REM sleep behavior disorder: update on diagnosis and management.

REM sleep behavior disorder (RBD) is characterized by a loss of atonia of skeletal muscles during REM sleep, associated with acting out behaviors during dreams. Knowledge of this pathology is important to predict neurodegenerative diseases since there is a strong association of RBD with diseases caused by the deposition of alpha-synuclein in neurons (synucleinopathies), such as Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Proper diagnosis of this condition will enable the use of future neuroprotective strategies before motor and cognitive symptoms. Diagnostic assessment should begin with a detailed clinical history with the patient and bed partner or roommate and the examination of any recorded home videos. Polysomnography (PSG) is necessary to verify the loss of sleep atonia and, when documented, the behaviors during sleep. Technical recommendations for PSG acquisition and analysis are defined in the AASM Manual for the scoring of sleep and associated events, and the PSG report should describe the percentage of REM sleep epochs that meet the criteria for RWA (REM without atonia) to better distinguish patients with and without RBD. Additionally, PSG helps rule out conditions that may mimic RBD, such as obstructive sleep apnea, non-REM sleep parasomnias, nocturnal epileptic seizures, periodic limb movements, and psychiatric disorders. Treatment of RBD involves guidance on protecting the environment and avoiding injuries to the patient and bed partner/roommate. Use of medications are also reviewed in the article. The development of neuroprotective medications will be crucial for future RBD therapy.

O transtorno comportamental do sono REM (TCSREM) é caracterizado por uma perda de atonia dos músculos esqueléticos durante o sono REM, associada a comportamentos de atuação durante os sonhos. O conhecimento desse transtorno é importante como preditor de doenças neurodegenerativas, uma vez que existe uma forte associação de TCSREM com doenças causadas pela deposição de alfa-sinucleína nos neurônios, como a doença de Parkinson (DP), atrofia de múltiplos sistemas (MSA) e demência com corpos de Lewy (DLB). O diagnóstico adequado dessa condição permitirá o uso de futuras estratégias neuroprotetoras antes do aparecimento dos sintomas motores e cognitivos. A avaliação diagnóstica deve começar com uma história clínica detalhada com o paciente e acompanhante, além de exame de vídeos. A polissonografia (PSG) é necessária para verificar a perda da atonia do sono e, quando documentados, os comportamentos durante o sono. As recomendações técnicas para aquisição e análise de PSG são definidas no Manual da AASM (Scoring of sleep and associated events) e o relatório de PSG deve descrever a porcentagem de períodos de sono REM que atendem aos critérios para REM sem atonia. Além disso, a PSG ajuda a descartar condições que podem mimetizar o TCSREM, como apneia obstrutiva do sono, parassonias do sono não REM, crises epilépticas noturnas, movimentos periódicos dos membros e transtornos psiquiátricos. O tratamento do TCSREM envolve orientações sobre adaptações do ambiente para evitar lesões ao paciente e ao colega de quarto. Medicamentos utilizados são revistos no artigo, assim como o crucial desenvolvimento de medicamentos neuroprotetores.

REM sleep behavior disorder: update on diagnosis and management / Transtorno comportamental do sono REM: atualização no diagnóstico e manejo

Abstract REM sleep behavior disorder (RBD) is characterized by a loss of atonia of skeletal muscles during REM sleep, associated with acting out behaviors during dreams. Knowledge of this pathology is important to predict neurodegenerative diseases since there is a strong association of RBD with diseases caused by the deposition of alpha-synuclein in neurons (synucleinopathies), such as Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Proper diagnosis of this condition will enable the use of future neuroprotective strategies before motor and cognitive symptoms. Diagnostic assessment should begin with a detailed clinical history with the patient and bed partner or roommate and the examination of any recorded home videos. Polysomnography (PSG) is necessary to verify the loss of sleep atonia and, when documented, the behaviors during sleep. Technical recommendations for PSG acquisition and analysis are defined in the AASM Manual for the scoring of sleep and associated events, and the PSG report should describe the percentage of REM sleep epochs that meet the criteria for RWA (REM without atonia) to better distinguish patients with and without RBD. Additionally, PSG helps rule out conditions that may mimic RBD, such as obstructive sleep apnea, non-REM sleep parasomnias, nocturnal epileptic seizures, periodic limb movements, and psychiatric disorders. Treatment of RBD involves guidance on protecting the environment and avoiding injuries to the patient and bed partner/roommate. Use of medications are also reviewed in the article. The development of neuroprotective medications will be crucial for future RBD therapy.

