The effect of prednisolone therapy on canine serum levels of 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase

Dissertação de Mestrado Integrado em Medicina VeterináriaABSTRACT - 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase is a widely available biomarker, increasingly used in the investigation of canine pancreatitis mainly due to its low cost compared to pancreatic lipase immunoreactivity (cPLI). A previous study showed a good agreement between cPLI and DGGR lipase concentration. While the effect of corticotherapy on cPLI quantification has been studied, its influence on DGGR lipase is unknown. This study aims to evaluate the effect of prednisolone therapy in canine DGGR lipase serum levels. A prospective cohort study was conducted, including the measurement of DGGR lipase in two groups: the study group (SG) composed of dogs treated with oral prednisolone for a medical reason, at the initial dosage of 0.5-1.7 mg/kg/day for at least 3 weeks, and the control group (CG) composed of healthy untreated dogs. As an inclusion criterion, animals had basal DGGR lipase within the reference range (<80 U/L). DGGR lipase was measured at three time points (Day 0(T0), Day 7-10(T1), and Day 21-30(T2)) in both groups. The analysis was performed using a previously validated kit (Randox® DGGR lipase). Thirty-four dogs were included (17 dogs for each group, which were age and sex-matched). At T0, there was no significant difference in DGGR lipase concentrations between groups (p=0.868). Mean starting dosage of prednisolone was 0.94 (±0.85) mg/kg/day, decreasing to 0.45 (±0.05) mg/kg/day after T1. The median DGGR lipase concentration in SG at each time point (T0, T1, and T2) was: 24.74 (14.45-31.48) U/L, 36.82 (23.8-80.16) U/L and 29.52 (15.91-48.48) U/L, respectively. There was a statistically significant effect of prednisolone on DGGR lipase values (p=0.007) over T0, T1, and T2. A poor correlation was verified between the variations of DGGR lipase and the correspondent prednisolone dosage of T0-T1 and T1-T2 (rs=0.371 e rs=0.121, respectively). In CG, DGGR lipase did not significantly change over the three time points (p=0.926). This study suggests that DGGR lipase levels are affected by oral prednisolone therapy in dogs treated for a medical reason. However, as values remained below the considered significant upper limit (160 U/L), this variation does not seem to be clinically relevant.RESUMO - O EFEITO DA PREDNISOLONA NO DOSEAMENTO DA 1,2-O-DILAURYL-RAC- -GLYCERO GLUTARIC ACID-(6′-METHYLRESORUFIN) ESTER (DGGR) LIPASE - 1,2-o-dilauryl-rac-glycero glutaric acid-(6'-methylresorufin) ester (DGGR) lipase é um biomarcador recentemente disponível, que tem vindo a ser cada vez mais utilizado na exploração clínica de pancreatite em cães, sobretudo pelo seu custo acessível face à lipase pancreática específica (cPLI). Foi demonstrada uma boa concordância entre a cPLI e a DGGR lipase. Estudos prévios avaliaram a influência da corticoterapia no doseamento de cPLI. Contudo, a influência na DGGR lipase ainda não é conhecida. Este estudo visa avaliar o efeito da prednisolona nos níveis sérios de DGGR lipase em cães. Foi efetuado um estudo prospetivo de coorte, que incluiu a medição da DGGR lipase em dois grupos: o grupo de estudo (GE) constituído por cães aos quais foi administrada prednisolona por via oral com justificação médica na dose inicial de 0.5-1.7mg/kg/dia durante pelo menos 3 semanas e o grupo controlo (GC) composto por cães saudáveis sem tratamento concomitante. Como critério de inclusão consideraram-se cães com valores de DGGR lipase abaixo do valor de referência (<80 U/L). A DGGR lipase foi quantificada em três pontos temporais (Dia 0 (T0), Dia 7-10 (T1) e Dia 21-30 (T2)). A análise foi efetuada com recurso a um kit previamente validado (Randox® DGGR lipase). Foram incluídos 34 cães (17 cães em cada grupo, emparelhados relativamente ao género e idade). Em T0 não se observou diferença estatisticamente significativa entre grupos (p=0.868). A dose inicial média de prednisolona foi de 0.94 (±0.85) mg/kg/dia, tendo decrescido para 0.45 (±0.05) mg/kg/dia após T1. A concentração mediana de DGGR lipase no GE em cada ponto temporal (T0, T1 e T2) foi: 24.74 (14.45-31.48) U/L, 36.82 (23.8-80.16) U/L e 29.52 (15.91-48.48) U/L, respetivamente. Observou-se um efeito estatisticamente significativo da prednisolona nos valores de DGGR lipase ao longo de T0, T1 e T2 (p=0.007). Foi verificada uma baixa correlação entre as variações de DGGR lipase e a dose de prednisolona correspondente em T0-T1 e T1-T2 (rs=0.371 e rs=0.121, respetivamente). Em relação ao GC não se observaram diferenças estatisticamente significativas ao longo de T0, T1 e T2 (p=0.926). Sugere-se que a DGGR lipase seja afetada pela administração oral de prednisolona por justificação médica. No entanto, como os valores permanecem abaixo do limite máximo considerado (160 U/L), esta variação não aparenta ser clinicamente relevante.N/

Disability as a Driving Force of Sustainable Business Models in the Fourth Sector

[EN] We are living in unprecedented times in which sustainability is essential to economic growth, quality of life and national stability. In this context, Solidaridad y Trabajo Virgen del Camino (SOLTRA) emerges as an example of a firm in the fourth sector that has achieved the triple bottom line of sustainability: economic, social and environmental performance. Although SOLTRA’s current efforts are mainly focused on the social sphere through the recruitment and integration of people with disabilities into the company and, consequently, into the labour market and society, it also pursues environmental and economic objectives. In the present study, we analysed SOLTRA’s business model by applying the theory of planned behaviour and the resource-based view of the firm. The information derived from in-depth interviews with SOLTRA’s CEO and top managers from the operations and human resources departments, as well as public financial and social reports, allowed us to identify the cornerstones of its business model. The model is based on incremental technology, holistic behaviour and the integration of social activities that help identify better business opportunities. In this study, several implications for managers, policymakers and citizens are provided. These findings may contribute to the development of managerial practices that can help companies to achieve better outcomes by using new approaches to solving social and environmental problems and identifying new opportunities for vulnerable citizens

Urethane-acrylate/aramid nanocomposites based on graphenic materials. A comparative study of their mechanical properties

Urethane-acrylate thermoset resins (UATR) are a new type of polymeric matrix that have recently made a strong breakthrough in the composites sector. This is because of their properties, which make them an advantageous alternative to epoxy resins, especially if they are reinforced with high-performance fibers such as aramids. Graphene-based nanocomposites are one of the most dynamic research fields in nanotechnology, because graphenic materials greatly improve the properties of traditional composites. This work represents a comparative study of the effect of adding three types of graphenic materials on the mechanical properties of UATR/aramid composites. Several UATR polymeric matrices were doped at 2% w/w with graphene nanoplatelets (GNPs), reduced graphene oxide (rGO) and pristine few-layer graphene (FLG), and reinforced with Twaron CT709 para-aramid fibers. The obtained laminates showed low density (1.38 g·cm−3), a high volumetric fiber–resin ratio (80:20), homogeneous dispersion of the nanoreinforcement, high reproducibility, and easy scalability. The tensile, flexural and impact strength properties of the undoped composite and the graphene-doped nanocomposites were determined. FLG-doped nanocomposites showed the highest increase in all the mentioned mechanical properties and attained a very significant relative improvement over the undoped laminate (up to 134.4% in aCU)This research was funded by the European Defence Agency, grant number 17.ESI.OP.066: Study on the Impact of Graphene on Defence Applications. The European Defence Agency authorizes the publication of this paper, however, the paper does not necessarily express the Agency’s offcial views; the views expressed and all recommendations made are those of the authors. Under no circumstances shall the European Defence Agency be held liable for any loss, damage, liability, or expense incurred or suffered that is claimed to have resulted from the use of any of the information included herei

An end-to-end framework for intima media measurement and atherosclerotic plaque detection in the carotid artery

Background and objectives: The detection and delineation of atherosclerotic plaque are usually manually performed by medical experts on the carotid artery. Evidence suggests that this manual process is subject to errors and has a large variability between experts, equipment, and datasets. This paper proposes a robust end-to-end framework for automatic atherosclerotic plaque detection. Methods: The proposed framework is composed of: (1) a semantic segmentation model based on U-Net, with EfficientNet as the backbone, that obtains a segmentation mask with the carotid intima-media region; and (2) a convolutional neural network designed using Bayesian optimization that simultaneously performs a regression to get the average and maximum carotid intima media thickness, and a classification to determine the presence of plaque. Results: Our approach improves the state-of-the-art in both co and bulb territories in the REGICOR database, with more than 8000 images, while providing predictions in real-time. The correlation coefficient was 0.89 in the common carotid artery and 0.74 for bulb region, and the F1 score for atherosclerotic plaque detecting was 0.60 and 0.59, respectively. The experimentation carried out includes a comparison with other fully automatic methods for carotid intima media thickness estimation found in the literature. Additionally, we present an extensive experimental study to evaluate the robustness of our proposal, as well as its suitability and efficiency compared to different versions of the framework. Conclusions: The proposed end-to-end framework significantly improves the automatic characterization of atherosclerotic plaque. The generation of the segmented mask can be helpful for practitioners since it allows them to evaluate and interpret the model's results by visual inspection. Furthermore, the proposed framework overcomes the limitations of previous research based on ad-hoc post-processing, which could lead to overestimations in the case of oblique forms of the carotid artery

