Tuning melatonin receptor subtype selectivity in oxadiazolone-based analogues: Discovery of QR2 ligands and NRF2 activators with neurogenic properties

New multi-target indole and naphthalene derivatives containing the oxadiazolone scaffold as a bioisostere of the melatonin acetamido group have been developed. The novel compounds were characterized at melatonin receptors MT1R and MT2R, quinone reductase 2 (QR2), lipoxygenase-5 (LOX-5), and monoamine oxidases (MAO-A and MAO-B), and also as radical scavengers. We found that selectivity within the oxadiazolone series can be modulated by modifying the side chain functionality and coplanarity with the indole or naphthalene ring. In phenotypic assays, several oxadiazolone-based derivatives induced signalling mediated by the transcription factor NRF2 and promoted the maturation of neural stem-cells into a neuronal phenotype. Activation of NRF2 could be due to the binding of indole derivatives to KEAP1, as deduced from surface plasmon resonance (SPR) experiments. Molecular modelling studies using the crystal structures of QR2 and the KEAP1 Kelch-domain, as well as the recently described X-ray free-electron laser (XFEL) structures of chimeric MT1R and MT2R, provided a rationale for the experimental data and afforded valuable insights for future drug design endeavoursThe authors gratefully acknowledge the following financial supports: Spanish Ministry of Science, Innovation and Universities; Spanish Research Agency; and European Regional Development Funds (grants RTI2018-093955-B-C21 and SAF2015-64948-C2-1-R to M.I.R.-F.; RTI2018-095793-B-I00 to M.G.L., SAF2015-64629-C2- 2-R to F.G.), General Council for Research and Innovation of the Community of Madrid and European Structural Funds (grant B2017/BMD-3827 e NRF24ADCM), Health Institute Carlos III (Miguel Servet II ProgramCP16/00014 and grant PI17/01700 to R.L.). CH-A and P.M. thank their PhD fellowships from Spanish Ministry of Education (MEC, PhD grant FPU16/01704 and mobility grant FPUEST17/00233 to CH-A and FPU13/03737 to P.M.)

