Browsing by Issue Date, starting with "2023-03"
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- Hepatitis C Virus infection, iron metabolism, liver fibrosis and response to Direct Acting Antivirals (DAAs)Publication . Ferreira, Joana; Faustino, Paula; Bicho, Manuel; Serejo, FátimaIntroduction: Chronic Hepatitis C (CHC) is characterized by hepatic and extra-hepatic manifestation. Among hepatic manifestations, liver fibrosis is probably the most significant as it can lead to cirrhosis, hepatocellular carcinoma and death. Iron overload is one of the extra-hepatic manifestations induced by Hepatitis C Virus (HCV) infection and can induce fibrosis-promoting signals in the parenchymal and non-parenchymal cells, which accelerate disease progression and exacerbate liver pathology. Aims: Evaluate the changes in iron metabolism induced by HCV elimination, the association of liver fibrosis with biochemical and genetic parameters of iron metabolism before and after DAAs treatment and baseline parameters that could predict the improvement of liver fibrosis after treatment. Materials and Methods: 329 patients with CHC (age: 49.93 [45.57-50.28] years; 124 female and 205 male). 134 treated with DAAs with sustained response (age: 53.42 [51.47-55.36]; 58 female and 56 male). Liver fibrosis stage was assessed by transient elastography using a Fibroscan and patients were divided in two groups (F1/2_mild and moderate fibrosis and F3/4_severe fibrosis and cirrhosis), biochemical parameters of iron metabolism (Total Iron_Fe, Total Iron Binding Capacity_TIBC, Transferrin Saturation_TS, Ferritin_FT, Haptoglobin_Hp) were evaluated by standard methods and genetic polymorphisms within Transferrin_TF HFE, Bone Morphogenetic Protein 2_BMP2, Hepcidin_HAMP and Ferroportin_SLC40A1 genes were analyzed by PCR, sequencing or NGS. Statistical analysis was performed using SPSS 26.0 for windows. Results: Patients showed lower values of Fe, TS and FT and higher values of Hp after treatment.
- Antisense oligonucleotide exon-skipping as a therapeutic approach for a rare diseasePublication . Gonçalves, Mariana; Matos, Liliana; Santos, Juliana I.; Coutinho, Maria Francisca; Prata, Maria João; Pires, Maria João; Oliveira, Paula; Omidi, Maryam; Pohl, Sandra; Alves, SandraMucolipidosis II (MLII) is a Lysosomal Storage Disorder caused by the deficiency of the enzyme GlcNAc-1-phosphotransferase, which is responsible for the Mannose- 6-Phosphate marker addition to lysosomal enzymes. Of all MLII mutations, the c.3503_3504delTC in GNPTAB exon 19 is the most frequent, making it a good target for a personalized therapy. Here, we explored an innovative therapeutic strategy based on the use of antisense oligonucleotides (ASOs) for MLII. Previously, on MLII patients’ fibroblasts, ASOs were used to skip exon 19 of the GNPTAB pre-mRNA, successfully resulting in the production of an in-frame mRNA[1]. Now, our aim is to analyze if these results are translated to the enzymatic and cellular phenotype level.
- Development and testing of microsatellite loci for the study of population genetics of Ixodes ricinus Linnaeus, 1758 and Ixodes inopinatus Estrada-Peña, Nava & Petney, 2014 (Acari: Ixodidae) in the western Mediterranean regionPublication . Velez, Rita; De Meeûs, Thierry; Beati, Lorenza; Younsi, Hend; Zhioua, Elyes; Antunes, Sandra; Domingos, Ana; Ataíde Sampaio, Daniel; Carpinteiro, Dina; Moerbeck, Leonardo; Estrada-Peña, Agustin; Santos-Silva, Maria Margarida; Santos, Ana SofiaIxodes ricinus is an important vector of several human and veterinary infectious agents. Its wide geographical distribution and permissive feeding behaviour have prompted earlier studies on its population genetics. Results were, nevertheless, not conclusive. Furthermore, no research has fully focused on the south-western distribution range of I. ricinus, where exchanges between European and North African populations are more likely to occur. The presence of an additional species, Ixodes inopinatus, in the area further confuses the topic, as the two species are hard to differentiate morphologically. The present work describes the testing of microsatellite markers previously described for I. ricinus using Portuguese and Tunisian tick populations of both species. In addition, new microsatellite loci were developed to complement the available marker toolbox. Loci showed different amplification successes across subpopulations, with Tunisian DNA less readily amplified. Altogether, 15 loci were considered suitable for genetic analyses of Portuguese subpopulations, 10 for Tunisian samples, and seven, common to both populations, were considered to be informative at the inter-continental level. A preliminary analysis of both datasets revealed two isolated populations, which can correspond to two different species. Furthermore, Tunisian specimens identified by sequencing of 16S rDNA as having I. ricinus or I. inopinatus sequence profiles all clustered together in one single population using the proposed microsatellites. This confirms that taxonomic decisions based only on 16S rRNA gene sequencing can be misleading. The application of the proposed set of microsatellite markers to a larger sample, representative of the south-western Ixodes’ distribution range, will be crucial to clarify the distribution of both species.
