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- FRIESA (FRIo Extremo na SAúde): relatório da época de inverno 2021/22Publication . Silva, Susana Pereira; Torres, Ana Rita; Rodrigues, Ana Paula; Neto, Mariana; Antunes, Sílvia; Marques, Jorge; Nunes, Baltazar; Matias Dias, CarlosEm termos climáticos, o inverno 2021/2022, com exceção do mês de novembro classificado como frio, variou entre o normal e o muito quente. Não se identificaram dias consecutivos com temperaturas mínimas do ar inferiores ao percentil 1. De acordo com o Sistema FRIESA o distrito de Lisboa vivenciou um maior número de dias com frio extremo com possíveis impactes na mortalidade comparativamente ao distrito do Porto. Tendo em conta as temperaturas mínimas e a taxa de incidência de síndroma gripal, foi identificado um período no distrito de Lisboa e um no distrito do Porto com possível impacte na mortalidade. Considerando a sobreposição entre os dias identificados para a população geral e e a população com 65 e mais anos de idade foi analisado apenas um período quer em Lisboa quer no Porto, correspondendo a períodos com mais do que um dia. Removendo das séries de mortalidade a mortalidade específica por COVID-19, não se estimaram quaisquer excessos de mortalidade no período identificado quer no distrito de Lisboa quer no distrito do Porto.
- Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance studyPublication . Sánchez-Busó, Leonor; Cole, Michelle J.; Spiteri, Gianfranco; Day, Michaela; Jacobsson, Susanne; Golparian, Daniel; Sajedi, Noshin; Yeats, Corin A.; Abudahab, Khalil; Underwood, Anthony; Bluemel, Benjamin; Aanensen, David M.; Unemo, Magnus; Pleininger, Sonja; Indra, Alexander; De Baetselier, Irith; Vanden Berghe, Wim; Hunjak, Blaženka; Blažić, Tatjana Nemeth; Maikanti-Charalambous, Panayiota; Pieridou, Despo; Zákoucká, Hana; Žemličková, Helena; Hoffmann, Steen; Cowan, Susan; Schwartz, Lasse Jessen; Peetso, Rita; Epstein, Jevgenia; Viktorova, Jelena; Ndeikoundam, Ndeindo; Bercot, Beatrice; Bébéar, Cécile; Lot, Florence; Buder, Susanne; Jansen, Klaus; Miriagou, Vivi; Rigakos, Georgios; Raftopoulos, Vasilios; Balla, Eszter; Dudás, Mária; Ásmundsdóttir, Lena Rós; Sigmundsdóttir, Guðrún; Hauksdóttir, Guðrún Svanborg; Gudnason, Thorolfur; Colgan, Aoife; Crowley, Brendan; Saab, Sinéad; Stefanelli, Paola; Carannante, Anna; Parodi, Patrizia; Pakarna, Gatis; Nikiforova, Raina; Bormane, Antra; Dimina, Elina; Perrin, Monique; Abdelrahman, Tamir; Mossong, Joël; Schmit, Jean-Claude; Mühlschlegel, Friedrich; Barbara, Christopher; Mifsud, Francesca; Van Dam, Alje; Van Benthem, Birgit; Visser, Maartje; Linde, Ineke; Kløvstad, Hilde; Caugant, Dominique; Młynarczyk-Bonikowska, Beata; Azevedo, Jacinta; Borrego, Maria-José; Nascimento, Marina Lurdes Ramos; Pavlik, Peter; Klavs, Irena; Murnik, Andreja; Jeverica, Samo; Kustec, Tanja; Vázquez Moreno, Julio; Diaz, Asuncion; Abad, Raquel; Velicko, Inga; Unemo, Magnus; Fifer, Helen; Shepherd, Jill; Patterson, LynseyBackground: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe. Methods: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data. Findings: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10. Interpretation: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.
