CD19 CAR T cells for B cell malignancies: a systematic review and meta-analysis focused on clinical impacts of CAR structural domains, manufacturing conditions, cellular product, doses, patient's age, and tumor types.

CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. However, long-term disease-free survival is still a challenge to overcome. Here, we evaluated the influence of different hinge, transmembrane (TM), and costimulatory CAR domains, as well as manufacturing conditions, cellular product type, doses, patient's age, and tumor types on the clinical outcomes of patients with B cell cancers treated with CD19 CAR T cells. The primary outcome was defined as the best complete response (BCR), and the secondary outcomes were the best objective response (BOR) and 12-month overall survival (OS). The covariates considered were the type of hinge, TM, and costimulatory domains in the CAR, CAR T cell manufacturing conditions, cell population transduced with the CAR, the number of CAR T cell infusions, amount of CAR T cells injected/Kg, CD19 CAR type (name), tumor type, and age. Fifty-six studies (3493 patients) were included in the systematic review and 46 (3421 patients) in the meta-analysis. The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS. The presence of CD28 in the CAR's hinge, TM, and costimulatory domains improved all outcomes evaluated. Doses from one to 4.9 million cells/kg resulted in better clinical outcomes. Our data also suggest that regardless of whether patients have had high objective responses, they might have survival benefits from CD19 CAR T therapy. This meta-analysis is a critical hypothesis-generating instrument, capturing effects in the CD19 CAR T cells literature lacking randomized clinical trials and large observational studies.

Efficacy of letrozole for the treatment of tubal ectopic pregnancy: A meta-analysis.

BACKGROUND: Tubal ectopic pregnancy (EP) is a life-threatening condition, especially if undiagnosed or misdiagnosed, tipically in low income countries and/or where women have limited access to health care. The current management protocol of tubal EP consists of either surgical management, or medical management with methotrexate. Recent studies, while few, have suggested that letrozole, an aromatase inhibitor, may play a role in the medical treatment of tubal EP. OBJECTIVES: To evaluate the effectiveness of letrozole alone in the medical treatment of tubal EP. SEARCH STRATEGY: Electronic databases were searched until 31 December 2023. SELECTION CRITERIA: Retrospective or prospective studies reporting the treatment of tubal EP with letrozole alone were considered eligible for inclusion. DATA COLLECTION AND ANALYSIS: Pooled results were expressed as OR with 95 %CI. Heterogeneity was assessed using Higgins I2. Subgroup analysis was performed to compare outcomes according to time after intervention. Subgroup differences were checked through χ2 test. RESULTS: A total of 152 patients were included. Seventy-nine patients (51.97 %) were treated with letrozole, 39 patients (16.54 %) with methotrexate, and 34 patients (31.49 %) underwent surgical treatment. Pooled data analysis supports the consistency of the effect of letrozole in reducing ß-hCG over time at a comparable rate among studies, and that treatment with letrozole is superior to surgery and has the same efficacy as methotrexate. However, all the included studies were judged at high risk of bias in terms of study design, sample representativeness, and sampling technique. Furthermore, short and long term side effects were not reported in any of the included studies. CONCLUSIONS: Letrozole is a promising alternative to methotrexate and surgical therapy in the treatment of tubal EP. Although this meta-analysis suggests efficacy and low hazard of the drug and encourages its application, the data available today remain extremely sparse, which weakens any claims that can be made, and is not sufficient to assert that letrozole is safe and effective in the treatment of EPs. There is an absolute need for randomized studies with accurate patient selection, fixed doses, large sample sizes, and reporting of short- and long-term side effects to refute or confirm this assumption.

Low and High-Normal FMR1 Triplet Cytosine, Guanine Guanine Repeats Affect Ovarian Reserve and Fertility in Women Who Underwent In Vitro Fertilization Treatment? Results from a Cross-Sectional Study.

