Design and synthesis of new inhibitors of p53–MDM2 interaction with a chalcone scaffold

The virtual screening of a library of chalcone derivatives led us to the identification of potential new MDM2 ligands. The chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two chalcones (3 and 4) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.This research was partially supported by the Strategic Funding UID/Multi/04423/2013 , ERDF , COMPETE , and FCT under the projects PTDC/MAR-BIO/4694/2014, and INNOVMAR – Innovation and Sustainability in the Management and Exploitation of Marine Resources, reference NORTE-01-0145-FEDER-000035 , Research Line NOVELMAR . This work also received financial support from the European Union (FEDER funds POCI/01/0145/FEDER/007265) and National Funds (FCT/MEC, Fundação para a Ciência e Tecnologia and Ministério da Educação e Ciência) under the Partnership Agreement PT2020 UID/QUI/50006/2013 and the FCT project PTDC/DTP-FTO/1981/2014, “PEst-C/SAU/LA0003/2013”, “NORTE-07-0162-FEDER-00018 – Contributos para o reforço da capacidade do IPATIMUP enquanto actor do sistema regional de inovação” and NORTE-07-0162-FEDER-000067 – Reforço e consolidação da capacidade infraestrutural do IPATIMUP para o sistema regional de inovação”, both supported by ON.2 – O Novo Norte, through FEDER funds under the QREN. IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT. The authors also thank FCT for the grants of R.T. Lima ( SFRH/BPD/68787/2010 ), J. Soares ( SFRH/BD/78971/2011 ), and S. Gomes ( SFRH/BD/96189/2013 ; Doctoral Programme BiotechHealth), L. Raimundo ( PD/BI/113926/2015 , Doctoral Programme BiotechHealth)

Operational stability of solution based zinc tin oxide/SiO2 thin film transistors under gate bias stress

In this study, we report solution-processed amorphous zinc tin oxide transistors exhibiting high operational stability under positive gate bias stress, translated by a recoverable threshold voltage shift of about 20% of total applied stress voltage. Under vacuum condition, the threshold voltage shift saturates showing that the gate-bias stress is limited by trap exhaustion or balance between trap filling and emptying mechanism. In ambient atmosphere, the threshold voltage shift no longer saturates, stability is degraded and the recovering process is impeded. We suggest that the trapping time during the stress and detrapping time in recovering are affected by oxygen adsorption/desorption processes. The time constants extracted from stretched exponential fitting curves are approximate to 10(6) s and 10(5) s in vacuum and air, respectively. (C) 2015 Author(s).FEDER through COMPETE 2020 Programme; European Communities 7th Framework Programme (i-FLEXIS project) [ICT-2013-10-611070]; National Funds through FCT-Portuguese Foundation for Science and Technology [UID/CTM/50025/2013, EXCL/CTM-NAN/0201/2012]info:eu-repo/semantics/publishedVersio

Inhibition of several bacterial species isolated from squid and shrimp skewers by different natural edible compounds

Seafood is an excellent source of nutrients, essential for a healthy diet, ranging from proteins and fatty acids to vitamins and minerals. Seafood products are highly perishable foods due to their nutritional characteristics and composition. The application of nontoxic, natural, and edible preservatives to extend the shelf-life and inhibit bacterial proliferation of several foods has been a hot topic. Consequently, this work aimed to perform the microbiological characterization of squid and shrimp skewers during their shelf-life (five days) and evaluate the susceptibility of randomly isolated microorganisms to several natural edible compounds so that their application for the preservation and shelf-life extension of the product might be analyzed in the future. The product had considerably high total microorganisms loads of about 5 log CFU/g at day zero and 9 log CFU/g at day five. In addition, high bacterial counts of Pseudomonas spp., Enterobacterales, and lactic acid bacteria (LAB) were found, especially on the last day of storage, being Pseudomonas the dominant genus. However, no Escherichia coli or Listeria monocytogenes were detected on the analyzed samples. One hundred bacterial isolates were randomly selected and identified through 16s rRNA sequencing, resulting in the detection of several Enterobacterales, Pseudomonas spp., and LAB. The antibacterial activity of carvacrol, olive leaf extract, limonene, Citrox®, different chitosans, and ethanolic propolis extracts was evaluated by the agar diffusion method, and the minimum inhibitory concentration was determined only for Citrox® since only this solution could inhibit all the identified isolates. At concentrations higher than or equal to 1.69% (v/v), Citrox® demonstrated bacteriostatic and bactericidal activity to 97% and 3% of the isolates, respectively. To our knowledge, there are no available data about the effectiveness of this commercial product on seafood isolates. Although preliminary, this study showed evidence that Citrox® has the potential to be used as a natural preservative in these seafood products, improving food safety and quality while reducing waste. However, further studies are required, such as developing a Citrox®-based coating and its application on this matrix to validate its antimicrobial effect.info:eu-repo/semantics/publishedVersio

Projeto de Estímulo a Docência : Um estudo sobre a inclusão nas aulas de Educação Física

