Obesity or diet? Levels and determinants of phthalate body burden – A case study on Portuguese children

In this study we analyzed one of the most comprehensive sets of 21 urinary phthalate metabolites representing exposure to 11 parent phthalates (DEP, DMP, DiBP, DnBP, BBzP, DEHP, DiNP, DiDP, DCHP, DnPeP, DnOP) in first morning urine samples of 112 Portuguese children (4-18 years) sampled in 2014/15. The study population consisted of two groups: group 1 with normal weight/underweight children (N = 43) following their regular diet and group 2 with obese/overweight children (N = 69) following a healthy diet (with nutritional counselling). Most of the metabolites were above the limits quantification (81-100%) except for MCHP, MnPEP and MnOP. Metabolite levels were generally comparable to other recent child and general populations sampled worldwide, confirming the steady decline in exposures to most phthalates. Compared to Portuguese children sampled in 2011/2012, median urinary metabolite levels decreased by approximately 50% for DEHP, DnBP, DiBP and BBzP. Risk assessments for individual phthalates and the sum of the anti-androgenic phthalates did not indicate to attributable health risks, also at the upper percentiles of exposure. In the healthy diet group the median concentration of the DEHP metabolites was significant lower, while all phthalate metabolites except MEP tended to be lower compared to the regular diet group. Multiple log-linear regression analyses revealed significantly lower daily intakes (DIs) for all phthalates in the healthy diet group compared to the regular diet group (geometric mean ratios (gMR) between 0.510-0.618; p ≤ 0.05), except for DEP (gMR: 0.811; p = 0.273). The same analyses with the continuous variable body mass index instead of the diet groups also showed effects on the DIs (gMRs between 0.926-0.951; p ≤ 0.05), however much smaller than the effects of the diet. The results indicate that obese children following a healthy diet composed of fresh and less packaged/processed food can considerably reduce their intake for most phthalates and can have lower phthalate intakes than regular weight/regular diet children.Luísa Correia-Sá is grateful to Fundação para a Ciência e a Tecnologia (FCT) by the grant (SFRH/BD/87019/2012), financed by POCH, subsidized by Fundo Social Europeu and Ministério da Ciência, Tecnologia e Ensino Superior. The authors are thankful to the project Qualidade e Segurança Alimentar – uma abordagem (nano)tecnológica, reference NORTE-01-0145-FEDER-000011.info:eu-repo/semantics/publishedVersio

Exposure assessment to bisphenol A (BPA) in Portuguese children by human biomonitoring

Exposure to bisphenol A (BPA) is known to be widespread and available data suggests that BPA can act as an endocrine disruptor. Diet is generally regarded as the dominant BPA exposure source, namely through leaching to food from packaging materials. The aim of this study was to evaluate the exposure of 110 Portuguese children (4-18 years old), divided in two groups: the regular diet group (n = 43) comprised healthy normal weight/underweight children with no dietary control; the healthy diet group (n = 67) comprised children diagnosed for obesity/overweight (without other known associated diseases) that were set on a healthy diet for weight control. First morning urine samples were collected and total urinary BPA was analyzed after enzymatic hydrolysis via on-line HPLC-MS/MS with isotope dilution quantification. Virtually, all the children were exposed to BPA, with 91% of the samples above the LOQ (limit of quantification) of 0.1 μg/L. The median (95th percentile) urinary BPA levels for non-normalized and creatinine-corrected values were 1.89 μg/L (16.0) and 1.92 μg/g creatinine (14.4), respectively. BPA levels in the regular diet group were higher than in the healthy diet group, but differences were not significant. Calculated daily BPA intakes, however, were significantly higher in children of the regular diet group than in children of healthy diet group. Median (95th percentile) daily intakes amounted to 41.6 (467) ng/kg body weight/day in the regular diet group, and 23.2 (197) ng/kg body weight/day in the healthy diet group. Multiple logistic regression analysis revealed that children in the healthy diet group had 33% lower intakes than children in the regular diet group (OR 0.67; 95% CI 0.51-0.89). For both groups, however, urinary BPA levels and daily BPA intakes were within the range reported for other children's populations and were well below health guidance values such as the European Food Safety Authority (EFSA) temporary tolerable daily intake (t-TDI) of 4 μg/kg body weight/day. In addition, lower daily BPA intakes were more likely linked with the inherent dietary approach rather than with high BMI or obesity.info:eu-repo/semantics/publishedVersio

Prenatal and postnatal exposure to persistent organic pollutants and Infant growth: A pooled analysis of seven european birth cohorts

Background: Infant exposure to persistent organic pollutants (POPs) may contribute to obesity. However, many studies so far have been small, focused on transplacental exposure, used an inappropriate measure to assess postnatal exposure through breastfeeding if any, or did not discern between prenatal and postnatal effects. Objectives: We investigated prenatal and postnatal exposure to POPs and infant growth (a predictor of obesity). Methods: We pooled data from seven European birth cohorts with biomarker concentrations of polychlorinated biphenyl 153 (PCB-153) (n = 2,487), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) (n = 1,864), estimating prenatal and postnatal POPs exposure using a validated pharmacokinetic model. Growth was change in weight-for-age z-score between birth and 24 months. Per compound, multilevel models were fitted with either POPs total exposure from conception to 24 months or prenatal or postnatal exposure. Results: We found a significant increase in growth associated with p,p´-DDE, seemingly due to prenatal exposure (per interquartile increase in exposure, adjusted β = 0.12; 95% CI: 0.03, 0.22). Due to heterogeneity across cohorts, this estimate cannot be considered precise, but does indicate that an association with infant growth is present on average. In contrast, a significant decrease in growth was associated with postnatal PCB-153 exposure (β = –0.10; 95% CI: –0.19, –0.01). Conclusion: To our knowledge, this is the largest study to date of POPs exposure and infant growth, and it contains state-of-the-art exposure modeling. Prenatal p,p´-DDE was associated with increased infant growth, and postnatal PCB-153 with decreased growth at European exposure levels

Rational design and direct fabrication of multi-walled hollow electrospun fibers with controllable structure and surface properties

Multi-walled hollow fibers with a novel architecture are fabricated through utilizing a direct,one-step tri-axial electrospinning process with a manufacturing methodology which does not require any post-treatments for the removal of core material for creating hollowness in the fiber structure. The hydrophilicity of both inner and outer layers’ solution needs to be dissimilar and carefully controlled for creating a two-walled/layered hollow fiber tructure with a sharp interface. To this end, Hansen solubility parameters are used as n index of layer solution affinity hence allowing for control of diffusion across the layers and the surface porosity whereby an ideal multi-walled hollow electrospun fiber is shown to be producible by tri-axial electrospinning process. Multi-walled hollow electrospun fibers with different inner and outer diameters and different surface morphology are successfully produced by using dissimilar material combinations for inner and outer layers (i.e., hydrophobic polymers as outer layer and hydrophilic polymer as inner layer). Upon using different material combinations for inner and outer layers, it is shown that one may control both the outer and inner diameters of the fiber. The inner layer not only acts as a barrier and thus provides an ease in the encapsulation of functional core materials of interest with different viscosities but also adds stiffness to the fiber. The structure and the surface morphology of fibers are controlled by changing applied voltage, polymer types, polymer concentration, and the evaporation rate of solvents. It is demonstrated that if the vapor pressure of the solvent for a given outer layer polymer is low, the fiber diameter decreases down to 100 nm whereas solvents with higher vapor pressure result in fibers with the outer diameter of up to 1 μm. The influence of electric field strength on the shape of Taylor cone is also monitored during the production process and the manufactured fibers are structurally investigated by relevant surface characterization techniques

Identifizierung und Charakterisierung von Interaktionen synaptischer Proteine aus Mus musculus\textit {Mus musculus}

Das postsynaptische Protein Neurobeachin brachte in einer Hefe-2-Hybrid-Suche die Interaktion zwischen der BEACH-Domäne mit dem Transkriptionsfaktor PLZF hervor. Diese Interaktion konnte in weiteren Experimenten aber nicht verifiziert werden. Interaktionen zwischen den Aktive-Zone-Proteinen Aczonin, Cast/ERC2, Rim1 und Munc13-1 wurden im Hinblick auf ihr hetero-oligomeres Zusammenspiel mittels Kopräzipitationsexperimenten mit rekombinanten Subdomänen untersucht. Es wurden direkte und indirekte Interaktionen zwischen Subdomänen von Aczonin-Cast, Aczonin-Munc13-1 sowie Aczonin-Rim1 in binären und zwischen Aczonin-Cast-Munc13-1, Aczonin-Cast-Rim1 in ternären Komplexen und ein quaternärer Komplex zwischen Aczonin-Cast-Rim1-Munc13-1 gezeigt. Cast hat sich als Mediator für die Bildung von Hetero-Oligomeren zwischen Aczonin-Rim1-Munc13-1 erwiesen, indem es direkt mit Aczonin interagiert und synergetische Effekte für die Aczonin-Interaktion zu Munc13-1 und Rim1 herbeiführt

Influence of Low-Level Prenatal Exposure to PCDD/Fs and PCBs on Empathizing, Systemizing and Autistic Traits: Results from the Duisburg Birth Cohort Study.

BackgroundPolychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are assumed to act as endocrine disruptor chemicals. Prenatal exposure to these pollutants might influence fetal steroid hormone levels, which are thought to be related to sex-typical development and autistic traits.ObjectivesWe examined associations of prenatal levels of PCDD/Fs and PCBs with autism traits and sex-typical behaviour in childhood.MethodsWe measured levels of PCDD/Fs and PCBs in maternal blood samples during pregnancy using gas chromatography/high-resolution mass spectrometry. Sex-typical behaviour was assessed at 9 years of age (n = 96) and autistic traits at 10 years of age using the Social Responsiveness Scale (SRS; n = 100). Multiple regression analyses were conducted to estimate the associations between prenatal exposure and outcome variables.ResultsBlood concentrations (WHO2005-TEq) of ƩPCDD/Fs ranged from 2.93-46.45 pg/g lipid base (median = 12.91 pg/g lipid base) and concentrations of ƩPCBs were in the range of 1.24-25.47 pg/g lipid base (median = 6.85 pg/g lipid base) which is within the range of German background exposure. We found significant negative associations between PCDD/F levels in maternal blood and SRS scores in the whole group (β = -6.66, p ConclusionsIn an earlier part of this study, prenatal exposure to PCDD/Fs and PCBs was found to be associated with lower testosterone levels, therefore, our findings are consistent with the idea that autism spectrum conditions are related to fetal androgen levels. Several possible mechanisms, through which PCDD/Fs and PCBs might influence autistic behaviour, are discussed

Pre-pubertal exposure with phthalates and bisphenol A and pubertal development.

Epidemiological studies indicate associations between childhood exposure with phthalates and bisphenol A (BPA) and the pubertal development. We examined associations between the pre-pubertal phthalate and BPA body burden and the longitudinally assessed sexual maturation of eight- to thirteen-year-old children.We started with eight- to ten-year-old children in the baseline study and quantified phthalate metabolites and BPA in 472 urine samples (250 boys; 222 girls; mean age: 8.8 years). Associations between the pubertal development, assessed in three annual follow-up studies by Puberty Development scale questionnaires (PD scales), and the chemical exposure from the baseline visit were longitudinally analyzed with generalized estimation equations.The number of children with both chemical measures and PD scores (calculated from the PD scales) was 408. In the third follow-up, 49% of the girls and 18% of the boys had reached mid-puberty. For girls, we observed a delayed pubertal development with the di-hexyl-ethyl phthalate (DEHP) metabolites (β: -0.16 to -0.23; p ≤ 0.05 or p ≤ 0.1), mono-n-butyl phthalate (β: -0.15; 95% CI: -0.31; 0.01), mono-benzyl phthalate (β: -0.11; 95% CI: -0,24; -0,01), and mono-ethyl phthalate (MEP) (β: -0.15; 95% CI: -0.28; -0.01). In addition, significant non-linear associations of the DEHP metabolites and BPA with the PD scores were found, when their quadratic effects were included in the GEE models. In boys, no consistent relationships between the PD scores and the chemicals were detected except of an accelerated development with the ∑DEHP metabolites (β: 0.16; 95% CI: -0.02; -0.34).We found indications that pre-pubertal exposures with phthalates and BPA were associated with pubertal timing in children, particularly in girls. For boys, associations were inconsistent, and not necessarily in line with the known anti-androgenicity of some phthalates during prenatal exposure

