Isogenic enteric neural progenitor cells can replace missing neurons and glia in mice with Hirschsprung disease

BACKGROUND: Transplanting autologous patient-derived enteric neuronal stem/progenitor cells (ENSCs) is an innovative approach to replacing missing enteric neurons in patients with Hirschsprung disease (HSCR). Using autologous cells eliminates immunologic and ethical concerns raised by other cell sources. However, whether postnatal aganglionic bowel is permissive for transplanted ENSCs and whether ENSCs from HSCR patients can be successfully isolated, cultured, and transplanted in vivo remains unknown. METHODS: ENSCs isolated from the ganglionic intestine of Ednrb-/- mice (HSCR-ENSCs) were characterized immunohistochemically and evaluated for their capacity to proliferate and differentiate in vitro. Fluorescently labeled ENSCs were co-cultured ex vivo with aganglionic Ednrb-/- colon. For in vivo transplantation, HSCR-ENSCs were labeled with lentivirus expressing green fluorescent protein (GFP) and implanted into aganglionic embryonic chick gut in ovo and postnatal aganglionic Ednrb-/- rectum in vivo. KEY RESULTS: HSCR-ENSCs maintain normal capacity self-renewal and neuronal differentiation. Moreover, the Ednrb-/- aganglionic environment is permissive to engraftment by wild-type ENSCs ex vivo and supports migratrion and neuroglial differentiation of these cells following transplantation in vivo. Lentiviral GFP-labeled HSCR-ENSCs populated embryonic chick hindgut and postnatal colon of Ednrb-/- HSCR, with cells populating the intermuscular layer and forming enteric neurons and glia. CONCLUSIONS & INFERENCES: ENSCs can be isolated and cultured from mice with HSCR, and transplanted into the aganglionic bowel of HSCR littermates to generate enteric neuronal networks. These results in an isogenic model establish the potential of using autologous-derived stem cells to treat HSCR and other intestinal neuropathies

Corporate Security Responsibility: Towards a Conceptual Framework for a Comparative Research Agenda

The political debate about the role of business in armed conflicts has increasingly raised expectations as to governance contributions by private corporations in the fields of conflict prevention, peace-keeping and postconflict peace-building. This political agenda seems far ahead of the research agenda, in which the negative image of business in conflicts, seen as fuelling, prolonging and taking commercial advantage of violent conflicts,still prevails. So far the scientific community has been reluctant to extend the scope of research on ‘corporate social responsibility’ to the area of security in general and to intra-state armed conflicts in particular. As a consequence, there is no basis from which systematic knowledge can be generated about the conditions and the extent to which private corporations can fulfil the role expected of them in the political discourse. The research on positive contributions of private corporations to security amounts to unconnected in-depth case studies of specific corporations in specific conflict settings. Given this state of research, we develop a framework for a comparative research agenda to address the question: Under which circumstances and to what extent can private corporations be expected to contribute to public security

Monte Carlo simulations of radio pulses in atmospheric showers using ZHAireS

We present predictions for the radio pulses emitted by extensive air showers using ZHAireS, an AIRES-based Monte Carlo code that takes into account the full complexity of ultra-high energy cosmic-ray induced shower development in the atmosphere, and allows the calculation of the electric field in both the time and frequency domains. We do not presuppose any emission mechanism, but our results are compatible with a superposition of geomagnetic and charge excess radio emission effects. We investigate the polarization of the electric field as well as the effects of the refractive index n and shower geometry on the radio pulses. We show that geometry, coupled to the relativistic effects that appear when using a realistic n>1, play a prominent role on the radio emission of air showers.Comment: Replaced with version published in Astroparticle Physic

DNA repair modulates the vulnerability of the developing brain to alkylating agents

Neurons of the developing brain are especially vulnerable to environmental agents that damage DNA (i.e., genotoxicants), but the mechanism is poorly understood. The focus of the present study is to demonstrate that DNA damage plays a key role in disrupting neurodevelopment. To examine this hypothesis, we compared the cytotoxic and DNA damaging properties of the methylating agents methylazoxymethanol (MAM) and dimethyl sulfate (DMS) and the mono- and bifunctional alkylating agents chloroethylamine (CEA) and nitrogen mustard (HN2), in granule cell neurons derived from the cerebellum of neonatal wild type mice and three transgenic DNA repair strains. Wild type cerebellar neurons were significantly more sensitive to the alkylating agents DMS and HN2 than neuronal cultures treated with MAM or the half-mustard CEA. Parallel studies with neuronal cultures from mice deficient in alkylguanine DNA glycosylase (Aag[superscript −/−]) or O6-methylguanine methyltransferase (Mgmt[superscript −/−]), revealed significant differences in the sensitivity of neurons to all four genotoxicants. Mgmt−/− neurons were more sensitive to MAM and HN2 than the other genotoxicants and wild type neurons treated with either alkylating agent. In contrast, Aag[superscript −/−] neurons were for the most part significantly less sensitive than wild type or Mgmt[superscript −/−] neurons to MAM and HN2. Aag[superscript −/−] neurons were also significantly less sensitive than wild type neurons treated with either DMS or CEA. Granule cell development and motor function were also more severely disturbed by MAM and HN2 in Mgmt[superscript −/−] mice than in comparably treated wild type mice. In contrast, cerebellar development and motor function were well preserved in MAM-treated Aag[superscript −/−] or MGMT-overexpressing (Mgmt[superscript Tg+]) mice, even as compared with wild type mice suggesting that AAG protein increases MAM toxicity, whereas MGMT protein decreases toxicity. Surprisingly, neuronal development and motor function were severely disturbed in Mgmt[superscript Tg+] mice treated with HN2. Collectively, these in vitro and in vivo studies demonstrate that the type of DNA lesion and the efficiency of DNA repair are two important factors that determine the vulnerability of the developing brain to long-term injury by a genotoxicant.United States. Army Medical Research and Materiel Command (Contract/Grant/Intergovernmental Project Order DAMD 17-98-1-8625)United States. National Institutes of Health (grants CA075576)United States. National Institutes of Health (RO1 C63193)United States. National Institutes of Health (P30 CA043703

ESTRATÉGIAS UTILIZADAS NO CUIDADO A PESSOAS HIPERTENSAS NO DOMICILIO: REFLEXÕES ACERCA DO PAPEL DA EQUIPE MULTIPROFISSIONAL DE SAÚDE

Introduction: primary health care is the first contact of users with public health, and is responsible for offering promotional, preventive and curative actions to the population, with home care having grown as a result of geographic, epidemiological, social and cultural practices that have been spreading around the world, seeking a care proposal that promotes greater comfort and well-being for families, including the public with chronic diseases, such as Systemic Arterial Hypertension. Objective: to reflect on the strategies used by the multiprofessional health team in the care of hypertensive patients at home, and to transcend a reflection related to the prevalent difficulties for these patients. Method: this is a narrative review. The search took place in the following databases: Lilacs, Bdenf and the SciELO portal, with the inclusion criteria, articles published in full that addressed the theme, theses, dissertations, books and documents in Portuguese, English and Spanish. Duplicate studies, in languages ​​other than those selected and studies available for a fee, were excluded. Results and discussion: In this context, the commonly used strategies were educational actions through conversation circles using personalized badges and debates about thematic references, health promotion, disease prevention, didactic guidelines about healthy eating habits, and emphasizing the importance of health care. Conclusion: The strategies implemented by the FHS are fundamental, as they help in the treatment of SAH and provide an improvement in the quality of life of patients.Introducción: la atención primaria de salud es el primer contacto de los usuarios con la salud pública, y el encargado de ofrecer acciones promocionales, preventivas y curativas a la población, con la atención domiciliaria creciendo debido a los cambios geográficos, epidemiológicos, sociales y culturales que se han ido extendiendo por todo el escenario mundial, buscando una propuesta de atención que promueva una mayor comodidad y bienestar para las familias, incluyendo al público con enfermedades crónicas, como la Hipertensión Arterial Sistémica. Objetivo: reflexionar sobre las estrategias utilizadas por el equipo multidisciplinario de salud en la atención de pacientes hipertensos en el hogar, y trascender una reflexión relacionada con las dificultades prevalentes para estos pacientes. Método: se trata de una revisión narrativa. La búsqueda se realizó en las bases de datos: Lilacs, Bdenf y en el portal SciELO, con los criterios de inclusión, artículos publicados en el integra que abordaron el tema, tesis, disertaciones, libros y documentos en portugués, inglés y español. Los estudios duplicados se excluyeron en idiomas distintos de los seleccionados y los estudios disponibles de manera remunerada. Resultados y discusión: En este contexto, las estrategias comúnmente utilizadas fueron las acciones educativas a través de ruedas de conversación utilizando insignias personalizadas y debates sobre temas temáticos, promoción de la salud, prevención de enfermedades, orientación didáctica sobre hábitos alimenticios saludables y enfatizando la importancia del cuidado de la salud. Conclusión: Las estrategias implementadas por la ESF son fundamentales, ya que ayudan en el tratamiento de la HSA.Introdução: a tenção primária a saúde constitui-se como primeiro contato dos usuários com a saúde pública, e o responsável pela oferta de ações promocionais, preventivas e curativas a população, tendo o atendimento domiciliar crescido em decorrência das mudanças geográficas, epidemiológicas, sociais e culturais que vem se alastrando pelo cenário mundial, buscando uma proposta de cuidados que promova maior conforto e bem-estar as famílias, incluindo o público portador de doenças crônicas, como a Hipertensão Arterial Sistêmica. Objetivo: refletir acerca das estratégias utilizadas pela equipe multiprofissional de saúde no cuidado a hipertensos no âmbito domiciliar, e transcender uma reflexão relacionada as dificuldades prevalentes para esses pacientes. Método: trata-se de uma revisão narrativa. A busca ocorreu nas bases de dados: Lilacs, Bdenf e no portal da SciELO, com os critérios de inclusão, artigos publicados na integra que abordassem a temática, teses, dissertações, livros e documentos nos idiomas português, inglês e espanhol. Excluíram-se estudos duplicados, em idiomas diferentes dos selecionados e estudos disponíveis de forma paga. Resultados e discussão: Nesse contexto as estratégias comumente utilizadas foram as ações educativas através de rodas de conversas utilizando crachás personalizados e debates acerca dos referentes temáticos, promoção de saúde, prevenção de agravos, orientações de forma didática acerca de hábitos alimentares saudáveis, e enfatizando a importância do acolhimento em saúde. Conclusão: As estratégias implementadas pelas ESF são fundamentais, pois auxiliam no tratamento da HAS e proporciona uma melhora na qualidade de vida dos pacientes

ESTRATÉGIAS UTILIZADAS NO CUIDADO A PESSOAS HIPERTENSAS NO DOMICILIO: REFLEXÕES ACERCA DO PAPEL DA EQUIPE MULTIPROFISSIONAL DE SAÚDE

Introduction: primary health care is the first contact of users with public health, and is responsible for offering promotional, preventive and curative actions to the population, with home care having grown as a result of geographic, epidemiological, social and cultural practices that have been spreading around the world, seeking a care proposal that promotes greater comfort and well-being for families, including the public with chronic diseases, such as Systemic Arterial Hypertension. Objective: to reflect on the strategies used by the multiprofessional health team in the care of hypertensive patients at home, and to transcend a reflection related to the prevalent difficulties for these patients. Method: this is a narrative review. The search took place in the following databases: Lilacs, Bdenf and the SciELO portal, with the inclusion criteria, articles published in full that addressed the theme, theses, dissertations, books and documents in Portuguese, English and Spanish. Duplicate studies, in languages ​​other than those selected and studies available for a fee, were excluded. Results and discussion: In this context, the commonly used strategies were educational actions through conversation circles using personalized badges and debates about thematic references, health promotion, disease prevention, didactic guidelines about healthy eating habits, and emphasizing the importance of health care. Conclusion: The strategies implemented by the FHS are fundamental, as they help in the treatment of SAH and provide an improvement in the quality of life of patients.Introducción: la atención primaria de salud es el primer contacto de los usuarios con la salud pública, y el encargado de ofrecer acciones promocionales, preventivas y curativas a la población, con la atención domiciliaria creciendo debido a los cambios geográficos, epidemiológicos, sociales y culturales que se han ido extendiendo por todo el escenario mundial, buscando una propuesta de atención que promueva una mayor comodidad y bienestar para las familias, incluyendo al público con enfermedades crónicas, como la Hipertensión Arterial Sistémica. Objetivo: reflexionar sobre las estrategias utilizadas por el equipo multidisciplinario de salud en la atención de pacientes hipertensos en el hogar, y trascender una reflexión relacionada con las dificultades prevalentes para estos pacientes. Método: se trata de una revisión narrativa. La búsqueda se realizó en las bases de datos: Lilacs, Bdenf y en el portal SciELO, con los criterios de inclusión, artículos publicados en el integra que abordaron el tema, tesis, disertaciones, libros y documentos en portugués, inglés y español. Los estudios duplicados se excluyeron en idiomas distintos de los seleccionados y los estudios disponibles de manera remunerada. Resultados y discusión: En este contexto, las estrategias comúnmente utilizadas fueron las acciones educativas a través de ruedas de conversación utilizando insignias personalizadas y debates sobre temas temáticos, promoción de la salud, prevención de enfermedades, orientación didáctica sobre hábitos alimenticios saludables y enfatizando la importancia del cuidado de la salud. Conclusión: Las estrategias implementadas por la ESF son fundamentales, ya que ayudan en el tratamiento de la HSA.Introdução: a tenção primária a saúde constitui-se como primeiro contato dos usuários com a saúde pública, e o responsável pela oferta de ações promocionais, preventivas e curativas a população, tendo o atendimento domiciliar crescido em decorrência das mudanças geográficas, epidemiológicas, sociais e culturais que vem se alastrando pelo cenário mundial, buscando uma proposta de cuidados que promova maior conforto e bem-estar as famílias, incluindo o público portador de doenças crônicas, como a Hipertensão Arterial Sistêmica. Objetivo: refletir acerca das estratégias utilizadas pela equipe multiprofissional de saúde no cuidado a hipertensos no âmbito domiciliar, e transcender uma reflexão relacionada as dificuldades prevalentes para esses pacientes. Método: trata-se de uma revisão narrativa. A busca ocorreu nas bases de dados: Lilacs, Bdenf e no portal da SciELO, com os critérios de inclusão, artigos publicados na integra que abordassem a temática, teses, dissertações, livros e documentos nos idiomas português, inglês e espanhol. Excluíram-se estudos duplicados, em idiomas diferentes dos selecionados e estudos disponíveis de forma paga. Resultados e discussão: Nesse contexto as estratégias comumente utilizadas foram as ações educativas através de rodas de conversas utilizando crachás personalizados e debates acerca dos referentes temáticos, promoção de saúde, prevenção de agravos, orientações de forma didática acerca de hábitos alimentares saudáveis, e enfatizando a importância do acolhimento em saúde. Conclusão: As estratégias implementadas pelas ESF são fundamentais, pois auxiliam no tratamento da HAS e proporciona uma melhora na qualidade de vida dos pacientes