The International Physical Activity Questionnaire and the symptom checklist 90 (SCL-90) were used to assess physical activity levels and mental health status, respectively. Analyses of variance and linear regression analyses were conducted to identify the relationship between physical activity and mental health. There were differences between different physical activity level in times of transfers, years of infertility, and times of abortions. Patients with high levels of physical activity had fewer symptoms than those with low levels of physical activity. Occupation, transport and household physical activity had significant negative correlations with the respective SCL-90 factor scores. Linear regression analysis revealed that occupation physical activity was associated with lower depression and anxiety, and transport physical activity and household physical activity were associated with lower obsessive-compulsive, interpersonal sensitivity, depression, anxiety, and psychoticism scores. The study indicates that increased engagement in physical activity, specifically activities related to occupation, transportation, and household, may be associated with improved mental health among IVF-ET patients.

Real-world national trends and influencing factors preference of non-vitamin K antagonist oral anticoagulants in China.

Backgrounds: Non-vitamin K antagonist oral anticoagulants (NOACs) have been recommended as the first choice over warfarin for non-valvular atrial fibrillation (AF). However, there is limited data about their usage in mainland China. Methods: Prescriptions of patients diagnosed with AF and containing OACs were extracted from Hospital Prescription Cooperation Project from January 2016 to March 2021. The primary outcome was the changing percentage of different OACs. The secondary outcomes were frequencies as well as factors with the choice of different OACs and dosage of NOACs. Univariate and Multivariate logistic regressions were conducted to explore possible factors. All statistical analyses were performed using SAS software (Version 9.4). Results: Among the 220,083 distinct prescriptions diagnosed with AF and prescribed with OACs, the percentage of NOACs increased over years, exceeding warfarin in 2018. Until March 2021, 83.53% of included patients were prescribed with NOACs. Rivaroxaban (62.25%) and dabigatran (37.65%) were the most commonly prescribed NOACs. Low dosage was common for NOACs (44.54%), this was mainly driven by rivaroxaban, 67.98% of which were low dosage. Multivariate logistic regression indicated that several factors were positively associated with the preference of low dosage, including outpatients (OR 1.32, 95% CI 1.26-1.39), patients with hypertension (OR 1.49, 95% CI 1.40-1.58), acute coronary syndrome (OR 1.17, 95% CI 1.12-1.22), stroke (OR 1.42, 95% CI 1.33-1.52), and kidney disease (OR 1.63, 95% CI 1.34-1.97), as well as concomitantly using antiplatelet agents (OR 1.52, 95% CI 1.40-1.66), and steroids (OR 1.76, 95% CI 1.50-2.07). On the contrary, they were less common in health insurance holder (OR 0.79, 95% CI 0.75-0.84), patients taking apixaban (vs. rivaroxaban, OR 0.39, 95% CI 0.18-0.81), dabigatran (vs. rivaroxaban, OR 0.01, 95% CI 0.01-0.01), edoxaban (vs. rivaroxaban, OR 0.36, 95% CI 0.23-0.55), diagnosed with heart failure (OR 0.87, 95% CI 0.81-0.93), deep vein thrombosis (OR 0.36, 95% CI 0.29-0.46), pulmonary embolism (OR 0.35, 95% CI 0.28-0.43), and peripheral artery disease (OR 0.68, 95% CI 0.55-0.85). Conclusion: The usage of OACs for AF was overall complying with updated guidelines. Low dosage was common for NOACs, further studies were warranted to verify its effectiveness and explore the underlying mechanism.

Population pharmacokinetics of rivaroxaban in Chinese deep vein thrombosis patients and the exposure simulation for dosing recommendation.

