Association between whole blood essential trace elements and cognitive function in older adults.

BACKGROUND: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. OBJECTIVES: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. METHODS: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. RESULTS: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: ß = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: ß = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 µg/L) increase of Se was positively associated with the MMSE score (ß = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. CONCLUSIONS: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

Per- and polyfluoroalkyl substances exposure and bone mineral density in the U.S. population from NHANES 2005-2014.

BACKGROUND: Environmental exposures such as perfluoroalkyl substances (PFASs) were considered potential risks for bone mineral density (BMD). OBJECTIVE: To examine the associations between PFASs and BMD among the U.S. population. METHODS: This study included a total of 6416 participants from the National Health and Nutrition Examination Survey (NHANES 2005-2014). Multiple linear regression models were used to analyze the associations between serum PFASs and BMD and the coefficient ß with 95% confidence intervals (95% CI) was calculated as the effect estimate. Covariates such as age, race, BMI, smoking, alcohol intake, milk intake, and physical activity were adjusted in these models. Additionally, gender and menopausal period were considered in further subgroup analyses. RESULTS: Based on the combined data of NHANES 2005-2014, the effects from exposure to PFASs on BMD were found with gender and menopausal status differences. Positive associations were found in PFOA (ß = 0.010; 95% CI: 0.003, 0.016), PFHxS (ß = 0.007; 95% CI: 0.003, 0.012), and PFNA (ß = 0.001; 95% CI: 0.001, 0.017) in total population. Negative associations for PFOA (ß = -0.020; 95% CI: -0.029, -0.012), PFOS (ß = -0.011; 95% CI: -0.028, -0.011), PFHxS (ß = -0.019; 95% CI: -0.025, -0.013), PFDE (ß = -0.010; 95% CI: -0.016, -0.005), and PFNA (ß = -0.011; 95% CI: -0.021, -0.002) were found in women, while no significant association was found in men. In further subgroup analyses, women in pre-menopause status showed consistent negative associations. SIGNIFICANCE: PFASs exposure may be associated with BMD and gender and menopausal status confound the associations.

HDL-C, longitudinal change and risk of mortality in a Chinese cohort study.

BACKGROUND AND AIMS: High-density lipoprotein cholesterol (HDL-C) concentration and variability are both important factors of cardiovascular disease (CVD) and mortality. We aimed to explore the associations of HDL-C and longitudinal change in HDL-C with risk of mortality. METHODS AND RESULTS: We recruited a total of 69,163 participants aged ≥40 years and had medical examination records of HDL-C during 2010-2014 from the Yinzhou District, Ningbo, China. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. We observed a non-linear association of HDL-C with risks of non-accidental and CVD mortality. Compared with the moderate concentration group (1.4-1.6 mmol/L), HDL-C <1 mmol/L was associated with a higher risk of non-accidental mortality (HR: 1.13 (95% CI: 1.01-1.27)) and both HDL-C <1 mmol/L and ≥2 mmol/L were associated with a higher risk of CVD mortality (HRs: 1.23 (95% CI: 1.01-1.50) and 1.37 (95% CI: 1.03-1.82), respectively). Compared with the stable group ([-0.1, +0.1 mmol/L]), a large decrease ([-0.5, -0.3 mmol/L]) and very large decrease (<-0.5 mmol/L) in HDL-C were associated with a higher risk of non-accidental mortality (HRs: 1.40 (95% CI: 1.21-1.63) and 1.78 (95% CI: 1.44-2.20), respectively). Similar results were observed for CVD mortality and cancer mortality. CONCLUSION: Extremely low or high HDL-C and a large decrease or very large decrease in HDL-C were associated with a higher risk of cause-specific mortality. Monitoring of HDL-C may have utility in identifying individuals at higher risk of mortality.

Low LDL-C levels are associated with risk of mortality in a Chinese cohort study.