Resumo O transtorno comportamental do sono REM (TCSREM) é caracterizado por uma perda de atonia dos músculos esqueléticos durante o sono REM, associada a comportamentos de atuação durante os sonhos. O conhecimento desse transtorno é importante como preditor de doenças neurodegenerativas, uma vez que existe uma forte associação de TCSREM com doenças causadas pela deposição de alfa-sinucleína nos neurônios, como a doença de Parkinson (DP), atrofia de múltiplos sistemas (MSA) e demência com corpos de Lewy (DLB). O diagnóstico adequado dessa condição permitirá o uso de futuras estratégias neuroprotetoras antes do aparecimento dos sintomas motores e cognitivos. A avaliação diagnóstica deve começar com uma história clínica detalhada com o paciente e acompanhante, além de exame de vídeos. A polissonografia (PSG) é necessária para verificar a perda da atonia do sono e, quando documentados, os comportamentos durante o sono. As recomendações técnicas para aquisição e análise de PSG são definidas no Manual da AASM (Scoring of sleep and associated events) e o relatório de PSG deve descrever a porcentagem de períodos de sono REM que atendem aos critérios para REM sem atonia. Além disso, a PSG ajuda a descartar condições que podem mimetizar o TCSREM, como apneia obstrutiva do sono, parassonias do sono não REM, crises epilépticas noturnas, movimentos periódicos dos membros e transtornos psiquiátricos. O tratamento do TCSREM envolve orientações sobre adaptações do ambiente para evitar lesões ao paciente e ao colega de quarto. Medicamentos utilizados são revistos no artigo, assim como o crucial desenvolvimento de medicamentos neuroprotetores.

Um instrumento de avaliação do interno de pediatria na Atenção Primária à Saúde / An instrument for evaluation of medical students during the internship of pediatrics Primary Health Care / Un instrumento de evaluación de estudiantes de pediatría en Atención Primaria de Salud

Os estudantes de Medicina têm contato com diferentes áreas e cenários durante o internato e devem ter seu desempenho avaliado em cada um deles. Contudo, muitos estudantes não se sentem devidamente avaliados e, diante disso, nosso objetivo foi desenvolver um instrumento de avaliação do desempenho de estudantes de Medicina, no período do internato em pediatria, para uso durante o estágio realizado na Atenção Primária à Saúde. Realizou-se uma pesquisa metodológica com elaboração de um instrumento e contribuição de especialistas com experiência em ensino, por meio de convites eletrônicos. Ao final do estudo, utilizando-se a técnica Delphi, dos vinte itens constantes no instrumento original, dezessete foram aceitos pelos 11 especialistas que participaram das duas rodadas de análise. Dessa forma, a pesquisa alcançou seu objetivo e, por meio deste artigo, divulgamos a proposta de um "Instrumento de avaliação de internos de Medicina no estágio de pediatria na Atenção Primária à Saúde".

Medical students have contact with different areas and scenarios during their internship and must have their performance evaluated in each of them. However, as many students do not feel properly evaluated, our objective was to develop an instrument to evaluate the performance of Medical students, during their internship in pediatrics, to be used during their practice in Primary Health Care. A methodological research was carried out with the elaboration of an instrument and the contribution of specialists with experience in teaching, using electronic invitations. At the end of the study, through the Delphi technique, seventeen of the twenty items contained in the original instrument were accepted by the 11 specialists who participated in the two rounds of analysis. Thus, the research reached its objective and, through this article, we disseminate the proposal of an "Instrument for the evaluation of Medical interns in the pediatric internship in Primary Health Care".

Los estudiantes de Medicina tienen contacto con diferentes áreas y escenarios durante su pasantía y deben evaluar su desempeño en cada uno de ellos. Sin embargo, muchos estudiantes no se sienten debidamente evaluados y, ante eso, nuestro objetivo fue desarrollar un instrumento para evaluar la actuación de los estudiantes de Medicina, durante su pasantía en pediatría, para ser utilizado mientras ejecutan la Atención Primaria de Salud. Se realizó una investigación metodológica con la elaboración de un instrumento y el aporte de especialistas con experiencia en la docencia, a través de invitaciones electrónicas. Al final del estudio, utilizando la técnica Delphi, de los veinte ítems contenidos en el instrumento original, se aceptaron diecisiete por los 11 especialistas que participaron en las dos rondas de análisis. De esta forma, la investigación alcanzó su objetivo y, por medio de este artículo, divulgamos la propuesta de un "Instrumento para la evaluación de Médicos internos en el internado de pediatría en Atención Primaria de Salud".

