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Around the world, groundwater salinity levels are increasing in coastal areas, as a result of its systematic overexploitation for domestic, agricultural and industrial demand and potentially due to climate change manifestations (such as, sea level rise). We hypothesized that the groundwater quality of many Mediterranean coastal areas is already being perturbed, especially for water salinity, depending on the groundwater distance from the seafront. The objectives of this study were: i) to evaluate the magnitude and temporal variance of drinking water sodium (Na) as a metric of salt intake used for public health purposes using drinking water data in Cyprus; and ii) to examine the degree of Na enrichment in drinking water as defined by the seawater coastline distance of each sampling point. Open access governmental data of drinking water Na (n = 3304), daily max ambient air temperature and total rainfall were obtained for the period of 2009-2020 from governmental repositories. Linear mixed-effect regression models of drinking water Na with unsupervised covariance matrix were used. After adjusting for temperature and rainfall data, there was a significant annual increase in drinking water Na levels over time (beta = 0.01; 95 % CI: 0.00, 0.02; p = 0.02) for the coastal areas (<10 km from coastline, cutoff used by the EU Environment Agency), but this was not the case for non-coastal areas (>10 km distance from coastline). The distance of each sampling point from the coastline in Cyprus was negatively associated with drinking water Na in coastal areas (beta = -0.04, 95%CI: -0.06, -0.01; p = 0.002); this was not the case for non-coastal areas. More research is warranted to better understand the impacts of global environmental change on water quality in association with the burden of disease in coastal areas., Competing Interests: Declaration of competing interest No conflict of interest for all co-authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Organic food consumption in children has been shown to reduce the body burden of chemical pesticides. However, there is little evidence of human health benefits associated with the consumption of organic foods. The objectives were to i) determine the effectiveness of an organic food intervention treatment in reducing the magnitude of an inflammation biomarker (C-reactive protein, CRP) in children (10-12 years) and ii) assess the association between the urinary biomarkers of exposure to pesticides and CRP. This work was part of the ORGANIKO cluster-randomized cross-over trial entailing a 40-day organic food treatment in healthy children. Urinary biomarkers of exposure to pesticides and inflammation (CRP) were measured using tandem mass spectrometry and ELISA immunoassay, respectively. Linear mixed-effect regression models of CRP were used to account for the effect and duration of organic food treatment. Multiple comparisons were handled using Benjamini-Hochberg correction. Results supported an anti-inflammatory effect of organic food treatment in children, albeit with mixed results, depending on the creatinine adjustment method; biomarker levels were divided by urinary creatinine (method a1), or urinary creatinine was used as a fixed effect variable (a2). In the a1 method, a time-dependent reduction for creatinine-adjusted CRP (β = -0.019; 95% CI: -0.031, -0.006; q = 0.045) was observed during the organic food intervention period. A statistically significant association (β = 0.104; 95% CI: 0.035, 0.173; q = 0.045) was found between the biomarker of pyrethroids exposure (3-PBA) and CRP inflammatory biomarker, but not for 6-CN. In the a2 method, similar trend of time-dependent reduction for creatinine-adjusted CRP (β = -0.008; 95% CI: -0.021, 0.004; p = 0.197) was observed during the organic food intervention period, but did not reach statistical significance (q > 0.05); the associations of pyrethroid and neonicotinoid biomarkers with CRP were not statistically significant (q > 0.05). More studies are warranted to sufficiently understand the potential anti-inflammatory response of an organic food treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Men are vulnerable to ambient heat-related kidney disease burden; however, limited evidence exists on how vulnerable women are when exposed to high ambient heat. We evaluated the sex-specific association between ambient temperature and urine electrolytes, and 24-hour urine total protein, and volume., Methods: We pooled a longitudinal 5624 person-visits data of 1175 participants' concentration and 24-hour excretion of urine electrolytes and other biomarkers (24-hour urine total protein and volume) from southwest coastal Bangladesh (Khulna, Satkhira, and Mongla districts) during November 2016 to April 2017. We then spatiotemporally linked ambient temperature data from local weather stations to participants' health outcomes. For evaluating the relationships between average ambient temperature and urine electrolytes and other biomarkers, we plotted confounder-adjusted restricted cubic spline (RCS) plots using participant-level, household-level, and community-level random intercepts. We then used piece-wise linear mixed-effects models for different ambient temperature segments determined by inflection points in RCS plots and reported the maximum likelihood estimates and cluster robust standard errors. By applying interaction terms for sex and ambient temperature, we determined the overall significance using the Wald test. Bonferroni correction was used for multiple comparisons., Results: The RCS plots demonstrated nonlinear associations between ambient heat and urine biomarkers for males and females. Piecewise linear mixed-effects models suggested that sex did not modify the relationship of ambient temperature with any of the urine parameters after Bonferroni correction ( P  < 0.004)., Conclusion: Our findings suggest that women are as susceptible to the effects of high ambient temperature exposure as men., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

