69 results on '"Flores F"'
Search Results
2. Volcano hazards and risks in Chile
- Author
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Lara, L.E., primary, Flores, F., additional, Calderón, R., additional, and Cardona, C., additional
- Published
- 2021
- Full Text
- View/download PDF
3. Contributors
- Author
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Adriana, Agudelo Restrepo, primary, Andrés, Narváez Zuñiga, additional, Aravena, Álvaro, additional, Arturo, Méndez Fajury Ricardo, additional, Bandibas, Joel C., additional, Biass, Sébastien, additional, Bonadonna, Costanza, additional, Calderón, R., additional, Cardona, C., additional, Cioni, Raffaello, additional, de' Michieli Vitturi, Mattia, additional, Del Bello, E., additional, Edmonds, Marie, additional, Flores, F., additional, Gaudin, D., additional, Gregg, Chris E., additional, Iguchi, Masato, additional, Jenkins, Susanna, additional, Johana, Castaño Vasco Leidy, additional, Kendrick, Jackie E., additional, Lallemant, David, additional, Lara, L.E., additional, Lavallée, Yan, additional, Lim, Tian Ning, additional, Lokmer, Ivan, additional, Lucía, Calvache Velasco Marta, additional, Luisa, Monsalve Bustamante María, additional, Marzocchi, Warner, additional, Mauricio, Gómez Martínez Diego, additional, Mauricio, López Vélez Cristián, additional, Menoni, Scira, additional, Miller, C. Dan, additional, Newhall, Christopher G., additional, Pallister, John S., additional, Paola, Narváez Obando, additional, Papale, Paolo, additional, Patricia, Cortés Jiménez Gloria, additional, Pistolesi, Marco, additional, Poland, Michael P., additional, Pompilio, Massimo, additional, Ricci, T., additional, Rouwet, Dmitri, additional, Saccorotti, Gilberto, additional, Sandri, Laura, additional, Scaillet, Bruno, additional, Scarlato, P., additional, Selva, Jacopo, additional, Sigmundsson, Freysteinn, additional, Spina, L., additional, Taddeucci, J., additional, Takarada, Shinji, additional, Tournigand, P-Y, additional, Williams, George, additional, Yun, Sang-Ho, additional, and de Zeeuw-van Dalfsen, Elske, additional
- Published
- 2021
- Full Text
- View/download PDF
4. Organo-montmorillonites as adsorbent materials for thiophanate-methyl removal: Adsorption-desorption studies and technological applications
- Author
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Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina), Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Educación (España), Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Flores, F. M. [0000-0001-9800-8614], Undabeytia López, Tomás [0000-0001-8116-7379], Jaworski, Maria [0000-0003-0696-759X], Morillo González, Esmeralda [0000-0002-4485-2315], Torres Sánchez, R. M. [0000-0002-9357-1210], Flores, F. M., Undabeytia López, Tomás, Jaworski, Maria, Morillo González, Esmeralda, Torres Sánchez, R. M., Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina), Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Educación (España), Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Flores, F. M. [0000-0001-9800-8614], Undabeytia López, Tomás [0000-0001-8116-7379], Jaworski, Maria [0000-0003-0696-759X], Morillo González, Esmeralda [0000-0002-4485-2315], Torres Sánchez, R. M. [0000-0002-9357-1210], Flores, F. M., Undabeytia López, Tomás, Jaworski, Maria, Morillo González, Esmeralda, and Torres Sánchez, R. M.
- Abstract
Thiophanate-methyl (TM) is a fungicide widely used in post-harvest treatment of pears and apples. The wastewater of this treatment usually is discharged to the natural rivers without treatment, with the consequent concern about the contamination of these waters. The fungicide adsorption on montmorillonites (Mt) and organo-montmorillonites (organo-Mt) can be a good alternative for wastewater treatment containing fungicides, used as filtering materials or flocculants. The TM adsorption on Mt and organo-Mt samples was studied in batch and column systems. Different organo-Mt samples were obtained, by cationic exchange reaction with octadecyltrimethylammonium (ODTMA) and didodecyldimethylammonium (DDAB) bromide at different surfactant loading. The anionic nature of the TM generated a very low adsorption in raw Mt, while the organo-Mt samples showed an increase of TM adsorption with the content of the surfactant. These results suggest two different types of interactions between organo-Mt samples and TM. At low surfactant contents, the adsorption occurs predominantly through hydrophobic interactions between the TM and the surfactant. While when the surfactant content is above the CEC value, additionally stronger interactions appear across water bridges between the TM molecules and the surfactant ammonium group. The similar TM adsorption percentages attained by organo-Mt with DDAB than those with activated carbon, points out the first material as a promising adsorbent that could be used to remove TM from wastewater in batch and also as filters or flocculants.
- Published
- 2020
5. Reconfigurable Fault Tolerant PID Networked Control for Magnetic Levitation Case Study
- Author
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Quiñones-Reyes, P, primary, Benítez-Pérez, H, additional, Mendez-Monroy, E, additional, Cárdenas-Flores, F, additional, and García-Nocetti, F, additional
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- 2007
- Full Text
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6. Charge Exchange Processes in Low Energy Ion–Metal Collisions
- Author
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Monreal, R.C., primary and Flores, F., additional
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- 2004
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7. Conductance simulation through single atom junctions at the scanning tunnelling microscope
- Author
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Jurczyszyn, L., primary, Mingo, N., additional, and Flores, F., additional
- Published
- 1996
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8. Theoretical Models on the Formation of Semiconductor Interface Barriers
- Author
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FLORES, F., primary, ORTEGA, J., additional, and PÉREZ, R., additional
- Published
- 1993
- Full Text
- View/download PDF
9. Dynamic Screening of Ions in Condensed Matter
- Author
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Echenique, P.M., primary, Flores, F., additional, and Ritchie, R.H., additional
- Published
- 1990
- Full Text
- View/download PDF
10. THE FRACTAL NATURE OF FRACTURE
- Author
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LOUIS, E., primary, GUINEA, F., additional, and FLORES, F., additional
- Published
- 1986
- Full Text
- View/download PDF
11. LIST OF CONTRIBUTORS AND DISCUSSANTS
- Author
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Archer, J.A., primary, Arimura, A., additional, Aurbach, G.D., additional, Axelrod, J., additional, Bar, R.S., additional, Bartke, A., additional, Bartosik, D.B., additional, Bartter, F.C., additional, Beato, M., additional, Beck, J.C., additional, Bell, N.H., additional, Bennett, V., additional, Birnbaumer, L., additional, Bogdanove, E.M., additional, Boss, B., additional, Boyar, R.M., additional, Bransome, E.D., additional, Brazeau, P., additional, Brodie, H.J., additional, Brown, J.C., additional, Brown, M., additional, Burgus, R., additional, Burrow, G.N., additional, Campbell, G.T., additional, Cataland, S., additional, Chang, Kwen-Jen, additional, Chase, L.R., additional, Cohen, S.L., additional, Colman, P., additional, Condliffe, P.G., additional, Cross, B.A., additional, Cuatrecasas, P., additional, Davies, I.J., additional, De Meyts, P., additional, Dobyns, B.M., additional, Dratman, M.B., additional, Drosdonsky, M., additional, Dryburgh, J.R., additional, Dupré, J., additional, Dyball, R.E.J., additional, Dyer, R.G., additional, Feigelson, P., additional, Flores, F., additional, Freychet, P., additional, Friesen, H.G., additional, Funder, J.W., additional, Gavin, J.R., additional, Gay, V.L., additional, George, J.M., additional, Gill, J.R., additional, Glick, S., additional, Goldfine, I.D., additional, Goodman, H.M., additional, Gorden, P., additional, Creep, R.O., additional, Greer, M.A., additional, Guillemin, R., additional, Gupta, S.L., additional, Haksar, A., additional, Hanjan, S.N.S., additional, Hedge, G.A., additional, Hellman, L., additional, Herman, M., additional, Hershman, J.M., additional, Hollenberg, M.D., additional, Jewelewicz, R., additional, Jones, C.W., additional, Kahn, C.R., additional, Kalimi, M., additional, Kapen, S., additional, Karsch, F.J., additional, Kenny, A.D., additional, Killewich, L.A., additional, Kitay, J.I., additional, Knobil, E., additional, Konishi, J., additional, Kowal, J., additional, Krieger, D.T., additional, Krishnaraj, R., additional, Kriss, J.P., additional, Kuhn, M., additional, Kumar, N., additional, Lasley, B.L., additional, Leblanc, H., additional, Lequin, R.M., additional, Lesniak, M.A., additional, Levy, R., additional, Lincoln, D.W., additional, Ling, N., additional, Lipsett, M.B., additional, McCann, S.M., additional, McKenzie, J.M., additional, McKnight, G.S., additional, Malarky, W.B., additional, Marks, B.H., additional, Megyesi, K., additional, Melby, J.C., additional, Monder, C., additional, Morris, J.F., additional, Naftolin, F., additional, Neville, D.M., additional, Nikitovitch-Winer, M.B., additional, Nillius, S.J., additional, Nolin, J.M., additional, Palacios, R., additional, Pandian, M.R., additional, Parsons, J.A., additional, Petro, Z., additional, Pickering, B.T., additional, Posner, B.I., additional, Raiti, S., additional, Ramaley, J.A., additional, Reddy, V.V., additional, Rice, B.F., additional, Rivier, C., additional, Rivier, J., additional, Roberts, J.S., additional, Rolland, R., additional, Rosenbloom, A.L., additional, Ross, S.A., additional, Roth, J., additional, Ryan, K.J., additional, Samaan, N., additional, Santen, R.J., additional, Saxena, R.K., additional, Schimke, R.T., additional, Schonbaum, E., additional, Schutz, G., additional, Schwartz, N.B., additional, Shaikh, A.A., additional, Shapiro, D.J., additional, Sherins, R.J., additional, Siler, T.M., additional, Sokol, H.W., additional, Soil, A.H., additional, Sterling, K., additional, Sulhvan, D., additional, Sunde, D., additional, Takaoka, Y., additional, Talwar, G.P., additional, Theoharides, T.C., additional, Vaitukaitis, J.L., additional, Vale, W., additional, Valtin, H., additional, Vander Laan, W.P., additional, Villee, C.A., additional, Wang, C.F., additional, Weick, R.F., additional, Weisz, J., additional, Weitzman, E.D., additional, White, A., additional, White, R.J., additional, Wolin, L., additional, and Yen, S.S.C., additional
- Published
- 1975
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- View/download PDF
12. The Formation of Estrogens by Central Neuroendocrine Tissues
- Author
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NAFTOLIN, F., primary, RYAN, K.J., additional, DAVIES, I.J., additional, REDDY, V.V., additional, FLORES, F., additional, PETRO, Z., additional, KUHN, M., additional, WHITE, R.J., additional, TAKAOKA, Y., additional, and WOLIN, L., additional
- Published
- 1975
- Full Text
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13. Numerical modelling and experimental validation of steel deep drawing processes - part ii: applications
- Author
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Garcia, C, Celentano, D, Flores, F, and Ponthot, JP
- Published
- 2006
14. Numerical modelling and experimental validation of steel deep drawing processes - part i. Material characterization
- Author
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Garcia, C, Celentano, D, Flores, F, and Ponthot, JP
- Published
- 2006
15. Organo-montmorillonites as adsorbent materials for thiophanate-methyl removal: Adsorption-desorption studies and technological applications
- Author
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María Angélica Jaworski, Tomas Undabeytia, Federico Manuel Flores, Esmeralda Morillo, Rosa Maria Torres Sanchez, Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina), Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Educación (España), Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina), Flores, F. M., Undabeytia López, Tomás, Jaworski, Maria, Morillo González, Esmeralda, Torres Sánchez, R. M., Flores, F. M. [0000-0001-9800-8614], Undabeytia López, Tomás [0000-0001-8116-7379], Jaworski, Maria [0000-0003-0696-759X], Morillo González, Esmeralda [0000-0002-4485-2315], and Torres Sánchez, R. M. [0000-0002-9357-1210]
- Subjects
Flocculation ,Fungicide ,Column filtration experiments ,02 engineering and technology ,010501 environmental sciences ,01 natural sciences ,Hydrophobic effect ,chemistry.chemical_compound ,Adsorption ,Pulmonary surfactant ,Bromide ,medicine ,Chemical Engineering (miscellaneous) ,Ammonium ,Waste Management and Disposal ,Organo-montmorillonite ,0105 earth and related environmental sciences ,Chemistry ,Process Chemistry and Technology ,Adsorption-desorption ,021001 nanoscience & nanotechnology ,Pollution ,Wastewater ,Water pollution ,0210 nano-technology ,Activated carbon ,medicine.drug ,Nuclear chemistry - Abstract
10 páginas.- 9 figuras.- 8 tablas.- 54 referencias.- Supplementary material related to this article can be found, in theonline version, at doi:https://doi.org/10.1016/j.jece.2020.103806., Thiophanate-methyl (TM) is a fungicide widely used in post-harvest treatment of pears and apples. The wastewater of this treatment usually is discharged to the natural rivers without treatment, with the consequent concern about the contamination of these waters. The fungicide adsorption on montmorillonites (Mt) and organo-montmorillonites (organo-Mt) can be a good alternative for wastewater treatment containing fungicides, used as filtering materials or flocculants. The TM adsorption on Mt and organo-Mt samples was studied in batch and column systems. Different organo-Mt samples were obtained, by cationic exchange reaction with octadecyltrimethylammonium (ODTMA) and didodecyldimethylammonium (DDAB) bromide at different surfactant loading. The anionic nature of the TM generated a very low adsorption in raw Mt, while the organo-Mt samples showed an increase of TM adsorption with the content of the surfactant. These results suggest two different types of interactions between organo-Mt samples and TM. At low surfactant contents, the adsorption occurs predominantly through hydrophobic interactions between the TM and the surfactant. While when the surfactant content is above the CEC value, additionally stronger interactions appear across water bridges between the TM molecules and the surfactant ammonium group. The similar TM adsorption percentages attained by organo-Mt with DDAB than those with activated carbon, points out the first material as a promising adsorbent that could be used to remove TM from wastewater in batch and also as filters or flocculants., Financial support of Argentine Ministry of Science, Technology and Innovation - FONARSEC FS-Nano 008 and Spanish Ministry of Economy and Competitiveness (ref. CTM2016-77168-R, supported by European Regional Development Fund funds) and Spanish Agency for International Cooperation for Development - Spanish Ministry of Education A/023433/10-09, are gratefully acknowledged. R.M.T.S. is member of National Council of Scientific and Technological Research (CONICET) and F.M. Flores, acknowledged CONICET and Argentine (BEC.AR) fellowships.
