Os neuroléticos na perturbação do espetro do autismo

Trabalho de projecto de mestrado em Medicina (Pediatria), apresentado á Faculdade de Medicina da Universidade de CoimbraIntrodução: A perturbação do espetro do autismo é uma patologia crónica do neurodesenvolvimento, com apresentação em idades precoces cujos principais sintomas são défices na comunicação, na interação social e padrões de comportamentos restritivos e estereotipados. Frequentemente os indivíduos apresentam associados sintomas disruptivos como auto e hetero agressividade, agitação psicomotora, birras, hiperatividade e alterações de humor, que interferem gravemente com a sua qualidade de vida e das suas famílias. O tratamento farmacológico destes sintomas baseia-se em várias classes de medicamentos, sendo os neuroléticos a mais utilizada, uma vez que demonstra maior eficácia e segurança. A farmacogenética tem sido decisiva na procura das causas para esta perturbação, demonstrando já alguns avanços na descoberta de genes que interferem na farmacodinâmica e no tipo de reações adversas dos neuroléticos e que prometem optimizar a utilização destes nos quadros de autismo. Objetivo: Rever as indicações dos neuroléticos nos quadros de autismo, no que à eficácia e reações adversas diz respeito. Materiais e Métodos: Revisão realizada com base na literatura disponível na base de dados Pubmed, referente à utilização dos neuroléticos na perturbação do espectro do autismo. Conclusões: Os resultados dos estudos analisados sugerem que os neuroléticos são úteis na abordagem dos sintomas associados ao autismo. Apenas a risperidona e o aripiprazol têm indicação legal para o tratamento da irritabilidade relacionada com as perturbações do espetro do autismo, contudo os restantes fármacos utilizados off label também demonstram eficácia nestes quadros. As reações adversas são frequentes, sendo os efeitos extrapiramidais, o aumento de peso e a sonolência os mais observadosIntroduction: Autism spectrum disorder is a chronic neurodevelopmental disease, which appears at early ages, whose core symptoms are deficits in communication, social interaction and restrictive and stereotyped behavior. Often these individuals have associated disruptive symptoms, like aggression and self-injury, agitation, tantrums, hyperactivity and mood swings, which interfere with their quality of life and their families. The pharmacological treatments are based on various classes of drugs, where neuroleptics are the most commonly used, since they show better efficacy and safety. Pharmacogenetics has been decisive in the search for the causes for autism, already showing advances in the discovery of genes that influence in pharmacodynamics and in the type of adverse reactions of neuroleptics drugs that promise to optimize that use in autism. Objective: Review the indications, related with efficacy and safety, of neuroleptics drugs in autism Spectrum disorders. Methods: was reviewed based on the literature available in the Pubmed database, regarding the use of neuroleptics in autism spectrum disorder. Conclusions: The results of the studies reviewed suggest that neuroleptics drugs are useful in the treatment of the symptoms associated with autism. Only risperidone and aripiprazole have legal statement for the treatment of irritability related to autism spectrum disorders, however the remaining drugs used off label also demonstrate efficacy in these disorders. Adverse reactions are common, where extrapyramidal side effects, weight gain and drowsiness are the most observe

Arbustus unedo essence: morphological and genetic characterization of the strawberry tree of Castelo de Paiva

O medronheiro é um arbusto da região mediterrânica que pode ser encontrada por todo o país. Ao contrário do que verifica na região sul do país, no concelho de Castelo de Paiva é atribuída uma reduzida importância económica a esta espécie. Com o intuito de preservar e potenciar a produção desta espécie e contribuir para a dinamização da economia do concelho, procedeu-se à caracterização morfológica e genética de uma amostra da população de medronheiros de Castelo de Paiva. A caracterização morfológica e genética foi realizada para um total de 10 genótipos. Para tal recolheram-se 70 folhas aleatoriamente em cada árvore. Em 40 folhas mediu-se o comprimento, largura, comprimento do pedúnculo, peso fresco, peso seco e determinou-se a área foliar. Dos caracteres morfológicos analisados, aqueles que se revelaram mais úteis na distinção dos vários genótipos foram: comprimento do pedúnculo, peso fresco e peso seco. As restantes 30 folhas foram utilizadas para a caracterização genética. Esta caracterização foi realizada recorrendo a um marcador de DNA, ISSR. Os 5 primeiros exemplaresutilizados na técnica de ISSR demonstraram-se polimórficos. Os resultados da caracterização genética sugerem que a variabilidade genética na população é média a alta.The strawberry tree is a shrub native in the Mediterranean region and it can be found throughout Portugal. Unlike the case in the southern region of the country, in Castelo de Paiva a minor economic importance is given to this species. In order to preserve, to enhance the production of this species and to contribute to the boosting of the economy of the region, we proceeded to the characterization of a small sample population of this fruit tree of Castelo de Paiva in what concerns to its morphology and genetics. The morphological and genetic characterization was performed for a total of 10 genotypes. For this, 70 leaves were randomly collected from each tree. For 40 leaves, it was measured the length, the width, the peduncle length, the wet weight, the dry weight and determined the leaf area. Of the morphological characteristics analyzed, the ones that proved most useful in distinguishing the various genotypes were: the length peduncle, the wet weight and the dry weight. The remaining 30 leaves were used in the genetic characterization. This characterization was performed using a DNA marker, the ISSR. The 5 primers used in the ISSR technique proved to be polymorphic. The results from the genetic characterization suggest that variability in population genetics is medium to high

Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity

Acknowledgements This work was supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01- 0145-FEDER-000013), the Fundação para a Ciência e Tecnologia (FCT) (SFRH/BD/136814/2018 to S.M.G., SFRH/BD/141127/2018 to C.D.O., PD/BD/137680/2018 to D.A., IF/00474/2014 to N.S.O., IF/01390/2014 to E.T., IF/00959/2014 to S.C., IF/00021/2014 to R.S., PTDC/SAU-SER/29635/2017 and CEECIND/04601/2017 to C.C., and CEECIND/03628/2017 to A.C.), the Institut Mérieux (Mérieux Research Grant 2017 to C.C.), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Research Grant 2017 to A.C.). M.G.N. was supported by a Spinoza grant of the Netherlands Organization for Scientific Research. A.A.B. was supported by the Deutsche Forschungsgemeinschaft Collaborative Research Center/Transregio TR124 FungiNet (project A1). G.D.B. was funded by the Wellcome Trust (102705), the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPublisher PD

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Informação e segurança no ciberespaço

info:eu-repo/semantics/publishedVersio

Saúde ambiental : caderno de notas soltas III

Junho de 2023 © AutoresNa sua 3.ª edição, o Caderno de Notas Soltas pretende reunir diferentes perspetivas e metodologias, celebrando a sua razão de ser e a nobreza da sua génese intimamente ligada à realidade dos estudantes. Na verdade, passados três anos retomamos uma colaboração firmada desde a primeira hora com a Associação de Estudantes da Faculdade de Medicina de Lisboa (AEFML), num registo de proximidade da comunidade estudantil e dos interesses das gerações futuras.info:eu-repo/semantics/publishedVersio

Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity

In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses. By remodeling the intracellular calcium machinery and impairing signaling via calmodulin, melanin drives an immunometabolic signaling axis towards glycolysis with activation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) and phagosomal recruitment of mammalian target of rapamycin (mTOR). These data demonstrate a pivotal mechanism in the immunometabolic regulation of macrophages during fungal infection and highlight the metabolic repurposing of immune cells as a potential therapeutic strategy.status: publishe