This study aimed to develop a population pharmacokinetic (PPK) model for rivaroxaban and establish a model-based dosing guideline tailored to Chinese patients with deep vein thrombosis (DVT). A nonlinear mixed-effects modeling approach was employed using Phoenix NLME 7.0 software to construct the PPK model for rivaroxaban. The PK of rivaroxaban was adequately characterized through a one-compartment model. Monte Carlo simulations were employed to formulate dosing guidelines applicable to different patient subgroups. Data from 60 Chinese DVT patients yielded 217 rivaroxaban plasma concentrations for analysis. The apparent clearance (CL/F) of rivaroxaban was found to be significantly influenced by the estimated glomerular filtration rate (eGFR), identified as a major covariate. Based on Monte Carlo simulations, for the acute DVT treatment, a regimen of 15 mg, 10 mg, or 5 mg twice daily was associated with the highest total probability target attainment (PTAtotal) in patients with normal, mildly impaired, or moderately impaired renal function, respectively. For the continued DVT treatment, a regimen of 20 mg, 15 mg, or 5 mg once daily exhibited the maximum PTAtotal in patients with normal, mildly impaired, or moderately impaired renal function, respectively. The recommendation label dose achieved the PK target in those with normal renal function. However, for patients with mild or moderate renal impairment, dose adjustments below the label recommendation might be necessary. The PPK model associated CL/F with the covariate eGFR. Utilizing the PPK model, a dosage regimen table was constructed to offer tailored dosing recommendations for Chinese DVT patients.

CXCL10 mediates CD8+ T cells to facilitate vessel normalization and improve the efficacy of cetuximab combined with PD-1 checkpoint inhibitors in colorectal cancer.

The immunotherapy and anti-EGFR targeted treatment occupying a pivotal position in colorectal cancer (CRC), is still limited to a group of patients who display specific molecular alterations and inevitably escape from resistance, further studies are still needed in colorectal cancer. We found that chemokine ligand 10 (CXCL10) expression correlates with intratumoral CD8+ T cell infiltration and reprograms tumor vasculatures in colorectal cancer. CXCL10 overexpression not only suppressed tumor growth but also increased CD8+ T cell infiltration and induced tumor vascular normalization in vivo. Additionally, the growth inhibition and tumor vascular normalization induced by CXCL10 can be reversed by the depletion of CD8+ T cells in vivo. Mechanically, CXCL10 interacts with VCAN to mediate tumor vascular normalization. The VCAN expression correlated inversely with the expression of CXCL10 and the infiltration of CD8+ T cells in CRC. Elevated CXCL10 expression sensitized colorectal cancer cells to cetuximab/anti-PD1 combination therapy compared with cetuximab or anti-PD1 alone. We propose that CXCL10 could be used to increase the anti-EGFR therapy and immunotherapy effect, targeting both tumor vessels and immune cells in colorectal cancer.

Measuring the suicidal mind: The 'open source' Suicidality Scale, for adolescents and adults.

Clinicians are expected to provide accurate and useful mental health assessments, sometimes in emergency settings. The most urgent challenge may be in calculating suicide risk. Unfortunately, existing instruments often fail to meet requirements. To address this situation, we used a sustainable scale development approach to create a publicly available Suicidality Scale (SS). Following a critical review of current measures, community input, and panel discussions, an international item pool survey included 5,115 English-speaking participants aged 13-82 years. Revisions were tested with two follow-up cross-sectional surveys (Ns = 814 and 626). Pool items and SS versions were critically examined through item response theory, hierarchical cluster, factor and bifactor analyses, resulting in a unidimensional eight-item scale. Psychometric properties were high (loadings > .77; discrimination > 2.2; test-retest r = .87; internal consistency, ω = .96). Invariance checks were satisfied for age, gender, ethnicity, rural/urban residence, first language, self-reported psychiatric diagnosis and suicide attempt history. The SS showed stronger psychometric properties, and significant differences in bivariate associations with depressive symptoms, compared with included suicide measures. The 'open source' Suicidality Scale represents a significant step forward in accurate assessment for people aged 13+, and diverse populations. This study provides an example of sustainable scale development utilizing community input, emphasis on strong psychometric evidence from diverse samples, and a free-to-use license allowing instrument revisions. These methods can be used to develop a wide variety of psychosocial instruments that can benefit clinicians, researchers, and the public.

Three Neolignan Glycosides from the Root of Nothopanax davidii.

