525 results on '"Figueroa, S"'
Search Results
202. ¡Diez de Octubre!
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FIGUEROA, S.
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CUBAN politics & government, 1895- ,POLITICAL autonomy - Published
- 1895
203. Las mujeres.
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Martínez Figueroa, S.
- Published
- 1915
204. THERMAL REDUCTION OF Cu2+ IN PRESENCE OF Ag+ IN CLINOPTILOLITE: STRUCTURAL STUDY BY EXAFS AND HR-XRD.
- Author
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CONCEPCIÓN-ROSABAL, B., RODRÍGUEZ-IZNAGA, I., PETRANOVSKII, V., CHÁVEZ-RIVAS, F., FIGUEROA, S. J. A., and PENTÓN-MADRIGAL, A.
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CLINOPTILOLITE , *EXTENDED X-ray absorption fine structure , *ZEOLITE Y , *AGGLOMERATION (Materials) , *X-ray diffraction , *SILVER , *COPPER compounds - Abstract
Cu2+-Ag+ bimetallic systems were exchanged and then thermally reduced in natural clinoptilolite (CLI) from Tasajeras deposit (Cuba). The systems were characterized by means of extended X-ray absorption fine structure (EXAFS) and high resolution X-ray diffraction (HR-XRD) experiments. The EXAFS signals of the bimetallic systems showed changes in the Cu2+ coordination as a result of their reduction at 150℃, which doesn't happen to CuCLI monometallic one. The presence of silver facilitates the reduction of Cu2+ in bimetallic systems forming only clusters. At higher reduction temperature (450℃) all mono- and bi-metallic samples exhibit mainly metallic particles of Cu and Ag with higher aggregation. These results are confirmed by HR-XRD studies. Aggregation of reduced copper species is restricted in the presence of silver. [ABSTRACT FROM AUTHOR]
- Published
- 2019
205. Synthesis, pharmacology and pharmacokinetics of 3-(4-Aryl-piperazin-1-ylalkyl)-uracils as uroselective α1A-antagonists
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Lopez, F. J., Arias, L., Chan, R., Clarke, D. E., Elworthy, T. R., Ford, A.P.D.W., Guzman, A., Jaime-Figueroa, S., Jasper, J. R., Morgans Jr., D. J., Padilla, F., Perez-Medrano, A., Quintero, C., Romero, M., Sandoval, L., Smith, S. A., Williams, T. J., and Blue, D. R.
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ADRENERGIC receptors , *MUSCLE contraction - Abstract
Predominance in the urethra and prostate of the α1A-adrenoceptor subtype, which is believed to be the receptor mediating noradrenaline induced smooth muscle contraction in these tissues, led to the preparation of α1A-selective antagonists to be tested as uroselective compounds for the treatment of benign prostatic hyperplasia. Thus, a number of selective α1A-adrenoceptor antagonists were synthesized and assayed in vitro for potency and selectivity. Dog pharmacokinetic parameters of 12 (RO700004) and its metabolite 40 (RO1104253) were established. The relative selectivity of intravenously administered 12, 40 and standard prazosin to inhibit hypogastric nerve stimulation-induced increases in intraurethral prostatic pressure versus phenylephrine-induced increases in diastolic blood pressure in anesthetized dogs was 76, 71 and 0.6, respectively. [Copyright &y& Elsevier]
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- 2003
- Full Text
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206. Global monitoring in the neurocritical care unit
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David Tirschwell, MCCOY STEPHEN ELI, Halinder Mangat, Stephen Figueroa, DaiWai Olson, David Seder, Giuseppe Citerio, J. Michael Schmidt, Sarah Livesay, Olson, D, Andrew Kofke, W, O'Phelan, K, Gupta, P, Figueroa, S, Smirnakis, S, Leroux, P, Suarez, J, and Citerio, G
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medicine.medical_specialty ,Brain Diseases ,Critical Care ,business.industry ,Less invasive ,Neurointensive care ,Brain monitoring ,Critical Care and Intensive Care Medicine ,medicine.disease ,Neurophysiological Monitoring ,Unit (housing) ,Electrophysiology, Intracranial pressure, Neurocritical care, Neuroimaging, Neuromonitoring, Neuroprotection ,medicine ,Intracranial pressure monitoring ,Humans ,Neurology (clinical) ,Medical emergency ,State of the science ,Intensive care medicine ,business - Abstract
Effective methods of monitoring the status of patients with neurological injuries began with non-invasive observations and evolved during the past several decades to include more invasive monitoring tools and physiologic measures. The monitoring paradigm continues to evolve, this time back toward the use of less invasive tools. In parallel, the science of monitoring began with the global assessment of the patient’s neurological condition, evolved to focus on regional monitoring techniques, and with the advent of enhanced computing capabilities is now moving back to focus on global monitoring. The purpose of this session of the Second Neurocritical Care Research Conference was to collaboratively develop a comprehensive understanding of the state of the science for global brain monitoring and to identify research priorities for intracranial pressure monitoring, neuroimaging, and neuro-electrophysiology monitoring.
- Published
- 2015
207. Predicting mortality in hospitalized patients with 2009 H1N1 influenza pneumonia
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Martin Gnoni, Charles Feldman, Francesco Blasi, M. Raya, Jordi Rello, Stefano Aliberti, S. Figueroa, M. L. Rioseco, Jose Bordon, Aran Singanayagam, D. Pryluka, M. Barros, M. Riquelme, A. Torres, Heidi Lopez, R. Riquelme, P. Fernandez, J. Riquelme, Kwabena Ayesu, Y. Gomez, Alejandro J. Videla, Raul Nakamatsu, F. Saavedra, P. Alvare, Paula Peyrani, Lucia Marzoratti, Mohamed Saad, Tobias Welte, J. Guardiola, Guillermo Benchetrit, Timothy L. Wiemken, C. Contreras, Roberto Cosentini, Forest W Arnold, P. Jiménez, G. Arbo, James D. Chalmers, C. Inzunza, Gustavo Lopardo, Julio A. Ramirez, A. Klotchko, Riquelme, R, Jiménez, P, Videla, A, Lopez, H, Chalmers, J, Singanayagam, A, Riquelme, M, Peyrani, P, Wiemken, T, Arbo, G, Benchetrit, G, Rioseco, M, Ayesu, K, Klotchko, A, Marzoratti, L, Raya, M, Figueroa, S, Saavedra, F, Pryluka, D, Inzunza, C, Torres, A, Alvare, P, Fernandez, P, Barros, M, Gomez, Y, Contreras, C, Rello, J, Bordon, J, Feldman, C, Arnold, F, Nakamatsu, R, Riquelme, J, Blasi, F, Aliberti, S, Cosentini, R, Lopardo, G, Gnoni, M, Welte, T, Saad, M, Guardiola, J, and Ramirez, J
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Pneumonia severity index ,Pneumonia, Viral ,medicine.disease_cause ,Severity of Illness Index ,Cohort Studies ,Influenza A Virus, H1N1 Subtype ,Risk Factors ,Internal medicine ,pneumonia, h1n1, influenza, mortality ,Influenza, Human ,Severity of illness ,medicine ,Influenza A virus ,Humans ,Obesity ,Respiratory sounds ,Intensive care medicine ,Aged ,Respiratory Sounds ,medicine.diagnostic_test ,MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO ,business.industry ,Mortality rate ,Middle Aged ,medicine.disease ,Community-Acquired Infections ,Hospitalization ,Pneumonia ,Infectious Diseases ,Blood pressure ,MED/17 - MALATTIE INFETTIVE ,Female ,business ,Forecasting ,Cohort study - Abstract
BACKGROUND: Community-acquired pneumonia (CAP) severity scores can identify patients at low risk for mortality who may be suitable for ambulatory care. Here, we follow the clinical course of hospitalized patients with CAP due to 2009 H1N1 influenza. OBJECTIVE: To evaluate the role of CAP severity scores as predictors of mortality. METHODS: This was a secondary data analysis of patients hospitalized with CAP due to 2009 H1N1 influenza confirmed by reverse transcriptase polymerase chain reaction enrolled in the CAPO (Community-Acquired Pneumonia Organization) international cohort study. CAP severity scores PSI (Pneumonia Severity Index), CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) and CRB-65 (confusion, respiratory rate, blood pressure, age ≥ 65 years) were calculated. Actual and predicted mortality rates were compared. A total of 37 predictor variables were evaluated to define those associated with mortality. RESULTS: Data from 250 patients with CAP due to 2009 H1N1 influenza were analyzed. Patients with low predicted mortality rates (0-1.5%) had actual mortality rates ranging from 2.6% to 17.5%. Obesity and wheezing were the only novel variables associated with mortality. CONCLUSIONS: The decision to hospitalize a patient with CAP due to 2009 H1N1 influenza should not be based on current CAP severity scores, as they underestimate mortality rates in a significant number of patients. Patients with obesity or wheezing should be considered at an increased risk for mortality. © 2011 The Union.
- Published
- 2011
208. The Staged Photocatalytic Reactor in the Removal of Acetaminophen: Aspects of Adsorption and Photocatalysis.
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Aguilar C, García M, Montalvo C, Anguebes F, Abatal M, Cerón J, Cerón R, Figueroa S, Ruiz A, and Rangel M
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The efficiency of a staged photocatalytic reactor prototype was evaluated on a semi-pilot scale with the removal of acetaminophen, for which anatase particles were synthesized by Sol-Gel and impregnated on rectangular plates of clay. X-ray diffraction and Energy Dispersive X-ray Fluorescence patterns show that the final composite is made up of Al
2 O3 (14 %), SiO2 (41 %), CaO (3 %) TiO2 (34 %), and Fe2 O3 (7 %). The impregnation method favors the dispersion of Anatase on the surface of the adsorbent. TiO2 -Anatase/Clay, classified as a macro-porous solid with H3-type hysteresis loops by N2 physisorption. Adsorption processes are improved when using TiO2 -Anatase/Clay compared to using TiO2 -Anatase. The external mass transfer has a greater influence on the removal rate. The dimensionless parameters of the Biot number indicate there are no limitations due to the diffusive effect on the interior of the particle. The evaluation of the kinetic data under the Langmuir-Hinshelwood equation shows a decrease in efficiency as the initial concentration increases. The acetaminophen molecule shows destabilization in the structure of the aromatic ring with a visible decrease in the signals of this functional group evaluated by High-Performance Liquid Chromatography and Raman Spectroscopy., (© 2024 The Authors. ChemistryOpen published by Wiley-VCH GmbH.)- Published
- 2024
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209. Synthesis, biosimulation and pharmacological evaluation of benzimidazole derivatives with antihypertensive multitarget effect.
