Differential effect of the duration of exposure on the carcinogenicity of cadmium in MCF10A mammary epithelial cells.

The carcinogenic role of cadmium (Cd2+) in breast cancer is still debatable. Current data points to duration of exposure as the most important element. In our study, we designed an in vitro model to investigate the effects of 3 weeks versus 6 weeks of low-level CdCl2 exposure on MCF10A cells. Our results demonstrated that after 3 weeks of CdCl2 exposure the cells displayed significant changes in the DNA integrity, but there was no development of malignant features. Interestingly, after 6 weeks of exposure, the cells significantly increased their invasion, migration and colony formation capacities. Additionally, MCF10A cells exposed for 6 weeks to CdCl2 had many dysregulated genes (4905 up-regulated and 4262 down-regulated). As follows, Cd-induced phenotypical changes are accompanied by a profound modification of the transcriptomic landscape. Furthermore, the molecular alterations driving carcinogenesis in MCF10A cells exposed to CdCl2 were found to be influenced by the duration of exposure, as in the case of MEG8. This long non-coding RNA was down-regulated at 3 weeks, but up-regulated at 6 weeks of exposure. In conclusion, even very low levels of Cd (0.5 µM) can have significant carcinogenic effects on breast cells in the case of subchronic exposure.

Ideonella sakaiensis Can Metabolize Bisphenol A as a Carbon Source.

Bisphenol A and its analogues represent a significant environmental and public health hazard, particularly affecting the endocrine systems of children and newborns. Due to the growing need for non-pathogenic biodegradation microbial agents as environmentally friendly and cost-effective solutions to eliminate endocrine disruptors, this study aimed to investigate the degradation of bisphenol A by Ideonella sakaiensis, based on its currently understood unique enzymatic machinery that is already well known for degrading polyethylene terephthalate. The present study provides novel insights into the metabolic competence and growth particularities of I. sakaiensis. The growth of I. sakaiensis exposed to bisphenol A exceeded that in the control conditions, starting with 72 h in a 70% nutrient-rich medium and starting with 48 h in a 100% nutrient-rich medium. Computational modeling showed that bisphenol A, as well as its analogue bisphenol S, are possible substrates of PETase and MHETase. The use of bisphenol A as a carbon and energy source through a pure I. sakaiensis culture expands the known substrate spectra and the species' potential as a new candidate for bisphenol A bioremediation processes.

Harnessing Code Interpreters for Enhanced Predictive Modeling: A Case Study on High-Density Lipoprotein Level Estimation in Romanian Diabetic Patients.

Diabetes is a condition accompanied by the alteration of body parameters, including those related to lipids like triglyceride (TG), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs). The latter are grouped under the term dyslipidemia and are considered a risk factor for cardiovascular events. In the present work, we analyzed the complex relationships between twelve parameters (disease status, age, sex, body mass index, systolic blood pressure, diastolic blood pressure, TG, HDL, LDL, glucose, HbA1c levels, and disease onset) of patients with diabetes from Romania. An initial prospective analysis showed that HDL is inversely correlated with most of the parameters; therefore, we further analyzed the dependence of HDLs on the other factors. The analysis was conducted with the Code Interpreter plugin of ChatGPT, which was used to build several models from which Random Forest performed best. The principal predictors of HDLs were TG, LDL, and HbA1c levels. Random Forest models were used to model all parameters, showing that blood pressure and HbA1c can be predicted based on the other parameters with the least error, while the less predictable parameters were TG and LDL levels. By conducting the present study using the ChatGPT Code Interpreter, we show that elaborate analysis methods are at hand and easy to apply by researchers with limited computational resources. The insight that can be gained from such an approach, such as what we obtained on HDL level predictors in diabetes, could be relevant for deriving novel management strategies and therapeutic approaches.

Urinary arsenic and spontaneous pregnancy loss - a hypothesis-generating case-control investigation in western Romania.

