Bisphenols and Oxidative Stress Biomarkers—Associations Found in Human Studies, Evaluation of Methods Used, and Strengths and Weaknesses of the Biomarkers

We thank our other HBM4EU colleagues (mentioned as co-authors in Mustieles et al., 2020) for their contribution to the first literature searches.Bisphenols, particularly bisphenol A (4,40 -(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with adverse health outcomes. We investigated the associations between exposure to bisphenols and biomarkers of oxidative stress in human studies over the last 12 years (2008-2019) related to six health endpoints and evaluated their suitability as effect biomarkers. PubMed database searches identified 27 relevant articles that were used for data extraction. In all studies, BPA exposure was reported, whereas some studies also reported other bisphenols. More than a dozen different biomarkers were measured. The most frequently measured biomarkers were 8-oxo-7,8-dihydro-20 -deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoprostane) and malondialdehyde (MDA), which almost always were positively associated with BPA. Methodological issues were reported for MDA, mainly the need to handle samples with caution to avoid artefact formation and its measurements using a chromatographic step to distinguish it from similar aldehydes, making some of the MDA results less reliable. Urinary 8-OHdG and 8-isoprostane can be considered the most reliable biomarkers of oxidative stress associated with BPA exposure. Although none of the biomarkers are considered BPAor organ-specific, the biomarkers can be assessed repeatedly and non-invasively in urine and could help to understand causal relationships.HBM4EU project - European Union's Horizon 2020 research and innovation program 73303

Genome‑wide distribution of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: a pilot study with human and in vitro data

Objective: To assess the genetic and epigenetic effects promoted by Bisphenol A (BPA) exposure in adolescent males from the Spanish INMA-Granada birth cohort, and in human cells. Methods: DNA methylation was analysed using MEDIP. Repeat number variation in genomic DNA was evaluated, along with the analysis of H3K4me3 by using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Analyses were performed with material extracted from whole blood of the adolescents, complemented by in vitro assessments of human (HeLa) cells exposed to 10 nM BPA, specifically, immunofluorescence evaluation of protein levels, gene expression analysis and ChIP‒qPCR analysis. Results: Adolescents in the high urinary BPA levels group presented a higher level of Satellite A (SATA) repetitive region copy numbers compared to those in the low BPA group and a tendency towards increase in telomere length. We also observed decreased DNA methylation at the promoters of the imprinted genes H19, KCNQ1, and IGF2; at LINE1 retroelements; and at the ARID2, EGFR and ESRRA and TERT genes. Genome-wide sequencing revealed increased H3K4me3 occupancy at the promoters of genes encoding histone acetyltransferases, telomeric DNA binding factors and DNA repair genes. Results were supported in HeLa cells exposed to 10 nM BPA in vitro. In accordance with the data obtained in blood samples, we observed higher H3K4me3 occupancy and lower DNA methylation at some specific targets in HeLa cells. In exposed cells, changes in the expression of genes encoding DNA repair factors (ATM, ARID2, TRP53) were observed, and increased expression of several genes encoding telomeric DNA binding factors (SMG7, TERT, TEN1, UPF1, ZBTB48) were also found. Furthermore, an increase in ESR1/ERa was observed in the nuclei of HeLa cells along with increased binding of ESR1 to KAT5, KMT2E and TERF2IP promoters and decreased ESR1 binding at the RARA promoter. The DNA damage marker p53/TP53 was also increased. Conclusion: In this pilot study, genome-wide analysis of histone trimethylation in adolescent males exposed to BPA revealed a global impact on the expression of genes encoding telomeric binding proteins and histone acetyltransferase factors with similar results in HeLa cells. Nevertheless, larger studies should confirm our findings.European Commission E17013NKInstitut National de la Sante et de la Recherche Medicale (Inserm) European CommissionNational Natural Science Foundation of China (NSFC) 3180106

Estrategia de reconocimiento de pacientes hospitalizados en áreas no controladas del servicio de urgencias de la Fundación Cardioinfantil

57 páginasLa FUNDACIÓN CARDIOINFANTIL es una institución privada sin ánimo de lucro constituida en 1973, dirigida principalmente a la atención de niños con problemas cardiovasculares, que por sus escasos recursos no pueden acceder a la calidad y tecnología de los servicios de salud que requieren. Dada la magnitud de los problemas cardiovasculares en otros grupos generacionales y con el fin de dar continuidad a la obra iniciada con los niños, en octubre de 1993 se creó el INSTITUTO DE CARDIOLOGÍA, extendiendo la atención cardiológica a pacientes de todas las edades y ampliando su portafolio de servicios con 51 especialidades médico-quirúrgicas para brindar atención integral a todos sus pacientes. Los iniciales cinco mil metros cuadrados de la Fundación Cardioinfantil pasaron a ser un complejo clínico de cuarto nivel de 70.000 metros cuadrados, con prometedores avances en cincuenta y tres (53) especialidades médico-quirúrgicas. La Fundación recibe aproximadamente un millón de visitantes al año, prestando atención mensualmente a un promedio de 1.100 pacientes hospitalizados, 9.000 consultas de urgencia, 9.500 consultas ambulatorias especializadas, cerca de 12.000 exámenes diagnósticos y 8.600 cirugías (de las cuales 1.200 corresponden a cirugías cardíacas), convirtiéndose así en uno de los complejos médicos de cuarto nivel más importantes del país y de Latinoamérica

