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- O papel da qualidade do sono na promoção da longevidadePublication . Alves, Sara; Fernandes, Hélder; Fernandes, Adília; Vaz, Josiana A.; Magalhães, Carlos Pires; Rodrigues, Carina; Monteiro, António M.O sono desempenha um papel vital tanto no bem-estar físico quanto mental, sendo indispensável para a manutenção da saúde geral. A longevidade, definida como a capacidade de viver uma vida mais longa e saudável, depende significativamente da qualidade do sono, uma vez uma vez que esta, se mantida de forma consistente e em quantidade e qualidade suficiente, parece ser uma das chaves promotoras do aumento da esperança de vida. Objetivos: A presente revisão sistemática tem por objetivo compreender a influência da qualidade de sono na manutenção do envelhecimento saudável e na promoção da longevidade. Material e métodos: Revisão sistemática seguindo a metodologia PRISMA. A pesquisa foi realizada durante o periodo de janeiro a fevereiro de 2024, através do recurso às bases de dados PubMed, Web of Science e MedLine (via Ovid), em língua inglesa, espanhola e portuguesa Os termos depesquisa foram: “healthy aging”. “longevity”, “sleep” and “determinants”. Aplicaram-se como critérios de inclusão: estudos primários produzidos nos últimos 20 anos (2004 – 2024), disponíveis em texto integral e acesso livre, resultando da pesquisa 278 artigos. Após eliminação de duplicados, 255 artigos sofreram análise do título e resumo. Concluída a aplicação dos critérios de seleção, 22 artigos foram selecionados para leitura completa, sendo que 6 atenderam aos critérios estabelecidos e foram integrados ao estudo.
- Ugt1a1 gene variants and total bilirubin levels in healthy subjects and in gilbert syndrome patientsPublication . Rodrigues, Carina; Vieira, Emília; Rosário, Santos; Carvalho, João; Santos-Silva, Alice; Costa, Elísio; Bronze-da-Rocha, ElsaGilbert syndrome (GS, OMIM 606785) is an autosomal recessive condition characterized by unconjugated hiperbilirubinemia in the absence of hemolysis or underlying liver disease due to the reduced activity of the uridine diphosphate-glucuronosyltransferase (UGT1A1). This enzyme is mainly expressed in the liver and has an important role in the glucuronidation of bilirubin, 17β-estradiol, some therapeutic drugs and mutagenic xenobiotics. Absence or severe reductions of UGT1A1 activity are associated with Crigler-Najjar syndrome type I and type II, respectively. Heterozygous carriers of Crigler-Najjar syndrome also present a high incidence of mild hyperbilirubinemia, a feature of GS. Aim: This work investigated the effect of UGT1A1 variants on total bilirubin levels in Gilbert patients (n=45) and healthy controls (n=161). Total bilirubin levels were determined using a colorimetric method. Molecular analysis of exons 1-5 and two UGT1A1 promoter regions were performed by direct sequencing and automatic analysis of fragments. Five in silico methods predicted the effect of new identified variants. A significant different allelic distribution, in Gilbert patients and in controls, was found for two promoter polymorphisms. Among patients, 82.2% were homozygous and 17.8% heterozygous for the c.-41_-40dupTA allele; in control group, 9.9% were homozygous and 43.5% heterozygous for this promoter variant, while 46.6% (n=75) presented the [A(TA)6TAA]. For the T>G transition at c.-3279 promoter region, in patients, 86.7% were homozygous and 13.3% heterozygous; in control group, 33.5% were homozygous for the wild type allele, 44.1% were heterozygous and 22.4% homozygous for the mutated allele. The two polymorphisms were in Hardy-Weinberg equilibrium in both groups. Sequencing of UGT1A1 coding region identified nine novel variants, five in patients and four in controls. In silico analysis of these amino acids replacements predicted four of them as benign and three as damaging. We demonstrated that total bilirubin levels are manly determined by the TA duplication in the TATA-box promoter and by the c.-3279T>G variant. Alterations in the UGT1A1 coding region seem to be associated with increased bilirubin levels, and therefore with Gilbert Syndrome.
