A Visual, In-Expensive, and Wireless Capillary Rheometer for Characterizing Wholly-Cellular Bioinks.

Rheological measurements with in situ visualization can elucidate the microstructural origin of complex flow behaviors of an ink. However, existing commercial rheometers suffer from high costs, the need for dedicated facilities for microfabrication, a lack of design flexibility, and cabling that complicates operation in sterile or enclosed environments. To address these limitations, a low-cost ($300) visual, in-expensive and wireless rheometer (VIEWR) using 3D-printed and off-the-shelf components is presented. VIEWR measurements are validated by steady-state and transient flow responses for different complex fluids, and microstructural flow profiles and evolution of yield-planes are revealed via particle image velocimetry. Using the VIEWR, a wholly-cellular bioink system comprised of compacted cell aggregates is characterized, and complex yield-stress and viscoelastic responses are captured via concomitantly visualizing the spatiotemporal evolution of aggregate morphology. A symmetric hyperbolic extensional-flow geometry is further constructed inside a capillary tube using digital light processing. Such geometries allow for measuring the extensional viscosity at varying deformation rates and further visualizing the alignment and stretching of aggregates under external flow. Synchronized but asymmetric evolution of aggregate orientation and strain through the neck is visualized. Using varying geometries, the jamming and viscoelastic deformation of aggregates are shown to contribute to the extensional viscosity of the wholly-cellular bioinks.

Habitual Exercise, Air Pollution, and Pneumonia Mortality: A Longitudinal Cohort Study of Approximately 0.4 Million Adults.

In this study, we aimed to examine the combined associations of particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5) and habitual exercise with pneumonia mortality. We included 384,130 persons aged ≥18 years from Taiwan, Republic of China, during 2001-2016. We followed participants until May 31, 2019, to obtain information on vital status. A time-dependent Cox regression model was used for statistical analysis. We found that risks of pneumonia mortality were reduced by 55% (hazard ratio (HR) = 0.45, 95% confidence interval (CI): 0.36, 0.55) and 36% (HR = 0.64, 95% CI: 0.52, 0.80) in participants who engaged in high and moderate levels of exercise, respectively, as compared with inactive persons. By contrast, each 10-µg/m3 increase in chronic PM2.5 exposure was associated with a 30% (HR = 1.30, 95% CI: 1.17, 1.45) higher risk of pneumonia mortality. Risk of pneumonia death was 72% lower (HR = 0.28, 95% CI: 0.20, 0.41) for persons with a high exercise level and a low PM2.5 level. Lower risk of pneumonia mortality was associated with both higher exercise and lower PM2.5 air pollution levels. For adults exposed to different levels of PM2.5, exercise benefits remained. Our findings suggest that engaging in exercise is a safe and effective strategy for alleviating the burden of pneumonia mortality, even for people who reside in a moderately polluted area.

Long-term Exposure to Fine Particulate Matter and Mortality A Longitudinal Cohort Study of 400,459 Adults.

BACKGROUND: Cohort studies on the association between long-term exposure to fine particulate matter (PM2.5) and mortality have been well established for America and Europe, but limited and inconsistent in Asia with much higher air pollution. This study aims to investigate the associations between ambient PM2.5 and all-cause and cause-specific mortality over a period of rising and then declining PM2.5. METHODS: We enrolled a total of 400,459 adults from an open cohort between 2001 and 2016, and followed them up until 31 May 2019. We obtained mortality data from the National Death Registry maintained by the Ministry of Health and Welfare in Taiwan. We estimated ambient PM2.5 exposures using a satellite-based spatiotemporal model. We performed a Cox regression model with time-dependent covariates to investigate the associations of PM2.5 with deaths from all causes and specific causes. RESULTS: This study identified 14,627 deaths and had a total of 5 million person-years of follow-up. Each 10 µg/m3 increase in PM2.5 was associated with an increased hazard risk of 29% (95% confidence interval: 24%-35%) in all-cause mortality. Risk of death increased by 30% for natural causes, 20% for cancer, 42% for cardiovascular disease (CVD) causes, and 53% for influenza and pneumonia causes, for each 10 µg/m3 increase in PM2.5. Sensitivity analyses generally yielded similar results. CONCLUSION: Long-term exposure to ambient PM2.5 was associated with increased risks of all-cause mortality and deaths from cancers, natural causes, CVD, and influenza and pneumonia. Longitudinal study design should be encouraged for air pollution epidemiologic investigation.