Xeno-estrogenic activity of real-life mixtures of perfluoroalkylated substances in human placenta homogenates

The authors thank the European Union's Horizon 2020 research and innovation programme HBM4EU under Grant Agreement No. 733032 for its financial support, as well as the Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Publica (CIBERESP) , and the Instituto de Salud Carlos III (ISCIII) (FIS-PI16/01820) . We thank pre-vious and current colleagues at Centre for Arctic Health and Molecular Epidemiology, Aarhus University for their valuable scientist support. The authors also thank the Spanish Ministry of Education for the pre-doctoral fellowship (FPU) granted to A. Rodriguez-Carrillo (FPU 16/03011) .Humans are simultaneously exposed to complex chemical mixtures, and its combined effect can affect human health. As part of the HBM4EU project, the actual mixture of perfluoroalkylated substances (PFAS) in 25 human placenta samples was extracted by chromatographic methods and assessed for xeno-estrogenic activity using two in-vitro bioassays: the estrogen receptor transactivity and the E-Screen assay. Most of the PFAS extracts displayed xeno-estrogenic activity, in one or both assays. The xeno-estrogenic activities in the two bioassays were not correlated, but both assays showed an overall negative correlation with placenta concentrations of single PFAS. Xeno-estrogenic activities were significantly related to maternal characteristics; being higher in young, smokers and primiparous women, but not with fetal growth (birth weight, birth length, head circumference, gestational age, placenta weight). The presented extraction method can be used to study the combined effect of real-life mixtures of PFAS in relation to health outcomes in large-scale human biomonitoring studies.European Union's Horizon 2020 research and innovation programme HBM4EU 733032Biomedical Research Networking Center-CIBER de Epidemiologia y Salud Pblica (CIBERESP)Instituto de Salud Carlos III Spanish Government FIS-PI16/01820Spanish Government FPU 16/0301

Assessment of chemical mixtures using biomarkers of combined biological activity: A screening study in human placentas

The authors thank the European Union’s Horizon 2020 research and innovation programme HBM4EU under Grant Agreement No. 733032 for its financial support. Vicente Mustieles and Stephan Couderq are under contract within the HBM4EU project. Additionally, we acknowledge the Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), and the Instituto de Salud Carlos III (ISCIII) (FIS-PI16/01820 and FIS-PI16/01858). The authors also thank the ISCIII and “Fondo Europeo de Desarrollo Regional” (ISCIII/FEDER) for the Sara Borrell postdoctoral research contract granted to F. Vela-Soria (grant no. CD17/00212), and the Spanish Ministry of Education for the predoctoral fellowship (FPU) granted to A. Rodríguez-Carrillo (FPU 16/03011). This article will be part of the doctoral thesis developed by Andrea Rodríguez-Carrillo in the context of the “Clinical Medicine and Public Health Program” of the University of Granada (Spain). The authors gratefully acknowledge the technical assistance of Birgitte Møller Plesning.Humans are simultaneously exposed to complex mixtures of chemicals with limited knowledge on potential health effects, therefore improved tools for assessing these mixtures are needed. As part of the Human Bio-monitoring for Europe (HBM4EU) Project, we aimed to examine the combined biological activity of chemical mixtures extracted from human placentas using one in vivo and four in vitro bioassays, also known as biomarkers of combined effect. Relevant endocrine activities (proliferative and/or reporter gene assays) and four endpoints were tested: the estrogen receptor (ER), androgen receptor (AR), and aryl hydrocarbon receptor (AhR) activities, as well as thyroid hormone (TH) signaling. Correlations among bioassays and their functional shapes were evaluated. Results showed that all placental extracts agonized or antagonized at least three of the above-mentioned endpoints. Most placentas induced ER-mediated transactivation and ER-dependent cell proliferation, together with a strong inhibition of TH signaling and the AR transactivity; while the induction of the AhR was found in only one placental extract. The effects in the two estrogenic bioassays were positively and significantly correlated and the AR-antagonism activity showed a positive borderline-significant correlation with both es-trogenic bioassay activities. However, the in vivo anti-thyroid activities of placental extracts were not correlated with any of the tested in vitro assays. Findings highlight the importance of comprehensively mapping the bio-logical effects of ?real-world? chemical mixtures present in human samples, through a battery of in vitro and in vivo bioassays. This approach should be a complementary tool for epidemiological studies to further elucidate the combined biological fingerprint triggered by chemical mixtures.European Commission 733032"Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) CD17/00212Spanish Government FPU 16/03011Instituto de Salud Carlos III CD17/0021

