Morning Void Urine Research Articles

Assessment of children’s exposure to currently used pesticides in wallonia, Belgium

In spring 2016, a study was carried out to characterize currently used pesticide (CUP) exposure among children living in Wallonia (Belgium). Pesticides were measured in both first morning urine voids of 258 children aged from 9 to 12 years and in ambient air collected close to the children’s schools. Out of the 46 pesticides measured in the air, 19 were detected with frequencies varying between 11 % and 100 %, and mean levels ranging from <0.04 to 2.37 ng/m³. Only 3 parent pesticides were found in 1–10% of the urine samples, while all the metabolites analyzed were positively detected at least once. The captan metabolite (THPI) was quantified in 23.5 % of the samples, while 3,5,6-trichloro-2-pyridinol (chlopryrifos metabolite) was detected in all urines with levels ranging from 0.36–38.96 μg/l. 3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (t-DCCA) and diethylphosphate were the most abundant pyrethroid metabolites and dialkylphosphate measured. The air inhalation was demonstrated to be a minor route of exposure for the selected CUPs. Statistical regressions highlighted predictors of exposure for some pesticides such like consumption of grey bread, presence of carpets at home or indoor use of pesticides, although no clear source was identified for most of them.

Within-subject and between-subject biological variation of first morning void urine amino acids in 12 healthy subjects.

Background Urine amino acid analysis is used for the assessment of various diseases. The aim of this study was to estimate the valid biological variation (BV) components (within- and between-subjects) required for the safe clinical application of free urine amino acids. Methods First morning void urine samples were taken from 12 healthy subjects (five females, seven males) once a week for 10 consecutive weeks, and amino acid analysis was performed using an Agilent 6470 triple quadrupole tandem mass spectrometer instrument. The obtained data were subjected to normality, outlier and variance homogeneity analyses prior to coefficient of variation (CV) analysis. Within- and between-subject BV values (CVI and CVG) of 39 amino acids were determined for all subjects. In addition, the index of individuality (II), reference change value (RCV), imprecision, bias and total error were estimated using BV data obtained from our study. Results The CVI values ranged from 8.9 (histidine) to 36.8% (trans-4-hydroxyprolin), while the CVG values ranged from 25.0 (1-methyl-L-histidine) to 63.3% (phenylalanine). The II value of most amino acids was less than 0.6 and ranged between 0.21 and 0.88. The imprecision, bias and total error ranged between 4.45 and 16.6, between 7.69 and 16.6, and between 18.4 and 43.2, respectively. Conclusions This study, designed according to a rigorous protocol, has the feature of being the first to give information about BV data of urine amino acids. We believe that the reference intervals have a limitation in the evaluation of consecutive results from an individual, so the use of RCV would be more appropriate.

Impact of fractional excretion of sodium on a single morning void urine collection as an estimate of 24-hour urine sodium.

The standard for assessing dietary sodium intake is to measure 24-hour urine sodium. On average, 93% of daily sodium intake is excreted over24-hours. Expense and difficulties in obtaining complete 24-hour collections have led to the measurement of sodium concentration in spot and single-void urine samples, using predictive equations to estimate 24-hour urine sodium. Although multiple predictive equations have been developed, in addition to having anaverage bias, all the equations overestimate 24-hour sodium at lower levels of 24-hour sodium and underestimate 24-hour urine sodium at higher levels of24-hour sodium. One of the least biased estimating equations is the INTERSALT equation, which incorporates a spot urine creatinine concentration. The authors hypothesized that differential fractional excretion of sodium (FeNa)(derived from a morning void collection) relative to creatinine would impacton the accuracy of the INTERSALT equation in estimating 24-hour urine sodium. In a prospective study of 139 adults aged 65years and over, three sequential morning void and 24-hour urine samples were examined. There was a significant correlation between increasing FENa and the difference between estimated and measured 24-hours urine sodium (r=0.358, P<.01). In the lowest quartile of FENa, the INTERSALT equation overestimated 24-hour urine sodium, but underestimated 24-hour urine sodium with greater magnitude in each of the subsequent quartiles of FENa. Differential excretion of sodium relative to creatinine, potentially impacted by renal blood flow and hydration, among other factors, affected the accuracy of the INTERSALT equation. Additional research may refine the INTERSALT and other predictive equations to increase their accuracy.

