Association of past and current sleep duration with structural brain differences: A large population-based study from the UK Biobank.

OBJECTIVE: This study aimed to examine the association between past/current sleep duration and macro-/micro-structural brain outcomes and explore whether hypertension or social activity plays a role in such association. METHODS: Within the UK Biobank, 40 436 dementia-free participants (age 40-70 years) underwent a baseline assessment followed by a brain magnetic resonance imaging (MRI) scan 9 years later. Past (baseline) and current (MRI scans) sleep duration (hours/day) were recorded and classified as short (≤5), intermediate (6-8), and long (≥9). Brain structural volumes and diffusion markers were assessed by MRI scans. RESULTS: Compared with past intermediate sleep, past short sleep was related to smaller cortex volumes (standardized ß [95 % CI]: -0.04 [-0.07, -0.02]) and lower regional fractional anisotropy (FA) (-0.08 [-0.13, -0.03]), while past long sleep was related to smaller regional subcortical volumes (standardized ß: -0.04 to -0.07 for thalamus, accumbens, and hippocampus). Compared to current intermediate sleep, current short sleep was associated with smaller cortex volumes (-0.03 [-0.05, -0.01]), greater white matter hyperintensities (WMH) volumes (0.04 [0.01, 0.08]), and lower regional FA (-0.07 [-0.11, -0.02]). However, current long sleep was related to smaller total brain (-0.03 [-0.05, -0.02]), grey matter (-0.05 [-0.07, -0.03]), cortex (-0.05 [-0.07, -0.03]), regional subcortical volumes [standardized ß: -0.05 to -0.09 for putamen, thalamus, hippocampus, and accumbens]), greater WMH volumes (0.06 [0.03, 0.09]), as well as lower regional FA (-0.05 [-0.09, -0.02]). The association between current long sleep duration and poor brain health was stronger among people with hypertension or low frequency of social activity (all Pinteraction <0.05). CONCLUSIONS: Both past and current short/long sleep are associated with smaller brain volume and poorer white matter health in the brain, especially in individuals with hypertension and low frequency of social activity. Our findings highlight the need to maintain 6-8 h' sleep duration for healthy brain aging.

Association of a low-inflammatory diet with survival among adults: The role of cardiometabolic diseases and lifestyle.

BACKGROUND & AIMS: Evidence on the association between dietary inflammation and longevity is limited. We aimed to examine the association of a low-inflammatory diet with mortality and longevity, and to explore whether cardiometabolic diseases (CMDs) and lifestyle factors may play a role in this association. METHODS: Within the UK Biobank, 188,443 participants aged 39-72 years (mean 56.07) were followed for up to 16 years to detect survival status from the death registry. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was calculated as weighted sum of 31 food groups (including 14 anti-inflammatory and 17 pro-inflammatory) based on plasma high-sensitivity C-reactive protein levels, and tertiled as low, moderate, and high IDI scores. Baseline lifestyle beyond diet was assessed by summing the number of healthy lifestyle factors (i.e., never smoking, regular physical activity, and normal BMI) and categorized as unfavorable (≤1) and favorable (≥2). Presence of CMDs was defined as having any one of type 2 diabetes, ischemic heart disease, atrial fibrillation, heart failure, and stroke. Data were analyzed using Cox regression, Laplace regression, and generalized structural equation modelling. RESULTS: During the follow-up (median 9.79 years, interquartile range: 9.68-10.57 years), 9178 (4.9%) participants died. In multi-adjusted Cox regression models, a low-inflammatory diet (i.e. low IDI score) was associated with lower risk of all-cause mortality [hazard ratio (HR) = 0.82, 95% confidence interval (CI): 0.78 to 0.86]. Laplace regression analysis showed that the multi-adjusted 10th percentile difference (10th PD, 95% CI) of death time was delayed by 0.80 (0.55, 1.06; P < 0.001) years for participants with a low IDI score compared to those with a high IDI score. In mediation analysis, 21.48% of the association between IDI and mortality was mediated by CMDs. In joint effect analysis, participants with a low IDI score and favorable lifestyle had a 42% lower risk of death (HR = 0.58, 95% CI: 0.54, 0.62) compared to those with a high IDI score and unfavorable lifestyle. There was a significant additive interaction between low IDI score and favorable lifestyle on decreased mortality. CONCLUSIONS: A low-inflammatory diet is associated with a lower risk of death and could prolong survival time. CMDs may partially mediate the IDI-mortality association. A favorable lifestyle beyond diet may augment the positive effect of a low-inflammatory diet on longevity.

