Browsing by Issue Date, starting with "2020-03"
Now showing 1 - 10 of 26
Results Per Page
Sort Options
- Exploring the potential relation between immune biomarkers and frailty syndrome in older adults: preliminary results from the BioFrail studyPublication . teixeira-gomes, Armanda; Costa, Solange; lage, Bruna; Fuchs, Dietmar; Valdiglesias, Vanessa; Laffon, Blanca; Teixeira, João PauloObjectives: On this basis, the main objective of the present work was to evaluate the possible association between immunological: biomarkers and the frailty status in a group of community dwellers.
- Methadone, Pierre Robin sequence and other congenital anomalies: case-control studyPublication . Cleary, Brian; Loane, Maria; Addor, Marie-Claude; Barisic, Ingeborg; de Walle, Hermien E.K.; Matias Dias, Carlos; Gatt, Miriam; Klungsoyr, Kari; McDonnell, Bob; Neville, Amanda; Pierini, Anna; Rissmann, Anke; Tucker, David F.; Zurriaga, Oscar; Dolk, HelenObjective: Methadone is a vital treatment for women with opioid use disorder in pregnancy. Previous reports suggested an association between methadone exposure and Pierre Robin sequence (PRS), a rare craniofacial anomaly. We assessed the association between gestational methadone exposure and PRS. Design/setting: This case-malformed control study used European Surveillance of Congenital Anomalies population-based registries in Ireland, the Netherlands, Italy, Switzerland, Croatia, Malta, Portugal, Germany, Wales, Norway and Spain, 1995-2011. Patients: Cases included PRS based on International Classification of Disease (ICD), Ninth Edition-British Paediatric Association (BPA) code 75 603 or ICD, Tenth Edition-BPA code Q8708. Malformed controls were all non-PRS anomalies, excluding genetic conditions, among live births, fetal deaths from 20 weeks' gestation and terminations of pregnancy for fetal anomalies. An exploratory analysis assessed the association between methadone exposure and other congenital anomalies (CAs) excluding PRS. Methadone exposure was ascertained from medical records and maternal interview. Results: Among 87 979 CA registrations, there were 127 methadone-exposed pregnancies and 336 PRS cases. There was an association between methadone exposure and PRS (OR adjusted for registry 12.3, 95% CI 5.7 to 26.8). In absolute terms, this association reflects a risk increase from approximately 1-12 cases per 10 000 births. A raised OR was found for cleft palate (adjusted OR 5.0, 95% CI 2.7 to 9.2). Conclusions: These findings suggest that gestational methadone exposure is associated with PRS. The association may be explained by unmeasured confounding factors. The small increased risk of PRS in itself does not alter the risk-benefit balance for gestational methadone use. The association with cleft palate, a more common CA, should be assessed with independent data.
- Canine lymphoma and vector‐borne diseases: Molecular and serological evaluation of a possible complicityPublication . Henriques, Joaquim; Felisberto, Ricardo; Almeida, Bruno; Ramos, Joana; Constantino‐Casas, Fernando; Dobson, Jane; Matos, Raquel; Santos, Ana; Sousa, Rita; Alves, MargaridaLymphoma is the most common haematological malignancy in dogs and its aetiology is largely unknown. The presence of canine vector-borne agents (CVBD) in lymphoma tissues has been described and its causative effects questioned. We intended to evaluate the presence and extent of Leishmania infantum, Ehrlichia canis, Anaplasma phagocytophilum and Bartonella henselae infection in dogs with lymphoma. Sixty-one dogs, living in the Lisbon metropolitan area, with a diagnosis of lymphoma were enrolled. Immunofluorescence assays were used to detect serum IgG's. The presence of DNA from CVBD agents in tumour tissue was assessed by PCR. All dogs tested negative for B. henselae, A. phagocytophilum and E. canis by both serology and PCR. Regarding L. infantum, 8.2% (n = 5) of the dogs had a positive serologic result. L. infantum DNA was detected in two samples of diffuse large B-cell lymphoma (DLBCL). These results show an increased, but not significant, seropositivity (8.2% vs 7.9%) and molecular detection (3.3% vs 1.2%) for L. infantum in dogs with lymphoma, when compared to the reported canine population in the same geographical area. We could not identify an association between lymphoma and E. canis, A. phagocytophilum, B. henselae or Leishmania infantum infection in the studied population. Nevertheless, further studies, following dogs trough their CVBD disease evolution, are worthwhile and may help clarify a possible role of CVBD agents in lymphomagenesis.
