National Institute of Health Dr. Ricardo Jorge
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Hazard assessment of bisphenol A alternatives to close data gaps of concern for human health and improve their risk assessment
No full textWHY? With the upcoming restrictions on BPA, BPA
alternatives’ tonnages and frequencies of use are
expected to severely increase in the coming years.
Therefore, this project aims to fill the identified
data gaps, providing a complete data set for at least
four relevant BPA alternatives identified in an ad hoc
Workshop together with ECHA and EFSA. We will fill the
knowledge gaps on human health on five toxicological
endpoints and by the identification of molecular
biomarkers we will contribute to develop methods to
rapidly predict the possible effects of BPA
alternatives.This work was carried out in the framework of the European Partnership for the Assessment of Risks from Chemicals (PARC) and has received funding from the European Union’s Horizon Europe research and innovation programme under Grant Agreement No 101057014.info:eu-repo/semantics/publishedVersio
HBM4EU diisocyanates study – results from a collaborative European human biological monitoring study on occupational exposure
No full textDiisocyanates have long been a leading cause of occupational asthma in Europe, and they are now restricted under the REACH regulation. As part of the European Human Biomonitoring project (HBM4EU), we conducted an occupational exposure survey on diisocyanates in five European countries. 116 workers were recruited across four job categories: (1) Use of diisocyanates-based glues, adhesives or sealants; (2) Polyurethane coating of large surfaces; (3) Spray application of urethane foam; (4) Spray coating of vehicles. Fifty controls (within the same companies) were also recruited. The study collected urine samples (analysed for diisocyanate-derived diamines and lysine conjugates), blood samples (analysed for diisocyanate-specific antibodies, inflammatory markers, and diisocyanate-specific haemoglobin adducts), buccal cells (micronucleus analysis) and measured fractional exhaled nitric oxide (FeNO). In addition, occupational hygiene measurements (air monitoring and skin wipe samples) and questionnaires were collected. Initial results showed significant airborne exposures for some tasks (spraying polyurethane foam insulation), with elevated urinary diamine levels compared to controls (p<0.001), and detection of the specific MDI-lysine conjugate. Most workers did not show increased FeNO, but some individuals had elevated results (controls max 30 ppb (n=49), workers max 161 ppb (n=108). Further ongoing data analysis will be presented.This work has received external funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 733032 and received co-funding from the author’s organizations and/or Ministries. The full HBM4EU diisocyanates study team has previously been acknowledged in the study protocol (https://doi.org/10.3390/ijerph19148811).info:eu-repo/semantics/publishedVersio
The Health Effects of Low Glycemic Index and Low Glycemic Load Interventions on Prediabetes and Type 2 Diabetes Mellitus: A Literature Review of RCTs
Get PDF(This article belongs to the Special Issue Effect of Dietary Patterns or Eating Habits on Diabetes)Diets with a low glycemic index (GI) and a low glycemic load (GL) can improve glycemic control, blood lipids, blood pressure and BMI in prediabetes and type 2 diabetes (T2DM), but evidence regarding other aspects of cardiometabolic health is limited. We searched the literature for RCTs published from 2013 to 2023 and reviewed the evidence on low-GI/GL diets and their effects on different aspects of health in prediabetes and T2DM, aiming to build a report on all relevant outcomes included in the studies. We included 14 RCTs with 1055 participants, who were mostly middle-aged individuals with T2DM. Interventions were mostly low GI and lasted 1–36 months. Low-GI/GL foods and diets showed benefits in terms of short-term glycemic control, weight and adiposity. Longer-term trials would be necessary to determine whether these benefits persist over time and/or lead to lower CVD risk and mortality. Effects on lipid profile were inconsistent. Some studies also reported positive effects of low-GI/GL interventions on blood pressure, inflammatory biomarkers, renal function and gut microbiota composition. Future trials should focus on some of these novel outcome measures, which may provide important insights into the metabolic effects of low-GI diets on individuals with diabetesThis research received financial support from the Foundation for Science and Technology (FCT) under the projects Food4DIAB (EXPL/BAA-AGR/1382/2021), UIDB/50006/2020 and by AgriFood XXI I&D&I project (NORTE-01-0145-FEDER-000041) co-financed by European Regional Development Fund (ERDF), through the NORTE 2020 (Programa Operacional Regional do Norte 2014/2020).info:eu-repo/semantics/publishedVersio
World Youth Day 2023 - non-endemic infectious disease surveillance through wastewater analyses
No full textThe World Youth Day (WYD) is an event that mobilizes millions of people from all over the world. It is an event promoted by the Catholic Church mainly focused on young people and aims to bring together representatives from all Catholic countries. In 2023, WYD was held in Portugal, hosted in Lisbon between August 1st and 6th. Other satellite events prior to WYD were promoted throughout the country. Portimão Municipality agreed to collaborate with the “Welcome to Paradise” festival between the 26th and 31st of July, before traveling to Lisbon for WYD.
THE PROBLEM:
4000 young people were expected to arrive from 27 countries, on 5 continents, that were accommodated in 10 schools in the municipality of Portimão. There was a very diverse epidemiological context, namely the endemic diseases in the origin countries. Taking into account the high proximity of the different groups in provisionary accommodation establishments, we could suppose that the conditions could favor the spread of a non-endemic infectious disease with the potential to pressure available health services beyond their capacity to respond.
AIM
Monitor possible introduction of non-endemic infectious disease into the community, through analyses of the wastewater.
THE APPROACH:
The Barlavento Public Health Unit carried out a survey of endemic diseases in each country of origin of the participants. In order to monitor the possible introduction of a non-endemic disease into the community, focused on poliovirus, a protocol was established with the National Institute of Health Doutor Ricardo Jorge to monitor some diseases through the analysis of wastewater from the Portimão WWTP before, during and after the event. Research was carried out on non-endemic Poliovirus, and other endemic agents as control: Non Polio Enterovirus, adenovirus, Hepatitis A virus and Norovirus GI and GII search.
RESULTS:
Monitoring carried out on wastewater in Portimão before arrival, upon departure and 10 days after departure was always negative for Poliovirus and Hepatitis A virus and always positive for Norovirus I and II, Non Polio Enterovirus and Adenovirus.
CONCLUSIONS:
This Case Study of the wastewater monitoring performed allowed to discard the worries raised with such a high dimension event.
This kind of approach is important, since we have already verified that wastewater analysis might be a relevant early warning system for public health risks.N/
Investigation of In Vitro Cytotoxicity and Genotoxicity of Novel Cellulose Nanomaterials in two intestinal cell models
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.Cellulose nanomaterials (CNMs) have been developed for applications in multiple food-related products, as food additives (e.g. stabilizers or thickeners), non-caloric fiber sources, or substitutes for petroleum-based food packaging materials(1,2). This work aimed to contribute for the safety assessment of two micro/nanofibrillated celluloses (CMF/CNFs), synthetized from industrial Eucalyptus globulus kraft. Based on the European Food Safety Authority nano guidance(3), the in vitro cyto- and genotoxic effects were investigated using the
Caco-2 and HT29-MTX-E12 human intestinal cell models. To incorporate the effect of the digestion process on the toxicological outcomes, a harmonized protocol for in vitro simulation of human digestion was used(3).
After exposure of cells to digested and undigested CNMs samples (concentrations of 3.1 to 200 μg/mL), the cytotoxicity was evaluated by the MTT and clonogenic assays, and the genotoxicity by the cytokinesis block
micronucleus (CBMN; OCDE TG 487(4)) and comet assays. No cytotoxic effects could be attributed to CNMs exposure, with and without digestion, regardless of the cell line used. No chromosomal damage was
detected in the two cell lines exposed to each CNMs for 52h, using the micronucleus assay. Conversely, the comet assay revealed the induction of DNA damage in HT29-MTX-E12 cells, after 3h and 24h of exposure to the two CNMs, without significant contribution of oxidative DNA damage. Additionally, in the same cell line, a mild increase in DNA damage, was observed after exposure to the digested CNF comparatively to not digested CNF, after 3h exposure.
To our knowledge, this is the first study in which CNMs were evaluated for their genotoxic effects using the CBMN and comet assays in Caco-2 and HT29MTXE12 cell models. Our findings show that cytotoxicity, the endpoint generally used to assess their biocompatibility, is not sufficient to assess their safety to humans. Ongoing studies will contribute to a more comprehensive early-stage assessment of CNMs safety, towards sustainable and innovative application in food technology.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
Mortality risks associated with floods in 761 communities worldwide: time series study
Get PDFMCC Collaborative Research Network: Rosana Abrutzky, Micheline de Sousa Zanotti Stagliorio Coelho Coelho, Paulo Hilario Nascimento Saldiva, Nicolás Valdés Ortega, Patricia Matus Correa, Haidong Kan, Samuel Osorio, Aleš Urban, Francesco Sera, Mathilde Pascal, Alexandra Schneider, Veronika Huber, Ariana Zeka, Patrick Goodman, Francesca de'Donato, Paola Michelozzi, Masahiro Hashizume, Yoonhee Kim, César De la Cruz Valencia, Magali Hurtado Diaz, Ala Overcenco, Caroline Ameling, Danny Houthuijs, Gabriel Carrasco-Escobar, Xerxes Seposo, Baltazar Nunes, Iulian-Horia Holobaca, Ana Maria Vicedo-Cabrera, Aurelio Tobias, Jouni J K Jaakkola, Yasushi Honda, Fiorella Acquaotta, Noah Scovronick, Ho Kim, Whanhee Lee, Carmen Íñiguez, Martina S Ragettli, Shih-Chun Pan, Yue Leon Guo, Antonella Zanobetti, Joel Schwartz, Simon Hales.Objective: To evaluate lag-response associations and effect modifications of exposure to floods with risks of all cause, cardiovascular, and respiratory mortality on a global scale.
Design: Time series study.
Setting: 761 communities in 35 countries or territories with at least one flood event during the study period.
Participants: Multi-Country Multi-City Collaborative Research Network database, Australian Cause of Death Unit Record File, New Zealand Integrated Data Infrastructure, and the International Network for the Demographic Evaluation of Populations and their Health Network database.
Main outcome measures: The main outcome was daily counts of deaths. An estimation for the lag-response association between flood and daily mortality risk was modelled, and the relative risks over the lag period were cumulated to calculate overall effects. Attributable fractions of mortality due to floods were further calculated. A quasi-Poisson model with a distributed lag non-linear function was used to examine how daily death risk was associated with flooded days in each community, and then the community specific associations were pooled using random effects multivariate meta-analyses. Flooded days were defined as days from the start date to the end date of flood events.
Results: A total of 47.6 million all cause deaths, 11.1 million cardiovascular deaths, and 4.9 million respiratory deaths were analysed. Over the 761 communities, mortality risks increased and persisted for up to 60 days (50 days for cardiovascular mortality) after a flooded day. The cumulative relative risks for all cause, cardiovascular, and respiratory mortality were 1.021 (95% confidence interval 1.006 to 1.036), 1.026 (1.005 to 1.047), and 1.049 (1.008 to 1.092), respectively. The associations varied across countries or territories and regions. The flood-mortality associations appeared to be modified by climate type and were stronger in low income countries and in populations with a low human development index or high proportion of older people. In communities impacted by flood, up to 0.10% of all cause deaths, 0.18% of cardiovascular deaths, and 0.41% of respiratory deaths were attributed to floods.
Conclusions: This study found that the risks of all cause, cardiovascular, and respiratory mortality increased for up to 60 days after exposure to flood and the associations could vary by local climate type, socioeconomic status, and older age.What is already known on this topic: - Flood events are projected to increase in severity, duration, and frequency as a
result of climate change.
- Deaths from natural causes might increase after flood events, but current
evidence is inconsistent.
- Previous studies had limitations in exposure assessments, sample sizes,
geographical areas, and study durations.
What this study adds: -The findings of this study suggest that the risks of all cause, cardiovascular, and
respiratory mortality reach a peak at around 25 days after exposure to floods and
last for up to 60 days.
- The associations appeared to vary with climate type and were stronger in
populations with a low socioeconomic status or a high proportion of older people
In communities impacted by floods, up to 0.10% of all cause deaths, 0.18% of
cardiovascular deaths, and 0.41% of respiratory deaths were attributed to floodsFunding: ZY was supported by a Monash graduate scholarship and a Monash international tuition scholarship. WH, PY, and BW were supported by the China Scholarship Council (202006380055, 201906210065, and 202006010043). YG was supported by a career development fellowship (APP1163693) and a leader fellowship (APP2008813) of the Australian National Health and Medical Research Council (NHMRC). SL was supported by an emerging leader fellowship of the NHMRC (APP2009866). JEM was supported by an NHMRC investigator grant (GNT2009612). AG was supported by a UK Medical Research Council grant (MR/V034162/1). This study was supported by the Australian Research Council (DP210102076), the Australian NHMRC (GNT2000581), and the European Union’s Horizon 2020 Project Exhaustion (grant ID 820655)info:eu-repo/semantics/publishedVersio
Decrypting the diversity of microbiome in aquaculture
Get PDFTese de doutoramento em Biologia, apresentada à Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2023Orientador: Manuela Caniça (INSA); Coorientadores: Vera Manageiro (INSA), Isabel Sá Nogueira (UNL)Aquaculture can play an important role in reducing the overexploitation of natural re- sources and feeding the world’s growing population. However, the use of e.g., antibiotics in aquaculture can favor the development of resistant bacteria and jeopardize the safety of its products. Thus, this Ph.D. thesis aimed to contribute to the deciphering of aquaculture’s mi- crobiome and resistome, as well as to the understanding of the role of mobile genetic elements (MGE) in the dissemination of resistance genes in these environments. Several approaches were used, to obtain the results that most reflect the microbiome and resistome of seabream and bivalve mollusks from aquaculture. All microbiomes studied were very diverse, encompassing commensal and pathogenic bacteria from seabream and bivalve mollusks (e.g., Aeromonas,Kocuria, Pseudomonas and Vibrio genera), as well as bacteria important in human medicine (e.g., Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae). Twenty-one new se- quence types were described in Aeromonas spp., Citrobacter sp., Enterobacter spp., Shewanella spp., Staphylococcus sp. and Vibrio spp. Decreased susceptibilities to phenicols, oxytetracy- cline, β-lactams (namely carbapenems), quinolones, glycopeptides, mupirocin, erythromycin, and colistin were found. The resistome also revealed a great diversity of genes in all samples studied associated with antibiotics (e.g., blaTEM-1B, mecA, sul2, mcr-9.1), disinfectants (e.g.,formA-type), and heavy metals (e.g., sil) resistance. Twenty-five different genes related with increased virulence were also detected. Thirteen new β-lactams resistance genes were identi- fied (e.g., blaCTX-M-246, blaFOX-18, and blaOXA-958) and 35 other resistance genes, namely for antibi- otics (e.g., mcr-9 and qnrD2), heavy metals (e.g., emrA and mdtE) and disinfectants ( sitABCD- type), and virulence factors (e.g., astA and hlyF) were here described for the first time associated with aquaculture. Our results suggest that some of these resistance genes (e.g., erm(T)-type,qnrB19, catA1-type, tet(A), dfrA-type, aph(6)-Id, qacE∆ 1 and merA) are being disseminated by MGE such as plasmids, class 1 integrons, and Tn As1. These findings not only expand our knowledge about aquaculture’s microbiome and resistome, but also provide the necessary xiv information to implement the most suitable measures to control antibiotic resistance in aqua- culture environments.A aquacultura pode desempenhar um papel importante na redução da sobre-exploração dos recursos naturais e no fornecimento de alimentos para a crescente população mundial. No entanto, o uso de, por exemplo, antibióticos em aquacultura pode favorecer o desenvolvi- mento de bactérias resistentes e comprometer a segurança dos seus produtos. Assim, esta tese de Doutoramento teve como objetivo contribuir para a decifração do microbioma e resistoma em aquacultura, bem como compreender o papel dos elementos genéticos móveis na disse- minação de genes de resistência nestes ambientes. Foram usadas diversas abordagens com o intuito de obter os resultados que melhor refletem o microbioma e o resistoma das douradas e moluscos bivalves de aquacultura. Os microbiomas estudados apresentaram uma grande diversidade, englobando bactérias comensais e patogénicas das douradas e moluscos bivalves (ex.: os géneros Aeromonas, Kocuria, Pseudomonas e Vibrio), assim como bactérias importan- tes em medicina humana (ex.: Staphylococcus aureus, Escherichia coli e Klebsiella pneumo- niae). Foram descritos 21 novos sequence type em Aeromonas spp., Citrobacter sp., Entero- bacter spp., Shewanella spp., Staphylococcus sp. e Vibrio spp. Foram encontradas suscetibili- dades diminuídas aos fenicois, oxitetraciclina, β-lactâmicos (como carbapenemes), quinolonas, glicopéptidos, mupirocina, eritromicina e colistina. Também os resistomas revelaram uma grande diversidade de genes associados a resistências aos antibióticos (ex.: blaTEM-1B, mecA,sul2, mcr-9.1), desinfetantes (ex.: formA-type) e metais pesados (ex.: sil). Foram também dete- tados 25 genes diferentes, associados a uma maior virulência. Encontram-se aqui descritos 13 novos genes de resistência aos β-lactâmicos (ex.: blaCTX-M-246, blaFOX-18, blaOXA-958) e outros 35 genes de resistência, nomeadamente aos antibióticos (ex.: mcr-9 e qnrD2), metais pesados (ex.:emrA e mdtE) e desinfetantes ( sitABCD-type), e fatores de virulência (ex.: astA e hlyF) são aqui identificados pela primeira vez associados à aquacultura. Os nossos resultados sugerem que alguns destes genes de resistência (como erm(T)-type, qnrB19, catA1-type, tet(A), dfrA-type, aph(6)-Id, qacE∆ 1 e merA) estarão a ser disseminados por elementos genéticos móveis, como plasmídeos, integrões de classe 1 e Tn As1. Estes estudos não só ampliam o nosso conhecimento sobre o microbioma e o resistoma em aquacultura, mas também providenciam a informação necessária para a implementação das medidas mais adequadas ao controlo da resistência aos antibióticos em aquacultura.Funding: Fundação para a Ciência e a Tecnologia (SFRH/BD/133100/2017).info:eu-repo/semantics/publishedVersio
Avaliação da exposição da população portuguesa a substâncias químicas perigosas
Get PDFSónia Namorado, investigadora do Departamento de Epidemiologia do INSA e uma das coordenadoras da Iniciativa Europeia em Biomonitorização Humana (HBM4EU) a nível nacional.Apresentação dos resultados do estudo INSEF-ExpoQuim, nomeadamente os referentes à exposição da população portuguesa a cádmio, bisfenóis e hidrocarbonetos aromáticos policíclicos (PAHs).
O conhecimento científico atual suporta a afirmação que a exposição a determinadas substâncias químicas ambientais pode causar efeitos adversos na saúde ou mesmo doença. Para avaliar o risco para a saúde humana é importante medir a quantidade dessas substâncias químicas no nosso organismo. Isto pode ser feito com recurso à biomonitorização humana, que consiste na medição da quantidade de uma determinada substância química em amostras biológicas como sangue, urina, unhas ou cabelo, e pode ser utilizada para a avaliação da exposição interna total a uma substância química resultante de todas as fontes e vias de exposição.
No âmbito da Iniciativa Europeia de Biomonitorização Humana (HBM4EU), Portugal contribuiu com o estudo INSEF-ExpoQuim, um estudo epidemiológico transversal realizado entre os participantes no primeiro Inquérito Nacional de Saúde com Exame Físico (INSEF 2015) com o objetivo de caracterizar a exposição da população adulta portuguesa a substâncias químicas.
Os resultados apresentados serão discutidos numa perspetiva de avaliação de risco, de apoio à tomada de decisão e de definição de prioridades a nível nacional para a realização de estudos futuros.O INSEF-ExpoQuim foi cofinanciado no âmbito da Iniciativa
Europeia em Biomonitorização Humana (projeto HBM4EU),
que recebeu financiamento do programa Horizonte 2020 da
Comissão Europeia (acordo de subvenção nº 733032).N/
Development of dietary fibre enriched bakery products by incorporating melon by-products
No full textRegular and sufficient intake of dietary fibre has many health benefits. One of these benefits is the ability to reduce the rate of glucose absorption after eating foods rich in carbohydrates with a high glycaemic index. Glycaemic control through dietary intervention is important for people with a high risk of Type 2 Diabetes Mellitus. According to some studies, it is recommended that the diabetic diet should provide 25-50 g/day of dietary fibre. However, the average daily intake of dietary fibre for the Portuguese population is 16.3 and 19.5 g/day, for women and men, respectively.