Processo de ensino-aprendizagem em nefrologia: uma revisão integrativa / Teaching-Learning Process in Nephrology: An Integrative Review

Resumo: Introdução: A redução da procura pelos Programas de Residência Médica em Nefrologia na última década é um assunto que vem ganhando relevância, notadamente nas discussões suscitadas pelas sociedades científicas e associações médicas por todo o mundo. Constata-se que há falta de interesse pela especialidade desencadeado por processos de ensino-aprendizagem inadequados no sentido de gerar interesse dos graduandos. Diante desse cenário, é fundamental compreender quais são os fatores que influenciam o processo de ensino-aprendizagem na nefrologia durante a graduação. Objetivo: Este estudo teve como objetivo analisar as estratégias de ensino-aprendizagem em nefrologia e seus resultados durante a graduação em Medicina. Método: Foi realizada uma revisão integrativa de artigos publicados em inglês, espanhol e português sobre o ensino de nefrologia na graduação em Medicina, com busca em quatro bases de dados (PubMed, ERIC, SciELO e Lilacs). Usamos as seguintes palavras-chave em nossas pesquisas: "educação médica", "estudantes de medicina", "nefrologia", "métodos de ensino" (em português), "medical education", "medical students", "nephrology" e "teaching methods" (em inglês) e "educación médica", "estudiantes de medicina", "nefrología" e "métodos de enseñanza" (em espanhol). Resultado: Observou-se um papel relevante do uso de metodologias ativas nos processos de ensino-aprendizagem como uma ferramenta promissora para ampliar o interesse dos estudantes pelo tema. Além disso, constatou-se que uma parcela dos educadores médicos envolvidos com o ensino da nefrologia é, na realidade, composta de não nefrologistas. Por fim, percebe-se um papel do uso de ferramentas on-line como estratégia para ampliar o interesse dos estudantes pela disciplina. Conclusão: Falta rigor no desenho dos estudos sobre a formação do estudante de Medicina em nefrologia, o que não permite aferir resultados precisos sobre o impacto das metodologias de ensino-aprendizagem. Estudos controlados randomizados bem desenhados, bem como o uso de estudos de coorte comparando metodologias de ensino-aprendizagem, são necessários para avaliar efetivamente as técnicas educacionais introduzidas nos currículos das escolas médicas.

Abstract: Introduction: The reduced demand for Medical Residency Programs in Nephrology in the last decade is a subject that has been gaining relevance, notably in discussions raised by scientific societies and medical associations around the world. It appears that there is a lack of interest in the specialty, triggered by teaching-learning processes that are inadequate to generate interest among undergraduates. Given this scenario, it is essential to understand which factors influence the teaching-learning process in Nephrology during undergraduate training. Objective: To analyze teaching-learning strategies in nephrology and their results during undergraduate medical training. Method: An integrative review of articles published in English, Spanish and Portuguese on teaching of nephrology in undergraduate medicine was carried out, searching four databases (PubMed, ERIC, SciELO and Lilacs). We used the following keywords in our searches: "medical education", "medical students", "nephrology", "teaching methods", "medical education", "medical students", "nephrology" and "teaching methods" (in English) and "educational medicine", "medicine students", "nephrology" and "metodos de enseñanza" (in Spanish). Results: A relevant role was observed in the use of active teaching-learning methodologies as a promising tool to increase student interest in the subject. In addition, it was found that a portion of medical educators involved in the teaching of Nephrology are, in fact, not nephrologists. Finally, there is a role for the use of online tools as a strategy to increase student interest in the discipline. Conclusion: There is a lack of rigor in the design of studies on the training of medical students in nephrology, which does not allow for accurate results on the impact of teaching-learning methodologies. Well-designed randomized controlled trials, as well as the use of cohort studies comparing teaching-learning methodologies, are needed to assess the effectiveness of educational techniques introduced in medical school curricula.

Consenso Abem para o ensino de comunicação nas escolas médicas brasileiras / ABEM consensus for the brazilian medical schools' communication curriculum

Resumo: Introdução: A comunicação é uma competência essencial para o(a) médico(a) e outras categorias profissionais, e deve ser desenvolvida durante sua formação profissional. A elaboração de um projeto de comunicação, incluindo um consenso brasileiro, visou subsidiar as escolas médicas a preparar os estudantes de Medicina para se comunicarem efetivamente com os(as) cidadãos/cidadãs brasileiros(as), de características plurais intra e inter-regionais, pautando-se no profissionalismo e nos princípios do Sistema Único de Saúde (SUS). Objetivo: Este manuscrito apresenta o consenso para o ensino de comunicação nas escolas médicas brasileiras. Método: O consenso foi construído colaborativamente com 276 participantes, experts em comunicação, docentes, profissionais de saúde e discentes, de 126 escolas médicas e cinco instituições de saúde, ao longo de nove encontros presenciais em congressos e de encontros virtuais quinzenais ou mensais. Nos encontros, compartilharam-se as experiências dos participantes e o material bibliográfico, incluindo os consensos internacionais, e apresentou-se o consenso em construção, com discussão em grupos para elencar novos componentes para o consenso brasileiro, seguida por debate com todos para pactuá-los. A versão final foi aprovada em reunião virtual, com convite a todos(as) os(as) participantes em julho de 2021. Após submissão, diversas alterações foram requeridas, o que demandou novos encontros para revisão da versão final do consenso. Resultado: O consenso tem como pressupostos que a comunicação deve ser centrada nas relações, pautada nos princípios do SUS, na participação social e no profissionalismo, e embasada nas Diretrizes Curriculares Nacionais do curso de graduação em Medicina, em referenciais teóricos e nas evidências científicas. São descritos objetivos específicos para desenvolver a competência em comunicação nos estudantes, abrangendo: fundamentos teóricos; busca e avaliação crítica da literatura; elaboração e redação de documentos; comunicação intrapessoal e interpessoal no ambiente acadêmico-científico, na atenção à saúde em diversos contextos clínicos e na gestão em saúde. Recomenda-se a inserção curricular da comunicação do início ao final do curso, integrada a outros conteúdos e áreas de saber. Conclusão: Espera-se que esse consenso contribua para a revisão ou implementação da comunicação nos currículos das escolas médicas brasileiras.

