TNF and IL6/Jak2 signaling pathways are the main contributors of the glia-derived neuroinflammation present in Lafora disease, a fatal form of progressive myoclonus epilepsy.

Lafora disease (LD; OMIM#254780) is a rare form of progressive myoclonus epilepsy (prevalence <1:1,000,000) characterized by the accumulation of insoluble deposits of aberrant glycogen (polyglucosans), named Lafora bodies, in the brain but also in peripheral tissues. LD is the most severe form of the group of progressive myoclonus epilepsies, since patients present a rapid deterioration and dementia with amplification of seizures, leading to death after a decade from the onset of the first symptoms. We have recently described that reactive glia-derived neuroinflammation should be considered a novel hallmark of LD since we observed a florid upregulation of differentially expressed genes in both LD mouse lines, which were mainly related to mediators of inflammatory response. In this work, we define an upregulation of the expression of mediators of the TNF and IL6/JAK2 signaling pathways in LD. In addition, we describe the activation of the non-canonical form of the inflammasome. Furthermore, we describe the infiltration of peripheral immune cells in the brain parenchyma, which could aggravate glia-derived neuroinflammation. Finally, we describe CXCL10 and S100b as blood biomarkers of the disease, which will allow the study of the progression of the disease using serum blood samples. We consider that the identification of these initial inflammatory changes in LD will be very important to implement possible anti-inflammatory therapeutic strategies to prevent the development of the disease.

Living with an intestinal ostomy and urinary incontinence / Vivir con una estomía intestinal e incontinencia urinaria / Convivendo com estomia intestinal e a incontinência urinária

ABSTRACT Objective: to understand how aged people with intestinal ostomies experience this situation together with urinary incontinence. Method: a qualitative, descriptive and exploratory research study, developed with 77 aged individuals with intestinal ostomies assisted by the Unified Health System, in four municipalities from the Metropolitan Region of Florianópolis. Data collection was conducted using semi-structured interviews from October 2019 to February 2020. The theoretical framework used was Dorothéa Orem's Self-Care Theory and the data were submitted to content analysis, in its thematic modality. Results: the analysis allowed generating three thematic categories: 1) Feelings generated by the intestinal ostomy and urinary incontinence: acceptance, denial, fear, insecurity, constraints experienced due to the ostomy and to the urinary incontinence symptoms; 2) Lifestyle changes; and 3) Deficit in self-image. Conclusion: it was evidenced that, for most of the research participants, it is difficult to accept the experience of living with an intestinal ostomy and urinary incontinence, which generally produce negative feelings. However, the participants proved to be resilient and able to adapt to the changes in lifestyle. Many of these behaviors are due to the health professionals' important contribution in providing them the necessary attention, encouraging self-care strategies in both situations.

RESUMEN Objetivo: comprender de qué manera los ancianos con ostomías intestinales viven esta situación junto con la incontinencia urinaria. Método: investigación cualitativa, descriptiva y exploratoria, desarrollada con 77 ancianos con estomías intestinales atendidos por el Sistema Único de Salud en cuatro municipios de la Región Metropolitana de Florianópolis. La recolección de datos se realizó entre octubre de 2019 y febrero de 2020 por medio de entrevistas semiestructuradas. El marco de referencia teórico empleado fue la Teoría de Autocuidado de Dorothéa Orem; los datos se sometieron a análisis de contenido, en su modalidad temática. Resultados: el análisis permitió generar tres categorías temáticas: 1) Sentimientos generados por la estomía intestinal y por la incontinencia urinaria: aceptación, negación, miedo, inseguridad, restricciones experimentadas a raíz de la ostomía y de los síntomas de la incontinencia urinaria; 2) Cambios en el estilo de vida; y 3) Déficit en la imagen propia. Conclusión: se hizo evidente que a la mayoría de los participantes de la investigación les resulta difícil aceptar la vida con una estomía intestinal e incontinencia urinaria, que generalmente les provocan sentimientos negativos. Sin embargo, los participantes se mostraron resilientes y aptos para adaptarse a los cambios en el estilo de vida. Muchos de estos comportamientos se deben al importante aporte de los profesionales de la salud al brindarles la atención necesaria, estimulando estrategias de autocuidado en ambas situaciones.

