Web application for tourist routes management

En este proyecto se aborda la creación de una aplicación web utilizando Django y los servicios web de Amazon (Amazon Web Services). En esta aplicación se pretende reunir a los viajeros de todo el mundo para que compartan sus experiencias con el resto de usuarios. La aplicación se alojaría en instancias de Amazon EC2, el servidor ofertado por Amazon. Estas instancias se administrarían en AWS Elastic Beanstalk por medio de AWS Auto Scaling, que aumentaría o reduciría la capacidad de Amazon EC2 en función al tráfico de carga. Para la base de datos se utilizaría una instancia de Amazon RDS, el servidor de bases de datos relacionales de Amazon, con una base de datos MySQL. También se haría un estudio del gasto que supone tener una aplicación alojada en AWS mediante el tablero de facturación que proporciona Amazon. Para comprobar que AWS Auto Scaling hace un balanceo de carga correcto, se utilizarían herramientas para simular un gran número de peticiones al servidor de la aplicación, de modo que haya que aumentar la capacidad de Amazon EC2

Scientific literature on pharmacoepidemiology. Bibliometric analysis of the period 1970-1999

Se estudió la producción científica sobre farmacoepidemiología durante el período de 1970 a 1999, a partir de los artículos originales recuperados en la base de datos IPA. Los 467 artículos recuperados procedían mayoritariamente de Estados Unidos (31.9%), predominando las áreas temáticas de farmacovigilancia y los estudios de utilización de medicamentos. La media de firmas por artículo era de 2.5 ± 1.3, con un grado de colaboración entre autores del 68.4% y un índice de transitoriedad del 80.1%. La distribución de autores por número de artículos publicados se ajustaba a la ley de Lotka. El país mayoritario de edición de las revistas en que se publicaron los artículos era Inglaterra (51.4%), siendo el inglés el idioma preferente (83.5%). La investigación científica sobre farmacoepidemiología presenta unas características que corresponden a una disciplina joven, siendo necesarios otros estudios que analicen la metodología y complejidad de dicha investigación.Objetive: The objetive of this study is to make a description of the scientific production on pharmacoepidemiology. Methods: We studied scientific literature on pharmacoepidemiology produced during the period 1970-99, using original articles retrieved from the IPA database. Results: The highest proportion of the 467 articles obtained originated from the United States (31.9%), and the most common thematic areas were pharmacovigilance and medicinal drug use. The mean number of authors per paper was 2.5 ± 1.3, with a 68.4% degree of collaboration and an 80.1% index of insularity. The distribution of authors per number of articles published was in accordance with Lotka’s law. Most journals were published in the United Kingdom (51.4%) and the most widely-used language of publication was English (83.5%). Conclusions: Scientific research into pharmacoepidemiology presents the characteristics that correspond to a young discipline, and further studies are required to analyse the methodology and complexity of such research

Thermochemical CO2 reduction catalyzed by homometallic and heterometallic nanoparticles generated from the thermolysis o supramolecularly assembled porous metal-adenine precursors

