A rational approach towards novel modulators of necroptosis

Necroptosis is a regulated form of necrosis that occurs in response to a cellular damage or infection. It is independent of caspases, occurring under conditions in which the classical pathway of cell death by apoptosis is inhibited. The execution of this type of cell death involves the recruitment of kinases as the RIPK1 and the RIPK3, which give rise to a complex necrosome and lead to the recruitment of the MLKL and consequent phosphorylation, triggering a necroptosis process. RIPK1 and RIPK3 are involved in a wide variety of pathologies for which they currently lack effective treatments, such as stroke, myocardial infarction or acute pancreatitis. Nec-1 was the first known inhibitor for necroptosis, acting through the blockade of RIPK1 activity. However, this presents some problems such as non-specificity for the target. As such, new inhibitors of RIPK1 have been developed, seeking to present better pharmacokinetic and pharmacodynamic properties, focusing on their stability and activity in vivo. Due to the great relevance of these new targets in the treatment of pathologies in which necroptosis is involved and based on a preliminary study of 21 Oxazol-5-(4H)-one derivatives in BV2 and L292 microglial cell lines, a lead compound, OXA 12, was found has an inhibitory activity similar to Nec-1. From OXA 12 and using the Erlenmeyer-Plöch reaction new OXAs were synthesized with the introduction of several groups. Besides these OXAs were further synthesized, altering the hippuric acid by other groups such as the hydrazones. These new compounds were subsequently used for biological evaluation

Parents' Emotional and Social Experiences of Caring a Child with Cleft Lip and/or Palate

Objective: To evaluate the emotional and social experiences of parents or caregivers of children with cleft lip and/or palate (CL/P) in a city in the Northeastern of Brazil. Material and Methods: A quantitative and cross-sectional study was conducted among parents or caregivers of children with CL/P by interviews based on a questionnaire. Interviews were conducted during the First Smile Project in Sobral, Ceará, Brazil. All participants (n=41) agreed to participate in the interview and signed an informed consent. The data was analyzed in SPSS software version 22.0. Results: The majority of participants were female (87.2%), with a mean age of 37 years, with a low level of education and low family income. The great majority (90.2%) of the parents were not prenatally diagnosed to have CL/P babies. Of those interviewed, 56.1% mentioned that the first diagnosis of cleft lip and palate was not presented by the professionals in a clarifying way to the family. Fear (36.6%) and sadness (19.5%) were the main feelings experienced when the child was diagnosed with fissure. Feeding (48.8%) was pointed out as the main concern in caring for a child with CL/P. Conclusion: The parents and caregivers interviewed faced important emotional and social problems that must be addressed by the professional team that assists the child with CL/P

Parents' Emotional and Social Experiences of Caring a Child with Cleft Lip and/or Palate

Objective: To evaluate the emotional and social experiences of parents or caregivers of children with cleft lip and/or palate (CL/P) in a city in the Northeastern of Brazil. Material and Methods: A quantitative and cross-sectional study was conducted among parents or caregivers of children with CL/P by interviews based on a questionnaire. Interviews were conducted during the First Smile Project in Sobral, Ceará, Brazil. All participants (n=41) agreed to participate in the interview and signed an informed consent. The data was analyzed in SPSS software version 22.0. Results: The majority of participants were female (87.2%), with a mean age of 37 years, with a low level of education and low family income. The great majority (90.2%) of the parents were not prenatally diagnosed to have CL/P babies. Of those interviewed, 56.1% mentioned that the first diagnosis of cleft lip and palate was not presented by the professionals in a clarifying way to the family. Fear (36.6%) and sadness (19.5%) were the main feelings experienced when the child was diagnosed with fissure. Feeding (48.8%) was pointed out as the main concern in caring for a child with CL/P. Conclusion: The parents and caregivers interviewed faced important emotional and social problems that must be addressed by the professional team that assists the child with CL/P

Effects of environmental exposure to tobacco on modulation of color vision

The chronic use of cigarettes causes toxic and oxidative effects on the visual system, which can cause changes in color vision. Although there are studies on the harmful effects of tobacco in active smokers, the literature on secondhand/passive smokers (or environmental tobacco smoke) is still scarce. Therefore, the aim of this study was to investigate the ability of color vision in active and passive smokers. This is a cross-sectional observational study in which 103 individuals were divided pseudorandomly into 3 groups: control group (CG) n = 44 individuals (72 eyes), with a mean age of 28.65 ± 7.90; group of passive smokers (GPS) n = 28 (56 eyes), mean age 28.74 ± 9.42; group of active smokers (GAS) n = 31 (60 eyes), mean age 34.91 ± 11.30. The psychophysical evaluation of color vision was performed using the Ishihara pseudoisochromatic plates, the computer program of the Freiburg Visual Acuity & Contrast Test, version 3.7, and the desaturated Lanthony D15 ordering test. The results indicate that there was no correlation in GAS and GPS with age, time of exposure to tobacco and daily consumption. It was observed that both GAS and GPS showed changes in visual acuity (P <0.05), and only GPS showed changes in color vision (P <0.05); GFP showed a deficit in visual acuity and worse color vision when compared to GAS (P <0.05). These results are discussed in relation to the biochemical and pathophysiological effects that exposure to cigarettes may have on the visual system, which would explain the functional changes observed. We conclude that passive and active smokers have impaired color vision and that the psychophysical methods used in this study are effective for the subclinical tracking of changes in color vision

Contextos sociais e locais do sucesso e insucesso: Edição de 2017

UID/SOC/04647/2013A Associação EPIS – Empresários Pela Inclusão Social mantém uma parceria com o centro de investigação CICS.NOVA desde 2012, tendo em vista a realização de estudos sobre o insucesso escolar em Portugal. Em 2014, foi publicado o estudo “Atlas da Educação – Desempenho e potencial de sucesso e insucesso escolar por concelho”, que permitiu, pela primeira vez, mapear o país e estabelecer uma base quantitativa de comparação do sucesso/ insucesso escolar por concelho. Em 2015, a mesma parceria permitiu lançar o estudo “Atlas da Educação - Contextos sociais e locais do sucesso e insucesso. Atualização de 2015”, tendo por objectivo detalhar o mapeamento anterior, feito por concelho, até ao nível de agrupamento de escola e aprofundar o entendimento sobre os factores que, numa mesma região, explicam os distintos desempenhos das escolas. Com o financiamento deste novo estudo, o “Atlas 2”, a EPIS quis disponibilizar um instrumento de trabalho «mais potente» ou, se quisermos, «de malha mais fina», cujo detalhe e mapeamento do país feito por agrupamento de escola permitisse uma leitura mais transparente e mais «accountable» das grandes conclusões que, em grande medida, já vinham a ser descortinadas desde o primeiro estudo. À semelhança do anterior, o Atlas da Educação 2017 tem como destinatários todos os profissionais e não profissionais ligados à Educação: equipas dos gabinetes governamentais, deputados, equipas das direções gerais e regionais do Ministério da Educação, autarcas e técnicos de autarquias, diretores de escolas, professores, pais e encarregados de educação, e cidadãos informados.publishersversionpublishe

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

COOPEDU IV — Cooperação e Educação de Qualidade

O quarto Congresso Internacional de Cooperação e Educação-IV COOPEDU, organizado pelo Centro de Estudos Internacionais (CEI) do Instituto Universitário de Lisboa e pela Escola Superior de Educação e Ciências Sociais do Instituto Politécnico de Leiria decorreu nos dias 8 e 9 de novembro de 2018, subordinado à temática Cooperação e Educação de Qualidade. Este congresso insere-se numa linha de continuidade de intervenção por parte das duas instituições organizadoras e dos elementos coordenadores e este ano beneficiou do financiamento do Instituto Camões, obtido através de um procedimento concursal, que nos permitiu contar com a participação presencial de elementos dos Países Africanos de Língua Portuguesa, fortemente implicados nas problemáticas da Educação e da Formação. Contou também com a participação do Instituto Camões e da Fundação Calouste Gulbenkian, entidades que sistematizaram a sua intervenção nos domínios da cooperação na área da educação nos últimos anos. A opção pela temática da qualidade pareceu aos organizadores pertinente e actual. Com efeito os sistemas educativos dos países que constituem a Comunidade de países de língua portuguesa têm implementado várias reformas mas em vários domínios mantem-se a insatisfação de responsáveis políticos, pedagogos, técnicos sociais face aos resultados obtidos. Aliás o caminho de procura da Qualidade é interminável porque vai a par da aposta na exigência e na promoção da cidadania e responsabilidade social. As comunicações que agora se publicam estão organizadas em dois eixos: o das Políticas da Educação e Formação e o das dimensões em que se traduzem essas políticas. Neste último eixo encontramos fios condutores para agregarmos as comunicações apresentadas