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Short-term complications and post-acute sequelae in hospitalized paediatric patients with COVID-19 and obesity: A multicenter cohort study.
Valenzuela, G, Alarcón-Andrade, G, Schulze-Schiapacasse, C, Rodríguez, R, García-Salum, T, Pardo-Roa, C, Levican, J, Serrano, E, Avendaño, MJ, Gutiérrez, M, et al
Pediatric obesity. 2023;(2):e12980
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Abstract
BACKGROUND Obesity increases the severity of coronavirus disease 2019 illness in adults. The role of obesity in short-term complications and post-acute sequelae in children is not well defined. OBJECTIVE To evaluate the relationship between obesity and short-term complications and post-acute sequelae of SARS-CoV-2 infection in hospitalized paediatric patients. METHODS An observational study was conducted in three tertiary hospitals, including paediatric hospitalized patients with a confirmatory SARS-CoV-2 RT-PCR from March 2020 to December 2021. Obesity was defined according to WHO 2006 (0-2 years) and CDC 2000 (2-20 years) growth references. Short-term outcomes were intensive care unit admission, ventilatory support, superinfections, acute kidney injury, and mortality. Neurological, respiratory, and cardiological symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms were considered as post-acute sequalae. Adjusted linear, logistic regression and generalized estimating equations models were performed. RESULTS A total of 216 individuals were included, and 67 (31.02%) of them had obesity. Obesity was associated with intensive care unit admission (aOR = 5.63, CI95% 2.90-10.94), oxygen requirement (aOR = 2.77, CI95% 1.36-5.63), non-invasive ventilatory support (aOR = 6.81, CI95% 2.11-22.04), overall superinfections (aOR = 3.02 CI95% 1.45-6.31), and suspected bacterial pneumonia (aOR = 3.00 CI95% 1.44-6.23). For post-acute sequalae, obesity was associated with dyspnea (aOR = 9.91 CI95% 1.92-51.10) and muscle weakness (aOR = 20.04 CI95% 2.50-160.65). CONCLUSIONS In paediatric hospitalized patients with COVID-19, severe short-term outcomes and post-acute sequelae are associated with obesity. Recognizing obesity as a key comorbidity is essential to develop targeted strategies for prevention of COVID-19 complications in children.
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Synthesis of diN-Substituted Glycyl-Phenylalanine Derivatives by Using Ugi Four Component Reaction and Their Potential as Acetylcholinesterase Inhibitors.
Prent-Peñaloza, L, de la Torre, AF, Velázquez-Libera, JL, Gutiérrez, M, Caballero, J
Molecules (Basel, Switzerland). 2019;(1)
Abstract
Ugi four component reaction (Ugi-4CR) isocyanide-based multicomponent reactions were used to synthesize diN-substituted glycyl-phenylalanine (diNsGF) derivatives. All of the synthesized compounds were characterized by spectroscopic and spectrometric techniques. In order to evaluate potential biological applications, the synthesized compounds were tested in computational models that predict the bioactivity of organic molecules by using only bi-dimensional molecular information. The diNsGF derivatives were predicted as cholinesterase inhibitors. Experimentally, all of the synthesized diNsGF derivatives showed moderate inhibitory activities against acetylcholinesterase (AChE) and poor activities against butyrylcholinesterase (BuChE). Compound 7a has significant activity and selectivity against AChE, which reveals that the diNsGF scaffold could be improved to reach novel candidates by combining other chemical components of the Ugi-4CR in a high-throughput combinatorial screening experiment. Molecular docking experiments of diNsGF derivatives inside AChE suggest that these compounds placed the phenylalanine group at the peripheral site of AChE. The orientations and chemical interactions of diNsGF derivatives were analyzed, and the changeable groups were identified for future exploration of novel candidates that could lead to the improvement of diNsGF derivative inhibitory activities.
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Design, facile synthesis, and evaluation of novel spiro- and pyrazolo[1,5-c]quinazolines as cholinesterase inhibitors: Molecular docking and MM/GBSA studies.