Arsenic occurs as a natural contaminant of drinking water supplies in arsenic endemic areas, posing a threat to public health. Our aim was to evaluate the relationship between urinary arsenic concentrations and spontaneous pregnancy loss in a population with low-moderate level drinking water arsenic exposure (mostly <10 µg/L). We enrolled 150 women with incident spontaneous pregnancy losses and 150 controls with ongoing pregnancies matched by gestational age. We measured arsenic species in urine using high performance liquid chromatography paired to inductively coupled plasma mass spectrometry. Urinary arsenic was not related to spontaneous pregnancy loss in conditional logistic regression models adjusted for confounding factors. However, a 10 µg/L increase in urinary arsenic (III + V) salt concentrations was associated with 8.00-fold (95% CI: 0.68, 3.35 × 105) greater odds of spontaneous loss among women using prenatal vitamins in an interaction model (P for interaction = 0.07), although the effect estimate was imprecise. In an additional interaction model, prenatal vitamin use was associated with lower odds of loss (OR = 0.30; 95% CI: 0.13, 0.66), although the association was diminished in the presence of a 10 µg/L increase in urinary inorganic arsenic (OR = 0.44; 95% CI: 0.70, 3.22). Total urinary arsenic was associated with 1.48-fold (95% CI: 0.20, 11.35) greater odds for loss among women with urinary cotinine >50 µg/L in another interaction model (P for interaction = 0.07). These results suggest a potential modest increase in the odds of pregnancy loss associated with increased total urinary arsenic among women smoking during pregnancy (urinary cotinine >50 µg/L). Prenatal vitamin use may act as a protective factor for arsenic exposure associated pregnancy loss, but appears to be less protective with increasing urinary inorganic arsenic concentrations.

Effect of Different Etching Times with Hydrofluoric Acid on the Bond Strength of CAD/CAM Ceramic Material.

The objective of this study was to evaluate the influence of hydrofluoric acid (HF) and conditioning time on the micro-shear bond strength (µSBS) between dual-cure resin cement and glass-ceramic materials, such as lithium disilicate ceramic (IPS e.max CAD, Ivoclar Vivadent) (EX) and leucite-reinforced ceramic (IPS Empress CAD, Ivoclar Vivadent) (EP), and also a hybrid ceramic (Vita Enamic, Vita Zahnfabrik) (VE). Eighteen sections with 1 mm thickness were cut from each CAD/CAM material and randomly divided into three groups, according to the surface etching time (30 s, 60 s, 90 s). The surface treatment was performed using 9.5% HF acid gel, then resin cement was applied on the prepared ceramic plates and light cured. µSBS values between resin cement and the ceramic material were measured with a universal testing machine at a crosshead speed of 0.5 mm/min until the failure occurred. The fractured surfaces of specimens were microscopically evaluated, and failure modes were classified as: adhesive between resin cement and ceramic, cohesive within ceramic or cement and mixed failure. Surface roughness of etched samples was examined using a scanning electron microscope. Obtained data were statistically analysed using one-way analysis of variance (ANOVA) and Bonferroni post hoc test with a level of significance α = 0.05. The results of the statistical methods applied indicate that µSBS mean difference for leucite-reinforced ceramic (EP) was statistically significant (p < 0.05). However, µSBS values for hybrid ceramic (VE) and lithium disilicate ceramic (EX) were not affected, from a statistical point of view, by the conditioning time (p > 0.05).

Epithelial Sodium Channel Inhibition by Amiloride Addressed with THz Spectroscopy and Molecular Modeling.

THz spectroscopy is important for the study of ion channels because it directly addresses the low frequency collective motions relevant for their function. Here we used THz spectroscopy to investigate the inhibition of the epithelial sodium channel (ENaC) by its specific blocker, amiloride. Experiments were performed on A6 cells' suspensions, which are cells overexpressing ENaC derived from Xenopus laevis kidney. THz spectra were investigated with or without amiloride. When ENaC was inhibited by amiloride, a substantial increase in THz absorption was noticed. Molecular modeling methods were used to explain the observed spectroscopic differences. THz spectra were simulated using the structural models of ENaC and ENaC-amiloride complexes built here. The agreement between the experiment and the simulations allowed us to validate the structural models and to describe the amiloride dynamics inside the channel pore. The amiloride binding site validated using THz spectroscopy agrees with previous mutagenesis studies. Altogether, our results show that THz spectroscopy can be successfully used to discriminate between native and inhibited ENaC channels and to characterize the dynamics of channels in the presence of their specific antagonist.

Microbial Contamination and Survival Rate on Different Types of Banknotes.

