Clinical Role of Codon 87 of the CYFIP2 Gene in Early Infantile Epileptic Encephalopathy: A Clinical Case Description

The diagnosis of early infantile epileptic encephalopathy (EIEE) remains challenging, and next-generation sequencing (NGS) techniques have played a key role in identifying genetic causes. Recent studies have shown an association between mutations in the CYFIP2 gene and EIEE, with 20 deleterious variants reported so far and a de novo mutational hotspot at codon 87. A male infant presented with seizures since the age of four months as well as significant developmental delay and microcephaly. The seizures were of different types, frequent and refractory to treatment, including different anticonvulsant drugs. Metabolic studies showed no significant changes. The initial electroencephalogram revealed bilateral paroxysmal activity with hemispherical diffusion. Brain MRI showed no pathological changes. Analysis of a whole exome sequencing (WES) based multigene panel for epilepsy disclosed a heterozygous CYFIP2 gene variant [c.258_266del; p.(Trp86_Ser88del)] established as de novo. We describe the case of an infant with EIEE due to a de novo heterozygous in-frame deletion of three amino acids in CYFIP2: c.258_266del; p.(Trp86_Ser88del). This in-frame deletion eliminates codon 87, a mutational hotspot associated with a particularly severe EIEE phenotype. All previous reports had missense variants with a presumably gain-of-function mechanism. The clinical picture of our patient is very similar to the ones with deleterious variants affecting codon 87 reported in the literature. Our case report is the first to describe a disease-causing in-frame deletion in CYFIP2 and reiterates a consistent genotype-phenotype correlation.info:eu-repo/semantics/publishedVersio

Intermolecular interactions of the malate synthase of Paracoccidioides spp

Background: The fungus Paracoccidioides spp is the agent of paracoccidioidomycosis (PCM), a pulmonary mycosis acquired by the inhalation of fungal propagules. Paracoccidioides malate synthase (PbMLS) is important in the infectious process of Paracoccidioides spp because the transcript is up-regulated during the transition from mycelium to yeast and in yeast cells during phagocytosis by murine macrophages. In addition, PbMLS acts as an adhesin in Paracoccidioides spp. The evidence for the multifunctionality of PbMLS indicates that it could interact with other proteins from the fungus and host. The objective of this study was to identify and analyze proteins that possibly bind to PbMLS (PbMLS-interacting proteins) because protein interactions are intrinsic to cell processes, and it might be possible to infer the function of a protein through the identification of its ligands. Results: The search for interactions was performed using an in vivo assay with a two-hybrid library constructed in S. cerevisiae; the transcripts were sequenced and identified. In addition, an in vitro assay using pull-down GST methodology with different protein extracts (yeast, mycelium, yeast-secreted proteins and macrophage) was performed, and the resulting interactions were identified by mass spectrometry (MS). Some of the protein interactions were confirmed by Far-Western blotting using specific antibodies, and the interaction of PbMLS with macrophages was validated by indirect immunofluorescence and confocal microscopy. In silico analysis using molecular modeling, dynamics and docking identified the amino acids that were involved in the interactions between PbMLS and PbMLS-interacting proteins. Finally, the interactions were visualized graphically using Osprey software. Conclusion: These observations indicate that PbMLS interacts with proteins that are in different functional categories, such as cellular transport, protein biosynthesis, modification and degradation of proteins and signal transduction. These data suggest that PbMLS could play different roles in the fungal cell. © 2013 de Oliveira et al.; licensee BioMed Central Ltd

IMPACTOS DA PANDEMIA DA COVID-19 NA ASSISTÊNCIA DE ENFERMAGEM AOS PACIENTES HIPERTENSOS E DIABÉTICOS NA ATENÇÃO PRIMÁRIA À SAÚDE: REVISÃO DA LITERATURA