Association of cognitive reserve with the risk of dementia in the UK Biobank: role of polygenic factors.

BACKGROUND: It remains unclear whether cognitive reserve can attenuate dementia risk among people with different genetic predispositions. AIMS: We aimed to examine the association between cognitive reserve and dementia, and further to explore whether and to what extent cognitive reserve may modify the risk effect of genetic factors on dementia. METHOD: Within the UK Biobank, 210 631 dementia-free participants aged ≥60 years were followed to detect incident dementia. Dementia was ascertained through medical and death records. A composite cognitive reserve indicator encompassing education, occupation and multiple cognitively loaded activities was created using latent class analysis, categorised as low, moderate and high level. Polygenic risk scores for Alzheimer's disease were constructed to evaluate genetic risk for dementia, categorised by tertiles (high, moderate and low). Data were analysed using Cox models and Laplace regression. RESULTS: In multi-adjusted Cox models, the hazard ratio (HR) of dementia was 0.66 (95% confidence interval (CI) 0.61-0.70) for high cognitive reserve compared with low cognitive reserve. In Laplace regression, participants with high cognitive reserve developed dementia 1.62 (95% CI 1.35-1.88) years later than those with low cognitive reserve. In stratified analysis by genetic risk, high cognitive reserve was related to more than 30% lower dementia risk compared with low cognitive reserve in each stratum. There was an additive interaction between low cognitive reserve and high genetic risk on dementia (attributable proportion 0.24, 95% CI 0.17-0.31). CONCLUSIONS: High cognitive reserve is associated with reduced risk of dementia and may delay dementia onset. Genetic risk for dementia may be mitigated by high cognitive reserve. Our findings underscore the importance of enhancing cognitive reserve in dementia prevention.

Association between psychosocial working conditions and well-being before retirement: a community-based study.

Psychosocial working conditions have been linked to mental health outcomes, but their association with well-being is poorly studied. We aimed to investigate the association between psychosocial working conditions and well-being before retirement, and to explore the role of gender and leisure activities in the association. From the Swedish National Study on Aging and Care in Kungsholmen, 598 community dwellers aged 60-65 years were included in the cross-sectional study. Lifelong occupational history was obtained through an interview. Job demands and job control in the longest-held occupation were graded with job exposure matrices. Psychosocial working conditions were classified into high strain (high demands, low control), low strain (low demands, high control), passive job (low demands, low control), and active job (high demands, high control). Well-being was assessed with the 10-item version of positive and negative affect schedule, and scored using confirmatory factor analysis. Engagement in leisure activities was categorized as low, moderate, and high. Data were analyzed using linear regression. Both high job control and high job demands were dose-dependently associated with higher well-being. Overall, compared to active jobs, passive jobs were associated with lower well-being (ß -0.19, 95% CI -0.35 to -0.02, P = 0.028). Passive (ß -0.28, 95% CI -0.51 to -0.04, P = 0.020) and high strain (ß -0.31, 95% CI -0.52 to -0.10, P = 0.004) jobs were associated with lower well-being in men, but not in women. The association between passive jobs and well-being was attenuated by high leisure activities, while the association between high strain and well-being was magnified by low leisure activities. In conclusion, negative psychosocial working conditions are associated with poor well-being, especially in men. Leisure activities may modulate the association. Our study highlights that promoting favorable working conditions can be a target to improve well-being among employees and active participation in leisure activities is encouraged to cope with work-related stress for better well-being.

Vertical porous aerogel based on polypyrrole and bimetallic modified ß-cyclodextrin polymer-chitosan for efficient solar evaporation.