- How to dissect viral infections and their interplay with the host-proteome by immunoaffinity and mass spectrometry: A tutorialPublication . Santos, Hugo M.; Carvalho, Luís B.; Lodeiro, Carlos; Martins, Gonçalo; Gomes, Inês L.; Antunes, Wilson D.T.; Correia, Vanessa; Almeida-Santos, Maria M.; Rebelo-de-Andrade, Helena; Matos, António P.A.; Capelo, J.L.The capabilities of bioanalytical mass spectrometry to (i) detect and differentiate viruses at the peptide level whilst maintaining high sample throughput and (ii) to provide diagnosis and prognosis for infected patients are presented as a tutorial in this work to aid analytical chemists and physicians to gain insights into the possibilities offered by current high-resolution mass spectrometry technology and bioinformatics. From (i) sampling to sample treatment; (ii) Matrix-Assisted Laser Desorption Ionization- to Electrospray Ionization -based mass spectrometry; and (iii) from clustering to peptide sequencing; a detailed step-by-step guide is provided and exemplified using SARS-CoV-2 Spike Y839 variant and the variant of concern SARS-CoV-2 Alpha (B.1.1.7 lineage), Influenza B, and Influenza A subtypes AH1N1pdm09 and AH3N2.
- Uso da ferramenta Microbial Source Tracking para identificar a origem da contaminação das águas balneares, após o 1º confinamento COVID-19 em PortugalPublication . Valério, Elisabete; Brandão, João; Porteiro, Filipe M.; Cardoso, Fernando J.A.P.; Costa, Margarida M.P.Os espaços balneares referem-se a qualquer área costeira, estuarina ou de água doce, onde um número significativo de pessoas realiza atividades recreativas. Dada a sua natureza, estes constituem um habitat favorável para o abrigo, a multiplicação e a disseminação de uma variedade de microrganismos, podendo assim expor os utilizadores a diversos riscos. Em Julho de 2020, após o levantamento das restrições após o 1º confinamento em Portugal devido à pandemia de COVID-19, verificou-se que a água balnear de uma praia vulcânica amplamente usada, na ilha de São Miguel - Açores, apresentava valores elevados de bactérias indicadoras de contaminação fecal (Enterococos e Escherichia coli). Importava averiguar se as bactérias fecais detetadas tinham origem humana, pecuária ou de aves marinhas selvagens, dado que no local existe nidificação de várias espécies de aves. Optou-se por aplicar a ferramenta Microbial Source Tracking (MST) para identificar a origem da contaminação destas águas balneares, uma vez que esta permite identificar de forma inequívoca as origens da contaminação fecal, tendo por base as seguintes permissas: 1) existe uma associação entre determinados microrganismos fecais e o respetivo hospedeiro; 2) as bactérias entéricas passam para o ambiente através das fezes. A metodologia MST tem já sido aplicada, surgiu no final do século XX e têm sido amplamente desenvolvidas de modo a dar resposta à limitação indicada anteriormente: identificar de forma inequívoca as fontes e origens da poluição fecal, incluindo as fontes difusas de contaminação fecal. Recentemente foi aplicada também a areias balneares, tendo permitido identificar com sucesso as várias origens de contaminação da praia em causa. Neste trabalho serão apresentados os principais resultados obtidos e discutidas as causas deste evento de contaminação.
