DCACA. Artículos de Investigación

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  • Publicación
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    Artificial Intelligence and Quantum Computing as the Next Pharma Disruptors
    (2021-11-04) Cova, Tânia; Vitorino, Carla; Ferreira, Márcio; Nunes, Sandra; Rondon-Villarreal, Paola; Pais, Alberto
    Artificial intelligence (AI) consists of a synergistic assembly of enhanced optimization strategies with wide application in drug discovery and development, providing advanced tools for promoting cost-effectiveness throughout drug life cycle. Specifically, AI brings together the potential to improve drug approval rates, reduce development costs, get medications to patients faster, and help patients complying with their treatments. Accelerated pharmaceutical development and drug product approval rates can further benefit from the quantum computing (QC) technology, which will ultimately enable larger profits from patent-protected market exclusivity. Key pharma stakeholders are endorsing cutting-edge technologies based on AI and QC , covering drug discovery, preclinical and clinical development, and postapproval activities. Indeed, AI-QC applications are expected to become standard in the pharma operating model over the next 5–10 years. Generalizing scalability to larger pharmaceutical problems instead of specialization is now the main principle for transforming pharmaceutical tasks on multiple fronts, for which systematic and cost-effective solutions have benefited in areas such as molecular screening, synthetic pathway design, and drug discovery and development. The information generated by coupling the life cycle of drugs and AI and/or QC through data-driven analysis, neural network prediction, and chemical system monitoring will enable (1) better understanding of the complexity of process data, (2) streamlining the design of experiments, (3) discovering new molecular targets and materials, and also (4) planning or rethinking upcoming pharmaceutical challenges The power of AI-QC makes accessible a range of different pharmaceutical problems and their rationalization that have not been previously addressed due to a lack of appropriate analytical tools, demonstrating the breadth of potential applications of these emerging multidimensional approaches. In this context, creating the right AI-QC strategy often involves a steep learning path, especially given the embryonic stage of the industry development and the relative lack of case studies documenting success. As such, a comprehensive knowledge of the underlying pillars is imperative to extend the landscape of applications across the drug life cycle. The topics enclosed in this chapter will focus on AI-QC methods applied to drug discovery and development, with emphasis on the most recent advances in this field.
  • Publicación
    Acceso abierto
    Role of Spanish Toddlers’ Education and Care Institutions in Achieving Physical Activity Recommendations in the COVID-19 Era. A Cross-Sectional Study
    (2022-01-03) Vega-Perona, Herminia; Estevan, Isaac; García-Ochoa, Yolanda Cabrera; Martínez-Bello, Daniel A.; Bernabé-Villodre, María del Mar; Martínez-Bello, Vladimir E.; CliniUDES
    To our knowledge, there are no published studies that describe the physical activity (PA) levels and objectively measure them through accelerometry in toddlers (2–3 years old) attending early childhood education and care (ECEC) institutions during the COVID-19 pandemic. The aims of this study were two-fold: (a) to analyse toddlers’ PA levels and sedentary behaviour (SB) during school hours in ECEC institutions, as well as the rate of adherence to specific recommendations on total PA (TPA) and moderate–vigorous PA (MVPA); and (b) to evaluate the characteristics correlates (age, gender, and body mass index –BMI) of young children and the school environment on toddlers’ TPA, light PA (LPA), MVPA, and SB during school hours in ECEC institutions. PA was evaluated with ActiGraph accelerometers. The main findings were that: (a) toddlers engaged in very high amounts of TPA and MVPA during ECEC hours; (b) girls and boys displayed similar levels of LPA, TPA, and SB, while girls had lower levels of MVPA, compared to boys, and younger toddlers were less active than older ones; (c) BMI was not associated with PA of any intensity or SB; (d) playground and classroom density were not associated with higher levels of PA of any intensity, though classroom density was associated with SB. These ECEC institutions provide and challenge the new COVID-19 scenario, as well as supportive environments for toddlers’ PA
  • Publicación
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    Enteroinvasive Escherichia coli O96:H19 is an Emergent Biofilm-Forming Pathogen
    (2022-03-28) Iqbal, Junaid; Malviya, Niharika; Gaddy, Jennifer A.; Zhang, Chengxian; Seier, Andrew J.; Haley, Kathryn P.; Doster, Ryan S.; Farfan-Garcia, Ana Elvira; Gómez-Duarte, Oscar G.; CliniUDES