Spectral characteristics of urine specimens from healthy human volunteers analyzed using Raman chemometric urinalysis (Rametrix).

Raman chemometric urinalysis (Rametrix™) was used to analyze 235 urine specimens from healthy individuals. The purpose of this study was to establish the “range of normal” for Raman spectra of urine specimens from healthy individuals. Ultimately, spectra falling outside of this range will be correlated with kidney and urinary tract disease. Rametrix™ analysis includes direct comparisons of Raman spectra but also principal component analysis (PCA), discriminant analysis of principal components (DAPC) models, multivariate statistics, and it is available through GitHub as the Rametrix™ LITE Toolbox for MATLAB®. Results showed consistently overlapping Raman spectra of urine specimens with significantly larger variances in Raman shifts, found by PCA, corresponding to urea, creatinine, and glucose concentrations. A 2-way ANOVA test found that age of the urine specimen donor was statistically significant (p < 0.001) and donor sex (female or male identification) was less so (p = 0.0526). With DAPC models and blind leave-one-out build/test routines using the Rametrix™ PRO Toolbox (also available through GitHub), an accuracy of 71% (sensitivity = 72%; specificity = 70%) was obtained when predicting whether a urine specimen from a healthy unknown individual was from a female or male donor. Finally, from female and male donors (n = 4) who contributed first morning void urine specimens each day for 30 days, the co-occurrence of menstruation was found statistically insignificant to Rametrix™ results (p = 0.695). In addition, Rametrix™ PRO was able to link urine specimens with the individual donor with an average of 78% accuracy. Taken together, this study established the range of Raman spectra that could be expected when obtaining urine specimens from healthy individuals and analyzed by Rametrix™ and provides the methodology for linking results with donor characteristics.

Mothers and children are related, even in exposure to chemicals present in common consumer products

BackgroundPhthalates, bisphenol A (BPA) and triclosan (TCS) are detectable in the vast majority of people. Most humans are continuously exposed to these chemicals due to their presence in food or in everyday consumer products. The measurement of these compounds in family members may help to explore the impact of major lifestyle factors on exposure. Mothers and (young) children are especially interesting to study, as they mostly share considerable parts of daily life together. Materials and methodsPhthalate metabolites, bisphenol A (BPA) and triclosan (TCS) were measured in first morning void urine, collected in mother-child pairs (n = 129) on the same day. The mothers (27-45y) and their children (6-11y) were recruited in the Brussels agglomeration and rural areas of Belgium in the context of the European COPHES-DEMOCOPHES human biomonitoring project. Face-to-face questionnaires gathered information on major exposure sources and lifestyle factors. Exposure determinants were assessed by multiple linear regression analysis. ResultsThe investigated compounds were detectable in nearly all mothers (92.8–100%) and all children (95.2–100%). The range (P90 vs. P10) of differences in urinary concentrations within each age group was for most compounds around 10–20 fold, and was very high for TCS up to 35 and 350-fold in children and mothers respectively. Some participants exceeded the tolerable daily intake guidelines as far as they were available from the European Food Safety Authority (EFSA). Overall, for BPA, the urinary concentrations were similar among both age groups. Most urinary phthalate metabolites were higher in children compared to the mothers, except for monoethyl phthalate (MEP). TCS levels were generally higher in the mothers. Despite the difference in mothers' and children's urinary concentrations, the creatinine-corrected levels were correlated for all biomarkers (Spearman rank r = 0.32 to 0.66, p < 0.001). Furthermore, for phthalates, similar home and lifestyle factors were associated with the urinary concentrations in both age groups: home renovation during last two years or redecoration during the last year for di-ethyl phthalate (DEP); PVC in home for di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP) and butyl benzyl phthalate (BBzP), and personal care products use for DiBP and DnBP. Based on questionnaire information on general food type consumption patterns, the exposure variability could not be explained. However, comparing the phthalate intake from the current study with earlier assessed Belgian food intake calculations for both ages, food in general was estimated to be the major intake source for di-ethyl hexyl phthalate (DEHP), with diminishing importance for BBzP, DiBP and DnBP. ConclusionOur results confirm, that children and their mothers, sharing diets and home environments, also share exposure in common consumer products related chemicals. By collecting morning urine levels on the same day, and using basic questionnaires, suspected exposure routes could be unraveled.

Longitudinal stability in cigarette smokers of urinary eicosanoid biomarkers of oxidative damage and inflammation.

