Los Receptores con Silenciador Beta2-Adrenérgicos, reducen la presión intraocular: Un nuevo acercamiento a la terapia del Glaucoma

oai:ojs.pkp.sfu.ca:article/1233The search for new treatments for ocular hypertension and glaucoma, due to the side effects commercial products present, is inviting to look for new strategies apart from the available ones. In this sense the interference RNA technique (RNAi), also known as siRNA to selectively silence beta 2 adrenergic receptors has been investigated. In this sense it has been obtained a reduction in intraocular pressure (IOP), the main factor triggering glaucoma, of 30 ± 5 %, compared to a control (scrambled siRNA). The results were in terms of IOP reduction similar to that obtained with commercial compounds but the duration of the siRNA for the beta 2 adrenoceptor lasted for almost 5 days, compared to the average of 8 hours in the case of the other commercial compounds. No apparent side effects were observed in the ocular structures. In summary, the use of siRNA against the beta 2 adrenergic receptors open a new perspective for the treatment of glaucoma.La búsqueda de nuevos tratamientos para la hipertensión ocular y el glaucoma, dado los efectos secundarios que presentan los fármacos actuales, sugieren el desarrollo de estrategias diferentes a las actualmente disponibles. En este sentido se ha puesto a punto la tecnología de los RNA de interferencia (RNAi) también llamados siRNA para silenciando selectivamente los receptores beta2 adrenérgicos tratar de obtener una reducción sustancial de la presión intraocular (PIO), principal factor desencadenante del glaucoma. El empleo de un siRNA de origen comercial para el receptor beta2 ha producido una reducción sustancial de la PIO de 30 ± 5 %, comparado con el control, un siRNA sin sentido (scramble). Estos resultados fueron en magnitud semejantes al de los fármacos comerciales salvo que la duración del siRNA para el receptor beta2 adrenérgico duró casi 5 días en comparación de las 8 horas que suelen durar los fármacos comerciales. Los estudios en relación con los efectos secundarios no mostraron ninguna modificación en las estructuras oculares. En resumen, el empleo de los siRNA frente a los receptores beta2 adrenérgicos presenta muy buenas perspectivas como aproximación novedosa para el tratamiento del glaucoma

Estrategia para la enseñanza experimental interdisciplinaria de la electroquímica a estudiantes de ciclo 5

Este trabajo propone una estrategia experimental interdisciplinaria para la enseñanza de la electroquímica. Se identificaron los conceptos fundamentales para la comprensión de los procesos electroquímicos y se hizo una prueba diagnóstica para identificar las concepciones previas de los estudiantes que estuvieran relacionadas con estos conceptos. A partir de esta información se diseñaron seis módulos experimentales bajo el enfoque del aprendizaje activo y una perspectiva interdisciplinar. La validación preliminar se realizó con los estudiantes de grado 1101 del instituto San Juan de Dios. La investigación de tipo cualitativo descriptivo tuvo como resultado principal que los estudiantes al finalizar la aplicación de cinco de los módulos lograrón, en su mayoría, ver que la ciencia natural es una sola y aprender que hay leyes naturales que les permite racionalizar distintos fenómenos físicos, químicos y biológicos relacionados con la electroquímica. El documento hace una introducción epistemológica del desarrollo de la electroquímica, una introducción de los conceptos básicos para entender los fenómenos electroquímicos, presenta distintas actividades didácticas encaminadas a comprender la electroquímica desde distintos puntos de vista y, finalmente, se discute las observaciones más relevantes hechas durante la implementación en el aula de clase de dichas actividades didácticas.Abstract. This work proposes an interdisciplinary experimental strategy for teaching electrochemistry. The fundamental concepts for the understanding of electrochemical processes were identified and it was done a test about the previous conceptions of the students related to those concepts. From this information there were designed six experimental modules based on the active learning approach and an interdisciplinary perspective. The preliminary validation of this work was performed with students of the high school “San Juan de Dios” of the eleventh grade. This work is a qualitative and descriptive research whose main achievements were that the students understood that science is only one and that the understanding of the natural laws allows them to rationalize physical, chemical or biological phenomena related to electrochemistry. This manuscript present and epistemological introduction about the development of the electrochemistry, an introduction to the main concepts related to electrochemistry, several learning activities whose main goal is to show the electrochemistry from several points of view and, finally, the main observations done during the implementation of this work in the class room are analyzed.Maestrí

Therapeutic potential of topical administration of siRNAs against HIF-1α for corneal neovascularization.

