Identification of different mechanisms leading to PAX6 down-regulation as potential events contributing to the onset of Hirschsprung disease

Hirschsprung disease (HSCR) is attributed to a failure of neural crest derived cells to migrate, proliferate, differentiate or survive in the bowel wall during embryonic Enteric Nervous System (ENS) development. This process requires a wide and complex variety of molecules and signaling pathways which are activated by transcription factors. In an effort to better understand the etiology of HSCR, we have designed a study to identify new transcription factors participating in different stages of the colonization process. A differential expression study has been performed on a set of transcription factors using Neurosphere-like bodies from both HSCR and control patients. Differential expression levels were found for CDYL, MEIS1, STAT3 and PAX6. A significantly lower expression level for PAX6 in HSCR patients, would suit with the finding of an over-representation of the larger tandem (AC)m(AG)n repeats within the PAX6 promoter in HSCR patients, with the subsequent loss of protein P300 binding. Alternatively, PAX6 is a target for DNMT3B-dependant methylation, a process already proposed as a mechanism with a role in HSCR. Such decrease in PAX6 expression may influence in the proper function of signaling pathways involved in ENS with the confluence of additional genetic factors to the manifestation of HSCR phenotype.Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad PI1301560Consejería de Innovación, Ciencia y Empresa CTS-744

Evidence in Favor of an Alternative Glucocorticoid Synthesis Pathway During Acute Experimental Chagas Disease

It is well-established that infectious stress activates the hypothalamus–pituitary–adrenal axis leading to the production of pituitary adrenocorticotropin (ACTH) and adrenal glucocorticoids (GCs). Usually, GC synthesis is mediated by protein kinase A (PKA) signaling pathway triggered by ACTH. We previously demonstrated that acute murine Chagas disease courses with a marked increase of GC, with some data suggesting that GC synthesis may be ACTH-dissociated in the late phase of this parasitic infection. Alternative pathways of GC synthesis have been reported in sepsis or mental diseases, in which interleukin (IL)-1β, prostaglandin E2 (PGE2), and/or cAMP-activated guanine nucleotide exchange factor 2 (EPAC2) are likely to play a role in this regard. Accordingly, we have searched for the existence of an ACTH-independent pathway in an experimental model of a major parasitic disease like Chagas disease, in addition to characterizing potential alternative pathways of GC synthesis. To this end, C57BL/6 male mice were infected with T. cruzi (Tc), and evaluated throughout the acute phase for several parameters, including the kinetic of GC and ACTH release, the adrenal level of MC2R (ACTH receptor) expression, the p-PKA/PKA ratio as ACTH-dependent mechanism of signal transduction, as well as adrenal expression of IL-1β and its receptor, EPAC2 and PGE2 synthase. Our results reveal the existence of two phases involved in GC synthesis during Tc infection in mice, an initial one dealing with the well-known ACTH-dependent pathway, followed by a further ACTH-hyporesponsive phase. Furthermore, inflamed adrenal microenvironment may tune the production of intracellular mediators that also operate upon GC synthesis, like PGE2 synthase and EPAC2, as emerging driving forces for GC production in the advanced course of Tc infection. In essence, GC production seems to be associated with a biphasic action of PGE2, suggesting that the effect of PGE2/cAMP in the ACTH-independent second phase may be mediated by EPAC2.Fil: da Silva Oliveira Barbosa, Esdras. Universidad Nacional de Rosario; ArgentinaFil: Roggero, Eduardo Angel. Universidad Nacional de Rosario; ArgentinaFil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Fernández, Rocío del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Carvalho, Vinicius Frias. Fundación Oswaldo Cruz; BrasilFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamentos de Atlántico, Bolívar, Córdoba, la Guajira

A lo largo del curso y de los temas trabajados se pueden abordar los distintos escenarios que se perciben en la sociedad en diferentes zonas geográficas del país, describiendo lo que se encuentran en todas ellas y a quienes hacen parte de estas realidades. Luego de abordar el enfoque narrativo se sigue el trabajo con un caso en específico el de Camilo y el de Peñas Coloradas con el cual se continua el ejercicio del análisis de relatos en donde se evidencia distintos tipos de violencia. En el último caso se elaboran preguntas circulares, reflexivas y estratégicas con el fin de un mejor análisis de intervención psicosocial comunitario, que se hace necesario como método de intervención con el fin de poder entender mejor la situación y darle una conclusión favorable. Se puede observar cómo en Colombia todavía se ven secuelas de la violencia que ha marcado gran parte de la historia de la nación, lo que lleva a reflexionar sobre el sistema de reparación de víctimas y la importancia de hacerla cada vez más eficiente y fácil de seguir por las víctimas de la violencia, se puede evidenciar también los distintos tipos de violencia que se siguen dando en las distintas zonas del país y la importancia del rol del psicólogo en la sociedad.Throughout the course and the topics studied, the different scenarios that are perceived in society in different geographical areas of the country can be addressed, describing what is found in all of them and who is part of these realities. After addressing the narrative approach, the work continues with a specific case that of Camilo and that of Peñas Coloradas, with which the exercise of the analysis of stories where different types of violence are evidenced is continued. In the latter case, circular, reflective and strategic questions are elaborated in order to better analyze the community psychosocial intervention, which is necessary as an intervention method in order to better understand the situation and give it a favorable conclusion. It can be seen how in Colombia there are still consequences of the violence that has marked a large part of the nation's history, which leads us to reflect on the victim reparation system and the importance of making it increasingly efficient and easy to follow. For the victims of violence, it is also possible to show the different types of violence that continue to occur in different areas of the country and the importance of the role of the psychologist in society

Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 Patients.

Objective To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD) patients with long follow-up. Methods Using the Kaplan-Meier method, we estimated the disease-free survival rate from defined neurodegenerative syndromes in all the consecutive IRBD patients diagnosed and followed-up in our tertiary referal sleep center between November 1991 and July 2013. Results The cohort comprises 174 patients with a median age at diagnosis of IRBD of 69 years and a median follow-up of four years. The risk of a defined neurodegenerative syndrome from the time of IRBD diagnosis was 33.1% at five years, 75.7% at ten years, and 90.9% at 14 years. The median conversion time was 7.5 years. Emerging diagnoses (37.4%) were dementia with Lewy bodies (DLB) in 29 subjects, Parkinson disease (PD) in 22, multiple system atrophy (MSA) in two, and mild cognitive impairment (MCI) in 12. In six cases, in whom postmortem was performed, neuropathological examination disclosed neuronal loss and widespread Lewy-type pathology in the brain in each case. Conclusions In a large IRBD cohort diagnosed in a tertiary referal sleep center, prolonged follow-up indicated that the majority of patients are eventually diagnosed with the synucleinopathies PD, DLB and less frequently MSA. IRBD represented the prodromal period of these conditions. Our findings in IRBD have important implications in clinical practice, in the investigation of the early pathological events occurring in the synucleinopathies, and for the design of interventions with potential disease-modifying agents

Regional patterns of 18F-florbetaben uptake in presenilin 1 mutation carriers

Individuals with autosomal dominant Alzheimer's disease (ADAD) present amyloid deposits before symptoms onset. We aimed to investigate efficacy and safety of 18F-florbetaben (FBB) for assessing amyloid deposition in ADAD. We acquired FBB positron emission tomography and magnetic resonance imaging of 25 individuals from PSEN1 families (NCT02362880). We studied individual uptake patterns, group differences, and correlation with estimated years to symptoms onset, as well as adverse events. We found that asymptomatic carriers (N = 14) showed increased FBB uptake across the cerebral cortex and in the caudate. FBB accumulation appeared more than 15 years before onset in the precuneus and bankssts, among other regions, overlapping regions showing increased cortical thickness in the same subjects. FBB uptake correlated with estimated years to symptoms onset in several areas, especially the rostral anterior cingulate. Symptomatic carriers (N = 7) had an elevated FBB uptake plateau. No adverse events were reported. Overall, we found progressive FBB uptake in ADAD starting 2 decades before symptoms. The rostral anterior cingulate is a candidate area to track Aβ deposition in addition to the precuneus

Quantitative analysis of dysautonomia in patients with autonomic dysreflexia

Autonomic dysreflexia (AD) is a life-threatening condition for individuals with cervical or high-thoracic spinal cord injury (SCI). The profile of autonomic dysfunction in AD using validated clinical autonomic tests has not been described so far, although it could be useful to identify SCI patients at greater risk of developing AD non-invasively. With this objective, 37 SCI patients (27% female) were recruited, and hemodynamic and cardiac parameters were continuously monitored to determine the presence of AD, defined as an increase of systolic blood pressure of 20 mmHg or higher after bladder filling with saline. Then, standard autonomic function testing was performed, including Deep Breathing, Valsalva Manoeuvre and Tilt Table Test. Finally, baroreflex sensitivity (BRS), and spectral analysis of heart rate and blood pressure variability were measured at rest. Catecholamines and vasopressin levels were also measured at supine and upright positions. The severity of SCI was assessed through clinical and radiological examinations. AD was observed in 73.3% of SCI patients, being 63.6% of them asymptomatic during the dysreflexive episode. AD patients displayed a drop in sympathetic outflow, as determined by decreased noradrenalin plasma levels, reduced sympathovagal balance and increased BRS. In line with decreased sympathetic activity, the incidence of neurogenic orthostatic hypotension was higher in AD patients. Our results provide novel evidence regarding the autonomic dysfunction in SCI patients with AD compared to non-AD patients, posing non-invasively measured autonomic parameters as a powerful clinical tool to predict AD in SCI patients

Terminología básica de conservación y restauración del Patrimonio Cultural 3. Español - Inglés - Francés - Italiano - Alemán - Portugués.

Versión 2018 Ampliación con portugués del PIMCD 2016 Glosario de 80 términos fundamentales de conservación y restauración del patrimonio cultural, con sus definiciones, imágenes ilustrativas, y traducción a inglés, francés, italiano y alemán, siguiendo las más recientes normativas y documentos internacionales

Impact of operator's experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry

Background The Watchman FLX is a device upgrade of the Watchman 2.5 that incorporates several design enhancements intended to simplify left atrial appendage occlusion (LAAO) and improve procedural outcomes. This study compares peri-procedural results of LAAO with Watchman FLX (Boston Scientific, Marlborough, Massachusetts) in centers with varying degrees of experience with the Watchman 2.5 and Watchman FLX. Methods Prospective, multicenter, ?real-world? registry including consecutive patients undergoing LAAO with the Watchman FLX at 26 Spanish sites (FLX-SPA registry). Implanting centers were classified according to the center?s prior experience with the Watchman 2.5. A further division of centers according to whether or not they had performed ? 10 or > 10Watchman FLX implants was prespecified at the beginning of the study. Procedural outcomes of institutions stratified according to their experience with the Watchman 2.5 and FLX devices were compared. Results 359 patients [mean age 75.5 (SD8.1), CHA2DS2-VASc 4.4 (SD1.4), HAS-BLED 3.8(SD0.9)] were included. Global success rate was 98.6%, successful LAAO with the first selected device size was achieved in 95.5% patients and the device was implanted at first attempt in 78.6% cases. There were only 9(2.5%) major peri-procedural complications. No differences in efficacy or safety results according to the cente?s previous experience with Watchman 2.5 and procedural volume with Watchman FLX existed. Conclusions The Watchman FLX attains high procedural success rates with complete LAA sealing in unselected, real-world patients, along with a low incidence of peri-procedural complications, regardless of operato?s experience with its previous device iteration or the number of Watchman FLX devices implanted.Acknowledgments: We would like to express our gratitude to Jose Santaursula Pastor for the production of the figures in this work

Aprendizaje-servicio para la promoción de la salud y la prevención de enfermedad en la población infantil

[ES] El presente proyecto de innovación docente consistió en una actividad de aprendizaje-servicio, basada en la metodología de acción participativa, llevada a cabo con estudiantes de los grados en Enfermería y Fisioterapia del Campus de Ponferrada. Objetivos: Con el diseño y puesta en práctica del proyecto, se pretendió desarrollar un aprendizaje significativo, adquirir diversas competencias transversales y específicas de cada titulación, así como aumentar su nivel de empatía y compromiso social. Descripción de la innovación: Los estudiantes, en el marco de distintas asignaturas de la titulación, diseñaron y llevaron a cabo diversos talleres de educación para la salud y promoción de hábitos de vida saludables destinados a escolares de primero y sexto de primaria de la ciudad de Ponferrada. Los talleres versaron sobre la promoción de la actividad física, la igualdad de géneros, la protección solar, el lavado de manos y los primeros auxilios. Principales resultados: Participaron un total de 67 estudiantes y 236 escolares. El 96,2% de los escolares mostraron satisfacción máxima con los talleres. A nivel de los estudiantes universitarios, los resultados medidos a través de la escala de empatía “Interpersonal Reactivity Index”, mostraron un cambio significativo en la dimensión de estrés personal, en la que hubo una disminución de la puntuación tras la actividad en la muestra total (p=0.006) y en el grupo de las mujeres (p=0.018). Los estudiantes, además de adquirir y consolidar resultados de aprendizaje específicos, manifestaron trabajar competencias relacionadas con la motivación por el trabajo, las relaciones interpersonales y el trabajo en equipo. Conclusiones: El aprendizaje-servicio se presenta como una estrategia interesante a nivel universitario. El aprendizaje significativo aporta a los universitarios una satisfacción y recompensa personal. En esta experiencia, se produjeron cambios significativos en la dimensión de estrés personal, factor fundamental para la toma de decisiones ante situaciones estresantes