Sex differences in the association of long-term exposure to heat stress on kidney function in a large Taiwanese population study.

The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM-2 PM) and working hours (8 AM-5 PM) periods based on the participants' residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2). Multivariable analysis revealed that in the male participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly positively associated with eGFR < 60 ml/min/1.73 m2 (odds ratio [OR], 1.096, 95% confidence interval [CI] = 1.002-1.199, p = 0.044 for 1 year; OR, 1.093, 95% CI = 1.000-1.196, p = 0.005 for 3 years; OR, 1.094, 95% CI = 1.002-1.195, p = 0.045 for 5 years). However, significant associations were not found for the working hours period. In the female participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.872, 95% CI = 0.778-0.976, p = 0.018 for 1 year; OR, 0.874, 95% CI = 0.780-0.978, p = 0.019 for 3 years; OR, 0.875, 95% CI = 0.784-0.977, p = 0.018 for 5 years). In addition, during the working hours period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were also significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.856, 95% CI = 0.774-0.946, p = 0.002 for 1 year; OR, 0.856, 95% CI = 0.774-0.948, p = 0.003 for 3 years; OR, 0.853, 95% CI = 0.772-0.943, p = 0.002 for 5 years). In conclusion, our results revealed that increased WBGT was associated with impaired kidney function in males, whereas increased WBGT was associated with a protective effect against impaired kidney function in females. Further studies are needed to elucidate the exact mechanisms underlying these sex-specific differences.

What is the spatiotemporal pattern of benzene concentration spread over susceptible area surrounding the Hartman Park community, Houston, Texas?

The Hartman Park community in Houston, Texas-USA, is in a highly polluted area which poses significant risks to its predominantly Hispanic and lower-income residents. Surrounded by dense clustering of industrial facilities compounds health and safety hazards, exacerbating environmental and social inequalities. Such conditions emphasize the urgent need for environmental measures that focus on investigating ambient air quality. This study estimated benzene, one of the most reported pollutants in Hartman Park, using machine learning-based approaches. Benzene data was collected in residential areas in the neighborhood and analyzed using a combination of five machine-learning algorithms (i.e., XGBR, GBR, LGBMR, CBR, RFR) through a newly developed ensemble learning model. Evaluations on model robustness, overfitting tests, 10-fold cross-validation, internal and stratified validation were performed. We found that the ensemble model depicted about 98.7% spatial variability of benzene (Adj. R2 =0.987). Through rigorous validations, stability of model performance was confirmed. Several predictors that contribute to benzene were identified, including temperature, developed intensity areas, leaking petroleum storage tank, and traffic-related factors. Analyzing spatial patterns, we found high benzene spread over areas near industrial zones as well as in residential areas. Overall, our study area was exposed to high benzene levels and requires extra attention from relevant authorities.

Air pollution as a potential risk factor for hepatocellular carcinoma in Taiwanese patients after adjusting for chronic viral hepatitis.

BACKGROUND: Air pollution is a risk factor for hepatocellular carcinoma (HCC). However, the effect of air pollution on HCC risk in patients with hepatitis remains unclear. METHODS: This cross-sectional study recruited 348 patients with chronic hepatitis who were tested for serum hepatitis B surface antigen (HBsAg) and for antibodies against hepatitis B core antigen (HBcIgG) and hepatitis C virus (anti-HCV) in 2022. The diagnosis of HCC was based on the International Classification of Diseases, 10th revision (ICD-10). Daily estimates of air pollutants were aggregated into mean estimates for the previous year based on the date of recruitment or HCC diagnosis. RESULTS: Out of 348 patients, 12 had HCC (3.4%). Patients with HCC were older (71.7 vs 50.9 years; p = 0.004), had higher proportion of HBsAg seropositivity (41.7% vs 5.1%; p < 0.001), and substantially higher levels of particulate matter 2.5 (PM 2.5 ) (21.5 vs 18.2 µg/m 3 ; p = 0.05). Logistic regression analysis revealed that the factors associated with HCC were age (odds ratio [OR]: 1.10; CI, 1.03-1.17; p = 0.01), PM 2.5 level (OR: 1.51; CI, 1.02-2.23; p = 0.04), and HBsAg seropositivity (OR: 6.60; CI, 1.51-28.85; p = 0.01) ( Table 3 ). There was a combined effect of PM 2.5 and HBsAg seropositivity on the risk of HCC development (OR: 22.17; CI, 3.33-147.45; p = 0.001). CONCLUSION: In this study, we demonstrated that PM 2.5 and HBsAg seropositivity were associated with HCC occurrence and had synergistic effects after adjusting for confounding factors.