The urinary metabolites (Z)-7-[1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopentyl]hept-5-enoic acid (8-iso-PGF2α), an F2-isoprostane and biomarker of oxidative damage, and “prostaglandin E2 metabolite” (PGE-M), a biomarker of inflammation, are elevated in cigarette smokers. However, there is little information in the literature on the longitudinal stability of these widely used biomarkers. In a large clinical trial involving 10 institutional sites, smokers were given, free of charge over a period of 20 weeks, Spectrum NRC600/601 research cigarettes containing 15.5 mg nicotine/g tobacco. All participants were instructed to smoke these cigarettes for the duration of the study. At weeks 4, 8, 12, 16, and 20, first morning urine voids were collected and analyzed for 8-iso-PGF2α and PGE-M using validated liquid chromatography-electrospray ionization-tandem mass spectrometry methods. The mean level of 8-iso-PGF2α at Week 4 was 1.34 ± 1.08 (S.D.) pmol/mg creatinine (N = 226) while that of PGE-M was 73.7 ± 113 (S.D.) pmol/mg creatinine (N = 232). The corresponding levels at Week 20 were 1.35 ± 0.93 (S.D.) pmol/mg creatinine (N = 209) for 8-iso-PGF2α and 74.2 ± 142 (S.D.) pmol/mg creatinine (N = 210) for PGE-M. There was variation in these values in the intervening weeks. The intra-class correlation coefficients (ICC) were 0.51 (95% CI, 0.45, 0.57) and 0.36 (0.30, 0.43), for 8-iso-PGF2α and PGE-M, respectively, indicating fair longitudinal stability for 8-iso-PGF2α and poorer longitudinal stability for PGE-M in cigarette smokers. Males had higher ICC values than females for both 8-iso-PGF2α and PGE-M. These results indicate that, in addition to cigarette smoking, endogenous processes of oxidative damage and inflammation influence the levels of these biomarkers over time among current smokers.

N-Acetyl-seryl-aspartyl-lysyl-proline is a potential biomarker of renal function in normoalbuminuric diabetic patients with eGFR ≥ 30ml/min/1.73m2.

A biomarker, by which we can predict alterations of renal function in normoalbuminuric diabetic patients, is not available. Here, we report that endogenous anti-fibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) represents a potential biomarker to predict alterations in eGFR in normoalbuminuric diabetic patients. We analyzed 21 normoalbuminuric diabetic patients with eGFR ≥ 30ml/min/1.73m2 and measured AcSDKP levels in first morning void urine. We divided patients into two groups based on the median values: low or high urinary AcSDKP groups (uAcSDKP/Crlow or uAcSDKP/Crhigh). At baseline, no significant differences in sex, age, HbA1c, BMI, serum creatinine levels, etc., were observed between the two groups. During ~ 4years, the alteration in eGFR [ΔeGFRop (ΔeGFR observational periods)] was significantly stable in uAcSDKP/Crhigh group compared with uAcSDKP/Crlow group over time (P = 0.003, χ2 = 8.58). We also evaluated urine kidney injury molecule-1 (uKim-1) levels and found that ΔeGFRop was also stable in low uKim-1 group compared with high uKim-1 group over time (P = 0.004, χ2 = 8.38). Patients who fulfilled the criteria for both uAcSDKP/Crhigh and uKim-1low exhibited stable ΔeGFRop (P < 0.001, χ2 = 30.4) when compared to the remaining patients. Plasma AcSDKP (P = 0.015, χ2 = 5.94) and urine β2-microglobulin (P = 0.038, χ2 = 4.31) also display weak but significant predictor of ΔeGFRop as well. AcSDKP represents a potentially useful biomarker to predict alterations in the renal function of patients with diabetes presenting normoalbuminuria.

Inter-Day Variability of Metabolites of DEHP and DnBP in Human Urine-Comparability of the Results of Longitudinal Studies with a Cross-Sectional Study.

