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.

[Distribution Characteristics of Arsenic in Drinking Water in China and Its Health Risk Based on Disability-adjusted Life Years].

Long-term exposure to arsenic can lead to functional damage to many organs and can be life-threatening. It is of great significance to analyze the distribution characteristics of arsenic in water and evaluate its potential risk for preventing and controlling human health hazards caused by water-derived arsenic. Based on the published data from 2000 to 2022, the geographical distribution characteristics of arsenic in drinking water across China were systematically analyzed in detail, and the health risk of arsenic in drinking water was quantitatively assessed using disability-adjusted life years (DALYs), which represent the burden of disease. The results showed that the average concentration of arsenic in drinking water in China was (2.88 ±0.33) µg·L-1, which was lower than the limit of 10 µg·L-1 set by the standard for drinking water quality (GB 5749-2022). Nevertheless, the arsenic in drinking water in some provinces, including Shanxi, Inner Mongolia, and Ningxia, was still higher than the limit. The arsenic concentration in drinking water in northern China was higher than that in southern China, and that in rural areas was higher than that in cities. The estimated health risk of arsenic in drinking water (1.63×10-6 DALYs per person-year) was higher than the acceptable risk level of waterborne exposure of 1.0×10-6 DALYs per person-year set by the World Health Organization. The personal health risks related to arsenic in drinking water in the six geographical regions were ranked as follows:North China > Northeast China > Central South China > Northwest China > Southwest China > East China. Almost all (99.4%) of the health burden associated with water arsenic was attributable to skin and lung cancer, which caused 2 905.25 and 1 513.96 DALYs per year, respectively. Most (78.0%) of the health burden was borne by people aged 45 years or older. In addition, given the proportion of each age group in the total population, older persons over the age of 60 bear a higher drinking-water-associated arsenic burden at the individual level than others, and attention should be consequently paid to them when controlling the risk of arsenic in water.

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.

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 Arsenic Toxicity, AS3MT Gene Polymorphism and Onset of Type 2 Diabetes.

Arsenic (As) exposure in drinking water has become a serious public health issue. AS3MT gene is involved in the metabolism of arsenic, so a single nucleotide polymorphism in this gene may lead to the development of type 2 diabetes in arsenic-exposed areas. This study aimed to evaluate the association of the AS3MT gene with the development of type 2 diabetes in highly arsenic-exposed areas of Punjab, Pakistan. Total 200 samples equal in number from high arsenic exposed-areas of Lahore (Nishtar) and Kasur (Mustafa Abad) were collected. rs11191439 was utilized as an influential variable to evaluate the association between arsenic metabolism and diabetes status to find a single nucleotide polymorphism in the AS3MT gene. We observed the arsenic level in drinking water of the arsenic-exposed selected areas 115.54 ± 1.23 µg/L and 96.88 ± 0.48 µg/L, respectively. The As level in the urine of diabetics (98.54 ± 2.63 µg/L and 56.38 ± 12.66 µg/L) was higher as compared to non-diabetics (77.58 ± 1.8 µg/L and 46.9 ± 8.95 µg/L) of both affected areas, respectively. Correspondingly, the As level in the blood of diabetics (6.48 ± 0.08 µg/L and 5.49 ± 1.43 µg/L) and non-diabetics (6.22 ± 0.12 µg/L and 5.26 ± 0.24 µg/L) in the affected areas. Genotyping showed significant differences in the frequencies of alleles among cases and controls. Nevertheless, notable disparities in genotype distribution were observed in SNPs rs11191439 (T/C) (P < 0.05) and when comparing T2D patients and non-diabetic control subjects. The AS3MT gene and clinical parameters show a significant association with the affected people with diabetes living in arsenic-exposed areas.

Prediction of human health risk and disability-adjusted life years induced by heavy metals exposure through drinking water in Fars Province, Iran.

