Les Caves du Vatican, ou la sotie de l’acte gratuit

Durante su estancia en África del Norte, André Gide cae gravemente enfermo. Una vez curado, es consciente de que la experiencia existencial que acaba de vivir lo ha liberado de todo determinismo. Probablemente debamos el origen de las soties a este aprendizaje. El término sotie es una adaptación gidiana del término sottie, que designa un género dramático medieval, interpretado por actores con trajes de bufón, que criticaban los vicios de su sociedad. Así pues, las soties son obras tanto clásicas como modernas, pues recuperan un género antiguo y se abren a técnicas nuevas. No obstante, lo que hace de Les Caves du Vatican una obra esencialmente moderna, es el replanteamiento de la razón que opera Gide en ella. Examinando la presencia en la obra de ideas de su época así como de la filosofía anterior, es como mejor podremos ilustrarlo.During his time in North Africa, André Gide fell gravely ill. It was this very illness, this existential experience that would liberate him from determinism. We probably owe the origin of the soties to this experience. The term sotie is a gidean adaptation of the term sottie, which in the Middle Ages denoted a dramatical genre where the actors dressed as jesters criticised the vices of their society. In this sense, the soties are classic and modern works at the same time, because they bring back an old genre but are open to new techniques. Nevertheless, what makes Les Caves du Vatican an essentially modern work is in the new approach that Gide makes to logical reason, which is best illustrated when investigating the work of ideas and previous philosophies

Una herencia olvidada: El convento de Nuestra Señora de los Ángeles de Híjar (Teruel).

Todos los autores coinciden en afirmar que la población turolense de Híjar es antiquísima. Además, de ella tomó su nombre uno de los Señoríos, luego Ducado, más importantes de España. Estos señores se convirtieron en grandes patronos y mecenas de las artes impulsando obras como el convento de Nuestra Señora de los Ángeles, situado en la localidad, objeto del presente trabajo. Este cenobio fue fundado por Luis II Fernández de Híjar y Arellano, IX Señor de Híjar y II Conde de Belchite y, aunque sus primeros moradores fueron los frailes franciscanos –que darían impulso a tradiciones que han llegado a nuestros días como la Semana Santa–, tras la desamortización sus muros albergaron comunidades pertenecientes a otras órdenes mendicantes. Sin embargo, la guerra civil y luego las inclemencias del tiempo han convertido este edificio en una ruina que debería ser rescatada.<br /

Novel and conventional embryo parameters as input data for artificial neural networks: an artificial intelligence model applied for prediction of the implantation potential

