136 results on '"Expósito J"'
Search Results
2. Sustainable expert virtual machine migration in dynamic clouds
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Seddiki, Doraid, Galán, Sebastián García, Expósito, J. Enrique Muñoz, Ibañez, Manuel Valverde, Marciniak, Tomasz, and -Pérez de Prado, Rocío J.
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- 2022
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3. High-J v=0 SiS Maser Emission in IRC+10216: A New Case of Infrared Overlaps
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Expósito, J. P. Fonfría, Agúndez, M., Tercero, B., Pardo, J. R., and Cernicharo, J.
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Astrophysics - Abstract
We report on the first detection of maser emission in the J=11-10, J=14-13 and J=15-14 transitions of the v=0 vibrational state of SiS toward the C-rich star IRC+10216. These masers seem to be produced in the very inhomogeneous region between the star and the inner dust formation zone, placed at 5-7 R*, with expansion velocities below 10 km/s. We interpret the pumping mechanism as due to overlaps between v=1-0 ro-vibrational lines of SiS and mid-IR lines of C2H2, HCN and their 13C isotopologues. The large number of overlaps found suggests the existence of strong masers for high-J v=0 and v=1 SiS transitions, located in the submillimeter range. In addition, it could be possible to find several rotational lines of the SiS isotopologues displaying maser emission., Comment: 4 pages, 1 figure, published in the ApJ Letters
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- 2007
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4. Understanding the Chemical Complexity in Circumstellar Envelopes of C-rich AGB Stars: the Case of IRC +10216
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Agundez, M., Cernicharo, J., Pardo, J. R., Exposito, J. P. Fonfria, Guelin, M., Tenenbaum, E. D., Ziurys, L. M., and Apponi, A. J.
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Astrophysics - Abstract
The circumstellar envelopes of carbon-rich AGB stars show a chemical complexity that is exemplified by the prototypical object IRC +10216, in which about 60 different molecules have been detected to date. Most of these species are carbon chains of the type CnH, CnH2, CnN, HCnN. We present the detection of new species (CH2CHCN, CH2CN, H2CS, CH3CCH and C3O) achieved thanks to the systematic observation of the full 3 mm window with the IRAM 30m telescope plus some ARO 12m observations. All these species, known to exist in the interstellar medium, are detected for the first time in a circumstellar envelope around an AGB star. These five molecules are most likely formed in the outer expanding envelope rather than in the stellar photosphere. A pure gas phase chemical model of the circumstellar envelope is reasonably successful in explaining the derived abundances, and additionally allows to elucidate the chemical formation routes and to predict the spatial distribution of the detected species., Comment: 4 pages, 4 figures; to appear in Astrophysics and Space Science, special issue of "Science with ALMA: a new era for Astrophysics" conference, November, 13-17 2006, ed. R. Bachiller
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- 2007
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5. Evaluation of WRF Parameterizations for Dynamical Downscaling in the Canary Islands
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Pérez, J. C., Díaz, J. P., González, A., Expósito, J., Rivera-López, F., and Taima, D.
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- 2014
6. Impacts of urbanization on groundwater hydrodynamics and hydrochemistry of the Toluca Valley aquifer (Mexico)
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Martín del Campo, M. A., Esteller, M. V., Expósito, J. L., and Hirata, R.
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- 2014
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7. Prognostic factors associated with lung cancer survival. A population-based study in the South of Spain: 33P
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Linares, I., Expósito, J., Arrebola, J. P., Sánchez-Cantalejo, J., Chang-Chan, Y. L., Molina, E., Guerrero, R., and Sánchez, M. J.
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- 2016
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8. Serum and adipose tissue as matrices for assessment of exposure to persistent organic pollutants in breast cancer patients
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Artacho-Cordón, F., Fernández-Rodríguez, M., Garde, C., Salamanca, E., Iribarne-Durán, L. M., Torné, P., Expósito, J., Papay-Ramírez, L., Fernández, M. F., Olea, N., and Arrebola, J. P.
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- 2015
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9. Real-time image texture analysis in quality management using grid computing: an application to the MDF manufacturing industry
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Sánchez Santiago, A. J., Yuste, A. J., Muñoz Expósito, J. E., García Galán, Sebastian, Prado, R. P., Maqueira, J. M., and Bruque, S.
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- 2012
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10. Characteristics of Virgin Olive Oils from the Olive Zone of Extremadura (Spain), and an Approximation to their Varietal Origin
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Casas, Jacinto Sánchez, De Miguel Gordillo, C., Osorio Bueno, E., Marín Expósito, J., Mendoza, M. Fuentes, Hierro, T. Ardila, González, L. Gallardo, and Martínez Cano, M.
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- 2009
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11. Too Little Democracy in All the Right Places A Comment on Kelty 2017 Reply
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Kelty, CM, Roura-Expósito, J, and Alonso González, P
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- 2018
12. Triple helix assembly and processing of human collagen produced in transgenic tobacco plants
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Ruggiero, F, Exposito, J.-Y, Bournat, P, Gruber, V, Perret, S, Comte, J, Olagnier, B, Garrone, R, and Theisen, M
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- 2000
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13. Productive HIV-1 infection upregulates CD32 in vitro and in vivo
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Serra Peinado, C., primary, Grau-Expósito, J., additional, Falcó, V., additional, Genescà, M., additional, Martinez-Picado, L.J., additional, Luque-Ballesteros, L., additional, Astorga, A., additional, Gálvez, C., additional, Castellví, J., additional, Willekens, R., additional, Ocaña, I., additional, Burgos, J., additional, Navarro, J., additional, Curran, A., additional, Ribera, E., additional, Montaner, L., additional, Martinez-Picado, J., additional, and Buzon, M.J., additional
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- 2017
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14. 33P Prognostic factors associated with lung cancer survival. A population-based study in the South of Spain
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Linares, I., primary, Expósito, J., additional, Arrebola, J.P., additional, Sánchez-Cantalejo, J., additional, Chang-Chan, Y.L., additional, Molina, E., additional, Guerrero, R., additional, and Sánchez, M.J., additional
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- 2016
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15. Estudio del estado nutricional de los ancianos de Cantabria
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Jiménez Sanz,M., Sola Villafranca,J. M., Pérez Ruiz,C., Turienzo Llata,M. J., Larrañaga Lavin,G., Mancebo Santamaría,M. A., Hernández Barranco,M. C., García Iglesias,A., Palacio Pellón,J. L., Pelillo García,T., Fernández del Moral Pinilla,S., Sañudo Pedrero,R. A., Gutiérrez García,L., Castro Ugalde,P., García Calderón,M. I., Cagigas Villoslada,M. J., Río Pelaz,M. R. Del, Besoy González,A. I., Canduela Fontaneda,B., Castañeda García,E., Cos Iglesia,A. De, Cos Seco,M. J. De, Domínguez Salas,R., García Mata,M. A., González Gutiérrez,T., Alonso Diez,P., Barriga Gómez,P., Biurrun Ruiz,I., Blanco Martínez,O., Cadaya Gabas,N., Carbajo Martínez,M. A., Cobo Martínez,N., Correas Gutiérrez,M. J., García Diez,R., González Expósito,J., Gualdrón Romero,M. A., Higuera Cobo,E., Higuera Ruiz,E., Lozano Barcena,R., Ortiz García,N., Ruiz Bolado,S., and Somonte Pérez,G.
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Desnutrición ,IMC ,MNA ,Estado nutricional ,Envejecimiento - Abstract
Introducción: El envejecimiento de la población representa uno de los retos más importantes desde el punto de vista biosanitario. Objetivo: Valorar el estado nutricional de las personas de 65 y más años de Cantabria. Métodos: Un total de 1605 personas fueron evaluadas por medio del MNA; a) en atención primaria (59,9% en la consulta y 4,7% en domicilios) y, b) en residencias de ancianos (35,4%). Resultados: La puntuación nutricional (PN) obtenida de la suma de los ítems del MNA fue 23,4 ± 4,1 para las mujeres y 24,4 ± 4 en los varones (p < 0,001). Destaca el hecho de que el 22,3% de las personas estudiadas en residencias está malnutrida o en riesgo de malnutrición, frente al 14,2% de las que acuden a consulta, y sólo el 3,3% de las estudiadas en su domicilio. La correlación entre los valores de la PN y la apreciación subjetiva del estado de nutrición mostró un valor elevado (0,65). Destacamos la correlación negativa (-0,53) entre los valores del IMC y la incidencia de lesiones cutáneas. Conclusiones: Nuestros resultados indican la importancia de la identificación de la desnutrición o su riesgo, en personas mayores, por las consecuencias negativas que presenta este estado carencial.