During recent years, we are moving away from the 'one exposure, one disease'-approach in occupational settings and towards a more comprehensive approach, taking into account the totality of exposures during a life course by using an exposome approach. Taking an exposome approach however is accompanied by many challenges, one of which, for example, relates to the collection of biological samples. Methods used for sample collection in occupational exposome studies should ideally be minimally invasive, while at the same time sensitive, and enable meaningful repeated sampling in a large population and over a longer time period. This might be hampered in specific situations e.g., people working in remote areas, during pandemics or with flexible work hours. In these situations, using self-sampling techniques might offer a solution. Therefore, our aim was to identify existing self-sampling techniques and to evaluate the applicability of these techniques in an occupational exposome context by conducting a literature review. We here present an overview of current self-sampling methodologies used to characterize the internal exposome. In addition, the use of different biological matrices was evaluated and subdivided based on their level of invasiveness and applicability in an occupational exposome context. In conclusion, this review and the overview of self-sampling techniques presented herein can serve as a guide in the design of future (occupational) exposome studies while circumventing sample collection challenges associated with exposome studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Food contaminants, such as, pesticides and metals are ubiquitous in the food chain. Studies routinely report on the metals content of organic and conventional food crops. However, comparative human studies on the body burden of metals associated with organic food consumption are currently lacking., Objectives: The objectives were to i) determine the effectiveness of an organic food intervention in reducing the body burden of urinary concentration of lead (Pb) and cadmium (Cd) and ii) evaluate the association between metal exposures and biomarkers of oxidative damage in primary school children in Cyprus., Methods: This study was part of the ORGANIKO cluster-randomized crossover trial, a 40-day organic food treatment to 149 healthy children (10-12 years) in Cyprus. Urinary biomarkers of Pb and Cd were determined using inductively coupled plasma mass spectrometry. Linear mixed-effect regression models were used to account for the effect and duration of the organic food treatment. Multiple comparisons were handled using Benjamini-Hochberg correction., Results: A time-dependent reduction for creatinine-adjusted Pb during the intervention period was observed (β = -0.021; 95% CI: -0.034, -0.008; p-adjusted = 0.01). A similar trend was observed for creatinine-adjusted Cd, but it was not significant (β = -0.013; 95% CI: -0.026, 0.000; p-adjusted = 0.15). The creatinine-adjusted oxidative damage biomarkers were significantly associated with both metal biomarkers; Pb (8-OHdG: β = 0.388, 95% CI: 0.303, 0.472; p-adjusted<0.001; MDA: β = 0.187, 95% CI: 0.109, 0.265; p-adjusted<0.001; 8-iso-PGF2a: β = 0.320, 95% CI: 0.244, 0.397; p-adjusted<0.001), and Cd (8-OHdG: β = 0.148, 95% CI: 0.063, 0.233; p-adjusted = 0.003; MDA: β = 0.107, 95% CI: 0.030, 0.184; p-adjusted = 0.018; 8-iso-PGF2a: β = 0.263, 95% CI: 0.186, 0.339; p-adjusted<0.001)., Discussion: A 40-day organic food treatment reduced primary school children's exposures to Pb over time. More human studies in settings with high food contaminant profiles across common crops are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Exposure to various pesticides, such as pyrethroids and chlorpyrifos, has been previously associated with adverse effects on children's health. Scientific evidence on the human toxicity of glyphosate (GLY) and its primary metabolite, aminomethylphosphonic acid (AMPA) is limited, particularly for children. This study aimed to i) assess the exposure determinants of the studied pesticides measured in children in Cyprus, and ii) determine the association between the urinary pesticides and the biomarkers of DNA and lipid oxidative damage., Methods: A children's health study was set up in Cyprus (ORGANIKO study) by aligning it with the methodology and tools used in the European Human Biomonitoring Initiative (HBM4EU). Urinary GLY and AMPA, pyrethroid metabolites and the chlorpyrifos metabolite TCPy were measured in 177 children aged 10-11 years old, using mass spectrometry. Oxidative stress was assessed with 8-iso-prostaglandin F2a (8-iso-PGF2α) as a marker of lipid damage and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a DNA oxidative damage marker, both measured with immunoassays. Questionnaires about demographic characteristics, pesticide usage, and dietary habits were filled out by the parents. Μultivariable regression models examined associations between pesticides and biomarkers of effect using