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En 1909, la Russell Sage Foundation promovió un experimento económico y social consistente en la implantación de una ciudad suburbio modelo en el barrio de Queens (Nueva York): Forest Hills Gardens. La que fuera primera ciudad-jardín americana sintetiza un ejercicio de equilibrio entre la filantropía y la especulación, entre la naturaleza y la ciudad, entre la comunidad y la privacidad, entre la segregación y la inclusión, entre el diseño urbano y el determinismo social, entre la industrialización y el arte, entre la tradición y la modernidad o entre la estandarización y la identidad. En Forest Hills Gardens se evidencian las contradicciones que surgen a menudo entre los resultados de lo que se hace y lo que se quiere hacer, en un momento de enorme trascendencia ante el cambio en la forma de hacer ciudad, alentado por los avances tecnológicos, en Estados Unidos.

De novo GRIN variants, encoding for the ionotropic glutamate NMDA receptor subunits, have been recently associated with GRIN-related disorders, a group of rare paediatric encephalopathies. Current investigational and clinical efforts are focused to functionally stratify GRIN variants, towards precision therapies of this primary disturbance of glutamatergic transmission that affects neuronal function and brain. In the present study, we aimed to comprehensively delineate the functional outcomes and clinical phenotypes of GRIN protein truncating variants (PTVs)-accounting for ~20% of disease-associated GRIN variants-hypothetically provoking NMDAR hypofunctionality. To tackle this question, we created a comprehensive GRIN PTVs variants database compiling a cohort of nine individuals harbouring GRIN PTVs, together with previously identified variants, to build-up an extensive GRIN PTVs repertoire composed of 293 unique variants. Genotype-phenotype correlation studies were conducted, followed by cell-based assays of selected paradigmatic GRIN PTVs and their functional annotation. Genetic and clinical phenotypes meta-analysis revealed that heterozygous GRIN1, GRIN2C, GRIN2D, GRIN3A and GRIN3B PTVs are non-pathogenic. In contrast, heterozygous GRIN2A and GRIN2B PTVs are associated with specific neurological clinical phenotypes in a subunit- and domain-dependent manner. Mechanistically, cell-based assays showed that paradigmatic pathogenic GRIN2A and GRIN2B PTVs result on a decrease of NMDAR surface expression and NMDAR-mediated currents, ultimately leading to NMDAR functional haploinsufficiency. Overall, these findings contribute to delineate GRIN PTVs genotype-phenotype association and GRIN variants stratification. Functional studies showed that GRIN2A and GRIN2B pathogenic PTVs trigger NMDAR hypofunctionality, and thus accelerate therapeutic decisions for this neurodevelopmental condition.

Background Despite the growing public awareness of the adverse health effects of sugar-sweetened beverages (SSB) consumption in Mexico, little is known about the population’s intention to reduce SSB consumption and the social value of interventions to accomplish such behavioral change. Therefore, the objective of this study was to assess the willingness to pay (WTP) for an intervention that reduces soda consumption by half in Mexico. Methods We applied contingent valuation methods in a sample of 471 Mexican adults from a cohort study. We assessed the relative value of benefits by providing incremental information to participants in three scenarios: soda consumption reduction, + health benefits, + social benefits. To estimate factors associated with the WTP, we ran an interval regression. Results 87% of respondents reported they would like to reduce SSB consumption. High soda consumption, intention to reduce soda consumption and higher household income are associated with higher WTP. We found that the WTP increases as additional benefits are provided. The WTP, as a proportion of income, is higher for the lowest income level. Conclusion The average WTP per person may be seen as the minimum amount the country should invest on interventions to reduce soda consumption.

BACKGROUND: Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy.METHODS: For this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABAA receptors and was compared to the respective GABAA receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes.FINDINGS: Statistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABAA receptors in cases (odds ratio [OR] 2·40 [95% CI 1·41-4·10]; pNonsyn=0·0014, adjusted pNonsyn=0·019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1·46 [95% CI 1·05-2·03]; pNonsyn=0·0081, adjusted pNonsyn=0·016). Comparison of genes encoding GABAA receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare missense variants for 15 GABAA receptor genes in cases compared with controls (OR 1·46 [95% CI 1·02-2·08]; pNonsyn=0·013, adjusted pNonsyn=0·027). Functional studies for two selected genes (GABRB2 and GABRA5) showed significant loss-of-function effects with reduced current amplitudes in four of seven tested variants compared with wild-type receptors.INTERPRETATION: Functionally relevant variants in genes encoding GABAA receptor subunits constitute a significant risk factor for genetic generalised epilepsy. Examination of the role of specific gene groups and pathways can disentangle the complex genetic architecture of genetic generalised epilepsy.FUNDING: EuroEPINOMICS (European Science Foundation through national funding organisations), Epicure and EpiPGX (Sixth Framework Programme and Seventh Framework Programme of the European Commission), Research Unit FOR2715 (German Research Foundation and Luxembourg National Research Fund).