Dynamic mutations in the 5' untranslated region of FMR1 are associated with infertility. Premutation alleles interfere with prenatal development and increase infertility risks. The number of CGG repeats that causes the highest decrease in ovarian reserves remains unclear. We evaluated the effect of FMR1 CGG repeat lengths on ovarian reserves and in vitro fertilization (IVF) treatment outcomes in 272 women with alleles within the normal range. FMR1 CGG repeat length was investigated via PCR and capillary electrophoresis. Alleles were classified as low-normal, normal, and high-normal. Serum levels of follicle-stimulating hormone and anti-Mullerian hormone (AMH) in the follicular phase of the menstrual cycle were measured, and antral follicles (AFC) were counted. IVF outcomes were collected from medical records. Regarding FMR1 CGG repeat length alleles, 63.2% of women presented at least one low-normal allele. Those carrying low-normal alleles had significantly lower AMH levels than women carrying normal or high-normal alleles. Low-normal/low-normal genotype was the most frequent, followed by low-normal/normal and normal/normal. A comparison of ovarian reserve markers and reproductive outcomes of the three most frequent genotypes revealed that AFC in the low-normal/normal genotype was significantly lower than the low-normal/low-normal genotype. The low number of FMR1 CGG repeats affected AMH levels and AFC but not IVF outcomes per cycle of treatment.

Implementing high-value, cost-conscious care: experiences of Irish doctors and the role of education in facilitating this approach.

BACKGROUND: Adopting high-value, cost-conscious care (HVCCC) principles into medical education is growing in importance due to soaring global healthcare costs and the recognition that efficient care can enhance patient outcomes and control costs. Understanding the current opportunities and challenges doctors face concerning HVCCC in healthcare systems is crucial to tailor education to doctors' needs. Hence, this study aimed to explore medical students, junior doctors, and senior doctors' experiences with HVCCC, and to seek senior doctors' viewpoints on how education can foster HVCCC in clinical environments. METHODS: Using a mixed-methods design, our study involved a cross-sectional survey using the Maastricht HVCCC-Attitude Questionnaire (MHAQ), with a subset of consultants engaging in semi-structured interviews. Descriptive analysis provided insights into both categorical and non-categorical variables, with differences examined across roles (students, interns, junior doctors, senior doctors) via Kruskal-Wallis tests, supplemented by two-group analyses using Mann-Whitney U testing. We correlated experience with MHAQ scores using Spearman's rho, tested MHAQ's internal consistency with Cronbach's alpha, and employed thematic analysis for the qualitative data. RESULTS: We received 416 responses to the survey, and 12 senior doctors participated in the semi-structured interviews. Overall, all groups demonstrated moderately positive attitudes towards HVCCC, with more experienced doctors exhibiting more favourable views, especially about integrating costs into daily practice. In the interviews, participants agreed on the importance of instilling HVCCC values during undergraduate teaching and supplementing it with a formal curriculum in postgraduate training. This, coupled with practical knowledge gained on-the-job, was seen as a beneficial strategy for training doctors. CONCLUSIONS: This sample of medical students and hospital-based doctors display generally positive attitudes towards HVCCC, high-value care provision, and the integration of healthcare costs, suggesting receptiveness to future HVCCC training among students and doctors. Experience is a key factor in HVCCC, so early exposure to these concepts can potentially enhance practice within existing healthcare budgets.

Endometriosis in infertile women: an observational and comparative study of quality of life, anxiety, and depression.

