National Institute of Health Dr. Ricardo Jorge
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Cumulus cell DNA damage linked to fertilization success in females with an ovulatory dysfunction phenotype
No full textIntracytoplasmic sperm injection (ICSI) is a widely used technique in fertility centers. ICSI success depends on both nuclear and cytoplasmic oocyte maturation. Cumulus cells, which surround the oocytes, play a pivotal role in oocyte competence. However, the significance of DNA damage in cumulus cells as a marker of fertilization success remains largely unexplored. This study aims to investigate the relationship between DNA damage in cumulus cells of females undergoing ICSI, and oocyte competence, with a focus on in vitro fertilization (IVF) outcomes. We employed the alkaline comet assay to assess DNA damage levels (%TDNA) in cumulus cells and whole blood from 22 potentially fertile females and 35 infertile females, including 20 with an ovulatory disfunction phenotype. Our results revealed significant differences between the levels of %TDNA in cumulus cells and blood. Females with an ovulatory dysfunction phenotype exhibited higher levels of %TDNA in cumulus cells compared to potentially fertile females. Additionally, within the group of females with ovulatory dysfunction, a significant correlation was observed between %TDNA levels and the number of oocytes with two pronuclei. Our findings suggest that blood does not accurately reflect DNA damage in cumulus cells, which was correlated with the fertilization success in females with ovulatory dysfunction. High levels of %TDNA in cumulus cells were associated with a higher likelihood of successful fertilization. Moreover, our results imply that low levels of %TDNA may be linked to oocytes that fail to complete maturation and, consequently, do not fertilize (oocytes with zero pronuclei). Further research with larger cohorts is necessary to validate these findings and to explore potential applications in female fertility. However, our study provides evidence that DNA damage in cumulus cells may serve as a valuable biomarker for predicting fertilization success and oocyte competence.This work was supported by national funds: FCT/ESF (Foundation for Science and Technology/European Social Fund) – Project Reference SFRH/BD/136398/2018 and COVID/BD/153204/2023 to B. Rodrigues and FCT/FSE–Project Reference EXPL/BIA-REP/0423/2021—X-EPIFERTILITY. UMIB - Unit for Multidisciplinary Research in Biomedicine is funded by the FCT Portugal (grant numbers UIDB/00215/2020, and UIDP/00215/2020), and ITR - Laboratory for Integrative and Translational Research in Population Health (LA/P/0064/2020). DEFI (Departamento de Ensino, Formação e Investigação) – Reference 2015-DEFI/145/12. Thanks are due to FCT/Ministry of Science, Technology, and Higher Education (MCTES) for the financial support to CESAM (UIDP/50017/2020+UIDB/50017/2020), through national funds. FE work is supported by FCT and ESF through the PhD individual grant UI/BD/150783/2020
Safety and efficacy of a feed additive consisting of 6‐phytase produced by Aspergillus oryzae DSM 33737 (HiPhorius™) for all poultry, all Suidae and all fin fish (DSM Nutritional Products Ltd)
No full textEFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) Members: Henriqueta Louro, Departamento de Genética Humana, INSA.Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of 6‐phytase produced by the genetically modified strain Aspergillus oryzae DSM 33737 (HiPhorius™ 10, 40, 20L and 50L) as a zootechnical feed additive for all poultry, all Suidae and all fin fish. The FEEDAP Panel concluded that the genetic modification of the production strain does not give rise to safety concerns. Based on the no observed adverse effect level identified in a subchronic oral toxicity study in rats, the additive was considered safe for all poultry, all Suidae and all fin fish at the proposed conditions of use. The Panel also concluded that the use of the product as a feed additive is of no concern for the consumers and the environment. The liquid formulations of the additive are not skin or eye irritants. The two solid ones are not skin irritants but are eye irritants. Owing to the lack of data, the Panel cannot conclude on the skin sensitisation of the final formulations of the additive. Due to the proteinaceous nature of the active substance (6‐phytase), the additive is considered a respiratory sensitiser. The Panel concludes that the additive is efficacious when included in the diet of poultry for fattening or reared for laying/breeding, reproductive Suidae, and all fin fish. Due to the lack of sufficient data, the Panel could not conclude on the efficacy for laying and reproductive poultry and growing Suidae.info:eu-repo/semantics/publishedVersio