[ES] Objetivo: Describir nuevas características de embriones capaces de predecir el potencial de implantación como datos de entrada para un modelo de red neuronal artificial (ANN). Diseño: Estudio de cohorte retrospectivo. Entorno: Centro de FIV privado afiliado a la universidad. Paciente (s): Este estudio incluyó a 637 pacientes del programa de donación de ovocitos que se sometieron a transferencia de un solo blastocisto durante dos años consecutivos. Intervención (es): Ninguna. Principales medidas de resultado: La investigación se dividió en dos fases. La fase 1 consistió en la descripción y análisis de las siguientes características embrionarias en embriones implantados y no implantados: distancia y velocidad de migración pronuclear, diámetro del blastocisto expandido, área de masa celular interna y duración del ciclo celular del trofoectodermo. La fase 2 consistió en el desarrollo de un algoritmo ANN para la predicción de la implantación. Se obtuvieron resultados para cuatro modelos alimentados con diferentes datos de entrada. El poder predictivo se midió con el uso del área bajo la curva característica operativa del receptor (AUC). Resultado (s): De los cinco nuevos parámetros descritos, el diámetro expandido del blastocisto y la duración del ciclo celular del trofoectodermo tenían valores estadísticamente diferentes en los embriones implantados y no implantados. Después de que los modelos ANN fueron entrenados y validados mediante validación cruzada cinco veces, estos fueron capaces de predecir la implantación en los datos de prueba con AUC de 0,64 para ANN1 (morfocinética convencional), 0,73 para ANN2 (morfodinámica novedosa), 0,77 para ANN3 (morfocinética convencional þ morfodinámica novedosa) y 0,68 para ANN4 (variables discriminatorias de prueba estadística). Conclusión (es): Las nuevas características embrionarias propuestas afectan al potencial de implantación y su combinación con parámetros morfocinéticos convencionales es eficaz como datos de entrada para un modelo predictivo basado en inteligencia artificial.[EN] Objective: To describe novel embryo features capable of predicting implantation potential as input data for an artificial neural network (ANN) model. Design: Retrospective cohort study. Setting: University-affiliated private IVF center. Patient(s): This study included 637 patients from the oocyte donation program who underwent single-blastocyst transfer during two consecutive years. Intervention(s): None. Main Outcome Measure(s): The research was divided into two phases. Phase 1 consisted of the description and analysis of the following embryo features in implanted and nonimplanted embryos: distance and speed of pronuclear migration, blastocyst expanded diameter, inner cell mass area, and trophectoderm cell cycle length. Phase 2 consisted of the development of an ANN algorithm for implantation prediction. Results were obtained for four models fed with different input data. The predictive power was measured with the use of the area under the receiver operating characteristic curve (AUC). Result(s): Out of the five novel described parameters, blastocyst expanded diameter and trophectoderm cell cycle length had statistically different values in implanted and nonimplanted embryos. After the ANN models were trained and validated using fivefold cross validation, they were capable of predicting implantation on testing data with AUCs of 0.64 for ANN1 (conventional morphokinetics), 0.73 for ANN2 (novel morphodynamics), 0.77 for ANN3 (conventional morphokinetics thorn novel morphodynamics), and 0.68 for ANN4 (discriminatory variables from statistical test). Conclusion(s): The novel proposed embryo features affect the implantation potential, and their combination with conventional morphokinetic parameters is effective as input data for a predictive model based on artificial intelligence. ((c) 2020 by American Society for Reproductive Medicine.)Supported by the Ministry of Science, Innovation, and Universities CDTI (IDI-20191102), an Industrial Ph.D. grant (DIN2018-009911), and Agencia Valenciana de Innovacio (INNCAD00-18-009) to E.P. and M.M.Bori, L.; Paya-Bosch, E.; Alegre, L.; Viloria, T.; Remohí, J.; Naranjo Ornedo, V.; Meseguer, M. (2020). Novel and conventional embryo parameters as input data for artificial neural networks: an artificial intelligence model applied for prediction of the implantation potential. Fertility and Sterility. 