BACKGROUND: A women's chances of getting pregnant decreases in cases of infertility, which may have several clinical etiologies. The prevalence of infertility is estimated as 10-15% worldwide. One of the causes of infertility is endometriosis, defined as the presence of an endometrial gland and/or stroma outside the uterus, inducing a chronic inflammatory reaction. Thus, infertility and endometriosis are diagnoses that significantly affect women's mental health. This study accessed and compared the levels of depression, anxiety, and quality of life in infertile women with and without endometriosis. METHODS: was an observational and cross-sectional study which included 201 infertile women, 81 of whom were also diagnosed with endometriosis. The STROBE Guidelines was used. The data were collected using validated scales: Hamilton D Questionnaire, Beck Depression Inventory, and Fertility Quality of Life Questionnaire; The data were collected at the Ideia Fertil Institute (Santo Andre, Brazil), between February 28 and June 8, 2019. RESULTS: the infertile women with endometriosis reported higher presence of depressive symptoms and a lower quality of life compared to women with infertility only. Similar presence of anxiety symptoms was observed regardless of being diagnosed with endometriosis. Women with infertility and endometriosis presented lower levels in quality-of-life domains when compared to women with infertility only - Mind and Body (58.33 × 79.17, p < 0.001), Relational (75 × 81.25, p = 0.009), Social (66.67 × 77.08, p = 0.001), Emotional (50.62 × 67.43, p < 0.001). CONCLUSION: the findings indicate the need for increased psychosocial support care for women suffering from infertility and endometriosis to assist them in maintaining and managing their own mental health and achieving their reproductive goals.

General Health Questionnaire (GHQ12): new evidence of construct validity / Questionário de Saúde Geral (QSG-12): novas evidências de validade de construto

Abstract This study aimed to gather evidence on the adequacy of the General Health Questionnaire (GHQ-12) in Brazil, considering a random sample of Brazilian physicians. Specifically aimed: (1) to test the GHQ-12 bifactor structure compared to alternative models, (2) to check its factorial invariance regarding to gender and the diagnosis of mental and behavioral disorders, and (3) to know the association of this measure with indicators of poor health (e.g., suicidal thoughts, decreased libido, medication use). The study included 1,085 physicians with a mean age of 45.7 (SD = 10.6), mostly male (61.5%), married (72.6%) and Catholic (59.2%). They answered the GHQ-12, the Positive and Negative Suicidal Ideation Inventory, and demographic questions. The best fit model was the bifactor structure composed of anxiety and depression, in addition to a general dimension, which presented Cronbach's alpha, McDonald's ω and composite reliability higher than 0.70 just for a general fact. Psychological distress scores correlated with suicidal ideation and indicators of health and sexual satisfaction. This is a psychometrically suitable instrument that can be used in terms of its total, but its specific factors need to be used with caution.

Resumo Este estudo teve como objetivo reunir evidências sobre a adequação do Questionário de Saúde Geral (QSG-12) no Brasil, considerando uma amostra aleatória de médicos brasileiros. Especificamente, objetivou-se: (1) testar uma estrutura bifactor em comparação com modelos alternativos, (2) verificar invariância fatorial em relação ao gênero e ao diagnóstico de transtornos mentais e comportamentais, e (3) conhecer a associação com indicadores de saúde precária (por exemplo: pensamentos suicidas, diminuição da libido e uso de medicamentos). Participaram do estudo 1.085 médicos, com média de idade de 45,7 (DP = 10,6), maioria de sexo masculino (61,5%), casados ​​(72,6%) e católicos (59,2%). Eles responderam ao QSG-12, ao Inventário de Ideação Suicida Positiva e Negativa e a questões demográficas. O modelo de melhor ajuste foi a estrutura bifactor (composta por ansiedade, depressão e uma dimensão geral), que apresentou alfa de Cronbach, ômega de McDonald e confiabilidade composta superior a 0,70 apenas para o fato geral. Pontuações de sofrimento psicológico se correlacionaram a ideação suicida e indicadores negativos de saúde e satisfação sexual. O instrumento foi psicometricamente adequado e pode ser utilizado em termos de sua pontuação total, mas seus fatores específicos precisam ser utilizados com cautela.

