Evaluación in vitro de la actividad antibacteriana de derivados de quinoxalina.

La proliferación de cepas resistentes como consecuencia del uso de antibióticos, es un proceso natural que se ha acelerado en las últimas décadas por la aplicación inadecuada de ciertos fármacos. Pese a ser un problema inevitable, se requiere el desarrollo de agentes alternativos capaces de combatir estos patógenos sin generar efectos adversos. Hoy en día, se han desarrollado distintos métodos para evaluar la bioactividad de numerosas familias de compuestos contra varias cepas de microorganismos. En el presente estudio se pretende realizar una contribución que permita la caracterización de la actividad biológica de derivados de quinoxalina, justificando así la búsqueda de alternativas para extender el espectro de actividad y lograr minimizar la resistencia generada. Para llevar a cabo la evaluación de los compuestos, se utilizaron modelos procarióticos representativos de gram-negativos y gram-positivos como Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa y Staphylococcus aureus. Así mismo los compuestos fueron ensayados sobre cepas control de S. aureus CDBB B 1001, P. aeruginosa CDBB B 1021 y P. mirabilis CDBB B 1343. La actividad antibacteriana de los compuestos fue determinada por medio de la prueba de difusión en agar, CMI y cuenta viable en placa; mientras que la actividad citotóxica de los mismos fue evaluada mediante el ensayo MTT sobre macrófagos murinos J774. Los resultados mostraron que la mayoría de los compuestos fueron eficaces frente a la cepa gram positivo. El compuesto AG2 obtuvo la mejor actividad antibacteriana y una citotoxicidad moderada

Spark Plasma Sintered Zirconia Ceramic Composites with Graphene-Based Nanostructures

The addition of graphene-based nanostructures (GBNs) can improve the inherent fragility of ceramics and provide them with improved electrical and thermal conductivities. However, both the starting material (ceramic matrix and GBNs) and the processing/sintering approach are crucial for the final composite microstructure and properties. This work focuses on the influence of the content and dimensions of the GBN filler (10 and 20 vol%; 3 and ~150 layers), the powder-processing conditions (dry versus wet), and the homogenization method (ultrasound sonication versus high-energy planetary ball milling) on GBN/tetragonal zirconia (3YTZP) composites. The microstructure and electrical properties of the spark plasma sintered (SPS) composites were quantified and analyzed. The highest microstructural homogeneity with an isotropic microstructure was achieved by composites prepared with thicker GBNs milled in dry conditions. A high content (20 vol%) of few-layered graphene as a filler maximizes the electrical conductivity of the composites, although it hinders their densification.Ministerio de Economía y Competitividad MAT2015-67889-P

La fosfoenolpiruvato carboxilasa (PEPC): enzima clave de los metabolismos fotosintéticos C4 y CAM