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Gutiérrez-Hernández A, Estrada-Soto S, Martínez-Conde C, Gaona-Tovar E, Medina-Franco JL, Hernández-Núñez E, Hidalgo-Figueroa S, Castro-Moreno P, Ibarra-Barajas M, and Navarrete-Vazquez G
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- Animals, Rats, Structure-Activity Relationship, Blood Pressure drug effects, Hypertension drug therapy, Receptor, Angiotensin, Type 1 metabolism, Molecular Structure, Angiotensin II Type 1 Receptor Blockers pharmacology, Angiotensin II Type 1 Receptor Blockers chemical synthesis, Angiotensin II Type 1 Receptor Blockers chemistry, Calcium Channel Blockers pharmacology, Calcium Channel Blockers chemical synthesis, Calcium Channel Blockers chemistry, Calcium Channels, L-Type metabolism, Benzimidazoles chemistry, Benzimidazoles pharmacology, Benzimidazoles chemical synthesis, Antihypertensive Agents pharmacology, Antihypertensive Agents chemical synthesis, Antihypertensive Agents chemistry, Rats, Inbred SHR, Molecular Docking Simulation
- Abstract
In this study, we synthesized a series of seven benzimidazole derivatives incorporating the structural acidic framework of angiotensin II (Ang II) type 1 receptor (AT
1 R) antagonists (ARA-II) employing a three-step reaction sequence. The chemical structures were confirmed by1 H NMR,13 C NMR and mass spectral data. Through biosimulation, compounds 1-7 were identified as computational safe hits, thus, best candidates underwent ex vivo testing against two distinct mechanisms implicated in hypertension: antagonism of the Ang II type 1 receptor and the blockade of calcium channel. Molecular docking studies helped to understand at the molecular level the dual vasorelaxant effects with the recognition sites of the AT1 R and the L-type calcium channel. In an in vivo spontaneously hypertensive rat model (SHR), intraperitoneally administration of compound 1 at 20 mg/kg resulted in a 25 % reduction in systolic blood pressure, demonstrating both ex vivo vasorelaxant action and in vivo antihypertensive multitarget efficacy. ©2024 Elsevier., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)- Published
- 2024
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210. Discovery of Palindrome Dual PPARγ-GPR40 Agonists for Treating Type 2 Diabetes.
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Rodríguez-Luévano A, Almanza-Pérez JC, Ortiz-Andrade R, Lara-González S, Santillán R, Navarrete-Vázquez G, Giacoman-Martínez A, Lazzarini-Lechuga RC, Bautista E, and Hidalgo-Figueroa S
- Abstract
This work describes a first attempt of palindromic design for dual compounds that act simultaneously on peroxisome proliferator-activated receptor gamma (PPARg) and G-protein-coupled receptor 40 (GPR40) for the treatment of type 2 diabetes. The compounds were synthesized by multi-step chemical reactions and the relative mRNA expression levels of PPARg, GPR40, and GLUT-4 were measured in cultured C2C12 muscle cells and RIN-m5f b-pancreatic cells. In addition, insulin secretion and GLUT-4 translocation were measured. Compound 2 displayed a moderate increase in the mRNA expression of PPARg and GPR40. However, the translocation of the GLUT-4 transporter was 400% with a similar effect to pioglitazone. The in vivo effect of compound 2 was determined at 25 mg/kg single dose using a normoglycemic and non-insulin dependent diabetes mellitus (NIDDM) rat models. Compound 2 showed basal plasma glucose in diabetic rats with feed intake, which is associated with the moderate release of insulin measured in cells. Surprisingly, the glucose does not decrease in normoglycemic rats. Compound 2 maintained significant interactions with the GPR40 and PPARg receptors during molecular dynamics. Altogether, the results demonstrate that compound 2, with a palindromic design, simultaneously activates PPARg and GPR40 receptors without inducing hypoglycemia., (© 2024 Wiley‐VCH GmbH.)
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- 2024
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211. In silico analysis of the interaction of de novo peptides derived from Salvia hispanica with anticancer targetsEvaluation of the anticancer potential of de novo peptides derived from Salvia hispanica through molecular docking.
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Quintal Bojórquez NDC, Morales Mendoza LF, Hidalgo-Figueroa S, Hernández Álvarez AJ, and Segura Campos MR
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- Humans, Computer Simulation, Molecular Dynamics Simulation, Amino Acid Sequence, Molecular Docking Simulation, Peptides chemistry, Peptides pharmacology, Salvia chemistry, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Protein Binding
- Abstract
Cancer is one of the leading causes of death worldwide. Conventional cancer therapies are not selective to cancer cells resulting in serious side effects on patients. Thus, the need for complementary treatments that improve the patient's response to cancer therapy is highly important. To predict and evaluate the physicochemical characteristics and potential anticancer activity of the peptides identified from S. hispanica protein fraction <1 kDa through the use of in silico tools. Peptides derived from Salvia hispanica 's protein fraction <1 kDa were identified and analyzed for the prediction of their physicochemical properties. The characterized peptide sequences were then submitted to a multi-criteria decision analysis to identify the peptides that possess the characteristics to potentially exert anticancer activity. Through molecular docking analysis, the potential anticancer activity of the Potentially Anticancer Peptide (PAP)-1, PAP-2, PAP-3, PAP-4, and PAP-5 was estimated by their binding interactions with cancer and apoptosis-related molecules. All five evaluated PAPs exhibited strong binding interactions (< -100 kcal/mol). However, PAP-3 showed the lowest binding free energies with several of the targets. Thus, PAP-3 shows potential to be used as a nutraceutical or ingredient for functional foods that adjuvate in cancer treatment. Conclusions: Through the molecular docking studies, the binding of the PAPs to target molecules of interest for cancer treatment was successfully simulated, from which PAP-3 exhibited the lowest binding free energies. Further in vitro and in vivo studies are required to validate the predictions obtained by the in silico analysis.Communicated by Ramaswamy H. Sarma.
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- 2024
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212. HPLC-Based Metabolomic Analysis and Characterization of Amaranthus cruentus Leaf and Inflorescence Extracts for Their Antidiabetic and Antihypertensive Potential.
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Araujo-León JA, Sánchez-Del Pino I, Ortiz-Andrade R, Hidalgo-Figueroa S, Carrera-Lanestosa A, Brito-Argáez LG, González-Sánchez A, Giácoman-Vallejos G, Hernández-Abreu O, Peraza-Sánchez SR, Xingú-López A, and Aguilar-Hernández V
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- Chromatography, High Pressure Liquid, Animals, Antioxidants pharmacology, Antioxidants chemistry, Male, Rats, Flavonoids chemistry, Flavonoids pharmacology, Flavonoids analysis, Amaranthus chemistry, Plant Extracts chemistry, Plant Extracts pharmacology, Plant Leaves chemistry, Hypoglycemic Agents pharmacology, Hypoglycemic Agents chemistry, Antihypertensive Agents pharmacology, Antihypertensive Agents chemistry, Metabolomics methods
- Abstract
The aim of this study was to investigate the potential of Amaranthus cruentus flavonoids (quercetin, kaempferol, catechin, hesperetin, naringenin, hesperidin, and naringin), cinnamic acid derivatives ( p -coumaric acid, ferulic acid, and caffeic acid), and benzoic acids (vanillic acid and 4-hydroxybenzoic acid) as antioxidants, antidiabetic, and antihypertensive agents. An analytical method for simultaneous quantification of flavonoids, cinnamic acid derivatives, and benzoic acids for metabolomic analysis of leaves and inflorescences from A. cruentus was developed with HPLC-UV-DAD. Evaluation of linearity, limit of detection, limit of quantitation, precision, and recovery was used to validate the analytical method developed. Maximum total flavonoids contents (5.2 mg/g of lyophilized material) and cinnamic acid derivatives contents (0.6 mg/g of lyophilized material) were found in leaves. Using UV-Vis spectrophotometry, the maximum total betacyanin contents (74.4 mg/g of lyophilized material) and betaxanthin contents (31 mg/g of lyophilized material) were found in inflorescences. The leaf extract showed the highest activity in removing DPPH radicals. In vitro antidiabetic activity of extracts was performed with pancreatic α-glucosidase and intestinal α-amylase, and compared to acarbose. Both extracts exhibited a reduction in enzyme activity from 57 to 74%. Furthermore, the in vivo tests on normoglycemic murine models showed improved glucose homeostasis after sucrose load, which was significantly different from the control. In vitro antihypertensive activity of extracts was performed with angiotensin-converting enzyme and contrasted to captopril; both extracts exhibited a reduction of enzyme activity from 53 to 58%. The leaf extract induced a 45% relaxation in an ex vivo aorta model. In the molecular docking analysis, isoamaranthin and isogomphrenin-I showed predictive binding affinity for α-glucosidases (human maltase-glucoamylase and human sucrase-isomaltase), while catechin displayed binding affinity for human angiotensin-converting enzyme. The data from this study highlights the potential of A. cruentus as a functional food.
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- 2024
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213. [Bioelectrical impedance vectors in the Colombian university population].
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Díaz Rincón M, Hincapie Villegas J, Páez Figueroa S, and Lora Díaz OL
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- Colombia, Humans, Female, Cross-Sectional Studies, Male, Universities, Young Adult, Adult, Italy, Adolescent, Electric Impedance, Students, Body Composition
- Abstract
Introduction: Introduction: body composition (BC) analysis is an essential element in clinical nutritional practice. Bioelectrical impedance is one of the most widely used techniques for estimating BC. Several approaches have been proposed to reduce the margin of error it presents, ensuring its application in all populations. One of them is the use of impedance vectors, using tolerance ellipses. Objective: to compare the sample vectors with the Italian population and to determine specific tolerance ellipses for the Colombian university population. Materials and methods: observational cross-sectional study in 608 university students. Participation was at convenience and voluntary, between February 2022 and March 2023. BIVA 2002 software was used to calculate the tolerance ellipses and BIVA confidence to compare the vectors of the ellipses with the Italian population using Hotelling's T2 test, which was considered as significant at p < 0.05. Results: R/H and Xc/H measurements were higher in females (420.75 ± 56.012 Ω/m vs 308.7508 ± 41.81 Ω/m) and (46.15 ± 5.79 Ω/m vs 39.44 ± 5.01 Ω/m), respectively. The impedance vectors were positioned over the upper quadrants of the RXc plot, evidencing significant differences in the distribution of the composition vectors between samples. Conclusions: the vectors of the Colombian university students were different from the reference population, so it was necessary to determine the specific ellipses.
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- 2024
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214. Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury.
