Qatar Biobank: COVID-19 biorepository project

Background: The rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its resulting disease (COVID-19) is one of the greatest global public health crisis of the recent decades 1 . The COVID-19 Biorepository is a national project aimed to support the high demand of biomedical research by multiple groups and the need to have access to high quality, curated clinical data, and specimens contributing to the understanding of, and response to, the COVID-19 pandemic and its impacts in Qatar 2, 3 . Methods/Case presentation: Patients with a laboratory diagnosis of COVID-19, who were Qatar residents that could communicate in Arabic, English, Hindi, and Urdu were eligible to participate in the study. COVID-19 diagnosed patients were recruited at the time of their disease period from the main three public hospitals (Communicable Disease Center, Cuban, and Hazm Mebaireek Hospitals) serving as isolation facilities of symptomatic patients in Qatar, during a 7-month period from March 2020 until September 2020. Consented participants were followed up on a weekly basis until recovery, and then monthly for a year. Sociodemographic and clinical data were collected in electronic questionnaires via a face-to-face interview by trained Qatar Biobank (QBB) staff. Results: A total of 2097 consented participants were recruited up to September 2020, males (N = 1050) and females (N = 1047), with a mean age of 41 years (SD: 15.5). 61.0% of the participants had at least one follow up while 27% adhered to monthly follow up visits. Data was collected for 99.7% of the participants, while the follow up process is still ongoing. In total there are 107,171 high quality specimens in the biorepository including plasma, erythrocytes, buffy coat, serum, PAXgene whole blood, nasopharyngeal secretions, and DNA. Conclusion: The COVID-19 Biorepository is a national asset to illuminate the pathophysiological and identify markers of disease prognosis as well as to describe the clinical features and epidemiology of COVID-19 in Qatar and worldwide.qscienc

Syndecan-1 and FGF-2, but Not FGF Receptor-1, Share a Common Transport Route and Co-Localize with Heparanase in the Nuclei of Mesenchymal Tumor Cells

Syndecan-1 forms complexes with growth factors and their cognate receptors in the cell membrane. We have previously reported a tubulin-mediated translocation of syndecan-1 to the nucleus. The transport route and functional significance of nuclear syndecan-1 is still incompletely understood. Here we investigate the sub-cellular distribution of syndecan-1, FGF-2, FGFR-1 and heparanase in malignant mesenchymal tumor cells, and explore the possibility of their coordinated translocation to the nucleus. To elucidate a structural requirement for this nuclear transport, we have transfected cells with a syndecan-1/EGFP construct or with a short truncated version containing only the tubulin binding RMKKK sequence. The sub-cellular distribution of the EGFP fusion proteins was monitored by fluorescence microscopy. Our data indicate that syndecan-1, FGF-2 and heparanase co-localize in the nucleus, whereas FGFR-1 is enriched mainly in the perinuclear area. Overexpression of syndecan-1 results in increased nuclear accumulation of FGF-2, demonstrating the functional importance of syndecan-1 for this nuclear transport. Interestingly, exogenously added FGF-2 does not follow the route taken by endogenous FGF-2. Furthermore, we prove that the RMKKK sequence of syndecan-1 is necessary and sufficient for nuclear translocation, acting as a nuclear localization signal, and the Arginine residue is vital for this localization. We conclude that syndecan-1 and FGF-2, but not FGFR-1 share a common transport route and co-localize with heparanase in the nucleus, and this transport is mediated by the RMKKK motif in syndecan-1. Our study opens a new perspective in the proteoglycan field and provides more evidence of nuclear interactions of syndecan-1

Влияние лечения тиотриазолином на состояние перекисного окисления липидов и уровни иммуновоспалительных и вазоактивных эндотелиальных факторов у больных с хронической сердечной недостаточностью и helicobacter pylori-негативными гастропатиями