Habitual exercise, chronic exposure to fine particulate matter and high-sensitivity C reactive protein in Asian adults.

OBJECTIVES: Exercise may increase the inhaled amount of air pollutants and exacerbate the adverse health effects. We investigated the combined effects of chronic exposure to fine particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and habitual exercise on C reactive protein (CRP), a sensitive marker of inflammation. METHODS: We selected 40 209 Taiwanese adults who joined a standard medical screening programme between 2001 and 2016. The PM2.5 exposure was estimated at each participant's address using a satellite-based spatiotemporal model. Information on habitual exercise was collected using a standard self-administered questionnaire. Mixed-effects linear regression models were used to investigate the associations of CRP with PM2.5 and exercise. An interaction term of PM2.5 and exercise was introduced in the models to test the modifying effects. RESULTS: A greater amount of habitual exercise was associated with a decreased level of CRP, while a higher concentration of PM2.5 exposure was associated with an increased level of CRP. The inverse associations of habitual exercise with CRP were not modified by chronic exposure to PM2.5. The participants in the group with a low level of exercise and a high level of PM2.5 exposure exhibited a 19.1% higher level of CRP than those in the group with a high level of exercise and a low level of PM2.5 exposure (95% CI: 13.7% to 24.8%; p<0.001). The longitudinal and sensitivity analyses yielded similar results. CONCLUSIONS: Increased levels of exercise and reduced exposure levels of PM2.5 are associated with a lower CRP level. Habitual exercise reduces CRP level regardless of the levels of chronic PM2.5 exposure. Our results support that habitual exercise is a safe approach for reducing systemic inflammation to improve cardiovascular health even for people residing in relatively polluted areas.

Multi-pollutant air pollution and renal health in Asian children and adolescents: An 18-year longitudinal study.

BACKGROUND: Few studies have examined the effects of multi-pollutant air pollution on renal health, especially in children and adolescents. This study investigated the association between long-term ambient air pollution exposure and renal health in Asian children and adolescents. METHODS: This study included 10,942 children and adolescents from Taiwan and Hong Kong between 2000 and 2017. PM2.5, NO2 and O3 concentrations were estimated using satellite-based spatiotemporal regression models. Two-year average concentrations, those of the year of visit and the preceding year, were used. Linear mixed models were used to examine the association between air pollution and yearly changes in estimated glomerular filtration rate (eGFR). Cox regression models with time-dependent covariates were used to examine the association between air pollution and the development of chronic kidney disease (CKD). RESULTS: Median age of the participants was 19 years (range: 2-25). The overall average concentration of PM2.5, NO2 and O3 was 26.7 µg/m3, 44.1 µg/m3 and 51.1 µg/m3, respectively. The mean yearly change in eGFR was 0.37 µL/min/1.73 m2 and the incidence rate of CKD was 6.8 per 1,000 person-years. In single-pollutant models, each 10 µg/m3 increase in PM2.5 was associated with a 0.45 µL/min/1.73 m2 [95% confidence interval (CI): 0.28-0.63] reduction in the yearly increase in eGFR and 53% [hazard ratio (HR): 1.53 (95%CI: 1.07-2.2)] greater risk of incident CKD. Each 10 µg/m3 increase in NO2 was associated with a 7% [HR (95%CI): 1.07 (1.00-1.15)] higher risk of incident CKD, while an equivalent increase in O3 was associated with a 19% [HR (95%CI): 0.81 (0.67-0.98)] lower risk. CONCLUSIONS: Long-term exposure to ambient PM2.5 and NO2 was associated with a slower growth of eGFR and a higher risk of incident CKD in children and adolescents. Our findings suggest that air pollution control in early life is imperative to improve lifelong renal health and alleviate the CKD burden.

Total and differential white blood cell count and cause-specific mortality in 436 750 Taiwanese adults.

