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ÍtemSolo MetadatosATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure(2019) Delcour C.; Amazit L.; Patino L.C.; Magnin F.; Fagart J.; Delemer B.; Young J.; Laissue P.; Binart N.; Beau I.Purpose: Primary ovarian insufficiency (POI) is a frequent disorder that affects ~1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone (FSH), leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene variants, most cases remain idiopathic. The aim of the present study was to identify and validate functionally new sequence variants in ATG (autophagy-related genes) leading to POI. Methods: We have reanalyzed, in silico, the exome sequencing data from a previously reported work performed in 69 unrelated POI women. Functional experiments using a classical hallmark of autophagy, the microtubule-associated protein 1 light chain 3? (LC3), were then used to link these genes to this lysosomal degradation pathway. Results: We venture a functional link between ATG7 and ATG9A variants and POI. We demonstrated that variant ATG7 and ATG9A led to a decrease in autophagosome biosynthesis and consequently to an impairment of autophagy, a key biological process implicated in the preservation of the primordial follicles forming the ovarian reserve. Conclusion: Our results unveil that impaired autophagy is a novel pathophysiological mechanism involved in human POI. © 2018, American College of Medical Genetics and Genomics.- ÍtemSolo MetadatosDid Mozart Suffer from Gilles de la Tourette Syndrome?(2017) Palacios Sánchez, Leonardo; Botero Meneses, Juan Sebastián; Vergara-Méndez L.D.; Pachón N.; Martínez A.; Ramírez Clavijo, Sandra RocíoThe personal and private lives of great men and women in history, like writers, painters and musicians, have been the subject of great interest for many years. A clear example of this is the vast scrutiny is cast over the famous composer, Wolfgang Amadeus Mozart. What may have started as curiosity, rapidly evolved into extensive research, as the answers about the musician's legendary talent may lie in the details of his life (his childhood, his relationships, his quirks and his mannerisms). It is usually up to historians, anthropologists or philosophers to delve into the pages of old books, trying to grasp answers and clues. However, for some time, Physicians have sought their own part in solving the puzzle. The long told hypothesis regarding Mozart's diagnosis of Gilles de la Tourette syndrome will be examined. Could all of the peculiarities and oddities of the genius be caused by a neurological disorder? Or was this musical genius just an eccentric brilliant man?. © 2016 Asociación Colombiana de Psiquiatría
- ÍtemSolo MetadatosTemporal gene expression in the hippocampus and peripheral organs to endotoxin-induced systemic inflammatory response in caspase-1-deficient mice(2015) Mastronardi, Claudio Alberto; Paz-Filho, Gilberto; Zanoni, Martina; Molano González, Nicolás; Arcos-Burgos, Mauricio; Licinio, Julio; Wong, Ma-LiObjectives: Caspase-1 (casp1), a key protease involved in the systemic inflammatory response syndrome (SIRS), controls the brain expression of a set of eight genes: Nos2 and Ptgs2 (nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, two inducible enzymes), Cxcl1 and Cxcl10 (C-X-C motif chemokine ligand 1 and ligand 10), Tgtp and Gbp2 (T cell-specific GTPase 1 and guanylate-binding protein 2, two GTPases), Adamts1 (a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 1, a metalloprotease) and Il1rn (interleukin-1 receptor antagonist). Our objective was to ascertain whether casp1 also controlled the peripheral expression of these genes and, if so, to compare their central versus peripheral patterns of gene expression in immune and endocrine tissues during SIRS. Methods: Wild-type (wt) and casp1 knockout (casp1-/-) mice were injected with either saline or a high dose of endotoxin/lipopolysaccharide (LPS; 800 ?g/mice i.p.). Saline-injected mice were immediately euthanized after injection, whereas LPS-injected mice were sacrificed 6 and 12 h after LPS administration. Hippocampal, splenic and adrenal gene expressions were determined by real-time PCR. Results: Overall, casp1-/- mice showed a lower inflammatory response than wt mice. The expression levels of powerful proinflammatory factors such as Nos2 and Ptgs2 was reduced in casp1-/- mice. Moreover, a hierarchical clustering analysis aimed at studying patterns of gene coexpression revealed large alterations in the hippocampal pattern of casp1-/- mice. Surprisingly, the expression of Adamts1 was increased in the hippocampus and adrenals of casp1-/- mice. Conclusions: The resilience of casp1-/- mice to SIRS lethality is associated with a lower inflammatory response, loss of hippocampal gene coexpression patterns, and increased hippocampal Adamts1 gene expression. The latter might be beneficial for casp1-/- mice, since ADAMTS1 is likely to play a role in neuronal plasticity. The mechanisms described here may help the development of either novel biomarkers or therapeutic targets against SIRS/sepsis. © 2015 S. Karger AG, Basel.