Formative research contributions to the development of Risaralda

Es importante establecer y visibilizar a los estudiantes los beneficios relacionados con la formación en investigación, dentro de los cuales encontramos el fortalecimiento de las capacidades de liderazgo así como el compromiso activo y las experiencias en independencia y colaboración. Así mismo, la formación integral hacia una mayor apreciación del valor de la literatura disciplinaria, generando de esta manera habilidades de pensamiento crítico, indagación y análisis. Además, esto permite forjar la confianza en sí mismo para presentar las propias ideas a la comunidad, permitiendo al estudiante la preparación de futuras actividades académicas, incluidos estudios de posgrado. La investigación formativa tiene como propósito la difusión de la información existente y permitir que el estudiante la integre como conocimientos, considerándolo como un aprendizaje permanente y necesario. Uno de los principales problemas que debe enfrentar la investigación formativa es el número de docentes con las capacidades necesarias para generar en el estudiante capacidades investigativas, exigiendo al profesor universitario adoptar una actitud contraria al objeto de enseñanza, generando un carácter complejo y dinámico del conocimiento.CONTENTS RETOS DE LA INVESTIGACIÓN EN PREGRADO..................................................5 CHALLENGES OF UNDERGRADUATE RESEARCH.............................................9 German Oved Acevedo Osorio CHAPTER 1 HEALTH AND SPORTS SCIENCES FACTORS ASSOCIATED WITH EXACERBATIONS OR CRISIS EVENTS OF CHRONIC NON COMMUNICABLE DISEASES.........................13 Giovanni García Castro, Sandra Milena Bedoya Gaviria, Isabela Patiño Pulgarín y Valentina Valencia Flórez ORAL ANTICOAGULATION IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION IN A UNIVERSITY HOSPITAL IN COLOMBIA.....................................................................................................29 María Leonor Galindo Márquez, Adrian Giraldo Diaconeasa, Juan Darío Franco Ramírez y Eduardo Ramírez Vallejo PERFORMANCE IN INITIAL TRAUMAASSESSMENT OF EMERGENCY TEAMS FROM PREHOSPITAL CARE TEAMS..................43 Giovanni García Castro, Yamileth Estrada Berrio, Manuela Aguirre Torres e Isabella Díaz Leal ACADEMIC TRAINING AND WORKING CONDITIONS OF NURSING PROFESSIONALS IN PEREIRA - RISARALDA 2020.....................55 Miguel Ángel Gómez Puerta, Laura Isabel Orozco Santamaría, Alexandra Villa Patiño y Gladys Judith Basto Hernández EFFECTS OF DYNAMIC TAPE WITH ANTI-VALGUS APPLICATION ON VERTICAL JUMP PERFORMANCE IN PHYSICALLY ACTIVE WOMEN: A CASE STUDY ..........................................73 María Camila Arias Castro, Alejandro Gómez Rodas y Ángela María Cifuentes Ríos PROPOSAL OF CARE FOR DIAGNOSTIC PREVALENT NURSES IN AN EMERGENCY DEPARTMENT................................................................89 Tatiana Restrepo Pérez, Jessica Viviana Ríos Uribe, Anyi Daniela Lemos Córdoba, Anyi Katherine Mapura Benjumea and Mónica Margarita Barón Castro FACTORS AND CONCEPTS ASSOCIATED WITH THE INITIATION OF CIGARETTE CONSUMPTION IN UNIVERSITY STUDENTS OF PEREIRA, COLOMBIA ............................................................................... 113 Giovanni García Castro, Claudia Milena Bernal Parra, Natalia Cardona Arroyave, Brahiam Stiven Moreno Bustamante y Daniela Ospina Sierra CHAPTER 2 ECONOMIC, ADMINISTRATIVE AND ACCOUNTING SCIENCES TECHNICAL-FINANCIAL EVALUATION OF BEAN (PHASEOLUS VULGARIS) VARIETY CARGAMANTO IN THE VILLAGE OF THE MUNICIPALITY OF SIBUNDOY IN THE DEPARTMENT OF PUTUMAYO ................................................................................................ 131 Adriana María Cuervo Rubio, Alejandra Arango Baranza IMPLEMENTATION OF THE NIF IN MICRO-ENTERPRISES OF PEREIRA CITY ............................................................................................ 151 Laura Cortes Correa y Nataly Andrea Gutiérrez STRATEGIC FRAMEWORK FOR SUSTAINABLE PRODUCTION IN COLOMBIA................................................................................................... 163 Paulina Murillo Gómez, Manuela Ramírez Osorio, Laura Juliana Rodríguez Henao, Lindy Neth Perea Mosquera, Isabel Redondo Ramírez SUSTAINABLE INNOVATION IN MANUFACTURING INDUSTRY........... 179 Mariana Buitrago Zuleta, Laura Juliana Rodríguez Henao, Lindy Neth Perea Mosquera y Marlen Isabel Redondo Ramírez CHAPTER 3 ARTS, HUMANITIES AND SOCIAL SCIENCES PERSONAL AND FAMILY CHANGES OF UNDERGRADUATE PSYCHOLOGY STUDENTS. IS A PROGRAM IN PSYCHOLOGY A PATHWAY TO PERSONALAND FAMILY CHANGE?...................................197 Linda Michelle De La Torre Álvarez, Mireya Ospina Botero PREGNANT MOTHERS DEPRIVED OF LIBERTY IN COLOMBIA AND MEXICO. A LOOK FROM COMPARATIVE LAW .................................225 Mary Luz Vélez Cárdenas, Katherine Almanza Astrid Milena Calderón Cárdenas CHAPTER 4 NATURAL SCIENCES DIFFERENTIAL DIAGNOSIS AND TREATMENT OF CUTANEOUS LYMPHOMA VS MASTOCYTOMA IN A 9 YEARS OLD CANINE: CASE REPORT...................................................................................................241 Diana Patricia Diaz García, Stephany Loaiza Pulgarín, Rafael R. Santisteban Arenas y Juan C. Ramírez Ante CHAPTER 5 TECHNOLOGÍES AND ENGINEERING STUDY OF INVENTORY-ROUTING PROBLEM IRP.....................................257 Frank Alejandro Hincapié Londoño, Jhonatan Stiven García Guevara y Eliana Mirldey Toro Ocamp

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Gestión del conocimiento: perspectiva multidisciplinaria. Volumen 12

El libro “Gestión del Conocimiento. Perspectiva Multidisciplinaria”, Volumen 12, de la Colección Unión Global, es resultado de investigaciones. Los capítulos del libro, son resultados de investigaciones desarrolladas por sus autores. El libro cuenta con el apoyo de los grupos de investigación: Universidad Sur del Lago “Jesús María Semprúm” (UNESUR), Zulia – Venezuela; Universidad Politécnica Territorial de Falcón Alonso Gamero (UPTAG), Falcón – Venezuela; Universidad Politécnica Territorial de Mérida Kleber Ramírez (UPTM), Mérida – Venezuela; Universidad Guanajuato (UG) - Campus Celaya - Salvatierra - Cuerpo Académico de Biodesarrollo y Bioeconomía en las Organizaciones y Políticas Públicas (C.A.B.B.O.P.P), Guanajuato – México; Centro de Altos Estudios de Venezuela (CEALEVE), Zulia – Venezuela, Centro Integral de Formación Educativa Especializada del Sur (CIFE - SUR) - Zulia - Venezuela, Centro de Investigaciones Internacionales SAS (CIN), Antioquia - Colombia.y diferentes grupos de investigación del ámbito nacional e internacional que hoy se unen para estrechar vínculos investigativos, para que sus aportes científicos formen parte de los libros que se publiquen en formatos digital e impreso

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat