RAIAGROS una alternativa para la enseñanza de la fitopatología en la Universidad Nacional Experimental Sur del Lago (UNESUR), Venezuela

La realidad educativa actual es protagonizada por estudiantes nacidos en la era digital, que deben responder a las demandas de un entorno laboral cambiante, digitalizado e interconectado. Esto hace necesario que se propongan diseños instruccionales que fomenten la participación, reflexión, comprensión, investigación y construcción de conocimientos en un ambiente colaborativo. En la UNESUR, la asignatura fitopatología es dictada utilizando metodologías de enseñanza-aprendizaje tradicionales: clases magistrales centradas en el profesor. Se propone un método alternativo de enseñanza-aprendizaje denominado: Reproducción de un Ambiente de Ingeniería Agropecuaria en el Salón de Clase centrado en el talento subestimado del estudiante, donde se fomenta las competencias profesionales con la realización de un producto de diagnóstico fitopatológico, alimentado por contenidos teóricos y prácticos estructurados. Las evaluaciones tradicionales son sustituidas por discusiones y negociaciones de contenidos, utilizando mapas conceptuales y mentales. Las competencias, habilidades y destrezas son logradas al organizar compañías de trabajo, bajo la supervisión del profesor, que convierten al estudiante en el gestor principal de su aprendizaje. Los logros del método se traducen en incremento de las calificaciones y disminución del porcentaje de deserción. Mejora el trabajo en equipo, búsqueda de información, interés en el área fitopatológica, y satisfacción por aprender de manera colaborativa con su equipo de trabajo.Eje temático 2: Los cambios e innovaciones en los procesos de formación a - Alternativas didácticas y experiencias de renovación de la enseñanzaFacultad de Ciencias Agrarias y Forestale

Efecto de la estigmatización del VIH/SIDA en usuarios de drogas intravenosas en el acceso a los servicios sanitarios según género

Se ha elaborado un estudio con enfoque cualitativo basado en encuestas semiestructuradas, en el periodo 2007-2008, de usuarios de drogas intravenosas de los Centros de Información y Prevención del Sida. Los profesionales, que atienden de forma esporádica a pacientes VIH los estigmatizan en mayor medida debido a la desinformación, miedo y falta de empatía. Se detecta diferente comportamiento de uso en ex consumidores de drogas. Las mujeres se ajustan más a las normas y son menos conflictivas, se desenganchan más y recaen menos. A las mujeres se les atiende rápidamente en los servicios sanitarios no específicos. Ambos sexos usan estrategias contra la estigmatizació

The PARP inhibitor olaparib enhances the sensitivity of Ewing sarcoma to trabectedin

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Recent preclinical evidence has suggested that Ewing Sarcoma (ES) bearing EWSR1-ETS fusions could be particularly sensitive to PARP inhibitors (PARPinh) in combination with DNA damage repair (DDR) agents. Trabectedin is an antitumoral agent that modulates EWSR1-FLI1 transcriptional functions, causing DNA damage. Interestingly, PARP1 is also a transcriptional regulator of EWSR1-FLI1, and PARPinh disrupts the DDR machinery. Thus, given the impact and apparent specificity of both agents with regard to the DNA damage/DDR system and EWSR1-FLI1 activity in ES, we decided to explore the activity of combining PARPinh and Trabectedin in in vitro and in vivo experiments. The combination of Olaparib and Trabectedin was found to be highly synergistic, inhibiting cell proliferation, inducing apoptosis, and the accumulation of G2/M. The drug combination also enhanced γH2AX intranuclear accumulation as a result of DNA damage induction, DNA fragmentation and global DDR deregulation, while EWSR1-FLI1 target expression remained unaffected. The effect of the drug combination was corroborated in a mouse xenograft model of ES and, more importantly, in two ES patient-derived xenograft (PDX) models in which the tumors showed complete regression. In conclusion, the combination of the two agents leads to a biologically significant deregulation of the DDR machinery that elicits relevant antitumor activity in preclinical models and might represent a promising therapeutic tool that should be further explored for translation to the clinical setting.Enrique de Álava’s lab is supported by the AECC (Asociación Española Contra el Cáncer), the Ministry of Economy and Competitiveness of Spain-FEDER (PI081828, RD06/0020/0059 RD12/0036/0017, PT13/0010/0056, PI110018, ISCIII Sara Borrell postdoc grant CD06/00001), the European Project EuroSARC (FP7-HEALTH-2011- two-stage, Project ID 278742 EUROSARC), Fundación Memoria de D. Manuel Solorzano Barruso, Fundación Cris contra el cancer, and Fundación María García Estrada. JLO was sponsored by the CSIC and the European Social Fund (post-doctoral grant JAE DOC) and is at present funded by the AECC. ATA is sponsored by the Fundaçao para a Ciência e Tecnologia, Portugal (fellowship SFRH/BD/69318/2010). OMT is funded by Fondo de Investigaciones Sanitarias-ISCIII (CES12/021) and the AECC. DHM is funded by the AECC. Work supported by the Xarxa de Bancs de Tumors de Catalunya (XBTC) sponsored by Pla Director d’Oncologia de Catalunya. AMC acknowledges funding from the European Union Seventh Framework Programme (FP7/2007-2013) under a Marie Curie International Reintegration Grant (PIRG-08- GA-2010-276998) and ISCIII-FEDER (CP13/00189).Peer Reviewe

Newly impaired glucose metabolism and prognosis after percutaneous revascularization

Background: Clinical practice guidelines recommend ad hoc screening of diabetes in patients admitted for macrovascular disease; however, these recommendations are rarely followed in real practice. This study was undertaken to assess whether impaired glucose metabolism, newly diagnosed after percutaneous coronary intervention (PCI) or known diabetes, provides prognostic information. Methods: We studied 374 patients who underwent PCI. An oral glucose tolerance test was carried out in the known non-diabetic patients with fasting glucose < 7 mmol/L. Results: Eighty-one percent of the patients presented impaired glucose metabolism, from which 35.3% were previously diagnosed with diabetics, 21.4% were newly detected diabetics, and 24.3% were pre-diabetics. After a mean follow-up of 35.8 ± 13.4 months, only a known history of diabetes was an independent predictor of revascularization (OR = 2.03, p = 0.025), non-fatal acute myocardial infarction (OR = 2.70, p = 0.029) and readmission due to heart failure during the follow-up (OR = 3.82, p = 0.022). Conclusions: Screening for impaired glucose metabolism after PCI permits the detection of a high proportion of patients with abnormal glucose regulations. However, previously known diabetes remains the only independent predictor of cardiovascular events in the follow-up.

Identification Of Actionable Genetic Targets In Primary Cardiac Sarcomas

Background: Primary cardiac tumors are extremely rare; most are myxomas with a benign prognosis. However, primary sarcomas are highly aggressive and treatment options are limited. Radical surgery is often not feasible and conventional therapies provide only modest results. Due to the rare nature of primary cardiac tumors, there are no proper randomized studies to guide treatment. Their complexity requires alternative approaches in order to improve treatment efficacy. Methods: We isolated DNA from 5 primary cardiac sarcomas; the quality of DNA from 3 of them was sufficient to perform high-resolution single nucleotide polymorphism (SNP) array analysis. Results: In the present study, molecular karyotyping revealed numerous segmental chromosomal alterations and amplifications affecting actionable genes that may be involved in disease initiation and/or progression. These include chromosomal break flanking AKT2 in undifferentiated pleomorphic rhabdomyosarcoma, chromosomal break in promoter of TERT, and gain of CDK4 and amplification of MDM2 in inflammatory myofibroblastic tumor. We detected segmental break flanking MOS in high-grade myxofibrosarcoma. In addition, the high number of chromosomal aberrations in high-grade myxofibrosarcoma may cause multiple tumor-specific epitopes, supporting the study of immunotherapy treatment in this type of aggressive tumor. Conclusion: Our results provide a genetic rationale that supports an alternative, personalized therapeutic management of primary cardiac sarcomas

Opioids and Ocular Surface Pathology : A Literature Review of New Treatments Horizons

Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.This review discusses the role of opioids in the corneal surface and the different pathways and therapeutic methods of management. A literature review was performed using PubMed database. For the database search, the main searching words “opioid” and “topical opioid treatment” were used with the descriptors “cornea”, “ocular surface”, “neuropathic corneal pain”, “corneal sensitivity” and “naltrexone”; original scientific articles and reviews were included to achieve the purpose of the review. The endogenous opioid system has relevant functions in the organism, and in daily use, opioids are used as painkillers. However, these drugs may be employed for other indications as opioid pathways have a wide spectrum. The corneal surface for topical treatment is easily accessible, hence sparing the side effects of systemic opioids. Instillation of opioid antagonist substances, such as naltrexone, increases corneal healing rates and stimulates the division of corneal epithelium cells without deleterious effects. The natural modulation of endogenous opioids controls different forms of pain, including inflammatory and neuropathic pain, both in the ocular surface and in the central nervous system. There are diverse methods in controlling pain using opioids, especially in refractory forms. This review attempts to collect the literature about corneal surface and opioid pathways to provide an overview image and a possible direction of the news treatments.publishersversionPeer reviewe

EphA2-induced angiogenesis in ewing sarcoma cells works through bFGF production and is dependent on caveolin-1

Angiogenesis is the result of the combined activity of the tumor microenvironment and signaling molecules. The angiogenic switch is represented as an imbalance between pro- and anti-angiogenic factors and is a rate-limiting step in the development of tumors. Eph receptor tyrosine kinases and their membrane-anchored ligands, known as ephrins, constitute the largest receptor tyrosine kinase (RTK) subfamily and are considered a major family of pro-angiogenic RTKs. Ewing sarcoma (EWS) is a highly aggressive bone and soft tissue tumor affecting children and young adults. As other solid tumors, EWS are reliant on a functional vascular network for the delivery of nutrients and oxygen and for the removal of waste. Based on the biological roles of EphA2 in promoting angiogenesis, we explored the functional role of this receptor and its relationship with caveolin-1 (CAV1) in EWS angiogenesis. We demonstrated that lack of CAV1 results in a significant reduction in micro vascular density (MVD) on 3 different in vivo models. In vitro, this phenomenon correlated with inactivation of EphA2 receptor, lack of AKT response and downregulation of bFGF. We also demonstrated that secreted bFGF from EWS cells acted as chemoattractant for endothelial cells. Furthermore, interaction between EphA2 and CAV1 was necessary for the right localization and signaling of the receptor to produce bFGF through AKT and promote migration of endothelial cells. Finally, introduction of a dominant-negative form of EphA2 into EWS cells mostly reproduced the effects occurred by CAV1 silencing, strongly suggesting that the axis EphA2-CAV1 participates in the promotion of endothelial cell migration toward the tumors favoring EWS angiogenesis

Non-spectral interferences due to the presence of sulfuric acid in inductively coupled plasma mass spectrometry

Results of a systematic study concerning non-spectral interferences from sulfuric acid containing matrices on a large number of elements in inductively coupled plasma–mass spectrometry (ICP-MS) are presented in this work. The signals obtained with sulfuric acid solutions of different concentrations (up to 5% w w− 1) have been compared with the corresponding signals for a 1% w w− 1− nitric acid solution at different experimental conditions (i.e., sample uptake rates, nebulizer gas flows and r.f. powers). The signals observed for 128Te+, 78Se+ and 75As+ were significantly higher when using sulfuric acid matrices (up to 2.2-fold for 128Te+ and 78Se+ and 1.8-fold for 75As+ in the presence of 5 w w-1 sulfuric acid) for the whole range of experimental conditions tested. This is in agreement with previously reported observations. The signal for 31P+ is also higher (1.1-fold) in the presence of sulfuric acid. The signal enhancements for 128Te+, 78Se+, 75As+ and 31P+ are explained in relation to an increase in the analyte ion population as a result of charge transfer reactions involving S+ species in the plasma. Theoretical data suggest that Os, Sb, Pt, Ir, Zn and Hg could also be involved in sulfur-based charge transfer reactions, but no experimental evidence has been found. The presence of sulfuric acid gives rise to lower ion signals (about 10–20% lower) for the other nuclides tested, thus indicating the negative matrix effect caused by changes in the amount of analyte loading of the plasma. The elemental composition of a certified low-density polyethylene sample (ERM-EC681K) was determined by ICP-MS after two different sample digestion procedures, one of them including sulfuric acid. Element concentrations were in agreement with the certified values, irrespective of the acids used for the digestion. These results demonstrate that the use of matrix-matched standards allows the accurate determination of the tested elements in a sulfuric acid matrix

Cardiac dysfunction and remodeling regulated by anti-angiogenic environment in patients with preeclampsia : the ANGIOCOR prospective cohort study protocol

Background: Cardiovascular diseases (CVD) are cause of increased morbidity and mortality in spite of advances for diagnosis and treatment. Changes during pregnancy affect importantly the maternal CV system. Pregnant women that develop preeclampsia (PE) have higher risk (up to 4 times) of clinical CVD in the short- and long-term. Predominance of an anti-angiogenic environment during pregnancy is known as main cause of PE, but its relationship with CV complications is still under research. We hypothesize that angiogenic factors are associated to maternal cardiac dysfunction/remodeling and that these may be detected by new cardiac biomarkers and maternal echocardiography. Methods: Prospective cohort study of pregnant women with high-risk of PE in first trimester screening, established diagnosis of PE during gestation, and healthy pregnant women (total intended sample size n = 440). Placental biochemical and biophysical cardiovascular markers will be assessed in the first and third trimesters of pregnancy, along with maternal echocardiographic parameters. Fetal cardiac function at third trimester of pregnancy will be also evaluated and correlated with maternal variables. Maternal cardiac function assessment will be determined 12 months after delivery, and correlation with CV and PE risk variables obtained during pregnancy will be evaluated. Discussion: The study will contribute to characterize the relationship between anti-angiogenic environment and maternal CV dysfunction/remodeling, during and after pregnancy, as well as its impact on future CVD risk in patients with PE. The ultimate goal is to improve CV health of women with high-risk or previous PE, and thus, reduce the burden of the disease. Trial registration: NCT04162236

Efecto de la quinasa activada por AMP (AMPK) sobre el metabolismo lipídico en células de carcinoma hepatocelular resistentes a sorafenib

El carcinoma hepatocelular (HCC) es la tercera causa de muerte por cáncer en todo el mundo, siendo su principal tratamiento la quimioterapia con el inhibidor de tirosina quinasas sorafenib. Sin embargo, este tratamiento está obstaculizado frecuentemente por la aparición de quimiorresistencia. Estudios recientes afirman que los cambios metabólicos en las células tumorales pueden causar una desregulación en la señalización que puede participar en el desarrollo, resistencia y recurrencia del tumor y, por ello el objetivo de este trabajo ha sido estudiar la relación entre el metabolismo lipídico y los mecanismos moleculares de resistencia. Para ello, creamos un modelo de HCC resistente a sorafenib, generando dos líneas celulares (HepG2SF1 y Huh7SF1) mediante incubación con concentraciones crecientes de sorafenib durante 12 meses .En estas líneas hemos analizado los cambios metabólicos que se producen a fin de encontrar una diana que permita combatir la quimiorresistencia. Las células HepG2SF1 y Huh7SF1 mostraron acumulación intracelular de lípidos neutros, determinados mediante citometría de flujo y microscopía confocal. El estudio del metabolismo lipídico reveló que las células HepG2SF1 y Huh7SF1 tenían aumentada la expresión de las enzimas involucradas en la síntesis de novo de lípidos, ATP-citrato liasa (ACLY), acetil-CoA carboxilasa (ACC) y ácido graso sintasa (FASN) y la del transportador de ácido grasos CD36. Por otro lado, analizamos la quinasa activada por AMP (AMPK), sensor metabólico celular, observando que tanto la fosforilación como los niveles totales de AMPK disminuyeron en las células resistentes en comparación con las células parentales. Es interesante resaltar que, la transfección de AMPK en las células HepG2SF1 y Huh7SF1 restableció los niveles de las enzimas lipogénicas y disminuyó la acumulación de lípidos intracelulares además de disminuir la resistencia a sorfenib. Estos resultados indican que AMPK puede ser una diana prometedora en células resistentes a sorafenib