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- 2011
16. La resonancia magnética en la patología glandular salival del paciente anciano
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Paz Expósito, J, Velasco Ortega, E, and Martínez-Sahuquillo Márquez, A
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anciano ,tumor ,tumour ,salivary glands ,aged patient ,salivary deseases ,patología salival ,submaxilar ,magnetic resonance ,submandibular gland ,glándulas salivales ,parotid gland ,parótida ,resonancia magnética - Abstract
Objetivo. Valorar la utilidad de la Imagen por Resonancia Magnética (RM) en el diagnóstico de la patología de las glándulas salivales en el paciente anciano. Pacientes y Método. Se presentan 18 pacientes mayores de 65 años con diversas patologías de las glándulas salivales, estudiados por RM, imán superconductivo de 1,5 Tesla, realizándose secuencias Spin Echo ponderada T1 en los planos de incidencia axial y coronal y secuencia Spin Echo T2 en plano axial, con un espesor de corte de 3 mm. Resultados. La RM muestra, fundamentalmente, imágenes homogéneas de una intensidad de señal baja o intermedia en las secuencias Spin Echo T1 y de intensidad alta en la secuencia Spin Echo T2 en la patología tumoral benigna, e imágenes heterogéneas de una intensidad de señal baja o intermedia en ambas secuencias Spin Echo T1 y T2 en la patología tumoral maligna. La RM permite identificar la lesión glandular salival, sus relaciones intraglandulares (nervio facial, paquete vascular) y extraglandulares (base de cráneo y cuello). Conclusiones. La RM constituye el método diagnóstico por la imagen de primera elección en el estudio de los procesos patológicos tumorales que afectan a las glándulas saliva les en el paciente anciano Objective. Assessment to Magnetic Resonance Imaging (MRI) as diagnosis method in salivary glands pathology of aged patients. Patients and Methods. We present eighteen 65 year and over patients with salivary glands diseases, studied by RMI, with the 1.5 T system, performed imaging spin echo T1-weighted sequences on coronal and tranverse plans, and spin echo T2-weighted sequences on tranverse plans. The scan thickness was 3 mm. Results. MRI showed, mainly, homogeneous imaging of low-to-intermediate signal intensity on spin echo TI and high signal intensity on T2 in tumoral benign pathology and heterogeneous imaging of low-to-intermediate signal intensity on spin echo TI and T2 in tumoral malign pathology. MRI confirmed the presence of the glands salivary diseases, and permits the evaluation of the relationship of lesions to the facial nerve and vascular complex; and extension on head and neck. Conclusions. Today MRI is the best imaging diagnosis method in the study of salivary glands tumours in aged patients
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- 2004
17. Use of palliative radiotherapy in brain and bone metastases
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Expósito, J., primary, Tovar, I., additional, Jaén, J., additional, and Alonso, E., additional
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- 2013
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18. Underuse of radiotherapy in lung cancer negatively impacts survival
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Expósito, J., primary, Tovar, I., additional, Jaén, J., additional, and Alonso, E., additional
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- 2013
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19. Stem-like cells from breast cancer: Crucial players in celullar response to radiotherapy
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Román Marinetto, E., primary, Jiménez, G., additional, Ríos Arrabal, S., additional, Artacho Cordón, F., additional, Expósito, J., additional, López Ruiz, E., additional, Ramírez, A., additional, León, J., additional, Marchal, J., additional, and Núñez Torres, M., additional
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- 2013
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20. Radiotherapy outcome could be influenced by antioxidant capacity in breast cancer cell lines
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Ríos Arrabal, S., primary, Román Marinetto, E., additional, Artacho Cordón, F., additional, León, J., additional, Expósito, J., additional, Salinas, M., additional, Calvente, I., additional, Martínez Galán, J., additional, Argote Camacho, A., additional, Torné, P., additional, and Núñez Torres, M., additional
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- 2013
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21. Radiosensitivity enhancement and MMP modulation: A dual role for epigenetic drugs in breast radiotherapy
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Artacho Cordón, F., primary, Román Marinetto, E., additional, Ríos Arrabal, S., additional, Storch, K., additional, Expósito, J., additional, León, J., additional, Salinas Asensio, M., additional, Calvente, I., additional, Cordes, N., additional, and Núñez Torres, M., additional
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- 2013
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22. Pattern of use of radiotherapy for lung cancer: Descriptive study
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Expósito, J., primary, Tovar, I., additional, Jaén, J., additional, and Alonso, E., additional
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- 2013
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23. Las termas y el Suburbium marítimo de Baelo Claudia. Avance de un reciente descubrimiento
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Bernal, Dario, primary, Arévalo, A., additional, Muñoz, A., additional, Expósito, J. A., additional, Díaz, J. J., additional, Lagóstena, J., additional, Vargas, J. M., additional, Lara, M., additional, Moreno, E., additional, Sáez, A. M., additional, and Bustamante, M., additional
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- 2013
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24. Real-time image texture analysis in quality management using grid computing: an application to the MDF manufacturing industry
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Sánchez Santiago, A. J., primary, Yuste, A. J., additional, Muñoz Expósito, J. E., additional, García Galán, Sebastian, additional, Prado, R. P., additional, Maqueira, J. M., additional, and Bruque, S., additional
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- 2011
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25. Evidencias arqueológicas de desplomes paramentales traumáticos en las Termas Marítimas de Baelo Claudia. Reflexiones arqueosismológicas.
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Bernal, D., Expósito, J. A., Díaz,, J. J., Bustamante, M., Lara, M., Vargas, J. M., Jiménez-Camino, R., Calvo, M., Luaces, M., Pascual, M. A., Blanco, E., Hoyo, L., Retamosa, J. A., Durante, A., Muñoz, N., and Bellido, A.
- Abstract
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- 2015
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26. High- J [FORMULA][F]v[/F][/FORMULA] = 0 SiS Maser Emission in IRC +10216: A New Case of Infrared Overlaps
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Expósito, J. P. Fonfría, primary, Agúndez, M., additional, Tercero, B., additional, Pardo, J. R., additional, and Cernicharo, J., additional
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- 2006
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27. Calidad del registro de quimioterapia en los servicios de farmacia hospitalaria de Andalucía
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Peña, J., primary, Santos, B., additional, Briones, E., additional, Corbacho, B., additional, Fernández Feijóo, A., additional, and Expósito, J., additional
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- 2006
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28. Underuse of radiotherapy in lung cancer has negative consequences for patients.
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Tovar I, Expósito J, Jaén J, and Alonso E
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- 2013
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29. Anales de Edafología y Agrobiología Tomo 47 Número 3-4
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Pérez Moreira, R., Díaz Fierros, F., Martínez Cortizas, A., Aragoneses, F. J., Casas, J., Martín de Vidales, J., Juárez, M., Sánchez-Andreu, J., Pla, L., Jordá, J., Espejo Serrano, R., Guerrero López, F., Saa Requejo, A., Bech, J., Garrido, J., Torrento, J. R., Rodríguez-Rodríguez, A., Ontañón Sánchez, J. M., Ortega, Carlos B., Ortega, M. C., Heras, J. G. de las, García-Serna, J., Mataix, J., Ibarra, M., López-Belmonte, F., Díez, Mª A., Marín Expósito, J., Miguel Gordillo, C., Maynar, J. I., Mesías, J. L., Ramos Hernández, S., Aguilera Herrera, N., and Vicente, C.
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Suelos. Física. Resistencia del suelo y susceptibilidad a la compactación en terrenos a monte sometidos a pastoreo. Por R. Pérez Moreira y F. Diaz-Fierros Viqueira.-- La reserva de agua útil de los suelos de Galicia. l. Relación con la textura y el contenido de materia orgánica. Por A. M. Martinez Cortizas.-- Química Empleo de aminas alifáticas en el estudio de asociaciones haloisita-esmectita en suelos. Por F. J. Aragoneses, J. Casas, y J. L. Martin de Vidales.-- Quelación por EDDHA de micronutrientes en suelos calizos. Ecuación de límite máximo. Por M. Juárez, J. Sánchez-Andréu, L. Pla y J. Jorda.-- Quelación por EDDHA de micronutrientes en suelos calizos. Ecuación de orden "n ".Por J. Sánchez-Andréu, M. Juarez, L. Pla y J. Jordá.-- Génesis, Clasificación y Cartografía Caracterización de un podsol ferro - húmico en el Puerto de la Quesera (Sierra del Ayllón). Por R. Espejo Serrano, F. Guerrero López y A. Saa Requejo.-- Natrixerales en el Baix Segre (Lleida). Por J. Bech i Borrás, J. Garrigo i Reixach y J. R. Torrento i Marselles.-- Aspectos micromorfológicos del horizonte superior en suelos artificiales (Sorribas) de las Islas Canarias. Por A. Rodríguez Rodríguez y J. M. Ontañón Sánchez.-- Fertilidad Influencia de diferentes factores del suelo sobre su contenido en microelementos asimilables: Mn, Fe, Cu y Zn. Por B. C. Ortega, Ma C. Ortega y J. G. de las Heras.--Incidencia de la salinidad del agua de riego en la mineralización del nitrógeno orgánico en suelos calizos del sureste español. Por J. García-Serna, J. Sánchez Andréu, M. Juárez y J. Mataix.-- Biología Vegetal-Fisiología Efectos de la toxicidad del flúor sobre el ciclo biológico en especies herbáceas dicotiledoneas. Por M. Ibarra, F. López Belmonte y Ma A. Diez.-- Efectos de la toxicidad del flúor sobre el ciclo biológico de especies de monocotiledoneas. Por M. Ibarra, F. López-Belmonte y Mª A . Diez.-- Proteasas ácidas en uvas Vitis vinifera (variedad Macabeo). l. Actividad proteásica durante su maduración. Por J. Marín Expósito, C. Miguel Gordillo, J. l. Maynar Mariño y J. L. Mesias Iglesias.-- Agro biología Efectos de enmiendas calcáreas en suelos fijadores de fósforo. Por S. G. Ramos Hernández y N. Aguilera Herrera.-- III. Trabajo Recapitulativo. Una deriva hacia hemiparasftismo de los líquenes epifitos: Análisis fisiológico de las relaciones con sus fitoforos. Por C. Vicente Peer reviewed 2019-08.- CopyBook.- Libnova.- Biblioteca ICA
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- 1988
30. Speech/music discrimination using a single Warped LPC-based feature
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Muñoz-Expósito, J. E., Garcia-Galán, S., Ruiz-Reyes, N., Pedro Vera-Candeas, and Rivas-Peña, F.