http://digital.csic.es/bitstream/10261/29768/13/echevarria.pdfLa fosfoenolpiruvato carboxilasa (PEPC; EC 4.1.1.31) cataliza la β-carboxilación del fosfoenolpiruvato (PEP) en presencia de HCO3 - y Mg2+, para producir oxaloacetato (OAA) y Pi (Chollet et al., 1996). La PEPC está ampliamente distribuida en plantas, algas verdes y microorganismos pero ausente en levaduras y animales (Chollet et al., 1996). En plantas vasculares su papel estelar está relacionado con la fotosíntesis C4 y CAM («Crassulacean acid metabolism»), sin embargo desempeña otras funciones como la anaplerótica, en relación a la síntesis de proteínas, homeostasis del pH citosólico, electroneutralidad y osmolaridad. Está formada por una pequeña familia multigénica algunos de cuyos representantes están regulados a nivel transcripcional por factores como luz, hormonas y metabolitos (Chollet et al., 1996; Vidal y Chollet, 1997). La naturaleza alostérica de la enzima permite una regulación fina en relación a diferentes ambientes metabólicos. La PEPC está regulada por fosforilación reversible, proceso ligado a una cascada de transducción de señales de alta complejidad. En la actualidad es uno de los mejores modelos de señalización descritos en plantas. Este capítulo se centra en los eventos relacionados con este proceso en plantas C4 y CAM, los dos sistemas mejor estudiados en la actualidad (Chollet et al., 1996; Echevarría y Vidal, 2003; Izui et al., 2004; Nimmo, 2000; Vidal y Chollet, 1997).Phosphoenolpyruvate carboxylase (EC 4.1.1.31, PEPC) catalyzes the b-carboxylation of phosphoenolpyruvate (PEP) by HCO3 - in the presence of Mg2+ to yiel oxaloacetate and Pi (Chollet et al., 1996). PEPC is a widely distributed enzyme in plants, green algae and micro-organisms but absent in yeast and animals (Chollet et al., 1996). In higher plants, it catalyses a pivotal reaction related to such important processes as C4 and Crassulacean acid metabolism (CAM) photosynthesis, the anaplerotic pathway linked to amino acid synthesis, homeostasis of cytosolic pH, electroneutrality and osmolarity. PEPC belongs to a small multigenic family (Chollet et al., 1996; Vidal y Chollet, 1997). At the transcriptional level, some PEPC genes respond to external and internal factors (light, hormones and metabolites), while at the protein level, the allosteric nature of the enzyme allows its activity to be fine-tuned in relation to a varying metabolic environment. PEPC undergoes a posttranslational control by a phosphorylation process linked to a highly complex signal transduction cascade. Today, it is one of the best-described models of plant signaling. This chapter will focus on what is known about these processes in leaves of C4 and CAM plants, the two systems that have been studied in detail so far (Chollet et al., 1996; Echevarría y Vidal, 2003; Izui et al., 2004; Nimmo, 2000; Vidal y Chollet, 1997)

New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis

This research was funded by the Spanish National Research Council (CSIC), project no. 202080E231, and the Agreement with the University of Barcelona and the University of Granada (Official State Gazette 311, on 27 November 2020).Vulvovaginal candidiasis (VVC) poses a significant problem worldwide affecting women from all strata of society. It is manifested as changes in vaginal discharge, irritation, itching and stinging sensation. Although most patients respond to topical treatment, there is still a need for increase the therapeutic arsenal due to resistances to anti-infective agents. The present study was designed to develop and characterize three hydrogels of chitosan (CTS), Poloxamer 407 (P407) and a combination of both containing 2% caspofungin (CSP) for the vaginal treatment of VVC. CTS was used by its mucoadhesive properties and P407 was used to exploit potential advantages related to increasing drug concentration in order to provide a local effect. The formulations were physically, mechanically and morphologically characterized. Drug release profile and ex vivo vaginal permeation studies were performed. Antifungal efficacy against different strains of Candida spp. was also evaluated. In addition, tolerance of formulations was studied by histological analysis. Results confirmed that CSP hydrogels could be proposed as promising candidates for the treatment of VVC.Spanish National Research Council (CSIC), project no. 202080E231Agreement with the University of Barcelona and the University of Granad

Comparative epigenomics in distantly related teleost species identifies conserved cis-regulatory nodes active during the vertebrate phylotypic period

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months. After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International).The complex relationship between ontogeny and phylogeny has been the subject of attention and controversy since von Baer's formulations in the 19th century. The classic concept that embryogenesis progresses from clade general features to species-specific characters has often been revisited. It has become accepted that embryos from a clade show maximum morphological similarity at the so-called phylotypic period (i.e., during mid-embryogenesis). According to the hourglass model, body plan conservation would depend on constrained molecular mechanisms operating at this period. More recently, comparative transcriptomic analyses have provided conclusive evidence that such molecular constraints exist. Examining cis-regulatory architecture during the phylotypic period is essential to understand the evolutionary source of body plan stability. Here we compare transcriptomes and key epigenetic marks (H3K4me3 and H3K27ac) from medaka (Oryzias latipes) and zebrafish (Danio rerio), two distantly related teleosts separated by an evolutionary distance of 115-200 Myr. We show that comparison of transcriptome profiles correlates with anatomical similarities and heterochronies observed at the phylotypic stage. Through comparative epigenomics, we uncover a pool of conserved regulatory regions (≈700), which are active during the vertebrate phylotypic period in both species. Moreover, we show that their neighboring genes encode mainly transcription factors with fundamental roles in tissue specification. We postulate that these regulatory regions, active in both teleost genomes, represent key constrained nodes of the gene networks that sustain the vertebrate body plan.The Andalusian government (JA) supported A.F-.M. as scientific manager of the Aquatic Vertebrates Platform at CABD. J.W.C. was supported by a studentship from The Institute of Cancer Research. Spanish and Andalusian government grants BFU2010-14839, CSD2007-00008, and P08-CVI-3488 to J.L.G-.S.; and BFU2011-22916 and P11-CVI-7256 to J.R.M-.M. supported this work.Peer Reviewe

Eculizumab in secondary atypical haemolytic uraemic syndrome

Background. Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods. We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 109/L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results. Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion. Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing conditionWork in this report was funded by the Instituto de Salud Carlos III: REDinREN (RD 016/009 Feder Funds), the Fondo de Investigaciones Sanitarias (13/02502 and ICI14/00350), the Ministerio de Economia y Competitividad (SAF2015-66287R) and the Autonomous Region of Madrid (S2010/BMD-2316; Grupo de Investigación Complemento-CM). SRdeC is funded by the Seventh Framework Programme European Union Project EURenOmics (305608

Carga de trabalho em três grupos de pacientes em uma UTI espanhola segundo Nursing Activites Score

The purpose of this study was to assess the nursing workload at admission to and discharge from intensive care of three groups of patients (i.e., acute coronary syndrome, acute respiratory failure, and sepsis). A prospective, descriptive study was performed over a 27-month period and included 563 patients. The workload was assessed using the Nursing Activities Score scale. Significant differences in the workload were determined on the days of admission and discharge: the workload was higher in both cases for patients with acute respiratory failure and sepsis compared with patients diagnosed with acute coronary syndrome. This difference was maintained over the first seven days of their hospital stay. From day 8 on, the difference disappeared, and a workload balance was achieved in the three groups. Good staffing requires adequate tools for measuring care needs and understanding the workload required in the groups of patients who are most frequently admitted to intensive care.Se objetivó valorizar la carga de trabajo al ingreso y al alta en tres grupos de pacientes (síndrome coronario agudo, insuficiencia respiratoria aguda y sepsis) en terapia intensiva. Estudio descriptivo, prospectivo, de 27 meses, incluyéndose 563 pacientes, valorando carga de trabajo según Nursing Activities Score. Existieron diferencias significativas en la carga de trabajo al ingreso y en el alta entre los grupos de pacientes, siendo superior en ambos momentos la de pacientes con insuficiencia respiratoria aguda y sepsis frente a pacientes coronarios. Durante los siete primeros días de estancia se mantuvo esta diferencia, desapareciendo a partir del octavo día, equilibrándose la carga de trabajo para los tres grupos. Para conseguir una adecuada dotación de personal es fundamental contar con instrumentos para medir las necesidades de cuidados y conocer la carga de trabajo de los distintos grupos de enfermos que ingresan con mayor frecuencia en las unidades de terapia intensiva.O objetivo deste estudo foi avaliar a carga de trabalho na admissão e alta dos pacientes de três grupos (síndrome coronária aguda, insuficiência respiratória aguda e sepsis) em cuidados intensivos. Trata-se de estudo prospectivo, descritivo, que decorreu durante 27 meses, incluindo 563 pacientes. Para a avaliação da carga de trabalho utilizou-se a escala Nursing Activities Score. A partir dos resultados do estudo parecem existir diferenças significativas na carga de trabalho no dia da admissão e alta entre os grupos de pacientes, sendo a carga maior em ambos os tempos a dos pacientes com insuficiência respiratória aguda e sepsis. Durante os primeiros sete dias de internamento essa diferença manteve-se, desaparecendo no oitavo dia, o que equilibrou a carga de trabalho para os três grupos. Conclui-se que para se conseguir os recursos adequados é essencial dispor de instrumentos para medir as necessidades de cuidados e conhecer a carga de trabalho dos diferentes grupos de pacientes que passam com mais frequência pelas unidades de cuidados intensivos

