Bipolar disorder associated miR-499-5p controls dendritic development and Cav1.2 calcium channel activity

Affective disorders, such as Major depressive disorder (MDD) and Bipolar disorder (BD), are a group of neuropsychiatric disorders characterized by rofound mood dysregulations. They constitute leading causes of disability and mortality, with especially high rates of suicide. However, the lack of understanding of the molecular mechanisms that trigger the development of affective disorders imposes a challenge to the discovery of novel and effective pharmacotherapies. It is currently accepted that a complex interaction between genetic predisposition and exposure to environmental stressors, such as childhood maltreatment, is required for the development of these disorders. The underlying causes, however, are only poorly understood. One of the main research areas focuses on the dysregulation of synaptic and neural plasticity, based on reports of altered structural and functional brain connectivity in the prefrontal cortex (PFC) and hippocampus of patients. Genes that are involved in neuronal development and plasticity are regulated by microRNAs (miRNAs or miRs), a class of small non-coding RNAs. Importantly, dysregulated miRNA expression is frequently observed in the brain and blood of MDD and BD patients, providing a rationale to consider miRNAs as therapeutic tools and disease biomarkers. This study aimed to investigate how changes in gene expression mediated by miRNAs interact with negative life events, especially during early life, and result in aberrant neuroplastic alterations that increase the susceptibility to affective disorders. For this purpose, I characterized the change in miR-499-5p expression in the blood of affective disorder patients and healthy individuals at higher risk of developing an affective disorder due to a history of childhood maltreatment. I found a significant up-regulation in circulating miR-499-5p in patients and maltreated subjects. Consistently, I observed higher levels of miR-499-5p in the hippocampus of a rat model of early life adversity. To understand how the dysregulation of miR499-5p causes neuronal abnormalities, I used primary cultures from the rat hippocampus to overexpress miR-499-5p and evaluate changes in neuronal morphology and function. In rat hippocampal neurons, miR-499-5p targets the Cacnb2 gene, the auxiliary β-subunit of the L-type Cav1.2 calcium channels, and a risk gene for psychiatric disorders. Elevated miR-499-5p expression inhibited Cacnb2 mRNA translation, impaired dendritic development, and reduced Cav1.2 surface expression and activity. Importantly, overexpression of miR-499-5p in the hippocampus induced short-term memory impairments in the Cacna1c+/- rat model. Based on these results, I propose a mechanism of miRNA-mediated calcium dysfunction in BD susceptibility whereby early life stress induces the expression of miR-499-5p, which in turn impairs dendritic development by inhibiting the expression of an auxiliary subunit of Cav1.2 calcium channels. My work further suggests that the increased blood expression of miR-499-5p could potentially be used as a biomarker of BD development and disease progression

Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene: Influence of modifiers on 35delG/35delG phenotype

Hereditary hearing loss (HL) is a very heterogeneous trait, with 46 gene identifications for non-syndromic HL. Mutations in GJB2 cause up to half of all cases of severe-to-profound congenital autosomal recessive non-syndromic HL, with 35delG being the most frequent mutation in Caucasians. Although a genotype-phenotype correlation has been established for most GJB2 genotypes, the HL of 35delG homozygous patients is mild to profound. We hypothesise that this phenotypic variability is at least partly caused by the influence of modifier genes. By performing a whole-genome association (WGA) study on 35delG homozygotes, we sought to identify modifier genes. The association study was performed by comparing the genotypes of mild/moderate cases and profound cases. The first analysis included a pooling-based WGA study of a first set of 255 samples by using both the Illumina 550K and Affymetrix 500K chips. This analysis resulted in a ranking of all analysed single-nucleotide polymorphisms (SNPs) according to their P-values. The top 250 most significantly associated SNPs were genotyped individually in the same sample set. All 192 SNPs that still had significant P-values were genotyped in a second independent set of 297 samples for replication. The significant P-values were replicated in nine SNPs, with combined P-values between 3 x 10(-3) and 1 x 10(-4). This study suggests that the phenotypic variability in 35delG homozygous patients cannot be explained by the effect of one major modifier gene. Significantly associated SNPs may reflect a small modifying effect on the phenotype. Increasing the power of the study will be of greatest importance to confirm these results.info:eu-repo/semantics/publishedVersio