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[TODO] Add abstract here.
31. Speech/music discrimination using a warped LPC-based feature and a fuzzy expert system for intelligent audio coding
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Muñoz-Expósito, J. E., Garcia-Galán, S., Ruiz-Reyes, N., Pedro Vera-Candeas, and Rivas-Peña, F.
- Abstract
Publication in the conference proceedings of EUSIPCO, Florence, Italy, 2006
32. Use of palliative radiotherapy in brain and bone metastases (VARA II study)
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Expósito Jose, Jaén Javier, Alonso Enrique, and Tovar Isabel
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Palliative radiation therapy ,Variability ,Bone metastases ,Brain metastases ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Introduction Metastases are detected in 20% of patients with solid tumours at diagnosis and a further 30% after diagnosis. Radiation therapy (RT) has proven effective in bone (BM) and brain (BrM) metastases. The objective of this study was to analyze the variability of RT utilization rates in clinical practice and the accessibility to medical technology in our region. Patients and methods We reviewed the clinical records and RT treatment sheets of all patients undergoing RT for BM and/or BrM during 2007 in the 12 public hospitals in an autonomous region of Spain. Data were gathered on hospital type, patient type and RT treatment characteristics. Calculation of the rate of RT use was based on the cancer incidence and the number of RT treatments for BM, BrM and all cancer sites. Results Out of the 9319 patients undergoing RT during 2007 for cancer at any site, 1242 (13.3%; inter-hospital range, 26.3%) received RT for BM (n = 744) or BrM (n = 498). These 1242 patients represented 79% of all RT treatments with palliative intent, and the most frequent primary tumours were in lung, breast, prostate or digestive system. No significant difference between BM and BrM groups were observed in: mean age (62 vs. 59 yrs, respectively); gender (approximately 64% male and 36% female in both); performance status (ECOG 0–1 in 70 vs. 71%); or mean distance from hospital (36 vs. 28.6 km) or time from consultation to RT treatment (13 vs. 14.3 days). RT regimens differed among hospitals and between patient groups: 10 × 300 cGy, 5 × 400 cGy and 1x800cGy were applied in 32, 27 and 25%, respectively, of BM patients, whereas 10 × 300cGy was used in 49% of BrM patients. Conclusions Palliative RT use in BM and BrM is high and close to the expected rate, unlike the global rate of RT application for all cancers in our setting. Differences in RT schedules among hospitals may reflect variability in clinical practice among the medical teams.
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- 2012
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33. Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication
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Jerneja Kladnik, Ana Dolinar, Jakob Kljun, David Perea, Judith Grau-Expósito, Meritxell Genescà, Marko Novinec, Maria J. Buzon, Iztok Turel, Institut Català de la Salut, [Kladnik J, Dolinar A, Kljun J, Novinec M, Turel I] Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia. [Perea D, Grau-Expósito J, Genescà M, Buzon MJ] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Pharmacology ,compuestos orgánicos::compuestos organometálicos [COMPUESTOS QUÍMICOS Y DROGAS] ,SARS-CoV-2 ,pirition ,zinc ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,General Medicine ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,udc:546.47:61:577 ,cink ,inhibition ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents [CHEMICALS AND DRUGS] ,inhibicija ,COVID-19 (Malaltia) - Tractament ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos [COMPUESTOS QUÍMICOS Y DROGAS] ,antiviral agents ,Drug Discovery ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Medicaments antivírics - Ús terapèutic ,protivirusna zdravila ,Compostos organometàl·lics ,Organic Chemicals::Organometallic Compounds [CHEMICALS AND DRUGS] ,pyrithione - Abstract
As SARS-CoV-2 triggered a global health crisis, there is an urgent need to provide patients with safe, effective, accessible, and preferably oral therapeutics for COVID-19 that complement mRNA vaccines. Zinc compounds are widely known for their antiviral properties. Therefore, we have prepared a library of zinc complexes with pyrithione (1-hydroxy-2(1H)-pyridinethione) and its analogues, all of which showed promising in vitro inhibition of cathepsin L, an enzyme involved in SARS-CoV-2 entry, and PLPro, an enzyme involved in SARS-CoV-2 replication both in (sub)micromolar range. Zinc pyrithione 1a is a well-established, commercially available antimicrobial agent and was therefore selected for further evaluation of its SARS-CoV-2 entry and replication inhibition in an ex vivo system derived from primary human lung tissue. Our results suggest that zinc pyrithione complex 1a provides a multitarget approach to combat SARS-CoV-2 and should be considered for repurposing as a potential therapeutic against the insidious COVID-19 disease.Featured imageIn our study, we show that zinc pyrithione holds immense potential for the development of a possible out-patient treatment for SARS-CoV-2 due to its inhibition of viral entry and replication.
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- 2022
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34. Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy
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Maria J. Buzon, Judith Grau-Expósito, Victor Urrea, Vicenç Falcó, Cristina Gálvez, Bonaventura Clotet, Javier Martinez-Picado, Institut Català de la Salut, [Gálvez C, Urrea V] IrsiCaixa AIDS Research Institute, Badalona, Spain. [Grau-Expósito J, Falcó V, Buzón MJ] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Clotet B] IrsiCaixa AIDS Research Institute, Badalona, Spain. University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain. Fundació Lluita contra la SIDA, Badalona, Spain. Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain. CIBER en Enfermedades Infecciosas, Madrid, Spain. [Martinez-Picado J] IrsiCaixa AIDS Research Institute, Badalona, Spain. University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain. Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain. CIBER en Enfermedades Infecciosas, Madrid, Spain. Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [ANATOMY] ,CD4-Positive T-Lymphocytes ,Gene Expression Regulation, Viral ,Male ,virosis::infecciones por virus ARN::infecciones por Retroviridae::infecciones por Lentivirus::infecciones por VIH [ENFERMEDADES] ,Anti-HIV Agents ,HIV-1 cure ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,HIV Infections ,In situ hybridization ,Biology ,CD38 ,HIV-1 DNA ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,Peripheral blood mononuclear cell ,Microbiology ,células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos [ANATOMÍA] ,Flow cytometry ,Blood cell ,T-Lymphocyte Subsets ,HIV-1 reservoir ,Virology ,medicine ,Humans ,HIV-1 RNA ,Virus Diseases::RNA Virus Infections::Retroviridae Infections::Lentivirus Infections::HIV Infections [DISEASES] ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos::antirretrovirales::fármacos anti-VIH [COMPUESTOS QUÍMICOS Y DROGAS] ,medicine.diagnostic_test ,Cell growth ,Antiretrovirals ,Provirus ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [CHEMICALS AND DRUGS] ,Viral Load ,Infeccions per VIH - Tractament ,QR1-502 ,medicine.anatomical_structure ,DNA, Viral ,Leukocytes, Mononuclear ,HIV-1 ,Female ,HIV-1 reservoir size ,Stem cell ,Immunologic Memory ,Research Article - Abstract
ADN del VIH-1; Cura del VIH-1; Reservorio de VIH-1 HIV-1 DNA; HIV-1 cure; HIV-1 reservoir ADN del VIH-1; Cura del VIH-1; Reservori del VIH-1 Knowing the mechanisms that govern the persistence of infected CD4+ subpopulations could help us to design new therapies to cure HIV-1 infection. We evaluated the simultaneous distribution of the HIV-1 reservoir in 13 CD4+ subpopulations from 14 HIV-1-infected individuals on antiretroviral therapy to analyze its relationship with HIV-1 transcription, immune activation, and cell proliferation. A unique large blood donation was used to isolate CD4, CD4 resting (CD4r), CD4 activated (CD4a), T naive (TN), T stem cell memory (TSCM), T central memory (TCM), T transitional memory (TTM), T effector memory (TEM), circulating T follicular helper (cTFH), TCD20, TCD32, and resting memory TCD2high (rmTCD2high) cells. HIV-1 DNA measured by droplet digital PCR ranged from 3,636 copies/106 in TTM to 244 in peripheral blood mononuclear cells (PBMCs), with no subpopulation standing out for provirus enrichment. Importantly, all the subpopulations harbored intact provirus by intact provirus DNA assay (IPDA). TCD32, cTFH, and TTM had the highest levels of HIV-1 transcription measured by fluorescent in situ hybridization with flow cytometry (FISH/flow), but without reaching statistical differences. The subpopulations more enriched in provirus had a memory phenotype, were less activated (measured by CD38+/HLA-DR+), and expressed more programmed cell death 1 (PD-1). Conversely, subpopulations transcribing more HIV-1 RNA were not necessarily enriched in provirus and were more activated (measured by CD38+/HLA-DR+) and more proliferative (measured by Ki-67). In conclusion, the HIV reservoir is composed of a mosaic of subpopulations contributing to the HIV-1 persistence through different mechanisms such as susceptibility to infection, provirus intactness, or transcriptional status. The narrow range of reservoir differences between the different blood cell subsets tested suggests limited efficacy in targeting only specific cell subpopulations during HIV-1 cure strategies. IMPORTANCE The main barrier for HIV-1 cure is the presence of latently infected CD4+ T cells. Although various cell subpopulations have been identified as major HIV-1 reservoir cells, the relative contribution of infected CD4 subpopulations in the HIV-1 reservoir remains largely unknown. Here, we evaluated the simultaneous distribution of the HIV-1 reservoir in 13 CD4+ T-cell subpopulations in peripheral blood from HIV-1-infected individuals under suppressive antiretroviral therapy. We found that the HIV-1 reservoir is composed of a mosaic of cell subpopulations, with heterogeneous proviral DNA, HIV-1 transcription, and activation status. Hence, each cell subpopulation contributes to the HIV-1 persistence through different mechanisms such as susceptibility to infection, rates of intact provirus, transcriptional status or half-life. This research provides new insights into the composition of the HIV-1 reservoir, suggesting that, to be effective, eradication strategies must simultaneously target multiple cell subpopulations. This work was sponsored in part by Grifols and by Gilead (GLD17/00204). The funding organizations had no input in the design of the study or in the collection, analyses, and interpretation of the data. Similarly, they played no role in the writing of the manuscript or in the decision to submit the study for publication. J.M.-P. is supported by grant PID2019-109870RB-I00 from the Spanish Ministry of Science and Innovation. J.M.-P. and M.J.B. are supported by the RETIC RD16/0025/0041 and RD16/0025/0007 (cofunded by the European Regional Development Fund/European Social Fund). M.J.B. is supported by grant RTI2018-101082-B-I00 (MINECO/FEDER) and by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). C.G. was supported by the Ph.D. fellowship of the Spanish Ministry of Education, Culture, and Sport (FPU15/03698).