In the current paper, we compare the inter-day variability of the metabolite concentration of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) in 247 morning urine samples obtained from 19 probands of different age and sex with the metabolite concentration in morning urine obtained from 215 probands of the “Tübingen Survey” cross-sectional study. In the first longitudinal study the morning urine of seven volunteers was collected four times a year for seven consecutive days (course of the year study). In a second study the morning urine of 12 students of a boarding school was collected on five consecutive days (course of a week study). For participants of the two different longitudinal studies we obtained mean concentrations in first void morning urine for mono(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP) in the range from 21.3 to 110 µg/L, 10.5 to 35.6 µg/L for mono(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), and 45.5 to 143 µg/L for mono(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP). The corresponding relative standard deviations (rel. Std.D in %) for these DEHP-metabolites vary between 45.2% and 262%. The 50th percentiles vary for 5OH-MEHP between 17.5 and 65.6 µg/L, for 5oxo-MEHP between 9.0 and 20.3 µg/L and for 5cx-MEPP between 42.5 and 82.0 µg/L. For participants of the “Tübingen Survey” cross-sectional study the means vary for 5OH-MEHP between 58.2 and 85.0 µg/L, between 33.6 and 38.7 µg/L for 5oxo-MEHP and between 110 and 158 µg/L for 5cx-MEPP with rel. standard deviations in a range between 86.5 to 175%. The corresponding 50th percentiles vary for 5OH-MEHP between 26.5 and 42.3 µg/L, for 5oxo-MEHP between 18.0 and 26.3 µg/L, and for 5cx-MEPP between 57.2 and 77.6 µg/L. In order to compare the data from the longitudinal studies with the data from the cross-sectional study, the frequency distribution of the results of both types of studies was compared first. In a second step, the results of a t-test (p-values) was used to check whether the results of the long-term studies differ statistically significantly from the results of the cross-sectional study (p < 0.05). The present data show that the frequency distributions of DEHP-metabolites are comparable. For most of the participants respectively subject groups t-test results prove that no statistical significant difference between results obtained from longitudinal studies compared to the results of the cross-sectional study are apparent. The available data on the exposure of individual subjects mirror the data obtained from cross-sectional studies of the general population and give hints to the risk of individual increased DEHP exposure. Results also highlight the importance of living conditions on the risk of increased DEHP exposure.

Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan

BackgroundLow-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children. To evaluate the OP exposure levels, single urine sampling is commonly adopted to measure the levels of dialkylphosphates (DAPs), common OP metabolites. However, the inter-day variations of urinary DAP concentrations within subjects are supposed to be large due to the short biological half-lives of the metabolites, and it is thus considered difficult to accurately assess OP exposure during pregnancy with single sampling. This study aimed to assess intra-individual variations of DAP concentrations and the reproducibility of the exposure dose categorization of OPs according to DAP concentration ranges in pregnant women in Japan.MethodsUrine samples were collected from 62 non-smoking pregnant women (12–22 weeks of gestation) living in Aichi Prefecture, Japan. First morning void (FMV) and spot urine samples taken between lunch and dinner on the same day were collected on five different days during 2 weeks. The concentrations of DAP and creatinine in urine samples were measured using an ultra performance liquid chromatography with tandem mass spectrometry. Creatinine-adjusted and unadjusted concentrations were used for the intraclass correlation coefficient (ICC) calculations and surrogate category analyses.ResultsFor all DAP metabolites, the creatinine-adjusted single ICCs exceeded 0.4, indicating moderate reliability. Overall, ICCs of spot urine samples taken in the afternoon were better than those taken as FMV. Surrogate category analyses showed that participants were categorized accurately into four exposure dose groups according to the quartile points.ConclusionThis study indicated that a single urine sample taken in the afternoon may be useful in assessing OP exposure as long as the exposure is categorized into quartiles when conducting epidemiological studies in early to mid-pregnant women in Japan.

A Cross-Over Health Intervention Trial of Children Consuming an Organic Diet

Introduction: The effectiveness of a systematic organic diet in improving key parameters of health in human studies has not been well studied. The objective of this study was to determine the intervention effectiveness of an organic diet in significantly reducing urinary pesticide metabolite concentrations and concomitantly affecting biomarkers of inflammation and oxidative stress in children.Methods: A 2 x 2 cluster-randomised cross-over trial at subject level study was designed for healthy children (n&amp;#61;150, 11-12 years old) from families historically consuming a conventional diet (&amp;gt;80% of weekly diet). The study period consisted of a 40-day conventional diet arm and a 40-day organic diet arm. Diaries were used to record the consumed diet and extent of compliance. A total of five morning urine voids samples per child in select time points of both conventional and organic phases were collected. Select metabolites of neonicotinoid/pyrethroid pesticides were monitored in children&amp;#8217;s urine using tandem mass spectrometry. Biomarkers of oxidative stress/inflammation and creatinine were measured in urine (isoprostane 8-iso-PGF2a and 8-OHdG) using immunoassay kits. Linear mixed-effects models of the biomarkers of effect were constructed to evaluate the main effects of organic diet and biomarker of exposure to pesticides accounting for both between- and within-subject variability.Results: The effect of organic diet on the biomarkers of oxidative stress/inflammation accounting for known confounders will be presented.Conclusions: To the best of our knowledge, this is the first time that the concomitant assessment of biomarkers of effect (oxidative stress/inflammation) along with biomarkers of exposure to pesticides in children systematically consuming an organic diet has been performed.