RESUMO Objetivo: compreender como o idoso com estomia intestinal vivencia essa situação em conjunto com a incontinência urinária. Método: pesquisa qualitativa, descritiva e exploratória, desenvolvida junto a 77 idosos com estomia intestinal atendidos pelo Sistema Único de Saúde, em quatro municípios da Região Metropolitana de Florianópolis. A coleta de dados foi realizada de outubro/2019 a fevereiro/2020, por meio de entrevista semiestruturada. O referencial teórico utilizado foi a Teoria de Autocuidado de Dorothéa Orem; os dados foram submetidos à análise de conteúdo, na modalidade temática. Resultados: a análise permitiu a geração de três categorias temáticas: 1) sentimentos gerados pela estomia intestinal e pela incontinência urinária: aceitação, negação, medo, insegurança, constrangimentos vivenciados pela estomia e os sintomas da incontinência urinária; 2) alterações do estilo de vida; 3) déficit na autoimagem. Conclusão: evidenciou-se que para a maioria dos participantes da pesquisa é difícil aceitar a vivência com estomia intestinal e incontinência urinária, que geralmente lhes provocam sentimentos negativos. No entanto, os participantes mostraram-se resilientes e aptos a se adaptar às mudanças no estilo de vida. Muitos desses comportamentos se devem à importante contribuição dos profissionais da saúde em dar-lhes a necessária atenção, estimulando estratégias de autocuidado em ambas as situações.

Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice.

Oropouche virus (OROV) infection of humans is associated with a debilitating febrile illness that can progress to meningitis or encephalitis. First isolated from a forest worker in Trinidad and Tobago in 1955, the arbovirus OROV has since been detected throughout the Amazon basin with an estimated 500,000 human infections over 60 years. Like other members of the family Peribunyaviridae, the viral genome exists as 3 single-stranded negative-sense RNA segments. The medium-sized segment encodes a viral glycoprotein complex (GPC) that is proteolytically processed into two viral envelope proteins, Gn and Gc, responsible for attachment and membrane fusion. There are no therapeutics or vaccines to combat OROV infection, and we have little understanding of protective immunity to infection. Here, we generated a replication competent chimeric vesicular stomatitis virus (VSV), in which the endogenous glycoprotein was replaced by the GPC of OROV. Serum from mice immunized by intramuscular injection with VSV-OROV specifically neutralized wild-type OROV, and using peptide arrays we mapped multiple epitopes within an N-terminal variable region of Gc recognized by the immune sera. VSV-OROV lacking this variable region of Gc was also immunogenic in mice producing neutralizing sera that recognize additional regions of Gc. Challenge of both sets of immunized mice with wild-type OROV shows that the VSV-OROV chimeras reduce wild-type viral infection and suggest that antibodies that recognize the variable N terminus of Gc afford less protection than those that target more conserved regions of Gc. IMPORTANCE Oropouche virus (OROV), an orthobunyavirus found in Central and South America, is an emerging public health challenge that causes debilitating febrile illness. OROV is transmitted by arthropods, and increasing mobilization has the potential to significantly increase the spread of OROV globally. Despite this, no therapeutics or vaccines have been developed to combat infection. Using vesicular stomatitis (VSV) as a backbone, we developed a chimeric virus bearing the OROV glycoproteins (VSV-OROV) and tested its ability to elicit a neutralizing antibody response. Our results demonstrate that VSV-OROV produces a strong neutralizing antibody response that is at least partially targeted to the N-terminal region of Gc. Importantly, vaccination with VSV-OROV reduces viral loads in mice challenged with wild-type virus. These data provide novel evidence that targeting the OROV glycoproteins may be an effective vaccination strategy to combat OROV infection.

Detection of respiratory viruses in primary cholesteatoma tissues.