Solar-driven interfacial evaporation (SDIE) stands out as a prospective technology for freshwater production, playing a significant role in mitigating global water scarcity. Herein, a cyclodextrin polymer/chitosan composite aerogel (PPy-La/Al@CDP-CS) with vertically aligned channels was prepared as a solar evaporator for efficient solar steam generation. The vertically aligned pore structure, achieved through directional freezing assisted by liquid nitrogen, not only improves water transport during evaporation but also enhances light absorption through multiple reflections of sunlight within the pores. The polypyrrole particles sprayed on the surface of the aerogel acted as a light-absorbing layer, resulting in an impressive absorbance of 98.15 % under wetting conditions. The aerogel has an evaporation rate of 1.85 kg m-2 h-1 under 1 kW m-2 irradiation. Notably, the vertical pore structure of the aerogel allows it to exhibit excellent evaporation performance and salt resistance even in highly concentrated salt solutions. Furthermore, this aerogel is an excellent solar-driven interfacial evaporator for purifying seawater and fluoride-containing wastewater. This photothermal aerogel has the advantages of excellent performance, low cost, and environmental friendliness, and thus this work provides a new approach to the design and fabrication of solar photothermal materials for water treatment.

3D Tea-Residue Microcrystalline Cellulose Aerogel with Aligned Channels for Solar-Driven Interfacial Evaporation Co-generation.

Solar-driven interfacial evaporation co-generation (SIE-CG) technology is of great significance in solving the problem of water and energy shortage. Herein, we report the ionic liquid-assisted alignment of waste biomass tea residue-based microcrystalline cellulose for aerogels (abbreviated as TPPA-5) with aligned channels for solar-driven interfacial evaporation co-generation. In the ionic liquid, strong H-bonding is formed between the pyranoid rings of cellulose combined with the slow freezing technique, resulting in the microcrystalline cellulose being reoriented, which allowed TPPA-5 to form abundant aligned channels after solvent replacement and freeze-drying. These aligned channels enable the brine to form a localized circulating flow, which is conducive to the improvement of the TPPA's evaporation rate and salt resistance. The salinity gradient is naturally formed in the channel of TPPA, which enables TPPA-5 to show excellent power generation performance. The evaporation rate of TPPA-5 can reach 3.39 kg m-2 h-1 under 1 kW m-2. With methanol as a highly polar proton solvent, the maximum output voltage obtained was 67.534 mV due to the overlapping electric double-layer effect formed by hydrogen protons on the TPPA surface, and the energy utilization efficiency is 95.95%. Moreover, TPPA-5 can purify pesticide-containing wastewater, which has the advantages of being recyclable and environmentally friendly, showing potential application value in the field of seawater desalination and steam co-generation.

What do the clinical features of positive nontuberculous mycobacteria isolates from patients with HIV/AIDS in China reveal? A systematic review and meta-analysis.

Background: China has a high burden of nontuberculous mycobacterial (NTM) infections. Immunocompromised populations, such as those with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), are at a higher risk of being infected with NTM than immunocompetent individuals. Yet, there is a paucity of information on the clinical features of positive NTM isolates from patients with HIV/AIDS in China. To address this gap, we conducted a systematic review and meta-analysis of existing studies, comparing them against current expert consensus to provide guidance for clinical practice. Methods: Two researchers independently searched eight databases (SinoMed, China National Knowledge Infrastructure, Wanfang, VIP, Cochrane Library, PubMed, Embase, and Web of Science) from inception to 26 December 2022 to retrieve published Chinese- and English-language studies reporting clinical features of NTM-positive isolates among patients with HIV/AIDS in China. Results: We included 28 studies with 1861 patients. The rate of positive NTM isolates detected from men among all patients was 87.3%. NTM species distribution was mainly Mycobacterium avium complex (64.3%), which was predominant in different regions. The five most common clinical symptoms were fever (68.5%), cough or expectoration (67.0%), appetite loss (49.4%), weight loss (45.5%), and superficial lymphadenectasis (41.1%). The prevalence of laboratory tests were as follows: albumin <35 g/L (55.6%), erythrocyte sedimentation rate >20 mm/h (91.4%), anaemia (59.0%), predominantly mild, CD4+ T cell count ≤50 pieces/µL (70.3%), and CD4+ T cell count 51-200 pieces/µL (22.1%). Lesion manifestations in thoracic imaging mainly included bilateral lung involvement (83.8%), showed stripe shadows (60.3%), patchy shadows (42.9%), nodules (40.6%), and bronchiectasis (38.6%). Accompanied signs included thoracic lymph node enlargement (49.5%). Seventy per cent of symptoms improved after treatment. Conclusions: Focusing on clinical symptoms, laboratory tests, and thoracic imaging helps with initial screening for NTM infections. Physicians should raise awareness of the diagnosis and treatment of Mycobacterium avium complex, providing guidance for experimental treatment, screening of priority populations for NTM infections, and prophylactic treatment of NTM disease. Registration: PROSPERO CRD42023388185.

