Association between drinking water quality and mental health and the modifying role of diet: a prospective cohort study.

BACKGROUND: Environmental factors play an important role in developing mental disorders. This study aimed to investigate the associations of metal and nonmetal elements in drinking water with the risk of depression and anxiety and to assess whether diets modulate these associations. METHODS: We conducted a prospective cohort study including 24,285 participants free from depression and anxiety from the Yinzhou Cohort study in the 2016-2021 period. The exposures were measured by multiplying metal and nonmetal element concentrations in local pipeline terminal tap water samples and total daily drinking water intakes. Cox regression models adjusted for multi-level covariates were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95%CIs). RESULTS: During an average follow-up period of 4.72 and 4.68 years, 773 and 1334 cases of depression and anxiety were identified, respectively. A 1 standard deviation (SD) increase in manganese exposure reduced the incidence of depression by 8% (HR 0.92, 95%CI 0.88 to 0.97). In contrast, with a 1 SD increase in copper and cadmium exposure, the incidence of depression increased by 6% (HR 1.06, 95%CI 1.01 to 1.11) and 8% (HR 1.08, 95%CI 1.00 to 1.17), respectively. The incidence of anxiety increased by 39% (HR 1.39, 95%CI 1.20 to 1.62), 33% (HR 1.33, 95%CI 1.03 to 1.71), and 14% (HR 1.14, 95%CI 1.03 to 1.25) respectively for a 1 SD increase in manganese, iron, and selenium exposure. Diets have a moderating effect on the associations of metal and nonmetal elements with the risk of anxiety. Stronger associations were observed in older, low-income groups and low-education groups. CONCLUSIONS: We found significant associations between exposure to metal and nonmetal elements and depression and anxiety. Diets regulated the associations to some extent.

Arsenic in drinking water and lung cancer: A systematic review of 35 years of evidence.

The association between higher arsenic concentrations in drinking water and lung cancer is well-established. However, the risk associated with lower levels of arsenic exposure remains uncertain. This systematic review and meta-analysis summarizes the evidence on the relationship between exposure to arsenic in drinking water and lung cancer outcomes as measured over a broad range of exposures, including lower levels. A total of 51 studies were included in the review and 15 met criteria for inclusion in meta-analysis. Risk estimates for lung cancer incidence and mortality were pooled and analyzed separately using Bayesian hierarchical random-effects models with a Gaussian observation submodel for log(Risk), computed using the "brms" R package. For lung cancer incidence, the predicted posterior mean relative risks (RRs) at arsenic concentrations of 10, 50 and 150 µg/L were 1.11 (0.86-1.43), 1.67 (1.27-2.17) and 2.21 (1.61-3.02), respectively, with posterior probabilities of 79%, 100% and 100%, respectively, for the RRs to be >1. The posterior mean mortality ratios at 20, 50 and 150 µg/L were 1.22 (0.83-1.78), 2.10 (1.62-2.71) and 2.41 (1.88-3.08), respectively, with posterior probabilities being above 80%. In addition to observing the dose-response relationship, these findings demonstrate that individuals exposed to low to moderate levels of arsenic (<150 µg/L) were at an elevated risk of developing or dying from lung cancer. Given the widespread exposure to lower levels of arsenic, there is an urgent need for vigilance and potential revisions to regulatory guidelines to protect people from the cancer risks associated with arsenic exposure.

Urate-Lowering Therapy Inhibits Thoracic Aortic Aneurysm and Dissection Formation in Mice.

BACKGROUND: Thoracic aortic aneurysm and dissection (TAAD) is a highly lethal vascular disease without effective drug therapy. Whether elevated serum concentrations of uric acid are involved in TAAD development remains unclear. METHODS: Serum uric acid levels were detected in different TAAD mouse models and patients. The urate-lowering drug allopurinol was administered in the drinking water of TAAD mice. Adenine diet-induced mice were established to investigate the role of hyperuricemia in TAAD formation and RNA-sequencing of thoracic aortas from these mice was performed. RESULTS: We found serum uric acid levels were elevated in various mouse TAAD models, including mice fed a ß-aminopropionitrile diet, Marfan mice with fibrillin-1 haploinsufficiency (Fbn1C1041G/+), and ApoE-/- mice infused with Ang II (angiotensin II), as well as in patients with TAAD. Administration of urate-lowering drug allopurinol in the drinking water significantly alleviated TAAD formation in ß-aminopropionitrile-treated mice, Fbn1C1041G/+ mice, and Ang II-infused ApoE-/- mice. Moreover, an adenine diet was used to induce hyperuricemia in mice. Intriguingly, a 4-week adenine diet feeding directly induced TAAD formation characterized by increased maximal thoracic aortic diameters and severe elastin degradation, which were ameliorated by allopurinol. Unbiased RNA-sequencing in mouse thoracic aortas suggested that FcγR (Fc gamma receptor) was upregulated upon adenine diet, but reciprocally repressed by allopurinol. Mechanistically, hyperuricemia activated FcγR-mediated ERK1/2 (extracellular signal-regulated kinase 1/2) phosphorylation to induce macrophage inflammation and TAAD development, which was abrogated by allopurinol or FcγR deficiency. CONCLUSIONS: This study uncovered an important and previously unrecognized role of hyperuricemia in mediating the pathogenesis of TAAD, and uric acid-lowering drug may represent a promising therapeutic approach for TAAD.

Endocrine Disruptors and Thyroid Health.

A wide variety of thyroidal endocrine-disrupting chemicals (EDCs) have been identified. Exposure to known thyroidal EDCs is ubiquitous, and many likely remain unidentified. The sources of exposure include contaminated drinking water, air pollution, pesticides and agricultural chemicals, flame retardants, cleaning supplies, personal care products, food additives and packaging materials, coatings and solvents, and medical products and equipment. EDCs can affect thyroid hormone synthesis, transport, metabolism, and action in a myriad of ways. Understanding the health effects of thyroidal EDCs has been challenging because individuals may have multiple concomitant EDC exposures and many potential EDCs are not yet well characterized. Because of the importance of thyroid hormone for brain development in early life, pregnant women and young infants are particularly vulnerable to the effects of environmental thyroid disruption. The thyroidal effects of some EDCs may be exacerbated in iodine-deficient individuals, those with thyroid autoimmunity, and those with mutations in deiodinase genes. Differential exposures to EDCs may exacerbate health disparities in disadvantaged groups. High-throughput in vitro assays and in silico methods and methods that can detect the effects of relevant EDC mixtures are needed. In addition, optimal methods for detecting the effects of thyroidal EDCs on neurodevelopment need to be developed. Common sense precautions can reduce some thyroidal EDC exposures; however, regulation of manufacturing and drinking water content will ultimately be needed to protect populations.

Association between type of drinking water and upper gastrointestinal cancer incidence in the Linxian General Population.

BACKGROUND: This study aimed to explore the association between drinking water source and risk of upper gastrointestinal (UGI) cancer, including esophageal cancer (EC) and gastric cancer (GC), in the Linxian General Population Nutrition Intervention Trial (NIT) cohort. METHODS: In this study, we used data from the Linxian NIT cohort, which included 29,584 healthy adults aged 40 to 69 years. Subjects were enrolled in April 1986 and followed up until March 2016. Tap water drinking status and demographic characteristics were collected at baseline. Subjects who drank tap water were treated as the exposed group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model. RESULTS: A total of 5,463 cases of UGI cancer were identified during the 30-year follow-up period. After adjusting for multiple factors, the incidence rate of UGI cancer in participants who drank tap water was significantly lower compared with individuals in the control (HR = 0.91, 95% CI: 0.86-0.97). A similar association was observed between tap water drinking and EC incidence (HR = 0.89, 95% CI: 0.82-0.97). The association between drinking tap water and risk of UGI cancer and EC incidence did not vary across the subgroup by age and gender (All Pinteraction > 0.05). For EC incidence, an interaction effect was observed for riboflavin/niacin supplements and drinking water source (Pinteraction = 0.03). No association was observed between drinking water source and GC incidence. CONCLUSIONS: In this prospective cohort study in Linxian, participants who drank tap water had a lower risk of EC incidence. As a source of drinking water, use of tap water may reduce the risk of EC by avoiding exposure to nitrate/nitrite. Measures should be taken to improve the quality of drinking water in high-incidence areas of EC. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT00342654, 21/06/2006), and the trial name is Nutrition Intervention Trials in Linxian Follow-up Study.