- Published
- 2020
16. Assessment of sulfonamide contamination in aquatic environments: A first report for Argentina and environmental risk assessment.
- Author
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Mac Loughlin TM, Bahl MF, Flores FM, Apartin CD, Marino DJG, and Peluso ML
- Subjects
- Argentina, Risk Assessment, Anti-Bacterial Agents analysis, Rivers chemistry, Geologic Sediments chemistry, Tandem Mass Spectrometry, Water Pollutants, Chemical analysis, Sulfonamides analysis, Environmental Monitoring
- Abstract
The global surge in pharmaceutical consumption, driven by increasing population and the demand for animal proteins, leads to the discharge of diverse pollutants, including antibiotic residues, into water bodies. Sulfonamides, being water-soluble compounds, can readily enter surface run-off, posing potential risks to non-target species despite their low environmental concentrations. Latin America has implemented intensive production systems highly dependent on antimicrobials for productivity and animal health, yet there is a paucity of information regarding their concentration in the region. The objective of this study was to evaluate the presence of sulfonamides in water and sediment samples and assess their potential ecological risks through an environmental risk assessment. The Río de la Plata basin collects the waters of the Paraguay, Paraná, and Uruguay rivers, together with their tributaries and various wetlands, passing through the provinces in Argentina known for their significant animal husbandry production. Two sampling campaigns were carried out for sediment, while only one campaign was conducted for surface waters. The samples were analyzed by high performance liquid chromatography tandem mass-spectrometry (HPLC-MS/MS). None of the examined sulfonamide antibiotics were detected in the sediment samples from both sampling campaigns. In contrast, sulfadiazine (95 %), sulfamethoxazole (91 %), and sulfathiazole (73 %) were detected in the water samples. Sulfadiazine was found in the concentration range of 8 to 128 ng/L, while sulfamethoxazole and sulfathiazole were observed at concentrations ranging from 3.0 to 32.5 ng/L and 2.9 to 8.1 ng/L, respectively. Based on the environmental risk assessment conducted using the sulfonamide concentrations, most samples indicated a medium risk for aquatic biota, with only one sample surpassing the high-risk threshold. This study represents the first report presenting data on the presence of sulfonamide antibiotics in the aquatic environment of Argentina., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
17. Molecular responses of sponge larvae exposed to partially weathered condensate oil.
- Author
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Luter HM, Laffy P, Flores F, Brinkman DL, Fisher R, and Negri AP
- Subjects
- Animals, Larva metabolism, Hydrocarbons analysis, Weather, Water analysis, Petroleum analysis, Water Pollutants, Chemical analysis, Petroleum Pollution analysis, Polycyclic Aromatic Hydrocarbons analysis
- Abstract
Anthropogenic inputs of petroleum hydrocarbons into the marine environment can have long lasting impacts on benthic communities. Sponges form an abundant and diverse component of benthic habitats, contributing a variety of important functional roles; however, their responses to petroleum hydrocarbons are largely unknown. This study combined a traditional ecotoxicological experimental design and endpoint with global gene expression profiling and microbial indicator species analysis to examine the effects of a water accommodated fraction (WAF) of condensate oil on a common Indo-Pacific sponge, Phyllospongia foliascens. A no significant effect concentration (N(S)EC) of 2.1 % WAF was obtained for larval settlement, while gene-specific (N(S)EC) thresholds ranged from 3.4 % to 8.8 % WAF. Significant shifts in global gene expression were identified at WAF treatments ≥20 %, with larvae exposed to 100 % WAF most responsive. Results from this study provide an example on the incorporation of non-conventional molecular and microbiological responses into ecotoxicological studies on petroleum hydrocarbons., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: INPEX provided the Ichthys condensate for the study. INPEX had no input into the conceptualization, methodology, investigation, analysis or writing of this manuscript., (Copyright © 2023 Australian Institute of Marine Science. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
18. Oleic acid regulates the circadian rhythm of adipose tissue in obesity.
- Author
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Martín-Reyes F, Ho-Plagaro A, Rodríguez-Díaz C, Lopez-Gómez C, Garcia-Serrano S, de Los Reyes DR, Gonzalo M, Fernández-Garcia JC, Montiel-Casado C, Fernández-Aguilar JL, Fernández JR, García-Fuentes E, and Rodríguez-Pacheco F
- Subjects
- Humans, ARNTL Transcription Factors genetics, ARNTL Transcription Factors metabolism, Circadian Rhythm drug effects, Obesity, Morbid physiopathology, Oleic Acid pharmacology, Subcutaneous Fat drug effects, Subcutaneous Fat physiology, Intra-Abdominal Fat drug effects, Intra-Abdominal Fat physiology
- Abstract
The effect of oleic acid (OA) on the regulation of the circadian rhythm present in human visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with morbid obesity has not been analyzed yet. VAT and SAT explants from patients with morbid obesity were incubated with OA to analyze the circadian regulation of clock and other genes related to lipid metabolism (SREBP-1c, FAS, LPL and CPT1), and their association with baseline variables and the improvement of these patients after bariatric surgery. There were significant differences in amplitude and acrophase in VAT with respect to SAT. In VAT, body weight negatively correlated with BMAL1 and CRY1 amplitude, and REVERBα acrophase; body mass index (BMI) negatively correlated with REVERBα acrophase; and waist circumference negatively correlated with PER3 acrophase. In SAT, BMI negatively correlated with CLOCK amplitude, and CLOCK, REVERBα and CRY2 MESOR; and waist circumference negatively correlated with PER3 amplitude and acrophase. A greater short-term improvement of body weight, BMI and waist circumference in patients with morbid obesity after bariatric surgery was associated with a lower CRY1 and CRY2 amplitude and an earlier PER1 and PER3 acrophase in SAT. OA produced a more relevant circadian rhythm and increased the amplitude of most clock genes and lipid metabolism-related genes. OA regulated the acrophase of most clock genes in VAT and SAT, placing CLOCK/BMAL1 in antiphase with regard to the other genes. OA increased the circadian rhythmicity, although with slight differences between adipose tissues. These differences could determine its different behavior in obesity., Competing Interests: Declaration of interest None., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
19. Coronary computed tomography angiography evaluation of plaque morphology and its relationship to HDL and total cholesterol to HDL ratio.
- Author
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Manubolu VS, Verghese D, Lakshmanan S, Alalawi L, Kinninger A, Bitar JA, Calicchio F, Ahmad K, Ghanem A, Javier DA, Mangaoang C, Flores F, Dailing C, Roy SK, and Budoff MJ
- Subjects
- Male, Humans, Middle Aged, Female, Computed Tomography Angiography methods, Cross-Sectional Studies, Disease Progression, Cholesterol, HDL, Risk Factors, Coronary Angiography methods, Plaque, Atherosclerotic diagnostic imaging, Plaque, Atherosclerotic complications, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease epidemiology
- Abstract
Background: While population studies have demonstrated that high density lipoprotein cholesterol (HDL-C) and the ratio of total cholesterol to HDL (TC/HDL) improve cardiovascular risk prediction, the mechanism by which these parameters protect the cardiovascular system remains uncertain., Objective: To investigate the relationship between the HDL-C level and the total cholesterol to HDL (TC/HDL) ratio with the morphology of coronary artery plaque as determined by coronary computed tomography angiography (CCTA)., Methods: This is a cross-sectional study involving 190 subjects with stable coronary artery disease. Semi-automated plaque analysis software was utilized to quantify plaque and plaque volumes are presented as total atheroma volume normalized (TAV
norm ). Multivariate regression models were used to evaluate the association of HDL-C and TC/HDL ratio with coronary plaque volumes., Results: Of the 190 subjects the average (SD) age was 58.9 (9.8) years, with 63% being male. After adjustment for cardiovascular risk factors, HDL- C (>40 mg/dl) is inversely associated with fibrous (p = 0.003), fibrous fatty (p = 0.007), low attenuation plaque (LAP) (p = 0.007), total non-calcified plaque (TNCP) (p = 0.002) and total plaque (TP)(p = 0.004) volume. Furthermore, the TC/HDL ratio (> 4.0) is associated with fibrous (p = 0.047) and total non-calcified plaque (p = 0.039), but not with fibrofatty, LAP, dense calcified plaque, or TP volume., Conclusion: There is a strong association between low HDL-C levels and increasing TC/HDL ratio with certain types of coronary plaque characteristics, independent of traditional risk factors. The findings of this study suggest mechanistic evidence supporting the protective role of HDL-C and the TC/HDL ratio's clinical relevance in coronary artery disease management., (Copyright © 2022. Published by Elsevier Inc.)- Published
