TRPV4 Contributes to Resting Membrane Potential in Retinal Müller Cells: Implications in Cell Volume Regulation

Neural activity alters osmotic gradients favoring cell swelling in retinal Müller cells. This swelling is followed by a regulatory volume decrease (RVD), partially mediated by an efflux of KCl and water. The transient receptor potential channel 4 (TRPV4), a nonselective calcium channel, has been proposed as a candidate for mediating intracellular Ca2+ elevation induced by swelling. We previously demonstrated in a human Müller cell line (MIO-M1) that RVD strongly depends on ion channel activation and, consequently, on membrane potential (Vm ). The aim of this study was to investigate if Ca2+ influx via TRPV4 contributes to RVD by modifying intracellular Ca2+ concentration and/or modulating Vm in MIO-M1 cells. Cell volume, intracellular Ca2+ levels, and Vm changes were evaluated using fluorescent probes. Results showed that MIO-M1 cells express functional TRPV4 which determines the resting Vmassociated with K+ channels. Swelling-induced increases in Ca2+ levels was due to both Ca2+ release from intracellular stores and Ca2+ influx by a pathway alternative to TRPV4. TRPV4 blockage affected swelling-induced biphasic response (depolarization-repolarization), suggesting its participation in modulating Vm changes during RVD. Agonist stimulation of Ca2+ influx via TRPV4 activated K+ channels hyperpolarizing Vm and accelerating RVD. We propose that TRPV4 forms a signaling complex with Ca2+ and/or voltage-dependent K+ channels to define resting Vm and Vm changes during RVD. TRPV4 involvement in RVD depends on the type of stimuli and/or degree of channel activation, leading to a maximum RVD response when Ca2+ influx overcomes a threshold and activates further signaling pathways in cell volume regulation.Fil: Netti, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Fernández, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Kalstein, Maia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pizzoni, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Di Giusto, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Rivarola, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Ford, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Capurro, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Ciencias Fisiológicas. Laboratorio de Biomembranas; Argentin

