Design and simulation of an imaging neutral particle analyzer for the ASDEX Upgrade tokamak

An Imaging Neutral Particle Analyzer (INPA) diagnostic has been designed for the ASDEX Upgrade (AUG) tokamak. The AUG INPA diagnostic will measure fast neutrals escaping the plasma after charge exchange reactions. The neutrals will be ionized by a 20 nm carbon foil and deflected toward a scintillator by the local magnetic field. The use of a neutral beam injector (NBI) as an active source of neutrals will provide radially resolved measurements, while the use of a scintillator as an active component will allow us to cover the whole plasma along the NBI line with unprecedented phase-space resolution (<12 keV and 8 cm) and a fast temporal response (up to 1 kHz with the high resolution acquisition system and above 100 kHz with the low resolution one), making it suitable to study localized fast-ion redistributions in phase space.European Union’s Horizon 2020 (Grant Agreement No. 805162)Ministerio de Ciencia, Innovación y Universidades (Grant No. FPU19/02486

Evaluation by re-derivation of a paternal line after 18 generations on seminal traits, proteome and fertility

[EN] Males from a paternal line selected for growth traits were used to produce semen doses at insemination centres and farms in a breeding scheme for rabbit meat production. The aim of this study was to assess whether a program of selection by daily gain in fattening period changed the seminal traits, plasma and sperm proteome and the fertility of semen when used in artificial insemination. Thirty-nine males from a paternal line were obtained by re-derivation from vitrified embryos with a difference of 18 generations (G21V and G39V). Sperm production parameters, morphological traits, sperm motility parameters and viability were evaluated from ejaculates. Seminal plasma and sperm proteome of three pool ejaculates from 10 mature males of each group were analysed and semen doses were used to inseminate 311 females. Only the percentage of abnormal sperm showed significant differences, with G21V presenting fewer abnormal sperm than G39V (10.5 +/- 2.63 vs 23.8 +/- 1.98). The discriminant analysis (DA-PLS) showed a clear effect of the generation for plasma and sperm proteome. In seminal plasma, 643 proteins were reported and 64 proteins were differentially expressed, of which 56 were overexpressed in G39V (87.5%). Sperm proteome reported 1360 proteins with 132 differentially abundant proteins. Of the total, 89 proteins were overexpressed in G39V (67.4%). From the 64 and 132 differentially abundant proteins of plasma and sperm, 19 and 26 had a FC >1.5, 12 and 13 of them belonging to the Oryctolagus cuniculus taxonomy, respectively. Despite observing differences in important proteins related to capacitation, sperm motility or immunoprotection and consequently to the fertilization process (TMPRSS2, Serpin family, Farn71f1, ATPase H+ transporting accessory protein 2, carbonic anhydrase 2, UDP-glucose glycoprotein glucosyltransferase 2), no differences in fertility and prolificacy were detected when commercial seminal doses were used for insemination from both male groups. However, overabundance of KIAA1324 protein can be related to the increase in abnormal sperm after selection by growth rate.This research was supported by AGL2017-85162-C2-1-R research project funded by Ministerio de Economia, Industria y Competitividad (MICINN, Spain). X Garcia-Dominguez was supported by a research grant from MICINN (BES-2015-072429). English text version was revised by N. Macowan English Language Service.Juárez, JD.; Marco-Jiménez, F.; Talaván, AM.; García-Domínguez, X.; Viudes-De-Castro, MP.; Lavara, R.; Vicente Antón, JS. (2020). Evaluation by re-derivation of a paternal line after 18 generations on seminal traits, proteome and fertility. Livestock Science. 