- 2022
- Full Text
- View/download PDF
20. Microbiota diversity in nonalcoholic fatty liver disease and in drug-induced liver injury.
- Author
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Rodriguez-Diaz C, Taminiau B, García-García A, Cueto A, Robles-Díaz M, Ortega-Alonso A, Martín-Reyes F, Daube G, Sanabria-Cabrera J, Jimenez-Perez M, Isabel Lucena M, Andrade RJ, García-Fuentes E, and García-Cortes M
- Subjects
- Bacteria, Humans, Liver metabolism, Liver Cirrhosis metabolism, Metagenome, Chemical and Drug Induced Liver Injury metabolism, Gastrointestinal Microbiome, Non-alcoholic Fatty Liver Disease metabolism
- Abstract
The gut microbiota could play a significant role in the progression of nonalcoholic fatty liver disease (NAFLD); however, its relevance in drug-induced liver injury (DILI) remains unexplored. Since the two hepatic disorders may share damage pathways, we analysed the metagenomic profile of the gut microbiota in NAFLD, with or without significant liver fibrosis, and in DILI, and we identified the main associated bacterial metabolic pathways. In the NAFLD group, we found a decrease in Alistipes, Barnesiella, Eisenbergiella, Flavonifractor, Fusicatenibacter, Gemminger, Intestinimonas, Oscillibacter, Parasutterella, Saccharoferementans and Subdoligranulum abundances compared with those in both the DILI and control groups. Additionally, we detected an increase in Enterobacter, Klebsiella, Sarcina and Turicibacter abundances in NAFLD, with significant liver fibrosis, compared with those in NAFLD with no/mild liver fibrosis. The DILI group exhibited a lower microbial bacterial richness than the control group, and lower abundances of Acetobacteroides, Blautia, Caloramator, Coprococcus, Flavobacterium, Lachnospira, Natronincola, Oscillospira, Pseudobutyrivibrio, Shuttleworthia, Themicanus and Turicibacter compared with those in the NAFLD and control groups. We found seven bacterial metabolic pathways that were impaired only in DILI, most of which were associated with metabolic biosynthesis. In the NAFLD group, most of the differences in the bacterial metabolic pathways found in relation to those in the DILI and control groups were related to fatty acid and lipid biosynthesis. In conclusion, we identified a distinct bacterial profile with specific bacterial metabolic pathways for each type of liver disorder studied. These differences can provide further insight into the physiopathology and development of NAFLD and DILI., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
- Full Text
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21. A dual treatment blocks alcohol binge-drinking relapse: Microbiota as a new player.
- Author
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Ezquer F, Quintanilla ME, Morales P, Santapau D, Munita JM, Moya-Flores F, Ezquer M, Herrera-Marschitz M, and Israel Y
- Subjects
- Acetylcysteine pharmacology, Acetylcysteine therapeutic use, Alcohol Drinking, Animals, Aspirin, Chronic Disease, Ethanol, Humans, Mice, Rats, Recurrence, Alcohol-Related Disorders, Alcoholism drug therapy, Microbiota
- Abstract
Rationale: Gut microbiota communicates information to the brain. Some animals are born with a gut microbiota that predisposes to high alcohol consumption, and transplantation of fecal material from alcoholics to mice increases animal preference for ethanol. Alcohol-use-disorders are chronic conditions where relapse is the hallmark. A predictive animal model of relapse is the "alcohol deprivation effect" where ethanol re-access is allowed following chronic alcohol intake and a long alcohol deprivation. The present study evaluates the effect of gut microbiota modification on relapse, as an adjunct to N-acetylcysteine + Acetylsalicylic acid administration, which inhibits the alcohol-induced hyper-glutamatergic condition., Methods: Rats bred as heavy alcohol consumers (UChB) were allowed ethanol intake for one month, were deprived of alcohol for two-weeks and subsequently offered re-access to ethanol. Prior to ethanol re-access animals received orally either (i) vehicle-control, (ii) Lactobacillus-rhamnosus-GG after antibiotic treatment (LGG); (iii) N-acetylcysteine+Acetylsalicylic acid (NAC/ASA) or (iv) both treatments: LGG+ (NAC/ASA)., Results: Marked binge drinking (1.75 g ethanol/kg in 60 min) and blood alcohol levels exceeding 80 mg/dl were observed in the control group upon ethanol-re-access. Lactobacillus-GG or (NAC+ASA) treatments inhibited alcohol intake by 66-80%. The combination of both treatments virtually suppressed (inhibition of 90%) the re-access binge-like drinking, showing additive effects. Treatment with NAC+ASA increased the levels of glutamate transporters xCT and GLT-1 in nucleus accumbens, while Lactobacillus-GG administration increased those of the dopamine transporter (DAT)., Conclusions: The administration of a well-accepted probiotic may be of value as an adjunct in the treatment of alcohol-use-disorders., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
22. Derivation of toxicity thresholds for gas condensate oils protective of tropical species using experimental and modelling approaches.
- Author
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Negri AP, Brinkman DL, Flores F, van Dam J, Luter HM, Thomas MC, Fisher R, Stapp LS, Kurtenbach P, Severati A, Parkerton TF, and Jones R
- Subjects
- Animals, Ecosystem, Fresh Water, Oils, Anthozoa, Water Pollutants, Chemical toxicity
- Abstract
Toxicity thresholds for dissolved oil applied in tropical ocean risk assessments are largely based on the sensitivities of temperate and/or freshwater species. To explore the suitability of these thresholds for tropical habitats we experimentally determined toxicity thresholds for eight tropical species for a partially weathered gas condensate, applied the target lipid model (TLM) to predict toxicity of fresh and weathered condensates and compared sensitivities of the tropical species with model predictions. The experimental condensate-specific hazard concentration (HC5) was 167 μg L
-1 total aromatic hydrocarbons (TAH), with the TLM-modelled HC5 (78 μg L-1 TAH) being more conservative, supporting TLM-modelled thresholds for tropical application. Putative species-specific critical target lipid body burdens (CTLBBs) indicated that several of the species tested were among the more sensitive species in the TLM database ranging from 5.1 (coral larvae) to 97 (sponge larvae) μmol g-1 octanol and can be applied in modelling risk for tropical marine ecosystems., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)- Published
- 2021
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23. Telemedicine and decentralized hepatitis C treatment as a strategy to enhance retention in care among people attending drug treatment centres.
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Morales-Arraez D, Hernández-Bustabad A, Medina-Alonso MJ, Santiago-Gutiérrez LG, García-Gil S, Diaz-Flores F, Pérez-Pérez V, Nazco J, Fernandez de Rota Martin P, Gutiérrez F, and Hernández-Guerra M
- Subjects
- Female, Hepacivirus, Humans, Male, Retrospective Studies, Substance Abuse Treatment Centers, Hepatitis C drug therapy, Retention in Care, Telemedicine
- Abstract
Background: People attending drug treatment centres have a high burden of hepatitis C virus (HCV) and face barriers to diagnosis and treatment. Dried blood spot (DBS) testing has been proposed to simplify diagnosis, but many patients remain untreated. In this retrospective study, we evaluated the reasons for non-retention in care in an intervention using on-site DBS testing and the effect of telemedicine and decentralized care compared to standard of care among people attending drug treatment centres who were lost to follow-up., Methods: In a first phase, retention in care, adherence to treatment, and predictive factors in the DBS testing program of patients in drug treatment centres were analyzed and compared to a cohort of patients treated at the hospital outpatient clinic. Subsequently, in a second phase we evaluated in patients lost to follow-up from drug treatment centres the efficacy of one-step testing and telemedicine linked to a decentralized dispensation of HCV treatment or standard of care., Results: Among 512 patients attending drug treatment centres, 467 (91.2%) agreed to be tested and 53.4% (237 patients/444 valid tests) tested positive (46 ± 9 years, 87.3% male) for HCV antibodies. After excluding patients negative for RNA or under surveillance, 178 patients were scheduled to meet with a specialist. Overall, 44 patients did not attend and 25 did not complete the pre-treatment evaluation. The only factor associated with retention in care was patient's knowledge of HCV infection. Treated patients attending drug treatment centres (n = 68) compared to the hospital outpatient clinic cohort (n = 135) had lower rates of treatment adherence. Among the patients who attended drug treatment centres that were lost to follow-up (n = 69), the proportion of patients who completed the program was significantly higher among those assisted by telemedicine than by standard of care (62.5% vs. 24.3%, p = 0.002)., Conclusion: Although there was a high participation rate in a DBS testing program in drug treatment centres, non-retention in care is a challenge. Importantly, telemedicine linked to a decentralized dispensation of HCV treatment re-engages patients and may be effective for HCV microelimination., Competing Interests: Declarations of Interest Dr. M. Hernandez-Guerra has received research grants from Abbvie and Gilead and has participated in consultant advisories for Bayer and Intercept. The rest of the authors do have not conflicts of interest to disclosure., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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24. Combined effects of climate change and the herbicide diuron on the coral Acropora millepora.
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Flores F, Marques JA, Uthicke S, Fisher R, Patel F, Kaserzon S, and Negri AP
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- Animals, Climate Change, Coral Reefs, Diuron toxicity, Anthozoa, Herbicides toxicity
- Abstract
The Great Barrier Reef (GBR) is threatened by climate change and local pressures, including contaminants in nearshore habitats. This study investigated the combined effects of a GBR-relevant contaminant, the herbicide diuron, under current and two future climate scenarios on the coral Acropora millepora. All physiological responses tested (effective quantum yield (ΔF/Fm'), photosynthesis, calcification rate) were negatively affected with increasing concentrations of diuron. Interactive effects between diuron and climate were observed for all responses; however, climate had no significant effect on ΔF/Fm' or calcification rates. Photosynthesis was negatively affected as the climate scenarios were adjusted from ambient (28.1 °C, pCO
2 = 397 ppm) to RCP8.5 2050 (29.1 °C, pCO2 = 680 ppm) and 2100 (30.2 °C, pCO2 = 858 ppm) with EC50 values declining from 19.4 to 10.6 and 2.6 μg L-1 diuron in turn. These results highlight the likelihood that water quality guideline values may need to be adjusted as the climate changes., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)- Published
- 2021
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25. Incidence and microbiological characteristics of neonatal late onset sepsis in a neonatal intensive care unit in Peru.
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Herbozo C, Julca I, Flores F, Hernandez R, and Zegarra J
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- Humans, Incidence, Infant, Infant, Newborn, Intensive Care Units, Neonatal, Peru epidemiology, Retrospective Studies, Neonatal Sepsis epidemiology, Sepsis epidemiology
- Abstract
Objectives: Our study aimed to determine the incidence of late onset sepsis and the most frequent microorganisms causing it in the neonatal unit at Hospital Cayetano Heredia in Lima, Peru., Methods: Descriptive and retrospective study. We reviewed all positive blood cultures and cultures of cerebrospinal fluid drawn from inborn patients beyond 72 h of life, admitted to the neonatal unit from January 2015 to December 2019., Results: The incidence of late onset sepsis was 7.4% of admitted patients and 10.04 per 1000 live births. During our study period, 234 episodes of late onset sepsis occurred in 204 patients. The incidence was higher in very low birth weight infants, reaching 36.2% and even higher in extremely low birth weight infants (40.7%). Coagulase-negative Staphylococcus and then Klebsiella spp. were the most frequent causative microorganisms. The most frequent cause of late onset sepsis in very low birth weight infants was gram-negative bacteria (Klebsiella spp., was the most frequent causative microorganism)., Conclusions: Late onset neonatal sepsis is prevalent in our neonatal unit. It is important to know which are the most prevalent causative microorganisms to be able to choose adequate antibiotic coverage and to design strategies to prevent infection., (Copyright © 2021. Published by Elsevier Ltd.)
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- 2021
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26. Effect of body mass index on bone mineral density is age-specific.
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Cherukuri L, Kinninger A, Birudaraju D, Lakshmanan S, Li D, Flores F, Mao SS, and Budoff MJ
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- Adult, Age Factors, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Multidetector Computed Tomography, Obesity complications, Obesity diagnosis, Osteoporosis diagnostic imaging, Osteoporosis etiology, Retrospective Studies, Risk Assessment, Risk Factors, Sex Factors, Thoracic Vertebrae diagnostic imaging, Young Adult, Body Mass Index, Bone Density, Obesity physiopathology, Osteoporosis physiopathology, Thoracic Vertebrae physiopathology
- Abstract
Background and Aims: Obesity and osteoporosis are two important and growing public health problems worldwide. Body mass index (BMI) has been found to be inversely related to the risk of osteoporotic fracture. We aimed to assess the association of BMI with thoracic vertebral bone mineral density (BMD) measured from a quantitative computed tomography (QCT)., Methods and Results: We retrospectively evaluated the data from 15,758 consecutive patients (5675 females and 10,083 males) between age 20-90 years, who underwent Coronary Artery Calcium (CAC) scoring. Quantitative data analyses of thoracic trabecular BMD (mg/cm
3 ) was performed with a phantom system or phantomless using validated software. The gender-specific subgroup was divided based on age (<45, 45-55, 55-65, >65 yrs in females; <40,40-60,>60 yrs in Males) and weight by BMI (kg/m2 ) as < 25 (normal or low weight), >25 - <30 (overweight) and >30 (obesity). Analysis of variance (ANOVA) and Scheffe's post hoc procedure tested the association of body weight/BMI on BMD. A significant positive association between the body weight and BMD existed in obese population in elder groups in both genders (p < 0.05). There was no significant difference in BMD in 40-60 years in men and <55 years in women with normal or low weight compared to overweight or obese cohorts., Conclusions: We concluded that the effect of weight on BMD is age-specific and the BMD should be monitored routinely with a cardiac CT scan in the senile population., Competing Interests: Declaration of competing interest Matthew J. Budoff, M.D., FACC discloses work for the National Institutes of Health and General Electric Healthcare; All other authors have no conflicts of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)- Published
- 2021
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27. Oleic acid restores the rhythmicity of the disrupted circadian rhythm found in gastrointestinal explants from patients with morbid obesity.
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Lago-Sampedro A, Ho-Plagaro A, Garcia-Serrano S, Santiago-Fernandez C, Rodríguez-Díaz C, Lopez-Gómez C, Martín-Reyes F, Ruiz-Aldea G, Alcaín-Martínez G, Gonzalo M, Montiel-Casado C, Fernández JR, García-Fuentes E, and Rodríguez-Pacheco F
- Subjects
- Adult, CLOCK Proteins drug effects, Circadian Rhythm genetics, Female, Gastrectomy adverse effects, Gastric Bypass adverse effects, Ghrelin genetics, Glucagon-Like Peptide 1 genetics, Humans, Jejunum metabolism, Male, Middle Aged, Obesity, Morbid surgery, Postoperative Period, Stomach metabolism, CLOCK Proteins metabolism, Circadian Rhythm drug effects, Gene Expression Regulation drug effects, Obesity, Morbid genetics, Oleic Acid pharmacology
- Abstract
Background & Aims: We investigated whether oleic acid (OA), one of the main components of the Mediterranean diet, participates in the regulation of the intestinal circadian rhythm in patients with morbid obesity., Methods: Stomach and jejunum explants from patients with morbid obesity were incubated with oleic acid to analyze the regulation of clock genes., Results: Stomach explants showed an altered circadian rhythm in CLOCK, BMAL1, REVERBα, CRY1, and CRY2, and an absence in PER1, PER2, PER3 and ghrelin (p > 0.05). OA led to the emergence of rhythmicity in PER1, PER2, PER3 and ghrelin (p < 0.05). Jejunum explants showed an altered circadian rhythm in CLOCK, BMAL1, PER1 and PER3, and an absence in PER2, REVERBα, CRY1, CRY2 and GLP1 (p > 0.05). OA led to the emergence of rhythmicity in PER2, REVERBα, CRY1 and GLP1 (p < 0.05), but not in CRY2 (p > 0.05). OA restored the rhythmicity of acrophase and increased the amplitude for most of the genes studied in stomach and jejunum explants. OA placed PER1, PER2, PER3, REVERBα, CRY1 and CRY2 in antiphase with regard to CLOCK and BMAL1., Conclusions: There is an alteration in circadian rhythm in stomach and jejunum explants in morbid obesity. OA restored the rhythmicity of the genes related with circadian rhythm, ghrelin and GLP1, although with slight differences between tissues, which could determine a different behaviour of the explants from jejunum and stomach in obesity., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)
- Published
- 2021
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28. Acclimation history modulates effect size of calcareous algae (Halimeda opuntia) to herbicide exposure under future climate scenarios.
- Author
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Marques JA, Flores F, Patel F, Bianchini A, Uthicke S, and Negri AP
- Subjects
- Acclimatization, Carbon Dioxide, Climate Change, Coral Reefs, Hydrogen-Ion Concentration, Seawater, Chlorophyta, Herbicides
- Abstract
Tropical marine habitat-builders such as calcifying green algae can be susceptible to climate change (warming and acidification). This study evaluated the cumulative effects of ocean warming (OW), ocean acidification (OA) and the herbicide diuron on the calcifying green algae Halimeda opuntia. We also assessed the influence of acclimation history to experimental climate change conditions on physiological responses. H. opuntia were exposed for 15 days to orthogonal combinations of three climate scenarios [ambient (28 °C, pCO
2 = 378 ppm), 2050 (29 °C, pCO2 = 567 ppm) and 2100 (30 °C, pCO2 = 721 ppm)] and to six diuron concentrations (up to 29 μg L-1 ). Half of the H. opuntia had been acclimated for eight months to the climate scenarios in a mesocosm approach, while the remaining half were not pre-acclimated, as is current practice in most experiments. Climate effects on quantum yield (ΔF/Fm'), photosynthesis and calcification in future climate scenarios were significantly stronger (by -24, -46 and +26%, respectively) in non-acclimated algae, suggesting experimental bias may exaggerate effects in organisms not appropriately acclimated to future-climate conditions. Thus, full analysis was done on acclimated plants only. Interactive effects of future climate scenarios and diuron were observed for ΔF/Fm', while the detrimental effects of climate and diuron on net photosynthesis and total antioxidant capacity (TAC) were additive. Calcification-related enzymes were negatively affected only by diuron, with inhibition of Ca-ATPase and upregulation of carbonic anhydrase. The combined and consistent physiological and biochemical evidence of negative impacts (across six indicators) of both herbicide and future-climate conditions on the health of H. opuntia highlights the need to address both climate change and water quality. Guideline values for contaminants may also need to be lowered considering 'climate adjusted thresholds'. Importantly, this study highlights the value of applying substantial future climate acclimation periods in experimental studies to avoid exaggerated organism responses to OW and OA., 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 © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2020
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29. Sleep loss disrupts pericyte-brain endothelial cell interactions impairing blood-brain barrier function.
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Medina-Flores F, Hurtado-Alvarado G, Contis-Montes de Oca A, López-Cervantes SP, Konigsberg M, Deli MA, and Gómez-González B
- Subjects
- Animals, Brain, Cell Communication, Endothelial Cells, Male, Rats, Rats, Wistar, Sleep, Tight Junctions, Blood-Brain Barrier, Pericytes
- Abstract
Sleep loss in the rat increases blood-brain barrier permeability to circulating molecules by disrupting interendothelial tight junctions. Despite the description of the ultrastructure of cerebral microvessels and the evidence of an apparent pericyte detachment from capillary wall in sleep restricted rats the effect of sleep loss on pericytes is unknown. Here we characterized the interactions between pericytes and brain endothelial cells after sleep loss using male Wistar rats. Animals were sleep-restricted 20 h daily with 4 h sleep recovery for 10 days. At the end of the sleep restriction, brain microvessels (MVs) were isolated from cerebral cortex and hippocampus and processed for Western blot and immunocytochemistry to evaluate markers of pericyte-endothelial cell interaction (connexin 43, PDGFR-β), tight junction proteins, and proinflammatory mediator proteins (MMP9, A
2A adenosine receptor, CD73, NFκB). Sleep restriction reduced PDGFR-β and connexin 43 expression in MVs; in addition, scanning electron microscopy micrographs showed that pericytes were detached from capillary walls, but did not undergo apoptosis (as depicted by a reduced active caspase-3 expression). Sleep restriction also decreased tight junction protein expression in MVs and increased BBB permeability to low- and high-molecular weight tracers in in vivo permeability assays. Those alterations seemed to depend on a low-grade inflammatory status as reflected by the increased expression of phosphorylated NFκB and A2A adenosine receptor in brain endothelial cells from the sleep-restricted rats. Our data show that pericyte-brain endothelial cell interaction is altered by sleep restriction; this evidence is essential to understand the role of sleep in regulating blood-brain barrier function., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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30. Indoleamine 2,3-dioxygenase in melanoma progression and BRAF inhibitor resistance.
- Author
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Sandri S, Watanabe LRM, Oliveira EA, Faião-Flores F, Migliorini S, Tiago M, Felipe-Silva A, Vazquez VL, da Costa Souza P, Consolaro MEL, Campa A, and Maria-Engler SS
- Subjects
- Cell Line, Tumor, Databases, Genetic, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase antagonists & inhibitors, Indoleamine-Pyrrole 2,3,-Dioxygenase genetics, Melanoma enzymology, Melanoma genetics, Molecular Targeted Therapy, Proto-Oncogene Proteins B-raf genetics, Proto-Oncogene Proteins B-raf metabolism, Skin Neoplasms enzymology, Skin Neoplasms genetics, Tryptophan analogs & derivatives, Tryptophan pharmacology, Antineoplastic Agents pharmacology, Drug Resistance, Neoplasm genetics, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Melanoma drug therapy, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Skin Neoplasms drug therapy, Vemurafenib pharmacology
- Abstract
Indoleamine 2,3-dioxygenase (IDO) is associated with the progression of many types of tumors, including melanoma. However, there is limited information about IDO modulation on tumor cell itself and the effect of BRAF inhibitor (BRAFi) treatment and resistance. Herein, IDO expression was analyzed in different stages of melanoma development and progression linked to BRAFi resistance. IDO expression was increased in primary and metastatic melanomas from patients' biopsies, especially in the immune cells infiltrate. Using a bioinformatics approach, we also identified an increase in the IDO mRNA in the vertical growth and metastatic phases of melanoma. Using in silico analyses, we found that IDO mRNA was increased in BRAFi resistance. In an in vitro model, IDO expression and activity induced by interferon-gamma (IFNγ) in sensitive melanoma cells was decreased by BRAFi treatment. However, cells that became resistant to BRAFi presented random IDO expression levels. Also, we identified that treatment with the IDO inhibitor, 1-methyltryptophan (1-MT), was able to reduce clonogenicity for parental and BRAFi-resistant cells. In conclusion, our results support the hypothesis that the decreased IDO expression in tumor cells is one of the many additional outcomes contributing to the therapeutic effects of BRAFi. Still, the IDO production changeability by the BRAFi-resistant cells reiterates the complexity of the response arising from resistance, making it not possible, at this stage, to associate IDO expression in tumor cells with resistance. On the other hand, the maintenance of 1-MT off-target effect endorses its use as an adjuvant treatment of melanoma that has become BRAFi-resistant., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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31. Association of high-density lipoprotein levels with baseline coronary plaque volumes by coronary CTA in the EVAPORATE trial.
