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Abstract Background Vasculogenic therapies explored for the treatment of peripheral artery disease (PAD) have encountered minimal success in clinical trials. Addressing this, B55α, an isoform of protein phosphatase 2A (PP2A), emerges as pivotal in vessel remodeling through activation of hypoxia-inducible factor 1α (HIF-1α). This study delves into the pharmacological profile of VCE-004.8 (Etrinabdione) and evaluates its efficacy in a preclinical model of critical limb ischemia, with a focus on its potential as a PP2A/B55α activator to induce angiogenesis and arteriogenesis. Methods Vascular endothelial cells were used for in vitro experiments. Aorta ring assay was performed to explore sprouting activity. Matrigel plug-in assay was used to assess the angiogenic potential. Critical limb ischemia (CLI) in mice was induced by double ligation in the femoral arteria. Endothelial vascular and fibrotic biomarkers were studied by immunohistochemistry and qPCR. Arteriogenesis was investigated by microvascular casting and micro-CT. Proteomic analysis in vascular tissues was analyzed by LC–MS/MS. Ex-vivo expression of B55α and biomarkers were investigated in artery samples from PAD patients. Results VCE-004.8 exhibited the ability to induce B55α expression and activate the intersecting pathways B55α/AMPK/Sirtuin 1/eNOS and B55α/PHD2/HIF-1α. VCE-004.8 prevented OxLDL and H2O2-induced cytotoxicity, senescence, and inflammation in endothelial cells. Oral VCE-004.8 increased aorta sprouting in vitro and angiogenesis in vivo. In CLI mice VCE-004.8 improved collateral vessel formation and induced endothelial cells proliferation, angiogenic gene expression and prevented fibrosis. The expression of B55α, Caveolin 1 and Sirtuin-1 is reduced in arteries from CLI mice and PAD patient, and the expression of these markers was restored in mice treated with VCE-004.8. Conclusions The findings presented in this study indicate that Etrinabdione holds promise in mitigating endothelial cell damage and senescence, while concurrently fostering arteriogenesis and angiogenesis. These observations position Etrinabdione as a compelling candidate for the treatment of PAD, and potentially other cardiovascular disorders.

Abstract Background The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ has afforded neuroprotection in experimental models of Parkinson’s disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties in a PD model that also involves protein dysregulation, other key event in PD pathogenesis. Methods To this end, an adeno-associated viral vector serotype 9 coding for a mutated form of the α-synuclein gene (AAV9-SynA53T) was unilaterally delivered in the substantia nigra pars compacta (SNpc) of mice. This model leads to motor impairment and progressive loss of tyrosine hydroxylase-labelled neurons in the SNpc. Results Oral administration of VCE-003.2 at 20 mg/kg for 14 days improved the performance of mice injected with AAV9-SynA53T in various motor tests, correlating with the preservation of tyrosine hydroxylase-labelled neurons in the SNpc. VCE-003.2 also reduced reactive microgliosis and astrogliosis in the SNpc. Furthermore, we conducted a transcriptomic analysis in the striatum of mice injected with AAV9-SynA53T and treated with either VCE-003.2 or vehicle, as well as control animals. This analysis aimed to identify gene families specifically altered by the pathology and/or VCE-003.2 treatment. Our data revealed pathology-induced changes in genes related to mitochondrial function, lysosomal cell pathways, immune responses, and lipid metabolism. In contrast, VCE-003.2 treatment predominantly affected the immune response through interferon signaling. Conclusion Our study broadens the neuroprotective potential of VCE-003.2, previously described against mitochondrial dysfunction, oxidative stress, glial reactivity and neuroinflammation in PD. We now demonstrate its efficacy against another key pathogenic event in PD as α-synuclein dysregulation. Furthermore, our investigation sheds light on the molecular mechanisms underlying VCE-003.2 revealing its role in regulating interferon signaling. These findings, together with a favorable ADMET profile, enhance the preclinical interest of VCE-003.2 towards its future clinical development in PD.

El seguimiento del punto de máxima potencia (MPPT) es una etapa esencial en la operación de las turbinas eólicas para garantizar una generación de energía eficiente. En los últimos años se han diseñado y aplicado técnicas de control avanzadas para lograr este objetivo, solventando algunas de las limitaciones de los métodos clásicos. Este artículo proporciona una visión general de las estrategias existentes y describe con más detalle algunas configuraciones de control específicas, explicando su utilidad y proporcionando una base para futuros desarrollos. En concreto incluye técnicas de control basadas en inteligencia artificial para el estudio del control MPPT en aerogeneradores. Se ejemplifican dos estrategias de control inteligente: una red neuronal y un controlador de lógica borrosa. Estos enfoques se enmarcan en la regulación del par electromagnético del generador y, en consecuencia, de la velocidad angular del sistema, mejorando la generación de potencia. Los resultados evidencian los beneficios de estos controladores inteligentes para maximizar la potencia y mejorar el proceso de conversión de energía.

BackgroundIntellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field.MethodsA Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them.DiscussionThe treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials.Trial registrationClinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

Este estudio aborda una comparación detallada de las habilidades y competencias requeridas para los ingenieros de sistemas y computación en Colombia y el resto de Latinoamérica. La investigación utiliza datos de 187 universidades, basados en el ranking del Laboratorio de Cibermetría del Consejo Superior de Investigaciones Científicas, para categorizar 16 competencias genéricas y 20 específicas que estos profesionales deben poseer. La comparación se lleva a cabo mediante Diagramas de Venn y análisis estadísticos de frecuencia y proporcionalidad, para identificar similitudes y diferencias entre los dos grupos regionales estudiados. Los hallazgos del estudio son críticos para entender las variaciones regionales en la preparación académica y las expectativas laborales de ingenieros en sistemas y computación. Este análisis comparativo resulta ser una herramienta valiosa tanto para empresas como para instituciones académicas en el proceso de toma de decisiones. Las empresas pueden usar esta información para identificar la idoneidad de candidatos, en función de competencias específicas, mientras que las universidades pueden adaptar sus currículos para satisfacer las demandas del mercado laboral y mejorar la calidad de la educación. En resumen, el estudio ofrece un panorama completo de las competencias esenciales de ingenieros de sistemas y computación en Colombia y Latinoamérica, permitiendo una toma de decisiones más informada y efectiva en el ámbito académico y empresarial.

Cu2ZnSnSe4 (CZTSe) nanoparticles (NPs) were successfully synthesized via a solvothermal method. Their structural, compositional, morphological, optoelectronic, and electrochemical properties have been characterized by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), Field-emission scanning electron microscopy (FE-SEM), transmission electron microscope (TEM), UV–vis absorption spectroscopy, and electrochemical impedance spectroscopy (EIS) techniques. Porosimetry and specific surface area in terms of the Brunauer–Emmett–Teller (BET) technique have also been studied. XRD indicates the formation of a polycrystalline kesterite CZTSe phase. Raman peaks at 173 and 190 cm−1 confirm the formation of a pure phase. TEM micrographs revealed the presence of nanoparticles with average sizes of ~90 nm. A BET surface area of 7 m2/g was determined. The CZTSe NPs showed a bandgap of 1.0 eV and a p-type semiconducting behavior. As a proof of concept, for the first time, the CZTSe NPs have been used as a visible-light-driven photocatalyst to Congo red (CR) azo dye degradation. The nanophotocatalyst material under simulated sunlight results in almost complete degradation (96%) of CR dye after 70 min, following a pseudo-second-order kinetic model (rate constant of 0.334 min−1). The prepared CZTSe was reusable and can be repeatedly used to remove CR dye from aqueous solutions.