Simultaneous quantification of urinary 6‑sulfatoxymelatonin and 8‑hydroxy‑2′‑deoxyguanosine using liquid chromatography-tandem mass spectrometry

Oxidative stress is involved in the pathophysiology of many diseases and natural aging. Urinary 8‑hydroxy‑2′‑deoxyguanosine (8‑OHdG), a stable product of DNA oxidative damage, has been widely used as an oxidative stress biomarker. However, only reporting 8‑OHdG level, as commonly done previously, does not take into account of damaged DNA molecules that have not been repaired and excreted in urine. Melatonin is known to help with DNA repairs and hence can modify 8‑OHdG levels. 6‑sulfatoxymelatonin (aMT6s) is a major metabolite of melatonin excreted in urine. Hence it is useful to measure both urinary 8‑OHdG and aMT6s together. Here we describe a newly developed and validated method to simultaneously measure these two compounds using high-performance liquid chromatography-tandem mass spectrometry. Using a liquid-liquid extraction (20% methanol) at a pH ~ 7, as opposed to a solid-phase extraction used previously, substantially expedited the sample pretreatment process. The calibration curves showed a linear range from 0.5 to 100 ng/mL for aMT6s with a R2 of 0.9999 and from 1.5 to 100 ng/mL for 8‑OHdG with R2 of 0.9985. The recovery for 8‑OHdG and aMT6s was 102 ± 2% and 88 ± 4%, respectively. The limits of detection were 0.1 ng/mL for aMT6s and 0.5 ng/mL for 8‑OHdG, while the lower limits of quantification were 0.3 ng/mL for aMT6s and 1.0 ng/mL for 8‑OHdG. For both compounds, the retention time standard deviation was 0.03 min, and inter-day and intra-day variability, expressed as relative standard deviation (RSD), ranged from 4.5%–15.8%. The new method was successfully applied to analyze both compounds in the first morning and midday urine voids from five volunteers. The results support that this method is capable of rapidly and accurately measuring urinary 8‑OHdG and aMT6s simultaneously. This new method is expected to have important applications in biomedical and environmental health studies involving the oxidative stress pathophysiological pathway.

Urinary miRNA as a Potential Biomarker in Kidney Transplantation

Introduction and Aims Kidney transplantation is the best available treatment for patients with end stage chronic kidney disease. The diagnosis of the pathology of the kidney graft relies on the determination of the creatinine, estimated glomerular filtration rate and proteinuria. These parameters are altered after the onset of renal injury and they are not able to discern between various pathologies. The kidney biopsy, an invasive and not extent of complications procedure, remains essential for the diagnosis of the renal pathology. Hence the importance of finding parameters that allow an early diagnosis of the pathology involved in graft dysfunction. Urine is ideal for the study of possible biomarkers, its collection is easy, non-invasive and repeatable. Our aim was to analyse the miRNA content of urinary extracellular vesicles of the transplanted patients and define differential patterns of expression of miRNA specific to the different pathologies of the transplanted kidney. Methods Kidney transplanted patients with a kidney biopsy performed for clinical indication were selected. The biopsies were assessed according to Banff classification. From all biopsies those exhibiting acute cellular rejection (ACR), interstitial fibrosis and tubular atrophy (IFTA) and calcineurin inhibitors toxicity (CIT) were selected. Kidney transplanted patients with normal function (defined as eGFR CKD-EPI >90ml/min/1,72m2) and without proteinuria were defined as control group. First morning void urine was collected from patients. After low speed centrifugation to eliminate cell debris, Urine EVs were obtained by Size exclusion chromatography after urine concentration. EV-contained fractions selected as CD63 and CD9 positive fractions were pooled. Then, total RNA was extracted using mirCURY kit and high-throughput sequencing was done. Taqman qPCR were performed using the Taqman Advance miRNA assays for the following miRNAs (hsa-miR-1; has-miR-2, hsa-miR-3; hsa-miR-4, hsa-miR-5, hsa-miR-6; hsa-miR-7; hsa-miR-8; hsa-miR-9, has-miR-10). hsa-miR-10a-5p was used as internal control and Total RNA kidney (Thermosfisher) was used as positive control. Ct values of triplicates were averaged and used for ΔCt calculations. Principal component analysis (PCA), Receiver Operating Characteristic (ROC) analysis and Mann-Whitney test were done using GraphPrims v5 and SPSS v15. P<0.05 were set as significant. Results A total of 8 control samples and 14 pathological samples (3 IFTA, 6 ACR and 5 CIT) were processed by next generation sequencing. A total of 1500 miRNAs were identified, then after normalization and principal component analysis 12 miRNAs were selected to be tested in a new cohort. A new control group(N=8) and patients (IFTA: n=9; ACR: n=9; CIT: n=6) were selected as mentioned before. Then, uEVs and total RNA were isolated as described above. We found that eight miRNAs had different expression patterns in the urine of patients with any kind of graft pathology compared to controls. Conclusion miRNA profiling in urine has potential as a novel method for detecting pathology in kidney transplant.