Air pollution associate with advanced hepatic fibrosis among patients with chronic liver disease.

We aimed to investigate the association between air pollution and advanced fibrosis among patients with metabolic associated fatty liver disease (MAFLD) and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. A total of 1376 participants who were seropositive for HBV surface antigen (HBsAg) or antibodies to HCV (anti-HCV) or had abnormal liver function in a community screening program from 2019 to 2021 were enrolled for the assessment of liver fibrosis using transient elastography. Daily estimates of air pollutants (particulate matter ≤2.5 µm in diameter [PM2.5 ], nitrogen dioxide [NO2 ], ozone [O3 ] and benzene) were aggregated into mean estimates for the previous year based on the date of enrolment. Of the 1376 participants, 767 (52.8%) and 187 (13.6) had MAFLD and advanced fibrosis, respectively. A logistic regression analysis revealed that the factors associated with advanced liver fibrosis were HCV viremia (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.05-4.77; p < 0.001), smoking (OR, 1.79; 95% CI, 1.16-2.74; p = 0.01), age (OR, 1.04; 95% CI, 1.02-1.05; p < 0.001) and PM2.5 (OR, 1.10; 95% CI, 1.05-1.16; p < 0.001). Linear regression analysis revealed that LSM was independently correlated with PM2.5 (ß: 0.134; 95% CI: 0.025, 0.243; p = 0.02). There was a dose-dependent relationship between different fibrotic stages and the PM2.5 level (the PM2.5 level in patients with fibrotic stages 0, 1-2 and 3-4: 27.9, 28.4, and 29.3 µg/m3 , respectively; trend p < 0.001). Exposure to PM2.5 , as well as HBV and HCV infections, is associated with advanced liver fibrosis in patients with MAFLD. There was a dose-dependent correlation between PM2.5 levels and the severity of hepatic fibrosis.

Exposure to PM2.5 Metal Constituents and Liver Cancer Risk in REVEAL-HBV.

BACKGROUND: Ambient particulate matter is classified as a human Class 1 carcinogen, and recent studies found a positive relationship between fine particulate matter (PM2.5) and liver cancer. Nevertheless, little is known about which specific metal constituent contributes to the development of liver cancer. OBJECTIVE: To evaluate the association of long-term exposure to metal constituents in PM2.5 with the risk of liver cancer using a Taiwanese cohort study. METHODS: A total of 13,511 Taiwanese participants were recruited from the REVEAL-HBV in 1991-1992. Participants' long-term exposure to eight metal constituents (Ba, Cu, Mn, Sb, Zn, Pb, Ni, and Cd) in PM2.5 was based on ambient measurement in 2002-2006 followed by a land-use regression model for spatial interpolation. We ascertained newly developed liver cancer (ie, hepatocellular carcinoma [HCC]) through data linkage with the Taiwan Cancer Registry and national health death certification in 1991-2014. A Cox proportional hazards model was utilized to assess the association between exposure to PM2.5 metal component and HCC. RESULTS: We identified 322 newly developed HCC with a median follow-up of 23.1 years. Long-term exposure to PM2.5 Cu was positively associated with a risk of liver cancer. The adjusted hazard ratio (HR) was 1.13 (95% confidence interval [CI], 1.02-1.25; P = 0.023) with one unit increment on Cu normalized by PM2.5 mass concentration in the logarithmic scale. The PM2.5 Cu-HCC association remained statistically significant with adjustment for co-exposures to other metal constituents in PM2.5. CONCLUSION: Our findings suggest PM2.5 containing Cu may attribute to the association of PM2.5 exposure with liver cancer.