Caracterização da zona entre-marés da Reserva Mundial de Surf da Ericeira: padrões gerais e pressões humanas

Tese de mestrado em Ecologia e Gestão Ambiental, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2017Localizada no litoral de Mafra, a Reserva Mundial de Surf da Ericeira (RMSE) estende-se sobre 4 Km que incluem 7 ondas de diferentes níveis, num litoral composto por várias praias arenosas e rochosas e elevada biodiversidade. As zonas de entre-marés rochosas permitem a colonização de uma variada fauna e flora, desde algas a invertebrados e peixes, ao invés do substrato arenoso. No sentido de contribuir para uma gestão sustentável da RMSE, este estudo descritivo teve o objectivo de contribuir para o conhecimento nos temas 1) biodiversidade e respectiva zonação; 2) caracterização das actividades costeiras praticadas, 3) impacte das actividades da sexta-feira santa sobre o mexilhão, 4) qualidade da água, e 5) possíveis medidas de gestão. A metodologia desenvolvida partiu da selecção de 4 praias distintas em termos de declive (Empa), extensão (Ribeira de Ilhas), isolamento (Cavalinho) e disposição em baía (Coxos). Em cada praia realizaram-se amostragens ao longo de 3 transectos no auge sazonal da diversidade (verão), por meio de métodos não destrutivos (registo fotográfico a quadrados de 20 cm de lado e identificação in loco) e destrutivos (raspagens aos quadrados nos casos de não ter sido possível identificar ou na presença de “turfa”). Foram ainda calculados índices de biodiversidade no sentido de avaliar a comunidade biológica estudada. Foram realizados inquéritos presenciais a 4 tipos de utentes, Pescadores lúdicos, Desportistas, Banhistas e Passeantes/Observadores, com o objectivo de caracterização genérica dos diferentes utentes. Selecionou-se uma praia de fácil acesso e de laje direita, Ribeira de Ilhas, para avaliar o impacte da festividade da sexta-feira santa sobre os bancos de mexilhão, através de 3 transectos, antes e depois da mesma. Foram facultados pela Entidade gestora valores de parâmetros físico-químicos e comparados com os Valores limite de emissão em legislação. Por fim, foi feita uma análise FOFA para aferir lacunas e pesquisa de medidas de gestão, com base também nas conclusões dos capítulos anteriores, formando um painel de várias possíveis recomendações de escolha a implementar de futuro. Os resultados concluem que 1) a praia do Cavalinho possuiu maior biodiversidade com 207 taxa, possivelmente por beneficiar de protecções laterais, apresentando por esse motivo uma zonação atípica, com a subida do horizonte infralitoral. É seguida pela Ribeira de Ilhas com 119 taxa, Empa com 94 taxa e Coxos com 22 taxa. As praias dos Coxos e Ribeira de ilhas apresentam uma zonação típica de costas expostas, apesar de a segunda possuir um tapete de Ulva spp. no supralitoral, possivelmente provocado pela interferência de água doce presente. A praia da Empa apresenta dominância pela macroalga Fucus spiralis no seu mesolitoral. Os índices a nível dos zoobentos revelaram elevada diversidade nas praias Empa, Cavalinho e Ribeira de Ilhas, dominância e igual abundância de espécies em todas as quatro praias. Quanto ao grupo dos fitobentos, Empa e Coxos revelaram diversidade e dominância medianas e igualdade de espécies. Ribeira de Ilhas e Cavalinho apresentaram resultados semelhantes, diversidade e homogeneidade e igualdade de espécies. Constatou-se a não existência de sazonalidade na prática das actividades, com a excepção dos utentes banhistas. A prática da actividade de pesca lúdica tem como principal captura o marisco para alimentação própria. O mexilhão e o polvo são os organismos mais capturados e em quantidades em inconformidade com a legislação. A maioria dos inquiridos opinou que os organismos capturados diminuíram muito em relação ao tamanho e à quantidade, tendo referido que o número de pessoas a capturar aumentou. A prática desportiva principal é o surf, seguida do bodyboard. A Ribeira de Ilhas é a praia com maior intensidade de praticantes, contabilizando mais de 20 praticantes por momento da prática da actividade, com a presença de 1 a 10 escolas de surf, cada com 6 a 10 alunos por turma. A maioria demonstrou apoio na iniciativa da criação de Área Protegida como forma de impor respeito ambiental e condicionar o exercício de escolas de surf não licenciadas na Ribeira de Ilhas. A captura ocasional de organismos é realizada essencialmente por Banhistas e Passeantes. À excepção da maioria dos Banhistas, os restantes utentes consideram que as suas actividades não são prejudiciais para o ecossistema rochoso. A maioria de todos os tipos de utentes revelou também elevado desconhecimento sobre a área classificada em termos de conservação da natureza. O impacte da sexta-feira santa revelou-se não expressivo. A qualidade da água não revelou preocupações sobre as comunidades naturais, apesar das análises recolhidas serem limitadas. Contudo, análises sobre poluentes revelaram contaminação de metais pesados (Pb, Cd e Hg) em lapas na praia dos Coxos. Por último as recomendações incluíram várias metodologias de monitorização para averiguação do estado ecológico do ecossistema marinho, estudos