How to measure and monitor albuminuria in healthy toddlers?

ObjectiveUrinary albumin:creatinine ratio (UACR) in first morning void (FMV) urine samples collected over three days is the recommended method for measuring and monitoring albuminuria in adults in the clinical setting. Such a guideline is not available for toddlers and young children. We tested several urine collection strategies for albuminuria measurement in toddlers in a prospective observational study.Main outcomes measuresBoth a FMV and a random daytime urine sample were collected on three consecutive days at week 0, 4, and 8 in toddlers aged 12–48 months. Intra-individual coefficients of variation (CV) of urinary albumin (UAC) and UACR were compared using only the first measurement and using all three measurements per time point. In addition, these were compared with published CV of adults.ResultsA total of 80 toddlers (mean age 26.6 months, 53% male) were included. Intra-individual CV of FMV samples appeared lower than with random samples. The intra-individual CV in UAC or UACR was smaller using multiple compared to single samples. The lowest intra-individual CV was observed when UAC was measured in FMV over three consecutive days (38.3%). CV of UAC was similar to values published for adults. However, UACR CV was considerably higher in toddlers.ConclusionsThese data show that—in analogy with adult data—multiple first morning void urine samples should be preferred to single or random urine samples for establishing and monitoring albuminuria in toddlers. Further studies are needed to investigate why creatinine correction for differences in urine dilution is less effective in children.

Health Risk Assessment and Urinary Excretion of Children Exposed to Arsenic through Drinking Water and Soils in Sonora, Mexico.

Environmental arsenic exposure is associated with increased risk of non-cancerous chronic diseases and a variety of cancers in humans. The aims of this study were to carry out for the first time a health risk assessment for two common arsenic exposure routes (drinking water and soil ingestion) in children living in the most important agricultural areas in the Yaqui and Mayo valleys in Sonora, Mexico. Drinking water sampling was conducted in the wells of 57 towns. A cross-sectional study was done in 306 children from 13 villages in the valleys. First morning void urine samples were analyzed for inorganic arsenic (InAs) and monomethyl and dimethyl arsenic (MMA and DMA) by HPLC/ICP-MS. The results showed a wide range of arsenic levels in drinking water between 2.7 and 98.7μg As/L. Arsenic levels in agricultural and backyard soils were in the range of < 10-27mg As/kg. The hazard index (HI) = ∑hazard quotient (HQ) for drinking water, agricultural soil, and backyard soil showed values > 1 in 100% of the study towns, and the carcinogenic risk (CR) was greater than 1E-04 in 85%. The average of arsenic excreted in urine was 31.7μg As/L, and DMA had the highest proportion in urine, with averages of 77.8%, followed by InAs and MMA with 11.4 and 10.9%, respectively, percentages similar to those reported in the literature. Additionally, positive correlations between urinary arsenic levels and HI values were found (r = 0.59, P = 0.000). These results indicated that this population is at high risk of developing chronic diseases including cancer.