- Building an International One Health Strain Level Database to Characterise the Epidemiology of AMR Threats: ESBL—AmpC Producing E. coli as An Example—Challenges and PerspectivesPublication . Perestrelo, Sara; Amaro, Ana; Brouwer, Michael S.M.; Clemente, Lurdes; Ribeiro Duarte, Ana Sofia; Kaesbohrer, Annemarie; Karpíšková, Renata; Lopez-Chavarrias, Vicente; Morris, Dearbháile; Prendergast, Deirdre; Pista, Angela; Silveira, Leonor; Skarżyńska, Magdalena; Slowey, Rosemarie; Veldman, Kees T.; Zając, Magdalena; Burgess, Catherine; Alvarez, JulioAntimicrobial resistance (AMR) is one of the top public health threats nowadays. Among the most important AMR pathogens, Escherichia coli resistant to extended spectrum cephalosporins (ESC-EC) is a perfect example of the One Health problem due to its global distribution in animal, human, and environmental sources and its resistant phenotype, derived from the carriage of plasmid-borne extended-spectrum and AmpC β-lactamases, which limits the choice of effective antimicrobial therapies. The epidemiology of ESC-EC infection is complex as a result of the multiple possible sources involved in its transmission, and its study would require databases ideally comprising information from animal (livestock, companion, wildlife), human, and environmental sources. Here, we present the steps taken to assemble a database with phenotypic and genetic information on 10,763 ESC-EC isolates retrieved from multiple sources provided by 13 partners located in eight European countries, in the frame of the DiSCoVeR Joint Research project funded by the One Health European Joint Programme (OH-EJP), along with its strengths and limitations. This database represents a first step to help in the assessment of different geographical and temporal trends and transmission dynamics in animals and humans. The work performed highlights aspects that should be considered in future international efforts, such as the one presented here.
- Comparative Effectiveness of COVID-19 Vaccines in Preventing Infections and Disease Progression from SARS-CoV-2 Omicron BA.5 and BA.2, PortugalPublication . Kislaya, Irina; Casaca, Pedro; Borges, Vítor; Sousa, Carlos; Ferreira, Bibiana I.; Fonte, Ana; Fernandes, Eugénia; Dias, Carlos Matias; Duarte, Sílvia; Almeida, José Pedro; Grenho, Inês; Coelho, Luís; Ferreira, Rita; Ferreira, Patrícia Pita; Borges, Cláudia Medeiros; Isidro, Joana; Pinto, Miguel; Menezes, Luís; Sobral, Daniel; Nunes, Alexandra; Santos, Daniela; Gonçalves, António Maia; Vieira, Luís; Gomes, João Paulo; Leite, Pedro Pinto; Nunes, Baltazar; Machado, Ausenda; Peralta-Santos, AndréWe estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 and BA.2 lineages against infection and disease progression. During April-June 2022, we implemented a case-case and cohort study and classified lineages using whole-genome sequencing or spike gene target failure. For the case-case study, we estimated the adjusted odds ratios (aORs) of vaccination using a logistic regression. For the cohort study, we estimated VE against disease progression using a penalized logistic regression. We observed no reduced VE for primary (aOR 1.07 [95% CI 0.93-1.23]) or booster (aOR 0.96 [95% CI 0.84-1.09]) vaccination against BA.5 infection. Among BA.5 case-patients, booster VE against progression to hospitalization was lower than that among BA.2 case-patients (VE 77% [95% CI 49%-90%] vs. VE 93% [95% CI 86%-97%]). Although booster vaccination is less effective against BA.5 than against BA.2, it offers substantial protection against progression from BA.5 infection to severe disease.
- Effects and Mechanisms of Action of Preussin, a Marine Fungal Metabolite, against the Triple-Negative Breast Cancer Cell Line, MDA-MB-231, in 2D and 3D CulturesPublication . Seabra, Rosária; Malhão, Fernanda; Correia, Alexandra; Costa, Carla; Kijjoa, Anake; Rocha, EduardoTriple-negative breast cancer (TNBC) represents an aggressive subtype of breast cancer (BC) with a typically poorer prognosis than other subtypes of BC and limited therapeutic options. Therefore, new drugs would be particularly welcome to help treat TNBC. Preussin, isolated from the marine sponge-associated fungus, Aspergillus candidus, has shown the potential to reduce cell viability and proliferation as well as to induce cell death and cell cycle arrest in 2D cell culture models. However, studies that better mimic the tumors in vivo, such as 3D cell cultures, are needed. Here, we studied the effects of preussin in the MDA-MB-231 cell line, comparing 2D and 3D cell cultures, using ultrastructural analysis and the MTT, BrdU, annexin V-PI, comet (alkaline and FPG modified versions), and wound healing assays. Preussin was found to decrease cell viability, both in 2D and 3D cell cultures, in a dose-dependent manner, impair cell proliferation, and induce cell death, therefore excluding the hypothesis of genotoxic properties. The cellular impacts were reflected by ultrastructural alterations in both cell culture models. Preussin also significantly inhibited the migration of MDA-MB-231 cells. The new data expanded the knowledge on preussin actions while supporting other studies, highlighting its potential as a molecule or scaffold for the development of new anticancer drugs against TNBC.