En este artículo se pretende dar cuenta de un modelo de clasificación de estudiantes que se ha utilizado en la asignatura Programación I en Ingeniería de Sistemas y su relación con procesos de aprendizaje colaborativo y preferencias de pensamiento en los que se aplica una metodología para la resolución de problemas computacionales. La investigación utilizó un estudio de modelo de caso desde una perspectiva cualito – cuantitativa durante el I semestre en varios periodos académicos. Se concluyó que el modelo de enseñanza y aprendizaje aplicado se inscribe en el paradigma constructivista, con un modelo didáctico enfocado al aprendizaje colaborativo, que evidencia un camino más simple y efectivo para la asimilación, apropiación y aplicación de los conceptos básicos de programación.

Inclusive education is complex due to adapting the learning process to specific learning needs. Besides, some current national education models for inclusive education lack an agile, flexible, and collaborative methodology where all relevant participants, like parents, educators' instructors, and even information technology (IT) developers, can be involved. COVID-19 accelerated e-learning but established new challenges. This research method includes the test of a proposed scrum-agile learning methodology in an elementary education institute for three students with dyscalculia based on Scrum as an agile methodology proposed to adapt inclusive education processes. Among the benefits of the proposed methodology is the testing of the iterative design and application of an agile approach, quick adaptation, and formation of IT applications and contents. Also, the student's learning improvements were measured in this research experience, demonstrating that the proposed methodology supports inclusive education by improving collaborative interventions, flexible curriculum, attention to learning needs, IT integration, and instructor training. Thus, it can be argued that the proposed methodology can meet the new challenges of the evolution of inclusive education and national models, such as accelerated IT integration, collaborators' involvement, and specific students' attitudes and needs. This methodology can evolve to an 'agile and inclusive learning methodology'.

Este artículo de investigación presenta un enfoque integral para mejorar la enseñanza de la programación, específicamente en el lenguaje Arduino, dentro del contexto académico de la Universidad Tecnológica de Pereira (UTP). El estudio aborda dos componentes clave: una metodología de enseñanza centrada en la pedagogía activa y una herramienta de software educativo. La metodología propuesta permite a los educadores actuar como facilitadores que adaptan la enseñanza a las necesidades individuales de los estudiantes. El software, una aplicación web desarrollada con tecnologías estándar como html, css y JavaScript, se organiza en módulos que van desde fundamentos teóricos hasta proyectos prácticos. La efectividad de este enfoque se evaluó con encuestas de satisfacción y análisis de datos aplicadas a dos grupos de estudiantes de la Facultad de Ingenierías de la utp. Los resultados indican que la combinación de la metodología y el software resultó en un avance significativo en el desarrollo educativo y la satisfacción general de los estudiantes. Además, se notó un aumento en el interés de los estudiantes por participar activamente en el proceso de aprendizaje respaldado por la adopción de tecnologías de la información y comunicación (TIC). El artículo contribuye de manera sustancial al campo de la enseñanza de la programación. Ofrece estrategias pedagógicas y tecnológicas eficaces para un entorno académico real, y resalta la importancia de las tic y la pedagogía activa. Aspira a impulsar un cambio significativo en la calidad de la educación en programación a nivel superior.

El presente artículo analiza la evidencia empírica que aportan los estudios sobre la influencia de los factores dinámicos asociados a la reincidencia criminal de menores infractores dentro del contexto español y portugués. La búsqueda de los términos Juvenile delinquency* OR juvenile offenders* AND recidivism* OR Risk factors * se realizó en las bases de datos Scopus, ScienceDirect, Web of science, Dialnet, Scielo y ProQuest. Aplicados los criterios de inclusión y exclusión, de un total de 105 653 artículos, se seleccionaron 20 para análisis cualitativo y 3 para incluir en el metaanálisis. El estudio permite concluir que los factores dinámicos con mayor capacidad de predicción son la educación, la relación con el grupo de pares, el tiempo de ocio, la familia y el consumo de SPA.

Objetivo: El propósito de la investigación consiste en comparar, a partir de los datos tanto cuantitativos como cualitativos, el aporte de la estrategia STEAMRW al proceso de aprendizaje de la programación de computadores. Metodología: En el presente artículo se exponen los resultados obtenidos en dos cursos paralelos de programación a lo largo de tres años. En uno de ellos se adoptó la metodología STEAM con lectoescritura (RW) activa y constante, y en el otro se impartió el curso a partir de la metodología tradicional de enseñanza universitaria. Resultados: Según los hallazgos, la metodología STEAMRW le provee al estudiante una serie de competencias allende el simple conocimiento temático y que son determinantes para el desarrollo de su perfil profesional en el siglo XXI. Conclusiones: Se concluye que es muy conveniente que se capacite a los docentes ingenieros de programas de Ingeniería para que comprendan la dimensión de esta metodología, y las ventajas a las cuales pueden acceder desde la perspectiva del aprendizaje por parte de sus alumnos. Financiamiento: Proyecto de investigación sin financiación.

Cimicifuga racemosa extracts (CREs) have gained well-established use for the treatment of menopausal symptoms such as hot flushes and excessive sweating, and weight gain. While the clinical effects of CREs have been well documented, the mechanisms underlying these effects are largely unknown. More recently, the metabolic effects of the CRE Ze 450 were demonstrated in cultured cells in vitro and in mouse models of obesity in vivo. At the molecular level, metabolic regulation, enhanced insulin sensitivity, and increased glucose uptake were linked to the activation of AMP-activated protein kinase (AMPK). Therefore, we tested the effects of Ze 450 on AMPK phosphorylation and thus activation in cells from different tissues, i.e., murine C2C12 myoblast cells, human HEPG2 liver cells, mouse HT22 neuronal cells, and in murine 3T3L1 adipocytes. Using a FRET-based HTRF-assay, we found that Ze 450 induced AMPK phosphorylation and the activation of this key enzyme of metabolic regulation in cells from various different tissues including C2C12 (muscle), HEPG2 (liver), HT22 (hippocampal), and 3T3-L1 (adipocyte) cells. In C2C12 muscle cells, enhanced AMPK activation was accompanied by reduced mitochondrial respiration and enhanced glucose uptake. Further, Ze 450 enhanced the resilience of the cells against oxidative death induced by ferroptosis inducers erastin or RSL3. Our findings suggest a general effect of Cimicifuga racemosa on AMPK activation in different tissues and across species. This may have a significant impact on expanded therapeutic applications of Ze 450, since AMPK activation and the related metabolic effects have been previously associated with anti-aging effects and the prevention of the metabolic syndrome.

La presente investigación aborda la campaña permanente llevada a cabo durante una década por el Partido Demócrata de Georgia, Estados Unidos. Cómo lograron tras veinte años de mayoría republicana, convertir al Estado en un campo de batalla político y competitivo. Se realiza una exposición del razonamiento y análisis que se ha desarrollado con el fin de entender desde la planificación hasta su ejecución. La investigación emplea bibliografía, así como entrevistas a expertos y miembros del partido. Por último, se exponen los resultados que ha tenido, así como los futuros retos.

