Browsing by Issue Date, starting with "2019-11"
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- Institutionalization of Health Impact Assessment (HIA): what's going on in Portugal?Publication . Costa, Luciana; Costa, Alexandra; Caldas de Almeida, TeresaHIA as a tool to support inter‐sector co‐operation and a “Health in All Policies” approach.
- Nanomaterials in foods and the standardized static in vitro digestion method: contributing to the study of the potential toxic effectsPublication . Martins, Carla; Assunção, Ricardo; Gramacho, A.; Alvito, Paula; Silva, Maria João; Louro, H.The use of nanoparticles (e.g. titanium dioxide) in commercial food products to modify some properties, such as brightness and whiteness, increased in the last years and is nowadays widespread. Despite the inhalation of nanoparticles is already a topic of concern, the potential adverse health effects due to ingestion still presents gaps of knowledge. In fact, gastrointestinal tract is the first interface between the body and the external environment and consequently could represent a target organ for compounds present in food that could exert toxic effects. The in vitro digestion models used to simulate the human digestion may contribute to fill these gaps. A standardized in vitro digestion model (IVD) was developed within the INFOGEST COST Action. This method considers a three-compartment model, simulating the digestion in the mouth, stomach and small intestine, applying standardized parameters such as pH, enzymatic activity and incubation periods. Within the scope of INGESTnano project (PTDC/SAU-PUB/29841/2017), and under physiological conditions, three TiO2 nanomaterials (NMs) were selected to setup a workflow to address the nanosafety regarding ingested NMs. The IVD was used to simulate the human gastrointestinal digestion of the NMs and the final product was used to test and ascertain NMs toxicity, using cell lines as intestinal models. The use of this standardized IVD model presented some challenges such as the high level of toxicity of the final digestion product for the bioassays. Several modifications to the initial protocol were investigated to overcome this issue. The results suggested that the addition of bile salts accounted for the majority of the observed toxicity. The applicability of the harmonized in vitro digestion method will be discussed in view of its potential use as a tool for addressing the toxicity of ingested NMs or other food contaminants, mimicking the physiological processes.
- Osteoporosis: gene interaction between haptoglobin and HFE polymorphismsPublication . Aguiar, Laura; Ferreira, Joana; Laires, Maria José; Mascarenhas, Mário Rui; Inácio, Ângela; Faustino, Paula; Bicho, ManuelOsteoporosis is a common metabolic bone disease characterized by reduced bone mass and increased risk of fragility fractures. The pathogenesis of this disease is complex and influenced by multiple risk factors, where genetic factors play an important role. Osteoporosis and iron metabolism have an important relationship. Iron overload suppresses osteoblast formation and also stimulate osteoclast resorption of bone, suggesting that polymorphisms in genes affecting iron homeostasis can increase the susceptibility for the development of osteoporosis. In the present study, we aimed to analyse the epistatic relationship between two iron metabolism related genes - haptoglobin (Hp) and HFE – in osteoporosis. To achieve this, 313 patients with osteoporosis and 450 controls with normal bone mineral density were enrolled. Haptoglobin phenotype was determined by polyacrylamide gel electrophoresis (PAGE) and HFE polymorphisms (H63D and C282Y) were evaluated by PCR-RFLP. All statistical tests were performed with SPSS 24.0 software. Results showed that, no significant differences were found between the two populations (patients vs controls) concerning Hp phenotypes or HFE (H63D and C282Y) genotypes. However, individuals that have co-inherited the Hp 2.2 and the HFE_H63D HH have an increased risk for developing osteoporosis [p=0.049; OR (95% CI) = 2.509 (1.003-6.279)] (adjusted for age and body mass index). In summary, a significant epistatic interaction was detected between haptoglobin and HFE and osteoporosis, where Hp 2.2 in combination with HFE_H63D HH genotype appear to increase the risk for developing osteoporosis. Since these genes are related to iron metabolism, the results of this study reinforce an important action of this metabolism in the development of osteoporosis.