A raíz de las bases de la teoría de grafos que surgieron en el siglo XVIII y sus desarrollos posteriores, es posible estudiar las relaciones o vínculos existentes en un conjunto de elementos y determinar las características y propiedades de dichas relaciones. En las últimas décadas, los importantes y continuos avances en el ámbito de las ciencias de la computación han permitido modelar y analizar grafos de cualquier escala y tipología correspondientes a sistemas reales de alta complejidad que proceden de multitud de áreas de conocimiento como ingeniería, física, ciencias sociales, etc. En la actualidad, gracias al modelado y análisis de grafos por computador, es posible obtener información valiosa sobre las relaciones funcionales o las características de un determinado sistema, por complejo que éste sea. Ello ha dado lugar a que investigadores de todo el mundo muestren un gran interés por resolver una amplia variedad de problemas relacionados con grafos, como pueden ser: partición de grafos, coloreado de grafos, problemas de enrutado, problemas de flujos en redes, etc. Todos estos problemas son altamente complejos, hasta el punto de estar incluidos en la categoría de problemas NP-completos, lo que implica que instancias lo suficientemente grandes de dichos problemas no pueden ser resueltos en un tiempo limitado En los últimos años, un problema relativamente nuevo que puede ser abordado mediante las técnicas de análisis basadas en grafos, ha despertado un gran interés dentro de la comunidad científica debido al potencial de analizar sistemas complejos que éste ofrece. Este problema, llamado detección de comunidades, nace a raíz de una característica común inherente a todos los sistemas complejos, la presencia de patrones de nodos más densamente conectados entre sí que con el resto de nodos de la red. De los nodos que muestran estos patrones de conexión, llamados comunidades, se espera que compartan ciertas propiedades que permitirán detectar nuevas características o relaciones funcionales de la red. La búsqueda de estos patrones o estructuras de comunidades es conocida como problema de la detección de comunidades, el cual ha sido clasificado en la literatura científica como problema NP-completo. Cómo encontrar la estructura de comunidades óptima que mejor representa las características de una red, se ha convertido en todo un hándicap, pues se han propuesto multitud de algoritmos y funciones objetivo para resolver el problema. Entre ellos, los algoritmos evolutivos y el índice de Modularidad han destacado como las principales soluciones aceptadas por la comunidad científica. Además de la importancia de la búsqueda de un algoritmo capaz de resolver el problema de la detección de comunidades eficientemente, el análisis de redes complejas a menudo se encuentra limitado a estudiar las características de una red desde una única perspectiva debido al enfoque propuesto por la mayoría de los algoritmos que encontramos en la literatura científica. Con el fin de lograr un análisis más completo y detallado de las redes objeto de estudio, esta tesis doctoral propone un enfoque novedoso, flexible y adaptativo para el análisis de comunidades de cualquier complejidad y tipología de red. En particular, se analizan redes de diferente topología y extensión comúnmente utilizadas en la literatura científica, y, además, se lleva a cabo un estudio pionero en el ámbito de ingeniería eléctrica sobre redes de transmisión de alta tensión. La importancia de este estudio radica en que estamos tratando con una de las mayores infraestructuras creadas por el hombre, con cientos de miles de kilómetros de líneas de alta tensión que interconectan no sólo regiones y países, sino también áreas continentales. Además, debido a la creciente demanda de electricidad y a la aparición de nuevos formatos de generación eléctrica, resulta imprescindible abordar el estudio sobre la ampliación y modificación de redes eléctricas mediante nuevos procedimientos complementarios a las técnicas tradicionales utilizadas en el estudio de sistemas eléctricos de potencia. La incorporación de estos nuevos formatos de generación de energía eléctrica renovables, está provocando que el diseño clásico de las redes eléctricas pase de un modelo centralizado, basado en disponer de un número relativamente acotado de centrales térmicas, nucleares e hidroeléctricas, a un modelo distribuido con unpeso creciente en energías renovables, originando así un aumento de laconectividad en las redes y, por consiguiente, un incremento de su complejidad. En este sentido, se hace indispensable la necesidad de aplicar estrategias de control más robustas, así como nuevas técnicas de optimización para gestionar sistemas a gran escala. Actualmente, aunque existen procedimientos de análisis y diseño de redes eléctricas, como es el caso de la resolución de flujos de potencia que permite analizar múltiples configuraciones del sistema eléctrico, el inmenso abanico de posibles configuraciones existentes provoca que sea necesario aplicar nuevos procedimientos complementarios de cara a hacer factible la búsqueda de soluciones. En este sentido, en la presente tesis doctoral se aplica la detección de comunidades en el estudio y análisis de redes eléctricas de gran tamaño a fin de ampliar las conclusiones obtenidas por los procedimientos tradicionales, además de analizar los resultados como posibles mejoras de control de la red, que supondrían de una mayor fiabilidad y capacidad de restauración ante graves perturbaciones como desastres naturales (tormentas, terremotos, etc.) mediante el desarrollo de nuevos planes de conmutación