Physical multimorbidity and lifetime suicidal ideation and plans among rural older adults: the mediating role of psychological distress.

BACKGROUND: Previous studies have revealed that single physical chronic condition was associated with suicidal ideation/plans, but few studies have examined the relationship between multimorbidity and suicidal ideation/plans, and no studies have explored the underlying potential mechanism on this relationship in China. This study aimed to explore association between physical multimorbidity and suicidal ideation as well as plans, and further examine the mediating role of psychological distress (PD) on this relationship. METHODS: This study was based on the data from a survey about the health service of rural elderly household in Shandong, China. A total of 3242 adults aged 60 years and older were included in this study. PD was measured by Kessler Psychological Distress Scale (K10). Ordinal and binary logistic regression analyses were employed to explore the association between physical multimorbidity, PD and suicide ideation/plans. Bootstrapping analysis was further used to examine the mediation effect of PD on the association of multimorbidity and suicidal ideations/plans. RESULTS: The prevalence of multimorbidity, lifetime suicidal ideation, and suicidal plan in rural older adults was 35.2, 10.6 and 2.2%, respectively. Older adults living in rural areas with two or more chronic physical conditions experienced significantly higher risk of suicidal ideation and suicidal plans. The association between multimorbidity and suicidal ideations/plans was partially mediated by PD, of which, the mediating effect of PD accounted for 31.7 and 25.5% of the total effect, respectively. CONCLUSION: This study demonstrated the associations between physical multimorbidity and suicidal ideation/plans, and the mediating role of PD on this relationship among Chinese rural elderly. Healthcare providers in rural community should provide regular surveillance for the mental health status among the rural elderly with multimorbidity, and carry out various effective intervention measures to improve the mental health status, so as to reduce the risk of suicide.

Body mass index and mild cognitive impairment among rural older adults in China: the moderating roles of gender and age.

BACKGROUND: Evidence concerning the association between body mass index (BMI) and cognitive function among older people is inconsistent. This study aimed to investigate gender and age as moderators in association between BMI and mild cognitive impairment (MCI) among rural older adults. METHODS: Data were derived from the 2019 Health Service for Rural Elderly Families Survey in Shandong, China. In total, 3242 people aged 60 years and above were included in the analysis. Multilevel mixed-effects logistic regression was used to examine the moderating roles of gender and age, then further to explore the relationship between BMI and MCI. RESULTS: There were 601 (18.5%) participants with MCI. Compared with normal BMI group, low BMI group had a higher risk of MCI among older people [adjusted odds ratio (aOR) = 2.08, 95% confidence interval (CI): 1.26-3.44], women (aOR = 2.06, 95% CI: 1.35-3.12), or the older elderly aged ≥75 years old (aOR = 3.20, 95% CI: 1.34-7.45). This effect remained statistically significant among older women (aOR = 3.38, 95% CI: 1.69-6.73). Among older men, elevated BMI group had a higher risk of MCI (aOR = 2.32, 95% CI: 1.17-4.61) than normal BMI group. CONCLUSIONS: Gender and age moderated the association between BMI and MCI among Chinese rural older adults. Older women with low BMI were more likely to have MCI, but older men with elevated BMI were more likely to have MCI. These findings suggest rural community managers strengthen the health management by grouping the weight of older people to prevent the risk of dementia.

Cognitive frailty and suicidal ideation among Chinese rural empty-nest older adults: Parent-child geographic proximity as a possible moderator?