BACKGROUND AND AIMS: White blood cell (WBC) count is an easily obtainable biomarker of systematic inflammation. Our study aimed to investigate the associations of differential WBC count with all-cause and cause-specific mortality in a general Asian population. METHODS AND RESULTS: Cox proportional hazards model was used to evaluate the associations of WBC count with mortality separately for men and women, with adjustment for multiple variables including age, smoking, and other lifestyle factors. Stratified analyses by age, smoking, diabetes, and hypertension were conducted to explore potential effect modification. Elevated WBC count was significantly associated with increased mortality risk. The adjusted hazard ratios of total WBC (10th decile compared to decile of lowest risk) for all-cause mortality were 1.42 (95% CI: 1.33, 1.53) for men and 1.54 (95% CI: 1.42, 1.68) for women. Similar risks were observed for neutrophils, monocytes, and neutrophil/lymphocyte (NL) ratio. The highest deciles of neutrophils, monocytes, and NL ratio were also positively associated with risk of cardiovascular/cerebrovascular, cancer, and respiratory mortality after adjusting for covariates. Results for all-cause mortality remained statistically significant for participants who were <60 years old, non-smokers, non-diabetic, and non-hypertensive. CONCLUSIONS: Total and differential WBC counts (neutrophils, monocytes, and NL ratios) are positively associated with increased risk of all-cause mortality, cardiovascular and cerebrovascular, cancer, and respiratory mortality among Taiwanese adults.

Habitual exercise is associated with reduced risk of diabetes regardless of air pollution: a longitudinal cohort study.

AIMS/HYPOTHESIS: Physical activity may increase a person's inhalation of air pollutants and exacerbate the adverse health effects. This study aimed to investigate the combined associations of chronic exposure to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and habitual physical activity with the incidence of type 2 diabetes in Taiwan. METHODS: We selected 156,314 non-diabetic adults (≥18 years old) who joined an ongoing longitudinal cohort between 2001 and 2016. Incident type 2 diabetes was identified at the follow-up medical examinations. Two-year mean PM2.5 exposure was estimated at each participant's address using a satellite-based spatiotemporal model. Information on physical activity and a wide range of covariates was collected using a standard self-administered questionnaire. We analysed the data using a Cox regression model with time-varying covariates. An interaction term between PM2.5 and physical activity was included to examine the overall interaction effects. RESULTS: Compared with high physical activity, moderate and inactive/low physical activity were associated with a higher risk of diabetes (HR [95% CI] 1.31 [1.22, 1.41] and 1.56 [1.46, 1.68], respectively). Participants with moderate/high PM2.5 had a higher risk of type 2 diabetes than the participants exposed to low PM2.5 (HR 1.31 [1.22, 1.40] and 1.94 [1.76, 2.14], respectively). The participants with high physical activity and low PM2.5 had a 64% lower risk of type 2 diabetes than those with inactive/low physical activity and high PM2.5. CONCLUSIONS/INTERPRETATION: Higher physical activity and lower PM2.5 exposure are associated with lower risk of type 2 diabetes. Habitual physical activity can reduce the risk of diabetes regardless of the levels of PM2.5 exposure. Our results indicate that habitual physical activity is a safe diabetes prevention strategy for people residing in relatively polluted regions.

Independent and Opposing Associations of Habitual Exercise and Chronic PM2.5 Exposures on Hypertension Incidence.

