National Institute of Health Dr. Ricardo Jorge
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Evolução do diagnóstico pré-natal em Portugal: dados do Registo Nacional de Anomalias Congénitas
Get PDFIntrodução:
O diagnóstico pré-natal (DPN), permite: o diagnóstico de patologia para programar tratamento, preparar pais para o nascimento de uma criança com anomalias e optar pela continuidade da gravidez. É objetivo deste estudo avaliar a evolução do DPN nas gravidezes com anomalia congénita (AC) ao longo do tempo e nas diferentes regiões do país.
Métodos:
Realizou-se um estudo transversal, descritivo, usando dados do Registo Nacional de Anomalias Congénitas (RENAC. A análise contemplou dois resultados de interesse: i) quando foi detetada a primeira AC e respetivo primeiro exame alterado, (dados de 2000-2019); ii) quais as AC mais diagnosticadas ecograficamente, tanto a nível nacional como por região NUTS II de residência da grávida (dados de 2011-2019).
Resultados:
Nos 23745 casos notificados ao RENAC, observou-se um aumento de casos diagnosticados na fase pré-natal (42,3% em 2000 e 62,9% em 2019) e uma redução ao nascer (40,2% em 2000 e 23,7% em 2019). O primeiro exame alterado foi a ecografia em 89,6% dos casos, e os exames invasivos reduziram de 6,4% em 2000 para 1,9% em 2019. Nos 11931 casos notificados entre 2011-2019, observou-se uma maior frequência de diagnóstico em algumas AC do Sistema Nervoso Central (89% a 93%), Aparelho Renal (93% a 96%), AC da Parede Abdominal (85% e 92%), Anomalias dos Cromossomas (85% a 98%) e coração esquerdo hipoplásico (95,1%). São também estes os grupos mais diagnosticados por NUTS II, registando-se na Região Norte frequências quase sempre superiores às nacionais.
Conclusões:
Nos anos em estudo, ao observou-se um impacto do diagnóstico pré-natal, com aumento de diagnósticos na fase pré-natal e redução ao nascer, sendo a ecografia o exame que mais frequentemente diagnostica ou suspeita da presença de uma AC. Nas AC potencialmente detetáveis por ecografia, observou-se variação na frequência de diagnostico de acordo com a região de residência da gravida.N/
The use of gene-specific classification guidelines VS ACMG 2015: MODY case study
Get PDFMaturity Onset Diabetes of the Young (MODY) is a form of diabetes characterized as a dominant monogenic disorder. It is caused by pathogenic or likely pathogenic variants in any of the 14 genes currently associated with the disease. Since 2015 our laboratory has employed the classification algorithm guidelines established by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) for variant classification. However the process of variant classification under these guidelines can be intricate and time intensive. To address these limitations the Monogenic Diabetes Variant Classification Expert Panel (MDEP VCEP) has developed specialized guidelines for classifying MODY variants particularly those found in the GCK, HNF1A, and HNF4A genes. Our objective is to determine whether variants initially classified as VUS under the 2015 ACMG guidelines can achieve a definitive classification when re-evaluated using the specific criteria set forth by the MDEP guidelines. In this study we conducted a comparative analysis of two variants identified in patients from the Portuguese MODY Study: HNF1A c.599 G>A/(p.Arg200Gln) and GCK c.1268 T>A/p.(Phe423Tyr). The HNF1A variant was reclassified as Pathogenic, a decision influenced not only by the updated guidelines but also by collaborative data sharing between institutions This robust evidence included the number of affected individuals and their phenotypes, what lead to the upgrade of the variant classification. While the classification of the GCK variant remained VUS, it has not yet been curated by the MDEP group, so it is possible that a future re-evaluation with additional evidence can lead to a definitive classification. In conclusion, the implementation of disease specific guidelines has improved the precision of variant classification, as evidenced by the reclassification of at least one variant in our MODY Diabetes Study. The MDEP group continues to review and update variant classifications submitted to ClinVar sharing their findings.N/
Nutritional evaluation of branded bakery and pastry products available in the Portuguese market
No full textBranded bakery and pastry products are greatly appreciated by the population, especially by the youngest ones. However, these products are often considered poor from a nutritional quality point of view because they are a source of fat, saturated fat, sugar, and salt. A high intake of these foods is considered a major risk factor for the development of non-communicable chronic diseases, such as obesity, diabetes, hypertension, cancer, among others.
This study aimed to develop a branded food database for bakery and pastry products, to assess the current situation on nutritional quality and to define further needs in terms of reformulation.
Between January and March of 2023, a branded food database with data for 1062 products was developed by compiling the existing information on the websites of major supermarket chains available in Portugal and websites of manufacturers and retailers. The collected information was analysed regarding: i) evaluation of nutritional adequacy; ii) application of traffic light system; and iii) application of Nutri-score.
After data cleaning and checking the absence of nutrition declaration, 966 foods were evaluated. Salt was above 0.3 g/100 g in 88.7% of the products and sugars were higher than 5 g/100 g in 79.1% of the products, which are goals of the Integrated Strategy for the Promotion of Healthy Eating, in Portugal. In the traffic light label analysis, the following percentages of foods are marked with red, meaning a high content: 53.5% for fat, 56.8% for saturated fatty acids, 53.9% for sugars and 9.4% for salt. According to Nutri-Score, 34.6% of the products are classified as “E” and 36.7% as “D”, indicating the poorest nutritional foods.
It is of utmost importance to follow up this study and include other categories of foods. Moreover, strategies for the reformulation of bakery and pastry products to promote public health are still needed.info:eu-repo/semantics/publishedVersio
A Shared Perspective on in Vitro and in Vivo Models to Assay Intestinal Transepithelial Transport of Food Compounds
No full textReviewAssessing nutrient bioavailability is complex, as the process involves multiple digestion steps, several cellular environments, and regulatory-metabolic mechanisms. Several in vitro models of different physiological relevance are used to study nutrient absorption, providing significant challenges in data evaluation. However, such in vitro models are needed for mechanistic studies as well as to screen for biological functionality of the food structures designed. This collaborative work aims to put into perspective the wide-range of models to assay the permeability of food compounds considering the particular nature of the different molecules, and, where possible, in vivo data are provided for comparison.M.A.F. thanks FCT (Fundação para a Ciência e Tecnologia)
for funding through program DL 57/2016 and the project
DIETxPOSOME (PTDC/SAU-NUT/6061/2020). P.A. acknowledges CESAM (UIDP/50017/2020+UIDB/50017/
2020+LA/P/0094/2020). Thanks are due to FCT/MCTES
through national funds EarlyMyco (PTDC/MED-TOX/28762/2017). S.B.-N. acknowledges the financial support by
the Dutch Ministry of Agriculture, Nature and Food Quality
via the “Healthy and Safe Food System (KB-37)” knowledge
base program (grand no. KB-37-001-007). P.R.-M. acknowl edges the financial support to the project PID2021-127362OB I00, funded by MCIN/AEI/10.13039/501100011033 and by
“ERDF A way of making Europe” (European Union). B.M.
acknowledges the financial support by project I-link22018
financed by CSIC and PID2019-107663RB-I00 and PCD2022-
133489-IOO funded b y MCIN/AEI/10.13039/
501100011033, the last counting with funds from EU
“NextGeneration EU”/PRTR. This work has been conducted
within the frame of the INFOGEST International Network
funded by INRAE.info:eu-repo/semantics/publishedVersio
Association between the adrenoreceptor β2 gene and pediatric asthma severity – a study of the PACMAN cohort
Get PDF"Pharmacogenetics of Asthma medication in Children: Medication with Anti-Inflammatory effects" (PACMAN) is an observational retrospective pharmacy-based study carried out in 2009, in the Netherlands, aiming to investigate the effects of genetic variation on treatment response to asthma medication in children and to identify (profiles of) SNPs that characterize response phenotypes. Data on respiratory symptoms and medication use, including medication type and amount, was collected from pharmaceutical records of asthmatic children and data on the children’s sex, age, genetic traits, and ethnicity. We aimed to assess the association between asthma severity and the Arg16Glu polymorphism of the β2 adrenoreceptor gene (ADRB2). This gene is expressed in bronchial muscle cells, which is involved in the physiological response of the airway response and has been associated with clinical drug response and asthma exacerbations. We used the PACMAN data and considered the dispensing of oral corticosteroid prescriptions as a proxy of the disease severity since corticoids are commonly used in uncontrolled asthmatic states (exacerbations).
We considered two different genetic models – additive and genotypic, which can be translated for analysis purposes into a numeric format, corresponding to the number of copies of the minor allele, and categorical (each genotype representing a category), respectively. We used models of the class of the Generalized Linear Mixed Models for count data with excess of zeros, namely zero-inflated and hurdle models, considering a Negative Binomial distribution to account for overdispersion. Both models included the polymorphism in the zero and count components and were adjusted for children’s baseline characteristics. In both approaches to deal with the excess of zeros, a significant effect of the polymorphism was found only in the binary component of the models. In the count component, only sex and age showed a significant effect. This points towards the existence of an effect of the polymorphism in the presence of asthma exacerbations, with not shown
effect in the frequency of OCS prescription.This work is partially financed by national funds through FCT – Fundação para a Ciência
e a Tecnologia under the project UIDB/00006/2020.info:eu-repo/semantics/publishedVersio
Microevolution of a Mycobacteroides abscessus subsp. bolletii strain in a clinical persistent infection
Get PDFMycobacteroides abscessus complex (MAB), a fast-growing nontuberculous mycobacterium, is emerging as a significant infectious disease threat, due to both intrinsic and acquired resistance mechanisms to antibiotics and disinfectants and the need for extensive and multidrug regimens for treatment. Despite the prolonged regimens, outcomes are poor and persistence cases have been reported. Here, we describe clinical, microbiologic and genomic features of a M. abscessus subsp. bolletii (M. bolletii) strain consecutively isolated from a patient within an eight-year infection period.
From April 2014 to September 2021, the National Reference Laboratory for Mycobacteria received eight strains isolated from a male patient. Species identification, molecular resistance profile and phenotypic drug susceptibility were determined. Five of these isolates were recovered for further in-depth genomic analysis.
Genomic analysis confirmed the multidrug resistant pattern of the strain and also other genetic changes associated with adaptation to environment and defence mechanisms. We highlight the identification of new mutations in locus MAB_1881c and in locus MAB_4099c (mps1 gene), already described as associated with macrolides resistance and morphotype switching, respectively. Additionally, we also observed the emergence and fixation of a mutation in locus MAB_0364c that appeared at a frequency of 36% for the 2014 isolate, 57% for the 2015 isolate and 100% for the 2017 and 2021 isolates, clearly illustrating a fixation process underlying a microevolution of the MAB strain within the patient.
Altogether these results suggest that the observed genetic alterations are a reflection of the bacterial population's continuous adaptation and survival to the host environment during infection, contributing to persistence and treatment failure.Highlights: - M. bolletii strain isolated from a patient in an eight-year infection period; - Bacterial population's continuous adaptation and survival during infection; - Microevolution of the strain contributing to persistence and treatment failure.info:eu-repo/semantics/publishedVersio
Looking at the Molecular Target of NS5A Inhibitors throughout a Population Highly Affected with Hepatitis C Virus
Get PDFHepatitis C virus (HCV) is associated with liver damage and an increased progression rate to cirrhosis and hepatocellular carcinoma. In Portugal, it is prevalent in vulnerable populations such as injection drug users (IDU). HCV is characterized by a high intra-host variability, and the selecting driving forces could select variants containing resistance-associated substitutions (RAS) that reduce treatment effectiveness. The main goal of this study was to analyze the sequence variation of NS5A in treatment-naïve IDU. The epidemiological and clinical status of hepatitis C were analyzed, and samples were sequenced by Sanger and Next-Generation sequencing (NGS) to assess RAS and confirm HCV subtypes. Phylogenetic classification was concordant: 1a, 52.4%; 1b, 10.7%; 3a, 20.2%; 4a, 8.3%; 4d, 7.1%; and one 2k/1b recombinant. A 1a/3a mixed infection was detected by NGS. RAS were found in 34.5% (29/84) of samples using Sanger sequencing, while in 42.9% (36/84) using NGS. In sequences from subtypes 1a and 1b, RAS K24R, M28V, Q30H/R, H58D/P/Q/R, and RAS L31M and P58S were detected, respectively. In subtype 3a, RAS A30S/T, Y93H and polymorphisms in position 62 were identified. Additionally, RAS P58L was detected in genotype 4. The strategy used for the molecular survey of baseline HCV resistance is of particular importance to achieve treatment effectiveness and contribute to the elimination of hepatitis C.info:eu-repo/semantics/publishedVersio
Putative Role of an ABC Efflux System in Aliarcobacter butzleri Resistance and Virulence
No full textAbstract: Aliarcobacter butzleri is considered a ubiquitous microorganism and emergent pathogen,
for which increasing rates of multidrug resistance have been described. In line with this, the present
work aimed to evaluate for the first time the contribution of an ABC efflux system, the YbhFSR, in
the resistance and virulence of this bacterium. Following the in silico characterization of the YbhFSR
transporter, a mutant strain was constructed by inactivating the gene responsible for ATP-binding.
After ensuring that the mutation did not have an impact on bacterial growth, the resistance profile
of parental and mutant strains to different antimicrobial agents was evaluated. The results suggest
that the efflux pump may influence the resistance to benzalkonium chloride, ethidium bromide,
and cadmium, and several other compounds were identified as potential substrates. Regarding
the evaluation of the accumulation of ethidium bromide, a slight increase was observed for the
mutant strain, demonstrating a potential role of the YbhFSR efflux pump in the extrusion of toxic
compounds from A. butzleri. Subsequently, the role of this efflux pump on the A. butzleri known
virulence properties was evaluated, but no difference was seen among mutant and parental strains
for the motility, biofilm formation ability, susceptibility to oxidative stress, or the ability to adhere and
invade Caco-2 cells. However, in contrast to the parental strain, the mutant strain showed a resistance
to human serum. Overall, the results support the role of efflux pumps in A. butzleri resistance to
antimicrobials, highlighting the particular role of the YbhFSR system.This work was developed within the scope of the CICS-UBI projects UIDB/00709/2020 and UIDP/00709/2020, funded by national funds through the Portuguese Foundation for Science and Technology/MCTES.info:eu-repo/semantics/publishedVersio
Are Food Producing animals a source of multidrug-resistant E. coli and Salmonella spp.?
Get PDFObjectives: To assess the role of food-producing animals as potential transmission vehicles of
Salmonella spp. and E. coli to Humans, in order to understand the epidemiology and
population structure of these zoonotic agents in Portugal.Faculty of Veterinary Medicine, Lusófona University, Research projects_ 2022_ ResisCampyOHN/
Levels of manganese, iron, zinc and mercury in vegetarian foods
Get PDFAbstract publicado em: https://icfc2023.com/bookofabstracts/The increasing popularity of vegetarian diet has induced science to better study this foods. As long as it includes the necessary intake of nutrients, such as minerals, can be beneficial to health. In addition, concern about food safety has increased in recent years, leading to studies to evaluate food contamination by toxic metals, regarding food poisoning prevention and public health improvement.
The purpose of this work was to quantify manganese, iron, zinc and mercury contents in different foods for a plant-based diet.
Mineral levels were determined by Inductive Plasma Coupled Optical Emission Spectrometry (ICP-OES). Total mercury content was determined by a thermal decomposition and amalgamation atomic absorption spectrophotometry (TDA/AAS).
Manganese level ranged from 0.10 mg/100g (<Limit of Quantification (LoQ)) in mushrooms, vegetable drinks and margarines to 22.6 mg/100g in seaweed Nori. Content of iron ranged from 0.22 mg/100g (<LoQ) in bamboo shoots mushrooms, brown mushrooms vegetable drinks, rice vegetable drink and margarines to 25.8 mg/100g in seaweed Nori. Level of zinc ranged from 0.22 mg/100g (<LoQ) in shoots, vegetable drinks and vegetable yogurt to 2.98 mg/100g in seaweed Nori.
Regarding mercury content, all samples presented levels below LoQ (1.1 µg/kg), with exception of pleurotus mushrooms, that presented a low but quantified value (8.9 µg/kg).
It was found that, in general, the analyzed foods presented mineral values below the Recommended Dietary Allowance (RDA) per 100 g of food, with exception of seaweed Nori, that exceed the RDA of manganese and iron, and chickpea that surpasses the RDA of manganese.
This study provides support for future studies regarding mineral content in vegetarian foods and supply the Portuguese Food Composition Table. As expected, vegetarian food samples presented low levels of studied minerals, with the exception of grain and seaweed. Since mercury is a contaminant, pleurotus mushrooms may require attention to its presence, despite there is no legislation for mercury levels in mushrooms. It is concluded, therefore, that the vegetarian dietary pattern must be well planned, taking into account the importance of a varied, balanced and complete diet, including adequate food choices, in order to supply the deficit and reduce exposure to toxic substances.N/