para proteger islas o desconexiones parciales de la red, evitando así una mayor degradación durante los incidentes. En resumen, el objetivo de esta tesis se centra en afrontar el problema de la detección de comunidades en ámbitos que precisan de la aparición de nuevas técnicas de diseño y control, a través del desarrollo de nuevos algoritmos evolutivos (mono-objetivo y multiobjetivo) que permitan analizar las características topológicas de una red desde distintas perspectivas, con mayor o menor nivel de detalle en función de las necesidades del analista. Para lograr este objetivo, en primer lugar, se han diseñado métodos de inicialización poblacional eficientes y operadores evolutivos avanzados basados en intercambios entre comunidades, que han sido incorporados al algoritmo genético mono-objetivo propuesto en esta tesis, el cual optimiza el popular Indice de Modularidad como función objetivo. Dicho algoritmo, denominado “Generational Genetic Algorithm” (GGA+), ha sido evaluado mediante un análisis de rendimiento sobre multitud de benchmarks populares basados en redes sociales, además de sobre grafos de gran escala con miles de nodos y aristas que representan redes reales de transmisión de alta tensión de escala nacional y continental. Tras el éxito de los resultados mostrados por la implementación del algoritmo mono-objetivo, con la finalidad de evaluar el rendimiento que los métodos de detección de comunidades evolutivos pueden ofrecer en el ámbito de ingeniería, distintos algoritmos como el mencionado GGA+ y otros algoritmos evolutivos referenciados en la literatura, como “Modularity and Improved Genetic Algorithm” (MIGA) o el bien conocido método de “Louvain”, se han aplicado sobre múltiples redes eléctricas, demostrando que los resultados obtenidos avalan su utilidad y buen rendimiento. Actualmente, la mayoría de métodos destinados a resolver el problema de la detección de comunidades, utilizan un enfoque mono-objetivo, siendo el índice Modularidad la función objetivo más extendida. Sin embargo, debido a la propia definición de comunidad en la que ésta puede ser vista desde un enfoque multiobjetivo, donde un objetivo puede ser maximizar el número de conexiones dentro de una comunidad y otro objetivo minimizar el número de conexiones con nodos externos a la comunidad, y, debido a que algunos estudios recientes han demostrado que al considerar Modularidad como único objetivo pueden surgir inconvenientes relacionados con el límite de resolución y desbalanceo de las soluciones, parece adecuado plantear el problema de la detección de comunidad desde un punto de vista multiobjetivo. Por estos motivos, en segundo lugar, basándonos en el buen rendimiento demostrado por GGA+, se ha diseñado una nueva versión multiobjetivo llamada MOGGA+, la cual incluye nuevos objetivos a optimizar en la detección de comunidades, abriendo de esta manera una nueva vía de investigación mediante la aplicación de algoritmos evolutivos multiobjetivo que optimizan simultáneamente diferentes objetivos. Más concretamente, MOGGA+ ha sido diseñado con nuevos métodos de inicialización avanzados y operadores evolutivos. Además, utiliza un conjunto de soluciones no dominadas basado en la dominancia de Pareto, y una estructura adicional para modificar dinámicamente la probabilidad de aplicar distintos operadores evolutivos en tiempo de ejecución. En cuanto a los diferentes objetivos optimizados, se ha analizado la combinación del índice de Modularidad con un novedoso objetivo propuesto en esta tesis, “Desbalanceo” de comunidades, propiedad a tener en cuenta a la hora de diseñar redes eléctricas resistentes a contingencias, donde es importante que la red pueda ser separada en islas (subredes) de escala aproximadamente similar, para evitar una mayor degradación de la red. También se ha analizado el objetivo Conductancia (como alternativa a Modularidad) junto con Desbalanceo. Conductancia es una medida de lafracción del volumen total de aristas en un subgrafo que están conectados a vértices o nodos de otros subgrafos de una red. Por último, cabe señalar que MOGGA+ incorpora técnicas de paralelismo para mejorar su rendimiento. Abstract: Following the foundations of graph theory that emerged in the eighteenth century, as well as its subsequent developments, it is possible to study the relationships or links existing in a set of elements and identify the characteristics and properties of those relationships. In the recent decades, the important and continuous advances in the field of computer science have made it possible to model and analyze graphs of any scale and typologycorresponding to highly complex real systems that come from many areas of knowledge, such as engineering, physics and social sciences. At present, thanks to computer graphics modeling and analysis, it is possible to obtain valuableinformation on the functional relationships or characteristics of a specificsystem, however complex it may be. This has led researchers around the world to show great interest in solving a wide variety of graph-related problems, among which can be found: graph partitioning, graph coloring, routing problems and network flow problems. All these problems are highly complex, to the extent that they are included in the category of NP-complete problems, which implies that sufficiently large instances of such problems cannot be solved in a limited time. In recent years, a relatively new problem that can be addressed through graphical analysis techniques has sparked great interest within the scientific community due to the potential to analyze the complex systems it offers. This