Exposure to heavy metals in contaminated drinking water is strongly correlated with various cancers, highlighting the burden of disease. This study aimed to assess the non-carcinogenic and carcinogenic risks associated with exposure to heavy metals (As, Pb, Cd, and Cr) in drinking water of Fars province and evaluate the attributed burden of disease. Non-carcinogenic risk assessment was performed using the hazard quotient (HQ) method, while the carcinogenic risk assessment utilized the excess lifetime cancer risk approach. The burden of disease was evaluated in terms of years of life lost, years lived with disability, and disability-adjusted life years (DALY) for three specific cancers: skin, lung, and kidney cancer. The average drinking water concentrations of arsenic (As), cadmium (Cd), chromium (Cr) and lead (Pb) were determined to be 0.72, 0.4, 1.10 and 0.72 µg/L, respectively. The total average HQ of heavy metals in drinking water in the study area were 0.127, 0.0047, 0.0009 and 0.0069, respectively. The average ILCRs of heavy metal in the entire country were in the following order: 1.15 × 10-5 for As, 2.22 × 10-7 for Cd and 3.41 × 10-7 for Cr. The results also indicated that among the various counties analyzed, Fasa experiences the greatest burden of disease in terms of DALYs, with a value of 87.56, specifically attributed to cancers caused by exposure to arsenic. Generally, it can be said that the burden of disease is a critical aspect of public health that requires comprehensive understanding and effective intervention.

Fluoride Exposure and Skeletal Fluorosis: a Systematic Review and Dose-response Meta-analysis.

PURPOSE OF REVIEW: We performed a systematic review and meta-analysis on the relation between fluoride exposure and skeletal fluorosis (SF) using a novel statistical methodology for dose-response modeling. RECENT FINDINGS: Skeletal fluorosis, a major health issue that is endemic in some regions, affects millions of people worldwide. However, data regarding the dose-response relation between fluoride exposure and SF are limited and outdated. We included twenty-three studies in the meta-analysis. When comparing the highest versus the lowest fluoride category, the summary risk ratio (RR) for SF prevalence was 2.05 (95% CI 1.60; 2.64), with a value of 2.73 (95% CI 1.92; 3.90) for drinking water and 1.40 (95% CI 0.90; 2.17) for urinary fluoride. The RR by the risk of bias (RoB) was 2.37 (95% CI 1.56; 3.58) and 1.78 (95% CI 1.34; 2.36) for moderate and high RoB studies, respectively. The dose-response curve based on a one-stage cubic spline regression model showed an almost linear positive relation between exposure and SF occurrence starting from relatively low concentrations up to 5 mg/L and 2.5 mg/L, respectively, for water and urinary fluoride, with no substantial increase above this threshold. The RR for developing moderate-severe forms increases at 5.00 mg/L and 2.5 mg/L of water and urinary fluoride, respectively. Better-quality studies are needed to confirm these results, but greater attention should be given to water fluoride levels to prevent SF, in addition to the other potential adverse effects of fluoride exposure.

Association between fluoride exposure in drinking water and cognitive deficits in children: A pilot study.

Fluoride (F) exposure in drinking water may lead to reduced cognitive function among children; however, findings largely remain inconclusive. In this pilot study, we examined associations between a range of chronic F exposures (low to high: 0.4 to 15.5 mg/L) in drinking water and cognition in school-aged children (5-14 years, n = 74) in rural Ethiopia. Fluoride exposure was determined from samples of community-based drinking water wells and urine. Cognitive performance was measured using: 1) assessments of ability to draw familiar objects (donkey, house, and person), and 2) a validated Cambridge Neuropsychological Test Automated Battery's (CANTAB) Paired Associate Learning (PAL), which examines memory and new learning and is closely associated with hippocampus function of the brain. Associations between F and cognitive outcomes were evaluated using regression analysis, adjusting for demographic, health status, and other covariates. The median (range) of water and urine F levels was 7.6 (0.4-15.5 mg/L) and 6.3 (0.5-15.7 mg/L), respectively; these measures were strongly correlated (r = 0.74), indicating that water is the primary source of F exposure. Fluoride in drinking water was negatively associated with cognitive function, measured by both drawing and CANTAB test performance. Inverse relationships were also found between F and drawing objects task scores, after adjusting for covariates (p < 0.05). Further analysis using CANTAB PAL tasks in the children confirmed that F level in drinking water was positively associated with the number of errors made by children (p < 0.01), also after adjusting for covariates (p < 0.05). This association between water F and total errors made became markedly stronger as PAL task difficulty increased. Fluoride exposure was also inversely associated with other PAL tasksthe number of patterns reached, first attempt memory score and mean errors to success. These findings provide supportive evidence that high F exposures may be associated with cognitive deficits in children. Additional well-designed studies are critically needed to establish the neurotoxicity of F in children and adults exposed to both low levels known to protect dental caries, as well as excess F levels in drinking water.