Análise de variáveis com potencial discriminante para classificação de escolas médicas / Analysis of discriminant variables for classification of medical schools

Resumo: Introdução: Este estudo metodológico pretendeu identificar em qual medida um conjunto de variáveis características de escolas médicas possui capacidade discriminante na classificação dos cursos por meio da análise de agrupamento. Nas últimas décadas, houve um aumento expressivo do número de vagas ofertadas para cursos médicos. Esse advento impôs desafios para os programas de avaliação, tanto pela necessidade de expandir o processo como pela necessidade de implantação de novos indicadores de qualidade. Objetivo: Esse estudo teve como objetivo propor técnicas de análise para aprimorar a capacidade discriminante na classificação de cursos médicos mediante variáveis objetivas relacionadas a aspectos estruturais e operacionais que possam ser incorporadas aos métodos já utilizados. Método: Trata-se de um estudo descritivo, analítico-metodológico e quantitativo que utilizou dados dos cursos médicos de São Paulo, em dezembro de 2020. Foi realizada análise por agrupamentos hierárquico e não hierárquico dos cursos para identificar variáveis com capacidade discriminante em busca de padrões que cooperem para a classificação das escolas médicas. As variáveis estudadas foram: início do curso, carga horária, regime letivo, metodologia, hospital universitário, categoria administrativa da instituição e gratuidade. Para a construção dos agrupamentos, adotaram-se o método de Ward e a distância euclidiana para estimar a discriminação entre os grupos. No agrupamento não hierárquico, a definição da quantidade de grupos foi determinada pela análise da diminuição da variância. Avaliou-se a correlação entre as variáveis por meio de mapas de calor. Resultado: As análises de agrupamento mostraram a existência de três grupos de escolas médicas por similaridade: um grupo composto por escolas mais antigas e com maior carga horária, e, nos outros dois, consideraram-se as escolas não gratuitas sem hospital universitário, diferenciando-se pela idade das escolas. Além disso, as correlações reforçaram que as variáveis adotadas cooperavam para a discriminabilidade entre grupos. Há reconhecida heterogeneidade entre os cursos de graduação no Brasil, e esse dado também se aplica aos cursos médicos que impõem desafios metodológicos para os processos de avaliação estabelecidos. Entretanto, a inclusão de variáveis requer métodos capazes de refinar a capacidade discriminante da análise. Conclusão: A análise aqui proposta mostrou-se capaz de identificar grupos de escolas médicas por meio de indicadores objetivos e pode auxiliar o processo de avaliação das escolas médicas.

Abstract: Introduction: This is a methodological study that aims to identify the extent to which a set of variables characteristic of medical schools have a discriminating capacity to classify the courses through cluster analysis. In the last two decades, there has been a significant increase of vacancies in medical courses. This advent has posed challenges for evaluation programs, both because of the need to expand the evaluation process and the need to implement new quality indicators. Objective: To propose analysis techniques to improve the discriminating capacity to classify medical courses through variables related to structural, operational, and objective aspects that can be incorporated into the already used methods. Method: Descriptive, analytical-methodological, quantitative study that used data from existing medical courses in December 2020, in the state of São Paulo. Analysis by hierarchical and non-hierarchical clustering of courses was performed to identify the discriminating elements that provide standards that cooperate for the classification of medical schools. The studied variables were: course start, workload, academic regime, methodology, University-Hospital, administrative category of the institution, gratuity. For the construction of the clusters, the Ward method and the Euclidean distance were used to estimate the discrimination between the groups. In the non-hierarchical clustering, the definition of the number of groups was determined by the analysis of the decrease in variance. The correlation between the variables was also evaluated through heatmaps. Results: The cluster analysis showed the existence of three groups of medical schools by similarity, with one group consisting of older schools with greater workload, and the other two consisting of private schools without a university-hospital, differing by the course time. Furthermore, the correlations reinforced that the adopted variables cooperated for the discriminability between the groups. Discussion: There is a known heterogeneity among undergraduate courses in Brazil and this also applies to medical courses, which poses methodological challenges for the established assessment processes. However, the inclusion of variables requires methods capable of refining the discriminant capacity of the analysis. Conclusion: The analysis proposed here proved to be capable of identifying groups of medical schools through objective indicators that can support the evaluation process of medical schools.

