75 research outputs found

    Peces de planicies de inundaciĂłn tropical de la cuenca baja del rĂ­o Magdalena, Colombia

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    We studied fish diversity and assessed determinant factors in the structure of fish assemblages captured in a tropical floodplain of the Magdalena River basin, Colombia. We identified that the fish richness reported in this study (43 species) corresponds to nearly 38 % of the diversity of the Magdalena River lower basin (112 species) and nearly 19 % of the total diversity of the Magdalena-Cauca system. The floodplains with greater connectivity among themselves and with the river presented more similar communities than the more distant and isolated habitats. Also, the structure of fish communities was determined by environmental conditions and habitat type in terms of connectivity. The environmental variables that most influenced community structure was associated to eutrophication processes, such as hardness, chlorides, nitrates, total nitrogen, total suspended solids and salinity, and to flow pulse such, such as depth, but the main regulating factor was the little or no connection between floodplains and the main channel of the Magdalena River. We considered that the information generated can be used to estimate the actual species composition of freshwater fishes, supporting decision-making by governmental entities, prioritize areas for biodiversity conservation, and/or contribute to the proper use and management of the natural resources present in this complex tropical lagoon system.Se estudió la diversidad de peces y se evaluaron los factores determinantes en la estructuración de los ensamblajes de peces capturados en una llanura de inundación tropical, de la cuenca del río Magdalena, Colombia. Se identificó que la riqueza íctica reportada en este estudio (43 especies) corresponde aproximadamente al 38 % de la diversidad de la cuenca baja del río Magdalena (112 especies) y a cerca del 19 % de la diversidad total del sistema Magdalena-Cauca. Las planicies con mayor conectividad entre sí y con el río presentaron comunidades más similares que los hábitats más distantes y aislados. Asimismo, la estructura de las comunidades de peces estuvo determinada por las condiciones del medio ambiente y el tipo de hábitat en términos de conectividad. Las variables ambientales que más influyeron en la estructura de las comunidades fueron las que estuvieron asociadas a procesos de eutrofización, tales como dureza, cloruros, nitratos, nitrógeno total, sólidos suspendidos totales y salinidad, y al pulso del caudal, como la profundidad, pero el principal factor de regulación fue la poca o nula conexión entre las zonas inundables y el cauce principal del rio Magdalena. Se considera que la información generada pueda ser empleada para estimar la composición real de especies de peces dulceacuícolas, sustentar la toma de decisiones por parte de las entidades gubernamentales, priorizar áreas para la conservación de la biodiversidad y/o contribuir al adecuado uso y manejo de los recursos naturales presentes en este complejo sistema lagunar tropica

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

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    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

    Investigation of the Differences in Activity between Hydroxycycloalkyl N1 Substituted Pyrazole Derivatives As Inhibitors of B-Raf Kinase by Using Docking, Molecular Dynamics, QM/MM, and Fragment-Based De Novo Design: Study of Binding Mode of Diastereomer Compounds

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    Caballero, J (Caballero, Julio)1; Alzate-Morales, JH (Alzate-Morales, Jans H.)1; Vergara-Jaque, A (Vergara-Jaque, Ariela)1. Addresses: 1. Univ Talca, Ctr Bioinformat & Simulac Mol, Talca, ChileN1 substituted pyrazole derivatives show diverse B-Raf kinase inhibitory activities when different hydroxy-substituted cycloalkyl groups are placed at this position. Docking, molecular dynamics (MD) simulations, and hybrid calculation methods (Quantum Mechanics/Molecular Mechanics (QM/MM)) were performed on the complexes, in order to explain these differences. Docking of the inhibitors showed the same orientation that X-ray crystal structure of the analogous (1E)-5-[1-(4-piperidinyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl]-2,3-dihydro-1H-inden-1-one oxirne. MD simulations of the most active diastereomer compounds containing cis- and trans-3-hydroxycyclohexyl substituents showed stable interactions with residue Ile463 at the entrance of the B-Raf active site. On the other hand, the less active diastereomer compounds containing cis- and trans-2-hydroxycyclopentyl substituents showed interactions with inner residues Asn580 and Ser465. We found that the differences in activity can be explained by considering the dynamic interactions between the inhibitors and their surrounding residues within the B-Raf binding site. We also explained the activity trend by using a testing scoring function derived from more reliable QM/MM calculations. In addition, we search for new inhibitors from a virtual screening carried out by fragment-based de novo design. We generated a set of approximately 200 virtual compounds, which interact with Ile463 and fulfill druglikeness properties according to Lipinski, Veber, and Chose rules

    Association of nicotinic acid with a poly(amidoamine) dendrimer studied by molecular dynamics simulations

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    Caballero, J (reprint author) Univ Talca, Ctr Bioinformat & Simulac Mol, 2 Norte 685,Casilla 721, Talca, Chile.The interaction of poly(amidoamine)-G3 (PAMAM-G3) dendrimer with nicotinic acid (NA) was investigated by using molecular dynamics (MD) simulations. First, sample free energy profiles of NA crossing PAMAM-G3 at pH 6 and 3 were computed using the adaptive biasing force (ABF) method. We found that PAMAM-G3 provides a more appropriate environment for NA inclusion when internal tertiary amine groups are unprotonated (at pH 6). However, when internal tertiary amine groups are protonated (at pH 3), the PAMAM cavities are less hydrophobic; therefore the drug-dendrimer interactions become similar to drug-solvent interactions. Traditional MD simulations were also performed to investigate the structural stability of the PAMAM-NA complexes near the free energy minima at pH 6. We found that association of NA and PAMAM adopts a preferred binding mode around the surface of PAMAM, where hydrogen bond (HB) interactions with the amino and amide NH groups of the nearby monomers are established. These interactions are very stable whether additional van der Waals interactions between pyridine ring of NA and methylene groups of the more external monomers of PAMAM are established. (C) 2012 Elsevier Inc. All rights reserved
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