V600e braf inhibition induces cytoprotective autophagy through ampk in thyroid cancer cells

The dysregulation of autophagy is important in the development of many cancers, including thyroid cancer, whereV600E BRAF is a main oncogene. Here, we analyse the effect ofV600E BRAF inhibition on autophagy, the mechanisms involved in this regulation and the role of autophagy in cell survival of thyroid cancer cells. We reveal that the inhibition ofV600E BRAF activity with its specific inhibitor PLX4720 or the depletion of its expression by siRNA induces autophagy in thyroid tumour cells. We show thatV600E BRAF downregulation increases LKB1-AMPK signalling and decreases mTOR activity through a MEK/ERK-dependent mechanism. Moreover, we demonstrate that PLX4720 activates ULK1 and increases autophagy through the activation of the AMPK-ULK1 pathway, but not by the inhibition of mTOR. In addition, we find that autophagy blockade decreases cell viability and sensitize thyroid cancer cells toV600E BRAF inhibition by PLX4720 treatment. Finally, we generate a thyroid xenograft model to demonstrate that autophagy inhibition synergistically enhances the anti-proliferative and pro-apoptotic effects ofV600E BRAF inhibition in vivo. Collectively, we uncover a new role of AMPK in mediating the induction of cytoprotective autophagy byV600E BRAF inhibition. In addition, these data establish a rationale for designing an integrated therapy targetingV600E BRAF and the LKB1-AMPK-ULK1-autophagy axis for the treatment ofV600E BRAF-positive thyroid tumours.This research was supported by grants from the Ministerio de Ciencia, Innovación y Universidades of Spain (SAF 2014-53639-R) and from UAH-Comunidad de Madrid (CAM) (CM/JIN/2019-019

Effect of Sucrose on Growth and Stress Status of Castanea sativa x C. crenata Shoots Cultured in Liquid Medium

[Abstract] Current breeding programs aim to increase the number of ink-tolerant chestnut trees using vegetative propagation of selected genotypes. However, the commercial vegetative propagation of chestnut species is still a bottleneck for the forest industry, mainly due to problems in the rooting and acclimation of propagules. This study aimed to explore the potential benefits of decreasing sucrose supplementation during chestnut micropropagation. Explants were cultured with high light intensity and CO2-enriched air in temporary or continuous immersion bioreactors and with different sucrose supplementation to evaluate the impact of these treatments on growth, rooting and physiological status (monosaccharide content, soluble phenolics and antioxidant activity). The proliferation and rooting performance of shoots cultured by continuous immersion decreased sharply with sucrose concentrations lower than 1%, whereas shoots cultured by temporary immersion grew and rooted successfully with 0.5% sucrose. These results suggest this system is appropriate to culture chestnut with low sucrose concentration and to explore photoautotrophic propagation of this species.This research was funded by Xunta de Galicia (Spain) (projects IN607A 2021), by CYTED (P117RT0522), and by CSIC (PIE 202140E015, COOPB20584)Xunta de Galicia; IN607A 2021Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo (CYTED); P117RT0522Consejo Superior de Investigaciones Científicas; PIE 202140E015Consejo Superior de Investigaciones Científicas; COOPB2058

Symptomatic plant viroid infections in phytopathogenic fungi: a request for a critical reassessment

Serra, P.; Carbonell, A.; Navarro, B.; Gago Zachert, S.; Li, S.; Di Serio, F.; Flores Pedauye, R. (2020). Symptomatic plant viroid infections in phytopathogenic fungi: a request for a critical reassessment. Proceedings of the National Academy of Sciences of the United States of America (Online). 117(19):10126-10128. https://doi.org/10.1073/pnas.1922249117S10126101281171

An analysis of portuguese and brazilian curriculums from the perspective of history education