Low-level lithium in drinking water and subsequent risk of dementia: Cohort study.

BACKGROUND: Lithium, a mood stabilizer, is known to exhibit neuroprotective effects in animal models and may have anti-dementia effects. AIMS: We used data from Scottish Mental Survey 1932, a population-based cohort study, to investigate the association between lithium in drinking water and dementia rate in humans. METHOD: Lithium levels in drinking water from 285 sampling sites across Scotland dating from 2014 were obtained from the sole public water provider (Scottish Water). Dementia and non dementia cases were identified from cohort data by electronic health records until 2012, and linked to postcode. RESULTS: The mean lithium level at all sampling sites was 1.45 µg/L (SD 1.83, range 0.5-18.2) and was 1.26 (SD 0.63, range 0.55-9.19) for sites matched to participant data. Of 37,597 study members, 3605 developed dementia until June 2012. Lithium levels were positively associated with the risk of dementia in women (highest in second quartile, HR 1.17, 95%CI 1.04-1.32), but there was no relationship in men (highest in second quartile, HR 0.95, 95% CI 0.81-1.12). The pattern of association was explored further by decile, and in females there was an association between lithium level and increased dementia risk compared to the lowest decile (0.55-0.68 µg/L) in all deciles except the highest, corresponding with lithium levels 0.68-2.1 µg/L. CONCLUSIONS: Lithium levels in drinking water are very low across Scotland which limited detection of potential effect. Our results do not support an association between extremely low levels of lithium and later dementia risk. We found a trend to increased risk in females at lithium levels below but not above 2.1 µg/L.

Critical endpoints of PFOA and PFOS exposure for regulatory risk assessment in drinking water: Parameter choices impacting estimates of safe exposure levels.

USEPA issued drinking water interim health advisories (iHA) for PFOA and PFOS. The Agency's choice for critical effect, toxic point-of-departure (PoD), benchmark dose (BMD), pharmacokinetic (PK) model extrapolation to ingested dose, and use of uncertainty factors, resulted in the iHA for PFOS and PFOA being lowered from 70 ppt to 0.04-0.2 ppt. This review addresses key steps in the iHA derivation that influence changes in iHA values and suggests analysis and modeling changes for higher confidence in the iHA derivation, and re-evaluation of critical endpoint data for immunotoxicity and associated BMD modeling to derive a serum antibody PoD in the clinically adverse range. Movement from empirical PK modeling of ingested human dose to a platform that captures biological realism will more accurately reflect PFAS elimination, which impacts model-optimized ingested dose. The uncertainty factor (UF) for human variability should be reconsidered, as in utero and neonate exposures used to derive the iHA represent the likely susceptible populations. Although not part of the iHA derivation, cancer was considered in the drinking water maximum contaminant level goal (MCLG) technical evaluation. We discuss weaknesses in the cancer epidemiological data that require re-evaluation as the drinking water regulation process proceeds to a national standard.

Effect of ethyl gallate and propyl gallate on dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6 J mice: preventive and protective.

