Desarrollo de métodos in vitro para la determinación de la penetración en el sistema nervioso central y nuevos híbridos anti-alzheimer derivados de tacrina o de dibencilmetilamina

En el Capítulo I se han desarrollado se han puesto en marcha dos tipos de experimentos in vitro para evaluar la penetración de moléculas en el SNC: difusión horizontal a través de membranas artificiales y la metodología PAMPA. En ambos, la barrera biológica se ha simulado empleando un extracto lipídico de cerebro de cerdo soportado en un filtro. El método de difusión horizontal tiene como ventaja que permite realizar estudios cinéticos, pero su principal inconveniente es su lentitud y que se necesitan cantidades relativamente elevadas de producto.El método PAMPA es más rápido, reproducible y de menor coste que el anterior. Permite la evaluación de series en poco tiempo y requiere poca cantidad de producto, entre 1 y 5 mg suelen ser suficientes para la evaluación in vitro de la penetración en el SNC. Empleando la metodología PAMPA, se ha optimizado el empleo de diferentes cosolventes en varias proporciones para poder evaluar moléculas de limitada solubilidad acuosa. Concretamente, se ha validado el empleo de mezclas PBS : etanol (90:10, 80:20 y 70:30), PBS : PEG-400 (90:10 y 80:20) y PBS : MeCN (90:10). Y en en Capítulo II se han obtenido varias familias de moléculas multifuncionales con propiedades colinérgicas, antioxidantes, neuroprotectoras y neurogénicas, dirigidas a un potencial tratamiento de la enfermedad de Alzheimer. Empleando fragmentos de conocidos inhibidores de AChE, se han diseñado híbridos derivados de tacrina y de N,N-dibencil(N-metil)amina, que en algunos casos han mostrado mejores propiedades biológicas que los fragmentos que los componen. Se han optimizado métodos de síntesis y se ha realizado la asignación de los datos espectroscópicos de 1H- y 13C-RMN de los productos obtenidos.Departamento de Química Física y Química InorgánicaDoctorado en Química: Química de Síntesis, Catálisis y Materiales Avanzado

Skeletal Class III Malocclusion in an Adult Patient – Orthodontics versus Orthognathic Surgery: Is there Another Alternative?

Class III malocclusions are considered to be one of the most difficult problems to treat. Due to the significant number of patients with Class III malocclusion who cannot undergo orthognathic surgery for different reasons, we have proposed an alternative treatment that we have called surgically assisted rapid palatal expansion (SARPE) + temporary anchorage devices (TADs) which allows solving mild and moderate Class III malocclusion combined with maxillary compression, obtaining acceptable esthetic and functional results. We present a case report of an adult female with skeletal Class III malocclusion with compression in the maxillary and mandibular asymmetry, who was treated with SARPE + TADs. The result is acceptable in terms of occlusion function, esthetic of the smile, and facial estheticsS

Analysis of the shoes in a population over 60

El calzado representa una de las partes indispensables en la indumentaria de las personas en la cultura occidental. Utilizado de manera adecuada sirve como un elemento de protección al pie y de ayuda a la deambulación. Sin embargo cuando se utiliza de manera no adecuada se relaciona directamente con caídas, alteraciones en la marcha y aparición o agravamiento de patologías en el pie. En el presente trabajo realizamos un estudio del tipo de calzado más utilizado en una población mayor de 60 años, si éste era adecuado o no y si la población geriátrica poseía información acerca de cuál es el calzado mas adecuado para ellos e intentamos relacionar la visita al Podólogo con la utilización de calzado adecuado o no.Footwear represents an essential part of garment of people in occidental culture. If utilized in a correct way, it provides protection and aid in human gait. Nevertheless, if utilized incorrectly, it’s related to falls, alterations in gait and appearance or worsening in foot pathology. In the present issue, we studied what style of footwear is the most commonly used in a community older of 60, if it was appropriate or inappropriate and if geriatric community had information enough to know what is the most appropriat

La incorporación de la voz del alumnado en el desarrollo de una estructura curricular modular. La experiencia del grado de educación social en la UPV-EHU

Con el objetivo de acercar las prácticas universitarias al discurso de democratización educativa, este artículo recoge la experiencia de la incorporación de la voz del alumnado en el desarrollo de la estructura modular del Grado de Educación Social de la UPV-EHU. Centrándonos en un análisis del efecto de la incorporación de la voz del alumnado en las estructuras organizativas, en diferentes contextos, en su propio aprendizaje y en el cambio de las prácticas docentes, hemos intentado desvelar el sentido otorgado a la participación del alumnado en la vida formativa y universitaria, detectar los claroscuros que se visualizan a su acción como sujeto y analizar el efecto producido en su aprendizaje.With the aim of bringing university practices to address educational democratization, this article describes the experiences of incorporating student voice in the development of the modular structure of Social Education degree from the UPV-EHU. Focusing on an analysis of the effect of the incorporation of student voice in organizational structures, in different contexts, in their own learning and changing teaching practices, we tried to reveal the meaning given to student participation in the life training and university detect shades that are displayed to its action as a subject and analyze the effect on their learning