Determinants of residential greenness and its association with prostate cancer risk: A case-control study in Singapore.

BACKGROUND: Exposure to greenness has been shown to be beneficial to health, but few studies have examined the association between residential greenness and prostate cancer (PCa) risk. Our main objectives were to identify the determinants of residential greenness, and to investigate if residential greenness was associated with PCa risk in Singapore. METHODS: The hospital-based case-control study was conducted between April 2007 and May 2009. The Singapore Prostate Cancer Study (SPCS) comprised 240 prostate cancer cases and 268 controls, whose demographics and residential address were collected using questionnaires. Residential greenness was measured by normalized difference vegetation index (NDVI) around the participants' homes using a buffer size of 1 km. Determinants of NDVI were identified using a multivariable linear regression model. Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of associations between NDVI and PCa risk, adjusting for potential confounders. RESULTS: Having a BMI within the second quartile, as compared to the lowest quartile, was associated with higher levels of NDVI (ß-coefficient = 0.263; 95% CI = 0.040-0.485) after adjusting for covariates. Additionally, being widowed or separated, as compared to being married, was associated with lower levels of NDVI (ß-coefficient = -0.393; 95% CI = -0.723, -0.063). An interquartile range (IQR) increase in NDVI was positively associated with prostate cancer risk OR = 1.45; 95% CI = 1.02-2.07). Stratified analysis by tumour grade and stage showed that higher NDVI was associated with higher risk of low grade PCa. CONCLUSION: Our findings suggested that residential greenness was associated with higher risk of PCa in Singapore. Future studies on the quality and type of green spaces, as well as other factors of residential greenness, in association with PCa risk should be conducted to better understand this relationship.

Determination of potential sources of heavy metals in patients with urothelial carcinoma in central Taiwan: a biomonitoring case-control study.

The clarification of possible exposure sources of multiple metals to identify associations between metal doses and urothelial carcinoma (UC) risk is currently limited in the literature. We sought to identify the exposure sources of 10 metals (Vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, cadmium, and lead) using principal component analysis (PCA) and then linked various principal component (PC) scores with environmental characteristics, including smoking-related indices, PM2.5, and distance to the nearest bus station. In addition, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA hypomethylation markers (5-methyl-2'-deoxycytidine levels; %5-MedC) were investigated in combination with UC risks. We conducted this hospital-based case control study in 359 UC patients with histologically confirmed disease and 718 controls. All data were collected from face-to-face interviews and medical records. Approximately 6 mL blood was collected from participants for analysis of multiple heavy metal and DNA methylation in leukocyte DNA. Further, a 20 mL urine sample was collected to measure urinary cotinine and 8-OHdG levels. In addition, average values for PM2.5 for individual resident were calculated using the hybrid kriging/land-use regression model. In UC patients, significantly higher cobalt, nickel, copper, arsenic, and cadmium (µg/L) levels were observed in blood when compared with controls. Three PCs with eigenvalues > 1 accounted for 24.3, 15.8, and 10.7% of UC patients, and 26.9, 16.7, and 11.1% of controls, respectively. Environmental metal sources in major clusters were potentially associated with industrial activities and traffic emissions (PC1), smoking (PC2), and food consumption, including vitamin supplements (PC3). Multiple metal doses were linked with incremental urinary 8-OHdG and DNA hypomethylation biomarkers. For individuals with high PC1 and PC2 scores, both displayed an approximate 1.2-fold risk for UC with DNA hypomethylation.In conclusion, we provide a foundation for health education and risk communication strategies to limit metal exposure in environment, so that UC risks can be improved potentially.