Abstract: Introduction: Communication is an essential competence for the physician and other professional categories, and must be developed their professional training. The creation of a communication project including a Brazilian consensus aimed to subsidize medical schools in preparing medical students to communicate effectively with Brazilian citizens, with plural intra and inter-regional characteristics, based on the professionalism and the Brazilian Unified System (SUS) principles. Objective: The objective of this manuscript is to present the consensus for the teaching of communication in Brazilian medical schools. Method: The consensus was built collaboratively with 276 participants, experts in communication, faculty, health professionals and students from 126 medical schools and five health institutions in face-to-face conference meetings and biweekly or monthly virtual meetings. In the meetings, the participants' experiences and bibliographic material were shared, including international consensuses, and the consensus under construction was presented, with group discussion to list new components for the Brazilian consensus, followed by debate with everyone, to agree on them. The final version was approved in a virtual meeting with invitation to all participants in July 2021. After the submission, several changes were required, which demanded new meetings to review the consensus final version. Result: The consensus is based on assumptions that communication should be relationship-centered, embedded on professionalism, grounded on the SUS principles and social participation, and based on the National Guidelines for the undergraduate medical course, theoretical references and scientific evidence. Specific objectives to develop communication competence in the students are described, covering: theoretical foundations; literature search and its critical evaluation; documents drafting and editing; intrapersonal and interpersonal communication in the academicscientific environment, in health care and in health management; and, communication in diverse clinical contexts. The inclusion of communication in the curriculum is recommended from the beginning to the end of the course, integrated with other contents and areas of knowledge. Conclusion: It is expected that this consensus contributes the review or implementation of communication in Brazilian medical schools' curricula.

Efetividade do sistema de triagem em serviço de emergência privado: estudo coorte / Effectiveness of the triage system in a private emergency service: cohort study

Fundamentos: A superlotação dos serviços de emergência é um fenômeno mundial. Isto torna imprescindível que os sistemas de triagem utilizados sejam efetivos na identificação de atendimentos prioritários. Entretanto, pouco se conhece sobre a efetividade dos sistemas de triagem em serviços de emergência, principalmente na rede suplementar de saúde no Brasil. Objetivo: identificar a efetividade do sistema de triagem em serviço de emergência privado, baseado na Escala de Triagem Canadense. Métodos: Estudo coorte retrospectivo, com 254.730 registros de atendimentos, entre 2017 e 2018, de um serviço de emergência privado, referência em medicina de alta complexidade, em São Paulo (SP), Brasil. Estatística descritiva foi utilizada para caracterizar os atendimentos, de acordo com ano, sexo, idade, classificação de prioridade e desfecho clínico pós-atendimento. Associação entre os graus de prioridades da escala e os desfechos clínicos foi verificada pelo teste Qui-quadrado de Pearson. Para analisar efetividade do sistema de triagem foi delineado um modelo de regressão logística univariada, para prever o desfecho "internações/óbitos", em comparação com "altas". Devido ao tamanho amostral robusto, o nível de significância considerado foi de 0,1%. Resultados: Cerca de 60% dos atendimentos foram classificados como não urgentes e 30,8%, como urgentes. A probabilidade de morte e internação corresponderam ao aumentou do grau de prioridade, variando entre mais de 12 vezes para os atendimentos de "semi-urgência" a mais de 100 vezes para o grau "emergência". Pacientes atendidos no ano de 2018, do sexo masculino e com idade acima de 50 anos apresentaram maior probabilidade de serem internados ou morrerem. Conclusão: O sistema de triagem analisado foi considerado efetivo para prever desfechos clínicos compatíveis com a gradação de gravidade estabelecida. Isto é relevante na medida que expressa, pela primeira vez no Brasil, a efetividade em um sistema de triagem, baseado na Escala de Triagem Canadense. Além disso, a caracterização da busca expressiva por atendimentos de baixa gravidade entre usuários do serviço analisado é semelhante aos apresentados em diversos estudos nacionais e internacionais. Reflete-se sobre as explicações socioculturais e econômicas no contexto brasileiro, expondo perspectivas a serem atingidas por políticas públicas.Palavras-chave: Triagem, Medicina de emergências, Enfermagem em emergência, Estudos de coortes. (AU)