BACKGROUND: We investigated the joint associations of habitual physical activity (PA) and long-term exposure to fine particulate matter (PM2.5) with the development of hypertension in a longitudinal cohort in Taiwan. METHODS: We selected 140 072 adults (≥18 years of age) without hypertension who joined a standard medical screening program with 360 905 medical examinations between 2001 and 2016. PM2.5 exposure was estimated at each participant's address using a satellite data-based spatiotemporal model with 1 km2 resolution. Information on habitual PA and a wide range of covariates was collected using a standard self-administered questionnaire. We used the Cox regression model with time-dependent covariates to examine the joint associations. RESULTS: The mean age of all observations was 41.7 years, and 48.8% were male. The mean value for systolic and diastolic blood pressure was 112.5 and 68.7mm Hg, respectively. Approximately 34.2% of all observations were inactive (0 metabolic equivalence values-hours), 29.8% had moderate-PA (median [interquartile range]; 3.75 [3.38 to 4.38] metabolic equivalence values-hours), and 36.0% had high-PA (15.7 [10.3 to 24.8] metabolic equivalence values-hours). The mean±SD of PM2.5 was 26.1±7.3 µg/m3. The prevalence of cardiovascular disease, diabetes mellitus, and cancer was 2.1%, 2.9%, and 1.5%, respectively. After adjusting for a wide range of covariates (including a mutual adjustment for PA or PM2.5), a higher PA level was associated with a lower risk of hypertension (hazard ratio [HR] for the moderate- and high-PA was 0.93 [95% CI, 0.89-0.97] and 0.92 [95% CI, 0.88-0.96], respectively, as compared with the inactive-PA), whereas a higher level of PM2.5 was associated with a higher risk of hypertension (HR for the moderate- and high-PM2.5 was 1.37 [95% CI, 1.32-1.43] and 1.92 [95% CI, 1.81-2.04], respectively, as compared with the low-PM2.5 group]. No significant interaction was observed between PA and PM2.5 (HR 1.01 [95% CI, 1.00-1.02]). CONCLUSIONS: A high-PA and low PM2.5 exposure were associated with a lower risk of hypertension. The negative association between PA and hypertension remained stable in people exposed to various levels of PM2.5, and the positive association between PM2.5 and hypertension was not modified by PA. Our results indicated that PA is a suitable hypertension prevention strategy for people residing in relatively polluted regions.

Associations of Reduced Ambient PM2.5 Level With Lower Plasma Glucose Concentration and Decreased Risk of Type 2 Diabetes in Adults: A Longitudinal Cohort Study.

It remains unknown whether reduced air pollution levels can prevent type 2 diabetes mellitus. In this study, we investigated the associations between dynamic changes in long-term exposure to ambient fine particulate matter, defined as particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5), and changes in fasting plasma glucose (FPG) levels and incidence of type 2 diabetes. A total of 151,398 adults (ages ≥18 years) were recruited in Taiwan between 2001 and 2014. All participants were followed up for a mean duration of 5.0 years. Change in PM2.5 (ΔPM2.5) was defined as the value at a follow-up visit minus the corresponding value at the immediately preceding visit. The PM2.5 concentration in Taiwan increased during 2002-2004 and began to decrease in 2005. Compared with participants with little or no change in PM2.5 exposure, those with the largest decrease in PM2.5 had a decreased FPG level (ß = -0.39, 95% confidence interval: -0.47, -0.32) and lower risk of type 2 diabetes (hazard ratio = 0.86, 95% confidence interval: 0.80, 0.93). The sensitivity analysis and analyses stratified by sex, age, body mass index, smoking, alcohol drinking, and hypertension generally yielded similar results. Improved PM2.5 air quality is associated with a better FPG level and a decreased risk of type 2 diabetes development.

Effects of air pollution and habitual exercise on the risk of death: a longitudinal cohort study.

BACKGROUND: Exercise may exacerbate the adverse health effects of air pollution by increasing the inhalation of air pollutants. We investigated the combined effects of long-term exposure to fine particle matter (PM2.5) and habitual exercise on deaths from natural causes in Taiwan. METHODS: We recruited 384 130 adults (aged ≥ 18 yr) with 842 394 medical examination records between 2001 and 2016, and followed all participants until May 31, 2019. We obtained vital data from the National Death Registry of Taiwan. We estimated PM2.5 exposure using a satellite-based spatiotemporal model, and collected information on exercise habits using a standard self-administered questionnaire. We analyzed the data using a Cox regression model with time-dependent covariates. RESULTS: A higher level of habitual exercise was associated with a lower risk of death from natural causes, compared with inactivity (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.80-0.88 for the moderate exercise group; HR 0.65, 95% CI 0.62-0.68 for the high exercise groups), whereas a higher PM2.5 exposure was associated with a higher risk of death from natural causes compared with lower exposure (HR 1.02, 95% CI 0.98-1.07, and HR 1.15, 95% CI 1.10-1.20, for the moderate and high PM2.5 exposure groups, respectively). Compared with inactive adults with high PM2.5 exposure, adults with high levels of habitual exercise and low PM2.5 exposure had a substantially lower risk of death from natural causes. We found a minor, but statistically significant, interaction effect between exercise and PM2.5 exposure on risk of death (HR 1.03 95% CI 1.01-1.06). Subgroup analyses, stratified by PM2.5 categories, suggested that moderate and high levels of exercise were associated with a lower risk of death in each PM2.5 stratum, compared with inactivity. INTERPRETATION: Increased levels of exercise and reduced PM2.5 exposure are associated with a lower risk of death from natural causes. Habitual exercise can reduce risk regardless of the levels of PM2.5 exposure. Our results suggest that exercise is a safe health improvement strategy, even for people residing in relatively polluted regions.