- Avaliação de idosos institucionalizados por espirometria e condensado brônquico do ar exalado: efeitos da exposição ambientalPublication . Belo, Joana; Carreiro-Martins, Pedro; Papoila, Ana Luísa; Palmeiro, Teresa; Caires, Iolanda; Alves, Marta; Nogueira, Susana; Aguiar, Fátima; Mendes, Ana; Cano, Manuela; Botelho, Maria A.; Neuparth, NunoNo estudo geriátrico dos efeitos na saúde da qualidade do ar interior em lares da 3.ª idade de Portugal (GERIA) foi estabelecido como objetivo principal de estudar os efeitos da qualidade do ar interior (IAQ) de equipamentos residenciais para pessoas idosos (ERPI) na saúde respiratória de idosos institucionalizados. Um total de 269 idosos responderam a um questionário elaborado pela equipa de investigadores do projeto GERIA, realizaram uma espirometria e a 150 idosos foi recolhida uma amostra de condensado brônquico exalado (EBC), para análise do respetivo pH e concentração de nitritos. Em relação aos dados sociodemográficos destaca se uma média de idade de 81,9±7,5 anos e uma maioria (70,6%) de idosos do sexo feminino. Relativamente aos resultados da espirometria, observou se que 14,5% apresentaram uma obstrução das vias aéreas. Os valores medianos das concentrações dos poluentes ambientais não revelaram uma concentração acima do referencial de segurança, porém foram observados valores máximos elevados e acima desse referencial. Da análise multivariada verificou se que cada incremento de 100 µg/m3 nos compostos orgânicos voláteis (TVOCS) se encontrava associado positiva mente a possibilidade acrescida dos idosos terem reportado infeção respiratória nos últimos três meses (=1.05; 95% CI: 1.00 to 1.09). Verificou se que o valor do pH diminuía com uma maior exposição a PM2,5 (= 0.04, 95%: 0.06 to 0.01e por cada aumento de 10 µg/m3). No que concerne à exposição a bactérias, verificou se que esta se associava positivamente à possibilidade dos idosos terem uma FVC diminuída (= 0,53, 95%: 0,87 a 0,20) e uma relação FEV1 /FVC aumentada (=0,22, 95%:0,08 a 0,37)
- Occupational secondhand smoke exposure may modify the proteoma expression of human nasal epitheliumPublication . Neves, Sofia; Pacheco, Solange; Vaz, Fátima; Martins, Inês; James, Peter; Simões, Tânia; Penque, DeborahThe tobacco is one of the biggest public health threats, smoking kills more than 7 million people/year worldwide and more than 890,000 are deaths resulting from exposure to Second Hand Smoke (SHS). In adults, SHS is associated to cardiovascular and respiratory diseases, including coronary heart disease and lung cancer, through pathological and molecular mechanisms not yet understood. In this study, we aimed to investigate the SHS effects on airway proteome in exposed workers. Nasal epithelium was collected from hospitality workers (non-smokers=40; smokers=12) long-term exposed and non-exposed to SHS at the workplace. Samples were analyzed by shotgun proteomics using an ESI-LQT Orbitrap XL mass spectrometer. The generated MS raw data was submitted to ‘PatternLab for Proteomics 4.0’ for peptide identification and relative quantification by label-free - extracted ion chromatograms (XIC). Golden rules were applied to obtain reliable data such as the inferred proteins must have at least one unique peptide identified to be considered and be detected in at least 80% of the cohort. Two proteins were found to be differentially expressed in the no-smokers exposed to SHS compared with the control: BPI fold-containing family A member 1 (BPIFA1) and Heat shock Protein Beta-1 (HSPB1). The first protein plays a role in the airway inflammatory response after exposure to irritants substances and the second is associated as a regulator of actin filament dynamics. Our findings support the indication that in non-smokers the prolonged exposure to SHS can lead to airway proteome modulation. When validated, the uncovered proteins can be promising candidates to “susceptibility/risk” and/or “response” biomarkers for SHS exposure.
- Kidney allocation rules simulatorPublication . Lima, Bruno A.; Henriques, Teresa S.; Alves, HelenaThe greatest challenge of any kidney transplant program lies in finding enough organ donors (in number and quality) for all waitlisted transplant candidates. Unfortunately, we must resign ourselves to a manifestly insufficient supply of organs for the current demand. Furthermore we must be able to predict kidney transplant success at organ allocation if we want to minimize the number of patients who return to an already overcrowded waiting list for transplantation. Therefore, the definition of deceased donors' kidney allocation rules on transplantation must be supported by simulations that allow foreseeing, as much as possible, the consequences of these rules. Here we present the Kidney Allocation Rules Simulator (KARS) application that enables testing different kidney transplant allocation' systems with different donors and transplant candidates' datasets. In this application, it is possible to simulate allocation rules implemented in Portugal, in the United Kingdom, in countries within Eurtotransplant, and a previously suggested color priority system. As inputs, this application needs three data files: a file with transplant candidates' information, a file with candidates' anti-HLA antibodies, and a file with donors' information. As output, we will have a file with donor-recipient pairs selected according to the kidney allocation system simulated. When seeking waste reduction while ensuring a fair distribution of organs from deceased donors, the definition of rules selecting donor-recipient pairs in renal transplantation must be based on evidence supported by data. On the continuously changing process for a better distribution of an increasingly scarce resource must, we must be able to predict transplant outcomes when defining the best allocation rules.