BACKGROUND: Few studies explored the relationship between cognitive frailty and suicidal ideation (SI), and whether geographic variable modified this relationship. This study aimed to explore the association between cognitive frailty and SI, and investigated whether parent-child geographic proximity is a moderator in this relationship among Chinese rural empty-nest older adults. METHODS: A total of 2,549 rural empty-nest older adults (60+) were included in the analysis. SI was assessed using questions from the National Comorbidity Survey. Fried frailty phenotype and Mini Mental State Examination were used to measure cognitive frailty. Moderating effect analysis was performed using logistic regression models and margins plot. RESULTS: The prevalence of SI and cognitive frailty were 10.1% and 6.2% among Chinese rural empty-nest older adults. Participants with cognitive frailty were more likely to suffer from SI (OR=1.16, 95% CI=1.03-2.86). We found that far geographic distance may aggravate this relationship (OR=4.30, 95% CI=1.02-10.24), especially for rural empty-nest older adults whose nearest adult child lived outside the same prefectural city with them. LIMITATIONS: The results cannot be interpreted as causality of the data due to cross-sectional design. CONCLUSIONS: Our findings suggested that cognitive frailty was associated with SI and parent-child geographic proximity moderated this relationship. Improving the cognitive frailty of older adults is helpful to prevent SI. Adult children living far away from rural empty-nest older adults should increase intergenerational contact and pay attention to their parents' physical and mental health.

Physical frailty and health-related quality of life among Chinese rural older adults: a moderated mediation analysis of physical disability and physical activity.

OBJECTIVES: The purpose of this study is to explore the mediating effect of physical disability as well as the role of physical activity (PA) as a moderator in the relationship between physical frailty and health-related quality of life (HRQoL) among rural older adults in China. DESIGN: Cross-sectional analysis. SETTING: Rural households in Shandong of China (Rushan, Qufu, Laolin). PARTICIPANTS AND METHODS: A survey was conducted among 3243 rural older adults. The data were collected using questionnaires measuring physical frailty, physical disability, HRQoL and PA. Bootstrap analyses were employed to explore the mediating effect of physical disability and also the moderating role of PA on physical frailty and HRQoL. RESULTS: After controlling for age and education, physical disability partially mediated the effect of physical frailty on HRQoL (indirect effect=-0.143, 95% CI -0.175 to -0.113), with the mediating effect accounting for 33.71% of the total effect. PA moderated the relationship between physical frailty and physical disability as well as the relationship between physical disability and HRQoL. Specifically, the interaction term between physical frailty and PA significantly predicted physical disability (ß=-0.120, t=-7.058, p<0.001), and the interaction term between physical disability and PA also had a significant predictive effect on HRQoL (ß=0.115, t=6.104, p<0.001). CONCLUSIONS: PA appears to moderate the indirect effect of physical disability on the association between physical frailty and HRQoL. This study provides support for potential mechanisms in the association between physical frailty and HRQoL. Encouraging rural older adults to increase PA appropriately might improve HRQoL for older adults with physical frailty and physical disability problems.

Catastrophic health expenditure among single empty-nest elderly with multimorbidity in rural Shandong, China: the effect of co-occurrence of frailty.

BACKGROUND: Previous studies have indicated that older adults with multimorbidity had higher risk of incurring catastrophic health expenditure (CHE). However, the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity remains unclear. This study aims to explore the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity, and whether this effect is moderated by economic status. METHODS: A cross-sectional household survey of the older adults in 2019 in Shandong province, China. A total of 606 single empty-nest elderly aged 60 years or older were included in this study. CHE was defined as the out-of-pocket payments for health care that equals or exceeds 40% of the household' s capacity to pay. Logistic regression models are employed to examine the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity. The interaction term is introduced to explore the economic status difference in this effect. RESULTS: The CHE incidence for single empty-nest elderly with multimorbidity alone is 64.2%, and the co-occurrence of frailty results in an increase by almost 1.3 times (84.0%) in CHE incidence among single empty-nest elderly with multimorbidity. The co-occurrence of frailty increases the risk of incurring CHE among the single empty-nest elderly with multimorbidity, with the odds of incurring CHE increased by 3.19 times (OR = 3.19; P = 0.005). Furthermore, the interaction analysis shows that the effect of co-occurrence of frailty on CHE among single empty-nest elderly with multimorbidity still exist in lower economic status groups (OR = 4.64; P = 0.027), but not in higher economic status (OR = 2.76; P = 0.062). CONCLUSIONS: This study demonstrates that there is a positive effect of co-occurrence of frailty on the CHE among the single empty-nest elderly with multimorbidity, and this effect varies by economic status. The health policy-makers should reorganize the healthcare system to make it pro-poor, so as to meet the multiple medical demand and reduce the potential economic burden and inequalities of older adults.