Disinfection by-products in drinking water and risk of colorectal cancer: a population-based cohort study.

BACKGROUND: Colorectal cancer is the third most common malignancy worldwide and is strongly linked to lifestyle and environmental risk factors. Although several drinking-water disinfection by-products are confirmed rodent carcinogens, the evidence in humans for carcinogenicity associated with these by-products, including colorectal cancer, is still inconclusive. METHODS: We assessed the association of long-term exposure to trihalomethanes (THMs), the most prevalent disinfection by-products in chlorinated drinking water, with incidence of colorectal cancer in 58 672 men and women in 2 population-based cohorts. Exposure was assessed by combining long-term information of residential history with drinking water-monitoring data. Participants were categorized according to no exposure, low exposure (<15 µg/L), and high exposure (≥15 µg/L). Incident cases of colorectal cancer were ascertained by use of the Swedish National Cancer Register. RESULTS: During an average follow-up of 16.8 years (988 144 person-years), 1913 cases of colorectal cancer were ascertained (1176 cases in men and 746 in women, respectively). High THM concentrations in drinking water (≥15 µg/L) were associated with increased risk of colorectal cancer in men (hazard ratio = 1.26, 95% confidence interval = 1.05-1.51) compared with no exposure. When subsites were assessed, the association was statistically significant for proximal colon cancer (hazard ratio = 1.59, 95% confidence interval = 1.11 to 2.27) but not for distal colon cancer or rectal cancer. In women, we observed overall no association of THMs with colorectal cancer. CONCLUSION: These results add further evidence that disinfection by-products in drinking water may be a possible risk factor for proximal colon cancer in men. This observation was made at THM concentrations lower than those in most previous studies.

An updated systematic review and dose-response meta-analysis on the relation between exposure to arsenic and risk of type 2 diabetes.

Arsenic is among the most critical environmental toxicants associated with many human disorders. However, its effect on type 2 diabetes mellitus (T2DM) is contradictory. This systematic review and dose-response meta-analysis aim to update information on the association between arsenic exposure and the risk of T2DM. The sample type (drinking water, urine, blood, and nails) conducted the subgroup analysis. Evaluation of the high vs. low arsenic concentrations showed a significant association between drinking water arsenic (OR: 1.58, 95% CI: 1.20-2.08) and urinary arsenic (OR: 1.37, 95% CI: 1.24-1.51) with the risk of T2DM. The linear dose-response meta-analysis showed that each 1 µg/L increase in levels of drinking water arsenic (OR: 1.01, 95% CI: 1.00-1.01) and urinary arsenic (OR: 1.01, 95% CI: 1.00-1.02) was associated with a 1% increased risk of T2DM. The non-linear dose-response analysis indicated that arsenic in urine was associated with the risk of T2DM (Pnon-linearity<0.001). However, this effect was not statistically significant for arsenic in drinking water (Pnon-linearity=0.941). Our findings suggest that blood arsenic was not significantly linked to the increased risk of T2DM in high vs. low (OR: 1.21, 95% CI: 0.85-1.71), linear (OR: 1.04, 95% CI: 0.99-1.09), and non-linear (Pnon-linearity=0.365) analysis. Also, nail arsenic was not associated with the risk of T2DM in this meta-analysis (OR: 1.33, 95% CI: 0.69-2.59). This updated dose-response meta-analysis indicated that arsenic exposure was significantly correlated with the risk of T2DM.

Nanocrystal-induced chronic tubular-nephropathy in tropical countries: diagnosis, mitigation, and eradication.