The study aimed to identify the impacts of the pandemic on the care of hypertensive and diabetic patients in primary health care and to reflect on the strategies used to monitor these patients in the pandemic context. This is an integrative review with search for articles on the open-access virtual search site, Google Academic, in September and October 2021.The following descriptors were used: “Diabetes Mellitus”; Hypertension; "COVID-19"; Nursing; “Primary Health Care”. Inclusion criteria were complete articles, available in full, published in Portuguese between 2020 and 2021.At the end of the process, six articles were selected that made up the study sample.It was evident that the pandemic affected the care of hypertensive and diabetic patients, since it limited the continuity of non-emergency services, but among the strategies that have been used to circumvent the limitations of social distancing can be highlighted, for example, telemonitoring/remote care, the stratification of risks of individuals followed up and the prior scheduling of appointments. The patients were affected by the impairment of care in primary health care, considering that their pathologies need continuous monitoring, in addition to being a risk factor for the severe form of covid-19. Despite the benefits, remote care has limitations, such as limited access to the internet network and the need for training professionals.El estudio tuvo como objetivo identificar los impactos de la pandemia en la atención de pacientes hipertensos y diabéticos en la atención primaria de salud y reflexionar sobre las estrategias utilizadas para monitorear a estos pacientes en el contexto de pandemia. Se trata de una revisión integradora con búsqueda de artículos en el sitio de búsqueda virtual de acceso gratuito, Google Academic, en los meses de septiembre y octubre de 2021. Se utilizaron los siguientes descriptores: "Diabetes Mellitus"; Hipertensión; "COVID-19"; Enfermería; "Atención Primaria de Salud". Los criterios de inclusión fueron artículos completos, disponibles en su totalidad, publicados en portugués entre 2020 y 2021. Al final del proceso, se seleccionaron seis artículos que componían la muestra del estudio. Fue evidente que la pandemia afectó la atención de pacientes hipertensos y diabéticos, ya que limitó la continuidad de los servicios no urgentes, pero entre las estrategias que se han utilizado para sortear las limitaciones del distanciamiento social se pueden destacar, por ejemplo, la telemonitorización/teleservicio, la estratificación de riesgos de los individuos seguidos y la programación previa de consultas. Los pacientes se vieron afectados por el compromiso de la atención en la atención primaria de salud, considerando que sus patologías requieren un seguimiento continuo, además de ser un factor de riesgo para la forma grave de covid-19. A pesar de los beneficios, la atención remota tiene limitaciones, como el acceso limitado a la red de Internet y la necesidad de capacitación de profesionales.O estudo teve como objetivos identificar os impactos da pandemia no atendimento dos pacientes hipertensos e diabéticos na atenção primária à saúde e refletir sobre as estratégias utilizadas para o acompanhamento desses pacientes no contexto pandêmico. Trata-se de uma revisão integrativa com busca de artigos no site virtual de pesquisa de livre acesso, o Google acadêmico, nos meses de setembro e outubro de 2021. Utilizou-se os seguintes descritores: “Diabetes Mellitus”; Hipertensão; “COVID-19”; Enfermagem; “Atenção Primária à Saúde”. Os critérios de inclusão foram artigos completos, disponíveis na íntegra, publicados no idioma português entre 2020 e 2021. Ao final do processo, foram selecionados seis artigos que compuseram a amostra do estudo. Ficou evidente que a pandemia afetou a assistência dos pacientes hipertensos e diabéticos, uma vez que limitou a continuidade dos serviços não emergenciais, mas dentre as estratégias que têm sido utilizadas para contornar as limitações do distanciamento social pode-se destacar, por exemplo, o telemonitoramento/teleatendimento, a estratificação de riscos dos indivíduos acompanhados e o agendamento prévio das consultas. Os pacientes foram afetados pelo comprometimento do atendimento na atenção primária à saúde, tendo em vista que suas patologias necessitam de acompanhamento contínuo, além de se tratarem de um fator de risco para a forma grave da covid-19. Apesar dos benefícios, o atendimento remoto possui limitações, como o acesso limitado à rede de internet e a necessidade de treinamento de profissionais

Transcriptome profile of the response of paracoccidioides spp. to a camphene thiosemicarbazide derivative