Introduction: Home hemodialysis (HDD) is implemented in the Valencian Community with a higher prevalence than to the rest of the national territory, with a prevalence of 13.4 patients pmp in December 2018. We carried out an assessment of the patients characteristics and the overall and technical survival in HDD depending on the historical moment of onset and its origin. Material and methods: We conducted a retrospective and descriptive study including patients of the Valencian Registry of Renal Patients from the beginning of data reported until December 2020. We calculated overall survival (combined event death-technical failure, censoring transplantation) and technical survival (event technical failure, censoring exitus and transplantation). Comparing technical survival according to the starting era: ancient (1976−2000) vs modern (2001−2020) and according to the modality of origin. We performed univariate and multivariate Cox regression in the total series for both overall and technical survival. Results: 236 patients on HDD (611.4 patient-years of follow-up), mean age 49.7 ± 16.3 years; median time of prior renal replacement therapy 0.2 years. The ratio of transplantation, death, and technical failure were 13.2, 4.4, and 7 events per 100 patient-years, respectively. In the comparison by ancient (n = 57) vs modern (n = 179) eras, age (37.5 vs 53.5 years), DM (3.5 vs 13.4%) and chronic tubuleinterstitial nephropathy (24.6 vs 8.9%) as a cause of chronic kidney disease were statistically significant. The probability of coming from outpatient consultation (33.3 vs 48.6%) and peritoneal dialysis (1.8 vs 12.8%) were higher in modern era with statistical significance. In the ancient era a single hospital centralized 57.9% of the patients, and in the modern era between two hospitals centralized 55.8% of the patients. Overall survival in the ancient era was 83.7% at 1 year, 77.4% at 2 years, and 61% at 5 years; and in the modern era 87.3% per year, 83% 2 years and 47.8% 5 years (Log Rank 0.521). Technical survival in the ancient era was 85.4% at 1 year, 79% 2 years, and 64.1% 5 years; and in the modern era 91.4% per year, 88.5% 2 years and 74.5% 5 years (Log Rank 0.195). There were no statistical differences in the comparison based on technical of provenance. In the Cox regression it was statistically significant for overall survival: the age and being diagnosed with heart disease, vascular disease or active neoplasia and for technical survival liver disease or social problem, both in univariate and multivariate. Conclusions: In the modern era there is a considerable increase in HDD patients in the Valencian Community. There was a center effect in the development of HDD programs, most of the patients depended on few healthcare centers. The patients were older and had greater comorbidity in the modern era, despite this without affecting the technical and overall survival of the HDD. Resumen: Introducción: La hemodiálisis (HD) domiciliaria (HDD) está especialmente implementada en la Comunidad Valenciana en comparación al resto del territorio nacional, con una prevalencia de 13,4 pacientes pmp a diciembre del 2018. Realizamos una valoración de las características de los pacientes y de la supervivencia global y técnica del paciente en HDD en función del momento histórico de inicio y de su procedencia. Material y métodos: Pacientes incluidos en el Registro de Enfermos Renales de la Comunidad Valenciana desde que se reportan datos al mismo hasta diciembre del 2020. Estudio descriptivo y retrospectivo, calculando supervivencia global (evento combinado muerte-fallo técnico, censurando trasplante) y supervivencia técnica (evento fallo técnico, censurando muerte y trasplante). Comparamos la supervivencia de la técnica en función de era de inicio: antigua (1976−2000) vs moderna (2001−2020), y en función de la modalidad de procedencia. Realizamos regresión de Cox uni y multivariante en el total de la serie tanto para supervivencia global como técnica. Resultados: 236 pacientes en HDD (611,4 pacientes-año de seguimiento), edad media 49,7 ± 16,3 años; tiempo terapia renal sustitutiva previa 0,2 años de mediana. Los ratios de trasplante, muerte y fallo técnico fueron 13,2; 4,4 y 7 eventos por 100 pacientes-año respectivamente. En la comparación por eras según inicio en HDD, antigua (n = 57) vs moderna (n = 179) fue estadísticamente significativo la edad (37,5 vs 53,5 años), la DM (3,5 vs 13,4%) y la nefropatía tubulointersiticial crónica (24,6 vs 8,9%) como causa de enfermedad renal crónica Hubo en la era moderna mayor probabilidad de provenir de consulta externa (33,3 vs 48,6%) y de diálisis peritoneal (1,8 vs 12,8%) con significación estadística. En era antigua un único hospital centralizaba el 57,9% de los pacientes, y en era moderna entre dos hospitales centralizaban el 55,8% de los pacientes. La supervivencia global en era antigua fue de 83,7% al año, 77,4% 2 años y 61% 5 años; y en era moderna 87,3% al año, 83% 2 años y 47,8% 5 años (Log Rank 0,521). La supervivencia técnica en era antigua fue 85,4% al año, 79% 2 años y 64,1% 5 años; y en era moderna 91,4% al año, 88,5% 2 años y 74,5% 5 años (Log Rank 0,195). No hubieron diferencias estadísticas en la comparación en función de la procedencia. En la regresión de Cox fue estadísticamente significativo para supervivencia global la edad y estar diagnosticado de cardiopatía, enfermedad vascular o neoplasia activa y para la supervivencia técnica hepatopatía o problema social, tanto en análisis uni como en multivariante. Conclusión: En la era moderna existe un incremento considerable de pacientes en HDD en la Comunidad Valenciana. Existió un efecto centro en el desarrollo de los programas de HDD, la mayoría de los pacientes dependían de pocos centros asistenciales. Los pacientes fueron de mayor edad y mayor comorbilidad en la era moderna, pese a ello sin afectar ni la supervivencia técnica y ni global de la HDD.