- ÍtemSolo MetadatosHistidine-tryptophan-ketoglutarate solution versus blood cardioplegia in cardiac surgery: A propensity-score matched analysis(2018) Pizano, Alejandro; Montes, Felix Ramon; Carreño, Marisol; Echeverri, Dario; Umaña, Juan PabloBackground: Choosing a cardioplegic solution is a significant issue in modern cardiac surgery. Although different options are available, the optimal strategy for myocardial protection has not been established. The aim of this study was to compare intraoperative and postoperative effects of histidine–tryptophan–ketoglutarate (HTK) solution with those of standard blood cardioplegia with St Thomas No 2 solution. The study was conducted using a large cohort of adult patients undergoing complex cardiac surgery. Methods: This study was a single center retrospective review of prospectively collected data. Between January 2008 and December 2015, 4480 patients underwent cardiac surgery using cardiopulmonary bypass (CPB) and cardioplegic arrest. Patients were divided into a blood cardioplegia group (n = 3852) and an HTK solution group (n = 628). Propensity score matching was used to adjust for differences between the two groups, and 292 matched pairs were identified. The primary end point was Intensive Care Unit (ICU) length of stay (LOS). Secondary end points included intraoperative changes in serum sodium concentration, readmission to ICU, transfusion of blood products, 30-day hospital readmission, 30-day mortality, and the incidence of major postoperative complications. Results: No significant differences were found between the matched groups with regard to baseline characteristics. Aortic cross-clamp and CPB times were longer for the blood cardioplegia (147.4 versus 132.8 min; P less than .001). Administration of HTK solution was associated with acute and transient hyponatremia (141 versus 130 mmol/L; P less than .001). ICU LOS was comparable between the groups (5.4 versus 5.4 days; P = .585). No significant differences were noted in any other secondary end point. Conclusions: During complex cardiac surgery, both cardioplegia techniques were equivalent in terms of early clinical outcomes. © 2018 Forum Multimedia Publishing, LLC.
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Factors associated with the onset of mediastinitis in 2073 myocardial revascularizations(2014) Parada, Julián M.; Carreño, Marisol; Camacho, Jaime; Sandoval, Néstor F.; Umaña, Juan P.Introduction: Mediastinitis is a multifactorial entity which occurs in up to 4% of patients undergoing coronary artery bypass graft (CABG). It has a hospital mortality of 14% to 47%, which generates increased costs of care and deterioration of the quality of life and patient survival in the long term. Objective: To determine which clinical antecedents and factors related to the surgical procedure are associated with the occurrence of mediastinitis. Materials and methods: A nested case control study in a historical cohort of patients undergoing CABG in the period January 2005 to July 2011. Patients with mediastinitis were compared with a control group without mediastinitis taken from the same risk group in a 1:4 ratio and matched for date of surgery. The diagnosis of mediastinitis was made on clinical and laboratory criteria and surgical findings. Results: Thirty cases were identified in the related period. Factors associated with the occurrence of the event were: diabetes mellitus OR 2.3 (1.1 to 4.9), use of extracorporeal circulation OR 2.4 (1.1-5.5), OR 1 perfusion time, 1 (1.1 to 1.3) and patients older than 70 years OR 1.1 (1.2-1.4). Conclusions: Mediastinitis remains complications of low prevalence with devastating consequences. The clinical and economic impact of this complication should compel surgical groups to create prevention strategies based on knowledge of the risk factors of the population. © 2012 Sociedad Colombiana de Cardiología y Cirugía Cardiovascular. Published by Elsevier España, S.L. All rights reserved. - ÍtemSolo MetadatosTemozolomide down-regulates P-glycoprotein in human blood-brain barrier cells by disrupting Wnt3 signaling(2014) Riganti, Chiara; Salaroglio, Iris C.; Pinzòn-Daza, Martha L.; Caldera, Valentina; Campia, Ivana; Kopecka, Joanna; Mellai, Marta; Annovazzi, Laura; Couraud, Pierre-Olivier; Bosia, Amalia; Ghigo, Dario; Schiffer, DavideLow delivery of many anticancer drugs across the blood-brain barrier (BBB) is a limitation to the success of chemotherapy in glioblastoma. This is because of the high levels of ATP-binding cassette transporters like P-glycoprotein (Pgp/ABCB1), which effluxes drugs back to the bloodstream. Temozolomide is one of the few agents able to cross the BBB; its effects on BBB cells permeability and Pgp activity are not known. We found that temozolomide, at therapeutic concentration, increased the transport of Pgp substrates across human brain microvascular endothelial cells and decreased the expression of Pgp. By methylating the promoter of Wnt3 gene, temozolomide lowers the endogenous synthesis of Wnt3 in BBB cells, disrupts the Wnt3/glycogen synthase kinase 3/?-catenin signaling, and reduces the binding of ?-catenin on the promoter of mdr1 gene, which encodes for Pgp. In co-culture models of BBB cells and human glioblastoma cells, pre-treatment with temozolomide increases the delivery, cytotoxicity, and antiproliferative effects of doxorubicin, vinblastine, and topotecan, three substrates of Pgp that are usually poorly delivered across BBB. Our work suggests that temozolomide increases the BBB permeability of drugs that are normally effluxed by Pgp back to the bloodstream. These findings may pave the way to new combinatorial chemotherapy schemes in glioblastoma. © 2013 Springer Basel.