- Prediction of deleterious nsSNPs in human UGT1A1 gene by web available algorithm toolsPublication . Rodrigues, Carina; Costa, Elísio; Vieira, Emília; Santos, Rosário; Santos-Silva, Alice; Bronze-da-Rocha, ElsaThe uridine diphosphate glucuronosyltransferase (UGT1A1) belongs to the class of phase II enzymes involved in the metabolism and detoxification of numerous xenobiotic and endogenous compounds (e.g. bilirubin). Genotyping data lead to the discovery of over 100 single nucleotide polymorphisms (SNPs) within the UGT1A1 gene. Some of the non-synonymous (ns) SNPs (nsSNPs) of the human UGT1A1 gene variants have been associated to hyperbilirubinemia in Gilbert’s and Crigler-Najjar syndromes, as well as altered drug clearance and/or drug response. In UGT1A1, and other genes, there are many nsSNPs which genotype-phenotype correlations were not established, since the study of the functional impact of all SNPs is time consuming and expensive. Alternatively, bioinformatics tools have gained an increased importance with the prospect of reducing the totality of detailed studies at protein level. The aim of this study was to investigate the potential of bioinformatics approaches, using five web available algorithms [Sorting Intolerant from Tolerant (SIFT); polymorphism phenotyping-2 (PolyPhen-2); Align Grantham Variance/Grantham Difference (Align-GVGD); Multivariate Analysis of Protein Polymorphism (MAPP); Block Substitution Matrix score 62 (BLOSUM62)], to predict the phenotype of 28 human UGT1A1 nsSNPs, previously characterized at protein level by in vivo and in vitro studies. From those, 24 SNPs were confirmed as responsible for changes in protein function and in 4 there were no detected impact. Information describing the UGT1A1 variants was obtained from mutation database websites: http://www.polydoms.cchmc.org/polydoms, http://www.mutdb.org, and http://www.ncbi.nlm.nih.gov/sites/entrez. Results from in silico analysis showed a correct prediction rate of 85.7% for Polyphen-2, 82.0% for both BLOSUM62 and SIFT, 60.7% for MAPP and 32.1% for Align-GVGD. In the total of 28 studied variants, 78.6% (n=22) had concordant results using Polyphen-2 and SIFT algorithms and 57.1% (n=16) using Polyphen-2, SIFT and BLOSUM62. Concordance in variants prediction, between the five used methods and with results obtained at protein levels, was observed in 14.3% (n=4) nsSNPs. In conclusion, our results showed that SIFT and Polyphen together, were the best predictor methods of nsSNPs phenotype in human UGT1A1 gene. These tools have the advantage of directing and complement functional assays. However, the observed discrepancy in variants prediction phenotype may be improved with a method combining all currently available criterions.
- Burnout nos estudantes do ensino superiorPublication . Galvão, Ana Maria; Rodrigues, Carina; Teixeira, CristinaOs estudantes fazem parte de uma organização de educação onde desempenham um determinado papel, realizam tarefas que exigem esforço, possuem metas a cumprir e seu desempenho é constantemente avaliado pelos seus professores, os quais exercem uma função muito semelhante à de uma chefia num contexto de trabalho. O burnout académico é definido como exaustão cognitiva e emocional devido às exigências académicas, a sentimentos de incapacidade e ineficácia e uma atitude cínica em relação aos estudos, aos professores e colegas.
- Observação e intervenção na dor no doente com atroplastia total do joelho e da ancaPublication . Quina, Ema; Rodrigues, Kátia; Rodrigues, Carina; Sousa, FilomenaA dor é um sintoma com grande prevalência no internamento hospitalar, sendo responsável pelo sofrimento e incapacidade dos doentes. Lidar com as vivências de dor de um doente é uma das particularidades do trabalho diário dos enfermeiros. É portanto a estes que cabe uma observação contínua dos doentes, adoção de medidas para alívio da dor, assim como deteção e despiste de efeitos secundários que possam aparecer. Objetivos: Identificar quais as dificuldades dos enfermeiros na observação/avaliação da dor e conhecer as atitudes tomadas pelos mesmos para o alívio da dor no pós-operatório em doentes submetidos a atroplastia total do joelho e da anca. Metodologia: Através de um estudo quantitativo observacional descritivo transversal tendo sido aplicado um questionário a 18 enfermeiros que exercem a sua atividade no serviço de ortopedia no Hospital de São Pedro de Vila Real. Resultados: Constatou-se que quanto à adoção de medidas para o alívio da dor a totalidade dos enfermeiros não sente dificuldade. Dos inquiridos, 50% usa frequentemente medidas farmacológicas, 44% usa medidas não farmacológicas frequentemente. Apenas 11% dos inquiridos respondeu que usava sempre medidas não farmacológicas, tais como massagem, exercícios, relaxamento, distração, posicionamento e termoterapia. Conclusão: A adoção das medidas não farmacológicas no controlo da dor apresentam bastante eficácia, principalmente como adjuvantes a medidas farmacológicas. A aplicação destas medidas trás resultados positivos e têm como principal vantagem serem pouco dispendiosas.
