La regulación del transporte de L-arginina vía HCAT-1 por insulina involucra activación diferencial de los subtipos A y B de receptores de insulina y receptores de adenosina en células endoteliales de vena umbilical humana de diabetes gestacional

Tesis descargada desde el repositorio de la Pontificia Universidad Católica de Chile: https://repositorio.uc.cl/handle/11534/4954Diabetes gestacional (DG) aumenta el transporte de L-arginina en la macrocirculación de la placenta. Insulina activa receptores de insulina (IRs) los cuales estimulan el transporte de Larginina via transportadores de aminoácidos catiónicos tipo 1 humano (hCAT-1) y la síntesis de óxido nítrico en células endoteliales de la vena umbilical humana (HUVEC) de embarazos normales, pero reduce el aumento inducido por DG sobre el transporte de L-arginina. Este efecto de insulina podría resultar de una expresión y activación diferencial de las isoformas A (IR-A) y B (IR-B) del receptor de insulina, involucrando mecanismos transcripcionales asociadas a la activación de la proteína específica 1 (Sp1). Como se ha propuesto que los efectos biológicos de insulina son regulados por receptores de adenosina, en este estudio se analizó si el aumento de la expresión y actividad de hCAT-1 causado por DG es bloqueado por insulina mediante activación diferencial de IR-A y/o IR-B, un mecanismo regulado por activación de receptores de adenosina en cultivos primarios de HUVEC. La actividad del transporte de L-arginina, la expresión de hCAT-1 y la unión de Sp1 están aumentadas en DG, efecto que es revertido por insulina. El efecto de insulina en DG requirió de la actividad de receptores de adenosina A1, un fenotipo que fue similar al observado en células knock-down para IR-B. En HUVEC normales, insulina aumentó la actividad del transporte de L-arginina, la expresión de hCAT-1 y la unión de Sp1 al promotor de SLC7A1, efectos que requirieron de la actividad del receptor de adenosina A2A. Sin embargo, el efecto de insulina fue bloqueado en HUVEC knock-down para IR-A y/o IRB. En conclusión, insulina revierte el efecto de diabetes gestacional vía IR-A sobre la actividad y expresión de hCAT-1, un mecanismo dependiente de receptores de adenosina A1 en HUVEC de DG. Sin embargo, insulina aumenta la actividad y expresión de hCAT-1, dependiendo de la actividad de receptores de adenosina A2A en HUVEC de embarazos normales.Gestational diabetes (GD) increases L-arginine transport in the placenta macrocirculation. Insulin activates insulin receptors (IRs) which stimulate L-arginine transport via human cationic amino acids transporters type 1 (hCAT-1) and nitric oxide synthesis in human umbilical vein endothelial cells (HUVEC) from normal pregnancies, but insulin reduces GD-increase Larginine transport. This insulin effect could be a result of differential expression and activation of the insulin receptor isoforms A (IR-A) and B (IR-B), involving transcriptional mechanisms associated with specific protein 1 (Sp1). As it has been proposed that the biological effects of insulin are regulated by adenosine receptors, in this study we analized whether insulin reverses GD-increase hCAT-1 activity and expression through differential IR-A and/or IR-B activation amd this mechanism is regulated by adenosine receptors in HUVEC. Herein, we demonstrated that L-arginine transport activity, hCAT-1 expression and Sp1-binding to promotor SLC7A1 are increased in GD, effects reverse by insulin. This insulin effect requires A1 adenosine receptor activity in GD, a phenotype that was similarly observed in cells knocked-down for IR-B. In normal HUVEC, insulin increased L-arginine activity, hCAT-1 expression and Sp1-binding to promotor SLC7A1, effects that required adenosine receptor A2A activity. However, these insulin effects were blocked in HUVEC knock-down for IR-A and/or IR-B. In conclusion, insulin via IR-A reverses the GD-increase in hCAT-1 activity and expression, a mechanism that is A1- adenosine receptor dependent in GD derived cells. However, insulin increases hCAT-1 activity and expression, through an A2A-adenosine receptor dependent mechanism in HUVEC from normal pregnancies

Mycobacterium tuberculosis TLR2 agonists LprA, LM and Man-LAM induce notch1 and socs3 transcription

"Mycobacterium tuberculosis employs a number of strategies to subvert host signaling events, leading to its persistence within macrophages. Upon infection, Mycobacterium bovis BCG induce the expression of suppressor of cytokine signaling 3 (socs3), in a Toll-like receptor 2 (TLR2)-Notch1-dependent manner. Purified phosphatidyl inositol di-mannosides (a TLR2 agonist) act as an inducer for the Notch1-socs3 pathway. This prompted us to analyze other TLR2 agonists seeking for additional molecules that may affect this pathway. We found that lipoprotein LprA, as well as glycolipids lipomannan (LM), and mannose-capped lipoarabinomannan (ManLAM) treatment of murine macrophages resulted in stimulation of notch1 and socs3 transcription.