The mood stabilizing properties of AF3581, a novel potent GSK-3β inhibitor

Glycogen synthase kinase 3β (GSK-3β) is a serine/threonine protein kinase mediating phosphorylation on serine and threonine amino acid residues of several target molecules. The enzyme is involved in the regulation of many cellular processes and aberrant activity of GSK-3β has been linked to several disease conditions. There is now large evidence on the role of GSK-3β in the pathophysiology of mood disturbances with special regard to bipolar disorders. In the present study we further investigated the role of GSK-3β in bipolar disorders by studying AF3581, the prototype of a novel class of ATP-competitive GSK-3β inhibitors having the common N-[(1- alkylpiperidin-4-yl) methyl]-1H-indazole-3-carboxamide scaffold. Based on previous studies, AF3581 inhibits GSK-3β in the nanomolar range on purified human enzyme and highly selective with respect to other kinases. Current study demonstrates that the compound has efficacy both in the chronic mild stress paradigm of depression (mimicking the down phase of bipolar disorder) and on mice aggressiveness in the resident intruder model (mimicking the up phase). These findings underline the importance of aberrant GSK-3β activity in the development/ maintenance of mood oscillation in this peculiar pathological condition. Moreover, the present work also suggests a therapeutic potential for selective GSK-3 β inhibitors in the management of bipolar disorders patients. Glycogen synthase kinase 3β (GSK-3β) is a serine/threonine protein kinase mediating phosphorylation on serine and threonine amino acid residues of several target molecules. The enzyme is involved in the regulation of many cellular processes and aberrant activity of GSK-3β has been linked to several disease conditions. There is now large evidence on the role of GSK-3β in the pathophysiology of mood disturbances with special regard to bipolar disorders. In the present study we further investigated the role of GSK-3β in bipolar disorders by studying AF3581, the prototype of a novel class of ATP-competitive GSK-3β inhibitors having the common N-[(1- alkylpiperidin-4-yl) methyl]-1H-indazole-3-carboxamide scaffold. Based on previous studies, AF3581 inhibits GSK-3β in the nanomolar range on purified human enzyme and highly selective with respect to other kinases. Current study demonstrates that the compound has efficacy both in the chronic mild stress paradigm of depression (mimicking the down phase of bipolar disorder) and on mice aggressiveness in the resident intruder model (mimicking the up phase). These findings underline the importance of aberrant GSK-3β activity in the development/ maintenance of mood oscillation in this peculiar pathological condition. Moreover, the present work also suggests a therapeutic potential for selective GSK-3 β inhibitors in the management of bipolar disorders patients. Glycogen synthase kinase 3β (GSK-3β) is a serine/threonine protein kinase mediating phosphorylation on serine and threonine amino acid residues of several target molecules. The enzyme is involved in the regulation of many cellular processes and aberrant activity of GSK-3β has been linked to several disease conditions. There is now large evidence on the role of GSK-3β in the pathophysiology of mood disturbances with special regard to bipolar disorders. In the present study we further investigated the role of GSK-3β in bipolar disorders by studying AF3581, the prototype of a novel class of ATP-competitive GSK-3β inhibitors having the common N-[(1- alkylpiperidin-4-yl) methyl]-1H-indazole-3-carboxamide scaffold. Based on previous studies, AF3581 inhibits GSK-3β in the nanomolar range on purified human enzymeand highly selective with respect to other kinases. Current study demonstrates that the compound has efficacy both in the chronic mild stress paradigm of depression (mimicking the down phase of bipolar disorder) and on mice aggressiveness in the resident intruder model (mimicking the up phase). These findings underline the importance of aberrant GSK-3β activity in the development/ maintenance of mood oscillation in this peculiar pathological condition. Moreover, the present work also suggests a therapeutic potential for selective GSK-3 β inhibitors in the management of bipolar disorders patients. Glycogen synthase kinase 3β (GSK-3β) is a serine/threonine protein kinase mediating phosphorylation on serine and threonine amino acid residues of several target molecules. The enzyme is involved in the regulation of many cellular processes and aberrant activity of GSK-3β has been linked to several disease conditions. There is now large evidence on the role of GSK-3β in the pathophysiology of mood disturbances with special regard to bipolar disorders. In the present study we further investigated the role of GSK-3β in bipolar disorders by studying AF3581, the prototype of a novel class of ATP-competitive GSK-3β inhibitors having the common