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Lakshmanan S, Shekar C, Kinninger A, Dahal S, Onuegbu A, Cai AN, Hamal S, Birudaraju D, Cherukuri L, Flores F, Dailing C, Roy SK, Bhatt DL, Nelson JR, and Budoff MJ
- Subjects
- Cholesterol, LDL, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Male, Middle Aged, Cholesterol, HDL blood, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease drug therapy, Plaque, Atherosclerotic
- Abstract
Background and Aims: Dyslipidemia with elevated triglycerides (TGL) and low high-density lipoprotein cholesterol (HDL-C) predicts residual cardiovascular risk, despite goal LDL-C levels and optimal statin therapy. Coronary plaque characterization by CCTA can provide mechanistic understanding of coronary artery disease and associated prognosis. The role of HDL-C in the pathogenesis of atherosclerosis is not well understood in statin-treated patients with elevated TGL. We sought to examine the association of HDL-C levels with baseline coronary plaque volumes, namely total plaque (TP) and total non-calcified plaque (TNCP) volumes by CCTA in participants enrolled in the EVAPORATE trial., Methods: We analyzed 80 participants who were enrolled in the trial. Linear regression analysis as a univariate and multivariate model adjusted for significant cardiovascular risk factors was performed to evaluate independent association of HDL-C and baseline coronary plaque volumes. In an exploratory analysis, stratified by sex, we compared the association of serum HDL-C levels with baseline coronary plaque volumes in males and females., Results: Mean (SD) age of participants (n = 80) was 57.1 (8.6) years and 43% were male. Median (Inter Quartile Range/IQR) log-TNCP volume was 83.0 (0.1-7.3) mm
3 and median (IQR) log-TP volume was 144.8 (0.1-7.1) mm3 . After adjustment for relevant clinical covariates including age, gender, BMI, hypertension, diabetes, past smoking and baseline TGL levels, increasing levels of HDL-C remain independently associated with lower baseline log-TNCP volumes (β: 0.043 ± 0.021, p = 0.042) and baseline log-TP volumes (β: 0.046 ± 0.022, p = 0.035) on CCTA. On stratifying by sex in a multivariable regression analysis, HDL-C levels were inversely associated with baseline log-TNCP volumes (β: 0.066 ± 0.026, p = 0.018) and log-TP volumes (β: 0.077 ± 0.025, p = 0.004) in females, but not in males (log-TNCP volumes β: 0.038 ± 0.034, p = 0.282) and log-TP volumes (β: -0.033 ± 0.036, p = 0.364)., Conclusions: In a cohort of statin treated patients with known atherosclerosis and residually elevated TGL, there was a significant inverse relationship between HDL-C levels and baseline coronary plaque, TP and TNCP volumes on CCTA. Our findings provide more detailed mechanistic evidence regarding the protective role of HDL-C in coronary atherosclerosis in a high-risk cohort. Further investigation to evaluate the interaction of HDL-C levels and coronary plaque volumes on differential CVD risk in statin-treated patients with elevated TGL levels is warranted., Competing Interests: Declaration of competing interest Dr Budoff has received grant support and is on the speaker's bureau for Amarin Pharmaceuticals. Dr. Deepak L. Bhatt discloses the following relationships - Advisory Board: Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, Takeda. Dr. John R. Nelson discloses the following relationships: Advisory Board: Amarin; Speaker Bureau: Amarin, Boehringer Ingelheim, Amgen, Bostonheart Diagnostics; Stock: Pfizer, Amgen. The remaining authors report no disclosures., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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32. Hopane-type triterpenes from Cnidoscolus spinosus and their bioactivities.
- Author
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López-Huerta FA, Nieto-Camacho A, Morales-Flores F, Hernández-Ortega S, Chávez MI, Méndez Cuesta CA, Martínez I, Espinoza B, Espinosa-García FJ, and Delgado G
- Subjects
- Animals, Anti-Inflammatory Agents isolation & purification, Antiparasitic Agents chemistry, Antiparasitic Agents pharmacology, Cell Line, Tumor, Cell Survival drug effects, Glycoside Hydrolase Inhibitors chemistry, Glycoside Hydrolase Inhibitors pharmacology, Humans, Male, Mice, Molecular Docking Simulation, Triterpenes isolation & purification, Yeasts enzymology, alpha-Glucosidases metabolism, Anti-Inflammatory Agents chemistry, Anti-Inflammatory Agents pharmacology, Euphorbiaceae chemistry, Triterpenes chemistry, Triterpenes pharmacology
- Abstract
Chemical investigation of the aerial parts of Cnidoscolus spinosus resulted in the isolation of relatively infrequent hopane-type triterpenes, 3β-acetoxy-hop-22(29)-ene (1), first reported here as natural product, together with 3-oxo-hop-22(29)-ene (2), and 3β-hydroxy-hop-22(29)-ene (3). β-Amyrin palmitate and three phytosterols were also characterized. The structures of the compounds were established using spectroscopic methods, and those of 1 and 2 were confirmed by crystallographic analysis. Selected biological activities for the isolated hopane-type triterpenes were tested through a series of assays for determining the cytotoxic, anti-inflammatory, α-glucosidase inhibition and antiparasitic activities. Compounds 1-3 did not show cytotoxic activity, compound 1 displayed an important inhibitory effect in the mouse ear induced inflammation assay, and significantly inhibited the yeast α-glucosidase activity in vitro and in silico. Additionally, compounds 2 and 3 showed marginal activities against Trypanosoma cruzi and Leishmania mexicana. Therefore, the bioactivities of hopane-type triterpenes deserve further investigation, particularly their anti-inflammatory properties., 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 © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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33. Bariatric surgery in the super-super morbidly obese: outcome analysis of patients with BMI >70 using the ACS-NSQIP database.
- Author
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Romero-Velez G, Pechman DM, Muñoz Flores F, Moran-Atkin E, Choi J, and Camacho DR
- Subjects
- Body Mass Index, Gastrectomy, Humans, New York, Postoperative Complications, Quality Improvement, Quality of Life, Retrospective Studies, Treatment Outcome, Bariatric Surgery, Gastric Bypass, Laparoscopy, Obesity, Morbid surgery
- Abstract
Background: Bariatric surgery offers patients short- and long-term benefits to their health and quality of life. Currently, we see more patients with superior body mass index (BMI) looking for these benefits. Evidence-based medicine is integral in the evaluation of risks versus benefit; however, data are lacking in this high-risk population., Objectives: To assess the morbidity and mortality of patients with BMI ≥70 undergoing bariatric surgery., Setting: University Hospital, Bronx, New York, United States using national database., Methods: Using the American College of Surgeons-National Surgical Quality Improvement Project (ACS-NSQIP) database for years 2005 to 2016, we identified patients who underwent primary laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass. Patients with BMI ≥70 were assigned to the BMI >70 (BMI70+) cohort and less obese patients were assigned to the BMI <70 (U70) cohort. Length of stay and 30-day morbidity and mortality were compared., Results: A total of 163,413 patients underwent non-revisional bariatric surgery. Of those, 2322 had a BMI ≥70. BMI70+ was associated with increased mortality (.4% versus .1%, P = .0001), deep vein thrombosis (.6% versus .3%, P = .007), pulmonary (1.9% versus .5%, P = .0001), renal (.9% versus .2%, P = .0001), and infectious complications (1.1% versus .4%, P = .0001). BMI70+ patients had longer mean length of stay (2.6 versus 2.1 d, P = .0001) and operative time (126.1 versus 114.5 min, P = .0001). There was no statistically significant difference in the number of myocardial infarctions (.1% versus .1%, P = .319), pulmonary embolisms (.3% versus .2%, P = .596), and transfusion requirements (.1% versus .1%, P = .105) between groups., Conclusions: Evaluation of risk and benefit is performed on a case-by-case basis, but evidence-based medicine is critical in empowering surgeons and patients to make informed decisions. The overall rate of morbidity and mortality for BMI70+ patients undergoing bariatric surgery was increased over U70 patients but was still relatively low. Our study will allow surgeons to incorporate objective data into their assessment of risk for super-obese patients pursuing bariatric surgery., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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34. Association of flow mediated vasodilation and burden of subclinical atherosclerosis by coronary CTA.
- Author
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Lakshmanan S, Shekar C, Kinninger A, Birudaraju D, Dahal S, Onuegbu A, Cherukuri L, Hamal S, Flores F, Dailing C, Roy SK, and Budoff M
- Subjects
- Aged, Brachial Artery diagnostic imaging, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Atherosclerosis diagnostic imaging, Coronary Angiography, Coronary Artery Disease diagnostic imaging, Plaque, Atherosclerotic, Vasodilation
- Abstract
Background and Aims: Endothelial dysfunction and atherosclerosis are linked by multiple mechanisms. Brachial artery flow-mediated dilation (FMD) rate is used to evaluate endothelial function and has been independently associated with adverse cardiac outcomes. The relationship between brachial artery FMD rate and severity of subclinical atherosclerosis by coronary computed tomography angiography (CCTA) is not understood. We hypothesized that brachial FMD is inversely associated with burden of subclinical atherosclerosis measured by CCTA., Methods: This is a retrospective study of 100 participants with intermediate cardiac risk and atypical symptoms to examine association between brachial artery FMD rate and surrogate markers of severity of subclinical atherosclerosis on CCTA. Multivariate linear regression analysis was used to understand the relationship between brachial artery FMD rate and markers of plaque burden on CCTA including coronary artery calcium (CAC) score, segment involvement score (SIS; total number of segments with any plaque), segment stenosis score (SSS, sum of maximal stenosis score per segment), and total plaque score (TPS, the sum of all segments plaque burden)., Results: 52 participants (42%) were female. Mean age of the cohort was 59.3 ± 10.4 years. After adjusting for traditional risk factors, brachial artery FMD rate was inversely associated with higher CAC, TPS, SIS and SSS (p < 0.05 for all). FMD <4.5 predicted the presence of CAC >0 and ≤ 100 most effectively, with a sensitivity of 62.2% and a specificity of 66.7%, respectively (area under the curve (AUC) of 0.5729, p = 0.0302). FMD <2.7 predicted the presence of CAC >100 most effectively, with a sensitivity of 34% and a specificity of 83% respectively (AUC of 0.6226, p = 0.0095)., Conclusions: Brachial FMD is independently associated with the presence and extent of subclinical atherosclerosis on CCTA. Our findings provide more detailed evidence that mechanistically, FMD, a surrogate marker of systemic endothelial dysfunction is a correlate of atherosclerotic burden, assessed by CCTA and CAC., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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35. Non-contrast cardiac CT-based quantitative evaluation of epicardial and intra-thoracic fat in healthy, recently menopausal women: Reproducibility data from the Kronos Early Estrogen Prevention Study.