OBJECTIVE AND DESIGN: Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition of the digestive system marked by oxidative stress, leukocyte infiltration, and elevation of inflammatory mediators. In this study, we demonstrate the protective effect of ethyl gallate (EG), a phytochemical, and propyl gallate (PG), an anti-oxidant, given through normal drinking water (DW) and copper water (CW) in various combinations, which had a positive effect on the amelioration of DSS-induced ulcerative colitis in C57BL/6 J mice. MATERIALS AND METHODS: We successfully determined the levels of proinflammatory cytokines and anti-oxidant enzymes by ELISA, tracked oxidative/nitrosative stress (RO/NS) by in vivo imaging (IVIS) using L-012 chemiluminescent probe, disease activity index (DAI), and histopathological and morphometric analysis of colon in DSS-induced colitis in a model. RESULTS: The results revealed that oral administration of ethyl gallate and propyl gallate at a dose of 50 mg/kg considerably reduced the severity of colitis and improved both macroscopic and microscopic clinical symptoms. The level of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, and IFN-γ) in colonic tissue was considerably reduced in the DSS + EG-treated and DSS + PG-treated groups, compared to the DSS alone-treated group. IVIS imaging of animals from the DSS + EG and DSS + PG-treated groups showed a highly significant decrease in RO/NS species relative to the DSS control group, with the exception of the DSS + PG/CW and DSS + EG + PG/CW-treated groups. We also observed lower levels of myeloperoxidase (MPO), nitric oxide (NO), and lipid peroxidation (LPO), and restored levels of GST and superoxide dismutase (SOD) in DSS + EG-DW/CW, DSS + PG/DW, and DSS + EG + PG/DW groups compared to DSS alone-treated group. In addition, we showed that the EG, PG, and EG + PG treatment significantly reduced the DAI score, and counteracted the body weight loss and colon shortening in mice compared to DSS alone-treated group. In this 21-day study, mice were treated daily with test substances and were challenged to DSS from day-8 to 14. CONCLUSION: Our study highlights the protective effect of ethyl gallate and propyl gallate in various combinations which, in pre-clinical animals, serve as an anti-inflammatory drug against the severe form of colitis, indicating its potential for the treatment of IBD in humans. In addition, propyl gallate was investigated for the first time in this study for its anti-colitogenic effect with normal drinking water and reduced effect with copper water.

Drinking water nitrate and risk of pregnancy loss: a nationwide cohort study.

BACKGROUND: Nitrate contamination is seen in drinking water worldwide. Nitrate may pass the placental barrier. Despite suggestive evidence of fetal harm, the potential association between nitrate exposure from drinking water and pregnancy loss remains to be studied. We aimed to investigate if nitrate in drinking water was associated with the risk of pregnancy loss. METHODS: We conducted a nationwide cohort study of 100,410 pregnancies (enrolled around gestational week 11) in the Danish National Birth Cohort (DNBC) during 1996-2002. Spontaneous pregnancy losses before gestational week 22 were ascertained from the Danish National Patient Registry and DNBC pregnancy interviews. Using the national drinking water quality-monitoring database Jupiter, we estimated the individual and time-specific nitrate exposure by linking geocoded maternal residential addresses with water supply areas. The nitrate exposure was analyzed in spline models using a log-transformed continuous level or classified into five categories. We used Cox proportional hazards models to estimate associations between nitrate and pregnancy loss and used gestational age (days) as the time scale, adjusting for demographic, health, and lifestyle variables. RESULTS: No consistent associations were found when investigating the exposure as a categorical variable and null findings were also found in trimester specific analyses. In the spline model using the continuous exposure variable, a modestly increased hazard of pregnancy loss was observed for the first trimester at nitrate exposures between 1 and 10 mg/L, with the highest. adjusted hazard ratio at 5 mg/L of nitrate of 1.16 (95% CI: 1.01, 1.34). This trend was attenuated in the higher exposure ranges. CONCLUSION: No association was seen between drinking water nitrate and the risk of pregnancy loss when investigating the exposure as a categorical variable. When we modelled the exposure as a continuous variable, a dose-dependent association was found between drinking water nitrate exposure in the first trimester and the risk of pregnancy loss. Very early pregnancy losses were not considered in this study, and whether survival bias influenced the results should be further explored.

Ectopically Localized Epithelial Cell Clumps in Ulcers Are Derived from Reserved Crypt Stem Cells in a Mouse Model of Ulcerative Colitis.