A family of unprecedented supramolecularly assembled porous metal–organic compounds (SMOFs), based on [Cu6M(μ-adeninato)6(μ3-OH)6(μ-H2O)6]2+ cations (MII: Cu, Co, Ni, and Zn) and different dicarboxylate anions (fumarate, benzoate, and naphthalene-2,6-dicarboxylate), have been employed as precursors of catalysts for the thermocatalytic reduction of CO2. The selected metal–organic cation allows us to tune the composition of the SMOFs and, therefore, the features and performance of the final homometallic and bimetallic catalysts. These catalysts were obtained by thermolysis at 600 °C under a N2 atmosphere and consist of big metal particles (10–20 μm) placed on the surface of the carbonaceous matrix and very tiny metal aggregates (<10 nm) within this carbonaceous matrix. The latter are the most active catalytic sites for the CO2 thermocatalytic reduction. The amount of this carbonaceous matrix correlates with the organic content present in the metal–organic precursor. In this sense, CO2 thermocatalytic reduction experiments performed over the homometallic, copper only, catalysts with different carbon contents indicate that above a certain value, the increase of the carbonaceous matrix reduces the overall performance by encapsulating the nanoparticles within this matrix and isolating them from interacting with CO2. In fact, the best performing homometallic catalyst is that obtained from the precursor containing a small fumarate counterion. On the other hand, the structural features of these precursors also provide a facile route to work with a solid solution of nanoparticles as many of these metal–organic compounds can replace up to 1/7 of the copper atoms by zinc, cobalt, or nickel. Among these heterometallic catalysts, the best performing one is that of copper and zinc, which provides the higher conversion and selectivity toward CO. XPS spectroscopy and EDX mappings of the latter catalyst clearly indicate the presence of Cu1–xZnx nanoparticles covered by small ZnO aggregates that provide a better CO2 adsorption and easier CO release sites.Eusko Jaurlaritza/Gobierno Vasco (IT1291-19; IT1722-22 and Investigo program for S.M.G. funded by the European Union-Next Generation EU). Universidad del País Vasco/Euskal Herriko Unibertsitatea (predoctoral fellowship for J.P.C. 17/051), Ministerio de Ciencia e Innovación (project PID2019-108028GB-C21 funded by MCIN/AEI/10.13039/501100011033; PID2022-138968NB-C22 funded by MCIN/AEI/10.13039/501100011033/FEDER/FEDER, and TED2021-129810B-C22 funded by MCIN/AEI/10.13039/501100011033 and by the European Union NextGeneration EU/PRTR)

Bestatin is a non-competitive inhibitor of porcine M1 family glutamyl aminopeptidase: Insights for selective inhibitor design

Glutamyl aminopeptidase (APA) is an M1 family membrane-bound ectoenzyme that is a target for the development of antihypertensive and anticancer agents. Bestatin is a natural product described as a classical inhibitor of metallo-aminopeptidases. Although the IC50 value of bestatin vs human APA has been reported, the mechanism of inhibition is unknown. In the present contribution, we demonstrated that bestatin is a non-competitive (α&gt;1) inhibitor of porcine APA (pAPA), with a Ki value of 31.59 µM (α=3.7). A model of the bestatin-pAPA complex predicted that bestatin binds to pAPA similarly to porcine aminopeptidase N (pAPN). The interaction involved catalytic and chelating residues conserved in the M1 family. Additionally, a salt bridge with R877 and a hydrogen bond interaction with T346, both key residues for APA specificity for N-terminal acidic residues were identified. These residues and E213, which forms a hydrogen bond interaction with bestatin, are not conserved in human and porcine APN. The extension of the in silico analysis to amastatin and bestatin analogs probestin, and phebestin, which are APA inhibitors, indicated that they may interact with the same residues. The results indicate that bestatin analogues currently reported to inhibit APN are dual inhibitors of APA and APN and that some APA residues could be targeted to improve inhibitor selectivity

Bestatin is a non-competitive inhibitor of porcine M1 family glutamyl aminopeptidase: Insights for selective inhibitor design

173-180Glutamyl aminopeptidase (APA) is an M1 family membrane-bound ectoenzyme that is a target for the development of antihypertensive and anticancer agents. Bestatin is a natural product described as a classical inhibitor of metallo-aminopeptidases. Although the IC50 value of bestatin vs human APA has been reported, the mechanism of inhibition is unknown. In the present contribution, we demonstrated that bestatin is a non-competitive (α>1) inhibitor of porcine APA (pAPA), with a Ki value of 31.59 μM (α=3.7). A model of the bestatin-pAPA complex predicted that bestatin binds to pAPA similarly to porcine aminopeptidase N (pAPN). The interaction involved catalytic and chelating residues conserved in the M1 family. Additionally, a salt bridge with R877 and a hydrogen bond interaction with T346, both key residues for APA specificity for N-terminal acidic residues were identified. These residues and E213, which forms a hydrogen bond interaction with bestatin, are not conserved in human and porcine APN. The extension of the in silico analysis to amastatin and bestatin analogs probestin, and phebestin, which are APA inhibitors, indicated that they may interact with the same residues. The results indicate that bestatin analogues currently reported to inhibit APN are dual inhibitors of APA and APN and that some APA residues could be targeted to improve inhibitor selectivity