- Polimorfismos genéticos e a sua interação na suscetibilidade para a hipertensão na população portuguesaPublication . Aguiar, Laura; Semente, Ildegário; Ferreira, Joana; Matos, Andreia; Mascarenhas, Mário Rui; Menezes Falcão, Luiz; Faustino, Paula; Bicho, Manuel; Inácio, ÂngelaIntrodução: A Hipertensão Arterial (HTA) é um fator de risco cardiovascular muito prevalente em Portugal. Esta patologia é multifatorial, envolvendo fatores genéticos e ambientais. Objetivo: Este estudo teve como objetivo investigar a potencial implicação de polimorfismos genéticos nos genes eNOS e ECA e da sua interação na suscetibilidade para a HTA na população portuguesa. Métodos: Foi realizado um estudo de caso-controlo para uma amostra de 377 indivíduos portugueses, dos quais 243 hipertensos (90 hipertensos ligeiros e 153 hipertensos graves) e 134 normotensos. As análises polimórficas do VNTR no intrão 4 do gene eNOS e do polimorfismo ECA inserção/deleção (I/D) foram realizadas por reação em cadeia da polimerase (PCR). Resultados: Encontrou-se uma associação entre o alelo 4a do gene eNOS e a hipertensão (p=0,001), sendo mais forte para a hipertensão grave (p<0,001). Em relação ao gene ECA, não se encontraram diferenças estatisticamente significativas entre doentes e controlos. No entanto, ao analisar os 2 polimorfismos em epistasia, encontrou-se uma tendência para associação entre a combinação do alelo 4a do gene eNOS e do alelo D do gene ECA e a hipertensão ligeira (p=0,061). Conclusão: Os nossos resultados evidenciam o contributo do gene eNOS na HTA, assim como da interação epistática entre os genes eNOS e ECA e a suscetibilidade para a hipertensão ligeira na população portuguesa. A identificação de polimorfismos genéticos que possam influenciar o desenvolvimento e gravidade da HTA, bem como as suas interações epistáticas, pode permitir um diagnóstico mais precoce e específico para esta doença tão prevalente em Portugal.
- Aging, Living Environment, and Sustainability: What Should be Taken into Account?Publication . Grazuleviciute-Vileniske, Indre; Seduikyte, Lina; Teixeira-Gomes, Armanda; Mendes, Ana; Borodinecs, Anatolijs; Buzinskaite, Deimantehe aging population presents numerous challenges and the design and management of living environments are not an exception. This literature review and analysis brings together topics related to the living environment of the aging population and the concept of sustainability. The article presents the review of the existing design concepts that are applied to planning the environment for the elderly, including (i) design for all, (ii) universal design, and (iii) inclusive design. Furthermore, this review highlights the aspects of sustainability and the peculiarities of the aging population that should be taken into account in the design and management of their living environment. Key points related to sustainable aging are highlighted, and the possibility of complementing the existing design concepts with the concept of biophilic design is proposed in order to strengthen their social, psychological, and ecological aspects.
