Targeting lipid peroxidation and mitochondrial imbalance in Friedreich's ataxia

Friedreich's ataxia (FRDA) is an autosomal recessive disorder, caused by reduced levels of the protein frataxin. This protein is located in the mitochondria, where it functions in the biogenesis of iron-sulphur clusters (ISCs), which are important for the function of the mitochondrial respiratory chain complexes. Moreover, disruption in iron biogenesis may lead to oxidative stress. Oxidative stress can be the cause and/or the consequence of mitochondrial energy imbalance, leading to cell death. Fibroblasts from two FRDA mouse models, YG8R and KIKO, were used to analyse two different categories of protective compounds: deuterised poly-unsaturated fatty acids (dPUFAs) and Nrf2-inducers. The former have been shown to protect the cell from damage induced by lipid peroxidation and the latter trigger the well-known Nrf2 antioxidant pathway. Our results show that the sensitivity to oxidative stress of YG8R and KIKO mouse fibroblasts, resulting in cell death and lipid peroxidation, can be prevented by d4-PUFA and Nrf2-inducers (SFN and TBE-31). The mitochondrial membrane potential (ΔΨm) of YG8R and KIKO fibroblasts revealed a difference in their mitochondrial pathophysiology, which may be due to the different genetic basis of the two models. This suggests that variable levels of reduced frataxin may act differently on mitochondrial pathophysiology and that these two cell models could be useful in recapitulating the observed differences in the FRDA phenotype. This may reflect a different modulatory effect towards cell death that will need to be investigated further.RA is supported by FARA and GoFar, A&C Simeone Foundation.PG has received funding from FARA and GoFar, A&C Simeone Foundation and the European Union Seventh Framework Programme(FP7/2007-2013) under grant agreement number 242193/EFACTS.PG is supported by the National Institute for Health Research, University College London Hospitals, Biomedical Research Centre. EU and IR were supported by MSc scholarships

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

Figurino

Este texto apresenta uma proposta metodológica para o trabalho com figurinos. Considera o figurino como um objeto mobilizador do processo criativo no teatro. A relação entre o corpo e o material são abordados em seis etapas: figuras e fantasmas, movimento com papel craft, invólucro de papel craft; criação de silhuetas com volumes; caracterização de figuras e caracterização de uma personagem de um texto dramático

Lentivirus-meditated frataxin gene delivery reverses genome instability in Friedreich ataxia patient and mouse model fibroblasts

Friedreich ataxia (FRDA) is a progressive neurodegenerative disease caused by deficiency of frataxin protein, with the primary sites of pathology being the large sensory neurons of the dorsal root ganglia and the cerebellum. FRDA is also often accompanied by severe cardiomyopathy and diabetes mellitus. Frataxin is important in mitochondrial iron–sulfur cluster (ISC) biogenesis and low-frataxin expression is due to a GAA repeat expansion in intron 1 of the FXN gene. FRDA cells are genomically unstable, with increased levels of reactive oxygen species and sensitivity to oxidative stress. Here we report the identification of elevated levels of DNA double strand breaks (DSBs) in FRDA patient and YG8sR FRDA mouse model fibroblasts compared to normal fibroblasts. Using lentivirus FXN gene delivery to FRDA patient and YG8sR cells, we obtained long-term overexpression of FXN mRNA and frataxin protein levels with reduced DSB levels towards normal. Furthermore, γ-irradiation of FRDA patient and YG8sR cells revealed impaired DSB repair that was recovered on FXN gene transfer. This suggests that frataxin may be involved in DSB repair, either directly by an unknown mechanism, or indirectly via ISC biogenesis for DNA repair enzymes, which may be essential for the prevention of neurodegeneration.Ataxia UK, FARA Australasia and FARA US

Play, playfullness and presence in theatre and dance pedagogy

Este texto discute as relações entre jogo, ludicidade e presença. Toma exemplos de utilização de jogos e as formas como eles se desdobram em estados lúdicos do corpo no ensino de teatro e no ensino de dança. Discute as contribuições da Antropologia Teatral para pensar as relações com a presença. Explora as possibilidades de contribuição que o campo das Artes Cênicas, a partir de sua experiência com a ludicidade e a presença, pode legar ao universo de saberes da Educação.The following article discusses the relationship between play, playfullness and presence. It argues about the use and forms of play used as tool for theatre and dance teaching to create a space of experimentation of body. It explores the contributions of Theatre Anthropology to think the problem of scenic presence, as well the possibilities for the field of education