In tropical countries, a mysterious tubulo-interstitial chronic renal disease (CKD), unrelated to diabetes, hypertension, and immunological causes, manifested four decades ago. Approximately 25,000 primarily middle-aged male farmers succumb annually to this crystal-tubular nephropathy (CTN). Without any known causative factors, it was identified as CKD of unknown aetiology (CKDu). Because multiple factors contribute to causing it later, was changed to CKD of multi-factorial (CKDmfo). Despite no evidence, it was hypothesised to cause by agrochemicals or heavy metals in food or drinking contaminated water. However, current data suggest that the CKD-CTN is due to natural geogenic water contamination. Consumption of concentrated stagnant groundwater from deep-dug wells and tube wells containing hard water and fluoride, overdecades is necessary for its clinical manifestations. In all affected countries have prolonged annual dry seasons that led to the evopo-concentration of ions and minerals in groundwater, making hard water even more unpalatable, thus, peasants consume lesser amounts of water. They develop chronic dehydration from daily exposure to hot climatic conditions aggravated by regular alcohol intake. These conditions provide a highly conducive environment-a perfect storm for calcium phosphate (CaPO4) crystal formation in renal tissues. Our recent histological and preliminary electron microscopic data reveal deposition of CaPO4 crystals and nano-tubes in kidneys. While CaPO4 nano-minerals are unstable, the presence of fluoride ions stabilises and allows their growth. This new concept paves the path for highly cost-effective, straightforward local solutions to protect farm workers and eliminate the disease, without embarking on expensive medications, interventions, or building hospitals. Chronic dehydration-associated CKD-CTN is preventable by increased consumption of potable water. Increasing clean water consumption reduces CKD-CTN incidence, and associated morbidities and premature deaths. However, the damage becomes irreversible when the disease advances beyond CKD stage IIIB. The incidence of this deadly renal failure can be prevented by its education, lifestyle changes, and increased water consumption, not by treating the renal disease or expanding dialysis centres/hospitals, or transplantation services. Eradication of CKD-CTN cost significantly less than the current approach of treating affected persons and unnecessarily expanding health infrastructure. Since the manifestation of CKD-CTN is due to consuming naturally contaminated drinking water (with calcium containing hard water and fluoride), it is not difficult to remove these to prevent CKD-CTN: thus, international assistance is unwarranted for its eradication. The straightforward approaches described here will prevent CKD-CTN and save thousands of lives in affected farming communities.

Prenatal Exposure to Nitrate in Drinking Water and Adverse Health Outcomes in the Offspring: a Review of Current Epidemiological Research.

PURPOSE OF REVIEW: Recently, several epidemiological studies have investigated whether prenatal exposure to nitrate from drinking water may be harmful to the fetus, even at nitrate levels below the current World Health Organization drinking water standard. The purpose of this review was to give an overview of the newest knowledge on potential health effects of prenatal exposure to nitrate. RECENT FINDINGS: We included 13 epidemiological studies conducted since 2017. Nine studies investigated outcomes appearing around birth, and four studies investigated health outcomes appearing in childhood and young adulthood. The reviewed studies showed some indications of higher risk of preterm delivery, lower birth weight, birth defects, and childhood cancer related to prenatal exposure to nitrate. However, the numbers of studies for each outcome were sparse, and some of the results were conflicting. We suggest that there is a need for additional studies and particularly for studies that include information on water consumption patterns, intake of nitrate from diet, and intake of nitrosatable drugs.

Association of obesity, diabetes, and hypertension with arsenic in drinking water in the Comarca Lagunera province (north-central Mexico).

Chronic endemic regional hydroarsenicism (CERHA) is a global issue that affects over 200 million people exposed to arsenic (As) in drinking water. This includes 1.75 million individuals residing in La Comarca Lagunera, a region in north-central Mexico. Arsenic levels in this region typically exceeds the WHO guideline of 10 µg L-1. Biochemical alterations related to the human As metabolism may increase the risk of overweight and obesity (O&O), type 2 diabetes (T2D), and hypertension (AHT). In our study, we investigated the role of As in drinking water as a risk factor for these metabolic diseases. We focused on populations with historically moderate (San Pedro) and low (Lerdo) drinking water As levels and people with no historical evidence of As water contamination. The exposure assessment to As was based on measurements of the drinking water (medians 67.2, 21.0, 4.3 µg L-1) and urinary As concentrations in women (9.4, 5.3, 0.8 µg L-1) and men (18.1, 4.8, 1.0 µg L-1). A significant correlation between As in drinking water and urine evidenced the As exposure in the population (R2 = 0.72). Adjusted odds ratios with 95% confidence intervals evidenced higher chances of being diagnosed with T2D (1.7, 1.2-2.0) and AHT (1.8, 1.7-1.9) in individuals living in San Pedro than those in Lerdo. Still, there was no significant association with obesity. Individuals living in CERHA towns were found to have a higher risk of obesity (1.3-1.9), T2D (1.5 to 3.3), and AHT (1.4 to 2.4) compared to those residing in non-CERHA towns. Finally, obesity is more probable in women [inverse of OR and 95%CI 0.4 (0.2-0.7)] compared to men, while men is more likely to be diagnosed with T2D [OR = 2.0 (1.4-2.3)] and AHT [OR = 2.0 (1.5-2.3)] than women, independently of the municipality.