- Unravelling the Potential Cytotoxic Effects of Metal Oxide Nanoparticles and Metal(Loid) Mixtures on A549 Human Cell LinePublication . Rosário, Fernanda; Bessa, Maria João; Brandão, Fátima; Costa, Carla; Lopes, Cláudia B.; Estrada, Ana C.; Tavares, Daniela S.; Teixeira, João Paulo; Reis, Ana TeresaHumans are typically exposed to environmental contaminants' mixtures that result in different toxicity than exposure to the individual counterparts. Yet, the toxicology of chemical mixtures has been overlooked. This work aims at assessing and comparing viability and cell cycle of A549 cells after exposure to single and binary mixtures of: titanium dioxide nanoparticles (TiO2NP) 0.75-75 mg/L; cerium oxide nanoparticles (CeO2NP) 0.0.75-10 μg/L; arsenic (As) 0.75-2.5 mg/L; and mercury (Hg) 5-100 mg/L. Viability was assessed through water-soluble tetrazolium (WST-1) and thiazolyl blue tetrazolium bromide (MTT) (24 h exposure) and clonogenic (seven-day exposure) assays. Cell cycle alterations were explored by flow cytometry. Viability was affected in a dose- and time-dependent manner. Prolonged exposure caused inhibition of cell proliferation even at low concentrations. Cell-cycle progression was affected by TiO2NP 75 mg/L, and As 0.75 and 2.5 μg/L, increasing the cell proportion at G0/G1 phase. Combined exposure of TiO2NP or CeO2NP mitigated As adverse effects, increasing the cell surviving factor, but cell cycle alterations were still observed. Only CeO2NP co-exposure reduced Hg toxicity, translated in a decrease of cells in Sub-G1. Toxicity was diminished for both NPs co-exposure compared to its toxicity alone, but a marked toxicity for the highest concentrations was observed for longer exposures. These findings prove that joint toxicity of contaminants must not be disregarded.
- Trends in Helicobacter pylori resistance to clarithromycin: from phenotypic to genomic approachesPublication . Marques, Andreia T.; Vítor, Jorge M.B.; Santos, Andrea; Oleastro, Mónica; Vale, Filipa F.For a long time Helicobacter pylori infections have been treated using the macrolide antibiotic, clarithromycin. Clarithromycin resistance is increasing worldwide and is the most common cause of H. pylori treatment failure. Here we review the mechanisms of antibiotic resistance to clarithromycin, detailing the individual and combinations of point mutations found in the 23S rRNA gene associated with resistance. Additionally, we consider the methods used to detect clarithromycin resistance, emphasizing the use of high-throughput next-generation sequencing methods, which were applied to 17 newly sequenced pairs of H. pylori strains isolated from the antrum and corpus of a recent colonized paediatric population. This set of isolates was composed of six pairs of resistant strains whose phenotype was associated with two point mutations found in the 23S rRNA gene: A2142C and A2143G. Other point mutations were found simultaneously in the same gene, but, according to our results, it is unlikely that they contribute to resistance. Further, among susceptible isolates, genomic variations compatible with mutations previously associated with clarithromycin resistance were detected. Exposure to clarithromycin may select low-frequency variants, resulting in a progressive increase in the resistance rate due to selection pressure.
- Impact of public health initiatives on acute coronary syndrome fatality rates in PortugalPublication . Abreu, Daisy; Sousa, Paulo; Matias Dias, Carlos; Pinto, FaustoIntroduction and objective: Every year cardiovascular disease (CVD) causes 3.9 million deaths in Europe. Portugal has implemented a set of public health policies to tackle CVD mortality: a smoking ban in 2008, a salt reduction regulation in 2010 and the coronary fast-track system (FTS) for acute coronary syndrome (ACS) in 2007. Our goal in this study was to analyze the impact of these three public health policies in reducing case-fatality rates from ACS between 2000 and 2016. Methods: The impact of these policies on monthly ACS case-fatalities was assessed by creating individual models for each of the initiatives and implementing multiple linear regression analysis, using standard methods for interrupted time series. We also implemented segmented regression analysis to test which year showed a significant difference in the case-fatality slopes. Results: Separate modeling showed that the smoking ban (beta=-0.861, p=0.050) and the FTS (beta=-1.27, p=0.003) had an immediate impact after implementation, but did not have a significant impact on ACS trends. The salt reduction regulation did not have a significant impact. For the segmented model, we found significant differences between case-fatality trends before and after 2009, with rates before 2009 showing a steeper decrease. Conclusions: The smoking ban and the FTS led to an immediate decrease in case-fatality rates; however, after 2009 no major decrease in case-fatality trends was found. Coronary heart disease constitutes an immense public health problem and it remains essential for decision-makers, public health authorities and the cardiology community to keep working to reduce ACS mortality rates.