ABSTARCT: Paracoccidioidomycosis (PCM) is a systemic granulomatous human mycosis caused by fungi of the genus Paracoccidioides, which is geographically restricted to Latin America. Inhalation of spores, the infectious particles of the fungus, is a common route of infection. The PCM treatment of choice is azoles such as itraconazole, but sulfonamides and amphotericin B are used in some cases despite their toxicity to mammalian cells. The current availability of treatments highlights the need to identify and characterize novel targets for antifungal treatment of PCM as well as the need to search for new antifungal compounds obtained from natural sources or by chemical synthesis. To this end, we evaluated the antifungal activity of a camphene thiosemicarbazide derivative (TSC-C) compound on Paracoccidioides yeast. To determine the response of Paracoccidioides spp. to TSC-C, we analyzed the transcriptional profile of the fungus after 8 h of contact with the compound. The results demonstrate that Paracoccidioides lutzii induced the expression of genes related to metabolism; cell cycle and DNA processing; biogenesis of cellular components; cell transduction/signal; cell rescue, defense and virulence; cellular transport, transport facilities and transport routes; energy; protein synthesis; protein fate; transcription; and other proteins without classification. Additionally, we observed intensely inhibited genes related to protein synthesis. Analysis by fluorescence microscopy and flow cytometry revealed that the compound induced the production of reactive oxygen species. Using an isolate with down-regulated SOD1 gene expression (SOD1-aRNA), we sought to determine the function of this gene in the defense of Paracoccidioides yeast cells against the compound. Mutant cells were more susceptible to TSC-C, demonstrating the importance of this gene in response to the compound. The results presented herein suggest that TSC-C is a promising candidate for PCM treatment

A tecnologia de informação e comunicação em saúde: Vivências e práticas educativas no Programa HIPERDIA / The technology and communication in health: Education experiences and practices in the HIPERDIA Program

Introdução: As tecnologias estão à disposição nos diversos tipos de serviços, no entanto na área da saúde, assumem um papel importante no cotidiano profissional, pois as máquinas e equipamentos são dispositivos voltados à mediação dos processos de cuidar. Nesse sentido, ressalta-se a aplicabilidade dessas tecnologias aplicadas por profissionais junto aos pacientes em todos os níveis de atenção em saúde. Assim, destaca-se que as Tecnologias de Informação e Comunicação (TIC´s) em saúde, são instrumentos importantes para desenvolver práticas educativas, disponibilizar informações, garantir confiabilidade, facilitar o fluxo de dados e informações, estabelecer rotinas e protocolos, além de proporcionar avaliações e qualificações no processo de assistir. Atualmente, o uso das TIC´s têm se intensificado em todos os espaços da atuação humana, auxiliando na tomada de decisão de gestores e dos profissionais de saúde, especialmente na Atenção Primária à Saúde (APS). Objetivo: Relatar a experiência dos discentes de enfermagem na aplicabilidade das Tecnologias de Informação e Comunicação em saúde no Programa HIPERDIA. Método: Estudo descritivo, tipo relato de experiência, qualitativo, realizado em uma unidade básica de saúde, no município de Niterói, do Estado do Rio de Janeiro. A experiência foi vivenciada pelos acadêmicos do Curso de Graduação em Enfermagem da Universidade Federal Fluminense, junto aos usuários cadastrados no Programa HIPERDIA. Foram utilizados, durante os atendimentos individuais e coletivos, várias tecnologias assistenciais como ferramentas educacionais: folders, vídeos, painéis e cartilhas de autocuidado com participação do usuário, equipe multiprofissional, acadêmicos de enfermagem e bolsistas de extensão. Resultado: A TIC´s é uma prática facilitadora para o diálogo pautado na horizontalidade entre o usuário e a equipe multiprofissional de saúde. No decorrer das atividades realizadas pelos acadêmicos de enfermagem, estabeleceram-se vínculos, responsabilização, autonomização, equidade e acolhimento, onde a consulta de enfermagem passou a ser mais inclusiva e agregadora. Dessa forma, percebe-se a mudança no estilo dos usuários e maior adesão ao plano assistencial, o que impacta na qualidade de vida dos portadores de hipertensão arterial e diabetes mellitus. Conclusão: As TIC´s utilizadas na consulta de enfermagem, na atenção primária, proporcionam a participação ativa dos usuários no processo saúde-doença e contribui na formação profissional. O ensino e o uso de tecnologia assistencial, no processo de cuidar, busca oferecer um cuidado equânime na atenção primária, facilitando o diálogo pautado na comunicação efetiva refletindo na qualidade de vida dos usuários