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Chase DH, Bebenek AM, Nie P, Jaime-Figueroa S, Butrin A, Castro DA, Hines J, Linhares BM, and Crews CM
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- Humans, Afatinib, T-Box Domain Proteins metabolism, Transcription Factors metabolism, Chordoma drug therapy, Chordoma metabolism, Chordoma pathology, Fetal Proteins
- Abstract
Brachyury is an oncogenic transcription factor whose overexpression drives chordoma growth. The downmodulation of brachyury in chordoma cells has demonstrated therapeutic potential, however, as a transcription factor it is classically deemed "undruggable". Given that direct pharmacological intervention against brachyury has proven difficult, attempts at intervention have instead targeted upstream kinases. Recently, afatinib, an FDA-approved kinase inhibitor, has been shown to modulate brachyury levels in multiple chordoma cell lines. Herein, we use afatinib as a lead to undertake a structure-based drug design approach, aided by mass-spectrometry and X-ray crystallography, to develop DHC-156, a small molecule that more selectively binds brachyury and downmodulates it as potently as afatinib. We eliminated kinase-inhibition from this novel scaffold while demonstrating that DHC-156 induces the post-translational downmodulation of brachyury that results in an irreversible impairment of chordoma tumor cell growth. In doing so, we demonstrate the feasibility of direct brachyury modulation, which may further be developed into more potent tool compounds and therapies., (© 2024 Wiley‐VCH GmbH.)
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- 2024
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215. Segmentectomy for lung cancer: dig deeper.
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Gonzalez M, Ojanguren A, Figueroa S, and Bédat B
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- Humans, Pneumonectomy, Thoracic Surgery, Video-Assisted, Treatment Outcome, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms surgery, Lung Neoplasms pathology
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- 2024
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216. Clinical effectiveness and cost-impact after 2 years of a ketogenic diet and virtual coaching intervention for patients with diabetes.
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Strombotne KL, Lum J, Pizer SD, Figueroa S, Frakt AB, and Conlin PR
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- Humans, Glycated Hemoglobin, Overweight, Obesity therapy, Treatment Outcome, Diet, Ketogenic methods, Diabetes Mellitus, Type 2, Mentoring
- Abstract
Aim: We previously evaluated the impacts at 5 months of a digitally delivered coaching intervention in which participants are instructed to adhere to a very low carbohydrate, ketogenic diet. With extended follow-up (24 months), we assessed the longer-term effects of this intervention on changes in clinical outcomes, health care utilization and costs associated with outpatient, inpatient and emergency department use in the Veterans Health Administration., Materials and Methods: We employed a difference-in-differences model with a waiting list control group to estimate the 24-month change in glycated haemoglobin, body mass index, blood pressure, prescription medication use, health care utilization rates and associated costs. The analysis included 550 people with type 2 diabetes who were overweight or obese and enrolled in the Veterans Health Administration for health care. Data were obtained from electronic health records from 2018 to 2021., Results: The virtual coaching and ketogenic diet intervention was associated with significant reductions in body mass index [-1.56 (SE 0.390)] and total monthly diabetes medication usage [-0.35 (SE 0.054)]. No statistically significant differences in glycated haemoglobin, blood pressure, outpatient visits, inpatient visits, or emergency department visits were observed. The intervention was associated with reductions in per-patient, per-month outpatient spending [-USD286.80 (SE 97.175)] and prescription drug costs (-USD105.40 (SE 30.332)]., Conclusions: A virtual coaching intervention with a ketogenic diet component offered modest effects on clinical and cost parameters in people with type 2 diabetes and with obesity or overweight. Health care systems should develop methods to assess participant progress and engagement over time if they adopt such interventions, to ensure continued patient engagement and goal achievement., (© 2023 John Wiley & Sons Ltd.)
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- 2024
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217. Continuous glucose monitoring for automatic real-time assessment of eating events and nutrition: a scoping review.
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Brummer J, Glasbrenner C, Hechenbichler Figueroa S, Koehler K, and Höchsmann C
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Background: Accurate dietary assessment remains a challenge, particularly in free-living settings. Continuous glucose monitoring (CGM) shows promise in optimizing the assessment and monitoring of ingestive activity (IA, i.e., consumption of calorie-containing foods/beverages), and it might enable administering dietary Just-In-Time Adaptive Interventions (JITAIs)., Objective: In a scoping review, we aimed to answer the following questions: (1) Which CGM approaches to automatically detect IA in (near-)real-time have been investigated? (2) How accurate are these approaches? (3) Can they be used in the context of JITAIs?, Methods: We systematically searched four databases until October 2023 and included publications in English or German that used CGM-based approaches for human (all ages) IA detection. Eligible publications included a ground-truth method as a comparator. We synthesized the evidence qualitatively and critically appraised publication quality., Results: Of 1,561 potentially relevant publications identified, 19 publications (17 studies, total N = 311; for 2 studies, 2 publications each were relevant) were included. Most publications included individuals with diabetes, often using meal announcements and/or insulin boluses accompanying meals. Inpatient and free-living settings were used. CGM-only approaches and CGM combined with additional inputs were deployed. A broad range of algorithms was tested. Performance varied among the reviewed methods, ranging from unsatisfactory to excellent (e.g., 21% vs. 100% sensitivity). Detection times ranged from 9.0 to 45.0 min., Conclusion: Several CGM-based approaches are promising for automatically detecting IA. However, response times need to be faster to enable JITAIs aimed at impacting acute IA. Methodological issues and overall heterogeneity among articles prevent recommending one single approach; specific cases will dictate the most suitable approach., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. CH and KK were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Brummer, Glasbrenner, Hechenbichler Figueroa, Koehler and Höchsmann.)
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- 2024
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218. Effects of the lockdown due to the COVID-19 pandemic on alcohol consumption in patients under treatment in an alcohol relapse prevention programme.
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Arias Horcajadas F, Marín M, Prieto R, López-Trabada JR, Parra A, Sanz P, Guerrero Y, Delgado P, González L, Sáiz N, Suárez de Figueroa S, Villalba A, and Rubio G
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- Female, Humans, Male, Alcohol Drinking epidemiology, Communicable Disease Control, Pandemics, Secondary Prevention, Alcoholism therapy, COVID-19 prevention & control
- Abstract
During the COVID-19 pandemic, several exceptional measures were put in place in order to avoid virus propagation, such as lockdown and the discontinuation of usual health care assistance services. It was considered that these changes might be associated with an increase in alcohol consumption and a higher risk of relapse for patients under treatment. The aim of this study was to assess changes in alcohol consumption during the lockdown period (between March and May, 2020) in patients following treatment under the Alcohol Use Disorders Programme at the "Hospital 12 de Octubre" in Madrid. A total of 311 patients were assessed through interviews carried out by telephone in accordance with usual clinical practice during that period. 76% of the total number of patients did not experience changes in their alcohol consumption, 9.2% stopped drinking and some experienced severe withdrawal syndrome, while 7.5% relapsed. The risk factors found for worsening the prognosis of the patients were: being female, drinking alcohol alone or at home, binge drinking, concomitant substance misuse and failure to attend therapy groups or self-help groups online during the lockdown. 31.6% of the sample described psychopathological symptoms due to the lockdown, especially those who already had psychiatric comorbidities. For this reason, we can conclude that during the lockdown as a result of the pandemic, most of our alcohol dependent patients did not modify their drinking patterns, but specific factors enabled us to identify a more vulnerable subgroup.
- Published
- 2023
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219. Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: Correlation with FDG-PET/CT.
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Fernández S, Cereceda L, Díaz E, Figueroa S, Reguera L, Menéndez V, Solórzano JL, Montalbán C, Estévez M, and García JF
- Abstract
The value of circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients has not yet been well established. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high spatial and temporal heterogeneity. Although ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based on measures of total ctDNA, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness., Competing Interests: The authors declare no competing financial interests., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2023
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220. Sociodemographic determinants and mortality of premature newborns in a medium and low-income population in Colombia, 2017-2019.
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Torres-Muñoz J, Alberto Cedeño D, Murillo J, Torres-Figueroa S, and Torres-Figueroa J
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- Infant, Child, Infant, Newborn, Pregnancy, Humans, Female, Child, Preschool, Colombia epidemiology, Cross-Sectional Studies, Infant, Premature, Poverty, Cesarean Section, Premature Birth epidemiology
- Abstract
Introduction: The birth of premature babies is a public health problem with a high impact on infant morbidity and mortality. About 40% of mortality in children under five years occurs in the first month of life., Objective: To identify the association between maternal sociodemographic factors, premature birth, and mortality in newborns under 37 weeks in Santiago de Cali, 2017-2019., Materials and Methods: We conducted a descriptive, cross-sectional study. We evaluated the records of Cali's Municipal Public Health Office. We calculated the crude and adjusted odd ratios and confidence intervals (95%) using the logistic regression model, data processing in Stata 16, and georeferencing the cases in the QGIS software., Results: From 2017 to 2019, premature babies in Cali corresponded to 11% of births. Poor prenatal care increased 3.13 times the risk of being born before 32 weeks (adjusted OR = 3.13; 95% CI = 2.75 - 3.56) and 1.27 times among mothers from outside the city (adjusted OR = 1.27; 95% CI = 1.15-1.41). Mortality was 4.29 per 1,000 live births. The mortality risk in newborns weighing less than 1,000 g increased 3.42 times (OR = 3.42; 95% CI = 2.85-4.12), delivery by cesarean section in 1.46 (OR = 1.46; CI 95% = 1.14-1.87) and an Apgar score - five minutes after birth- lower than seven in 1.55 times (OR = 1.55; CI 95% = 1.23-1.96)., Conclusions: We found that less than three prenatal controls, mothers living outside Cali, afro-ethnicity, and cesarean birth were associated with prematurity of less than 32 weeks. We obtained higher mortality in newborns weighing less than 1,000 g.
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- 2023
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221. Device-associated infections in neonatal care units in a middle-income country, 2016-2018.
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Torres-Muñoz J, Hoyos IV, Murillo J, Holguin J, Dávalos D, López E, and Torres-Figueroa S
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- Infant, Newborn, Infant, Humans, Cross-Sectional Studies, Intensive Care Units, Neonatal, Birth Weight, Hospitalization, Intensive Care Units, Cross Infection epidemiology, Cross Infection microbiology, Catheter-Related Infections epidemiology
- Abstract
Objective: Describe the device-associated infections in the NICUs in Cali - Colombia, a middle-income country, between August 2016 to December 2018., Methods: Observational cross-sectional study evaluating reports of device-associated infections in 10 NICUs in Cali, Colombia, between August 2016 and December 2018. Socio-demographic and microbiological data were obtained from the National Public Health surveillance system, through a specialized notification sheet. The relationship of device-associated infections with several outcomes including birth weight, microorganisms, and mortality was evaluated using OR CI95%, using the logistic regression model. Data processing was performed using the statistical program STATA 16., Results: 226 device-associated infections were reported. The rate of infection with central line-associated bloodstream infections was 2.62 per 1000 days of device use and 2.32 per 1000 days for ventilator-associated pneumonia. This was higher in neonates under 1000 g; 4.59 and 4.10, respectively. 43.4% of the infections were due to gram-negative bacteria and 42.3% were due to gram-positive bacteria. Time from hospitalization to diagnosis of all device-associated infections had a median of 14 days. When compared by weight, infants with a weight lower than 1000 g had a greater chance of death (OR 3.61; 95% CI 1.53-8.49, p = 0.03). Infection by gram-negative bacteria was associated with a greater chance of dying (OR 3.06 CI 95 1.33-7.06, p = 0.008)., Conclusions: These results highlight the need to maintain epidemiological surveillance processes in neonatal intensive care units, especially when medical devices are used., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)
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- 2023
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222. Neuropharmacological Effects of the Dichloromethane Extract from the Stems of Argemone ochroleuca Sweet (Papaveraceae) and Its Active Compound Dihydrosanguinarine.