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Jayawardena E, Li D, Nakanishi R, Dey D, Dailing C, Qureshi A, Dickens B, Hathiramani N, Kim M, Flores F, Kearns AE, Lui LY, Black D, and Budoff MJ
- Subjects
- Female, Healthy Volunteers, Humans, Middle Aged, Observer Variation, Predictive Value of Tests, Radiographic Image Interpretation, Computer-Assisted, Reproducibility of Results, Retrospective Studies, United States, Adipose Tissue diagnostic imaging, Adiposity, Menopause, Pericardium diagnostic imaging, Radiography, Thoracic, Tomography, X-Ray Computed
- Abstract
Background: Cardiac fat is emerging as an important parameter for cardiovascular risk stratification. Accurate and reproducible volumetric measurements can facilitate in the serial assessment of cardiac fat by computed tomography (CT). We assessed the intra- and inter-observer variability of cardiac fat volumetric measurements using a semi-automated CT software., Methods: We used non-contrast coronary calcium CT scans to quantify epicardial and intra-thoracic fat volumes. Two expert readers analyzed baseline and follow up CT scans of 45 subjects by using a semi-automated CT software (QFAT 2.0, Cedars Sinai-Medical Center). Correlation and Bland-Altman analysis was performed for both intra- and inter-observer comparisons for each cardiac fat type., Results: The intra-observer correlation coefficients ranged between 0.86 to 0.99 and 0.87 to 0.99 for epicardial (median fat per reader (cm
3 ) 20.9 to 25.7) and intra-thoracic (median fat per reader (cm3 ) 27.1 to 31.6) fat volumes respectively, with no significant differences between individual data points (all p > 0.38). The inter-observer correlation coefficient was 0.99 (p < 0.0001 for correlation) for both epicardial and intra-thoracic fat. By Bland-Altman analysis for epicardial fat measurements, mean difference of intra-observer was 0.90 cm3 with 95% confidence intervals (0.22,1.7) and -1.8 cm3 for inter-observer, with 95% CI (-2.9, -0.69). Bland-Altman plots for intra-thoracic fat measurements were similarly impressive for both inter- and intra-observer reads., Conclusions: Our data showed that measuring epicardial and intra-thoracic fat volumes by CT using a semi-automated software has excellent intra-observer and inter-observer reliability. Cardiac fat volumes can be obtained easily and reproducibly from routine calcium scoring scans and may help in assessing cardiovascular risk., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00154180; Keywords: Epicardial fat volume; intra-thoracic fat volume; computed tomography; intra-observer; inter-observer., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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36. Bariatric surgery in the elderly: outcomes analysis of patients over 70 using the ACS-NSQIP database.
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Pechman DM, Muñoz Flores F, Kinkhabwala CM, Salas R, Berk RH, Weithorn D, and Camacho DR
- Subjects
- Aged, Aged, 80 and over, Bariatric Surgery methods, Bariatric Surgery mortality, Body Mass Index, Cohort Studies, Databases, Factual, Female, Follow-Up Studies, Gastrectomy mortality, Gastric Bypass mortality, Geriatric Assessment, Hospitals, University, Humans, Incidence, Laparoscopy methods, Laparoscopy mortality, Male, Morbidity, New York City, Obesity, Morbid diagnosis, Patient Safety, Retrospective Studies, Risk Assessment, Survival Analysis, Treatment Outcome, Gastrectomy methods, Gastric Bypass methods, Obesity, Morbid mortality, Obesity, Morbid surgery, Quality Improvement
- Abstract
Background: Bariatric surgery offers patients with morbid obesity and related diseases short- and long-term benefits to their health and quality of life. Evidence-based medicine is integral in the evaluation of risk versus benefit; however, data are lacking for several high-risk patient populations, including the elderly., Objectives: This study assessed morbidity and mortality data for patients age ≥70 undergoing laparoscopic sleeve gastrectomy (SG) or laparoscopic Roux-en-Y gastric bypass (RYGB)., Setting: University Hospital, Bronx, New York, United States using national database., Methods: We used the American College of Surgeons-National Surgical Quality Improvement Project database for years 2005-2016 and identified patients who underwent primary SG or RYGB. Patients age ≥70 were assigned to the over age 70 (AGE70+) cohort and younger patients were assigned to the under age 70 (U70) cohort. Postoperative length of stay and 30-day morbidity and mortality were assessed., Results: A total of 1498 patients age ≥70 underwent nonrevisional bariatric surgery, including 751 (50.1%) SG and 747 (49.9%) RYGB. AGE70+ was associated with increased mortality and increased rates of cardiac, pulmonary, renal, and cerebrovascular morbidity. AGE70+ patients had longer mean length of stay, and were more likely to require transfusion and return to operative room. When stratified by procedure, rates of organ-space surgical site infection, acute renal failure, urinary tract infection, myocardial infarction, deep vein thrombosis/thrombophlebitis, and septic shock were significantly increased in AGE70+ patients undergoing RYGB but not SG. Impaired functional status was associated with increased rates of morbidity and mortality for AGE70+ patients and for U70 patients, although the small number of patients within each category limited statistical analysis., Conclusions: Evaluation of risk versus benefit is performed on a case-by-case basis, but evidence-based medicine is critical in empowering surgeons and patients to make informed decisions. The overall rate of morbidity and mortality for AGE70+ patients undergoing bariatric surgery was increased relative to U70 patients. Rates of several adverse events, including acute renal failure and myocardial infarction, were increased in AGE70+ patients undergoing RYGB but not SG, suggesting that SG may be the preferred procedure for elderly patients with organ-specific risk factors. The increased rates of morbidity and mortality observed for patients with impaired functional status supports consideration of functional status when evaluating preoperative risk., (Copyright © 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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37. The use of postoperative prophylactic antibiotics in stented distal hypospadias repair: a systematic review and meta-analysis.
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Chua ME, Kim JK, Rivera KC, Ming JM, Flores F, and Farhat WA
- Subjects
- Child, Humans, Hypospadias pathology, Male, Urologic Surgical Procedures, Male methods, Antibiotic Prophylaxis, Bacterial Infections prevention & control, Hypospadias surgery, Postoperative Care, Postoperative Complications prevention & control, Stents
- Abstract
Introduction: The current literature on the use of antibiotics perioperatively for many pediatric procedures, including hypospadias, is inconsistent. There is currently no clear evidence for the use of postoperative antibiotic prophylaxis for stented distal hypospadias repair., Objective: This study aims to synthesize and assess the available literature on the use versus non-use of postoperative antibiotic prophylaxis for stented distal hypospadias repair., Methodology: Systematic literature search was performed on March 2018 for evaluation of trials that assessed the use and non-use of postoperative prophylactic antibiotics among stented distal hypospadias repair in children. Methodological quality of the studies was assessed according to the study design as recommended by the Cochrane Collaboration. The outcome assessed includes composite overall posthypospadias repair complications of infection and wound healing complications. The event rate for each treatment group was extracted to extrapolate intervention relative risk (RR) and corresponding 95% confidence interval (CI). Mantel-Haenszel method with random effect model was used in pooling of effect estimates from the included studies. Heterogeneity was assessed with subgroup analysis performed according to the study design. Publication bias was likewise determined. The protocol of this review was registered in PROSPERO (CRD42018087301) and reported in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines., Result: A total of seven studies (four cohorts, three randomized controlled trials) with 986 stented distal hypospadias repairs (408 with no post-operative prophylactic antibiotics and 578 given postoperative prophylactic antibiotics) were included for the meta-analysis. Moderate to serious risk of bias was noted among the cohort studies, while the included randomized controlled trials (RCT) were of high risk of bias. Inconsistencies of effect estimates between subgroups and publication bias with small study effect were likely present. The overall pooled effect estimates comparing treatment groups showed no significant difference for outcomes of overall composite postoperative complication (RR 0.93, 95% CI 0.45, 1.93). Assessment of composite infection related complications and wound healing complications likewise did not show any significant between-group differences (RR 1.28, 95% CI 0.49, 3.35 and RR 1.01, 95% CI 0.48, 2.12; respectively) (Table). Asymptomatic bacteriuria was noted to be significantly higher among the intervention group with no postoperative prophylactic antibiotics (RR 4.01, 95% CI 1.11, 14.54)., Conclusion: The available evidence to date was assessed to be of high risk. The low level of evidence generated suggests that there is limited utility in the use of postoperative prophylactic antibiotics to prevent clinically significant posthypospadias repair complications., (Copyright © 2018. Published by Elsevier Ltd.)
- Published
- 2019
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38. ER stress promotes antitumor effects in BRAFi/MEKi resistant human melanoma induced by natural compound 4-nerolidylcathecol (4-NC).
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Alves-Fernandes DK, Oliveira ÉA, Faião-Flores F, Alicea-Rebecca G, Weeraratna AT, Smalley KSM, Barros SBM, and Maria-Engler SS
- Subjects
- Apoptosis drug effects, Cell Line, Tumor, Humans, Melanoma drug therapy, Skin Neoplasms drug therapy, Antineoplastic Agents pharmacology, Catechols pharmacology, Drug Resistance, Neoplasm drug effects, Endoplasmic Reticulum Stress drug effects, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins B-raf antagonists & inhibitors
- Abstract
Melanoma accounts for only 4% of malignant neoplasms of the skin, but is considered the most serious because it is highly deadly. Mutations in the MAPK (Ras-Raf-MEK-ERK) pathway is closely linked to the lack of control of cell proliferation. Especially in melanoma, this pathway has become a target for the development of oncogene-targeted therapies, such as the potent inhibitors of v-Raf murine sarcoma viral oncogene homolog B (BRAFi) and mitogen-activated protein kinase kinase (MEKi). Very high rates of response have been achieved, but most patients are relapsed due to the development of resistance, justifying the constant search for new therapeutic compounds. Early results from our group indicated that 4-nerolidylcatechol (4-NC), a catechol compound extracted from Pothomorphe umbellata, induces DNA damage, ROS production, increased p53 expression culminating in apoptosis in melanoma but with no data regarding the 4-NC effects in cells resistant to BRAFi or MEKi. Therefore, here we evaluated the role of 4-NC alone or in combination with BRAFi/MEKi in resistant melanoma cells. Double-resistant cells were generated and characterized by MAPK pathway reactivation. 4-NC alone or in combination (30 μM) with MAPK inhibitors was cytotoxic, inhibited colony formation and decreased invasiveness in two and three-dimensional cell culture models of treatment-naïve, BRAFi-resistant and BRAF/MEKi double-resistant melanoma cells. Apoptosis induction was demonstrated in resistant and double-resistant melanoma cell lines after 4-NC treatments. 4-NC showed important ability to induce apoptosis via Endoplasmatic Reticulum (ER) stress and specifically BiP and CHOP that had increased protein expression in all melanoma cell lines proving to be part of the ER stress pathway activation. CHOP knockdown slightly but enough increases cellular viability following 4-NC treatment indicating that apoptosis observed is partially dependent on CHOP. In summary, we show that 4-NC is a compound with activity against cutaneous melanoma, including resistant cells to clinically approved therapies., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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39. Occurrence, integrity and functionality of AcaML1-like viruses infecting extreme acidophiles of the Acidithiobacillus species complex.
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Covarrubias PC, Moya-Beltrán A, Atavales J, Moya-Flores F, Tapia PS, Acuña LG, Spinelli S, and Quatrini R
- Subjects
- Acidithiobacillus genetics, Acidithiobacillus metabolism, Bacterial Proteins genetics, Bacterial Proteins metabolism, Bacteriophages genetics, Bacteriophages isolation & purification, Proviruses genetics, Proviruses isolation & purification, Viral Proteins genetics, Viral Proteins metabolism, Virus Integration, Acidithiobacillus virology, Bacteriophages physiology, Proviruses physiology
- Abstract
General knowledge on the diversity and biology of microbial viruses infecting bacterial hosts from extreme acidic environments lags behind most other econiches. In this study, we analyse the AcaML1 virus occurrence in the taxon, its genetic composition and infective behaviour under standard acidic and SOS-inducing conditions to assess its integrity and functionality. Occurrence analysis in sequenced acidithiobacilli showed that AcaML1-like proviruses are confined to the mesothermophiles Acidithiobacillus caldus and Thermithiobacillus tepidarius. Among A. caldus strains and isolates this provirus had a modest prevalence (30%). Comparative genomic analysis revealed a significant conservation with the T. tepidarius AcaML1-like provirus, excepting the tail genes, and a high conservation of the virus across strains of the A. caldus species. Such conservation extends from the modules architecture to the gene level, suggesting that organization and composition of these viruses are preserved for functional reasons. Accordingly, the AcaML1 proviruses were demonstrated to excise from their host genomes under DNA-damaging conditions triggering the SOS-response and to produce DNA-containing VLPs. Despite this fact, under the conditions evaluated (acidic) the VLPs obtained from A. caldus ATCC 51756 could not produce productive infections of a candidate sensitive strain (#6) nor trigger it lysis., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2018
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40. Tumour-to-Tumour Metastasis Phenomenon: Metastatic Prostatic Adenocarcinoma within an Anaplastic Oligodendroglioma in the Brain of a Dog.