Reduced Ambient PM2.5 Was Associated with a Decreased Risk of Chronic Kidney Disease: A Longitudinal Cohort Study.

Many countries have dedicated to the mitigation of air pollution in the past several decades. However, evidence of beneficial effects of air quality improvement on chronic kidney disease (CKD) remains limited. We thus investigated the effects of dynamic changes (including deterioration and improvement) in air quality on the incidence of CKD in a longitudinal study in Taiwan. During 2001-2016, this study recruited a total of 163,197 Taiwanese residents who received at least two standard physical examinations. The level of fine particle matter (PM2.5) was estimated using a high-resolution (1 km2) satellite-based spatio-temporal model. We defined changes of PM2.5 concentrations (ΔPM2.5) as the difference between the two-year average measurements during follow-up and during the immediately preceding visit. The time-dependent Cox regression model was adopted to evaluate the relationships between ΔPM2.5 and the incidence of CKD after adjusting for a series of covariates. The concentrations of PM2.5 in Taiwan peaked around 2004 and began to decrease since 2005. We observed an approximate linear concentration-response relationship of ΔPM2.5 with CKD incidence. Every 5 µg/m3 decrease in the ambient concentration of PM2.5 was associated with a 25% reduced risk of CKD development [hazard ratio (HR): 0.75; 95% CI: 0.73, 0.78]. In conclusion, this study demonstrated that the improvement of PM2.5 air quality might be associated with a lower risk of CKD development. Our findings indicate that reducing air pollution may effectively prevent the development of CKD.

Does fine particulate matter (PM2.5) affect the benefits of habitual physical activity on lung function in adults: a longitudinal cohort study.

BACKGROUND: Physical activity (PA) increases a person's inhalation of air pollutants due to greater ventilation, possibly leading to larger adverse health effects. This study aims to investigate the combined effects of long-term exposure to fine particulate matter (PM2.5) and habitual PA on lung function in adults. METHODS: This was a longitudinal cohort study that included 278,065 Taiwan residents with an age of 20 years old or above who joined a standard medical screening programme between 2001 and 2014. Each participant received at least one medical examination (including spirometric, blood, and urinary tests and a standard self-administered questionnaire survey) during the study period. We estimated the 2-year average PM2.5 concentrations at each participant's address using a new physical model based on observational data. Information on the participants' PA was collected using the standard self-administrated questionnaire. Generalised linear mixed models were used to investigate the combined effects of PM2.5 and PA on pulmonary function. We also performed stratified analyses by different levels of PM2.5 exposure and habitual PA. RESULTS: Each 10 MET-h increase in PA was associated with a higher level of 0.20%, 0.16%, and 0.19% in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and maximum mid-expiratory flow (MMEF), respectively, after adjusting for PM2.5 exposure and a wide range of covariates including age, sex education, body mass index, lifestyles, and health conditions. Each 10 µg/m3 increase in PM2.5 was associated with a lower FVC, FEV1, and MMEF (2.43%, 2.78% and 3.10%, respectively). Negative interactions were observed, and PM2.5 exposure was associated with a greater reduction in lung function among the participants with higher PA levels. CONCLUSIONS: We found significant negative interaction effects between long-term exposure to PM2.5 and habitual PA, suggesting that the increased intake of PM2.5 due to PA may attenuate the benefits of habitual PA on lung function. However, the PA benefits generally remained stable at different stratum of PM2.5 in the stratified analyses, and habitual PA may still be recommended to people residing in relatively polluted regions.

Habitual physical activity, renal function and chronic kidney disease: a cohort study of nearly 200 000 adults.