- Ambient air pollution and lipid profile: Systematic review and meta-analysisPublication . Gaio, Vânia; Roquette, Rita; Dias, Carlos Matias; Nunes, BaltazarAmbient air pollution (AAP) is recognized a cardiovascular risk factor and lipid profile dysregulation seems to be one of the potential mediators involved. However, results from epidemiologic research on the association between exposure to AAP and altered lipid profile have been inconsistent. This study aims to systematically review and meta-analyse epidemiologic evidence on the association between exposure to ambient air pollutants (particulate matter, nitrogen oxides, sulphur dioxide, ozone, carbon monoxide, back carbon) and lipid profile parameters (Total cholesterol; High-Density Lipoprotein Cholesterol; Low-Density Lipoprotein Cholesterol; TG-Triglycerides) or dyslipidaemia. Systematic electronic literature search was performed in PubMed, Web of Science and Scopus databases (last search on 24th May 2019) using keywords related to the exposure (ambient air pollutants) and to the outcomes (lipid profile parameters/dyslipidaemia). Qualitative and quantitative information of the studies were extracted and fixed or random-effects models were used to obtain a pooled effect estimate per each pollutant/outcome combination. 22 studies were qualitatively analysed and, from those, 3 studies were quantitatively analysed. Particulate matters were the most studied pollutants and a considerable heterogeneity in air pollution assessment methods and outcomes definitions was detected. Age, obesity related measures, tobacco consumption, sex and socioeconomic factors were the most frequent considered variables for confounding adjustment in the models. In a long-term exposure scenario, we found a 3.14% (1.36%-4.95%) increase in TG levels per 10 μg/m3 PM10 increment and a 4.24% (1.37%-7.19%) increase in TG levels per 10 μg/m3 NO2 increment. No significant associations were detected for the remaining pollutant/outcome combinations. Despite the few studies included in the meta-analysis, our study suggests some epidemiologic evidence supporting the association between PM10 and NO2 exposures and increased TG levels. Due to the very low level of evidence, more studies are needed to clarify the role of lipid profile dysregulation as a mediator on the AAP adverse cardiovascular effects.
- The European 1+MGenomes InitiativePublication . Moura Vicente, AstridPersonalised Medicine - concept: Characterisation of individuals’ phenotypes and genotypes (e.g. molecular profiling, medical imaging, lifestyle data) for tailoring the right therapeutic strategy for the right person at the right time, and/or to determine the predisposition to disease and/or to deliver timely and targeted prevention". According to: Horizon2020 and the European Council Conclusions on personalised medicine for patients (2015/C 421/03)
- VCAM1 modulation on endothelial cells – implications for vasculopathy in sickle cell anemiaPublication . Silva, Marisa; Vargas, Sofia; Coelho, Andreia; Lavinha, João; Faustino, PaulaSickle cell anemia (SCA) is a highly heterogeneous and multifactorial-like monogenic disease that arises from homozygosity for the c.20A>T mutation in the HBB gene. Vascular disease is systemic in SCA, with profound effects in organs like the brain, where stroke is the most severe end of the cerebral vasculopathy (CVA) spectrum. Endothelial dysfunction plays a major role in vasculopathy with several adhesion molecules, such as VCAM1, being produced by the endothelium altered as a response to inflammatory cytokine (e.g., TNF-α) signalling. In previous association studies, we found positive associations between the presence of four specific VCAM1 gene promoter haplotypes and i) high blood flow velocities in the median cerebral artery, and ii) a chronic hemolysis biochemical marker. In this study, we aimed to assess the functional role of those VCAM1 promoter haplotypes in endothelial cell response following endothelial activation through TNF-α stimulation. After molecular cloning of 3 haplotype constructs, using a pGL4 promoterless vector, haplotype sequence was confirmed, by Sanger sequencing, prior to transfection. We used EAhy926, HUVEC and HBEC as different endothelial cell models, and performed transfection experiments for each construct, with and without TNF-α stimulation. Differences in promoter activity were assessed by luciferase reporter assay. All haplotypes showed differences in promoter activity, after TNF-α stimulation, in all cell models. Haplotype 1 showed decreased promoter activity, while haplotypes 7 and 8 showed increased activity after TNF-α stimulation, in all cell models. These results are consistent with lower VCAM1 expression due to haplotype 1, and therefore a protective effect. Conversely, a higher expression due to haplotypes 7 and 8, suggests an increased vasculopathy risk, in a pro-inflammatory milieu. The association between specific haplotypes and endothelial cell response further enhances the modifier effect of VCAM1 on endothelial dysfunction and its impact in SCA pathophysiology, as well as its potential role as a biomarker of SCA vasculopathy risk, severity and prognosis.