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Ros C, Fernández-Flores F, de la Fuente C, Pi D, Añor S, Planellas M, and Pumarola M
- Subjects
- Animals, Dogs, Male, Adenocarcinoma veterinary, Brain Neoplasms veterinary, Dog Diseases pathology, Neoplasms, Multiple Primary veterinary, Oligodendroglioma veterinary, Prostatic Neoplasms veterinary
- Abstract
A 10-year-old entire male French bulldog was presented following clusters of generalized tonic-clonic epileptic seizures. Neurolocalization was consistent with a lesion in the left forebrain. Magnetic resonance imaging of the brain revealed a large, ill-defined, intra-axial, space-occupying lesion at the level of the left temporal and parietal lobes, causing marked compression of the adjacent parenchyma. Computed tomography of the thorax and abdomen was consistent with disseminated metastatic disease. The dog was humanely destroyed and subjected to necropsy examination. Histological examination of the brain revealed a metastasis of prostatic carcinoma within an anaplastic oligodendroglioma in the left forebrain. To the author's knowledge, this is the first report describing clinical, imaging and histopathological features of an intracranial tumour-to-tumour metastasis in the brain of a dog., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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41. Get with the Program! Stemness and Reprogramming in Melanoma Metastasis.
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Faião-Flores F and Smalley KSM
- Subjects
- Disease Progression, Humans, MSX1 Transcription Factor, Neural Crest, Transcription Factors, Gene Expression Regulation, Neoplastic, Melanoma genetics
- Abstract
Cancer cells are highly plastic and adopt multiple phenotypic states that contribute to tumor progression. Heppt et al. demonstrate that the homeodomain transcription factor Msh homeobox 1 reprograms melanoma cells to a precursor state associated with melanoma progression and increased liver metastasis. Identification of this new role for Msh homeobox 1 may facilitate the development of new therapies that limit melanoma dissemination., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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42. Toxicogenomic and bioinformatics platforms to identify key molecular mechanisms of a curcumin-analogue DM-1 toxicity in melanoma cells.
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Oliveira ÉA, Lima DS, Cardozo LE, Souza GF, de Souza N, Alves-Fernandes DK, Faião-Flores F, Quincoces JAP, Barros SBM, Nakaya HI, Monteiro G, and Maria-Engler SS
- Subjects
- Cell Line, Tumor, Computational Biology, Humans, Mutation, Toxicogenetics, Curcumin analogs & derivatives, Curcumin pharmacology, Gene Expression Regulation, Fungal drug effects, Melanoma genetics, Saccharomyces cerevisiae genetics
- Abstract
Melanoma is a highly invasive and metastatic cancer with high mortality rates and chemoresistance. Around 50% of melanomas are driven by activating mutations in BRAF that has led to the development of potent anti-BRAF inhibitors. However resistance to anti-BRAF therapy usually develops within a few months and consequently there is a need to identify alternative therapies that will bypass BRAF inhibitor resistance. The curcumin analogue DM-1 (sodium 4-[5-(4-hydroxy-3-methoxy-phenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate) has substantial anti-tumor activity in melanoma, but its mechanism of action remains unclear. Here we use a synthetic lethal genetic screen in Saccharomyces cerevisiae to identify 211 genes implicated in sensitivity to DM-1 toxicity. From these 211 genes, 74 had close human orthologues implicated in oxidative phosphorylation, insulin signaling and iron and RNA metabolism. Further analysis identified 7 target genes (ADK, ATP6V0B, PEMT, TOP1, ZFP36, ZFP36L1, ZFP36L2) with differential expression during melanoma progression implicated in regulation of tumor progression, cell differentiation, and epithelial-mesenchymal transition. Of these TOP1 and ADK were regulated by DM-1 in treatment-naïve and vemurafenib-resistant melanoma cells respectively. These data reveal that the anticancer effect of curcumin analogues is likely to be mediated via multiple targets and identify several genes that represent candidates for combinatorial targeting in melanoma., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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43. Inhibition of proliferation and invasion in 2D and 3D models by 2-methoxyestradiol in human melanoma cells.
- Author
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Massaro RR, Faião-Flores F, Rebecca VW, Sandri S, Alves-Fernandes DK, Pennacchi PC, Smalley KSM, and Maria-Engler SS
- Subjects
- 2-Methoxyestradiol, Apoptosis drug effects, Cell Cycle, Cell Cycle Checkpoints drug effects, Cell Line, Tumor, Estradiol pharmacology, Humans, Melanoma pathology, Neoplasm Invasiveness pathology, Skin pathology, Skin Neoplasms pathology, Antineoplastic Agents pharmacology, Cell Proliferation drug effects, Estradiol analogs & derivatives, Melanoma drug therapy, Neoplasm Invasiveness prevention & control, Skin drug effects, Skin Neoplasms drug therapy
- Abstract
Despite the recent advances in the clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is a metabolite of estrogen that has shown anti-tumor effects in many cancer types. In this study we show that 2ME treatment leads to growth inhibition in melanoma cells, an effect associated with entry into senescence, decreased pRb and Cyclin B1 expression, increased p21/Cip1 expression and G2/M cell cycle arrest. 2ME treatment also inhibits melanoma cell growth in colony formation assay, including cell lines with acquired resistance to BRAF and BRAF+MEK inhibitors. We further show that 2ME is effective against melanoma with different BRAF and NRAS mutational status. Moreover, 2ME induced the retraction of cytoplasmic projections in a 3D spheroid model and significantly decreased cell proliferation in a 3D skin reconstruct model. Together our studies bring new insights into the mechanism of action of 2ME allowing melanoma targeted therapy to be further refined. Continued progress in this area is expected to lead to improved anti-cancer treatments and the development of new and more effective clinical analogues., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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44. Glucosinolate diversity within a phylogenetic framework of the tribe Cardamineae (Brassicaceae) unraveled with HPLC-MS/MS and NMR-based analytical distinction of 70 desulfoglucosinolates.
- Author
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Olsen CE, Huang XC, Hansen CIC, Cipollini D, Ørgaard M, Matthes A, Geu-Flores F, Koch MA, and Agerbirk N
- Subjects
- Barbarea chemistry, Chromatography, High Pressure Liquid, Gene Duplication, Glucosinolates chemistry, Humans, Molecular Structure, Seeds chemistry, Brassicaceae chemistry, Glucosinolates analysis, Phylogeny
- Abstract
As a basis for future investigations of evolutionary trajectories and biosynthetic mechanisms underlying variations in glucosinolate structures, we screened members of the crucifer tribe Cardamineae by HPLC-MS/MS, isolated and identified glucosinolates by NMR, searched the literature for previous data for the tribe, and collected HPLC-MS/MS data for nearly all glucosinolates known from the tribe as well as some related structures (70 in total). This is a considerable proportion of the approximately 142 currently documented natural glucosinolates. Calibration with authentic references allowed distinction (or elucidation) of isomers in many cases, such as distinction of β-hydroxyls, methylthios, methylsulfinyls and methylsulfonyls. A mechanism for fragmentation of secondary β-hydroxyls in MS was elucidated, and two novel glucosinolates were discovered: 2-hydroxy-3-methylpentylglucosinolate in roots of Cardamine pratensis and 2-hydroxy-8-(methylsulfinyl)octylglucosinolate in seeds of Rorippa amphibia. A large number of glucosinolates (ca. 54 with high structural certainty and a further 28 or more suggested from tandem MS), representing a wide structural variation, is documented from the tribe. This included glucosinolates apparently derived from Met, Phe, Trp, Val/Leu, Ile and higher homologues. Normal side chain elongation and side chain decoration by oxidation or methylation was observed, as well as rare abnormal side chain decoration (hydroxylation of aliphatics at the δ rather than β-position). Some species had diverse profiles, e.g. R. amphibia and C. pratensis (19 and 16 individual glucosinolates, respectively), comparable to total diversity in literature reports of Armoracia rusticana (17?), Barbarea vulgaris (20-24), and Rorippa indica (>20?). The ancestor or the tribe would appear to have used Trp, Met, and homoPhe as glucosinolate precursor amino acids, and to exhibit oxidation of thio to sulfinyl, formation of alkenyls, β-hydroxylation of aliphatic chains and hydroxylation and methylation of indole glucosinolates. Two hotspots of apparent biochemical innovation and loss were identified: C. pratensis and the genus Barbarea. Diversity in other species mainly included structures also known from other crucifers. In addition to a role of gene duplication, two contrasting genetic/biochemical mechanisms for evolution of such combined diversity and redundancy are discussed: (i) involvement of widespread genes with expression varying during evolution, and (ii) mutational changes in substrate specificities of CYP79F and GS-OH enzymes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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45. Current data regarding the structure-toxicity relationship of boron-containing compounds.
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Farfán-García ED, Castillo-Mendieta NT, Ciprés-Flores FJ, Padilla-Martínez II, Trujillo-Ferrara JG, and Soriano-Ursúa MA
- Subjects
- Animals, Boron Compounds adverse effects, Boron Compounds chemistry, Boron Compounds therapeutic use, Drug Design, Drugs, Investigational adverse effects, Drugs, Investigational chemistry, Drugs, Investigational therapeutic use, Environmental Pollutants chemistry, Humans, Molecular Structure, Mutagens chemistry, Mutagens toxicity, Structure-Activity Relationship, Toxicity Tests, Acute, Toxicity Tests, Chronic, Boron Compounds toxicity, Environmental Pollutants toxicity
- Abstract
Boron is ubiquitous in nature, being an essential element of diverse cells. As a result, humans have had contact with boron containing compounds (BCCs) for a long time. During the 20th century, BCCs were developed as antiseptics, antibiotics, cosmetics and insecticides. Boric acid was freely used in the nosocomial environment as an antiseptic and sedative salt, leading to the death of patients and an important discovery about its critical toxicology for humans. Since then the many toxicological studies done in relation to BCCs have helped to establish the proper limits of their use. During the last 15 years, there has been a boom of research on the design and use of new, potent and efficient boron containing drugs, finding that the addition of boron to some known drugs increases their affinity and selectivity. This mini-review summarizes two aspects of BCCs: toxicological data found with experimental models, and the scarce but increasing data about the structure-activity relationship for toxicity and therapeutic use. As is the case with boron-free compounds, the biological activity of BCCs is related to their chemical structure. We discuss the use of new technology to discover potent and efficient BCCs for medicinal therapy by avoiding toxic effects., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
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46. Vemurafenib resistance increases melanoma invasiveness and modulates the tumor microenvironment by MMP-2 upregulation.