BACKGROUND AND AIMS: Although low-density lipoprotein cholesterol (LDL-C) has been considered as a risk factor of atherosclerotic cardiovascular disease, limited studies can be available to evaluate the association of LDL-C with risk of mortality in the general population. This study aimed to examine the association of LDL-C level with risk of mortality using a propensity-score weighting method in a Chinese population, based on the health examination data. METHODS: We performed a retrospective cohort study with 65,517 participants aged 40 years or older in Ningbo city, Zhejiang. LDL-C levels were categorized as five groups according to the Chinese dyslipidemia guidelines in adults. To minimize potential biases resulting from a complex array of covariates, we implemented a generalized boosted model to generate propensity-score weights on covariates. Then, we used Cox proportional hazard regression models with all-cause and cause-specific mortality as the dependent variables to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During the 439,186.5 person years of follow-up, 2403 deaths occurred. Compared with the median LDL-C group (100-130 mg/dL), subjects with extremely low LDL-C levels (group 1) had a higher risk of deaths from all-cause (HR = 2.53, 95% CI:1.80-3.53), CVD (HR = 1.84, 95% CI: 1.28-2.61), ischemic stroke (HR = 2.29, 95% CI:1.32-3.94), hemorrhagic stroke (HR = 3.49, 95% CI: 1.57-7.85), and cancer (HR = 2.12, 95% CI: 1.04-4.31) while the corresponding HRs in LDL-C group 2 were relatively lower than that in group 1. CONCLUSIONS: Low LDL-C levels were associated with an increased risk of all-cause, CVD, ischemic stroke, hemorrhagic stroke, and cancer mortality in the Chinese population.

Effect of COVID-19 on hospital visits in Ningbo, China: an interrupted time-series analysis.

OBJECTIVE: Unprecedented rigorous public health measures were implemented during the coronavirus disease 2019 (COVID-19) epidemic, but it is still unclear how the intervention influenced hospital visits for different types of diseases. We aimed to evaluate the impact of the intervention on hospital visits in Yinzhou District, Ningbo, Zhejiang province, China. METHODS: We conducted an interrupted time-series analysis from 1 January 2017 to 6 September 2020 based on the Yinzhou Health Information System in Ningbo, Zhejiang province. The beginning of the intervention was on 23 January 2020, and thus, there were 160 weeks before the intervention and 32 weeks after the implementation of the intervention. Level changes between expected and observed hospital visits in the post-intervention period were estimated using quasi-Poisson regression models. RESULTS: Compared with the expected level, there was an estimated decrease of -22.60% (95% confidence interval (CI): -27.53%, -17.36%) in the observed total hospital visits following the intervention. Observed hospital visits for diseases of the respiratory system were found to be decreased dramatically (-62.25%; 95% CI: -65.62%, -58.60%). However, observed hospital visits for certain diseases were estimated to be increased, including diseases of the nervous system (+11.17%; 95% CI: +3.21%, +19.74%); diseases of pregnancy, childbirth and the puerperium (+27.01%; 95% CI: +17.89%, +36.85%); certain conditions originating in the perinatal period (+45.05%; 95% CI: +30.24%, +61.56%); and congenital malformation deformations and chromosomal abnormalities (+35.50%; 95% CI: +21.24%, +51.45%). CONCLUSIONS: Our findings provided scientific evidence that cause-specific hospital visits evolve differently following the intervention during the COVID-19 epidemic.

Short-term associations between ambient fine particulate matter pollution and hospital visits for chronic obstructive pulmonary disease in Yinzhou District, China.

Ambient particulate matter is one of the main risk factors of chronic obstructive pulmonary disease (COPD) in developing countries. However, the studies were scant in China concerning the health effects of the fine particulate matter (PM2.5; particulate matter ≤ 2.5 µm in diameter) on hospital visits for COPD. We applied a generalized additive model (GAM) to calculate relative risks (RRs) with 95% confidence intervals (CIs) for the associations between hospital visits for COPD and an interquartile range (24.50 µg/m3) increment of ambient PM2.5 concentrations in Yinzhou District between 2016 and 2018. The ambient PM2.5 concentration was positively associated with hospital visits for COPD at a distributed lag of 0-7 days (RR = 1.073, 95% CI, 1.016, 1.133). In the stratified analysis, we found that the association between ambient PM2.5 and COPD was stronger during the warm season (April to September) than that during the cold season (October to March), but we did not observe statistically significant differences in age groups (< 60 years and ≥ 60 years) or gender groups (male and female) related to the effects of PM2.5. The associations between ambient PM2.5 and COPD became partially attenuated after the adjustment for gaseous pollutants in subgroups. Our findings could provide evidence that regulations for controlling both PM2.5 and gaseous pollutants should be implemented to protect the overall population.

Regression-based normative data for social health scale for the elderly (short version) in eastern China.

BACKGROUNDS: Social Health Scale for the Elderly short version (SHSE-S) is a psychometrically sound instrument that comprehensively assesses the social health status of older adults in China. The aim of the present study was to establish continuous normative data of SHSE-S. METHODS: We conducted a multicenter cross-sectional study among 31 communities in eastern China. Older adults aged 60 years and above were invited to participate in the study. Each participant was interviewed in-person to finish a structured questionnaire. The SHES-S score was calculated and standardized for each participant. We split the sample into generation and validation datasets and compared the distribution of SHSE-S score between two datasets. Multivariable linear regression was used to assess the SHSE-S score and demographic variables. Regression-based norms were built using a four-step process. RESULTS: A total of 6089 participants (51.2% females) aged 60 years old and above (mean age = 71.3, SD = 8.0) were enrolled as the normative sample. No significant difference was found between the distribution of SHSE-S standardized score in the generation (N = 2392) and validation (N = 3697) datasets. Multivariable linear regression showed that females, higher education levels were positive indicators while aging, living alone, divorced or never married, multimorbidity were negative factors. The regression-based norm which taking demographic factors into account was established and a user-friendly worksheet was also provided to facilitate the scoring and norming of the SHSE-S. CONCLUSIONS: The population-based regression norm of SHSE-S can be a useful tool for assessing the social health status of the Chinese elderly population.

Association between visit-to-visit variability of HbA1c and cognitive decline: a pooled analysis of two prospective population-based cohorts.

AIMS/HYPOTHESIS: The aim of this study was to investigate the association between visit-to-visit variability in HbA1c and cognitive function decline in the elderly population. METHODS: We performed a pooled analysis of two prospective population-based cohorts (the Health Retirement Study [HRS] and the English Longitudinal Study of Ageing [ELSA]). Cognitive function, including memory and executive function, were assessed at baseline and every 2 years, while HbA1c levels were assessed at baseline and every 4 years. Visit-to-visit variability (VVV) in HbA1c was calculated using the CV, SD and variation independent of the mean (VIM) during the follow-up period. Linear mixed models were used to evaluate the association between HbA1c variability and cognitive function decline with adjustment for demographics, mean HbA1c, education, smoking, alcohol consumption, BMI, baseline hypertension, baseline diabetes status and HDL-cholesterol. RESULTS: The study enrolled 6237 participants (58.23% women, mean age 63.38 ± 8.62 years) with at least three measurements of HbA1c. The median follow-up duration was 10.56 ± 1.86 years. In the overall sample, compared with the lowest quartile of HbA1c variability, participants in the highest quartile of HbA1c variability had a significantly worse memory decline rate (-0.094 SD/year, 95% CI -0.185, -0.003) and executive function decline rate (-0.083 SD/year, 95% CI -0.125, -0.041), irrespective of mean HbA1c values over time. Among individuals without diabetes, each 1-SD increment in HbA1c CV was associated with a significantly higher rate of memory z score decline (-0.029, 95% CI -0.052, -0.005) and executive function z score decline (-0.049, 95% CI -0.079, -0.018) in the fully adjusted model. CONCLUSIONS/INTERPRETATION: We observed a significant association between long-term HbA1c variability and cognitive decline among the non-diabetic population in this study. The effect of maintaining steady glucose control on the rate of cognitive decline merits further investigation.

Association between CPR-related genetic variants and risk of ischemic stroke: a nested case-control study.

Background: Serum C-reactive protein (CRP) has been reported to be associated with risk of ischemic vascular disease including ischemic stroke. Genome-wide association studies have revealed several gene variants related to CRP concentration. Methods: We investigated genetic variants in CRP-related genes associated with ischemic stroke in a nested case-control study with 138 ischemic stroke cases and 276 controls. We sequenced the whole coding region of six CPR-related genes and selected eligible SNPs. Three genetic models (additive, dominant and recessive) were calculated by a multivariable conditional logistic regression to estimate the association between SNPs and risk of ischemic stroke. We also calculated gene-environment interactions by using a crossover analysis. Results: Three out of 10 eligible SNPs were shown to be associated with risk of ischemic stroke. rs1800947 in CRP gene (additive model: OR = 2.08, 95% CI: 1.00-4.23) and rs1169288 in HNF1A gene (additive model: OR = 1.45, 95% CI: 1.03-2.06) were associated with an increased risk of ischemic stroke. rs440446 in APOE gene (additive model: OR = 0.63, 95%CI: 0.44-0.88) was associated with a decreased risk of ischemic stroke. Genetic risk scores models including SC-GRS and OR-GRS both showed a significant association with risk of ischemic stroke. These three SNPs interacted with smoking and red meat intake. Conclusions: Our study showed genetic variants of CRP-related genes were associated with risk of ischemic stroke. Our findings could provide useful data for the etiology of ischemic stroke.

Rab32 GTPase, as a direct target of miR-30b/c, controls the intracellular survival of Burkholderia pseudomallei by regulating phagosome maturation.

Burkholderia pseudomallei is a gram-negative, facultative intracellular bacterium, which causes a disease known as melioidosis. Professional phagocytes represent a crucial first line of innate defense against invading pathogens. Uptake of pathogens by these cells involves the formation of a phagosome that matures by fusing with early and late endocytic vesicles, resulting in killing of ingested microbes. Host Rab GTPases are central regulators of vesicular trafficking following pathogen phagocytosis. However, it is unclear how Rab GTPases interact with B. pseudomallei to regulate the transport and maturation of bacterial-containing phagosomes. Here, we showed that the host Rab32 plays an important role in mediating antimicrobial activity by promoting phagosome maturation at an early phase of infection with B. pseudomallei. And we demonstrated that the expression level of Rab32 is increased through the downregulation of the synthesis of miR-30b/30c in B. pseudomallei infected macrophages. Subsequently, we showed that B. pseudomallei resides temporarily in Rab32-positive compartments with late endocytic features. And Rab32 enhances phagosome acidification and promotes the fusion of B. pseudomallei-containing phagosomes with lysosomes to activate cathepsin D, resulting in restricted intracellular growth of B. pseudomallei. Additionally, Rab32 mediates phagosome maturation depending on its guanosine triphosphate/guanosine diphosphate (GTP/GDP) binding state. Finally, we report the previously unrecognized role of miR-30b/30c in regulating B. pseudomallei-containing phagosome maturation by targeting Rab32 in macrophages. Altogether, we provide a novel insight into the host immune-regulated cellular pathway against B. pseudomallei infection is partially dependent on Rab32 trafficking pathway, which regulates phagosome maturation and enhances the killing of this bacterium in macrophages.

Association of Visit-to-Visit Variability of Blood Pressure with Cardiovascular Disease among Type 2 Diabetes Mellitus Patients: A Cohort Study.