Thyroid hormones and menstrual cycle function in a longitudinal cohort of premenopausal women.

Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well-understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterised the relationship between thyroid hormone concentrations and prospectively collected menstrual function outcomes. Between 2004-2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary oestrogen and progesterone metabolites (estrone 3-glucuronide (E1 3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). Total thyroxine (T4 ) concentrations were positively associated with Pd3G and E1 3G. Women with higher (vs lower) T4 had greater luteal phase maximum Pd3G (Pd3G=11.7μg/mg Cr for women with high T4 vs Pd3G=9.5 and 8.1μg/mg Cr for women with medium and low T4 , respectively) and greater follicular phase maximum E1 3G (E1 3G=41.7ng/mg Cr for women with high T4 vs E1 3G=34.3 and 33.7ng/mg Cr for women with medium and low T4 , respectively). Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease.

Temporal trends of phthalate exposures during 2007-2010 in Swedish pregnant women.

The general population is exposed to phthalates, a group of chemicals with strong evidence for endocrine disrupting properties, commonly used in a large number of consumer products. Based on published research and evidence compiled by environmental agencies, certain phthalate applications and products have become restricted, leading to an increasing number of "new generation compounds" coming onto the market during recent years replacing older phthalates. Some examples of such newer compounds are di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP), and most recently di-isononyl-cyclohexane-1,2-dicarboxylate (DiNCH). In order to evaluate temporal trends in phthalate exposure, first trimester urinary biomarkers of phthalates were measured in the Swedish SELMA study over a period of 2.5 years (2007-2010). We collected first morning void urine samples around week 10 of pregnancy from 1651 pregnant women. Spot samples were analyzed for 13 phthalate metabolites and one phthalate replacement and least square geometric mean (LSGM) levels of the metabolites were compared between the sampling years when adjusted for potential confounders. All 14 metabolites were detectable in more than 99% of the SELMA subjects. The levels were generally comparable to other studies, but the SELMA subjects showed slightly higher exposure to butyl-benzyl phthalate (BBzP) and di-butyl phthalate (DBP). Di-ethyl-hexyl phthalate (DEHP) metabolites levels decreased while DiNP, DiDP/di-2-propylheptyl phthalate (DPHP), and DiNCH metabolites levels increased during the sampling period. Urinary metabolite levels of the older phthalates and more recently introduced phthalate replacement compound changed during the short sampling period in this Swedish pregnancy cohort. Our results indicate that replacement of phthalates can make an impact on human exposure to these chemicals. During this particularly vulnerable stage of life, phthalate exposures are of particular concern as the impacts, though not immediately noticeable, may increase the risk for health effects later in life.

Are Demographic, Psychosocial, and Behavioral Factors Associated with Urinary Salt Excretion in Japanese Workers?

Although high salt intake is a major public health problem, little is known about the predictors of salt intake in Japanese. The present study aims to investigate the association of demographic, psychosocial, and behavioral factors with urinary salt excretion in Japanese workers. From September to November 2014, a self-administered questionnaire was completed by Japanese workers at 8 workplaces in Niigata, Japan. Demographic factors (shift work, household income, family structure, the person responsible for cooking, and smoking habit) were assessed by questionnaire. Psychosocial factors (self-efficacy, perceived social support, and knowledge) were measured using a scale similar to items from an existing scale. Behavioral factors (intake frequency of foods and alcohol, and general dietary behavior) were assessed using a validated, brief-type self-administered diet history questionnaire. Estimated 24-hour urinary salt excretion was calculated from sodium and creatinine concentrations in second morning void or spot urine samples. Analysis of covariance was used to examine the association of factors with urinary salt excretion while adjusting for age and body mass index. Of 457 respondents, 406 participants’ data were analyzed. Urinary salt excretion was not associated with any demographic and psychosocial factors. The intake frequency of pickled vegetables and buckwheat noodles, and the amount of soup consumed with noodles were significantly and positive association with urinary salt excretion in women. Conversely, amount of soy sauce and Worcestershire sauce used at the table was significantly and negative association with urinary salt excretion in men. The association with salt intake was found only behavioral factors in Japanese workers.

Urinary Concentrations of Insecticide and Herbicide Metabolites among Pregnant Women in Rural Ghana: A Pilot Study.

