Bioactive Materials for Next-Generation Dentistry

Teeth were some of the first organs whose function was effectively restored by inert refilling materials that have become widely known to the general public; amalgams, polymeric resin composites, and gutta-percha are some such examples [...]This research was funded by a Basque Government Grant to Consolidated University Research Groups/Ikerketa Taldeak (IT1751-22)

El ultimatum de María Jesús

Duración (en horas): Más de 50 horas. Destinatario: Estudiante y DocenteEl planteamiento del presente proyecto está fundamentado en los principios del Aprendizaje Basado en Problemas, de manera que se presenta una situación problema (escenario) a partir del cual los estudiantes agrupados en pequeños grupos, deben poner en evidencia sus conocimientos previos en relación a los contenidos conceptuales del problema, plantear hipótesis, identificar sus necesidades de aprendizaje para el abordaje del problema, organizar su estudio de forma autodirigida, cooperativa y dinámica, aplicar el nuevo conocimiento obtenido al problema y reflexionar sobre el aprendizaje adquirido, tanto en su contenido, como en la forma y proceso en la cual lo han adquirido. Junto con la presentación del problema inicial, se van presentando de forma dinámica nuevas contextualizaciones del mismo y actividades para la aplicación de los nuevos conocimientos adquiridos. La propuesta se puso en marcha en el curso 2012/2013, en un grupo único de 12 estudiantes de primer curso de Grado en Odontología, dentro de la asignatura Giza Histologia/Histología Humana, de 6 créditos ECTS, impartida en el 2º cuatrimestre. La implementación de dicha metodología de enseñanza-aprendizaje, para los temas seleccionados, se realizó desde la primera semana de curso, y sin haber impartido contenidos previos. Las metodologías de enseñanza ABP (40% del temario) y tradicional (60% del temario) convivieron en el desarrollo de la asignatura, desde el principio hasta el final del curso. Tras el análisis de su implementación, podemos afirmar que este es un modelo que permite el desarrollo de todas las competencias sin excepción, tanto transversales como específicas, establecidas en el programa de la asignatura Giza Histología

Stem and Cancer Stem Cell Identities, Cellular Markers, Niche Environment and Response to Treatments to Unravel New Therapeutic Targets

Adult stem cells are a partially quiescent cell population responsible for natural cell renewal and are found in many different regions of the body, including the brain, teeth, bones, muscles, skin, and diverse epithelia, such as the epidermal or intestinal epithelium, among others [...

Notch/Wnt Cross-Signalling Regulates Stemness Of Dental Pulp Stem Cells Through Expression Of Neural Crest And Core Pluripotency Factors

Dental pulp stem cells (DPSCs) from adult teeth express neural crest (NC) markers together with core transcriptional factors associated with stem cell pluripotency, such as Oct4a, Sox2, c-Myc, Rex1, Stella/Dppa3, Ssea1/Fut4, Lin28 and Nanog. The possibility to boost the natural stemness features of DPSCs by mild methods, that do not involve gene and/or chromatin modification or gene transfection, is highly desirable for cell therapy. Canonical Wnt and Notch are two highly conserved developmental signalling pathways that are involved in NC emergence and stem cell self-renewal. We determined that both pathways coordinate to regulate the expression of core pluripotency and NC factors in DPSCs. Pharmacological inhibition of the Notch pathway for 48 h, by the gamma-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), abolished the expression of NC and core factors. In addition, it induced a silencing of the canonical Wnt signalling and a clear reduction in the stemness potential of DPSCs, as shown by a reduced ability to generate mature, fully differentiated osteoblasts and adipocytes. Conversely, pharmacological activation of the Wnt pathway for 48 h, by either the glycogen synthase kinase 3 beta (GSK3-beta) inhibitor 6-bromoindirubin-3'-oxime (BIO) or the human recombinant protein Wnt-3a, not only largely increased the expression of NC and core factors, but also increased the efficiency of DPSCs to differentiate into mature osteoblasts and adipocytes. These results showed that a short preconditioning activation of Wnt/Notch signalling by small molecules and/or recombinant proteins enhanced the stemness and potency of DPSCs in culture, which could be useful for optimising the therapeutic use of these and other tissue-specific stem cells.Technical and human support provided by the analytical microscopy service of SGIKER (UPV/EHU, MINECO, GV/EJ, ERDF and ESF) is gratefully acknowledged. This work was funded by the UPV/EHU (GIU16/66, UFI 11/44) and the Basque Government (GV/EJ; IT831-13). V.U. received a fellowship from The Global Training Grant (GV/EJ) to fund a research stage at The Institute of Cancer Research (London, UK)