Economic evaluation of an active search system to monitor the outcomes of health-related claims / Avaliação econômica de um sistema de busca ativa para monitoramento de desfechos em demandas de saúde judicializadas

ABSTRACT Objective: Economic evaluation of a scientific advisory program with the Public Defenders Office to mitigate the impacts of the judicialization on health in the municipality, as well as the implementation of an active follow-up program to monitor health outcomes arising from court demands. Methods: A two-step study, the first documental, retrospective, with data collection of lawsuits in the region of Barbalha (CE), Brazil, from 2013 to 2018, and the second stage, prospective and intervention, through mediation between the citizen and the Public Defenders Office, aiming to reduce the occurrence of the judicialization, and the monitoring of the health outcomes of the processes. The study adopted the Consolidated Health Economic Evaluation Reporting Standards protocol for economic health assessments. The data obtained from the processes were grouped and treated for characterization of the scenario. A comparison of the profile of the lawsuits in the period of 12 months before and after the installation of the program to delimit a complete fiscal cycle was carried out. Results: The advisory service promoted a decrease of 40% (p=0.01) in lawsuits. There was a 31% reduction in court costs (p=0.003), with medicines accounting for 33% of this amount. There was a decrease in inputs outside the Sistema Único de Saúde lists (27%; p=0.003), however there was no statistical difference among several demanding groups, suggesting an equanimous approach. Conclusion: Data from the initial survey were comparable to those reported in Brazil regarding the profile of judicial demands. In view of the scenario, the proposal proved feasible as a means to mitigate the costs of the judicialization through mediation. Finally, the initiative can serve as a model for adoption by municipalities that have characteristics similar to those presented in this study.

RESUMO Objetivo: Avaliação econômica de um programa de aconselhamento científico junto à defensoria pública para minimizar o impacto da judicialização da saúde no município, bem como da implementação de um programa de pesquisa ativa para monitorar os desfechos em saúde provenientes de demandas judiciais. Métodos: Estudo conduzido em duas etapas. A primeira foi documental, retrospectiva, e composta por dados coletados de processos judiciais de 2013 a 2018 da região de Barbalha, no estado do Ceará. A segunda etapa foi prospectiva e de intervenção, conduzida por meio da mediação entre o cidadão e a defensoria pública, com o objetivo de reduzir a ocorrência da judicialização e monitorar os resultados dos processos de saúde. O estudo adotou o protocolo para avaliações econômicas em saúde Roteiro para Relato de Estudos de Avaliação Econômica. Os dados obtidos foram agrupados e tratados para caracterização do cenário. Comparou-se o perfil dos processos no período de 12 meses antes e após a instalação do programa para delimitar ciclo fiscal completo. Resultados: O serviço de consultoria promoveu redução de 40% (p=0,01) nas ações judiciais. Além disso, observou-se redução de 31% nos custos judiciais (p=0,003) com a medicação sendo responsável por 33% desse valor. Observou-se redução no uso de insumos não constantes nas listas do Sistema Único de Saúde (27%; p=0,003), contudo, sem diferença estatística entre os grupos. Conclusão: Os dados desta pesquisa foram comparáveis aos já relatados em pesquisas brasileiras quanto ao perfil de demandas. A proposta mostrou-se viável como meio de mitigar os custos da judicialização por meio da mediação. Essa iniciativa pode servir como modelo para os municípios que possuem características similares às apresentadas em nosso estudo.

Irlen syndrome: systematic review and level of evidence analysis / Síndrome de Irlen: revisão sistemática e análise do nível de evidência

ABSTRACT Background: Scotopic sensitivity syndrome, later called Meares-Irlen syndrome or simply Irlen syndrome (IS) has been described as symptoms of poor reading ability due to poor color matching and distorted graphic images. Individuals with this syndrome are considered slow, ineffective readers with low comprehension and visual fatigue. It is still uncertain whether the disease pathophysiology is an independent entity or part of the dyslexia spectrum. Nevertheless, treatments with lenses and colored filters have been proposed to alleviate the effect of the luminous contrast and improve patients' reading performance. However, no evidence of treatment effectiveness has been achieved. Objective: The aim of the present study was to obtain evidence about IS etiology, diagnosis and intervention efficacy. Methods: A systematic review was performed covering the available studies on IS, assessing the available data according to their level of evidence, focusing on diagnostic tools, proposed interventions and related outcomes. Results: The data showed high heterogeneity among studies, and lack of evidence on the existence of IS and treatment effectiveness. Conclusion: The syndrome as described, as well as its treatments, require further strong evidence.

