Toxicological Profiling and Long-Term Effects of Bare, PEGylated- and Galacto-Oligosaccharide-Functionalized Mesoporous Silica Nanoparticles

[EN] Mesoporous silica nanoparticles (MSNs) are amongst the most used nanoparticles in biomedicine. However, the potentially toxic effects of MSNs have not yet been fully evaluated, being a controversial matter in research. In this study, bare MSNs, PEGylated MSNs (MSNs-PEG), and galacto-oligosaccharide-functionalized MSNs (MSNs-GAL) are synthesized and characterized to assess their genotoxicity and transforming ability on human lung epithelial BEAS-2B cells in short- (48 h) and long-term (8 weeks) exposure scenarios. Initial short-term treatments show a dose-dependent increase in genotoxicity for MSNs-PEG-treated cells but not oxidative DNA damage for MSNs, MSNs-PEG, or for MSNs-GAL. In addition, after 8 weeks of continuous exposure, neither induced genotoxic nor oxidative DNA is observed. Nevertheless, long-term treatment with MSNsPEG and MSNs-GAL, but not bare MSNs, induces cell transformation features, as evidenced by the cell¿s enhanced ability to grow independently of anchorage, to migrate, and to invade. Further, the secretome from cells treated with MSNs and MSNs-GAL, but not MSNs-PEG, shows certain tumor-promoting abilities, increasing the number and size of HeLa cell colonies formed in the indirect soft-agar assay. These results show that MSNs, specifically the functionalized ones, provoke some measurable adverse effects linked to tumorigenesis. These effects are in the order of other nanomaterials, such as carbon nanotubes or cerium dioxide nanoparticles, but they are lower than those provoked by some approved drugs, such as doxorubicin or dexamethasone.This work was supported by PID2021-126304OB-C41, PID2021-128141OB-C22, and PID2020-116789RB-C43 funded by MCIN/AEI/10.13039/501100011033/, by the European Regional Development Fund `A way of doing Europe¿, by Generalitat Valenciana (CIPROM/2021/007), and by the Generalitat de Catalunya (2021-SGR-00731). The work was also supported by CIBER `Consorcio Centro de Investigación Biomédica en Red¿ (CB06/01/2012), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación. This study forms part of the Advanced Materials programme (MFA/2022/049) and was supported by MCIN with funding from European Union NextGenerationEU (PRTR-C17.I1) and from Generalitat Valenciana. This project has also received funding from the European Union¿s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 965196. Alba Hernández was granted an ICREA ACADEMIA award. Vicente Candela-Noguera thanks the Spanish Government for his fellowship (FPU15/02753). Paula Díez thanks the Generalitat Valenciana for her contract APOSTD/2020/153 and thanks the Instituto de Salud Carlos III and the European Social Fund for the financial support `Sara Borrell¿, CD20/00120. The authors thank the Electron Microscopy Service at UPV for support.Barguilla, I.; Candela-Noguera, V.; Oliver, P.; Annangi, B.; Diez-Sánchez, P.; Aznar, E.; Martínez-Máñez, R.... (2023). Toxicological Profiling and Long-Term Effects of Bare, PEGylated- and Galacto-Oligosaccharide-Functionalized Mesoporous Silica Nanoparticles. International Journal of Molecular Sciences. 24(22):1-14. https://doi.org/10.3390/ijms242216158114242

Monitoring the antimicrobial susceptibility of Gramnegative organisms involved in intraabdominal and urinary tract infections recovered during the SMART study (Spain, 2016 and 2017)

OBJECTIVE: Continuous antimicrobial resistance surveillance is recommended by Public Health authorities. We up-dated data from the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study in Spain. METHODS: The antimicrobial susceptibility data and extended-spectrum beta-lactamase (ESBL) production in isolates recovered from intra-abdominal (IAI) (n=1,429) and urinary tract (UTI) (n=937) infections during the 2016- 2017 SMART study in 10 Spanish hospitals were analysed. RESULTS: Escherichia coli was the most frequently microorganism isolated (48.3% and 53.7%) followed by Klebsiella spp. (11.5% and 21.9%) in IAIs and UTIs, respectively. Figures for Pseudomonas aeruginosa were 9.0% and 6.1%, being more frequently recovered from patients with nosocomial infections. Overall, 9.9% (IAI) and 14.0% (UTI) of E. coli, Klebsiella spp. and Proteus mirabilis isolates were ESBL-producers, being Klebsiella pneumoniae (34.5%) from UTI of nosocomial origin the most frequent. ESBL-producers were higher in patients >60 years in both IAIs and UTIs. As in previous years, amikacin (96.3%-100% susceptibility), ertapenem (84.2%-100%) and imipenem (70.3%- 100%) were the most active antimicrobials tested among Enterobacterales species. The activity of amoxicillin-clavulanic, piperacillin-tazobactam, and ciprofloxacin susceptibility was lower, particularly among ESBL-producers. Ertapenem susceptibility (88.9%-100%) was retained in ESBL-E. coli isolates that were resistant to these antimicrobials but decreased (28.6%-100%) in similar isolates of K. pneumoniae. CONCLUSIONS: Continuous antimicrobial resistance surveillance from the SMART study reveals overall maintenance of ESBL-producers in Spain, although with higher presence in isolates from UTIs than from IAIs. Moreover, ertapenem activity was high in E. coli irrespective of ESBL production but decreased in K. pneumoniae, particularly among ESBL-producers

Joint stakeholder decision-making on the management of the Silao-Romita aquifer using AHP

Over-exploitation and pollution have been identified as the main problems facing the Silao-Romita aquifer in Guanajuato, Mexico. The objective of this paper is to analyze the current situation, characterized by a clear lack of legislative enforcement, dispersion of competences, and scarcity of economic resources, in order to establish a new prioritization of action plans, and choose from among three specific management options. One of the main challenges when addressing these problems in a holistic manner is the conflicting viewpoints of the sectors involved. As each stakeholder has a different perception, there is a clear need for appropriate mechanisms to reach a consensus in decision-making. To achieve the objective, we use the Analytic Hierarchy Process (AHP), because of its flexibility and the availability of mathematical axiomatic principles and techniques to obtain group preferences and priorities. In addition, we use several tools developed by the authors to obtain consistency, streamline the trade-off between stakeholder know-how and synthetic consistency, and consistently complete partial judgments given by some of the stakeholders. The problem of obtaining a consensus among the actors involved regarding criteria and alternatives is also considered. The obtained results are intended to serve as guidelines for conducting priority actions to help solve the general problem of the study area, and to identify the management model that best meets the needs of the aquifer, according to the actors involved. (C) 2013 Elsevier Ltd. All rights reserved.This work has been supported by project IDAWAS, DPI2009-11591 of the Spanish Ministry of Science and Innovation; with supplementary support from ACOMP/2011/188 of the education department of the Generalitat Valenciana. The first author wishes to thank CONACYT for the 10007-2011-01 scholarship program. The use of English in this paper was revised by John Rawlins.Delgado Galván, XV.; Izquierdo Sebastián, J.; Benítez López, J.; Pérez García, R. (2014). Joint stakeholder decision-making on the management of the Silao-Romita aquifer using AHP. Environmental Modelling & Software. 51:310-322. https://doi.org/10.1016/j.envsoft.2013.10.008S3103225

Development and Testing of a New Instrument for Researching on Cancer Treatment Technologies Based on Magnetic Hyperthermia

(c) 2016 IEEE. Personal use of this material is permitted. Permission from IEEE must be obtained for all other users, including reprinting/ republishing this material for advertising or promotional purposes, creating new collective works for resale or redistribution to servers or lists, or reuse of any copyrighted components of this work in other works.A power electronics circuit allows the generation of high-frequency magnetic field that can be used to increase the temperature of cancer cells previously invaded with the magnetic nanoparticles. The circuit designed for this purpose is a high-frequency phase-shift inverter implemented with SiC devices and natural zero voltage switching. The inductive load has been optimized to increase as much as possible the magnetic field at the center of it considering the physical restrictions. Into this inductor, an adiabatic probe filled with nanoparticles is placed being the main objective to increase its temperature. The control of the inverter has been designed in such a way that it is easy to try waveforms different from the classical sine waves to see its effect on the temperature of the sample. Although the research is in one of the early stages, the first conclusions about the optimal frequency and field have been obtained showing that this technique could be a real option in the future.García, O.; Moreno-Arrones, N.; Cuesta, A.; Gutierrez, A.; Alou, P.; Oliver, J.; Cobos, J.... (2016). Development and Testing of a New Instrument for Researching on Cancer Treatment Technologies Based on Magnetic Hyperthermia. IEEE Journal of Emerging and Selected Topics in Power Electronics. 4(1):243-251. https://doi.org/10.1109/JESTPE.2015.2479092S2432514

