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- Talc and AcrylonitrilePublication . IARC Working Group on the Identification of Carcinogenic Hazards to HumansThis volume of the IARC Monographs provides evaluations of the carcinogenicity of talc and acrylonitrile. Talc was defined as mineral (natural) or synthetic product, a hydrated magnesium silicate, that exists in both lamellar and fibrous (including asbestiform) types. Asbestiform talc is not asbestos; however, asbestos is present in some talc deposits and has been shown to contaminate some talc products. A mineral with a high production volume, talc is used in plastics, ceramics, paint, paper, roofing materials, rubber products, animal feed, food, fertilizers, cosmetics, and pharmaceuticals. It is also used in clinical settings for pleurodesis. Occupational exposure to talc dust occurs predominantly during mining and milling, mainly via inhalation, but can also occur among workers in downstream industries. The general population may be exposed via talc-based consumer products, and pathways of exposure include ingestion, inhalation, and dermal contact, including via the perineum. Acrylonitrile is a chemical with a high production volume that is mostly used as a monomer to prepare polymers for the manufacture of fibres for textiles (acrylic fibres) used in clothing and carpets and other textiles, resins, synthetic rubber, and plastics. Occupational exposure occurs mainly in production industries via inhalation and dermal routes. The general population can be exposed to acrylonitrile via cigarette smoking, air pollution, and contact with contaminated consumer products. An IARC Monographs Working Group reviewed evidence from epidemiological studies, cancer bioassays in experimental animals, and mechanistic studies to assess the carcinogenic hazard to humans of exposure to these agents and concluded that: - Talc is probably carcinogenic to humans (Group 2A); - Acrylonitrile is carcinogenic to humans (Group 1).
- Implementation of genetic tests for disease prevention: challenges in evidence synthesis across clinical utility domainsPublication . Gris, Angelica Valz; Vicente, Astrid M.; Boccia, StefaniaExcerpt: Robust evidence supports the critical role of genetic risk in shaping the frequency of a broad range of diseases, underscoring its significance as a determinant of health outcomes [1]. Accordingly, genetic and genomic tests hold significant potential for disease prevention by stratifying populations based on individual genetic profiles and guiding targeted interventions. However, despite the enthusiasm surrounding these technologies, their integration into preventive healthcare faces significant hurdles, primarily due to the insufficient evidence supporting their clinical utility [2]. Clinical utility, though not universally defined, generally refers to the test’s usefulness to provide actionable information that improves health outcomes. (...)
- Dissecting the DIS3L2 target-specificity of transcripts committed to nonsense-mediated decay in human cellsPublication . Garcia-Moreno, Juan F.; Carvalho, Miguel P.; Lacerda, Rafaela; Romão, LuísaNonsense-mediated mRNA decay (NMD) is a conserved surveillance mechanism that eliminates mRNAs harboring premature termination codons (PTCs) and regulates the expression of certain physiological transcripts. The 3’-to-5’ exoribonuclease DIS3L2 degrades different RNAs independently of the RNA exosome, following uridylation at the 3' end by the terminal uridylyl transferases TUT4 and TUT7. We and others have shown that DIS3L2 is involved in NMD in an uridylation-dependent manner, being its function in NMD target-specific (Kurosaki et al. 2018; da Costa et al. 2019). Now, we aim to characterize the mechanisms involved in DIS3L2/NMD-target specificity. We used our RNA-seq data already obtained and validated and compared the transcripts upregulated upon DIS3L2 knockdown (REF) with a validated NMD-target set (Colombo et al., 2017). We observed that about 7% of DIS3L2-sensitive transcripts overlap with known NMD-targets. Considering the different groups of transcripts, we then analyzed specific features that make some NMD-targets sensitive to DIS3L2 (so called DIS3L2/NMD-targets; group 1), versus the remaining NMD-targets (DIS3L2-resistant NMD-targets; group 2), the remaining DIS3L2-sensitive targets (group 3), or the remaining transcriptome (DIS3L2-resistant NMD-targets plus NMD-resistant transcriptome; group 4). We assessed the following genomic features: 5’ and 3’ untranslated region (UTR) lengths, 3’UTR GC-, AU-, G-, C-, A-, and U-contents, presence of 5’UTR upstream open reading frames (uORFs), and 3’UTR introns. Elevated G-, C-, and GC-contents in the 3’UTRs were the most consistent features distinguishing DIS3L2/NMD-targets from the group 4. Comparison between group 1 and 2, and 1 and 3 was not significant. To better characterize the importance of each transcript portion, we are also analyzing hybrid constructs combining regions of the DIS3L2/NMD-resistant human β-globin (HBB) gene and the DIS3L2/NMD-sensitive GADD45A gene expressed in DIS3L2 depleted cultured cells.
- Regulatory practices on the genotoxicity testing of nanomaterials and outlook for the futurePublication . Andreoli, Cristina; Dusinska, Maria; Bossa, Cecilia; Battistelli, Chiara Laura; Silva, Maria João; Louro, HenriquetaHighlights: - Genotoxicity testing of chemicals requires multiple tests to cover key endpoints; - NMs have distinct properties that require adaptations of conventional testing; - Approaches for genotoxicity testing of the NMs reviewed show challenges; - The level of harmonization between different frameworks is debated; - New approach methodologies are underlined to support NMs'regulation.
- Toward harmonizing protein data in food composition databases: evaluating perspectives, methods and implicationsPublication . Pferdmenges, Larissa E.; Colombani, Paolo C.; Carlsen, Monica Hauger; Pajari, Anne-Maria; Poulsen, Anders; Dias, Maria da Graça; Moller, Anders; Lisciani, Silvia; Wust, Matthias; Bonsmann, Stefan; Schweiggert-Weisz, UteProtein content in foods has historically been estimated by multiplying measured nitrogen content with a universal nitrogen-to-protein conversion factor (NCF) of 6.25. Despite scientific consensus that this approach leads to systematic overestimations due to variations in amino acid composition and non-protein nitrogen (NPN) content, no universally accepted revision has been implemented. This review critically examines diverse perspectives on protein quantification and their implications for Food Composition Databases (FCDBs). A structured definition of protein for FCDBs is proposed, including amino acid residues, free amino acids and small peptides, while explicitly excluding NPN and prosthetic groups. Furthermore, analytical methods and NCF calculations are evaluated in order to provide more accurate assessments of protein content across a range of food matrices. The review highlights the importance of selecting food-specific NCFs to reduce overestimations, ensuring both scientific accuracy and practical feasibility. By addressing methodological shortcomings and proposing a refined protein quantification framework, this work aims to facilitate the transition toward more precise and harmonized protein values in FCDBs, benefiting nutritional research, dietary guidelines, and food labeling regulations.
- Dengue and Oropouche virus co-infection in a traveller from Cuba to PortugalPublication . Zé-Zé, Líbia; Laranjinha, Joana; Borges, Vítor; Graça, Ana Luísa; Sobral, Daniel; Santos, João Dourado; Carvalho, Ana Cláudia; Faria, Nuno R.; Gomes, João Paulo; Alves, Maria JoãoIn 2024, unprecedented outbreaks of dengue and Oropouche were reported in the Americas. We describe a documented co-infection with dengue and Oropouche viruses in a 35-year-old traveller from Cuba detected in Portugal. RT-PCR and next-generation sequencing confirmed both viruses. Our findings highlight the need for multiplex arboviral diagnostics in travellers from regions with concurrent outbreaks.
- Re‐assessment of the risks to public health related to the genotoxicity of styrene present in plastic food contact materialsPublication . EFSA Panel on Food Contact Materials (FCM); Claude, Lambré; Crebelli, Riccardo; Silva, Maria Da; Grob, Konrad; Lampi, Evgenia; Milana, Maria Rosaria; Pronk, Marja; Ščetar, Mario; Theodoridis, Georgios; Van Hoeck, Els; Waegeneers, Nadia; Bolognesi, Claudia; Consiglio, Emma Di; Mengelers, Marcel; Al Harraq, Zainab; Pilar, Irene Muñoz; Rainieri, Sandra; Rivière, GillesThe EFSA Panel on Food Contact Materials (FCM) was requested by the European Commission to re‐evaluate the potential genotoxicity of styrene after oral exposure and its safety for use in plastic FCM with a specific migration limit (SML) of 40 μg/kg food. A rigorous assessment of the in vivo genotoxicity studies (i) provided by third parties, (ii) identified by a targeted literature search and (iii) reported in the 2019 IARC Monograph was performed. All studies were assessed for reliability and relevance and the results integrated in the weight of evidence. The results provided by reliable in vivo oral genotoxicity studies, covering different genetic endpoints and target tissues, including liver, the primary site of metabolism, demonstrated that the oral administration of styrene in mice and rats up to the maximum tolerated dose (300 and 500 mg/kg body weight (bw), respectively) did not induce genotoxic effects. The Panel concluded that there was no evidence that styrene is genotoxic following oral exposure. For substances demonstrated to be non‐genotoxic, according to the EFSA Note for Guidance for FCM, an SML up to 50 μg/kg food would not be of safety concern. Consequently, the use of styrene in the manufacture of FCM respecting the SML of 40 μg/kg food proposed by the European Commission is not of safety concern.