Regulation of drug prices in Colombia : the case of tenecteplase

Q4Carta al editor45

Chagas: a complex problem to approach from multiple dimensions

Hablar de Chagas es mucho más que hablar de una enfermedad, ya que en realidad se trata de una problemática de salud socio-ambiental compleja. Considerarla de esta manera implica abordar aspectos culturales, educativos, políticos, económicos, ambientales y sociales, además del tradicional abordaje biomédico. Por lo tanto, creemos fundamental pensar al Chagas de manera integral sumando diferentes perspectivas, resaltando la importancia multiplicativa de la educación en la prevención y sensibilización, para lo cual pensamos una propuesta interdisciplinaria e innovadora a través de la cual hemos ido articulando con diferentes instituciones. Contando con la participación de personas provenientes de distintas disciplinas conformamos el grupo ?¿De qué hablamos cuando hablamos de Chagas?? (CONICET - UNLP - CIIE) mediante el cual apuntamos a difundir el tema en museos, escuelas y otros ámbitos institucionales. En este texto queremos compartir nuestra experiencia realizando el taller: ¿POR QUÉ, CUÁNDO Y CÓMO HABLAR DE CHAGAS EN EL AULA? que desarrollamos durante los años 2014, 2016 y 2017 en el marco de la Semana de la Enseñanza de las Ciencias (FCEN, UBA).When we discuss Chagas, we refer not only to a disease but also to a very complex health problem that involves social and environmental aspects as well. Considering this perspective of Chagas implies taking into account cultural, educational, political, economic, environmental and social aspects, besides the traditional biomedical approach. We consider it fundamental to think about Chagas in an integrated way, adding different perspectives including the important role of education in preventing and raising awareness. To achieve this goal, we have worked on an innovative and interdisciplinary pedagogical proposal that has allowed us to work together with different institutions. With the participation of people from different disciplines, we have created the group "¿De qué hablamos cuando hablamos de Chagas?" (CONICET - UNLP - CIIE) whose aim is to communicate this approach in museums, schools, and other institutional settings. In this text we want to share our experience doing the workshop "WHY, WHEN AND HOW TO SPEAK OF CHAGAS IN THE CLASSROOM" that we developed during the Semana de la Enseñanza de las Ciencias in 2014, 2016 and 2017 (FCEN UBA).Fil: MATEYCA, ANDREA CELESTE. Grupo de Didáctica de Las Ciencias; ArgentinaFil: Ruiz MD. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; ArgentinaFil: Boveda E. Ministerio de Justicia y Derechos Humanos; ArgentinaFil: Rodriguez A. Universidad Nacional de La Plata; ArgentinaFil: Scazzola MS. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Estudios Parasitológicos y de Vectores. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Estudios Parasitológicos y de Vectores; ArgentinaFil: Sanmartino, Mariana. Grupo de Didáctica de Las Ciencias; ArgentinaFil: Carrillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Ciencia y Tecnología "Dr. César Milstein". Fundación Pablo Cassará. Instituto de Ciencia y Tecnología "Dr. César Milstein"; Argentin

Chagas: a complex problem to approach from multiple dimensions

Hablar de Chagas es mucho más que hablar de una enfermedad, ya que en realidad se trata de una problemática de salud socio-ambiental compleja. Considerarla de esta manera implica abordar aspectos culturales, educativos, políticos, económicos, ambientales y sociales, además del tradicional abordaje biomédico. Por lo tanto, creemos fundamental pensar al Chagas de manera integral sumando diferentes perspectivas, resaltando la importancia multiplicativa de la educación en la prevención y sensibilización, para lo cual pensamos una propuesta interdisciplinaria e innovadora a través de la cual hemos ido articulando con diferentes instituciones. Contando con la participación de personas provenientes de distintas disciplinas conformamos el grupo ?¿De qué hablamos cuando hablamos de Chagas?? (CONICET - UNLP - CIIE) mediante el cual apuntamos a difundir el tema en museos, escuelas y otros ámbitos institucionales. En este texto queremos compartir nuestra experiencia realizando el taller: ¿Por qué, cuándo y cómo hablar de Chagas en el aula? que desarrollamos durante los años 2014, 2016 y 2017 en el marco de la Semana de la Enseñanza de las Ciencias (FCEN, UBA).When we discuss Chagas, we refer not only to a disease but also to a very complex health problem that involves social and environmental aspects as well. Considering this perspective of Chagas implies taking into account cultural, educational, political, economic, environmental and social aspects, besides the traditional biomedical approach. We consider it fundamental to think about Chagas in an integrated way, adding different perspectives including the important role of education in preventing and raising awareness. To achieve this goal, we have worked on an innovative and interdisciplinary pedagogical proposal that has allowed us to work together with different institutions. With the participation of people from different disciplines, we have created the group "¿De qué hablamos cuando hablamos de Chagas?" (CONICET - UNLP - CIIE) whose aim is to communicate this approach in museums, schools, and other institutional settings. In this text we want to share our experience doing the workshop "Why, when and how to speak of chagas in the classroom" that we developed during the Semana de la Enseñanza de las Ciencias in 2014, 2016 and 2017 (FCEN UBA).Instituto de Física de Líquidos y Sistemas BiológicosFacultad de Ciencias Naturales y Muse