N-[(1- alkylpiperidin-4-yl) methyl]-1H-indazole-3-carboxamide scaffold. Based on previous studies, AF3581 inhibits GSK-3β in the nanomolar range on purified human enzyme and highly selective with respect to other kinases. Current study demonstrates that the compound has efficacy both in the chronic mild stress paradigm of depression (mimicking the down phase of bipolar disorder) and on mice aggressiveness in the resident intruder model (mimicking the up phase). These findings underline the importance of aberrant GSK-3β activity in the development/ maintenance of mood oscillation in this peculiar pathological condition. Moreover, the present work also suggests a therapeutic potential for selective GSK-3 β inhibitors in the management of bipolar disorders patients. Glycogen synthase kinase 3β (GSK-3β) is a serine/threonine protein kinase mediating phosphorylation on serine and threonine amino acid residues of several target molecules. The enzyme is involved in the regulation of many cellular processes and aberrant activity of GSK-3β has been linked to several disease conditions. There is now large evidence on the role of GSK-3β in the pathophysiology of mood disturbances with special regard to bipolar disorders. In the present study we further investigated the role of GSK-3β in bipolar disorders by studying AF3581, the prototype of a novel class of ATP-competitive GSK-3β inhibitors having the common N-[(1- alkylpiperidin-4-yl) methyl]-1H-indazole-3-carboxamide scaffold. Based on previous studies, AF3581 inhibits GSK-3β in the nanomolar range on purified human enzyme and highly selective with respect to other kinases. Current study demonstrates that the compound has efficacy both in the chronic mild stress paradigm of depression (mimicking the down phase of bipolar disorder) and on mice aggressiveness in the resident intruder model (mimicking the up phase). These findings underline the importance of aberrant GSK-3β activity in the development/ maintenance of mood oscillation in this peculiar pathological condition. Moreover, the present work also suggests a therapeutic potential for selective GSK-3 β inhibitors in the management of bipolar disorders patients. Glycogen synthase kinase 3β (GSK-3β) is a serine/threonine protein kinase mediating phosphorylation on serine and threonine amino acid residues of several target molecules. The enzyme is involved in the regulation of many cellular processes and aberrant activity of GSK-3β has been linked to several disease conditions. There is now large evidence on the role of GSK-3β in the pathophysiology of mood disturbances with special regard to bipolar disorders. In the present study we further investigated the role of GSK-3β in bipolar disorders by studying AF3581, the prototype of a novel class of ATP-competitive GSK-3β inhibitors having the common N-[(1- alkylpiperidin-4-yl) methyl]-1H-indazole-3-carboxamide scaffold. Based on previous studies, AF3581 inhibits GSK-3β in the nanomolar range on purified human enzyme and highly selective with respect to other kinases. Current study demonstrates that the compound has efficacy both in the chronic mild stress paradigm of depression (mimicking the down phase of bipolar disorder) and on mice aggressiveness in the resident intruder model (mimicking the up phase). These findings underline the importance of aberrant GSK-3β activity in the development/ maintenance of mood oscillation in this peculiar pathological condition. Moreover, the present work also suggests a therapeutic potential for selective GSK-3 β inhibitors in the management of bipolar disorders patients. Glycogen synthase kinase 3β (GSK-3β) is a serine/threonine protein kinase mediating phosphorylation on serine and threonine amino acid residues of several target molecules. The enzyme is involved in the regulation of many cellular processes and aberrant activity of GSK-3β has been linked to several disease conditions. There is now large evidence on the role of GSK-3β in the pathophysiology of mood disturbances with special regard to bipolar disorders. In the present study we further investigated the role of GSK-3β in bipolar disorders by studying AF3581, the prototype of a novel class of ATP-competitive GSK-3β inhibitors having the common N-[(1- alkylpiperidin-4-yl) methyl]-1H-indazole-3-carboxamide scaffold. Based on previous studies, AF3581 inhibits GSK-3β in the nanomolar range on purified human enzyme and highly selective with respect to other kinases. Current study demonstrates that the compound has efficacy both in the chronic mild stress paradigm of depression (mimicking the down phase of bipolar disorder) and on mice aggressiveness in the resident intruder model (mimicking the up phase). These findings underline the importance of aberrant GSK-3β activity in the development/ maintenance of mood oscillation in this peculiar pathological condition. Moreover, the present work also suggests a therapeutic potential for selective GSK-3 β inhibitors in the management of bipolar disorders patients