Three neolignan glycosides, including a new compound (7S,8R)-dihydro-3'-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1'-benzofuranpropanol-9-O-ß-D-xylopyranoside (1), were isolated from the root of Nothopanax davidii. Their structures were determined by extensive spectroscopic analyses, particularly NMR, HR-ESI-MS, and ECD experiments, and the absolute configuration of 2 was first definitively determined. The anti-tumor activity was assessed on four tumor cells by MTT assay, the anti-inflammatory activity was determined by inhibition of NO production in LPS reduced RAW264.7 cells, and the interaction with iNOS was predicted by molecular docking. At the dose of 100 µM, the three neolignan glycosides showed no cytotoxic activity against HepG2, HCT116, HeLa and A549 human tumor cells, but significantly inhibited LPS induced NO generation in RAW264.7 cells with inhibition rates of 31.53 %, 23.95 %, and 20.79 %, respectively, showing weak anti-inflammatory activity, possibly due to their binding to key residues of iNOs involved in inhibitor binding.

Lower insulin level is associated with sarcopenia in community-dwelling frail and non-frail older adults.

Background: Sarcopenia is common among older individuals with and without type 2 diabetes mellitus (T2DM). There are conflicting evidence in support of the role of insulin in the development of age-related and T2DM-related sarcopenia. We investigated the relationships between the levels of fasting insulin and other blood biomarkers related to insulin or lipid metabolism with the presence of sarcopenia in two independent studies. Materials and methods: In 246 pre-frail frail older individuals with (n = 41) and without T2DM (n = 205) in the Singapore Frailty Interventional Trial, sarcopenia was defined by low appendicular lean mass (ALM) relative to total body mass (skeletal muscle index, SMI = ALM/height2) and low lower limb strength or gait speed according to the Asian Working Group for Sarcopenia (AWGS) criteria released in 2019, and related to levels of fasting insulin and glucose, C-peptide, IGF-1, leptin, and active ghrelin. This investigation was validated in another independent study sample of 189 robust and pre-frail frail elderly in the Singapore Longitudinal Aging Study Wave 2 (SLAS-2). Results: Compared to non-sarcopenic individuals, those with sarcopenia and possible sarcopenia showed significantly lower fasting insulin (p < 0.05) in pre-frail/frail and non-frail older individuals. Consistent trends of relationships were observed for serum levels of C-peptide, IGF-1, leptin, and active ghrelin. In multivariable logistic regression models, sarcopenia was independently associated with low insulin (p < 0.05). Levels of fasting insulin, C-peptide, and leptin were also significantly associated with BMI, SMI, knee extension strength, gait speed, and physical activity score. Conclusion: Dysregulated insulin secretion in diabetic and non-diabetic older individuals may play an important role in age-related and diabetes-related sarcopenia.

Effects of illness perception on negative emotions and fatigue in chronic rheumatic diseases: Rumination as a possible mediator.

BACKGROUND: Illness perception has long been hypothesized to be linked to psychological well-b eing in patients with rheumatic diseases, although substantial evidence is lacking, and the contribution of ruminative coping style to this relationship is unclear. AIM: To investigate the roles of illness perception and rumination in predicting fatigue and negative emotions in patients with chronic rheumatic diseases. METHODS: Illness perception, rumination, fatigue and negative emotions (i.e. depression, anxiety and stress) were assessed by the Illness Perception Questionnaire-Revised, Stress Reactive Rumination Scale, Multidimensional Assessment of Fatigue, and the Depression, Anxiety and Stress Scale respectively. Multivariate regression analysis, the Sobel test, and the bootstrap were used to identify the mediating effect of rumination. RESULTS: All five subscales of illness perception, including perceived illness identity, chronicity, cyclical nature, consequences and coherence of illness, were significantly associated with fatigue and negative emotions. In mediational analysis, rumination was found to mediate three components of illness perception (the identity, cyclical nature and consequences of illness) and negative emotions/fatigue. CONCLUSION: Perceived identity, cyclical nature, and consequences of illness are significantly associated with fatigue and negative emotions in patients with chronic rheumatic diseases and these associations are mediated by rumination. Our findings suggest that psychological intervention should target rumination to improve physical and emotional well-being of patients with chronic rheumatic diseases.

Factors associated with mental health outcomes among caregivers of older adults in long-term care facilities during COVID-19 post-epidemic era in Shandong, China.

Background: COVID-19 pandemic has altered the work mode in long-term care facilities (LTCFs), but little is known about the mental health status of caregivers of older adults. Methods: A total of 672 formal caregivers of older adults in LTCFs and 1,140 formal patient caregivers in hospitals (comparison group) responded to an online survey conducted from March 25, 2022 to April 6, 2022. Five psychological scales, including Insomnia Severity Index (ISI), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), The 5-item World Health Organization Wellbeing Index (WHO-5) and Perceived Stress Scale-14 item (PSS-14), were applied to assess participants' mental health status. Factors, including sex, profession, marital status, economic conditions, length of working experience, frequent night shift beyond 1 day per week and having organic diseases, were included in logistic regression analysis to identify associated factors with mental health outcomes of formal caregivers of older adults in LTCFs. Results: Caregivers of older adults in LTCFs developed similar severe psychological symptoms with patient caregivers in hospital setting. For caregivers of older adults in LTCFs, unmarried status was a potent risk factor for insomnia, anxiety, impaired wellbeing and health risk stress, with odds ratios ranging from 1.91 to 3.64. Frequent night shift beyond 1 day per week was associated with higher risks of insomnia, depression and impaired wellbeing. Likewise, having organic disease or inferior economic condition, and being nurses appeared to be independent predictors for multiple mental health-related outcomes. Conclusion: During COVID-19 post-epidemic era, caregivers of older adults in LTCFs had a higher prevalence of psychological symptoms, especially those with particular risk factors. Special attention should be paid to promote their mental health.

Effects of Mindful Awareness Practice (MAP) on Subclinical Depressive and Anxiety Symptoms and General Cognitive Function in Older Adults with Mild Cognitive Impairment: A 5-Year Follow-Up of the MAP-Randomized Controlled Trial.

BACKGROUND: Few randomized controlled trials (RCTs) investigated the effects of mindfulness intervention on affective and cognitive symptoms in older adults with mild cognitive impairment (MCI). Furthermore, no RCTs on mindfulness followed participants beyond two years. OBJECTIVE: To examine the longitudinal effects of a mindful awareness practice (MAP) intervention on depressive, anxiety, and cognitive symptoms in MCI. METHODS: In this parallel-arm and assessor-blinded RCT, 55 community-dwelling older adults with MCI were randomized into the MAP or active control, i.e., health education program (HEP). Intervention sessions were conducted weekly for three months and monthly for the subsequent six months. Assessments and follow-up were conducted at baseline, 3-month, 9-month, and 5-year time points. Depressive, anxiety, and cognitive symptoms were measured using the Geriatric Depression Scale-15 (GDS-15), Geriatric Anxiety Inventory-20 (GAI-20), and Mini-Mental State Examination (MMSE), respectively. Linear-mixed models, following the intention-to-treat principle, were used for data analyses. RESULTS: A total of 55 participants aged 60 to 86 (Mean age: 71.3±6 years old) was recruited, with n = 28 allocated to the MAP arm and n = 27 allocated to the HEP arm. Compared to HEP, GDS-15, GAI-20, and MMSE scores did not differ significantly in MAP during follow-ups. CONCLUSION: Compared to HEP, MAP did not improve affective symptoms nor delay deteriorations in general cognition in community-dwelling older adults with MCI. Compared to our previous findings showing domain-specific improvements in MAP over HEP in attention and memory up to 9 months, this study highlights the importance of examining domain-specificity using detailed cognitive measures in non-pharmacological intervention with MCI.

circEXOC6B interacting with RRAGB, an mTORC1 activator, inhibits the progression of colorectal cancer by antagonizing the HIF1A-RRAGB-mTORC1 positive feedback loop.