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Yáñez-Barrientos E, Barragan-Galvez JC, Hidalgo-Figueroa S, Reyes-Luna A, Gonzalez-Rivera ML, Cruz Cruz D, Isiordia-Espinoza MA, Deveze-Álvarez MA, Villegas Gómez C, and Alonso-Castro AJ
- Abstract
Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography-mass spectrometry (GC-MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1-50 mg/kg p.o.) and DHS (0.1-10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED
50 ) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED50 = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED50 = 3 mg/kg) and the tail suspension test (ED50 = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED50 = 2 mg/kg) in the hole board test. The AOE (1-50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABAA receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS.- Published
- 2023
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223. Stellate ganglion block for non-pain indications: a scoping review.
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Feigin G, Velasco Figueroa S, Englesakis MF, D'Souza R, Hoydonckx Y, and Bhatia A
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- Female, Humans, Pain, Research Design, Stellate Ganglion, Autonomic Nerve Block methods
- Abstract
Introduction: Stellate ganglion block (SGB) is performed to relieve head, face, neck, or upper limb pain, and several non-pain indications for performing this block have emerged over the years. To date, there has been no attempt to synthesize evidence on SGB for treating non-pain indications. This scoping review presents a summary of the efficacy and adverse effects of SGB when performed for 6 non-pain indications., Methods: This scoping review was accomplished through the use of Arksey and O'Malley framework. A literature search was conducted for relevant articles in medical databases to identify publications on SGB and specified study types. Two reviewers independently assessed the risk of bias for randomized controlled trials, nonrandomized comparative studies, and case series. Results were summarized and recommendations were made on the basis of the strength of the available evidence according to the US Preventative Services Task Force grading system., Results: Twenty-four studies (19 randomized controlled trials and 5 nonrandomized studies) were included in this review. On the basis of the evidence, SGB is recommended for obtunding cardiovascular sympathetic stimulation, improving perfusion in limbs, and alleviating menopausal symptoms with a Grade B or C recommendation and a moderate-to-low level of certainty. There was insufficient evidence to recommend SGB for the other indications., Conclusions: SGB can be considered for obtunding cardiovascular sympathetic stimulation and stress response, reducing vascular tone to improve vascular insufficiency in the limbs and perioperative hemodynamic stability, and alleviating hot flashes in menopause, in conditions refractory to conventional medical management., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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224. Symptomatic Intracranial Hemorrhage With Tenecteplase vs Alteplase in Patients With Acute Ischemic Stroke: The Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) Collaboration.
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Warach SJ, Ranta A, Kim J, Song SS, Wallace A, Beharry J, Gibson D, Cadilhac DA, Bladin CF, Kleinig TJ, Harvey J, Palanikumar L, Doss VT, Marescalco R, Fink JN, Tyson A, Schlick KH, Noh L, Wilson D, Figueroa S, Pech MA Jr, Paletz LB, Lewis MK, Castro M, Sahlein DH, Lafranchise EF, Sandall J, Asif KS, Geraghty SR, Cullis PA, Malisch T, Neill TA Jr, LaMonte MP, Campbell BCV, and Wu TY
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- Humans, Male, Female, Aged, Aged, 80 and over, Tissue Plasminogen Activator therapeutic use, Tenecteplase therapeutic use, Retrospective Studies, Fibrinolytic Agents, Intracranial Hemorrhages etiology, Intracranial Hemorrhages chemically induced, Treatment Outcome, Ischemic Stroke drug therapy, Brain Ischemia drug therapy, Brain Ischemia complications, Stroke drug therapy, Stroke complications
- Abstract
Importance: Symptomatic intracranial hemorrhage (sICH) is a serious complication of stroke thrombolytic therapy. Many stroke centers have adopted 0.25-mg/kg tenecteplase instead of alteplase for stroke thrombolysis based on evidence from randomized comparisons to alteplase as well as for its practical advantages. There have been no significant differences in symptomatic intracranial hemorrhage (sICH) reported from randomized clinical trials or published case series for the 0.25-mg/Kg dose., Objective: To assess the risk of sICH following ischemic stroke in patients treated with tenecteplase compared to those treated with alteplase., Design, Setting, and Participants: This was a retrospective observational study using data from the large multicenter international Comparative Effectiveness of Routine Tenecteplase vs Alteplase in Acute Ischemic Stroke (CERTAIN) collaboration comprising deidentified data on patients with ischemic stroke treated with intravenous thrombolysis. Data from more than 100 hospitals in New Zealand, Australia, and the US that used alteplase or tenecteplase for patients treated between July 1, 2018, and June 30, 2021, were included for analysis. Participating centers included a mix of nonthrombectomy- and thrombectomy-capacity comprehensive stroke centers. Standardized data were abstracted and harmonized from local or regional clinical registries. Consecutive patients with acute ischemic stroke who were considered eligible and received thrombolysis at the participating stroke registries during the study period were included. All 9238 patients who received thrombolysis were included in this retrospective analysis., Main Outcomes and Measures: sICH was defined as clinical worsening of at least 4 points on the National Institutes of Health Stroke Scale (NIHSS), attributed to parenchymal hematoma, subarachnoid, or intraventricular hemorrhage. Differences between tenecteplase and alteplase in the risk of sICH were assessed using logistic regression, adjusted for age, sex, NIHSS score, and thrombectomy., Results: Of the 9238 patients included in the analysis, the median (IQR) age was 71 (59-80) years, and 4449 patients (48%) were female. Tenecteplase was administered to 1925 patients. The tenecteplase group was older (median [IQR], 73 [61-81] years vs 70 [58-80] years; P < .001), more likely to be male (1034 of 7313 [54%] vs 3755 of 1925 [51%]; P < .01), had higher NIHSS scores (median [IQR], 9 [5-17] vs 7 [4-14]; P < .001), and more frequently underwent endovascular thrombectomy (38% vs 20%; P < .001). The proportion of patients with sICH was 1.8% for tenecteplase and 3.6% for alteplase (P < .001), with an adjusted odds ratio (aOR) of 0.42 (95% CI, 0.30-0.58; P < .01). Similar results were observed in both thrombectomy and nonthrombectomy subgroups., Conclusions and Relevance: In this large study, ischemic stroke treatment with 0.25-mg/kg tenecteplase was associated with lower odds of sICH than treatment with alteplase. The results provide evidence supporting the safety of tenecteplase for stroke thrombolysis in real-world clinical practice.
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- 2023
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225. In Vivo Neuropharmacological Effects of Neophytadiene.
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Gonzalez-Rivera ML, Barragan-Galvez JC, Gasca-Martínez D, Hidalgo-Figueroa S, Isiordia-Espinoza M, and Alonso-Castro AJ
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- Animals, Anticonvulsants therapeutic use, Flumazenil pharmacology, Molecular Docking Simulation, Hypnotics and Sedatives pharmacology, Hypnotics and Sedatives therapeutic use, Seizures chemically induced, Seizures drug therapy, Plant Extracts therapeutic use, Antidepressive Agents pharmacology, Antidepressive Agents therapeutic use, Behavior, Animal, Anti-Anxiety Agents therapeutic use
- Abstract
Neophytadiene (NPT) is a diterpene found in the methanolic extracts of Crataeva nurvala and Blumea lacera , plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1-10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light-dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.
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- 2023
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226. MSH-5: malignant knee tumors timely detection index.
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Rivera-Saldívar G, Torres-González R, Cario-Méndez A, Técualt-Gómez R, Amaya-Zepeda RA, Alcántara-Corona A, and Fuentes-Figueroa S
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- Humans, Mexico, Predictive Value of Tests, Retrospective Studies, Bone Neoplasms diagnostic imaging, Knee diagnostic imaging, Knee pathology
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Background: Bone neoplasms are usually misdiagnosed causing a delay in their treatment. Bone neoplasms are usually confused with tendinitis, 31% of the cases corresponds to osteosarcomas and in 21% to Ewing's sarcomas., Objective: To create a clinical-radiographic instrument of high diagnostic suspicion of knee bone neoplasms to prevent a delay in diagnosis., Method: A clinimetric study (sensitivity, consistency and validity) was performed in the bone tumor service, Hospital de Ortopedia de la Unidad Médica de Alta Especialidad Dr. Victorio de la Fuente Narváez, Instituto Mexicano del Seguro Social, in México City., Results: Characteristics of 153 patients were collected. For the sensitivity phase, 3 domains (signs, symptoms, and radiology) and 12 items were included. Consistency was evaluated with ICC (0.944), 95%CI (0.865-0.977), p < 0.001 and a-Cronbach (0.863). Index obtained a sensitivity of 0.80 and a specificity of 0.882 were obtained. The positive predictive value of the test was 66.6% and the negative predictive value was 93.75%. The positive likelihood ratio was 6.8 and the negative likelihood ratio was 0.2. Validity was evaluated using r-Pearson (0.894; p < 0.001)., Conclusions: A high suspicion clinical-radiographic index was designed to detect malignant knee tumors with adequate sensitivity, specificity, appearance, content, criteria, and construct validity., (Copyright: © 2023 Permanyer.)
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- 2023
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227. Neuropharmacological Activities of Ceiba aesculifolia (Kunth) Britten & Baker f (Malvaceae).
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Bustos-Gómez CI, Gasca-Martínez D, Yáñez-Barrientos E, Hidalgo-Figueroa S, Gonzalez-Rivera ML, Barragan-Galvez JC, Zapata-Morales JR, Isiordia-Espinoza M, Corrales-Escobosa AR, and Alonso-Castro AJ
- Abstract
Ceiba aesculifolia (Kunth) Britten & Baker f (Malvaceae) is used for the folk treatment of mood disorders. C. aesculifolia bark was extracted in ethanol, and the extract (CAE) was chemically standardized using gas chromatography-mass spectrometry (GC-MS). This study evaluated the effects of CAE (10-100 mg/kg p.o.) on anxiolytic-like activity, sedation, locomotor activity, depression-like activity, and spatial working memory using in vivo rodent models. A possible mechanism for the anxiolytic-like and antidepressant-like actions induced by CAE was assessed using neurotransmission pathway inhibitors. Myristic acid was one of the compounds found in CAE using GC-MS. This study also evaluated the anxiolytic-like activity and the sedative actions of myristic acid and assessed a possible mechanism of action using neurotransmission pathway inhibitors and an in silico analysis. CAE elicited anxiolytic-like activity and antidepressant-like effects (ED
50 = 57 mg/kg). CAE (10-100 mg/kg) did not affect locomotor coordination or induce sedation. The anxiolytic-like and antidepressant-like actions of CAE were reverted by prazosin, suggesting a possible participation of the noradrenergic system. The anxiolytic-like activity of myristic acid was reverted by the co-administration of prazosin and partially reverted by ketanserin. The docking study revealed that myristic acid can form favorable interactions within 5-HT2A and α1A-adrenoreceptor binding pockets.- Published
- 2022
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228. nAMD: optimization of patient care and patient-oriented information with the help of an internet-based survey.