Показано, что включение в схему патогенетического лечения больных с ХСН, hp-негативной гастропатией и умеренным или высоким риском сердечно-сосудистых осложнений (ССО) антиоксиданта тиотриазолина сопровождается достоверно более выраженными позитивными эффектами на процессы перекисного окисления липидов и содержание в крови иммуновоспалительных и вазоактивных эндотелиальных факторов по сравнению с динамикой при лечении без использования тиотриазолина, причем степень положительной динамики у больных с высоким риском ССО достоверно больше.Показано, що включення у схему патогенетичного лікування хворих із ХСН, hр-негативною гастропатією і з помірним або високим ризиком серцево-судинних ускладнень (ССУ) антиоксиданта тіотриазоліна супроводжується достовірно більш вираженими позитивними ефектами на процеси перекисного окислення ліпідів та вміст у крові імунозапальних і вазоактивних ендотеліальних факторів порівняно з динамікою при лікуванні без використання тіотриазоліну, причому ступінь позитивної динаміки у хворих із високим ризиком ССУ достовірно більший.It is shown that the use of tiotriazolin in the scheme of pathogenetic treatment of patients with chronic heart failure, Hp-negative gastropathy, and moderate or high risk of cardiovascular complications (CVC) is accompanied by significantly higher positive effect on the processes of lipid peroxidation and the amount of immune inflammation and vasoactive endothelial factors in the blood when compared with the dynamics at treatment without the use of tiotriazolin, the degree of positive dynamics in patients with a high risk of CVC being significantly higher

Specific Syndecan-1 Domains Regulate Mesenchymal Tumor Cell Adhesion, Motility and Migration

Malignant mesothelioma is an asbestos induced cancer that is difficult to diagnose. Several studies have combined biomarkers to improve mesothelioma diagnosis, but with moderate success, and there is a need for new mesothelioma biomarkers. The tumour is often resistant to treatment and most patients will survive less than a year. An indicator of patient survival is the tumours growth pattern, which in turn is influenced by expressed proteoglycans. In this thesis work, we aim to improve the possibilities to diagnose malignant mesothelioma by combining biomarkers and by identifying new ones. We also investigate tumour driving mechanisms with focus on one of these suggested biomarkers, the cell-bound proteoglycan syndecan-1. We were able to construct a diagnostic two-step model based on biomarkers in patient material. By implementing a cut-off level and thereafter focusing on unresolved patients we combined hyaluronan and N-ERC/mesothelin (paper I), which significantly increased the diagnostic accuracy for malignant mesothelioma. To further improve diagnosis, we used mass spectrometry to find new biomarkers. We identified and validated galectin-1, which was excellent in discriminating mesotheliomas from adenocarcinomas (paper II). In the same study, we were also the first to describe aldo-keto reductase 1B10 as a novel prognostic mesothelioma biomarker. Syndecan-1 has been indicated as a marker for carcinomas. In paper I we describe how higher levels of syndecan-1 indicate the presence of a carcinoma over a mesothelioma. This was verified in paper II when syndecan-1 was identified as downregulated in fluids from mesothelioma patients compared to lung cancer patients. Paper III and paper IV focus on this proteoglycan. Malignant cell lines transfected with syndecan-1 and various truncated forms of syndecan-1 affected adhesion and migration, which are key features of cancer invasion (paper III). The results showed a domain- and cell type specific effect on the cells’ motility. Regulating syndecan-1 levels and analysing the global gene expression of mesothelioma cells made it evident that this proteoglycan has a strong influence on transforming growth factor β signalling and several growth factor pathways (paper IV). Links to cell migration and proliferation were furthermore identified, along with glycosaminoglycan modifying enzymes. These results can shed light on the complex role of syndecan-1 in invasion and growth of malignant mesenchymal cells. Taken together, this thesis work describes a complement to conventional mesothelioma diagnosis and identifies novel biomarkers. Furthermore, the potential biomarker syndecan-1 was shown to have an effect on cell motility and proliferation. These results increase our understanding of this aggressive malignancy

Environmental, Dietary, Maternal, and Fetal Predictors of Bulky DNA Adducts in Cord Blood: A European Mother–Child Study (NewGeneris)

Background:Bulky DNA adducts reflect genotoxic exposures, have been associated with lower birth weight, and may predict cancer risk.Objective:We selected factors known or hypothesized to affect in utero adduct formation and repair and examined their associations with adduct levels in neonates.Methods:Pregnant women from Greece, Spain, England, Denmark, and Norway were recruited in 2006–2010. Cord blood bulky DNA adduct levels were measured by the 32P-postlabeling technique (n = 511). Diet and maternal characteristics were assessed via questionnaires. Modeled exposures to air pollutants and drinking-water disinfection by-products, mainly trihalomethanes (THMs), were available for a large proportion of the study population.Results:Greek and Spanish neonates had higher adduct levels than the northern European neonates [median, 12.1 (n = 179) vs. 6.8 (n = 332) adducts per 108 nucleotides, p < 0.001]. Residence in southern European countries, higher maternal body mass index, delivery by cesarean section, male infant sex, low maternal intake of fruits rich in vitamin C, high intake of dairy products, and low adherence to healthy diet score were statistically significantly associated with higher adduct levels in adjusted models. Exposure to fine particulate matter and nitrogen dioxide was associated with significantly higher adducts in the Danish subsample only. Overall, the pooled results for THMs in water show no evidence of association with adduct levels; however, there are country-specific differences in results with a suggestion of an association in England.Conclusion:These findings suggest that a combination of factors, including unknown country-specific factors, influence the bulky DNA adduct levels in neonates.Citation:Pedersen M, Mendez MA, Schoket B, Godschalk RW, Espinosa A, Landström A, Villanueva CM, Merlo DF, Fthenou E, Gracia-Lavedan E, van Schooten FJ, Hoek G, Brunborg G, Meltzer HM, Alexander J, Nielsen JK, Sunyer J, Wright J, Kovács K, de Hoogh K, Gutzkow KB, Hardie LJ, Chatzi L, Knudsen LE, Anna L, Ketzel M, Haugen M, Botsivali M, Nieuwenhuijsen MJ, Cirach M, Toledano MB, Smith RB, Fleming S, Agramunt S, Kyrtopoulos SA, Lukács V, Kleinjans JC, Segerbäck D, Kogevinas M. 2015. Environmental, dietary, maternal, and fetal predictors of bulky DNA adducts in cord blood: a European mother–child study (NewGeneris). Environ Health Perspect 123:374–380; http://dx.doi.org/10.1289/ehp.140861

Micronuclei in cord blood lymphocytes and associations with biomarkers of exposure to carcinogens and hormonally active factors, gene polymorphisms, and gene expression: The NewGeneris cohort

Background: Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure-outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG-DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN frequency. Polymorphisms in EPHX1/2 and CYP2E1 were associated with MNBN. Conclusion: We measured in utero exposure to selected environmental carcinogens and circulating hormonally acting factors and detected associations with MN frequency in newborns circulating T lymphocytes. The results highlight mechanisms that may contribute to carcinogen-induced leukemia and require further research

Βιοχημική και ανοσολογική μελέτη της δράσης των αυξητικών παραγόντων στη σύνθεση μεμβρανικών και εκκρινόμενων πρωτεογλυκανών σε κυτταρικές σειρές ινοσαρκώματος και φυσιολογικών ινοβλαστών

