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.

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.

Greenness and Birth Outcomes in a Range of Pennsylvania Communities.

Living in communities with more vegetation during pregnancy has been associated with higher birth weights, but fewer studies have evaluated other birth outcomes, and only one has been conducted in the Eastern United States, in regions with a broad range, including high levels, of greenness. We evaluated associations between prenatal residential greenness and birth outcomes (term birth weight, small for gestational age, preterm birth, and low 5 min Apgar score) across a range of community types using electronic health record data from 2006-2013 from the Geisinger Health System in Pennsylvania. We assigned greenness based on mother's geocoded address using the normalized difference vegetation index from satellite imagery. We used propensity scores to restrict the study population to comparable groups among those living in green vs. less-green areas. Analyses were adjusted for demographic, clinical, and environmental covariates, and stratified by community type (city, borough, and township). In cities, higher greenness (tertiles 2-3 vs. 1) was protective for both preterm (OR = 0.78, 95% CI: 0.61-0.99) and small for gestational age birth (OR = 0.73, 95% CI: 0.58-0.97), but not birth weight or Apgar score. We did not observe associations between greenness and birth outcomes in adjusted models in boroughs or townships. These results add to the evidence that greener cities might be healthier cities.

Surrogates of protection in repeated low-dose challenge experiments.

A critical step toward developing a successful vaccine to control the human immunodeficiency virus pandemic entails evaluation of vaccine candidates in non-human primates (NHPs). Historically, these studies have usually entailed challenges (i.e., exposures) with very high doses of a simian version of human immunodeficiency virus, resulting in infection of all NHPs in the experiment after a single challenge. More recently, researchers have begun to conduct repeated low-dose challenge (RLC) studies in NHPs that are believed to more closely mimic typical exposure in natural human transmission settings. One objective of RLC studies is to assess whether measured immune responses to vaccination can serve as surrogate endpoints for the primary endpoint of interest, namely infection. In this paper, different designs of RLC studies for assessing a binary surrogate of protection are considered.