Educación híbrida: desafíos de los modelos educativos universitarios

The health emergency as a result of COVID19 evidenced the need to rethink higher education, the new normal generated challenges for educational actors, and it was necessary to evaluate the Educational Models (EM) of universities. The objective of the research was to analyze ME of two universities in the city of Cusco and identify opportunities for improvement towards a hybrid education. The EM of the National University of San Antonio Abad of Cusco (UNSAAC) and the EM of the Andean University of Cusco (UAC) were reviewed. The type of research was descriptive, explanatory and non-experimental design. The results present the characterization of the EM, their diagnosis, evaluation and relevance, considering opportunities for improvement, likewise, guiding principles, macro features and specific features of the educational evaluator that could contribute to restructuring them were identified. It was concluded that the EMs evaluated are outdated, therefore, inadequate to face post-pandemic challenges, they merit changes, not only due to the current situation, but also due to the emergence of new educational demands. The recommendations as opportunities for improvement of the ME could contribute, strengthen and contribute to the educational quality of the university, making it more functional, competent and sustainable over time.La emergencia sanitaria a consecuencia del COVID19 evidenció la necesidad de repensar la educación superior, la nueva normalidad generó retos para los actores educativos, y fue necesario evaluar a los Modelos Educativos (ME) de universidades. El objetivo de la investigación fue analizar ME de dos universidades de la ciudad del Cusco e identificar oportunidades de mejora hacia una educación híbrida. Se revisaron los ME de la Universidad Nacional de San Antonio Abad del Cusco (UNSAAC) y el ME de la Universidad Andina del Cusco (UAC). El tipo de investigación fue descriptivo, explicativo y diseño no experimental. Los resultados presentan la caracterización de los ME, su diagnóstico, evaluación y pertinencia, planteándose oportunidades de mejora, asimismo, se identificaron principios rectores, macro rasgos y rasgos específicos del evaluador educativo que podría contribuir a reestructurar los mismos. Se concluyó que los ME evaluados están desfasados, por tanto, inadecuados para enfrentar desafíos pospandemia, ameritan cambios, no solo por la coyuntura, sino por el surgimiento de nuevas demandas educativas. Las recomendaciones como oportunidades de mejora de los ME podrían contribuir, afianzar y coadyuvar a la calidad educativa de la universidad, haciéndola más funcional, competente y sostenible en el tiempo

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Novel Tools to Study Modulation of Adenylyl Cyclase Isoforms

Adenylyl cyclases (AC) are a major component of the cAMP signaling pathway. The differential regulatory properties and tissue expression patterns of the nine transmembrane AC isoforms provide unique mechanisms to regulate cAMP signaling in a precise and organized manner. However, the understanding of the individual roles of AC isoforms in the overall cellular response presents considerable challenges due to the expression of multiple AC isoforms in cells, and the lack of available tools to accurately detect isoform-specific AC expression or selectively modulate its catalytic activity. For these reasons, the research aims of this study were to develop a series of tools to characterize isoform-specific AC responses. In the first approach, a cell line with low cAMP levels in response to drug-stimulated conditions was developed by disrupting the expression of two of the most abundant ACs (i.e. AC3 and AC6) expressed in HEK293 cells using the CRISPR-Cas9 gene editing technology. Our HEK-ACΔ3/6 cell line displayed a substantially reduced cAMP response to forskolin (less than 95%) and to endogenous Gαs-coupled receptors, β2AR and EP 2R (75% and 85% reduction respectively), compared to the cAMP responses of the parental HEK293 cells. Characterization of the cAMP responses of the nine membrane-bound AC isoforms to stimulatory and inhibitory paradigms in the HEK-ACΔ3/6 knockout cell line indicated that the regulatory properties of the AC isoforms previously reported in the literature were recapitulated. Furthermore, a comparison of the cAMP responses of a series of AC1 mutants demonstrated that the HEK-ACΔ3/6 cell line provided an enhanced signal window over the parental HEK293 cells to characterize AC constructs with reduced catalytic activity. A second approach to better understand the individual role of AC isoforms in biological responses is by exploiting isoform-specific interactions with AC regulators to modulate AC activity. Thus, it was also determined in these studies that juxtamembrane domains derived from AC2 could modulate Gβγ-mediated AC activity. Based on the high degree of sequence homology between the juxtamembrane region of the C2a domain of Gβγ-stimulated cyclases, AC2, AC4, and AC7, together with surface plasmon resonance analysis with a C2a derived peptide (C2–20), it was demonstrated that Gβγ subunits bind with high affinity to this C2a juxtamembrane region. In addition, a minigene expressing the C2-20 peptide downstream of a membrane-anchoring domain, CD8, abolished Gβγ-mediated potentiation of PMA-stimulated AC2 activity. Mutagenesis studies indicated that several residues towards the middle of the sequence of the C2–20 peptide mediated the inhibitory activity on Gβγ-signaling, and the inhibitory effects of the minigene appeared to be selective for Gβγ-mediated stimulation of AC2. In the last approach to study isoform-specific AC responses, a series of structure activity relationship (SAR) studies were carried out towards the development of potent and selective AC1 and AC8 inhibitors. Initial SAR studies included analogs of the selective AC1 inhibitor, ST034307, that revealed a structure relationship between AC1 and AC8 selective inhibition. Furthermore, two new scaffolds were identified from a 10,000-compound screening campaign from the Life Chemicals compound collection, that showed dual inhibitory activity of calcium-stimulated AC1 and AC8 activity or selective inhibition of AC1 activity with sub-micromolar potency. Preliminary SAR analysis of various analogs of the dual AC1/AC8 inhibitory scaffold led to analogs with differential selectivity profiles for AC1 and AC8 and improved potency on both Ca2+/calmodulin-stimulated AC isoforms. In conclusion, throughout this work, a cellular model, a peptide/minigene, and a series of inhibitor scaffolds were developed as cellular and pharmacological tools to facilitate the study of the individual responses and respective roles of AC isoforms in cellular signaling

