Kidins220 sets the threshold for survival of neural stem cells and progenitors to sustain adult neurogenesis.

In the adult mammalian brain, neural stem cells (NSCs) located in highly restricted niches sustain the generation of new neurons that integrate into existing circuits. A reduction in adult neurogenesis is linked to ageing and neurodegeneration, whereas dysregulation of proliferation and survival of NSCs have been hypothesized to be at the origin of glioma. Thus, unravelling the molecular underpinnings of the regulated activation that NSCs must undergo to proliferate and generate new progeny is of considerable relevance. Current research has identified cues promoting or restraining NSCs activation. Yet, whether NSCs depend on external signals to survive or if intrinsic factors establish a threshold for sustaining their viability remains elusive, even if this knowledge could involve potential for devising novel therapeutic strategies. Kidins220 (Kinase D-interacting substrate of 220 kDa) is an essential effector of crucial pathways for neuronal survival and differentiation. It is dramatically altered in cancer and in neurological and neurodegenerative disorders, emerging as a regulatory molecule with important functions in human disease. Herein, we discover severe neurogenic deficits and hippocampal-based spatial memory defects accompanied by increased neuroblast death and high loss of newly formed neurons in Kidins220 deficient mice. Mechanistically, we demonstrate that Kidins220-dependent activation of AKT in response to EGF restraints GSK3 activity preventing NSCs apoptosis. We also show that NSCs with Kidins220 can survive with lower concentrations of EGF than the ones lacking this molecule. Hence, Kidins220 levels set a molecular threshold for survival in response to mitogens, allowing adult NSCs growth and expansion. Our study identifies Kidins220 as a key player for sensing the availability of growth factors to sustain adult neurogenesis, uncovering a molecular link that may help paving the way towards neurorepair.

Elucidation of the Cellular Interactome of African Swine Fever Virus Fusion Proteins and Identification of Potential Therapeutic Targets.

African swine fever virus (ASFV) encodes more than 150 proteins, most of them of unknown function. We used a high-throughput proteomic analysis to elucidate the interactome of four ASFV proteins, which potentially mediate a critical step of the infection cycle, the fusion and endosomal exit of the virions. Using affinity purification and mass spectrometry, we were able to identify potential interacting partners for those ASFV proteins P34, E199L, MGF360-15R and E248R. Representative molecular pathways for these proteins were intracellular and Golgi vesicle transport, endoplasmic reticulum organization, lipid biosynthesis, and cholesterol metabolism. Rab geranyl geranylation emerged as a significant hit, and also Rab proteins, which are crucial regulators of the endocytic pathway and interactors of both p34 and E199L. Rab proteins co-ordinate a tight regulation of the endocytic pathway that is necessary for ASFV infection. Moreover, several interactors were proteins involved in the molecular exchange at ER membrane contacts. These ASFV fusion proteins shared interacting partners, suggesting potential common functions. Membrane trafficking and lipid metabolism were important categories, as we found significant interactions with several enzymes of the lipid metabolism. These targets were confirmed using specific inhibitors with antiviral effect in cell lines and macrophages.

Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1.

Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-κB/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders.

Eventos adversos en un hospital pediátrico de tercer nivel de Bogotá / Adverse Events in a third level pediatric hospital in Bogotá / Eventos adversos num hospital pediátrico de terceiro nível de Bogotá