Association of smoking status and health-related quality of life: difference among young, middle-aged, and older adults in Shandong, China.

PURPOSE: Few studies explored the relationship between smoking status and health-related quality of life (HRQOL) among adults in China. This study aims to explore the relationship between smoking status and HRQOL among adults (18 +) and examine whether there is a difference in this relationship among young, middle-aged, and older adults in China. METHODS: A total of 23,021 respondents were included in this study. The HRQOL is measured by EQ-5D-3L. The smoking status is divided into never smokers, current smokers, and former smokers. Tobit regression and Logistic regression are employed to explore the association between smoking status and HRQOL. The interaction term is included to explore the difference among young, middle-aged, and older adults. RESULTS: This study finds smoking status is significantly associated with HRQOL. An interaction analysis shows that the association between smoking status and HRQOL is significantly different among young, middle-aged, and older adults (P < 0.05). The smoking status is only significantly associated with HRQOL in middle-aged and older adults, but not for young adults. Compared with never smokers, former smokers report significantly lower EQ-5D-3L utility value in middle-aged adults (coefficient = - 0.089; 95%CI - 0.128 to - 0.050), current smokers report significantly higher EQ-5D-3L utility value in older adults (coefficient = 0.041; 95%CI 0.005 to 0.076). CONCLUSIONS: This study demonstrates a significant association between smoking status and HRQOL among adults in China, and there is a difference in this relationship among young, middle-aged, and older adults. The government should take efforts to formulate a variety of measures to control tobacco use among adults.

The relationship between activities of daily living and suicidal ideation among Chinese rural older adults: a multiple mediation model through sleep quality and psychological distress.

Few studies clarified the mechanisms underlying the relationship between activities of daily living and suicidal ideation among older adults. This study aimed to explore the multiple mediating roles of sleep quality and psychological distress between this relationship. A total of 3,243 rural older adults were included. Multiple mediation analysis was performed using Mplus 8.3. Activities of daily living was found to directly affect suicidal ideation (ß=0.092, 95% CI=0.043-0.140) and through three significantly mediation pathways: (1) the path through sleep quality (ß=0.019, 95% CI=0.007-0.031), which accounted for 9.79 % of the total effect; (2) the path through psychological distress (ß=0.049, 95% CI=0.036-0.063), which accounted for 25.26 % of the total effect; (3) the path through sleep quality and psychological distress (ß=0.034, 95% CI=0.026-0.042), which accounted for 17.53 % of the total effect. The total mediating effect was 52.58%. Attention should be paid to sleep quality and mental health among the Chinese rural older adults with activities of daily living limitation. For early detection and prevention of suicidal ideation, it is necessary to take sleep-based and positive psychological interventions for older adults with activities of daily living limitation.

What Role Does Activity Engagement Play in the Association between Cognitive Frailty and Falls among Older Adults? Evidence from Rural Shandong, China.

INTRODUCTION: Previous studies have demonstrated the relationship between cognitive frailty and falls among older adults. Activity engagement (AE) is known to be related to falls in older adults but the subject has been limited to empirical study. This study aimed to explore the mediating role of AE between cognitive frailty and falls among older adults in rural Shandong, China. METHODS: A total of 3,242 rural seniors (age ≥60 years; 63.6% women) were included in this cross-sectional study. Regression and bootstrap analyses were performed to explore the mediating role of AE between cognitive frailty and falls. RESULTS: The prevalence of falls was 13.1% and the prevalence of cognitive frailty was 6.6% among the participants. AE mediated the association between cognitive frailty and falls (95% CI 0.077-0.223). However, the direct effect was no longer significant after being adjusted for AE (95% CI -0.037 to 0.684; p = 0.078). CONCLUSION: Cognitive frailty was found to be associated with falls among rural older adults, and AE mediated this association. More attention should be paid to promote AE among Chinese rural older adults with cognitive frailty.