Cholesteatomas are frequent middle ear benign tumors of unknown etiology. Infectious agents have been considered as possible contributing factors in the pathogenesis of cholesteatomas. Aiming to investigate the presence of respiratory viruses in primary cholesteatoma tissues, 26 formalin-fixed paraffin-embedded primary cholesteatoma tissues obtained from patients seen at the of the Clinical Hospital of the University of São Paulo School of Medicine, in Ribeirão Preto, Brazil were tested by real-time polymerase chain reaction (PCR). Considering the PCR results, 35% of the tissues were positive for human rhinovirus (HRV), 15.3% for human enterovirus (EV), 3.8% for human metapneumovirus (HMPV), and 3.8% for human bocavirus (HBoV). Serial immunohistochemistry for virus antigens and cell surface markers evidenced that the viruses were associated with fibroblasts, dendritic cells, macrophages, B lymphocytes, CD4+ , and CD8+ T lymphocytes. These findings indicate for the first time the presence of active respiratory virus infection in primary cholesteatoma tissues, suggesting that persisting virus infection in the middle could play a role in the pathogenesis and evolution of cholesteatomas.

Human Respiratory Syncytial Virus Infection in a Human T Cell Line Is Hampered at Multiple Steps.

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory disease in children. The main targets of HRSV infection are epithelial cells of the respiratory tract, and the great majority of the studies regarding HRSV infection are done in respiratory cells. Recently, the interest on respiratory virus infection of lymphoid cells has been growing, but details of the interaction of HRSV with lymphoid cells remain unknown. Therefore, this study was done to assess the relationship of HRSV with A3.01 cells, a human CD4+ T cell line. Using flow cytometry and fluorescent focus assay, we found that A3.01 cells are susceptible but virtually not permissive to HRSV infection. Dequenching experiments revealed that the fusion process of HRSV in A3.01 cells was nearly abolished in comparison to HEp-2 cells, an epithelial cell lineage. Quantification of viral RNA by RT-qPCR showed that the replication of HRSV in A3.01 cells was considerably reduced. Western blot and quantitative flow cytometry analyses demonstrated that the production of HRSV proteins in A3.01 was significantly lower than in HEp-2 cells. Additionally, using fluorescence in situ hybridization, we found that the inclusion body-associated granules (IBAGs) were almost absent in HRSV inclusion bodies in A3.01 cells. We also assessed the intracellular trafficking of HRSV proteins and found that HRSV proteins colocalized partially with the secretory pathway in A3.01 cells, but these HRSV proteins and viral filaments were present only scarcely at the plasma membrane. HRSV infection of A3.01 CD4+ T cells is virtually unproductive as compared to HEp-2 cells, as a result of defects at several steps of the viral cycle: Fusion, genome replication, formation of inclusion bodies, recruitment of cellular proteins, virus assembly, and budding.

Desafios para enfermeiros e fisioterapeutas assistirem mulheres idosas com incontinência urinária / Challenges for nurses and physiotherapeuts to assist old women with urinary incontinence

estudo qualitativo, do tipo exploratório-descritivo, com análise temática descritiva. Foram realizadas entrevistas semiestruturadas com 10 enfermeiros e 14 fisioterapeutas atuantes em um Distrito Sanitário de Saúde de uma capital do Sul do Brasil. Resultados: os achados ratificam que o cuidado à população idosa fica fragmentado dentro da Atenção Primária de Saúde. Os idosos são atendidos de acordo com a doença crônica que possuem ou a queixa principal que apresentam. O mesmo ocorre com relação à incontinência urinária, que não é investigada nem priorizada no cuidado. Conclusão: é necessária uma educação permanente ou capacitação para que os profissionais possam responder aos desafios do envelhecimento populacional, em todos os aspectos da saúde, com vistas ao autocuidado. (AU)

Objective: To know how nurses and physiotherapists care for elderly women with urinary incontinence in Primary Health Care. Method: qualitative, exploratory-descriptive study, with descriptive thematic analysis. Semi-structured interviews were conducted with 10 nurses and 14 physiotherapists working in a Health District of a capital of southern Brazil. Results: the findings confirm that care for the elderly population is fragmented within Primary Health Care. The elderly are treated according to their chronic disease or their main complaint. The same is true of urinary incontinence, which is neither investigated nor prioritized in care. Conclusion: Continuing education or training is necessary for professionals to respond to the challenges of population aging, in all aspects of health, with a view to self-care. (AU)

Objectivo: conocer cómo las enfermeras y fisioterapeutas atienden a las mujeres mayores con incontinencia urinaria en atención primaria de salud. Metodo: estudio cualitativo, exploratorio-descriptivo, con análisis descriptivo temático. Se realizaron entrevistas semiestructuradas con 10 enfermeras y 14 fisioterapeutas que trabajan en un distrito de salud de una capital del sur de Brasil. Resultados: los hallazgos confirman que la atención a la población anciana está fragmentada dentro de la Atención Primaria de Salud. Los ancianos son tratados de acuerdo con su enfermedad crónica o su queja principal. Lo mismo ocurre con la incontinencia urinaria, que no se investiga ni se prioriza en la atención. Conclusión: la educación o capacitación continua es necesaria para que los profesionales respondan a los desafíos del envejecimiento de la población, en todos los aspectos de la salud, con miras al autocuidado. (AU)

Regulation of the autophagic PI3KC3 complex by laforin/malin E3-ubiquitin ligase, two proteins involved in Lafora disease.

Lafora progressive myoclonus epilepsy is a fatal rare neurodegenerative disorder characterized by the accumulation of insoluble abnormal glycogen deposits in the brain and peripheral tissues. Mutations in at least two genes are responsible for the disease: EPM2A, encoding the glucan phosphatase laforin, and EPM2B, encoding the RING-type E3-ubiquitin ligase malin. Both laforin and malin form a functional complex in which laforin recruits the substrates to be ubiquitinated by malin. We and others have described that, in cellular and animal models of this disease, there is an autophagy impairment which leads to the accumulation of dysfunctional mitochondria. In addition, we established that the autophagic defect occurred at the initial steps of autophagosome formation. In this work, we present evidence that in cellular models of the disease there is a decrease in the amount of phosphatidylinositol-3P. This is probably due to defective regulation of the autophagic PI3KC3 complex, in the absence of a functional laforin/malin complex. In fact, we demonstrate that the laforin/malin complex interacts physically and co-localizes intracellularly with core components of the PI3KC3 complex (Beclin1, Vps34 and Vps15), and that this interaction is specific and results in the polyubiquitination of these proteins. In addition, the laforin/malin complex is also able to polyubiquitinate ATG14L and UVRAG. Finally, we show that overexpression of the laforin/malin complex increases PI3KC3 activity. All these results suggest a new role of the laforin/malin complex in the activation of autophagy via regulation of the PI3KC3 complex and explain the defect in autophagy described in Lafora disease.

The daily lives of people with Parkinson's disease / El cotidiano de las personas con la enfermedad de Parkinson / O cotidiano das pessoas com a doença de Parkinson

ABSTRACT Objective: To understand the daily lives of people with Parkinson's disease. Method: Qualitative research, using as methodological and theoretical referential the Grounded Theory and Symbolic Interactionism, respectively. The in-depth interview was conducted with 30 people with Parkinson's disease. Results: From data analysis, three themes were selected: Living with the disease - living with the treatment and changes in lifestyle; Modifying of one's job performance - revealing incapacity for work and the need to anticipate retirement and; Living with the stigma - the feeling of prejudice against the disease and the perceived limitations of the health services. Final considerations: Living with a chronic and non-transferable disease encompasses social, physical and cultural effects, along with the personal experiences of each unique individual. This study assists the improvement of care to people with the disease, because the care practice emerges from the interactions between the subjects.

RESUMEN Objetivo: Comprender el cotidiano de las personas con la enfermedad de Parkinson. Método: Investigación cualitativa, utilizando como referencial metodológico y teórico la Teoría Fundamentada en Datos y el Interaccionismo Simbólico, respectivamente. La entrevista en profundidad fue realizada con 30 personas con la enfermedad de Parkinson. Resultados: Por medio de la codificación de los datos, emergieron tres categorías: Viviendo la rutina de la enfermedad: la convivencia con el tratamiento y las modificaciones en vivir; Modificando su rendimiento en el trabajo: revelando incapacidad para el trabajo y la necesidad de anticipar la jubilación y; Conviviendo con estigmas: el sentimiento de prejuicio por la enfermedad y la percepción de limitaciones de los servicios de salud. Consideraciones finales: La convivencia con una enfermedad crónica no transmisible engloba efectos sociales, físicos, culturales y las experiencias personales de cada uno. Este estudio auxilia la mejora de la asistencia a las personas con la enfermedad, pues la práctica de cuidados emerge de las interacciones entre los sujetos.