two creatinine adjustments (cr1: adding it as covariate and cr2: biomarkers of exposure and effect were creatinine-adjusted)., Results: Parental educational level was a significant predictor of urinary pyrethroids but not for GLY/AMPA. Median [interquartile range, IQR] values for GLY and AMPA were  0.05). Similar significant associations with 8-OHdG were shown for a pyrethroid metabolite (3-PBA) and the chlorpyrifos metabolite (TCPy). No associations were observed between the aforementioned pesticides and 8-iso-PGF2α (p > 0.05)., Conclusions: This is the first children's health dataset demonstrating the association between AMPA and DNA oxidative damage, globally. More data is needed to replicate the observed trends in other children's populations around the globe., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Vitamin D, an important hormone with a central role in calcium and phosphate homeostasis, is required for bone and muscle development as well as preservation of musculoskeletal function. The most abundant vitamin D metabolite is 25-hydroxyvitamin D [25(OH)D], which is currently considered the best marker to evaluate overall vitamin D status. 25(OH)D is therefore the most commonly measured metabolite in clinical practice. However, several other metabolites, although not broadly measured, are useful in certain clinical situations. Vitamin D and all its metabolites are circulating in blood bound to vitamin D binding protein, (VDBP). This highly polymorphic protein is not only the major transport protein which, along with albumin, binds over 99% of the circulating vitamin D metabolites, but also participates in the transport of the 25(OH)D into the cell via a megalin/cubilin complex. The accurate measurement of 25(OH)D has proved a difficult task. Although a reference method and standardization program are available for 25(OH)D, the other vitamin D metabolites still lack this. Interpretation of results, creation of clinical supplementation, and generation of therapeutic guidelines require not only accurate measurements of vitamin D metabolites, but also the accurate measurements of several other "molecules" related with bone metabolism. IFCC understood this priority and a committee has been established with the task to support and continue the standardization processes of vitamin D metabolites along with other bone-related biomarkers. In this review, we present the position of this IFCC Committee on Bone Metabolism on the latest developments concerning the measurement and standardization of vitamin D metabolites and its binding protein, as well as clinical indications for their measurement and interpretation of the results., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Endocrine disrupting chemicals (EDCs) include non-persistent exogenous substances such as parabens, bisphenols and phthalates which have been associated with a range of metabolic disorders and disease. It is unclear if exposure remains consistent over time. We investigated change in indicators of EDC exposure between 2009 and 2016 and assessed its consistency between and within individuals over a median follow-up time of 47 months in a sample of Dutch individuals. Of 500 Dutch individuals, two 24 h urine samples were analysed for 5 parabens, 3 bisphenols and 13 metabolites of in total 8 different phthalates. We calculated per-year differences using meta-analysis and assessed temporal correlations between and within individuals using Spearman correlation coefficients, intra-class correlation coefficients (ICC) and kappa-statistics. We found a secular decrease in concentrations of methyl, ethyl, propyl and n-butyl paraben, bisphenol A, and metabolites of di-ethyl phthalate (DEP), di-butyl phthalate (DBP), di-(2-ethyl-hexyl) phthalate (DEHP), and butylbenzyl phthalate (DBzP) which varied from 8 to 96% (ethyl paraben, propyl paraben) between 2009 and 2016. Within-person temporal correlations were highest for parabens (ICC: 0.34 to 0.40) and poorest for bisphenols (ICC: 0.15 to 0.23). For phthalate metabolites, correlations decreased most between time periods (ICC < 48 months: 0.22 to 0.39; ≥48 months: 0.05 to 0.32). When categorizing EDC concentrations, 33-54% of individuals remained in the lowest or highest category and temporal correlations were similar to continuous measurements. Exposure to most EDCs decreased between 2009 and 2016 in a sample of individuals with impaired fasting glucose from the Dutch population. Temporal consistency was generally poor. The inconsistency in disease associations may be influenced by individual-level or temporal variation exhibited by EDCs. Our findings call for the need for repeated measurements of EDCs in observational studies before and during at-risk temporal windows for the disease., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Parathyroid hormone (PTH) determination is of greatest importance for patients suffering from parathyroid gland disorders and for the follow-up of bone turnover in patients suffering from chronic kidney disease (CKD). Two generations of PTH assays are simultaneously present on the market for PTH quantification. As these assays are not yet standardized, this results in a significant level of confusion in the care of CKD patients. One key objective of the IFCC Committee for Bone Metabolism is to improve this situation. In this position paper, we will highlight the current state of PTH testing and propose a pathway to ultimately overcome issues resulting from PTH assay variability., (Copyright © 2020. Published by Elsevier B.V.)