BACKGROUND: Increasing evidence has shown that visit-to-visit variability (VVV) of blood pressure (BP) is associated with an increased risk of cardiovascular disease (CVD). The objective of this study was to evaluate the impact of VVV of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on the risk of CVD among patients with type 2 diabetes mellitus (T2DM) in China. METHODS: We conducted a retrospective cohort study of 10,163 T2DM patients who were not previously diagnosed with CVD from January 2008 to December 2012 in Ningbo, China. The VVV of BP was calculated using five metrics, including standard deviation (SD), coefficient of variation (CV), variation independent of mean, average real variability, and successive variability (SV) of measurements, obtained over a 24-month measurement period. Hazard ratios and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression models for the associations of variability in BP with risk of CVD. RESULTS: A total of 894 CVD events were observed during a median follow-up of 49.5 months. The hazard ratio in the highest quintile of SD of SBP was 1.24 (95% CI, 1.01 to 1.52) compared with patients in the lowest quintile. The association between higher VVV of DBP and risk of CVD was not consistent across different metrics and sensitivity analyses. CONCLUSION: Higher VVV of SBP was associated with an increased risk of CVD, irrespective of the mean SBP level. Future studies are needed to confirm these findings.

Acute effect of fine and coarse particular matter on cardiovascular visits in Ningbo, China.

Although a growing number of epidemiological studies have been conducted on size-specific health effects of particulate matter in China, results remain inconsistent. In this study, we investigated acute effect of fine and coarse particular matter on cardiovascular hospital visits in Ningbo, China. We used generalized additive models to examine short-term effects of PM2.5 and PM10-2.5 on cardiovascular hospital visits by adjustment for temporal, seasonal, and meteorological effects. Subgroup analyses were conducted by age, sex, and season. We also examined the stability of their effects in multi-pollutant models. We found that PM2.5 were associated with cardiovascular hospital visits (RR = 1.006; 95% CI 1.000, 1.011) and results remained similar after adjustment for PM10-2.5 (RR = 1.005; 95% CI 0.998, 1.013). There was a borderline association between PM10-2.5 and cardiovascular hospital visits (RR = 1.007; 95% CI 0.997, 1.016), which disappeared after controlling for PM2.5 (RR = 1.000; 95% CI 0.988, 1.013). The associations appeared to be stronger in the cold season and among the elderly (≥ 75 years). The findings of this study suggested significant adverse effects of PM2.5, but no independent effects of PM10-2.5 on cardiovascular hospital visits. Additional studies are needed to confirm these findings.

Air pollution and hospital visits for acute upper and lower respiratory infections among children in Ningbo, China: A time-series analysis.

Acute upper and lower respiratory infections are main causes of mortality and morbidity in children. Air pollution has been recognized as an important contributor to development and exacerbation of respiratory infections. However, few studies are available in China. In this study, we investigated the short-term effect of air pollution on hospital visits for acute upper and lower respiratory infections among children under 15 years in Ningbo, China. Poisson generalized models were used to estimate the associations between air pollution and hospital visits for acute upper and lower respiratory infections adjusted for temporal, seasonal, and meteorological effects. We found that four pollutants (PM2.5, PM10, NO2, and SO2) were significantly associated with hospital visits for acute upper and lower respiratory infections. The effect estimates for acute upper respiratory infections tended to be higher (PM2.5 ER = 3.46, 95% CI 2.18, 4.76; PM10 ER = 2.81, 95% CI 1.93, 3.69; NO2 ER = 11.27, 95% CI 8.70, 13.89; SO2 ER = 15.17, 95% CI 11.29, 19.19). Significant associations for gaseous pollutants (NO2 and SO2) were observed after adjustment for particular matter. Stronger associations were observed among older children and in the cold period. Our study suggested that short-term exposure to outdoor air pollution was associated with hospital visits for acute upper and lower respiratory infections in Ningbo.