RESUMO Objetivo: Compreender o cotidiano das pessoas com a doença de Parkinson. Método: Pesquisa qualitativa, utilizando como referencial metodológico e teórico a Teoria Fundamentada nos Dados e o Interacionismo Simbólico, respectivamente. A entrevista em profundidade foi realizada com 30 pessoas com a doença de Parkinson. Resultados: Por meio da codificação dos dados, emergiram três categorias: Vivendo a rotina da doença - a convivência com o tratamento e as modificações no viver; Modificando seu desempenho no trabalho - revelando incapacidade para o trabalho e a necessidade de antecipar a aposentadoria e; Convivendo com estigmas - o sentimento de preconceito pela doença e a percepção de limitações dos serviços de saúde. Considerações finais: A convivência com uma doença crônica não transmissível engloba efeitos sociais, físicos, culturais e as experiências pessoais de cada um. Este estudo auxilia no aprimoramento da assistência às pessoas com a doença, pois a prática de cuidados emerge das interações entre os sujeitos.

Urinary incontinence in elderly people: care practices and care proposal in primary health care / Incontinencia urinaria en mujeres ancianas: prácticas de cuidado y propuesta de cuidados en el contexto de la atención primaria salud / Incontinência urinária em idosas: práticas assistenciais e proposta de cuidado âmbito da atenção primária de saúde

ABSTRACT Objective: identify the knowledge and care practices concerning urinary incontinence in elderly women and develop a care proposal for these women for the purpose of health promotion in Primary Health Care. Method: a qualitative, convergent care research was undertaken. The data were collected between August and October 2014 through semistructured interviews and thematic workshops with 14 physiotherapists and ten nurses. The analysis involved apprehension, synthesis, theorization and transference processes, revealing two thematic axes: the professionals' perception of urinary incontinence in elderly women; and the conception of a care proposal for elderly women with urinary incontinence. Results: the professionals' limited knowledge of urinary incontinence was verified, as well as the lack of information on the possible orientations for self-care concerning the urinary symptoms. Conclusion: training actions should be implemented for these professionals with a view to health promotion for self-care.

RESUMEN Objetivo: identificar los conocimientos y prácticas de cuidado de la incontinencia urinaria en mujeres ancianas y desarrollar propuesta de la atención a estas mujeres para promover la salud en el contexto de la atención primaria de salud. Método: investigación cualitativa, el tipo de investigación atención convergente, cuyos datos fueron recolectados entre agosto y octubre / 2014 a través de entrevistas semiestructuradas y talleres temáticos con 14 fisioterapeutas y 10 enfermeras. El análisis incluyó la confiscación de los procesos, la síntesis, teorización y transferencia, dando lugar a dos temas principales: la percepción de los profesionales sobre la incontinencia urinaria en mujeres de edad avanzada; y el diseño de una atención propuesta a anciana con incontinencia urinaria. Resultados: se encontró el poco conocimiento de los profesionales acerca de la incontinencia urinaria, así como la falta de información sobre las posibilidades de directrices para el cuidado personal respecto a los síntomas urinarios. Conclusión: se recomienda llevar a cabo actividades de formación con estos profesionales, con el objetivo de promoción de la salud para el autocuidado.

RESUMO Objetivo: identificar o conhecimento e as práticas assistenciais sobre a incontinência urinária em mulheres idosas e desenvolver proposta de cuidado a essas mulheres para a promoção da saúde no âmbito da atenção primária de saúde. Método: pesquisa qualitativa, do tipo convergente-assistencial, cujos dados foram coletados entre agosto e outubro/2014, através de entrevistas semiestruturadas e oficinas temáticas com 14 fisioterapeutas e dez enfermeiros. A análise envolveu processos de apreensão, síntese, teorização e transferência, fazendo emergir dois eixos temáticos: percepção dos profissionais acerca da incontinência urinária em mulheres idosas; e a concepção de uma proposta de cuidado à mulher idosa com incontinência urinária. Resultados: constatou-se o pouco conhecimento dos profissionais acerca da incontinência urinária, bem como a falta de informação em relação às possibilidades de orientações para o autocuidado a respeito dos sintomas urinários. Conclusão: recomenda-se implementar ações de capacitação com estes profissionais, com vistas à promoção da saúde para o autocuidado.