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Schmid A, Bucher F, Liczenczias E, Maslanka Figueroa S, Müller B, and Agostini H
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- Aged, Aged, 80 and over, Angiogenesis Inhibitors therapeutic use, Cross-Sectional Studies, Female, Humans, Internet, Male, Patient Care, Quality of Life, Surveys and Questionnaires, Macular Degeneration drug therapy
- Abstract
Purpose: This survey was conducted to identify factors that influence how patients with neovascular age-related macular degeneration (nAMD) deal with their disease and information that are considered useful from a patient's point of view., Methods: A total of 5035 patients with nAMD living in Germany were interviewed via internet-based cross-sectional survey, where the following information was collected: personal data, disease awareness, and patients' needs. In addition, a Quality of Life questionnaire (SF-12v2) could be completed., Results: Out of the 5035 participants, more males than females participated (55% vs 45%), and most participants were in the age groups 76 to 85 years (37%) and 66 to 75 years (35%). Seventy-three percent of patients rated their understanding of the disease as at least sufficient, and more than two-thirds of the patients (68%) were aware that their disease needs to be controlled on a regular basis and treated on an "as needed" basis. Regarding potential risk factors for AMD, most participants were aware of age (89%), but only 39% of hereditary load and 33% of smoking as evidence-based risk factors, indicating a need for further information. The doctor remains the major source of information (93%), with internet (29%), brochures (14%), opticians (13%), or patient support groups (4%) with only limited contribution. Distance to the treatment center was identified as one of the factors, which had the greatest influence on patients' compliance. A "treat as needed" regime turned out to be the preferred control and treatment schedule in contrast to a "fixed appointment" every 4 weeks., Conclusion: This internet-based survey appears to be representative for nAMD patients. To increase patients' compliance, proximity to the treatment center and a "treat as needed" regime turned out to be important factors as well as patients' awareness of their disease. In this regard, the reported desire for more information indicates that patients' knowledge still needs to be improved. Our results will help to further optimize patient care and patient-oriented information., (© 2022. The Author(s).)
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- 2022
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229. Outcomes From a Nursing-Driven Acute Stroke Care Protocol for Telehealth Encounters.
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Olson DM, Provencher M, Stutzman SE, Hynan LS, Novakovic S, Guttikonda S, Figueroa S, Novakovic-White R, Yang JP, and Goldberg MP
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- Fibrinolytic Agents therapeutic use, Humans, Prospective Studies, Thrombolytic Therapy, Time Factors, Time-to-Treatment, Tissue Plasminogen Activator therapeutic use, Treatment Outcome, Clinical Protocols, Ischemic Stroke nursing, Ischemic Stroke therapy, Telemedicine
- Abstract
Introduction: Nursing care is widely recognized to be a vital element in stroke care delivery. However, no publications examining clinical education and optimal workflow practices as predictors of acute ischemic stroke care metrics exist. This study aimed to explore the impact of a nurse-led workflow to improve patient care that included telestroke encounters in the emergency department., Methods: A nonrandomized prospective pre- and postintervention unit-level feasibility study design was used to explore how implementing nurse-driven acute stroke care affects the efficiency and quality of telestroke encounters in the emergency department. Nurses and providers in the emergency department received education/training, and then the Nursing-Driven Acute Ischemic Stroke Care protocol was implemented., Results: There were 180 acute ischemic stroke encounters (40.3%) in the control phase and 267 (59.7%) in the postintervention phase with similar demographic characteristics. Comparing the control with intervention times directly affected by the nurse-driven protocol, there was a significant reduction in median door-to-provider times (5 [interquartile range 12] vs 2 [interquartile range 9] minutes, P < .001) and in median door-to-computed tomography scan times (9 [interquartile range 18] vs 5 [interquartile range 11] minutes, P < .001); however, the metrics potentially affected by extraneous variables outside of the nurse-driven protocol demonstrated longer median door-to-ready times (21 [interquartile range 24] vs 25 [interquartile range 25] minutes, P < .001). Door-to-specialist and door-to-needle times were not significantly different., Discussion: In this sample, implementation of the nurse-driven acute stroke care protocol is associated with improved nurse-sensitive stroke time metrics but did not translate to faster delivery of thrombolytic agents for acute ischemic stroke, emphasizing the importance of well-outlined workflows and standardized stroke code protocols at every point in acute ischemic stroke care., (Copyright © 2022 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)
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- 2022
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230. 4-Hydroxybenzoic Acid and β -Sitosterol from Cucurbita ficifolia Act as Insulin Secretagogues, Peroxisome Proliferator-Activated Receptor-Gamma Agonists, and Liver Glycogen Storage Promoters: In Vivo , In Vitro , and In Silico Studies.
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Rosiles-Alanis W, Zamilpa A, García-Macedo R, Zavala-Sánchez MA, Hidalgo-Figueroa S, Mora-Ramiro B, Román-Ramos R, Estrada-Soto SE, and Almanza-Perez JC
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- Animals, Hypoglycemic Agents therapeutic use, Insulin metabolism, Liver Glycogen, PPAR gamma agonists, PPAR gamma genetics, Parabens, Plant Extracts chemistry, RNA, Messenger, Secretagogues therapeutic use, Sitosterols, Cucurbita chemistry, Diabetes Mellitus, Experimental drug therapy
- Abstract
Insulin secretion and GLUT4 expression are two critical events in glucose regulation. The receptors G-protein-coupled receptor 40 (GPR40) and peroxisome proliferator-activated receptor-gamma (PPAR γ ) modulate these processes, and they represent potential therapeutic targets for new antidiabetic agent's design. Cucurbita ficifolia fruit is used in traditional medicine for diabetes control. Previous studies demonstrated several effects: a hypoglycemic effect mediated by an insulin secretagogue action, antihyperglycemic effect, and promoting liver glycogen storage. Anti-inflammatory and antioxidant effects were also reported. Moreover, some of its phytochemicals have been described, including d-chiro-inositol. However, to understand these effects integrally, other active principles should be investigated. The aim was to perform a chemical fractionation guided by bioassay to isolate and identify other compounds from C. ficifolia fruit that explain its hypoglycemic action as insulin secretagogue, its antihyperglycemic effect by PPAR γ activation, and on liver glycogen storage. Three different preparations of C. ficifolia were tested in vivo . Ethyl acetate fraction derived from aqueous extract showed antihyperglycemic effect in an oral glucose tolerance test and was further fractioned. The insulin secretagogue action was tested in RINm5F cells. For the PPAR γ activation, C2C12 myocytes were treated with the fractions, and GLUT4 mRNA expression was measured. Chemical fractionation resulted in the isolation and identification of β -sitosterol and 4-hydroxybenzoic acid (4-HBA), which increased insulin secretion, GLUT4, PPAR γ , and adiponectin mRNA expression, in addition to an increase in glycogen storage. 4-HBA exhibited an antihyperglycemic effect, while β -sitosterol showed hypoglycemic effect, confirming the wide antidiabetic related results we found in our in vitro models. An in silico study revealed that 4-HBA and β -sitosterol have potential as dual agonists on PPAR γ and GPR40 receptors. Both compounds should be considered in the development of new antidiabetic drug development.
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- 2022
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231. T-Cell Receptor/HLA Humanized Mice Reveal Reduced Tolerance and Increased Immunogenicity of Posttranslationally Modified GAD65 Epitope.
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Jing Y, Kong Y, McGinty J, Blahnik-Fagan G, Lee T, Orozco-Figueroa S, Bettini ML, James EA, and Bettini M
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- Animals, Autoantigens, Epitopes, Epitopes, T-Lymphocyte, HLA-DR4 Antigen, Mice, Receptors, Antigen, T-Cell genetics, Diabetes Mellitus, Type 1, Islets of Langerhans
- Abstract
Accumulating evidence supports a critical role for posttranslationally modified (PTM) islet neoantigens in type 1 diabetes. However, our understanding regarding thymic development and peripheral activation of PTM autoantigen-reactive T cells is still limited. Using HLA-DR4 humanized mice, we observed that deamidation of GAD65115-127 generates a more immunogenic epitope that recruits T cells with promiscuous recognition of both the deamidated and native epitopes and reduced frequency of regulatory T cells. Using humanized HLA/T-cell receptor (TCR) mice, we observed that TCRs reactive to the native or deamidated GAD65115-127 led to efficient development of CD4+ effector T cells; however, regulatory T-cell development was reduced in mice expressing the PTM-reactive TCR, which was partially restored with exogenous PTM peptide. Upon priming, both the native-specific and the deamidated-specific T cells accumulated in pancreatic islets, suggesting that both specificities can recognize endogenous GAD65 and contribute to anti-β-cell responses. Collectively, our observations in polyclonal and single TCR systems suggest that while effector T-cell responses can exhibit cross-reactivity between native and deamidated GAD65 epitopes, regulatory T-cell development is reduced in response to the deamidated epitope, pointing to regulatory T-cell development as a key mechanism for loss of tolerance to PTM antigenic targets., (© 2022 by the American Diabetes Association.)
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- 2022
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232. Expanding the Study of the Cytotoxicity of Incomptines A and B against Leukemia Cells.
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Calzada F, Garcia-Hernandez N, Hidalgo-Figueroa S, Bautista E, Barbosa E, Velázquez C, and Hernández-Caballero ME
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- Humans, Cell Line, Tumor, Lactones pharmacology, Lactones chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents, Phytogenic pharmacology, Antineoplastic Agents, Phytogenic chemistry, Cell Survival drug effects, Molecular Structure, HL-60 Cells, Molecular Docking Simulation, Sesquiterpenes pharmacology, Sesquiterpenes chemistry, Leukemia drug therapy, Leukemia pathology
- Abstract
Heliangolide-type sesquiterpene lactones (HTSLs) are phytocompounds with several pharmacological activities including cytotoxic and antitumor activity. Both bioactivities are related to an α-methylene-γ-lactone moiety and an ester group on carbon C-8 in the sesquiterpene lactone (SL) structure. Two HTSLs, incomptines A ( AI ) and B ( IB ) isolated from Decachaeta incompta , were evaluated for their cytotoxic activity on three leukemia cell lines: HL-60, K-562, and REH cells. Both compounds were subjected to a molecular docking study using target proteins associated with cancer such as topoisomerase IIα, topoisomerase IIβ, dihydrofolate reductase, methylenetetrahydrofolate dehydrogenase, and Bcl-2-related protein A1. Results show that IA and IB exhibit cytotoxic activity against all cell lines used. The CC
50 value of IA was 2-4-fold less than etoposide and methotrexate, two anticancer drugs used as positive controls. The cytotoxic activity of IB was close to that of etoposide and methotrexate. The molecular docking analysis showed that IA and IB have important interaction on all targets used. These findings suggest that IA and IB may serve as scaffolds for the development of new treatments for different types of leukemia.- Published
- 2022
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233. Understanding the Anti-Diarrhoeal Properties of Incomptines A and B: Antibacterial Activity against Vibrio cholerae and Its Enterotoxin Inhibition.
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Calzada F, Bautista E, Hidalgo-Figueroa S, García-Hernández N, Velázquez C, Barbosa E, Valdes M, and Solares-Pascasio JI
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Incomptines A ( IA ) and B ( IB ) are two sesquiterpene lactones with antiprotozoal, antibacterial, cytotoxic, antitumor, spermicidal, and phytotoxic properties. The antibacterial activity of IA and IB against bacteria causing diarrhoea have been reported; however, no information is available regarding their antibacterial activity on Vibrio cholerae . In this work, both compounds were evaluated for their anti-diarrhoeal potential using the bacterium V. cholerae , sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on cholera toxin, and a cholera toxin-induced diarrhoea model in male Balb/c mice. In addition, a molecular docking study was carried out to understand the interaction of IA and IB with cholera toxin. In terms of antibacterial activity, IB was three times more active than IA on V. cholerae . In the case of SDS-PAGE analysis and the in silico study, IA was most effective, revealing its potential binding mode at a molecular level. In terms of anti-diarrhoeal activity, IA was 10 times more active than IB and racecadotril, an antisecretory drug used as positive control; the anti-diarrheal activity of IB was also closer than racecadotril. The results obtained from in vitro, in vivo, and computational studies on V. cholerae and cholera toxin support the potential of IA and IB as new anti-diarrhoeal compounds.
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- 2022
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234. Synthesis, In Vitro, In Vivo and In Silico Antidiabetic Bioassays of 4-Nitro(thio)phenoxyisobutyric Acids Acting as Unexpected PPARγ Modulators: An In Combo Study.
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Colin-Lozano B, Torres-Gomez H, Hidalgo-Figueroa S, Chávez-Silva F, Estrada-Soto S, Almanza-Pérez JC, and Navarrete-Vazquez G
- Abstract
Four isobutyric acids (two nitro and two acetamido derivatives) were prepared in two steps and characterized using spectral analysis. The mRNA concentrations of PPARγ and GLUT-4 (two proteins documented as key diabetes targets) were increased by 3T3-L1 adipocytes treated with compounds 1 - 4 , but an absence of in vitro expression of PPARα was observed. Docking and molecular dynamics studies revealed the plausible interaction between the synthesized compounds and PPARγ. In vivo studies established that compounds 1 - 4 have antihyperglycemic modes of action associated with insulin sensitization. Nitrocompound 2 was the most promising of the series, being orally active, and one of multiple modes of action could be selective PPARγ modulation due to its extra anchoring with Gln-286. In conclusion, we demonstrated that nitrocompound 2 showed strong in vitro and in vivo effects and can be considered as an experimental antidiabetic candidate.
- Published
- 2022
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235. Modulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs).
- Author
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Chen PH, Hu Z, An E, Okeke I, Zheng S, Luo X, Gong A, Jaime-Figueroa S, and Crews CM
- Subjects
- Apoptosis Regulatory Proteins, Catalytic Domain, Enzyme Activation, Forkhead Box Protein O3, HeLa Cells, Holoenzymes chemistry, Humans, Phosphorylation, RNA-Binding Proteins, Structure-Activity Relationship, Chimera metabolism, Phosphoproteins chemistry, Protein Tyrosine Phosphatases metabolism
- Abstract
Protein phosphorylation, which regulates many critical aspects of cell biology, is dynamically governed by kinases and phosphatases. Many diseases are associated with dysregulated hyperphosphorylation of critical proteins, such as retinoblastoma protein in cancer. Although kinase inhibitors have been widely applied in the clinic, growing evidence of off-target effects and increasing drug resistance prompts the need to develop a new generation of drugs. Here, we propose a proof-of-concept study of phosphorylation targeting chimeras (PhosTACs). Similar to PROTACs in their ability to induce ternary complexes, PhosTACs focus on recruiting a Ser/Thr phosphatase to a phosphosubstrate to mediate its dephosphorylation. However, distinct from PROTACs, PhosTACs can uniquely provide target gain-of-function opportunities to manipulate protein activity. In this study, we applied a chemical biology approach to evaluate the feasibility of PhosTACs by recruiting the scaffold and catalytic subunits of the PP2A holoenzyme to protein substrates such as PDCD4 and FOXO3a for targeted protein dephosphorylation. For FOXO3a, this dephosphorylation resulted in the transcriptional activation of a FOXO3a-responsive reporter gene.
- Published
- 2021
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236. High sensitivity-low cost detection of SARS-CoV-2 by two steps end point RT-PCR with agarose gel electrophoresis visualization.
- Author
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Figueroa S, Freire-Paspuel B, Vega-Mariño P, Velez A, Cruz M, Cardenas WB, and Garcia-Bereguiain MA
- Subjects
- COVID-19 genetics, COVID-19 Nucleic Acid Testing economics, COVID-19 Testing methods, Coronavirus Nucleocapsid Proteins genetics, DNA Primers, Electrophoresis, Agar Gel methods, Humans, Laboratories, Nasopharynx virology, RNA, Viral genetics, Ribonuclease P genetics, Ribonuclease P metabolism, SARS-CoV-2 pathogenicity, Sensitivity and Specificity, COVID-19 diagnosis, COVID-19 Nucleic Acid Testing methods, SARS-CoV-2 genetics
- Abstract
More than one year since Coronavirus disease 2019 (COVID-19) pandemic outbreak, the gold standard technique for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is still the RT-qPCR. This is a limitation to increase testing capacities, particularly at developing countries, as expensive reagents and equipment are required. We developed a two steps end point RT-PCR reaction with SARS-CoV-2 Nucleocapsid (N) gene and Ribonuclease P (RNase P) specific primers where viral amplicons were verified by agarose gel electrophoresis. We carried out a clinical performance and analytical sensitivity evaluation for this two-steps end point RT-PCR method with 242 nasopharyngeal samples using the CDC RT-qPCR protocol as a gold standard technique. With a specificity of 95.8%, a sensitivity of 95.1%, and a limit of detection of 20 viral RNA copies/uL, this two steps end point RT-PCR assay is an affordable and reliable method for SARS-CoV-2 detection. This protocol would allow to extend COVID-19 diagnosis to basic molecular biology laboratories with a potential positive impact in surveillance programs at developing countries., (© 2021. The Author(s).)
- Published
- 2021
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237. Antilymphoma Effect of Incomptine A: In Vivo, In Silico, and Toxicological Studies.
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Calzada F, Bautista E, Hidalgo-Figueroa S, García-Hernández N, Barbosa E, Velázquez C, Ordoñez-Razo RM, and Arietta-García AG
- Subjects
- Animals, Cell Line, Tumor, Disease Models, Animal, Dose-Response Relationship, Drug, Humans, Lethal Dose 50, Ligands, Mice, Molecular Conformation, Molecular Docking Simulation, Molecular Dynamics Simulation, Molecular Structure, Structure-Activity Relationship, Xenograft Model Antitumor Assays, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Sesquiterpenes chemistry, Sesquiterpenes pharmacology
- Abstract
Incomptine A ( IA ) is a sesquiterpene lactone isolated from Decachaeta incompta that induces apoptosis, reactive oxygen species production, and a differential protein expression on the U-937 (diffuse histiocytic lymphoma) cell line. In this work, the antitumor potential of IA was investigated on Balb/c mice inoculated with U-937 cells and through the brine shrimp lethality (BSL) test. Furthermore, IA was subjected to molecular docking study using as targets proteins associated with processes of cancer as apoptosis, oxidative stress, and glycolytic metabolism. In addition to determining the potential toxicity of IA in human, its acute toxicity was performed in mice. Results reveals that IA showed high antilymphoma activity and BSL with an EC
50 of 2.4 mg/kg and LC50 16.7 µg/mL, respectively. The molecular docking study revealed that IA has strong interaction on all targets used. In the acute oral toxicity, IA had a LD50 of 149 mg/kg. The results showed that the activities of IA including antilymphoma activity, BSL, acute toxicity, and in silico interactions were close to the methotrexate, an anticancer drug used as positive control. These findings suggest that IA may serve as a candidate for the development of a new drug to combat lymphoma.- Published
- 2021
- Full Text
- View/download PDF
238. 'Real-life' experience with direct-acting antiviral agents for HCV after kidney transplant.
- Author
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Fabrizi F, Alonso C, Palazzo A, Anders M, Reggiardo MV, Cheinquer H, Zuain MGV, Figueroa S, Mendizabal M, Silva M, and Ridruejo E
- Subjects
- 2-Naphthylamine therapeutic use, Administration, Oral, Adult, Aged, Anilides therapeutic use, Benzofurans, Cohort Studies, Creatinine blood, Cyclopropanes therapeutic use, Drug Combinations, Female, Glomerular Filtration Rate, Hepatitis C complications, Hepatitis C pathology, Humans, Imidazoles, Lactams, Macrocyclic therapeutic use, Male, Middle Aged, Proline analogs & derivatives, Proline therapeutic use, Quinoxalines, Ribavirin therapeutic use, Ritonavir therapeutic use, Sofosbuvir therapeutic use, Sulfonamides therapeutic use, Uracil analogs & derivatives, Uracil therapeutic use, Valine therapeutic use, Antiviral Agents therapeutic use, Hepatitis C drug therapy, Kidney Transplantation, Sustained Virologic Response
- Abstract
Introductions and Objectives: The introduction of direct-acting antiviral (DAA) agents promises to change dramatically the management of hepatitis C in kidney transplant recipients, a patient group where the treatment of hepatitis C is historically challenging. The purpose of the current study was to assess (in a 'real-life' setting) the safety and efficacy of all-oral, interferon-free, direct-acting antiviral agents in kidney transplant recipients with HCV., Material and Methods: We performed a single-arm, multi-center study in a cohort (n = 95) of kidney transplant recipients who underwent antiviral therapy with DAAs. The primary end-point was sustained virologic response (SVR) (serum HCV RNA < 15 IU/mL, 12 weeks after treatment ended; SVR12). We recorded data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities., Results: Various regimens were adopted at the discretion of the treating physician: elbasvir/grazoprevir (n = 11), paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens ± ribavirin (n = 23), and sofosbuvir-based regimens ± ribavirin (n = 61). The SVR12 rate was 93.7% (89/95) (95% CI, 88%; 98%), according to intention-to-treat analysis; three patients without viral response (n = 3) were found. Ribavirin was administered in 8 (8.4%) allograft recipients. The frequency of drop-outs was 4.2% (4/95) (95% CI, 0.2%; 8.2%); these were related to arthralgia/myalgia (n = 2), fatigue (n = 1), and lowered estimated glomerular filtration rate (eGFR) (n = 1). There were no differences with regard to serum creatinine and eGFR before and after antiviral therapy and during follow-up in the whole cohort. The patient who interrupted antiviral treatment due to raised serum creatinine was on sofosbuvir/daclatasvir regimen; one of the four drop-outs obtained SVR., Conclusions: All-oral, interferon-free therapy with DAAs for chronic HCV after kidney transplantation was effective and well-tolerated in a 'real-life' clinical setting. Identical results have been observed in patients with intact kidneys or advanced chronic kidney disease. Careful evaluation of kidney function over follow-up in kidney transplant recipients who received DAAs regimens is recommended. Clinical trials aimed to assess whether sustained viral response translates into improved patient/graft survival are under way., (Copyright © 2021 AEDV. Published by Elsevier España, S.L.U. All rights reserved.)
- Published
- 2021
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239. Synthesis, molecular docking, dynamic simulation and pharmacological characterization of potent multifunctional agent (dual GPR40-PPARγ agonist) for the treatment of experimental type 2 diabetes.
- Author
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Hidalgo-Figueroa S, Rodríguez-Luévano A, Almanza-Pérez JC, Giacoman-Martínez A, Ortiz-Andrade R, León-Rivera I, and Navarrete-Vázquez G
- Subjects
- Animals, Mice, Diabetes Mellitus, Experimental drug therapy, Diabetes Mellitus, Experimental metabolism, Glucose Transporter Type 4 metabolism, Male, Insulin metabolism, 3T3-L1 Cells, Rats, Insulin-Secreting Cells drug effects, Insulin-Secreting Cells metabolism, Humans, Insulin Secretion drug effects, Adipocytes drug effects, Adipocytes metabolism, PPAR gamma agonists, PPAR gamma metabolism, Molecular Docking Simulation, Receptors, G-Protein-Coupled agonists, Receptors, G-Protein-Coupled metabolism, Hypoglycemic Agents pharmacology, Hypoglycemic Agents chemistry, Hypoglycemic Agents chemical synthesis, Hypoglycemic Agents therapeutic use, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 metabolism, Molecular Dynamics Simulation
- Abstract
The current manuscript describes two molecules that were designed against PPARγ and GPR40 receptors. The preparation of the compounds was carried out following a synthetic route of multiple steps. Then, the mRNA expression levels of PPARγ, GLUT4, and GPR40 induced by compounds were measured and quantified in adipocyte and β-pancreatic cell cultures. The synthesized compound 1 caused an increase in the 4-fold expression of mRNA of PPARγ regarding the control and had a similar behavior to the pioglitazone, while compound 2 only increased 2-fold the expression. Also, the compound 1 increased to 7-fold the GLUT4 expression levels, respect to the control and twice against the pioglitazone. On the other hand, the 1 increase 3-fold GPR40 expression, and compound 2 had a minor activity. Besides, 1 and 2 showed a moderated increase on insulin secretion and calcium mobilization versus the glibenclamide. Based on the molecular docking studies, the first compound had a similar conformation to co-crystal ligands into the binding site of both receptors. The poses were docked keeping the most important interactions and maintaining the interaction along the Molecular Dynamics simulation (20 ns). Finally, compound (1) showed an antihyperglycemic effect at 5 mg/kg, however at higher doses of 25 mg/kg it controlled blood glucose levels associated with feeding intake and without showing the adverse effects associated with insulin secretagogues (hypoglycemia). For these reasons, we have concluded that molecule 1 acts as a dual PPARγ and GPR40 agonist offering a better glycemic control than current treatments., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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240. Clinical Results of the Implementation of a Breast Milk Bank in Premature Infants (under 37 Weeks) at the Hospital Universitario del Valle 2018-2020.
- Author
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Torres-Muñoz J, Jimenez-Fernandez CA, Murillo-Alvarado J, Torres-Figueroa S, and Castro JP
- Subjects
- Adult, Cross-Sectional Studies, Female, Gestational Age, Humans, Infant Nutritional Physiological Phenomena, Infant, Newborn, Intensive Care Units, Neonatal, Male, Odds Ratio, Treatment Outcome, Young Adult, Infant, Premature growth & development, Infant, Premature, Diseases prevention & control, Milk Banks, Milk, Human, Nutritional Support methods
- Abstract
Breast milk is widely recognized as the best source of nutrition for both full term and premature babies. We aimed to identify clinical results of the implementation of a breast milk bank for premature infants under 37 weeks in a level III hospital. 722 neonates under 37 weeks, hospitalized in the Neonatal intensive care unit (ICU), who received human breast milk from the institution's milk bank 57% ( n = 412) vs. mixed or artificial 32% ( n = 229), at day 7 of life. An exploratory data analysis was carried out. Measures of central tendency and dispersion were used, strength of association of odds ratio (OR) and its confidence intervals (95% confidence interval (CI)). 88.5% had already received human milk before day 7 of life. Those who received human milk, due to their clinical condition, had 4 times a greater chance of being intubated (OR 4.05; 95% CI 1.80-9.11). Starting before day 7 of life decreases the opportunity to develop necrotizing enterocolitis by 82% (adjusted odds ratio (ORa) 0.18; 95% CI 0.03-0.97), intraventricular hemorrhage by 85% (ORa 0.15; 95% CI 0.06-0.45) and sepsis by 77% (ORa 0.23; 95% CI 0.15-0.33). Receiving human milk reduces the probability of complications related to prematurity, evidencing the importance that breast milk banks play in clinical practice.
- Published
- 2021
- Full Text
- View/download PDF
241. Synthesis of Isoquinolones by Sequential Suzuki Coupling of 2-Halobenzonitriles with Vinyl Boronate Followed by Cyclization.
- Author
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Jaime-Figueroa S, Bond MJ, Vergara JI, Swartzel JC, and Crews CM
- Subjects
- Catalysis, Cyclization, Nitriles
- Abstract
A novel, facile, and expeditious two-step synthesis of 3,4-unsubstituted isoquinolin-1(2 H )-ones from a Suzuki cross-coupling between 2-halobenzonitriles and commercially available vinyl boronates followed by platinum-catalyzed nitrile hydrolysis and cyclization is described.
- Published
- 2021
- Full Text
- View/download PDF
242. Targeted degradation of transcription factors by TRAFTACs: TRAnscription Factor TArgeting Chimeras.
- Author
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Samarasinghe KTG, Jaime-Figueroa S, Burgess M, Nalawansha DA, Dai K, Hu Z, Bebenek A, Holley SA, and Crews CM
- Subjects
- Animals, Binding Sites, Cells, Cultured, DNA-Binding Proteins chemistry, DNA-Binding Proteins metabolism, HEK293 Cells, Humans, Zebrafish, Oligonucleotides metabolism, Transcription Factors metabolism
- Abstract
Many diseases, including cancer, stem from aberrant activation or overexpression of oncoproteins that are associated with multiple signaling pathways. Although proteins with catalytic activity can be successfully drugged, the majority of other protein families, such as transcription factors, remain intractable due to their lack of ligandable sites. In this study, we report the development of TRAnscription Factor TArgeting Chimeras (TRAFTACs) as a generalizable strategy for targeted transcription factor degradation. We show that TRAFTACs, which consist of a chimeric oligonucleotide that simultaneously binds to the transcription factor of interest (TOI) and to HaloTag-fused dCas9 protein, can induce degradation of the former via the proteasomal pathway. Application of TRAFTACs to two oncogenic TOIs, NF-κB and brachyury, suggests that TRAFTACs can be successfully employed for the targeted degradation of other DNA-binding proteins. Thus, TRAFTAC technology is potentially a generalizable strategy to induce degradation of other transcription factors both in vitro and in vivo., Competing Interests: Declaration of interests C.M.C. is founder, shareholder, and consultant to Arvinas, Inc. and Halda, LLC, which support research in his laboratory., (Published by Elsevier Ltd.)
- Published
- 2021
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- View/download PDF
243. Reply.
- Author
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Lalloo D, Gallagher J, Macdonald EB, McDonnell C, and Vargas-Prada Figueroa S
- Subjects
- Health Personnel, Humans, Peer Review, Physicians
- Published
- 2021
- Full Text
- View/download PDF
244. Targeted Delivery of Soluble Guanylate Cyclase (sGC) Activator Cinaciguat to Renal Mesangial Cells via Virus-Mimetic Nanoparticles Potentiates Anti-Fibrotic Effects by cGMP-Mediated Suppression of the TGF-β Pathway.
- Author
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Fleischmann D, Harloff M, Maslanka Figueroa S, Schlossmann J, and Goepferich A
- Subjects
- Animals, Benzoates pharmacokinetics, Biomimetic Materials, Cells, Cultured, Cyclic GMP metabolism, Diabetic Nephropathies drug therapy, Diabetic Nephropathies metabolism, Diabetic Nephropathies pathology, Enzyme Activation drug effects, Enzyme Stability drug effects, Fibrosis, Humans, Mesangial Cells pathology, Models, Biological, Nanoparticles administration & dosage, Rats, Signal Transduction drug effects, Transforming Growth Factor beta metabolism, Benzoates administration & dosage, Drug Delivery Systems, Mesangial Cells drug effects, Mesangial Cells metabolism, Soluble Guanylyl Cyclase metabolism
- Abstract
Diabetic nephropathy (DN) ranks among the most detrimental long-term effects of diabetes, affecting more than 30% of all patients. Within the diseased kidney, intraglomerular mesangial cells play a key role in facilitating the pro-fibrotic turnover of extracellular matrix components and a progredient glomerular hyperproliferation. These pathological effects are in part caused by an impaired functionality of soluble guanylate cyclase (sGC) and a consequentially reduced synthesis of anti-fibrotic messenger 3',5'-cyclic guanosine monophosphate (cGMP). Bay 58-2667 (cinaciguat) is able to re-activate defective sGC; however, the drug suffers from poor bioavailability and its systemic administration is linked to adverse events such as severe hypotension, which can hamper the therapeutic effect. In this study, cinaciguat was therefore efficiently encapsulated into virus-mimetic nanoparticles (NPs) that are able to specifically target renal mesangial cells and therefore increase the intracellular drug accumulation. NP-assisted drug delivery thereby increased in vitro potency of cinaciguat-induced sGC stabilization and activation, as well as the related downstream signaling 4- to 5-fold. Additionally, administration of drug-loaded NPs provided a considerable suppression of the non-canonical transforming growth factor β (TGF-β) signaling pathway and the resulting pro-fibrotic remodeling by 50-100%, making the system a promising tool for a more refined therapy of DN and other related kidney pathologies.