PERCEPÇÃO DE DISCENTES E DOCENTES SOBRE A MONITORIA ACADÊMICA NA FORMAÇÃO EM ENFERMAGEM

Objetivou-se conhecer a percepção de discentes e docentes sobre a monitoria acadêmica na formação em Enfermagem. Estudo descritivo de abordagem qualitativa desenvolvido em uma universidade pública do estado do Ceará, com 17 monitores e seis docentes vinculados ao curso de graduação em Enfermagem. Os dados foram coletados a partir de grupo focal com discentes e entrevistas com docentes, balizados por um roteiro semiestruturado. Para a organização do material, foi feita análise de conteúdo, da qual emergiram duas categorias temáticas: a monitoria acadêmica na perspectiva discente e a monitoria acadêmica na perspectiva docente. Na perspectiva discente, essa prática de apoio pedagógico promove a consolidação de competências profissionais como aquisição de conhecimentos, desenvolvimento da comunicação, postura, criatividade e fortalecimento das relações interpessoais, interação, responsabilidade e organização. Na perspectiva dos docentes, essa prática incentiva a docência, o desenvolvimento da comunicação, liderança, criatividade, postura e contribui na resolução de problemas. Conclui-se que a monitoria acadêmica é uma prática relevante durante a graduação e, dessa forma, deve receber maiores incentivos institucionais, visto contribuir no processo ensino-aprendizagem da tríade discentes apoiados pedagogicamente, docentes e monitores

Transcriptional profiles of the human pathogenic fungus paracoccidioides brasiliensis in mycelium and yeast cells

This work was supported by MCT, CNPq, CAPES, FUB, UFG, and FUNDECT-MS. PbGenome Network: Alda Maria T. Ferreira, Alessandra Dantas, Alessandra J. Baptista, Alexandre M. Bailão, Ana Lídia Bonato, André C. Amaral, Bruno S. Daher, Camila M. Silva, Christiane S. Costa, Clayton L. Borges, Cléber O. Soares, Cristina M. Junta, Daniel A. S. Anjos, Edans F. O. Sandes, Eduardo A. Donadi, Elza T. Sakamoto-Hojo, Flábio R. Araújo, Flávia C. Albuquerque, Gina C. Oliveira, João Ricardo M. Almeida, Juliana C. Oliveira, Kláudia G. Jorge, Larissa Fernandes, Lorena S. Derengowski, Luís Artur M. Bataus, Marcus A. M. Araújo, Marcus K. Inoue, Marlene T. De-Souza, Mauro F. Almeida, Nádia S. Parachin, Nadya S. Castro, Odair P. Martins, Patrícia L. N. Costa, Paula Sandrin-Garcia, Renata B. A. Soares, Stephano S. Mello, and Viviane C. B. ReisParacoccidioides brasiliensis is the causative agent of paracoccidioidomycosis, a disease that affects 10 million individuals in Latin America. This report depicts the results of the analysis of 6,022 assembled groups from mycelium and yeast phase expressed sequence tags, covering about 80% of the estimated genome of this dimorphic, thermo-regulated fungus. The data provide a comprehensive view of the fungal metabolism, including overexpressed transcripts, stage-specific genes, and also those that are up- or down-regulated as assessed by in silico electronic subtraction and cDNA microarrays. Also, a significant differential expression pattern in mycelium and yeast cells was detected, which was confirmed by Northern blot analysis, providing insights into differential metabolic adaptations. The overall transcriptome analysis provided information about sequences related to the cell cycle, stress response, drug resistance, and signal transduction pathways of the pathogen. Novel P. brasiliensis genes have been identified, probably corresponding to proteins that should be addressed as virulence factor candidates and potential new drug targets

Educomunicação e suas áreas de intervenção: Novos paradigmas para o diálogo intercultural

oai:omp.abpeducom.org.br:publicationFormat/1O material aqui divulgado representa, em essência, a contribuição do VII Encontro Brasileiro de Educomunicação ao V Global MIL Week, da UNESCO, ocorrido na ECA/USP, entre 3 e 5 de novembro de 2016. Estamos diante de um conjunto de 104 papers executivos, com uma média de entre 7 e 10 páginas, cada um. Com este rico e abundante material, chegamos ao sétimo e-book publicado pela ABPEducom, em seus seis primeiros anos de existência. A especificidade desta obra é a de trazer as “Áreas de Intervenção” do campo da Educomunicação, colocando-as a serviço de uma meta essencial ao agir educomunicativo: o diálogo intercultural, trabalhado na linha do tema geral do evento internacional: Media and Information Literacy: New Paradigms for Intercultural Dialogue

