Nuevas nanopartículas metálicas conjugadas con agentes terapéuticos y ligandos proteicos dirigidos a receptores EGFR, para la terapia selectiva contra el cáncer

Programa de Doctorado en Biotecnología, Ingeniería y Tecnología QuímicaLínea de Investigación: Experimentación y Computación en Materiales y Sistemas ComplejosClave Programa: DBICódigo Línea: 15Las nanopartículas plasmónicas han cobrado especial interés biomédico en los últimos años gracias a las propiedades ópticas asociadas al característico plasmón de superficie, así como a su capacidad de unir moléculas de interés terapéutico en superficie. La combinación diagnóstica y terapéutica en un mismo sistema, es decir, teragnóstica, ha sido abordada desde diferentes enfoques en esta tesis con el objeto de desarrollar herramientas frente a la problemática que representa en la actualidad el tratamiento oncológico. La presente memoria se divide en varios capítulos. El capítulo introductorio describe la relevancia de las nanopartículas plasmónicas en el contexto de la biomedicina, resaltando sus propiedades y utilidad como herramientas versátiles en la terapia del cáncer. El segundo capítulo detalla el método general de síntesis in situ desarrollado en esta tesis de nanopartículas plasmónicas altamente funcionalizadas en superficie. En el tercer y cuarto capítulo se implementan, siguiendo la metodología desarrollada en el capítulo segundo, nanopartículas de oro y plata funcionalizadas con un derivado aminotiolado de pirimidina. Ambas nanoestructuras se estudiarán como agente teragnóstico y vehículo de drogas dirigido a EGFR, determinando su toxicidad selectiva en modelos tanto in vitro como in vivo, así como su capacidad como agente de transfección génica. Por último, el quinto capítulo recoge el abordaje de nanopartículas plasmónicas funcionalizadas con ácido tánico en el tratamiento selectivo de tumores con sobreexpresión de EGFR.Universidad Pablo de Olavide de Sevilla. Departamento de Sistemas Físicos, Químicos y NaturalesPostprin

Synthesis and Characterization of Elongated-Shaped Silver Nanoparticles as a Biocompatible Anisotropic SERS Probe for Intracellular Imaging: Theoretical Modeling and Experimental Verification

Progress in the field of biocompatible SERS nanoparticles has promising prospects for biomedical applications. In this work, we have developed a biocompatible Raman probe by combining anisotropic silver nanoparticles with the dye rhodamine 6G followed by subsequent coating with bovine serum albumin. This nanosystem presents strong SERS capabilities in the near infrared (NIR) with a very high (2.7 × 107) analytical enhancement factor. Theoretical calculations reveal the effects of the electromagnetic and chemical mechanisms in the observed SERS effect for this nanosystem. Finite element method (FEM) calculations showed a considerable near field enhancement in NIR. Using density functional quantum chemical calculations, the chemical enhancement mechanism of rhodamine 6G by interaction with the nanoparticles was probed, allowing us to calculate spectra that closely reproduce the experimental results. The nanosystem was tested in cell culture experiments, showing cell internalization and also proving to be completely biocompatible, as no cell death was observed. Using a NIR laser, SERS signals could be detected even from inside cells, proving the applicability of this nanosystem as a biocompatible SERS probe.España, Regional Ministry of Economy, Junta de Andalucía, P07-FQM-02595 (to CC), P10-FQM-06615 (to JMOM), P10-CTS-6928 (to DP) and PAIDI2020 Program (FQM319 to RFM and CTS677 to DP)Junta de Andalucía, PI-0070/2008 (to PZ) and PI-0068/2008 (to DP

What aspects of the scientific competence are evaluated in entrance examinations to the university in the subject of Chemistry?

Se caracterizan las preguntas de la Prueba de Acceso a la Universidad en la asignatura de Química en las universidades andaluzas desde la perspectiva de sus demandas respecto a la competencia científica. Para ello se analizan 576 peguntas planteadas en el período 2002-2013, cuyos resultados indican sesgos y ausencias importantes para una evaluación integral de la competencia del alumnado en Química, sin apenas evolución con el tiempo. Es de destacar, en particular, una pobre presencia de aspectos experimentales de la química, relacionados con el diseño experimental y el trabajo práctico de laboratorio, y sobre todo una ausencia de preguntas que evalúen aspectos creativos y sobre la naturaleza de la química, o alrededor de problemas y situaciones de la vida cotidiana o de la dimensión tecnológica y ambiental. A partir del análisis se formulan implicaciones para la mejora de las pruebas externas selectivas y también para la formación del profesorado..From the point of view of the competences assessment, in this paper the Andalusian higher education access test in the subject of Chemistry is analysed. For this purpose, a content analysis was done, taking as reference 576 questions corresponding to the PAU questions raised between 2002 and 2013 in the Andalusian universities. The results indicate bias and important absences for a comprehensive assessment of the competence of students in chemistry, hardly any evolution over time. It is noteworthy, in particular, a poor presence of experimental aspects of chemistry, related to experimental design and practical laboratory work, and above all an absence of questions that assess creative aspects and about the nature of the chemistry or around its relations with problems and situations of daily life or the technological and environmental dimension. From the analysis implications for improving selective external testing and also for teacher training are formulated.peerReviewe

¿QUÉ ASPECTOS DE LA COMPETENCIA CIENTÍFICA EVALÚAN LAS PRUEBAS DE ACCESO A LA UNIVERSIDAD EN LA ASIGNATURA DE QUÍMICA? What aspects of the scientific competence are evaluated in entrance examinations to the University in the subject of Chemistry?

Se caracterizan las preguntas de la Prueba de Acceso a la Universidad en la asignatura de Química en las universidades andaluzas desde la perspectiva de sus demandas respecto a la competencia científica. Para ello se analizan 576 peguntas planteadas en el período 2002-2013, cuyos resultados indican sesgos y ausencias importantes para una evaluación integral de la competencia del alumnado en Química, sin apenas evolución con el tiempo. Es de destacar, en particular, una pobre presencia de aspectos experimentales de la química, relacionados con el diseño experimental y el trabajo práctico de laboratorio, y sobre todo una ausencia de preguntas que evalúen aspectos creativos y sobre la naturaleza de la química, o alrededor de problemas y situaciones de la vida cotidiana o de la dimensión tecnológica y ambiental. A partir del análisis se formulan implicaciones para la mejora de las pruebas externas selectivas y también para la formación del profesorado..AbstractFrom the point of view of the competences assessment, in this paper the Andalusian higher education access test in the subject of Chemistry is analysed. For this purpose, a content analysis was done, taking as reference 576 questions corresponding to the PAU questions raised between 2002 and 2013 in the Andalusian universities. The results indicate bias and important absences for a comprehensive assessment of the competence of students in chemistry, hardly any evolution over time. It is noteworthy, in particular, a poor presence of experimental aspects of chemistry, related to experimental design and practical laboratory work, and above all an absence of questions that assess creative aspects and about the nature of the chemistry or around its relations with problems and situations of daily life or the technological and environmental dimension. From the analysis implications for improving selective external testing and also for teacher training are formulated

Análisis de contenido de las pruebas de acceso a la universidad en la asignatura de Química en Andalucía

In this work, the test question typology to higher education access in chemistry subject has been studied. This study was performed in the autonomous community of Andalusia. According to curriculum topics and the category system proposed by Smith, Nakhleh y Bretz (2010) for chemistry exams, 576 questions were analyzed. The most frequent topics were stoichiometry, formulation and chemical nomenclature and acid-base equilibria, which accounted for about two thirds of the questions. The three categories of questions used were: definition, algorithmic and conceptual questions were used. It was observed a predominance of the algorithmic questions, although in recent years, some progresses of conceptual questions have been observed, but not statistically significant changes. A clear dependence between the type of question and the specific issue involved was observed. Therefore, questions about formulation were mostly included in the “definition” category, question about stoichiometry and thermodynamic in the “algorithmic” category and atom, periodic table and chemical bond questions were included in the conceptual category. From the data obtained, the need for a reorientation in the future of PAU tests is discussed.Se estudia la tipología de preguntas formuladas en las pruebas de Química de acceso a la universidad en la Comunidad Autónoma Andaluza. Se analizaron 576 preguntas según los temas del currículum implicados y de acuerdo al sistema de categorías propuesto por Smith, Nakhleh y Bretz (2010) para exámenes de Química. Los temas más frecuentes fueron los de estequiometría, formulación-nomenclatura química y equilibrio ácido-base, que conjuntamente acaparaban alrededor de dos tercios de las preguntas formuladas. Las tres categorías de preguntas empleadas fueron: de Definición, Algorítmicas y Conceptuales, predominando principalmente las segundas, aunque con un cierto avance en los últimos años de las de tipo Conceptual, aunque los cambios no resultaran estadísticamente significativos. Se observó una clara dependencia del tipo de preguntas de la temática concreta implicada en las mismas, siendo aquellas sobre formulación las que más se prestan a la categoría de “definición”, las de estequiometría y termoquímica a las “algorítmicas”, y las de átomo, Tabla periódica y enlace químico a las de tipo conceptual. A partir de los datos proporcionados se discute la necesidad de una reorientación de estas pruebas con vistas al futuro.Palabras clave: enseñanza de la química; pruebas externas; PAU; Pruebas de acceso a la universidad; Preguntas de examen.Type of test questions to higher education access in chemistry subjectIn this work, the test question typology to higher education access in chemistry subject has been studied. This study was performed in the autonomous community of Andalusia. According to curriculum topics and the category system proposed by Smith, Nakhleh y Bretz (2010) for chemistry exams, 576 questions were analyzed. The most frequent topics were stoichiometry, formulation and chemical nomenclature and acid-base equilibria, which accounted for about two thirds of the questions. The three categories of questions used were: definition, algorithmic and conceptual questions were used. It was observed a predominance of the algorithmic questions, although in recent years, some progresses of conceptual questions have been observed, but not statistically significant changes. A clear dependence between the type of question and the specific issue involved was observed. Therefore, questions about formulation were mostly included in the “definition” category, question about stoichiometry and thermodynamic in the “algorithmic” category and atom, periodic table and chemical bond questions were included in the conceptual category. From the data obtained, the need for a reorientation in the future of PAU tests is discussed.Keywords: chemical Education; College entrance exam; external testing, PAU; test questions

Type of test questions to higher education access in chemistry subject

Se estudia la tipología de preguntas formuladas en las pruebas de Química de acceso a la universidad en la Comunidad Autónoma Andaluza. Se analizaron 576 preguntas según los temas del currículum implicados y de acuerdo al sistema de categorías propuesto por Smith, Nakhleh y Bretz (2010) para exámenes de Química. Los temas más frecuentes fueron los de estequiometría, formulación-nomenclatura química y equilibrio ácido-base, que conjuntamente acaparaban alrededor de dos tercios de las preguntas formuladas. Las tres categorías de preguntas empleadas fueron: de Definición, Algorítmicas y Conceptuales, predominando principalmente las segundas, si bien con un cierto avance en los últimos años de las de tipo Conceptual aun cuando los cambios no resultaran estadísticamente significativos. Se observó una clara dependencia del tipo de preguntas de la temática concreta implicada en las mismas, siendo aquellas sobre formulación las que más se prestan a la categoría de “definición”, las de estequiometría y termoquímica a las “algorítmicas”, y las de átomo, Tabla periódica y enlace químico a las de tipo conceptual. A partir de los datos proporcionados se discute la necesidad de una reorientación de estas pruebas con vistas al futuro.In this work, the test question typology to higher education access in chemistry subject has been studied. This study was performed in the autonomous community of Andalusia. According to curriculum topics and the category system proposed by Smith, Nakhleh y Bretz (2010) for chemistry exams, 576 questions were analyzed. The most frequent topics were stoichiometry, formulation and chemical nomenclature and acid-base equilibria, which accounted for about two thirds of the questions. The three categories of questions used were: definition, algorithmic and conceptual questions were used. It was observed a predominance of the algorithmic questions, although in recent years, some progresses of conceptual questions have been observed, but not statistically significant changes. A clear dependence between the type of question and the specific issue involved was observed. Therefore, questions about formulation were mostly included in the “definition” category, question about stoichiometry and thermodynamic in the “algorithmic” category and atom, periodic table and chemical bond questions were included in the conceptual category. From the data obtained, the need for a reorientation in the future of PAU tests is discussed

Oral fosfomycin for the treatment of lower urinary tract infections among kidney transplant recipients—Results of a Spanish multicenter cohort

Preliminary results of this study were presented at the 29th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), held in Amsterdam, The Netherlands, from 13 to 16 April, 2019 (oral communication O‐0699).Oral fosfomycin may constitute an alternative for the treatment of lower urinary tract infections (UTIs) in kidney transplant recipients (KTRs), particularly in view of recent safety concerns with fluroquinolones. Specific data on the efficacy and safety of fosfomycin in KTR are scarce. We performed a retrospective study in 14 Spanish hospitals including KTRs treated with oral fosfomycin (calcium and trometamol salts) for posttransplant cystitis between January 2005 and December 2017. A total of 133 KTRs developed 143 episodes of cystitis. Most episodes (131 [91.6%]) were produced by gram‐negative bacilli (GNB), and 78 (54.5%) were categorized as multidrug resistant (including extended‐spectrum β‐lactamase‐producing Enterobacteriaceae [14%] or carbapenem‐resistant GNB [3.5%]). A median daily dose of 1.5 g of fosfomycin (interquartile range [IQR]: 1.5‐2) was administered for a median of 7 days (IQR: 3‐10). Clinical cure (remission of UTI‐attributable symptoms at the end of therapy) was achieved in 83.9% (120/143) episodes. Among those episodes with follow‐up urine culture, microbiological cure at month 1 was achieved in 70.2% (59/84) episodes. Percutaneous nephrostomy was associated with a lower probability of clinical cure (adjusted odds ratio: 10.50; 95% confidence interval: 0.98‐112.29; P = 0.052). In conclusion, fosfomycin is an effective orally available alternative for treating cystitis among KTRs.This study was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016)—cofinanced by the European Development Regional Fund “A way to achieve Europe”; the Group for Study of Infection in Transplantation and the Immunocompromised Host (GESITRA‐IC) of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC); and the Spanish Network for Research in Renal Diseases (REDInREN RD16/0009). MFR holds a research contract “Miguel Servet” (CP 18/00073) from the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III

Efficacy and Safety of Oral Fosfomycin for Asymptomatic Bacteriuria in Kidney Transplant Recipients: Results from a Spanish Multicenter Cohort

Current guidelines recommend against systematic screening for or treating asymptomatic bacteriuria (AB) among kidney transplant (KT) recipients, although the evidence regarding episodes occurring early after transplantation or in the presence of anatomical abnormalities is inconclusive. Oral fosfomycin may constitute a good option for the treatment of posttransplant AB, particularly due to the emergence of multidrug-resistant (MDR) uropathogens. Available clinical evidence supporting its use in this specific setting, however, remains scarce. We performed a retrospective study in 14 Spanish institutions from January 2005 to December 2017. Overall, 137 episodes of AB diagnosed in 133 KT recipients treated with oral fosfomycin (calcium and trometamol salts) with a test-of-cure urine culture within the first 30 days were included. Median time from transplantation to diagnosis was 3.1 months (interquartile range [IQR], 1.1 to 10.5). Most episodes (96.4% [132/137]) were caused by Gram-negative bacteria (GNB), and 56.9% (78/137) were categorized as MDR (extended‐spectrum β‐lactamase‐producing Enterobacterales [20.4%] and carbapenem‐resistant GNB [2.9%]). Rate of microbiological failure at month 1 was 40.1% (95% confidence interval [CI], 31.9% to 48.9%) for the whole cohort and 42.3% (95% CI, 31.2% to 54.0%) for episodes due to MDR pathogens. Previous urinary tract infection (odds ratio [OR], 2.42; 95% CI, 1.11 to 5.29; P value = 0.027) and use of fosfomycin as salvage therapy (OR, 8.31; 95% CI, 1.67 to 41.35; P value = 0.010) were predictors of microbiological failure. No severe treatment-related adverse events were detected. Oral fosfomycin appears to be a suitable and safe alternative for the treatment (if indicated) of AB after KT, including those episodes due to MDR uropathogens.This study was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III (ISCIII), Subdirección General de Redes y Centros de Investigación Cooperativa, Ministry of Science and Innovation, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), and Spanish Network for Research in Renal Diseases (REDInREN RD16/0009) and cofinanced by the European Development Regional Fund entitled A way to achieve Europe. M.F.-R. holds a research contract (Miguel Servet, CP18/00073), from the Spanish Ministry of Science and Innovation, ISCIII.Peer reviewe

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group