- Seasonal variation of chub mackerel (Scomber colias) selenium and vitamin B12 content and its potential role in human healthPublication . Rego, A.; Coelho, I.; Motta, C.; Cardoso, C.; Gomes-Bispo, A.; Afonso, C.; Prates, J.A.M.; Bandarra, N.M.; Silva, J.A.L.; Castanheira, I.Chub mackerel (Scomber colias), an underutilised fish species, has been identified as an excellent source of selenium and vitamin B12, which may prevent and delay cognitive decline and dementia. Given these nutrients’ contents seasonal variability, a complete monthly sampling, involving a specifically adjusted methodology for the determination of vitamin B12 (LC-MS/MS) and its main vitamers and a sensitive analytical technique (ICPMS) for Se, was carried out. Regarding total vitamin B12 in the chub mackerel muscle, its content varied from 10.0 ± 1.0 μg/100 g in February to 18.9 ± 1.9 μg/100 g in August. It was also shown that methylcobalamin content ranged from 1.12 ± 0.43 (March) to 6.77 ± 0.80 μg/100 g (August), a sixfold increase. Hydroxocobalamin content varied between 3.49 ± 0.12 (February) and 9.62 ± 0.41 μg/100 g (August). The content of Se also had seasonal variability, ranging from 451 ± 14 μg/kg (December) to 606 ± 11 μg/kg (July). In the worst-case scenario, a weekly 160 g meal of this fish would almost guarantee B12 requirements. Three weekly 160 g meals of S. colias would cover, at least, 56% of the Se requirements. Therefore, as first explored here, it is highly relevant a complete, year-round assessment of the chub mackerel’s nutritional value, in order to elaborate finely tuned dietary recommendations.
- The 2020s Tooth Fairy: from loose tooth to neuronal cell cultures, an innovative method for in vitro genetic disease modeling of a rare neurological disorderPublication . Carvalho, Sofia; Santos, Juliana Inês; Ribeiro, Diogo; Moreira, Luciana; Duarte, Ana Joana; Encarnação, Marisa; Gaspar, Paulo; Gonçalves, Mariana; Matos, Liliana; Prata, Maria João; Luísa, Pereira de Almeida; Coutinho, Maria Francisca; Alves, SandraThe development of adequate in vitro disease models is a major issue in Biomedical Genetics. Those models allow for the initial screening of novel therapeutics and help us get an insight on the cellular mechanisms that underly pathology in each case. In fact, one of the best ways to get those insights is the analysis of patient-derived cells. Yet, not every cell holds potential to recapitulate relevant disease features. For neurodegenerative diseases in particular, it is challenging to grow neuronal cultures that accurately represent them because of the obvious inability to access live neurons. This scenario changed significantly when induced pluripotent stem cells (iPSC) were first described. From then on several differentiation protocols to generate neurons from iPSC were developed. Still, iPSC generation is a laborious/expensive protocol with significant limitations in terms of production and subsequent uses. Here we present an alternative to establish patient-derived neuronal cells in a much more expedite way. We are taking advantage of the existence of a population of multipotent stem cells (SC) in human dental pulp, the dental pulp stem cells (DPSC), to establish mixed neuronal and glial cultures for a rare neurological genetic disorder: the Sanfilippo syndrome. Sanfilippo-derived DPSC have never been used for differentiation into specific cell types even though they represent a natural source of SC that may be used to investigate human disease especially for the infantile forms. This is a total innovation in the field and we believe it holds potential to set a new trend for investigating the cellular/gene expression changes that occur in Sanfilippo and other related diseases as it relies on a non-invasive, cost-effective approach that can be set as a routine in any lab with standard cell culture conditions. Ultimately, the same method may be applied for virtually any monogenic disorder with neurological presentation.
- Doença invasiva meningocócica em Portugal - Vigilância epidemiológica integrada, 2003-2020: relatório anual da Rede de Laboratórios VigLab Doença MeningocócicaPublication . Simões, Maria João; Bettencourt, Célia; Fernandes, TeresaRelatório da Rede de Laboratórios VigLab-Doença Meningocócica, elaborado pelo seu Laboratório Nacional de Referência de Neisseria meningitidis, em colaboração com a Direção-Geral da Saúde. O presente relatório tem como objetivo divulgar os dados da Vigilância Epidemiológica Integrada da Doença Invasiva Meningocócica relativa ao período de 2003 a 2020 e da sua evolução ao longo deste período de 18 anos. Dos principais resultados e conclusões apresentados, destaca-se o seguinte: − No período de 18 anos em análise, em Portugal registaram-se 1665 casos de doença invasiva meningocócica (DIM); − Observou-se uma tendência decrescente da incidência da DIM, em linha com a tendência observada na maioria dos países europeus, que em muito se deve às políticas de vacinação implementadas; − A incidência global da DIM variou entre 1,99 casos por 100.000 habitantes, em 2003, e 0,39 casos por 100.000 habitantes em 2020. Este decréscimo foi mais acentuado nos grupos etários que registam as taxas de incidência mais elevadas – crianças menores de 12 meses de idade (redução de cerca de 60%) e dos 1-4 anos (redução de cerca de 70%), uma vez que são estas os principais alvos dos programas de vacinação; − A DIM por serogrupo B (MenB) foi sempre a mais frequente, representando cerca de 70% dos casos. As estirpes MenB apresentaram uma grande diversidade de genótipos, distribuindo-se em 17 complexos clonais (cc), dos quais os mais frequentes foram os cc hipervirulentos cc ST41/44 (26,8%) e cc ST213 (16,1%). O número de casos de DIM por serogrupo Y (MenY), o segundo mais frequente, teve um pico em 2011, tendo-se mantido estável desde então. No seu conjunto, representam cerca de 5% do total de casos. As estirpes MenY mostraram um carater clonal e hipervirulento, sendo maioritariamente cc ST23. A DIM por serogrupo C diminuiu a partir de 2004 e tornou- -se residual a partir de 2007, após a introdução da vacina no Programa Nacional de Vacinação em 2006. Mostraram um caracter clonal e hipervirulento, sendo predominante o cc ST11 (61,1%). A DIM por serogrupo W tem sido residual. A partir de 2017, foram detetadas estirpes hipervirulentas, emergentes da linhagem sul-americana, observando-se um aumento progressivo do número de casos até 2019, do cc11; − No período de 18 anos em análise, registaram-se 118 óbitos, correspondendo a uma taxa de letalidade de 7,1% (valor médio), valor próximo do reportado pela maioria dos países europeus, no período entre 2003 e 2018 (9,1%); − A vigilância da DIM constitui um enorme desafio face a uma espécie com elevada competência natural de troca de material genético que leva à emergência constante de novas variantes, algumas das quais com elevado potencial epidémico. Os dados da vigilância são uma base importante de apoio à tomada de decisão no controlo da DIM e este relatório evidencia a importância do Sistema de Vigilância Epidemiológica Integrada da Doença Invasiva Meningocócica em Portugal.