RESUMO Background: A síndrome da sensibilidade escotópica, posteriormente denominada síndrome de Meares-Irlen ou simplesmente síndrome de Irlen (SI), foi descrita como indivíduos com sintomas de baixa capacidade de leitura devido à combinação de cores e distorções nas imagens. Indivíduos com essa síndrome podem apresentar leitura lenta e ineficaz, com baixo nível de compreensão e fadiga visual. A fisiopatologia da doença ainda é incerta como uma entidade independente ou como parte do espectro da dislexia. No entanto, tratamentos com lentes e filtros coloridos foram propostos com o objetivo de aliviar o efeito do contraste luminoso e melhorar o desempenho de leitura dos pacientes. Outrossim, nenhuma evidência de eficácia do tratamento foi alcançada. Objetivos: Obter evidências sobre a etiologia, eficácia diagnóstica e intervenção da SI. Métodos: Foi realizada uma revisão sistemática, cobrindo os estudos disponíveis sobre a SI, avaliando os dados disponíveis de acordo com seu nível de evidência, com foco em ferramentas de diagnóstico, intervenções propostas e desfechos relacionados. Resultados: Os dados mostram alta heterogeneidade, falta de evidência sobre a existência da SI e eficácia do tratamento. Conclusões: A síndrome descrita e seus tratamentos exigem evidências mais robustas.

Formulation, implementation and evaluation of a distance course for accreditation in patient safety / Formulação, desenvolvimento e avaliação de um curso a distância para acreditação em segurança do paciente

ABSTRACT Objective To formulate and to implement a virtual learning environment course in patient safety, and to propose ways to estimate the impact of the course in patient safety outcomes. Methods The course was part of an accreditation process and involved all employees of a public hospital in Brazil. The whole hospital staff was enrolled in the course. The accreditation team defined the syllabus. The education guidelines were divided into 12 modules related to quality, patient safety and required organizational practices. The assessment was performed at the end of each module through multiple-choice tests. The results were estimated according to occurrence of adverse events. Data were collected after the course, and employees' attitude was surveyed. Results More than 80% of participants reached up to 70% success on tests after the course; the event-reporting rate increased from 714 (16,264 patients) to 1,401 (10,180 patients). Conclusion Virtual learning environment was a successful tool data. Data on course evaluation is consistent with increase in identification and reporting of adverse events. Although the report increment is not positive per si, it indicates changes in patient safety culture.

RESUMO Objetivo Elaborar e implantar um curso de segurança do paciente em um ambiente virtual de aprendizagem, e propor métodos para estimar seu impacto nos resultados de segurança do paciente. Métodos O curso fez parte de um processo de acreditação e envolveu todos os colaboradores de um hospital público. Toda a equipe do hospital foi matriculada no curso. A equipe de acreditação definiu o programa. As diretrizes de instrução foram divididas em 12 módulos relacionados à qualidade, segurança do paciente e práticas organizacionais requeridas. A avaliação foi realizada no final de cada módulo, por meio de testes de escolha múltipla. Os resultados foram estimados pela ocorrência de eventos adversos. Os dados foram coletados após o curso, e a atitude dos empregados foi pesquisada. Resultados Mais de 80% dos participantes atingiram até 70% de sucesso em testes; após o curso, a taxa de notificação de eventos aumentou de 714 (16.264 pacientes) para 1.401 notificações (10.180 pacientes). Conclusão O ambiente virtual de aprendizagem foi uma ferramenta bem-sucedida. Os dados da avaliação do curso são coerentes com o aumento da identificação e da notificação de eventos adversos. Embora o incremento de notificação não seja positivo por si só, é indicativo de mudanças na cultura de segurança do paciente.