Vasculogenesis from Human Dental Pulp Stem Cells Grown in Matrigel with Fully Defined Serum-Free Culture Media

The generation of vasculature is one of the most important challenges in tissue engineering and regeneration. Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types to induce vasculogenesis and angiogenesis as they not only secrete vascular endothelial growth factor (VEGF) but can also differentiate in vitro into both endotheliocytes and pericytes in serum-free culture media. Moreover, hDPSCs can generate complete blood vessels containing both endothelial and mural layers in vivo, upon transplantation into the adult brain. However, many of the serum free media employed for the growth of hDPSCs contain supplements of an undisclosed composition. This generates uncertainty as to which of its precise components are necessary and which are dispensable for the vascular differentiation of hDPSCs, and also hinders the transfer of basic research findings to clinical cell therapy. In this work, we designed and tested new endothelial differentiation media with a fully defined composition using standard basal culture media supplemented with a mixture of B27, heparin and growth factors, including VEGF-A165 at different concentrations. We also optimized an in vitro Matrigel assay to characterize both the ability of hDPSCs to differentiate to vascular cells and their capacity to generate vascular tubules in 3D cultures. The description of a fully defined serum-free culture medium for the induction of vasculogenesis using human adult stem cells highlights its potential as a relevant innovation for tissue engineering applications. In conclusion, we achieved efficient vasculogenesis starting from hDPSCs using serum-free culture media with a fully defined composition, which is applicable for human cell therapy purposes.This work was financed by the «Ramón y Cajal» program RYC-2013-13450 (JRP); UPV/EHU (GIU16/66, UFI 11/44 and COLAB19/03; FU); MINECO Retos I + D + I (SAF2015-70866-R; JRP, PID2019-104766RB-C21; JRP); Basque Government (GV/EJ; IT831-13; GI) TERSAFURNA-2020333039 and ELKARTEK KK-2019-00093. J.L. has a grant from UPV/EHU (DOKBERRI 2019(DOCREC19/49)). I.I. has a grant from the Basque Government (PRE_2019_2_0300 or GIU16/66)

Human DenPulp Stem Cells Grown in Neurogenic Media Differentiate Into Endothelial Cells and Promote Neovasculogenesis in the Mouse Brain

Dental pulp stem cells (DPSCs) have the capacity to give rise to cells with neuronal-like phenotypes, suggesting their use in brain cell therapies. In the present work, we wanted to address the phenotypic fate of adult genetically unmodified human DPSCs cultured in Neurocult (TM) (Stem Cell Technologies), a cell culture medium without serum which can be alternatively supplemented for the expansion and/or differentiation of adult neural stem cells (NSCs). Our results show that non-genetically modified human adult DPSCs cultured with Neurocult NS-A proliferation supplement generated neurosphere-like dentospheres expressing the NSC markers Nestin and glial fibrillary acidic protein (GFAP), but also the vascular endothelial cell marker CD31. Remarkably, 1 month after intracranial graft into athymic nude mice, human CD31+/CD146+ and Nestin+ DPSC-derived cells were found tightly associated with both the endothelial and pericyte layers of brain vasculature, forming full blood vessels of human origin which showed an increased laminin staining. These results are the first demonstration that DPSC-derived cells contributed to the generation of neovasculature within brain tissue, and that Neurocult and other related serum-free cell culture media may constitute a fast and efficient way to obtain endothelial cells from human DPSCs.This work was funded by "Ramon y Cajal" program RYC-2013-13450 (JRP) and RYC 2012-11137 (JME); Spanish Ministry of Economy and Competitiveness SAF2015-70866-R; UPV/EHU (GIU16/66, UFI 11/44); and Basque Government (GV/EJ; IT831-13). JL and OP-A obtained a Ph.D. fellowship from the University of the Basque Country (UPV/EHU)

The impact of creativity on functional outcome in schizophrenia: a mediational model

Functional impairment remains one of the most challenging issues for treatment in schizophrenia. However, previous studies have mainly focused on the negative impact of symptoms excluding variables that could positively impact functional outcome, such as creativity, which is considered an adaptive capacity for real-life problem-solving. This study analyzed the predictive role of creativity on functional outcome in 96 patients with schizophrenia through a mediational model, including sociodemographic, clinical, neurocognitive, and social cognitive variables. Path analysis revealed that creativity significantly mediated the relationship between neurocognition and functional outcome, and that creativity mediated between negative symptoms and functional outcome. Additionally, neurocognition was directly associated with functional outcome and social functioning was associated with creativity. The involvement of creativity in functional outcome could have relevant implications for the development of new interventions. These findings open up a new field of research on additional personal resources as possible factors of functional outcome in schizophrenia and other diseases