Background: the overcrowding of emergency services is a worldwide phenomenon. This makes it essential that the triage systems used are effective in identifying priority care. However, little is known about the effectiveness of triage systems in emergency services, especially in the supplementary health network in Brazil. Objective: identify the effectiveness of the triage system in a private emergency department, based on the Canadian Triage and Acuity Scale. Methods: a retrospective cohort study, with 254,730 records of care, between 2017 and 2018, from a private emergency service, reference in high complexity medicine, in São Paulo (SP), Brazil. Descriptive statistics were used to characterize the attendances, according to year, gender, age, priority rating, and post-acute clinical outcome. Association between the scale priority grades and clinical outcomes was verified by Pearson's chi-square test. To analyze the effectiveness of the screening system, a univariate logistic regression model was designed to predict the outcome "hospitalizations/hospitalizations" compared to "discharges". Due to the robust sample size, the significance level considered was 0.1%. Results: about 60% of the cases were classified as non-urgent and 30.8% as urgent. The probability of death and hospitalization corresponded to the increased degree of priority, ranging from more than 12 times for the "semi-urgent" attendances to more than 100 times for the "emergency" degree. Patients seen in 2018, male and over 50 years old, were more likely to be hospitalized or die. Conclusion: the screening system analyzed was considered effective in predicting clinical outcomes compatible with the established severity gradation. This is relevant as it expresses, for the first time in Brazil, the effectiveness of a triage system based on the Canadian Triage and Acuity Scale. Moreover, the characterization of the expressive search for low severity care among users of the analyzed service is similar to those presented in several national and international studies. Reflections on sociocultural and economic explanations in the Brazilian context are made, exposing perspectives to be achieved by public policies. (AU)

Endocytosis of nutrient transporters in fungi: The ART of connecting signaling and trafficking.

Plasma membrane transporters play pivotal roles in the import of nutrients, including sugars, amino acids, nucleobases, carboxylic acids, and metal ions, that surround fungal cells. The selective removal of these transporters by endocytosis is one of the most important regulatory mechanisms that ensures a rapid adaptation of cells to the changing environment (e.g., nutrient fluctuations or different stresses). At the heart of this mechanism lies a network of proteins that includes the arrestin-related trafficking adaptors (ARTs) which link the ubiquitin ligase Rsp5 to nutrient transporters and endocytic factors. Transporter conformational changes, as well as dynamic interactions between its cytosolic termini/loops and with lipids of the plasma membrane, are also critical during the endocytic process. Here, we review the current knowledge and recent findings on the molecular mechanisms involved in nutrient transporter endocytosis, both in the budding yeast Saccharomyces cerevisiae and in some species of the filamentous fungus Aspergillus. We elaborate on the physiological importance of tightly regulated endocytosis for cellular fitness under dynamic conditions found in nature and highlight how further understanding and engineering of this process is essential to maximize titer, rate and yield (TRY)-values of engineered cell factories in industrial biotechnological processes.

Adapting to survive: How Candida overcomes host-imposed constraints during human colonization.

Successful human colonizers such as Candida pathogens have evolved distinct strategies to survive and proliferate within the human host. These include sophisticated mechanisms to evade immune surveillance and adapt to constantly changing host microenvironments where nutrient limitation, pH fluctuations, oxygen deprivation, changes in temperature, or exposure to oxidative, nitrosative, and cationic stresses may occur. Here, we review the current knowledge and recent findings highlighting the remarkable ability of medically important Candida species to overcome a broad range of host-imposed constraints and how this directly affects their physiology and pathogenicity. We also consider the impact of these adaptation mechanisms on immune recognition, biofilm formation, and antifungal drug resistance, as these pathogens often exploit specific host constraints to establish a successful infection. Recent studies of adaptive responses to physiological niches have improved our understanding of the mechanisms established by fungal pathogens to evade the immune system and colonize the host, which may facilitate the design of innovative diagnostic tests and therapeutic approaches for Candida infections.

Carboxylic Acid Transporters in Candida Pathogenesis.