Colombian consensus recommendations for diagnosis, management and treatment of the infection by SARS-COV-2/ COVID-19 in health care facilities - Recommendations from expert´s group based and informed on evidence

La Asociación Colombiana de Infectología (ACIN) y el Instituto de Evaluación de Nuevas Tecnologías de la Salud (IETS) conformó un grupo de trabajo para desarrollar recomendaciones informadas y basadas en evidencia, por consenso de expertos para la atención, diagnóstico y manejo de casos de Covid 19. Estas guías son dirigidas al personal de salud y buscar dar recomendaciones en los ámbitos de la atención en salud de los casos de Covid-19, en el contexto nacional de Colombia

5to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

El V Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2019, realizado del 6 al 8 de febrero de 2019 y organizado por la Universidad Politécnica Salesiana, ofreció a la comunidad académica nacional e internacional una plataforma de comunicación unificada, dirigida a cubrir los problemas teóricos y prácticos de mayor impacto en la sociedad moderna desde la ingeniería. En esta edición, dedicada a los 25 años de vida de la UPS, los ejes temáticos estuvieron relacionados con la aplicación de la ciencia, el desarrollo tecnológico y la innovación en cinco pilares fundamentales de nuestra sociedad: la industria, la movilidad, la sostenibilidad ambiental, la información y las telecomunicaciones. El comité científico estuvo conformado formado por 48 investigadores procedentes de diez países: España, Reino Unido, Italia, Bélgica, México, Venezuela, Colombia, Brasil, Estados Unidos y Ecuador. Fueron recibidas un centenar de contribuciones, de las cuales 39 fueron aprobadas en forma de ponencias y 15 en formato poster. Estas contribuciones fueron presentadas de forma oral ante toda la comunidad académica que se dio cita en el Congreso, quienes desde el aula magna, el auditorio y la sala de usos múltiples de la Universidad Politécnica Salesiana, cumplieron respetuosamente la responsabilidad de representar a toda la sociedad en la revisión, aceptación y validación del conocimiento nuevo que fue presentado en cada exposición por los investigadores. Paralelo a las sesiones técnicas, el Congreso contó con espacios de presentación de posters científicos y cinco workshops en temáticas de vanguardia que cautivaron la atención de nuestros docentes y estudiantes. También en el marco del evento se impartieron un total de ocho conferencias magistrales en temas tan actuales como la gestión del conocimiento en la universidad-ecosistema, los retos y oportunidades de la industria 4.0, los avances de la investigación básica y aplicada en mecatrónica para el estudio de robots de nueva generación, la optimización en ingeniería con técnicas multi-objetivo, el desarrollo de las redes avanzadas en Latinoamérica y los mundos, la contaminación del aire debido al tránsito vehicular, el radón y los riesgos que representa este gas radiactivo para la salud humana, entre otros

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

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

FIREARM INJURIES IN THE SPINE. EFFECTIVE STRATEGY FOR DIAGNOSIS AND TREATMENT

The incidence of gunshot wounds to the spine on civilians has increased alarmingly and accounts for 13% to 17% of all traumatic spinal injuries, placing them in third place among the most frequent mechanisms. However, the management of these injuries is still controversial. At present there is little information on the management of these lesions, conservative treatment (non-surgical) being recommended in most publications. Based on the current literature, we propose a procedural protocol aimed at improving the quickness of management, as well as the prognosis of the patient. For this purpose, once the patient is hemodynamically stabilized, the following should be assessed: 1) Stability; 2) Compressive extrusion; 3) Accommodation or not in the discal space, and 4) Contact with CSF. These points are relevant to make the best decision

Fungal Alcohol Dehydrogenases: Physiological Function, Molecular Properties, Regulation of Their Production, and Biotechnological Potential

Fungal alcohol dehydrogenases (ADHs) participate in growth under aerobic or anaerobic conditions, morphogenetic processes, and pathogenesis of diverse fungal genera. These processes are associated with metabolic operation routes related to alcohol, aldehyde, and acid production. The number of ADH enzymes, their metabolic roles, and their functions vary within fungal species. The most studied ADHs are associated with ethanol metabolism, either as fermentative enzymes involved in the production of this alcohol or as oxidative enzymes necessary for the use of ethanol as a carbon source; other enzymes participate in survival under microaerobic conditions. The fast generation of data using genome sequencing provides an excellent opportunity to determine a correlation between the number of ADHs and fungal lifestyle. Therefore, this review aims to summarize the latest knowledge about the importance of ADH enzymes in the physiology and metabolism of fungal cells, as well as their structure, regulation, evolutionary relationships, and biotechnological potential

New insights into the methylation of mycobacterium tuberculosis heparin binding hemagglutinin adhesin expressed in rhodococcus erythropolis

In recent years, knowledge of the role that protein methylation is playing on the physiopathogenesis of bacteria has grown. In Mycobacterium tuberculosis, methylation of the heparin binding hemagglutinin adhesin modulates the immune response, making this protein a subunit vaccine candidate. Through its C-terminal lysine-rich domain, this surface antigen interacts with heparan sulfate proteoglycans present in non-phagocytic cells, leading to extrapulmonary dissemination of the pathogen. In this study, the adhesin was expressed as a recombinant methylated protein in Rhodococcus erythropolis L88 and it was found associated to lipid droplets when bacteria were grown under nitrogen limitation. In order to delve into the role methylation could have in host–pathogen interactions, a comparative analysis was carried out between methylated and unmethylated protein produced in Escherichia coli. We found that methylation had an impact on lowering protein isoelectric point, but no differences between the proteins were found in their capacity to interact with heparin and A549 epithelial cells. An important finding was that HbhA is a Fatty Acid Binding Protein and differences in the conformational stability of the protein in complex with the fatty acid were observed between methylated and unmethylated protein. Together, these results suggest that the described role for this mycobacteria protein in lipid bodies formation could be related to its capacity to transport fatty acids. Obtained results also provide new clues about the role HbhA methylation could have in tuberculosis and point out the importance of having heterologous expression systems to obtain modified proteins