Resumen: Introducción: La hemodiálisis domiciliaria (HDD) está especialmente implementada en la Comunidad Valenciana en comparación con el resto del territorio nacional, con una prevalencia de 13,4 pacientes pmp a diciembre de 2018. Realizamos una valoración de las características de los pacientes y de la supervivencia global y técnica del paciente en HDD en función del momento histórico de inicio y de su procedencia. Material y métodos: Pacientes incluidos en el Registro de Enfermos Renales de la Comunidad Valenciana desde que se reportan datos al mismo hasta diciembre de 2020. Estudio descriptivo y retrospectivo, calculando supervivencia global (evento combinado muerte-fallo técnico, censurando trasplante) y supervivencia técnica (evento fallo técnico, censurando muerte y trasplante). Comparamos la supervivencia de la técnica en función de era de inicio: antigua (1976-2000) vs. moderna (2001-2020), y en función de la modalidad de procedencia. Realizamos regresión de Cox uni- y multivariante en el total de la serie tanto para supervivencia global como técnica. Resultados: Doscientos treinta y seis pacientes en HDD (611,4 pacientes-año de seguimiento), edad media 49,7 ±16,3 años; tiempo terapia renal sustitutiva previa 0,2 años de mediana. Los ratios de trasplante, muerte y fallo técnico fueron 13,2; 4,4 y 7 eventos por 100 pacientes-año respectivamente. En la comparación por eras según inicio en HDD, antigua (n = 57) vs. moderna (n = 179) fue estadísticamente significativa la edad (37,5 vs. 53,5 años), la DM (3,5 vs. 13,4%) y la nefropatía tubulointersiticial crónica (24,6 vs. 8,9%) como causa de enfermedad renal crónica. Hubo en la era moderna mayor probabilidad de provenir de consulta externa (33,3 vs. 48,6%) y de diálisis peritoneal (1,8 vs. 12,8%) con significación estadística. En era antigua un único hospital centralizaba el 57,9% de los pacientes, y en era moderna entre 2 hospitales centralizaban el 55,8% de los pacientes. La supervivencia global en era antigua fue del 83,7% al año, del 77,4% a 2 años y del 61% a 5 años; y en era moderna del 87,3% al año, del 83% a 2 años y del 47,8% a 5 años (Log Rank: 0,521). La supervivencia técnica en era antigua fue 85,4% al año, 79% a 2 años y 64,1% a 5 años; y en era moderna 91,4% al año, 88,5% a 2 años y 74,5% a 5 años (Log Rank: 0,195). No hubo diferencias estadísticas en la comparación en función de la procedencia. En la regresión de Cox fueron estadísticamente significativos para supervivencia global la edad y estar diagnosticado de cardiopatía, enfermedad vascular o neoplasia activa, y para la supervivencia técnica hepatopatía o problema social, tanto en análisis univariante como en multivariante. Conclusión: En la era moderna existe un incremento considerable de pacientes en HDD en la Comunidad Valenciana. Hubo un efecto centro en el desarrollo de los programas de HDD, la mayoría de los pacientes dependían de pocos centros asistenciales. Los pacientes fueron de mayor edad y mayor comorbilidad en la era moderna, pese a ello sin afectar ni la supervivencia técnica y ni global de la HDD. Abstract: Introduction: Home hemodialysis (HDD) is implemented in the Valencian Community with a higher prevalence than to the rest of the national territory, with a prevalence of 13.4 patients’ pmp in December 2018. We carried out an assessment of the patients’ characteristics and the overall and technical survival in HDD depending on the historical moment of onset and its origin. Material and methods: We conducted a retrospective and descriptive study including patients of the Valencian Registry of Renal Patients from the beginning of data reported until December 2020. We calculated overall survival (combined event death-technical failure, censoring transplantation) and technical survival (event technical failure, censoring exitus and transplantation). Comparing technical survival according to the starting era: ancient (1976–2000) vs modern (2001–2020) and according to the modality of origin. We performed univariate and multivariate Cox regression in the total series for both overall and technical survivals. Results: 236 patients on HDD (611.4 patient-years of follow-up), mean age 49.7 ± 16.3 years; median time of prior renal replacement therapy 0.2 years. The ratio of transplantation, death, and technical failure were 13.2, 4.4, and 7 events per 100 patient-years, respectively. In the comparison by ancient (n = 57) vs modern (n = 179) eras, age (37.5 vs 53.5 years), DM (3.5 vs 13.4%) and chronic tubuleinterstitial nephropathy (24.6 vs 8.9%) as a cause of chronic kidney disease were statistically significant. The probability of coming from outpatient consultation (33.3 vs 48.6%) and peritoneal dialysis (1.8 vs 12.8%) were higher in modern era with statistical significance. In the ancient era a single hospital centralized 57.9% of the patients, and in the modern era between two hospitals centralized 55.8% of the patients. Overall survival in the ancient era was 83.7% at 1 year, 77.4% at 2 years, and 61% at 5 years; and in the modern era 87.3% per year, 83% 2 years and 47.8% 5 years (Log Rank 0.521). Technical survival in the ancient era was 85.4% at 1 year, 79% 2 years, and 64.1% 5 years; and in the modern era 91.4% per year, 88.5% 2 years and 74.5% 5 years (Log Rank 0.195). There were no statistical differences in the comparison based on technical of provenance. In the Cox regression it was statistically significant for overall survival: the age and being diagnosed with heart disease, vascular disease or active neoplasia and for technical survival liver disease or social problem, both in univariate and multivariate. Conclusion: In the modern era there is a considerable increase in HDD patients in the Valencian Community. There was a center effect in the development of HDD programs, most of the patients depended on few healthcare centers. The patients were older and had greater comorbidity in the modern era, despite this without affecting the technical and overall survival of the HDD.

One of the main global causes of mortality and morbidity is traumatic brain injury (TBI). Neuroinflammation and brain-blood barrier (BBB) disruption play a pivotal role in the pathogenesis of acute and chronic TBI onset. The activation of the hypoxia pathway is a promising approach for CNS neurodegenerative diseases, including TBI. Herein, we have studied the efficacy of VCE-005.1, a betulinic acid hydroxamate, against acute neuroinflammation in vitro and on a TBI mouse model. The effect of VCE-005.1 on the HIF pathway in endothelial vascular cells was assessed by western blot, gene expression, in vitro angiogenesis, confocal analysis and MTT assays. In vivo angiogenesis was evaluated through a Matrigel plug model and a mouse model of TBI induced by a controlled cortical impact (CCI) was used to assess VCE-005.1 efficacy. VCE-005.1 stabilized HIF-1α through a mechanism that involved AMPK and stimulated the expression of HIF-dependent genes. VCE-005.1 protected vascular endothelial cells under prooxidant and pro-inflammatory conditions by enhancing TJ protein expression and induced angiogenesis both in vitro and in vivo. Furthermore, in CCI model, VCE-005.1 greatly improved locomotor coordination, increased neovascularization and preserved BBB integrity that paralleled with a large reduction of peripheral immune cells infiltration, recovering AMPK expression and reducing apoptosis in neuronal cells. Taken together, our results demonstrate that VCE-005.1 is a multitarget compound that shows anti-inflammatory and neuroprotective effects mainly by preventing BBB disruption and has the potential to be further developed pharmacologically in TBI and maybe other neurological conditions that concur with neuroinflammation and BBB disruption.

Bidens pilosa L., native to South America and commonly used for medicinal purposes, has been understudied at molecular and genomic levels and in its relationship with soil microorganisms. In this study, restriction site-associated DNA markers (RADseq) techniques were implemented to analyze genetic diversity and population structure, and metabarcoding to examine microbial composition in soils from Palmira, Sibundoy, and Bogotá, Colombia. A total of 2,984,123 loci and 3485 single nucleotide polymorphisms (SNPs) were identified, revealing a genetic variation of 12% between populations and 88% within individuals, and distributing the population into three main genetic groups, FST = 0.115 (p < 0.001) and FIT = 0.013 (p > 0.05). In the soil analysis, significant correlations were found between effective cation exchange capacity (ECEC) and apparent density, soil texture, and levels of Mg and Fe, as well as negative correlations between ECEC and Mg, and Mg, Fe, and Ca. Proteobacteria and Ascomycota emerged as the predominant bacterial and fungal phyla, respectively. Analyses of alpha, beta, and multifactorial diversity highlight the influence of ecological and environmental factors on these microbial communities, revealing specific patterns of clustering and association between bacteria and fungi in the studied locations.

Abstract Background Traumatic brain injury (TBI) is characterized by a primary mechanical injury and a secondary injury associated with neuroinflammation, blood–brain barrier (BBB) disruption and neurodegeneration. We have developed a novel cannabidiol aminoquinone derivative, VCE-004.8, which is a dual PPARγ/CB2 agonist that also activates the hypoxia inducible factor (HIF) pathway. VCE-004.8 shows potent antifibrotic, anti-inflammatory and neuroprotective activities and it is now in Phase II clinical trials for systemic sclerosis and multiple sclerosis. Herein, we investigated the mechanism of action of VCE-004.8 in the HIF pathway and explored its efficacy in a preclinical model of TBI. Methods Using a phosphoproteomic approach, we investigated the effects of VCE-004.8 on prolyl hydroxylase domain-containing protein 2 (PHD2) posttranslational modifications. The potential role of PP2A/B55α in HIF activation was analyzed using siRNA for B55α. To evaluate the angiogenic response to the treatment with VCE-004.8 we performed a Matrigel plug in vivo assay. Transendothelial electrical resistance (TEER) as well as vascular cell adhesion molecule 1 (VCAM), and zonula occludens 1 (ZO-1) tight junction protein expression were studied in brain microvascular endothelial cells. The efficacy of VCE-004.8 in vivo was evaluated in a controlled cortical impact (CCI) murine model of TBI. Results Herein we provide evidence that VCE-004.8 inhibits PHD2 Ser125 phosphorylation and activates HIF through a PP2A/B55α pathway. VCE-004.8 induces angiogenesis in vivo increasing the formation of functional vessel (CD31/α-SMA) and prevents in vitro blood–brain barrier (BBB) disruption ameliorating the loss of ZO-1 expression under proinflammatory conditions. In CCI model VCE-004.8 treatment ameliorates early motor deficits after TBI and attenuates cerebral edema preserving BBB integrity. Histopathological analysis revealed that VCE-004.8 treatment induces neovascularization in pericontusional area and prevented immune cell infiltration to the brain parenchyma. In addition, VCE-004.8 attenuates neuroinflammation and reduces neuronal death and apoptosis in the damaged area. Conclusions This study provides new insight about the mechanism of action of VCE-004.8 regulating the PP2A/B55α/PHD2/HIF pathway. Furthermore, we show the potential efficacy for TBI treatment by preventing BBB disruption, enhancing angiogenesis, and ameliorating neuroinflammation and neurodegeneration after brain injury.