Fibrosarcoma is an uncommon tumor with a rich extracellular matrix, there are no specific biomarkers for its diagnosis. Versican, a large chondroitin sulphate proteoglycan and hyaluronan (HA), a non-sulphated glycosaminoglycan are major constituents of the pericellular matrix. Inmany neoplastic tissues, changes in the expression of versican and HAaffect tumour progression. In this study, it was analysed the synthesis of versican and hyaluronan by fibrosarcoma cells, and document how the latter is affected by PDGF-BB, bFGF and TGFB2, growth factors endogenously produced by these cells. Fibrosarcoma cell lines B6FS and HT1080were utilised and compared with normal lung fibroblasts (DLF). The major versican isoforms expressed by DLF and B6FS cells were V0 and V1. Treatment of B6FS cells with TGFB2 showed a significant increase ofV0 and V1mRNAs. Versican expression in HT1080 cells was not significantly affected by any of the growth factors. In addition, TGFB2 treatment increased versican protein in DLF cells. HA, showed approximately a 2-fold and a 9-fold higher production in DLF cells compared to B6FS and HT1080 cells, respectively. In HT1080 cells, HA biosynthesis was significantly increased by bFGF, whereas, in B6FS cells it was increased by TGFB2 and PDGF-BB. Furthermore, analysis of HA synthases (HAS) expression indicated that HT1080 expressed similar levels of all three HAS isoforms in the following order: HAS2N HAS3N HAS1. bFGF shifted that balance by increasing the abundance of HAS1. The major HAS isoform expressed by B6FS cells was HAS2. PDGFBB and TGFB2 showed the most prominent effects by increasing both HAS2 and HAS1 isoforms. In conclusion, these growth factors modulated, through upregulation of specific HAS isoforms, HA synthesis, secretion and net deposition to the pericellular matrix. Syndecan-1 is suggested to participate in the regulation of a number of cellular processes such as cell proliferation and migration. Recent studies have suggested the putative mechanisms of synmdecan-1 cytoplasmic, transmembrane and extracellular domain action on cell functions and signal transduction. The aim of this study was to investigate the effect of specific syndecan-1 domains on fibrosarcoma cell migration and proliferation. Transfected B6FS fibrosarcoma cells with full length (FL/EGFP)of syndecan-1 construct, a variant coding for the endodomain (77/EGFP) and a variant coding for the RMKKK cytoplasmic sequence, were used. The expression and cellular localization of the FL, 77 and RMKKK recombinant proteins was analysed using confocal microscopy, after six weeks selection 1 5 using geneticin (400μg/ml). Recombinant FL/EGFP showed cell membrane reactivity while RMKKK/EGFP showed distinct nuclear localization. The overexpression of 77/EGFP that lacks the ectodomain resulted in altered morphology, the cells became smaller and rounded. The proliferation of transfected fibrosarcoma cells with the respective constructs was measured using WST-1 colorimetric reagent. Our results demonstrated that the expression of both full length and the two truncated recombinant proteins, compared to vector transfected cells, significantly inhibited fibrosarcoma cell proliferation. B6FS transfected with the 77/ EGFP and the RMKKK/EGFP constructs lack the ectodomain of syndecan-1, enhancing the suggestion that the syndecan-1 ectodomain is responsible for the stimulation of proliferation.Furthermore, we studied the effect of FL/EGFP, the endodomain 77/EGFP and the cytoplasmic RMKKK/EGFP recombinant proteins on the migrative response of B6FS fibrosarcoma cells. Our results demonstrated that B6FS cells transfected with FL/EGFP and RMKKK/EGFP constructs had an enhanced migration capability compared to EGFP vector transfected cells. In contrast, the expression of 77/EGFP recombinant protein inhibited B6FS cell migration. This study suggets that syndecan-1 ectodomain may have a “switch” function , resulting in activation of the cytoplasmic domain, after ligand binding. Platelet derived growth factor is involved in the autocrine growth stimulation of malignant cells, the stimulation of angiogenesis and the recruitment and regulation of tumor fibroblasts. PDGF has been shown to physically interact with glycosaminoglycans which are abundant in the fibrosarcoma cell microenvironment. Aim of the present study was to examine the effects of glycosaminoglycans on the mitogenic function of platelet derived growth factor in two