Cross-sectional associations of persistent organic pollutants measured in adipose tissue and metabolic syndrome in clinically diagnosed middle-aged adults.

INTRODUCTION: Although often overlooked in clinical settings, accumulation of persistent organic pollutants (POPs) in visceral adipose tissue (VAT) is thought to be a relevant risk factor for metabolic syndrome (MetS). METHODS: One hundred and seventeen patients undergoing non-oncological surgery were randomly recruited and classified as MetS + if presented 3 out of the 5 MetS components: waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP, respectively), serum glucose, insulin, triglycerides (TG) and high-density lipoprotein (HDL) cholesterol levels, according International Diabetes Federation (IDF) criteria. Seventeen organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in adipose tissue samples. Linear, logistic and weighted quantile sum (WQS) regression models, adjusted for age and sex, were performed. RESULTS: One third of the participants were males (36.8%) with a median age of 44 years, showing clinical evidences of MetS (35.0%). Adjusted linear regression models showed that WC correlated positively with all OCP concentrations. Higher fasting serum glucose levels were related to higher HCB and γ-HCH concentrations. The remaining OCPs and PCBs were not associated with this MetS component. HCB was inversely associated with HDL cholesterol levels, while PCB-180 was positively associated. HCB and γ-HCH concentrations were also positively correlated with DBP and SBP levels. PCB-138 was also positively associated with SBP. Adjusted logistic models revealed that exposure to HCB and γ-HCH were associated with increased odds of MetS [ORs (95%CI) 1.53 (1.22-1.92) and 1.39 (1.10-1.76) respectively; p < 0.01]. No associations were observed for the remaining POPs. WQS models showed a positive and significant mixture effect of POPs on the odds of MetS (exp [beta] = 2.34; p < 0.001), with γ-HCH (52.9%), o,p'-DDT (26.9%) and HCB (19.7%) driving the association. CONCLUSIONS: Our findings support that POPs accumulated in VAT, specifically HCB and (gamma)-HCH, are associated with both isolated components and clinically diagnosed SMT.

Obesity II: Establishing causal links between chemical exposures and obesity.

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.

Exposure to non-persistent pesticides, BDNF, and behavioral function in adolescent males: Exploring a novel effect biomarker approach.

BACKGROUND: Numerous contemporary non-persistent pesticides may elicit neurodevelopmental impairments. Brain-derived neurotrophic factor (BDNF) has been proposed as a novel effect biomarker of neurological function that could help to understand the biological responses of some environmental exposures. OBJECTIVES: To investigate the relationship between exposure to various non-persistent pesticides, BDNF, and behavioral functioning among adolescents. METHODS: The concentrations of organophosphate (OP) insecticide metabolites 3,5,6-trichloro-2-pyridinol (TCPy), 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMPy), malathion diacid (MDA), and diethyl thiophosphate (DETP); metabolites of pyrethroids 3-phenoxybenzoic acid (3-PBA) and dimethylcyclopropane carboxylic acid (DCCA), the metabolite of insecticide carbaryl 1-naphthol (1-N), and the metabolite of ethylene-bis-dithiocarbamate fungicides ethylene thiourea (ETU) were measured in spot urine samples, as well as serum BDNF protein levels and blood DNA methylation of Exon IV of BDNF gene in 15-17-year-old boys from the INMA-Granada cohort in Spain. Adolescents' behavior was reported by parents using the Child Behavior Check List (CBCL/6-18). This study included 140 adolescents of whom 118 had data on BDNF gene DNA methylation. Multivariable linear regression, weighted quantile sum (WQS) for mixture effects, and mediation models were fit. RESULTS: IMPy, MDA, DCCA, and ETU were detected in more than 70% of urine samples, DETP in 53%, and TCPy, 3-PBA, and 1-N in less than 50% of samples. Higher levels of IMPy, TCPy, and ETU were significantly associated with more behavioral problems as social, thought problems, and rule-breaking symptoms. IMPy, MDA, DETP, and 1-N were significantly associated with decreased serum BDNF levels, while MDA, 3-PBA, and ETU were associated with higher DNA methylation percentages at several CpGs. WQS models suggest a mixture effect on more behavioral problems and BDNF DNA methylation at several CpGs. A mediated effect of serum BDNF within IMPy-thought and IMPy-rule breaking associations was suggested. CONCLUSION: BDNF biomarkers measured at different levels of biological complexity provided novel information regarding the potential disruption of behavioral function due to contemporary pesticides, highlighting exposure to diazinon (IMPy) and the combined effect of IMPy, MDA, DCCA, and ETU. However, further research is warranted.

BDNF as a potential mediator between childhood BPA exposure and behavioral function in adolescent boys from the INMA-Granada cohort.

BACKGROUND: Bisphenol A (BPA) exposure has been linked to altered behavior in children. Within the European Human Biomonitoring Initiative (HBM4EU), an adverse outcome pathway (AOP) network was constructed supporting the mechanistic link between BPA exposure and brain-derived neurotrophic factor (BDNF). OBJECTIVE: To test this toxicologically-based hypothesis in the prospective INMA-Granada birth cohort (Spain). METHODS: BPA concentrations were quantified by LC-MS/MS in spot urine samples from boys aged 9-11 years, normalized by creatinine and log-2 transformed. At adolescence (15-17 years), blood and urine specimens were collected, and serum and urinary BDNF protein levels were measured using immunoassays. DNA methylation levels at 6 CpGs in Exon IV of the BDNF gene were also assessed in peripheral blood using bisulfite-pyrosequencing. Adolescent's behavior was parent-rated using the Child Behavior Checklist (CBCL/6-18) in 148 boys. Adjusted linear regression and mediation models were fit. RESULTS: Childhood urinary BPA concentrations were longitudinally and positively associated with thought problems (ß = 0.76; 95% CI: 0.02, 1.49) and somatic complaints (ß = 0.80; 95% CI: -0.16, 1.75) at adolescence. BPA concentrations were positively associated with BDNF DNA methylation at CpG6 (ß = 0.21; 95% CI: 0.06, 0.36) and mean CpG methylation (ß = 0.10; 95% CI: 0.01, 0.18), but not with total serum or urinary BDNF protein levels. When independent variables were categorized in tertiles, positive dose-response associations were observed between BPA-thought problems (p-trend = 0.08), BPA-CpG6 (p-trend ≤ 0.01), and CpG6-thought problems (p-trend ≤ 0.01). A significant mediated effect by CpG6 DNA methylation was observed (ß = 0.23; 95% CI: 0.01, 0.57), accounting for up to 34% of the BPA-thought problems association. CONCLUSIONS: In line with toxicological studies, BPA exposure was longitudinally associated with increased BDNF DNA methylation, supporting the biological plausibility of BPA-behavior relationships previously described in the epidemiological literature. Given its novelty and preliminary nature, this effect biomarker approach should be replicated in larger birth cohorts.

Adipose Tissue Redox Microenvironment as a Potential Link between Persistent Organic Pollutants and the 16-Year Incidence of Non-hormone-Dependent Cancer.

We aimed to assess the relationships among the adipose tissue's (AT) oxidative microenvironment, in situ accumulated persistent organic pollutant (POP) concentrations, and cancer development. POP and oxidative stress levels were quantified in AT samples from 382 adults recruited within the GraMo cohort (2003-2004) in Granada (Spain). The 16-year cancer incidence was ascertained by reviewing health/administrative databases. Cox-regression models and mediation analyses were performed. The enzymes superoxide dismutase (SOD) and glutathione reductase (GRd) were positively associated with the risk of non-hormone-dependent (NHD) cancer [adjusted hazard ratio (HR) 1.76; 95% confidence interval (CI): 1.17, 2.64 and HR 2.35; 95% CI: 1.41, 3.94, respectively]. After adjustment for covariates, polychlorinated biphenyl-138 (PCB-138) (HR 1.78; 95% CI: 1.03, 3.09), ß-hexachlorocyclohexane (ß-HCH) (HR 1.70; 95% CI: 1.09, 2.64), and hexachlorobenzene (HR 1.54; 95% CI: 1.02, 2.33) were also positively associated with the risk of NHD cancer. Although confidence intervals included the null value, probably because of the modest number of cancer cases, we observed a potential mediation effect of SOD and GRd on the associations between ß-HCH and the risk of NHD tumors (percent mediated = 33 and 47%, respectively). Our results highlight the relevance of human AT's oxidative microenvironment as a predictor of future cancer risk as well as its potential mediating role on POP-related carcinogenesis. Given their novelty, these findings should be interpreted with caution and confirmed in future studies.

Associations of persistent organic pollutants in human adipose tissue with retinoid levels and their relevance to the redox microenvironment.

Humans are exposed to a myriad of chemical substances in both occupational and environmental settings. Persistent organic pollutants (POPs) have drawn attention for their adverse effects including cancer and endocrine disruption. Herein, the objectives were 1) to describe serum and adipose tissue retinol levels, along with serum retinol binding protein 4 (RBP4) concentrations, and 2) to assess the associations of adipose tissue POP levels with these retinoid parameters, as well as their potential interaction with the previously-observed POP-related disruption of redox microenvironment. Retinol was measured in both serum and adipose tissue along with RBP4 levels in serum samples of 236 participants of the GraMo adult cohort. Associations were explored by multivariable linear regression analyses and Weighted Quantile Sum regression. Polychlorinated biphenyls (PCBs) 180, 153 and 138 were related to decreased adipose tissue retinol levels and increased serum RBP4/retinol ratio. Dicofol concentrations > limit of detection were associated with decreased retinol levels in serum and adipose tissue. Additionally, increased adipose tissue retinol levels were linked to an attenuation in previously-reported associations of adipose tissue PCB-153 with in situ superoxide dismutase activity. Our results revealed a suggestive link between retinoids, PCBs and redox microenvironment, potentially relevant for both mechanistic and public health purposes.

How polluted is your fat? What the study of adipose tissue can contribute to environmental epidemiology.

The study of the potential contribution of low-dose exposure to environmental chemicals on the development of chronic conditions in human populations is often hampered by methodological issues, including exposure misclassification and the inability to assess biological effects in target organs. White adipose tissue (WAT) presents the unique feature of being both an advantageous matrix for assessing long-term exposure to mixtures of persistent organic pollutants and an interesting tissue to investigate early preclinical effects. Moreover, other lipophilic non-persistent chemicals and heavy metals have been recently quantified in fat, suggesting that human WAT contains chemical mixtures more complex than initially thought. However, WAT has been scarcely used in environmental epidemiology due to collection difficulties. In this essay we discuss the potential of using human WAT as a source of both exposure and effect biomarkers, with the aim of advancing the epidemiological research of obesity-related diseases, including metabolic syndrome and cancer. Overall, we discuss the implications of investigating WAT in a multidisciplinary framework combining toxicological and epidemiological knowledge in order to improve the inference of causal relationships in observational settings. We finalise by suggesting feasible designs and scenarios in which WAT samples may be reasonably collected.

Contribution of sociodemographic, occupational, lifestyle and dietary characteristics to the oxidative stress microenvironment in adipose tissue.

The present study was conceived on the basis of the few previous reports suggesting a potential relevance of the oxidative stress microenvironment in the adipose tissue, a biological matrix which is closely related to the development of several chronic pathologies. Thus, our aim was to describe the levels of enzymatic and non-enzymatic antioxidants and markers of oxidative damage in adipose tissue samples from a Spanish cohort, as well as their main sociodemographic, lifestyle, and dietary predictors. The study was conducted in a subsample (n = 271 adults) of GraMo cohort, recruited in Granada (Southern Spain). A face-to-face questionnaire was used to gather data regarding sociodemographic characteristics, lifestyle, dietary habits, health status, and perceived exposure to chemicals. We analyzed adipose tissue levels of lipid peroxidation (TBARS), total superoxide dismutase (SOD) activity, heme oxygenase-1 (HO-1) activity, and glutathione cycle biomarkers. Potential predictors of oxidative stress markers were assessed using stepwise multivariable linear regression analyses. SOD and TBARS levels were mainly related to sociodemographic and occupational characteristics, while the components of the glutathione cycle and HO-1 were predominantly associated with dietary habits. Men showed significantly lower levels of oxidative stress levels than women. In the regression models including only women, the use of oral contraceptive and hormonal therapy was associated with lower levels of oxidative stress, while the number of children was positively associated with increased oxidative biomarkers. Our results suggest that adipose tissue is potentially important matrix for the assessment of oxidative stress, which can be affected by specific environmental factors. These findings might be relevant for public health.

A review of exposure assessment methods for epidemiological studies of health effects related to industrially contaminated sites.

BACKGROUND: this paper is based upon work from COST Action ICSHNet. Health risks related to living close to industrially contaminated sites (ICSs) are a public concern. Toxicology-based risk assessment of single contaminants is the main approach to assess health risks, but epidemiological studies which investigate the relationships between exposure and health directly in the affected population have contributed important evidence. Limitations in exposure assessment have substantially contributed to uncertainty about associations found in epidemiological studies. OBJECTIVES: to examine exposure assessment methods that have been used in epidemiological studies on ICSs and to provide recommendations for improved exposure assessment in epidemiological studies by comparing exposure assessment methods in epidemiological studies and risk assessments. METHODS: after defining the multi-media framework of exposure related to ICSs, we discussed selected multi-media models applied in Europe. We provided an overview of exposure assessment in 54 epidemiological studies from a systematic review of hazardous waste sites; a systematic review of 41 epidemiological studies on incinerators and 52 additional studies on ICSs and health identified for this review. RESULTS: we identified 10 multi-media models used in Europe primarily for risk assessment. Recent models incorporated estimation of internal biomarker levels. Predictions of the models differ particularly for the routes 'indoor air inhalation' and 'vegetable consumption'. Virtually all of the 54 hazardous waste studies used proximity indicators of exposure, based on municipality or zip code of residence (28 studies) or distance to a contaminated site (25 studies). One study used human biomonitoring. In virtually all epidemiological studies, actual land use was ignored. In the 52 additional studies on contaminated sites, proximity indicators were applied in 39 studies, air pollution dispersion modelling in 6 studies, and human biomonitoring in 9 studies. Exposure assessment in epidemiological studies on incinerators included indicators (presence of source in municipality and distance to the incinerator) and air dispersion modelling. Environmental multi-media modelling methods were not applied in any of the three groups of studies. CONCLUSIONS: recommendations for refined exposure assessment in epidemiological studies included the use of more sophisticated exposure metrics instead of simple proximity indicators where feasible, as distance from a source results in misclassification of exposure as it ignores key determinants of environmental fate and transport, source characteristics, land use, and human consumption behaviour. More validation studies using personal exposure or human biomonitoring are needed to assess misclassification of exposure. Exposure assessment should take more advantage of the detailed multi-media exposure assessment procedures developed for risk assessment. The use of indicators can be substantially improved by linking definition of zones of exposure to existing knowledge of extent of dispersion. Studies should incorporate more often land use and individual behaviour.

Socio-demographic, lifestyle, and dietary determinants of essential and possibly-essential trace element levels in adipose tissue from an adult cohort.

There is increasing evidence linking levels of trace elements (TEs) in adipose tissue with certain chronic conditions (e.g., diabetes or obesity). The objectives of this study were to assess concentrations of a selection of nine essential and possibly-essential TEs in adipose tissue samples from an adult cohort and to explore their socio-demographic, dietary, and lifestyle determinants. Adipose tissue samples were intraoperatively collected from 226 volunteers recruited in two public hospitals from Granada province. Trace elements (Co, Cr, Cu, Fe, Mn, Mo, Se, V, and Zn) were analyzed in adipose tissue by high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS). Data were collected on socio-demographic characteristics, lifestyle, diet, and health status by face-to-face interview. Predictors of TE concentrations were assessed by using multivariable linear and logistic regression. All TEs were detected in all samples with the exception of Se (53.50%). Iron, zinc, and copper showed the highest concentrations (42.60 mg/kg, 9.80 mg/kg, and 0.68 mg/kg, respectively). Diet was the main predictor of Cr, Fe, Mo, and Se concentrations. Body mass index was negatively associated with all TEs (ß coefficients = -0.018 to -0.593, p = 0.001-0.090) except for Mn and V. Age showed a borderline-significant positive correlation with Cu (ß = 0.004, p = 0.089). Residence in a rural or semi-rural area was associated with increased Co, Cr, Fe, Mo, Mn, V and Zn concentrations and with ß coefficients ranging from 0.196 to 0.544 (p < 0.05). Furthermore, individuals with higher educational level showed increased Cr, Co, Fe and V concentrations (ß coefficients = 0.276-0.368, p = 0.022-0.071). This is the first report on the distribution of these TEs in adipose tissue and on their determinants in a human cohort and might serve as an initial step in the elucidation of their clinical relevance.

Bisphenol A and reproductive hormones and cortisol in peripubertal boys: The INMA-Granada cohort.

INTRODUCTION: Bisphenol A (BPA) is a well-known endocrine disrupting compound. Although several studies have investigated the effect of BPA exposure and reproductive hormones in humans, results have been inconsistent. OBJECTIVE: To explore the cross-sectional relationship between bisphenol A (BPA) exposure and reproductive hormones/cortisol among peripubertal boys. MATERIAL AND METHODS: Urinary BPA and serum hormones were assessed in 172 boys belonging to the INMA "Environment and Childhood" Granada birth cohort in their follow-up at 9-11years of age. BPA concentrations were quantified by liquid chromatography-mass spectrometry, and levels of serum total testosterone (TT), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol were measured by electrochemiluminescence immunoassay. RESULT(S): After adjustment for confounders, linear regression models showed that each natural-log unit increase in urinary BPA concentrations was associated with a 19% increase in geometric mean (GM) serum TT levels, and a 16% decrease in GM serum cortisol levels. When urinary BPA concentrations were categorized in tertiles, boys in the 3rd tertile showed 49% higher TT levels and 23% lower cortisol concentrations compared to boys in the 1st tertile. Additionally, urinary BPA concentrations were also significantly associated with higher TT:LH and TT:cortisol ratios, but not with serum LH or FSH levels. CONCLUSION(S): Our results suggest the possible endocrine disrupting potential of BPA during this important period of development. Although action at the testis or pituitary cannot be ruled out, our findings are compatible with a possible involvement of BPA at the adrenal gland, resulting in a differential production of androgens/cortisol. However, given the cross-sectional design of our study, the heterogeneous results reported in the literature, and the scant experimental research on BPA effects at the adrenal gland, the present findings should be interpreted with caution.

Human adipose tissue levels of persistent organic pollutants and metabolic syndrome components: Combining a cross-sectional with a 10-year longitudinal study using a multi-pollutant approach.

We aimed to assess the influence of long-term exposure to POPs on the risk of metabolic syndrome, combining a cross-sectional with a 10-year longitudinal follow-up design. Residues of eight POPs were quantified in adipose tissue samples from 387 participants recruited between 2003 and 2004 in Granada province (Spain). The outcome ("metabolically compromised") was defined as having ≥1 diagnosis of type 2 diabetes, hypertension, hypertriglyceridemia, and/or low HDL cholesterol. The cross-sectional analysis was conducted in the initial cohort, while the 10-year longitudinal analysis was conducted in those 154 participants free of any of the so-mentioned metabolic diseases and classified as "metabolically healthy" at recruitment. Statistical analyses were performed using single and multi-pollutant approaches through logistic and Cox regression analyses with elastic net penalty. After adjusting for confounders, ß-hexachlorocyclohexane (ß-HCH) and hexachlorobenzene (HCB) were independently associated with an increased risk of being metabolically compromised (unpenalized ORs=1.17, 95% CI=1.01-1.36 and 1.17, 95% CI=0.99-1.38, respectively). Very similar results were found in the 10-year longitudinal analysis [HRs=1.28, 95% CI=1.01-1.61 (ß-HCH); 1.26, 95% CI=1.00-1.59 (HCB)] and were in line with those obtained using elastic net regression. Finally, when the arithmetic sum of both compounds was used as independent variable, risk estimates increased to OR=1.25, 95% CI=1.03-1.52 and HR=1.32, 95% CI=1.02-1.70. Our results suggest that historical exposure to HCB and ß-HCH is consistently associated with the risk of metabolic disorders, and that these POPs might be partly responsible for the morbidity risk traditionally attributed to age and obesity.

Changes in the total effective xenoestrogen burden (TEXB) of breast cancer patients during an 18-month post-surgical follow-up.

We aimed to assess changes in the total effective xenoestrogen burden (TEXB) -a biomarker of combined effect of mixtures of xenoestrogens- in breast cancer patients at surgery (breast adipose tissue) and at different time points during an 18-month follow-up (abdominal adipose tissue), and to analyze the potential influence of socio-demographic, reproductive, tumor, and treatment characteristics on TEXB levels. TEXB-alpha (due to persistent organohalogenated chemicals) and TEXB-beta (due mainly to endogenous estrogens) were quantified in 44 women. TEXB values significantly increased over follow-up (p <0.001); the largest difference was observed at 6-12 months post-surgery (p <0.001); then decreased over time. TEXB-alpha at 6-18 months was significantly higher in younger patients with estrogen receptor positivity (p=0.034) and in those receiving anti-neoplasm chemotherapy. Cancer treatment may be responsible for the increase in TEXB-alpha observed in patients with hormone-dependent tumors, which may confer to xenoestrogens a role in the progression of the disease.

Contribution of Persistent Organic Pollutant Exposure to the Adipose Tissue Oxidative Microenvironment in an Adult Cohort: A Multipollutant Approach.

Despite growing in vitro and in vivo evidence of the putative role of persistent organic pollutants (POPs) in the induction of oxidative damage in cell structures, this issue has been poorly addressed from an epidemiologic perspective. The aim of this study was to explore associations between adipose tissue POP concentrations and the in situ oxidative microenvironment. A cross-sectional study was conducted in a subsample (n = 271) of a previously established cohort, quantifying levels of eight POPs and four groups of oxidative stress biomarkers in adipose tissue. Associations were explored using multivariate linear regression analyses adjusted for potential confounders. We assessed the combined effect of POPs on oxidative stress/glutathione system biomarkers using weighted quantile sum regression (WQS). Increased concentrations of p,p'-DDE, HCB, ß-HCH, dicofol, and PCBs (congeners -138, -153, and -180) were predominantly associated with higher lipid peroxidation (TBARS) [exp(ß) = 1.09-1.78, p < 0.01-0.04)] and SOD activity [exp(ß) = 1.13-1.48, p < 0.01-0.05)] levels. However, only a few associations were observed with glutathione system biomarkers, e.g., PCB-180 with total glutathione [exp(ß) = 1.98, p = 0.03]. The WQS index was found to be positively associated with SOD activity, and PCB-138, PCB-180, and ß-HCH were the main contributors to the index. Likewise, the WQS index was positively associated with TBARS levels, with the three PCBs acting as the main contributors. This is the first epidemiological evidence of the putative disruption by POPs of the adipose tissue oxidative microenvironment. Our results indicate that POP exposure may enhance alternative pathways to the glutathione detoxification route, which might result in tissue damage. Further research is warranted to fully elucidate the potential health implications.

Associations of maternal o,p'-DDT and p,p'-DDE levels with birth outcomes in a Bolivian cohort.

This study examined the potential association of maternal serum levels of o,p'-DDT and p,p'-DDE with gestation time and with anthropometric measurements and thyroid-stimulating hormone (TSH) levels of newborns in a Bolivian birth cohort. Two hundred mothers were consecutively recruited between January and March 2013 at the "Hospital de la Mujer Dr. Percy Boland" in Santa Cruz de la Sierra. Potential confounders were derived from an ad hoc questionnaire. o,p'-DDT and p,p'-DDE were quantified in cord serum by high-resolution gas chromatography coupled with mass spectrometry. Multivariable linear regression analyses were performed, with POP concentrations as independent variables and log-transformed newborn birth outcomes (newborn weight, gestational age, head circumference, birth height, ponderal index, and TSH levels) as dependent variables. o,p'-DDT was detected in 82.5% of samples at median concentration of 0.22ng/mL and p,p'-DDE in 86.5% of samples at median concentration of 1.01ng/mL. Opposite associations with birth weight were found for p,p'-DDE (ß=0.012, p=0.006) and o,p'-DDT (ß=-0.014, p=0.039), and these associations were stronger when both chemicals were entered in the same model. p,p'-DDE was negatively associated with gestation time (ß=-0.004, p=0.012), and o,p'-DDT was borderline negatively associated with newborn head circumference (ß=-0.004, p=0.054). We observed no relevant changes in the magnitude of the coefficients or in statistical significance after adjustment for newborn TSH levels. This study indicates a possible impact of prenatal exposure to o,p'-DDT and p,p'-DDE on newborn anthropometric measurements in a population showing evidence of recent exposure to the pesticide DDT.

Assessment of essential and nonessential dietary exposure to trace elements from homegrown foodstuffs in a polluted area in Makedonska Kamenica and the Kocani region (FYRM).

UNLABELLED: The main purpose of the present study is to assess human dietary exposure to essential and non-essential trace elements via consumption of selected homegrown foodstuffs. Twelve essential and non-essential trace elements (Cd, Co, Cu, Cr, Hg, Mo, Ni, Pb, Sb, Se, Zn and As) were detected in various homegrown foodstuffs. Detailed questionnaires were also applied among a sample of the local population to collect information on sociodemographic characteristics. The results of the present study clearly indicate that the majority of the trace elements are at highly elevated levels in the studied foodstuffs, in comparison to international recommendations. The maximum measured levels of ETE and NETE are as follows [µgkg(-1)]: Cd 873, Co 1370, Cu 21700, Cr 59633, Hg 26, Mo 6460, Ni14.5, Pb 11100, Sb 181, Se 0.30, Zn 102 and As 693. Additionally, age, body mass index and gender were significantly associated with levels of dietary exposure. Further research is warranted on the potential health implication of this exposure. CAPSULE ABSTRACT: The study merges the accumulation of ETE and NETE in home-grown foodstuffs and reflects considerably high health risks for inhabitants.

Bisphenol A and other phenols in human placenta from children with cryptorchidism or hypospadias.

Embryo-foetal exposure to low doses of endocrine disrupting chemicals (EDCs) has been related to reproductive tract diseases in experimental animals but not convincingly in human populations. The aim of this case-control study was to explore the relationship between exposure to non-persistent EDCs during pregnancy and male genital development. Exposure to bisphenol-A (BPA), benzophenones (BPs) [BP-1, BP-2, BP-3, BP-6, BP-8 and 4-hydroxybenzophenone (4-OH-BP),] and parabens (PBs) [methyl-, ethyl-, propyl- and butyl-PB] was analyzed by means of ultra-high performance liquid chromatography-tandem mass spectrometry in placenta samples from a subsample of 28 cases and 51 healthy controls nested in a cohort of newborns recruited between 2000 and 2002. The multivariable regression analyses indicated a statistically significant association between exposure to BPA and propyl-PB and the risk of malformations [adjusted odd ratio (95% CIs) in the third tertile of exposure: 7.2 (1.5-35.5) and 6.4 (1.2-35.5) for BPA and propyl-PB, respectively].

Role of radiosurgery in the management of glomus tumors.

BACKGROUND: Glomus tumors are benign slow-growing hypervascular neoplasms. The role of radiosurgery for the treatment of these tumors has increased. The purpose of this study was to show our experience with glomus tumors and to analyze different prognostic factors. METHODS: Data from 39 adult patients were retrospectively analyzed. All of them underwent head frame stereotactic radiosurgery with linear accelerator (LINAC). Tumor and symptomatic control were calculated using the Kaplan-Meier method. Bivariate statistical analyses were performed to examine different prognostic factors. RESULTS: The median follow-up was 71 months. The radiological local and symptomatic control was achieved in 37 patients (94.8%) and 29 patients (74.3%), respectively. Toxicity was detected in 4 patients (10%). In the bivariate analysis, dose coverage and maximum dose were associated with tumor control with an odds ratio (OR) of 5.29 (p = .041) and 2.67 (p = .056), respectively. CONCLUSION: Stereotactic radiosurgery is a safe and efficient treatment for glomus tumors that is associated with high probability of radiological and symptomatic control and low incidence of morbidity. © 2015 Wiley Periodicals, Inc. Head Neck 38: E798-E804, 2016.

A novel biomarker for anti-androgenic activity in placenta reveals risks of urogenital malformations.

It has been hypothesized that the rise in male reproductive disorders over recent decades may at least be partially attributable to environmental factors, including chemical exposures, but observed associations with single chemicals were rather weak. The aim of this case-control study was to explore the relationship between exposure to mixtures of (anti-)androgenic chemicals during pregnancy and the risk of cryptorchidism and/or hypospadias in offspring, using the total effective xenobiotic burden of anti-androgens (TEXB-AA) as a biomarker. A subsample of 29 cases (16 of cryptorchidism, 12 of hypospadias, and one of both disorders) and 60 healthy controls was nested in a cohort of male newborns recruited between October 2000 and July 2002. The (anti-)androgenic activity of placenta samples collected at delivery was assessed using TEXB-AA biomarker, combined with a bioassay-directed fractionation protocol that separated endogenous hormones from most (anti-)androgenic chemicals by normal-phase HPLC. The bioassay measures the androgen-induced luciferase activity and the inhibition of this pathway by (anti-)androgens. First, we collected 27 HPLC fractions in each placenta extract, which were all tested in the bioassay. The multivariable statistical analyses indicated a statistically significant positive dose-response association between the potent anti-androgenic activity of the HPLC fraction collected during minutes 1-2 (F2) and the risk of malformations (odds ratio: 2.33, 95% CI: 1.04-5.23). This study represents a novel approach for the estimation of combined effects of the total anti-androgenic load and the associations suggest an effect of environmental pollutants on the development of fetal reproductive tract.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/149/6/605/suppl/DC1.