BACKGROUND: There is limited information on the association between habitual physical activity (PA) and renal function. OBJECTIVE: To report the longitudinal association between self-reported habitual PA and measures of renal function in a large cohort in Taiwan. METHODS: A total of 199 421 participants (aged ≥20 years) were selected from a Taiwan cohort between 1996 and 2014. All participants underwent at least two standardised medical examinations between 1996 and 2014. Self-administrated questionnaires were used to collect information on habitual PA. We used a generalised linear mixed model to investigate the associations between habitual PA and yearly change in estimated glomerular filtration rate (eGFR). The Cox proportional hazard regression model was used to investigate the associations between habitual PA and incident chronic kidney disease (CKD). RESULTS: Participants had a median follow-up duration of 4.2 years (0.2-18.9). The yearly mean (±SD) decrease in eGFR in participants with baseline very low-PA, low-PA, moderate-PA and high-PA was 0.46±1.01, 0.36±0.97, 0.30±0.94 and 0.27±0.91 mL/min/1.73 m2, respectively. Relative to the participants with very low-PA, the coefficients of yearly eGFR change were -43.93 (95% CI -79.18 to -8.68), 35.20 (95% CI -2.56 to 72.96) and 53.56 (95% CI 10.42 to 96.70) µL/min/1.73 m2, respectively, for the participants with low-PA, moderate-PA and high-PA, after controlling for a wide range of covariates. Relative to the very low-PA participants, those who had low-PA, moderate-PA and high-habitual PA had HRs of 0.93 (95% CI 0.88 to 0.98), 0.94 (95% CI 0.89 to 0.99) and 0.91 (95% CI 0.85 to 0.96) to develop CKD, respectively, after controlling for the covariates. CONCLUSIONS: A higher level of habitual PA is associated with a smaller decrease in the level of eGFR and a lower risk of developing CKD.

Negative ability bias from conditioning on a confounded mediator: A directed interaction test and case study.

Sociologists increasingly recognize the problem of endogenous selection bias in mediation analysis. Building on a sub-model of Elwert and Winship (2014), we propose that a widely-overlooked endogenous selection bias exists in the form of a negative ability bias in sociological models of economic outcomes where job attributes are often included as mediators but confounded by unobserved abilities. We use simulations to show that the bias size increases with collider selectivity under common modeling assumptions, and we leverage this property to develop a directed interaction test to detect this bias. To demonstrate the principles of the test and the practical significance of the bias, we re-examine the paradox of Communist Party Premiums in post-2000 China-the sudden disappearance of income returns to Party members, as found in recent studies. The results are strikingly consistent with the hypothesis that a negative ability bias has recently overwhelmed the persistent Party premiums in China.

Long-term exposure to ambient fine particulate matter (PM2.5) and incident type 2 diabetes: a longitudinal cohort study.

AIMS/HYPOTHESIS: Information on the associations of long-term exposure to fine particulate matter (with an aerodynamic diameter less than 2.5 µm; PM2.5) with the development of type 2 diabetes is scarce, especially for south-east Asia, where most countries are experiencing serious air pollution. This study aimed to investigate the long-term effects of exposure to ambient PM2.5 on the incidence of type 2 diabetes in a population of Taiwanese adults. METHODS: A total of 147,908 participants without diabetes, at least 18 years of age, were recruited in a standard medical examination programme between 2001 and 2014. They were encouraged to take medical examinations periodically and underwent at least two measurements of fasting plasma glucose (FPG). Incident type 2 diabetes was identified as FPG ≥7 mmol/l or self-reported physician-diagnosed diabetes in the subsequent medical visits. The PM2.5 concentration at each participant's address was estimated using a satellite-based spatiotemporal model with a resolution of 1 × 1 km2. The 2 year average of PM2.5 concentrations (i.e. the year of and the year before the medical examination) was treated as an indicator of long-term exposure to ambient PM2.5 air pollution. We performed Cox regression models with time-dependent covariates to analyse the long-term effects of exposure to PM2.5 on the incidence of type 2 diabetes. A wide range of covariates were introduced in the models to control for potential effects, including age, sex, education, season, year, smoking status, alcohol drinking, physical activity, vegetable intake, fruit intake, occupational exposure, BMI, hypertension and dyslipidaemia (all were treated as time-dependent covariates except for sex). RESULTS: Compared with the participants exposed to the first quartile of ambient PM2.5, participants exposed to the second, third and fourth quartiles of ambient PM2.5 had HRs of 1.28 (95% CI 1.18, 1.39), 1.27 (95% CI 1.17, 1.38) and 1.16 (95% CI 1.07, 1.26), respectively, for the incidence of type 2 diabetes. Participants who drank occasionally or regularly (more than once per week) or who had a lower BMI (<23 kg/m2) were more sensitive to the long-term effects of exposure to ambient PM2.5. CONCLUSIONS/INTERPRETATION: Long-term exposure to ambient PM2.5 appears to be associated with a higher risk of developing type 2 diabetes in this Asian population experiencing high levels of air pollution.