- Published
- 2021
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- View/download PDF
245. Mutant-selective degradation by BRAF-targeting PROTACs.
- Author
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Alabi S, Jaime-Figueroa S, Yao Z, Gao Y, Hines J, Samarasinghe KTG, Vogt L, Rosen N, and Crews CM
- Subjects
- Animals, Cell Line, Tumor, Cell Proliferation drug effects, Female, Humans, Mice, Mice, Nude, Molecular Targeted Therapy, Mutation, Neoplasms enzymology, Neoplasms genetics, Neoplasms physiopathology, Proteolysis drug effects, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Ubiquitination drug effects, Xenograft Model Antitumor Assays, Antineoplastic Agents administration & dosage, Neoplasms drug therapy, Protein Kinase Inhibitors administration & dosage, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf metabolism, Vemurafenib administration & dosage
- Abstract
Over 300 BRAF missense mutations have been identified in patients, yet currently approved drugs target V600 mutants alone. Moreover, acquired resistance inevitably emerges, primarily due to RAF lesions that prevent inhibition of BRAF V600 with current treatments. Therefore, there is a need for new therapies that target other mechanisms of activated BRAF. In this study, we use the Proteolysis Targeting Chimera (PROTAC) technology, which promotes ubiquitination and degradation of neo-substrates, to address the limitations of BRAF inhibitor-based therapies. Using vemurafenib-based PROTACs, we achieve low nanomolar degradation of all classes of BRAF mutants, but spare degradation of WT RAF family members. Our lead PROTAC outperforms vemurafenib in inhibiting cancer cell growth and shows in vivo efficacy in a Class 2 BRAF xenograft model. Mechanistic studies reveal that BRAF
WT is spared due to weak ternary complex formation in cells owing to its quiescent inactivated conformation, and activation of BRAFWT sensitizes it to degradation. This study highlights the degree of selectivity achievable with degradation-based approaches by targeting mutant BRAF-driven cancers while sparing BRAFWT , providing an anti-tumor drug modality that expands the therapeutic window.- Published
- 2021
- Full Text
- View/download PDF
246. Biomedical nanoparticle design: What we can learn from viruses.
- Author
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Maslanka Figueroa S, Fleischmann D, and Goepferich A
- Subjects
- Tissue Distribution, Nanoparticles, Nanostructures, Viruses
- Abstract
Viruses are nanomaterials with a number of properties that surpass those of many synthetic nanoparticles (NPs) for biomedical applications. They possess a rigorously ordered structure, come in a variety of shapes, and present unique surface elements, such as spikes. These attributes facilitate propitious biodistribution, the crossing of complex biological barriers and a minutely coordinated interaction with cells. Due to the orchestrated sequence of interactions of their stringently arranged particle corona with cellular surface receptors they effectively identify and infect their host cells with utmost specificity, while evading the immune system at the same time. Furthermore, their efficacy is enhanced by their response to stimuli and the ability to spread from cell to cell. Over the years, great efforts have been made to mimic distinct viral traits to improve biomedical nanomaterial performance. However, a closer look at the literature reveals that no comprehensive evaluation of the benefit of virus-mimetic material design on the targeting efficiency of nanomaterials exists. In this review we, therefore, elucidate the impact that viral properties had on fundamental advances in outfitting nanomaterials with the ability to interact specifically with their target cells. We give a comprehensive overview of the diverse design strategies and identify critical steps on the way to reducing them to practice. More so, we discuss the advantages and future perspectives of a virus-mimetic nanomaterial design and try to elucidate if viral mimicry holds the key for better NP targeting., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
247. COVID-19 Impact on Acute Ischemic Stroke Treatment at 9 Comprehensive Stroke Centers across Los Angeles.
- Author
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Padrick MM, Sangha N, Paletz L, Mirocha J, Figueroa S, Manoukian V, Schlick K, Lyden PD, Liebeskind DS, Chatfield FK, Tarpley JW, Burgos A, Tenser M, Gaffney D, Pech MA, Nazareth E, Jackson R, Kauffman H, Arnold L, Cox J, Joyce T, Nakamura C, Fitzgerald D, Ogami K, Steiner N, Wolber N, Robertson B, Izzo R, Gorski S, Manuel H, Valdez K, Reyes L, Sharma LK, and Song SS
- Subjects
- Brain Ischemia diagnosis, Brain Ischemia therapy, Humans, Los Angeles epidemiology, Retrospective Studies, SARS-CoV-2, Stroke diagnosis, Stroke epidemiology, Thrombectomy, Time-to-Treatment, Treatment Outcome, Brain Ischemia epidemiology, COVID-19, Fibrinolytic Agents adverse effects, Ischemic Stroke, Stroke therapy, Thrombolytic Therapy
- Abstract
Objective: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC)., Methods: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution., Results: There was a 17.3% decrease in stroke code activations across LAC in 2020 compared to 2019 (1,786 vs. 2,159, respectively, χ2 goodness of fit test p < 0.0001) across 9 participating comprehensive stroke centers. Patients who did not receive any reperfusion therapy decreased by 16.6% in 2020 (1,527) compared to 2019 (1,832). Patients who received only intravenous thrombolytic (IVT) therapy decreased by 31.8% (107 vs. 157). Patients who received only mechanical thrombectomy (MT) increased by 3% (102 vs. 99). Patients who received both IVT and MT decreased by 31.8% (45 vs. 66). Recanalization treatment times in 2020 were comparable to 2019. CSCs serving a higher proportion of Latinx populations in the eastern parts of LAC experienced a higher incidence of MT in 2020 compared to 2019. Mild increase in stroke severity was seen in 2020 compared to 2019 (8.95 vs. 8.23, p = 0.046). A higher percentage of patients were discharged home in 2020 compared to 2019 (59.5 vs. 56.1%, p = 0.034), a lower percentage of patients were discharged to skilled nursing facility (16.1 vs. 20.7%, p = 0.0004), and a higher percentage of patients expired (8.6 vs. 6.3%, p = 0.008)., Conclusion: LAC saw a decrease in overall stroke code activations in 2020 compared to 2019. Reperfusion treatment times remained comparable to prepandemic metrics. There has been an increase in severe stroke incidence and higher volume of thrombectomy treatments in Latinx communities within LAC during the pandemic of 2020. More patients were discharged home, less patients discharged to skilled nursing facilities, and more patients expired in 2020, compared to the same time frame in 2019., (© 2021 S. Karger AG, Basel.)
- Published
- 2021
- Full Text
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248. Automated Pupillometry as a Triage and Assessment Tool in Patients with Traumatic Brain Injury.
- Author
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El Ahmadieh TY, Bedros N, Stutzman SE, Nyancho D, Venkatachalam AM, MacAllister M, Ban VS, Dahdaleh NS, Aiyagari V, Figueroa S, White JA, Batjer HH, Bagley CA, Olson DM, and Aoun SG
- Subjects
- Adult, Automation, Female, Humans, Male, Middle Aged, Pilot Projects, Prospective Studies, Reflex, Pupillary physiology, Brain Injuries, Traumatic diagnosis, Neurologic Examination methods, Pupil Disorders diagnosis, Pupil Disorders etiology, Triage methods
- Abstract
Objective: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young adults. Automated infrared pupillometry (AIP) has shown promising results in predicting neural damage in aneurysmal subarachnoid hemorrhage and ischemic stroke. We aimed to explore potential uses of AIP in triaging patients with TBI. We hypothesized that a brain injury severe enough to require an intervention would show Neurologic Pupil Index (NPI) changes., Methods: We conducted a prospective pilot study at a level-1 trauma center between November 2019 and February 2020. AIP readings of consecutive patients seen in the emergency department with blunt TBI and abnormal imaging findings on computed tomography were recorded by the assessing neurosurgery resident. The relationship between NPI and surgical intervention was studied., Results: Thirty-six patients were enrolled, 9 of whom received an intervention. NPI was dichotomized into normal (≥3) versus abnormal (<3) and was predictive of intervention (Fisher exact test; P < 0.0001). Six of the 9 patients had a Glasgow Coma Scale (GCS) score ≤8 and imaging signs of increased intracranial pressure (ICP) and underwent craniectomy (n = 4) or ICP monitor placement (n = 2) and had an abnormal NPI. Three patients underwent ICP monitor placement for GCS score ≤8 in accordance with TBI guidelines despite minimal imaging findings and had a normal NPI. The GCS score of these patients improved within 24 hours, requiring ICP monitor removal. NPI was normal in all patients who did not require intervention., Conclusions: AIP could be useful in triaging comatose patients after blunt TBI. An NPI ≥3 may be reassuring in patients with no signs of mass effect or increased ICP., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
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249. CXCL3 Signaling in the Tumor Microenvironment.
- Author
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Reyes N, Figueroa S, Tiwari R, and Geliebter J
- Subjects
- Chemokines, Chemokines, CXC genetics, Humans, Signal Transduction, Neoplasms genetics, Tumor Microenvironment
- Abstract
Cancer progression is driven, to a large extent, by the action of immune cells that have been recruited to tumor sites through interactions between chemokines and their receptors. Chemokines of the CXC subfamily are secreted by both tumor and non-tumor cells within the microenvironment of the tumor, where they induce either antitumor or protumor activity that fosters either clearance or progression of the tumor, respectively. Understanding the nature of these interactions is important to envisage novel approaches targeting the essential components of the tumor microenvironment, increasing the odds for favorable patient outcomes. In this chapter we describe the involvement of the chemokine (C-X-C motif) ligand 3 (CXCL3) in the human tumor microenvironment and its effects on immune and non-immune cells. Because of the limited data on the CXCL3 signaling in the tumor microenvironment, we extend the review to other members of the CXC subfamily of chemokines. This review also addresses the future trends or directions for therapeutic interventions that target signaling pathways used by these molecules in the tumor microenvironment., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
- Published
- 2021
- Full Text
- View/download PDF
250. Toxicological Screening of Four Bioactive Citroflavonoids: In Vitro, In Vivo, and In Silico Approaches.
- Author
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Ortiz-Andrade R, Araujo-León JA, Sánchez-Recillas A, Navarrete-Vazquez G, González-Sánchez AA, Hidalgo-Figueroa S, Alonso-Castro ÁJ, Aranda-González I, Hernández-Núñez E, Coral-Martínez TI, Sánchez-Salgado JC, Yáñez-Pérez V, and Lucio-Garcia MA
- Subjects
- Administration, Oral, Animals, Cell Survival drug effects, Chlorocebus aethiops, Cytochrome P-450 Enzyme System chemistry, Cytochrome P-450 Enzyme System metabolism, Dogs, ERG1 Potassium Channel antagonists & inhibitors, ERG1 Potassium Channel metabolism, Female, Flavanones chemistry, Flavanones metabolism, Flavanones pharmacology, Flavonoids chemistry, Flavonoids metabolism, Lethal Dose 50, Madin Darby Canine Kidney Cells, Medicine, Traditional, Quercetin chemistry, Quercetin metabolism, Quercetin pharmacology, Rats, Rats, Wistar, Vero Cells, Body Weight drug effects, Flavonoids pharmacology
- Abstract
Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC
50 of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD50 value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD50 was LD50 > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.- Published
- 2020
- Full Text
- View/download PDF
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