Intron retention generates ANKRD1 splice variants that are co-regulated with the main transcript in normal and failing myocardium

[Abstract] The cardiac ankyrin repeat domain 1 protein (ANKRD1, also known as CARP) has been extensively characterized with regard to its proposed functions as a cardio-enriched transcriptional co-factor and stress-inducible myofibrillar protein. The present results show the occurrence of alternative splicing by intron retention events in the pig and human ankrd1 gene. In pig heart, ankrd1 is expressed as four alternatively spliced transcripts, three of which have non-excised introns: ankrd1-contained introns 6, 7 and 8 (i.e., ankrd1-i6,7,8), ankrd1-contained introns 7 and 8 (i.e., ankrd1-i7,8), and ankrd1 retained only intron 8 (i.e., ankrd1-i8). In the human heart, two orthologues of porcine intron-retaining ankrd1 variants (i.e., ankrd1-i8 and ankrd1-i7,8) are detected. We demonstrate that these newly-identified intron-retaining ankrd1 transcripts are functionally intact, efficiently translated into protein in vitro and exported to the cytoplasm in cardiomyocytes in vivo. In the piglet heart, both the intronless and intron-retaining ankrd1 mRNAs are co-expressed in a chamber-dependent manner being more abundant in the left as compared to the right myocardium. Our data further indicate co-upregulation of the ankrd1 spliced variants in myocardium in the porcine model of diastolic heart failure. Most significantly, we demonstrate that in vivo forced expression of recombinant intronless ankrd1 markedly increases the levels of intron-retaining ankrd1 variants (but not of the endogenous main transcript) in piglet myocardium, suggesting that ANKRD1 may positively regulate the expression of its own intron-containing RNAs in response to cardiac stress. Overall, our findings demonstrate that in cardiomyocytes ANKRD1 can exist in multiple isoforms which may contribute to the functional diversity of this factor in heart development and disease.Ministerio de Ciencia e Innovación; SAF2004-01462Ministerio de Ciencia e Innovación; SAF2008-00337Galicia. Consellería de Economía e Industria; 08CSA008161P

Delimiting adolescent aggression: A differential study of patterns of reactive and proactive aggression

La conducta agresiva constituye un fenómeno complejo en el que se recogen, bajo una misma etiqueta, diversos comportamientos que van a diferir en múltiples aspectos. Dicha diversidad ha llevado a plantear modelos de clasificación entre los que cabe destacar la diferenciación entre agresión de tipo reactivo, considerada como una reacción defensiva ante un acontecimiento determinado, y agresión proactiva, definida por su carácter instrumental, premeditado y ofensivo. Con el fin de analizar los correlatos de la agresión reactiva y proactiva se ha examinado su relación con un conjunto de variables analizadas en una muestra de 138 participantes (12-17 años). Los resultados permitieron observar la presencia de relaciones diferenciales y delimitar el fenómeno de la conducta agresiva adolescente, justificando la diferenciación entre agresión reactiva, relacionada con impulsividad, problemas de internalización o menor competencia a nivel social, y agresión proactiva, caracterizada por menores niveles de ansiedad o neuroticismo, y una mayor presencia de rasgos psicopáticosAggressive behaviour is a complex phenomenon that covers, under the same label, different behaviours which will differ in many ways. This diversity has led to propose a number of classification models among which it must be underlined the differentiation between reactive aggression, considered a defensive reaction to a particular event, and proactive aggression, defined by its instrumental, deliberate and offensive nature. In order to analyse the correlates of reactive and proactive aggression, this study has examined their relationship with a set of variables analysed in a sample of 138 participants (aged 12 to 17). The results showed a pattern of differential correlations, and allowed to delimit the phenomenon of adolescent aggressive behaviour. These results justify the distinction between reactive aggression, related to impulsivity, internalizing problems and lower social competence level, and proactive aggression, characterized by lower levels of anxiety or neuroticism, and greater presence of psychopathic traitsS