An in solution adsorption characterization technique based on the response to an external magnetic field of porous paramagnetic materials: application on supramolecular metal–adenine frameworks containing heterometallic heptameric clusters

Herein we explore the opportunities arising from combining magnetic properties and porosity in metal–organic materials. In this sense, we have prepared an adenine based homometallic wheel-shaped heptameric [Cu7(μ-adeninato)6(μ3-OH)6(μ-OH2)4]2+ entity containing two metal coordination environments: CuO6 at the core of the wheel with an unusually modest Jahn–Teller distortion and six peripheral CuN2O4 with a more pronounced elongation. The difference in the coordination environments of this compound facilitates the selective replacement of the central metal position by other metal centers (ZnII, NiII, CoII and CrIII) and boosts the magnetic properties of the homometallic heptameric entity. The nature of the central metal modulates the complex net of ferro- and antiferromagnetic superexchange pathways within the heptameric entity to tune the total spin (ST = 3 (Cu6Zn), 5/2 (Cu6Cu), 2 (Cu6Ni), 3/2 (Cu6Co), and 9/2 (Cu6Cr)). No evidence of single-molecule magnet behavior has been observed at 2 K, but at room temperature, where these compounds are still in the paramagnetic regime, the attraction force exerted by an external magnetic field (H) on particles immersed in a liquid is enough to keep them attached to an electromagnet pole. The 4S(S + 1) value of the central metal follows a linear dependence with respect to the 1/[H·∇(H)] value at which the particles are detached from the pole of the electromagnet. There is also a linear dependence of the H·∇(H) term with respect to the adsorbate mass incorporated inside the pores of the paramagnetic adsorbent which has allowed performing straightforward sorption selectivity experiments on Cu6Cu directly in solution, which are based on a property of the adsorbent and not as usually based on an indirect assessment of the adsorbate remaining in solution.Eusko Jaurlaritza/Gobierno Vasco (IT1291-19; IT1722-22; ELKARTEK program KK-2022/00032), Ministerio de Universidades and the European Union-Next Generation EU (marsa21/52, R. P. A.), Ministerio de Ciencia e Innovación (PID2019-108028GB-C21). SGIker (UPV/EHU, MICINN, GV/EJ, ESF). ELKARTEK program KK-2022/0003

Isoreticular chemistry and applications of supramolecularly assembled copper−adenine porous materials

The useful concepts of reticular chemistry, rigid and predictable metal nodes together with strong and manageable covalent interactions between metal centers and organic linkers, have made the so-called metal–organic frameworks (MOFs) a flourishing area of enormous applicability. In this work, the extension of similar strategies to supramolecularly assembled metal–organic materials has allowed us to obtain a family of isoreticular compounds of the general formula [Cu7(μ-adeninato-κN3:κN9)6(μ3-OH)6(μ-OH2)6](OOC-R-COO)·nH2O (R: ethylene-, acetylene-, naphthalene-, or biphenyl-group) in which the rigid copper–adeninato entities and the organic dicarboxylate anions are held together not by covalent interactions but by a robust and flexible network of synergic hydrogen bonds and π–π stacking interactions based on well-known supramolecular synthons (SMOFs). All compounds are isoreticular, highly insoluble, and water-stable and show a porous crystalline structure with a pcu topology containing a two-dimensional (2D) network of channels, whose dimensions and degree of porosity of the supramolecular network are tailored by the length of the dicarboxylate anion. The partial loss of the crystallization water molecules upon removal from the mother liquor produces a shrinkage of the unit cell and porosity, which leads to a color change of the compounds (from blue to olive green) if complete dehydration is achieved by means of gentle heating or vacuuming. However, the supramolecular network of noncovalent interactions is robust and flexible enough to reverse to the expanded unit cell and color after exposure to a humid atmosphere. This humidity-driven breathing behavior has been used to design a sensor in which the electrical resistance varies reversibly with the degree of humidity, very similar to the water vapor adsorption isotherm of the SMOF. The in-solution adsorption properties were explored for the uptake and release of the widely employed 5-fluorouracil, 4-aminosalycilic acid, 5-aminosalycilic acid, and allopurinol drugs. In addition, cytotoxicity activity assays were completed for the pristine and 5-fluorouracil-loaded samples.Basque Goverment (IT1722-22 and ELKARTEK KK-2022/00032) . Spanish Ministry of Science and Innovation (TED2021-129810B-C22 financed by MCIN/AEI/10.13039/501100011033 and by the European Union Next Generation EU/PRTR, and the PID2019-108028GB-C21 project funded by MCIN/AEI/10.13039/501100011033). Basque Government and the European Union Next GenerationEU (Investigo Program 2022-46)