- Author
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Sandri S, Faião-Flores F, Tiago M, Pennacchi PC, Massaro RR, Alves-Fernandes DK, Berardinelli GN, Evangelista AF, de Lima Vazquez V, Reis RM, and Maria-Engler SS
- Subjects
- Cell Line, Tumor, Drug Resistance, Neoplasm physiology, GPI-Linked Proteins genetics, GPI-Linked Proteins metabolism, Humans, Interleukin-8 metabolism, Matrix Metalloproteinase 14 genetics, Matrix Metalloproteinase 14 metabolism, Matrix Metalloproteinase 2 genetics, Matrix Metalloproteinase 9 genetics, Matrix Metalloproteinase 9 metabolism, Melanoma genetics, Melanoma metabolism, Neoplasm Invasiveness, Proto-Oncogene Proteins B-raf genetics, Tissue Inhibitor of Metalloproteinase-2 genetics, Tissue Inhibitor of Metalloproteinase-2 metabolism, Tumor Microenvironment drug effects, Up-Regulation, Vemurafenib, Antineoplastic Agents pharmacology, Indoles pharmacology, Matrix Metalloproteinase 2 metabolism, Melanoma pathology, Protein Kinase Inhibitors pharmacology, Proto-Oncogene Proteins B-raf antagonists & inhibitors, Sulfonamides pharmacology
- Abstract
The BRAF(V600E) mutation confers constitutive kinase activity and accounts for >90% of BRAF mutations in melanoma. This genetic alteration is a current therapeutic target; however, the antitumorigenic effects of the BRAF(V600E) inhibitor vemurafenib are short-lived and the majority of patients present tumor relapse in a short period after treatment. Characterization of vemurafenib resistance has been essential to the efficacy of next generation therapeutic strategies. Herein, we found that acute BRAF inhibition induced a decrease in active MMP-2, MT1-MMP and MMP-9, but did not modulate the metalloproteinase inhibitors TIMP-2 or RECK in naïve melanoma cells. In vemurafenib-resistant melanoma cells, we observed a lower growth rate and an increase in EGFR phosphorylation followed by the recovery of active MMP-2 expression, a mediator of cancer metastasis. Furthermore, we found a different profile of MMP inhibitor expression, characterized by TIMP-2 downregulation and RECK upregulation. In a 3D spheroid model, the invasion index of vemurafenib-resistant melanoma cells was more evident than in its non-resistant counterpart. We confirmed this pattern in a matrigel invasion assay and demonstrated that use of a matrix metalloproteinase inhibitor reduced the invasion of vemurafenib resistant melanoma cells but not drug naïve cells. Moreover, we did not observe a delimited group of cells invading the dermis in vemurafenib-resistant melanoma cells present in a reconstructed skin model. The same MMP-2 and RECK upregulation profile was found in this 3D skin model containing vemurafenib-resistant melanoma cells. Acute vemurafenib treatment induces the disorganization of collagen fibers and consequently, extracellular matrix remodeling, with this pattern observed even after the acquisition of resistance. Altogether, our data suggest that resistance to vemurafenib induces significant changes in the tumor microenvironment mainly by MMP-2 upregulation, with a corresponding increase in cell invasiveness., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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47. Aged Garlic Extract Reduces Low Attenuation Plaque in Coronary Arteries of Patients with Metabolic Syndrome in a Prospective Randomized Double-Blind Study.
- Author
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Matsumoto S, Nakanishi R, Li D, Alani A, Rezaeian P, Prabhu S, Abraham J, Fahmy MA, Dailing C, Flores F, Hamal S, Broersen A, Kitslaar PH, and Budoff MJ
- Subjects
- Calcium metabolism, Coronary Artery Disease etiology, Coronary Vessels pathology, Disease Progression, Double-Blind Method, Female, Humans, Male, Metabolic Syndrome complications, Metabolic Syndrome pathology, Middle Aged, Plant Extracts pharmacology, Plaque, Atherosclerotic etiology, Prospective Studies, Risk Factors, Coronary Artery Disease prevention & control, Coronary Vessels drug effects, Garlic, Metabolic Syndrome drug therapy, Phytotherapy, Plant Extracts therapeutic use, Plaque, Atherosclerotic prevention & control
- Abstract
Background: Although several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification, its effect on noncalcified plaque (NCP) has been unclear., Objective: This study investigated whether AGE reduces coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with metabolic syndrome (MetS)., Methods: Fifty-five patients with MetS (mean ± SD age: 58.7 ± 6.7 y; 71% men) were prospectively assigned to consume 2400 mg AGE/d (27 patients) or placebo (28 patients) orally. Both groups underwent CCTA at baseline and follow-up 354 ± 41 d apart. Coronary plaque volume, including total plaque volume (TPV), dense calcium (DC), NCP, and low-attenuation plaque (LAP), were measured based upon predefined intensity cutoff values. Multivariable linear regression analysis, adjusted for age, gender, number of risk factors, hyperlipidemia medications, history of coronary artery disease, scan interval time, and baseline %TPV, was performed to examine whether AGE affected each plaque change., Results: The %LAP change was significantly reduced in the AGE group compared with the placebo group (-1.5% ± 2.3% compared with 0.2% ± 2.0%, P = 0.0049). In contrast, no difference was observed in %TPV change (0.3% ± 3.3% compared with 1.6% ± 3.0%, P = 0.13), %NCP change (0.2% ± 3.3% compared with 1.4% ± 2.9%, P = 0.14), and %DC change (0.2% ± 1.4%, compared with 0.2% ± 1.7%, P = 0.99). Multivariable linear regression analysis found a beneficial effect of AGE on %LAP regression (β: -1.61; 95% CI: -2.79, -0.43; P = 0.008)., Conclusions: This study indicates that the %LAP change was significantly greater in the AGE group than in the placebo group. Further studies are needed to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events. This trial was registered at clinicaltrials.gov as NCT01534910., (© 2016 American Society for Nutrition.)
- Published
- 2016
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48. A novel technology for multiplex gene expression analysis directly from whole blood samples stabilized at ambient temperature using an RNA-stabilizing buffer.
- Author
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Kim CH, Abedi M, Liu Y, Panuganti S, Flores F, Shah KR, Catterall H, Morampudi KS, and Terbrueggen R
- Subjects
- Buffers, Humans, Multiplex Polymerase Chain Reaction, RNA Stability, Temperature, RNA chemistry
- Abstract
We describe a novel method, based on target-dependent chemical ligation of probes, which simplifies the multiplexed quantitation of gene expression from blood samples by eliminating the RNA purification step. Gene expression from seven genes was evaluated over a range of sample inputs (16.7 to 0.25 μL of whole blood in serial dilutions) from three healthy donors. Mean CVs were ≤11% for five technical replicates for whole blood inputs ≥2.1 μL. The method showed a limit of detection of 300 copies of RNA by using titration of in vitro transcripts for four genes. Gene expression measured on stabilized blood samples was highly correlated (Spearman rank correlation method, ρ = 0.80) to gene expression results obtained with RNA isolated from matched samples (three donors, five technical replicates). Gene expression changes determined with seven radiation-responsive genes on six healthy donor blood samples before and after ex vivo irradiation were highly correlated (ρ = 0.93) to those measured with a TaqMan quantitative real-time RT-PCR assay on RNA purified from matched samples. Thus, this method is reproducible, sensitive, and correlated to quantitative real-time RT-PCR and may be used to streamline the multiplex gene expression analysis of large numbers of stabilized blood samples without RNA purification., (Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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49. Increased epicardial adipose tissue is associated with coronary artery disease and major adverse cardiovascular events.
- Author
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Hajsadeghi F, Nabavi V, Bhandari A, Choi A, Vincent H, Flores F, Budoff M, and Ahmadi N
- Subjects
- Aged, Cardiovascular Diseases pathology, Coronary Angiography, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Myocardial Infarction pathology, Proportional Hazards Models, ROC Curve, Risk Factors, Sensitivity and Specificity, Smoking, Tomography, X-Ray Computed, Adipose Tissue pathology, Coronary Artery Disease pathology, Pericardium pathology
- Abstract
Background: Increased-epicardial-adipose tissue (EAT) is associated with the presence and severity of subclinical-atherosclerosis. This study investigates the long-term clinical-outcome of subjects with and without increased-EAT., Methods: Two hundred and forty-five subjects, aged 61 ± 9 years and 34% women underwent clinically-indicated computed-tomography-angiography (CTA), and body-surface-area adjusted EAT was measured and were followed prospectively. CTA-diagnosed coronary-artery-disease (CAD) was defined as obstructive (luminal-stenosis ≥ 50%), non-obstructive (luminal-stenosis: 1-49%) and zero-obstruction. Major-adverse-cardiac-event (MACE) was defined as myocardial-infarction or cardiovascular-death., Results: EAT increased significantly from subjects with zero-obstruction-coronaries (93 ± 37 cm(3)/m(2)) to non-obstructive-CAD (132 ± 25 cm(3)/m(2)) to obstructive-CAD (145 ± 35 cm(3)/m(2)) (P = 0.01). During the 48-month follow-up, the event-rate was 8.6% (21). The event free survival-rate decreased significantly from 99% in the lowest-quartile to 86.6% in the highest-quartile of EAT. After adjustment for risk-factors, the hazard ratio of MACE was 1.4, 3.1 and 5.7 in lower mid-, upper mid- and highest-quartiles of EAT as compared to lowest-quartile of EAT (P < 0.05)., Conclusion: Increased EAT is directly associated with CAD and predicts MACE independent of the age, gender and conventional-risk-factors., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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50. Coronary CT angiography versus standard of care strategies to evaluate patients with potential coronary artery disease; effect on long term clinical outcomes.
- Author
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Budoff MJ, Liu S, Chow D, Flores F, Hsieh B, Gebow D, DeFrance T, and Ahmadi N
- Subjects
- Adult, Aged, Case-Control Studies, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Patient Compliance, Proportional Hazards Models, Prospective Studies, Risk Factors, Standard of Care, Treatment Outcome, Coronary Angiography, Coronary Artery Disease diagnosis, Coronary Artery Disease diagnostic imaging, Tomography, X-Ray Computed
- Abstract
Background: Previous studies have shown that computed tomography coronary angiography (CTA) in patients with suspected coronary artery disease (CAD) predicts short term adverse events. However, there is no current data on whether identifying atherosclerosis on CTA impacts outcomes. We performed a case-control study to assess whether information from CTA can improve outcomes., Methods: 4244 symptomatic patients (mean age 58 ± 9, 62.5% male) without known CAD who underwent CTA (n = 2538) to rule out CAD were matched to 1706 patients who underwent standard of care in an academic cardiology clinic. Patients were propensity-matched by gender, age, ethnicity, CAD risk factors and follow-up duration. The primary outcome measure was all-cause mortality. Multivariable Cox proportional hazards models incorporated age, gender and traditional risk factors for coronary disease as well as pre-test probability of CAD., Results: There were no significant differences in age, gender, conventional risk factors between groups (p > 0.05). During a mean follow up of 80 ± 11 months, the overall death rate was 6.3% (270 deaths). Death rate was significantly lower in CTA group (n = 106, 4.2%) as compared to the control group (n = 184, 10.8%, p = 0.001). Event free survival was 95.8% and 89.2% in CTA and standard of care groups, respectively. Risk-adjusted hazard ratio of death were 2.5 (95%CI: 1.6-6.7, p = 0.003) in standard of care cohort as compared to CTA group. Multivariate analysis demonstrated that undergoing coronary CTA resulted in a risk reduction of 32%, p = 0.0001., Conclusions: Improved knowledge of atherosclerosis or increased anti-atherosclerotic therapies among those undergoing CTA may have contributed to improved survival. Our results provide evidence of potential benefit from scanning for atherosclerosis with CTA in symptomatic patients. Large randomized trials are warranted., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
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