Click-tambjamines as efficient and tunable bioactive anion transporters

A novel class of transmembrane anion carriers, the click-tambjamines, display remarkable anionophoric activities in model liposomes and living cells. The versatility of this building block for the generation of molecular diversity offers promise to develop future drugs based on this design.European Union’s Horizon 2020 research and innovation programme (TAT-CF project, grant agreement 667079), Instituto de Salud Carlos III (Grant PI18/00441) (co-funded by the European Regional Development Fund (ERDF), a way to build Europe) and “La Caixa” Foundation and Caja Burgos Foundation (CAIXAUBU004

Multidisciplinary Collaboration in the Treatment of Patients With Type 2 Diabetes in Primary Care: Analysis Using Process Mining

[EN] Background: Public health in several countries is characterized by a shortage of professionals and a lack of economic resources. Monitoring and redesigning processes can foster the success of health care institutions, enabling them to provide a quality service while simultaneously reducing costs. Process mining, a discipline that extracts knowledge from information system data to analyze operational processes, affords an opportunity to understand health care processes. Objective: Health care processes are highly flexible and multidisciplinary, and health care professionals are able to coordinate in a variety of different ways to treat a diagnosis. The aim of this work was to understand whether the ways in which professionals coordinate their work affect the clinical outcome of patients. Methods: This paper proposes a method based on the use of process mining to identify patterns of collaboration between physician, nurse, and dietitian in the treatment of patients with type 2 diabetes mellitus and to compare these patterns with the clinical evolution of the patients within the context of primary care. Clustering is used as part of the preprocessing of data to manage the variability, and then process mining is used to identify patterns that may arise. Results: The method is applied in three primary health care centers in Santiago, Chile. A total of seven collaboration patterns were identified, which differed primarily in terms of the number of disciplines present, the participation intensity of each discipline, and the referrals between disciplines. The pattern in which the three disciplines participated in the most equitable and comprehensive manner had a lower proportion of highly decompensated patients compared with those patterns in which the three disciplines participated in an unbalanced manner. Conclusions: By discovering which collaboration patterns lead to improved outcomes, health care centers can promote the most successful patterns among their professionals so as to improve the treatment of patients. Process mining techniques are useful for discovering those collaborations patterns in flexible and unstructured health care processes.This paper was partially funded by the National Commission for Scientific and Technological Research, the Formation of Advanced Human Capital Program and the National Fund for Scientific and Technological Development (CONICYT-PCHA/Doctorado Nacional/2016-21161705 and CONICYT-FONDECYT/1150365; Chile). The authors would like to thank Ancora UC primary health care centers for their help with this research. The founding sponsors had no role in the design of the study in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.Conca, T.; Saint Pierre, C.; Herskovic, V.; Sepulveda, M.; Capurro, D.; Prieto, F.; Fernández Llatas, C. (2018). Multidisciplinary Collaboration in the Treatment of Patients With Type 2 Diabetes in Primary Care: Analysis Using Process Mining. JOURNAL OF MEDICAL INTERNET RESEARCH. 20(4). https://doi.org/10.2196/jmir.8884S204Chen, C.-C., Tseng, C.-H., & Cheng, S.