232:1-13. https://doi.org/10.1016/j.livsci.2019.103894S113232Antalis, T. M., Bugge, T. H., & Wu, Q. (2011). Membrane-Anchored Serine Proteases in Health and Disease. Proteases in Health and Disease, 1-50. doi:10.1016/b978-0-12-385504-6.00001-4Bezerra, M. J. B., Arruda-Alencar, J. M., Martins, J. A. M., Viana, A. G. A., Viana Neto, A. M., Rêgo, J. P. A., … Moura, A. A. (2019). Major seminal plasma proteome of rabbits and associations with sperm quality. Theriogenology, 128, 156-166. doi:10.1016/j.theriogenology.2019.01.013Brun, J.-M., Theau-Clément, M., & Bolet, G. (2002). The relationship between rabbit semen characteristics and reproductive performance after artificial insemination. Animal Reproduction Science, 70(1-2), 139-149. doi:10.1016/s0378-4320(01)00197-xBrun, J.-M., Theau-Clément, M., Esparbié, J., Falières, J., Saleil, G., & Larzul, C. (2006). Semen production in two rabbit lines divergently selected for 63-d body weight. Theriogenology, 66(9), 2165-2172. doi:10.1016/j.theriogenology.2006.07.004Brun, J. M., Sanchez, A., Ailloud, E., Saleil, G., & Theau-Clément, M. (2016). Genetic parameters of rabbit semen traits and male fertilising ability. Animal Reproduction Science, 166, 15-21. doi:10.1016/j.anireprosci.2015.12.008Bünger, L., Lewis, R. M., Rothschild, M. F., Blasco, A., Renne, U., & Simm, G. (2005). Relationships between quantitative and reproductive fitness traits in animals. Philosophical Transactions of the Royal Society B: Biological Sciences, 360(1459), 1489-1502. doi:10.1098/rstb.2005.1679Casares-Crespo, L., Fernández-Serrano, P., Vicente, J. S., Marco-Jiménez, F., & Viudes-de-Castro, M. P. (2018). Rabbit seminal plasma proteome: The importance of the genetic origin. Animal Reproduction Science, 189, 30-42. doi:10.1016/j.anireprosci.2017.12.004Casares-Crespo, L., Fernández-Serrano, P., & Viudes-de-Castro, M. P. (2019). Proteomic characterization of rabbit (Oryctolagus cuniculus) sperm from two different genotypes. Theriogenology, 128, 140-148. doi:10.1016/j.theriogenology.2019.01.026Castellini, C., Lattaioli, P., Moroni, M., & Minelli, A. (2000). Effect of seminal plasma on the characteristics and fertility of rabbit spermatozoa. Animal Reproduction Science, 63(3-4), 275-282. doi:10.1016/s0378-4320(00)00181-0Castellini, C., Cardinali, R., Dal Bosco, A., Minelli, A., & Camici, O. (2006). Lipid composition of the main fractions of rabbit semen. Theriogenology, 65(4), 703-712. doi:10.1016/j.theriogenology.2005.05.053Castellini, C., Mourvaki, E., Cardinali, R., Collodel, G., Lasagna, E., Del Vecchio, M. T., & Dal Bosco, A. (2012). Secretion patterns and effect of prostate-derived granules on the sperm acrosome reaction of rabbit buck. Theriogenology, 78(4), 715-723. doi:10.1016/j.theriogenology.2012.02.012Courtens, J., Bolet, G., & Theau-Clément, M. (1994). Effect of acrosome defects and sperm chromatin decondensation on fertility and litter size in the rabbit. Preliminary electron-microscopic study. Reproduction Nutrition Development, 34(5), 427-437. doi:10.1051/rnd:19940504Choucair, F., 2018. Unraveling the sperm transcriptome by nextgeneration sequencing and the global epigenetic and landscape in infertile men. Molecular Biology.Université Côted’ Azur; Université libanaise, NNT:2018AZUR4058. https://tel.archives-ouvertes.fr/tel-01958881.Davis, B. K., & Davis, N. V. (1983). Binding by glycoproteins of seminal plasma membrane vesicles accelerates