Costos Y Presupuestos-CM28-201502

Curso general en la carrera de Comunicación y Marketing de carácter teórico-práctico dirigido a los estudiantes de cuarto ciclo que busca desarrollar la competencia general de Razonamiento Cuantitativo y la competencia específica de Gestión Comercial y de Marketing.El curso de Costos y Presupuestos brinda al estudiante las herramientas necesarias para entender el comportamiento de los costos e interpretar el lenguaje de los mismos con el fin de contribuir en la gestión de la empresa resaltando la importancia del planeamiento y control a través de la elaboración de presupuestos

Costos Y Presupuestos-CM28-201601

Curso general en la carrera de Comunicación y Marketing de carácter teórico-práctico dirigido a los estudiantes de cuarto ciclo que busca desarrollar la competencia general de razonamiento cuantitativo y la competencia específica de gestión comercial y de marketing.El curso de Costos y Presupuestos brinda al estudiante las herramientas necesarias para entender el comportamiento de los costos e interpretar el lenguaje de los mismos con el fin de contribuir en la gestión de la empresa resaltando la importancia del planeamiento y control a través de la elaboración de presupuestos

Sistemas Avanzados De Costeo-CA05-201702

Curso de especialidad en la carrera de Contabilidad y Administración de carácter teórico-práctico dirigido a los estudiantes de quinto ciclo que busca desarrollar la competencia específica de implementación de soluciones integrales.Según Charles T. Horngren: ¿El estudio de la contabilidad de costos es una de las mejores inversiones de negocios que puede realizar un estudiante. ¿Por qué? Porque el éxito en cualquier organización (desde la pequeña tienda de la esquina hasta la mayor corporación multinacional) requiere l uso de los conceptos y las prácticas de la contabilidad de costos la cual proporciona datos clave a los gerentes para la planeación y el control así como para el costeo de productos servicios e incluso clientes.En este sentido en el curso de sistemas avanzados de costeo se desarrollaran los conceptos de costos en el contexto de una empresa industrial donde el estudiante podrá aplicar los conceptos de asignación de costos ejemplificará los conceptos de desperdicio reproceso y desecho aplicará los conceptos de costeo estándar y analizará los conceptos de toma de decisiones

Optimization of a Pyrimidinone Series for Selective Inhibition of Ca2+/Calmodulin-Stimulated Adenylyl Cyclase 1 Activity for the Treatment of Chronic Pain

Adenylyl cyclase type 1 is an emerging target for the treatment of chronic pain that is downstream on the analgesic pathway from the traditional µ-opioid receptor. AC1 is expressed in the central nervous system and critical for signaling in pain sensitization. Behavioral studies have revealed AC1 knockout mice exhibit reduced behavioral pain sensitization responses similar to morphine administration. AC1, and a closely related isoform AC8, are also implicated to have a role in learning and memory signaling processes. However, reports suggest selectively targeting AC1 over AC8 may be a viable strategy to eliminate potential deleterious effects on learning and memory. Our team has carried out cellular screening for inhibitors of AC1 that yielded a pyrazolyl-pyrimidinone scaffold with potency comparable to previously published AC1 inhibitors, selectivity versus AC8, and improved drug-like physicochemical properties. Structure-activity relationship (SAR) studies produced 36 analogs that balanced improvements in potency with cellular IC50 values as low as 0.25 µM and selectivity versus AC8. Prioritized analogs were selective for AC1 compared to other AC isoforms and other common neurological targets. A representative analog was assessed for efficacy in a mouse model of inflammatory pain and displayed modest anti-allodynic effects. This series of compounds represents the most potent and selective inhibitors of Ca2+/Calmodulin-stimulated AC1 activity to date with reduced off-target liabilities and improved drug-like physicochemical properties making them promising lead compounds for the treatment of inflammatory pain

Optimization of a 1,3,4-oxadiazole series for inhibition of Ca; 2+; /calmodulin-stimulated activity of adenylyl cyclases 1 and 8 for the treatment of chronic pain

Adenylyl cyclases type 1 (AC1) and 8 (AC8) are group 1 transmembrane adenylyl cyclases (AC) that are stimulated by Ca; 2+; /calmodulin. Studies have shown that mice depleted of AC1 have attenuated inflammatory pain response, while AC1/AC8 double-knockout mice display both attenuated pain response and opioid dependence. Thus, AC1 has emerged as a promising new target for treating chronic pain and opioid abuse. We discovered that the 1,3,4-oxadiazole scaffold inhibits Ca; 2+; /calmodulin-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in cells stably expressing either AC1 or AC8. We then carried out structure-activity relationship studies, in which we designed and synthesized 65 analogs, to modulate potency and selectivity versus each AC isoform in cells. Furthermore, molecular docking of the analogs into an AC1 homology model suggests the molecules may bind at the ATP binding site. Finally, a prioritized analog was tested in a mouse model of inflammatory pain and exhibited modest analgesic properties. In summary, our data indicate the 1,3,4-oxadiazoles represent a novel scaffold for the cellular inhibition of Ca; 2+; /calmodulin-stimulated AC1- and AC8 cAMP and warrant further exploration as potential lead compounds for the treatment of chronic inflammatory pain