BACKGROUND: We previously reported that clumps of a few epithelial cells were scattered in ulcer regions in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis (UC). AIMS: To determine the ectopically localized epithelial clumps might be derived from stem cells or their daughter progenitor cells. METHODS: Female BALB/c mice were administered DSS in drinking water for 6 days, followed by withdrawal of DSS for 6 days. Histological and immunohistochemical examinations were conducted in the distal region and proximal region of the colorectum to determine expression of stem cell markers in the epithelial clumps. RESULTS: Similar to the characteristics of UC, the ulcers were more severe in the distal region close to the anus than in the proximal region of the colorectum. Quantitative analyses revealed that the epithelial clumps appeared in relation to the severity of the ulcer, and they expressed the cell adhesion molecules E-cadherin and ß-catenin. Among stem cell markers, the epithelial clumps primarily expressed +5 cell marker Dll1 as reserved intestinal stem cells, followed by +4 cell marker Bmi1 and crypt stem cell marker Lgr5 in that order. Nuclear expression of Sox9, but not nuclear ß-catenin, was identified in the clumps. CONCLUSION: The present results suggest that most epithelial clumps comprised crypt-derived, reserved stem cells, which might have potential for mucosal healing.

Associations among drinking water quality, dyslipidemia, and cognitive function for older adults in China: evidence from CHARLS.

BACKGROUND: The current study aimed to examine the association between drinking water quality and cognitive function and to identify the direct and indirect effects of drinking water quality and dyslipidemia on cognitive function among older adults in China. METHODS: Primary data for the study were selected from China Health and Retirement Longitudinal Study (CHARLS, 2015) and 4,951 respondents aged 60 and above were included. Data on drinking water quality were selected from the 2015 prefectural water quality data from the Institute of Public and Environment Affairs in China and measured by the Blue City Water Quality Index. Dyslipidemia was measured by self-reported dyslipidemia diagnosis and lipid panel. Three composite measures of cognitive function included mental status, episodic memory, and global cognition. Mixed effects models were conducted to assess the associations between drinking water quality or dyslipidemia and cognitive function. The mediation effects of dyslipidemia were examined by path analyses. RESULTS: Exposure to high quality drinking water was significantly associated with higher scores in mental status, episodic memory, and global cognition (ß = 0.34, p < 0.001 for mental status; ß = 0.24, p < 0.05 for episodic memory; ß = 0.58, p < 0.01 for global cognition). Respondents who reported dyslipidemia diagnosis had higher scores in the three composite measures of cognitive function (ß = 0.39, p < 0.001 for mental status; ß = 0.27 p < 0.05 for episodic memory; ß = 0.66, p < 0.001 for global cognition). An elevated blood triglycerides was only associated with higher scores in mental status (ß = 0.21, p < 0.05). Self-reported dyslipidemia diagnosis was a suppressor, which increased the magnitude of the direct effect of drinking water quality on mental status, episodic memory, and global cognition. CONCLUSION: Drinking water quality was associated with cognitive function in older Chinese and the relationship was independent of natural or socioeconomic variations in neighborhood environments. Improving drinking water quality could be a potential public health effort to delay the onset of cognitive impairment and prevent the dementia pandemic in older people.

Taurine Alleviates LPS-Induced Acute Lung Injury by Suppressing TLR-4/NF-κB Pathway.

Taurine has the function of immune regulation, relieving acute and chronic inflammation caused by various agents, and maintaining cell homeostasis. This investigation focused on the protective functions of taurine targeting acute lung injury (ALI) induced by LPS. Sixty male SD rats aged 6-7 weeks were segregated at random: blank control group (C group), taurine control group (T group), ALI model group (LPS group), and taurine prevention groups (LPST1, LPST, LPST3 Groups). C group and LPS group were given normal drinking water, while T group and LPST group were given 2% taurine in drinking water. LPST1 group was given 1% taurine in drinking water while. LPST3 group was given 3% taurine in drinking water. On the 14th and 28th day, LPS group and LPST1, LPST, and LPST3 groups were subjected to injection of LPS (25 mg/kg) into the trachea of rats. Serum, peripheral blood, lung tissue, and bronchoalveolar lavage fluid (BALF) were collected at 6 h post-LPS injection. The wet/dry ratio (W/D) of lung was measured by hot drying method. The population of white blood cells and the abundance of inflammatory-related cells within peripheral blood were counted by an automatic blood cell analyzer. The population of white blood cells within BALF was counted by a white blood cell counting plate combined with Swiss Giemsa staining, while the proportion of related white blood cells was calculated. BCA reagent was used to determine the protein concentration in BALF. The levels of pro-inflammatory factors (IL-1 ß, IL-6, IL-18, TNF - α), anti-inflammation factors (IL-10, IL-4), and taurine within serum and lung tissue were detected by ELISA. Lung structural tissue alterations were observed through HE staining techniques. Myeloperoxidase (MPO) activities within lung tissue were detected through colorimetry. Protein expression levels of TLR4, MyD88, NF-κ Bp65, NF-κ Bp-p65, MCP-1, together with CD68 within lung tissue, were analyzed by Western blot (WB) and immunohistochemistry (IHC). The taurine pretreatment group contained significantly reduced W/D, MPO activity, and the number of inflammatory cells in BALF induced by LPS. In addition, compared with ALI model group, the taurine pretreatment group contained significantly reduced levels of pro-inflammatory factors in lung tissue, increased levels of anti-inflammatory factors, and decreased expression levels of key proteins in TLR-4/NF-κ B pathway. Taurine can protect rats from ALI by inhibiting the activation of neutrophils, macrophages, and TLR-4/NF-κ B signaling pathway.

Effect of ozone versus naringin on testicular injury in experimentally induced ulcerative colitis in adult male albino rats.

Testicular dysfunction is caused by the continuous inflammation and oxidative stress that are present at the local site in ulcerative colitis (UC) spreading to the testes via systemic circulation. The influence of ozone and naringine on colitis-mediated testicular dysfunction was investigated in this study. Forty-eight adult male rats were divided into four groups: I control group, II dextran sodium sulfate (DSS) UC-induced group, III DSS+naringine, and IV DSS+ozone groups. UC was induced in groups II, III, and IV using 0.1 ml of 4% DSS in their drinking water per day for 6 days by gastric gavage. All animals were sacrificed 45 days from the start. Blood samples were obtained to estimate serum testosterone hormone. Testicular tissues were processed for measurement of tissue malondialdehyde (MDA) and examined by light and electron microscopes. Ultrastructurally, group II revealed a relatively thick basement membrane enveloping the seminiferous tubule. Sertoli cell cytoplasm appears rarified with wide intracellular spaces, vacuoles, and multiple lysosomes; distorted spermatogonia with electron dense nuclei and cytoplasm; and primary spermatocytes with small nuclei and electron dense cytoplasm. Abnormal sperm profiles were visible in middle pieces, mid, principle, and end pieces that were markedly affected with disorganization of axoneme and outer dense fibers. Leydig cells revealed dilated cisternae of smooth endoplasmic reticulum. Morphometric and statistical analyses were performed. Group III showed some improvement; however, group IV showed more improvement. The results indicated that ozone caused marked improvement than naringine against UC-induced testicular damage via their antioxidant and anti-inflammatory properties.

[Interactive effect of chemical fertilizer exposure and drinking untreated water on the risk of birth defects].