Neurocognitive, social cognitive, and clinical predictors of creativity in schizophrenia

Background: Creativity is considered an essential human accomplishment and a key component for daily life problem solving. It has been suggested that impairment in working memory, cognitive flexibility, and theory of mind could lead to lower creativity in schizophrenia. Additionally, other neurocognitive and social cognitive domains, as well as clinical symptoms could play a role in this relationship. However, the extent to which each of these domains influences creativity in schizophrenia remains unknown. Therefore, the aim of this study was to simultaneously investigate the specific contribution of neurocognitive, social cognitive, and clinical variables to creativity in schizophrenia. Methods: One hundred and one patients with schizophrenia were assessed in terms of sociodemographic, clinical, neurocognitive, social cognitive, and creativity variables. Results: After controlling for sociodemographic variables, regression analyses showed that higher social perception (beta = 0.286, p = .004) and processing speed (beta = 0.219, p = .023) predicted creativity total score. Higher social perception (beta = 0.298, p = .002) and processing speed (beta = 0.277, p = .004) explained figural creativity. Finally, lower negative symptoms (beta =-0.302, p = .002) and higher social perception (beta = 0.210, p = .029) predicted verbal creativity. Conclusions: Results suggest that neurocognitive, social cognitive, as well as clinical symptoms influence creativity of patients with schizophrenia. Moreover, these findings point out the prominent role of social cognition in creativity in schizophrenia.This study has been supported by the Spanish Ministry of Economy and Competitiveness (PI16/01022) and the Department of Education and Science of the Basque Government (Team A) (IT946-16). AS was supported by a Fellowship from the Fundacion Tatiana Perez de Guzman el Bueno. The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cognitive, creative, functional, and clinical symptom improvements in schizophrenia after an integrative cognitive remediation program: a randomized controlled trial

[EN] This study analyzed the effectiveness of an integrative cognitive remediation program (REHACOP) in improving neurocognition, social cognition, creativity, functional outcome, and clinical symptoms in patients with schizophrenia. In addition, possible mediators predicting improvement in functional outcomes were explored. The program combined cognitive remediation with social cognitive training and social and functional skill training over 20 weeks. The sample included 94 patients, 47 in the REHACOP group and 47 in the active control group (occupational activities). Significant differences were found between the two groups in change scores of processing speed, working memory, verbal memory (VM), inhibition, theory of mind, emotion processing (EP), figural creative strengths, functional competence, disorganization, excitement, and primary negative symptoms. A mediational analysis revealed that changes in VM, inhibition, and EP partially explained the effect of cognitive remediation on functional competence improvement. This study provides initial evidence of the effect of integrative cognitive remediation on primary negative symptoms and creativity.This work was supported by the Carlos III Health Institute of the Spanish Ministry of Economy and Competitiveness (PI16/01022); the Department of Education and Science of the Basque Government (Team A) (IT946-16); the Fundacion Tatiana Perez de Guzman el Bueno (to AS); and the University of the Basque Country (UPV/EHU) (PIF 19/40 to MTE). The funding agencies had no role in the design, data collection, and analysis, decision to publish, or preparation of the study. The authors thank all the participants and clinical teams who were involved in this study as well as the English language editing service. Our special thanks to Amaia Ortiz de Zarate, Edorta Elizagarate, and Isabel Hervella for all the support in the recruitment and management of patients

Structural correlates of facial emotion recognition deficits in Parkinson's disease patients

The ability to recognize facial emotion expressions, especially negative ones, is described to be impaired in Parkinson's disease (PD) patients. Previous neuroimaging work evaluating the neural substrate of facial emotion recognition (FER) in healthy and pathological subjects has mostly focused on functional changes. This study was designed to evaluate gray matter (GM) and white matter (WM) correlates of FER in a large sample of PD. Thirty-nine PD patients and 23 healthy controls (HC) were tested with the Ekman 60 test for FER and with magnetic resonance imaging. Effects of associated depressive symptoms were taken into account. In accordance with previous studies, PD patients performed significantly worse in recognizing sadness, anger and disgust. In PD patients, voxel-based morphometry analysis revealed areas of positive correlation between individual emotion recognition and GM volume: in the right orbitofrontal cortex, amygdala and postcentral gyrus and sadness identification; in the right occipital fusiform gyrus, ventral striatum and subgenual cortex and anger identification, and in the anterior cingulate cortex (ACC) and disgust identification. WM analysis through diffusion tensor imaging revealed significant positive correlations between fractional anisotropy levels in the frontal portion of the right inferior fronto-occipital fasciculus and the performance in the identification of sadness. These findings shed light on the structural neural bases of the deficits presented by PD patients in this skill