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- Re‐evaluation of sucralose (E 955) as a food additive and evaluation of a new application on extension of use of sucralose (E 955) in fine bakery waresPublication . EFSA FAF Panel (EFSA Panel on Food Additives and Flavourings); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria Lourdes; Boon, Polly; Fallico, Biagio; FitzGerald, Reginald; Fernandez, Maria Jose Frutos; Grasl-Kraupp, Bettina; Gundert-Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Batke, Monika; Dourus, Antonios; Chipman, James; Crebelli, Riccardo; Fürst, Peter; Halldorsson, Thorhallur; Mirat, Manuela; Mortensen, Alicja; Wright, Matthew; Lindtner, Oliver; Barmaz, Stefania; Civitella, Consuelo; Horvath, Zsuzsanna; Levorato, Sara; Mazzoli, Elena; Rasinger, Josef Daniel; Rincon, Ana Maria; Smeraldi, Camilla; Tard, Alexandra; Lodi, FedericaThe present opinion deals with the re‐evaluation of sucralose (E 955) as food additive and with the safety of a proposed extension of use in food category (FC) 7.2 ‘Fine bakery wares’. Based on the available data, no safety concerns arose for genotoxicity of sucralose (E 955) and its impurities and degradation products. Based on the weight of evidence (WoE), the Panel considered the decrease in body weight observed in rats as the relevant endpoint for the derivation of a reference point (RP). The Panel performed a benchmark dose (BMD) analysis on the data from the longest study (combined chronic and carcinogenicity study) with a modified benchmark dose response to account for the poor palatability of sucralose. The resulting RP was 55 mg/kg bw per day (benchmark dose lower confidence limit; BMDL). The Panel considered it appropriate to derive chemical‐specific assessment factor for sucralose and concluded that there is no need to revise the current ADI of 15 mg/kg bw per day of sucralose (E 955) previously established by the Scientific Committee on Food. The exposure estimates considering the currently authorised uses did not exceed the ADI. Therefore, the Panel concluded that there is no safety concern at the reported uses and use levels of sucralose (E 955). The overall exposure did not increase substantially when considering the proposed extension of use. However, based on the available data and the identified uncertainties regarding the potential formation of chlorinated compounds under the wide range of baking processes that may be applicable for FC 7.2, the Panel could not conclude on the safety of the proposed extension of use of E 955 in this FC. The Panel issued recommendations to the European Commission, primarily to consider a revision of the EU specifications for sucralose.
- Scientific opinion on the amendment of the specifications for vegetable carbon (E 153) as a food additivePublication . EFSA Panel on Food Additives and Flavourings (FAF); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria Lourdes; Boon, Polly; Fallico, Biagio; FitzGerald, Rex; Frutos Fernandez, Maria Jose; Grasl-Kraupp, Bettina; Gundert-Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Furst, Peter; Gaffet, Eric; Loeschner, Katrin; Mast, Jan; Mirat, Manuela; Oomen, Agnes; Undas, Anna; Mech, Agnieszka; Smeraldi, Camilla; Rincon, Ana MariaThe food additive vegetable carbon (E 153) was re‐evaluated by the EFSA ANS Panel in 2012. During that re‐evaluation, data gaps were identified, in particular with respect to impurities and particle characterisation. Following a European Commission call for data to address these gaps, one interested business operator (IBO) submitted analytical data on toxic elements, polycyclic aromatic hydrocarbons (PAHs) and particle size distribution of commercial samples of E 153. The present opinion deals with the assessment of the data provided by the IBO in response to the European Commission call. Based on the analytical data provided, the Panel concluded that the information on toxic elements supports a revision of the current EU specification limits for arsenic, cadmium, mercury and lead, and the introduction of a limit for aluminium. Regarding PAHs, the Panel assessed the risks associated with benzo[a]pyrene and PAH4 under several scenarios and concluded that the resulting margins of exposure (MOE) were above the level of concern but recommended lowering the current limit for benzo[a]pyrene and introducing a limit for PAH4 in the EU specifications for E 153. For what concerns the data on particle size distribution and morphology, the Panel considered that, due to methodological limitations, these data did not allow a full characterisation of the materials used as a food additive and did not adequately support an amendment of the specifications in relation to particle properties. Nevertheless, the Panel concluded that a fraction of small particles, including nanoparticles, is present in vegetable carbon (E 153) and noted that the substance is insoluble in water. Therefore, in line with the EFSA Guidance on Particles‐TR, the Panel concluded that the risk assessment of E 153 performed by the EFSA ANS Panel in 2012 should be complemented with nanoscale considerations.
