Biomarkers of Exposure: Arsenic Concentrations in Keratin in Populations Exposed to Arsenic in Drinking Water

<p>Arsenic (As) exposure via groundwater consumption is a global health problem affecting millions. Monitoring exposure is a key step in understanding and predicating future health outcomes. This thesis explores the relationships between arsenic concentrations in toenails and arsenic in water. Three case studies were investigated, with residents from: North Carolina, USA (n=103); the Rift Valley, Ethiopia (n=60); and the Mekong Delta, Vietnam (n=65). Arsenic concentrations above the WHO's recommended 10ppb limit were found in groundwater from the three research sites. </p><p>Arsenic in toenails was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). </p><p>In the Rift Valley of Ethiopia, 53% of the tested drinking wells (n=34) had As above the WHO's limit. Arsenic concentrations in toenails (n=60) were significantly correlated to As concentrations in groundwater (r=0.72; p<0.001), reflecting the direct exposure of rural communities to As in well water, which is their principle water source. Male minors (<18 years old) were found to have greater nail-As concentrations compared with adults consuming equal amounts of As (p<0.05). Estimated As dose specifically from drinking water sources was also associated with nail concentrations (p<0.01). </p><p>In the Mekong Delta of Vietnam (Dong Thap Province), 36 out of the 68 tested wells had As content above the WHO's recommended limit of 10ppb, with levels as high as 981 ppb. Arsenic contents in nails collected from local residents (n=62) were significantly correlated to As in drinking water (r=0.49, p<0.001). Demographic and survey data show that the ratio of As in nail to As in water varies among residents that reflects differential As accumulation in the exposed population. The data show that water filtration and diet, particularly increased consumption of animal protein and dairy and reduced consumption of seafood, were associated with lower ratios of As in nail to As in water and thus could play important roles in mitigating As exposure.</p><p>Sixty-one wells were tested from Union County, North Carolina, with 15 out of 61 wells exceeded the WHO's 10 ppb limit. Arsenic values ranged from below the limit of detection (0.07) to 130ppb, with a mean of 11ppb (median=1.5ppb). Nails were collected from county residents (n=103) and were statistically correlated with As-water concentrations (r=0.48, p<0.001). </p><p>Integration of the data from the three cases studies across different populations and ethnicities show high correlation between As concentrations in groundwater and As in nails in all the three locations (r(Union County)= 0.48, p<0.001; r(Ethiopia)=0.72 p<0.001; r(Vietnam)=0.49, p<0.001). For As-nail to As-water pairs in which As in water was above 1ppb, these three locations are statistically indistinguishable from one another (r=0.62, p<0.001, n=176). These results support the hypothesis that nails can be used as a biomarker of exposure regardless of geographic or ethnic differences in populations considered. Nutrition (meat, seafood, and milk consumption) rather than gender, ethnicity, or dose is suggested to be the major confounding issue affecting the magnitude of As exposure in the human body.</p>Dissertatio

Groundwater Quality and Its Health Impact: An Assessment of Dental Fluorosis in Rural Inhabitants of the Main Ethiopian Rift

This study aims to assess the link between fluoride content in groundwater and its impact on dental health in rural communities of the Ethiopian Rift. A total of 148 water samples were collected from two drainage basins within the Main Ethiopian Rift (MER). In the Ziway-Shala basin in particular, wells had high fluoride levels (mean: 9.4 ± 10.5 mg/L; range: 1.1 to 68 mg/L), with 48 of 50 exceeding the WHO drinking water guideline limit of 1.5 mg/L. Total average daily intake of fluoride from drinking groundwater (calculated per weight unit) was also found to be six times higher than the No-Observed-Adverse-Effects-Level (NOAEL) value of 0.06 mg/kg/day. The highest fluoride levels were found in highly alkaline (pH of 7 to 8.9) groundwater characterized by high salinity; high concentrations of sodium (Na+), bicarbonate (HCO3−), and silica (SiO2); and low concentrations of calcium (Ca2+). A progressive Ca2+ decrease along the groundwater flow path is associated with an increase of fluoride in the groundwater. The groundwater quality problem is also coupled with the presence of other toxic elements, such as arsenic (As) and uranium (U). The health impact of fluoride was evaluated based on clinical examination of dental fluorosis (DF) among local residents using the Thylstrup and Fejerskov index (TFI). In total, 200 rural inhabitants between the ages of 7 and 40 years old using water from 12 wells of fluoride range of 7.8–18 mg/L were examined. Signs of DF (TF score of ≥ 1) were observed in all individuals. Most of the teeth (52%) recorded TF scores of 5 and 6, followed by TF scores of 3 and 4 (30%), and 8.4% had TF scores of 7 or higher. Sixty percent of the teeth exhibited loss of the outermost enamel. Within the range of fluoride contents, we did not find any correlation between fluoride content and DF. Finally, preliminary data suggest that milk intake has contributed to reducing the severity of DF. The study highlights the apparent positive role of milk on DF and emphasizes the importance of nutrition in management efforts to mitigate DF in the MER and other parts of the world