- Harmonization of Human Biomonitoring Studies in Europe: Characteristics of the HBM4EU-Aligned Studies ParticipantsPublication . Gilles, Liese; Govarts, Eva; Rodriguez Martin, Laura; Andersson, Anna-Maria; Appenzeller, Brice M.R.; Barbone, Fabio; Castano, Argelia; Coertjens, Dries; Den Hond, Elly; Dzhedzheia, Vazha; Eržen, Ivan; Esteban, Marta; Fábelová, Lucia; Fillol, Clémence; Franken, Carmen; Frederiksen, Hanne; Gabriel, Catherine; Haug, Line Småstuen; Horvat, Milena; Halldórsson, Thórhallur Ingi; Janasik, Beata; Holcer, Nataša Janev; Kakucs, Réka; Karakitsios, Spyros; Katsonouri, Andromachi; Klánová, Jana; Kold-Jensen, Tina; Kolossa-Gehring, Marike; Konstantinou, Corina; Koponen, Jani; Lignell, Sanna; Lindroos, Anna Karin; Makris, Konstantinos C.; Mazej, Darja; Morrens, Bert; Murínová, Ľubica Palkovičová; Namorado, Sónia; Pedraza-Diaz, Susana; Peisker, Jasmin; Probst-Hensch, Nicole; Rambaud, Loïc; Rosolen, Valentina; Rucic, Enrico; Rüther, Maria; Sarigiannis, Dimosthenis; Tratnik, Janja Snoj; Standaert, Arnout; Stewart, Lorraine; Szigeti, Tamás; Thomsen, Cathrine; Tolonen, Hanna; Eiríksdóttir, Ása; Van Nieuwenhuyse, An; Verheyen, Veerle J.; Vlaanderen, Jelle; Vogel, Nina; Wasowicz, Wojciech; Weber, Till; Zock, Jan-Paul; Sepai, Ovnair; Schoeters, GreetHuman biomonitoring has become a pivotal tool for supporting chemicals’ policies. It provides information on real-life human exposures and is increasingly used to prioritize chemicals of health concern and to evaluate the success of chemical policies. Europe has launched the ambitious REACH program in 2007 to improve the protection of human health and the environment. In October 2020 the EU commission published its new chemicals strategy for sustainability towards a toxic-free environment. The European Parliament called upon the commission to collect human biomonitoring data to support chemical’s risk assessment and risk management. This manuscript describes the organization of the first HBM4EU-aligned studies that obtain comparable human biomonitoring (HBM) data of European citizens to monitor their internal exposure to environmental chemicals. The HBM4EU-aligned studies build on existing HBM capacity in Europe by aligning national or regional HBM studies. The HBM4EU-aligned studies focus on three age groups: children, teenagers, and adults. The participants are recruited between 2014 and 2021 in 11 to 12 primary sampling units that are geographically distributed across Europe. Urine samples are collected in all age groups, and blood samples are collected in children and teenagers. Auxiliary information on sociodemographics, lifestyle, health status, environment, and diet is collected using questionnaires. In total, biological samples from 3137 children aged 6–12 years are collected for the analysis of biomarkers for phthalates, HEXAMOLL® DINCH, and flame retardants. Samples from 2950 teenagers aged 12–18 years are collected for the analysis of biomarkers for phthalates, Hexamoll® DINCH, and per and polyfluoroalkyl substances (PFASs), and samples from 3522 adults aged 20–39 years are collected for the analysis of cadmium, bisphenols, and metabolites of polyaromatic hydrocarbons (PAHs). The children’s group consists of 50.4% boys and 49.5% girls, of which 44.1% live in cities, 29.0% live in towns/suburbs, and 26.8% live in rural areas. The teenagers’ group includes 50.6% girls and 49.4% boys, with 37.7% of residents in cities, 31.2% in towns/suburbs, and 30.2% in rural areas. The adult group consists of 52.6% women and 47.4% men, 71.9% live in cities, 14.2% in towns/suburbs, and only 13.4% live in rural areas. The study population approaches the characteristics of the general European population based on age-matched EUROSTAT EU-28, 2017 data; however, individuals who obtained no to lower educational level (ISCED 0–2) are under represented. The data on internal human exposure to priority chemicals from this unique cohort will provide a baseline for Europe’s strategy towards a non-toxic environment and challenges and recommendations to improve the sampling frame for future EU-wide HBM surveys are discussed.
- Ongoing monkeypox virus outbreak, Portugal, 29 April to 23 May 2022Publication . Duque, M.P.; Ribeiro, S.; Martins, J.V.; Casaca, P.; Leite, P. P.; Tavares, M.; Mansinho, K.; Duque, L.M.; Fernandes, C.; Cordeiro, R.; Borrego, M.J.; Pelerito, A.; Lopes de Carvalho, I.; Núncio, S.; Manageiro, V.; Minetti, C; Machado, J.; Haussig, J.M.; Croci, R.; Spiteri, G.; Casal, A.S.; Mendes, D.; Souto, T.; Pocinho, S.; Fernandes, T.; Firme, A.; Vasconcelos, P.; Freitas, G.Up to 27 May 2022, Portugal has detected 96 confirmed cases of monkeypox. We describe 27 confirmed cases (median age: 33 years (range: 22–51); all males), with an earliest symptom onset date of 29 April. Almost all cases (n = 25) live in the Lisbon and Tagus Valley health region. Most cases were neither part of identified transmission chains, nor linked to travel or had contact with symptomatic persons or with animals, suggesting the possible previously undetected spread of monkeypox.