Game of mirrors: A critical dialogue between Goya and “El Roto”

Francisco de Goya, a través de sus dibujos y grabados, plasma una visión grotesca de la realidad. Andrés Rábago (El Roto) representa en sus viñetas la misma mirada satírica. Un legado que también comparten artistas contemporáneos como Estampa Popular, los miembros del informalismo español, Eduardo Arroyo o Equipo Crónica. El presente trabajo busca establecer una tradición artística nacional donde la risa y la crítica se unen para denunciar problemas sociales, políticos y culturales. Analogías temáticas y visuales, puntos de encuentros en el gran atlas del arte español

A lupine (Lupinus angustifolious L.) peptide prevents non-alcoholic fatty liver disease in high-fat-diet-induced obese mice

Bioactive peptides are related to the prevention and treatment of many diseases. GPETAFLR is an octapeptide that has been isolated from lupine (Lupinus angustifolius L.) and shows anti-inflammatory properties. The aim of this study was to evaluate the potential activity of GPETAFLR to prevent non-alcoholic fatty liver disease (NAFLD) in high-fat-diet (HFD)-induced obese mice. C57BL/6J mice were fed a standard diet or HFD. Two of the groups fed the HFD diet were treated with GPETAFLR in drinking water at 0.5 mg kg-1 day-1 or 1 mg kg-1 day-1. To determine the ability of GPETAFLR to improve the onset and progression of non-alcoholic fatty liver disease, histological studies, hepatic enzyme profiles, inflammatory cytokine and lipid metabolism-related genes and proteins were analysed. Our results suggested that HFD-induced inflammatory metabolic disorders were alleviated by treatment with GPETAFLR. In conclusion, dietary lupine consumption can repair HFD-induced hepatic damage possibly via modifications of liver's lipid signalling pathways

Activity of cefiderocol against high-risk clones of multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia

BACKGROUND: Cefiderocol is a novel siderophore cephalosporin, developed for activity against MDR Gram-negative bacilli (MDR-GNB). OBJECTIVES: To assess the in vitro antibacterial activity of cefiderocol against a collection of MDR-GNB clinical isolates from hospitals in southern Spain. METHODS: Two hundred and thirty-one isolates of successful clones were tested: 125 Enterobacterales (121 ESBL- and/or carbapenemase-producing Klebsiella pneumoniae and 4 carbapenemase-producing Enterobacter cloacae), 80 Acinetobacter baumannii, 6 Pseudomonas aeruginosa and 20 Stenotrophomonas maltophilia. Ceftolozane/tazobactam, ceftazidime, ceftazidime/avibactam, cefepime, aztreonam, meropenem, amikacin, ciprofloxacin, colistin and tigecycline were used as comparators against Enterobacterales, P. aeruginosa and A. baumannii. Minocycline, levofloxacin and trimethoprim/sulfamethoxazole were studied against S. maltophilia instead of aztreonam, ciprofloxacin and cefepime. MICs were determined by broth microdilution according to CLSI guidelines. MIC determination was performed in CAMHB for all antimicrobials except cefiderocol, where iron-depleted CAMHB was used. RESULTS: Cefiderocol showed potent in vitro activity against the isolates analysed. MIC50 and MIC90 values were in the ranges 0.125-8 mg/L and 0.5-8 mg/L, respectively, and 98% of isolates were inhibited at ≤4 mg/L. Only five isolates showed cefiderocol MICs of >4 mg/L: three ST2/OXA-24/40-producing A. baumannii, one ST114/VIM-1-producing E. cloacae and one ST114/VIM-1 + OXA-48-producing E. cloacae. All KPC-3-producing K. pneumoniae were susceptible to cefiderocol, even those resistant to ceftazidime/avibactam. P. aeruginosa isolates showed cefiderocol MICs of <4 mg/L, including those resistant to ceftolozane/tazobactam. S. maltophilia isolates displayed cefiderocol MICs of <4 mg/L, including those resistant to levofloxacin and/or trimethoprim/sulfamethoxazole. CONCLUSIONS: Cefiderocol showed excellent activity against MDR-GNB, including carbapenem-resistant isolates, and was the most active antimicrobial tested against this collection

Solving ordinary differential equations with range conditions. Applications

This paper introduces the problem of solving ordinary differential equations with extra linear conditions written in terms of ranges, and deals with the corresponding existence and uniqueness problems. Some methods for analyzing the existence of solutions and obtaining the set of all solutions, based on the theory of cones and polyhedra, are given. These solutions are found by first converting the problem to a system of linear algebraic equations and then applying the corresponding well-known theory for solving and discussing the existence and uniqueness of solutions of these systems. Finally, the methods are illustrated by their application to some practical examples of the beam problem

The use of a web application – SciFinder to complement the Organic Chemistry teaching to the student of the Degree in Pharmacy

La necesidad de motivación del alumno, además de la adaptación de la actual enseñanza a los créditos ECTS, han sido los motores que nos han llevado a proponer el uso de una aplicación web denominada SciFinder en la enseñanza de la Química Orgánica. Se trata de una herramienta imprescindible en la investigación avanzada que se utiliza en cualquier laboratorio de síntesis química. La Universidad de Granada dispone de una suscripción que permite 6 usos simultáneos a la que el alumno puede acceder a través de un acceso directo a SciFinder on Web en el sólo es necesario registrarse como usuario. Permitir al alumno transportarse a un laboratorio virtual es una de las múltiples posibilidades que ofrece esta aplicación web ayudándoles a complementar los conocimientos científicos básicos que se han explicado en clase. Durante el desarrollo de los distintos temas que componen la asignatura se plantearán reacciones concretas que el alumno deberá ampliar con la información que esta aplicación les proporciona: reactivos empleados en dichas reacciones condiciones de reacción (estequiometría, tiempo, temperatura…) bibliografía actual. Al final del curso académico se evaluará esta nueva experiencia mediante encuestas de opinión del alumnado para determinar dos aspectos fundamentales de la misma, el aumento de interés por la asignatura durante el desarrollo del trabajo y la dificultad en la realización del mismo.The need to motivate the students, besides adapting the teaching to the ECTS credits, have been the driving force that leads us to propose the use of a web application called Sci Finder in the education of Organic Chemistry. It is an essential tool used in any advanced research laboratory of synthetic chemistry. The University of Granada provides a subscription with 6 simultaneous accesses. The students may accede directly to the SciFinder on Web being only necessary the registration as users. One of the many possibilities that offers this web application allows to the student be transported to a virtual laboratory and complement the basic scientific knowledge explained in class. During the development of the different topics, specific reactions will be presented to the student and they may increase the information by using this application: reagents of the reactions reaction conditions (stoichiometry, time, temperature…) up-to-date bibliography At the end of the academic year this new experience will be evaluate through opinion poll to the student in order to determinate two essential aspect, the interest increase for the subject during the development of this work and the difficulty in carrying out it

Efficacy of Colistin and Its Combination With Rifampin in Vitro and in Experimental Models of Infection Caused by Carbapenemase-Producing Clinical Isolates of Klebsiella pneumoniae.