- Published
- 2021
35. Entrectinib—A SARS-CoV-2 Inhibitor in Human Lung Tissue (HLT) Cells
- Author
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Vikram Ayinampudi, Jana Selent, Mirjam Zimmermann, Tomasz Maciej Stepniewski, Judit Grau-Expósito, Mariona Torrens-Fontanals, Maria J. Buzon, Meritxell Genescà, Alejandro Peralta-Garcia, Maria Waldhoer, David Perea, Institut Català de la Salut, [Peralta-Garcia A, Torrens-Fontanals M] Research Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences, Hospital del Mar Medical Research Institute (IMIM), Pompeu Fabra University (UPF), 08003 Barcelona, Spain. [Stepniewski TM] Research Programme on Biomedical Informatics (GRIB), Department of Experimental and Health Sciences, Hospital del Mar Medical Research Institute (IMIM), Pompeu Fabra University (UPF), 08003 Barcelona, Spain. InterAx Biotech AG, PARK InnovAARE, 5234 Villigen, Switzerland. [Grau-Expósito J, Perea D, Buzón MJ, Genescà M] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Ayinampudi V] InterAx Biotech AG, PARK InnovAARE, 5234 Villigen, Switzerland, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Drug Evaluation, Preclinical ,Drug repurposing ,Entrectinib ,Drug resistance ,COVID-19 (Malaltia) ,Chlorocebus aethiops ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Biology (General) ,Medicaments antivírics ,Lung ,Spectroscopy ,media_common ,Communication ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,General Medicine ,Computer Science Applications ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents [CHEMICALS AND DRUGS] ,Molecular Docking Simulation ,Drug repositioning ,Chemistry ,Other subheadings::/pharmacology [Other subheadings] ,Benzamides ,Drug ,Virtual screening ,Indazoles ,medicine.drug_class ,QH301-705.5 ,media_common.quotation_subject ,Virus Attachment ,Medicaments - Ús ,Antiviral Agents ,Virus ,Catalysis ,Cell Line ,Inorganic Chemistry ,técnicas de investigación::desarrollo de medicamentos::nuevas indicaciones de medicamentos [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Vero Cells ,QD1-999 ,Molecular Biology ,business.industry ,SARS-CoV-2 ,Organic Chemistry ,Drug Repositioning ,COVID-19 ,Viral membrane ,Virology ,COVID-19 Drug Treatment ,Viral cell entry assays ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos [COMPUESTOS QUÍMICOS Y DROGAS] ,Otros calificadores::/farmacología [Otros calificadores] ,Investigative Techniques::Drug Development::Drug Repositioning [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Antiviral drug ,business - Abstract
COVID-19; Drug repurposing; Viral cell entry assays COVID-19; Reutilización de medicamentos; Ensayos de entrada de células virales COVID-19; Reutilització de medicaments; Assajos d'entrada de cèl·lules virals Since the start of the COVID-19 outbreak, pharmaceutical companies and research groups have focused on the development of vaccines and antiviral drugs against SARS-CoV-2. Here, we apply a drug repurposing strategy to identify drug candidates that are able to block the entrance of the virus into human cells. By combining virtual screening with in vitro pseudovirus assays and antiviral assays in Human Lung Tissue (HLT) cells, we identify entrectinib as a potential antiviral drug. This research was funded by the Spanish Ministry of Science, Innovation, and Universities (FPU16/01209 to M.T.-F.); the Health department of the Government of Catalonia (DGRIS 3_9 to A.P.G. and J.S. and DGRIS 1_5 to M.J.B. and M.G.).
- Published
- 2021
36. Peripheral and lung resident memory T cell responses against SARS-CoV-2
- Author
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Grau Expósito, Judith, Sánchez-Gaona, Nerea, Massana, Núria, Suppi, Marina, Astorga-Gamaza, Antonio, Perea, David, Rosado Rodríguez, Joel, Falcó, Anna, Kirkegaard, Cristina, Torrella Domingo, Adriana, Planas, Bibiana, Navarro, Jordi, Suanzes, Paula, Álvarez-Sierra, Daniel, Ayora, Alfonso, Sansano, Irene, Esperalba, Juliana, Andrés, Cristina, Antón, Andrés, Ramón y Cajal, Santiago, Almirante Gragera, Benito, Pujol-Borrell, Ricardo, Falcó, Vicenç, Burgos, Joaquín, Buzón, Maria José, Genescà Ferrer, Meritxell, Universitat Autònoma de Barcelona, Institut Català de la Salut, [Grau-Expósito J, Sánchez-Gaona N, Massana N, Suppi M, Astorga-Gamaza A, Perea D, Falcó A, Kirkegaard C, Torrella A, Planas B, Navarro J, Suanzes P, Almirante B, Falcó V, Burgos J, Buzón MJ, Genescà M] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Rosado J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Cirurgia Toràcica i Trasplantament Pulmonar, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Álvarez-Sierra D] Grup d'Immunologia Diagnòstica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ayora A] Unitat de Prevenció de Riscos Laborals, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Sansano I, Ramón Y Cajal S] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Ciències morfològiques, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Esperalba J, Andrés C, Antón A] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat de Virus Respiratoris, Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pujol-Borrell R] Grup d'Immunologia Diagnòstica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. FOCIS Center of Excellence, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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0301 basic medicine ,CD4-Positive T-Lymphocytes ,viruses ,T-Lymphocytes ,General Physics and Astronomy ,Apoptosis ,CD8-Positive T-Lymphocytes ,0302 clinical medicine ,Cell Movement ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes [ANATOMY] ,Interferon gamma ,Otros calificadores::Otros calificadores::/inmunología [Otros calificadores] ,Lung ,Multidisciplinary ,Degranulation ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,respiratory system ,Cellular immunity ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cytokines ,Mucosal immunology ,Infectious diseases ,células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T [ANATOMÍA] ,medicine.drug ,COVID-19 (Malaltia) - Immunologia ,Science ,T cell ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Interferon-gamma ,Other subheadings::Other subheadings::/immunology [Other subheadings] ,sistema respiratorio::pulmón [ANATOMÍA] ,Parenchyma ,medicine ,Humans ,Interleukin 4 ,Cèl·lules T - Immunologia ,business.industry ,SARS-CoV-2 ,Pulmons - Immunologia ,COVID-19 ,General Chemistry ,Respiratory System::Lung [ANATOMY] ,respiratory tract diseases ,030104 developmental biology ,Viral infection ,Immunology ,Interleukin-4 ,business ,Memory T cell ,Immunologic Memory ,Respiratory tract - Abstract
Resident memory T cells (TRM) positioned within the respiratory tract are probably required to limit SARS-CoV-2 spread and COVID-19. Importantly, TRM are mostly non-recirculating, which reduces the window of opportunity to examine these cells in the blood as they move to the lung parenchyma. Here, we identify circulating virus-specific T cell responses during acute infection with functional, migratory and apoptotic patterns modulated by viral proteins and associated with clinical outcome. Disease severity is associated predominantly with IFNγ and IL-4 responses, increased responses against S peptides and apoptosis, whereas non-hospitalized patients have increased IL-12p70 levels, degranulation in response to N peptides and SARS-CoV-2-specific CCR7+ T cells secreting IL-10. In convalescent patients, lung-TRM are frequently detected even 10 months after initial infection, in which contemporaneous blood does not reflect tissue-resident profiles. Our study highlights a balanced anti-inflammatory antiviral response associated with a better outcome and persisting TRM cells as important for future protection against SARS-CoV-2 infection., Lung resident memory T (TRM) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung TRM cells that might be important to limit reinfection.