- Contribution of red cell mass and UGT1A1 alleles in serum bilirubin levels of the portuguese populationPublication . Rodrigues, Carina; Costa, Elísio; Santos-Silva, Alice; Santos, Rosário; Bronze-da-Rocha, ElsaHepatic glucuronization of insoluble bilirubin is catalyzed by isoenzyme 1A1 of UDP-glucuronosyltransferase (UGT1A1), which is essential for efficient biliary excretion of bilirubin. The main cause of Gilbert syndrome (GS) in all populations studied to date is a TA duplication [(TA)7 allele] in the repetitive TATA-box sequence of the gene promoter, which normally consists of six TA repeats. However, this genetic polymorphism is not sufficient for the clinical phenotype of GS. By this reason, some studies have been performed to provide information about additional factors that could contribute to the pathogenesis of this disease. Recently, it was described that increased red cell mass probably plays a role in the pathogenesis of GS (Buyukasik et al. 2008 Am J Med Sci. 335,115-119). The aim of this work is to investigate the putative role of increased red cell mass and the (TA)7 allele in bilirubin serum levels, in the Portuguese population. This study was performed in 109 volunteer healthy young adults (20.3±1.9 years) without liver and/or hematological disorders, chronic infection, recent inflammation, malignancy, hemorrhage and medication. Blood samples were collected and processed in order to determine bilirubin serum levels, complete blood cells count, and DNA extraction. The TATA-box region was analyzed by PCR amplification followed by subsequent analysis by automated capillary electrophoresis. Among our population, 6 were homozygous for the (TA)7 allele, 55 were heterozygous and 48 were homozygous for the normal allele. One of the subjects was a compound heterozygous for the (TA)5 and (TA)7 alleles. Comparing the blood cells counts and the bilirubin serum levels according to the UGT1A1 genotype, we found statistically differences only in bilirubin levels [(TA)6/(TA)6: 0.49±0.20 mg/dL; (TA)6/(TA)7: 0.70±0.32 mg/dL; (TA)7/(TA)7: 1.10±0.74 mg/dL, p<0.05]. A positive statistically significant correlation (p<0.05) were found between bilirubin serum levels and haematocrit and mean cell volume. Our work showed that higher bilirubin serum levels are correlated with an increase red blood mass. However, no association was found between higher red blood mass and abnormal number of TA repeats in the promoter of UGT1A1 gene. This data suggests that in our population the presence of abnormal number of TA repeats in the UGT1A1 gene is associated with increased bilirubin levels but not with higher red blood mass, as previously described for GS patients.