Medicinal plants maintain structures and diversities of bacteria, fungi, and arbuscular mycorrhizal fungi (AMF) that can interact to promote growth and therapeutic properties. Therefore, the purpose of this research was to evaluate the microbiome of Lippia alba and Petiveria alliacea, species known for their high potential for medicinal benefits in Colombia. To achieve this, rhizosphere soils and roots were sampled from five departments in Colombia: Boyacá, Cundinamarca, Tolima, Putumayo, and Valle del Cauca. The results revealed that the dominant bacterial groups in both plants were primarily Proteobacteria, Acidobacteriota, and Actinobacteriota, with the first phylum showing the highest number of differentially abundant genera between the sampling points. In fungi, Ascomycota tended to dominate in most of the sampled locations, while Mortierellomycota was particularly abundant in roots of P. alliacea in Valle. Furthermore, the study of AMF indicated differentiation in the colonization for both plants, with the genera Glomus and Paraglomus being predominant. Differences in the Shannon diversity index were recorded between sampling types within these sampling points, possibly influenced by local and environmental factors. Our findings reveal that the microbiomes of both medicinal plants exhibit distinct community assemblies, which could be a significant factor for their future therapeutic use.

Objetivo: Analizar y establecer si existe relación entre la disposición estética de elementos en el tablero y su impacto en el aprendizaje de la programación de computadores. Metodología: Este estudio se realizó en paralelo entre dos grupos por semestre del año 2015 al 2018. Los elementos estéticos referidos en esta investigación se aplicaron en un grupo, y dichos elementos fueron removidos en el otro. La investigación es de carácter cualitativo, con un componente final cuantitativo. Resultados: Los resultados evidencian una relación directa entre el aprendizaje de la programación de computadores por parte de los estudiantes y la disposición estética a la que se refiere este artículo. Conclusiones: Se concluye que el conocimiento es más comprensible y significativo para el estudiante cuando está estéticamente distribuido con los recursos del aula, lo cual facilita la ubicación del conocimiento en la memoria a largo plazo. Financiamiento: Universidad Tecnológica de Pereira

Este artículo compara la metodología tradicional de enseñanza de la programación frente a la teoría del Conectivismo y su articulación con BBL (Brain-based Learning) en un curso inicial de programación de computadores en Ingeniería de Sistemas. Se procedió a trabajar con dos subgrupos de forma que en cada uno se aplicó una metodología diferente de evaluación para, posteriormente, compararlas en lo cuantitativo y en lo cualitativo, de manera que pudiera sugerirse qué metodología promueve mejor el aprendizaje de la programación. Los resultados demuestran una gran favorabilidad hacia la metodología de evaluación apoyada en Conectivismo debido a varios factores: la tecnología como lenguaje natural de los jóvenes de hoy, el océano de respuestas que Internet puede brindar y los elementos teóricos que constituyen las bases del Conectivismo como teoría de aprendizaje, así como la aplicación de BBL en un contexto evaluativo. Se concluye que es posible alcanzar la motivación requerida para un aprendizaje efectivo, duradero y sintonizado con los jóvenes de hoy a partir de las bondades que proporcionan ambas teorías.

Un gran reto que tienen los ingenieros docentes consiste en encontrar aplicaciones en donde la ingeniería específica sea solución a problemas de otras áreas de tal forma que se maximice su potencial conceptual e instrumental. Tal es el caso de la programación de computadores que, como parte de la ingeniería de sistemas, permite resolver problemas gracias a las grandes capacidades tecnológicas para aprovechar lo que el conocimiento humano ha desarrollado. En este artículo se presenta una solución algorítmica al problema de hallar números primos gemelos en un rango especificado por el usuario. Se acudió al paradigma de programación funcional y a conceptos como función, recursividad y ciclos de manera que facilitaron la resolución del problema. Desde esta perspectiva se obtuvieron resultados confiables que cumplen tanto con la definición de los números primos gemelos, como con los principios de eficiencia algorítmica. Se concluye que en la medida en que se puedan compartir con los estudiantes de programación aplicaciones que resuelvan problemas de otras áreas, se harán mucho más entendibles y aplicables conceptos propios de un paradigma y se podrá encontrar el sentido del aprovechamiento de la tecnología en favor del ser humano.

Cannabidiol (CBD) has been suggested as a potential therapy for inflammatory and fibrotic diseases. Cannabidiol was demonstrated to reduce alcohol-induced liver inflammation and steatosis but its specific activity on the fibrotic process was not investigated. Herein, the antifibrotic effects of cannabidiol in the skin were analysed in vitro using NIH-3T3 fibroblasts and human dermal fibroblasts and in vivo using the bleomycin-induced model of skin fibrosis. In a second model, non-alcoholic liver fibrosis was induced in mice by CCl4 exposure. Cannabidiol was administered daily, intraperitoneally in mice challenged with bleomycin and orally in CCl4 mice, and skin and liver fibrosis and inflammation were assessed by immunochemistry. Cannabidiol inhibited collagen gene transcription and synthesis and prevented TGFβ-and IL-4 induced fibroblast migration. In the bleomycin model, cannabidiol prevented skin fibrosis and collagen accumulation around skin blood vessels, and in the CCl4 model cannabidiol significantly attenuated liver fibrosis measured by picrosirius red and Tenascin C staining and reduced T cell and macrophage infiltration. Altogether, our data further support the rationale of the medicinal use of this cannabinoid, as well as cannabis preparations containing it, in the management of fibrotic diseases including Systemic Sclerosis and Non-Alcoholic Fatty Liver Disease.

(1) Background: A cannabigerol aminoquinone derivative, so-called VCE-003.2, has been found to behave as a neuroprotective agent (administered both i.p. and orally) in different experimental models of Parkinson’s disease (PD) in mice. These effects were exerted through mechanisms that involved the activation of a regulatory site within the peroxisome proliferator-activated receptor-γ (PPAR-γ). (2) Methods: We are now interested in comparing such neuroprotective potential of VCE-003.2, orally administered, with the effect of the classic dopaminergic replacement therapy with L-DOPA/benserazide in similar conditions, using 6-hydroxydopamine-lesioned mice. (3) Results: The oral administration of VCE-003.2 during 14 days at the dose of 20 mg/kg improved, as expected, the neurological status (measured in motor tests) in these mice. This correlated with a preservation of TH-labelled neurons in the substantia nigra. By contrast, the treatment with L-DOPA/benserazide (during 7 days at 2 mg/kg) was significantly less active in these experimental conditions, in concordance with their profile as a mere symptom-alleviating agent. (4) Conclusions: Our results confirmed again the therapeutic profile of VCE-003.2 in experimental PD and revealed a different and more relevant effect, as a disease modifier, compared to the classic symptom-alleviating L-DOPA treatment. This reinforces the interest in VCE-003.2 for a future clinical development in this disease.

(1) Background: Non-Hodgkin Lymphoma is a neoplasm that can significantly compromise the immune system, but timely assessment can change the patient outcome. In cancer, the activation of the immune system could lead to the secretion of autoantibodies. (2) Methods: A retrospective cohort study was performed from 2017 to 2019 in patients with Non-Hodgkin Lymphoma diagnosed with a biopsy. (3) Results: We included 39 patients who were newly diagnosed, untreated, and without any autoimmune disease previously reported. Thirty patients had the presence of autoantibodies (antiphospholipid antibodies, anti-cytoplasmic neutrophils antibodies, antinuclear antibodies), and nine were without autoantibodies. There were no statistical differences among groups regarding clinical, demographic, staging, and prognosis characteristics. Also, there were no differences in the outcomes of the patients after finishing chemotherapy and one year after initiating treatment. (4) Conclusions: Further investigations must be conducted regarding an extended panel of autoantibodies because the panel of autoantibodies in this study did not show a relationship between the presence and the clinical outcome of the patients.

