Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.

Trimester-Specific Urinary Strontium Concentrations during Pregnancy and Longitudinally Assessed Fetal Growth: Findings from a Prospective Cohort.

BACKGROUND: Studies have claimed that strontium (Sr) is associated with fetal growth, but the research evidence is insufficient. OBJECTIVES: Our study aimed to evaluate associations of trimester-specific urinary Sr concentrations with fetal growth parameters and birth size indicators. METHODS: In this prospective cohort, 9015 urine samples (first trimester: 3561, 2nd trimester: 2756, 3rd trimester: 2698) from 3810 mothers were measured for urinary Sr levels using inductively coupled plasma mass spectrometry (ICP-MS) and adjusted to urine specific gravity. We calculated standard deviation scores (SD-scores) for ultrasound-measured fetal growth parameters (head circumference, abdominal circumference, femur length, and estimated fetal weight) at 16, 24, 31, and 37 wk of gestation and birth size indicators (birth weight, birth length, and Ponderal index). Generalized linear models and generalized estimating equations models were used. Models were adjusted for potential covariates (gestational age, maternal age, body mass index, parity, passive smoking during pregnancy, education, folic acid supplements use, physical activity, maternal and paternal height, and infant sex). RESULTS: Positive associations of naturally logarithm-transformed Sr concentrations with fetal growth parameters and birth size indicators were observed. With each doubling increase in the urinary ln-Sr level in all 3 trimesters resulting in a percent change in SD-scores fetal growth parameters at 24, 31, and 37 wk of gestation and birth size indicators, 5.09%-8.23% in femur length, 7.57%-11.53% in estimated fetal weight, 6.56%-10.42% in abdominal circumference, 6.25% in head circumference, 5.15%-7.85% in birth weight, and 5.71%-9.39% in birth length, respectively. Most of the above statistical results could only be observed in male fetuses. CONCLUSIONS: Our findings suggest a potential association between Sr concentration and increased fetal growth, but these results and underlying mechanisms need further confirmation and clarification.

Association of exposure to per- and polyfluoroalkyl substances with hemoglobin and hematocrit during pregnancy.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are common environmental contaminants and are widely detected in humans. Previous studies have linked PFASs exposure to adverse birth outcomes. However, the association between maternal exposure to PFASs and hemoglobin (Hb) and hematocrit (HCT) remains unclear. OBJECTIVES: We aimed to explore the relationship between PFASs exposure with Hb and HCT during pregnancy. METHODS: The present birth cohort study included 1044 pregnant women from Wuhan, China. Maternal HCT and Hb were measured in the first, second and third trimesters, and 13 PFASs were detected in the cord sera. Mixed linear models and general linear regression were applied to analyze the association between each single PFASs and Hb and HCT. Weighted quantile sum (WQS) regressions were used to investigate the association between PFASs mixture and Hb and HCT during pregnancy. RESULTS: In single-PFAS models, 10 PFASs were positively associated with HCT and Hb across pregnancy (a 10-fold increase in PFASs was associated with 1.47-3.54 % change in HCT and 1.46-3.20 % change in Hb (All P-FDR < 0.05). In addition, Hb and HCT were more positively related to PFASs in the second and third trimesters rather than the first trimester. The association between PFASs exposure and maternal HCT and Hb was not significant in the iron supplementation group, whereas significant in the non-iron supplementation group. A significant interaction between iron supplementation and non-iron supplementation was also detected. WQS regressions showed that perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS) contributed most to the association between PFASs and HCT and Hb in the second and third trimesters, respectively. CONCLUSION: Maternal PFASs exposure was positive with serum Hb and HCT. Moreover, maternal iron supplementation may play a modifying effect in influencing the relationship between PFASs and HCT and Hb.

Association of adverse birth outcomes with prenatal uranium exposure: A population-based cohort study.

Uranium (U) is a well-recognized hazardous heavy metal with embryotoxicity and fetotoxicity. However, little is known about its association with adverse birth outcomes. We aimed to investigate the potential correlation between prenatal U exposure and birth outcomes. Urine samples of 8500 women were collected before delivery from a birth cohort in Wuhan, China. Concentrations of urinary U and other metals were measured by inductively coupled plasma mass spectrometry. We used multivariable logistic regressions to evaluate the associations between urinary U concentrations and adverse birth outcomes, such as preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). Associations of urinary U concentrations with gestational age, birth weight, and birth length were investigated by linear regressions. The geometric mean of U concentration was 0.03 µg/L. After adjustment for potential confounders, we found each Log2-unit increase in U concentration was associated with a significant decrease in gestational age [adjusted ß = -0.32 day; 95% confidence interval (CI): -0.44, -0.20] and a significant increased likelihood of PTB (adjusted OR = 1.18, 95% CI: 1.07, 1.29). This birth cohort uncovered an association of maternal exposure to U during pregnancy with decreased gestational age and increased risk of PTB. Our findings reveal an association of maternal exposure to U during pregnancy with decreased gestational age and increased risk of PTB.