- UGT1A1 gene variations in individuals with and without clinical diagnosis of Gilbert SyndromePublication . Rodrigues, Carina; Vieira, Emília; Carvalho, João; Costa, Elísio; Santos, Rosário; Santos-Silva, Alice; Bronze-da-Rocha, ElsaUGT1A1 gene variations in individuals with and without clinical diagnosis of Gilbert Syndrome Bilirubin is a non-polar metabolite, results from catabolism of haemoglobin and is bound to glucuronic acid in the liver by the uridine diphosphate glucuronosyltransferase (UGT1A1) activity. Molecular studies showed that the presence of two extra bases (TA duplication) in the promoter region of the UGT1A1 gene is responsible for the reduced UGT1A1 glucuronization activity and is the main cause of unconjugated hyperbilirubinemia observed in patients with Gilbert Syndrome (GS). However, individuals with normal bilirubin levels and no clinical symptoms of SG may also present this polymorphism in homozygosity 1,2,3. Consequently, the aim of this work is to determine the presence of other mutations in the UGT1A1gene, downstream of the TA duplication, and how they may contribute towards the inter-individual variation of serum bilirubin levels. This study was carried out in two groups: one comprising 36 individuals without clinical diagnosis of GS (14 with 6/6TA, 11 with 6/7TA, and 11 with 7/7TA repeats); the other group consisting of 36 patients clinically diagnosed with GS. In both, bilirubin levels were determined and direct sequencing of the UGT1A1 was performed. Among the individuals without clinical diagnosis of GS, two new sequence variants were found in heterozygosity (c.643A>G, and c.1156G>A), in the 6/6TA group. No additional mutations were detected in the 6/7 and 7/7 TA groups. In patients clinically diagnosed with GS, 28 were homozygous and 7 heterozygous for the TA duplication, and one with a normal number of repeats. Molecular analysis showed that one (3,6%) of the 7/7TA patients had another mutation in the UGT1A1 gene (c.674T>G). In the 6/7TA group, one additional mutation was also found in three patients (43%), two of which had been previously described (c.674T>G and c.923G>A) and a new one (c.1423C>T). No further mutations were detected in the 6/6TA group. Additionally, 4 polymorphisms were found (c.864+89C>T; c.997-37T>C; c.997-82A>C; c.997-87A>C). In conclusion, we can infer that homozygosity for the TA duplication is associated with GS. In the group without GS, no further mutations were detected in the 6/7 and 7/7 clusters, but in the 6/6 group, two new mutations were found in heterozygosity. These mutations are not associated with increased bilirubin levels. However, they could be associated with GS in the presence of other UGT1A1 mutations. Furthermore, in the GS group with heterozygosity for the TA duplication, we found mutations in 43% of the patients, emphasizing the importance of complete UGT1A1 analysis.
- Influence of genetic and aquired factors that modify serum bilirubin levels in the portuguese populationPublication . Rodrigues, Carina; Costa, Elísio; Santos, Rosário; Santos-Silva, Alice; Bronze-da-Rocha, ElsaThe isoenzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) catalyzes bilirubin glucuronidation by converting bilirubin in water-soluble glucuronides that then undergo biliary or renal elimination. During the last years, molecular studies have suggested that the presence of two extra bases in the repetitive promoter TATA box region of the UGT1A1 gene, described as (TA)7 allele, is responsible for the reduced UGT1A1 activity leading to hyperbilirubinemia. Gilbert’s syndrome (GS) is a genetic recessive disorder characterized by a mild unconjugated hyperbilirubinemia occurring in the absence of haemolysis or other evidence of liver disease. Patients with GS are often homozygous for the TA duplication. Several studies establish that unconjugated hyperbilirubinemia exhibits a mode of inheritance where a “major” recessive gene (UGT1A1) accounts for only a part of the serum bilirubin concentration. Recently, it was described that increased red cell mass probably plays a role in the pathogenesis of GS. Objective: Our study aims to determine the influence of the TA polymorphism, the presence of some environmental factors and increased red cell mass in serum bilirubin levels variation in Portuguese population. Material and Methods: We include in this study we recruit 165 young adults with average age (19.5 ± 2.1 years). All volunteers give their written informed consent and standardized interviewer-administered questionnaire was performed that included questions about smoking habits, oral contraceptive therapy, caloric intake, fasting time and physical activity. Exclusion criteria included the presence of liver and/or hematological disorders. After an overnight fasting, venous blood samples were collected in order to determine total and direct-reacting bilirubin, blood cell count and surrogate markers and isolate genomic DNA to perform the molecular study of UGT1A1 promoter region. Results: For the UGT1A1 genotyping we identified 15 homozygous individuals for (TA7/TA7), 79 heterozygous (TA6/TA7) and 71 were homozygous for the normal allele (TA6/TA6). Estimated frequency of (TA) was 33%, close to the 38,7% described for caucasians. A trend to higher bilirubin levels, without statistical significance, was found in males than in females, in non-smoking subjects and in female subjects that were under oral contraceptive therapy. Statistically significant correlations were found between bilirubin serum levels and fasting time (p=0.001) and caloric intake (p=0.03). No significant association was found between serum bilirrubin levels and physical activity. Our results strongly suggest that genetic background plays a major role in serum bilirubin levels variation but caloric intake, fasting time and red blood cell mass also contribute to this inter-individual variation. Conclusions: Our results strongly suggest that genetic background plays a major role in serum bilirubin levels variation but red blood mass and fasting time contribute to this inter-individual variation.
- Genetic identification and technological potential of indigenous lactic acid bacteria isolated from Alheira, a traditional portuguese sausagePublication . Fernandes, Nathália; Faria, Ana Sofia; Carvalho, Laís; Choupina, Altino; Rodrigues, Carina; Gonzales-Barron, Ursula; Cadavez, VascoAlheira is a naturally fermented meat sausage traditionally made in the Portuguese region of Trás-os-Montes. Lactic acid bacteria (LAB) are the dominant microorganisms in alheira and can endow it with various technological properties. This study aimed (1) to characterize technological features and in vitro antimicrobial activity of LAB isolated from alheira, and (2) to reveal associations between such phenotypic characteristics and the isolates species identified through amplification and sequencing of the 16S ribosomal gene. Sixty-two LAB isolates were identified and Enterococcus (E.) faecium corresponded to 32.3% of isolates, followed by Leuconostoc (L.) mesenteroides (19.4%) and Latilactobacillus (Lb.) sakei (17.7%), aligning with previous research on traditional Portuguese fermented meat sausages. The phenotypic analysis of LAB isolates indicated diverse acidification capacities, proteolytic activities, and inhibitory effects against foodborne pathogens Listeria (L.) monocytogenes, Salmonella (S.) Typhimurium and Staphylococcus (S.) aureus. Overall, lactobacilli displayed high inhibition activity against the pathogens S. aureus, L. monocytogenes, and S. Typhimurium. Although the mechanisms for the inhibition of pathogen growth need to be further elucidated, these findings enhance our understanding of LAB diversity and functionality in alheira sausages, contributing to product safety and quality.
- Time-trends in cervical cancer mortality in PortugalPublication . Teixeira, Cristina; Pereira, Ana Maria Geraldes Rodrigues; Anes, Eugénia; Rodrigues, Carina; Castanheira, Maria JoséA mortalidade por cancro do colo do útero em Portugal apresenta valores mais elevados em relação a outros países europeus. O objetivo deste estudo é avaliar a variação da mortalidade por cancro do colo do útero, observada em Portugal nas últimas seis décadas. Material e Métodos: Obtivemos taxas de mortalidade por cancro do colo do útero (padronizadas para a idade) reportadas em Portugal (1955–2014), através da International Agency for Research on Cancer. Utilizando análise de regressão linear joinpoint, obtivemos a percentagem de variação anual da taxa (%VA) e respetivo intervalo de confiança a 95% (IC 95%) de acordo com a idade (30–39; 40–49, 50–64; 65–74 e ≥ 75 anos) Resultados: No grupo com 30–39 anos, a mortalidade por CCU diminuiu 1,9% ao ano, durante todo o período (IC 95%: –2,3; –1,4), atingindo 0,5/100 000 em 2014. Nas mulheres com 40–49 anos houve decréscimo acentuado entre 1971 e 1981 (%VA = –11,6; IC 95%: –14,6; –8,6), com subsequente aumento de 2,4% ao ano (IC 95%: 1,0; 3,8) até 2001, mas que reverteu a partir desse ano (%VA = –5,2; IC 95%: –7,7; –2,6), atingindo 3,0/100 000 em 2014. A mortalidade por cancro do colo do útero diminuiu de 29,2 para 6,7/100 000, de 34,3 para 7,7/100 000, e de 24,7 a 9,2/100 000, respetivamente, nas mulheres com 50–64, 65–74 e com 75 ou mais anos. Nestes três grupos o decréscimo ocorreu principalmente nas décadas de 70 e 80, não havendo variação significativa da taxa nas últimas três décadas. Discussão: O maior decréscimo da mortalidade por cancro do colo do útero observada em Portugal ocorreu na década de 70 em paralelo com profundas alterações no Sistema Nacional de Saúde caracterizadas pelo aumento do acesso ao diagnóstico precoce e da qualidade do tratamento. Nas últimas três décadas, a mortalidade por cancro do colo do útero estabilizou em idades mais avançadas, o que pode ser explicado parcialmente por fatores com impacto na adesão aos programas de rastreio. Conclusão: Houve marcado declínio da mortalidade por cancro do colo do útero em todos os grupos etários, embora com estagnação deste indicador desde meados da década de 80 para grupos etários mais avançados. Os resultados sugerem a necessidade de incrementar a adesão a programas de rastreio em Portugal.