complementares para colmatar falhas de conhecimentos, apelando a uma cogestão do território, entre os gestores oficiais e a população.Located on the coastline of Mafra, the Ericeira World Surf Reserve (EWSR), stretches over 4 km including 7 waves of different levels, on a coastline composed of several sandy and rocky beaches and high biodiversity. The rocky intertidal zones allow the colonization of a varied fauna and flora, from algae to invertebrates and fish, instead of the sandy substrate. In order to contribute for the sustainable management of EWSR, this descriptive study had the objective to contribute to the knowledge on the themes 1) biodiversity and patterns of distribution; 2) characterization of the coastal activities practiced, 3) impact of the activities of Good Friday on the mussel population, 4) water quality, and 5) possible management measures. Four distinct beaches were selected in terms of slope (Empa), extension (Ribeira de Ilhas), isolation (Cavalinho) and bay layout (Coxos). In each beach, samples were taken along 3 transects at the seasonal sum of the diversity (summer), by means of non-destructive methods (photographic records to squares of 20 cm of side and identification in place) and destructive (scraping to the squares in the cases where it is not possible to identify or in the presence of "peat"). Biodiversity indexes α were also calculated in order to evaluate the biological community studied. Face-to-face surveys were carried out on 4 types of users, Recreational Fishermen, Sportsmen, Bathers and Walkers/Observers, in order to characterize the different users. A beach of easy access and right slab, Ribeira de Ilhas, was selected to evaluate the impact of the feast of Good Friday on the banks of mussels. Three transects were observed, before and after the festivities. For the assessment of water quality the Management Entity provided physical-chemical parameters that were compared to the emission limit values in legislation. Finally, a SWOT analysis was carried out to gauge gaps and research of management measures, based also on the conclusions of the previous chapters, forming a panel of several possible recommendations of choice to be implemented in the future. The results conclude that Cavalinho beach had a higher biodiversity with 207 taxa, possibility due to the lateral protections, thus presenting an atypical pattern of distribution, with the ascent of the lower (sub-littoral fringe) horizon. It was followed by Ribeira de Ilhas with 119 taxa, Empa with 94 taxa and 22 taxa for Coxos. The beaches of the Coxos and Ribeira de Ilhas have a typical pattern of distribution of exposed coasts, although the second has a rug of Ulva spp. in the upper zone (littoral fringe), possibly caused by the interference of fresh water present. Empa beach is dominated by the macroalgae Fucus spiralis in its mesotidal. In all the beaches it was verified the absence of the gastropod Nucella lapilis on the upper zone floor. The indexes at the level of the zoobentos revealed high diversity in the beaches Empa, Cavalinho and Ribeira de Ilhas, dominance and equal abundance of species in all four beaches. As for the phytobent group, Empa and Coxos revealed medium diversity and dominance and species equality. Ribeira de Ilhas and Cavalinho presented similar results, diversity and homogeneity and species equality. It was verified the non-existence of seasonality in the practice of activities, with the exception of bathers users. The practice of the activity of recreational fishing has as main capture the seafood for its own meal. Mussels and octopus are the most capture organisms and in amounts not in compliance with the legislation. Most felt that the captured organisms have greatly decreased in size, quantity and increased the number of people to capture. The main sport is surfing, followed by bodyboarding. The Ribeira de Ilhas is the beach with the highest intensity of practitioners, counting more than 20 practitioners per moment of practice of the activity, with the presence of 1 to 10 surf schools, each with 6 to 10 students per class. Most of them demonstrated their support in the initiative to create a Protected Area as a way to impose environmental respect and condition the practice of unlicensed surf schools in Ribeira de Ilhas. The occasional capture of organisms is carried out essentially by Bathers and Walkers. Except for most bathers, the remaining users consider that their activities are not harmful to the rocky ecosystem, revealing that most of all types of users have no knowledge about the classified area in terms of nature conservation. The impact of the Good Friday festivities proved not expressive. Water quality did not reveal concerns, even though the data available was limited. However, previous studies revealed contamination of heavy metals (Pb, Cd and Hg), in limpets in Coxos beach. Lastly, the recommendations present several monitoring methodologies for ascertaining the ecological status of the marine ecosystem, complementary studies to fill knowledge gaps, and a call for the co-management of the territory, between official managers and the population