Given the implications of the problem of neovascularization on ocular health, as well as the growth in the number of cases, the purpose of the present study has been testing the efficacy of siRNAs (small interfering RNA) designed to silence Hypoxia Inducible Factor -1α (HIF-1α) and to demonstrate that their use stops neovascularization in a model of corneal burn. Corneal wounds in the limbic zone were made in the eyes of New Zealand white rabbits. Topical applications of siRNAs were done the next day to the wound for four consecutive days and eyes were examined with a slit lamp. Evaluation of neovascularization progress was done by analyzing images by ImageJTM and to determine the neovascular area in Matlab ® was used. At the same time, a rabbit corneal cell line was used for in vitro study of hypoxia exposure and Western blot analysis of the cell's extracts were done. Under normal cell culture oxygenation, the expression of HIF-1α was lower than that observed under hypoxic conditions. After 2 h of hypoxia, there was a significant increase in the HIF-1α expression, effect that was maintained up to 6 h. The increased in HIF-1α was mimicked by a cell permeable prolyl-4-hydroxylase inhibitor. Cobalt chloride showed no capacity to increase HIF-1α in vitro. The effect of three different siRNA on HIF-1α was tested after 4 h of hypoxia. siRNA#1 was able to silence 80% of HIF-1α expression, siRNA#2 and siRNA#3 reduce the expression in 45% and 40% respectively. In addition, the three siRNA were tested in a corneal model of neovascularization. scrambledsiRNA#2 was the most effective inhibitor of blood vessel production, followed by siRNA#3 and siRNA#1. Compared to the scrambled siRNA (100% of blood vessel generation), siRNA#2 blocked the presence of blood vessels by 83 ± 2%, siRNA#3 inhibited 45 ± 7% and siRNA#1 only inhibited 18 ± 5%. The necessary time to observe the 50% of effect showed values of NV50 of 10.2 ± 2.4 days for the scrambled siRNA, 9.1 ± 1.4 for siRNA#1, 6.5 ± 1.85 for siRNA#2 and 4.8 ± 1.8 days for siRNA#3. In conclusion, the topical application of siRNA towards HIF-1α seems to be an effective and reliable method to stop neovascularization.This work was supported by a grant from Ministerio de Ciencia e Innovación (SAF2010-16024 and SAF2013-44416-R) and RETICS (RD12/0034/0003), and a grant from the Instituto de Salud Carlos III of Spain and Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”) (FIS-FEDER PI07-1168 to J. Mateo)S

Specificity and nanomolar potency of melatonin on G-protein coupled melatonin MT1 and MT2 receptors expressed in HEK-293T human embryo kidney cells

This is a pre-registered study, i.e. a study whose hypotheses and experiments designed to address these hypotheses has been deposited in a database before starting the experiments. The study aims at assessing the Gs versus Gi coupling and the potency of melatonin in the human version of melatonin MT1 and MT2 G-protein-coupled receptors expressed in HEK-293T cells. The results show that these receptors are Gi but not Gs coupled. By using a standard procedure of modulation of 0.5 μM forskolin-induced cAMP levels, it was found that the potency of MT2 receptor-mediated actions is in the low nanomolar range, but the potency of MT1 is in the high nanomolar range. The potency of melatonin to stimulate the MT2 receptor is similar to that of a selective agonist, N-[2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl)ethyl]butanamide (IIK7). Overall, the new data on the potency of melatonin on its receptors will provide a new look for melatonin research. It is important to consider this finding for appropriately addressing physiological or therapeutical effects based on melatonin potency. Thus, the low doses of melatonin used in the existing prolonged release preparations or in other supplements should be revisited

Diagnóstico y lineamientos de políticas públicas para pequeños productores. Hacia la configuración de territorialidades.

Los objetivos generales que se plantearon son: 1. Contribuir al desarrollo productivo y la inclusión social de los pequeños productores, pertenecientes a las fracciones más vulnerables de la Provincia de San Juan. 2. Proponer líneas programáticas de desarrollo que incluyan a los pequeños productores como sujetos reales de políticas públicas.EEA San JuanFil: De la Torre, Delia Inés. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Tinto, Cecilia. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Moscheni, Margarita. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaHernández, Juan Jesús. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; ArgentinaFil: Gili Diez, Valeria. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Grimalt, Miguel. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Checcarelli Pintor, Angelo Emmanuel. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Godoy, María Victoria. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; Argentin

p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1

During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases in the heart. We demonstrate that p38γ/δ contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38γ/δ activation in cardiomyocytes of newborn mice results in an early GYS1 phosphorylation and inhibition of cardiac glycogen production, triggering an early metabolic shift that induces a deficit in cardiomyocyte fuel supply, leading to whole-body metabolic deregulation and maladaptive cardiac pathogenesis. Notably, the adverse effects of forced premature cardiac p38γ/δ activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. These results suggest that diet interventions have a potential for treating human cardiac genetic diseases that affect heart metabolism.G.S. is a YIP EMBO member. B.G.T. was a fellow of the FPI Severo Ochoa CNIC program (SVP-2013-067639) and currently is funded by the AHA-CHF (AHA award number: 818798). V.M.R. is a FPI fellow (BES-2014-069332) and A.M.S. is a fellow of the FPI Severo Ochoa CNIC program (BES-2016-077635). This work was funded by the following grants: to G.S.: funding from the EFSD/Lilly European Diabetes Research Programme Dr Sabio, from Spanish Ministry of Science, Innovation and Universities (MINECO-FEDER SAF2016-79126-R and PID2019-104399RB-I00), Comunidad de Madrid (IMMUNOTHERCAN-CM S2010/BMD-2326 and B2017/BMD-3733) and Fundación Jesús Serra; to P.A.: Ayudas para apoyar grupos de investigación del sistema Universitario Vasco (IT971-16 to P.A.), MCIU/AEI/FEDER, funding from Spanish Ministry of Science, Innovation and Universities (RTI2018-095134-B-100); Excellence Network Grant from MICIU/AEI (SAF2016-81975-REDT and 2018-PN188) to PA and GS; to J.V.: funding from Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00), the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3 (PT17/0019/0003- ISCIII-SGEFI / ERDF, ProteoRed), and “la Caixa” Banking Foundation (project code HR17-00247); to J.P.B.: funding from Spanish Ministry of Science, Innovation and Universities (PID2019-105699RB-I00, RED2018‐102576‐T) and Escalera de Excelencia (CLU-2017-03); to J.A.E.: funding from Spanish Ministry of Science, Innovation and Universities MINECO (RED2018-102576-T, RTI2018-099357-B-I00), CIBERFES (CB16/10/00282), and HFSP (RGP0016/2018). RAP (XPC/BBV1602 and MIN/RYC1102). The CNIC is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Entramado productivo minero en San Juan. Herramientas de intervención desde un abordaje territorial.

Esta investigación es un proyecto de desarrollo tecnológico social (PDTS) orientado a generar por un lado, conocimiento sobre la dinámica socio-técnica de la principal actividad económica en la provincia y por otro, realizar propuestas innovadoras que aprovechen y fortalezcan las capacidades territoriales generadas y acumuladas por la minería en San Juan.EEA San JuanFil: Moscheni, Margarita. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Ureta, Adriana Alimé. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Checcarelli Pintor, Angelo Emmanuel. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Heredia Flores, Augusto Marcos. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: De la Torre, Delia Inés. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Funes Poblete, Eliana Gabriela. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Esquivel, Fabiana Eugenia. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Hernández, Juan Jesús. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria San Juan; ArgentinaFil: Neffa, Julio César. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: De los Ríos, Leonardo. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Doncel Ramallo, Lourdes Romina. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Perez, Marta Lidia. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Godoy, María Victoria. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Grimalt, Miguel. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Luna, Pedro. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Ortiz Flores, Renzo Federico. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; ArgentinaFil: Gili Diez, Valeria. Universidad Nacional de San Juan. Facultad de Ciencias Sociales; Argentin

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A cross-cultural comparison of group support systems (GSS) outcomes: A United States and Mexico field experiment.

This research project was a cross-cultural field experiment designed to measure the effects of "national culture" (U.S. and Mexican) upon group performance in GSS (Group Support Systems) and non-GSS environments. Relatively few studies have considered cultural dimensions in their analysis of GSS and even fewer have employed empirical data to test their hypotheses. In view of the significant global developments in information technology, this has been a disappointing shortcoming of current information technology (IT) research. Two groups of hypotheses were developed that predicted the effects of three independent variables; national culture, support technology and identification features upon group performance, consensus levels and satisfaction perceptions, both within and between each national culture (U.S. and Mexico). Hofstede's model of cultural differentiation was used to predict the relative performance and perceptions of U.S. and Mexican participants. The research methodology utilized an abbreviated version of Hofstede's Cultural Values Survey as a pre-test questionnaire and a GSS Group Perceptions questionnaire as a post-test questionnaire to measure group and individual perceptions. A double translated Spanish version of each questionnaire was developed by the author for the Mexican sample. Experimental results within each culture indicate that Mexican participants generated more comments, more comment lines and more idea categories per participant using GSS technology than manual technology. Similar results, as expected, were reported for the U.S. sample. With regard to consensus, Mexican manual groups generated higher consensus levels than Mexican GSS groups. However, there were no significant differences in consensus levels between GSS and Manual groups for the U.S. sample. With regard to satisfaction levels, there were no significant differences between GSS and manual groups for the U.S. sample. However, the Mexican sample reported significant differences between GSS and manual groups in "satisfaction with the group decision" and perceived "participation equity". Experimental results comparing cultures indicate that while U.S. GSS groups were more productive than Mexican groups, Mexican groups, across all experimental treatments, generated higher levels of consensus than U.S. groups. However, there were no significant differences in changes in consensus levels between U.S. and Mexican groups. With regard to satisfaction and perceived participation equity, Mexican groups expressed more "satisfaction with their group's decision" and perceived more "participation equity" than U.S. groups. These differences were especially pronounced in comparing U.S. GSS and Mexican GSS groups