Procesos Neuropatológicos Comunes Asociados a las Paredes Ventriculares en la Hidrocefalia Congénita Humana

La hidrocefalia se define hoy en como una distensión activa del sistema ventricular debida a una acumulación neta de líquido cefalorraquídeo (LCR). Puede deberse a varias razones, donde se pueden encontrar obstrucciones en las diferentes vías por donde circular el LCR. Una de las regiones es el acueducto de Silvio, siendo ese tipo de hidrocefalia clasificada de tipo obstructiva. Otras hidrocefalias denominadas comunicantes en realidad pueden considerarse que existen obstrucciones en las vías meníngeas. La hidrocefalia puede tener un carácter feto-neonatal por diversas razones, algunas ligadas a malformaciones genéticas y determinados síndromes. Otras veces se ocasiona por hemorragias ventriculares en el periodo fetal. Estas finalmente, se transforman en obstructivas. La espina bífida con mielomeningocele, que aparece como un defecto del cierre del tubo neural, frecuentemente se acompaña de hidrocefalia. En la presente Tesis Doctoral se han estudiado necropsias de 18 casos con hidrocefalia feto-neonatal diagnosticadas con carácter comunicante, es decir sin obstrucción en el acueducto de Silvio. En el estudio se incluyen algunos casos con mielomeningocele y poshemorrágica. También se han empleado, tomándose como casos controles, necropsias de fetos que no manifestaban neuropatologías. Los casos comprendían edades que oscilaban entre las 12 semanas de gestación, estados gestación atérmino y de tres meses de edad posnatal. En las necropsias se llevó a cabo un estudio de las características histopatológicas presentes, principalmente en las paredes de la corteza cerebral, empleando técnicas generales y de inmunohistoquímica/inmunofluorescencia. Mediante las segundas se detectaron proteínas marcadoras de diferentes tipos celulares presentes en las paredes. Algunos marcadores se emplearon para obtener una información funcional, como la presencia de canales acuosos, caveolas, endosomas o la producción de la citoquina proinflamatoria TNF. Además de las necropsias se han empleado muestras de LCR de casos hidrocefálicos con diferentes tipos de hidrocefalias. En ellas se ha analizado la presencia del factor TNF. Las muestras de LCR también se han analizado y mediante espectrometría de protón de hidrógeno con resonancia magnética de alta resolución en ángulo mágico (1H HR-MAS-RMN). Así se han detectado y cuantificado ciertos metabolitos que pueden ser indicadores de la presencia de condiciones isquémicas y de reacciones gliales. Finalmente en algunos casos se han podido comparar los datos histopatológicos con la información aportada en el análisis del LCR y de estudio de imagen. En las necropsias de los fetos hidrocefálicos se han encontrado de forma común la existencia de tres aspectos neuropatológicos: • Ausencia de neuroepitelio/epéndimo, según edad gestacional y tipo de células que se presentan en la zona ventricular. Este denudamiento se encontró ocupando regiones más o menos extensas de la cavidad ventricular. Estas zonas coexisten con otras donde permanece el neuroepitelio/epéndimo. • Aparición de una reacción astrocitaria que cubre las zonas denudadas de epéndimo. • Alteración en la distribución de los progenitores neurales/neuroblastos en la pared cortical cerebral en regiones denudadas de epéndimo

The current situation of radiology training in medical studies in Spain

La radiología es actualmente una parte esencial de la medicina clínica, pero la formación en pregrado no refleja su importancia en la práctica médica. En el curso actual, hay 46 facultades de medicina en nuestro país. Según la información publicada en las web institucionales, los planes de estudio son muy diferentes en cuanto a la presencia del radiodiagnóstico y a la organización de la docencia. El número de horas docentes de radiodiagnóstico estimadas (media ± desviación estándar) es de 67,0 ± 21,9 h (rango de 26 h a 137 h). Hay gran escasez de profesores universitarios clínicos y es imprescindible un recambio generacional. La situación actual plantea diversos retos, entre ellos adaptarnos a los nuevos métodos y tecnologías docentes y fomentar la presencia de la radiología en los planes de estudio de medicina, prestando especial atención a las prácticas hospitalarias, el trabajo fin de grado (TFG) y la evaluación clínica objetiva estructurada (ECOE).Funding for open access charge: Universidad de Málaga /CBU

A metabolite profile reveals the presence of neurodegenerative conditions according to severity of hydrocephalus

Introduction: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure (ICP), ischemia/hypoxia, metabolic impairment, neuronal damage and astrocytic reaction. The hyh mutant mice exhibit two different forms of hydrocephalus evolution: severe and moderate. A study was carried out in hyh mice to detect a metabolite profile that define the tissue response in each hydrocephalus form. Methods: Metabolites levels in brain cortex were analyzed with 1H High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS) spectroscopy. The study was complemented with ICP recording and histopathological analysis. Results: Mice with severe hydrocephalus were found to have higher ICP and stronger astrocytic reaction. Several metabolites including glutamate and glutamine were found to correlate with the severity of hydrocephalus. The whole metabolite profile may be explained based in differential astrocyte reactions, neurodegenerative and ischemic conditions. The glutamate transporter EAAT2 and the metabolite taurine were found as key histopathological markers for the damaged parenchyma. Conclusions: Spectroscopy allowed the detection of a metabolite profile related to intracranial pressure and hydrocephalus severity, and therefore can be useful to monitor the efficacy of experimental therapies. Supported by Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech, and PI15/0619 (ISCIII/FEDER).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Supported by Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech, and PI15/0619 (ISCIII/FEDER)

Improving oral presentation skills for radiology residents through clinical session meetings in the virtual world Second Life