PM2.5 exposure and risk of lung adenocarcinoma in women of Taiwan: A case-control study with density sampling.

BACKGROUND AND OBJECTIVE: The prevalence of smoking among women in Taiwan is <5%, but the incidence of lung cancer remains high. This study determined the association between PM2.5 (fine particulate matter with an aerodynamic diameter of ≤2.5 µm) exposure and lung cancer among women in Taiwan. METHODS: In total, 21,301 female lung cancer cases nationwide were newly diagnosed between 2012 and 2017. Each case was age-, sex- and calendar year-matched with four controls randomly selected from the general population. Allowing a latent period of 5 years, we estimated the PM2.5 and nitrogen dioxide (NO2 ) exposures for each individual according to the residential changes from 2000. We adopted self-reported smoking statuses for the cases, while those of controls were estimated using annual surveys in each residential county. We performed multiple logistic regression analyses to examine the associations between PM2.5 and NO2 exposures and incident lung cancer cases. RESULTS: The ORs of lung adenocarcinoma for the third (30.5-35.1 µg/m3 ), fourth (35.1-39.3 µg/m3 ) and fifth PM2.5 exposure quintiles (39.3-48.1 µg/m3 ) relative to the first quintile were 1.10 (95% CI: 1.04-1.16), 1.12 (95% CI: 1.06-1.19) and 1.10 (95% CI: 1.04-1.16), respectively, after adjusting for smoking, residence and comorbidities. A dose-response relationship (p = 0.004) was found. The associations persisted with a 10-year latency and were not detected for small-cell and squamous cell carcinoma after control for smoking. We did not observe a similar effect for NO2 exposure. CONCLUSION: Residential PM2.5 exposure higher than 30 µg/m3 was associated with an increased risk of lung adenocarcinoma in women of Taiwan.

A mixed spatial prediction model in estimating spatiotemporal variations in benzene concentrations in Taiwan.

It is well known benzene negatively impacts human health. This study is the first to predict spatial-temporal variations in benzene concentrations for the entirety of Taiwan by using a mixed spatial prediction model integrating multiple machine learning algorithms and predictor variables selected by Land-use Regression (LUR). Monthly benzene concentrations from 2003 to 2019 were utilized for model development, and monthly benzene concentration data from 2020, as well as mobile monitoring vehicle data from 2009 to 2019, served as external data for verifying model reliability. Benzene concentrations were estimated by running six LUR-based machine learning algorithms; these algorithms, which include random forest (RF), deep neural network (DNN), gradient boosting (GBoost), light gradient boosting (LightGBM), CatBoost, extreme gradient boosting (XGBoost), and ensemble algorithms (a combination of the three best performing models), can capture how nonlinear observations and predictions are related. The results indicated conventional LUR captured 79% of the variability in benzene concentrations. Notably, the LUR with ensemble algorithm (GBoost, CatBoost, and XGBoost) surpassed all other integrated methods, increasing the explanatory power to 92%. This study establishes the value of the proposed ensemble-based model for estimating spatiotemporal variation in benzene exposure.

Long-Term Exposure to Fine Particulate Matter and the Deterioration of Estimated Glomerular Filtration Rate: A Cohort Study in Patients With Pre-End-Stage Renal Disease.

