Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Central and Peripheral Immune Dysregulation in Posttraumatic Stress Disorder: Convergent Multi-Omics Evidence

Posttraumatic stress disorder (PTSD) is a chronic and multifactorial disorder with a prevalence ranging between 6–10% in the general population and ~35% in individuals with high lifetime trauma exposure. Growing evidence indicates that the immune system may contribute to the etiology of PTSD, suggesting the inflammatory dysregulation as a hallmark feature of PTSD. However, the potential interplay between the central and peripheral immune system, as well as the biological mechanisms underlying this dysregulation remain poorly understood. The activation of the HPA axis after trauma exposure and the subsequent activation of the inflammatory system mediated by glucocorticoids is the most common mechanism that orchestrates an exacerbated immunological response in PTSD. Recent high-throughput analyses in peripheral and brain tissue from both humans with and animal models of PTSD have found that changes in gene regulation via epigenetic alterations may participate in the impaired inflammatory signaling in PTSD. The goal of this review is to assess the role of the inflammatory system in PTSD across tissue and species, with a particular focus on the genomics, transcriptomics, epigenomics, and proteomics domains. We conducted an integrative multi-omics approach identifying TNF (Tumor Necrosis Factor) signaling, interleukins, chemokines, Toll-like receptors and glucocorticoids among the common dysregulated pathways in both central and peripheral immune systems in PTSD and propose potential novel drug targets for PTSD treatment

I. Conservación de grandes vertebrados en áreas no protegidas de Colombia, Venezuela y Brasil

Con esta publicación inicia de manera oficial la Serie Editorial “Fauna Silvestre Neotropical”, la cual abordará diferentes enfoques sobre los vertebrados del Neotrópico, sintetizando aspectos básicos de su conocimiento como la taxonomía y sistemática hasta la gestión y la toma de decisiones, pasando por la biogeografía, ecología, biología, genética, evolución, conservación in y ex situ, y uso y manejo de la fauna silvestre, entre otros.Bogotá, D. C., ColombiaInstituto de Investigación de Recursos Biológicos Alexander von Humbold

Biotecnología y sus aplicaciones en el sector salud

Este libro es el resultado de la ejecución del proyecto “Desarrollo de Capacidades Científicas y Tecnológicas Aplicadas a los Sectores de la Salud y la Agroindustria en el Departamento de Risaralda (2014-2019)” financiado por el Sistema General de Regalías. Contiene tres capítulos que abarcan desde la información básica asociada a los ácidos nucleicos, el estudio de las células madre, las proteínas y enzimas, para continuar con el uso de la biotecnología en procesos como la inmovilización de enzimas y la producción de proteínas recombinantes. Finalmente, el lector encontrará información relacionada a los múltiples usos de la biotecnología roja, con especial énfasis en aplicaciones clínicas de las células madre, los biomateriales, la metagenómica, la metabolómica, la producción de vacunas y finalmente, la importancia de las plantas medicinales como fuente de moléculas con actividad biológica (bioprospección). Los autores han tratado de presentar la información compleja de una manera sencilla y comprensible para el público en general y, por lo tanto, se considera que el libro podrá ser de utilidad para lectores de diversas disciplinas científicas, así como para estudiantes de pre y posgrado. Adicionalmente, el lenguaje empleado. permite convertir al libro en una guía para los docentes de la básica y la media, como texto para orientar los conceptos básicos y aplicaciones de la Biotecnología en sus estudiantes. Es importante mencionar que los autores realizaron un gran trabajo al elaborar sus propias figuras, excepto en los casos donde se indica la fuente a partir de la cual se realizó la modificación correspondiente.Resúmen del Contrato o Licitación Objeto Asesoría para definir e implementar un protocolo de identificación y colecta de micorrizadas en plantas del orden de las Zingiberales marco del programa Desarrollo de Capacidades Científicas y tecnológicas en biotecnología aplicada a los sectores de la salud y la agroindustria en el Departamento de Risaralda. Código BPIN 2012000100050 financiado con cargo a recursos del Sistema General de Regalías. Cuantia $2,500,000 Vigencia Proceso asignado o cerrado. No se aceptan nuevos aplicantes. Entidad RISARALDA - UNIVERSIDAD TECNOLÓGICA DE PEREIRAResúmenBuscar Estado CelebradoResúmenBuscar Tipo Régimen EspecialResúmenBuscar Tipo de Fecha Fecha de Celebración del Primer ContratoResúmenBuscar Fecha de Detección 2019-07-17 19:18:52 Cód. Secop 1 19-4-9710142 Número del Proceso ORDEN DE SERVICIOS 2061Sistema General de Regalías de ColombiaCONTENIDO INTRODUCCIÓN.................................................................................................8 CAPÍTULO 1.......................................................................................................10 GENERALIDADES O FUNDAMENTOS BÁSICOS..........................................11 La Biotecnología..................................................................................................11 Fermentaciones microbianas..............................................................................15 Enzimas: generalidades, aislamiento y purificación ..........................................27 El ácido desoxirribonucleico (ADN) ..................................................................53 Células madre: generalidades .............................................................................67 CAPÍTULO 2.......................................................................................................93 HERRAMIENTAS CLAVE EN LA BIOTECNOLOGÍA ....................................94 Inmovilización enzimática y sus aplicaciones....................................................94 Producción de proteínas recombinantes de interés farmacológico.................112 Bacteriocinas: péptidos bioactivos con propiedad antimicrobial ...................141 CAPÍTULO 3. ...................................................................................................175 APLICACIONES EN LA BIOTECNOLOGÍA MÉDICA .................................176 La biotecnología como herramienta para la generación de vacunas de uso humano y animal...............................................................................................176 Aplicaciones clínicas de las células madre y de productos de células madre...216 Biomateriales y su aplicación en el campo de la Salud.....................................282 Metagenómica y Metabolómica: Generalidades y Potencial en Salud Humana .............................................................................................................316 Plantas Medicinales...........................................................................................343 Actividad Biológica de Plantas de la Familia Bignoniaceae ............................35

II. Conflictos entre felinos y humanos en América Latina.

Este libro contó con el liderazgo del Instituto Humboldt y de las Fundaciones Herencia Ambiental Caribe y Panthera. En 32 capítulos se recoge el esfuerzo de 77 instituciones y 110 autores que representan 18 países y abordan el conflicto entre humanos y felinos en América Latina. Es la compilación más completa que se ha elaborado acerca del tema en Latinoamérica, involucrando el análisis, la planificación, el manejo y la resolución de los conflictos entre humanos y felinos.BogotáCiencias de la Biodiversida

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module

•We report INICC device-associated module data of 50 countries from 2010-2015.•We collected prospective data from 861,284 patients in 703 ICUs for 3,506,562 days.•DA-HAI rates and bacterial resistance were higher in the INICC ICUs than in CDC-NHSN's.•Device utilization ratio in the INICC ICUs was similar to CDC-NHSN's. Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically