Medidas poblacionales para la seguridad vial: más allá de la responsabilidad individual

Las lesiones causadas por el tránsito (LCT) se encuentran dentro de las principales causas de mortalidad y discapacidad a nivel mundial, hecho reflejado en el puesto que ocupan dentro de las primeras diez causas de vida ajustados por discapacidad, con importantes costos e impacto económico y social para las sociedades que las padecen. En 2004, la Organización Mundial de la Salud (OMS) lanzó el primer informe sobre prevención de LCT. Sin embargo, en años posteriores esa situación no mejoró, por lo cual las Naciones Unidas lanzó la Década de Acción para la Seguridad Vial (2011-2020), donde se invitaba a los gobiernos a diseñar e implementar acciones para reducir la carga asociada a este problema; entre estas se encuentra diseño y mejoramiento de vías, atención oportuna pos siniestro, control de la velocidad, medidas de control administrativo, diseño y mejoramiento de estándares vehiculares, entre otras. Las medidas basadas en enfoque poblacional han demostrado ser más poderosas que las medidas que inducen cambios de comportamiento individual.

Injuries caused by traffic (ICT) are among the main causes of mortality and disability worldwide, reflected in the fact that they occupy the first ten causes of disability adjusted life years with economic and social cost impacts for the societies that suffer from them. In 2004, the World Health Organization (WHO) released the first Prevention Report about ICT. Nevertheless, in subsequent years this situation has not improved, motivating the United Nations to launch the Decade of Action for Road Safety (2011-2020), where governments were invited to design and implement actions to reduce the burden associated with this problem: designing and improving of roads, increasing timely post-crash care, speed control, administrative control measures, designing and improving vehicle safety standards, among others. Population-based measures have been shown to be more powerful than measures that induce individual behavior changes.

miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly.

Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449-/- mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449-/- mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449-/- mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449-/- cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis.

Joint Transcriptomic Analysis of Lung Cancer and Other Lung Diseases.

Background: Epidemiological and clinical evidence points cancer comorbidity with pulmonary chronic disease. The acquisition of some hallmarks of cancer by cells affected with lung pathologies as a cell adaptive mechanism to a shear stress, suggests that could be associated with the establishment of tumoral processes. Objective: To propose a bioinformatic pipeline for the identification of all deregulated genes and the transcriptional regulators (TFs) that are coexpressed during lung cancer establishment, and therefore could be important for the acquisition of the hallmarks of cancer. Methods: Ten microarray datasets (six of lung cancer, four of lung diseases) comparing normal and diseases-related lung tissue were selected to identify hub differentiated expressed genes (DEGs) in common between lung pathologies and lung cancer, along with transcriptional regulators through the utilization of specialized libraries from R language. DAVID bioinformatics tool for gene enrichment analyses was used to identify genes with experimental evidence associated to tumoral processes and signaling pathways. Coexpression networks of DEGs and TFs in lung cancer establishment were created with Coexnet library, and a survival analysis of the main hub genes was made. Results: Two hundred ten DEGs were identified in common between lung cancer and other lung diseases related to the acquisition of tumoral characteristics, which are coexpressed in a lung cancer network with TFs, suggesting that could be related to the establishment of the tumoral pathology in lung. The comparison of the coexpression networks of lung cancer and other lung diseases allowed the identification of common connectivity patterns (CCPs) with DEGs and TFs correlated to important tumoral processes and signaling pathways, that haven´t been studied to experimentally validate their role in the early stages of lung cancer. Some of the TFs identified showed a correlation between its expression levels and the survival of lung cancer patients. Conclusion: Our findings indicate that lung diseases share genes with lung cancer which are coexpressed in lung cancer, and might be able to explain the epidemiological observations that point to direct and inverse comorbid associations between some chronic lung diseases and lung cancer and represent a complex transcriptomic scenario.

FGF23 expression in rodents is directly induced via erythropoietin after inhibition of hypoxia inducible factor proline hydroxylase.

Plasma levels of FGF23 are increased in patients with chronic kidney disease. Beside its role in phosphate homeostasis, iron deficiency and anemia are associated with increased FGF23 plasma levels. Recently, FGF23 plasma levels were shown to be increased in mice after treatment with hypoxia inducible factor-proline hydroxylase (HIF-PH) inhibitors which are strong inducers of erythropoietin and erythropoiesis and are known to modulate iron uptake and availability. Therefore we investigated a potential context between expression of FGF23 and stimulation of erythropoiesis using a HIF-PH inhibitor and erythropoietin in rats. FGF23 plasma levels are induced at peak levels 2 h after intravenous injection of recombinant human Erythropoietin (rhEPO). Likewise induction of endogenous EPO using a HIF-PH inhibitor (BAY 85-3934) is followed by an increase of FGF23 plasma levels. In contrast to rhEPO the HIF-PH inhibitor induces lower peak levels of FGF23 applying equivalent hematopoietic doses. Bone and bone marrow were identified as sources of EPO-induced FGF23. Immediate induction of FGF23 mRNA was also detected in EPO receptor positive murine hematopoietic BAF3 cells after treatment with rhEPO but not after treatment with the HIF-PH inhibitor. Pretreatment of mice with a neutralizing anti-EPO antibody abrogated FGF23 induction by the HIF-PH inhibitor. Thus, direct impact on FGF23 expression by HIF-PH inhibition in vivo via hypoxia mimicking and modulation of iron metabolism appears unlikely. Collectively, the findings point to an EPO dependent regulation pathway of FGF23 gene expression which might be important in the context of erythropoiesis stimulating therapies in patients with renal anemia.

The electric fence to cell-cycle progression: Do local changes in membrane potential facilitate disassembly of the primary cilium?: Timely and localized expression of a potassium channel may set the conditions that allow retraction of the primary cilium.

Kv10.1 is a voltage-gated potassium channel relevant for tumor biology, but the underlying mechanism is still unclear. We propose that Kv10.1 plays a role coordinating primary cilium disassembly with cell cycle progression through localized changes of membrane potential at the ciliary base. Most non-dividing cells display a primary cilium, an antenna-like structure important for cell physiology. The cilium is disassembled when the cell divides, which requires an increase of Ca2+ concentration and a redistribution of phospholipids in its basal region, both of which would be facilitated by local hyperpolarization. Cells lacking Kv10.1 show impaired ciliary disassembly and delayed entrance into mitosis. Kv10.1 is predominantly expressed during G2/M, a critical period for ciliary resorption, and localizes to the ciliary base and vesicles associated with the centrosome. This could explain the influence of Kv10.1 in cell proliferation, as well as phenotypic features of patients carrying gain of function mutations in the gene.

Periodic expression of Kv10.1 driven by pRb/E2F1 contributes to G2/M progression of cancer and non-transformed cells.

Progression of cell cycle is associated with changes in K(+) channel expression and activity. In this study, we report that Kv10.1, a K(+) channel that increases cell proliferation and tumor growth, is regulated at the transcriptional level by the pRb/E2F1 pathway. De-repression of E2F1 by HPV-E7 oncoprotein leads to increased expression of Kv10.1. In proliferating cells, E2F1 transcription factor binds directly to the Kv10.1 promoter during (or close to) G2/M, resulting in transient expression of the channel. Importantly, this happens not only in cancer cells but also in non-transformed cells. Lack of Kv10.1 in both cancer and non-transformed cells resulted in prolonged G2/M phase, as indicated by phosphorylation of Cdk1 (Y15) and sustained pRb hyperphosphorylation. Our results strongly suggest that Kv10.1 expression is coupled to cell cycle progression and facilitates G2/M progression in both healthy and tumor cells.

Cyclic expression of the voltage-gated potassium channel KV10.1 promotes disassembly of the primary cilium.

The primary cilium, critical for morphogenic and growth factor signaling, is assembled upon cell cycle exit, but the links between ciliogenesis and cell cycle progression are unclear. KV10.1 is a voltage-gated potassium channel frequently overexpressed in tumors. We have previously reported that expression of KV10.1 is temporally restricted to a time period immediately prior to mitosis in healthy cells. Here, we provide microscopical and biochemical evidence that KV10.1 localizes to the centrosome and the primary cilium and promotes ciliary disassembly. Interference with KV10.1 ciliary localization abolishes not only the effects on ciliary disassembly, but also KV10.1-induced tumor progression in vivo Conversely, upon knockdown of KV10.1, ciliary disassembly is impaired, proliferation is delayed, and proliferating cells show prominent primary cilia. Thus, modulation of ciliogenesis by KV10.1 can explain the influence of KV10.1 expression on the proliferation of normal cells and is likely to be a major mechanism underlying its tumorigenic effects.

Layer 5 Pyramidal Neurons' Dendritic Remodeling and Increased Microglial Density in Primary Motor Cortex in a Murine Model of Facial Paralysis.

This work was aimed at characterizing structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with microglial density induced by facial nerve lesion using a murine facial paralysis model. Adult transgenic mice, expressing green fluorescent protein in microglia and yellow fluorescent protein in projecting neurons, were submitted to either unilateral section of the facial nerve or sham surgery. Injured animals were sacrificed either 1 or 3 weeks after surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1). It was found that facial nerve lesion induced long-lasting changes in the dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Dendritic arborization of the pyramidal cells underwent overall shrinkage. Apical dendrites suffered transient shortening while basal dendrites displayed sustained shortening. Moreover, dendrites suffered transient spine pruning. Significantly higher microglial cell density was found surrounding vM1 layer 5 pyramidal neurons after facial nerve lesion with morphological bias towards the activated phenotype. These results suggest that facial nerve lesions elicit active dendrite remodeling due to pyramidal neuron and microglia interaction, which could be the pathophysiological underpinning of some neuropathic motor sequelae in humans.

Experiencia en la coordinación de programasde bienestar universitario: la tensión entre elasistencialismo y el desarrollo humano de losestudiantes / Experience in the coordination of university wellness programs, the tension between assistentialism and the human development of students

Objetivo: comprender la experiencia en la coordinación deprogramas de bienestar universitario en facultades e institutosde la Universidad de Antioquia, Colombia. Metodología: serealizó una investigación cualitativa utilizando como métodola teoría fundada, participaron coordinadores de bienestaruniversitario del campus central y sedes regionales enentrevistas a profundidad individuales, además se realizaronregistros de observación. Resultados: Cuando se habla deprogramas de intervención dirigidos por las coordinaciones debienestar universitario aparece una tensión entre los programasde tipo asistencialista, enfocados en el subsidio y la supleciónde necesidades inmediatas como alimentación y transporte,y los programas que apuntan a promover el bienestar como una dimensión del desarrollo humano, además de ser parte dela formación de los estudiantes en su proceso de aprendizajedurante el paso por la universidad. También aparecencondiciones de precariedad laboral y direccionamiento disparde las intervenciones con diferentes niveles de implementacióny de alcance. Discusión: se debate en cuanto al alcance,la pertinencia y la finalidad de los programas, como uncomplemento en la formación de profesionales, albergandola posibilidad de generar nuevas propuestas a partir delreconocimiento de necesidades que tienen los coordinadorespara el desarrollo de su tarea...

Objective: to understand the experience regarding thecoordination of university welfare programs in schoolsand departments of the University of Antioquia, Colombia.Methodology: a qualitative, grounded theory approach wastaken to this study. University welfare coordinators of the centralcampus and of six regional branch offices of the Universitytook part in this research. In-depth interviews and observationrecords were made. Results: tension was observed in thefield of intervention programs directed by university wellnesscoordination offices. This tension occurs between assistentialistprograms, which focus on subsidizing and addressingimmediate needs such as nutrition and transportation, and theprograms that aim to promote well-being as a dimension ofhuman development and are part of the studentsÆ training duringtheir stay at the university. Also precarious working conditionsand dissimilar direction of the interventions with differentlevels of implementation and scope appear. Discussion: Thescope, relevance and purpose of the programs are discussedas a complement of the professionalsÆ training, considering thepossibility of generating new proposals by recognizing what thecoordinators need in order to carry out their tasks...

Potassium channels in cell cycle and cell proliferation.

Normal cell-cycle progression is a crucial task for every multicellular organism, as it determines body size and shape, tissue renewal and senescence, and is also crucial for reproduction. On the other hand, dysregulation of the cell-cycle progression leading to uncontrolled cell proliferation is the hallmark of cancer. Therefore, it is not surprising that it is a tightly regulated process, with multifaceted and very complex control mechanisms. It is now well established that one of those mechanisms relies on ion channels, and in many cases specifically on potassium channels. Here, we summarize the possible mechanisms underlying the importance of potassium channels in cell-cycle control and briefly review some of the identified channels that illustrate the multiple ways in which this group of proteins can influence cell proliferation and modulate cell-cycle progression.

Retracción a largo plazo del árbol dendrítico de neuronas piramidales córtico-faciales por lesiones periféricas del nervio facial / Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons

Introducción. Poco se sabe sobre las modificaciones morfológicas de las neuronas de la corteza motora tras lesiones en nervios periféricos, y de la implicancia de dichos cambios en la recuperación funcional tras la lesión. Objetivo. Caracterizar en ratas el efecto de la lesión del nervio facial sobre la morfología de las neuronas piramidales de la capa V de la corteza motora primaria contralateral. Materiales y métodos. Se reconstruyeron neuronas piramidales teñidas con la técnica de Golgi-Cox, de animales control (sin lesión) y animales con lesiones y sacrificados a distintos tiempos luego de la lesión. Se utilizaron cuatro grupos: sham (control), lesión 1S, lesión 3S y lesión 5S (animales con lesiones y evaluados 1, 3 y 5 semanas después de la lesión irreversible del nervio facial, respectivamente). Se evaluaron mediante el análisis de Sholl, las ramificaciones dendríticas de las células piramidales de la corteza motora contralateral a la lesión. Resultados. Los animales con lesiones presentaron parálisis completa de las vibrisas mayores durante las cinco semanas de observación. Comparadas con neuronas de animales sin lesiones, las células piramidales córtico-faciales de los lesionados mostraron una disminución significativa de sus ramificaciones dendríticas. Esta disminución se mantuvo hasta cinco semanas después de la lesión. Conclusiones. Las lesiones irreversibles de los axones de las motoneuronas del núcleo facial, provocan una retracción sostenida del árbol dendrítico en las neuronas piramidales córtico-faciales. Esta reorganización morfológica cortical persistente podría ser el sustrato fisiopatológico de algunas de las secuelas funcionales que se observan en los pacientes con parálisis facial periférica.

Introduction. Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. Objective. Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. Materials and methods. Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. Results. Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the fiveweek observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. Discussion. Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients.

[Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons]. / Retracción a largo plazo del árbol dendrítico de neuronas piramidales córtico-faciales por lesiones periféricas del nervio facial.

INTRODUCTION: Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. OBJECTIVE: Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. MATERIALS AND METHODS: Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. RESULTS: Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the five week observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. DISCUSSION: Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients.

Inmovilización de bacillus licheniformis y Saccharomyces cerevisiae para la producción de etanol a partir de almidón de papa / Inmobilization of bacillus licheniformis and Saccharomyces cerevisiae for ethanol production from potato starch

Se evaluó un sistema discontinuo secuencial compuesto por células de Bacillus licheniformis y Saccharomyces cerevisiae para producción de etanol, utilizando en la segunda fase del proceso, un hidrolizado de almidón de papa, obtenido con el uso de células de B. licheniformis. Ambos microorganismos fueron inmovilizados en matriz de alginato de calcio al 3,2 por ciento y 2,5 por ciento (p/v), observando que a estas concentraciones se retiene la mayor cantidad de células (26x106 y 10x107 UFC/g) y permite la difusión de los productos, obteniendo 3,3 g/L de azúcares reductores y 642 UA/L (unidades amilolíticas) para B. licheniformis y 0,866 por ciento (v/v) de etanol con S. cerevisiae. Mediante un diseño factorial 22 se seleccionaron las condiciones de operación a escala de reactor para la producción del hidrolizado, encontrando que al cultivar a B. licheniformis con 3 v.v.m. y 150 r.p.m. se produjeron 3,7 g/L de azúcares reductores y 669 UA/L a las 4 horas de proceso. El hidrolizado se caracterizó por cromatografía HPLC determinando que es rico en oligómeros, dextrinas y que tiene baja concentración de glucosa y maltosa. El uso del hidrolizado para la producción de etanol, generó porcentajes bajos (0,47por ciento y 0,74 por ciento v/v), tanto en células libres como inmovilizadas, respectivamente.

We evaluated a sequential discontinuous system composed by Bacillus licheniformis and Saccharomyces cerevisiae forethanol production. For the second phase of the process potato starch hydrolyzed were used, which was obtained from B. licheniformis cells. Both microorganisms were immobilized in a calcium alginate matrix of 3,2% and 2,5% (w/v), where was observed that these concentrations retained the majority of the cells (26x106 and 10x107 UFC/g) and alloweddissemination of its products, gaining 3.3 g/L of reducing sugars and 642 AU/L (units Amylolytic) for B. licheniformis and 0,866% (v/v) ethanol with S. cerevisiae. By means of a 22 factorial design were selected operating conditions at a reactor scale for production of hydrolyzed, finding that by cultivating B. licheniformis with 3 v.v.m. and 150 r.p.m. there were 3.7 g/L of reducing sugars and 669 AU/L after 4 hours of the process. The hydrolyzed was characterized using HPLC chromatography, which determined that it is rich in oligomers and dextrin, and it has low concentration of glucose andmaltose. The use of hydrolyzed for ethanol production, generated low percentages (0,47% and 0,74% v/v) in free and immobilized cells respectively.

Estilos de vida saludable en profesionales de la salud colombianos. Estudio exploratorio / Healthy life styles in colombian health professionals. Exploratory study

El objetivo del presente estudio fue establecer la frecuencia de comportamientos saludables en una muestra de profesionales de la salud colombianos y establecer si existe alguna relación entre su nivel de acuerdo con el modelo biomédico y su estilo de vida. Para ello se adaptó el cuestionario de Prácticas y Creencias Sobre Estilos de Vida, tomado de Salazar y Arrivillaga (1) y se tomó una muestra de 606 profesionales de la salud voluntarios (500 médicos y 106 enfermeras) en las principales ciudades de Colombia. Se encontró que sólo el 11,5 por ciento de los médicos y el 6,73 por ciento de las enfermeras presentan un estilo de vida saludable y que el principal problema está relacionado con la actividad física y el deporte. No se encontró relación entre el nivel de acuerdo con el modelo biomédico y el estilo de vida de los profesionales. Se concluyó que esta situación puede estar induciendo en los profesionales, además de una pobre salud en el futuro, una actitud que no favorece la promoción de hábitos saludables en sus pacientes y la práctica de una medicina más curativa que preventiva, tal como lo sustenta Erika Frank (2).