human fibrosarcoma cell lines (B6FS, HT1080). For this purpose exogenously added glycosaminoglycans, regulators of endogenous glycosaminoglycan synthesis (sodium chlorate as selective inhibitor and β- D--xyloside as a stimulator) and specific glycosidases to cleave cell-associated glycosaminoglycans, were utilized. Platelet derived growth factor demonstrated a growth stimulating effect on B6FS, whereas no effect was evident on HT1080 fibrosarcoma cells. β-D-xyloside had no effect on the basal level or the platelet derived growth factor-induced cell proliferation, whereas sodium chlorate severely reduced the basal level of proliferation in both cell lines. Significant co-stimulatory effects of chondroitin sulfate A in combination with platelet derived growth factor BB on the growth of HT1080 and B6FS cells were found. The co-stimulatory effect of chondroitin sulfate A was not due to transcriptional up regulation of platelet derived growth factor receptors genes, but rather to more efficient signalling of tyrosine kinase receptors. In conclusion, this study shows that chondroitin sulfate A can enhance the mitogenic activity of platelet-derived growth factor in fibrosarcoma cells utilizing a pathway which involves tyrosine kinases. This result introduces a new modulating...Το ινοσάρκωμα ορίζεται ως κακοήθης όγκος των μαλακών μορίων , αποτελούμενος από ινοβλάστες. Είναι ασυνήθης όγκος καθώς αριθμεί λιγότερο του 1% στους ενήλικες και του 7% όλων των παιδιατρικών κακοηθειών. Δεν υπάρχουν ανοσολογικοί δείκτες για αυτόν τον τύπο κυττάρων, με αποτέλεσμα η διάγνωση του ινοσαρκώματος με ανοσοϊστοχημικές μεθόδους να γίνεται εξ αποκλεισμού από τους άλλους τύπους σαρκωμάτων. Οι πρωτεογλυκάνες είναι θειομένες πρωτεΐνες αποτελούμενες από έναν πρωτεινικό κορμό συνδεδεμένο με γλυκοζαμινογλυκάνες. Συμμετέχουν στη ρύθμιση σημαντικών κυτταρικών γεγονότων όπως, κυτταρική προσκόλληση, διήθηση, διαφοροποίηση και πολλαπλασιασμό. Συμμετέχουν επίσης στην οργάνωση του εξωκυττάριου χώρου μέσω των αλληλεπιδράσεων τους με σημαντικά μακρομόρια όπως, το κολλαγόνο, τις λιποπρωτεϊνες και τους αυξητικούς παράγοντες. Λίγα είναι γνωστά για τις PGs και GAGs στους όγκους των μαλακών μορίων. Όγκοι του στρώματος και όγκοι ινώδους ιστού περιέχουν PGs και GAGs σε υψηλότερα επίπεδα από ότι ο περιβάλλον ιστός. Η ανάπτυξη του καρκίνου ως εξέλιξη με πολλά βήματα χρειάζεται μεταξύ των άλλων και επιπλέον μελέτες για των χαρακτηρισμό της ανάμειξης των διαφόρων πρωτεογλυκανών σε κάθε βήμα των νεοπλασιών. Καθορισμός του ρόλου της κάθε πρωτεογλυκάνης και ξεχωριστά των εκκρινόμενων ή/και των συνδεδεμένων με την κυτταρική μεμβράνη πρωτεογλυκανών στους παθολογικούς μηχανισμούς. Η πληρέστερη ανάλυση της δομής των γλυκοζαμινογλυκανικών αλυσίδων πρέπει επίσης να συσχετίζεται με την παθολογική ανατομική. Πιστεύεται, ότι η γνώση της δομής και του ρόλου ειδικών πρωτεογλυκανών θα προσφέρει μηχανισμούς δράσης που θα βοηθήσουν την θεραπεία του καρκίνου. Για την μελέτη της έκφρασης των πρωτεογλυκάνων σε κύτταρα ινοσαρκώματος χρησιμοποιήσαμε ως βιολογικά μοντέλα δυο κυτταρικές σειρές ινοσαρκώματος από άνθρωπο την HT1080 και την B6FS. Τα κύτταρα ΗΤ1080 χαρακτηρίζονται ως επιθηλιακά, ενώ τα B6FS κύτταρα ως ινοβλαστοειδή, καθώς επίσης και φυσιολογικούς ινοβλάστες (DLF) απο πνεύμονα ανθρώπου. Ξεκινήσαμε με τον χαρακτηρισμό των πρωτεογλυκανών και των υποδοχέων των αυξητικών παραγόντων που εκφράζει η κάθε μια από τις κυτταρικές σειρές. Στη συνέχεια, μελετήσαμε την επίδραση των αυξητικών παραγόντων, και συγκεκριμένα των PDGF-BB, FGF, και TGF, στα επίπεδα των έκφρασης των πρωτεογλυκανών. Η περιοχή γύρω από το κύτταρο αποτελείται κυρίως από τη πρωτεογλυκάνη βερσικάνη και το υαλουρονικό οξύ που σχηματίζουν ένα σύμπλοκο. Σε πολλούς νεοπλαστικούς ιστούς η αλλαγή της έκφρασης της βερσικάνης και του υαλουρονικού οξέους σχετίζεται με την εξέλιξη του καρκίνου. Στον καρκίνο του μαστού και του προστάτη η αυξημένη έκφραση βερσικάνης στα στρωματικά κύτταρα και σε αυτά γύρω από τον όγκο χρησιμοποιείται σαν καρκινικός δείκτης. Συμπληρωματικά, αυξημένη έκφραση του υαλουρονικού οξέος σχετίζεται με την εξέλιξη του καρκίνου του παχέος εντέρου , του πνεύμονα και του μαστού. Στόχοι της μελέτης ήταν 1) ο χαρακτηρισμός των επιπέδων έκφρασης της βερσικάνης και του υαλουρονικού οξέος στα κύτταρα ινοσαρκώματοςκαι 2) η επίδραση των PDGF-BB, FGF, και TGF αυξητικών παραγόντων στη βιοσύνθεση των παραπανω. Οι κυτταρικές σειρές ινοσαρκώματος που χρησιμοποιήθηκαν ήταν οι HT1080 και B6FS..