Gálvez, J, Polo, S, Insuasty, B, Gutiérrez, M, Cáceres, D, Alzate-Morales, JH, De-la-Torre, P, Quiroga, J
Computational biology and chemistry. 2018;:218-229
Abstract
Given the wide spectrum of biological uses of pyrazolo[1,5-c]quinazoline and spiro-quinazoline derivatives as anticancer, anti-inflammatory analgesic agents, and their therapeutic applications in neurodegenerative disorders, it is compulsory to find easy, efficient, and simple methods to obtain and chemically diversify these families of compounds, thereby improving their biological applications. In this paper, we report the design and eco-friendly two-step synthesis of novel, fused spiro-pyrazolo[1,5-c]quinazoline derivatives as cholinesterase inhibitors. In addition, we studied their protein-ligand interactions via molecular docking and MM/GBSA calculations for a further rational design of more potent inhibitors. In first step, 2-(1H-pyrazol-5-yl)anilines were obtained through microwave (MW) assisted solvent-free/catalyst-free conditions and the second step involved the synthesis of the spiro-pyrazolo[1,5-c]quinazolines by a cyclocondensation reaction between 2-(1H-pyrazol-5-yl)anilines and cyclic ketones, or acetophenones, using stirring at room temperature. The compounds were obtained in high purity, good yields (50-97%), and at varying reaction times. The spiro-compounds were evaluated as acetylcholinesterase and butyrylcholinesterase inhibitors (AChEIs/BuChEIs) respectively, and the most potent compound exhibited a moderate AChE inhibitory activity (5f: IC50 = 84 μM). Molecular docking studies indicated that the binding mode of the compound 5f share common characteristics with the galantamine/donepezil-AChE complexes. Moreover, free binding energy (ΔG) calculations showed a good agreement with the experimental biological activity values. Our theoretical results indicated that halogen bond interactions could be involved with differential potency of these compounds and provide a new starting point to design novel pyrazolo[1,5-c]quinazolines as new anti-Alzheimer agents.
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The added value of musculoskeletal ultrasound to clinical evaluation in the treatment decision of rheumatoid arthritis outpatients: physician experience matters.
Sifuentes-Cantú, C, Contreras-Yáñez, I, Saldarriaga, L, Lozada, AC, Gutiérrez, M, Pascual-Ramos, V
BMC musculoskeletal disorders. 2017;(1):390
Abstract
BACKGROUND Musculoskeletal ultrasound improves the accuracy of detecting the level of disease activity (DA) in RA patients, although its impact on the final treatment decision in a real clinical setting is uncertain. The objectives were to define the percentage of clinical scenarios from an ongoing cohort of RA outpatients in which the German Ultrasound Score on 7 joints (GUS-7) impacted the treatment and to explore if the impact differed between a senior rheumatologist (SR) vs. a trainee (TR). METHODS Eighty-five consecutive and randomly selected RA outpatients underwent 170 assessments, 85 each by the SR and the TR. Initially, both physicians (blinded to each other) performed a rheumatic assessment and recommended a preliminary treatment. Then, the patients underwent the GUS-7 evaluation by an experienced rheumatologist blinded to clinical evaluations; selected joints of the clinically dominant hand were assessed by gray-scale and power Doppler (PD). In the final step, the TR and the SR integrated the GUS-7 findings with their previous evaluation and reviewed their recommendations. The patients received the final recommendation from the SR to avoid patient confusion. The study was approved by the Internal Review Board and all the patients signed informed consent. GUS-7 usefulness was separately evaluated by the SR and the TR according to a visual analogue scale (0 = not useful at all, 10 = very useful). Descriptive statistics were used. RESULTS The patients were primarily middle-aged females (91.4%) with (mean ± SD) disease duration of 7.5 ± 3.9 years. The majority of them (69.2% according to TR and 71.8% to SR) were in DAS28-ESR-remission. In 34 of 170 clinical scenarios (20%), the GUS-7 findings modified the final treatment proposal; 24 of these scenarios were determined by the TR vs. 10 by the SR: 70.5% vs. 29.5%, p = 0.01. Treatment changes (increase, decrease and joint injection) were similar between both specialists. As expected, the TR rated the GUS-7 usefulness higher than the SR, particularly in the clinical scenarios where the GUS-7 findings impacted treatment. CONCLUSIONS Musculoskeletal ultrasound added to standard rheumatic assessments impacted the treatment proposal in a limited number of patients; the impact was greater in the TR.
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Arbuscular mycorrhizal symbiosis regulates physiology and performance of Digitaria eriantha plants subjected to abiotic stresses by modulating antioxidant and jasmonate levels.