Pyrosequencing-Based Comparative Genome Analysis of Vibrio vulnificus Environmental Isolates

Between 1996 and 2006, the US Centers for Disease Control reported that the only category of food-borne infections increasing in frequency were those caused by members of the genus Vibrio. The Gram-negative bacterium Vibrio vulnificus is a ubiquitous inhabitant of estuarine waters, and is the number one cause of seafood-related deaths in the US. Many V. vulnificus isolates have been studied, and it has been shown that two genetically distinct subtypes, distinguished by 16S rDNA and other gene polymorphisms, are associated predominantly with either environmental or clinical isolation. While local genetic differences between the subtypes have been probed, only the genomes of clinical isolates have so far been completely sequenced. In order to better understand V. vulnificus as an agent of disease and to identify the molecular components of its virulence mechanisms, we have completed whole genome shotgun sequencing of three diverse environmental genotypes using a pyrosequencing approach. V. vulnificus strain JY1305 was sequenced to a depth of 33×, and strains E64MW and JY1701 were sequenced to lesser depth, covering approximately 99.9% of each genome. We have performed a comparative analysis of these sequences against the previously published sequences of three V. vulnificus clinical isolates. We find that the genome of V. vulnificus is dynamic, with 1.27% of genes in the C-genotype genomes not found in the E- genotype genomes. We identified key genes that differentiate between the genomes of the clinical and environmental genotypes. 167 genes were found to be specifically associated with environmental genotypes and 278 genes with clinical genotypes. Genes specific to the clinical strains include components of sialic acid catabolism, mannitol fermentation, and a component of a Type IV secretory pathway VirB4, as well as several other genes with potential significance for human virulence. Genes specific to environmental strains included several that may have implications for the balance between self-preservation under stress and nutritional competence

Seguimiento de la sensibilidad antimicrobiana de microorganismos gramnegativos procedentes de infecciones intraabdominales y urinarias del estudio smart (España, 2016 y 2017)

Introducción. Las autoridades de Salud Pública recomiendan la vigilancia continua de la resistencia a los antimicrobianos. Se actualizan los datos del estudio SMART (Study for Monitoring Antimicrobial Resistance Trends) en España. Material y métodos. Se analizaron los datos de sensibilidad antimicrobiana y la producción de betalactamasas de espectro extendido (BLEE) en aislamientos obtenidos en el estudio SMART de infecciones intraabdominales (IIA) (n=1.429) y del tracto urinario (ITU) (n=937) durante 2016-2017 en 10 hospitales españoles. Resultados. Escherichia coli fue el microorganismo más frecuente (54,5% y 57,5%, respectivamente), seguido de Klebsiella spp. (18,4% y 25,4%) en IIA y en ITU. En Pseudomonas aeruginosa estas cifras fueron 9% y 6%, siendo más frecuente en la infección nosocomial. El 9,9% (IIA) y el 14% (ITU) del total de los aislados de E. coli, Klebsiella spp. y Proteus mirabilis producían BLEE, obteniéndose la tasa más alta en Klebsiella pneumoniae (34.5%) en ITU nosocomial. El mayor porcentaje de aislados con BLEE se observó en pacientes >60 años, tanto en IIA como en ITU. Como en años anteriores, amikacina (sensibilidad 96,3%-100%), ertapenem (84,2%-100%) e imipenem (70,3%-100%) fueron los antimicrobianos más activos en Enterobacterales. La sensibilidad a amoxicilina-ácido clavulánico, piperacilina-tazobactam y ciprofloxacino fue menor, en particular en los productores de BLEE. La sensibilidad a ertapenem (88,9%-100%) se mantuvo en E. coli con BLEE resistente a estos antimicrobianos, pero disminuyó (28,6%-100%) en aislados similares de K. pneumoniae. Conclusiones. La vigilancia continua de la resistencia a los antimicrobianos en el estudio SMART revela el mantenimiento de la frecuencia de aislados productores de BLEE en España, pero con mayor presencia en las ITUs que en las IIAs. Además, la sensibilidad a ertapenem fue alta en E. coli con independencia de la producción de BLEE, pero disminuyó en K. pneumoniae, sobre todo en los productores de BLEE. Introduction. Continuous antimicrobial resistance surveillance is recommended by Public Health authorities. We updated data from the SMART (Study for Monitoring Antimicrobial Resistance Trends) surveillance study in Spain. Material and methods. The antimicrobial susceptibility data and extended-spectrum beta-lactamase (ESBL) production in isolates recovered from intra-abdominal (IAI) (n=1,429) and urinary tract (UTI) (n=937) infections during the 2016-2017 SMART study in 10 Spanish hospitals were analysed. Results. Escherichia coli was the most frequently microorganism isolated (48.3% and 53.7%) followed by Klebsiella spp. (11.5% and 21.9%) in IAIs and UTIs, respectively. Figures for Pseudomonas aeruginosa were 9.0% and 6.1%, being more frequently recovered from patients with nosocomial infections. Overall, 9.9% (IAI) and 14.0% (UTI) of E. coli, Klebsiella spp. and Proteus mirabilis isolates were ESBL-producers, being Klebsiella pneumoniae (34.5%) from UTI of nosocomial origin the most frequent. ESBL-producers were higher in patients >60 years in both IAIs and UTIs. As in previous years, amikacin (96.3%-100% susceptibility), ertapenem (84.2%-100%) and imipenem (70.3%-100%) were the most active antimicrobials tested among Enterobacterales species. The activity of amoxicillin-clavulanic, piperacillin-tazobactam, and ciprofloxacin susceptibility was lower, particularly among ESBL-producers. Ertapenem susceptibility (88.9%-100%) was retained in ESBL-E. coli isolates that were resistant to these antimicrobials but decreased (28.6%-100%) in similar isolates of K. pneumoniae. Conclusions. Continuous antimicrobial resistance surveillance from the SMART study reveals overall maintenance of ESBL-producers in Spain, although with higher presence in isolates from UTIs than from IAIs. Moreover, ertapenem activity was high in E. coli irrespective of ESBL production but decreased in K. pneumoniae, particularly among ESBL-producers