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.

Large Study Links Industrial Solvent in Drinking Water to Parkinson Disease Risk in Camp Lejeune Veterans.

This Medical News story discusses a new study in JAMA Neurology that links exposure to contaminated drinking water at Marine Corps Base Camp Lejeune to an increased risk of Parkinson disease.

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.

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.

Prenatal exposure to tap water containing nitrate and the risk of small-for-gestational-age: A nationwide register-based study of Danish births, 1991-2015.

BACKGROUND: Prenatal nitrate exposure from household tap water has been associated with increased risk of fetal growth restriction, preterm birth, birth defects, and childhood cancer. We aim to examine the association between maternal consumption of drinking-water nitrate during pregnancy and small-for-gestational-age (SGA) in a nationwide study of Danish-born children, as only one prior study has examined this association. METHODS: We linked individual-level household estimates of nitrate in tap water and birth registry data to all live singleton Danish births during 1991-2015 from Danish-born parents where the mother resided in Denmark throughout the pregnancy. Exposure was both binned into four categories and modeled as an ln-transformed continuous variable. SGA was defined as the bottom 10% of births by birth weight per sex and gestational week. Multiple logistic regression models with generalized estimating equations were used to account for siblings born to the same mother while controlling for relevant confounders. RESULTS: In the cohort of 1,078,892 births, the median pregnancy nitrate exposure was 1.9 mg/L nitrate. Compared to the reference group (≤2 mg/L), we found an increased risk of SGA in the second category (>2-5 mg/L) (OR = 1.04, 95% CI: 1.03-1.06) and third category (>5-25 mg/L) (OR = 1.02, 95% CI: 1.00-1.04) but not in the highest (>25 mg/L). There was strong (p = 0.002) evidence of an increase in SGA with nitrate in the model with continuous exposure (OR = 1.02, 95% CI: 1.01-1.04 per 10-fold increase in nitrate). Results were robust when restricting to households with nitrate levels at or below the current Danish and European Union regulatory drinking water standard (50 mg/L nitrate). CONCLUSIONS: Our findings suggest that exposure from nitrate in household tap water, even below current regulatory standards, may increase risk of SGA, raising concerns of whether current allowable nitrate levels in drinking water protect children from SGA.

Evaluation of the effect of tramadol, paracetamol and metamizole on the severity of experimental colitis.

Application of dextran sodium sulfate (DSS) is often used to induce experimental colitis. Current state of the art is to refrain from the use of analgesics due to their possible interaction with the model. However, the use of analgesics would be beneficial to reduce the overall constraint imposed on the animals. Here, we analyzed the effect of the analgesics Dafalgan (paracetamol), Tramal (tramadol) and Novalgin (metamizole) on DSS-induced colitis. To study the effect of those analgesics in colitis mouse models, acute and chronic colitis was induced in female C57BL6 mice by DSS administration in the drinking water. Analgesics were added to the drinking water on days four to seven (acute colitis) or on days six to nine of each DSS cycle (chronic colitis). Tramadol and paracetamol had minor effects on colitis severity. Tramadol reduced water uptake and activity levels slightly, while mice receiving paracetamol presented with a better overall appearance. Metamizole, however, significantly reduced water uptake, resulting in pronounced weight loss. In conclusion, our experiments show that tramadol and paracetamol are viable options for the use in DSS-induced colitis models. However, paracetamol seems to be slightly more favorable since it promoted the overall wellbeing of the animals upon DSS administration without interfering with typical readouts of colitis severity.