The existence of the nucleus distinguishes prokaryotes and eukaryotes. Apart from containing most of the genetic material, the nucleus possesses several nuclear bodies composed of protein and RNA molecules. The nucleus is separated from the cytoplasm by a double membrane, regulating the trafficking of molecules in- and outwards. Here, we investigate the composition and function of the different plant nuclear bodies and molecular clues involved in nuclear trafficking. The behavior of the nucleolus, Cajal bodies, dicing bodies, nuclear speckles, cyclophilin-containing bodies, photobodies and DNA damage foci is analyzed in response to different abiotic stresses. Furthermore, we research the literature to collect the different protein localization signals that rule nucleocytoplasmic trafficking. These signals include the different types of nuclear localization signals (NLSs) for nuclear import, and the nuclear export signals (NESs) for nuclear export. In contrast to these unidirectional-movement signals, the existence of nucleocytoplasmic shuttling signals (NSSs) allows bidirectional movement through the nuclear envelope. Likewise, nucleolar signals are also described, which mainly include the nucleolar localization signals (NoLSs) controlling nucleolar import. In contrast, few examples of nucleolar export signals, called nucleoplasmic localization signals (NpLSs) or nucleolar export signals (NoESs), have been reported. The existence of consensus sequences for these localization signals led to the generation of prediction tools, allowing the detection of these signals from an amino acid sequence. Additionally, the effect of high temperatures as well as different post-translational modifications in nuclear and nucleolar import and export is discussed.

A hydrothermal method was successfully employed to synthesize kesterite Cu2ZnSnS4 (CZTS) nanoparticles. X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), and optical ultraviolet-visible (UV-vis) spectroscopy were used for characterization of structural, chemical, morphological, and optical properties. XRD results confirmed that a nanocrystalline CZTS phase corresponding to the kesterite structure was formed. Raman analysis confirmed the existence of single pure phase CZTS. XPS results revealed the oxidation states as Cu+, Zn2+, Sn4+, and S2−. FESEM and TEM micrograph images revealed the presence of nanoparticles with average sizes between 7 nm to 60 nm. The synthesized CZTS nanoparticles bandgap was found to be 1.5 eV which is optimal for solar photocatalytic degradation applications. The properties as a semiconductor material were evaluated through the Mott–Schottky analysis. The photocatalytic activity of CZTS has been investigated through photodegradation of Congo red azo dye solution under solar simulation light irradiation, proving to be an excellent photo-catalyst for CR where 90.2% degradation could be achieved in just 60 min. Furthermore, the prepared CZTS was reusable and can be repeatedly used to remove Congo red dye from aqueous solutions.

With the increasing negative impacts on worldwide food production caused by pests, the recovery of native entomopathogenic nematodes (EPNs) is relevant, since they are adapted to local environments, entomofauna, and significant virulence. Therefore, the present study was designed to recover and understand the phylogenetic diversity of EPNs and their associated bacterial endosymbionts, from banana and plantain crops, as alternatives for the control of weevil species. An extensive sampling of western Colombia covered 325 ha, yielding the recovery of three EPNs’ isolates (0.49% of the samples). The molecular characterization included four mitochondrial and nuclear loci, which, after merging with the sequences of 48 species, confirmed the presence of Steinernema carpocapsae, the first report of S. costaricense in South America, and monophyly in most of the Steinernema clades. The tree topologies were consistent for the nuclear loci but not for mitochondrial, probably due to the high nucleotide substitution rate, deficit in the number of species available for these loci, and incomplete lineage sorting. The endosymbiotic bacteria associated with S. carpocapsae were identified as Xenorhabdus nematophila. However, the S. costaricense bacterial symbiont presented a genetic similarity to X. koppenhoeferi and X. khoisanae, which are still uncertain in their classification. The identification of S. costaricense in South America indicates the wide range distribution of this species in the Americas and its ability to persist in different soil types. For the first time, EPN isolation and phylogenetic characterization are directed to plantain and banana crops. Leveraging EPNs’ diversity promises novel applications for crop protection, while the genetic resources from the bacterial endosymbionts may provide metabolites with a wide spectrum of uses, either for agricultural or medicinal purposes.

Soils play important roles in the proper functioning of agroecosystems. Using molecular characterization methods such as metabarcoding, soils from eight farms (57 samples) belonging to three production system types—agroecological (two farms with twenty-two sampling points), organic (three farms with twenty-one sampling points), and conventional (three farms with fourteen sampling points)—were compared from the rural villages of El Arenillo and El Mesón in Palmira, Colombia. Amplification and sequencing of the hypervariable V4 region of the 16S rRNA gene was performed using next-generation sequencing (Illumina MiSeq) to estimate the bacterial composition and the alpha and beta diversity present. Across all soil samples, we found 2 domains (Archaea and Bacteria), 56 phylum, 190 classes, 386 orders, 632 families, and 1101 genera to be present. The most abundant phyla in the three systems were Proteobacteria, (agroecological 28%, organic 30%, and conventional 27%), Acidobacteria (agroecological 22%, organic 21%, and conventional 24%), and Verrucomicrobia (agroecological 10%, organic 6%, and conventional 13%). We found 41 nitrogen-fixing and phosphate-dissolving genera which promote growth and pathogens. Alpha and beta diversity indices were very similar across the three agricultural production systems, as reflected by shared amplicon sequence variants (ASVs) among them, likely due to the proximity of the sampling sites and recent management changes.

Research on the plant growth promoting microorganisms (PGPM) is increasing strongly due to the biotechnological potential for the agricultural, forestry, and food industry. The benefits of using PGPM in crop production are well proven; however, their incorporation in agricultural management is still limited. Therefore, we wanted to explore the gaps and challenges for the transfer of biotechnological innovations based on PGPM to the agricultural sector. Our systematic review of the state of the art of PGPM research and knowledge transfer takes Chile as an example. Several transfer limiting aspects are identified and discussed. Our two main conclusions are: neither academia nor industry can meet unfounded expectations during technology transfer, but mutually clarifying their needs, capabilities, and limitations is the starting point for successful collaborations; the generation of a collaborative innovation environment, where academia as well as public and private stakeholders (including the local community) take part, is crucial to enhance the acceptance and integration of PGPM on the way to sustainable agriculture.

El presente artículo tiene como finalidad efectuar un análisis de los criterios jurisprudenciales de la Corte Suprema en lo relativo a la no renovación de los empleos a contrata, para lo cual se considerará los precedentes a contar del año 2015 hasta el 2019, procediendo a evidenciar las falencias y cambios en el ejercicio interpretativo de la judicatura ante las acciones constitucionales de protección ejercidos por parte del personal de los empleos a contrata. Para ello se tendrá en especial consideración la relevancia del principio de confianza legitima y la relación de los criterios adoptados con el principio de eficiencia en contraposición a un ejercicio profundo de razonamiento exigido en cada caso concreto.

Radiosondes are the most widely used method for studies of vertical atmospheric behavior, but the high costs associated, and the logistic limitations have forced researchers to look for alternative methods for atmospheric profiling, such as lidar and satellite measurements, or modeling. However, the assessment of the accuracy of alternative methods is recommended, especially in complex terrain, such as the tropical Andes. In this research, the atmospheric profiling of satellite data from AIRS and MODIS products, simulations of the Weather Research and Forecasting model, WRF, and drone measurements are evaluated for a campaign of 10 radio soundings, between August 2021 and January 2022. Additionally, the capability to capture the planetary boundary layer height, hPBL, is studied. The measurements were conducted at Izobamba station near Quito, Ecuador. Temperature, T, Dew Point Temperature, TD, Mixing Ratio, Q, and Potential Temperature, PT, were evaluated from 0 to 300 m above ground level (magl.) for satellite, WRF, and drone data, and from 0 km to 15 km for satellite and WRF data. Additionally, the capability to capture the planetary boundary layer height, HPBL, was assessed. The results show that drone profiles best represented the magnitude of the analyzed variables showing mean RMSE of 0.79 for T, but the noise of the measurements caused a low correlation with radio sounding profiles, which was partially corrected with a quadratic fit on the profile. The WRF results achieved a positive representation in terms of correlation, but error metrics show that there are remarkable differences in magnitude in the first 300 magl., up to the tropopause height, which surpasses satellite representations for all variables. The MODIS profiles do not generally perform well due to their low vertical resolution and limitations with cloud coverage. However, AIRS data, despite its low resolution, show a better representation of vertical profiles than MODIS, for T and TD, surpassing WRF simulations in some dates. For the HPBL, the WRF results show that physical and atmospheric conditions limit its determination, and the methods and conditioning factors should be further analyzed.

Bushy matgrass (Lippia alba, Verbenaceae) is a promising plant genetic resource, by their active compounds. The present document studied the molecular genetic diversity and spatial genetic structure of two contrasting populations of L. alba in Colombia. Eight RAM, evaluated total DNA of 59 accessions of non-cultivated plants collected in two Colombia regions, Chicamocha and Sumapaz. The expected average heterozygosity (or average heterozygosity genetic diversity of Nei) for the sample had low value (0.0≤He=0.2467≤0.5). The values of molecular diversity (MD) indicated values in the range of 0.1219 to 0.3425 for seven RAM. The frequency of variants is based on an effective number of alleles [Ae] and expected heterozygosity [He], genetic diversity by locus (hj=1-p2-q2) had maximum values (near 0.5) in the primers ACA, AG, CGA, and CEC. RAM suitably analyzed Lippia alba as an endemic genetic resource. A DNA bank composed of 59 Colombian accessions from Lippia alba was set up. The analysis of the spatial global structure shows that the subpopulation Sumapaz is structured, whilst the subpopulation Chicamocha, is in the structuring process. The results suggest in all cases the need for implementing: a) exchange of gene-seed, (b) gene banks with maximum genetic variability and c) induce genetic diversity.

This study reports CdTe quantum dots synthesis in an aqueous medium using cadmium chloride and sodium tellurite as precursors and sodium borohydride and mercaptosuccinic acid as reducing and capping agents, respectively. The synthesis process was optimized through experimental design, and particle characterization was carried out by UV-Vis spectroscopy and molecular fluorescence. In the first stage, a factorial design was used to establish the significance of each of the synthesis variables; i.e., the temperature, pH, reaction time and precursor molar ratios. In the second stage, a multivariate design was constructed to relate the synthesis variables with the maximum absorbance wavelengths, which allowed for predictions of the diameters of the CdTe quantum dots, which were compared with direct measurements of the particles analyzed by high-resolution transmission electron microscopy, HR-TEM and X-ray diffraction, XRD. Finally, there is a brief discussion regarding the existing models predicting particle sizes. Keywords: Experimental design, Quantum dots, Cadmium telluride, Synthesis and characterization

Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment. We aimed to study in an IVH model in immature rats the neuroprotective effect of betulinic acid hydroxamate (BAH), a B55α/PP2A activator that inhibits the activity of the hypoxia-inducing factor prolyl-hydroxylase type 2. IVH was induced in 1-day-old (P1) Wistar rats by the left periventricular injection of Clostridial collagenase. Then, pups received i.p. vehicle or BAH 3 mg/kg single dose. At P6, P14 and P45, brain damage (area of damage, neurobehavioral deficits, Lactate/N-acetylaspartate ratio), white matter injury (WMI: corpus callosum atrophy and myelin basic protein signal reduction) and inflammation (TLR4, NF-κB and TNFα expression), excitotoxicity (Glutamate/N-acetylspartate) and oxidative stress (protein nitrosylation) were evaluated. BAH treatment did not reduce the volume of brain damage, but it did reduce perilesional tissue damage, preventing an IVH-induced increase in Lac/NAA. BAH restored neurobehavioral performance at P45 preventing WMI. BAH prevented an IVH-induced increase in inflammation, excitotoxicity and oxidative stress. In conclusion, in immature rats, BAH reduced IVH-induced brain damage and prevented its long-term functional consequences, preserving normal myelination in a manner related to the modulation of inflammation, excitotoxicity and oxidative stress.

An emerging number of studies address the involvement of neuroinflammation and oxidative stress in the pathophysiology of central nervous system (CNS) disorders such as depression, schizophrenia, anxiety, and neurodegenerative diseases. Different cytokines and molecules, such as prostaglandin (PG) E2, are associated with neuroinflammatory processes. The active acetaminophen metabolite AM404 has been shown to prevent inflammation and neuroinflammation in primary microglia and organotypic hippocampal slice cultures. However, its effects on pathophysiological conditions in the CNS and especially on neurons are still poorly understood. In this study, we therefore evaluated the effects of AM404 and acetaminophen on the arachidonic acid cascade and oxidative stress induced by interleukin (IL)-1β in human SK-N-SH neuronal cells. We observed that AM404 and acetaminophen significantly and concentration-dependent inhibited IL-1β-induced release of PGE2, independent of cyclooxygenases (COX)-1 and COX-2 enzymatic activity as well as COX-2 mRNA and protein levels in SK-N-SH-cells. The reduction of IL-1β-induced PGE2-release by AM404 and acetaminophen treatment might be mediated by the 8-iso-PGF2α pathway since IL-1β-induced synthesis of this free radical marker is dose-dependently reduced by both compounds, respectively. Therefore, understanding of the potential therapeutic properties of AM404 in neuroinflammation and oxidative stress might lead to future treatment options of different neurological disorders.

Some cannabinoids showed anti-inflammatory and antifibrotic activities. EHP-101 is an oral lipidic formulation of the novel non-psychotropic cannabidiol aminoquinone VCE-004.8, which showed antifibrotic activity in murine models of systemic sclerosis induced by bleomycin. We herein examined the effect of EHP-101 on cardiac and other organ fibrosis in a mouse model induced by Angiotensin II. VCE-004.8 inhibited TGFβ- and Ang II-induced myofibroblast differentiation in cardiac fibroblasts detected by α-SMA expression. VCE-004.8 also inhibited Ang II-induced ERK 1 + 2 phosphorylation, NFAT activation and mRNA expression of IL1β, IL6, Col1A2 and CCL2 in cardiac fibroblasts. Mice infused with Ang II resulted in collagen accumulation in left ventricle, aortic, dermal, renal and pulmonary tissues; oral administration of EHP-101, Ajulemic acid and Losartan improved these phenotypes. In myocardial tissue, Ang II induced infiltration of T cells and macrophages together with the accumulation of collagen and Tenascin C; those were all reduced by either EHP-101 or Losartan treatment. Cardiac tissue RNA-Seq analyses revealed a similar transcriptomic signature for both treatments for inflammatory and fibrotic pathways. However, the gene set enrichment analysis comparing data from EHP-101 vs Losartan showed specific hallmarks modified only by EHP-101. Specifically, EHP-101 inhibited the expression of genes such as CDK1, TOP2A and MKi67 that are regulated to the E2 factor family of transcription factors. This study suggests that the oral administration of EHP-101 prevents and inhibits cardiac inflammation and fibrosis. Furthermore, EHP-101 inhibits renal, pulmonary and dermal fibrosis. EHP-101 could offer new opportunities in the treatment of cardiac fibrosis and other fibrotic diseases.

Fosfomycin is currently a viable option against urinary tract infections, particularly against extended-spectrum β-lactamases (ESBL)-producing E. coli, due to its unique mechanism of action and its low resistance among bacteria. The objective of this study was to investigate two of the three most common mechanisms of resistance against this antibiotic among 350 ESBL-producing E. coli strains isolated from the urine of Mexican patients. The prevalence of fosfomycin resistance in our study was 10.9% (38/350). Of all resistant isolates analyzed, 23 (60.5%) were identified as fos-producing organisms, with 14 strains carrying fosA3 and 9, fosA1. Additionally, 11 (28.9%) fosfomycin-resistant isolates presented resistance due to impaired antibiotic transport and 8 (21.0%) both mechanisms. No resistance mechanism investigated in the study was found on 12 strains. All 38 confirmed ESBL-producing isolates carried a blaCTX-M subtype, 36 (94.5%) belonged to the O25b-ST131 clone, and all of them were able to transfer the fosfomycin resistance trait to recipient strains horizontally. This is the first study in Mexico demonstrating a plasmid-mediated fosfomycin resistance mechanism among clinical E. coli strains. Since our results suggest a strong association among fos and blaCTX-M genes and ST131 clones in uropathogenic E. coli, plasmid-mediated fosfomycin resistance should be closely monitored.

In the present work, a control strategy for Maximum Power Point Tracking (MPPT) of a wind turbine based on a Doubly Fed Induction Generator (DFIG) is described. This strategy is developed according to the theory of Di-rect Speed Control (DSC) which includes a state observer. This strategy con-siders the Low Shaft Speed (LSS) as an input and the Iqr reference current as the output. This control mechanism allows monitoring the MPPT; thus, changing the Power coefficient (Cp) to its optimal value during the operation of the wind turbine. The controller, among its main features, is configured to work with the incorporation of different wind inputs; fact that permits evaluating the system response to disturbances and variations. For simulations tests, a 1,5 MW wind turbine has been modeled in Matlab and Fatigue, Aero-dynamics, and Structures and Turbulence FAST software. The strategy has been compared to a PI MPPT controller and has demonstrated improvements in terms of speed and output power extraction.

Esta investigación propone una metodología de control aplicada a una técnica en Sistemas de Generación de Energía Eólica (WEGS) para el Seguimiento del Punto de Máxima Potencia (MPPT) basada en un observador Fuzzy y complementada con un controlador PI mediante el método de Control Directo de Velocidad (DSC). Este enfoque permite controlar la corriente de referencia del lado del rotor a través de las variaciones de par y potencia eléctrica en un modelo de Generador de Inducción Doblemente Alimentado (DFIG). En consecuencia, la velocidad del generador se controla para obtener una respuesta rápida del máximo Coeficiente de Potencia (). La construcción de esta estrategia comienza con mediciones directas de las variables eléctricas y mecánicas utilizando herramientas computacionales como FAST y Matlab-Simulink para las simulaciones del modelo del aerogenerador. Esta estrategia DSC presenta un rápido desempeño en el seguimiento del considerando la dinámica de un aerogenerador de 1,5MW; esta estrategia ha sido comparada con un controlador PI tradicional mejorando la extracción de la potencia de salida.

Resumen: Objetivo: Conocer mejor las variables clínicas, funcionales y analíticas que se asocian al síndrome confusional agudo (SCA) en urgencias y la evolución de las mismas con el fin de obtener una mejora en el abordaje terapéutico del paciente anciano previniendo así la morbimortalidad en este tipo de pacientes. Diseño: Se trata de un estudio descriptivo prospectivo de SCA en urgencias. Emplazamiento: Hospital General Universitario de Ciudad Real. Participantes: Se incluyó, en el intervalo de las 24 h siguientes al ingreso en el Servicio de Geriatría, a todos los pacientes procedentes del Servicio de Urgencias con diagnóstico de SCA. Mediciones principales: Se realizó un análisis de las variables del conjunto de datos (variables sociodemográficas y clínicas), calculando tablas de frecuencias para variables de tipo cualitativo y estadísticos descriptivos para las variables cuantitativas. Posteriormente, se han empleado técnicas de inferencia estadística. Resultados: El antecedente médico más frecuente fueron la enfermedad neurológica y la HTA, seguida de las enfermedades reumatológicas. Los motivos de consulta principales fueron el deterioro del estado general, la disnea, la disminución del nivel de consciencia y la fiebre. Se debe destacar la incidencia de la polifarmacia, especialmente de fármacos como los diuréticos, benzodiacepinas o hipnóticos. En relación con la etiología principal, destaca el papel de las infecciones de tipo urinario y respiratorio. Conclusiones: Se destaca el papel fundamental de las enfermedades neurológicas (especialmente la demencia), la HTA, la polifarmacia (uso inadecuado de benzodiacepinas e hipnóticos) y las infecciones urinarias y respiratorias como factores tratables o prevenibles del delirium en el paciente de Atención Primaria en nuestro medio. Abstract: Objective: To better understand the clinical, functional and analytical variables associated with delirium in emergencies and their evolution in order to obtain an improvement in the therapeutic approach of the elderly patient, thus preventing morbidity and mortality in this type of patient. Design: This is a prospective descriptive study of acute confusional syndrome in the emergency department. Site: General University Hospital of Ciudad Real. Participants: All patients from the emergency department with a diagnosis of delirium were included in the 24-h interval following admission to the geriatric service. Main measurements: An analysis of the variables of the data set (sociodemographic and clinical variables) was performed, calculating frequency tables for qualitative variables and descriptive statistics for quantitative variables. Subsequently, statistical inference techniques have been used. Results: The most frequent medical antecedent were neurological pathology and hypertension, followed by rheumatologic diseases. The main reasons for consultation were deterioration in general condition, dyspnea, decreased level of consciousness, and fever. Highlight the incidence of polypharmacy, especially drugs such as diuretics, benzodiazepines or hypnotics. In relation to the main etiology, the role of urinary and respiratory infections is noteworthy. Conclusions: Highlight the fundamental role of neurological diseases (especially dementia), hypertension, polypharmacy (inappropriate use of benzodiazepines and hypnotics) and urinary and respiratory infections as treatable and/or preventable factors of delirium in Primary Care patients in our setting.

The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and anti-diabetic agents provided a rationale to investigate the dimerization of the substituted salicylate Δ9-tetrahydrocannabinolic acid (THCA-A, 3a) as a strategy to solve its instability to decarboxylation and to generate analogues and/or pro-drugs of this native pre-cannabinoid. Activation of the carboxylic group with the DCC-HOBt-DMAP protocol afforded a high yield of the OBt ester 4, that was next converted into the highly crystalline di-depsidic dimer 5 upon treatment with DMAP. The mono-depsidic dimer 6 was also formed when the reaction was carried out with partially decarboxylated THCA-A samples. The structure of the depsidic dimers was established by spectroscopic methods and by aminolysis of 5 into the pre-cannabinoid amide 7. Both dimers showed excellent shelf stability and did not generate significant amounts of Δ9-THC upon heating. However, only the didepsidic dimer 5 activated PPAR-γ, the major target of pre-cannabinoids, but strong binding to serum proteins abolished this activity, also shielding it from the action of esterases. Key words: Phytocannabinoids, Dimerization, Δ9-Tetrahydrocannabinolic acid A, Δ9-Tetrahydrocannabinol, PPAR-γ