problem, called community detection, arises from a common characteristic inherent in all complex systems, the presence of node patterns more densely connected to each other than to the rest of the nodes in the network. The nodes that show these connection patterns, called communities, are expected to share certain properties that will allow them to detect new features or functional relationships in the network. The search for these community structures is known as the community detection problem, which has also been classified in the scientific literature as an NP-complete problem. How to find the optimal community structure that best represents the characteristics of a network has become a real handicap, since many objective algorithms and functions have been proposed to solve the problem. Among them, evolutionary algorithms and the Modularity Index have stood out as the main solutions accepted by the scientific community. In addition to the importance of searching for an algorithm capable of solving the community detection problem efficiently, complex network analysis is often limited to studying the characteristics of a network from a single perspective due to the approach proposed by most of the algorithms found in the scientific literature. In order to achieve a more complete and detailed analysis of the networks under study, this doctoral thesis proposes a novel, flexible and adaptive approach for the analysis of communities of any complexity and network typology. More specifically, networks of different topology and extension commonly used in the scientific literature are analyzed, and, in addition, a pioneering study in the field of electrical engineering on high-voltage transmission networks is carried out. The importance of this study lies in the fact that we are dealing with one of the largest infrastructures created by humanity, with hundreds of thousands of kilometers of high-voltage lines that interconnect regions, countries and continental areas. What is more, due to the growing demand for electricity and the appearance of new formats of electricity generation, it is essential to undertake the study on the expansion and modification of electrical networks through new complementary procedures to the traditional techniques used in the study of electrical power systems. The incorporation of these new renewable electricity generation formats is causing the classic design of electrical networks to change from a centralized model, based on having a relatively limited number of thermal, nuclear and hydroelectric plants, to a distributed model with an increasing weight in renewable energy, thus causing an increase in network connectivity and, consequently, an increase in its complexity. In this sense, the need to apply more robust control strategies, as well as new optimization techniques to manage systems on a large scale, is essential. Currently, although there are analysis and design procedures for electrical networks, such as the resolution of power flows that allow multiple configurations of the electrical system to be analyzed, the immense range of possible existing configurations means that it is necessary to apply new complementary procedures in order to make the search for solutions feasible. In this sense, in this doctoral thesis, community detection is applied in the study and analysis of large electrical networks in order to expand the conclusions obtained by traditional procedures and analyze the results as possible improvements in network control, thus enhancing its reliability and allowing a faster and more efficient restoration in the face of serious disturbances such as natural disasters (storms, earthquakes, etc.), all through the development of new switching plans to protect islands or partial disconnections from the network, thus avoiding further degradation during incidents. In summary, the objective of this thesis is based on facing the problem of detecting communities in areas that require the appearance of new design and control techniques, through the development of new evolutionary algorithms that allow analyzing the topological characteristics of a network from different perspectives, with a greater or lesser level of detail depending on the analyst's needs. To achieve this objective, firstly, efficient population initialization methods and advanced genetic operators based on exchanges between communities have been designed, which have been incorporated into the single-objective genetic algorithm proposed in this thesis, which optimizes the popular Modularity Index as an objective function. This algorithm, called "Generational Genetic Algorithm" (GGA+), has been evaluated through a performance analysis on a multitude of popular benchmarks based on social networks, as well as on large-scale graphs with thousands of nodes and edges that represent real high-voltage transmission networks on a national and continental scale. After the success of the results shown by the implementation of the single-objective algorithm, in order to evaluate the performance that evolutionary community detection methods can offer in the engineering field, different algorithms such as the aforementioned GGA+, along with other evolutionary algorithms referenced in the literature, such as "Modularity and Improved Genetic Algorithm" (MIGA) or the well-known "Louvain" method, have been applied to multiple electrical networks, showing index being the most widely chosen objective function to optimize. However, due to the definition of community in which it can be viewed from a multiobjective approach, where one objective may be to maximize the number of connections within a community and another objective to minimize the number of connections with nodes external to the community, and since some recent studies have shown that when considering Modularity as the only objective, problems related to the resolution limit and imbalance of the solutions may arise, it seems appropriate to approach the problem of community detection from a multi-objective point of view. For these reasons, secondly, based on the good performance demonstrated by GGA+, the decision was made to design the multi-objective version called MOGGA+, which includes new objectives to be optimized in the detection of communities, thus opening a new avenue of research by applying multi-objective evolutionary algorithms that simultaneously optimize different objectives. More specifically, MOGGA+ has been designed with new advanced initialization methods and evolutionary operators. In addition, it uses a set of non-dominated solutions based on Pareto dominance, and an additional structure to dynamically modify the probability of applying different evolutionary operators at run time. Regarding the different optimized objectives, the combination of the Modularity index has been analyzed with a novel objective proposed in this thesis, Imbalance, a property to take into account when designing electrical networks resistant to contingencies, in which it is important that the network can be separated into islands (subnets) of approximately similar scale, to avoid further degradation of the network. nodes of other subgraphs in a network. Finally, it should be noted that MOGGA+ incorporates parallelism techniques to improve its performance. The objective Conductance (as an alternative to Modularity), along with Imbalance, has also been analyzed. Conductance is a measure of the fraction of the total volume of edges in a subgraph that are connected to vertices or that the results obtained support their usefulness and good performance. Currently, most of the methods aimed at solving the problem of community detection use a mono-objective approach, with the Modularity

[Background]: The disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of APP. Some ADAM10 gene variants have been associated with higher susceptibility to develop late-onset AD, though clear clinical-genetic correlates remain elusive., [Methods]: Clinical-genetic and biomarker study of a first family with early- and late-onset AD associated with a nonsense ADAM10 mutation (p.Tyr167*). CSF analysis included AD core biomarkers, as well as Western blot of ADAM10 species and sAPPα and sAPPβ peptides. We evaluate variant’s pathogenicity, pattern of segregation, and further screened for the p.Tyr167* mutation in 197 familial AD cases from the same cohort, 200 controls from the same background, and 274 AD cases from an independent Spanish cohort., [Results]: The mutation was absent from public databases and segregated with the disease. CSF Aβ42, total tau, and phosphorylated tau of affected siblings were consistent with AD. The predicted haploinsufficiency effect of the nonsense mutation was supported by (a) ADAM10 isoforms in CSF decreased around 50% and (b) 70% reduction of CSF sAPPα peptide, both compared to controls, while sAPPβ levels remained unchanged. Interestingly, sporadic AD cases had a similar decrease in CSF ADAM10 levels to that of mutants, though their sAPPα and sAPPβ levels resembled those of controls. Therefore, a decreased sAPPα/sAPPβ ratio was an exclusive feature of mutant ADAM10 siblings. The p.Tyr167* mutation was not found in any of the other AD cases or controls screened., [Conclusions]: This family illustrates the role of ADAM10 in the amyloidogenic process and the clinical development of the disease. Similarities between clinical and biomarker findings suggest that this family could represent a genetic model for sporadic late-onset AD due to age-related downregulation of α-secretase. This report encourages future research on ADAM10 enhancers., This work was supported by grants from the Ministry of Sciences and Technology, (SAF2010-18277), Instituto de Salud Carlos III (FIS14/00099), Direcció General d’Universitat, Investigació i Ciència, GVA (AICO/2018/090), and FEDER funds, Spain. MSGA is supported by a Miguel Servet II Grant from Instituto de Salud Carlos III (CPII16/00011).

Vivimos en un mundo complejo y en permanente cambio social. La educacion esta transformandose de forma progresiva en una sociedad interconectada y en red. No se trata unicamente de contemplar la relevancia de la incorporacion de las nuevas tecnologias y la digitalizacion de los contenidos curriculares, sino de replantearnos el sentido, la orientacion y el caracter de propuestas y experiencias educativas que deben ser promotoras de mayor inclusion, justicia, libertad y democracia. En este libro confluyen estudios y experiencias que aportan reflexiones y posicionamientos constructivos, innovadores y creativos en relacion con un desarrollo educativo intercultural e inclusivo. La diversidad es la principal caracteristica o cualidad que verdaderamente supone un reto clave en la configuracion de una nueva educacion. Gran parte de estos trabajos tornan un significado mas potente y lucido en momentos de incertidumbre y perplejidad en tiempos de crisis sanitaria provocada a nivel mundial por el Covid-19. El trabajo en red y la solidaridad van a ser ejes prioritarios de una nueva educacion donde los elementos y significados de interculturalidad e inclusion van a adoptar orientaciones y sentidos pedagogicos de gran impacto. Se trata de un libro de transferencia cientifica de valor social ineludible al conectar experiencias y estudios que buscan la proyeccion practica de la inclusion educativa en una amplia amalgama de espacios formativos y de desarrollo humano. Es, ademas, un libro de caracter y vocacion netamente internacional por la participacion de numerosos colegas de distintas universidades de reconocido prestigio en el ambito de la educacion y la ensenanza (Mexico, Peru y Espana)