Molecular basis of basal cell carcinoma

Abstract: Basal cell carcinoma is the most common cancer, presenting low mortality but high morbidity, and it has as risk factor exposure to sunlight, especially UVB spectrum. The most important constitutional risk factors for basal cell carcinoma development are clear phototypes (I and II, Fitzpatrick classification), family history of basal cell carcinoma (30-60%), freckles in childhood, eyes and light hair. The environmental risk factor better established is exposure to ultraviolet radiation. However, different solar exposure scenarios probably are independent risk factors for certain clinical and histological types, topographies and prognosis of this tumor, and focus of controversy among researchers. Studies confirm that changes in cellular genes Hedgehog signaling pathway are associated with the development of basal cell carcinoma. The cellular Hedgehog signaling pathway is activated in organogenesis, but is altered in various types of tumors.

The advances and new technologies for the study of mitochondrial diseases / Avanços e novas tecnologias para o estudo das doenças mitocondriais

ABSTRACT Genetic mitochondrial disorders are responsible for the most common inborn errors of metabolism, caused by mutations in either nuclear genes or in mitochondrial DNA. This article presents the prokaryotic origin of the organelle and the relation between nuclear and mitochondrial genomes, as well as current evolutionary models for such mechanisms. It also addresses the structure of mitochondrial genes, their expression pattern, clinical features of gene defects, risk of transmission and current techniques to avoid these events in assisted human reproduction. Finally, it discusses the ethical implications of these possibilities.

RESUMO As doenças genéticas mitocondriais são responsáveis pelos erros inatos do metabolismo mais comuns, causados por mutações tanto em genes nucleares como no DNA mitocondrial. Este artigo apresenta a origem procariótica dessa organela, e a relação entre os genomas nuclear e mitocondrial, bem como modelos evolutivos correntes para esses mecanismos. Também trata da estrutura dos genes mitocondriais, seu padrão de expressão, características clínicas de defeitos genéticos, riscos de transmissão e técnicas atualmente utilizadas para evitar esses eventos em reprodução humana assistida. Finalmente, discute as implicações éticas dessas possibilidades.

A formação acadêmica do fisioterapeuta para sua atuação na gestão em saúde / The academic formation of physiotherapist for the performance in health management

INTRODUÇÃO: A formação do profissional fisioterapeuta declara em suas diretrizes a necessidade de preparar o egresso para desempenhar funções de gestor. Entretanto, não define com clareza qual a natureza dessa atuação, tampouco prescreve ou recomenda componentes curriculares para tanto. OBJETIVO: Verificar nos cursos de fisioterapia mais bem colocados segundo índices oficiais de desempenho quais abordagens eram utilizadas para essa demanda. MÉTODOS: Por meio da análise de ementas e currículos dos dez melhores cursos de fisioterapia segundo o Índice Geral de Cursos (IGC), foi feito um levantamento das iniciativas declaradas em documentos oficiais que atendessem às demandas das Diretrizes Curriculares para fisioterapia. RESULTADOS: Mostraram que apesar da clara indicação nas diretrizes, não existe de forma organizada e sistematizada o assunto "gestão" em disciplinas, módulos ou unidades didáticas. CONCLUSÃO: Tal fato revela o descompasso entre o declarado em documentos oficiais e o que é praticado em cursos considerados modelo segundo o IGC.

INTRODUCTION: The physiotherapist formation guidelines state the need to prepare the graduate to perform manager duties. However not clearly define the nature of these activities, either prescribed or recommended curriculum components for both. OBJECTIVE: Evaluate top ten best rated physiotherapy courses according to official indices of performance and which approaches were used for this demand. METHODS: Through course data analysis and resumes of the top ten physiotherapy courses according tothe General Index of Courses (IGC), a survey of the initiatives stated in official documents that met the demands of Curriculum Guidelines for physical therapy was done. RESULTS: Showed that despite the clear statement in the guidelines, there is not an organized and systematic manner the subject "management" courses, modules or teaching units are dealt with. CONCLUSION: This fact reveals the disconnect between official documentsstatements and what is practiced in courses considered model by the IGC.