    Enteroinvasive Escherichia coli (EIEC) is a diarrheagenic E. coli pathotype carrying a virulence plasmid that encodes a type III secretion system (TTSS) directly implicated in bacterial cell invasion. Since 2012, EIEC serotype O96:H19 has been recognized in Europe, Colombia, and most recently Uruguay. In addition to the invasion phenotype, the strains isolated from Colombian children with moderate-to-severe gastroenteritis had a strong biofilm formation phenotype, and as a result, they are referred to as biofilm-forming enteroinvasive E. coli (BF-EIEC). The objective of this study was to characterize the biofilm formation phenotype of the BF-EIEC O96:H19 strain 52.1 isolated from a child with moderate-to-severe gastroenteritis in Colombia. Random mutagenesis using Tn5 transposons identified 100 mutants unable to form biofilm; 20 of those had mutations within the pgaABCD operon. Site-directed mutagenesis of pgaB and pgaC confirmed the importance of these genes in N-acetylglucosamine-mediated biofilm formation. Both biofilm formation and TTSS-mediated host cell invasion were associated with host cell damage on the basis of cytotoxic assays comparing the wild type, invasion gene mutants, and biofilm formation mutants. Multilocus sequence typing-based phylogenetic analysis showed that BF-EIEC strain 52.1 does not cluster with classic EIEC serotype strains. Instead, BF-EIEC strain 52.1 clusters with EIEC serotype O96:H19 strains described in Europe and Uruguay. In conclusion, BF-EIEC O96:H19, an emerging pathogen associated with moderate-to-severe acute gastroenteritis in children under 5 years of age in Colombia, invades cells and has a strong biofilm formation capability. Both phenotypes are independently associated with in vitro cell cytotoxicity, and they may explain, at least in part, the higher disease severity reported in Europe and Latin America. IMPORTANCE Enteroinvasive Escherichia coli (EIEC), a close relative of Shigella, is implicated in dysenteric diarrhea. EIEC pathogenicity involves cell invasion mediated by effector proteins delivered by a type III secretion system (TTSS) that disrupt the cell cytoskeleton. These proteins and the VirF global regulator are encoded by a large (>200 kb) invasion plasmid (pINV). This study reports an emergent EIEC possessing a cell invasion phenotype and a strong polysaccharide matrix-mediated biofilm formation phenotype. Both phenotypes contribute to host cell cytotoxicity in vitro and may contribute to the severe disease reported among children and adults in Europe and Latin America.
  • Publicación
    Acceso abierto
    Cardiovascular Risk Factors in Colombian Penitentiary Staff. An Interdisciplinary View of a High-Risk Occupation
    (2021-09-16) Contreras-Ramos, Luz Mery; Dominguez-Amorocho, Omar Alberto; CliniUDES
    Introduction: Cardiovascular risk factors have been measured under different conditions, there is some missing information related to specific occupations, such as penitentiary staff which due to their characteristics could have an increased cardiovascular risk. Objective: To determine cardiovascular risk factors on military staff from penitentiary institutions in Santander—Colombia. Methods: Cross-sectional study conducted with 182 workers. Anthropometric parameters, blood pressure, serum lipid profile, and glucose levels were measured. Univariate and bivariate analyses were carried out to establish differences between individuals. Results: Anthropometric and biochemical measures showed that 71.3% participants were overweight or obese, 29.4% presented high blood pressure with increased levels of total cholesterol (27.5%), triglycerides (40.7%), glucose (9.3%), and 84.1% presented low levels of HDL cholesterol. Bivariate analysis found a negative correlation between BMI and HDL cholesterol (p < .05) and a positive correlation between BMI with triglycerides (p < .01), systolic and diastolic blood pressure (DBP) (p < .01). Conclusion: The studied military population presented increased levels of cardiovascular risk in comparison with a similar group in age, gender of nonmilitary individuals. However, it is important to carry out comparative studies between military staff in order to determine the prevalence and other risk predicting factors present in this specific population.
  • Publicación
    Acceso abierto
    Mecanismos de acción de péptidos antimicrobianos ib-m contra escherichia coli. un estudio estructural y proteómico
    (2021-04-29) Farfán-García, Ana Elvira; Restrepo-Pineda, Eliana Durley; Flórez-Castillo, Johanna Marcela; Cliniudes
    os péptidos antimicrobianos (AMPs) son una buena opción terapéutica contra bacterias multidrogoresistentes. Sin embargo, el uso terapéutico de los AMPs se ha obstaculizado, debido a su inestabilidad en ambientes específicos, propensión al clivaje por proteasas o en algunos casos citotoxicidad. Los AMPs exhiben pequeño tamaño, carga neta positiva y anfipaticidad, necesarios para adquirir estructura secundaria, en superficies hidrofóbicas e hidrofílicas, lo que facilita la interacción electrostática con las membranas bacterianas. Los péptidos Ib-M1, Ib-M2 e Ib-M6, que se usarán en este estudio, son análogos sintéticos del péptido Ib-AMP4, nativo de la planta Impatiens balsamina, que fueron obtenidos después de modificar su carga neta e hidrofobicidad mediante la inserción de arginina y triptófano. Estudios de la actividad biológica de Ib-M contra E. coli O157:H7, mostraron actividad inhibitoria menor a 10 µM, sin evidencia de citotoxicidad en células Vero, por lo que se consideran agentes antibacterianos promisorios.