- Health Intervention’s Evaluation – from concept to practicePublication . Gómez, VerónicaLecture invited by the IHMT, within the scope of the VAX-TRUST project - Workshop for evaluators in the session Health Intervention’s Evaluation – from concept to practice Background: The InfAct (Information for Action) is a Joint Action of the European Commission’s 3rd Health Programme with the main goal to build a health information system infrastructure for a stronger European Union and to strengthen its core elements. The InfAct Joint Action was developed along 36 months and structured in 10 work packages. Portugal co-led the Work Package 6 (WP6) of this project, which included the development of the proposal of a flagship capacity building programme - the European Health Information Training Programme - and its evaluation. The evaluation objectives included: to evaluate the adequacy of the training programme to the health information needs in the European Member States; to identify possible changes regarding the participants selection process, the training activities and the pedagogical project; and to contribute to the understanding of the potential of the programme to add to available offers in learning on the topics of Public Health information, on the capacity building and behavioural changes in Public Health activities which can be attributed to the course, and of the potential of the programme to contribute to the alignment of health information criteria and procedures between the European Member States. Methods: The evaluation process was developed using an observational descriptive study design using a mixed methodological approach with both document analysis and primary data collected by questionnaires and interviews analysis. Mixed quantitative and qualitative data collection methods and analysis were used. Results: The proposal of the European Health Intervention’s Training Programme seemed adequate to the formative needs and capacities in line with the work performed by the InfAct project. In what concerns about its main thematic areas, it was also aligned with the areas identified in the previous formative needs and capacities mapping. The participants selection process proposed seemed, in general, adequate. The potential of the European Health Information Training Programme proposal to learning, capacity building and behavioral changes at work attributable to the course was considered positive, as well as the potential to the alignment of health information criteria and procedures between European Union Member States. Discussion: In general, we found high consistency between the results obtained from data collected by the techniques used. However, different suggestions for improvement were outlined by the evaluation study population.
- Health risk posed by direct ingestion of yeasts from polluted river waterPublication . Steffen, Heidi Christa; Smith, Katrin; van Deventer, Corné; Weiskerger, Chelsea; Bosch, Caylin; Brandão, João; Wolfaardt, Gideon; Botha, AlfredRiver water is an essential human resource that may be contaminated with hazardous microorganisms. However, the risk of yeast infection through river water exposure is unclear because it is highly dependant on individual susceptibility and has therefore not been well-studied, to date. To evaluate this undefined risk, we analysed the fungal communities in less polluted (LP) and highly polluted (HP) river water, as determined using principal coordinate analysis of pollution indicators. We enumerated culturable yeasts using a thermally selective isolation procedure (37 °C) and thus promoted the growth of potentially opportunistic species. Yeast species identified as clinically relevant were then tested for antifungal resistance. In addition, we propose a quantitative microbial risk assessment (QMRA) framework to quantitatively assess the potential risk of yeast infection. Our results indicated that pollution levels significantly altered fungal communities (p = 0.007) and that genera representing opportunistic and pathogenic members were significantly more abundant in HP waters (p = 0.038). Additionally, the yeast species Candida glabrata and Clavispora lusitaniae positively correlated with other pollution indicators, demonstrating the species' indicator potential. Our QMRA results further indicate that higher risk of infection is associated with increased water pollution levels (considering both physicochemical and bacterial indicators). Furthermore, yeast species with higher pathogenic potential present an increased risk of infection despite lower observed concentrations in the river water. Interestingly, the bloom of Meyerozyma guilliermondii during the wet season suggests that other environmental factors, such as dissolved oxygen levels and water turbulence, might affect growth characteristics of yeasts in river water, which consequently affects the distribution of annual infection risks. The presence of antifungal resistant yeasts, observed in this study, could further contribute to variation in risk distribution. Research on the ecophysiology of yeasts in these environments is therefore necessary to ameliorate the uncertainty and sensitivity of the proposed QMRA model. In addition to the vital knowledge on opportunistic and pathogenic yeast occurrence in river water and their observed association with pollution, this study provides valuable methods and insights to initiate future QMRAs of yeast infections.
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