- ÍtemSolo MetadatosExperimental intra-abdominal hypertension influences airway pressure limits for lung protective mechanical ventilation(2013) Cortes-Puentes, Gustavo A.; Cortes-Puentes, Luis A.; Adams, Alexander B.; Anderson, Christopher P.; Marini, John J.; Dries, David J.BACKGROUND: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) may complicate monitoring of pulmonary mechanics owing to their impact on the respiratory system. However, recommendations for mechanical ventilation of patients with IAH/ACS and the interpretation of thoracoabdominal interactions remain unclear. Our study aimed to characterize the influence of elevated intra-abdominal pressure (IAP) and positive end-expiratory pressure (PEEP) on airway plateau pressure (PPLAT) and bladder pressure (PBLAD). METHODS: Nine deeply anesthetized swineweremechanically ventilated via tracheostomy: volume-controlled mode at tidal volume (VT) of 10mL/kg, frequency of 15, inspiratory-expiratory ratio of 1:2, and PEEP of 1 and 10 cm H2O (PEEP1 and PEEP10, respectively). A tracheostomy tube was placed in the peritoneal cavity, and IAP levels of 5, 10, 15, 20, and 25 mm Hg were applied, using a continuous positive airway pressure system. At each IAP level, PBLAD and airway pressure measurements were performed during both PEEP1 and PEEP10. RESULTS: PBLAD increased as experimental IAP rose (y = 0.83x + 0.5; R2 = 0.98; p G 0.001 at PEEP1). Minimal underestimation of IAP by PBLAD was observed (j2.5 T 0.8 mm Hg at an IAP of 10-25 mm Hg). Applying PEEP10 did not significantly affect the correlation between experimental IAP and PBLAD. Approximately 50% of the PBLAD (in cm H2O) was reflected by changes in P PLAT, regardless of the PEEP level applied. Increasing IAP did not influence hemodynamics at any level of IAP generated. CONCLUSION: With minimal underestimation, PBLAD measurements closely correlated with experimentally regulated IAP, independent of the PEEP level applied. For each PEEP level applied, a constant proportion (approximately 50%) of measured PBLAD (in cm H2O) was reflected in PPLAT. A higher safety threshold for PPLAT should be considered in the setting of IAH/ACS as the clinician considers changes in VT. A strategy of reducing V T to cap PPLAT at widely recommended values may not be warranted in the setting of increased IAP. Copyright © 2013 Lippincott Williams and amp; Wilkins.