114(6):1232-1241. https://doi.org/10.1016/j.fertnstert.2020.08.023S123212411146De Geyter, C., Calhaz-Jorge, C., Kupka, M. S., Wyns, C., Mocanu, E., Motrenko, T., … Goossens, V. (2018). ART in Europe, 2014: results generated from European registries by ESHRE†. Human Reproduction, 33(9), 1586-1601. doi:10.1093/humrep/dey242Edwards, R. G., Fishel, S. B., Cohen, J., Fehilly, C. B., Purdy, J. M., Slater, J. M., … Webster, J. M. (1984). Factors influencing the success of in vitro fertilization for alleviating human infertility. Journal of In Vitro Fertilization and Embryo Transfer, 1(1), 3-23. doi:10.1007/bf01129615Ferraretti, A. P., Goossens, V., de Mouzon, J., Bhattacharya, S., Castilla, J. A., … Korsak, V. (2012). Assisted reproductive technology in Europe, 2008: results generated from European registers by ESHRE†. Human Reproduction, 27(9), 2571-2584. doi:10.1093/humrep/des255Zhang, J. Q., Li, X. L., Peng, Y., Guo, X., Heng, B. C., & Tong, G. Q. (2010). Reduction in exposure of human embryos outside the incubator enhances embryo quality and blastulation rate. Reproductive BioMedicine Online, 20(4), 510-515. doi:10.1016/j.rbmo.2009.12.027Cruz, M., Garrido, N., Herrero, J., Pérez-Cano, I., Muñoz, M., & Meseguer, M. (2012). Timing of cell division in human cleavage-stage embryos is linked with blastocyst formation and quality. Reproductive BioMedicine Online, 25(4), 371-381. doi:10.1016/j.rbmo.2012.06.017Kirkegaard, K., Agerholm, I. E., & Ingerslev, H. J. (2012). Time-lapse monitoring as a tool for clinical embryo assessment. Human Reproduction, 27(5), 1277-1285. doi:10.1093/humrep/des079Montag, M., Liebenthron, J., & Köster, M. (2011). Which morphological scoring system is relevant in human embryo development? Placenta, 32, S252-S256. doi:10.1016/j.placenta.2011.07.009Aparicio, B., Cruz, M., & Meseguer, M. (2013). Is morphokinetic analysis the answer? Reproductive BioMedicine Online, 27(6), 654-663. doi:10.1016/j.rbmo.2013.07.017Gallego, R. D., Remohí, J., & Meseguer, M. (2019). Time-lapse imaging: the state of the art†. Biology of Reproduction, 101(6), 1146-1154. doi:10.1093/biolre/ioz035Zaninovic, N., Irani, M., & Meseguer, M. (2017). Assessment of embryo morphology and developmental dynamics by time-lapse microscopy: is there a relation to implantation and ploidy? Fertility and Sterility, 108(5), 722-729. doi:10.1016/j.fertnstert.2017.10.002Athayde Wirka, K., Chen, A. A., Conaghan, J., Ivani, K., Gvakharia, M., Behr, B., … Shen, S. (2014). Atypical embryo phenotypes identified by time-lapse microscopy: high prevalence and association with embryo development. Fertility and Sterility, 101(6), 1637-1648.e5. doi:10.1016/j.fertnstert.2014.02.050Zhan, Q., Ye, Z., Clarke, R., Rosenwaks, Z., & Zaninovic, N. (2016). Direct Unequal Cleavages: Embryo Developmental Competence, Genetic Constitution and Clinical Outcome. PLOS ONE, 11(12), e0166398. doi:10.1371/journal.pone.0166398Goodman, L. R., Goldberg, J., Falcone, T., Austin, C., & Desai, N. (2016). Does the addition of time-lapse morphokinetics in the selection of embryos for transfer improve pregnancy rates? A randomized controlled trial. Fertility and Sterility, 105(2), 275-285.e10. doi:10.1016/j.fertnstert.2015.10.013Desai, N., Ploskonka, S., Goodman, L., Attaran, M., Goldberg, J. M., Austin, C., & Falcone, T. (2016). Delayed blastulation, multinucleation, and expansion grade are independently associated with live-birth rates in frozen blastocyst transfer cycles. Fertility and Sterility, 106(6), 1370-1378. doi:10.1016/j.fertnstert.2016.07.1095Aguilar, J., Rubio, I., Muñoz, E., Pellicer, A., & Meseguer, M. (2016). Study of nucleation status in the second cell cycle of human embryo and its impact on implantation rate. Fertility and Sterility, 106(2), 291-299.e2. doi:10.1016/j.fertnstert.2016.03.036Rubio, I., Kuhlmann, R., Agerholm, I., Kirk, J., Herrero, J., Escribá, M.-J., … Meseguer, M. (2012). Limited implantation success of direct-cleaved human zygotes: a time-lapse study. Fertility and Sterility, 98(6), 1458-1463. doi:10.1016/j.fertnstert.2012.07.1135Desai, N., Ploskonka, S., Goodman, L. R., Austin, C., Goldberg, J., & Falcone, T. (2014). Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles. Reproductive Biology and Endocrinology, 12(1), 54. doi:10.1186/1477-7827-12-54Ebner, T., Höggerl, A., Oppelt, P., Radler, E., Enzelsberger, S.-H., Mayer, R. B., … Shebl, O. (2017). Time-lapse imaging provides further evidence that planar arrangement of blastomeres is highly abnormal. Archives of Gynecology and Obstetrics, 296(6), 1199-1205. doi:10.1007/s00404-017-4531-5Azzarello, A., Hoest, T., Hay-Schmidt, A., & Mikkelsen, A. L. (2017). Live birth potential of good morphology and vitrified blastocysts presenting abnormal cell divisions. Reproductive Biology, 17(2), 144-150. doi:10.1016/j.repbio.2017.03.004Desch, L., Bruno, C., Luu, M., Barberet, J., Choux, C., Lamotte, M., … Fauque, P. (2017). Embryo multinucleation at the two-cell stage is an independent predictor of intracytoplasmic sperm injection outcomes. Fertility and Sterility, 107(1), 97-103.e4. doi:10.1016/j.fertnstert.2016.09.022Kirkegaard, K., Hindkjaer, J. J., Grøndahl, M. L., Kesmodel, U. S., & Ingerslev, H. J. (2012). A randomized clinical trial comparing embryo culture in a conventional incubator with a time-lapse incubator. Journal of Assisted Reproduction and Genetics, 29(6), 565-572. doi:10.1007/s10815-012-9750-xWong, C. C., Loewke, K. E., Bossert, N. L., Behr, B., De Jonge, C. J., Baer, T. M., & Pera, R. A. R. (2010). Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage. Nature Biotechnology, 28(10), 1115-1121. doi:10.1038/nbt.1686Conaghan, J., Chen, A. A., Willman, S. P., Ivani, K., Chenette, P. E., Boostanfar, R., … Shen, S. (2013). Improving embryo selection using a computer-automated time-lapse image analysis test plus day 3 morphology: results from a prospective multicenter trial. Fertility and Sterility, 100(2), 412-419.e5. doi:10.1016/j.fertnstert.2013.04.021Milewski, R., Kuć, P., Kuczyńska, A., Stankiewicz, B., Łukaszuk, K., & Kuczyński, W. (2015). A predictive model for blastocyst formation based on morphokinetic parameters in time-lapse monitoring of embryo development. Journal of Assisted Reproduction and Genetics, 32(4), 571-579. doi:10.1007/s10815-015-0440-3Chamayou, S., Patrizio, P., Storaci, G., Tomaselli, V., Alecci, C., Ragolia, C., … Guglielmino, A. (2013). The use of morphokinetic parameters to select all embryos with full capacity to implant. Journal of Assisted Reproduction and Genetics, 30(5), 703-710. doi:10.1007/s10815-013-9992-2Milewski, R., Czerniecki, J., Kuczyńska, A., Stankiewicz, B., & Kuczyński, W. (2016). Morphokinetic parameters as a source of information concerning embryo developmental and implantation potential. Ginekologia Polska, 87(10), 677-684. doi:10.5603/gp.2016.0067Motato, Y., de los Santos, M. J., Escriba, M. J., Ruiz, B. A., Remohí, J., & Meseguer, M. (2016). Morphokinetic analysis and embryonic prediction for blastocyst formation through an integrated time-lapse system. Fertility and Sterility, 105(2), 376-384.e9. doi:10.1016/j.fertnstert.2015.11.001Petersen, B. M., Boel, M., Montag, M., & Gardner, D. K. (2016). Development of a generally applicable morphokinetic algorithm capable of predicting the implantation potential of embryos transferred on Day 3. Human Reproduction, 31(10), 2231-2244. doi:10.1093/humrep/dew188Meseguer, M., Herrero, J., Tejera, A., Hilligsoe, K. M., Ramsing, N. B., & Remohi, J. (2011). The use of morphokinetics as a predictor of embryo implantation. Human Reproduction, 26(10), 2658-2671. doi:10.1093/humrep/der256Liu, Y., Chapple, V., Feenan, K., Roberts, P., & Matson, P. (2016). Time-lapse deselection model for human day 3 in vitro fertilization embryos: the combination of qualitative and quantitative measures of embryo growth. Fertility and Sterility, 105(3), 656-662.e1. doi:10.1016/j.fertnstert.2015.11.003VerMilyea, M. D., Tan, L., Anthony, J. T., Conaghan, J., Ivani, K., Gvakharia, M., … Shen, S. (2014). Computer-automated time-lapse analysis results correlate with embryo implantation and clinical pregnancy: A blinded, multi-centre study. Reproductive BioMedicine Online, 29(6), 729-736. doi:10.1016/j.rbmo.2014.09.005Basile, N., Vime, P., Florensa, M., Aparicio Ruiz, B., García Velasco, J. A., Remohí, J., & Meseguer, M. (2014). The use of morphokinetics as a predictor of  implantation: a multicentric study to define and validate an algorithm for embryo selection. Human Reproduction, 30(2), 276-283. doi:10.1093/humrep/deu331Aparicio-Ruiz, B., Romany, L., & Meseguer, M. (2018). Selection of preimplantation embryos using time-lapse microscopy in in vitro fertilization: State of the technology and future directions. Birth Defects Research, 110(8), 648-653. doi:10.1002/bdr2.1226Barrie, A., Homburg, R., McDowell, G., Brown, J., Kingsland, C., & Troup, S. (2017). Preliminary investigation of the prevalence and implantation potential of abnormal embryonic phenotypes assessed using time-lapse imaging. Reproductive BioMedicine Online, 34(5), 455-462. doi:10.1016/j.rbmo.2017.02.011Campbell, A., Fishel, S., Bowman, N., Duffy, S., Sedler, M., & Hickman, C. F. L. (2013). Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics. Reproductive BioMedicine Online, 26(5), 477-485. doi:10.1016/j.rbmo.2013.02.006Desai, N., Goldberg, J. M., Austin, C., & Falcone, T. (2018). Are cleavage anomalies, multinucleation, or specific cell cycle kinetics observed with time-lapse imaging predictive of embryo developmental capacity or ploidy? Fertility and Sterility, 109(4), 665-674. doi:10.1016/j.fertnstert.2017.12.025Amir, H., Barbash-Hazan, S., Kalma, Y., Frumkin, T., Malcov, M., Samara, N., … Ben-Yosef, D. (2018). Time-lapse imaging reveals delayed development of embryos carrying unbalanced chromosomal translocations. Journal of Assisted Reproduction and Genetics, 36(2), 315-324. doi:10.1007/s10815-018-1361-8Del Carmen Nogales, M., Bronet, F., Basile, N., Martínez, E. M., Liñán, A., Rodrigo, L., & Meseguer, M. (2017). Type of chromosome abnormality affects embryo morphology dynamics. Fertility and Sterility, 107(1), 229-235.e2. doi:10.1016/j.fertnstert.2016.09.019Dyer, S., Chambers, G. M., de Mouzon, J., Nygren, K. G., Zegers-Hochschild, F., Mansour, R., … Adamson, G. D. (2016). International Committee for Monitoring Assisted Reproductive Technologies world report: Assisted Reproductive Technology 2008, 2009 and 2010. Human Reproduction, 31(7), 1588-1609. doi:10.1093/humrep/dew082Simopoulou, M., Sfakianoudis, K., Maziotis, E., Antoniou, N., Rapani, A., Anifandis, G., … Koutsilieris, M. (2018). Are computational applications the «crystal ball» in the IVF laboratory? The evolution from mathematics to artificial intelligence. Journal of Assisted Reproduction and Genetics, 35(9), 1545-1557. doi:10.1007/s10815-018-1266-6Milewski, R., Kuczyńska, A., Stankiewicz, B., & Kuczyński, W. (2017). How much