-H. (2013). Continuity of Care, Medication Adherence, and Health Care Outcomes Among Patients With Newly Diagnosed Type 2 Diabetes. Medical Care, 51(3), 231-237. doi:10.1097/mlr.0b013e31827da5b9International Diabetes FederationIDF20152018-03-19IDF Diabetes Atlas 7th Edition (2015) https://www.idf.org/e-library/epidemiology-research/diabetes-atlas/13-diabetes-atlas-seventh-edition.htmlMinisterio de Salud de Chileminsal.cl20102018-03-23Encuesta Nacional de Salud ENS Chile 2009-2010 http://www.minsal.cl/estudios_encuestas_salud/Ministerio de Salud de Chileminsal.cl20102018-03-20Guía Clinica Diabetes Mellitus Tipo 2 http://www.minsal.cl/portal/url/item/72213ed52c3e23d1e04001011f011398.pdfSapunar Z., J. (2016). EPIDEMIOLOGÍA DE LA DIABETES MELLITUS EN CHILE. Revista Médica Clínica Las Condes, 27(2), 146-151. doi:10.1016/j.rmclc.2016.04.003World Health Organizationwho.int2018-03-20Global Report on Diabetes http://www.who.int/diabetes/global-report/en/Poblete, F., Glasinovic, A., Sapag, J., Barticevic, N., Arenas, A., & Padilla, O. (2015). Apoyo social y salud cardiovascular: adaptación de una escala de apoyo social en pacientes hipertensos y diabéticos en la atención primaria chilena. Atención Primaria, 47(8), 523-531. doi:10.1016/j.aprim.2014.10.010Tuligenga, R. H., Dugravot, A., Tabák, A. G., Elbaz, A., Brunner, E. J., Kivimäki, M., & Singh-Manoux, A. (2014). Midlife type 2 diabetes and poor glycaemic control as risk factors for cognitive decline in early old age: a post-hoc analysis of the Whitehall II cohort study. The Lancet Diabetes & Endocrinology, 2(3), 228-235. doi:10.1016/s2213-8587(13)70192-xGamiochipi, M., Cruz, M., Kumate, J., & Wacher, N. H. (2016). Effect of an intensive metabolic control lifestyle intervention in type-2 diabetes patients. Patient Education and Counseling, 99(7), 1184-1189. doi:10.1016/j.pec.2016.01.017Wagner, E. H. (2001). Effect of Improved Glycemic Control on Health Care Costs and Utilization. JAMA, 285(2), 182. doi:10.1001/jama.285.2.182McDonald, J., Jayasuriya, R., & Harris, M. F. (2012). The influence of power dynamics and trust on multidisciplinary collaboration: a qualitative case study of type 2 diabetes mellitus. BMC Health Services Research, 12(1). doi:10.1186/1472-6963-12-63Gucciardi, E., Espin, S., Morganti, A., & Dorado, L. (2016). Exploring interprofessional collaboration during the integration of diabetes teams into primary care. BMC Family Practice, 17(1). doi:10.1186/s12875-016-0407-1Caron, F., Vanthienen, J., Vanhaecht, K., Limbergen, E. V., De Weerdt, J., & Baesens, B. (2014). Monitoring care processes in the gynecologic oncology department. Computers in Biology and Medicine, 44, 88-96. doi:10.1016/j.compbiomed.2013.10.015Rothman, A. A., & Wagner, E. H. (2003). Chronic Illness Management: What Is the Role of Primary Care? Annals of Internal Medicine, 138(3), 256. doi:10.7326/0003-4819-138-3-200302040-00034Organisation for Economic Co-operation and DevelopmentOECD20162018-03-20OECD Health Policy Overview: Health Policy in Chile http://www.oecd.org/els/health-systems/health-policy-in-your-country.htmRojas, E., Munoz-Gama, J., Sepúlveda, M., & Capurro, D. (2016). Process mining in healthcare: A literature review. Journal of Biomedical Informatics, 61, 224-236. doi:10.1016/j.jbi.2016.04.007Fernandez-Llatas, C., Lizondo, A., Monton, E., Benedi, J.-M., & Traver, V. (2015). Process Mining Methodology for Health Process Tracking Using Real-Time Indoor Location Systems. Sensors, 15(12), 29821-29840. doi:10.3390/s151229769Mans, R. S., van der Aalst, W. M. P., & Vanwersch, R. J. B. (2015). Process Mining in Healthcare. SpringerBriefs in Business Process Management. doi:10.1007/978-3-319-16071-9Van der Aalst, W. M. P. (2011). Process Mining. doi:10.1007/978-3-642-19345-3Kim, E., Kim, S., Song, M., Kim, S., Yoo, D., Hwang, H., & Yoo, S. (2013). Discovery of Outpatient Care Process of a Tertiary University Hospital Using Process Mining. Healthcare Informatics Research, 19(1), 42. doi:10.4258/hir.2013.19.1.42Harper, P. R., Sayyad, M. G., de Senna, V., Shahani, A. K., Yajnik, C. S., & Shelgikar, K. M. (2003). A systems modelling approach for the prevention and treatment of diabetic retinopathy. European Journal of Operational Research, 150(1), 81-91. doi:10.1016/s0377-2217(02)00787-7Rebuge, Á., & Ferreira, D. R. (2012). Business process analysis in healthcare environments: A methodology based on process mining. Information Systems, 37(2), 99-116. doi:10.1016/j.is.2011.01.003Ferreira, D., Zacarias, M., Malheiros, M., & Ferreira, P. (2007). Approaching Process Mining with Sequence Clustering: Experiments and Findings. Business Process Management, 360-374. doi:10.1007/978-3-540-75183-0_26Cheong, L. H., Armour, C. L., & Bosnic-Anticevich, S. Z. (2013). Multidisciplinary collaboration in primary care: through the eyes of patients. Australian Journal of Primary Health, 19(3), 190. doi:10.1071/py12019Boyle, E., Saunders, R., & Drury, V. (2016). A qualitative study of