Characteristics of the study population and the phthalate metabolite and BPA concentrations in urine.

<p>Characteristics of the study population and the phthalate metabolite and BPA concentrations in urine.</p

Influence of low-level prenatal exposure to PCDD/Fs and PCBs on empathizing, systemizing and autistic traits

$\bf Background$ Polychlorinated dibenzo-$\it p$-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) are assumed to act as endocrine disruptor chemicals. Prenatal exposure to these pollutants might influence fetal steroid hormone levels, which are thought to be related to sex-typical development and autistic traits. $\bf Objectives$ We examined associations of prenatal levels of PCDD/Fs and PCBs with autism traits and sex-typical behaviour in childhood. $\bf Methods$ We measured levels of PCDD/Fs and PCBs in maternal blood samples during pregnancy using gas chromatography/high-resolution mass spectrometry. Sex-typical behaviour was assessed at 9 years of age (n = 96) and autistic traits at 10 years of age using the Social Responsiveness Scale (SRS; n = 100). Multiple regression analyses were conducted to estimate the associations between prenatal exposure and outcome variables. $\bf Results$ Blood concentrations (WHO$_{2005}$-TEq) of $\Sigma$PCDD/Fs ranged from 2.93–46.45 pg/g $_{\textit {lipid base}}$ (median = 12.91 pg/g $_{\textit {lipid base}}$) and concentrations of $\Sigma$PCBs were in the range of 1.24–25.47 pg/g $_{\textit {lipid base}}$ (median = 6.85 pg/g $_{\textit {lipid base}}$) which is within the range of German background exposure. We found significant negative associations between PCDD/F levels in maternal blood and SRS scores in the whole group ($\beta$ = -6.66, $\it p$ < .05), in girls ($\beta$ = -10.98, $\it p$ < .05) and, in one SRS subscale, in boys ($\beta$ = -6.86, $\it p$ < .05). For PCB levels, associations with one SRS subscale were significant for the whole study group as were associations with two subscales in girls. We did not find significant associations between PCDD/F or PCB levels and sex-typical behaviour for either sex. $\bf Conclusions$ In an earlier part of this study, prenatal exposure to PCDD/Fs and PCBs was found to be associated with lower testosterone levels, therefore, our findings are consistent with the idea that autism spectrum conditions are related to fetal androgen levels. Several possible mechanisms, through which PCDD/Fs and PCBs might influence autistic behaviour, are discussed

SRS total and subscale scores and EQ-SQ scores for the whole group and for each sex separately.

<p>M = mean; SD = standard deviation; n = numbers; SRS = Social Responsiveness Scale; SRS total = total score of the SRS; SRS SA = Social Awareness subscale score; SRS SC = Social Cognition subscale score; SRS SCO = Social Communication subscale score; SRS SM = Social Motivation subscale score; SRS AM = Autistic Mannerisms subscale score; SRS ASC Score = T-score compared to children with autism; EQ = Empathy Quotient; SQ = Systemizing Quotient.</p><p>SRS total and subscale scores and EQ-SQ scores for the whole group and for each sex separately.</p