- Safety evaluation of pectin‐rich extract derived from Coffea arabica as food additivePublication . EFSA Panel on Food Additives and Flavourings (FAF); Castle, Laurence; Andreassen, Monica; Aquilina, Gabriele; Bastos, Maria Lourdes; Boon, Polly; Fallico, Biagio; FitzGerald, Rex; Frutos Fernandez, Maria Jose; Grasl-Kraupp, Bettina; Gundert-Remy, Ursula; Gürtler, Rainer; Houdeau, Eric; Kurek, Marcin; Louro, Henriqueta; Morales, Patricia; Passamonti, Sabina; Barat Baviera, José Manuel; Degen, Gisela; Gott, David; Leblanc, Jean-Charles; Moldeus, Peter; Waalkens-Berendsen, Ine; Wölfle, Detlef; Mech, Agnieszka; Tard, Alexandra; Zakidou, Panagiota; Ruggeri, LauraThe EFSA Panel on Food Additives and Flavourings (FAF Panel) provides a scientific opinion on the safety assessment of the proposed use of pectin rich extract derived from Coffea arabica L. as a food additive. The proposed food additive consists of 70%–85% dietary fibres (of which the major part is pectin), 4%–6.5% proteins and substances of potential concern including caffeine, chlorogenic acid, ■■■■■, caffeic acid, ■■■■■, trigonelline. The Panel integrated all available information including existing EFSA evaluations on pectins, coffee fruit pulp, and conducted a new quantitative structure–activity relationship (QSAR) analysis for the substances of potential concern. Studies from literature confirmed that the pectins are not absorbed intact but extensively fermented by intestinal microbiota. No adverse effects were reported in two 90‐day toxicity studies in rats up to 7.8 g/kg body weight (bw) per day and in one human study on sugar beet pectin at 0.2 g/kg bw per day for 4 weeks. The calculated MOE for ■■■■■ indicated that there is a low concern from a public health point of view. The Panel considered that the exposure to caffeine, caffeic acid, ■■■■■, chlorogenic acid, ■■■■■ and trigonelline from use of the proposed food additive would contribute only to a minimal increase over existing dietary exposure and is not of safety concern. Considering the composition of the proposed food additive, the absence of genotoxic concern of its components and lack of adverse effects of the major component (i.e. pectins), the Panel considered that there was no need for a numerical acceptable daily intake. The Panel concluded that the use of pectin‐rich extract derived from Coffea arabica as a new food additive does not raise a safety concern at the proposed use and use levels.
- The p.Ala1035Val variant in Niemann–Pick type C1: Clinical and molecular characterization in Brazilian and Portuguese patients suggests a shared founder effectPublication . Alegretti, Ana Paula; Hammerschmidt, Tatiane; Ribeiro, Isaura; Quelhas, Dulce; Polese-Bonato, Márcia; Saraiva-Pereira, Maria Luiza; Martins, Esmeralda; Guigliani, Roberto; Encarnação, Marisa; Alves Sandra; Regla Vargas, CarmenIntroduction: Niemann–Pick disease type C1 (NPC1, OMIM 257220) is a rare, progressive, and fatal autosomal recessive lysosomal storage disorder caused by pathogenic variants in the NPC1 gene. These variants disrupt intracellular lipid trafficking, leading to the accumulation of cholesterol and glycosphingolipids and resulting in severe, multisystem dysfunction for which no cure currently exists. Materials and methods: To investigate the potential founder effect and shared ancestry of the p.Ala1035Val variant, we analyzed 30 genetically confirmed NPC1 cases, comprising 18 Brazilian (12 of whom were homozygous) and 12 Portuguese participants (3 of whom were homozygous), each carrying at least one p.Ala1035Val allele. Diagnosis was established by clinical evaluation, biochemical assays, and filipin staining, with molecular confirmation by NPC1 genotyping. Results: All analyzed individuals exhibited a conserved haplotype across the SNVs in exons 