Opportunistic pathogens such as Candida species can use carboxylic acids, like acetate and lactate, to survive and successfully thrive in different environmental niches. These nonfermentable substrates are frequently the major carbon sources present in certain human body sites, and their efficient uptake by regulated plasma membrane transporters plays a critical role in such nutrient-limited conditions. Here, we cover the physiology and regulation of these proteins and their potential role in Candida virulence. This review also presents an evolutionary analysis of orthologues of the Saccharomyces cerevisiae Jen1 lactate and Ady2 acetate transporters, including a phylogenetic analysis of 101 putative carboxylate transporters in twelve medically relevant Candida species. These proteins are assigned to distinct clades according to their amino acid sequence homology and represent the major carboxylic acid uptake systems in yeast. While Jen transporters belong to the sialate:H+ symporter (SHS) family, the Ady2 homologue members are assigned to the acetate uptake transporter (AceTr) family. Here, we reclassify the later members as ATO (acetate transporter ortholog). The new nomenclature will facilitate the study of these transporters, as well as the analysis of their relevance for Candida pathogenesis.

Transcriptional responses of Candida glabrata biofilm cells to fluconazole are modulated by the carbon source.

Candida glabrata is an important human fungal pathogen known to trigger serious infections in immune-compromised individuals. Its ability to form biofilms, which exhibit high tolerance to antifungal treatments, has been considered as an important virulence factor. However, the mechanisms involving antifungal resistance in biofilms and the impact of host niche environments on these processes are still poorly defined. In this study, we performed a whole-transcriptome analysis of C. glabrata biofilm cells exposed to different environmental conditions and constraints in order to identify the molecular pathways involved in fluconazole resistance and understand how acidic pH niches, associated with the presence of acetic acid, are able to modulate these responses. We show that fluconazole treatment induces gene expression reprogramming in a carbon source and pH-dependent manner. This is particularly relevant for a set of genes involved in DNA replication, ergosterol, and ubiquinone biosynthesis. We also provide additional evidence that the loss of mitochondrial function is associated with fluconazole resistance, independently of the growth condition. Lastly, we propose that C. glabrata Mge1, a cochaperone involved in iron metabolism and protein import into the mitochondria, is a key regulator of fluconazole susceptibility during carbon and pH adaptation by reducing the metabolic flux towards toxic sterol formation. These new findings suggest that different host microenvironments influence directly the physiology of C. glabrata, with implications on how this pathogen responds to antifungal treatment. Our analyses identify several pathways that can be targeted and will potentially prove to be useful for developing new antifungals to treat biofilm-based infections.

Simultaneous co-localized super-resolution fluorescence microscopy and atomic force microscopy: combined SIM and AFM platform for the life sciences.

Correlating data from different microscopy techniques holds the potential to discover new facets of signaling events in cellular biology. Here we report for the first time a hardware set-up capable of achieving simultaneous co-localized imaging of spatially correlated far-field super-resolution fluorescence microscopy and atomic force microscopy, a feat only obtained until now by fluorescence microscopy set-ups with spatial resolution restricted by the Abbe diffraction limit. We detail system integration and demonstrate system performance using sub-resolution fluorescent beads and applied to a test sample consisting of human bone osteosarcoma epithelial cells, with plasma membrane transporter 1 (MCT1) tagged with an enhanced green fluorescent protein (EGFP) at the N-terminal.

Morphological and Genetic Structure of Two Equivalent Astyanax Species (Characiformes: Characidae) in the Region of Paranaíba Arc.

The Astyanax scabripinnis complex is composed of a large number of almost morphological indistinguishable species, including Astyanax paranae and Astyanax rivularis, which exist in the Paraná and São Francisco Basins, respectively, and sometimes are considered subspecies of the A. scabripinnis group or even are cited just as A. scabripinnis. The two river basins are separated by the Upper Paranaíba Arc, likely the main cause of the isolation of these species. We used geometric morphometric tools and DNA analyses of populations of both species to identify the differences between them. Geometric morphometrics separated the two species into distinct groups, whose main difference was the body depth. This is generally related to the speed of the water flow in the river basins. The maximum likelihood phylogram based on mitochondrial DNA sequences formed two main clades: one composed of the population of A. rivularis and the other, of A. paranae. In the haplotype network, the species were similarly separated into two groups from the same ancestral haplotype, with A. rivularis dispersing into two lineages in the São Francisco River Basin. The distribution of A. paranae is a consequence of a secondary dispersion event in the Paraná River Basin. It forms two lineages from a haplotype derived from the ancestor. The vicariant effect of separate basins, through the elevation of the Upper Paranaíba Arc, led to the allopatric speciation of the populations originating the present species. The results of geometric morphometrics and molecular data of the fish show the importance of this geological event in the biogeography and evolutionary history of the ichthyofauna of the region and indicate that the isolation of these species seems to be effective.