Defeating Melanoma Through a Nano-Enabled Revision of Hypoxic and Immunosuppressive Tumor Microenvironment.

Rationale: Reversing the hypoxic and immunosuppressive tumor microenvironment (TME) is crucial for treating malignant melanoma. Seeking a robust platform for the effective reversion of hypoxic and immunosuppressive TME may be an excellent solution to revolutionizing the current landscape of malignant melanoma treatment. Here, we demonstrated a transdermal and intravenous dual-administration paradigm. A tailor-made Ato/cabo@PEG-TK-PLGA NPs were administrated transdermally to melanoma with the help of a gel spray containing a skin-penetrating material borneol. Nanoparticles encased Ato and cabo were released and thereby reversed the hypoxic and immunosuppressive tumor microenvironment (TME). Methods: Ato/cabo@PEG-TK-PLGA NPs were synthesized through a self-assembly emulsion process, and the transdermal ability was assessed using Franz diffusion cell assembly. The inhibition effect on cell respiration was measured by OCR, ATP, and pO2 detection and in vivo photoacoustic (PA) imaging. The reversing of the immunosuppressive was detected through flow cytometry analysis of MDSCs and T cells. At last, the in vivo anti-tumor efficacy and histopathology, immunohistochemical analysis and safety detection were performed using tumor-bearing mice. Results: The transdermally administrated Ato/cabo@PEG-TK-PLGA NPs successfully spread to the skin surface of melanoma and then entered deep inside the tumor with the help of a gel spray and a skin puncturing material borneol. Atovaquone (Ato, a mitochondrial-respiration inhibitor) and cabozantinib (cabo, a MDSCs eliminator) were concurrently released in response to the intratumorally overexpressed H2O2. The released Ato and cabo respectively reversed the hypoxic and immunosuppressive TME. The reversed hypoxic TME offered sufficient O2 for the intravenously administrated indocyanine green (ICG, an FDA-approved photosensitizer) to produce adequate amount of ROS. In contrast, the reversed immunosuppressive TME conferred amplified systemic immune responses. Conclusion: Taken together, we developed a transdermal and intravenous dual-administration paradigm, which effectively reversed the hypoxic and immunosuppressive tumor microenvironment in the treatment of the malignant melanoma. We believe our study will open a new path for the effective elimination of the primary tumors and the real-time control of tumor metastasis.

Assessing Healthy Aging Score and Its Association With All-Cause Mortality: Findings From the China Health and Retirement Longitudinal Study.