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- 2021
37. Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa
- Author
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[Cantero-Pérez J, Grau-Expósito J, Serra-Peinado C, Rosero DA, Luque-Ballesteros L, Astorga-Gamaza A, Falcó V, Buzon MJ, Genescà M] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Malalties Infeccioses, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Castellví J] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Mañalich-Barrachina L, Centeno-Mediavilla C] Servei de Ginecologia i Obstetrícia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain and Hospital Universitari Vall d'Hebron
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Hemic and Immune Systems::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [ANATOMY] ,Cèl·lules T ,Coll uterí ,Sistemas Sanguíneo e Inmunológico::Sistemas Sanguíneo e Inmunológico::Sistema Inmunológico::Leucocitos::Leucocitos Mononucleares::Linfocitos::Linfocitos T::Linfocitos T CD4-Positivos [ANATOMÍA] ,Urogenital System::Genitalia::Genitalia, Female::Uterus::Cervix Uteri [ANATOMY] ,Infeccions per VIH ,sistema urogenital::genitales::genitales femeninos::útero::cuello del útero [ANATOMÍA] ,Enfermedades del Sistema Inmune::Síndromes de Inmunodeficiencia::Infecciones por VIH [ENFERMEDADES] ,Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [DISEASES] - Published
- 2021
38. Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab
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[Serra-Peinado C, Grau-Expósito J, Luque-Ballesteros L, Astorga-Gamaza A, Navarro J, Gallego-Rodriguez J, Martin M, Curran A, Burgos J, Ribera E, Raventós B, Willekens R, Torrella A, Planas B, Badía R, Genescà M, Falcó V, Buzon MJ] Servei de Malalties Infeccioses, Hospital Universitari Vall d’Hebron, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR). Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Castellví J] Servei de Patologia, Hospital Universitari Vall d’Hebron. Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain and Hospital Universitari Vall d'Hebron
- Subjects
Hemic and Immune Systems::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [ANATOMY] ,Cèl·lules T ,Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Murine-Derived::Rituximab [CHEMICALS AND DRUGS] ,Aminoácidos, Péptidos y Proteínas::Proteínas::Proteínas Sanguíneas::Inmunoproteínas::Inmunoglobulinas::Anticuerpos::Anticuerpos Monoclonales::Anticuerpos Monoclonales de Origen Murino::Rituximab [COMPUESTOS QUÍMICOS Y DROGAS] ,Sistemas Sanguíneo e Inmunológico::Sangre::Células Sanguíneas::Leucocitos::Leucocitos Mononucleares::Linfocitos::Linfocitos T::Sistemas Sanguíneo e Inmunológico::Linfocitos T CD4-Positivos [ANATOMÍA] ,Infeccions per VIH ,Rituximab ,Enfermedades del Sistema Inmune::Síndromes de Inmunodeficiencia::Infecciones por VIH [ENFERMEDADES] ,Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [DISEASES] - Published
- 2021
39. Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa
- Author
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Cantero, Jon, Grau-Expósito, Judith, Serra-Peinado, Carla, Rosero, D. A., Luque-Ballesteros, Laura, Astorga-Gamaza, Antonio, Castellvi, Josep., Sanhueza, T., Tapia Melendo, Gustavo, Lloveras, B., Fernández, Marco A., Prado, Julia G., Solé-Sedeno, J. M., Tarrats, A., Lecumberri, Carla, Mañalich-Barrachina, L., Centeno-Mediavilla, C., Falcó, Vicenç, Buzón, Maria José, Genescà Ferrer, Meritxell., Universitat Autònoma de Barcelona, [Cantero-Pérez J, Grau-Expósito J, Serra-Peinado C, Rosero DA, Luque-Ballesteros L, Astorga-Gamaza A, Falcó V, Buzon MJ, Genescà M] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Malalties Infeccioses, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Castellví J] Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Mañalich-Barrachina L, Centeno-Mediavilla C] Servei de Ginecologia i Obstetrícia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
CD4-Positive T-Lymphocytes ,0301 basic medicine ,CD32 ,Human immunodeficiency virus (HIV) ,Urogenital System::Genitalia::Genitalia, Female::Uterus::Cervix Uteri [ANATOMY] ,General Physics and Astronomy ,HIV Infections ,Cervix Uteri ,medicine.disease_cause ,Pathogenesis ,0302 clinical medicine ,Coll uterí ,sistema urogenital::genitales::genitales femeninos::útero::cuello del útero [ANATOMÍA] ,Dna viral ,lcsh:Science ,Multidisciplinary ,biology ,virus diseases ,Middle Aged ,Viral Load ,Phenotype ,3. Good health ,Cèl·lules T ,Anti-Retroviral Agents ,Female ,HIV infections ,Adult ,Female circumcision ,Science ,Article ,General Biochemistry, Genetics and Molecular Biology ,Viral reservoirs ,03 medical and health sciences ,enfermedades del sistema inmune::síndromes de inmunodeficiencia::infecciones por VIH [ENFERMEDADES] ,VIH (Virus) ,medicine ,Humans ,Mucosa cervical ,Aged ,Disease Reservoirs ,Hemic and Immune Systems::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [ANATOMY] ,Mucous Membrane ,Cluster of differentiation ,RNA ,General Chemistry ,Virology ,Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [DISEASES] ,sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::sistema inmunológico::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos [ANATOMÍA] ,030104 developmental biology ,HIV-1 ,biology.protein ,Infeccions per VIH ,lcsh:Q ,Immunologic Memory ,030217 neurology & neurosurgery - Abstract
HIV viral reservoirs are established very early during infection. Resident memory T cells (TRM) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4+TRM display a unique repertoire of clusters of differentiation, with enrichment of several molecules associated with HIV infection susceptibility, longevity and self-renewing capacities. These protein profiles are enriched in a fraction of CD4+TRM expressing CD32. Cervical explant models show that CD4+TRM preferentially support HIV infection and harbor more viral DNA and protein than non-TRM. Importantly, cervical tissue from ART-suppressed HIV+ women contain high levels of viral DNA and RNA, being the TRM fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4+TRM as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider TRM phenotypes, which are widely distributed in tissues., Using cervical explant models and cervical tissue from ART-suppressed HIV+ women, the authors here show that resident memory T cells (TRM) in the cervical mucosa are preferentially infected and harbor more viral DNA, RNA and protein than non-TRM, suggesting that TRM may serve as viral reservoir in the cervical mucosa.
- Published
- 2019
40. Latency reversal agents affect differently the latent reservoir present in distinct CD4+ t subpopulations
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Grau-Expósito, Judith, Luque-Ballesteros, Laura, Navarro Mercadé, Jordi, Curran, Adrian, Burgos, Joaquín, Ribera, Esteban, Torrella Domingo, Adriana, Planas, Bibiana, Badía, Rosa, Martin-Castillo, Mario, Fernández-Sojo, Jesús, Genescà Ferrer, Meritxell., Falcó, Vicenç, Buzon, Maria J., Universitat Autònoma de Barcelona, [Grau-Expósito J, Luque-Ballesteros L, Navarro J, Curran A, Burgos J, Ribera E, Torrella A, Planas B, Badía R, Martin-Castillo M, Genescà M, Falcó V, Buzon MJ] Servei de Malalties Infeccioses, Hospital Universitari Vall d’Hebron, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR). Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Fernández-Sojo J] Banc de Sang i Teixits, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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RNA viruses ,CD4-Positive T-Lymphocytes ,Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::Hemic and Immune Systems::CD4-Positive T-Lymphocytes [ANATOMY] ,Apoptosis ,HIV Infections ,Pathology and Laboratory Medicine ,Toxicology ,medicine.disease_cause ,Microbiological Phenomena::Virus Physiological Phenomena::Virus Latency [PHENOMENA AND PROCESSES] ,Memory T cells ,Romidepsin ,White Blood Cells ,Immunodeficiency Viruses ,Animal Cells ,Depsipeptides ,Medicine and Health Sciences ,Biology (General) ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos::antirretrovirales::fármacos anti-VIH [COMPUESTOS QUÍMICOS Y DROGAS] ,0303 health sciences ,Cell Death ,T Cells ,030302 biochemistry & molecular biology ,Antiretrovirals ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Anti-HIV Agents [CHEMICALS AND DRUGS] ,Viral Load ,Viral Persistence and Latency ,3. Good health ,Virus Latency ,medicine.anatomical_structure ,Cèl·lules T ,Medical Microbiology ,Cell Processes ,Viral Pathogens ,Viruses ,Pathogens ,Cellular Types ,Stem cell ,Diterpenes ,Viral load ,fenómenos microbiológicos::fenómenos fisiológicos de los virus::latencia viral [FENÓMENOS Y PROCESOS] ,Research Article ,medicine.drug ,QH301-705.5 ,Viral protein ,Anti-HIV Agents ,Immune Cells ,T cell ,Immunology ,Biology ,Microbiology ,03 medical and health sciences ,Virology ,Retroviruses ,Genetics ,medicine ,Humans ,Microbial Pathogens ,Molecular Biology ,030304 developmental biology ,Blood Cells ,Toxicity ,Lentivirus ,Virus - Reproducció ,Organisms ,Biology and Life Sciences ,HIV ,RNA ,Cell Biology ,RC581-607 ,Viral Replication ,sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::sistema inmunológico::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos [ANATOMÍA] ,Viral replication ,HIV-1 ,Parasitology ,Virus Activation ,Immunologic diseases. Allergy ,Ex vivo - Abstract
Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs., Author summary HIV infection is an incurable disease. Despite antiretroviral therapy, a pool of cells with HIV in a latent state persists and precludes fully eradication of the viral infection. The cells that contain this latent viral reservoir are very diverse, and therefore different therapeutic strategies would be necessary to target and eliminate all infected cells. Latency Reversal Agents (LRAs) are compounds able to awake the latent virus from its dormant state with the purpose of making infected cells visible to the immune system. But the ability of the LRAs to target different cell types containing HIV is currently unknown. Here, using a novel methodology that interrogates individual cells, we found that current LRAs do not impact equally all infected cells. In fact, certain types of memory lymphocytes, recognized to harbor latent HIV for decades, are not fully impacted by most of the LRAs tested. Our study highlights the difficulty to cure HIV with the currently available LRAs. Different therapeutic approaches aimed at reversing HIV latency from diverse cellular reservoirs are needed to reduce HIV persistence.