6 (c.644 A > G, p.His215Arg), 12 (c.1926G > C, p.Ile642Met), 17 (c.2572 A > G, p.Ile858Val), and 18 (c.2793C > T, p.Asn931=), strongly supporting a shared founder effect consistent with an Iberian-associated ancestral background. Among Brazilian (n = 14), visceral involvement occurred in 10/14 (71.4%), predominantly hepatosplenomegaly (6/14, 42.9%), and developmental/cognitive alterations in 10/14 (71.4%), followed by ataxia or gait disturbance in 4/14 (28.6%). Among the Portuguese (n = 3), all presented with visceral involvement, characterized by hepatosplenomegaly (3/3, 100%); one had developmental delay (1/3, 33.3%), and none exhibited ataxia/gait disturbance. Despite the small sample size, clinical patterns appeared similar between the two groups, with differences likely reflecting sampling variability. Discussion: These findings expand the known variant spectrum of NPC1 in Brazilian and Portuguese populations, supporting a possible founder effect resulting from Portuguese colonisation. They also highlight the clinical value of haplotype analysis as a tool for tracing disease origin and improving stratification in medical settings. Furthermore, they emphasise the importance of refining early diagnostic strategies to optimise patient management and improve outcomes in NPC, while highlighting the need for larger, multicenter studies to corroborate this hypothesis and refine its clinical and genetic implications.
- An introduction to BASIC Guide: human biomonitoring and surveillance of chemical exposure in occupational settingsPublication . Zare Jeddi, Maryam; Jones, Kate; Leese, Elizabeth; Fustinoni, Silvia; Galea, Karen S.; Santonen, Tiina; Porras, Simo P.; Hopf, Nancy B.; Göen, Thomas; Bader, Michael; Tranfo, Giovanna; Tristram, Adrian; Iavicoli, Ivo; Leso, Veruscka; Koch, Holger M.; Pasanen-Kase, Robert; Boogaard, Peter J.; Persoons, Renaud; Esteban-López, Marta; Verpaele, Steven; Kasiotis, Konstantinos M.; Machera, Kyriaki; Carrieri, Mariella; Palmen, Nicole; Duca, Radu-Corneliu; van Nieuwenhuyse, An; Gonzales, Melissa; Haynes, Erin N.; Viegas, Susana; Bessems, Jos; Makris, Konstantinos C.; Connolly, Alison; Teixeira, João Paulo; Chung, Ming Kei; Parsons, Patrick J.; Kumar, Eva; Lin, Elizabeth Ziying; Kil, Jihyon; Kwon, Jung-Hwan; Tavares, Ana Maria; Vekic, Ana Maria; Souza, Gustavo; Scheepers, Paul T. J.Human biomonitoring (HBM) complements air and surface measurements by integrating exposure from all routes and sources, strengthening occupational exposure assessment and control. In occupational settings, HBM can quantify exposure during routine work and nonroutine activities, evaluate controls, investigate incidents (potential overexposures), and support medical surveillance. To use HBM to its full potential, occupational health and safety professionals (OHPs) should adopt harmonized biomonitoring approaches reflecting best practice. This short communication presents the BASIC Guide series (Human Biomonitoring and Surveillance of Chemical Exposure in Occupational Settings), initiated by the International Society of Exposure Science Human Biomonitoring working group (ISES Europe HBM WG) as an integral part of the HBM Global Network. These chemical-specific practical documents operationalize the OECD (Organisation for Economic Co-operation and Development) occupational biomonitoring guidance, supporting the consistent implementation of exposure biomonitoring programs. Each BASIC Guide provides clear instructions on biomarker selection, sample handling, analytical methods, quality assurance, and result interpretation and communication. By translating international frameworks into actionable protocols, the BASIC Guides improve reproducibility and regulatory alignment in occupational HBM and enable more defensible exposure assessments worldwide.
- Atypical MEGDHEL Syndrome: A Milder Phenotype With Hepatic Presentation and Failure to Thrive Associated With a Homozygous Nonsense Variant of SERAC1Publication . Marchante Pita, Rita; Amaral, Raquel; Vilarinho, Laura; Diogo, Luísa; Gonçalves, Isabel; Nobre, SusanaMEGDHEL syndrome, caused by a gene defect, is clinically defined as the association of 3-MGA-uria (MEG), deafness (D), hepatopathy (H), encephalopathy (E), and Leigh-like features (L). Clinical presentation typically begins in the neonatal period, with neurological symptoms becoming more evident by 2 years of age. Severe liver involvement has also been reported. We report the case of a 3-year-old boy with increased transaminases and failure to thrive of unknown cause. He was born prematurely at 35 weeks and needed neonatal intensive care support for 24 h due to transient tachypnea. At 18 months, laboratory investigations for failure to thrive revealed elevated transaminases without cholestasis, which persisted on subsequent evaluations. Abdominal wall collateral veins were found during physical examination, and the liver ultrasound revealed steatosis, prompting the decision to proceed with a liver biopsy. Common causes of chronic liver disease were ruled out. Following liver biopsy, performed under general anesthesia, he had an episode of unexplained decompensation (metabolic acidosis, hyperlactatemia, and 3-methylglutaconic aciduria). The aciduria persisted upon subsequent evaluation. Liver histology showed macro/microvesicular steatosis (25%), portal tract inflammation, and mild fibrosis. Cardiac evaluation, along with brain magnetic resonance imaging and spectroscopy, was normal. Further investigations revealed decreased hepatic activity of respiratory mitochondrial chain complexes and marginal mtDNA depletion (28.1%). Analysis of the gene showed homozygosity for p.Y259* (c.777T>G, exon 9). This case report raises awareness for an atypical presentation of MEGDHEL syndrome associated with a homozygous nonsense variant of SERAC1 clinically characterized by mild hypertransaminasemia, failure to thrive, no neurological involvement, and starting in early childhood rather than infancy.
- A 30-year experience in neuro-Behçet diseasePublication . Silva, Lénia; Silva, Isabel Fonseca; Fonseca, Tomás; Pinto, Luísa Serpa; Leal, Bárbara; Pinho e Costa, Paulo; Igreja, Liliana; Moreira, Bruno; Santos, Ernestina; Vasconcelos, Carlos; Marinho, António; Correia, João AraújoBackground: Behçet disease (BD) is a systemic vasculitis affecting multiple organs with a wide range of severity. Neuro-Behçet (NBD) is a severe form, characterized by high morbidity, disability, and mortality rates. Methods: Retrospective analysis (1993-2023) of neurological involvement in BD patients at a tertiary center. Results: Of 296 BD patients, 93(31.4 %) underwent neurological evaluation. Definite NBD was identified in 30(10.1 %), probable NBD in 2(0.5 %) and "other neurological symptoms in BD" in 26(8.6 %) patients. The definite NBD group (median age: 36 years, 50 % female) had 44 neurological attacks: 24(55 %) parenchymatous and 20(45 %) non-parenchymatous. The most common syndromes were brainstem (27.3 %) and multifocal (25.6 %), with ataxia being the most frequent sign (40.9 %). One-third had a relapsing course. NBD onset concurred with BD diagnosis in 50 % of cases, followed in 30 %, and preceded in 20 %. Brain MRI revealed predominant involvement of the brainstem and diencephalic regions. The HLA-B*51 allele was more prevalent in definite NBD versus BD patients (53.8 % vs 31.2 %, p = 0.036). Treatments included corticosteroids (70.5 %), cyclophosphamide (15.9 %), infliximab (9.1 %), and conventional synthetic disease-modifying antirheumatic drugs (13.6 %). Better outcomes were achieved with cyclophosphamide and infliximab. The probable NBD and "other neurological symptoms in BD" groups (median age: 37 years) were mostly female (92.9 %). Headache (85 %) and cognitive complaints (23 %) were common symptoms.
