National Institute of Health Dr. Ricardo Jorge
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Maternal dietary exposure to mycotoxin aflatoxin B1 promotes intestinal immune alterations and microbiota modifications increasing infection susceptibility in mouse offspring
No full textAbstract: Mycotoxins are secondary metabolites produced by fungi occurring in food that are toxic to animals and humans. Early-life mycotoxins exposure has been linked to diverse pathologies. However, how maternal exposure to mycotoxins impacts on the intestinal barrier function of progeny has not been explored. Here, exposure of pregnant and lactating C57Bl/6J female mice to aflatoxin B1 (AFB1; 400 μg/kg body weight/day; 3 times a week) in gelatine pellets, from embryonic day (E)11.5 until weaning (postnatal day 21), led to gut immunological
changes in progeny. The results showed an overall increase of lymphocyte number in intestine, a reduction of
expression of epithelial genes related to microbial defence, as well as a decrease in cytokine production by intestinal
type 2 innate lymphoid cells (ILC2). While susceptibility to chemically induced colitis was not worsened,
immune alterations were associated with changes in gut microbiota and with a higher vulnerability to infection
by the protozoan Eimeria vermiformis at early-life. Together these results show that maternal dietary exposure to AFB1 can dampen intestinal barrier homeostasis in offspring decreasing their capability to tackle intestinal
pathogens. These data provide insights to understand AFB1 potential harmfulness in early-life health in the
context of intestinal infections.Highlights: Effect of maternal AFB1 dietary exposure was studied in intestinal mucosa of offspring mice; Maternal AFB1 exposure leads to lymphocyte expansion and alters cytokine expression; Maternal AFB1 exposure reduces microbial-related epithelial gene expression in offspring;
Maternal AFB1 exposure modifies offspring gut microbiota.; Maternal AFB1-exposed offspring are more vulnerable to intestinal parasite infection.EarlyMyco (PTDC/MED-TOX/28762/ 2017), investigator FCT Exploratory (IF/00425/2015/CP1324/CT0001) and CESAM (UIDP/50017/2020+UIDB/50017/2020+LA/P/0094/ 2020)info:eu-repo/semantics/publishedVersio
Effect of Quorum Sensing Molecule Farnesol on Mixed Biofilms of Candida albicans and Staphylococcus aureus
Get PDFThis article belongs to the Special Issue Microbial Biofilms, Antimicrobials, and Virulence Determinants.The natural bioactive molecule farnesol (FAR) is widely studied mainly for its antibiofilm
and antimicrobial properties. In addition, it increases the effectiveness of some antimicrobial substances,
which makes it interesting for the development of combined therapy. In the present work,
the effect of FAR either alone or in combination with oxacillin (OXA) on mixed biofilms formed
by clinically relevant pathogens, Candida albicans and Staphylococcus aureus, was studied. S. aureus
isolates used for biofilm formation originated from blood cultures and central venous catheters (CVC)
were characterized in terms of antimicrobial resistance. The minimal biofilm inhibitory concentration
(MBIC50) for FAR of 48 h mixed biofilms formed by the C. albicans and methicillin-sensitive S. aureus
(MSSA) was determined to be 125 M, and for the mixed biofilms with methicillin-resistant S. aureus
(MRSA) was determined to be 250 M. Treatment of mixed biofilms with OXA (2 mg/mL) showed
4% inhibition; however, the combination of OXA (2 mg/mL) and FAR (300 M) resulted in 80%
inhibition of biofilms. In addition, planktonic cells of S. aureus exhibited an increased susceptibility
to OXA, cefoxitin and kanamycin in the presence of FAR (150 and 300 M). Scanning electron microscopy
(SEM) micrographs confirmed patchy biofilm and lack of candidal hyphae in the samples
treated with FAR and FAR/OXA in comparison to control and mixed biofilms treated only with
OXA. Intriguingly, in a pilot experiment using fluorescence in situ hybridization (FISH), considerable
differences in activity (as indicated by ribosome content) of staphylococcal cells were detected. While
the activity rate of the staphylococci in mixed biofilms treated with FAR was high, no FISH-positive
signal for staphylococcal cells was found in the biofilm treated with FAR/OXA.This research was funded by the Slovak Research and Development Agency under contracts of SK-PT-18-0006 as part of the Bilateral Cooperation Program (2019–2022), APVV-21-0302 and APVV-18-0075. This work was also supported by the EU Grant number 952398—CEMBO, Call: H2020-WIDESPREAD-05-2020—Twinning.info:eu-repo/semantics/publishedVersio
How to use human biomonitoring in chemical risk assessment: Methodological aspects, recommendations, and lessons learned from HBM4EU
Get PDFThe need for such information is pressing, as previous research has indicated that regulatory risk assessors
generally lack knowledge and experience of the use of HBM data in RA. By recognising this gap in expertise, as well as the added value of incorporating HBM data into RA, this paper aims to support the integration of HBM into regulatory RA. Based on the work of the HBM4EU, we provide examples of different approaches to including HBM in RA and in estimations of the environmental burden of disease (EBoD), the benefits and pitfalls involved, information on the important methodological aspects to consider, and recommendations on how to overcome obstacles. The examples are derived from RAs or EBoD estimations made under the HBM4EU for the following HBM4EU priority substances: acrylamide, o-toluidine of the aniline family, aprotic solvents, arsenic, bisphenols,
cadmium, diisocyanates, flame retardants, hexavalent chromium [Cr(VI)], lead, mercury, mixture of per-/polyfluorinated compounds, mixture of pesticides, mixture of phthalates, mycotoxins, polycyclic aromatic hydrocarbons (PAHs), and the UV-filter benzophenone-3. Although the RA and EBoD work presented here is not intended to have direct regulatory implications, the results can be useful for raising awareness of possibly needed policy actions, as newly generated HBM data from HBM4EU on the current exposure of the EU population has been used in many RAs and EBoD estimations.This project received funding from the European Union’s Horizon
2020 research and innovation programme under grant agreement No
733032 HBM4EU, and co-funding from the authors’ organisations.info:eu-repo/semantics/publishedVersio
Effectiveness of antimicrobial interventions directed at tackling antimicrobial resistance in animal production: A systematic review and meta-analysis
No full textReviewBackground: In the last decades, a more prudent and rational use of antimicrobials has been progressively directed towards animal production to reduce antimicrobial selective pressure and antimicrobial resistance (AMR) in microorganisms and safeguard the antimicrobial efficacy of treatments in human medicine. This systematic review evaluated the effectiveness of interventions that have been applied to reduce or improve veterinary antimicrobial usage and aimed at decreasing resistant bacteria in chicken broiler and pig production contexts.
Methods: Original articles were identified by searching PubMed™, Scopus™, The Cochrane Library™, and Web of Science™, and grey literature by searching DANS EASY™, WorldCat™ and RCAAP™. Inclusion criteria included: chicken broiler or pig populations (predestined for meat production), interventions intended to reduce/improve antimicrobial use, comparator with standard or no use of antimicrobials, outcomes related to prevalence of resistant bacteria, farm level studies, original data, and analytical observational studies. Data was extracted from eligible studies and meta-analysis using random or fixed effects models was conducted for combinations including type of intervention, bacterial species, production type and animal populations. Models were selected according to heterogeneity between studies. The effectiveness of interventions was assessed using pooled odds ratio of resistance to antimicrobial substances/classes by bacteria for associations between animal populations with and without intervention.
Results: A total of 46 studies were eligible for review. For chicken broilers, most interventions were identified as antimicrobial restrictions on all non-therapeutic use (46%), complete restriction (27%), and prohibition on antimicrobials used for growth promotion (23%). As for pig populations, restrictions were mainly observed on all non-therapeutic use (37%), complete restriction (37%) and group treatments (22%). For meta-analysis, 21 studies were pooled after assessment of existing combinations. These combinations demonstrated a protective effect for most antimicrobial classes in Escherichia coli, Campylobacter and Enterococcus isolates from samples of chicken broilers as well in Escherichia coli and Campylobacter spp. from samples of pigs, compared to animals raised under conventional production or without intervention. Increased odds of resistance were only observed for cephalosporins in E. coli and broilers raised without antimicrobials, and to fluoroquinolones and quinolones in Campylobacter and pigs raised without antimicrobials, compared to conventional production.
Conclusions: Our study indicates that organic production, antimicrobial-free farms, and group treatment restrictions are recommended for AMR reduction, providing information that may support decision-making to tackle AMR and better reporting to improve comparability of results between studies.info:eu-repo/semantics/publishedVersio
COVID-19 vaccine effectiveness among healthcare workers: a hospital-based cohort study
Get PDFObjectives: Healthcare workers (HCWs) were the first to be prioritised for COVID-19 vaccination. This study aims to estimate the COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 symptomatic infection among HCWs in Portuguese hospitals.
Design: Prospective cohort study.
Setting and participants: We analysed data from HCWs (all professional categories) from three central hospitals: one in the Lisbon and Tagus Valley region and two in the central region of mainland Portugal, between December 2020 and March 2022. VE against symptomatic SARS-CoV-2 infection was estimated as one minus the confounder adjusted HRs by Cox models considering age group, sex, self-reported chronic disease and occupational exposure to patients diagnosed with COVID-19 as adjustment variables.
Results: During the 15 months of follow-up, the 3034 HCWs contributed a total of 3054 person-years at risk, and 581 SARS-CoV-2 events occurred. Most participants were already vaccinated with a booster dose (n=2653, 87%), some are vaccinated with only the primary scheme (n=369, 12.6%) and a few remained unvaccinated (n=12, 0.4%) at the end of the study period. VE against symptomatic infection was 63.6% (95% CI 22.6% to 82.9%) for HCWs vaccinated with two doses and 55.9% (95% CI -1.3% to 80.8%) for HCWs vaccinated with one booster dose. Point estimate VE was higher for individuals with two doses taken between 14 days and 98 days (VE=71.9%; 95% CI 32.3% to 88.3%).
Conclusion: This cohort study found a high COVID-19 VE against symptomatic SARS-CoV-2 infection in Portuguese HCWs after vaccination with one booster dose, even after Omicron variant occurrence. The small sample size, the high vaccine coverage, the very low number of unvaccinated individuals and the few events observed during the study period contributed to the low precision of the estimates.The data of the study were originally collected as part of the project
‘Developing an infrastructure and performing vaccine effectiveness studies for
COVID-19 vaccine in the EU/EEA’ (Contract ECD.11486 Lot3 (HCW) and amendment
Nº ECD.11486), and the Enhanced laboratory support to perform assessment of
vaccine effectiveness against SARS-CoV-2 infection (ECD.12175) and the ‘Vaccine
Effectiveness, Burden and Impact Studies (VEBIS) of COVID-19 and Influenza’,
funded by the European Centre for Disease Prevention and Control through a
service contract with Epiconcept (ECD.12609).info:eu-repo/semantics/publishedVersio
Determinação da atividade antioxidante, compostos fenólicos e flavonoides totais em frutos vermelhos e hortícolas de folha verde
No full textAtualmente, vários estudos demonstram uma relação inversa entre o consumo de frutas e hortícolas e o aparecimento de doenças crónicas não transmissíveis, devido à sua riqueza em vitaminas, minerais e antioxidantes. Apesar destes benefícios, o consumo destes alimentos continua abaixo do valor recomendado pela Organização Mundial de Saúde (400 g por dia).
Foram analisadas diferentes marcas de frutos vermelhos (morangos, framboesas e mirtilos) e de hortícolas de folha verde (espinafres e alfaces), para estudar a variabilidade da atividade antioxidante e do teor de compostos fenólicos e de flavonoides totais. As amostras foram recolhidas em grandes superfícies comerciais da região de Lisboa, tendo sido adquiridas 3 marcas de cada alimento (identificadas de A a C), exceto de morangos em que foram analisadas apenas 2 marcas. Determinou-se a atividade antioxidante pelo método DPPH• e o teor de fenólicos e flavonoides totais pelos métodos Folin-Ciocalteau e de complexação de alumínio, respetivamente.
No método DPPH•, os morangos B evidenciaram maior atividade antioxidante, com 21,5 ± 1,0 µmol de equivalentes de trolox (ET)/g de amostra, seguindo-se os mirtilos A e as framboesas A. Por outro lado, os hortícolas de folha verde demonstraram menor atividade antioxidante, principalmente as alfaces (0,3 – 0,8 µmol ET/g). Relativamente aos flavonoides totais, os morangos B apresentaram o maior valor (504,2 ± 17,7 mg de equivalentes de epicatequina/100 g de amostra), seguido dos espinafres A e dos mirtilos A. De entre os vários ingredientes, as alfaces B e C foram as que apresentaram menor teor de flavonoides. No que diz respeito aos fenólicos totais, evidencia-se o elevado teor em todos os frutos vermelhos analisados, destacando-se os morangos que apresentaram cerca de 500 mg de equivalentes de ácido gálhico (EAG)/100 g. A alface, entre os alimentos analisados, foi o menos rico em fenólicos (73,0 ± 6,2 – 100,1 ± 1,8 mg de EAG/100 g de amostra).