OBJECTIVE: To explore the interactive effect of chemical fertilizer exposure and drinking untreated water during pregnancy on the risk of birth defects. METHODS: The data were collected from a population-based birth surveillance system in Pingding County, Shanxi Province, from 2007 to 2012. Totally, 157 cases of birth defects were followed up and 204 healthy newborns taken as controls. The additive model and relative excess risk of interaction (RERI) were used to evaluate the interactive effect of chemical fertilizer exposure and drinking untreated water during pregnancy on the risk of birth defects. RESULTS: After adjusted for potential confounding factors, mothers living in villages with ≥ 65 ton/year chemical fertilizer application and drinking untreated water, as from deep underground, cellars, mountain spring, rivers, lakes or ponds, showed a higher risk of birth defects than those living in villages with <65 ton/year chemical fertilizer application and drinking tap or purified water (aOR = 2.12, 95% CI: 1.11－4.07). A strengthened interaction was observed between the annual application of chemical fertilizer at the village level and drinking untreated water (RERI = 2.08, 95% CI: 0.23－3.92, P < 0.05). CONCLUSION: The pollution of drinking water may be an important pathway for chemical fertilizer exposure affecting birth outcomes.

Risk factors for esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional study.

BACKGROUND: Despite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions. METHODS: We performed an endoscopic examination of 44,857 individuals aged 40-69 years from five high incidence regions of China in 2017-2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors. RESULTS: We identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52-3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03-3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05-1.37) was essential risk factor of LGIN. CONCLUSIONS: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

Arsenic exposure from groundwater: environmental contamination, human health effects, and sustainable solutions.

Arsenic (As) occurs naturally in geologic conditions, but groundwater contamination might also be found due to the consequences of mining, agricultural and industrial processes. Human exposure to As after drinking contaminated water is commonly associated with acute toxicity outcomes and chronic effects ranging from skin lesions to cancer. Integrated actions from environmental and health authorities are needed to reduce exposure, monitoring outcomes, and promotion of actions to offer sustainable As-safe water alternatives. Considering recent research trends, the present review summarizes and discusses current issues associated with the process and effects of contamination and decontamination in an environmental health perspective. Recent findings reinforce the harmful effects of the consumption of As-contaminated water and broaden the scope of related diseases including intestinal maladies, type 2 diabetes, cancers of bladder, kidneys, lung, and liver. Among the main strategies to diminish or remove As from water, the following are highlighted (1) ion exchange system and membrane filtration (micro, ultra, and nanofiltration) as physicochemical treatment systems; (2) use of cyanobacteria and algae in bioremediation programs and (3) application of nanotechnology for water treatment.

Progress in the prevention and control of water-borne arsenicosis in China.

In this report, we provided an overview of the prevalence, control, and prevention of water-borne arsenicosis in China during 2001-2016. Random sampling was continuously performed during 2001-2010 to find villages having high levels of arsenic (>50 µg/L) in drinking water. The high-arsenic-exposure villages with more geographically dispersed water supplies were subsequently analyzed for characteristics of arsenic distribution, and villages with relatively large populations were investigated for arsenicosis. The results showed that among 32,673,677 inhabitants in 36,820 villages, 1,894,587 inhabitants in 2,476 villages were at risk of high arsenic exposure. Among the 33,318 drinking water sources surveyed in 625 high-arsenic-exposure villages, 9,807 drinking water sources that contained high levels of arsenic (>50 µg/L) were identified. The overall prevalence rate of arsenicosis was 1.93%. Further, some representative villages were chosen to monitor arsenicosis annually, showing that the prevalence rate of arsenicosis was lower in villages with arsenic-safe water supplies than in villages without arsenic-safe water supplies. To the best of our knowledge, this report provides the most comprehensive assessment of the distribution of high arsenic exposure and arsenicosis in China until now.

Ingested Nitrate and Nitrite and Bladder Cancer in Northern New England.