Background and Objectives: To construct a comprehensive healthy aging score (HAS) and explore its association with all-cause mortality and its potential interactions with other demographics on mortality. Research Design and Methods: This study included 5,409 participants aged ≥60 years from the China Health and Retirement Longitudinal Study. An HAS was constructed based on three dimensions of healthy aging including intrinsic capacity (IC), environmental support (ES), and chronic disease (CD), which were assessed at baseline, and categorized by tertiles (poor, moderate, and high). Participants were followed up biennially for all-cause mortality through the death registration or family interview from 2011 to 2018. Data were analyzed using Cox regression, Laplace regression, and receiver-operating characteristic analysis. Results: During 7 years of follow-up, 877 (16.21%) participants died. An HAS was constructed based on the cognition, mobility, and instrumental activity of daily living in the IC dimension; housing in the ES dimension; and hypertension, diabetes, chronic lung disease, stroke, and cancer in the CD dimension, which was associated with death. HAS seems a good predictor of all-cause mortality, with an area under the curve of 0.749. The hazard ratios and 95% confidence intervals for all-cause mortality related to moderate and poor HAS (vs high HAS) were 1.26 (1.01-1.56) and 2.38 (1.94-2.91), respectively. The median survival time was 2.46 years shorter in participants with poor HAS than those with high HAS. There were significant additive interactions of HAS with age, sex, and marital status on death. Discussion and Implications: Poor HAS may increase mortality and shorten survival, especially among older, male, and single adults.

Association of lifespan reproductive duration with depression in Swedish twins: The role of hormone replacement therapy.

OBJECTIVE: To examine the association between reproductive duration and postmenopausal depression (taking the use of hormone replacement therapy [HRT] into account). METHODS: In this population-based cohort study, 11 320 postmenopausal women (mean age 63.6 years) were followed for up to 18 years. Reproductive duration was categorized into three groups: short (≤34 years), average (35-39 years), and long (≥40 years). Depression was ascertained from the Sweden National Patient Registry. RESULTS: During the follow up, 593 (5.24%) women developed depression. In the multi-adjusted generalized estimating equation model, the odds ratios (ORs) of depression were 1.28 (95% confidence interval [CI] 1.05-1.55) and 1.25 (95% CI 1.01-1.55) for women with short and long reproductive durations, respectively, compared with those women with average reproductive duration. Women with a non-typical reproductive duration (≤34 or ≥40 years) who received HRT were at a higher risk of depression (OR 1.82, 95% CI 1.42-2.33). There was a significant additive interaction between non-typical reproductive duration and the use of HRT on depression (attributable proportion 0.26, 95% CI 0.03-0.50). CONCLUSION: Women with a short or long reproductive duration, especially those with a history of HRT use, have a higher risk of depression after menopause compared with those with an average reproductive duration.

Asymmetric wettable polycaprolactone-chitosan/chitosan oligosaccharide nanofibrous membrane as antibacterial dressings.

Wound infection and inflammation hinder the process of wound healing and bother human beings chronically. As a naturally degradable macromolecule, chitosan (CS) has been widely used in antibacterial wound dressings. However, the antibacterial property of chitosan is inhibited by its water insolubility. In this study, we prepared a bilayered asymmetric nanofibrous membrane with the hydrophilic CS/chitosan oligosaccharide (COS) nanofibrous membrane as the bottom layer and the hydrophobic polycaprolactone (PCL) nanofibrous membrane as the top layer. Results showed that incorporating COS improved the CS membrane's wettability, and adding 0.5 % COS increased the inhibition zone diameter of Escherichia coli and Staphylococcus aureus by 23 % and 26 %, respectively. Moreover, the PCL layer could prevent the adhesion of water and bacteria. The PCL-CS/COS0.5% membrane showed relatively good mechanical properties, excellent water absorptivity (460 %), and appropriate cytocompatibility. This asymmetric wettable membrane has a massive potential to serve as a new antibacterial dressing for wound healing.

Association of impaired kidney function with dementia and brain pathologies: A community-based cohort study.