Uma Ferramenta para Desenvolver e Monitorar o Ensino da Saúde Coletiva no Curso Médico / A Tool to Develop and Monitor Collective Health Education in Medical School

RESUMO Introdução As novas Diretrizes Curriculares Nacionais do curso médico (DCN 2014) enfatizam a saúde coletiva como forma de assegurar o compromisso social na educação médica. Porém, elas não indicam claramente as competências a serem adquiridas e os conteúdos a serem trabalhados nesse campo. Essa lacuna precisa ser preenchida, tendo em vista a necessidade de orientar o vasto número de novos cursos de Medicina, que acompanhou a política do Programa Mais Médicos. Objetivos Identificar os desafios da saúde coletiva no ensino médico e construir uma ferramenta de planejamento estratégico para apoiar as escolas médicas no desenho e monitoramento desse componente do currículo de seus cursos. Metodologia A metodologia compreendeu duas etapas: 1. análise crítica de documentos-chave da educação médica (DCN e Matriz do Revalida) e 2. construção de ferramenta de planejamento estratégico para apoio à elaboração do currículo de saúde coletiva na graduação, por meio da condução de oficinas em que se utiliza o "método do mapeio de alcances". Resultados Os documentos analisados revelam grande variabilidade no entendimento do lugar da saúde coletiva na formação e nas práticas médicas. Enquanto a Matriz do Revalida, publicada em 2009, estabelece as cinco áreas médicas sem fazer alusão à saúde coletiva, as DCN, publicadas em 2014, parecem supervalorizar esse campo. Porém, como não há uma definição clara acerca das competências e dos conteúdos, muitas vezes a saúde coletiva sofre um reducionismo e aparece confundida com medicina de família e comunidade ou sobreposta a ela. As oficinas participativas tomaram como desafio a reversão dessa visão reducionista ao construírem uma ferramenta apoiada na visão do médico no futuro, tendo como missão precisar competências e conteúdos de saúde coletiva no currículo. Identificaram-se os parceiros na implementação desse componente, as atitudes e mudanças esperadas de cada parceiro e o modo de monitorar seus progressos. Conclusão A ferramenta que se baseia no método de mapeio de alcances focaliza as conquistas e mudanças das pessoas. Apresenta-se como um dispositivo flexível e participativo e pode contribuir para a construção de currículos que formem médicos comprometidos com a realidade social.

ABSTRACT Introduction The new National Curriculum Guidelines of the undergraduate medical course (DCN-2014) emphasize collective health as a way to ensure social commitment in medical education. However, they do not clearly indicate the skills to be acquired and content to be worked in this field. This gap needs to be filled, given the need to guide the vast number of new medical courses, which followed the "More Doctors" policy in Brazil. Objective To identify the challenges of collective health in medical education and to build a strategic planning tool to support medical schools in designing and monitoring this component of the curriculum of their courses. Method The method comprised two stages: 1) critical analysis of key medical education documents (DCN and REVALIDA Matrix) and 2) construction of a strategic planning tool to support the development of the collective health curriculum in undergraduate programs by conducting workshops using the "outcome mapping method'. Results The documents analyzed disclose great variability in the understanding of the collective health role in medical training and practice. While the REVALIDA Matrix, published in 2009, establishes the 5 medical areas with no reference to collective health, the DCN, published in 2014, seems to overestimate this field. However, since there is no clear definition of skills and content, collective health often suffers from reductionism and seems to be mistaken by or overlap with family and community medicine. The participatory workshops took on the challenge of reversing this reductionist vision, building a tool based on the physician's vision in the future, with the mission of requiring collective health skills and contents in the curriculum. Partners have been identified for the implementation of this component, as well as the attitudes and changes expected from each partner, and how to monitor their progress. Conclusion The tool, based on the outcome mapping method, focuses on people's achievements and changes. It is a flexible, participatory device and can contribute to the construction of curricula that will train physicians committed to the social reality.

The Palliative Care Screening Tool as an instrument for recommending palliative care for older adults / Escala Palliative Care Screening Tool como instrumento para indicação de cuidados paliativos em idosos

Abstract The objective of the present study was to evaluate the use of the Palliative Care Screening Tool (PCST) for the recommendation of palliative care among older patients admitted to an Intensive Care Unit, as well as to evaluate the prevalence of basic diseases, religion and agreement between the results of the PCST and the Palliative Performance Scale (PPS). A cross-sectional, descriptive, analytical, retrospective, documental study with a quantitative approach was performed. Analysis of 594 medical records revealed that cardiovascular diseases accounted for 26.8% of hospitalizations among older adults, followed by neoplasia 20.2% and renal failure 16.8%, and that aspects related to the religiosity and spirituality of the older adults were not considered. There was agreement of 1.0 between the PCST and PPS scales, as measured by the Kappa test, a score considered to be perfect. The PCST can therefore be considered an excellent tool for the evaluation of palliative care among older adults. It can be concluded that, in view of the significant level of agreement between the scales, new studies using the PCST with larger samples should be performed, with the aim of extending the use of the tool, and to assess if there is a need for adjustments aimed at adapting it more closely to the Brazilian population.