AI literacy in K‑12: a systematic literature review

The successful irruption of AI-based technology in our daily lives has led to a growing educational, social, and political interest in training citizens in AI. Education systems now need to train students at the K-12 level to live in a society where they must interact with AI. Thus, AI literacy is a pedagogical and cognitive challenge at the K-12 level. This study aimed to understand how AI is being integrated into K-12 education worldwide. We conducted a search process following the systematic literature review method using Scopus. 179 documents were reviewed, and two broad groups of AI literacy approaches were identified, namely learning experience and theoretical perspective. The first group covered experiences in learning technical, conceptual and applied skills in a particular domain of interest. The second group revealed that significant efforts are being made to design models that frame AI literacy proposals. There were hardly any experiences that assessed whether students understood AI concepts after the learning experience. Little attention has been paid to the undesirable consequences of an indiscriminate and insufficiently thought-out application of AI. A competency framework is required to guide the didactic proposals designed by educational institutions and define a curriculum reflecting the sequence and academic continuity, which should be modular, personalized and adjusted to the conditions of the schools. Finally, AI literacy can be leveraged to enhance the learning of disciplinary core subjects by integrating AI into the teaching process of those subjects, provided the curriculum is co-designed with teachersThis work has partially been funded by the Spanish Ministry of Science, Innovation and Universities (PID2021-123152OB-C21), and the Consellería de Educación, Universidade e Formación Profesional (accreditation 2019–2022 ED431C2022/19 and reference competitive group, ED431G2019/04) and the European Regional Development Fund (ERDF), which acknowledges the CiTIUS— Centro Singular de Investigación en Tecnoloxías Intelixentes da Universidade de Santiago de Compostela as a Research Center of the Galician University System. This work also received support from the Educational Knowledge Transfer (EKT), the Erasmus + project (reference number 612414-EPP-1-2019-1- ES-EPPKA2-KA) and the Knowledge Alliances call (Call EAC/A03/2018)S

Determination of the Presence of Three Antimicrobials in Surface Water Collected from Urban and Rural Areas

Due to the continuous release of antimicrobials into the environment, the aim of this study was to compare the frequency of detection of sulfamethazine, sulfamethoxypyridazine and trimethoprim in surface water collected from urban and rural areas in Northwestern Spain. A monitoring study was conducted with 314 river water samples analyzed by high-performance liquid chromatography coupled to tandem mass spectrometry. The results indicated that 37% of the samples contained residues of at least one of the investigated antimicrobials, and every sampling site yielded positive samples. At sites located near the discharge points of wastewater treatment plants and near the collection point of a drinking-water treatment plant, more than 6% of the samples were positive for the presence of antimicrobial residuesThe authors wish to thank the Fondo Europeo Agrícola de Desarrollo Rural (FEADER) and the Consellería de Medio Rural for funding this study through the Project FMR331AS

Oxaliplatin–Biomimetic Magnetic Nanoparticle Assemblies for Colon Cancer-Targeted Chemotherapy: An In Vitro Study

Conventional chemotherapy against colorectal cancer (CRC), the third most common cancer in the world, includes oxaliplatin (Oxa) which induces serious unwanted side effects that limit the efficiency of treatment. Therefore, alternative therapeutic approaches are urgently required. In this work, biomimetic magnetic nanoparticles (BMNPs) mediated by MamC were coupled to Oxa to evaluate the potential of the Oxa–BMNP nanoassembly for directed local delivery of the drug as a proof of concept for the future development of targeted chemotherapy against CRC. Electrostatic interactions between Oxa and BMNPs trigger the formation of the nanoassembly and keep it stable at physiological pH. When the BMNPs become neutral at acidic pH values, the Oxa is released, and such a release is greatly potentiated by hyperthermia. The coupling of the drug with the BMNPs improves its toxicity to even higher levels than the soluble drug, probably because of the fast internalization of the nanoassembly by tumor cells through endocytosis. In addition, the BMNPs are cytocompatible and non-hemolytic, providing positive feedback as a proof of concept for the nanoassembly. Our study clearly demonstrates the applicability of Oxa–BMNP in colon cancer and offers a promising nanoassembly for targeted chemotherapy against this type of tumor.This work was also supported by the Consejería de Salud de la Junta de Andalucía (projects PI-0476-2016 and PI-0102-2017). Y.J. and B.G.-P. acknowledge FPU2016 grants (FPU16_04580 and FPU16_01716, respectively) from the Ministerio de Educación, Ciencia, y Deporte y Competitividad (Spain)

Registro de paisajes de interés cultural de Andalucía: criterios y metodología

La importancia que están adquiriendo los estudios y prácticas sobre el paisaje hacen de este recurso espacial uno de los grandes protagonistas de todas las políticas públicas que tienen incidencia territorial. Por otro lado, los compromisos adquiridos al reconocer el Convenio Europeo del Paisaje obligan a las instancias públicas a dar respuestas a situaciones y problemas que precisan reflexión previa y metodologías de análisis rigurosas al tiempo que flexibles en relación con este objeto de estudio. Además, en los estudios sobre paisaje, la categoría de paisajes culturales o patrimoniales, asimilables a los paisajes protegidos del Convenio, ofrece una nueva escala en la que entender los valores de los bienes culturales. Superados como paradigma de la tutela patrimonial, los conjuntos históricos y los entornos se revelan insuficientes para una responsabilidad de protección que se fija ahora en la escala general del territorio. Esto motiva no sólo un cambio de escala, sino también un cambio en la concepción de la propia protección. Este artículo pretende, a través de la presentación de los paisajes de interés cultural, proporcionar nuevas claves, métodos y temas de debate sobre cómo entender y gestionar el patrimonio cultural y hacer de éste un verdadero factor de calidad de poblaciones y territorios