Comportamento sexual das mulheres em tratamento radioterápico / Sexual behavior of women in radiotherapytreatment

Women with cancer undergoing radiotherapy, radiotherapy and / or brachytherapy may change in sexual behavior, with influence on psychosocial, sexual and functional aspects as well as quality of life. This study aims to analyze the scientific evidence related to sexual behavior and quality of life of women who underwent radiotherapy. It is literature type integrative review. Data collection was conducted in May 2014 and was carried out through the Virtual Health Library, from the bottom of LILACS and MEDLINE, by combining the descriptors: "sexual behavior and radiotherapy" and "sexual behavior and brachytherapy". They selected 23 studies for the sample with no time limit. With the intention of promoting the contributions the production of knowledge about sexual behavior / symptoms after cancer treatment in women with brachytherapy and radiation, emerging two main themes: psychosocial, sexual and functional changes; quality of life. Identifies what is needed directed multidisciplinary action women with cancer in relation to sexuality, there are weaknesses in the care geared to these. Such assistance needs to be planned for the woman and her partner, so that living with cancer and treatment is quality.

As mulheres com câncer submetidas à radioterapia, teleterapia e/ou braquiterapia podem ter alteração nocomportamento sexual, com influência nos aspectos psicossociais, sexuais e funcionais, bem como na qualidade de vida. Este estudo tem como objetivo analisar as evidências científicas relacionadas ao comportamento sexual e qualidade de vida de mulheres que realizaram tratamento com radioterapia. Trata-se de pesquisa bibliográfica do tipo revisão integrativa. A coleta dos dados foi realizada no mês de maio de 2014, e ocorreu por meio da Biblioteca Virtual em Saúde, a partir das bases de dados LILACS e MEDLINE, através da combinação dos descritores: "sexual behaviorandradiotherapy" e "sexual behaviorandbrachytherapy". Foram selecionados 23 estudos para compor a amostra sem tempo limite. Com a intenção de promover os contributos da produção do conhecimento sobre o comportamento sexual/sintomas após tratamento de câncer em mulheres com braquiterapia e radioterapia, emergindo dois eixos temáticos: alterações psicossociais, sexuais e funcionais; qualidade de vida. Identifica-se que é necessária ação multidisciplinar direcionada as mulheres com câncer em relação à sexualidade, há fragilidade no cuidado voltado a essas. Tal assistência necessita ser planejada para a mulher e seu parceiro, de forma que a convivência com o câncer e tratamento seja de qualidade.

Evaluation and classification of vaginal stenosis after brachytherapy / Evaluación y clasificación de estenosis después de la branquiterapia vaginal / Avaliação e classificação da estenose vaginal pós-braquiterapia

ABSTRACT This narrative review identified, in the scientific production, the methods used for evaluating and classifying vaginal stenosis in women who have undergone brachytherapy. Data collection was undertaken in July 2013 in the publications of SciELO, MEDLINE and PubMed, without time limits, and in studies cited by two scientific reviews which addressed the issue investigated here. The search protocol included the description of the method for evaluating and classifying vaginal stenosis. Comparative analysis between the findings showed there to be diversity among the methods used by different researchers. In the light of this finding, this study proposes elements for making an evaluative instrument to be applied by nurses. The standardization of the technique will help in the early detection of vaginal stenosis and in the care for women subsequent to vaginal brachytherapy.

RESUMEN Revisión narrativa que identificó en los métodos de producción científicos utilizados para la evaluación y clasificación de las estenosis vaginal en mujeres después de braquiterapia vaginal. La recolección de datos se llevó a cabo en julio de 2013 en las publicaciones de la SciELO, Medline y PubMed, sin límite de tiempo, y estudios citados dos revisiones científicas que abordan el tema investigado aquí. El protocolo de búsqueda incluyó la descripción del método para la evaluación y clasificación de la estenosis vaginal. Análisis comparativo de los resultados mostró que existen diferencias entre los métodos utilizados por diferentes investigadores. Teniendo en cuenta este resultado, este estudio propone constituyentes para hacer un instrumento de evaluación para ser utilizado por las enfermeras. La estandarización de la técnica le ayudará en la detección precoz de la estenosis vaginal y atención a la mujer después de la braquiterapia vaginal.