- ÍtemAcceso AbiertoPerception of violence from schoolchildren of two educational institutions in the locality of Kennedy, Bogotá(2018) Barreto Zorza, Yenny Marcela; Enriquez-Guerrero C.; Cordoba-Sastoque A.M.; Rincon-Garcia K.P.; Bustos-Sanchez J.D.; Lopez-Bernal A.S.; Mendez-Rivas D.; Rincon-Lopez J.V.Objective To describe the perception of violence in schoolchildren of two schools of the borough of Kennedy, Bogotá. Methods Participatory action research (PAR) and qualitative study. The participants in these focus groups were chosen randomly, 5 students per course, for a total of 15 focus groups and 75 students included, prior informed consent from parents and students. Ethical aspects were taken into account. Results 61 participants, 30 boys (49.1%) and 31 girls (50.8%), were included in the study, with an age range between 5 and 12 years. 10 participants (16.3%) were kindergarten students, 3 were first-grade students (4.9%), 10 second-grade students (16.3%), 18 third-grade students (29.5%), 10 fourth-grade students (16.3%), and 10 fifth-grade students (16.3%). The socioeconomic status of the children was ranked as 1 and 2. The results are presented in four categories: causes, problems, consequences and solutions, from which 8 subcategories emerged; they describe the perception that children have about violence at home and schools, highlighting physical and verbal domestic violence, the use of psychoactive substances and sexual abuse. Conclusion There is evidence in the school population of the borough of Kennedy that violence is a public health problem established in homes and in schools. The origin of this violence is mainly children's homes, therefore, it is important to build and generate proposals for intervention based on the solutions raised by the children themselves regarding the structural and family levels. © 2018, Universidad Nacional de Colombia. All rights reserved.
- ÍtemAcceso AbiertoImpact of smoking and physical inactivity on self-rated health in women in Colombia(2019) Romero, Dario Mendoza; Montenegro, Amparo Cristancho; Urbina Bonilla, Adriana del Pilar; Rombaldi, AirtonThe aim of this study was to assess the association between poor and fair self-rested health, smoking, and leisure-time physical inactivity in Colombian women. A cross-sectional study using the data from the 2010 Colombian National Demographics and Health (ENDS) and Nutritional Situation (ENSIN) Surveys was conducted. Multivariate logistic analysis for self-perceived health status in 12,431 women aged 13–49 years old and 8224 women aged 18–64 years old were performed. Independent variables included smoking, leisure-time physical inactivity, anthropometric and socio-demographic information. Current smoking and leisure-time physical inactivity were associated with poor and fair self-rated health status (OR 1.78, CI 1.41, 2.25; OR 1.30, CI 1.03, 1.62; respectively). Other significantly associated variables were age (OR 1.68, CI 1.46, 1.92 for 30–49 years; OR 2.32, CI 1.96, 2.74 for 50–64 years), socio-economic strata (OR 7.24, CI 3.81, 13.76 for strata 1–3), educational level (OR 1.70 to 2.77 compared to technical or university), obesity (OR 0.81, CI 0.70, 0.93 for normal body mass index), geographical region (OR 0.67, CI 0.53, 0.85 for Bogotá, compared to Amazon and Orinoco regions), and no affiliation to health system (OR 1.22, CI 1.03, 1.44). Smoking and leisure-time physical inactivity were significantly associated with poor and fair self-rated health in Colombian women. Promoting leisure-time physical activity and implementing smoking cessation strategies specifically in female population, mainly from low to medium strata are suggested to improve their self-perceived health status and control chronic noncommunicable diseases. © 2019
- ÍtemSolo MetadatosPrevalence of delayed neurodevelopment in children from Bogotá, Colombia, South America(2007) Vélez van Meerbeke, Alberto Francisco; Talero Gutiérrez, Claudia; González Reyes, Rodrigo EstebanBackground: Undiagnosed children with neurodevelopment delay disorders (NDD) frequently experience school difficulties, leading to school desertion or academic failure with subsequent familial, social and work-related problems. Methods: In 2004-2005, we conducted a cross-sectional study to determine the prevalence of developmental delay among preschoolers in Bogotá (Colombia); convenience samples in several socioeconomic areas of the city were screened to define the prevalence of NDD. Parents and teachers were interviewed to identify children with possible NDD. Selected children were evaluated with a neurodevelopmental abbreviated scale (EAD-1). Results: We screened 2,043 preschool children aged less than 60 months; 288 suspected cases were examined individually using the EAD-1 scale. One or more abnormal items (alert category) were found in 67 (23.3%) children, for an estimated prevalence of 32.8‰ children less than 5 years of age, including deficits in gross motor function (9.3‰), personal-social interactions (9.8‰), fine motor skills (10.3‰), auditory language delay (18.6‰) and overall delay (10.8‰). Conclusions: There is limited information regarding the prevalence of neurodevelopmental delay in nonindustrialized countries. The prevalence obtained in Bogotá, Colombia, is within the expected range; however, we identified NDD among apparently healthy children from nurseries and kindergartens, who had previously been undiagnosed and untreated. Lack of evaluation of developmental milestones in children in Colombia is a substantial public health problem that will require effective intervention. Copyright © 2007 S. Karger AG.