SummaryBackgroundInequalities and burden of comorbidities of the Coronavirus disease 2019 (COVID-19) vary importantly inside the countries. We aimed to analyze the Municipality-level factors associated with a high COVID-19 mortality rate of in Mexico.MethodsWe retrieved information from 142,643 cumulative confirmed symptomatic cases and 18,886 deaths of COVID-19 as of June 20th, 2020 from the publicly available database of the Ministry of Health of Mexico. Public official data of the most recent census and surveys of the country were used to adjust a negative binomial regression model with the quintiles (Q) of the distribution of sociodemographic and health outcomes among 2,457 Municipality-level. Expected Mortality Rates (EMR), Incidence Rate Ratios (IRR) and 95% Confidence Intervals are reported.ResultsFactors associated with high MR of COVID-19, relative to Quintile 1 (Q1), were; diabetes prevalence (Q4, IRR=2.60), obesity prevalence (Q5, IRR=1.93), diabetes mortality rate (Q5, IRR=1.58), proportion of indigenous population (Q2, IRR=1.68), proportion of economically active population (Q5, IRR=1.50), density of economic units that operate essential activities (Q4, IRR=1.54) and population density (Q5, IRR=2.12). We identified 1,351 Municipality-level without confirmed COVID-19 deaths, of which, 202 had nevertheless high (Q4, Mean EMR= 8.0 deaths per 100,000) and 82 very high expected COVID-19 mortality (Q5, Mean EMR= 13.8 deaths per 100,000).ConclusionThis study identified 1,351 Municipality-level of Mexico that, in spite of not having confirmed COVID-19 deaths yet, share characteristics that could eventually lead to a high mortality scenario later in the epidemic and warn against premature easing of mobility restrictions. Local information should be used to reinforce strategies of prevention and control of outbreaks in communities vulnerable to COVID-19.Key messagesPredictors of COVID-19 mortality varied importantly between Municipality-level.Municipality-level factors associated with high mortality of COVID-19 were the prevalence of obesity and diabetes, mortality rate of diabetes, the proportion of indigenous and economically active population and population density.Municipality-level with high case-fatality rates of COVID-19 are likely undergoing insufficient testing and should improve its availability.Identified predictors ought to be considered by local governments to reinforce tailored strategies to prevent casualties in populations vulnerable to COVID-19, as mortality is expected to be eventually high in some Municipality-level that may not have reached the apex of the epidemic yet.

De novo GRIN variants, encoding for the ionotropic glutamate NMDA receptor subunits, have been recently associated with GRIN-related disorders, a group of rare paediatric encephalopathies. Current investigational and clinical efforts are focused to functionally stratify GRIN variants, towards precision therapies of this primary disturbance of glutamatergic transmission that affects neuronal function and brain. In the present study, we aimed to comprehensively delineate the functional outcomes and clinical phenotypes of GRIN protein truncating variants (PTVs)—accounting for ~20% of disease-associated GRIN variants—hypothetically provoking NMDAR hypofunctionality. To tackle this question, we created a comprehensive GRIN PTVs variants database compiling a cohort of nine individuals harbouring GRIN PTVs, together with previously identified variants, to build-up an extensive GRIN PTVs repertoire composed of 293 unique variants. Genotype–phenotype correlation studies were conducted, followed by cell-based assays of selected paradigmatic GRIN PTVs and their functional annotation. Genetic and clinical phenotypes meta-analysis revealed that heterozygous GRIN1, GRIN2C, GRIN2D, GRIN3A and GRIN3B PTVs are non-pathogenic. In contrast, heterozygous GRIN2A and GRIN2B PTVs are associated with specific neurological clinical phenotypes in a subunit- and domain-dependent manner. Mechanistically, cell-based assays showed that paradigmatic pathogenic GRIN2A and GRIN2B PTVs result on a decrease of NMDAR surface expression and NMDAR-mediated currents, ultimately leading to NMDAR functional haploinsufficiency. Overall, these findings contribute to delineate GRIN PTVs genotype–phenotype association and GRIN variants stratification. Functional studies showed that GRIN2A and GRIN2B pathogenic PTVs trigger NMDAR hypofunctionality, and thus accelerate therapeutic decisions for this neurodevelopmental condition., ISCIII, cofunded by European Regional Development Fund (ERDF), a way to build Europe (grants PI19/00348 and PI16/00851); Miguel Servet Program (CPII16/00021, ISCIII) and Serra Húnter Fellow to X.A.; SAF2016-77830-R to M.O.; European Regional development Fund (ERDF)-Ministerio de Ciencia e Innovación (grant BFU2017-83317-P) and Ministerio de Ciencia e Innovación-María de Maeztu (MDM-2017-0729) to D.S. and PI18/00111 [ISCIII, cofunded by European Regional Development Fund (ERDF), a way to build Europe] to À.G.-C. and N.J.-P.; Fundación Tatiana Pérez de Guzmán el Bueno PhD fellowship to A.S.-G.; crowdfunding initiative Precipita (FECYT) to F.M.