People with diabetes are required to regularly check their glucose to make therapy decisions. So far, systems for self-monitoring of blood glucose were used, but nowadays minimally invasive continuous glucose monitoring (CGM) systems are increasingly more often employed, sometimes to partially replace self-monitoring of blood glucose. Most CGM systems on the market measure glucose concentrations continuously in the interstitial fluid of the subcutaneous fatty tissue. However, CGM has a principle limitation. Collecting interstitial fluid frequently in sufficiently large volumes over short time periods is not easy. As a consequence, no internationally accepted reference measurement procedure is currently available for glucose in interstitial fluid which is a prerequisite to achieve an optimal metrological traceability. Recent studies indicate that the analytical performance of minimally invasive CGM systems differs not only between manufacturers but also between individual sensors of the same system, sometimes even in the same subject. Because manufacturers don't provide detailed information about the traceability chain and the measurement uncertainty of their systems glucose values obtained with CGM can currently not be adequately traced to higher-order standards or methods. Therefore, the Working Group on Continuous Glucose Monitoring aims at establishing a traceability chain for minimally invasive CGM systems, as well as procedures and metrics for the assessment of their analytical performance., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (β-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and β-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of β-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and β-CTX., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The link between exposure to endocrine disrupting chemicals (EDCs) and the rapid increase in prevalence of obesity has recently been suggested. However, the magnitude and health impact of EDC exposure in at-risk populations remain largely unclear. In this study, we investigated the effect of a dietary intervention driven reduction in adipose tissue on the magnitude of urinary EDC exposure and mobilization, and whether higher EDC exposure leads to impaired weight loss in obese individuals. In this post-hoc analysis of the Lifestyle, OverWeight, Energy Restriction (LOWER) study from the Netherlands, 218 subjects were included. Five parabens, three bisphenols and thirteen metabolites of eight phthalates were measured in 24-h urine using LC-MS/MS, before and after three-months of a calory-restricted weight reduction intervention program. Associations between adiposity-related traits and EDCs were tested using multivariable linear regression and linear mixed effects models. A multiple testing correction based on the false discovery rate (FDR) was applied. After the 3-month intervention, urinary paraben and bisphenol excretions remained similar. Excretions of mono-butyl phthalates and most high-molecular-weight phthalates decreased, whereas mono-ethyl phthalate increased (all FDR<0.05). A reduction in adipose tissue was not associated with higher urinary EDC excretions. Higher baseline EDC excretions were associated with higher post-intervention body-mass index (methyl-, propylparaben), waist circumference (propylparaben, mono-n-butyl phthalate, mono-benzyl phthalate), and body fat percentage (mono-ethyl phthalate, mono-benzyl phthalate). Associations between parabens and body-mass index, and mono-benzyl phthalate and waist circumference and body fat percentage remained after multiple testing correction (all FDR<0.05). In a study of obese participants, we observed a reduction in most phthalates after a weight reduction intervention. A reduction in adipose tissue may not lead to mobilization and successively to higher urinary EDC excretions. Higher baseline paraben and phthalate exposures were associated with reduced weight loss, suggesting obesogenic properties., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The manifestation of elevated and sustained air temperature gradient profiles in urban dwellings represents an emerging planetary health phenomenon. There is currently limited evidence about the effect of elevated air temperatures on metabolic health. The aim of this work was to assess changes in metabolic and stress hormonal profiles during a short-term stay in a mountainous, climate-cooler setting against those observed in the urban setting. A prospective, randomized, 2 x 2 cross-over trial of non-obese healthy adults in urban and mountainous areas of a Mediterranean country (Cyprus) was set up during summer, under real-life conditions. The intervention was a short-term stay (mean ± SD: 7 ± 3 days) in a mountainous, climate-cooler setting (altitude range: 650-1200 m), being ~1-h drive away from the main urban centres of Cyprus. The primary endpoint was the change in metabolic hormones levels (leptin and adiponectin) and stress hormone levels (cortisol) between the two settings. Personal air and skin temperature sensors were deployed while biospecimen were collected in each setting. A total of 41 participants between 20 and 60 years old were enrolled and randomized during July 2018, of whom 39 received the allocated intervention, 8 were lost to follow up or excluded from analysis and a total of 31 participants were analysed. A significant leptin reduction (β = -0.255; 95% CI: -0.472, -0.038; p = 0.024) was observed for non-obese healthy adults during their short-term stay in the mountainous environment. The intervention effect on adiponectin or cortisol levels was not statistically significant (β = 0.058; 95% CI: -0.237, 0.353; p = 0.702), and (β = -0.026; 95% CI: -0.530, 0.478; p = 0.920), respectively. In additional analyses, daily max skin temperature surrogate measures were significantly associated with leptin levels (β = 0.34; 95% CI: 0.051, 0.633; p = 0.024). During summer season, a short-term stay in climatologically cooler areas improved the leptin levels of non-obese healthy adults who permanently reside in urban areas of a Mediterranean country. A larger sample is needed to confirm the trial findings that could provide the rationale for such public health interventions in climate-impacted urban areas of our planet., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Minimally invasive thymectomy (MIT) has demonstrated improved short-term outcomes compared with open thymectomy (OT). Although adoption of MIT for thymoma is increasing, oncologic outcomes have not been well characterized., Methods: This was a retrospective cohort study of adult patients from the National Cancer Database who underwent MIT or OT for Masaoka stage I to II thymoma between 2010 and 2014. The primary outcome was R0 resection. Secondary outcomes included MIT use, perioperative mortality, and length of stay., Results: Nine hundred forty-three patients from 395 hospitals underwent thymectomy for stage I to II thymoma. MIT was performed in 31.3% (59.7% robotic, 40.3% thoracoscopic). Over the study period MIT utilization increased from 21.0% to 40.2% (trend test, p < 0.001). R0 resection was achieved in 83.1% of MITs (86.6% stage I, 72.7% stage II) and 79% of OTs (85.5% stage I, 65.8% stage II). In multivariable analyses, the likelihood of incomplete resection (R1/2) was associated with stage II tumors (odds ratio, 2.51) and World Health Organization B3 histology (odds ratio, 3.66). R0 resection was not associated with surgical approach (p = 0.17) and did not vary with tumor size (trend test, p = 0.90). Mortality rates at 30 and 90 days were 0% and 0.5%, respectively. MIT was associated with significantly shorter lengths of stay than OT (-1.03 days [95% confidence interval, -1.68 to -0.38])., Conclusions: The use of MIT for resection of early-stage thymoma is increasing and is not associated with lower rates of R0 resection than OT. Reasons for the relatively low rates of R0 resection among all thymectomies requires further investigation, and long-term outcomes data are needed to better define the oncologic effectiveness of MIT., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Horizontal challenges, such as climate change or the growing populations, and their manifestations require the development of multidisciplinary research synergies in urban health that could benefit from concepts, such as the human exposome. Cities are composed of interconnected systems which are influenced, by global trends, national policies and local complexities. In this context, the exposome concept could be expanded having the city setting in its core, providing the conceptual framework for the new generation of urban studies. The objectives of this work were to define the urban exposome and outline its utility. The urban exposome can be defined as the continuous spatiotemporal surveillance/monitoring of quantitative and qualitative indicators associated with the urban external and internal domains that shape up the quality of life and the health of urban populations, using small city areas, i.e. neighborhoods, quarters, or smaller administrative districts, as the point of reference. Research should focus on the urban exposome's measurable units at different levels, i.e. the individuals, small, within-city areas and the populations. The urban exposome framework applied in the city of Limassol, Cyprus combines three elements: (i) a mixed-methods study on stakeholders' opinions about quality of life in the city; (ii) a systematic assessment of secondary data from the cancer and death registries, including city infrastructure data; and (iii) a population health and biomonitoring survey. Continuous assessment of environmental and health indicators that are routinely collected, and the incorporation of primary data from population studies, will allow for the timely identification of within-city health and environmental disparities to inform policy making and public health interventions. The urban exposome could facilitate evidence-based public health response, offering researchers, policy-makers, and citizens effective tools to address the societal needs of large urban centers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A cohort-friendly biomonitoring protocol has been developed for measuring biomarkers of exposure to disinfection by-products (trihalomethanes, THM) in urine using small initial volume (3mL) and short analysis time (∼10min) that facilitates the throughput of a large number of samples. The objective of this study was to optimise a cohort-friendly biomonitoring protocol for the determination of four THM analytes in human urine using gas chromatography coupled with triple quadrupole mass spectrometry (GC-QqQ-MS/MS). The proposed methodology will facilitate the inclusion of such urinary THM measurements into large population health studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Non-iodo-containing trihalomethanes (TTHM) are frequently detected in chlorinated tap water and currently regulated against their carcinogenic potential. Iodinated THM (ITHM) may also form in disinfected with chlorine waters that are high in iodine content, but little is known about their magnitude and variability within the drinking-water pipe distribution network of urban areas. The main objective of this study was to determine the magnitude and variability of ITHM and TTHM levels and their corresponding daily intake estimates within the drinking water distribution systems of Limassol and Nicosia cities of Cyprus, using tap samples collected from individual households (n=37). In Limassol, mean household tap water ITHM and TTHM levels was 0.58 and 38 μg L(-1), respectively. Dichloroiodomethane (DCIM) was the dominant species of the two measured ITHM compounds accounting for 77% of total ITHM and in the range of 0.032 and 1.65 μg L(-1). The range of DCIM concentrations in Nicosia tap water samples was narrower (0.032 - 0.848 μg L(-1)). Mean total iodine concentration in tap water samples from the seaside city of Limassol was 15 μg L(-1) and approximately twice to those observed in samples from the mainland Nicosia city. However, iodine concentrations did not correlate with the ITHM levels. The calculated chronic daily intake rates of ITHM were low when compared with those of TTHM, but because of their widespread occurrence in tap water and their enhanced mammalian cell toxicity, additional research is warranted to assess the magnitude and variability of human ITHM exposures., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A pesticide monitoring study covering the main rivers and lakes of Northern Greece (Macedonia, Thrace and Thessaly) was undertaken. A total of 416 samples were collected over a 1.5-year sampling period (September 1999- February 2001) from six rivers and ten lakes. The water samples were analyzed with an off-line solid phase extraction technique coupled with a gas chromatography ion trap mass spectrometer using an analytical method for 147 pesticides and their metabolites, including organochlorines, organophosphates, triazines, chloroacetanilides, pyrethroids, carbamates, phthalimides and other pesticides (herbicides, insecticides and fungicides). Based on the pesticide survey results, a human health carcinogenic and non-carcinogenic risk assessment was conducted for adults and children. Ecotoxicological risk assessment was also conducted using default endpoint values and the risk quotient method. Results showed that the herbicides metolachlor, prometryn, alachlor and molinate, were the most frequently detected pesticides (29%, 12.5%, 12.5% and 10%, respectively). They also exhibited the highest concentration values, often exceeding 1 μg/L. Chlorpyrifos ethyl was the most frequently detected insecticide (7%). Seasonal variations in measured pesticide concentrations were observed in all rivers and lakes. The highest concentrations were recorded during May-June period, right after pesticide application. Concentrations of six pesticides were above the maximum allowable limit of 0.1 μg/L set for drinking water. Alachlor, atrazine and a-HCH showed unacceptable carcinogenic risk estimates (4.5E-06, 4.6E-06 and 1.3E-04, respectively). Annual average concentrations of chlorpyriphos ethyl (0.031 μg L), dicofol (0.01 μg/L), dieldrin (0.02 μg/L) and endosulfan a (0.065 μg/L) exceeded the EU environmental quality standards. The risk quotient estimates for the insecticides chorpyrifos ethyl, diazinon and parathion methyl and herbicide prometryn were above acceptable risk values. The coupling of monitoring data to probabilistic human and ecotoxicological risk estimates could find use by Greek regulatory authorities, proposing effective pollution management schemes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Gradually-changing shocks associated with potable water quality deficiencies are anticipated for urban drinking-water distribution systems (UDWDS). The impact of structural UDWDS features such as, the number of pipe leaking incidences on the formation of water trihalomethanes (THM) at the geocoded household level has never been studied before. The objectives were to: (i) characterize the distribution of water THM concentrations in households from two district-metered areas (DMAs) with contrasting UDWDS characteristics sampled in two seasons (summer and winter), and (ii) assess the within- and between-household, spatial variability of water THM accounting for UDWDS characteristics (household distance from chlorination tank and service pipe leaking incidences). A total of 383 tap water samples were collected from 193 households located in two DMAs within the UDWDS of Nicosia city, Cyprus, and analyzed for the four THM species. The higher intraclass correlation coefficient (ICC) values for water tribromomethane (TBM) (0.75) followed by trichloromethane (0.42) suggested that the two DMAs differed with respect to these analytes. On the other hand, the low ICC values for total THM levels between the two DMAs suggested a large variance between households. The effect of households nested under each DMA remained significant (p<0.05) for TBM (not for the rest of the THM species) in the multivariate mixed-effect models, even after inclusion of pipe network characteristics. Our results could find use by water utilities in overcoming techno-economic difficulties associated with the large spatiotemporal variability of THM, while accounting for the influence of UDWDS features at points of water use., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Domestic cleaning has been proposed as a determinant of trihalomethanes (THMs) exposure in adult females. We hypothesized that parental housekeeping activities could influence children's passive exposures to THMs from their mere physical presence during domestic cleaning. In a recent cross-sectional study (n = 382) in Cyprus [41 children (< 18 y) and 341 adults (≥ 18 y)], we identified 29 children who met the study's inclusion criteria. Linear regression models were applied to understand the association between children sociodemographic variables, their individual practices influencing ingestion and noningestion exposures to ΣTHMs, and their urinary THMs levels. Among the children-specific variables, age alone showed a statistically significant inverse association with their creatinine-adjusted urinary ΣTHMs (rS = -0.59, p < 0.001). A positive correlation was observed between urinary ΣTHMs (ng g(-1)) of children and matched-mothers (rS = 0.52, p = 0.014), but this was not the case for their matched-fathers (rS = 0.39, p = 0.112). Time spent daily by the matched-mothers for domestic mopping, toilet and other cleaning activities using chlorine-based cleaning products was associated with their children's urinary THMs levels (rS = 0.56, p = 0.007). This trend was not observed between children and their matched-fathers urinary ΣTHMs levels, because of minimum amount of time spent by the latter in performing domestic cleaning. The proportion of variance of creatinine-unadjusted and adjusted urinary ΣTHMs levels in children that was explained by the matched-mothers covariates was 76% and 74% (p < 0.001), respectively. A physiologically-based pharmacokinetic model adequately predicted urinary chloroform excretion estimates, being consistent with the corresponding measured levels. Our