National Institute of Health Dr. Ricardo Jorge
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Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer
No full text(This article belongs to the Special Issue Advances in Molecular Oncology and Therapeutics)Simple Summary: Patients with ulcerative colitis (UC) face a higher risk of developing colorectal cancer (CRC) due to chronic inflammation, a known promoter of tumour growth. Here, we review the molecular differences between colitis-associated cancer (CAC) and sporadic CRC, with a focus on “alternative splicing”, a mechanism by which the same gene can produce various protein forms. We explore how inflammation triggers changes in this process, increasing cancer risk for UC patients. The revised data emphasize that additional research into these molecular changes could help identify new biomarkers (molecules that indicate disease progression) and pave the way for innovative treatments targeting these alterations. Such advances would improve outcomes and quality of life for patients while contributing to cancer prevention and care.Abstract: The risk of developing colorectal cancer (CRC) is increased in ulcerative colitis patients compared to the general population. This increased risk results from the state of chronic inflammation, a well-known tumour-promoting condition. This review explores the pathologic and molecular characteristics of colitis-associated colon cancer (CAC), emphasizing the distinct features from sporadic CRC. We focus on the key signalling pathways involved in the transition to CAC, highlighting the emerging role of alternative splicing in these processes, namely on how inflammation-induced alternative splicing can significantly contribute to the increased CRC risk observed among UC patients. This review calls for more transcriptomic studies to elucidate the molecular mechanisms through which inflammation-induced alternative splicing drives CAC pathogenesis. A better understanding of these splicing events is crucial as they may reveal novel biomarkers for disease progression and have the potential to target changes in alternative splicing as a therapeutic strategy.Work in the authors’ laboratory was supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal, through grant doi: 10.54499/UIDB/04046/2020 to Research Unit BioISI—Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, Portuga
Update of the safety assessment of N,N‐bis(2‐hydroxyethyl)alkyl(C8‐C18)amines (FCM No 19) and N,N‐bis(2‐hydroxyethyl)alkyl(C8‐C18)amine hydrochlorides (FCM No 20) for their use in plastic materials and articles intended to come into contact with food
No full textMaria João Silva, Departamento de Genética Humana, INSAThe European Commission asked EFSA to review whether the authorisation of N,N‐bis(2‐hydroxyethyl)alkyl(C8‐C18)amine (FCM No 19) and N,N‐bis(2‐hydroxyethyl)alkyl(C8‐C18)amine hydrochlorides (FCM No 20) is still in accordance with Regulation (EC) No 1935/2004, as provided for in Article 12(3). The FCM Panel concluded that some uses of the substance N,N‐bis(2‐hydroxyethyl)alkyl(C8‐C18)amine (FCM No 19) are not in accordance with this Regulation, since the migration is likely to exceed the current SML(T) of 1.2 mg/kg food under certain conditions of use. Based on the provided data, the FCM Panel concluded that the FCM substance No 19, N,N‐bis(2‐hydroxyethyl)alkyl(C8‐C18)amine, is not of safety concern for the consumer if (i) the substance is used at up to 0.1% w/w as polymer production aid and as processing aid to manufacture polyolefin materials and articles of thickness up to 1 mm that are intended for contact with all types of food except infant foods. This exception for infant foods and the restriction for maximum thickness do not apply to caps of bottles; (ii) the migration does not exceed 5 mg/kg food; (iii) the source of the alkyl group is either from hydrogenated vegetable oil or synthetic from ethylene oligomers with a high degree of linear structure and (iv) the impurities do not exceed 5% w/w. As they bear unsaturation, PFAEO‐coco, PFAEO‐oleyl, PFAEO‐HT, PFAEO‐T and PFAO‐C18 do not fall within the scope of the FCM substance No 19. The information related to these substances was only considered supportive for FCM substance No 19. If they were intended to be used to manufacture FCMs, a proper application following the EFSA Guidance documents should be submitted. No uses of the FCM substance No 20, N,N‐bis(2‐hydroxyethyl)alkyl(C8‐C18)amine hydrochlorides, were claimed and no information was provided to support that the current authorisation is in accordance with the Regulation (EC) No 1935/2004
European pilot interlaboratory comparison study on Mpox virus whole genome sequencing
No full textObjectives: Since 2022, distinct Mpox virus (MPXV) clades have been spreading across different geographic regions, causing a challenging epidemiological situation. Whole genome sequencing (WGS) proved to be instrumental for patient management and global public health. We report a pilot interlaboratory comparison study for MPXV WGS.
Methods: We distributed noninfectious DNA samples, including the main MPXV clades I and II, to eight European laboratories. We included one cowpox (CPXV) sample as a specificity control. Participants were free to choose their WGS pipeline of choice to mimic a real-world scenario and were asked to report on the sequencing pipeline used, average genome coverage, and MPXV species, clade, and subclade assignments.
Results: Seven of the eight invited laboratories reported results back. All participants largely identified the MPXV clades and reported high-quality genomes with minimal variations, specifically for MPXV clade IIb 2022 outbreak strains. However, reconstructed genomes showed high variability for nonclade IIb MPXV strains. The CPXV sample was correctly identified by three laboratories.
Conclusions: Although results for MPXV clade IIb 2022 outbreak strains are reassuring, the inclusion of MPXV clade I and IIa strains highlights pitfalls for targeted sequencing approaches and subsequent bioinformatic analyses. Our findings underscore the need for standardized external quality assessment studies.The European Society of Clinical Microbiology and Infectious Diseases study group on Genomic and Molecular Diagnostics (ESGMD) supported this study. Institute of Tropical Medicine Structurele Onderzoeksfinanciering (ITM's SOFI) programme supported by the Flemish Government, Science & Innovation cosupported this study. This study was cofunded by the European Union project “Sustainable use and integration of enhanced infrastructure into routine genome-based surveillance and outbreak investigation activities in Portugal”—GENEO (project number 101113460) on behalf of the EU4H programme (EU4H-2022-DGA-MS-IBA-01-02)
Boletim Epidemiológico Observações: Vol. 14 (2025), Número Especial 17, Doenças genéticas
No full textFollow‐up of the re‐evaluation of silver (E 174) as a food additive (EFSA‐Q‐2023‐00169)
No full textSilver (E 174) is a food colour that was re‐evaluated by the EFSA ANS Panel (2016). The ANS Panel concluded that the information available then, was insufficient to assess the safety of silver as food additive. The major issues included limited characterisation of silver E 174 (e.g. quantity of nanoparticles) and release of ionic silver. Following a European Commission call for further data to fill the data gap, the Panel on Food Additives and Flavourings (FAF) was requested to assess the safety of silver (E 174). One interested business operator (IBO) submitted limited data on particle size distribution and morphology, two genotoxicity studies and one subchronic study. The Panel concluded that the technical data submitted on physicochemical characterisation of all types of silver used as food additive E 174 were not adequate. As a result, the Panel was unable to propose changes to the EU specifications of E174 on particle size and morphology. As the additional information requested was not provided, the assessment was based solely on the submitted data. Nonetheless, given the data provided and silver insolubility in water, the Panel concluded that E174 requires risk assessment at the nanoscale following the EFSA Guidance on Risk assessment of nanomaterials to be applied in the food and feed chain, to complement the conventional risk assessment. The Panel considered that the genotoxicity data and sub‐chronic toxicity data were inadequate. Consequently, the Panel could not conclude on the safety of the food additive silver E 174
Aromatic L-amino acid decarboxylase deficiency: possibility for inclusion in Portuguese Newborn Screening Program
No full textA deficiência da descarboxilase dos L-aminoácidos aromáticos (AADC) é uma doença genética rara que afeta a síntese de neurotransmissores, resultando em sintomas neurológicos e de desenvolvimento graves. A quantificação da 3-O-metildopa (3-OMD), em amostras de sangue seco, tem-se mostrado um método fiável, sensível e específico para a deteção desta patologia no período neonatal. Este facto, associado ao desenvolvimento de novas terapias com vantagens de início precoce, tem feito equacionar o rastreio neonatal desta patologia. Este estudo teve como objetivo avaliar a possibilidade de integrar a quantificação de 3-OMD no protocolo existente, de espectrometria de massa, no Programa Nacional de Rastreio Neonatal (PNRN), assim como implementar uma prova de segundo nível para melhorar a sensibilidade e especificidade da deteção da patologia. A quantificação da 3-OMD foi incorporada no procedimento existente, sem comprometimento do mesmo, sendo eficaz na quantificação de valores de concentração clinicamente relevantes. Como prova de segundo nível foi desenvolvida uma abordagem por LC-MS/MS que se revelou eficaz na deteção de eventuais interferentes. A possibilidade de inclusão da quantificação da 3-OMD, incluída na abordagem multiplex de MS/MS já utilizada, sem custos diretos relevantes associados, permite que se equacione a eventual inclusão desta patologia no PNRN.Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder that affects neurotransmitter synthesis, resulting in severe neurological and developmental symptoms. Quantification of 3-O-methyldopa (3-OMD), a metabolite accumulated in this condition, in dried blood spot’s (DBS) has proven to be a sensitive and specific method for newborn screening. This fact, combined with the development of new therapies offering advantages when started earlier, has led to discussions about considering the neonatal screening for this condition. This study aimed to assess the possibility of integrating the quantification of 3-OMD into the existing mass spectrometry protocol of the Portuguese Neonatal Screening Program (PNRN), as well as to implement a second-tier test to improve the sensitivity and specificity of the detection. The quantification of 3-OMD was incorporated into the existing procedure without compromising it, being effective in quantifying clinically relevant concentration values. A second-tier test was developed using an LC-MS/MS approach, which proved effective in discriminating potential interferences. The possibility of including 3-OMD quantification, as part of the already used multiplex MS/MS approach, with no significant associated direct costs, allows for the consideration of including this condition in the PNRN
Infográfico Anomalias congénitas: Glaucoma congénito − 1997-2023
No full textO Glaucoma Congénito (GC) é uma condição rara e severa que afeta crianças nos primeiros anos de vida, com potencial para causar baixa visão e cegueira irreversível se não for diagnosticado e tratado precocemente. Apesar da sua gravidade, há uma carência de dados robustos sobre a prevalência, diagnóstico e impacto desta condição em Portugal. Este infográfico pretende sensibilizar e aumentar a consciencialização para o impacto desta doença rara, focando-se na importância do diagnóstico e tratamento precoce, baseado em dados sobre tratamentos cirúrgicos oculares com anestesia.
O infográfico apresentado abrange o período 1997-2023 e tem como fonte de dados o Registo Nacional de Anomalias Congénitas (RENAC) e o Bilhete de Identidade para a Morbilidade Hospitalar (BI MH). Em conjunto com a Unidade Local de Saúde de Santa Maria - Serviço de Oftalmologia, foram definidos os critérios para definição de diagnóstico e procedimento hospitalar. Os resultados mostram que o nascimento de crianças com GC é irregular ao longo dos anos, e em média foram reportados anualmente ao RENAC cerca de 2 casos em cada 100.000 nascimentos. Nas 17 crianças nascidas com GC entre 2012 e 2023 foram observados 222 episódios de procedimentos oculares realizados em bloco operatório, 74% dos quais referentes a cirurgia ocular com anestesia.
Em Portugal, a vigilância epidemiológica das anomalias congénitas é desenvolvida, desde 1997, pelo RENAC, registo nosológico de base populacional que recebe notificações de nascimentos com anomalias congénitas que ocorreram em Portugal, que tem como objetivos, entre outros, avaliar o efeito de fatores de risco e de medidas preventivas
Programa Nacional de Vigilância da Gripe e Outros Vírus Respiratórios: relatório da época 2024/2025
No full textRelatório anual do Programa Nacional de Vigilância da Gripe e Outros Vírus Respiratórios relativo à época 2024/2025. A presente publicação descreve a caraterização clínica e laboratorial da atividade gripal e de vírus respiratórios detetados nesta época.
O Programa Nacional de Vigilância da Gripe e Outros Vírus Respiratórios (PNVGVR) assegura a vigilância epidemiológica em Portugal, integrando as componentes de vigilância clínica e laboratorial. Nas últimas épocas, foi reforçada a vigilância dos vírus respiratórios e a caraterização genética, não apenas do vírus da gripe e do SARS-CoV-2, mas também do vírus sincicial respiratório (RSV), dos coronavírus, rinovírus e enterovírus.
As atividades do PNVGVR são desenvolvidas pelo Instituto Nacional de Saúde Doutor Ricardo Jorge através do Laboratório Nacional de Referência para o Vírus da Gripe e Outros Vírus Respiratórios do Departamento de Doenças Infeciosas e do Departamento de Epidemiologia, em colaboração com a Direção-Geral da Saúde. Colaboram no PNVGVR a Rede Médicos-Sentinela, a Rede de Unidades de Saúde Sentinela e a Rede Portuguesa de Laboratórios para o Diagnóstico da Gripe e Outros Vírus Respiratórios
Exposure assessment of cadmium, arsenic and lead in the first harmonized Total Diet Study in Portugal
No full textEste estudo avaliou a exposição crónica da população portuguesa adulta (18--74 anos) ao arsénio inorgânico (iAs), cádmio (Cd) e chumbo (Pb) através da alimentação, usando a metodologia harmonizada dos Estudos de Dieta Total (TDS).
Os dados de consumo alimentar foram combinados com dados de ocorrência dos contaminantes em 164 amostras de alimentos, representativas da dieta da população, preparadas “como consumidas” e analisadas por espectrometria de massa com plasma indutivo acoplado (ICP-MS).
Os resultados indicaram que a exposição média ao iAs (0,28 μg/kg de peso corporal/dia) e os valores de P95 para iAs, Cd e Pb não permitem excluir riscos para a saúde, como cancro, efeitos cardiovasculares, nefrotoxicidade e disfunções renais. Os grupos de alimentos “pratos compostos”, “cereais e derivados” e “peixes, marisco, anfíbios, répteis e invertebrados” foram as principais fontes de exposição, sendo o pão a única fonte comum aos três contaminantes.
Recomenda-se a continuidade do TDS nacional com o refinamento dos procedimentos analíticos, incluindo a redução dos limites de deteção e a análise de especiação do arsénio, assim como a utilização de dados de consumo obtidos por duas vezes, com questionários às 24 horas anteriores, a fim de orientar de forma mais eficaz as estratégias de gestão de risco em saúde pública.This study assessed the chronic dietary exposure of the Portuguese adult population (ages 18-74) to inorganic arsenic (iAs), cadmium (Cd), and lead (Pb) using the harmonized methodology of Total Diet Studies (TDS).
Food consumption data were combined with occurrence data on 164 food samples prepared "as consumed" and analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS).
Results showed that the mean exposure to iAs (0.28 μg/kg of body weight /day) and the 95th percentile (P95) values for iAs, Cd, and Pb suggest potential health risks, including cancer, cardiovascular effects, nephrotoxicity, and kidney dysfunction. The food groups “composite dishes,” “grains and grain-based products,” and “ fish, seafood, and invertebrates” contributed significantly to the overall exposure, with bread being the only common source of all three contaminants.
It is recommended to continue the national TDS (Total Diet Study), with refined analytical procedures, including lower detection limits and arsenic speciation analysis, as well as the use of consumption data obtained through two 24-hour dietary recall questionnaires. These measures aim to more effectively guide public health risk management strategies
Autism Spectrum Disorder: contribution of genetic variants involved in the nonsense-mediated mRNA decay
No full textIntroduction:
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impairedsocial/communication skills and stereotyped/repetitive behaviors. Genetic factors account for 50-80% of the familialrisk of ASD, but genetic determinants are not fully understood and a role for regulatory processes is plausible. Inthis study, we explored the contribution to ASD etiology of genes involved in an important post-transcriptionalregulatory mechanism implicated in neurodevelopment, the Nonsense-Mediated Decay (NMD).
Methods:
We first compiled a group of 46 genes encoding NMD factors and regulators. In these genes wesearched for Single Nucleotide Variants (SNVs) and Copy Number Variants (CNVs) in two samples of ASD patients(N=1828 and N=3570, respectively). We observed the frequency of these variants in 60146 controls from gnomADv2.1.1 (for SNVs) and in 10355 controls from the Database of Genomic Variant ( for CNVs). In genes with rarevariants (MAF<1% in controls) predicted to be pathogenic
in silico
, we further investigated whether these variantsaffect protein domains required for NMD.
Results:
We identified 270 predicted pathogenic SNVs within 38 genes in 524 ASD patients (28.7% of the total ASDcases) and 38 CNVs located in 18 genes in 38 ASD patients (1% of the ASD cases). Five of these genes,
RBM8A
,
UPF2
,
FMR1
,
SMG6
and
EIF4G1,
were previously associated with ASD. We found that 136 variants (122 SNVsand 11 CNVs), in 23 genes, were located within known protein domainsrequired for NMD. These variants, identifiedin 258 ASD patients, may affect proper NMD function and consequently contribute to changes in the expression ofNMD targets.
Discussion
:
In this study we identified genetic variants that may affect NMD function in ASD patients. Since mostNMD targets encode proteins expressed in the brain, we hypothesize that NMD impairment can constitute a riskfactor to ASD pathophysiology. Further studies are needed to better understand the impact of these genetic variantson NMD function and their relevance for ASD.A full understanding of these regulatory mechanisms may constitutean opportunity for the development of therapeutic interventions.A.R.Marques is recipient of a fellowship from BioSys PhD programme (Ref PD/BD/113773/2015 from FCT (Portugal).info:eu-repo/semantics/publishedVersio