Este artículo tiene como objetivo analizar dos documentos curriculares relacionados con la enseñanza de la Historia, los Aprendizajes Esenciales (AE) aprobados en 2018 en Portugal y las Habilidades de la Base de currículo nacional común (BNCC) aprobadas en 2017 en Brasil. Realizaremos un análisis cualitativo, utilizando la estrategia metodológica de análisis documental. En un primer momento contextualizaremos brevemente ambos documentos, verificando en qué contextos históricos fueron aprobados y cómo se explican los conceptos de aprendizaje histórico en ambas propuestas. Nuestro análisis forma parte del campo de la Educación Histórica, que en Portugal y Brasil se ha constituido como una propuesta de enseñanza de la historia que articula teoría y práctica en la perspectiva de la epistemología de la historia y que se ha posicionado como un campo de estudio para una enseñanza de la historia comprometida con el pluralismo democrático. En este sentido, el análisis se enfocará en identificar elementos claves del campo de la Educación Histórica en estos documentos curriculares, como el abordaje de conceptos metahistóricos, conceptos sustantivos y el tema de temas controvertidos. También establecimos un recorte de análisis en los planes de estudio de 9º grado en ambos países sobre los enfoques a los supuestos del aprendizaje histórico presentados por los documentos del plan de estudios.Este artigo tem como objetivo analisar dois documentos curriculares ligados ao ensino de História, as Aprendizagens Essenciais (AE) aprovadas em 2018 em Portugal e as Habilidades da Base Nacional Comum Curricular (BNCC) aprovadas em 2017, no Brasil. Realizaremos uma análise qualitativa, utilizando a estratégia metodológica da análise documental. Em um primeiro momento, faremos uma breve contextualização de ambos documentos, verificando em quais contextos históricos eles foram aprovados e como são explicitadas as concepções de aprendizagem histórica em ambas propostas. Nossa análise insere-se no campo da Educação histórica, que em Portugal e no Brasil tem se constituído como uma proposta de ensino de história que articula teoria e prática na perspectiva da epistemologia da história e que tem se colocado como um campo de estudo para um ensino de história comprometido com o pluralismo democrático. Nesse sentido, a análise terá como foco a identificação de elementos-chave do campo da Educação histórica nesses documentos curriculares, como a abordagem de conceitos meta-históricos, de conceitos substantivos e a questão dos temas controversos. Também estabelecemos um recorte de análise nos currículos do 9º ano em ambos países sobre as abordagens dos pressupostos da aprendizagem histórica apresentada pelos documentos curriculares.This article aims to analyze two curricular documents related to the teaching of History, the Essential Learnings (AE) approved in 2018 in Portugal and the Common National Curriculum Base Skills (BNCC) approved in 2017 in Brazil. We will carry out a qualitative analysis, using the methodological strategy of document analysis. At first, we will briefly contextualize both documents, verifying in which historical contexts they were approved and how the concepts of historical learning in both proposals are explained. Our analysis is part of the field of History Education, which in Portugal and Brazil has been constituted as a proposal for teaching history that articulates theory and practice in the perspective of the epistemology of history and which has been positioned as a field of study for a history teaching committed to democratic pluralism. In this sense, the analysis will focus on identifying key elements of the field of History Education in these curricular documents, such as the approach to meta-historical concepts, substantive concepts and the issue of controversial themes. We also established an analysis cutout in the 9th grade curricula in both countries on the approaches to the assumptions of historical learning presented by the curriculum documents

Surface waters of the NW Iberian margin: upwelling on the shelf versus outwelling of upwelled waters from the Rías Baixas

A set of hydrographic surveys were carried out in the Ría of Vigo (NW Spain) at 2–4 d intervals during four 2–3 week periods in 1997, covering contrasting seasons. Residual exchange fluxes with the adjacent shelf were estimated with a 2-D, non-steady-state, salinity–temperature weighted box model. Exchange fluxes consist of a steady-state term (dependent on the variability of continental runoff) and a non-steady-state term (dependent on the time changes of density gradients in the embayment). More than 95% of the short-time-scale variability of the exchange fluxes in the middle and outer ría can be explained by the non-steady-state term that, in turns, is correlated (R2>75%) with the offshore Ekman transport. Conversely, 96% of the variability of exchange fluxes in the inner ría rely on the steady-state term. The outer and middle ría are under the direct influence of coastal upwelling, which enhances the positive residual circulation pattern by an order of magnitude: from 10 2 to 10 3 m3s−1. On the contrary, downwelling provokes a reversal of the circulation in the outer ría. The position of the downwelling front along the embayment depends on the relative importance of Ekman transport (Qx, m3s−1km−1) and continental runoff (R, m3s−1). When Qx/ R>7±2 the reversal of the circulation affects the middle ría. Our results are representative for the ‘Rías Baixas’, four large coastal indentations in NW Spain. During the upwelling season (spring and summer), 60% of shelf surface waters off the ‘Rías Baixas’ consist of fresh Eastern North Atlantic Central Water (ENACW) upwelled in situ. The remaining 40% consists of upwelled ENACW that previously enters the rías and it is subsequently outwelled after thermohaline modification. During the downwelling season (autumn and winter), 40% of the warm and salty oceanic subtropic surface water, which piled on the shelf by the predominant southerly winds, enters the rias

Errores de medicación en niños que acuden a los servicios de urgencias pediátricas

Errores de medicación; Servicios de urgencias; PediatríaMedication errors; Emergency departments; PediatricsErrors de medicació; Servei d'urgències; PediatriaObjectives: Medication safety represents an important challenge in children. There are limited studies on medication errors in pediatric patients visiting emergency departments. To help bridge this gap, we characterized the medication errors detected in these patients, determining their severity, the stages of the medication process in which they occurred, the drugs involved, and the types and causes associated with the errors. Methods: We conducted a multicenter prospective observational study in the pediatric emergency departments of 8 Spanish public hospitals over a 4-month period. Medication errors detected by emergency pediatricians in patients between 0 and 16 years of age were evaluated by a clinical pharmacist and a pediatrician. Each medication error was analyzed according to the updated Spanish Taxonomy of Medication Errors. Results: In 99,797 visits to pediatric emergency departments, 218 (0.2%) medication errors were detected, of which 74 (33.9%) resulted in harm (adverse drug events). Preschoolers were the age group with the most medication errors (126/218). Errors originated mainly in the prescribing stage (66.1%), and also by self-medication (16.5%) and due to wrong administration of the medication by family members (15.6%). Dosing errors (51.4%) and wrong/improper drugs (46.8%) were the most frequent error types. Anti-infective drugs (63.5%) were the most common drugs implicated in medication errors with harm. Underlying causes associated with a higher proportion of medication errors were "medication knowledge deficit" (63.8%), "deviation from procedures/guidelines" (48.6%) and "lack of patient information" (30.3%). Conclusions: Medication errors presented by children attending emergency departments arise from prescriptions, self-medicationand administration, and lead to patient harm in one third of cases. Developing effective interventions based on the types of errors and the underlying causes identified will improve patient safety.Objetivos La seguridad de medicamentos en pediatría supone un verdadero reto. Se dispone de escasos estudios que hayan analizado los errores de medicación en los pacientes pediátricos que acuden a los servicios de urgencias. El objetivo de este estudio ha sido caracterizar los errores detectados en estos pacientes, determinando su severidad, los procesos afectados, los medicamentos implicados, y los tipos de errores y causas asociados. Métodos Estudio multicéntrico observacional prospectivo realizado en los servicios de urgencias de 8 hospitales públicos españoles durante 4 meses. Los errores de medicación detectados por los pediatras de urgencias en pacientes entre 0 y 16 años fueron evaluados por un farmacéutico y un pediatra. Los errores de medicación fueron analizados utilizando la Taxonomía Española de Errores de Medicación actualizada. Resultados En 99.797 visitas a urgencias se detectaron 218 (0,2%) errores de medicación, de los cuales 74 (33,9%) causaron daños (eventos adversos por medicamentos). Los preescolares fueron el grupo poblacional con mayor número de errores de medicación (126/218). Los errores se originaron mayoritariamente en la prescripción (66,1%), por automedicación (16,5%) y por administración equivocada por parte de familiares (15,6%). Los tipos de errores más frecuentes fueron “dosis incorrectas” (51,4%) y “medicamento inapropiado” (46,8%). Los antiinfecciosos (63,5%) fueron los fármacos más comúnmente implicados en los errores con daño. Las causas subyacentes asociadas a una mayor proporción de errores de medicación fueron: “falta de conocimiento del medicamento” (63,8%), “falta de seguimiento de los procedimientos” (48,6%) y “falta de información del paciente” (30,3%). Conclusiones Los errores de medicación en la población pediátrica que acude a urgencias se producen en la prescripción, por automedicación y en la administración, provocando daños a los pacientes en un tercio de las ocasiones. Desarrollar prácticas seguras basadas en los tipos de errores detectados y sus causas subyacentes, mejorará la seguridad de los pacientes.This study has been carried out with the support of a grant provided by the Spanish Society of Hospital Pharmacists for the period 2015–2016