findings highlighted the influence of mothers' domestic cleaning activities towards enhancing passive THMs exposures of their children. The duration of such activities could be further tested as a valid indicator of children's THMs body burden., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A complex network of sources and routes of exposure to disinfection by-products (DBP), such as trihalomethanes (THM) has been driving the wide variability of daily THM intake estimates in environmental epidemiological studies. We hypothesized that the spatiotemporal variability of THM exposures could be differentially expressed with their urinary levels among residents whose households are geographically clustered in district-metered areas (DMA) receiving the same tap water. Each DMA holds unique drinking-water pipe network characteristics, such as pipe length, number of pipe leaking incidences, number of water meters by district, average minimum night flow and average daily demand. The present study assessed the spatial and seasonal variability in urinary THM levels among residents (n=310) of geocoded households belonging to two urban DMA of Nicosia, Cyprus, with contrasting water network properties. First morning urine voids were collected once in summer and then in winter. Results showed that the mean sum of the four urinary THM analytes (TTHM) was significantly higher during summer for residents of both areas. Linear mixed effects models adjusted for age, season and gender, illustrated spatially-resolved differences in creatinine-adjusted urinary chloroform and TTHM levels between the two studied areas, corroborated by differences observed in their pipe network characteristics. Additional research is warranted to shed light on the contribution of spatially-resolved and geographically-clustered environmental exposures coupled with internal biomarker of exposure measurements towards better understanding of health disparities within urban centers., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) after open repair (OR) and endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) is associated with increased mortality and hospital costs. Early detection of AKI is critical to prevent its progression. Recent findings demonstrate that elevated levels of urinary cystatin C (uCysC) may reflect tubular dysfunction. We prospectively evaluated whether uCysC can detect renal dysfunction earlier than serum creatinine (sCr)., Methods: In a prospective study, 126 consecutive patients (mean age ± SD, 69.1 ± 8.66 years) with AAA (EVAR = 87, OR = 39) were enrolled. sCr and uCysC were measured preoperatively (baseline) and at 6, 24, and 48 hr postoperatively. A final measurement was made on day 5. AKI was defined according to Acute Kidney Injury Network criteria., Results: The incidence of AKI was significantly higher (χ(2) test, P < 0.05) in the OR group (n = 13, 33%) than in the EVAR group (n = 15, 17%). The baseline median (interquartile range) value of uCysC was significantly higher (t-test, P < 0.05) in patients of both groups (OR-EVAR) who developed AKI from those who did not (OR/AKI group: 0.06 [0.02-0.12] mg/L, EVAR/AKI group: 0.08 [0.05-0.11] mg/L versus no-AKI subjects: 0.04 [0.02-0.07] mg/L). Subsequent analysis showed that at 6 hr postoperatively, the patients who developed AKI increased their uCysC levels significantly from baseline (OR/AKI group: 0.58 [0.42-0.70] mg/L, EVAR/AKI group: 0.59 [0.30-1.07] mg/L). The median value of uCysC in AKI patients increased at 24 hr (OR/AKI group: 1.37 [0.78-3.40] mg/L, EVAR/AKI group: 2.11 [0.70-2.42] mg/L) and peaked at 48 hr (OR/AKI group: 6.16 [1.74-10.73] mg/L, EVAR/AKI group: 2.57 [1.21-7.40] mg/L), while no increase was observed among those who did not develop AKI at the same time points (0.06 [0.04-0.14] vs. 0.08 [0.04-0.19] mg/L). The diagnostic accuracy of uCysC at 6 hr post-surgery was excellent (area under the curve - receiver-operating characteristic [AUC-ROC] = 0.968), significantly higher than sCr (AUC-ROC = 0.844) and a cutoff value set at 0.30 mg/L can diagnose AKI with a sensitivity of 85.71% and a specificity of 98.97%., Conclusions: uCysC is superior to sCr in the early diagnosis of AKI following open and endovascular AAA repair., (Copyright © 2014 Elsevier Inc. All rights reserved.)

With the exception of chloroform, the rest of trihalomethanes (THM), the so-called brominated THM (Br-THM) are composed of bromine-substituted molecules with increased lipophilicity and potency to biological tissues. The THM are formed within disinfected tap water and their health effects, under research, range from cancer to adverse reproductive outcomes. However, the association between human exposures to Br-THM and the risk of developing type II diabetes mellitus (T2DM) and metabolic co-morbidities, such as obesity and non-alcoholic steatohepatitis has never been previously explored. The objective of this exploratory analysis was to address obesity-mediated associations between urinary concentrations of brominated THM and incidences of T2DM in a Cypriot adult population (n=326). First morning urine voids were collected once during summer and another time during winter while a detailed questionnaire was administered to participants. Creatinine-adjusted urinary Br-THM analyte concentrations were significantly (p<0.05) higher in T2DM cases when compared with those in healthy individuals. Multivariate logistic regression models adjusted for potential confounders showed that participants with ≥30 kg m(-2) BMI were at a higher T2DM risk (OR=8.42, 95% CI: 1.97, 45.5; p<0.01) when compared with that of normal weight participants (<25 kg m(-2)). About 4 times higher risk for developing T2DM was observed for individuals in the upper tertile of urinary Br-THM levels (OR=3.99, 95% CI: 1.07, 19.7; p<0.05) when compared with the lower tertile participants. Among the participants with BMI≥25 kg m(-2), urinary Br-THM levels were significantly (p<0.001) higher in diabetics than in healthy individuals. Ingestion and non-ingestion exposures to Br-THM deserve careful consideration in relevant epidemiological