Microbiologia na formação em Enfermagem

Poster apresentado no 2º Congresso Politécnico de Setúbal: 40 anos a construir o futuro, outubro 2019, Setúbal, PortugalN/

Biofísica na Licenciatura em Acupuntura

Poster apresentado no 2º Congresso Politécnico de Setúbal: 40 anos a construir o futuro, outubro 2019, Setúbal, PortugalN/

Biologia marinha: manual de práticas de laboratório

info:eu-repo/semantics/publishedVersio

G6PD variants, malaria and sensorineural hearing loss in São Tomé and Príncipe: a case-control study

Background: São Tomé and Príncipe (STP) is a least developed country (LDC) on Sub-Saharan Africa, in which was detected a high prevalence of sensorineural Hearing Loss (SNHL). HL is a common condition with both genetic and environmental causes, and it greatly impacts on global health. STP population has leading with additional health problems over the years, such as anaemia and malaria infection. The present study aims to identify the correlation between the most prevalent G6PD variants and the high prevalence of HL in STP population. Methods: A sample of 316 individuals collected during Humanitarian Missions in STP, was retrospectively studied in a case-control approach to evaluate the role of G6PD gene variants in individual susceptibility to HL and it correlation with other potential risk factors. Results: The results obtained showed an increased risk for those cases that have reported malaria infection (OR 1.867, CI 95% [1.107-3.48]) in global population. The same effect of increased risk was found after stratification for male gender (OR 3.721 CI 95% [1.631-8.489]). Conclusions: Our results did not allow us to correlate any specific variant of G6PD gene with HL. However, emphasize the hypothetical correlation between malaria infection and the increased risk for HL.info:eu-repo/semantics/publishedVersio