- Mapping susceptibility to air pollution and its association with birth defects: a tool for public health interventionPublication . Aniceto, Carlos; Braz, Paula; Machado, Ausenda; Dias, Carlos MatiasEpidemiological studies evaluating the relation of environmental air pollution (AP) and birth defect (BD) are relevant to public health. Some limitations on these studies may derive from multiple factors contributing to the spatial variation of AP. This study aimed to integrate multifactorial AP indicators into an index and explore its application in a case-control study conducted in Portugal between 2016 and 2021. Spatial multicriteria analysis was employed to identify areas susceptible to AP. Variables included: (i) Euclidean distance to industrial units; (ii) kernel estimation of industrial units density; (iii) land occupation; (iv) Euclidean distance to main roads; and (v) areas conductive to radiation fog formation. Variables were classified into high, moderate, and low susceptibility. An AP susceptibility map was generated using the weighted linear combination method, with the analytic hierarchy process assigning weights to the variables. Georeferenced BD cases and controls were overlaid with environmental exposure variables and the AP index. Three AP susceptibility areas were identified: consolidated urban, peri-urban area, and a residential–industrial area. In areas of high susceptibility, 47 cases (29%) and 65 controls (31%) were observed; and in areas of low susceptibility 25 cases (15%) and 21 controls (10%) were observed. The development of the AP susceptibility map has been demonstrated to be a valuable tool for identifying patterns, generating hypotheses regarding the potential environmental exposure of NB to AP agents during pregnancy. When integrated into more complex analyses, these findings may contribute to assess the potential risk factors that play a major role in BD.
- A genetic variant in the 3′-UTR of PIWIL4 confers risk for extreme phenotypes of male infertility by altering miR-215 and miR-136 binding affinityPublication . González-Muñoz, Sara; Cerván-Martín, Miriam; Guzmán-Jiménez, Andrea; Rodríguez-Martín, Ana Isabel; Garrido, Nicolás; Castilla, José A.; Gonzalvo, M. Carmen; Clavero, Ana; Molina, Marta; Vilches, Miguel Ángel; Espuch-Oliver, Andrea; Maldonado, Vicente; García-Peña, María Luisa; Galiano-Gutiérrez, Noelia; Santamaría, Esther; González, Cristina; Quintana-Ferraz, Fernando; Gómez, Susana; Amorós, David; Martínez-Granados, Luis; Ortega-González, Yanira; Burgos, Miguel; Pereira-Caetano, Iris; Pinto, Graça S.; Aguiar, Ana; Pereira, Isabel S.; López-Rodrigo, Olga; Bassas, Lluís; Seixas, Susana; Gonçalves, João; Lopes, Alexandra M.; Larriba, Sara; Bossini-Castillo, Lara; Carmona, F. David; Palomino-Morales, Rogelio J.Study question: What is the functional impact of the rs508485 genetic polymorphism, located in the 3'-untranslated region (UTR) region of the PIWIL4 gene, on non-obstructive azoospermia (NOA)? Summary answer: The rs508485 genetic variant contributes to the pathogenesis of extreme patterns of NOA by modulating PIWIL4 expression through microRNA (miRNA) interactions. What is known already: Male infertility represents a significant global health challenge with profound societal and economic consequences. One of the most severe forms of male infertility is NOA, which is characterized by severe spermatogenic failure (SPGF) of idiopathic origin in most cases. Cumulating knowledge increasingly suggests that this idiopathic form of NOA may represent a multifactorial condition involving complex interactions between genetic and environmental factors. The PIWI protein subfamily, particularly PIWIL4, plays a pivotal role in spermatogenesis by processing PIWI-interacting RNAs, which silence retrotransposons to protect genomic integrity. Genetic variations in this gene have been found to be associated with susceptibility to NOA. Study design, size, duration: A case-control study was conducted in a European cohort including 1516 infertile men with SPGF and 2451 fertile controls. Logistic regression and functional assays were employed to investigate the functional role of the rs508485 polymorphism in PIWIL4. Participants/materials, setting, methods: Participants were genotyped for the rs508485 polymorphism. Associations between the polymorphism and NOA phenotypes, including Sertoli cell-only (SCO) syndrome and testicular sperm extraction (TESE) outcomes, were assessed. In silico tools predicted miRNA binding effects, which were subsequently validated using luciferase reporter assays. Main results and the role of chance: The T allele of rs508485 was significantly associated with the SCO phenotype (P = 2.69E-03, OR = 1.34) and unfavourable TESE outcomes (P = 1.09E-03, OR = 1.54). In silico analyses predicted that the rs508485 variant might alter binding sites in the 3'-UTR region of PIWIL4 for different miRNAs, such as hsa-miR-215-3p and hsa-miR-136-3p. Functional validation using luciferase assays confirmed that these miRNAs differentially bind to the T and C alleles of this polymorphism, influencing PIWIL4 regulation. Large scale data: N/A. Limitations, reasons for caution: The study is limited to a single genetic polymorphism and functional assays were performed in vitro. Additional studies are required to validate these findings across diverse populations and explore additional genetic interactions. Wider implications of the findings: These findings highlight the critical role of miRNA regulation in extreme forms of male infertility by influencing the expression of essential spermatogenesis genes, such as PIWIL4. Our study sheds light on the genetic mechanisms underlying spermatogenesis and suggests potential therapeutic targets for NOA.
- Influenza vaccine effectiveness in Europe and the birth cohort effect against influenza A(H1N1)pdm09: VEBIS primary care multicentre study, 2023/24Publication . Kissling, Esther; Maurel, Marine; Pozo, Francisco; Pérez-Gimeno, Gloria; Buda, Silke; Sève, Noémie; Domegan, Lisa; Hooiveld, Mariëtte; Oroszi, Beatrix; Martínez-Baz, Iván; Guiomar, Raquel; Latorre-Margalef, Neus; Mlinarić, Ivan; Lazar, Mihaela; Giménez Duran, Jaume; Dürrwald, Ralf; Enouf, Vincent; McKenna, Adele; de Lange, Marit; Túri, Gergő; Trobajo-Sanmartín, Camino; GOMEZ TEIXEIRA PINTO, VERÓNICA DEL PILAR; Samuelsson Hagey, Tove; Višekruna Vučina, Vesna; Cherciu, Maria Carmen; García Vazquez, Miriam; Erdwiens, Annika; Masse, Shirley; Bennett, Charlene; Meijer, Adam; Kristóf, Katalin; Castilla, Jesús; Rodrigues, Ana Paula; Kurečić Filipović, Sanja; Ivanciuc, Alina Elena; Bacci, Sabrina; Kaczmarek, MarlenaIntroduction: Influenza A(H1N1)pdm09, A(H3N2) and B/Victoria viruses circulated in Europe in 2023/24, with A(H1N1)pdm09 dominance. First influenza infections in childhood may lead to different vaccine effectiveness (VE) in subsequent years. Aim: The VEBIS primary care network estimated influenza VE in Europe using a multicentre test-negative study. Methods: Primary care practitioners collected information and specimens from patients consulting with acute respiratory infection. We estimated VE against influenza (sub)type and clade, by age group and by year of age for A(H1N1)pdm09, using logistic regression. Results: We included 29,958 patients, with 3,054, 1,053 and 311 influenza A(H1N1)pdm09, A(H3N2) and B cases, respectively. All-age VE against influenza A(H1N1)pdm09 was 52% (95% CI: 44-59). By year of age, VE was 27% (95% CI: -2 to 47) at 44 years with peaks at 72% (95% CI: 52-84) and 54% (95% CI: 41-64) among children and those 65 years and older, respectively. All-age A(H1N1)pdm09 VE against clade 5a.2a was 41% (95% CI: 24-54) and -11% (95% CI: -69 to 26) against clade 5a.2a.1. The A(H3N2) VE was 35% (95% CI: 20-48) among all ages and ranged between 34% and 40% by age group. All-age VE against clade 2a.3a.1 was 38% (95% CI: 1-62). All-age VE against B/Victoria was 83% (95% CI: 65-94), ranging between 70 and 92% by age group. Discussion: The 2023/24 VEBIS primary care VE against medically attended symptomatic influenza infection was high against influenza B/Victoria, but lower against influenza A(H1N1)pdm09 and A(H3N2). Clade- and age-specific effects may have played a role in the lower A(H1N1)pdm09 VE.