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- 2019
41. Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab
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Serra-Peinado, Carla, Grau-Expósito, Judith, Luque-Ballesteros, Laura, Astorga-Gamaza, Antonio, Navarro, Jordi, Gallego-Rodriguez, Jenny, Martín Castillo, Mario, Curran, Adrian, Burgos, Joaquín, Ribera, Esteban, Raventós, Berta, Willekens, Rein, Torrella Domingo, Adriana, Planas, Bibiana, Badía, Rosa, García, Felipe, Castellvi, Josep, Genescà Ferrer, Meritxell, Falcó, Vicenç, Buzón, Maria José, Universitat Autònoma de Barcelona, [Serra-Peinado C, Grau-Expósito J, Luque-Ballesteros L, Astorga-Gamaza A, Navarro J, Gallego-Rodriguez J, Martin M, Curran A, Burgos J, Ribera E, Raventós B, Willekens R, Torrella A, Planas B, Badía R, Genescà M, Falcó V, Buzon MJ] Servei de Malalties Infeccioses, Hospital Universitari Vall d’Hebron, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR). Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Castellví J] Servei de Patologia, Hospital Universitari Vall d’Hebron. Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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0301 basic medicine ,CD4-Positive T-Lymphocytes ,General Physics and Astronomy ,HIV Infections ,02 engineering and technology ,Lymphocyte Activation ,hemic and lymphatic diseases ,Virus latency ,lcsh:Science ,Lymph node ,CD20 ,Multidisciplinary ,biology ,Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Murine-Derived::Rituximab [CHEMICALS AND DRUGS] ,021001 nanoscience & nanotechnology ,Flow Cytometry ,3. Good health ,Virus Latency ,medicine.anatomical_structure ,Cell killing ,Cèl·lules T ,RNA, Viral ,Rituximab ,0210 nano-technology ,Cell activation ,Infection ,medicine.drug ,Anti-HIV Agents ,Science ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Viral reservoirs ,Antigen ,enfermedades del sistema inmune::síndromes de inmunodeficiencia::infecciones por VIH [ENFERMEDADES] ,medicine ,Humans ,Immunologic Factors ,Hemic and Immune Systems::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes [ANATOMY] ,General Chemistry ,Translational research ,medicine.disease ,Antigens, CD20 ,Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [DISEASES] ,sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::sistema inmunológico::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos [ANATOMÍA] ,030104 developmental biology ,aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales de origen murino::rituximab [COMPUESTOS QUÍMICOS Y DROGAS] ,Immunology ,biology.protein ,HIV-1 ,Leukocytes, Mononuclear ,lcsh:Q ,Infeccions per VIH ,Virus Activation ,Lymph Nodes ,Immunologic Memory ,Ex vivo - Abstract
The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4+) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART., Here, the authors identify B lymphocyte antigen CD20 as a marker for HIV-infected T cells and provide evidence for the potential use of anti-CD20 antibodies in combination with latency reversing agents for depletion of viral reactivated CD4 T cells in patients on antiretroviral therapy.
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- 2018
42. Adipose tissue concentrations of persistent organic pollutants and total cancer risk in an adult cohort from Southern Spain: Preliminary data from year 9 of the follow-up
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José Expósito, Jens Peter Bonde, José-Manuel Molina-Molina, Emilio Sánchez-Cantalejo, Mariana F. Fernández, Nicolás Olea, Elena Molina-Portillo, Maria Jose Sanchez-Perez, Piedad Martin-Olmedo, Juan P. Arrebola, [Arrebola, JP, Expósito, J] Oncology Unit. Virgen de las Nieves University Hospital, Granada, Spain. [Fernández, MF, Olea, N] Instituto de Investigación Biosanitaria ibs.Granada, University of Granada, San Cecilio University Hospital. Granada, Spain.[Martín-Olmedo, P, Sánchez-Pérez, MJ, Sánchez-Cantalejo, E, Molina-Portillo, E] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada, Granada, Spain. [Bonde, JP] Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, University of Copenhagen, Denmark, This study was supported in part by research grants from the Spanish Ministry of Health (FIS 02/974, EUS2008-03574), CIBER de Epidemiología, and Junta de Andalucía (01/264, P09-CTS-5488 Project of Excellence, PI-0675-2010,and PI-0513-2012), and the Instituto de Salud Carlos III (FIS PI11/0610).
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Male ,Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants [Medical Subject Headings] ,Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Neoplasms ,estudios prospectivos ,Medicine ,Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Follow-Up Studies [Medical Subject Headings] ,Prospective cohort study ,Waste Management and Disposal ,Cancer ,Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings] ,education.field_of_study ,Follow-up ,Incidence (epidemiology) ,Persistent organic pollutants ,Hazard ratio ,Middle Aged ,Diseases::Neoplasms [Medical Subject Headings] ,Pollution ,Anatomy::Tissues::Connective Tissue::Adipose Tissue [Medical Subject Headings] ,Health Care::Environment and Public Health::Public Health::Environmental Pollution::Environmental Exposure [Medical Subject Headings] ,Adipose Tissue ,Cohort ,Regression Analysis ,Environmental Pollutants ,Estudios de seguimiento ,Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Statistics as Topic::Regression Analysis [Medical Subject Headings] ,Adult ,Tejido adiposo ,Environmental Engineering ,Population ,Adipose tissue ,Check Tags::Male [Medical Subject Headings] ,Hazardous Substances ,Environmental health ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,Humans ,Environmental Chemistry ,Prospective study ,education ,Contaminantes orgánicos ,business.industry ,Environmental Exposure ,medicine.disease ,Confidence interval ,Cancer registry ,Spain ,Chemicals and Drugs::Chemical Actions and Uses::Toxic Actions::Environmental Pollutants::Hazardous Substances [Medical Subject Headings] ,business ,Follow-Up Studies - Abstract
There is an increasing trend in the incidence of cancer worldwide, and it has been accepted that environmental factors account for an important proportion of the global burden. The present paper reports preliminary findings on the influence of the historical exposure to a group of persistent organic pollutants on total cancer risk, at year 9 in the follow-up of a cohort from Southern Spain. A cohort of 368 participants (median age 51 years) was recruited in 2003. Their historical exposure was estimated by analyzing residues of persistent organic pollutants in adipose tissue. Estimation of cancer incidence was based on data from a population-based cancer registry. Statistical analyses were performed using multivariable Cox-regression models. In males, PCB 153 concentrations were positively associated with total cancer risk, with an adjusted hazard ratio (95% confidence interval) of 1.20 (1.01–1.41) for an increment of 100 ng/g lipid. Our preliminary findings suggest a potential relationship between the historical exposure to persistent organic pollutants and the risk of cancer in men. However, these results should be interpreted with caution and require verification during the future follow-up of this cohort., This study was supported in part by research grants from the Spanish Ministry of Health (FIS 02/974, EUS2008-03574), CIBER de Epidemiología; Junta de Andalucía (01/264, P09-CTS-5488 Project of Excellence, PI-0675-2010, and PI-0513-2012), and the Instituto de Salud Carlos III (FIS PI11/0610).