patient experiences of Type 2 Diabetes care delivered comparatively by General Practice Nurses and Medical Practitioners. Journal of Clinical Nursing, 25(13-14), 1977-1986. doi:10.1111/jocn.13219UddinSHossainLEffects of Physician Collaboration Network on Hospital Outcomes2012Fifth Australasian Workshop on Health Informatics and Knowledge Management (HIKM 2012)2012Melbourne, AustraliaBorgermans, L., Goderis, G., Van Den Broeke, C., Verbeke, G., Carbonez, A., Ivanova, A., … Grol, R. (2009). Interdisciplinary diabetes care teams operating on the interface between primary and specialty care are associated with improved outcomes of care: findings from the Leuven Diabetes Project. BMC Health Services Research, 9(1). doi:10.1186/1472-6963-9-179Bosch, M., Dijkstra, R., Wensing, M., van der Weijden, T., & Grol, R. (2008). Organizational culture, team climate and diabetes care in small office-based practices. BMC Health Services Research, 8(1). doi:10.1186/1472-6963-8-180Counsell, S. R., Callahan, C. M., Clark, D. O., Tu, W., Buttar, A. B., Stump, T. E., & Ricketts, G. D. (2007). Geriatric Care Management for Low-Income Seniors. JAMA, 298(22), 2623. doi:10.1001/jama.298.22.2623Anderson, J. G. (2002). Evaluation in health informatics: social network analysis. Computers in Biology and Medicine, 32(3), 179-193. doi:10.1016/s0010-4825(02)00014-8Gray, J. E., Davis, D. A., Pursley, D. M., Smallcomb, J. E., Geva, A., & Chawla, N. V. (2010). Network Analysis of Team Structure in the Neonatal Intensive Care Unit. PEDIATRICS, 125(6), e1460-e1467. doi:10.1542/peds.2009-2621Mian, O., Koren, I., & Rukholm, E. (2012). Nurse practitioners in Ontario primary healthcare: Referral patterns and collaboration with other healthcare professionals. Journal of Interprofessional Care, 26(3), 232-239. doi:10.3109/13561820.2011.650300Crossley, N., Bellotti, E., Edwards, G., Everett, M. G., Koskinen, J., & Tranmer, M. (2015). Social Network Analysis for Ego-Nets. doi:10.4135/9781473911871Ministerio de Salud de Chile2018-03-20Fondo Nacional de Salud https://www.fonasa.cl/sites/fonasa/beneficiariosGoldstein, D. E., Little, R. R., Lorenz, R. A., Malone, J. I., Nathan, D., Peterson, C. M., & Sacks, D. B. (2004). Tests of Glycemia in Diabetes. Diabetes Care, 27(7), 1761-1773. doi:10.2337/diacare.27.7.1761Meduru, P., Helmer, D., Rajan, M., Tseng, C.-L., Pogach, L., & Sambamoorthi, U. (2007). Chronic Illness with Complexity: Implications for Performance Measurement of Optimal Glycemic Control. Journal of General Internal Medicine, 22(S3), 408-418. doi:10.1007/s11606-007-0310-5Vermeire, E., Hearnshaw, H., Van Royen, P., & Denekens, J. (2001). Patient adherence to treatment: three decades of research. A comprehensive review. Journal of Clinical Pharmacy and Therapeutics, 26(5), 331-342. doi:10.1046/j.1365-2710.2001.00363.xKarter, A. J., Parker, M. M., Moffet, H. H., Ahmed, A. T., Ferrara, A., Liu, J. Y., & Selby, J. V. (2004). Missed Appointments and Poor Glycemic Control. Medical Care, 42(2), 110-115. doi:10.1097/01.mlr.0000109023.64650.73World Health Organization20032018-03-20Adherence to long-term therapies: evidence for action http://www.who.int/chp/knowledge/publications/adherence_report/en/Toth, E. L., Majumdar, S. R., Guirguis, L. M., Lewanczuk, R. Z., Lee, T. K., & Johnson, J. A. (2003). Compliance with Clinical Practice Guidelines for Type 2 Diabetes in Rural Patients: Treatment Gaps and Opportunities for Improvement. Pharmacotherapy, 23(5), 659-665. doi:10.1592/phco.23.5.659.32203Melnikow, J., & Kiefe, C. (1994). Patient compliance and medical research. Journal of General Internal Medicine, 9(2), 96-105. doi:10.1007/bf02600211Fernandez-Llatas, C., Valdivieso, B., Traver, V., & Benedi, J. M. (2014). Using Process Mining for Automatic Support of Clinical Pathways Design. Data Mining in Clinical Medicine, 79-88. doi:10.1007/978-1-4939-1985-7_5Fernández-Llatas, C., Benedi, J.-M., García-Gómez, J., & Traver, V. (2013). Process Mining for Individualized Behavior Modeling Using Wireless Tracking in Nursing Homes. Sensors, 13(11), 15434-15451. doi:10.3390/s131115434Wishah, R. A., Al-Khawaldeh, O. A., & Albsoul, A. M. (2015). Impact of pharmaceutical care interventions on glycemic control and other health-related clinical outcomes in patients with type 2 diabetes: Randomized controlled trial. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 9(4), 271-276. doi:10.1016/j.dsx.2014.09.00