De forma geral, os frutos vermelhos, principalmente os morangos B, destacam-se enquanto alimentos ricos em antioxidantes, verificando-se alguma variabilidade entre marcas do mesmo alimento, que se pode dever a diferentes práticas de cultivo, estado de maturação, variedades, características do solo, condições ambientais e de armazenamento. Contrariamente, os hortícolas analisados têm menos antioxidantes, principalmente a alface, e os resultados entre marcas mantêm-se com pouca variação.Este trabalho foi apoiado financeiramente pelo INSA, I.P., no âmbito do projeto TradFRUIT
(2012DAN668) e pela União Europeia (fundos FEDER através de COMPETE), no âmbito do Acordo
de Parceria PT2020, e por Fundos Nacionais (FCT, Fundação para a Ciência e Tecnologia) através
dos projetos UIDB/50006/2020 e pelo projeto I&D&I AgriFood XXI (NORTE-01-0145-FEDER-
000041) cofinanciado pelo Fundo Europeu de Desenvolvimento Regional (FEDER), através do
NORTE 2020 (Programa Operacional Regional do Norte 2014/2020).info:eu-repo/semantics/publishedVersio
Assessment of multiple mycotoxins in maize flour samples from Portugal under SafeGrains project
No full textOne of the most relevant problems in stored grains is the contamination by insects and mycotoxin-producing fungi. Tribolium castaneum is one of the most common insect pests of stored products. Its presence makes cereals more susceptible to the spread of the fungi Aspergillus flavus, which may produce mycotoxins. The aim of this work was to evaluate the mycotoxin profile of maize flour infested by T. castaneum adults, alone or in combination with mycotoxigenic A. flavus strain (MUM-UMinho). Maize collected directly from fields was stored at 4 ºC and then ground and sieved to obtain maize fl our. Multiple mycotoxin profile of maize flour was determined in three different assays: i) controls (n=8), ii) inoculated with T. castaneum adults (insect assay, n = 24), iii) inoculated with A. flavus conidia (fungus assay, n = 8) and iv) inoculated with both organisms (mixed assay, n = 24). Samples were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) according to Franco et al. (2019) for determination of aflatoxins (AFs) B1, B2, G1 and G2, deoxynivalenol (DON), zearalenone(ZEN) and fumonisins (FBs) B1 and B2. The limits of detection (LOD) and quantification (LOQ) of the analytical method were 6.1 and 18.0 μg/ kg for DON, respectively. For AFs, ZEN and FBs, LOD and LOQ varied between 0.2 – 0.9 and 0.6 – 2.5 μg/kg, respectively. DON, ZEA, FB1 and FB2 were detected in control assays at mean levels ranging from 33-50, 2-6, 112-144 and 49-75 μg/kg, respectively. AFs were not detected in controls. Insect, fungi and mixed assays presented the same mycotoxin profile (with contents in the same order of magnitude), except for AFB1, which was detected only in mixed assays. Although the levels of mycotoxins are below the legislated ones (Commission Regulation (EU) 2023/915), they point out to the presence of multiple mycotoxins in raw maize flour and to a potential impact between insects and mycotoxigenic strains in which concerns AFB1. Data presented here agree with previous assays from this team describing significantly higher concentration in the maize flour inoculated with both organisms (Duarte et al, 2021).This study was supported by national funds from Portuguese Foundation for Science and Technology (FCT), through the research unit ID/AGR/04129/2013-LEAF and by the project SafeGrains (PTDC/ASP-PLA/28350/2017) and FCT/MEC – FEDER, within the PT2020 Partnership Agreement and Compete 2020. Thanks are also due to CESAM (UIDP/50017/2020+UIDB/50017/2020+LA/P/0094/2020),
through national funds.info:eu-repo/semantics/publishedVersio
The first harmonised total diet study in Portugal: Vitamin D occurrence and intake assessment
Get PDFVitamin D acts in calcium and phosphate homeostasis and also as an immunomodulatory hormone. To estimate the vitamin D intake by the ‘adults’ and ‘elderly’ Portuguese populations TDS methodology was used, since in the absence of skin UVB exposure, food and supplements are the only vitamin D sources. Vitamin D was quantifiable in 78 (24 from the fish group) of the 164 TDS samples. Sea bream contained the most vitamin D (13.8 µg/100 g), followed by plaice (9.2 µg/100 g). MCRA software (semi-probabilistic approach) was used to estimate the median vitamin D intake that ranged between 2.47 (‘adults’ ‘males’) − 1.45 (‘elderly’ ‘females’) µg/day, well below the Dietary Reference Values (5–15 µg/day). Plaice, sea bream and sardine were the main contributors to intake. A prevalence of 94% inadequate vitamin D intake for ‘adults’ and ‘elderly’ was found based on the estimated average requirement of 10 µg/day.Highlights: - TDS samples covered at least 90% of food items consumed by the Portuguese population; - Top 7 foods for vitamin D level belonged to fish group (max: seabream 13.8 µg/100 g); Main food groups for vitamin D intake were fish (38%) and composite dishes (22%); Top 5 foods for vitamin D intake were plaice, sea bream, sardine, octopus rice, milk; Vitamin D inadequacy was 94% and median intake was 2.2 µg/day.This research was partially funded by the European Commission’s
Seventh Framework Programme [FP7/2012–2016] as a part of TDSExposure project [grant agreement number 289108]info:eu-repo/semantics/publishedVersio
Congenital anomalies and environmental exposure - susceptibility to atmospheric pollution
Get PDFBackground & objectives. Environmental exposure to teratogenic factors during pregnancy is associated with some congenital anomalies (CA). In 2015, a cluster of anorectal anomalies in newborns (NB) was detected in the district of Setúbal, so an epidemiological study was developed with the aim of studying the association of births with CA and atmospheric pollution, having developed a susceptibility map
Methods. An observational case-control study was developed between 2016 and 2021. It was adopted a spatial multicriteria analysis using Geographic Information System software to identify the susceptibility to atmospheric pollution in pregnant women's residences. The variables used for the susceptibility map were: (i) Euclidean distance to the PRTR industrial units, defining 3 levels of susceptibility: high -2000m and 4000m; (ii) density of PRTR industrial units per km2, by kernel estimation; (iii) type of land occupation: high susceptibility - industrial areas, roads, landfills and dumps; moderate susceptibility - residencial areas; low susceptibility - natural, forest and agricultural areas; (iv) Euclidean distance to the main roads, defining 3 levels of susceptibility: high 100m and 300m; (v) areas of low elevation subject to fog, modeled by the digital terrain model and classified into 3 classes by Jenks' Natural Break method. The variables were normalized, weighted and crossed in raster matrices using the weighted linear combination, originating the map of susceptibility to atmospheric pollution, divided into three classes (High, Moderate and Low)
Results. In geographical terms, 3 areas of greater susceptibility to atmospheric pollution stand out, the consolidated urban core of Barreiro and Baixa da Banheira, the peri-urban area of Palhais, and the southern zone of the urban core of Montijo. 21 cases (21%) and 53 controls (25%) were observed in high susceptibility sites; 77 cases (75%) and 146 controls (70%) located in areas of moderate susceptibility; 4 cases (9%) and 9 controls (5%) referred to areas of low susceptibility
Conclusion. The creation of a map of susceptibility to atmospheric pollution proved to be useful to assess the possible environmental exposure of newborns to chemical agents during pregnancy. The results, integrated into a more complex analysis, may contribute to the establishment of causal links in NBs with anorectal CA in the territory under analysisinfo:eu-repo/semantics/publishedVersio
Avaliação de diferenças bioquímicas entre indivíduos diabéticos com e sem variantes patogénicas causadores de MODY. (PO 47)
Get PDFA diabetes tipo MODY (Maturity-onset diabetes of the young) é um tipo de diabetes causada por mutações em um único gene. Existe 14 genes associados a essa doença, no entanto, a maioria dos casos de MODY é causada por alterações nos genes GCK, HNF1A, HNF1B e HNF4A. Cada subtipo desta patologia apresenta características fenotípicas, metabólicas e complicações para a saúde distintas o que exige uma adequação terapêutica diferente. Contudo a grane maioria dos casos de MODY é erroneamente diagnosticada como diabetes tipo 1 ou tipo 2, o que prejudica o diagnóstico do doente. O objetivo deste trabalho consiste na caracterização bioquímica dos participantes do Estudo Molecular de diabetes tipo MODY com base nos valores de glicémia e hemoglobina A1c inicial, indicados nos inquéritos do estudo, pelos médicos que os referenciaram, para perceber se estes valores são ou não um bom indicador de diabetes tipo MODY. Para tal foram analisados os valores de 76 participantes do estudo, com e sem mutação. Para análise estatística dos valores utilizou-se o Rstudio. Com os testes de Shapiro e Wilcox para avaliou-se e distribuição das amostras, bem como as diferenças entre os dois grupos. Os resultados desta análises não revelaram diferença estatística significativa (valor p=0.5) entre os valores de glicémia inicial dos participantes do estudo com mutação e sem mutação, nem com os valores de hemoglobina A1c (valor p= 0.19). Os resultados apresentados sustentam o argumento de que não é possível identificar corretamente pacientes com diabetes tipo MODY apenas com base nos resultados bioquímicos da glicémia e da hemoglobina A1c e que o diagnóstico genético é essencial para que o conceito de medicina personalizada seja uma realidade acessível aos pacientes diabéticos em Portugal.N/