An Overview of Monkeypox Virus Detection in Different Clinical Samples and Analysis of Temporal Viral Load Dynamics
No full textMpox is a zoonotic disease caused by the Monkeypox virus (MPXV), and since May 2022, tens of thousands of cases have been reported in non-endemic countries. We aimed to evaluate the suitability of different sample types for mpox diagnostic and assess the temporal dynamics of viral load. We evaluated 1914 samples from 953 laboratory-confirmed cases. The positivity rate was higher for lesion (91.3%) and rectal swabs (86.1%) when compared with oropharyngeal swabs (69.5%) and urines (41.2%), indicating higher viral loads for the former. Supporting this, lesion and rectal swabs showed lower median PCR C values (C = 23 and C = 24), compared to oropharyngeal swabs and urines (C = 31). Stable MPXV loads were observed in swabs from lesions up to 30 days after symptoms onset, contrasting with a considerable decrease in viral load in rectal and oropharyngeal swabs. Overall, these results point to lesion swabs as the most suitable samples for detecting MPXV in the 2022-2023 multicountry outbreak and show comparable accuracy to rectal swabs up to 8 days after symptoms onset. These findings, together with the observation that about 5% of patients were diagnosed through oropharyngeal swabs while having negative lesions, suggest that multisite testing should be performed to increase diagnostic sensitivity
The role of UPF1 cap-independent translation in colorectal cancer
No full textColorectal cancer (CRC) is one of the deadliest diseases worldwide with projections pointing towards an increase for the next two decades. Translation dysregulation of many genes contributes to CRC development, and here we are studying the role of translation dysregulation of up-frameshift 1 (UPF1) in CRC. This protein is involved in many cellular mechanisms such as nonsense-mediated mRNA decay, cell cycle progression, or telomere maintenance and homeostasis. It also works as a tumour suppressor protein in most cancers but not in CRC, in which UPF1 plays an oncogenic role. We used the Xena platform to perform in silico analyses that revealed UPF1 protein overexpressed in CRC, contrary to several other analysed cancers. Besides, UPF1 protein levels are increased in CRC compared to the counterpart normal tissues. Experimentally, we confirmed that UPF1 protein expression is maintained in different CRC cell lines under normal conditions or endoplasmic reticulum (ER) stress. To understand the mechanism underlying such maintenance, we used a bicistronic reporter construct to test whether UPF1 5’ untranslated region (UTR) can mediate alternative translation initiation and we concluded that such sequence drives cap-independent translation initiation, in both normal and stress conditions. Deletional and mutational analyses of UPF1 5’UTR showed that nucleotides 1–100 [stem-loop (SL) I] and 151–275 (SL III) — out of 275 nucleotides — are the minimal required sequences for the cap-independent translation initiation mechanism to work properly. Using RNA antisense oligonucleotides (ASOs) targeting UPF1 SL I and III, we observed a reduced UPF1 expression in HCT116 (CRC) cells, supporting the functional role of SL I and SL III in mediating cap-independent translation. Altogether, these results highlight the importance of cap-independent translation initiation in UPF1 expression regulation, in conditions that mimic the tumour microenvironment, and this might be used as a therapeutic target
Is a tiered restrictions system an effective intervention for COVID-19 control? Results from Portugal, November-December 2020
No full textBackground: In November 2020, similar to other European countries, Portugal implemented a tiered restrictions
system to control the COVID-19 pandemic. We aimed to compare the COVID-19 growth rate across tiers to assess the effect of a tiered restrictions system in Portugal, using models with different times between tiers assessment. Our hypothesis was that being in a higher tier brings a faster deceleration in the growth rate than being in a lower tier.
Methods: The national database of notified COVID-19 cases and publicly available data were used to analyse the effect of the tiered restrictions system on the COVID-19 incidence growth rate. The tiers were based on the European Centre for Disease Control risk classification: moderate, high, very and extremely high. We used a generalised mixed effects regression model to estimate the growth rate ratio (GRR) for each tier, comparing the growth rates of higher tiers using moderate tier as reference. Three models were fitted using different times between tiers assessment, separated by 14 days.
Results: We included 156 034 cases. Very high tier was the most frequent combination in all the three moments assessed (21.2%), and almost 50% of the municipalities never changed tier during the study period. Immediately after the tiers implementation, a reduction was identified in the municipalities in high tier (GRR high tier: 0.90 [95%CI: 0.79; 1.02]) and very high tier (GRR very high tier: 0.68 [95%CI: 0.61; 0.77]), however with some imprecision in the 95% confidence interval for the high tier. A reduction in very high tier growth rate was identified two weeks (GRR: 0.79 [95%CI: 0.71; 0.88]) and four weeks (GRR: 0.77 [95%CI: 0.74; 0.82]) after the implementation, compared to moderate tier. In high tier, a reduction was also identified in both times, although smaller.
Conclusions: We observed a reduction in the growth rate in very high tier after the tiered restriction system was
implemented, but we also observed a lag between tiered restriction system implementation and the onset of
consequent effects. This could suggest the importance of early implementation of stricter measures for pandemic control. Thus, studies analysing a broader period of time are needed.This work was funded by the Foundation for Science and Technology through a PhD research scholarship [2020.09525.BD] granted under the Call DOCTORATES 4 COVID-19; and Comprehensive Health Research Center [UIDP/04923/2020].info:eu-repo/semantics/publishedVersio
Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study
No full textClinical TrialBackground: Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE.
Methods: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68).
Conclusions: Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.The project was supported by the Instituto Nacional de Saúde de Dr Ricardo Jorge (INSA I.P), ToxOmics-Centre for Toxicogenomics and Human Health (FCT-UID/BIM/00009/2013), RNEM-National Mass Spectrometry Networking-FCT Strategic Infrastructure (LISBOA-01-0145-FEDER-022125 • POCI-01-0145-FEDER-022125) and Fundação para a Ciência e a Tecnologia (FCT)- Fellowship 202214435.BD. This works was also partially financed by Targeted Research Project 2301110175 UOS
A critical review to identify data gaps and improve risk assessment of bisphenol A alternatives for human health
No full textBisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).All authors developed the work in the course of their employment at their respective organizations and under the scope of the Partnership for the Assessment of Risks from Chemicals (PARC) that has received funding from the European Union’s Horizon Europe Research and Innovation Programme under Grant Agreement No. 101057014. The European Partnership for the Assessment of Risks from Chemicals has received funding from the European Union’s Horizon Europe Research and Innovation Programme under Grant Agreement No. 101057014. This work was also supported from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 857560. The authors also acknowledge co-funding by their organizations and the following entities: Centre for Toxicogenomics and Human Health (ToxOmics), DOI 10.54499/UIDP/00009/2020 https://doi.org/10.54499/UIDP/00009/2020) and DOI 10.54499/UIDB/00009/2020 (https://doi.org/10.54499/UIDB/00009/2020); Spanish Ministerio de Ciencia e Innovacion (MICIN) and Fondo Europeo de Desarrollo Regional (FEDER) PID2021-125948OB-I00/AEI/10.13039/501100011033. Dr. Adamovsky thanks The Czech Science Foundation (GACR), Project 23-13617L, for support in plastic and plastic additives research.info:eu-repo/semantics/publishedVersio
Plano Estratégico 2024-2026
No full textConselho Diretivo do INSA: Fernando de Almeida (Presidente), Cristina Abreu Santos (Vogal).Plano Estratégico 2024-2026 homologadoPlano Estratégico do Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA) para 2024-2026. O INSA é um organismo público integrado na administração indireta do Estado, sob a tutela do Ministério da Saúde. Enquanto Instituto Público de interesse estratégico nacional, tem por missão contribuir para ganhos em saúde pública, enquanto Laboratório do Estado e Laboratório Nacional de Referência. Este instrumento tem como objetivo apresentar a visão, os valores institucionais e as linhas estratégicas a adotar neste triénio.info:eu-repo/semantics/publishedVersio
Inorganic contaminants and micronutrients in foods consumed by the vegetarian Portuguese population