In the COVID-19 pandemic context, numerous concerns have been raised regarding the hygienic status of certain objects we interact with on a daily basis, and especially cash money and their potential to harbor and transmit pathogenic bacteria. Therefore, in the present study, we analyzed different currency bills represented by British pounds (5 £, 10 £ and 20 £), Romanian lei (1 leu, 5 lei and 10 lei), U.S. dollars (1 $, 5 $ and 10 $) and Euros (5 €, 10 € and 20 €) in order to evaluate the bacterial survival rate and bacterial adherence. We used five reference microorganisms by American Type Culture Collection (ATCC, Manassas, VA, USA): Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 8739, Enterococcus sp. ATCC 19952, Salmonella enterica subsp. enterica serovar Typhi ATCC 6539, and Listeria monocytogenes ATCC 7644. Microorganisms were selected in accordance with the criteria of prevalence, pathogenicity, opportunism, and incidence. However, Maldi-TOF analysis from samples taken from the banknotes revealed only a few of the common pathogens that are traditionally thought to be found on banknotes. Some of the most important factors for the survival of pathogenic agents on surfaces are the presence of organic matter, temperature and humidity. Our data showed that Salmonella enterica survived 72 h on every banknote tested, while L. monocytogenes tended to improve persistence in humid conditions. Survival rate is also influenced by the substrate composition, being lower for polymer-based banknotes especially for Salmonella enterica, Listeria monocytogenes and Enterococcus sp. The adherence of bacterial strains was lower for polymer-based banknotes British pounds and Romanian Leu, in contrast to the cotton-based U.S dollars and Euro banknotes. The risk of bacterial contamination from the banknote bills is high as indicated by both a strong survival capacity and low adherence of tested bacteria with differences between the two types of materials used for the tested banknotes.

The expression of copper transporters associated with the ototoxicity induced by platinum-based chemotherapeutic agents.

BACKGROUND: Antitumor agents based on platinum have gained a well-established place in the treatment of several forms of cancer. Their efficiency is hampered by serious toxic effects against healthy tissues as well. Ototoxicity is a serious side effect leading to hearing impairment and represents an important issue affecting the patients' quality of life. The currently used platinum chemotherapeutics exert different toxicity towards cochlear cells. The aim of our study was to answer some questions regarding the differential uptake and cellular pharmacodynamics of Cisplatin (CDDP), Carboplatin (CBDCA) and Oxaliplatin (L-OHP) in the HEI-OC1 cochlear cell line. METHODS: We studied the expression of copper transporters CTR1, ATP7A and ATP7B which are presumably involved in the uptake, cellular transport and efflux of platinum compounds by immunofluorescence microscopy and flow-cytometry. The cellular uptake of the compounds was evaluated through the determination of intracellular platinum concentration by atomic absorption spectroscopy. The effects of the treatment of HEI-OC1 cells with platinum compounds were also evaluated: cytotoxicity with the Cell Titer Blue viability test, formation of reactive oxygen species with 2',7' -dichlorofluorescein diacetate, genotoxicity with the comet assay and apoptosis with the cleaved PARP ELISA test. RESULTS: CTR1, ATP7A and ATP7B were all expressed by HEI-OC1 cells. The treatment with the platinum compounds led to a modulation of their expression, manifested in a differential platinum uptake. Treatment with Cisplatin led to the highest intracellular concentration of platinum compared to Oxaliplatin and Carboplatin at the same dose. Treatment with CuSO4 reduced platinum uptake of all the compounds, significantly in the case of Cisplatin and Carboplatin. CDDP was the most cytotoxic against HEI-OC1 cells, with an IC50 = 65.79  µM, compared to 611.7 µM for L-OHP and 882.9 µM for CBDCA, at the same molar concentration. The production of ROS was the most intense after CDDP, followed by L-OHP and CBDCA. In the comet assay, at the 100 µM concentration, L-OHP and CBDCA induced DNA adducts while CDDP induced adducts as well as DNA strand breaks. CBDCA and L-OHP lead to a significant increase of cleaved PARP at 24h (p < 0.001), suggesting an important apoptotic process induced by these compounds at the used concentrations. CONCLUSIONS: The results obtained in the current study suggest that the modulation of copper transporters locally may represent a new strategy against platinum drugs ototoxicity.

Assessment of heavy metals (total chromium, lead, and manganese) contamination of residential soil and homegrown vegetables near a former chemical manufacturing facility in Tarnaveni, Romania.

Our aim was to assess local population exposure to heavy metals resulting from soil and vegetable contamination in Tarnaveni, Romania, an area located near a former chemical factory. We collected residential soil and vegetable samples from Tarnaveni and measured chromium (Cr), lead (Pb), and manganese (Mn) levels by atomic absorption spectrometry. We evaluated the relationship between soil and vegetable metals and the distance from the shuttered chemical factory, and calculated the hazard index to assess local population metal exposure via contaminated vegetable ingestion. Soil metal concentrations ranged between 15.6 and 525.8 mg/kg for total Cr, between 25.4 and 559.5 mg/kg for Pb, and between 363.1 and 1389.6 mg/kg for Mn. We found average concentrations of 17.8 mg/kg for total Cr, 2.2 mg/kg for Pb, and 116.6 mg/kg for Mn in local vegetables. We found soil concentrations for all three metals that exceeded normal background levels according to Romanian regulations (Pb exceeded 100 mg/kg in some of the samples), as well as measurable concentrations of metals in all analyzed vegetable samples. These preliminary data underscore a need for a more extensive investigation into associated adverse health effects in the exposed population.

Low-level arsenic exposure via drinking water consumption and female fecundity - A preliminary investigation.

High level arsenic exposure is associated with reproductive toxicity in experimental and observational studies; however, few data exist to assess risks at low levels. Even less data are available to evaluate the impact of low level arsenic exposure on human fecundity. Our aim in this pilot study was a preliminary evaluation of associations between low level drinking water arsenic contamination and female fecundity. This retrospective study was conducted among women previously recruited to a hospital-based case-control study of spontaneous pregnancy loss in Timis County, Romania. Women (n=94) with planned pregnancies of 5-20 weeks gestation completed a comprehensive physician-administered study questionnaire and reported the number of menstrual cycles attempting to conceive as the time to pregnancy (TTP). Drinking water samples were collected from residential drinking water sources and we determined arsenic levels using hydride generation-atomic absorption spectrometry (HG-AAS). Multivariable Cox-proportional hazards regression with Efron approximation was employed to evaluate TTP as a function of drinking water arsenic concentrations among planned pregnancies, adjusted for covariates. There was no main effect for drinking water arsenic exposure, yet the conditional probability for pregnancy was modestly lower among arsenic exposed women with longer TTPs, relative to women with shorter TTPs, and relative to unexposed women. For example, 1µg/L average drinking water arsenic conferred 5%, 8%, and 10% lower likelihoods for pregnancy in the 6th, 9th, and 12th cycles, respectively (P=0.01). While preliminary, our results suggest that low level arsenic contamination in residential drinking water sources may further impair fecundity among women with longer waiting times; however, this hypothesis requires confirmation by a future, more definitive study.

Impact of exposure to tobacco smoke, arsenic, and phthalates on locally advanced cervical cancer treatment-preliminary results.

BACKGROUND: Cancer research is a national and international priority, with the efficiency and effectiveness of current anti-tumor therapies being one of the major challenges with which physicians are faced. OBJECTIVE: To assess the impact of exposure to tobacco smoke, arsenic, and phthalates on cervical cancer treatment. METHODS: We investigated 37 patients with locally advanced cervical carcinoma who underwent chemotherapy and radiotherapy. We determined cotinine and five phthalate metabolites in urine samples collected prior to cancer treatment, by gas chromatography coupled to mass spectrometry, and urinary total arsenic by atomic absorption spectrometry with hydride generation. We used linear regression to evaluate the effects of cotinine, arsenic, and phthalates on the change in tumor size after treatment, adjusted for confounding variables. RESULTS: We detected no significant associations between urinary cotinine, arsenic, or phthalate monoesters on change in tumor size after treatment, adjusted for urine creatinine, age, baseline tumor size, and cotinine (for arsenic and phthalates). However, higher %mono-ethylhexyl phthalate (%MEHP), a putative indicator of phthalate diester metabolism, was associated with a larger change in tumor size (ß = 0.015, 95% CI [0.003-0.03], P = 0.019). CONCLUSION: We found no statistically significant association between the urinary levels of arsenic, cotinine, and phthalates metabolites and the response to cervical cancer treatment as measured by the change in tumor size. Still, our results suggested that phthalates metabolism may be associated with response to treatment for locally advanced cervical cancer. However, these observations are preliminary and will require confirmation in a larger, more definitive investigation.