Resumo O objetivo do estudo foi avaliar a utilização da escala Palliative Care Screening Tool (PCST) na indicação de cuidados paliativos em idosos internados em Unidade de Terapia Intensiva, bem como, a prevalência das doenças de base, religião e concordância entre os resultados na aplicação das escalas PCST e Palliative Performance Scale (PPS). Estudo transversal, descritivo, analítico, retrospectivo, documental com abordagem quantitativa. A análise de 594 prontuários revelou que as doenças cardiovasculares corresponderam a 26,8%, das internações, seguida de neoplasias 20,2% e insuficiência renal 16,8% entre os idosos e que os aspectos relacionados a religiosidade e espiritualidade dos idosos não foram considerados. Houve concordância de 1,0 na aplicação do teste de kappa, considerada perfeita, entre as escalas PCST e PPS e, desta forma, a escala PCST pode ser um excelente instrumento na avaliação de cuidados paliativos em idosos. Conclui-se que frente ao significativo nível de concordância entre as escalas, novos estudos com amostras maiores devem ser realizados utilizando essa escala PCST, visando ampliar a utilização da mesma e analisar se há necessidade de ajustes voltados à maior adequação na população brasileira.

The Role of Candida albicans Transcription Factor RLM1 in Response to Carbon Adaptation.

Candida albicans is the main causative agent of candidiasis and one of the most frequent causes of nosocomial infections worldwide. In order to establish an infection, this pathogen supports effective stress responses to counter host defenses and adapts to changes in the availability of important nutrients, such as alternative carbon sources. These stress responses have clear implications on the composition and structure of Candida cell wall. Therefore, we studied the impact of lactate, a physiologically relevant carbon source, on the activity of C. albicans RLM1 transcriptional factor. RLM1 is involved in the cell wall integrity pathway and plays an important role in regulating the flow of carbohydrates into cell wall biosynthesis pathways. The role of C. albicans RLM1 in response to lactate adaptation was assessed in respect to several virulence factors, such as the ability to grow under cell wall damaging agents, filament, adhere or form biofilm, as well as to immune recognition. The data showed that growth of C. albicans cells in the presence of lactate induces the secretion of tartaric acid, which has the potential to modulate the TCA cycle on both the yeast and the host cells. In addition, we found that adaptation of C. albicans cells to lactate reduces their internalization by immune cells and consequent % of killing, which could be correlated with a lower exposure of the cell wall ß-glucans. In addition, absence of RLM1 has a minor impact on internalization, compared with the wild-type and complemented strains, but it reduces the higher efficiency of lactate grown cells at damaging phagocytic cells and induces a high amount of IL-10, rendering these cells more tolerable to the immune system. The data suggests that RLM1 mediates cell wall remodeling during carbon adaptation, impacting their interaction with immune cells.

Quantitative transcranial sonography in Wilson's disease and healthy controls: Cut-off values and functional correlates.

To compare transcranial sonography (TCS) findings in patients with predominantly neurological Wilson's disease (WD) to those from controls, and to correlate TCS data with the clinical profile of WD. Patients with WD (n=40/f=18) and healthy, matched controls (n=49/f=20) were assessed in terms of TCS, serum copper and iron parameters, and clinical scales, such as the Unified Wilson's Disease Rating Scale (UWDRS), Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini Mental State Examination (MMSE), and Beck Depression Inventory. Lenticular nuclei and substantia nigra echogenic area cut-off values clearly differentiated WD patients from controls (area under the curve: 95.4% and 79.4%). Substantia nigra echogenic area was significantly larger in male than in female patients (p=0.001). Compared with controls, patients showed hyperechogenicity also in thalami and midbrain tegmentum/tectum; third ventricle width was increased and midbrain axial area was reduced. In the WD group, male gender correlated with substantia nigra echogenic area (r=0.515, p=0.0007) and serum ferritin levels (r=0.479, p=0.002); lenticular nuclei hyperechogenicity correlated with dystonia (r=0.326, p=0.04) and dysarthria (r=0.334, p=0.035); third ventricle width correlated with dystonia (r=0.439 p=0.005), dysarthria (r=0.449, p=0.004), parkinsonism (r=0.527, p<0.001), UWDRS neurological and total scores (both r=0.504, p=0.0009), MMSE (r=-0.496, p=0.001), and ACE-R (r=-0.534, p=0.0004). Lenticular nuclei echogenic area allowed highly accurate discrimination between patients and controls. The gender differences in substantia nigra echogenicity and iron metabolism are of interest in further studies in WD. TCS reflects different dimensions of WD pathology clearly differentiable from healthy controls and correlating with various clinical characteristics of WD.