Qatar Biobank: A Paradigm of Translating Biobank Science into Evidence-Based Health Care Interventions

Biobank science is progressively becoming indispensable for the development of novel diagnostic tools in health care, by pairing standardized high-quality biological samples, phenotypic, and omics data required to best characterize the underlying biological mechanisms of response to therapy and survival. Qatar Biobank (QBB), Qatar's National Repository Centre for biological samples and health information, aligning with these endeavors, has developed a strategic framework to enable biobanking science that can be transformed into tangible health care diagnostic tools. In this concept, QBB works closely with multidisciplinary stakeholders: (1) governmental authorities ( = 2), (2) health providers ( = 3), (3) academic institutions ( = 28), (4) other research institutions ( = 6), and (5) the Qatar National Research Fund, by providing data and biospecimens to research projects. The local community organizes campaigns through social media and interactive events, spreading the concept of biobanking to inform and encourage people to participate. Up to now, QBB has recruited up to 30% of the targeted population and collaborated with 35 national and international research entities contributing to more than 170 research projects. QBB is referring about 53% of its participants to the Hamad general hospital through the integrated information system, revealing the need of new health screening approaches for public health policy makers. QBB contributed to the development of a customized genetic screening microarray tailored to the Qatari population that will be used in research as well as for the screening of variants of medical relevance in Qatar, promoting precision medicine in Qatar's health care system. The QBB strategic plan is a paradigm for the optimal utilization of resources, infrastructure, and investments engaging the local authorities and the research entities, and committing them to data sharing and working together toward the discovery of evidence-based health care interventions

Phthalate esters, parabens and bisphenol-A exposure among mothers and their children in Greece (Rhea cohort)

Exposure to endocrine disruptors, used as additives, preservatives, plasticisers and solvents in numerous consumer products, might cause adverse health effects. Humans exposed to these chemicals, metabolise and excrete them mostly via urine. Urinary metabolite concentrations are used as biomarkers of exposure. We evaluated the exposure of 4-month pregnant women and their children at 2 years of age to phthalates, parabens and bisphenol-A. Concentrations of eight phthalate metabolites, six parabens and bisphenol-A were measured in 239 mother-child pairs of the “Rhea” cohort in Greece. Concentration levels in mother and children were comparable with corresponding concentrations in other countries worldwide. Low Spearman correlation coefficients (CC 0.1-0.2, p-value &lt; 0.01) were observed for di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), butyl-benzyl phthalate (BBP) and ethyl paraben (EPB) between mothers and their children. We observed higher median daily intake (DIu) for mothers (e.g. di-ethyl phthalate 6.9 mu g d(-1) kg(-1)) than for their children (1.4 mu g d(-1) kg(-1)) for all examined compounds, except for di-2-ethylhexyl phthalate (DEHP) and bisphenol-A. Principal component analysis (PCA) indicated two main sources of exposure (plastic related and personal carehygiene products) for phthalates, parabens and bisphenol-A. Differences in DEHP metabolism were observed among mothers-children and female-male children. (C) 2015 Elsevier Ltd. All rights reserved