A inclusao está cada vez mais presente e vigente na sociedade e nao poderia ser diferente no que se refere à educaçao. Através do PIBID-PED, Subprojeto Educaçao Física (EF) da Universidade Federal de Ouro Preto (UFOP), Brasil, buscamos discutir questoes referentes às implicaçoes de se ter turmas mistas, com a presença de alunos com deficiência, bem como, as implicaçoes e possibilidades dentro da área do conhecimento da EF escolar. Objetiva-se neste trabalho, problematizar e discutir as questoes pedagógicas de inclusao dos alunos com deficiência nas aulas de EF Escolar. Para este estudo foram produzidos Diários de Campos, através da observaçao e intervençao de turmas de 1° ao 5° ano do ensino fundamental. Pode-se observar que EF auxilia o aluno com deficiência no que diz respeito a sua valorizaçao e integraçao no meio escolar. Existiram dificuldades a cerca do planejamento e intervençao e para solucionar tal impasse, passou-se a buscar estratégias e alternativas para dinamizar e qualificar as aulas e a partir daí pode-se observar o quanto a EF auxilia o aluno com deficiência no que diz respeito a sua valorizaçao e integraçao. Contudo, é necessário que se discuta e se crie iniciativas para que os alunos com deficiência possam, de fato, ser incluídos nas aulas e juntos superarem suas diferença

Genome-Scale Characterization of Mycobacterium abscessus Complex Isolates from Portugal

(This article belongs to the Special Issue Advances in Molecular Biology on Mycobacteria)The Mycobacterium abscessus complex (MABC) is an emerging, difficult to treat, multidrug-resistant nontuberculous mycobacteria responsible for a wide spectrum of infections and associated with an increasing number of cases worldwide. Dominant circulating clones (DCCs) of MABC have been genetically identified as groups of strains associated with higher prevalence, higher levels of antimicrobial resistance, and worse clinical outcomes. To date, little is known about the genomic characteristics of MABC species circulating in Portugal. Here, we examined the genetic diversity and antimicrobial resistance profiles of 30 MABC strains isolated between 2014 and 2022 in Portugal. The genetic diversity of circulating MABC strains was assessed through a gene-by-gene approach (wgMLST), allowing their subspecies differentiation and the classification of isolates into DCCs. Antimicrobial resistance profiles were defined using phenotypic, molecular, and genomic approaches. The majority of isolates were resistant to at least two antimicrobials, although a poor correlation between phenotype and genotype data was observed. Portuguese genomes were highly diverse, and data suggest the existence of MABC lineages with potential international circulation or cross-border transmission. This study highlights the genetic diversity and antimicrobial resistance profile of circulating MABC isolates in Portugal while representing the first step towards the implementation of a genomic-based surveillance system for MABC at the Portuguese NIH.Funding: The acquisition of equipment for whole-genome sequencing used in this study was funded by the HERA (Human and Environmental Risk Assessment) project (Grant/2021/PHF/23776) supported by the European Commission through the European Centre for Disease Prevention and Control (ECDC). This work was also partially funded by 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 the Portuguese Science and Technology Foundation (FCT). SC was supported by a PhD fellowship from the FCT (2020.08503.BD).info:eu-repo/semantics/publishedVersio

ATENÇÃO PRIMÁRIA À SAÚDE E COVID-19: DESAFIOS PARA UNIVERSIDADES, TRABALHADORES E GESTORES EM SAÚDE

Objetivo: descrever experiência do grupo de apoio à Atenção Primária à Saúde, do Comitê de Enfermagem para Enfrentamento da COVID-19. Método: coleta de informações nas unidades de saúde sobre estrutura física, planos de ação, fluxos de atendimentos e força de trabalho, entre março e maio de 2020. Resultados: Foram identificados problemas em 46 unidades: fragilidades na vigilância em saúde; estrutura física; inadequação de equipamentos; afastamento de profissionais infectados pelo SARS-CoV-2; capacitação insuficiente para as demandas. Foram disponibilizados às unidades: materiais de apoio técnico-científico, espaços virtuais de debates, encaminhamento de demandas trabalhistas, materiais para adequar rotinas dos serviços e recomendações para instância superior da gestão municipal de saúde. Considerações finais: condições precárias da Atenção Primária à Saúde implicam em desestruturação de resposta adequada em momentos de emergências sanitárias. Descritores: COVID-19. Sistemas de Saúde. Enfermagem. Atenção Primária à Saúde. Universidades. Gestão em Saúde. Vigilância em Saúde Pública