The ecological risk of heavy metals in sediment from the Danube Delta.

The objectives of this study were to assess the sediment contamination with heavy metals and to investigate accordingly the ecological risk posed in the SE of the Danube Delta. Sediments are important in assessing the contamination as they act as reservoirs, transporters and contamination sources. Sediment samples were collected and analysed for lead, cadmium, arsenic and mercury, revealing levels higher than the background, especially for cadmium and mercury (Pb > As > Cd > Hg). Concentrations exceeding the probable effect limit were noticed for arsenic and mercury. The contamination indexes describe the study area as having almost half of the samples as contaminated (pollution load index-PLI 1.04), however the contamination is mostly low-to moderate (modified contamination degree-mCd 1.36). The sediment contamination poses mostly a low ecological risk (RI 94.8). The sediment quality guideline quotient (SQG-Q 0.29) describes a moderate impact, while the probable effect concentration quotient (PEC-Q 0.16) confirms that there are no levels likely to affect the aquatic biota. In our study area, the main Branch of the Danube River and the Secondary Delta are the most affected by contamination, while the narrow, reed abundant channels as the preferred habitat of most aquatic organisms, have a low contamination level.

Low level arsenic contaminated water consumption and birth outcomes in Romania-An exploratory study.

Women are exposed to drinking water with low arsenic concentrations (<10.0µg/L) worldwide, yet little work has been done to assess the risk. To begin to address this data gap, we conducted an exploratory study of birth outcomes in Timis County, Romania. We prospectively followed 122 women with singleton deliveries, for whom we constructed individual exposure indicators using self-reported water consumption weighted by arsenic measured in drinking water sources. There were no overall confounder-adjusted effects for arsenic exposure on birth outcomes. Yet, higher average arsenic (10µg/L) was associated with a -2.45 lower birth weight Z-score (P=0.021) and a -1.17 shorter birth length Z-score (P=0.029) among smokers. Higher average iAs (10µg/L) was also associated with smaller ponderal index in boys (P=0.023). Our results suggest smoking may potentiate an otherwise benign arsenic exposure. A larger, more definitive biomarker-based study is needed to investigate the potential risks in conjunction with smoking.

A pilot study of low-moderate drinking water arsenic contamination and chronic diseases among reproductive age women in Timis County, Romania.

We conducted a pilot study of associations between drinking water contaminated by inorganic arsenic (iAs), mostly <10 µg/L, and self-reported chronic diseases in 297 pregnant women. Adjusted for confounding variables, we identified a positive association between iAs and heart disease (OR = 1.63, 95%CI 0.81-3.04, p = 0.094), which was stronger for women living at their current residence ≥ 10 years (OR = 2.47, 95%CI 0.87-10.43, p = 0.058). Confounder-adjusted associations were also suggested for iAs with kidney disease (OR = 1.32, 95%CI 0.77-2.21, p = 0.265) and with high blood pressure (OR = 1.36, 95%CI 0.68-2.39, p = 0.300). A post hoc power analysis indicated the need for a larger study with more statistical power.

Robotic-assisted radical prostatectomy - the 5-year Romanian experience.

PURPOSE: Radical prostatectomy is the standard therapeutic approach for localized prostate cancer. After the implementation of robotic surgery in Romania, the indication extended progressively to locally advanced prostate cancer. Our objective was to evaluate the oncological and functional outcomes in patients undergoing robotic-assisted radical prostatectomy (RARP), 5 years after the first intervention in Romania. METHODS: Between November 2009 and July 2014, 207 RARPs were performed using the da Vinci SI Surgical System. Perioperative data were prospectively collected. The oncological and functional follow-up was up to 55 months (range 3-55). RESULTS: Patient stratification according to D'Amico risk categories was 16% low risk, 56.7% intermediate risk and 27.3% high risk. Median console time was 210 min (range 160-360). Median blood loss was 300 ml (range 50-1300), transfusion being required in 2.9% of the cases. Histopathological examinations showed pT3 in 40.8% of the cases, with a positive surgical margin rate of 21.1%, 13.6% for pT2, and 32.1% for pT3. Continence rate (0-1 daily safety pad) at 6, 12, 24 and 55 months was 88.3, 88.8, 90.1, and 93.7% respectively. Overall sexual function restoration rate at 6, 12, 24 and 55 months was 41.1, 44.4, 47.4 and 53%, respectively. Biochemical recurrence rate during follow-up was 6.9%. CONCLUSIONS: RARP is a minimally invasive therapeutic approach for prostate cancer, with acceptable outcomes, even in countries such as Romania, where the detection rate for localized prostate cancer is lower compared to other European countries due to lack of national screening programs.