Use of pesticides by households in rural Ghana is common for residential pest control, agricultural use, and for the reduction of vectors carrying disease. However, few data are available about exposure to pesticides among this population. Our objective was to quantify urinary concentrations of metabolites of organophosphate (OP), pyrethroid, and select herbicides during pregnancy, and to explore exposure determinants. In 2014, 17 pregnant women from rural Ghana were surveyed about household pesticide use and provided weekly first morning urine voids during three visits (n = 51 samples). A total of 90.1% (46/51) of samples had detectable OP metabolites [geometric mean, GM (95% CI): 3,5,6-trichloro-2-pyridinol 0.54 µg/L (0.36–0.81), para-nitrophenol 0.71 µg/L (0.51–1.00)], 75.5% (37/49) had detectable pyrethroid metabolites [GM: 3-phenoxybenzoic acid 0.23 µg/L (0.17, 0.32)], and 70.5% (36/51) had detectable 2,4-dichlorophenoxyacetic acid levels, a herbicide [GM: 0.46 µg/L (0.29–0.73)]. Concentrations of para-nitrophenol and 2,4-dichlorophenoxyacetic acid in Ghanaian pregnant women appear higher when compared to nonpregnant reproductive-aged women in a reference U.S. population. Larger studies are necessary to more fully explore predictors of exposure in this population.

Relation of renal dysfunction with incident atrial fibrillation and cardiovascular morbidity and mortality: The PREVEND study.

Renal dysfunction is a risk factor for cardiovascular disease, including atrial fibrillation (AF) and mortality. However, the exact pathobiology linking different renal dysfunction measures, such as albumin excretion or glomerular filtration rate (GFR), to cardiovascular- and AF risk are unclear. In this study, we investigated the association of several renal function measures and incident AF, and whether the relation between renal measures and outcomes is modified by AF. We examined 8265 individuals (age 49 ± 13 years, 50% women) included in the PREVEND study. We used albumin excretion (morning void and 24-h urine samples), serum creatinine, cystatin C, and Cystatin C-based, creatinine-based, and creatinine-cystatin C-based GFR as renal function measures; results: During a follow-up of 9.8 ± 2.3 years, 267 participants (3.2%) developed AF. In the multivariate-adjusted model, GFR, estimated by creatinine, cystatin C, or the combination was not associated with incident AF. However, increased albumin excretion was strongly associated with incident AF; urine albumin concentration and excretion (HRmorning void 1.10, P = 0.005 and HR24-hr collection 1.05, P = 0.033) and albumin creatinine ratio (HRmorning void 1.05, P = 0.010 and HR24-hr collection 1.06, P < 0.001). Interaction terms of incident AF and renal measures were not significant for incident cerebrovascular events, peripheral vascular events, ischemic heart disease, heart failure, and mortality. In this community-based cohort, increased albumin excretion, and not GFR, was associated with incident AF, independent of established cardiovascular risk factors. Incidence of AF did not largely alter the association of renal dysfunction and cardiovascular outcomes.

Spatial characteristics of urinary BTEX concentrations in the general population

Benzene, toluene, ethylbenzene, o-, m-, and p-xylenes (BTEX) are ubiquitous outdoor and indoor air pollutants associated with both environmental and health effects. The objective of this exploratory study was to determine the magnitude and variability of urinary BTEX levels among residents of two areas located in the same city (Nicosia, Cyprus). The two areas differed with respect to their proximity to an industrial cluster and an intercity-highway. First morning urine voids were collected during a random campaign from selected households in the two urban areas (n = 48). Urinary BTEX measurements were obtained using headspace solid phase micro extraction coupled with gas chromatography-mass spectrometry. The majority of participants were females (65%) and non-smokers (85%) with a mean age of 49 years. Median urinary BTEX levels were: 118 ng L−1, 124 ng L−1, 9 ng L−1, 29 ng L−1 and 28 ng L−1 for benzene, toluene, ethylbenzene, (p + m)-xylene and o-xylene, respectively. With the exception of benzene, participants from area 2 (closer to the industrial cluster and an intercity road than area 1) had significantly (p < 0.05) higher urinary BTEX levels than those from area 1 (regression analysis). The residence location (in area 2) was the sole significant (p < 0.05) predictor of urinary BTEX levels after adjusting for sex, smoking, age, body mass index, and educational level. This observational study showed differences in BTEX exposures between two urban areas of the same city. This baseline BTEX dataset may prove useful for future activities of natural gas extraction and handling nearby urban settings.