Resumen En Colombia la seguridad del paciente es una prioridad en la atención en salud; los eventos adversos e incidentes son una muestra de atención insegura en las instituciones. El compromiso interdisciplinario es fundamental para trabajo proactivo en promoción de prácticas seguras, prevención y detección de fallas latentes y activas en un hospital. Objetivo: determinar la frecuencia de eventos adversos mediante revisión de historias clínicas de un hospital pediátrico de tercer nivel de Bogotá, con el fin de fomentar prácticas seguras. Metodología: Investigación cuantitativa, transversal y descriptiva, dirigida a pacientes hospitalizados el 16 de mayo de 2013, sobre factores de riesgo, antecedentes hospitalarios, eventos adversos y complicaciones relacionados al cuidado de la salud. Resultados: Hubo 169 casos clasificados para algún suceso, de los cuales 59 Eventos Adversos, 57 incidentes, y 53 descartados por falsos positivos. Discusión: Se evidencia responsabilidad de prevención y control de infecciones por los profesionales de la salud, encargados de minimizar el riesgo del paciente vulnerable y, ante todo, proporcionar un manejo y mantenimiento adecuado de dispositivos médicos invasivos. Conclusiones: El 34,4% de historias clínicas presentaban algún tipo de evento adverso o incidente, revelando que algunos de estos fueron causados por la asistencia hospitalaria.

Abstract In Colombia, patients' safety is a priority in healthcare. Adverse events and incidents are an example of unsafe healthcare in institutions. An interdisciplinary commitment is fundamental in proactive work to promote safe practices, prevention, and detection of latent and active failures in hospital. Objective: To determine the frequency of Adverse Events by reviewing clinical histories in a third level pediatric hospital in Bogotá to foster safe practices. Methodology: A descriptive cross-sectional quantitative research was conducted focusing on hospitalized patients on May 16, 2013, working risk factors, hospital backgrounds, adverse events, and healthcare related complications. Results: There were 169 cases classified for a given event, of which 59 were Adverse Events, 57 were incidents and 53 were discarded as false positives. Discussion: Researchers evidenced the responsibility in infection prevention and control by healthcare professionals in charge of minimizing a vulnerable patient's risk, and above all, they provided a suitable use and maintenance of invasive medical devices. Conclusions: 34.4% of the clinical histories show some type of adverse event or incident, revealing evidence that in some cases they were caused by hospital care.

Resumo Na Colômbia a seguridade do paciente é uma prioridade na atenção em saúde; os eventos adversos e incidentes são uma mostra de atenção insegura nas instituições. O compromisso interdisciplinar e fundamental para trabalho proativo em promoção de práticas seguras, prevenção e detecção de falhas latentes e ativas num hospital. Objetivo: Determinar a frequência de eventos adversos mediante revisão de histórias clínicas dum hospital pediátrico de terceiro nível de Bogotá, com o fim de fomentar práticas seguras. Metodologia: Investigação quantitativa, transversal e descritiva, dirigida a pacientes hospitalizados o 16 de maio de 2013, sobre fatores de risco, antecedentes hospitalários, eventos adversos e complicações relacionados ao cuidado da saúde. Resultados: Houve 169 casos classificados para algum acontecimento, dos quais 59 Eventos Adversos, 57 incidentes, e 53 descartados por serem falsos positivos. Discussão: Se evidencia responsabilidade de prevenção e controle de infecções pelos professionais da saúde, encarregados de minimizar o risco do paciente vulnerável e, por acima de todo, proporcionar um manejo e mantimento adequado de dispositivos médicos invasivos. Conclusões: O 34.4% das histórias clínicas apresentavam algum jeito de Evento Adverso ou incidente, revelando evidência de que alguns destes foram causados pela assistência hospitalar.

Por un futuro mejor: programa de promoción de la salud para Afrodescendientes / Por um futuro melhor: programa de promoção da saúde para Afro-descendentes / For a better future: program of health promotion for Afro-descend