INTRODUCTION: The relationship between impaired kidney function (KF), dementia, and brain pathologies remains unclear. METHODS: A total of 1354 dementia- and kidney disease-free participants including 895 with normal and 459 with impaired KF were followed from 2002 until 2020 (median [interquartile range]: 5 [2-9]) to detect incident dementia. KF was assessed at baseline and categorized as normal or impaired. Over the follow-up, 453 participants died and underwent autopsies for neuropathological assessment. RESULTS: Compared to those with normal KF, the hazard ratios (95% confidence intervals [CIs]) of those with impaired KF was 1.48 (1.15, 1.90)/1.44 (1.10, 1.88) for dementia/Alzheimer's dementia. Furthermore, impaired KF was related to a significantly higher burden of cerebral amyloid angiopathy (CAA; odds ratio = 1.96, 95% CI: 1.17, 3.30), but not to other brain pathologies. DISCUSSION: Impaired KF is associated with an increased risk of dementia and Alzheimer's dementia. CAA may underlie, in part, this association. HIGHLIGHTS: Impaired kidney function (KF) was associated with higher dementia and Alzheimer's dementia risk. Impaired KF anticipated dementia and Alzheimer's dementia onset by more than 1.5 years. Impaired KF was significantly related to a higher burden of cerebral amyloid angiopathy (CAA) but not to other brain pathologies.

High lifelong cognitive reserve prolongs disability-free survival: The role of cognitive function.

INTRODUCTION: The association between cognitive reserve (CR) and survival with independence is unknown. We examined whether lifelong CR accumulation is associated with disability-free survival and explored the extent to which cognitive function mediates this association. METHODS: Within the Rush Memory and Aging Project, 1633 dementia- and disability-free participants were followed annually for up to 22 years. Lifelong CR including education, early-/mid-/late-life cognitive activities, and late-life social activity was assessed and tertiled. RESULTS: CR score was dose-dependently associated with disability/death (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.93-0.99). Compared to low CR, the HR (95% CI) of disability/death was 0.82 (0.70-0.95) for high CR. The median disability-free survival time was prolonged by 0.99 (95% CI 0.28-1.71) years for participants with high CR. Cognitive function mediated 35.7% of the association between CR and disability-free survival. DISCUSSION: High lifelong CR was associated with prolonged disability-free survival. Cognitive function mediates about one-third of this association. Our findings underscore the importance of CR for healthy aging.

Association of life-course traumatic brain injury with dementia risk: A nationwide twin study.

INTRODUCTION: The impact of life-course traumatic brain injury (TBI) on dementia is unclear. METHODS: Within the Swedish Twin Registry (STR), 35,312 dementia-free twins were followed for up to 18 years. TBI history was identified via medical records. Data were analyzed using generalized estimating equation (GEE) and conditional logistic regression. RESULTS: In multi-adjusted GEE models, the odds ratio (OR, 95% confidence interval [CI]) of dementia was 1.27 (1.03-1.57) for TBI at any age, 1.55 (1.04-2.31) for TBI at 50 to 59 years, and 1.67 (1.12-2.49) for TBI at 60 to 69 years. Cardiometabolic diseases (CMDs) increased dementia risk associated with TBI at age 50 to 69 years. The ORs in GEE and conditional logistic regression did not differ significantly (P = .37). DISCUSSION: TBI, especially between ages 50 and 69 years, is associated with an increased risk of dementia, and this is exacerbated among people with CMDs. Genetic and early-life environmental factors may not account for the TBI-dementia association.

Pulmonary Function Trajectories Preceding Death Among Older Adults: A Long-Term Community-Based Cohort Study.

BACKGROUND: Poor pulmonary function (PF) has been linked to mortality, but the timing of PF changes before death remains unclear. We aimed to examine the association between PF and mortality and identify different PF trajectories precedes death. METHODS: Within the Rush Memory and Aging Project, 1 438 participants without chronic obstructive pulmonary disease were followed for up to 22 years. PF was assessed annually using a composite score (tertiled as low, medium, and high) based on forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), and peak expiratory flow (PEF). Survival status was observed during the follow-up period. Data were analyzed using Cox regression, Laplace regression, and mixed-effect models. RESULTS: During the follow-up, 737 (51.25%) participants died. Compared to high PF, the hazard ratio (95% confidence interval [CI]) of mortality was 1.35 (1.05, 1.72)/1.63 (1.25, 2.12) for medium/low PF. The median survival time (95% CI) was shortened by 0.80 (0.01-1.61)/1.72 (0.43-3.01) years for participants with medium/low PF, compared to high PF. In multiadjusted trajectory analysis, the significant differences between decedents and survivors occurred at 7 years before death for composite PF (mean difference [95% CI]: 0.14 [0.02-0.25]), 6 years for FEV1 (0.21 [0.08-0.33]) and FVC (0.21 [0.08-0.34]), and 8 years for PEF (0.21 [0.06-0.37]), and became greater thereafter. CONCLUSION: Poor PF is associated with elevated mortality and shortens survival for nearly 2 years. An acceleration in PF decline tends to occur 7 years before death. Poor PF, together with its decline, might be a predictor of mortality among community-dwelling older adults.