This study aimed to develop two innovative food products based on melon peel flour and to evaluate their nutritional composition.
In 2022, melon peels were recovered from melon production and distribution companies, mainly discarded fruits, which do not correspond to market needs in terms of size, and/or shape, or colour. Melon peels were dehydrated and homogenised until a fine powder (melon peel flour) was obtained. The nutritional composition was analytically determined. The energy value and available carbohydrates were calculated.
The incorporation of melon peel flour allowed the development of a biscuit and a muffin with 15 and 13 g/100 g of dietary fibre, respectively. According to Regulation (EC) No 1924/2006 on nutrition and health claims, it is possible to say that the products developed can be considered high in fibre (> 6 g/100 g). Moreover, one portion of the developed biscuit (35 g) and muffin (48 g) can contribute with 21% and 25% of the recommended needs, respectively.
The developed bakery products rich in dietary fibre could contribute to glycaemic control. The dietary fibre content present in the developed food products can also contribute to the valorisation of melon peel flour by reducing food waste, the environmental impact and contribute to improve public health.This work was financially supported by Foundation for Science and Technology (FCT) under the projects Food4DIAB (EXPL/BAA-AGR/1382/2021); and UIDB/50006/2020 and by AgriFood XXI I&D&I project (NORTE-01-0145-FEDER-000041) co-financed by European Regional Development Fund (ERDF), through the NORTE 2020 (Programa Operacional Regional do Norte 2014/2020). Rita C. Alves thanks to FCT the CEECIND/01120/2017 contract.N/
Deletional alpha-thalassemia and hematological phenotype: predictive parameters of different deletions
No full textIntroduction: Thalassemias are characterized by a quantitative imbalance of the globin chains due to the reduction or suppression of the synthesis of one of the globin chains.The hematological tests usually used as indicative for the investigation of α-thalassemia are the blood count with MCV (Mean Cell Volume) < 80 fL and/or MCH (Mean Cell Hemoglobin) < 27 pg and normal Hb A2 (< 3.5%).
Aim: This study aimed to correlate the different deletional α-thalassemia genetic alterations with the corresponding hematological phenotype, based on casuistry
from 2015 to 2019.
Methodology: Was evaluated retrospectively 496 cases suspected of deletional α-thalassemia from 2015 to 2019 and correlated them with the hematological data available. We searched for α-thalassemia deletions by Gap-PCR and Multiplex Gap-PCR.
Haematological evaluation was carried out by the erythrogram, Hb isoelectric focusing and quantification of Hb A2 and Hb F (Ion exchange high performance liquid chromatography).
The statistical analysis of the results was carried out through calculating the mean, standard deviation, median, and t-Student test, with a significance level of 0.05.
Results and discussion: Most patients (n=190) had a normal genotype (αα/αα), followed by heterozygosity (-α3.7/αα) (n=148) and homozygosity (-α3.7/α3.7) (n=141) for the 3.7kb deletion. We also detected 5 cases of heterozygosity for the 4.2Kb deletion (-α4.2/αα), 4 of double heterozygosity (α3.7/α4.2), 7 heterozygosity α0 (--SEA /αα) and 1 of HbH (--SEA/-α3.7).
The results showed that the MCV and the MCH are excellent hematological indices for screening and selection of patients for molecular testing (their value being the lower the greater the number of deleted genes). Our results are in line
with those described in the literature and reinforce that the cut-off value of 25 pg (MCH) is sensitive enough to infer the presence of α0 -thalassemia deletion.
The detection of the α0 deletion is very important in preventing the occurrence of Hb Bart's in the offspring of a carrier couple.
The diagnosis of deletional α-thalassemia is realised by genetic testing, however hematological indices are relevant predictive markers of the number of deleted alpha genes and the phenotype /genotype correlation.N/