The Acinetobacter baumannii website (Ab-web): a multidisciplinary knowledge hub, communication platform, and workspace

Acinetobacter baumannii is a Gram-negative bacterium increasingly implicated in hospital-acquired infections and outbreaks. Effective prevention and control of such infections are commonly challenged by the frequent emergence of multidrug-resistant strains. Here we introduce Ab-web (https://www.acinetobacterbaumannii.no), the first online platform for sharing expertise on A. baumannii. Ab-web is a species-centric knowledge hub, initially with ten articles organized into two main sections, ‘Overview’ and ‘Topics’, and three themes, ‘epidemiology’, ‘antibiotic resistance’, and ‘virulence’. The ‘workspace’ section provides a spot for colleagues to collaborate, build, and manage joint projects. Ab-web is a community-driven initiative amenable to constructive feedback and new ideas

Bienvenida sonrisa : Parte II

La Facultad de Odontología de la Universidad Nacional de La Plata, desde el año 1997, desarrolla un Programa de Salud Bucal en la ciudad de La Plata y sus alrededores, a través de la Asignatura Odontología Preventiva y Social. Esto ha permitido obtener datos estadísticos y de relevamiento de zonas, que impulsa la formulación de nuevas iniciativas en poblaciones vulnerables donde el índice de incidencia de enfermedades bucodentales, es elevado. Entendemos a la salud bucal como un valor que no debe ser considerado como un privilegio, sino como un derecho de todas las personas, reforzando el trabajo multidisciplinario de manera de que la salud recuperada, se mantenga a lo largo del tiempo, con el objetivo de disminuir las desigualdades en salud y con el propósito de brindar atención a poblaciones de difícil acceso, por este motivo, creemos que es fundamental la gestión del Trabajo Social , trabajando de forma efectiva con la comunidad, colaborando en la promoción de la salud y prevención de la enfermedad. Teniendo conocimiento de que la escuela es un espacio privilegiado y del encuentro con el otro, enfocamos nuestros esfuerzos en colaborar para modificar la realidad que se presenta.Este Proyecto surge debido a la necesidad de la Comunidad Educativa perteneciente a la Escuela Nº 45 “Manuel Rocha” del barrio El Mondongo de la Ciudad de La Plata, quienes manifiestan la carencia de información y atención de la comunidad educativa en cuanto a acciones preventivas. Este proyecto se lleva a cabo desde fines del 2019, atravesando el contexto de Pandemia por el virus causante de la enfermedad Covid-19, reacondicionando nuestras actividades.Facultad de Odontologí

Neuroprotective Effects of Genistein in Mongolian Gerbils: Estrogen Receptor-β Involvement

Genistein is a naturally occurring plant-derived phytoestrogen, present in the human diet, known to possess some beneficial effects. The present study investigated the effect of genistein on neuroprotection evaluated through electroencephalographic and behavioural correlates in a model of global cerebral ischemia in gerbils. Over the dose range tested, genistein (3 and 10 mg/ kg), given 5 min after recirculation antagonized the ischemia-induced electroencephalographic total spectral power decrease 7 days after ischemia; fully prevented ischemia-induced hyperlocomotion evaluated 1 day after ischemia; reversed ischemia-induced memory impairment evaluated through both nest building behaviour and object recognition test; decreased malondialdehyde overproduction in the brain, evaluated 7 days after reperfusion; and fully promoted the survival of pyramidal cells in the CA1 hippocampal subfield. The selective antagonist for estrogen receptor–β (ERβ), 4-[2-phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP) given 30 min before carotid occlusion, fully prevented the neuroprotective effect of genistein at the dose of 3 mg/kg. These results demonstrate the neuroprotective effect of genistein through the activation of ERβ and provide further grounds for the growing interest concerning the true potential of phytoestrogens as compounds to beneficially affect brain injury without having the disadvantages of estrogens. Keywords:: ischemia, electroencephalography (EEG), phytoestrogen, CA1, estrogen receptor–

SUMOylation Inhibition Enhances Protein Transcription under CMV Promoter: A Lesson from a Study with the F508del-CFTR Mutant

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), a selective anion channel expressed in the epithelium of various organs. The most frequent mutation is F508del. This mutation leads to a misfolded CFTR protein quickly degraded via ubiquitination in the endoplasmic reticulum. Although preventing ubiquitination stabilizes the protein, functionality is not restored due to impaired plasma membrane transport. However, inhibiting the ubiquitination process can improve the effectiveness of correctors which act as chemical chaperones, facilitating F508del CFTR trafficking to the plasma membrane. Previous studies indicate a crosstalk between SUMOylation and ubiquitination in the regulation of CFTR. In this study, we investigated the potential of inhibiting SUMOylation to increase the effects of correctors and enhance the rescue of the F508del mutant across various cell models. In the widely used CFBE41o-cell line expressing F508del-CFTR, inhibiting SUMOylation substantially boosted F508del expression, thereby increasing the efficacy of correctors. Interestingly, this outcome did not result from enhanced stability of the mutant channel, but rather from augmented cytomegalovirus (CMV) promoter-mediated gene expression of F508del-CFTR. Notably, CFTR regulated by endogenous promoters in multiple cell lines or patient cells was not influenced by SUMOylation inhibitors