- Infeções fúngicas - Agentes etiológicos, epidemiologia e diagnósticoPublication . Sabino, RaquelAs infeções fúngicas têm vindo a aumentar e o número de agentes fúngicos possíveis agentes etiológicos de infeção são cada vez mais diversos. Nesta palestra discutem-se as principais infeções fúngicas profundas e superficiais e o diagnóstico das mesmas.
- Antagonistic effects of RAC1 and tumor-related RAC1b on NIS expression in thyroidPublication . Faria, Márcia; Félix, Daniela; Domingues, Rita; Bugalho, Maria João; Matos, Paulo; Silva, Ana LuísaThyroid cancer (TC) is the most common endocrine malignancy. The Sodium Iodide Symporter (NIS), responsible for active transport of iodide into thyroid cells, allows the use of radioactive iodine (RAI) as the systemic treatment of choice for TC metastatic disease. Still, patients with advanced forms of TC often lose the ability to respond to RAI therapy, which results in worse survival rates. We have shown that the overexpression of RAC1b, a tumor-related RAC1 splice variant, is associated with less favorable clinical outcomes in differentiated TCs derived from the follicular epithelial (DTCs). RAC1b overexpression is also significantly associated with the presence of MAPK-activating BRAFV600E mutation, which has been previously implicated in the loss of NIS expression. Here, we show that increased RAC1b levels are associated with NIS downregulation in DTCs and demonstrate that ectopic overexpression of RAC1b in non-transformed thyroid cells is sufficient to decrease TSH-induced NIS expression, antagonizing the positive effect of the canonically spliced RAC1 GTPase. Moreover, we clearly document for the first time in thyroid cells that both NIS expression and iodide uptake are hampered by RAC1 inhibition, highlighting the role of RAC1 in promoting TSH-induced NIS expression. Our findings support a role for RAC1 and RAC1b signaling in the regulation of NIS expression in thyroid cells and suggest that RAC1b in cooperation with other cancer-associated signaling cues may be implicated in the response of DTCs to RAI therapy.
- Infeção VIH e SIDA em Portugal – 2019Publication . Direção-Geral da Saúde; Instituto Nacional de Saúde Doutor Ricardo JorgeNeste relatório conjunto da DGS e do INSA, são apresentados os dados mais recentes da vigilância epidemiológica da infeção por VIH em Portugal, das estimativas relativas à epidemia nacional, da monitorização dos objetivos 90-90-90 e das iniciativas de prevenção e rastreio no país. Até 30 de junho de 2019, foram notificados em Portugal 973 novos casos de infeção por VIH com diagnóstico durante o ano 2018, o que corresponde a uma taxa de 9,5 casos por 105 habitantes, não ajustada para o atraso da notificação. Foram reportados 2,5 casos em homens por cada caso comunicado em mulheres, a mediana das idades à data do diagnóstico foi de 40,0 anos e em 28,0% dos novos casos os indivíduos tinham idades ≥50 anos. Os casos em homens que têm relações sexuais com homens (HSH) apresentaram a idade mediana mais baixa (31,0 anos) e correspondem a 63,2% dos casos diagnosticados em indivíduos de idade inferior a 30 anos. A taxa de diagnóstico mais elevada registou-se no grupo etário 25-29 anos, 23,8 casos por 105 habitantes. A residência de 47,2% dos indivíduos situava-se na Área Metropolitana de Lisboa (16,1 casos/105 habitantes) e a região do Algarve apresentou a segunda taxa mais elevada de diagnósticos (10,3 casos/105 habitantes). A maioria dos novos casos ocorreu em indivíduos naturais de Portugal (64,2%). Manteve-se o predomínio de casos de transmissão heterossexual, no entanto, os casos em HSH corresponderam 49,2% dos novos diagnósticos em homens. Embora a maioria dos novos casos se apresentasse sem sintomas na primeira avaliação clínica, em 15,9% houve um diagnóstico concomitante de SIDA e 55,8% apresentaram-se tardiamente (CD4<350 cél/mm3). Nos casos com diagnóstico de novo em 