BACKGROUND: In recent years, an increasing number of studies have indicated that circular RNA plays crucial roles in regulating tumor development and chemoresistance. Using two high-throughput RNA sequence datasets, we previously found that circEXOC6B was downregulated in colon cancer. However, its role and mechanism in colorectal cancer (CRC) remained unknown. METHODS: Real-time quantitative PCR was used to examine the expression of circEXOC6B in CRC tissues. In vivo and in vitro functional experiments were performed to determine the suppressor role of circEXOC6B in CRC progression. RNA pull-down, mass spectrometry, RNA-binding protein immunoprecipitation, co-immunoprecipitation, fluorescence in situ hybridization, and immunofluorescence were applied to investigate the possible mechanisms connecting circEXOC6B to CRC growth and 5-fluorouracil-induced apoptosis. Chromatin immunoprecipitation, dual-luciferase assay, western blot, and immunohistochemistry were used to explore the mechanisms underlying the HIF1A regulation of RRAGB transcription. RESULTS: circEXOC6B was downregulated in CRC tissues, and its lower expression was associated with poor prognosis of patients. Functional experiments showed that circEXOC6B inhibited growth and increased the 5-fluorouracil-induced apoptosis of CRC cells in vitro and in vivo. Mechanistically, circEXOC6B inhibited the heterodimer formation of RRAGB by binding to it, thereby suppressing the mTORC1 pathway and HIF1A level. In addition, HIF1A upregulated the transcription of RRAGB by binding to its promoter region. Altogether, the results demonstrated that a HIF1A-RRAGB-mTORC1 positive feedback loop drives tumor progression in CRC, which could be interrupted by circEXOC6B. CONCLUSIONS: circEXOC6B inhibits the progression of CRC and enhances the chemosensitivity of CRC cells to 5-fluorouracil by antagonizing the HIF1A-RRAGB-mTORC1 positive feedback loop. circEXOC6B is a possible therapeutic target for CRC treatment.

Inflammatory markers and incident depression: Evidence in a population-based prospective study.

The association between pro-inflammatory cytokines and depression is widely acknowledged. However, longitudinal data that show they lead to depression are few. In a community-based sample of older individuals (n = 2761, ages = 55-98 y) in the Singapore Longitudinal Ageing Study (SLAS), we analyzed the associations between inflammatory markers (CRP, IL6, TNFα, and inflammation risk score) and depression (defined as the presence of depressive symptoms, depression history or treatment). Cross-sectional analysis showed that CRP, IL-6 and TNFα were significantly associated with depression at baseline. Longitudinal analysis controlling for a host of potentially confounding risk factors and initial depression revealed that IL-6, TNFα, and inflammation risk score were associated with elevated risk of depression at follow-ups. However, there was no significant association between CRP and subsequent depression after adjusting for sociodemographic, lifestyles and inflammatory medical condition variables. In summary, this prospective study shows that inflammation predicts depression in older adults, and suggests that the heterogeneous findings among studies may be due to differences in study population characteristics, depression, inflammatory markers, and the extent of adjusting for confounders.

Effect of Intensive Psychological Nursing Intervention on HAMD and SF-36 Scores in Patients with Severe Liver Cancer in ICU.

The aim of the study was to explore the effect of intensive psychological nursing intervention on HAMD and SF-36 scores in patients with severe liver cancer in intensive care unit (ICU). 134 critically ill patients with liver cancer in ICU who underwent resection of primary liver cancer from July 2019 to November 2021 were selected. The patients were randomly divided into control group and study group. The patients in the control group received routine nursing. The patients in the study group received intensive psychological nursing intervention on the basis of routine nursing. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the MOS 36-item short-form health survey (SF-36) scores before and after nursing were compared between the two groups. The satisfaction of the two groups of patients with nursing was counted. The HAMA, HAMD, and SF-36 scores of patients receiving intensive psychological nursing intervention were significantly better than those receiving routine nursing. The nursing satisfaction of patients receiving intensive psychological nursing intervention was significantly higher than that of patients receiving routine nursing. Intensive psychological nursing intervention for patients with severe liver cancer in ICU can significantly reduce HAMD, improve SF-36 score, and patient nursing satisfaction. It is worthy of wide clinical promotion.

Malnutrition Risk and Kidney Function and Decline in Community-Dwelling Older Adults.

OBJECTIVES: The association of malnutrition with chronic kidney disease (CKD) is well established. However, there is a paucity of studies of the effect of malnutrition risk (MR) on kidney function decline among older persons who do not have end-stage or dialyzable CKD. This study aimed to examine the association between MR status and kidney function, and future risks of kidney function decline and CKD progression in community-dwelling older adults. DESIGN AND METHODS: Nutrition Screening Initiative's DETERMINE Your Nutritional Health Checklist and estimated glomerular filtration rate (eGFR) were assessed at baseline among 5,122 participants free of end-stage renal failure or dialyzed CKD in the Singapore Longitudinal Aging Studies (SLAS-1 and SLAS-2). Follow-up eGFR was assessed in a subcohort of SLAS-2 participants without CKD (eGFR > 60 mL/min/1.73 m2) at baseline (N = 786) who were followed up at 3-5 years. RESULTS: In baseline cross-sectional analyses adjusting for other risk factors, low, moderate, and high MR was significantly associated with decreasing eGFR coefficients of -1.5, -3.3, and -5.0 mL/min/1.73 m2 respectively, and increasing CKD odds ratios of 1.81, 2.18, and 3.11 respectively. In longitudinal analysis, low, moderate, and high MR was significantly associated with increased risk of eGFR (>25%) decline (odds ratio of 2.37, 3.34, and 2.18 respectively). CONCLUSIONS: Among older adults without advanced kidney disease, MR is associated with poor kidney function and increased risk of kidney function decline and CKD. Preventive interventions to modify MR may help to reduce the deterioration of renal function in older people.