BACKGROUND: N-nitroso compounds are hypothesized human bladder carcinogens. We investigated ingestion of N-nitroso compound precursors nitrate and nitrite from drinking water and diet and bladder cancer in the New England Bladder Cancer Study. METHODS: Using historical nitrate measurements for public water supplies and measured and modeled values for private wells, as well as self-reported water intake, we estimated average nitrate concentrations (mg/L NO3-N) and average daily nitrate intake (mg/d) from 1970 to diagnosis/reference date (987 cases and 1,180 controls). We estimated overall and source-specific dietary nitrate and nitrite intakes using a food frequency questionnaire (1,037 cases and 1,225 controls). We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). We evaluated interactions with factors that may affect N-nitroso compound formation (i.e., red meat, vitamin C, smoking), and with water intake. RESULTS: Average drinking water nitrate concentration above the 95th percentile (>2.07 mg/L) compared with the lowest quartile (≤0.21 mg/L) was associated with bladder cancer (OR = 1.5, 95% CI = 0.97, 2.3; P trend = 0.01); the association was similar for average daily drinking water nitrate intake. We observed positive associations for dietary nitrate and nitrite intakes from processed meat (highest versus lowest quintile OR for nitrate = 1.4, 95% CI = 1.0, 2.0; P trend = 0.04; OR for nitrite = 1.5, 95% CI = 1.0, 2.1; P trend = 0.04, respectively), but not other dietary sources. We observed positive interactions between drinking water nitrate and red meat (P-interaction 0.05) and processed red meat (0.07). CONCLUSIONS: Our results suggest the importance of both drinking water and dietary nitrate sources as risk factors for bladder cancer.

Inorganic arsenic and its methylated metabolites as endocrine disruptors in the placenta: Mechanisms underpinning glucocorticoid receptor (GR) pathway perturbations.

Exposure to inorganic arsenic (iAs) is a significant public health concern with individuals around the globe exposed to harmful levels through contaminated drinking water. Exposure to iAs during pregnancy is of particular concern and has been associated with pregnancy complications and adverse child health later in life. Effects of in utero exposure may be mediated through alterations in key signaling pathways in the placenta that regulate fetal growth and development. A pathway of interest is the glucocorticoid receptor (GR)- signaling pathway, which is known to regulate fetal and placental development. While prior research has shown that iAs alters GR-associated gene expression in trophoblasts, the mechanisms that underlie these perturbations remain unknown. In the present study, we set out to elucidate the molecular mechanisms that underpin observed alterations in GR-associated gene expression. We also aimed to determine whether the methylated metabolites of iAs, namely monomethyl­arsenic (MMA) and dimethyl­arsenic (DMA), also influence GR-associated signaling in the placenta. The data indicate that iAs alters GR activation in a dose-dependent manner, reduces nuclear translocation, and reduces DNA binding. Additionally, the results demonstrate that MMA and DMA alter the expression of eight GR-associated genes, modulate GR activation, and alter DNA binding. These data are significant as they highlight the role of iAs as an endocrine disruptor and for the first time explore the effects of MMA and DMA on endocrine signaling in the placenta.

'Evidence for waterborne origin of an extended mixed gastroenteritis outbreak in a town in Northern Greece, 2019'.

We investigated a large gastroenteritis outbreak that occurred in Northern Greece in 2019. A case was defined as anyone presenting with diarrhoea and/or vomiting from 24 January 2019 to 04 February 2019. We conducted a case-control study (CCS) using random selection of participants >16 years of age, residents of town X, who visited the health care centre between 25 and 28 January 2019. Moreover, we conducted a retrospective cohort study (CS) at the four elementary schools of the town. We collected clinical and water samples and the water supply system was inspected. In total, we recorded 638 cases (53% female; median age was 44 years (range 0-93)). Forty-eight cases and 52 controls participated in the CCS and 236 students in the CS. Both CCS and CS indicated tap water as the most likely source (OR 10, 95% CI 2.09-93.4, explaining 95.7% of cases; RR = 2.22, 95% CI 1.42-3.46, respectively). More than one pathogen was detected from stool samples of 6 of the 11 cases tested (norovirus, Campylobacter jejuni, Enterohemorrhagic E. coli (EHEC) and Enteropathogenic E. coli (EPEC)). Water samples, collected after ad-hoc chlorination, tested negative. Technical failures of the water tanks' status were identified. Our results suggested a waterborne outbreak. We recommended regular monitoring of the water supply system and immediate repair of technical failures.