Congenital defects and exposure to pesticides in São Francisco Valley

PURPOSE: to evaluate associations between parental exposure to pesticides and births with congenital defects in São Francisco Valley, as well as the demographic profile and the defects found. METHODS: in this case-control study, each case (newborns with congenital defects) had two controls (healthy newborns). The subjects were born in the city of Petrolina, in São Francisco Valley, in 2009. The sample consisted of 42 cases and 84 controls. Data were gathered by a structured questionnaire adapted from Latin-American Collaborative Study of Congenital Malformations (ECLAMC), with the addition of questions related to exposure to pesticides, analysis of the medical records and contact with the hospital's pediatrician. The χ2 test was performed with a significance level of 5% to identify the variables with the greatest differences between case and control groups. Odds Ratio (OR) for the sample was calculated, as well as the OR obtained by logistic regression analysis, and finally, multivariate logistic regression analysis was performed. RESULTS: there was a greater exposure to pesticides during pregnancy in infants with congenital defects compared to healthy subjects. Increased risk was observed when at least one parent was exposed to pesticides (adjusted OR = 1.3; 95%CI = 0.4 - 3.9). The sociodemographic variables associated with congenital defects were: low school level, low weight, prematurity, young parents, chronic diseases, and physical factors. Multiple malformations and defects of the musculoskeletal and nervous systems were more frequently found. CONCLUSIONS: the present study suggests an association between exposure to pesticides and the occurrence of congenital defects, although the data were not significant.OBJETIVO: avaliar a associação entre a exposição dos genitores aos agrotóxicos e nascimentos com defeitos congênitos no Vale do São Francisco, bem como o perfil sociodemográfico e os defeitos encontrados. MÉTODOS: estudo tipo caso-controle, sendo que para cada caso (recém-nascido com defeito congênito), eram dois controles (recém-nascidos saudáveis) nascidos na cidade de Petrolina, no Vale do São Francisco, em 2009. A amostra constou de 42 casos e 84 controles. Os dados formam colhidos com uso de questionário estruturado, adaptado do Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC), acrescido de questões relacionadas à exposição aos agrotóxicos, análise do prontuário e contato com a pediatra do hospital. Foi realizado o teste do χ2 com nível de significância de 5% para identificar as variáveis com maiores diferenças entre os grupos caso e controle. Em seguida, foi calculado o Odds Ratio (OR) amostral, bem como o OR obtido por análise de regressão logística e, finalmente, realizou-se uma análise de regressão logística multivariada. RESULTADOS: houve maior exposição aos agrotóxicos durante a gestação em neonatos com defeitos congênitos se comparados aos saudáveis. Maior risco foi observado quando pelo menos um dos genitores foi exposto aos agrotóxicos (OR ajustado = 1,3; IC95% = 0,4-3,9). As variáveis sociodemográficas associadas aos defeitos congênitos foram: baixa escolaridade, baixo peso, prematuridade, genitores jovens, doenças crônicas e fatores físicos. Foram encontrados com maior frequência os polimalformados e os defeitos dos sistemas musculoesquelético e nervoso. CONCLUSÃO: o presente estudo, a despeito de não apresentar significância, sugere associação entre a exposição aos agrotóxicos e a ocorrência de defeitos congênitos.Universidade Federal do Vale do São Francisco Colegiado de Enfermagem Disciplina de Bases MorfofisiológicasUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Cirurgia PediátricaUniversidade Federal do Vale do São FranciscoHospital Memorial de PetrolinaUniversidade Federal do Vale do São Francisco Colegiado de MedicinaUNIFESP, EPM, Depto. de Cirurgia PediátricaSciEL

Inhibition of NF-kB activation and cytokines production in THP-1 monocytes by 2-styrylchromones

Nuclear factor kappa B (NF-kB) is one of the most important transcription factors whose modulation triggers a cascade of signaling events, namely the expression of many cytokines, enzymes, chemokines, and adhesion molecules, some of which being potential key targets for intervention in the treatment of inflammatory conditions. The 2-styrylchromones (2-SC) designation represents a well-recognized group of natural and synthetic chromones, vinylogues of flavones (2-phenylchromones). Several 2-SC were recently tested for their anti-inflammatory potential, regarding the arachidonic acid metabolic cascade, showing some motivating results. In addition, several flavones with structural similarities to 2-SC have shown NF-kB inhibitory properties. Hence, the aim of the present work was to continue the investigation on the interference of 2-SC in inflammatory pathways. Herein we report their effects on lipopolysaccharide (LPS)-induced NF-kB activation and consequent production of proinflammatory cytokines/chemokine, using a human monocytic cell line (THP-1). From the twelve 2-SC tested, three of them were able to significantly inhibit the NF-kB activation and to reduce the production of the proinflammatory cytokines/chemokine. The compound 3',4',5-trihydroxy-2- styrylchromone stood up as the most active in both assays, being a promising candidate for an anti-inflammatory drug

O TRABALHO DO PROFESSOR NO DESENVOLVIMENTO MOTOR DE CRIANÇAS AUTISTAS NO ENSINO FUNDAMENTAL I

No intuito de analisar quaisquer dificuldades que o profissional de educação física possa enfrentar em sua carreira dentro do ambiente escolar, deu-se o desenvolvimento deste artigo. A metodologia aplicada a este trabalho foi a revisão de literatura baseada em outro artigos já publicados, livros e sites especializados. Uma das possíveis dificuldades que o professor de Educação Física pode se deparar é o TEA - Transtorno do Espectro Autista. Sabe-se que cada indivíduo portador reage de diferentes formas, por isso não se deve criar apenas uma maneira de trabalho. O professor terá que observar qual a melhor maneira de se trabalhar com esse deficiente intelectual, para que ele possa se desenvolver de forma natural e prazerosa, sendo assim incluso e visto perante todos como iguais.