Limited literature has explored the effect of air pollutants on chronic kidney disease (CKD) progression, especially for patients with pre-end-stage renal disease (pre-ESRD). In this study, we reported the linear and nonlinear relationships of air pollutants of particles with diameter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) with estimated glomerular filtration rate (eGFR) deterioration after adjusting for smoking status and other traditional clinical factors. This study adopted a retrospective cohort of patients with stage 3b to stage 5 CKD (N = 11,479) from Taichung Veterans General Hospital during January 2006 to December 2020. The eGFR deterioration was defined as a decline in eGFR > 5 ml/min/1.73 m2/year. Hybrid kriging/land-use regression models were used to estimate the individual exposure levels of PM2.5 and NO2. The relationships of air pollutants with eGFR deterioration were evaluated using Cox proportional hazard models. After adjusting for smoking status, baseline eGFR stages, and other traditional clinical factors, the risk of eGFR deterioration was found to increase with increasing PM2.5 and NO2 level (p < 0.0001 and p = 0.041, respectively), especially for those exposed to PM2.5 ≥ 31.44 µg/m3 or NO2 ≥ 15.00 ppb. Similar results were also found in the two-pollutant models. Nonlinear dose-response relationships of eGFR deterioration were observed for concentrations of 26.11 µg/m3 for PM2.5 and 15.06 ppb for NO2. In conclusion, linear and nonlinear associations between PM2.5 and NO2 levels and the incidence risk of eGFR deterioration were observed in patients with pre-ESRD.

Integrated analysis of source-specific risks for PM2.5-bound metals in urban, suburban, rural, and industrial areas.

The levels and characteristics of atmospheric metals vary in time and location, can result in various health impacts, which increases the challenge of air quality management. We aimed to investigate PM2.5-bound metals in multiple locations and propose a methodology for comparing metal elements across study regions and prioritizing source contributions through integrated health risk assessments. PM2.5-bound metals were collected in the urban, suburban, rural, and industrial regions of Taiwan between 2016 and 2018. We incorporated the positive matrix factorization (PMF) with health risk assessments (considering estimates of the margin of exposure (MOE) and excess cancer risk (ECR)) to prioritize sources for control. We found that the concentrations of Fe, Zn, V, Cu, and Mn (industry-related metals) were higher at the industrial site (Kaohsiung) and Ba, Cr, Ni, Mo, and Co (traffic-related metals) were higher at the urban site (Taipei). The rural site (Hualian) had good air quality, with low PM2.5 and metal concentrations. Most metal concentrations were higher during the cold season for all study sites, except for the rural. Ambient concentrations of Mn, Cr, and Pb obtained from all study sites presents a higher health risk of concern. In Kaohsiung, south Taiwan, PM2.5-bound metals from the iron ore and steel factory is suggested as the first target for control based on the calculated health risks (MOE < 1 and ECR > 10-6). Overall, we proposed an integrated strategy for initiating the source management prioritization of PM2.5-bound metals, which can aid an effort for policymaking.

Association between Surrounding Greenness and Mortality: An Ecological Study in Taiwan.

Exposure to surrounding greenness is associated with reduced mortality in Caucasian populations. Little is known however about the relationship between green vegetation and the risk of death in Asian populations. Therefore, we opted to evaluate the association of greenness with mortality in Taiwan. Death information was retrieved from the Taiwan Death Certificate database between 2006 to 2014 (3287 days). Exposure to green vegetation was based on the normalized difference vegetation index (NDVI) collected by the Moderate Resolution Imagine Spectroradiometer (MODIS). A generalized additive mixed model was utilized to assess the association between NDVI exposure and mortality. A total of 1,173,773 deaths were identified from 2006 to 2014. We found one unit increment on NDVI was associated with a reduced mortality due to all-cause (risk ratio [RR] = 0.901; 95% confidence interval = 0.862-0.941), cardiovascular diseases (RR = 0.892; 95% CI = 0.817-0.975), respiratory diseases (RR = 0.721; 95% CI = 0.632-0.824), and lung cancer (RR = 0.871; 95% CI = 0.735-1.032). Using the green land cover as the alternative green index showed the protective relationship on all-cause mortality. Exposure to surrounding greenness was negatively associated with mortality in Taiwan. Further research is needed to uncover the underlying mechanism.

The effects of fine and coarse particulate matter on lung function among the elderly.

Impaired lung function is associated with morbidity and mortality in the elderly. However, there is a paucity of data regarding the long-term effects of particulate matter (PM) on lung function among the elderly. This study evaluated the exposure-response relationship between ambient PM and different lung function indices among the elderly in Taiwan. A cross-sectional survey of individuals aged ≥65 years was conducted in Taiwan from October 2015 to September 2016. Those who attended the annual health examination for the elderly in five hospitals of varying background PM concentrations were enrolled. The long-term (2015 annual mean concentration) exposure to air pollution was estimated by the Kriging method at the residence of each subject. The association between ambient PM exposure and lung function was evaluated by linear regression modeling, with adjustments for age, sex, height, weight, educational attainment, presence of asthma or chronic obstructive pulmonary disease, smoking status, season, and co-pollutants. There were 1241 subjects (mean age, 70.5 years). The mean residential PM2.5 and PM2.5-10 in 2015 was 26.02 and 18.01 µg/m3, respectively. After adjustments for confounders and co-pollutants, the FVC decrease was best associated with fine particles (PM2.5), whereas the FEV1, FEF25-75%, FEF25% and FEF50% decreases were best associated with coarse particles (PM2.5-10). An IQR (10 µg/m3) increase in PM2.5 decreased FVC by 106.38 ml (4.47%), while an IQR (7.29 µg/m3) increase in PM2.5-10 decreased FEV1 and FEF25-75% by 91.23 ml (4.85%) and 104.44 ml/s (5.58%), respectively. Among the Taiwanese elderly, long-term PM2.5 exposure mainly decreases the vital capacity of lung function. Moreover, PM2.5-10 has a stronger negative effect on the function of conductive airways than PM2.5.

Residential greenness and mortality in oldest-old women and men in China: a longitudinal cohort study.

BACKGROUND: Exposure to natural vegetation, or greenness, might affect health through several pathways, including increased physical activity and social engagement, improved mental health, and reductions in exposure to air pollution, extreme temperatures, and noise. Few studies of the effects of greenness have focused on Asia, and, to the best of our knowledge, no study has assessed the effect on vulnerable oldest-old populations. We assessed the association between residential greenness and mortality in an older cohort in China. METHODS: We used five waves (February, 2000-October, 2014) of the China Longitudinal Healthy Longevity Survey (CLHLS), a prospective cohort representative of the general older population in China. We assessed exposure to greenness through satellite-derived Normalised Difference Vegetation Index (NDVI) values in the 250 m and 1250 m radius around the residential address for each individual included in the study. We calculated contemporaneous NDVI values, cumulative NDVI values, and changes in NDVI from the start of the study over time. The health outcome of the study was all-cause mortality, excluding accidental deaths. Mortality rate ratios were estimated with Cox proportional hazards models, adjusted for age, sex, ethnicity, marital status, geographical region, childhood and adult socioeconomic status, social and leisure activity, smoking status, alcohol consumption, and physical activity. FINDINGS: Among 23 754 individuals (mean age at baseline 93 years [SD 7·5]) totaling 80 001 person-years, we observed 18 948 deaths during 14 years of follow-up, between June, 2000, and December, 2014. Individuals in the highest quartile of contemporaneous NDVI values had 27% lower mortality than those in the lowest quartile for the 250 m radius (hazard ratio [HR] 0·73, 95% CI 0·70-0·76), and 30% lower mortality for the 1250 m radius (0·70, 0·67-0·74). No clear association was observed for cumulative NDVI measurements and mortality. We did not detect an association between area-level changes in NDVI and mortality. INTERPRETATION: Our research suggests that proximity to more green space is associated with increased longevity, which has policy implications for the national blueprint of ecological civilisation and preparation for an ageing society in China. FUNDING: Bill & Melinda Gates Foundation, US National Institute on Aging, US National Institute of Health, Natural Science Foundation of China, UN Population Fund, China Social Sciences Foundation, and Hong Kong Research Grants Council.

Fine Particle Pollution, Alanine Transaminase, and Liver Cancer: A Taiwanese Prospective Cohort Study (REVEAL-HBV).

BACKGROUND: Exposure to fine particulate matter (PM2.5) may promote hepatic tumorgenesis through low-grade inflammation. Therefore, we assessed the association of long-term exposure levels of PM2.5 and subsequent risk of hepatocellular carcinoma (HCC) and investigated the mediation effect of inflammation as represented by alanine aminotransferase (ALT) on this association. METHODS: Between 1991 and 1992, we recruited 23 820 participants in Taiwan with no history of HCC. Case patients of HCC were ascertained through computerized data linkage with the National Cancer Registry and death certification systems. Participants' exposures to PM2.5 were based on a four-year average retrieved from stationary monitoring sites. Cox proportional hazards models were used to assess the association between PM2.5 exposure and HCC incidence. Mediation effects of ALT on PM2.5-associated HCC incidence were estimated. RESULTS: A total of 464 HCC cases were newly diagnosed with a median follow-up of 16.9 years. Statistically significantly increasing trends between PM2.5 exposures and ALT were observed on the Main Island and Penghu Islets. The adjusted hazard ratio (HR) for HCC on the Penghu Islets was 1.22 (95% confidence interval [CI] = 1.02 to 1.47) per PM2.5 interquartile range (IQR) increment (0.73 µg/m(3)) exposure. We also found a positive association between PM2.5 exposure (per IQR increment, 13.1 µg/m(3)) and HCC incidence on the Main Island. Furthermore, ALT had a statistically significant mediation effect on PM2.5-associated HCC incidence (HR = 1.17, 95% CI = 1.02 to1.52 on the Main Island; HR = 1.04, 95% CI = 1.03 to 1.07 on the Penghu Islets) per PM2.5 IQR increment. CONCLUSIONS: Long-term PM2.5 exposure increased the risk for liver cancer, and chronic inflammation of the liver may underlie the pathogenesis.

Acoustic radiation force beam sequence performance for detection and material characterization of atherosclerotic plaques: preclinical, ex vivo results.

This work presents preclinical data demonstrating performance of acoustic radiation force (ARF)-based elasticity imaging with five different beam sequences for atherosclerotic plaque detection and material characterization. Twelve trained, blinded readers evaluated parametric images taken ex vivo under simulated in vivo conditions of 22 porcine femoral arterial segments. Receiver operating characteristic (ROC) curve analysis was carried out to quantify reader performance using spatially-matched immunohistochemistry for validation. The beam sequences employed had high sensitivity (sens) and specificity (spec) for detecting Type III+ plaques (sens: 85%, spec: 79%), lipid pools (sens: 80%, spec: 86%), fibrous caps (sens: 86%, spec: 82%), calcium (sens: 96%, spec: 85%), collagen (sens: 78%, spec: 77%), and disrupted internal elastic lamina (sens: 92%, spec: 75%). 1:1 single-receive tracking yielded the highest median areas under the ROC curve (AUC), but was not statistically significantly higher than 4:1 parallel-receive tracking. Excitation focal configuration did not result in statistically different AUCs. Overall, these results suggest ARF-based imaging is relevant to detecting and characterizing plaques and support its use for diagnosing and monitoring atherosclerosis.

Enhanced control of pathogenic Simian immunodeficiency virus SIVmac239 replication in macaques immunized with an interleukin-12 plasmid and a DNA prime-viral vector boost vaccine regimen.

DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (P < 0.01). In 5 out of 6 infected RMs, strong suppression of viremia was observed, with intermittent "blips" in virus replication. In 2 RMs, we could not detect the presence of SIV RNA in tissue and lymph nodes, even after 13 viral challenges. RMs immunized without pIL-12 demonstrated a typical maximum of 1.5 log reduction in virus load. There was no significant difference in the overall magnitude of SIV-specific antibodies or CD8 T-cell responses between groups; however, pDNA delivery by EP with pIL-12 induced a greater magnitude of SIV-specific CD4 T cells that produced multiple cytokines. This vaccine strategy is relevant for existing vaccine candidates entering clinical evaluation, and this model may provide insights into control of retrovirus replication.