Introducción: Las familias afrocolombianas se caracterizan por vivir en contextos de alta vulnerabilidad, que requieren su fortalecimiento con programas en promoción de la salud. Objetivo: Construir un programa de promoción de la salud, con familias afrocolombianas en situación de pobreza en Tumaco, año 2012. Materiales y Métodos: Investigación - Acción - Participativa, conformando un grupo y comisión de seguimiento, esto permitió la adaptación de la propuesta de Martí a través de cuatro etapas en el proceso. Resultados: El programa de Promoción de la Salud fue una construcción colectiva entre el grupo Investigación Acción Participación, la comisión de seguimiento y las familias, realizada en cuatro fases: Etapa 1: Inicio y preparación del campo. Etapa 2. Diagnóstico: Aproximación al universo de las familias afrocolombianas. Etapa 3. Construcción y aplicación de programa de promoción de la salud: “Del dicho al hecho superamos los trechos”. Etapa 4. Evaluación y proyección del programa: “Evaluando vamos terminando”. Discusión y Conclusiones: La construcción social del programa de promoción de la salud, así como el abordaje pedagógico y didáctico para el desarrollo del mismo, se desarrolló en función del contexto cultural, desde la perspectiva de la Investigación Acción Participación. El programa “Por un futuro mejor” permitió crear nuevos conocimientos a familias, líderes y profesionales de la salud a partir de la realidad e intercambio de saberes, con acciones dirigidas a fortalecer el amor propio, la comunicación, el entorno y la participación, con el fin de mejorar las condiciones de salud.

Introdução: As famílias afro-colombianas caracterizam-se por viver em contextos de alta vulnerabilidade, que requerem seu fortalecimento com programas em promoção da saúde. Objetivo: Construir um programa da promoção da saúde, com famílias afro-colombianas em situação de pobreza em Tumaco, ano 2012. Materiais e Métodos: Investigação-Ação-Participativa, formando um grupo e a comissão de seguimento, este permitiu a adaptação da proposta do Martí através de quatro etapas no processo. Resultados: O programa de Promoção da Saúde foi uma construção coletiva entre o Grupo Investigação Ação Participação, a comissão de seguimento e as famílias, realizado em quatro fases: Etapa 1: Inicio e preparação do campo. Etapa 2. Diagnóstico: Aproximação ao universo das famílias afro-colombianas. Etapa 3. Construção e aplicação do programa de promoção da saúde: “Do dizer ao fazer, superamos as distâncias”. Passo 4. Avaliação e projeção do programa: "Avaliando vamos terminando" Discussão e Conclusões: A construção social do programa de promoção da saúde, bem como a abordagem pedagógica e didática para o desenvolvimento do mesmo, desenvolveu-se em função do contexto cultural, desde a perspectiva da Investigação Ação Participação. O programa “Por um futuro melhor” permitiu criar novos conhecimentos às famílias, líderes e profissionais da saúde a partir da realidade e intercâmbio de saberes, com ações dirigidas a fortalecer o amor próprio, a comunicação, o entorno e a participação, com o fim de melhorar as condições de saúde.

Introduction: Afro-Colombian families live in contexts characterized by high vulnerability that require strengthening programs in health promotion. Objective: To build a program of health promotion, with Afro-Colombian families in poverty in Tumaco, 2012. Materials and Methods: Research - Action - Participatory, forming a group and monitoring committee, this allowed the adaptation of the proposal Martí through four stages in the process. Results: The program of Health Promotion was a collective effort between the Research Action Group Participation, the monitoring committee and families, carried out in four stages: Stage 1: Initiation and preparation of the field. Step 2. Diagnosis: An approach to the universe of Afro-Colombian families. Stage 3. Construction and application of program health promotion: "Easier said than done overcome the stretches". Step 4. Evaluation and projection of the program: "Evaluating we finished." Discussion and Conclusions: The social construction of program health promotion as well as the educational and training to develop the same approach, developed depending on the cultural context, from the perspective of Action Research Participation. The "For a better future" allowed families to create new knowledge, leaders and health professionals from reality and knowledge exchange, with actions aimed at strengthening self-esteem, communication, the environment and participation, to improve health conditions.

ATP-P2X7 Receptor Modulates Axon Initial Segment Composition and Function in Physiological Conditions and Brain Injury.