Socio-Demographic Health Determinants Are Associated with Poor Prognosis in Spanish Patients Hospitalized with COVID-19

Introduction Social vulnerability is a known determinant of health in respiratory diseases. Our aim was to identify whether there are socio-demographic factors among COVID-19 patients hospitalized in Spain and their potential impact on health outcomes during the hospitalization. Methods A multicentric retrospective case series study based on administrative databases that included all COVID-19 cases admitted in 19 Spanish hospitals from 1 March to 15 April 2020. Socio-demographic data were collected. Outcomes were critical care admission and in-hospital mortality. Results We included 10,110 COVID-19 patients admitted to 18 Spanish hospitals (median age 68 (IQR 54–80) years old; 44.5% female; 14.8% were not born in Spain). Among these, 779 (7.7%) cases were admitted to critical care units and 1678 (16.6%) patients died during the hospitalization. Age, male gender, being immigrant, and low hospital saturation were independently associated with being admitted to an intensive care unit. Age, male gender, being immigrant, percentile of average per capita income, and hospital experience were independently associated with in-hospital mortality. Conclusions Social determinants such as residence in low-income areas and being born in Latin American countries were associated with increased odds of being admitted to an intensive care unit and of in-hospital mortality. There was considerable variation in outcomes between different Spanish centers.JPA is under contract within the Ramón y Cajal Program (RYC-2016-20155, Ministerio de Economía, Industria y Competitividad, Spain). Investigators of Spanish Social-Environmental COVID-19 Register: Steering Committee: F. Javier Martín-Sánchez, Adrián Valls Carbó, Carmen Martínez Valero, Juan de D. Miranda, Juan Pedro Arrebola, Marta Esteban López, Annika Parviainen, Òscar Miró, Pere Llorens, Sònia Jiménez, Pascual Piñera, Guillermo Burillo, Alfonso Martín, Jorge García Lamberechts, Javier Jacob, Aitor Alquézar, Juan González del Castillo, Amanda López Picado and Iván Núñez. Participating centers: Oscar Miró y Sonia Jimenez. Hospital Clinic de Barcelona. José María Ferreras Amez. Hospital Clínico Universitario Lozano Blesa. Rafael Rubio Díaz. Complejo Hospitalario de Toledo. Julio Javier Gamazo del Rio. Hospital Universitario de Galdakao. Héctor Alonso. Hospital Universitario Miguel de Valdecilla. Pablo Herrero. Hospital Universitario Central de Asturias. Noemí Ruiz de Lobera. Hospital San Pedro de Logroño. Carlos Ibero. Complejo Hospitalario de Navarra. Plácido Mayan. Hospital Clínico Universitario de Santiago. Rosario Peinado. Complejo Hospitalario Universitario de Badajoz. Carmen Navarro Bustos. Hospital Universitario Virgen de la Macarena. Jesús Álvarez Manzanares. Hospital Universitario Rio Hortega. Francisco Román. Hospital Universitario General de Alicante. Pascual Piñera. Hospital Universitario Reina Sofia de Murcia. Guillermo Burillo. Hospital Universitario de Canarias de Tenerife. Javier Jacob. Hospital Universitario de Bellvitge. Carlos Bibiano. Hospital Universitario Infanta Leonor.Peer reviewe

La producción científica de los químicos españoles y el índice h de Hirsch

El físico J. E. Hirsch ha revolucionado el mundo científico desde la publicación a finales de 2005 de un índice h: un indicador para cuantificar la producción científica de un investigador. En el presente artículo se discute la aplicación de h para evaluar la actividad científica de los químicos españoles considerando sus ventajas, inconvenientes y utilidad. Sin duda alguna, el índice h va a ser el centro de atención y debate en los próximos años por su posible uso para la concesió