The Effect of Non-fluoride Factors on Risk of Dental Fluorosis: Evidence from Rural Populations of the Main Ethiopian Rift

Elevated level of fluoride (F−) in drinking water is a well-recognized risk factor of dental fluorosis (DF). While considering optimization of region-specific standards for F−, it is reasonable, however, to consider how local diet, water sourcing practices, and non-F− elements in water may be related to health outcomes. In this study, we hypothesized that non-F− elements in groundwater and lifestyle and demographic characteristics may be independent predictors or modifiers of the effects of F− on teeth. Dental examinations were conducted among 1094 inhabitants from 399 randomly selected households of 20 rural communities of the Ziway-Shala lake basin of the Main Ethiopian Rift. DF severity was evaluated using the Thylstrup-Fejerskov Index (TFI). Household surveys were performed and water samples were collected from community water sources. To consider interrelations between the teeth within individual (in terms of DF severity) and between F− and non-F− elements in groundwater, the statistical methods of regression analysis, mixed models, and principal component analysis were used. About 90% of study participants consumed water from wells with F− levels above the WHO recommended standard of 1.5 mg/l. More than 62% of the study population had DF. F− levels were a major factor associated with DF. Age, sex, and milk consumption (both cow’s and breastfed) were also statistically significantly (p \u3c 0.05) associated with DF severity; these associations appear both independently and as modifiers of those identified between F− concentration and DF severity. Among 35 examined elements in groundwater, Ca, Al, Cu, and Rb were found to be significantly correlated with dental health outcomes among the residents exposed to water with excessive F− concentrations. Quantitative estimates obtained in our study can be used to explore new water treatment strategies, water safety and quality regulations, and lifestyle recommendations which may be more appropriate for this highly populated region

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Arsenic exposure from groundwater in Union County, North Carolina

Arsenic contamination of groundwater is a global problem affecting human health. The highest concentrations occur overseas in areas such as Bangladesh, India, Vietnam, and Thailand. The United States is not immune and also has hotspots of arsenic in dangerously high concentrations. The focus of this project was to evaluate the extent and concentration of arsenic in one such area, Union County, North Carolina, and to attempt to use arsenic in toenails as a biomarker of exposure. Arsenic concentration above the EPA’s maximum contaminant level (MCL) of 10ppb was found in 22 out of 64 households tested (34%). The measurement of arsenic in toenails was successfully used as a biomarker of exposure. Data showed that men had a greater sensitivity to arsenic and their nail data had better correlation. Children also showed a greater sensitivity. Out of 69 participants in the toenail-biomarker study, 4 had arsenic concentrations in their toenails above a level deemed safe. Based on these results it is evident that arsenic contamination of drinking water in Union County is an issue of concern

Groundwater Quality and Its Health Impact: An Assessment of Dental Fluorosis in Rural Inhabitants of the Main Ethiopian Rift

This study aims to assess the link between fluoride content in groundwater and its impact on dental health in rural communities of the Ethiopian Rift. A total of 148 water samples were collected from two drainage basins within the Main Ethiopian Rift (MER). In the Ziway-Shala basin in particular, wells had high fluoride levels (mean: 9.4 ± 10.5 mg/L; range: 1.1 to 68 mg/L), with 48 of 50 exceeding the WHO drinking water guideline limit of 1.5 mg/L. Total average daily intake of fluoride from drinking groundwater (calculated per weight unit) was also found to be six times higher than the No-Observed-Adverse-Effects-Level (NOAEL) value of 0.06 mg/kg/day. The highest fluoride levels were found in highly alkaline (pH of 7 to 8.9) groundwater characterized by high salinity; high concentrations of sodium (Na+), bicarbonate (HCO3−), and silica (SiO2); and low concentrations of calcium (Ca2+). A progressive Ca2+ decrease along the groundwater flow path is associated with an increase of fluoride in the groundwater. The groundwater quality problem is also coupled with the presence of other toxic elements, such as arsenic (As) and uranium (U). The health impact of fluoride was evaluated based on clinical examination of dental fluorosis (DF) among local residents using the Thylstrup and Fejerskov index (TFI). In total, 200 rural inhabitants between the ages of 7 and 40 years old using water from 12 wells of fluoride range of 7.8–18 mg/L were examined. Signs of DF (TF score of ≥ 1) were observed in all individuals. Most of the teeth (52%) recorded TF scores of 5 and 6, followed by TF scores of 3 and 4 (30%), and 8.4% had TF scores of 7 or higher. Sixty percent of the teeth exhibited loss of the outermost enamel. Within the range of fluoride contents, we did not find any correlation between fluoride content and DF. Finally, preliminary data suggest that milk intake has contributed to reducing the severity of DF. The study highlights the apparent positive role of milk on DF and emphasizes the importance of nutrition in management efforts to mitigate DF in the MER and other parts of the world