Lifetime pathogen burden, inflammatory markers, and depression in community-dwelling older adults.

The link between pathogen exposure and mental health has long been hypothesized, but evidence remains limited. We investigated the association of seropositivity to common pathogens and total pathogen burden with depression and mental health and explored the role of mediating inflammatory cytokines. We profiled in 884 participants in the Singapore Longitudinal Ageing Studies, mean (SD) age: 67.9 (8.1) years, their seropositivities for 11 pathogens (CMV, HSV 1, HSV 2, HHV-6, EBV, VZV, RSV, Dengue, Chikungunya, H. Pylori and Plasmodium) and pathogen burden, Geriatric Depression Scale (GDS) score at baseline and 3-4 and 6-8 years follow-up, and baseline Mental Component Score (MCS) of 12-Item Short Form Survey (SF-12). Inflammatory markers included CRP, TNF-α, IL-6, MIP-1α, sgp130, sTNF-RI, sTNF-RII, C3a, and MCP-2. Controlling for age, sex, ethnicity, education, marital status, living alone, and smoking status, high pathogen burden (7 + cumulative infections) compared to low pathogen burden (1-5 cumulative infections) was significantly associated with period prevalence (the highest GDS score from baseline and follow-up measurements) of depressive symptoms (OR = 2.36, 95% CI = 1.05-5.33) and impaired mental health (OR = 2.25, 95% CI = 1.18-4.30). CMV seropositivity and HSV1 seropositivity, which are highly prevalent and most widely studied, were associated with estimated 2-fold increased odds of depression, but only HSV1 seropositivity was significantly associated with depression after adjusting for confounders. Notably, adjusted for confounders, RSV, H. pylori and Plasmodium seropositivity were significantly associated with increased odds, and Dengue seropositivity was associated with unexpectedly deceased odds of depressive symptoms and impaired mental health. The association of pathogen exposure with depression and mental health were at least in parts explained by inflammatory markers. Adding certain inflammatory markers to the models attenuated or weakened the association. Bootstrap method showed that MIP-1α significantly mediated the association between pathogen burden and mental health. In conclusion, lifelong pathogen burden and specific infections are associated with depression and impaired mental health in older adults.

Cardiometabolic and Vascular Disease Factors and Mild Cognitive Impairment and Dementia.

INTRODUCTION: There is empirical evidence that cardiovascular risk factors and vascular pathology contribute to cognitive impairment and dementia. METHODS: We profiled cardiometabolic and vascular disease (CMVD) and CMVD burden in community-living older adults in the Singapore Longitudinal Ageing Study cohort and examined the association of CMVD risk markers with the prevalence and incidence of mild cognitive impairment (MCI) and dementia from a median 3.8 years of follow-up. RESULTS: Prevalent MCI and dementia, compared with normal cognition, was associated with higher proportions of persons with any CMVD, hypertension, diabetes, coronary heart disease, atrial fibrillation, or stroke. Diabetes, stroke, and the number of CMVD risk markers remained significantly associated with dementia or MCI after adjusting for age, sex, formal education level, APOE-ε4 genotype, and level of physical, social, or productive activities, with odds ratios ranging from 1.3 to 5.7. Among cognitively normal participants who were followed up, any CMVD risk factor, dyslipidemia, diabetes, or heart failure at baseline predicted incident MCI or its progression to dementia after adjusting for potential confounders. CONCLUSION: Older adults with higher burden of CMVD, driven especially by diabetes, are likely to increase the risk of prevalent and incident MCI and dementia.

Prevalence, risk and protective factors for mild cognitive impairment in a population-based study of Singaporean elderly.