No full textAim: The present study aimed to determine the profile of micronutrients and inorganic contaminants in the plant-based and dairy food products most consumed by the Portuguese population. Methods: The sampling plan followed the Total Diet Studies (TDS) methodology and included representative samples of the Portuguese vegetarian diet, chosen based on the National Food and Physical Activity Survey. Five main food groups were selected: Grains and grain-based products (n = 48); Dairy products (n = 60); Products for non-standard diets (n = 72); Pulses, dried fruits, and oilseeds (n = 132); and Fruiting vegetables (n = 12). The sampling plan included 324 individual samples, prepared as 27 pooled samples for laboratory analyses. Each pooled sample was analyzed for 13 elements: As, Cd, Co, Cr, Cu, I, Li, Mn, Mo, Pb, Se, Sr, and Zn. The methodology used for the analysis was ICP-MS with samples previously subjected to acid digestion through closed vessel microwave-assisted, except for I, which required an alkaline extraction. Results: The results of this study indicate that food samples from the group of Pulses, dried fruits, and oilseeds had the highest content of Mn, Zn, Mo, and Se. On the other hand, Products for non-standard diets and Dairy products had the highest content of Cu and I, respectively. The As, Cd, and Pb levels were below the limit of quantification for most of the analyzed samples from every food group. Conclusions: This research enabled updating the Portuguese Food Composition Database (FCD), underscoring the importance of regular dietary assessments and the role of FCDs and TDS in safeguarding public health by ensuring nutritional adequacy and safety in the food supply.Strategic projects UIDB/04292/2020 (https://doi.org/10.54499/UIDB/04292/2020) and UIDP/04292/2020 (https://doi.org/10.54499/UIDP/04292/2020) granted to MARE—Marine and Environmental Sciences Centre, and the project LA/P/0069/2020 (https://doi.org/10.54499/LA/P/0069/2020) granted to the Associate Laboratory ARNET—Aquatic Research Network
Mackerel and Seaweed Burger as a Functional Product for Brain and Cognitive Aging Prevention
No full text(This article belongs to the Special Issue Novel Food and Beverages: Production and Characterization: 2nd Edition)Most world countries are experiencing a remarkable aging process. Meanwhile, 50 million people are affected by Alzheimer’s disease (AD) and related dementia and there is an increasing trend in the incidence of these major health problems. In order to address these, the increasing evidence suggesting the protective effect of dietary interventions against cognitive decline during aging may suggest a response to this challenge. There are nutrients with a neuroprotective effect. However, Western diets are poor in healthy n-3 polyunsaturated fatty acids (n-3 PUFAs), such as docosahexaenoic acid (DHA), iodine (I), and other nutrients that may protect against cognitive aging. Given DHA richness in chub mackerel (Scomber colias), high vitamin B9 levels in quinoa (Chenopodium quinoa), and I abundance in the seaweed Saccorhiza polyschides, a functional hamburger rich in these nutrients by using these ingredients was developed and its formulation was optimized in preliminary testing. The effects of culinary treatment (steaming, roasting, and grilling vs. raw) and digestion on bioaccessibility were evaluated. The hamburgers had high levels of n-3 PUFAs in the range of 42.0–46.4% and low levels of n-6 PUFAs (6.6–6.9%), resulting in high n-3/n-6 ratios (>6). Bioaccessibility studies showed that the hamburgers could provide the daily requirements of eicosapentaenoic acid (EPA) + DHA with 19.6 g raw, 18.6 g steamed, 18.9 g roasted, or 15.1 g grilled hamburgers. Polyphenol enrichment by the seaweed and antioxidant activity were limited. The hamburgers contained high levels of Se and I at 48–61 μg/100 g ww and 221–255 μg/100 g ww, respectively. Selenium (Se) and I bioaccessibility levels were 70–85% and 57–70%, respectively, which can be considered high levels. Nonetheless, for reaching dietary requirements, considering the influence of culinary treatment and bioaccessibility, 152.2–184.2 g would be necessary to ensure daily Se requirements and 92.0–118.1 g for I needs.The experimental work was funded by international and national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., CIISA grant (UIDB/00276/2020) and AL4AnimalS grant (LA/P/0059/2020), I9 + PROALGA (Ref.: 16-01-03-FMP-0011), and InterReg AQUAFISH 0.0 (EAPA_0062/2022) entitled “Improving the acceptance and social awareness in the consumption of sustainable marine food products developed under the zero-waste philosophy”. The author Joana Matos also acknowledges the project AQUAFISH 0.0 (EAPA_0062/2022).info:eu-repo/semantics/publishedVersio