The role of mental health and physical activity in the association between sleep quality and quality of life among rural elderly in China: A moderated mediation model.

BACKGROUND: Several studies have found that poor sleep quality appeared to be negatively associated with quality of life in older adults, but the mechanism underlying this association remained unclear. In this study, we aimed to examine whether mental health mediated the association between sleep quality and quality of life among rural elderly and to explore the moderated role of physical activity between mental health and quality of life. METHODS: Data were extracted from the baseline survey of rural elderly household health services in Shandong province, in which 3,243 older adults aged 60 years and above were included. The moderated mediation models were examined using SPSS PROCESS Version 3.4 software, in which the mediation variable was mental health, and the moderation variable was physical activity. RESULTS: We found that mental health partially mediated the effect of sleep quality on quality of life [indirect effect = -0.158, 95% confidence intervals (CI) = -0.185, -0.133], with the mediating effect accounting for 51% of the total effect. The indirect effect was moderated by physical activity (ß = 0.056, p < 0.001), and a greater effect was observed among older adults with lower level of physical activity. LIMITATIONS: We included two mediators in one model, and interpretation of the observed associative direction was limited. CONCLUSIONS: Physical activity moderated the indirect effect of mental health on association between sleep quality and quality of life. Encouraging the rural elderly to increase physical activity appropriately might improve the quality of life for the elderly with poor sleep quality and mental health problems.

Structural insights into G domain dimerization and pathogenic mutation of OPA1.

The fusion of mammalian inner mitochondrial membranes (IMMs) is mediated by dynamin-like GTPase OPA1. Mutations in human OPA1 cause optic atrophy, but the molecular basis for membrane fusion and pathogenesis is not clear. Here, we determined the crystal structure of the minimal GTPase domain (MGD) of human OPA1. A three-helix bundle (HB) domain including two helices extending from the GTPase (G) domain and the last helix of OPA1 tightly associates with the G domain. In the presence of GDP and BeF3-, OPA1-MGD forms a dimer, the interface of which is critical for the maintenance of mitochondrial morphology. The catalytic core of OPA1 possesses unique features that are not present in other dynamin-like proteins. Biochemical experiments revealed that OPA1-MGD forms nucleotide-dependent dimers, which is important for membrane-stimulated GTP hydrolysis, and an N-terminal extension mediates nucleotide-independent dimerization that facilitates efficient membrane association. Our results suggest a multifaceted assembly of OPA1 and explain the effect of most OPA1 mutations on optic atrophy.

Structural analysis of a trimeric assembly of the mitochondrial dynamin-like GTPase Mgm1.

The fusion of inner mitochondrial membranes requires dynamin-like GTPases, Mgm1 in yeast and OPA1 in mammals, but how they mediate membrane fusion is poorly understood. Here, we determined the crystal structure of Saccharomyces cerevisiae short Mgm1 (s-Mgm1) in complex with GDP. It revealed an N-terminal GTPase (G) domain followed by two helix bundles (HB1 and HB2) and a unique C-terminal lipid-interacting stalk (LIS). Dimers can form through antiparallel HB interactions. Head-to-tail trimers are built by intermolecular interactions between the G domain and HB2-LIS. Biochemical and in vivo analyses support the idea that the assembly interfaces observed here are native and critical for Mgm1 function. We also found that s-Mgm1 interacts with negatively charged lipids via both the G domain and LIS. Based on these observations, we propose that membrane targeting via the G domain and LIS facilitates the in cis assembly of Mgm1, potentially generating a highly curved membrane tip to allow inner membrane fusion.