Background: The objective of this study was to conduct a clinical session meeting in the virtual world of Second Life to improve the oral presentation skills of radiology residents and to assess the perception of the attendees. Methods: A clinical session meeting (10 two-hour sessions over four weeks), where participants presented their own clinical sessions, followed by a turn of interventions by the attendees, was designed and carried out. Attendees were asked to complete an evaluation questionnaire. Descriptive statistics were performed. Results: Twenty-eight radiology residents attended the meeting, and 23 (81.2%) completed the evaluation questionnaire; 95.7–100% of them agreed that the virtual environment was attractive and suitable for holding the meeting and that the content was appropriate for their training as residents. They rated with ≥8.9 points (from 1 to 10) different aspects of the experience, highlighting the role of teachers (9.7 ± 0.6) and the usefulness of their training (9.4 ± 0.9). Conclusions: Second Life can be used effectively to train oral communication skills in public, in an environment perceived as attractive and suitable for learning, through an experience described by the attendees as interesting and useful, highlighting the advantages of social contact with their peersWe want to acknowledge the Asociación de Radiólogos del Sur, a subsidiary of SERAM, for its contribution to the maintenance costs of the Medical Master Island during the development of this project. Partial funding for open access charge: Universidad de Málag

Effects of Leadership Training from Full Range Theory

El presente artículo tiene como objetivo analizar los efectos del entrenamiento del programa de formación "Liderazgo Transformacional Ecuador 2014" en resultados de liderazgo como eficacia, satisfacción, extra esfuerzo desde la teoría de rango completo planteada por Bass (1985). En la fase de levantamiento de información se aplicó el Cuestionario Multifactorial de Liderazgo (MLQ) validado por Bass y Avolio (1991), durante tres momentos del proceso y con ello se consolidó una muestra pareada; a partir de la cual, se generaron análisis de regresión y correlación, que muestran la preeminencia explicativa en todas las dimensiones del estilo de liderazgo transformacional (estimulación intelectual, motivación inspiracional, influencia idealizada atributos, influencia idealizada comportamiento, consideración individual) y dos dimensiones del liderazgo transaccional (recompensa contingente y dirección por excepción activa) que inciden en los resultados de un líder.This article aims to analyze the effects of the training program "Transformational Leadership Ecuador 2014" on leadership results such as effectiveness, satisfaction and extra effort according to full range theory raised by Bass (1985). In the information gathering phase, the Multifactorial Leadership Questionnaire (MLQ), validated by Bass and Avolio (1991), was applied on three different moments of the training process and a paired sample was created. Then, regression and correlation analysis showed that all dimensions included in the survey have explanatory preeminence in transformational leadership style (intellectual stimulation, inspirational motivation, influences of idealized influence, influence of idealized behavior, individual consideration) and also in two dimensions of transactional leadership (contingent reward and active management by exception) that affect the results of a leader

Metabolite fingerprint detected with HR-MAS spectroscopy in ex vivo samples of cases with congenital hydrocephalus

Background: Changes in the profile of metabolites in brain and/or fluids can be useful to evaluate the severity and evolution of hydrocephalus, and consequently to help in treatment decisions. Magnetic Resonance Spectroscopy can be used in ex vivo samples for such purposes. This study was designed to evaluate the levels of metabolites in the hyh mouse brain with congenital hydrocephalus by High Resolution Magic Angle Spinning (HR-MAS) Magnetic Resonance Spectroscopy (MRS). Materials and Methods: Wild type and hydrocephalic hyh mice at 30 days of postnatal age were sacrificed (n = 10-15 mice/disease condition), and hippocampus and neocortex were quickly dissected out, frozen in dry ice, and stored at -80ºC, before analysis by HR-MAS. Results: Similar levels of choline (Cho) were detected in the hippocampus and neorcortex of hydrocephalic mice compared to control samples, however phosphocholine (PCh) and glycerophosphorylcholine (GPC) displayed lower levels. These molecules are implied in the Kennedy pathway of phosphatidylcholine metabolism. The antioxidant tripeptide glutathione (GSH) was detected in higher quantities in the hydrocephalic mice, probably revealing a response to an oxidative metabolism. Other metabolites displayed remarkably higher levels in samples from hydrocephalic mice, such as creatine (Cr), taurine (Tau) and glutamine (Gln). Conclusions: HR-MAS was found as a reliable technique to detect differential levels of metabolites in small tissue biopsies samples from mice models with hydrocephalus. This technique represents a valuable tool for monitoring the degree of severity and/or the evolution of the disease in such models.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Supported by the grants PI12/0631 to AJJ; SERAM to MIM

Generation of periventricular reactive astrocytes overexpressing aquaporin 4 Is stimulated by mesenchymal stem cell therapy

Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.The present work was supported by grants PI15/00619 and PI19/00778 (to A.J.J. and P.P.-G.), PI21/000914 (to J.V.) and PI21/000915 (to A.G.) from the Instituto de Salud Carlos III, Spain, co-financed by FEDER funds from the European Union; PI18-RT-2233 from Junta de Andalucía (to A.G.) co-financed by Programa Operativo FEDER 2014–2020; PID2020-115218RB-I00 to T.I., funded by MCIN/AEI/10.13039/501100011033; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED, Instituto de Salud Carlos III, Spain) to J.V., T.I. and A.G.; FPU13/02906 to MG-B from the Ministerio de Educación, Cultura y Deporte, Spain; RYC-2014-16980 to P.P.-G. from the Ministerio de Economía y Competitividad, Spain; UMA18-FEDERJA-277 from Plan Operativo FEDER Andalucía 2014–2020 and Universidad de Málaga to P.P.-G.; Proyectos dirigidos por jóvenes investigadores from Universidad de Málaga to P.P.-G. The cost of this publication has been paid in art by “ERDF A way of making Europe” funds. Partial funding for open access charge: Universidad de Málaga