International Society of Human and Animal Mycology (ISHAM)-ITS reference DNA barcoding database - the quality controlled standard tool for routine identification of human and animal pathogenic fungi

Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and biochemical identification methods are time-consuming and require trained experts. Alternatively, molecular methods, such as DNA barcoding, a powerful and easy tool for rapid monophasic identification, offer a practical approach for species identification and less demanding in terms of taxonomical expertise. However, its wide-spread use is still limited by a lack of quality-controlled reference databases and the evolving recognition and definition of new fungal species/complexes. An international consortium of medical mycology laboratories was formed aiming to establish a quality controlled ITS database under the umbrella of the ISHAM working group on "DNA barcoding of human and animal pathogenic fungi." A new database, containing 2800 ITS sequences representing 421 fungal species, providing the medical community with a freely accessible tool at http://www.isham.org and http://its.mycologylab.org/ to rapidly and reliably identify most agents of mycoses, was established. The generated sequences included in the new database were used to evaluate the variation and overall utility of the ITS region for the identification of pathogenic fungi at intra-and interspecies level. The average intraspecies variation ranged from 0 to 2.25%. This highlighted selected pathogenic fungal species, such as the dermatophytes and emerging yeast, for which additional molecular methods/genetic markers are required for their reliable identification from clinical and veterinary specimens.This study was supported by an National Health and Medical Research Council of Australia (NH&MRC) grant [#APP1031952] to W Meyer, S Chen, V Robert, and D Ellis; CNPq [350338/2000-0] and FAPERJ [E-26/103.157/2011] grants to RM Zancope-Oliveira; CNPq [308011/2010-4] and FAPESP [2007/08575-1] Fundacao de Amparo Pesquisa do Estado de So Paulo (FAPESP) grants to AL Colombo; PEst-OE/BIA/UI4050/2014 from Fundacao para a Ciencia e Tecnologia (FCT) to C Pais; the Belgian Science Policy Office (Belspo) to BCCM/IHEM; the MEXBOL program of CONACyT-Mexico, [ref. number: 1228961 to ML Taylor and [122481] to C Toriello; the Institut Pasteur and Institut de Veil le Sanitaire to F Dromer and D Garcia-Hermoso; and the grants from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and the Fundacao de Amparo a Pesquisa do Estado de Goias (FAPEG) to CM de Almeida Soares and JA Parente Rocha. I Arthur would like to thank G Cherian, A Higgins and the staff of the Molecular Diagnostics Laboratory, Division of Microbiology and Infectious Diseases, Path West, QEII Medial Centre. Dromer would like to thank for the technical help of the sequencing facility and specifically that of I, Diancourt, A-S Delannoy-Vieillard, J-M Thiberge (Genotyping of Pathogens and Public Health, Institut Pasteur). RM Zancope-Oliveira would like to thank the Genomic/DNA Sequencing Platform at Fundacao Oswaldo Cruz-PDTIS/FIOCRUZ [RPT01A], Brazil for the sequencing. B Robbertse and CL Schoch acknowledge support from the Intramural Research Program of the NIH, National Library of Medicine. T Sorrell's work is funded by the NH&MRC of Australia; she is a Sydney Medical School Foundation Fellow.info:eu-repo/semantics/publishedVersio

The complete genome sequence of Chromobacterium violaceum reveals remarkable and exploitable bacterial adaptability

Chromobacterium violaceum is one of millions of species of free-living microorganisms that populate the soil and water in the extant areas of tropical biodiversity around the world. Its complete genome sequence reveals (i) extensive alternative pathways for energy generation, (ii) ≈500 ORFs for transport-related proteins, (iii) complex and extensive systems for stress adaptation and motility, and (iv) wide-spread utilization of quorum sensing for control of inducible systems, all of which underpin the versatility and adaptability of the organism. The genome also contains extensive but incomplete arrays of ORFs coding for proteins associated with mammalian pathogenicity, possibly involved in the occasional but often fatal cases of human C. violaceum infection. There is, in addition, a series of previously unknown but important enzymes and secondary metabolites including paraquat-inducible proteins, drug and heavy-metal-resistance proteins, multiple chitinases, and proteins for the detoxification of xenobiotics that may have biotechnological applications