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- 2014
43. Evaluation of the utilization of external radiotherapy in the treatment of localized prostate cancer in Andalusia, Spain
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Francisco Peracaula, Maria J. Ortiz, José Antonio Sánchez, J. A. Medina, Amalia Palacios, Pilar Vargas, I. Linares, Isabel Castillo, Miguel Angel Martinez, Eloisa Bayo, José Expósito, Ismael Herruzo, Javier Jaén, [Expósito,J, Linares,I, Vargas,P, and Castillo,I] Radiotherapy and Oncology Department, Granada General Hospital, Granada, Spain. [Martínez,M] Radiotherapy and Oncology Department, Jaén General Hospital, Jaén, Spain. [Herruzo,I] Radiotherapy and Oncology Department, Carlos Haya University Hospital, Málaga, Spain. [Medina,JA] Radiotherapy and Oncology Department, Virgen de la Victoria University Hospital, Málaga, Spain. [Palacios,A] Radiotherapy and Oncology Department, Reína Sofía University Hospital, Córdoba, Spain. [Bayo,E] Radiotherapy and Oncology Department, Juan Ramón Jiménez Hospital, Huelva, Spain. [Peracaula,F] Radiotherapy and Oncology Department, Punta de Europa Algeciras Hospital, Algeciras, Cádiz, Spain.. [Jaén,J] Radiotherapy and Oncology Department, Puerta del Mar University Hospital, Cádiz, Spain. [Sánchez,JA] Radiotherapy and Oncology Department, Virgen Macarena University Hospital, Sevilla, Spain. [Ortiz,MJ] Radiotherapy and Oncology Department, Virgen del Rocío University Hospital, Sevilla, Spain.
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Oncology ,Male ,Neoplasias de la próstata ,medicine.medical_treatment ,España ,External Beam RT ,Health Care::Health Care Facilities, Manpower, and Services::Health Services::Patient Care::Hospitalization::Patient Discharge [Medical Subject Headings] ,Disease ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Prostate cancer ,Risk Factors ,Longitudinal Studies ,Practice Patterns, Physicians' ,Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings] ,Alta del paciente ,Anatomy::Urogenital System [Medical Subject Headings] ,Middle Aged ,Hospitals ,Radiology Nuclear Medicine and imaging ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings] ,Adult ,medicine.medical_specialty ,Check Tags::Male [Medical Subject Headings] ,Riesgo ,External radiotherapy ,Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings] ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,In patient ,Use ,Variability ,Aged ,Retrospective Studies ,Radiotherapy ,business.industry ,Research ,Sistema urogenital ,Prostatic Neoplasms ,Andalucía ,Retrospective cohort study ,medicine.disease ,Radiation therapy ,Spain ,Localized disease ,business - Abstract
Journal Article; BACKGROUND Around 27,000 new cases of prostate cancer are diagnosed every year in Spain and 5400 die from this disease. Radiotherapy (RT), alone or combined, has proven to be effective as initial treatment in patients with localized disease. Our objective was to evaluate the use of external beam RT (EBRT) in our region, comparing the indication rate and irradiation rate and examining variability in its application among hospitals. METHODS We conducted a review of RT guidelines and indication studies for prostate cancer (% expected irradiation). Data were gathered from all twelve public healthcare centers in Andalusia (Spain) on RT-treated prostate cancer patients during 2013 (% actual irradiation) and from nine of the centers on RT discharge reports. Information was classified according to type of hospital, tumor risk category and RT treatment (technique, dosage, volume, toxicity). RESULTS The estimated RT rate was 67 % (1289/1917), 43 % were aged > 70 years, 44.7 % had ECOG performance status of 0); 44.7 % had high-risk tumors; 57 % underwent RT associated with hormone therapy; 70 % of patients receiving RT were treated with 3D planning (30 % IGRT); and doses were 70-76 Gy in 70 % of cases and >76 Gy in 10.7 %. Acute gastrointestinal and genitourinary toxicities were
- Published
- 2015
44. Pattern of use of radiotherapy for lung cancer: a descriptive study
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Javier Jaén, I. Tovar, Miguel Martínez, Rosa Guerrero, Enrique Alonso, José Expósito, Rosario Del Moral, Juan P. Arrebola, [Tovar,I, Expósito,J, Martínez,M, Guerrero,R, Arrebola,JP, Moral,R Del] Radiation Oncology Department, Virgen de las Nieves Universitary Hospital, Granada, Spain. [Jaén,J] Institute of Oncology, Cartuja, Sevilla, Spain. [Alonso,E] Radiation Oncology Department, Puerta del Mar Universitary Hospital, Cádiz, Spain. [Arrebola,JP] CIBER en Epidemiología y Salud Pública (CIBERESP), Granada, Spain., and This work was supported by the Public Health System of Andalusia (Grant number 0266/2007).
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Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Pautas en la Práctica de los Médicos ,medicine.medical_treatment ,España ,Clinical practice patterns ,Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [Medical Subject Headings] ,Non-small cell lung cancer ,Radioterapia ,Surgical oncology ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Genetics ,medicine ,Humans ,Health Care::Health Services Administration::Patient Care Management::Physician's Practice Patterns [Medical Subject Headings] ,Stage (cooking) ,Lung cancer ,Neoplasm Staging ,Retrospective Studies ,Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings] ,Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung [Medical Subject Headings] ,Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Small Cell Lung Carcinoma [Medical Subject Headings] ,Radiotherapy ,Small cell lung cancer ,business.industry ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Radiotherapy [Medical Subject Headings] ,Cancer ,Retrospective cohort study ,Radiotherapy Dosage ,medicine.disease ,Andalucia ,Radiation therapy ,Regimen ,Treatment Outcome ,Spain ,Concomitant ,Neoplasias Pulmonares ,business ,Research Article - Abstract
Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND Lung cancer remains one of the most prevalent forms of cancer. Radiotherapy, with or without other therapeutic modalities, is an effective treatment. Our objective was to report on the use of radiotherapy for lung cancer, its variability in our region, and to compare our results with the previous study done in 2004 (VARA-I) in our region and with other published data. METHODS We reviewed the clinical records and radiotherapy treatment sheets of all patients undergoing radiotherapy for lung cancer during 2007 in the 12 public hospitals in Andalusia, an autonomous region of Spain. Data were gathered on hospital, patient type and histological type, radiotherapy treatment characteristics, and tumor stage. RESULTS 610 patients underwent initial radiotherapy. 37% of cases had stage III squamous cell lung cancer and were treated with radical therapy. 81% of patients with non-small and small cell lung cancer were treated with concomitant chemo-radiotherapy and the administered total dose was ≥60 Gy and ≥45 Gy respectively. The most common regimen for patients treated with palliative intent (44.6%) was 30 Gy. The total irradiation rate was 19.6% with significant differences among provinces (range, 8.5-25.6%; p
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- 2014
45. Use of palliative radiotherapy in brain and bone metastases (VARA II study)
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Enrique Alonso, I. Tovar, Javier Jaén, José Expósito, [Expósito,J, Tovar,I] Radiation Oncology Department, Virgen de las Nieves University Hospital, Granada, Spain. [Jaén,J] Institute of Oncology Cartuja, Sevilla, Spain. [Alonso,E] Radiation Oncology Department, Puerta del Mar University Hospital, Cádiz, Spain., and The VARA II project was funded by Health Andalusia Authority grant PI-0266/2007 (BOJA n 14, 21 January 2008) .
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Male ,Oncology ,Palliative care ,medicine.medical_treatment ,VARA II ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Prostate ,Neoplasms ,Palliative radiation therapy ,Longitudinal Studies ,Young adult ,Aged, 80 and over ,Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings] ,Brain Neoplasms ,Palliative Care ,Radiotherapy Dosage ,Middle Aged ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Humanos ,medicine.anatomical_structure ,Radiology Nuclear Medicine and imaging ,Female ,Adult ,lcsh:Medical physics. Medical radiology. Nuclear medicine ,medicine.medical_specialty ,lcsh:R895-920 ,Diseases::Neoplasms::Neoplasms by Site::Nervous System Neoplasms::Central Nervous System Neoplasms::Brain Neoplasms [Medical Subject Headings] ,Bone Neoplasms ,Neoplasias Encefálicas ,lcsh:RC254-282 ,Young Adult ,Dosificación Radioterapéutica ,Internal medicine ,Diseases::Neoplasms::Neoplastic Processes::Neoplasm Metastasis [Medical Subject Headings] ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Variability ,Neoplasias Óseas ,Aged ,Neoplasm Staging ,Retrospective Studies ,Lung ,Performance status ,business.industry ,Radiotherapy Planning, Computer-Assisted ,Research ,Bone metastases ,Cancer ,Andalucía ,Retrospective cohort study ,Brain metastases ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Radiotherapy::Radiotherapy Dosage [Medical Subject Headings] ,medicine.disease ,Health Care::Health Care Facilities, Manpower, and Services::Health Services::Patient Care::Palliative Care [Medical Subject Headings] ,Radiation therapy ,Diseases::Neoplasms::Neoplasms by Site::Bone Neoplasms [Medical Subject Headings] ,Atención paliativa ,business - Abstract
Introduction Metastases are detected in 20% of patients with solid tumours at diagnosis and a further 30% after diagnosis. Radiation therapy (RT) has proven effective in bone (BM) and brain (BrM) metastases. The objective of this study was to analyze the variability of RT utilization rates in clinical practice and the accessibility to medical technology in our region. Patients and methods We reviewed the clinical records and RT treatment sheets of all patients undergoing RT for BM and/or BrM during 2007 in the 12 public hospitals in an autonomous region of Spain. Data were gathered on hospital type, patient type and RT treatment characteristics. Calculation of the rate of RT use was based on the cancer incidence and the number of RT treatments for BM, BrM and all cancer sites. Results Out of the 9319 patients undergoing RT during 2007 for cancer at any site, 1242 (13.3%; inter-hospital range, 26.3%) received RT for BM (n = 744) or BrM (n = 498). These 1242 patients represented 79% of all RT treatments with palliative intent, and the most frequent primary tumours were in lung, breast, prostate or digestive system. No significant difference between BM and BrM groups were observed in: mean age (62 vs. 59 yrs, respectively); gender (approximately 64% male and 36% female in both); performance status (ECOG 0–1 in 70 vs. 71%); or mean distance from hospital (36 vs. 28.6 km) or time from consultation to RT treatment (13 vs. 14.3 days). RT regimens differed among hospitals and between patient groups: 10 × 300 cGy, 5 × 400 cGy and 1x800cGy were applied in 32, 27 and 25%, respectively, of BM patients, whereas 10 × 300cGy was used in 49% of BrM patients. Conclusions Palliative RT use in BM and BrM is high and close to the expected rate, unlike the global rate of RT application for all cancers in our setting. Differences in RT schedules among hospitals may reflect variability in clinical practice among the medical teams.