Psoriasis and Cardiovascular Disease: Novel Mechanisms and Evolving Therapeutics

Purpose of Review: Psoriasis is a chronic inflammatory skin condition that is associated with increased cardiovascular risk compared to those without psoriasis. This review will cover emerging mechanisms of cardiovascular risk, key pathways targeted with biologic therapies, and the current evidence on therapies to modulate this risk in patients with psoriasis. Recent Findings: Recent scientific work has highlighted mechanisms that contribute to this enhanced risk, including the role of vascular endothelial dysfunction, platelet activation, dyslipidemia, and increased cardiometabolic comorbidities. Newer biologic and targeted synthetic therapies have transformed psoriasis treatment with high rates of clinical remission and durable skin disease control now possible. Epidemiological evidence suggests that many of these therapies may lower cardiovascular risk in psoriasis, although prospective interventional data is lacking (or mixed). Recently, caution has also been raised that some treatments may negatively affect cardiovascular risk. Summary: Overall, the current data suggests a positive or neutral ability to reduce cardiovascular risk for TNF, IL-17A, and IL-12/23p40 inhibitors, but current evidence remains conflicting for anti-IL-23/p19 and JAK inhibitors. More studies that include prospective cohorts, larger number of patients, treatment duration, and validated surrogate outcomes are needed to better evaluate the role of biologic therapies on cardiovascular risk in psoriasis

Isotopic Imprints of Mountaintop Mining Contaminants

Mountaintop mining (MTM) is the primary procedure for surface coal exploration within the central Appalachian region of the eastern United States, and it is known to contaminate streams in local watersheds. In this study, we measured the chemical and isotopic compositions of water samples from MTM-impacted tributaries and streams in the Mud River watershed in West Virginia. We systematically document the isotopic compositions of three major constituents: sulfur isotopes in sulfate (δ³⁴S_SO4), carbon isotopes in dissolved inorganic carbon (δ¹³C_DIC), and strontium isotopes (⁸⁷Sr/⁸⁶Sr). The data show that δ³⁴S_SO4, δ¹³C_DIC, Sr/Ca, and ⁸⁷Sr/⁸⁶Sr measured in saline- and selenium-rich MTM impacted tributaries are distinguishable from those of the surface water upstream of mining impacts. These tracers can therefore be used to delineate and quantify the impact of MTM in watersheds. High Sr/Ca and low ⁸⁷Sr/⁸⁶Sr characterize tributaries that originated from active MTM areas, while tributaries from reclaimed MTM areas had low Sr/Ca and high ⁸⁷Sr/⁸⁶Sr. Leaching experiments of rocks from the watershed show that pyrite oxidation and carbonate dissolution control the solute chemistry with distinct ⁸⁷Sr/⁸⁶Sr ratios characterizing different rock sources. We propose that MTM operations that access the deeper Kanawha Formation generate residual mined rocks in valley fills from which effluents with distinctive ⁸⁷Sr/⁸⁶Sr and Sr/Ca imprints affect the quality of the Appalachian watersheds

Isotopic Imprints of Mountaintop Mining Contaminants

Mountaintop mining (MTM) is the primary procedure for surface coal exploration within the central Appalachian region of the eastern United States, and it is known to contaminate streams in local watersheds. In this study, we measured the chemical and isotopic compositions of water samples from MTM-impacted tributaries and streams in the Mud River watershed in West Virginia. We systematically document the isotopic compositions of three major constituents: sulfur isotopes in sulfate (δ³⁴S_SO4), carbon isotopes in dissolved inorganic carbon (δ¹³C_DIC), and strontium isotopes (⁸⁷Sr/⁸⁶Sr). The data show that δ³⁴S_SO4, δ¹³C_DIC, Sr/Ca, and ⁸⁷Sr/⁸⁶Sr measured in saline- and selenium-rich MTM impacted tributaries are distinguishable from those of the surface water upstream of mining impacts. These tracers can therefore be used to delineate and quantify the impact of MTM in watersheds. High Sr/Ca and low ⁸⁷Sr/⁸⁶Sr characterize tributaries that originated from active MTM areas, while tributaries from reclaimed MTM areas had low Sr/Ca and high ⁸⁷Sr/⁸⁶Sr. Leaching experiments of rocks from the watershed show that pyrite oxidation and carbonate dissolution control the solute chemistry with distinct ⁸⁷Sr/⁸⁶Sr ratios characterizing different rock sources. We propose that MTM operations that access the deeper Kanawha Formation generate residual mined rocks in valley fills from which effluents with distinctive ⁸⁷Sr/⁸⁶Sr and Sr/Ca imprints affect the quality of the Appalachian watersheds