information about embryo implantation potential is included in morphokinetic data? A prediction model based on artificial neural networks and principal component analysis. Advances in Medical Sciences, 62(1), 202-206. doi:10.1016/j.advms.2017.02.001Curchoe, C. L., & Bormann, C. L. (2019). Artificial intelligence and machine learning for human reproduction and embryology presented at ASRM and ESHRE 2018. Journal of Assisted Reproduction and Genetics, 36(4), 591-600. doi:10.1007/s10815-019-01408-xTran, D., Cooke, S., Illingworth, P. J., & Gardner, D. K. (2019). Deep learning as a predictive tool for fetal heart pregnancy following time-lapse incubation and blastocyst transfer. Human Reproduction, 34(6), 1011-1018. doi:10.1093/humrep/dez064Khosravi, P., Kazemi, E., Zhan, Q., Malmsten, J. E., Toschi, M., Zisimopoulos, P., … Hajirasouliha, I. (2019). Deep learning enables robust assessment and selection of human blastocysts after in vitro fertilization. npj Digital Medicine, 2(1). doi:10.1038/s41746-019-0096-yCerrillo, M., Herrero, L., Guillén, A., Mayoral, M., & García-Velasco, J. A. (2017). Impact of Endometrial Preparation Protocols for Frozen Embryo Transfer on Live Birth Rates. Rambam Maimonides Medical Journal, 8(2), e0020. doi:10.5041/rmmj.10297Panchal, G., Ganatra, A., Kosta, Y. P., & Panchal, D. (2011). Behaviour Analysis of Multilayer Perceptronswith Multiple Hidden Neurons and Hidden Layers. International Journal of Computer Theory and Engineering, 332-337. doi:10.7763/ijcte.2011.v3.328Azzarello, A., Hoest, T., & Mikkelsen, A. L. (2012). The impact of pronuclei morphology and dynamicity on live birth outcome after time-lapse culture. Human Reproduction, 27(9), 2649-2657. doi:10.1093/humrep/des210Dal Canto, M., Coticchio, G., Mignini Renzini, M., De Ponti, E., Novara, P. V., Brambillasca, F., … Fadini, R. (2012). Cleavage kinetics analysis of human embryos predicts development to blastocyst and implantation. Reproductive BioMedicine Online, 25(5), 474-480. doi:10.1016/j.rbmo.2012.07.016Barrie, A., Homburg, R., McDowell, G., Brown, J., Kingsland, C., & Troup, S. (2017). Examining the efficacy of six published time-lapse imaging embryo selection algorithms to predict implantation to demonstrate the need for the development of specific, in-house morphokinetic selection algorithms. Fertility and Sterility, 107(3), 613-621. doi:10.1016/j.fertnstert.2016.11.014Coticchio, G., Mignini Renzini, M., Novara, P. V., Lain, M., De Ponti, E., Turchi, D., … Dal Canto, M. (2017). Focused time-lapse analysis reveals novel aspects of human fertilization and suggests new parameters of embryo viability. Human Reproduction, 33(1), 23-31. doi:10.1093/humrep/dex344Aguilar, J., Motato, Y., Escribá, M. J., Ojeda, M., Muñoz, E., & Meseguer, M. (2014). The human first cell cycle: impact on implantation. Reproductive BioMedicine Online, 28(4), 475-484. doi:10.1016/j.rbmo.2013.11.014Barberet, J., Bruno, C., Valot, E., Antunes-Nunes, C., Jonval, L., Chammas, J., … Fauque, P. (2019). Can novel early non-invasive biomarkers of embryo quality be identified with time-lapse imaging to predict live birth? Human Reproduction, 34(8), 1439-1449. doi:10.1093/humrep/dez085Richter, K. S., Harris, D. C., Daneshmand, S. T., & Shapiro, B. S. (2001). Quantitative grading of a human blastocyst: optimal inner cell mass size and shape. Fertility and Sterility, 76(6), 1157-1167. doi:10.1016/s0015-0282(01)02870-9Shapiro, B. S., Daneshmand, S. T., Garner, F. C., Aguirre, M., & Thomas, S. (2008). Large blastocyst diameter, early blastulation, and low preovulatory serum progesterone are dominant predictors of clinical pregnancy in fresh autologous cycles. Fertility and Sterility, 90(2), 302-309. doi:10.1016/j.fertnstert.2007.06.062Almagor, M., Harir, Y., Fieldust, S., Or, Y., & Shoham, Z. (2016). Ratio between inner cell mass diameter and blastocyst diameter is correlated with successful pregnancy outcomes of single blastocyst transfers. Fertility and Sterility, 106(6), 1386-1391. doi:10.1016/j.fertnstert.2016.08.009Shapiro, B. S., Harris, D. C., & Richter, K. S. (2000). Predictive value of 72-hour blastomere cell number on blastocyst development and success of subsequent transfer based on the degree of blastocyst development. Fertility and Sterility, 73(3), 582-586. doi:10.1016/s0015-0282(99)00586-5Coello, A., Meseguer, M., Galán, A., Alegre, L., Remohí, J., & Cobo, A. (2017). Analysis of the morphological dynamics of blastocysts after vitrification/warming: defining new predictive variables of implantation. Fertility and Sterility, 108(4), 659-666.e4. doi:10.1016/j.fertnstert.2017.07.1157Huang, T. T., Huang, D. H., Ahn, H. J., Arnett, C., & Huang, C. T. (2019). Early blastocyst expansion in euploid and aneuploid human embryos: evidence for a non-invasive and quantitative marker for embryo selection. Reproductive BioMedicine Online, 39(1), 27-39. doi:10.1016/j.rbmo.2019.01.010Sundvall, L., Ingerslev, H. J., Breth Knudsen, U., & Kirkegaard, K. (2013). Inter- and intra-observer variability of time-lapse annotations. Human Reproduction, 28(12), 3215-3221. doi:10.1093/humrep/det36