Long-term exposure to ambient fine particulate matter and liver enzymes in adults: a cross-sectional study in Taiwan.

OBJECTIVES: Animal experiments indicate that exposure to particulate matter (PM) can induce hepatotoxic effects but epidemiological evidence is scarce. We aimed to investigate the associations between long-term exposure to PM air pollution and liver enzymes, which are biomarkers widely used for liver function assessment. METHODS: A cross-sectional analysis was performed among 351 852 adult participants (mean age: 40.1 years) who participated in a standard medical screening programme in Taiwan. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) levels were measured. A satellite-based spatio-temporal model was used to estimate the concentrations of ambient fine particles (PM with an aerodynamic diameter ≤2.5 µm, PM2.5) at each participant's address. Linear and logistic regression models were used to investigate the associations between PM2.5 and the liver enzymes with adjustment for a wide range of potential confounders. RESULTS: After adjustment for confounders, every 10 µg/m3 increment in 2-year average PM2.5 concentration was associated with 0.02%(95% CI: -0.04% to 0.08%), 0.61% (95% CI: 0.51% to 0.70%) and 1.60% (95% CI: 1.50% to 1.70%) increases in AST, ALT and GGT levels, respectively. Consistently, the odds ratios of having elevated liver enzymes (>40 IU/L) per 10 µg/m3 PM2.5 increment were 1.06 (95% CI: 1.04 to 1.09), 1.09 (95% CI: 1.07 to 1.10) and 1.09 (95% CI: 1.07 to 1.11) for AST, ALT and GGT, respectively. CONCLUSIONS: Long-term exposure to PM2.5 was associated with increased levels of liver enzymes, especially ALT and GGT. More studies are needed to confirm our findings and to elucidate the underlying mechanisms.

Association of long-term exposure to fine particulate matter and incident dyslipidaemia: A longitudinal cohort study.

BACKGROUND: Evidence of the effects of long-term exposure to fine particulate matter (PM2.5) air pollution on the development of dyslipidaemia is limited. This study aimed to investigate the association between long-term exposure to ambient PM2.5 and incident dyslipidaemia in a large cohort. METHODS: We studied 66,702 participants aged ≥18 years belonging to a cohort from a standard medical examination programme conducted in Taiwan between 2001 and 2014. The PM2.5 concentration at each participant's address was estimated using a satellite-based spatiotemporal model at a high resolution (1 km2). A time-varying Cox regression model was used to examine the association between long-term exposure to ambient PM2.5 and the development of dyslipidaemia. Additionally, sensitivity analyses were conducted to examine the stability of these associations. RESULTS: Compared with participants exposed to the 1st tertile of PM2.5, participants exposed to the 2nd and 3rd tertiles of PM2.5 had respective hazard ratios of 1.02 [95% confidence interval (CI): 0.98-1.06] and 1.08 (95%CI: 1.04-1.13) for incident dyslipidaemia. Sensitivity analyses generally yielded similar results. CONCLUSION: Long-term exposure to ambient PM2.5 is associated with a higher risk of dyslipidaemia. Global strategies for reducing air pollution are needed to prevent the development of dyslipidaemia.

Increased leisure-time physical activity associated with lower onset of diabetes in 44 828 adults with impaired fasting glucose: a population-based prospective cohort study.