Pedranzani, H, Rodríguez-Rivera, M, Gutiérrez, M, Porcel, R, Hause, B, Ruiz-Lozano, JM
Mycorrhiza. 2016;(2):141-52
Abstract
This study evaluates antioxidant responses and jasmonate regulation in Digitaria eriantha cv. Sudafricana plants inoculated (AM) and non-inoculated (non-AM) with Rhizophagus irregularis and subjected to drought, cold, or salinity. Stomatal conductance, photosynthetic efficiency, biomass production, hydrogen peroxide accumulation, lipid peroxidation, antioxidants enzymes activities, and jasmonate levels were determined. Stomatal conductance and photosynthetic efficiency decreased in AM and non-AM plants under all stress conditions. However, AM plants subjected to drought, salinity, or non-stress conditions showed significantly higher stomatal conductance values. AM plants subjected to drought or non-stress conditions increased their shoot/root biomass ratios, whereas salinity and cold caused a decrease in these ratios. Hydrogen peroxide accumulation, which was high in non-AM plant roots under all treatments, increased significantly in non-AM plant shoots under cold stress and in AM plants under non-stress and drought conditions. Lipid peroxidation increased in the roots of all plants under drought conditions. In shoots, although lipid peroxidation decreased in AM plants under non-stress and cold conditions, it increased under drought and salinity. AM plants consistently showed high catalase (CAT) and ascorbate peroxidase (APX) activity under all treatments. By contrast, the glutathione reductase (GR) and superoxide dismutase (SOD) activity of AM roots was lower than that of non-AM plants and increased in shoots. The endogenous levels of cis-12-oxophytodienoc acid (OPDA), jasmonic acid (JA), and 12-OH-JA showed a significant increase in AM plants as compared to non-AM plants. 11-OH-JA content only increased in AM plants subjected to drought. Results show that D. eriantha is sensitive to drought, salinity, and cold stresses and that inoculation with AM fungi regulates its physiology and performance under such conditions, with antioxidants and jasmonates being involved in this process.
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Novel N-allyl/propargyl tetrahydroquinolines: Synthesis via Three-component Cationic Imino Diels-Alder Reaction, Binding Prediction, and Evaluation as Cholinesterase Inhibitors.
Rodríguez, YA, Gutiérrez, M, Ramírez, D, Alzate-Morales, J, Bernal, CC, Güiza, FM, Romero Bohórquez, AR
Chemical biology & drug design. 2016;(4):498-510
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Abstract
New N-allyl/propargyl 4-substituted 1,2,3,4-tetrahydroquinolines derivatives were efficiently synthesized using acid-catalyzed three components cationic imino Diels-Alder reaction (70-95%). All compounds were tested in vitro as dual acetylcholinesterase and butyryl-cholinesterase inhibitors and their potential binding modes, and affinity, were predicted by molecular docking and binding free energy calculations (∆G) respectively. The compound 4af (IC50 = 72 μm) presented the most effective inhibition against acetylcholinesterase despite its poor selectivity (SI = 2), while the best inhibitory activity on butyryl-cholinesterase was exhibited by compound 4ae (IC50 = 25.58 μm) with considerable selectivity (SI = 0.15). Molecular docking studies indicated that the most active compounds fit in the reported acetylcholinesterase and butyryl-cholinesterase active sites. Moreover, our computational data indicated a high correlation between the calculated ∆G and the experimental activity values in both targets.
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Occurrence and treatment of arsenic in groundwater and soil in northern Mexico and southwestern USA.
Camacho, LM, Gutiérrez, M, Alarcón-Herrera, MT, Villalba, Mde L, Deng, S
Chemosphere. 2011;(3):211-25
Abstract
This review focuses on the occurrence and treatment of arsenic (As) in the arid region of northern Mexico (states of Chihuahua and Coahuila) and bordering states of the southwestern US (New Mexico, Arizona, and Texas), an area known for having high As concentrations. Information assembled and assessed includes the content and probable source of As in water, soil, and sediments and treatment methods that have been applied in the area. High As concentrations were found mainly in groundwater, their source being mostly from natural origin related to volcanic processes with significant anthropogenic contributions near mining and smelting of ores containing arsenic. The affinity of As for solid phases in alkaline conditions common to arid areas precludes it from being present in surface waters, accumulating instead in sediments and shifting its threat to its potential remobilization in reservoir sediments and irrigation waterways. Factors such as oxidation and pH that affect the mobility of As in the subsurface environment are mentioned. Independent of socio-demographic variables, nutritional status, and levels of blood lead, cognitive development in children is being affected when exposed to As. Treatments known to effectively reduce As content to safe drinking water levels as well as those that are capable of reducing As content in soils are discussed. Besides conventional methods, emergent technologies, such as phytoremediation, offer a viable solution to As contamination in drinking water.