Axon properties, including action potential initiation and modulation, depend on both AIS integrity and the regulation of ion channel expression in the AIS. Alteration of the axon initial segment (AIS) has been implicated in neurodegenerative, psychiatric, and brain trauma diseases, thus identification of the physiological mechanisms that regulate the AIS is required to understand and circumvent AIS alterations in pathological conditions. Here, we show that the purinergic P2X7 receptor and its agonist, adenosine triphosphate (ATP), modulate both structural proteins and ion channel density at the AIS in cultured neurons and brain slices. In cultured hippocampal neurons, an increment of extracellular ATP concentration or P2X7-green fluorescent protein (GFP) expression reduced the density of ankyrin G and voltage-gated sodium channels at the AIS. This effect is mediated by P2X7-regulated calcium influx and calpain activation, and impaired by P2X7 inhibition with Brilliant Blue G (BBG), or P2X7 suppression. Electrophysiological studies in brain slices showed that P2X7-GFP transfection decreased both sodium current amplitude and intrinsic neuronal excitability, while P2X7 inhibition had the opposite effect. Finally, inhibition of P2X7 with BBG prevented AIS disruption after ischemia/reperfusion in rats. In conclusion, our study demonstrates an involvement of P2X7 receptors in the regulation of AIS mediated neuronal excitability in physiological and pathological conditions.

Adenylate cyclase 5 coordinates the action of ADP, P2Y1, P2Y13 and ATP-gated P2X7 receptors on axonal elongation.

In adult brains, ionotropic or metabotropic purinergic receptors are widely expressed in neurons and glial cells. They play an essential role in inflammation and neurotransmission in response to purines secreted to the extracellular medium. Recent studies have demonstrated a role for purinergic receptors in proliferation and differentiation of neural stem cells although little is known about their role in regulating the initial neuronal development and axon elongation. The objective of our study was to investigate the role of some different types of purinergic receptors, P2Y1, P2Y13 and P2X7, which are activated by ADP or ATP. To study the role and crosstalk of P2Y1, P2Y13 and P2X7 purinergic receptors in axonal elongation, we treated neurons with specific agonists and antagonists, and we nucleofected neurons with expression or shRNA plasmids. ADP and P2Y1-GFP expression improved axonal elongation; conversely, P2Y13 and ATP-gated P2X7 receptors halted axonal elongation. Signaling through each of these receptor types was coordinated by adenylate cyclase 5. In neurons nucleofected with a cAMP FRET biosensor (ICUE3), addition of ADP or Blue Brilliant G, a P2X7 antagonist, increased cAMP levels in the distal region of the axon. Adenylate cyclase 5 inhibition or suppression impaired these cAMP increments. In conclusion, our results demonstrate a crosstalk between two metabotropic and one ionotropic purinergic receptor that regulates cAMP levels through adenylate cyclase 5 and modulates axonal elongation triggered by neurotropic factors and the PI3K-Akt-GSK3 pathway.

In vivo P2X7 inhibition reduces amyloid plaques in Alzheimer's disease through GSK3ß and secretases.

ß-Amyloid (Aß) peptide production from amyloid precursor protein (APP) is essential in the formation of the ß-amyloid plaques characteristic of Alzheimer's disease. However, the extracellular signals that maintain the balance between nonpathogenic and pathologic forms of APP processing, mediated by α-secretase and ß-secretase respectively, remain poorly understood. In the present work, we describe regulation of the processing of APP via the adenosine triphosphate (ATP) receptor P2X7R. In 2 different cellular lines, the inhibition of either native or overexpressed P2X7R increased α-secretase activity through inhibition of glycogen synthase kinase 3 (GSK-3). In vivo inhibition of the P2X7R in J20 mice, transgenic for mutant human APP, induced a significant decrease in the number of hippocampal amyloid plaques. This reduction correlated with a decrease in glycogen synthase kinase 3 activity in J20 mice, increasing the proteolytic processing of APP through an increase in α-secretase activity. The in vivo findings presented here demonstrate for the first time the therapeutic potential of P2X7R antagonism in the treatment of familiar Alzheimer's disease (FAD).

Ca2+/calmodulin-dependent kinase II signalling cascade mediates P2X7 receptor-dependent inhibition of neuritogenesis in neuroblastoma cells.

ATP, via purinergic P2X receptors, acts as a neurotransmitter and modulator in both the central and peripheral nervous systems, and is also involved in many biological processes, including cell proliferation, differentiation and apoptosis. Previously, we have reported that P2X7 receptor inhibition promotes axonal growth and branching in cultured hippocampal neurons. In this article, we demonstrate that the P2X7 receptor negatively regulates neurite formation in mouse Neuro-2a neuroblastoma cells through a Ca2+/calmodulin-dependent kinase II-related mechanism. Using both molecular and immunocytochemical techniques, we characterized the presence of endogenous P2X1, P2X3, P2X4 and P2X7 subunits in these cells. Of these, the P2X7 receptor was the only functional receptor, as its activation induced intracellular calcium increments similar to those observed in primary neuronal cultures, exhibiting pharmacological properties characteristic of homomeric P2X7 receptors. Patch-clamp experiments were also conducted to fully demonstrate that ionotropic P2X7 receptors mediate nonselective cation currents in this cell line. Pharmacological inhibition of the P2X7 receptor and its knockdown by small hairpin RNA interference resulted in increased neuritogenesis in cells cultured in low serum-containing medium, whereas P2X7 overexpression significantly reduced the formation of neurites. Interestingly, P2X7 receptor inhibition also modified the phosphorylation state of focal adhesion kinase, Akt and glycogen synthase kinase 3, protein kinases that participate in the Ca2+/calmodulin-dependent kinase II signalling cascade and that have been related to neuronal differentiation and axonal growth. Taken together, our results provide the first mechanistic insight into P2X7 receptor-triggered signalling pathways that regulate neurite formation in neuroblastoma cells.

Inhibition of the ATP-gated P2X7 receptor promotes axonal growth and branching in cultured hippocampal neurons.

During the establishment of neural circuits, the axons of neurons grow towards their target regions in response to both positive and negative stimuli. Because recent reports show that Ca2+ transients in growth cones negatively regulate axonal growth, we studied how ionotropic ATP receptors (P2X) might participate in this process. Our results show that exposing cultured hippocampal neurons to ATP induces Ca2+ transients in the distal domain of the axon and the concomitant inhibition of axonal growth. This effect is mediated by the P2X7 receptor, which is present in the growth cone of the axon. Pharmacological inhibition of P2X7 or its silencing by shRNA interference induces longer and more-branched axons, coupled with morphological changes to the growth cone. Our data suggest that these morphological changes are induced by a signalling cascade in which CaMKII and FAK activity activates PI3-kinase and modifies the activity of its downstream targets. Thus, in the absence or inactivation of P2X7 receptor, axons grow more rapidly and form more branches in cultured hippocampal neurons, indicative that ATP exerts a negative influence on axonal growth. These data suggest that P2X7 antagonists have therapeutic potential to promote axonal regeneration.

Morbilidad por accidentes en menores de 15 años / Accidents morbidity in children under 15

Se estudiaron los accidentes ocurridos en el Area de Salud del Policlínico :Chiqui Gómez" durante el semestre correspondiente a octubre de 1986 a marzo de 1987, con el objetivo de determinar su incidencia en atención a la edad, sexo, tipos de accidentes y lesiones, lugar de ocurrencia y sitio de atención médica inmediata. Se tomaron como muestra los 674 niños de 5 consultorios de dicha Area de Salud. Se obtuvo la información necesaria mediante visitas realizadas directamente en el hogar. Se encontró predominio de accidentes en los niños de 5 a 9 años de edad, para ser el sexo masculino el más afectado. Se demostró que los accidentes ocurren con mayor frecuencia en el hogar, y ocupan un lugar destacado las caídas y las heridas. Se enfatiza en la necesidad de incrementar las acciones educativas dirigidas a la población, tendentes a reducir los accidentes en la edad pediátrica; en dichas acciones debe participar especialmente el médico de la familia

El encuentro: forma organizativa del proceso docente; su aplicación en la especialidad de licenciatura en enfermería / The encounter: an organizational from of the teaching process. its aplicatin in the speciality of bacchalaureate nursing

Dada la importancia del estudio dirigido para la formación o superación de los trabajadores que aspiran a alcanzar un nivel superior, se analiza esta nueva modalidad de enseñanza en el Instituto Superior de Ciencias Médicas de Villa Clara en la disciplina de Licenciatura en Enfermería. Se señalan los los beneficios de éste y se descubre la estructura metodológica del curso por encuentros (como se le denomina a partir de 1981 como resultado del perfeccionamiento del proceso docente- educativo). Entre las ventajas se señalan la estrecha relación profesor-alumno y la autopreparación que permite desarrollar las capacidades independientes del alumno

Calidad de las clases y promoción en la especialidad licenciatura en enfermería / Lesson quality and passing grades in the collage course for becoming a bachelor of nursing

Se realizó un estudio acerca de la calidad de las clases y los resultados de la promoción en los cursos comprendidos desde 1983-1984 hasta 1986-1987 en la especialidad Licenciatura en Enfermería del ISCM-VC con los objetivos de analizar la promoción por año, semestre y asignatura, detectar las asignaturas que resulten más difíciles para los estudiantes, así como el tiempo y la forma que utilizan para el estudio independiente y compararlos con los resultados de los controles a clases. Se empleó el método de observación y se obtuvo un incremento en la promoción total de 90,8%en primer año a 97,6%en 4to año. La calidad de la promoción es muy buena y las asignaturas de mayor dificultad fueron: metodología de la Investigación y Estadística de la Salud, Filosofía y Psicología. La forma más utilizada para el estudio fue la individual y colectiva, con un tiempo de estudio de 2 horas diarias como promedio

Actividad de la enfermera de la familia como agente preventivo de las principales causas de muerte en Cuba / Activity of the family nurse as a preventive agent of main causes of death in Cuba

Se hace una valoración del plan del médico de la familia y su estrecha relación con la enfermera, la familia y la comunidad. Se analiza la labor de tipo educativo y preventivo que realiza el personal de enfermería, así como su educación sanitaria sobre los riesgos que puedan ocasionar accidentes y la forma de evidenciarlos, todo ello tendente a reducir los índices de morbimortalidad con el propósito de prevenir las enfermedades cardiovasculares, cerebrovasculares, la diabetes mellitus y las enfermedades del sistema respiratorio que se encuentran entre las primeras causas de muerte en Cuba

La especialidad de licenciatura en enfermería en el Instituto Superior de Ciencias Médicas de Villa Clara / The licentiate specialty in nursing at the Villa Clara High Institute of Medical Sciences

La especialidad de Licenciatura en Enfermería se introdujo en el Instituto Superior de Ciencias Médicas de Villa Clara en el curso de 1981 a 1982 con las características de un curso regular por encuentros para trabajadores. Actualmente, este centro cuenta con una matrícula de 190 estudiantes. En este trabajo nos proponemos brindar una panorámica sobre el desarrollo de la especialidad y sus perspectivas, al enfatizar en la importancia de elevar el nivel cientificotécnico del personal de Enfermería. Se describe cómo se desarrolla la especialidad a través de estos cursos, el comportamiento y análisis de la promoción y retención desde el curso de 1981 a 1982, hasta el curso de 1983 a 1984. Se reseña el trabajo científico-metodológico de la especialidad y se destaca la participación de los estudiantes en los distintos eventos