2018 a prevalência de mutações de resistência para alguma classe de fármacos foi de 14,6%, sendo mais frequente para os inibidores da transcritase reversa não nucleósidos (11,2%). Durante o ano 2018 foram também diagnosticados 227 novos casos de SIDA (2,2 casos/105 habitantes) nos quais a pneumonia por Pneumocystis jirovecii foi a doença definidora de SIDA mais frequente. Foram ainda notificados 261 óbitos ocorridos em 2018, 26,8% dos quais ocorreram nos cinco anos subsequentes ao diagnóstico da infeção. Encontram-se notificados em Portugal 59913 casos de infeção por VIH, com diagnóstico entre 1983 e 2018, dos quais 22551 atingiram estádio SIDA. A análise das tendências temporais revela que entre 2008 e 2017 observou-se uma redução de 46% no número de novos casos de infeção por VIH e de 67% em novos casos de SIDA. Não obstante esta tendência decrescente mantida, Portugal tem apresentado das mais elevadas taxas de novos casos de infeção VIH e SIDA da Europa ocidental. As estimativas realizadas para o ano 2017 revelaram que, em Portugal, viviam 39820 pessoas com infeção por VIH, 7,8% das quais não estavam diagnosticadas. A proporção de infeções não diagnosticadas era mais elevada para os casos em homens heterossexuais (13,9%) e mais baixa em UDI (1,5%). O tempo médio entre a infeção e o diagnóstico era 3,4 anos, no final de 2017. Os dados da monitorização da estratégia 90-90-90 revelaram que Portugal atingiu no final de 2017 os 3 objetivos, com 92,2% das pessoas que vivem com VIH diagnosticadas, destas 90,3% em tratamento e dessas 93,0% com virémia suprimida. Apesar desta conquista, a aposta na disponibilização de meios preventivos e de redução de riscos e minimização de danos, assim como a promoção do rastreio da infeção e da referenciação das pessoas com resultados reativos para os cuidados hospitalares mantêm-se como eixos prioritários da resposta nacional à infeção. Em 2018, foram distribuídos cerca de cinco milhões de preservativos masculinos, cento e setenta mil preservativos femininos e um milhão e trezentas mil seringas, e até ao presente iniciaram PrEP cerca de 1000 pessoas, maioritariamente cisgénero masculino. Foram realizados mais de cinquenta mil testes rápidos para VIH em diversas estruturas de Saúde e Organizações Não-Governamentais, registando-se um aumento de cerca de 28% no número de testes realizados, comparativamente ao ano de 2017. O incremento da qualidade dos dados e da informação disponível permite a tomada de decisões mais sustentada, bem como avaliar a efetividade de medidas adotadas e identificar necessidades de intervenção.
- Comparative study between a Logistic Regression Model and Simon Broome Criteria for the Diagnosis of Pediatric Patients with Familial HypercholesterolemiaPublication . Albuquerque, João; Alves, Ana Catarina; Medeiros, Ana Margarida; Bourbon, Mafalda; Antunes, MaríliaIntroduction: Familial Hypercholesterolemia (FH) is an inherited disorder of lipid metabolism, resulting in severe dyslipidemia and increased cardiovascular disease risk. Simon Broome (SB) criteria for the diagnostic of FH are among the most frequently used in clinical setting, and are based on elevated total cholesterol (TC) and low density lipoprotein cholesterol (LDLc) levels, presence of tendinous xanthomas and family history, although only genetic testing can confirm the diagnosis [1]. According to the Portuguese FH Study, only around 42% of the patients with clinical criteria reveal a positive diagnostic for FH [2], a high false positive rate that represents a heavy burden in terms of healthcare costs. The main purpose of this work was to develop an alternative classification method for FH diagnosis based on a logistic regression (LR) model, using several biochemical indicators as predictor variables. For this purpose, different operating characteristics (OC) were compared between both models, through bootstrap resampling techniques.