The prevalence of dementia has been widely reported, and its potential risk and protective factors are well-characterized. However, there is a scarcity of related information regarding mild cognitive impairment (MCI). Thus this population-based study aimed to determine the prevalences of MCI and its subtypes, as well as to identify the risk and protective factors for MCI in the Chinese elderly population of Singapore. Results showed that the overall prevalence of MCI was 12.5%, while the gender-adjusted prevalence of MCI was 12.3%. Gender was found to be significantly associated with the subtypes of MCI, with males more likely to have amnestic MCI and females more likely to have non-amnestic MCI. Older age, lower educational levels, lower social activity levels, depression, hypertension, hyperlipidemia, diabetes and stroke were found to be risk factors for MCI in univariate analysis. However, multivariable analysis showed that only hypertension and stroke were the significant risk factors for MCI. Higher educational levels and active social engagements were significant protective factors for MCI in multivariable analysis. Age and depression had boundary significant associations with the prevalence of MCI. After adjusting for gender, the influence of hypertension, stroke, social engagement, age and depression on MCI remained unchanged, except that education became a boundary significant lower risk factor of MCI development. In conclusion, this study presented the prevalence, risk and protective factors for MCI among Singaporean Chinese older adults, which facilitates the screening of vulnerable groups for MCI.

Physiological Dysregulation, Frailty, and Impacts on Adverse Health and Functional Outcomes.

Background: Multi-system physiological dysregulation (PD) may represent a biological endo-phenotype of clinical frailty. We investigated the co-occurrence of PD with physical frailty and its contributions to the known impact of frailty on adverse health outcomes. Methods: Data of 2,725 participants from the Singapore Longitudinal Aging Studies (SLAS-2), included baseline measures of physical frailty and PD derived from Mahalanobis distance (Dm) value of 23 blood biomarkers. We analyzed their concurrent association and their impacts on 9-year mortality, MMSE cognition, GDS depression, number of medications, disability, and hospitalization at baseline and follow up (mean 4.5 years). Results: Global PD (Log10Dm, mean = 1.24, SD = 0.24) was significantly but weakly associated with pre-frailty-and-frailty. Controlling for age, sex and education, pre-frailty-and-frailty (HR = 2.12, 95% CI = 1.51-3.00) and PD (HR = 3.88, 95% CI = 2.15-6.98) predicted mortality. Together in the same model, mortality HR associated with pre-frailty-and-frailty (HR = 1.83, 95% CI = 1.22-2.73) and PD (HR = 3.06, 95% CI = 1.60-5.85) were reduced after additionally adding global PD to the prediction model. The predictive accuracy for mortality were both approximately the same (PD: AUC = 0.62, frailty: AUC = 0.64), but AUC was significantly increased to 0.68 when combined (p < 0.001). Taken into account in the same model, frailty remained significantly associated with all health and functional outcomes, and PD was significantly associated with only MMSE, disability and medications used. In secondary analyses, there were mixed associations of system-specific PDs with frailty and different adverse outcomes. Conclusions: Co-existing PD and physical frailty independently predict mortality and functional and health outcomes, with increased predictive accuracy when combined. PD appears to be a valid representation of a biological endo-phenotype of frailty, and the potential utility of such subclinical measures of frailty could be further studied.

Endoplasmic reticulum stress response and bile acid signatures associate with multi-strain seroresponsiveness during elderly influenza vaccination.

The elderly are an important target for influenza vaccination, and the determination of factors that underlie immune responsiveness is clinically valuable. We evaluated the immune and metabolic profiles of 205 elderly Singaporeans administered with Vaxigrip. Despite high seroprotection rates, we observed heterogeneity in the response. We stratified the cohort into complete (CR) or incomplete responders (IR), where IR exhibited signs of accelerated T cell aging. We found a higher upregulation of genes associated with the B-cell endoplasmic-reticulum stress response in CR, where XBP-1 acts as a key upstream regulator. B-cells from IR were incapable of matching the level of XBP-1 upregulation observed in CR after inducing ER stress with tunicamycin in vitro. Metabolic signatures also distinguished CR and IR - as CR presented with a greater diversity of bile acids. Our findings suggest that the ER-stress pathway activation could improve influenza vaccination in the elderly.