decapacitation in rabbit spermatozoa. Biochimica et Biophysica Acta (BBA) - Biomembranes, 727(1), 70-76. doi:10.1016/0005-2736(83)90370-xEllerman, D. A., Myles, D. G., & Primakoff, P. (2006). A Role for Sperm Surface Protein Disulfide Isomerase Activity in Gamete Fusion: Evidence for the Participation of ERp57. Developmental Cell, 10(6), 831-837. doi:10.1016/j.devcel.2006.03.011Estany, J., Camacho, J., Baselga, M., & Blasco, A. (1992). Selection response of growth rate in rabbits for meat production. Genetics Selection Evolution, 24(6), 527. doi:10.1186/1297-9686-24-6-527García-Tomás, M., Sánchez, J., Rafel, O., Ramon, J., & Piles, M. (2006). Variability, repeatability and phenotypic relationships of several characteristics of production and semen quality in rabbit. Animal Reproduction Science, 93(1-2), 88-100. doi:10.1016/j.anireprosci.2005.06.011García-Tomás, M., Sánchez, J., Rafel, O., Ramon, J., & Piles, M. (2006). Heterosis, direct and maternal genetic effects on semen quality traits of rabbits. Livestock Science, 100(2-3), 111-120. doi:10.1016/j.livprodsci.2005.08.004Garénaux, E., Kanagawa, M., Tsuchiyama, T., Hori, K., Kanazawa, T., Goshima, A., … Kitajima, K. (2015). Discovery, Primary, and Crystal Structures and Capacitation-related Properties of a Prostate-derived Heparin-binding Protein WGA16 from Boar Sperm. Journal of Biological Chemistry, 290(9), 5484-5501. doi:10.1074/jbc.m114.635268Gerena, R. L., Irikura, D., Urade, Y., Eguchi, N., Chapman, D. A., & Killian, G. J. (1998). Identification of a Fertility-Associated Protein in Bull Seminal Plasma As Lipocalin-Type Prostaglandin D Synthase1. Biology of Reproduction, 58(3), 826-833. doi:10.1095/biolreprod58.3.826Gervasi, M. G., & Visconti, P. E. (2017). Molecular changes and signaling events occurring in spermatozoa during epididymal maturation. Andrology, 5(2), 204-218. doi:10.1111/andr.12320Jeyendran, R. S., Van der Ven, H. H., Perez-Pelaez, M., Crabo, B. G., & Zaneveld, L. J. D. (1984). Development of an assay to assess the functional integrity of the human sperm membrane and its relationship to other semen characteristics. Reproduction, 70(1), 219-228. doi:10.1530/jrf.0.0700219Kim, T. S., Heinlein, C., Hackman, R. C., & Nelson, P. S. (2006). Phenotypic Analysis of Mice Lacking the Tmprss2 -Encoded Protease. Molecular and Cellular Biology, 26(3), 965-975. doi:10.1128/mcb.26.3.965-975.2006Kwon, J. T., Ham, S., Jeon, S., Kim, Y., Oh, S., & Cho, C. (2017). Expression of uncharacterized male germ cell-specific genes and discovery of novel sperm-tail proteins in mice. PLOS ONE, 12(7), e0182038. doi:10.1371/journal.pone.0182038Larzul, C., Gondret, F., Combes, S., & de Rochambeau, H. (2005). Divergent selection on 63-day body weight in the rabbit: response on growth, carcass and muscle traits. Genetics Selection Evolution, 37(1), 105. doi:10.1186/1297-9686-37-1-105Lavara, R., Mocé, E., Lavara, F., Viudes de Castro, M. P., & Vicente, J. S. (2005). Do parameters of seminal quality correlate with the results of on-farm inseminations in rabbits? Theriogenology, 64(5), 1130-1141. doi:10.1016/j.theriogenology.2005.01.009Lavara, R., Vicente, J. S., & Baselga, M. (2010). Genetic parameter estimates for semen production traits and growth rate of a paternal rabbit line. Journal of Animal Breeding and Genetics, 128(1), 44-51. doi:10.1111/j.1439-0388.2010.00889.xLavara, R., Vicente, J. S., & Baselga, M. (2012). Estimation of genetic parameters for semen quality traits and growth rate in a paternal rabbit line. Theriogenology, 78(3), 567-575. doi:10.1016/j.theriogenology.2012.03.002Lavara, R., Vicente, J. S., & Baselga, M. (2013). Genetic