National Institute of Health Dr. Ricardo Jorge
Repositório Científico do Instituto Nacional de SaúdeNot a member yet
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Deciphering a potential toxic synergy between persistent organic pollutants
Get PDFPlastic, massively used in everyday life, inevitably accumulates in the environment, becoming a
persistent pollutant due to its reduced and/ or extremely slow recyclability1. Plastic particles
in the micro and nano range, known as micro (MP) and nanoplastics (NP), respectively represent a
huge ecotoxicological challenge. Due to their high surface areas, they might ad/absorb other
persistent pollutants with similar chemical properties, such as polycyclic aromatic hydrocarbons
(PAHs), with unpredictable effects on persistence and distribution in the environment2. MPs/NPs, with
or without pollutants ad/absorbed, could enter the trophic chain at the level of invertebrates, inflicting
toxicological effects through all levels of the ecosystem3.
Polystyrene MPs and PAHs previously found in water samples (e.g. fluoranthene, phenanthrene)4 and
known to be adsorbed by MPs (Pyrene, benzo(a) pyrene)5 will be used in the study. PAH’s mixtures
will be used to mimic environmental samples and single compounds will be used in order to
understand the individual contribution of each compound for the observed toxic effect. This
experimental approach will also allow to evaluate a potential synergy between compounds with effect
on toxicity. Since PAHs and MPs have similar chemical properties, they are known to adsorb to each
other. We will use PAHs adsorbed to MPs to test higher concentrations of PAHs (not soluble in aqueous
solutions such as cell culture medium) and to document the intracellular distribution of adsorbed
versus free PAHs. Concerning MPs only one material will be used at this stage. Polystyrene was
selected because it is commercially available in spheres suitable for internalization by HepG2 cells and
was previously isolated from environmental samples 4. This study could contribute to identify
differences in toxicity and contribute to the elucidation of the underlying toxicity mechanisms using
molecular biology protocols, light/electron microscopy and FTIR micro/spectrometry.Funding: Infrared spectroscopy measurements were carried out at the IRISbeamline at the BESSY II electron
storage ring operated by the Helmholtz- Zentrum Berlin für Materialien und Energie (Proposals No
231-11744-ST/2022).N/
D5.1 B1MG maturity level model and country-specific alignment within the model
Get PDFNo âmbito do projeto B1MG, WP5, o INSA coordenou o desenvolvimento, validação e teste em sistemas reais, de um modelo de maturidade que se pretende como uma ferramenta de suporte à implementação da genómica na pratica clinica nos sistemas de saúde. Este documento, que constitui o deliverable 5.1 do projeto B1MG, descreve o contexto, metodologia e resultados desta tarefa.Beyond One Million Genomes B1MG has received funding from the European Union’s Horizon 2020 Research
and Innovation programme under grant agreement No 951724N/
Cascade Screening in Familial Hypercholesterolemia: Adult cascade screening versus CHILD reverse cascade screening
No full textFamilial hypercholesterolemia (FH) is an inherited lipid disorder that increases the risk of developing cardiovascular disease (CVD). Despite most cascade screening programs are initiated by adult index cases, reverse cascade screening pediatric index cases is starting to be described. Therefore, in this work, we aimed to assess the outcome of both creening strategies (adult cascade screening and child reverse cascade screening) in families from the Portuguese FH Study (PFHS). The PFHS database was consulted, and 423 index cases genetically identified with FH (224 adults and 199 children) and their 997 relatives referred to the PFHS were analysed. From 224 adults with FH, 485 relatives were enrolled for cascade screening and 290 were identified with FH. From 199 paediatric cases with FH, 512 relatives were screened and 286 were identified with FH. Child reverse cascade screening presented a slightly higher diagnostic rate than adult cascade screening, 1.44 vs 1.29 new cases with FH per index case, and the age of the relatives identified was younger, 29 vs 37 years. For 94% of index children, relatives were referred (2.56 relatives per index), in contrast with the adult cohort whereas only 70% were referred with family-members (2.17 relatives per index). Overall, both screening approaches constitute valuable tools to identify new cases with FH, but the child reverse cascade screening notably creates the opportunity for more relatives to be tested at a younger age. However, it remains crucial to improve relatives' recruitment rate since early identification allows a correct FH diagnosis and treatment to prevent CVD.N/
Investigating ingested nanomaterials’ safety – the case of TiO2 and innovative nanocelluloses.
No full textThanks to P. Ferreira, J.Pedrosa (University of Coimbra) and A.F.Lourenço (RAIZ) for the CMNs; to P.Alvito, R.Assunção, M.Silva (Food Safety Department, INSA) for in vitro digestion.Introduction: The development of nanomaterials(NMs)-based technologies led to their increased use in key sectors and products related to food, food contact materials and feed. Many available products have NMs, as intentional constituents or contaminants from process ou food packaging release, such as silicon or titanium dioxide(TiO2) NMs. Others are being developed, like nanocelluloses(CNMs; doi:10.3390/nano12193375). However, it is recognised that the NMs’ specific physicochemical properties, conferring them unique benefi cial
characteristics, can also elicit nano-bio interactions leading to toxic potential. Also, their dynamic behaviour in the surrounding matrix, may lead to secondary features determining the toxicological outcomes.
Recognizing that processes like intake or digestion may modify the NMs’ characteristics leading to unexpected toxicity in human cells, EFSA included the use of in vitro digestion models in their specific guidelines
concerning risk assessment of nanomaterials for food and feed(DOI:10.2903/j.efsa.2021.6768). Methodology: With the aim to contribute to the safety assessment of NMs, intestinal cell models (Caco-2 and HT29-MTX-E12 cells) were exposed to TiO2 NMs or innovative CNMs. Additionally, samples submitted previously to in vitro simulation of human digestion were used, and the genotoxicity(comet and micronucleus assays) was investigated with and without the digestion process.
Results: After TiO2 NMs’ exposure, the micronucleus assay, an indicator of cancer risk, suggested eff ects on the chromosomal integrity in the HT29-MTX-E12 cells, for all the tested TiO2 NMs, especially after the
in vitro digestion. Upon exposure to the two CNMs, no chromosomal damage was observed in the micronucleus assay, but the comet assay revealed DNA damage in the same cells, after 3h and 24h exposure,
an effect slightly more relevant after the digestion of the cellulose nanofibril.
Conclusion: Overall, the results show diff erent outcomes when using different NMs, and with/without digestion. Thus, it is important to consider the primary and secondary NMs’ characteristics determining the adverse eff ects, taking into account the human digestion for nanosafety assessment.Funded by FCT/MCTES through 2020.07168.BD (NV), PTDC/SAUPUB/29481/2017, and ToxOmics (UIDB/00009/2020;UIDP/00009/2020).info:eu-repo/semantics/publishedVersio
The establishing of the program the human biomonitoring in the European Union - the portuguese perspetive
No full textThe portuguese perspetive about the establishing of the program the human biomonitoring in the European Union - the portuguese perspetiveFunding: FCT UIDB/00009/2020; UIDP/00009/2020; Horizont 2020 N. 733032.N/
Seroprevalence of Specific SARS-CoV-2 Antibodies during Omicron BA.5 Wave, Portugal, April-June 2022
Get PDFMembers of ISN4COVID-19 Group: Paulo Gonçalves, Rita Matos, Inês Costa, Nuno Verdasca, Fátima Martins, Jorge Machado, Raquel Guiomar, Ana Rita Torres, Carlos Matias Dias, Ana Loureiro, Filomena Caldeira, Adriana Coutinho, M. Paula Falcão, Alzira Louro, Igor Filipciuc, Marisa Isabel da Conceição Belchior, Claudia Sofia Barão Ferreira, Ingrid Villanueva, Sara Moura, Marlene Silva, Rita Paulino, Conceição Cardoso, Ana Margarida Casaca, Maria Vitória Antunes de Matos, Lúcia Coimbra, Nazaré Boavida, Paula Cristina Justino Gama, Afonso Tavares Leite Barros dos Santos, Ana Maria Cabrita Frota Fernandes, Bela Jerónima Nogueira, Rui Pedro Vieira Ferreira, Rui Manuel Borges Vassal, Paula Barbeiro, Aurora Direito, Ana Paula Peleta Marques, Margarida Freitas, Gil Sequeira, Sandra Vieira, Gil