Fish granzymes and their role in the innate cell-mediated cytotoxicity against nodavirus-infected cells

Granzymes (Gzm) are granule-associated serine proteases, which are important effector molecules in cell-mediated cytotoxicity, classified by its proteolytic activity in: tryptase (GzmA and GzmK), Asp-ase (GzmB), Met-ase (GzmM) or chymase (others). In fish, even at gene level, very few studies have partially identified and characterize them. In this work we have identified the activity of these four granzymes, using colorimetric assays, in leucocytes from gilthead seabream (Sparus aurata) and European sea bass (Dicentrarchus labrax), and how they are increased upon cytotoxic activity against nodavirus-infected tumor cells. The results also showed that GzmA was the most abundant and GzmB the lowest. Deeper characterization of the GzmB led us to identify that seabream leucocytes under cytotoxic response against nodavirus-infected cells showed significantly increased GzmB activity whilst this pattern failed to do so in sea bass leucocytes. Moreover, flow cytometry studies also suggested the presence of GzmB into the cytoplasm of effector cells. At gene level, seabream GzmB gene was found to be up-regulated in leucocytes under cytotoxic activity, mainly if the target cells were infected with nodavirus. These data will through some light in the importance of granzymes in the cytotoxic response of fish and their defense against nodavirus infection