Poor Sleep Quality Is Associated with a Higher Risk of Pulmonary tuberculosis in Patients with a Type 2 Diabetes Mellitus Course for More than 5 Years.

A case-control study was conducted in Shandong from January to December 2017 to explore the relationship between sleep quality and the risk of active pulmonary tuberculosis (PTB). Seventy-nine patients with type 2 diabetes mellitus coincident with newly diagnosed pulmonary tuberculosis (DM-PTB) and 169 age, sex, and DM course frequency-matched controls (DM alone) were enrolled. Univariate and multivariable unconditional logistic regression analyses were conducted. We further conducted subgroup analyses to explore the relationship between sleep quality and PTB risk, including DM course (≤5 and ＞5 years), age, sex, and the presence of overweight or obesity (body mass index (BMI) ＞ 24 kg/m2). Multivariate logistic regression demonstrated that poor sleep quality had a borderline negative association with the odds of PTB (P ＝ 0.065). Subgroup multivariate analyses showed that poor sleep quality increased the risk of PTB to more than 3 times among patients with a DM course ＞ 5 years (odds ratio 3.31, 95% confidence interval: 1.08-10.13; P ＝ 0.036) after adjusting for potential confounding factors including residential area, educational level, BMI, history of contact with tuberculosis patients, smoking, alcohol consumption, physical exercise, immune status, and frequency of blood glucose monitoring. In conclusion, poor sleep quality is an independent risk factor of PTB among DM patients with a course of ＞ 5 years, which indicates significant epidemiological implications for PTB control.

Structural basis for GTP hydrolysis and conformational change of MFN1 in mediating membrane fusion.

Fusion of the outer mitochondrial membrane is mediated by the dynamin-like GTPase mitofusin (MFN). Here, we determined the structure of the minimal GTPase domain (MGD) of human MFN1 in complex with GDP-BeF3-. The MGD folds into a canonical GTPase fold with an associating four-helix bundle, HB1, and forms a dimer. A potassium ion in the catalytic core engages GDP and BeF3- (GDP-BeF3-). Enzymatic analysis has confirmed that efficient GTP hydrolysis by MFN1 requires potassium. Compared to previously reported MGD structures, the HB1 structure undergoes a major conformational change relative to the GTPase domains, as they move from pointing in opposite directions to point in the same direction, suggesting that a swing of the four-helix bundle can pull tethered membranes closer to achieve fusion. The proposed model is supported by results from in vitro biochemical assays and mitochondria morphology rescue assays in MFN1-deleted cells. These findings offer an explanation for how Charcot-Marie-Tooth neuropathy type 2 A (CMT2A)-causing mutations compromise MFN-mediated fusion.

Structures of human mitofusin 1 provide insight into mitochondrial tethering.

Mitochondria undergo fusion and fission. The merging of outer mitochondrial membranes requires mitofusin (MFN), a dynamin-like GTPase. How exactly MFN mediates membrane fusion is poorly understood. Here, we determined crystal structures of a minimal GTPase domain (MGD) of human MFN1, including the predicted GTPase and the distal part of the C-terminal tail (CT). The structures revealed that a helix bundle (HB) formed by three helices extending from the GTPase and one extending from the CT closely attaches to the GTPase domain, resembling the configuration of bacterial dynamin-like protein. We show that the nucleotide-binding pocket is shallow and narrow, rendering weak hydrolysis and less dependence on magnesium ion, and that association of HB affects GTPase activity. MFN1 forms a dimer when GTP or GDP/BeF3-, but not GDP or other analogs, is added. In addition, clustering of vesicles containing membrane-anchored MGD requires continuous GTP hydrolysis. These results suggest that MFN tethers apposing membranes, likely through nucleotide-dependent dimerization.

DWARF14 is a non-canonical hormone receptor for strigolactone.

Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The α/ß hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.