Despite the relevance of carbapenemase-producing Klebsiella pneumoniae (CP-Kp) infections there are a scarce number of studies to evaluate in vivo the efficacy of combinations therapies. The bactericidal activity of colistin, rifampin, and its combination was studied (time-kill curves) against four clonally unrelated clinical isolates of CP-Kp, producing VIM-1, VIM-1 plus DHA-1(acquired AmpC β-lactamase), OXA-48 plus CTX-M-15 (extended spectrum β-lactamase) and KPC-3, respectively, with colistin MICs of 0.5, 64, 0.5, and 32 mg/L, respectively. The efficacies of antimicrobials in monotherapy and in combination were tested in a murine peritoneal sepsis model, against all the CP-Kp. Their efficacies were tested in the pneumonia model against the OXA-48 plus CTX-M-15 producers. The development of colistin-resistance was analyzed for the colistin-susceptible strains in vitro and in vivo. In vitro, colistin plus rifampin was synergistic against all the strains at 24 h. In vivo, compared to the controls, rifampin alone reduced tissue bacterial concentrations against VIM-1 and OXA-48 plus CTX-M-15 strains; CMS plus rifampin reduced tissue bacterial concentrations of these two CP-Kp and of the KPC-3 strain. Rifampin and the combination increased the survival against the KPC-3 strain; in the pneumonia model, the combination also improved the survival. No resistant mutants appeared with the combination. In conclusion, CMS plus rifampin had a low and heterogeneous efficacy in the treatment of severe peritoneal sepsis model due to CP-Kp producing different carbapenemases, increasing survival only against the KPC-3 strain. The combination showed efficacy in the less severe pneumonia model. The combination prevented in vitro and in vivo the development of colistin resistant mutants.España, Consejería de Salud Junta de Andalucía PI-0622-201

GPETAFLR, a biopeptide from Lupinus angustifolius L., protects against oxidative and inflammatory damage in retinal pigment epithelium cells

GPETAFLR, an octapeptide released from the enzymatic hydrolysis of lupine (Lupinus angustifolius L.) protein, has demonstrated anti-inflammatory effect in myeloid lineage. This work aims to evaluate in retinal pigment epithelium (RPE) cells the protective role of GPETAFLR on both oxidative and inflammatory markers known to be involved in age-related macular degeneration (AMD). In comparison with stimulated control cells, GPETAFLR increased glutathione production and diminished the secretion and gene expression of VEFG, IL-1β, IL-6, IFNγ, and TNF-α, as well as reactive oxygen species, and nitrite output. Our findings reveal that GPETAFLR, a novel plant peptide, is able to protect against RPE oxidative stress and inflammation. Taken together, these results strongly support innovative nutritional strategies considering Lupinus angustifolius L. as source of proteins to prevent the onset and progression of AMD. Practical applications: We reveal a novel nutraceutical impact of GPETAFLR peptide in human RPE cells to prevent oxidative and inflammatory mediators. Our results support that the intake of Lupine angustifolius L., proposed to be a reservoir of GPETAFLR, could lessen the functional decay of RPE cells, leading therefore to a slowdown of the progress of AMD during age. Not only this work, but also future simple clinical studies should raise new nutritional strategies focused on understanding the etiological role of the foods, nutrition, and metabolism in the pathogenesis of ocular disorders.Ministerio de Economía y Competitividad AGL2012‐40247‐C02‐0

MUFAs in High-Fat Diets Protect against Obesity-Induced Bias of Hematopoietic Cell Lineages

Scope: The role of dietary fatty acids in the generation of bone marrow (BM) immune cells and their trafficking to extramedullary compartments in the obesity is not yet fully understood. Methods and Results: C57BL/6J mice are randomly assigned to isocaloric high-fat diets (HFDs) formulate with dietary fats rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs fortified with eicosapentaenoic and docosahexaenoic acids for 20 weeks, followed by profiling of the obese metabolic phenotype and immunophenotypic features of immune cells in blood, spleen, and BM. All HFDs induce an obese phenotype, but it becomes largely less disruptive after the HFDs are enriched in MUFAs, which also induce signs of granulopoiesis and an expansion of long-term hematopoietic stem and granulocyte-macrophage progenitor cells in BM. In contrast, a HFD enriched in SFAs disturbs the fitness of medullary lymphocytes and promotes monopoiesis in favor of pro-inflammatory activated subsets. Conclusion: The reshaping of the fatty acid pools with MUFAs from the diet serves to manipulate the generation and trafficking of immune cells that are biased during obesity. These findings reveal a novel strategy by which dietary MUFAs may be instrumental in combating HFD-induced dysfunctional immune systems.Ministerio de Ciencia, Innovación y Universidades AGL2016-80852-

Efficacy of cefepime and imipenem in experimental murine pneumonia caused by porin-deficient Klebsiella pneumoniae producing CMY-2 β-lactamase

Previous studies have shown decreased in vitro activity of zwitterionic cephalosporins and carbapenems against porin-deficient Klebsiella pneumoniae expressing a plasmid-mediated AmpC-type β-lactamase (PACBL). The in vitro and in vivo activities of cefepime and imipenem were evaluated against the porin-deficient strain K. pneumoniae C2 and its CMY-2-producing derivative [K. pneumoniae C2(pMG248)]. The MICs (in micrograms/milliliter) of cefepime and imipenem against K. pneumoniae C2 were 0.125 and 0.25, respectively, while the corresponding values against K. pneumoniae C2(pMG248) were 8 and 16. Cefepime showed a greater inoculum effect than imipenem against both strains. Imipenem showed a significant post-antibiotic effect (> 2 h) against K. pneumoniae C2(pMG248) at 1x, 2x, 4x, 6x, and 8x MIC. The maximum concentrations of drug in serum of cefepime and imipenem in a pneumonia model using mice were 124.1 and 16.9 μg/ml, respectively. ΔT/MIC for K. pneumoniae C2 and C2(pMG248) were 1.29 h and 0.34 h for imipenem and 2.96 h and 1.27 h for cefepime. Both imipenem (30 mg/kg of body weight every 3 h) and cefepime (60 mg/kg every 4 h), administered for 72 h, increased the survival rate (86.6% and 100%) compared with untreated control animals (26.6%, P < 0.003) infected with K. pneumoniae C2. For the CMY-2-producing strain, imipenem, but not cefepime, increased the survival rate compared to the controls (86.6% and 40% versus 40%, P < 0.01). Bacterial concentration of the lungs was significantly decreased by both antimicrobials. In conclusion, imipenem was more active in terms of survival than cefepime for the treatment of murine pneumonia caused by a porin-deficient K. pneumoniae expressing PACBL CMY-2.Consejería de Salud, Junta de Andalucía 00/153Red Española para la Investigación en Patología Infecciosa REIPI-ISCIII-C03/1

CD4+ and CD8+ T-cell responses in bone marrow to fatty acids in high-fat diets

Obesity is associated with disruptions in the adaptive immune system; however, dietary fatty acids in high-fat diets (HFDs) that induce obesity have consequences that are currently unclear regarding T-cell maintenance in bone marrow (BM). C57BL/6J mice were randomly assigned to isocaloric HFDs formulated with dietary fats rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), or MUFAs supplemented with eicosapentaenoic and docosahexaenoic acids for 20 weeks, followed by an analysis of the immunophenotypic feature of lymphocytes (CD3+) T and their subsets CD4+ and CD8+ T cells in spleen and BM, identification of fatty acids in BM extracellular fluid and analysis of the correspondence between fatty acids with the frequency of T-cell subsets in BM. Splenic CD3+ T cells were reduced irrespective of HFDs. In BM, CD3+ T cells were reduced after HFD-SFAs, while CD4+ T cells were increased after HFDs enriched in MUFAs and CD8+ T cells were reduced irrespective of HFDs. In BM extracellular fluid, the content of palmitic and myristic acids increased after HFD-SFAs and that of oleic acid increased after HFDs enriched in MUFAs. There was a statistical correspondence between HFD-induced changes in fatty acids in BM extracellular fluid and HFD-induced changes in the frequency of CD3+ and CD4+ T cells in BM. These findings reveal an undervalued critical role for dietary fatty acids in the selective acquisition of T-cell subsets in BM, highlighting that oleic acid existing in the surroundings of T-cell niches during HFD-induced obesity could be instrumental in the maintenance of CD4+ T cells.Fondo Social Europeo y Universidad de Sevilla-VPPI-USConsejo Superior de Investigaciones Científicas (CSIC)/Juan de la Cierva-FJCI-2017-3313