RESUMO Revisão narrativa que identificou, na produção científica, os métodos utilizados para avaliação e classificação da estenose vaginal em mulheres pós-braquiterapia. A coleta de dados foi realizada em julho 2013 nas publicações da SciELO, MEDLINE e PubMed, sem limite de tempo, e em estudos citados por duas revisões científicas que abordam a temática aqui investigada. O protocolo de busca incluiu a descrição do método para avaliação e classificação da estenose vaginal. Análise comparativa entre os achados mostrou que há diversidade entre os métodos utilizados por diferentes pesquisadores. Diante deste achado, este estudo propõe constituintes para composição de instrumento avaliativo a ser aplicado por enfermeiros. A padronização da técnica auxiliará na detecção precoce da estenose vaginal e nos cuidados à mulher pós-braquiterapia vaginal.

The laforin/malin E3-ubiquitin ligase complex ubiquitinates pyruvate kinase M1/M2.

BACKGROUND: Lafora disease (LD, OMIM 254780) is a fatal neurodegenerative disorder produced mainly by mutations in two genes: EPM2A, encoding the dual specificity phosphatase laforin, and EPM2B, encoding the E3-ubiquitin ligase malin. Although it is known that laforin and malin may form a functional complex, the underlying molecular mechanisms of this pathology are still far from being understood. METHODS: In order to gain information about the substrates of the laforin/malin complex, we have carried out a yeast substrate-trapping screening, originally designed to identify substrates of protein tyrosine phosphatases. RESULTS: Our results identify the two muscular isoforms of pyruvate kinase (PKM1 and PKM2) as novel interaction partners of laforin. CONCLUSIONS: We present evidence indicating that the laforin/malin complex is able to interact with and ubiquitinate both PKM1 and PKM2. This post-translational modification, although it does not affect the catalytic activity of PKM1, it impairs the nuclear localization of PKM2.

O uso da eletroestimulação no nervo tibial posterior no tratamento da incontinência urinária / Electrostimulation of the posterior tibial nerve in treatment of urinary incontinence / Uso de la electroestimulación en el nervio tibial posterior en el tratamiento de la incontinencia urinaria

O objetivo deste estudo foi avaliar a eletroestimulação no nervo tibial posterior no tratamento da incontinência urinária de urgência ou mista. Trata-se de uma pesquisa quase experimental com oito pacientes, com diagnóstico de incontinência urinária de urgência ou mista, realizada no Estado de Santa Catarina, em 2010. A avaliação incluiu ficha de avaliação fisioterapêutica, diário miccional e questionário de qualidade de vida - King’s Health Questionnaire. Foram realizados 12 atendimentos de 30 minutos com eletroestimulação no nervo tibial posterior. Os resultados mostram redução na frequência de perdas urinárias diurnas em 62% das pacientes, diminuição da frequência miccional noturna em 37,5% e redução da quantidade das perdas urinárias, de intensa para moderada e de moderada para leve. Não se observou diferença significativa nos escores do questionário de qualidade de vida após o tratamento. Conclui-se que o método estudado apresentou impacto positivo nas pacientes em relação às perdas involuntárias de urina e à quantidade de urina perdida...

The aim of this study was to evaluate electrostimulation of the posterior tibial nerve in treating urgency or mixed urinary incontinence. This quasi-experimental study of eight patients with a diagnosis of urgency or mixed urinary incontinence, was conducted in Santa Catarina State, Brazil, in 2010. The assessment included a physical therapy evaluation form, bladder diary and King’s Health Quality of Life Questionnaire. Twelve 30-minutes procedures of electro-stimulation of the posterior tibial nerve were performed. The results show reduced frequency of daytime urinary incontinence in 62% of the patients, decreased nocturnal urinary frequency in 37.5%, and reduction of urinary leakage from severe to moderate and moderate to mild. No significant difference in quality of life questionnaire scores was observed after treatment. It was concluded that the method studied had positive impact on patients’ involuntary urine loss and the amount of urine lost...