BRAF V600E mutational load as a prognosis biomarker in malignant melanoma

Analyzing the mutational load of driver mutations in melanoma could provide valuable information regarding its progression. We aimed at analyzing the heterogeneity of mutational load of BRAF V600E in biopsies of melanoma patients of different stages, and investigating its potential as a prognosis factor. Mutational load of BRAF V600E was analyzed by digital PCR in 78 biopsies of melanoma patients of different stages and 10 nevi. The BRAF V600E load was compared among biopsies of different stages. Results showed a great variability in the load of V600E (0%-81%). Interestingly, we observed a significant difference in the load of V600E between the early and late melanoma stages, in the sense of an inverse correlation between BRAF V600E mutational load and melanoma progression. In addition, a machine learning approach showed that the mutational load of BRAF V600E could be a good predictor of metastasis in stage II patients. Our results suggest that BRAF V600E is a promising biomarker of prognosis in stage II patients.This research was supported by the Basque Government (grants ELKARTEK-KK2016-036 and KK2017-041 to MDB, grant IT1138-16 to SA and predoctoral fellowship PRE_2014_1_419 to AS), and by the University of the Basque Country (UPV/EHU) (grant GIU17/066). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Estado nutricional, prácticas y percepciones sobre alimentación y actividad física en familias de comunidades suburbanas de San Luis Potosí, México

Introducción: Las zonas de pobreza suburbanas son importantes en salud pública, por sus implicaciones epidemiológicas debidas a asentamientos insalubres y a la adopción de estilos de vida urbanos no saludables, por lo que estos contextos son propicios para la doble carga de la malnutrición. Objetivo: Se evaluó el estado nutricional y se analizaron percepciones y prácticas sobre alimentación y actividad física en familias de dos comunidades suburbanas del municipio de San Luis Potosí, México. Metodología: Los datos provienen de una evaluación antropométrica y nutricional realizada a 29 familias de Real Peñasco y Milpillas, de cuestionarios y entrevistas aplicadas a adultos, y de la técnica del dibujo en niños. Resultados: Se encontró rezago social en las familias, y su principal problema nutricional es el sobrepeso y la obesidad; la calidad de la alimentación y el sedentarismo fueron factores de riesgo. En los participantes existe conocimiento sobre alimentación saludable y no saludable, sin embargo, las prácticas de consumo indican malnutrición y las oportunidades para realizar ejercicio son escasas. Conclusiones: Es evidente la necesidad de implementar intervenciones basadas en evidencia; la experiencia del presente estudio, aporta bases para replantear futuros programas sociales y de salud en estas comunidades, acorde a su contexto

Plasma Gelsolin Reinforces the Diagnostic Value of FGF-21 and GDF-15 for Mitochondrial Disorders

Mitochondrial disorders (MD) comprise a group of heterogeneous clinical disorders for which non-invasive diagnosis remains a challenge. Two protein biomarkers have so far emerged for MD detection, FGF-21 and GDF-15, but the identification of additional biomarkers capable of improving their diagnostic accuracy is highly relevant. Previous studies identified Gelsolin as a regulator of cell survival adaptations triggered by mitochondrial defects. Gelsolin presents a circulating plasma isoform (pGSN), whose altered levels could be a hallmark of mitochondrial dysfunction. Therefore, we investigated the diagnostic performance of pGSN for MD relative to FGF-21 and GDF-15. Using ELISA assays, we quantified plasma levels of pGSN, FGF-21, and GDF-15 in three age- and gender-matched adult cohorts: 60 genetically diagnosed MD patients, 56 healthy donors, and 41 patients with unrelated neuromuscular pathologies (non-MD). Clinical variables and biomarkers’ plasma levels were compared between groups. Discrimination ability was calculated using the area under the ROC curve (AUC). Optimal cut-offs and the following diagnostic parameters were determined: sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and efficiency. Comprehensive statistical analyses revealed significant discrimination ability for the three biomarkers to classify between MD and healthy individuals, with the best diagnostic performance for the GDF-15/pGSN combination. pGSN and GDF-15 preferentially discriminated between MD and non-MD patients under 50 years, whereas FGF-21 best classified older subjects. Conclusion: pGSN improves the diagnosis accuracy for MD provided by FGF-21 and GDF-15