Consumption of arsenic-contaminated drinking water and anemia among pregnant and non-pregnant women in northwestern Romania.

Anemia is a global health problem. To evaluate the impact of low-moderate water arsenic exposure (mostly <10 µg/L) on anemia, we conducted a cross-sectional study of 217 Romanian women. The adjusted prevalences for 'any' anemia (prevalence proportion ratio (PPR)=1.71, 95% CI 0.75-3.88) and pregnancy anemia (PPR=2.87, 95% CI 0.62-13.26) were higher among drinking water arsenic exposed women than among unexposed women. These preliminary data underscore the need for a more definitive study in this area.

Pregnant women in Timis County, Romania are exposed primarily to low-level (<10µg/l) arsenic through residential drinking water consumption.

Excessive arsenic content in drinking water poses health risks to millions of people worldwide. Inorganic arsenic (iAs) in groundwater exceeding the 10µg/l maximum contaminant level (MCL) set by the World Health Organization (WHO) is characteristic for intermediate-depth aquifers over large areas of the Pannonian Basin in Central Europe. In western Romania, near the border with Hungary, Arad, Bihor, and Timis counties use drinking water coming partially or entirely from iAs contaminated aquifers. In nearby Arad and Bihor counties, more than 45,000 people are exposed to iAs over 10µg/l via public drinking water sources. However, comparable data are unavailable for Timis County. To begin to address this data gap, we determined iAs in 124 public and private Timis County drinking water sources, including wells and taps, used by pregnant women participating in a case-control study of spontaneous loss. Levels in water sources were low overall (median=3.0; range=<0.5-175µg/l), although higher in wells (median=3.1, range=<0.5-1.75) than in community taps (median=2.7, range=<0.5-36.4). In a subsample of 20 control women we measured urine biomarkers of iAs exposure, including iAs (arsenite and arsenate), dimethylarsinic acid (DMA), and methylarsonic acid (MMA). Median values were higher among 10 women using iAs contaminated drinking water sources compared to 10 women using uncontaminated sources for urine total iAs (6.6 vs. 5.0µg/l, P=0.24) and DMA (5.5 vs. 4.2µg/l, P=0.31). The results suggested that the origin of urine total iAs (r=0.35, P=0.13) and DMA (r=0.31, P=0.18) must have been not only iAs in drinking-water but also some other source. Exposure of pregnant women to arsenic via drinking water in Timis County appears to be lower than for surrounding counties; however, it deserves a more definitive investigation as to its origin and the regional distribution of its risk potential.

Consumption of low-moderate level arsenic contaminated water does not increase spontaneous pregnancy loss: a case control study.

BACKGROUND: Previous work suggests an increased risk for spontaneous pregnancy loss linked to high levels of inorganic arsenic (iAs) in drinking water sources (>10 µg/L). However, there has been little focus to date on the impact of low-moderate levels of iAs in drinking water (<10 µg/L). To address this data gap we conducted a hospital-based case-control study in Timis County, Romania. METHODS: We recruited women with incident spontaneous pregnancy loss of 5-20 weeks completed gestation as cases (n = 150), and women with ongoing pregnancies matched by gestational age (±1 week) as controls (n = 150). Participants completed a physician-administered questionnaire and we collected water samples from residential drinking sources. We reconstructed residential drinking water exposure histories using questionnaire data weighted by iAs determined using hydride generation-atomic absorption spectrometry (HG-AAS). Logistic regression models were used to generate odds ratios (OR) and 95% confidence intervals (CI) for associations between iAs exposure and loss, conditioned on gestational age and adjusted for maternal age, cigarette smoking, education and prenatal vitamin use. We explored potential interactions in a second set of models. RESULTS: Drinking water arsenic concentrations ranged from 0.0 to 175.1 µg/L, with median 0.4 µg/L and 90th%tile 9.4 µg/L. There were no statistically significant associations between loss and average or peak drinking water iAs concentrations (OR 0.98, 95% CI 0.96-1.01), or for daily iAs intake (OR 1.00, 95% CI 0.98-1.02). We detected modest evidence for an interaction between average iAs concentration and cigarette smoking during pregnancy (P = 0.057) and for daily iAs exposure and prenatal vitamin use (P = 0.085). CONCLUSIONS: These results suggest no increased risk for spontaneous pregnancy loss in association with low to moderate level drinking water iAs exposure. Though imprecise, our data also raise the possibility for increased risk among cigarette smokers. Given the low exposures overall, these data should reassure pregnant women and policy makers with regard to the potential effect of drinking water iAs on early pregnancy, though a larger more definitive study to investigate the potential risk increase in conjunction with cigarette smoking is merited.

The European COPHES/DEMOCOPHES project: towards transnational comparability and reliability of human biomonitoring results.

COPHES/DEMOCOPHES has its origins in the European Environment and Health Action Plan of 2004 to "develop a coherent approach on human biomonitoring (HBM) in Europe". Within this twin-project it was targeted to collect specimens from 120 mother-child-pairs in each of the 17 participating European countries. These specimens were investigated for six biomarkers (mercury in hair; creatinine, cotinine, cadmium, phthalate metabolites and bisphenol A in urine). The results for mercury in hair are described in a separate paper. Each participating member state was requested to contract laboratories, for capacity building reasons ideally within its borders, carrying out the chemical analyses. To ensure comparability of analytical data a Quality Assurance Unit (QAU) was established which provided the participating laboratories with standard operating procedures (SOP) and with control material. This material was specially prepared from native, non-spiked, pooled urine samples and was tested for homogeneity and stability. Four external quality assessment exercises were carried out. Highly esteemed laboratories from all over the world served as reference laboratories. Web conferences after each external quality assessment exercise functioned as a new and effective tool to improve analytical performance, to build capacity and to educate less experienced laboratories. Of the 38 laboratories participating in the quality assurance exercises 14 laboratories qualified for cadmium, 14 for creatinine, 9 for cotinine, 7 for phthalate metabolites and 5 for bisphenol A in urine. In the last of the four external quality assessment exercises the laboratories that qualified for DEMOCOPHES performed the determinations in urine with relative standard deviations (low/high concentration) of 18.0/2.1% for cotinine, 14.8/5.1% for cadmium, 4.7/3.4% for creatinine. Relative standard deviations for the newly emerging biomarkers were higher, with values between 13.5 and 20.5% for bisphenol A and between 18.9 and 45.3% for the phthalate metabolites. Plausibility control of the HBM results of all participating countries disclosed analytical shortcomings in the determination of Cd when using certain ICP/MS methods. Results were corrected by reanalyzes. The COPHES/DEMOCOPHES project for the first time succeeded in performing a harmonized pan-European HBM project. All data raised have to be regarded as utmost reliable according to the highest international state of the art, since highly renowned laboratories functioned as reference laboratories. The procedure described here, that has shown its success, can be used as a blueprint for future transnational, multicentre HBM projects.

Aggregation of red blood cells in suspension: study by light-scattering technique at small angles.

Red blood cells (RBCs) in the presence of plasma proteins or other macromolecules have a tendency to form aggregates. Light-scattering technique was used to investigate the RBC aggregation process. A highly diluted suspension of RBCs was illuminated with a 632.8-nm HeNe laser. Angular-resolved measurements of light intensity scattered by an RBC suspension from a 200-microm thick optical glass cuvette during 10 min of their aggregation process were performed at 1 to 4 off-axis deg with a very high angular resolution, at hematocrits in the range of 3.5 x 10(-2) to 10(-1). The angular spreading of forward-scattered light at small angles during the RBC aggregation process was described in terms of a new, effective phase function model that has been used for fitting the experimental data. The aggregated RBCs' optical properties, such as effective scattering anisotropy and scattering cross section, were determined. The results were compared with prediction of Mie theory for equivolumetric spherical particles. The time dependence of the aggregates mean radius and of the mean number of cells per aggregate was also calculated. Last, the potential of the proposed technique (forward-scattering light technique) as a new quantitative investigation of cellular aggregation process was estimated.