Injurious falls before, during and after dementia diagnosis: a population-based study.

BACKGROUND: the timing of incident injurious falls at different stages of dementia diagnosis is unclear. OBJECTIVES: to identify when the occurrence of injurious falls begins to increase among individuals who are going to develop dementia, to explore the time point at which people living with dementia are at highest risk of injurious falls and to ascertain differences in fall-related factors pre- and post-dementia diagnosis. DESIGN: this study included 2,707 participants with incident dementia and 2,707 1:1 matched (i.e. same birth year and sex) controls without dementia. METHODS: dementia diagnosis and date of onset were identified from the National Patient Registry (NPR) and the Swedish Cause of Death Register following international criteria. Information on injurious falls and history of chronic disease was obtained from the NPR. Data were analysed using conditional Poisson regression and generalized estimating equation models. RESULTS: compared with controls, the incidence of injurious falls among participants with dementia started to increase beginning 4 years pre-diagnosis (incidence rate ratio [IRR] 1.70, 95% confidence interval [CI] 1.30-2.22), reaching a peak (IRR 3.73, 95% CI 3.16-4.41) in the year of dementia diagnosis. Heavy drinking, physically active and cardiometabolic diseases (CMDs) were associated with incident falls among those with dementia. CONCLUSION: people with dementia have a higher incidence of injurious falls beginning 4 years leading up to diagnosis and peaking during the year of diagnosis. Older age, female, heavy drinking, physically active and CMDs may predict injurious falls among people with dementia.

Association of depression with mortality in nationwide twins: The mediating role of dementia.

BACKGROUND: The differential impact of depression across different periods in life on mortality remains inconclusive. We aimed to examine the association of depression that occurs at different age with all-cause mortality, and to explore the roles of dementia, as well as genetic and early-life environmental factors, in this association. METHODS: From the Swedish Twin Registry, 44,919 twin individuals were followed for up to 18 years. Depression was ascertained using the National Patient Registry and categorized as early-life (<45 years), midlife (45-64 years), and late-life (≥65 years) depression according to the age of the first diagnosis. Deaths were identified through the Cause of Death Register. Generalized estimating equation, generalized structural equation, and conditional logistic regression were used for unmatched, mediation, and co-twin matched analyses, respectively. RESULTS: In unmatched analyses, the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of mortality were 1.71 (1.46-2.00) for depression at any age, 1.72 (1.36-2.17) for early-life, 1.51 (1.19-1.90) for midlife, and 4.10 (2.02-8.34) for late-life depression. Mortality was significantly higher in individuals with late-life depression than those with earlier-life depression (p < 0.05). The mediation analysis showed that 59.83% of the depression-mortality association was mediated by dementia. No significant difference in ORs between the unmatched and co-twin matched analyses was observed (p = 0.09). CONCLUSIONS: Depression is associated with an increased risk of all-cause mortality, and dementia mediates approximately 60% of the impact of depression on mortality in late life. Genetic and early-life environmental factors may not play a significant role in the depression-mortality association.

Association of life-course reproductive duration with mortality: a population-based twin cohort study.