Characterization of a novel Mycobacterium tuberculosis serine protease (Rv3194c) activity and pathogenicity.

Mycobacterium tuberculosis (MTB) serine proteases are important pathogen-associated virulence factors that are involved in the invasion, bacterial persistence, and degradation of host defense factors. The current study identified and characterized a novel serine protease, Rv3194c, of MTB. A heterologous Rv3194c protein, purified from Escherichia coli, possessed proteolytic activity that could hydrolyze bovine serum albumin (BSA), milk, casein, and gelatin at an optimal temperature of 40 °C and a pH of 8.0. Furthermore, the divalent metal ions Ca2+ and Mn2+ increased the activity of Rv3194c. Betulinic acid, a Traditional Chinese Medicine (TCM) monomer; PMSF, a chemical inhibitor; and the Roche inhibitor cocktail inhibited proteolytic activity. Site-directed mutagenesis demonstrated that D308 and particularly S309 play a crucial role in the catalytic activity of Rv3194c protease. The cellular assays revealed that Rv3194c inhibits THP1-derived macrophage migration. Moreover, Rv3194c degraded the complement components, C3b and C5a, causing inhibition of phagocytosis and chemotaxis. In mice, Rv3194c enhanced the persistence of Mycobacterium smegmatis (Ms) in the lung, induced lung lesions, and promoted the release of inflammatory cytokines. The results of this study indicate that Rv3194c may play an important role in the pathogenicity of mycobacteria.

Association between prenatal nickel exposure and preterm low birth weight: possible effect of selenium.

There is a proposed link between prenatal nickel (Ni) exposure and preterm low birth weight (PLBW); however, this association remains unclear. Selenium (Se) may modify this relationship by protecting against Ni toxicity. Concentrations of Ni and Se were measured in urine samples collected from 408 pregnant women (102 PLBW cases and 306 matched controls) in China. Conditional logistic regression was utilized to explore the association between Ni levels and PLBW, as well as the effect modification by Se on this association. A significant association was observed between higher maternal urinary Ni levels and risk of PLBW [adjusted odds ratio (OR) = 2.80 (95% confidence interval (CI): 1.44, 5.44) for the highest tertile], and this association was more apparent among female infants than that among male infants. Further analyses showed that mothers with high urinary Ni and low urinary Se levels had a significantly increased risk for PLBW [adjusted OR = 2.87 (95% CI: 1.09, 7.56)] compared with the mothers with low urinary Ni and high urinary Se levels. Our study indicates that prenatal exposure to Ni was a risk factor for PLBW. Se might provide protection against the toxicity of Ni.

Predictors of thallium exposure and its relation with preterm birth.

Thallium (Tl) is a well-recognized hazardous toxic heavy metal that has been reported to have embryotoxicity and fetotoxicity. However, little is known about its association with preterm birth (PTB) in humans. We aimed to evaluate the predictors of Tl exposure and assessed its relation with PTB. The study population included 7173 mother-infant pairs from a birth cohort in Wuhan, China. Predictors of Tl concentrations were explored using linear regression analyses, and associations of Tl exposure with risk of PTB or gestational age at birth were estimated using logistic regression or generalized linear models. The geometric mean and median values of urinary Tl concentrations were 0.28 µg/L (0.55 µg/g creatinine) and 0.29 µg/L (0.53 µg/g creatinine). We found that maternal urinary Tl concentrations varied by gestational weight gain, educational attainment, multivitamin and iron supplementations. Women with Tl concentrations higher than 0.80 µg/g creatinine were at higher risk of giving birth prematurely versus those with Tl concentrations lower than 0.36 µg/g creatinine [adjusted odds ratio (95% confidence interval (CI)): 1.55 (1.05, 2.27)], and the association was more pronounced in PTB with premature rupture of membranes (PROM) rather than in PTB without PROM. About 3-fold increase in creatinine-corrected Tl concentrations were associated with 0.99-day decrease in gestational length (95% CI: -1.36, -0.63). This is the first report on the associations between maternal Tl exposure and the risk of PTB.