El objetivo de este estudio fue evaluar la electroestimulación del nervio tibial posterior en el tratamiento de la incontinencia urinaria de urgencia o mixta. Se trata de una investigación casi experimental con ocho pacientes, con diagnóstico de incontinencia urinaria de urgencia o mixta, realizada en el Estado de Santa Catarina – Brasil, en 2010. La evaluación incluye ficha de evaluación fisioterapéutica, diario miccional y cuestionario de calidad de vida King’s Health Questionnaire. Se realizaron 12 atenciones de 30 minutos con electroestimulación del nervio tibial posterior. Los resultados muestran reducción en la frecuencia de pérdidas urinarias diurnas en 62% de las pacientes, disminución de la frecuencia miccional nocturna en 37,5% y reducción de la cantidad de orina de las pérdidas urinarias, de intensa a moderada y de moderada a leve. No se observó diferencia significativa en los resultados del cuestionario de calidad de vida después del tratamiento. Se concluye que el método estudiado presentó impacto positivo en las pacientes con relación a las pérdidas involuntarias de orina y a la cantidad de orina perdida...

Tumor suppressor p27(Kip1) undergoes endolysosomal degradation through its interaction with sorting nexin 6.

A large body of evidence supports the hypothesis that proteasomal degradation of the growth suppressor p27(Kip1) (p27) facilitates mammalian cell cycle progression. However, very few studies have addressed the possibility of proteasome-independent mechanisms of p27 proteolysis. Here we provide evidence for a novel pathway of p27 degradation via the lysosome that is mediated by its interaction with the endosomal protein sorting nexin 6 (SNX6), a member of the sorting nexin family of vesicular trafficking regulators. p27 and SNX6 interact in vitro and in vivo in mammalian cells, partially colocalize in endosomes, and are present in purified endosomal fractions. Gain- and loss-of-function studies revealed that SNX6 induces endosomal accumulation of p27. Moreover, p27 is detected in lysosomes and inhibition of lysosome-dependent proteolysis impairs serum-mediated down-regulation of p27 in a SNX6-dependent manner. To validate the localization of p27 in these organelles, we analyzed several cell lines using two different anti-p27 antibodies, several organelle-specific markers [e.g., early endosome antigen 1, lysosomal-associated membrane protein (LAMP) 1, LAMP2, and LysoTracker], and overexpression of fluorescent p27 and SNX6. Remarkably, silencing of SNX6 attenuates p27 down-regulation in the G(1) phase of the mitotic cell cycle and delays cell cycle progression. We therefore conclude that, in addition to the proteasome-dependent pathway, SNX6-mediated endolysosomal degradation of p27 also contributes to cell cycle progression in mammalian cells.

A conserved sequence immediately N-terminal to the Bateman domains in AMP-activated protein kinase gamma subunits is required for the interaction with the beta subunits.

Mammalian AMP-activated protein kinase is a serine/threonine protein kinase that acts as a sensor of cellular energy status. AMP-activated protein kinase is a heterotrimer of three different subunits, i.e. alpha, beta, and gamma, with alpha being the catalytic subunit and beta and gamma having regulatory roles. Although several studies have defined different domains in alpha and beta involved in the interaction with the other subunits of the complex, little is known about the regions of the gamma subunits involved in these interactions. To study this, we have made sequential deletions from the N termini of the gamma subunit isoforms and studied the interactions with alpha and beta subunits, both by two-hybrid analysis and by co-immunoprecipitation. Our results suggest that a conserved region of 20-25 amino acids in gamma1, gamma2, and gamma3, immediately N-terminal to the Bateman domains, is required for the formation of a functional, active alphabetagamma complex. This region is required for the interaction with the beta subunits. The interaction between the alpha and gamma subunits does not require this region and occurs instead within the Bateman domains of the gamma subunit, although the alpha-gamma interaction does appear to stabilize the beta-gamma interaction. In addition, sequential deletions from the C termini of the gamma subunits indicate that deletion of any of the CBS (cystathionine beta-synthase) motifs prevents the formation of a functional complex with the alpha and beta subunits.

Açäo educativa na pesquisa ambiental: a proposta do projeto APA-VIVA / Educational action on the environmental: a proposal to APA-VIVA project

Este trabalho visa contribuir para o debate acerca do papel da Universidade na problemática ambiental apresentando a proposta de atuaçao da linha de Pesquisas Ambientais da Universidade Sao Francisco-USF com o projeto APAVIVA.