Estudio de la localización de canales K2P en entornos lipídicos en neuronas granulares de cerebelo

72 p.Los canales de potasio (K+) forman parte de una de las familias más abundantes de proteínas de transmembra. Estas proteínas, y en particular los canales de K+ de dos dominios de poros (K2P), permiten el flujo de iones K+ a través de la membrana plasmática controlando de esta forma la excitabilidad en las células neuronales. En mamíferos se han identificado 15 canales de tipo K2P, también conocidos como canales de tipo leak, los que son agrupados en 6 subfamilias basados en sus propiedades estructurales y funcionales. Cada subunidad K2P está formada por cuatro segmentos de transmembrana (4STM) y dos dominios formadores de poro (2P), debiendo dimerizar para la formación de un poro selectivo y funcional. Estudios realizados en nuestro laboratorio, han demostrado que la alteración de los niveles de colesterol presentes en la membrana plasmática, generan una disminución de la corriente de tipo leak en neuronas granulares de cerebelo (NGC). Sin embargo, la asociación entre los dominios ricos en colesterol y los canales K2P no había sido estudiada. En esta tesis evaluamos la expresión de los canales K2P en células NGC y su colocalización con marcadores de balsas lipídicas, mediante técnicas bioquímicas y de biología celular. Nuestros resultados confirmaron la presencia de los canales K2P1, -3, -9 y -18 en NGC de rata mediante estudios de Western Blot e Inmunofluorescencia. Además se evaluó su colocalización con marcadores de balsas lipídicas. Se encontró una colocalización con caveolina, marcador de balsas lipídicas asociadas a caveolas, del ~56% para K2P1, ~33% para K2P3, ~41% para K2P9 y ~27% para K2P18. Por otro lado, con flotilina que es un marcador de balsas lipídicas no asociados a caveolas se encontró una colocalización del ~21% en el caso de K2P1, un ~27% para K2P3, ~54% para K2P9 y ~46% para el canal K2P18. También se identificó una fracción de canales expresados en la membrana que no están asociados a balsas lipídicas, lo que fue evaluado mediante la colocalización con el marcador β-adaptina, presentando un rango de ~26% a ~53% de colocalización./ABSTRACT: Potassium (K+) channels form part of one of the most abundant transmembre proteins super-families. These proteins, particularly the two-pore domain potassium (K2P) channels, allow the flow of K+ ions through the plasma membrane thereby modulating the excitability of neuronal cells. In mammals, K2P channels family is formed by 15 members, also known as potassium leak channels, which are divided in 6 subfamilies based on the structural and functional properties. Each K2P subunit contains four trasmembrane domains (4STM) and two pore forming domains in tandem (2P), and must dimerize to form a selective and functional pore. Studies in our laboratory have shown that cholesterol disruption of the plasma membrane generates a decrease of leak potassium current in cerebellar granule neurons (CGN). However, the association between cholesterol-rich domains and K2P channels had not been studied. In this thesis, we evaluated the expression of K2P channels in CGN cells and the colocalization with lipid rafts markers, using molecular biology and immunological approaches. Our results confirmed the presence of K2P1, -3, -9, and -18 channels in CGN using Western blotting and immunofluorescence studies. Moreover, its colocalization with lipid rafts markers was assessed. Colocalization with caveolin, a marker of lipid rafts associated with caveolae, was found of ~56% for K2P1, ~33% for K2P3, ~41% for K2P9 and ~27% for K2P18. Furthermore, with flotillin, a lipid rafts not associated with caveolae marker, was found a colocalization of ~21% for K2P1, ~27% for K2P3, ~54% for K2P9 and ~46% for K2P18. Finally, a fraction of channels that are not associated with lipid rafts was identified, which was assessed by colocalization with β-adaptin marker, presenting a range of ~26% to ~53% of colocalization

Tópicos en educación y humanidades. Tomo I

Se publica este libro en el marco del recurso otorgado por la SEP-PFCE- 2017 a los Cuerpos académicos de la Dependencia de Educación y Humanidades (DES), de la Universidad Autónoma del Estado de México. Los trabajos son reflejo de la investigación desarrollada en diversas disciplinas de la Facultad de Humanidades, así como del Centro de Estudios sobre la Universidad y el Centro de Investigación en Ciencias Sociales y Humanidades.Publicación financiada con recursos PFCE 2017

GEODIVULGAR: Geología y Sociedad

Se incluyen los dos volúmenes resultantes de los concursos de relatos e Ilustración que han tenido lugar en el desarrollo del ProyectoDepto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasFALSEsubmitte

GEODIVULGAR: Geología y Sociedad

Depto. de Geodinámica, Estratigrafía y PaleontologíaFac. de Ciencias GeológicasFALSEsubmitte

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research