Retrospective study about the incidence and treatment of epistaxis in a health area in the period 2011 to 2017

Introduction and objective: Epistaxis is a frequent clinical sign and it is a usual reason for urgent consultation. We have limited data about its epidemiology and its treatment in our Region. The objectives of the study consist on: to know its incidence in our area and its epidemiological characteristics, to identify the factors associated with it and to know its different treatments. Method: An observational retrospective study that describes and analyzes all patients treated for epistaxis in the emergency department in Rafael Méndez Hospital, in Lorca (Murcia, Spain), during a period of 7 years. We studied 2.138 patients. Results: The global incidence was 1.75 cases /1,000 inhabitants per year. 96.5% were anterior epistaxis. Predominance in males, male: female ratio of 2:1. More frequent in people over 50 years old, with an average age of 54.94 years. The highest incidence was in spring and winter. 96% of the total were discharged from hospital. It is related to arterial hypertension, although without statistical significance. The most commonly used treatment was anterior nasal packing. 46% of the posterior epistaxis required surgical treatment, with a mean hospital stay of 6 days. Conclusions: Epistaxis seen in the emergency department usually has a anterior origin, affects men older than 50 years with added comorbidity, and usually resolves on an outpatient basis. Posterior epistaxis requires hospital admission and, frequently, surgical treatment.Introducción y objetivo: La epistaxis es un signo clínico frecuente y un motivo de consulta urgente habitual. Tenemos escasos datos sobre su epidemiología y el tratamiento aplicado en nuestra Región. Los objetivos del estudio son conocer su incidencia en nuestro medio, conocer sus características epidemiológicas, determinar factores asociados a ella y conocer sus distintos tratamientos. Método: Estudio observacional retrospectivo que describe y analiza los pacientes atendidos por epistaxis en la Unidad de Urgencias del Hospital Rafael Méndez, de Lorca (Murcia, España), durante un período de 7 años. Se estudian 2.138 pacientes. Resultados: La incidencia global fue de 1,75 casos /1.000 habitantes por año. El 96,5% fueron anteriores. Predominio en varones, ratio hombre/mujer de 2/1. Fue más frecuente en mayores de 50 años, con una edad media de 54,94 años. La mayor incidencia se dio en primavera e invierno. El 96% del total fueron dados de alta a domicilio. Presenta relación con la hipertensión arterial, aunque sin significación estadística. El tratamiento más utilizado en general fue taponamiento anterior. El 46% de las epistaxis posteriores precisó tratamiento quirúrgico, con una estancia media hospitalaria de 6 días. Conclusiones: Las epistaxis atendidas en urgencias suelen tener un origen anterior, afectar a varones mayores de 50 años con comorbilidad añadida, y suelen resolverse de manera ambulatoria. Las epistaxis posteriores requieren ingreso hospitalario y, con frecuencia, tratamiento quirúrgico