BACKGROUND: Although age at menopause has been linked to mortality, the association between the entire reproductive lifespan and mortality remains unclear. OBJECTIVE: This study aimed to examine to what extent life-course reproductive duration is associated with all-cause mortality and explore the role of a healthy lifestyle and familial background in such an association. STUDY DESIGN: A total of 11,669 women (mean age, 63.54 years) from the Swedish Twin Registry were followed for up to 19 years. Information on reproductive duration (the interval between ages at menarche and menopause) and lifestyle factors (including smoking, alcohol consumption, and physical activity; divided into unfavorable/intermediate/favorable) was collected on the basis of a structured questionnaire. Survival status was obtained from the Sweden Cause of Death Register. The data were analyzed using generalized estimating equation models, Laplace regression, and conditional logistic regression. RESULTS: In the generalized estimating equation model, compared with those with ≤34 reproductive years, the odds ratio (95% confidence interval) of all-cause mortality was 0.79 (0.68-0.90) for those with ≥40 reproductive years, which prolonged survival time by 0.84 (0.24-1.43) years. Women with ≥40 reproductive years plus a favorable lifestyle (odds ratio, 0.28; 95% confidence interval, 0.23-0.35) were at a lower risk of all-cause mortality than those with <40 reproductive years plus an unfavorable lifestyle. An additive interaction between ≥40 reproductive years and a favorable lifestyle on all-cause mortality was observed (attributable proportion, 0.584; 95% confidence interval, 0.016-1.151). The odds ratios in conditional logistic regression and generalized estimating equation models did not differ significantly (P=.67). CONCLUSION: A longer reproductive lifespan is associated with reduced all-cause mortality and prolongs survival by 0.84 years. A favorable lifestyle may amplify the beneficial effect of longer reproductive lifespan on mortality. Familial background does not account for the observed association.

Association of Sleep Duration, Napping, and Sleep Patterns With Risk of Cardiovascular Diseases: A Nationwide Twin Study.

Background Although sleep disorders have been linked to cardiovascular diseases (CVDs), the association between sleep characteristics and CVDs remains inconclusive. We aimed to examine the association of nighttime sleep duration, daytime napping, and sleep patterns with CVDs and explore whether genetic and early-life environmental factors account for this association. Methods and Results In the Swedish Twin Registry, 12 268 CVD-free twin individuals (mean age=70.3 years) at baseline were followed up to 18 years to detect incident CVDs. Sleep duration, napping, and sleep patterns (assessed by sleep duration, chronotype, insomnia, snoring, and daytime sleepiness) were self-reported at baseline. CVDs were ascertained through the Swedish National Patient Registry and the Cause of Death Register. Data were analyzed using a Cox model. In the multiadjusted Cox model, compared with 7 to 9 hours/night, the hazard ratios (HRs) of CVDs were 1.14 (95% CI, 1.01-1.28) for <7 hours/night and 1.10 (95% CI, 1.00-1.21) for ≥10 hours/night, respectively. Compared with no napping, napping 1 to 30 minutes (HR, 1.11 [95% CI, 1.03-1.18]) and >30 minutes (HR, 1.23 [95% CI, 1.14-1.33]) were related to CVDs. Furthermore, a poor sleep pattern was associated with CVDs (HR, 1.22 [95% CI, 1.05-1.41]). The co-twin matched control analyses showed similar results as the unmatched analyses, and there was no significant interaction between sleep characteristics and zygosity (P values >0.05). Conclusions Short or long sleep (<7 or ≥10 hours/night), napping, and poor sleep patterns are associated with an increased CVD risk. Genetic and early-life environmental factors may not account for the sleep-CVD association.

Research Progress of H2S Donors Conjugate Drugs Based on ADTOH.

H2S is an endogenous gas signaling molecule and its multiple biological effects have been demonstrated. The abnormal level of H2S is closely related to the occurrence and development of many diseases, and H2S donors has important pharmacological implications. In recent years, H2S donors represented by ADTOH (5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione) are often used to synthesize new 'conjugate' compounds that can release H2S and parent drugs. These hybrids retain the pharmacological activity of the parent drugs and H2S and have a synergistic effect. ADTOH and parent drug hybrids have become one of the important strategies for the development of H2S donor conjugate drugs. This review summarizes molecular hybrids between ADTOH and clinical drugs to provide new ideas for the study of H2S donor drug design.