- The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditionsPublication . Martins-Ferreira, Ricardo; Calafell-Segura, Josep; Leal, Bárbara; Rodríguez-Ubreva, Javier; Martínez-Saez, Elena; Mereu, Elisabetta; Pinho e Costa, Paulo; Laguna, Ariadna; Ballestar, EstebanDysregulated microglia activation, leading to neuroinflammation, is crucial in neurodegenerative disease development and progression. We constructed an atlas of human brain immune cells by integrating nineteen single-nucleus RNA-seq and single-cell RNA-seq datasets from multiple neurodegenerative conditions, comprising 241 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) included 90,716 nuclei/cells and revealed nine populations distributed across all conditions. We identified four subtypes of disease-associated microglia and disease-inflammatory macrophages, recently described in mice, and shown here to be prevalent in human tissue. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution in shaping pathological phenotypes. A GPNMB-high subpopulation was expanded in AD and MS. In situ hybridization corroborated this increase in AD, opening the question on the relevance of this population in other pathologies.
- Distinct exercise modalities on GUT microbiome in sarcopenic older adults: study protocol of a pilot randomized controlled trialPublication . Merelim, Ana Sofia; Zacca, Rodrigo; Moreira-Gonçalves, Daniel; Costa, Paulo P.; C. Baptista, LilianaBackground: Sarcopenia is a progressive and age-related skeletal muscle disease related to adverse health outcomes and to an increased economic burden. Recent evidence pinpoints the human gut microbiota (GM) as a contributing factor in the development of sarcopenia via the gut-muscle axis. To date, no study specifically analyzed the optimal type of exercise modality in older adults with sarcopenia considering the impact of GM composition in skeletal muscle mass and function. Therefore, the DEMGUTS study intents to explore the impact of three different exercise regimens on GM composition and gut-derived metabolites in older adults with sarcopenia. Methods:: This pilot single center three-arm parallel open-label randomized control trial (RCT) will randomly assign eligible participants to: (i) moderate aerobic exercise (AER); (ii) resistance exercise (RES); or (iii) concurrent exercise training (RES + AER). Participants will engage in a supervised center-based exercise intervention (12-weeks, 3 d/week, 60 min/d), and will be assessed at (i) baseline, (ii) end of intervention (14 weeks), and (iii) at close-out (26-weeks). The primary outcome will be the change in the relative abundance of Faecalibacterium prausnitzi and other short-chain fatty acid producing bacteria after the intervention (14-weeks). A set of complementary outcomes will also be assessed to broadly characterize the impact of each exercise intervention on body composition, skeletal muscle function, functional performance and general GM composition. Conclusion: Unraveling the impact of these exercise regimens on GM is crucial to help clarify the optimal exercise modality to manage sarcopenia disease, contributing to clinical guidance and enhancing exercise prescription in older adults with sarcopenia. Clinical trial registration identifier NCT06545123
- Do (xeno)estrogens pose a risk to earthworms? Soy isoflavones and estradiol impact gonad structure and induce oxidative stress in Eisenia fetidaPublication . Azevedo, Tiago; Silva-Reis, Rita; Medeiros-Fonseca, Beatriz; Gonçalves, Mariana; Mendes, Gabriel; Roboredo, Marta; Rocha, Maria J.; Peixoto, Francisco; Pinto, Maria de Lurdes; Matos, Manuela; Sousa, João R.; Oliveira, Paula A.; Coimbra, Ana M.Understanding the impact of endocrine disruptor compounds (EDCs) across a wide range of species is crucial, given their ubiquitous presence. Although invertebrate species lack sex steroid hormone pathways, they exhibit sensitivity to EDCs, which could affect population dynamics. This study assessed reproductive endpoints and oxidative stress parameters in Eisenia fetida following exposure to estradiol and soy isoflavones, resembling the concentrations found in livestock manure. The experiment used artificial soil, as recommended by OECD guidelines (7:2:1 sand, kaolin and peat). Adult specimens were randomly divided into seven groups (n = 11/replicate): one control, three estradiol (156.1, 283.4 and 633.8 μg/kg of dry soil) and three soy isoflavones (113.0, 215.3 and 405.0 mg/kg of dry soil) concentrations. After eight weeks, samples were collected for cytological, histological and biochemical analysis. Offspring development was assessed after 12 additional weeks. Higher estradiol and isoflavone concentrations led to lower germ cell number and increased abnormalities, especially in the seminal vesicles and ovaries. Catalase and peroxidase activities were significantly increased in all treated groups. The exposure did not significantly affect the number of E. fetida offspring. These findings highlight E. fetida’s sensitivity to EDCs at a biochemical and tissue level, suggesting its use as a bioindicator for assessing EDC contamination in soils.