The objectively structured clinical examination for safe nursing care: a scoping review

Introduction: The Objective Structured Clinical Examination (OSCE) has been utilized as an educational strategy in the training of health professionals. Its application in this context can enhance the development of both technical and non-technical skills, as well as safety in care.Objective: To map the patient safety skills developed by nursing professionals through the Objective Structured Clinical Examination as found in the literature.Method: This is a scoping review structured according to the JBI framework and guided by the Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. The review is registered in the Open Science Framework with the DOI number 10.17605/OSF.IO/MESC3. A search was conducted in the following databases: PubMed, Scopus, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), the CAPES Catalog of Theses and Dissertations, and Google Scholar, between February and April 2023.Results: Twenty-five studies were selected, demonstrating that the OSCE is used to train nursing teams with a focus on safety skills such as communication, teamwork, decision-making, clinical care, and situational safety awareness.Conclusion: The OSCE has been used as an educational strategy to improve the quality and safety of care. It is applied from primary care to high-complexity settings to evaluate professional skills that are technical, attitudinal, or behavioral in nature. The use of OSCE aids in the development of professional skills related to patient safety

Education in Health care: a challenge to change in nursing care praxis

O artigo apresenta a trajetória de implementação de uma proposta de educação em serviço do Hospital de Clínicas de Porto Ale-gre (RS) para os profissionais de enfermagem. Aborda os caminhos percorridos pelas educadoras em serviço da Escola Técnica de Enfermagem no sentido de promover mudanças nas práticas educativas que vinham sendo realizadas com base no paradigma da edu-cação continuada. A proposta está fundamentada na Política Nacional de Educação Permanente para os trabalhadores do Sistema Único de Saúde e na Política de Humanização em Saúde do Ministério da Saúde e visa à criação de espaços educativos que permitam a reflexão dialógica sobre os processos de trabalho das equipes de enfermagem. Nessa perspectiva, as mudanças na organização e no exercício da atenção são construídas no cotidiano do trabalho de maneira articulada entre gestão, atenção à saúde, ensino e pesquisa, buscando a superação das concepções tradicionais e o fortalecimento de uma nova visão de educação em saúde. Unitermos: Educação em saúde, educadores em saúde, enfermagem.This paper presents the implementation of an education proposal in health care services for nursing professionals at Hospital de Clínicas in Porto Alegre, Brazil. It approaches the routes followed by educators in service from the Nursing Technical School in the sense of promoting changes in educational practices that had been performed based on the paradigm of continuing education. The proposal is based on the National Policy for Permanent Education for those working for the Brazilian Unified Health System and on the Health Hu-manization Policy of the Brazilian Health Ministry. This experiment aims at the creation of educational spaces that can bring about dis-cussions and some reflection upon work processes by nursing teams. Under such perspective, changes in organization and attention focusing are built throughout everyday work, articulating between management, health care, teaching and research, aiming at overcom-ing the traditional concepts of education in health care and at consolidating a new paradigm in health education

IDENTIFICAÇÃO DE BARREIRAS DE SEGURANÇA NO PREPARO E ADMINISTRAÇÃO DE MEDICAMENTOS POR PROFISSIONAIS DE ENFERMAGEM

Objetivo: descrever o padrão de conformidade profissional em relação ao conhecimento sobre as barreiras de segurança no preparo e administração dos medicamentos.Método: estudo descritivo, quantitativo, retrospectivo, realizado entre janeiro e dezembro de 2021, em hospital do Sul do Brasil, com profissionais de enfermagem. Implementou-se o Exame Clínico Objetivo Estruturado em estação clínica simulada, por aplicação de checklist contemplando barreiras de segurança. Realizou-se análise descritiva em números absolutos e percentual.Resultados: participaram 1.682 profissionais. As barreiras sinalizadas foram: prescrição médica eletrônica (86,1%), pulseira de identificação do paciente (80,3%), etiquetas de medicamentos preenchidas previamente ao preparo (74,5%) e tabela de diluição de medicamentos (63,9%). O padrão de conformidade em relação ao conhecimento sobre as barreiras apresentou-se em 73,8% dos profissionais como conforme; em 19% deles como parcial conforme e em 7,1% como não conforme.Conclusão: a conformidade em relação às barreiras de segurança identificadas, demonstrou o conhecimento dos profissionais na assistência.