El libro presenta un trabajo riguroso en el que se detalla la experiencia de un dispositivo de atención psicosocial único en nuestro país y los efectos de las intervenciones en la población atendida. A través de la exposición de casos clínicos, logra presentar los efectos subjetivos de las intervenciones, el acogimiento de la palabra y demanda de los usuarios del servicio y la orientación que tiene cada una de ellas, sostenida éticamente y con la especificidad del caso por caso. El libro ilustra muy bien el funcionamiento y valor del dispositivo de intervención, al igual que su papel fundamental frente a las demandas psicológicas en un contexto social, cultural, económico y político como el colombiano. Es una experiencia que merece ser replicada en otros contextos del país y que además puede ser de gran interés para otros países (latinoamericanos, principalmente) que pueden tener demandas de atención psicológica, si bien muy distintas, en algún punto similares. El trabajo está bien organizado y las temáticas de cada uno de los casos presentados son relevantes. Cada caso tiene un comentario que permite comprender su complejidad y su profundidad [Miguel Gutiérrez-Peláez]. CONTENIDO: Prólogo, Miguel Gutiérrez-Peláez – Presentación, Ximena Castro-Sardi -- El dispositivo de atención y supervisión clínica: La experiencia del CAPsi: una invención y sus enseñanzas, Ximena Castro Sardi -- Supervisión y formación clínica, Mónica Patricia Larrahondo Arana -- Los casos : Autismo y psicosis en la infancia, Mónica Patricia Larrahondo Arana -- / Síntomas contemporáneos en la adolescencia, Nuris Martelo y Mario Marín Murillo -- Mujeres, entre la violencia y la palabra, Diana Marcela Huertas Sicachá y Margarita M. Munévar Rojas -- / Efectos subjetivos del conflicto armado colombiano, Ximena Castro-Sardi --/ Salud mental en el ámbito laboral, Paula Andrea Ledesma Cepeda y Lina Mercedes Guerrero López --Epílogo. Subjetividad y escucha, Ángela María Jaramillo Burgos – Anexo,: Consultorio de Atención Psicosocial (CAPsi). Informe de actividades (2014-2019) -- Sobre los autores Incluye referencias bibliográficas y ejercicios

© 2021 The Authors., Idiopathic pulmonary fibrosis is a lethal lung fibrotic disease, associated with aging with a mean survival of 2-5 years and no curative treatment. The GSE4 peptide is able to rescue cells from senescence, DNA and oxidative damage, inflammation, and induces telomerase activity. Here, we investigated the protective effect of GSE4 expression in vitro in rat alveolar epithelial cells (AECs), and in vivo in a bleomycin model of lung fibrosis. Bleomycin-injured rat AECs, expressing GSE4 or treated with GSE4-PLGA/PEI nanoparticles showed an increase of telomerase activity, decreased DNA damage, and decreased expression of IL6 and cleaved-caspase 3. In addition, these cells showed an inhibition in expression of fibrotic markers induced by TGF-β such as collagen-I and III among others. Furthermore, treatment with GSE4-PLGA/PEI nanoparticles in a rat model of bleomycin-induced fibrosis, increased telomerase activity and decreased DNA damage in proSP-C cells. Both in preventive and therapeutic protocols GSE4-PLGA/PEI nanoparticles prevented and attenuated lung damage monitored by SPECT-CT and inhibited collagen deposition. Lungs of rats treated with bleomycin and GSE4-PLGA/PEI nanoparticles showed reduced expression of α-SMA and pro-inflammatory cytokines, increased number of pro-SPC-multicellular structures and increased DNA synthesis in proSP-C cells, indicating therapeutic efficacy of GSE4-nanoparticles in experimental lung fibrosis and a possible curative treatment for lung fibrotic patients., R.P laboratory was funded by grants P17-01401 (Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain supported by FEDER funds), CIBER 576/805_ER16PE06P2016 and MINECO from the Spanish Government (INNPACTO, IPT-2012-0674-090000). M.M-M. laboratory was funded by Instituto de Salud Carlos III PI18/00367, supported by FEDER (Fondos Europeos de Desarrollo Regional (a way to build Europe)), JC received funds from MINECO CICYT SAF2014-55322-P, and GG laboratory was funded by grant SAF2015-68073-R (MINECO/FEDER) supported by FEDER funds. C.MG and R G-L are granted by the CIBERER.