Ferreira, Teresa Reis, Lucilia Araujo, Teresa Rodrigues, Lurdes Correia, Susana Gomes, Sílvia Campos, Maira João Cardoso, Angélica Ramos, Carlos Caldas, Eliana Costa, Joana Costa, José Alves, Jácome Bruges Armas, Ana Rita Couto, Paula Genuína de la Cerda Sarmento Escobar, Sónia Oliveira Dias Ávila, Luís Silva, Patricia Vargas, Maria Noia, Vanessa Cordeiro, Teresa Damião, Rita Pinto, Helena Rodrigues, Filomena Reis, André Ferreira Pinto, Fátima Vale, Ricardo Rodrigues, Ricardo Castro, Bernardo Silva, Jesuína Duarte, Isabel Santos, Ana Miranda Rosa, Adilia Vicente, José Alves, Raquel Sebastião, Patrícia Pereira, Gizela Ferreira Alves dos Santos, Ana Catarina Faria Guerreiro, Armindo Miguel Rosado Gonçalves, Maria de Fátima Narciso Rolo Raimundo, Manuel Cirne Carvalho, Mário João Santos, Nuno Aguiar, Rui Campaínha, Ana Margarida Godinho, João Pedro Freitas, Rita Batista Coelho, Maria Conceição Miranda Senra Furtado, Miguel Eduardo Magalhães Gouveia, Laura Brum, Ana Paula Farto, Susana Agostinho, Luísa Ponte, Maria Beatriz Tomaz, Joana Ramos, Alexandra Santos, Isabel Forjaz Sampaio, Ana Abreu, Paulo Aguiar, Rita Ribeiro, Ana Guia Pereira, Sandra Vieira, Jorge Nunes Oliveira, Inês Stilwell, Sandra Nóbrega, Iolanda Rodrigues, Marco Marques, Sofia Jorge, Jorge Queiroz, Mavilde Vargues, Carlos Cardoso, Rui Pinto, Ana Filipa Alves, João Fernandes.After the rapid spread of SARS-CoV-2 BA.5 Omicron lineage in Portugal, we developed a seroepidemiologic survey based on a sample of 3,825 residents. Results indicated that from April 27 through June 8, 2022, the estimated seroprevalence of SARS-CoV-2 nucleocapsid or spike IgG was 95.8%, which indicates a high level of protection.Acesso de acordo com política editorial da revista.info:eu-repo/semantics/publishedVersio
Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses
Get PDF(This article belongs to the Special Issue Molecular Mechanisms in Lysosomal Storage Diseases: From Pathogenesis to Therapeutic Strategies 2.0)ReviewDespite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological symptoms are currently incurable, even in the cases where a disease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every patient-derived cell recapitulates relevant disease features. For the neuronopathic forms of MPSs, for example, this is particularly evident because of the obvious inability to access live neurons. This scenario changed significantly with the advent of induced pluripotent stem cell (iPSC) technologies. From then on, a series of differentiation protocols to generate neurons from iPSC was developed and extensively used for disease modeling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPSs and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analyses. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also hypothesize on a tempting alternative to establish MPS patient-derived neuronal cells in a much more expedite way, by taking advantage of the existence of a population of multipotent stem cells in human dental pulp to establish mixed neuronal and glial cultures.Funding: This work was partially supported by the Portuguese Society for Metabolic Disorders, SPDM (Bolsa SPDM de apoio à investigação Dr. Aguinaldo Cabral 2018; 2019DGH1629/SPDM2018I&D), Sanfilippo Children’s Foundation (2019DGH1656/SCF2019I&D), and Fundação para a Ciência e a Tecnologia, FCT: EXPL/BTM-SAL/0659/2021; UIDB/00211/2020—Centro de Estudos de Ciência Animal/Center for the Study of Animal Science; LA/P/0059/2020—Laboratório Associado para Ciência Animal e Veterinária/Associate Laboratory for Animal and Veterinary Sciences.info:eu-repo/semantics/publishedVersio
Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series study
No full textBackground: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019.
Methods: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5° × 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects.
Findings: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions.
Interpretation: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate.This work was supported by the Australian Research Council (DP210102076) and the Australian National Health and Medical Research Council (GNT2000581). WH and RX were supported by China Scholarship Council funds (numbers 202006380055 and 201806010405). YG was supported by a Career Development Fellowship (GNT1163693) and Leader Fellowship (GNT2008813) of the Australian National Health and Medical Research Council. SL was supported by an Emerging Leader Fellowship of the Australian National Health and Medical Research Council (GNT2009866). TV received funding from the German Federal Ministry of Education and Research (BMBF) under the research project QUIDIC (01LP1907A), and through the CHIPS project, part of AXIS, an ERA-NET initiated by JPI Climate, and funded by FORMAS (Sweden), Deutsches Zentrum für Luft- und Raumfahrt (German Aerospace Center)/Bundesministerium für Bildung und Forschung (German Ministry of Education and Research) (grant number 01LS1904A), Agencia Estatal de Investigación (Spanish State Research Agency), and Agence Nationale de la Recherche (French National Agency for Research) with co-funding by the EU (grant number 776608). JM was supported by a fellowship of Fundação para a Ciência e a Tecnlogia (SFRH/BPD/115112/2016). AG was supported by the UK Medical Research Council (grant ID MR/R013349/1), the UK Natural Environment Research Council (grant ID NE/R009384/1), and the EU's Horizon 2020 project, Exhaustion (grant ID 820655). AT was supported by MCIN/AEI/10.13039/501100011033 (grant CEX2018-000794-S)
Overview of in vitro approaches to investigate chemical contaminants intestinal transport
No full textThe occurrence of chemical contaminants in food products is a serious threat to public health and can lead from mild gastroenteritis to fatal liver, kidney and neurological syndromes. The main route of exposure to chemical contaminants is ingestion, with the intestine being the first organ to come into contact with these compounds. In vitro intestinal cell assays may constitute a useful tool to predict the impact of chemical contaminants on the intestinal barrier. Differentiated Caco-2 cells cultivated in porous Transwell inserts, as an in vitro model to evaluate the intestinal transport of food chemical contaminants, is recurrent. These toxicants can be transported via transcellular (transport that occurs through the epithelial cell) or paracellular (transport that occurs in between cells) pathway. This study aims to make an overview of in vitro approaches to investigate chemical contaminants intestinal transport and associated pathways. A bibliographical search was carried out in two databases of scientific publications, “PUBMED” and “WEB OF SCIENCE”, using the keywords “food”, “chemical contaminants”, “cell transport”, in scientific publications from 1999 to 2021. Forty publications were used for data extraction. In sum, Caco-2 cells were the most frequently used model for the evaluation of the food contaminants intestinal transport. In a few works, this cell line was combined with the human HT-29 cells. In other studies, specifically evaluating the implication of membrane transporters, Madin-Darby canine kidney (MDCK) cells were used. HTC-8 intestinal organoids were also reported and gastric absorption of food toxicants was described in a single work using NCI-N87 cells. The use intestinal mucosa explants mounted in Ussing chambers, in studies of food contaminants intestinal transport in farmed animals, was also reported, although in much less extension. The transcellular route was the most reported pathway for chemical contaminants, with paracellular being less referred (mycotoxins and chloropropanols). Further studies concerning absorption and transport of chemical contaminants are needed to better characterize its permeability across epithelial membranes which will contribute to a comprehensive understanding of its impact on human health. In addition, their frequent co-occurrence raises an additional number of questions that can only be answered using high throughput in vitro methods.Thanks are due to the EarlyMyco project (PTDC/MEDTOX/28762/2017), and to CESAM (UIDP/50017/2020+UIDB/50017/2020+LA/P/0094/2020), funded by FCT/MCTES through national funds.info:eu-repo/semantics/publishedVersio
Diabetes Tipo MODY – Caracterização Molecular
No full textFolheto técnico sobre caracterização molecular da Diabetes Tipo MODY.N/