El impacto del aprendizaje universitario colaborativo el rendimiento académico del estudiante: Una wiki para la ciencia política y de la administración

El objetivo del proyecto es llevar a la práctica una acción formativa basada en la web 2.0 con la participación de profesores y alumnos pertenecientes a distintos grados, facultades y universidades. En concreto, esta iniciativa pretende continuar con la wiki, www.dcpa.wikidot.com, que comenzó a realizarse en 2015 en virtud de la convocatoria de PIMCD. La wiki contribuye a que los estudiantes, de manera colaborativa, diseñen un proyecto educativo de integración curricular a partir de unos supuestos establecidos previamente por el profesor. Por lo tanto, este tipo de experiencia permite crear una base documental de gran utilidad para otros alumnos que estudian este tipo de asignaturas o para cualquier persona que muestren una inquietud o necesidad de buscar, encontrar o ampliar el conocimiento sobre determinadas cuestiones relacionadas con la ciencia política y la ciencia de la administració

Discurso inaugural leído en la solemne apertura del curso académico de 1928 a 1929 ante el claustro de la Universidad de Barcelona / por el doctor Eusebio Oliver Aznar

Discurs inaugural del curs 1928 a 192

Estado actual de la lucha antituberculosa: discurso que para su acto de recepción leyó ante la Real Academia de Medicina y Cirugía de Barcelona el académico electo Dr. D. Eusebio Oliver Aznar

No es lógico, aun cuando sea muy humano, que las naciones se turben ante la amenaza de una epidemia exótica como la peste, el cólera ó la fiebre amarilla que las visita muy de tarde en tarde, y sin embargo permanezcan indiferentes y ociosas enfrente de un formidable enemigo que vive matando incesantemente á nuestro lado, sin reparar en edades ni en condiciones, y del que ni aún queda para los pusilánimes el recurso de la huída, porque no hay país habitado donde el enemigo no exista. Tal es el caso para la tuberculosis. Sabido es que en Espana, esta enfermedad, minando los pulmones unas veces, el intestino, las meninges, los huesos otras, é insinuándose por fin en los más apartados órganos, produce anualmente unas 54.000 defunciones. Para comprender la magnitud de este desastre, cada doce meses renovado, no hay sino imaginar que todas esas víctimas, en lugar de repartirse entre toda la nación española, se reuniesen en una sola localidad, y entonces nos alarmaríamos al ver que Espana pierde cada año una capital como Alicante. Tamaña hecatombe, incomparablemente más grave que los accidentes públicos tales como catástrofes ferroviarias, incendios de teatros, etc., no hacen mella sino en el ánimo de los que estudian el fenómeno de cerca, y apenas si merecen unas líneas en los periódicos al noticiar las variantes en la salud pública