Characterization of the interferon pathway in the teleost fish gonad against the vertically transmitted viral nervous necrosis virus

One of the most powerful innate immune responses against viruses is mediated by type I IFN. In teleost fish, it is known that virus infection triggers the expression of ifn and many IFN-stimulated genes, but the viral RNA sensors and mediators leading to IFN production are scarcely known. Thus, we have searched for the presence of these genes in gilt-head sea bream (Sparus aurata) and European sea bass (Dicentrarchus labrax), and evaluated their expression after infection with viral nervous necrosis virus (VNNV) in the brain, the main viral target tissue, and the gonad, used to transmit the virus vertically. In sea bream, a fish species resistant to the VNNV strain used, we found an upregulation of the genes encoding MDA5 (melanoma differentiation-associated gene 5), TBK1 (TANK-binding kinase 1), IRF3 (IFN regulatory factor 3), IFN, Mx [myxovirus (influenza) resistance protein] and PKR (dsRNA-dependent protein kinase receptor) proteins in the brain, which were unaltered in the gonad and could favour the dissemination by gonad fluids or gametes. Strikingly, in European sea bass, a very susceptible species, we also identified, transcripts coding for LGP2 (Laboratory of Genetics and Physiology 2), MAVS (mitochondrial antiviral signalling), TRAF3 (TNF receptor-associated factor 3), TANK (TRAF family member-associated NFkappaB activator) and IRF7 (IFN regulatory factor 7), and found that all the genes analysed were upregulated in the gonad, but only mda5, lgp2, irf3, mx and pkr were upregulated in the brain. These findings supported the notion that the European sea bass brain innate immune response is unable to clear the virus and pointed to the importance of gonad immunity to control the dissemination of VNNV to the progeny - an aspect that is worth investigating in aquatic animals.Postprin

Transmembrane and truncated (SEC) isoforms of MUC1 in the human endometrium and Fallopian tube

The cell surface mucin MUC1 is expressed by endometrial epithelial cells with increased abundance in the secretory phase of the menstrual cycle, when it is found both at the apical cell surface and in secretions. This suggests the presence of a maternal cell surface glycoprotein barrier to embryo implantation, arising from the anti-adhesive property of MUC1. In previous work, we demonstrated alternatively spliced MUC1 variant forms in tumour cells. The variant MUC1/SEC lacks the transmembrane and cytoplasmic sequences found in the full-length variant. We now show that MUC1/SEC mRNA is present in endometrial carcinoma cell lines, endometrial tissue and primary cultured endometrial epithelial cells. The protein can be detected using isoform-specific antibodies in uterine flushings, suggesting release from endometrium in vivo. However, on the basis of immunolocalisation studies, MUC1/SEC also remains associated with the apical epithelial surface both in tissue and in cultured cells. Transmembrane MUC1 and MUC1/SEC are both strikingly localised to the apical surface of tubal epithelium. Thus MUC1 may contribute to the anti-adhesive character of the tubal surface, inhibiting ectopic implantation. The mechanism by which this barrier is overcome in endometrium at implantation is the subject of ongoing investigation

Determination of testicular cell proliferation and characterization of Sertoli cells in testes of the gilthead seabream Sparus auratus Linnaeus, 1758

Testicular Sertoli cells in the gilthead seabream Sparus auratus Linnaeus, 1758 were characterized with antibodies previously obtained in our laboratory. Testicular cell suspensions were studied using light microscopy and flow citometry. 5-bromo-2' -deoxiruridine (BrdU) was used to analyse the proliferation of testicular cells, which were later detected with an indirect immunohistochemical technique.Se han caracterizado las células de Sertoli del testículo de dorada, Sparus auratus Linnaeus, 1758, utilizando anticuerpos monoclonales que previamente han sido obtenidos en nuestro laboratorio. Se han obtenido suspensiones celulares testiculares que han sido estudiadas mediante microscopía óptica y analizadas mediante citometría de flujo. Se ha determinado el estado de proliferación celular testicular mediante el tratamiento de los ejemplares con 5-bromo-2'-deoxiuridina (BrdU) y su posterior detección con una técnica inmunocitoquímica indirecta.Instituto Español de Oceanografí