Background The disintegrin metalloproteinase 10 (ADAM10) is the main alpha-secretase acting in the non-amyloidogenic processing of APP. Some ADAM10 gene variants have been associated with higher susceptibility to develop late-onset AD, though clear clinical-genetic correlates remain elusive. Methods Clinical-genetic and biomarker study of a first family with early- and late-onset AD associated with a nonsense ADAM10 mutation (p.Tyr167*). CSF analysis included AD core biomarkers, as well as Western blot of ADAM10 species and sAPP alpha and sAPP beta peptides. We evaluate variant's pathogenicity, pattern of segregation, and further screened for the p.Tyr167* mutation in 197 familial AD cases from the same cohort, 200 controls from the same background, and 274 AD cases from an independent Spanish cohort. Results The mutation was absent from public databases and segregated with the disease. CSF A beta 42, total tau, and phosphorylated tau of affected siblings were consistent with AD. The predicted haploinsufficiency effect of the nonsense mutation was supported by (a) ADAM10 isoforms in CSF decreased around 50% and (b) 70% reduction of CSF sAPP alpha peptide, both compared to controls, while sAPP beta levels remained unchanged. Interestingly, sporadic AD cases had a similar decrease in CSF ADAM10 levels to that of mutants, though their sAPP alpha and sAPP beta levels resembled those of controls. Therefore, a decreased sAPP alpha/sAPP beta ratio was an exclusive feature of mutant ADAM10 siblings. The p.Tyr167* mutation was not found in any of the other AD cases or controls screened. Conclusions This family illustrates the role of ADAM10 in the amyloidogenic process and the clinical development of the disease. Similarities between clinical and biomarker findings suggest that this family could represent a genetic model for sporadic late-onset AD due to age-related downregulation of alpha-secretase. This report encourages future research on ADAM10 enhancers.

Trabajo social Con el fin de mejorar la calidad del agua la cual es usada por los vendedores afiliados de la Asociación de Vendedores del Cerro de Guadalupe, se diseñó y construyó un prototipo que removiera las partículas sólidas que se encuentran en el agua captada, dicho prototipo está compuesto por un sedimentador de alta tasa y un filtro de flujo ascendente. Pregrado Ingeniero Civil INTRODUCCIÓN 1. GENERALIDADES 2. MARCO REFERENCIAL 3. MARCO REFERENCIAL 4. DESARROLLO DEL PROYECTO 5. RESULTADOS 6. ANÁLISIS DE LOS RESULTADOS 7. SOCIALIZACIÓN CON LA COMUNIDAD CONCLUSIONES RECOMENDACIONES BIBLIOGRAFÍA ANEXOS

Trabajo presentado al 6th Congress of the European Academy of Neurology, celebrado de forma virtual del 23 al 26 de mayo de 2020., [Background and aims]: The disintegrin metalloproteinase 10 (ADAM 10) us the main α-secretase acting in the non-amyloidogenic processing of the amyloid precursor protein. Some ADAM10 gene variants have been associated with higher susceptibility to develop late-onset disease, though a clear clinical-genetic correlate has not been reported yet. We present a family in whom development of AD was associated with a nonsense ADAM10 prodomain mutation (p.Tyr167*) causing haploinsufficiency, [Methods]: Clinical-genetic and CSF biomarker study of a family with AD., [Results]: The p.Tyr167* mutation was absent from public databases and segregated with the disease. Age at onset for 3 affected siblings ranged from 58 to 68 years, and their clinical phenotypes have been noteworthy for the slow disease evolution. CSF Ab42, total tau, and phosphorylated tau biomarkers were consistent with AD. Haploinsufficiency was demonstrated by: a) ADAM10 isoforms in CSF decreased around 50%, and b) 70% reduction of CSF sAPPα peptide, both compared to controls. Sporadic AD cases had a similar decrease in CSF ADAM10 levels to that of mutants, though their sAPPα levels resembled those of controls., [Conclusion]: This family provides the first example of a deleterious coding variant in ADAM10 associated with familial AD, and further implicates the amyloidogenic process in the development of the disease. Similarities between clinical and biomarker findings suggest that this family could represent a genetic model of sporadic late-onset AD due to an age-related down-regulation of α-secretase.

El presente ensayo se llevo a cabo en la comunidad “El Empalme” ubicada en el canton Quero, se realizo en 240 pollos por medio de necropsias para obtener la morfometria de los organos linfoides primarios realizadas a los 31 y 51 dias de edad de las aves, mientras que para la medicion del nivel de inmunoglobulinas se obtuvo 5 mL de sangre a los 51 dias de edad, de la vena braquial, luego se midio sus niveles en un laboratorio. El objetivo fue evaluar los efectos de la tintura de propoleo sobre las inmunoglobulinas en pollos parrilleros. Se utilizo tres dosis de propoleo que fueron 25 mg/Kg PV, 50 mg/Kg PV, y 75 mg/Kg PV. y un testigo, como patron para las mediciones de los niveles, se establecio que una dosis de 50 mg/Kg PV., de propoleo mejora el peso de la Bolsa de Fabricio, de esta manera ayudando al sistema inmune en los pollos, ya que al estar funcional durante mas tiempo la Bolsa incrementa la secrecion de linfocitos B, siendo este el tratamiento que tuvo mayor medicion en todos los parametros usados como fueron indice morfometrico de los organos linfoide primarios (Bolsa de Fabricio, Bazo), niveles de inmunoglobulinas (IgG, IgM). Cabe recalcar que en las inmunoglobulinas solo existio diferencia matematica ya que no se elevo considerablemente sobre los niveles normales en aves a los 51 dias de edad.