AIMS: To evaluate the effects of habitual leisure-time physical activity (LTPA) on incident type 2 diabetes in a prospective cohort of Chinese adults with impaired fasting glucose (IFG). METHODS: 44 828 Chinese adults aged 20-80 years with newly detected IFG but free from cardiovascular and cerebrovascular disease were recruited and followed up from 1996 to 2014. Incident type 2 diabetes was identified by fasting plasma glucose ≥7 mmol/L. The participants were classified into four categories based on their self-reported weekly LTPA: inactive, low, moderate, or high. Hazard ratios (HRs) and population attributable fractions (PAFs) were estimated with adjustment for established diabetic risk factor. RESULTS: After 214 148 person-years of follow-up, we observed an inverse dose-response relationship between LTPA and diabetes risk. Compared with inactive participants, diabetes risk in individuals reporting low, moderate and high volume LTPA were reduced by 12% (HR 0.88, 95% CI 0.80 to 0.99; P=0.015), 20% (HR 0.80, 95% CI 0.71 to 0.90; P<0.001), and 25% (HR 0.75, 95% CI 0.67 to 0.83; P<0.001), respectively. At least 19.2% (PAF 19.2%, 95% CI 5.9% to 30.6%) of incident diabetes cases could be avoided if the inactive participants had engaged in WHO recommendation levels of LTPA. This would correspond to a potential reduction of at least 7 million diabetic patients in the Greater China area. CONCLUSIONS: Our results show higher levels of LTPA are associated with a lower risk of diabetes in IFG subjects. These data emphasise the urgent need for promoting physical activity as a preventive strategy against diabetes to offset the impact of population ageing and the growing obesity epidemic.

Exposure to ambient fine particulate matter and semen quality in Taiwan.

OBJECTIVES: Environmental exposure to chemicals has been considered a potential factor contributing to deteriorated semen quality. However, previous literature on exposure to air pollution and semen quality is inconsistent. We therefore investigated the health effects of short-term and long-term exposure to fine particulate matter (PM2.5) on semen quality in Taiwanese men from the general population. METHODS: A cross-sectional study was conducted among 6475 male participants aged 15-49 years who participated in a standard medical examination programme in Taiwan between 2001 and 2014. Semen quality was assessed according to the WHO 1999 guidelines, including sperm concentration, total motility, progressive motility and morphology. Three-month and 2-year average PM2.5 concentrations were estimated at each participant's address using a spatiotemporal model based on satellite-derived aerosol optical depth data. Multivariable linear and logistic regressions were used to examine the associations between PM2.5 and semen quality. RESULTS: A robust association was observed between exposure to PM2.5 and decreased normal morphology. Every increment of 5 µg/m3 in 2-year average PM2.5 was significantly associated with a decrease of 1.29% in sperm normal morphology and a 26% increased risk of having the bottom 10% of sperm normal morphology, after adjusting for a wide range of potential confounders (p<0.001). On the other hand, an increment of 5 µg/m3 in 2-year average PM2.5 was associated with an increase of 1.03×106/mL in sperm concentration and a 10% decreased risk of being the bottom 10% of sperm concentration (both p<0.001). Similar results were found for 3-month PM2.5. CONCLUSIONS: Exposure to ambient PM2.5 air pollution is associated with a lower level of sperm normal morphology and a higher level of sperm concentration.

Characterization of the direct interaction between KcsA-Kv1.3 and its inhibitors.

Integral membrane proteins (IMPs) are of therapeutic interest and are targeted by a majority of approved drugs. It's difficult to express, purify, and maintain the functional conformation of IMPs. Nanodisc presents a reliable method to solubilize and stabilize IMPs in detergent-free condition. In this study, we demonstrate the assembly and purification of a chimeric ion channel, KcsA-Kv1.3 Nanodisc. We further detail biophysical analysis of the assembled Nanodisc using analytical ultracentrifugation (AUC), surface plasmon resonance (SPR), and back scattering interferometry (BSI). AUC is employed to determine the molecular composition of the empty and KcsA-Kv1.3 Nanodisc. Combination of SPR and BSI overcomes each other's limitation and provides insight of equilibrium binding properties of peptide and small molecule ligands to KcsA-Kv1.3.