studies, as a possible environmental risk factor of T2DM., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Changes in disinfectant type could trigger a cascade of reactions releasing pipe-anchored metals/metalloids into finished water. However, the effect of pre-formed disinfection by-products on the release of sorbed contaminants (arsenic-As in particular) from drinking water distribution system pipe scales remains unexplored. A bench-scale study using a factorial experimental design was performed to evaluate the independent and interaction effects of trihalomethanes (TTHM) and haloacetic acids (HAA) on arsenic (As) release from either scales-only or scale-biofilm conglomerates (SBC) both anchored on asbestos/cement pipe coupons. A model biofilm (Pseudomonas aeruginosa) was allowed to grow on select pipe coupons prior experimentation. Either TTHM or HAA individual dosing did not promote As release from either scales only or SBC, detecting <6 μg AsL(-1) in finished water. In the case of scales-only coupons, the combination of the highest spike level of TTHM and HAA significantly (p<0.001) increased dissolved and total As concentrations to levels up to 16 and 95 μg L(-1), respectively. Similar treatments in the presence of biofilm (SBC) resulted in significant (p<0.001) increase in dissolved and total recoverable As up to 20 and 47 μg L(-1), respectively, exceeding the regulatory As limit. Whether or not, our laboratory-based results truly represent mechanisms operating in disinfected finished water in pipe networks remains to be investigated in the field., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Because of the plethora of exposure sources and routes through which humans are exposed to trihalomethanes (THM), the limitation of their short half-lives could be overcome, if a highly sensitive method was available to quantify urinary THM concentrations at sub-ppb levels. The objective of this study was to develop a fast and reliable method for the determination of the four THM analytes in human urine. A sensitive methodology was developed for THM in urine samples using gas chromatography coupled with triple quadrupole mass spectrometry (GC-QqQ-MS/MS) promoting its use in epidemiological and biomonitoring studies. The proposed methodology enjoys limits of detection similar to those reported in the literature (11-80 ng L(-1)) and the advantages of small initial urine volumes (15 mL) and fast analysis per sample (12 min) when compared with other methods. This is the first report using GC-QqQ-MS/MS for the determination of THM in urine samples. Because of its simplicity and less time-consuming nature, the proposed method could be incorporated into detailed (hundreds of participants' urine samples) exposure assessment protocols providing valuable insight into the dose-response relationship of THM and cancer or pregnancy anomalies., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Water contamination and noise have been consistently the least assessed environmental/lifestyle exposures in pregnancy-birth cohorts (PBC). Water quality surveillance data collected during the past decade within urban drinking-water distribution systems call for re-evaluation of water and health issues in the developed world. The objectives of this scientific commentary were to (i) highlight the extent of appraisal of water contamination in exposure assessment studies of PBC, worldwide, and (ii) propose recommendations to increase awareness of emerging water-related risks through their improved representation into PBC study designs in urban centers. Three scientific literature databases (Scopus, PubMed, and Web of Science) were used for a systematic search on worldwide PBC and their publications that considered water contamination and health outcomes. Publicly-available e-databases (ENRIECO, BIRTHCOHORTS, and CHICOS) were also employed for detailed exploration of existing European Union (EU)-based PBC. Out of the 76 PBC identified in the EU territory, only 12 of them incorporated water contamination into their study designs. Among which only 6 PBC published scientific articles that either included data on water contamination and/or water intake estimates. Trihalomethanes but not other disinfection by-products were mostly studied in the PBC around the globe, while fluoride, atrazine, perfluorinated compounds, tetrachloroethylene, and lead were studied to a lesser extent as water contaminants. It appears that chemical-based water contamination and corresponding human exposures represent a largely underappreciated niche of exposure science pertaining to pregnant mother and children's health in PBC. Future PBC studies should grasp this opportunity to substantially reform elements of water contamination in their exposure assessment protocols and effectively combine them with their epidemiological study designs., (© 2013.)

Historic applications of arsenical pesticides to agricultural land have resulted in accumulation of residual arsenic (As) in such soils. In situ immobilization represents a cost-effective and least ecological disrupting treatment technology for soil As. Earlier work in our laboratory showed that drinking-water treatment residuals (WTRs), a low-cost, waste by-product of the drinking-water treatment process exhibit a high affinity for As. Wet chemical experiments (sorption kinetics and desorption) were coupled with X-ray absorption spectroscopy measurements to elucidate the bonding strength and type of As(V) and As(III) sorption by an aluminum-based WTR. A fast (1h), followed by a slower sorption stage resulted in As(V) and As(III) sorption capacities of 96% and 77%, respectively. Arsenic desorption with a 5mM oxalate from the WTR was minimal, being always <4%. X-ray absorption spectroscopy data showed inner-sphere complexation between As and surface hydroxyls. Reaction time (up to 48h) had no effect on the initial As oxidation state for sorbed As(V) and As(III). A combination of inner-sphere bonding types occurred between As and Al on the WTR surface because mixed surface geometries and interatomic distances were observed.