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- 2012
46. Functional and Physiological Characterization of Tyrosine Decarboxylases from Olea europaea L. Involved in the Synthesis of the Main Phenolics in Olive Fruit and Virgin Olive Oil.
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Luaces P, Sánchez R, Expósito J, Pérez-Pulido AJ, Pérez AG, and Sanz C
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- Gene Expression Regulation, Plant, Plant Proteins genetics, Plant Proteins metabolism, Phenylethyl Alcohol metabolism, Phenylethyl Alcohol analogs & derivatives, Olea genetics, Olea enzymology, Olea metabolism, Olive Oil metabolism, Olive Oil chemistry, Fruit metabolism, Fruit genetics, Phenols metabolism, Tyrosine Decarboxylase metabolism, Tyrosine Decarboxylase genetics
- Abstract
The phenolic composition of virgin olive oil (VOO) primarily depends on the phenolic content of the olive fruit. The purpose of this work was to characterize the first metabolic step in the synthesis of tyrosol (Ty) and hydroxytyrosol (HTy), whose derivatives are by far the predominant phenolics in both olive fruit and VOO. To this end, two genes encoding tyrosine/DOPA decarboxylase enzymes, OeTDC1 and OeTDC2 , have been identified and functionally and physiologically characterized. Both olive TDC proteins exclusively accept aromatic amino acids with phenolic side chains, such as tyrosine and 3,4-dihydroxyphenylalanine (DOPA), as substrates to produce tyramine and dopamine, respectively. These proteins exhibited a higher affinity for DOPA than for tyrosine, and the catalytic efficiency of both proteins was greater when DOPA was used as a substrate. Both olive TDC genes showed a fairly similar expression profile during olive fruit ontogeny, with OeTDC1 consistently expressed at higher levels than OeTDC2 . Expression was particularly intense during the first few weeks after fruit set, coinciding with the active accumulation of Ty and HTy derivatives. The data suggest that both olive TDCs are responsible for the initial step in the synthesis of the most important phenolics, both quantitatively and functionally, in VOO.
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- 2024
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47. Correction: Torné-Ruiz et al. Evolution of Scientific Production on Phlebitis Secondary to Vascular Access: A 71-Year Bibliometric Analysis. Nurs. Rep. 2023, 13 , 1635-1647.
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Torné-Ruiz A, García-Expósito J, Bonet A, Masot O, Roca J, and Selva-Pareja L
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Error in Figure [...].
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- 2024
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48. Management from a multidisciplinary perspective of phlebitis related to peripheral venous catheter insertion: An international Delphi study.
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Torné-Ruiz A, Sanromà-Ortiz M, Corral-Nuñez A, Medel D, Roca J, and García-Expósito J
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- Humans, Surveys and Questionnaires, Consensus, Female, Male, Adult, Middle Aged, Internationality, Delphi Technique, Phlebitis etiology, Catheterization, Peripheral adverse effects
- Abstract
Aim: To determine the consensus and importance of care practices related to the management of peripheral venous catheter (PVC)-related phlebitis in hospitalized patients through the views of experts from different disciplines., Background: PVCs are commonly used in hospitals but are associated with complications such as phlebitis. Their management differs widely, and studies are heterogeneous., Design: Delphi method., Methods: Four stages: problem area (with Web of Science bibliometric review in July 2022), panel members, two Delphi rounds and closing criteria. In the Delphi survey, experts answered an online questionnaire based on assessment, treatment and follow-up dimensions (September 2022-February 2023). Statistical analyses were conducted of frequencies, percentages, measures of central tendency and levels of dispersion (QD). A space for comments was created, and a thematic analysis conducted of them., Results: Eighteen experts (nurses, doctors and pharmacists) participated in the Delphi rounds. Forty-five activities were identified: 19 in assessment, 15 in treatment and 11 in follow-up. A high consensus level (QD ≤ 0.6) was found in five activities (11.12%), moderate level (0.6 < QD < 1.0) in 19 (42.22%) and low level (QD > 1.0) in 21 (46.66%). Seven themes were determined (patient perspective, lack of consensus, low evidence-based practices, stage-based treatments, prevention activities, high variability in practice and specialist teams and interdisciplinary work)., Conclusion: The importance of systematic assessment scales is highlighted together with consensus on signs and symptoms (pain, redness, inflammation, palpable cord and induration). Treatment according to severity and daily visual recording and monitoring are emphasized along with the need for patient participation and healthcare literacy. A high level of consensus was obtained in 11% of the activities, showing the large variability of criteria and interventions for phlebitis management. Highlighted needs include working in a team, the use of specialist teams and promoting evidence- and prevention-based activities., Relevance to Clinical Practice: Clinical variability is noted and, therefore, the importance of consensus on standardized care for PVC phlebitis and evidence-based practice., Reporting Method: Delphi studies (CREDES)., Patient or Public Contribution: Experts contribution., (© 2024 The Author(s). Nursing Open published by John Wiley & Sons Ltd.)
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- 2024
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49. Assessment, Treatment, and Follow-Up of Phlebitis Related to Peripheral Venous Catheterisation: A Delphi Study in Spain.
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Torné-Ruiz A, Reguant M, Sanromà-Ortiz M, Piriz M, Roca J, and García-Expósito J
- Abstract
Background: Phlebitis related to peripheral venous catheters (PVCs) is a common complication in patients who require these devices and can have important consequences for the patients and the healthcare system. The management and control of the PVC-associated complications is related to nursing competency. The present study aims to determine, at the national level in Spain, the consensus on the assessment, treatment, and follow-up of PVC-related phlebitis and the importance of the actions taken., Method: A three-round Delphi technique was used with clinical care nurses who are experts in the field of in-hospital intravenous treatment in Spain. For this, an online questionnaire was developed with three open-ended questions on the dimensions of phlebitis assessment, treatment, and follow-up. For the statistical analysis of the results, frequencies and percentages were used to determine consensus, and the measures of central tendency (mean, standard deviation, and the coefficient of variation) were used to rank importance. The coefficient of variation was set as acceptable at ≤30%., Results: The final sample was 27 expert nurses. At the conclusion of round 3, actions were ranked according to their importance, with six items included in the PVC-related phlebitis assessment (symptomatology/observation, redness, the Maddox scale, induration, temperature, and pain), two in treatment (catheter removal, pentosan polysulphate sodium ointment + application of cold), and just one in follow-up (general monitoring + temperature control)., Conclusions: There is a major disparity in relation to the PVC-related phlebitis assessment, treatment, and follow-up actions. More clinical studies are therefore needed to minimise the complications associated with the use of PVCs, given their impact on the quality of care and patient safety and their economic cost.
- Published
- 2024
- Full Text
- View/download PDF
50. Matrix Metalloproteinases and Their Inhibitors as Potential Prognostic Biomarkers in Head and Neck Cancer after Radiotherapy.
- Author
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Fornieles G, Núñez MI, and Expósito J
- Subjects
- Humans, Squamous Cell Carcinoma of Head and Neck, Prognosis, Matrix Metalloproteinases, Tumor Microenvironment, Radiation Oncology, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms radiotherapy
- Abstract
Head and neck cancer (HNC) is among the ten most frequent tumours, with 5-year survival rates varying from 30% to 70% depending on the stage and location of the tumour. HNC is traditionally known as head and neck squamous cell carcinoma (HNSCC), since 90% arises from epithelial cells. Metastasis remains a major cause of mortality in patients with HNSCC. HNSCC patients with metastatic disease have an extremely poor prognosis with a survival rate of less than a year. Matrix metalloproteinases (MMPs) have been described as biomarkers that promote cell migration and invasion. Radiotherapy is widely used to treat HNSCC, being a determining factor in the alteration of the tumour's biology and microenvironment. This review focuses on analysing the current state of the scientific literature on this topic. Although few studies have focused on the role of these proteinases in HNC, some authors have concluded that radiotherapy alters the behaviour of MMPs and tissue inhibitors of metalloproteinases (TIMPs). Therefore, more research is needed to understand the roles played by MMPs and their inhibitors (TIMPs) as prognostic biomarkers in patients with HNC and their involvement in the response to radiotherapy.
- Published
- 2023
- Full Text
- View/download PDF
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