- Metabolic tumor cell adaptation: tyrosine phosphorylation modulates cell surface expression of NKCC2 and KCC3Publication . Loureiro, Cláudia; Barros, Patrícia; Matos, Paulo; Jordan, PeterIntroduction: Tumor cells require cellular chloride and potassium transport to adapt to a changing microenvironment, both for cell volume regulation and membrane potential maintenance. Cellular chloride and potassium entry or exit are mediated at the plasma membrane by cotransporter proteins of the solute carrier 12 family. For example, NKCC2 resorbs chloride with sodium and potassium ions at the apical membrane of epithelial cells in the kidney, whereas KCC3 releases chloride with potassium ions at the basolateral membrane. Their ion transport activity is regulated by protein phosphorylation in response to signaling pathways. An additional regulatory mechanism concerns the amount of cotransporter molecules inserted into the plasma membrane. Material and Methods: Cotransporter constructs were transfected into HEK293 cells and the activity of spleen tyrosine kinase (SYK) modulated by incubation with SYK inhibitors or by co-transfection with siRNAs, kinase-dead, or constitutively active SYK mutants. Cotransporter abundance in the plasma membrane was analyzed by biotinylation of cell surface proteins. Results and Discussions: Here we describe that tyrosine phosphorylation of NKCC2 and KCC3 regulates their plasma membrane expression levels. We identified that SYK phosphorylates a specific N-terminal tyrosine residue in each cotransporter. Experimental depletion of endogenous SYK or pharmacological inhibition of its kinase activity increased the abundance of NKCC2 at the plasma membrane of human embryonic kidney cells. In contrast, overexpression of a constitutively active SYK mutant decreased NKCC2 membrane abundance. Intriguingly, the same experimental approaches revealed the opposite effect on KCC3 abundance at the plasma membrane, compatible with the known antagonistic roles of NKCC and KCC cotransporters in cell volume regulation. Conclusion: We identified a novel pathway modulating the cell surface expression of NKCC2 and KCC3 and show that this same pathway has opposite functional outcomes for these two cotransporters. The findings add knowledge on how tumor cells may respond to microenvironmental changes that affect their cell volume or metabolic crosstalk.
- Microenvironment-induced changes in expression of tumor-promoting RAC1B in colorectal cellsPublication . Pereira, Joana; Gonçalves, Vânia; Matos, Paulo; Jordan, PeterIntroduction: An inflammatory microenvironment is a tumor-promoting condition that provides survival signals to which cancer cells respond with changes in their gene expression. One key gene regulatory mechanism that responds to extracellular signals is alternative splicing. For example RAC1B, a RAC1 alternative splicing variant, that we previously identified in a subset of BRAF-mutated colorectal tumors, was found increased in samples from inflammatory bowel disease patients or following experimentally-induced acute colitis in a mouse model.The main goal of this work is to determine the pro-inflammatory signals from stromal cells that lead to increased RAC1B expression in colorectal cells. Material and Methods: Caco-2 colorectal cells were either grown as polarized cell monolayer on porous filter membranes and then co-cultured with different stromal cell lines (fibroblasts, monocytes and macrophages) or grown as cysts in 3D matrices. RAC1B expression was analyzed by RT-PCR, Western blot and confocal fluorescence microscopy. Results and Discussions: Culture conditions for polarized 2D and 3D models were established as physiologically more relevant colon cell models. Co-culture experiments with polarized cells revealed that the presence of fibroblasts and/or M1 macrophages induced a transient increase in RAC1B protein levels in the colorectal cells, accompanied by a progressive loss of epithelial organization. The cytokines secreted by stromal cells are currently being identified. Conclusion: Our data indicate that extracellular signals from stromal cells can affect gene expression in colorectal cancer cells. The observed increase in alternatively spliced RAC1B will help to understand the tumor-promoting effect of inflammation and identify novel therapeutic strategies.
- «
- 1 (current)
- 2
- 3
- »