Prevalência da algaliação sem indicação: um factor de risco evitável

A Infecção Associada aos Cuidados de Saúde constitui um problema com consequências importantes a nível socio-económico em todo o Mundo. A Infecção do Tracto Urinário é uma das Infecções Associadas aos Cuidados de Saúde com maior importância pela grande repercussão em termos de morbilidade, de impacto pessoal para os doentes e suas familias além do impacto económico para as instituições. A algaliação é reconhecida como o principal factor de risco associado à infecção do tracto urinário. No entanto, a sua utilização é, por vezes, essencial na prestação de cuidados de saúde. A frequência com que os doentes são algaliados e o tempo de algaliação determina o maior ou menor risco de infecção do tracto urinário. Se o doente estiver inapropriadamente algaliado então esse risco é evitável. O objectivo do presente estudo foi determinar a frequência da algaliação evitável num Departamento de Medicina, o que envolveu a análise de todos os doentes internados para determinar a presença de algaliação, em dois dias diferentes, e ainda a posterior consulta dos processos clínicos dos doentes algaliados para identificar os casos onde tinham surgido infecções do tracto urinário. Dos 160 doentes internados no período do estudo, 20% tinham catéter vesical. A indicação da algaliação foi na sua maioria (84,4%) médica. Nos indivíduos estudados, foi observado que 25% não tinham indicação apropriada para estarem algaliados naquele dia, verificando-se como justificações para a permanência da algália a gestão da incontinência (6,2%) e a ausência de indicação para a sua remoção (18,8%). Verificámos que doze dos indivíduos da amostra (37,5%) desenvolveram Infecção do Tracto Urinário e que cinco desses casos não tinham indicação apropriada para estarem algaliados. Concluiu-se que cinco casos de Infecção do Tracto Urinário eram potencialmente evitáveis. Este número corresponde a 41,7% do total das Infecções do Tracto Urinário identificadas. Este é um dado relevante se considerarmos o objectivo de melhorar continuamente a prestação de cuidados, bem como todos os custos associados ao tratamento de infecções do tracto urinário.Abstract:Healthcare-associated infection is an issue with major socio-economic implications worldwide. Urinary Tract Infection is a Healthcare-Associated infection with a high influence on morbidity and personal impact for patients and their families, also has a great economic impact on institutions. The financial cost of each infection is difficult to estimate. Urinary catheterization is recognized as a main risk factor associated with urinary tract infection. However, their use is often essential in providing health care. The frequency with which catheters are placed and the duration of catheterization determines the magnitude of the risk of infection. If the presence of a urinary catheter is inappropriate, then that risk is an avoidable one. The purpose of this study was to quantify the presence of inappropriate urinary catheterization in a Medicine Department in a general hospital, which involved the analysis of all admitted patients to determine the presence of indwelling catheters, on two different days, and later by means of review of the medical records, to identify the cases that develop urinary tract infection. At the moment of the study there were 160 inpatients and a bladder catheter was present in 20%. The prescription for catheterization was mainly (84,4%) a clinician one. Reason for the permanence of the urinary catheter without appropriate indication, was maybe the absence of an order to remove the catheter. In our study, we found that 25% of patients with a urinary catheter had no clear medical order for it on that day. Another result of the study showed that 12 individuals developed urinary tract infection. In this 12 patients group, five cases had no proper order for a urinary catheter. It might be argued that five urinary tract infections were potentially preventable. These five potentially avoidable infections represent 41.7% of the urinary tract infections diagnosed. This is important data considering the need to improve the quality of care as well as all costs associated with the treatment of urinary tract infections

Bioinformática, uma licenciatura no IPS do século XXI: curso em associação

Poster apresentado no 2º Congresso Politécnico de Setúbal: 40 anos a construir o futuro, Setúbal, outubro 2019, Setúbal, PortugalN/

Biomarkers of presbycusis and tinnitus in a Portuguese older population

Trabalho apresento em TRI / TINNET Conference 2018, 14-16 março de 2018, Regensburg, GermanyN/