variation in head morphometry of rabbit sperm. Theriogenology, 80(4), 313-318. doi:10.1016/j.theriogenology.2013.04.015Law, R. H., Zhang, Q., McGowan, S., Buckle, A. M., Silverman, G. A., Wong, W., … Whisstock, J. C. (2006). Genome Biology, 7(5), 216. doi:10.1186/gb-2006-7-5-216Leone, M. G., Haq, H. A., & Saso, L. (2002). Lipocalin type prostaglandin D-synthase: which role in male fertility? Contraception, 65(4), 293-295. doi:10.1016/s0010-7824(02)00280-9Lestari, S. W., Miati, D. N., Seoharso, P., Sugiyanto, R., & Pujianto, D. A. (2017). Sperm Na+, K+-ATPase α4 and plasma membrane Ca2+-ATPase (PMCA) 4 regulation in asthenozoospermia. Systems Biology in Reproductive Medicine, 63(5), 294-302. doi:10.1080/19396368.2017.1348565Liao, T.-T., Xiang, Z., Zhu, W.-B., & Fan, L.-Q. (2009). Proteome analysis of round-headed and normal spermatozoa by 2-D fluorescence difference gel electrophoresis and mass spectrometry. Asian Journal of Andrology, 11(6), 683-693. doi:10.1038/aja.2009.59Llobat, L., Marco-Jiménez, F., Peñaranda, D., Thieme, R., Navarrete, A., & Vicente, J. (2011). mRNA Expression in Rabbit Blastocyst and Endometrial Tissue of Candidate Gene Involved in Gestational Losses. Reproduction in Domestic Animals, 47(2), 281-287. doi:10.1111/j.1439-0531.2011.01855.xLoveland, K., Major, A., Butler, R., Jans, D., Miyamoto, Y., & Young, J. (2015). Putting things in place for fertilization: discovering roles for importin proteins in cell fate and spermatogenesis. Asian Journal of Andrology, 17(4), 537. doi:10.4103/1008-682x.154310Lukefahr, S. D., Odi, H. B., & Atakora, J. K. (1996). Mass selection for 70-day body weight in rabbits. Journal of Animal Science, 74(7), 1481. doi:10.2527/1996.7471481xMa, Q., Li, Y., Luo, M., Guo, H., Lin, S., Chen, J., … Gui, Y. (2017). The expression characteristics of FAM71D and its association with sperm motility. Human Reproduction, 32(11), 2178-2187. doi:10.1093/humrep/dex290Marai, I. F. ., Habeeb, A. A. ., & Gad, A. . (2002). Rabbits’ productive, reproductive and physiological performance traits as affected by heat stress: a review. Livestock Production Science, 78(2), 71-90. doi:10.1016/s0301-6226(02)00091-xMocé, E., Vicente, J. S., & Lavara, R. (2003). Effect of freezing–thawing protocols on the performance of semen from three rabbit lines after artificial insemination. Theriogenology, 60(1), 115-123. doi:10.1016/s0093-691x(02)01329-8Naturil-Alfonso, C., Lavara, R., Millán, P., Rebollar, P. G., Vicente, J. S., & Marco-Jiménez, F. (2016). Study of failures in a rabbit line selected for growth rate. World Rabbit Science, 24(1), 47. doi:10.4995/wrs.2016.4016Nizza, A., Di Meo, C., & Taranto, S. (2003). Effect of Collection Rhythms and Season on Rabbit Semen Production. Reproduction in Domestic Animals, 38(6), 436-439. doi:10.1046/j.1439-0531.2003.00458.xOsada, T., Watanabe, G., Kondo, S., Toyoda, M., Sakaki, Y., & Takeuchi, T. (2001). Male Reproductive Defects Caused by Puromycin-Sensitive Aminopeptidase Deficiency in Mice. Molecular Endocrinology, 15(6), 960-971. doi:10.1210/mend.15.6.0643Pascual, J. J., García, C., Martínez, E., Mocé, E., & Vicente, J. S. (2004). Rearing management of rabbit males selected by high growth rate: the effect of diet and season on semen characteristics. Reproduction Nutrition Development, 44(1), 49-63. doi:10.1051/rnd:2004016Pascual, J. J., Marco-Jiménez, F., Martínez-Paredes, E., Ródenas, L., Fabre, C., Juvero, M. A., & Cano, J. L. (2016). Feeding programs promoting daily feed intake stability in rabbit males reduce sperm abnormalities and improve fertility. Theriogenology, 86(3), 730-737. doi:10.1016/j.theriogenology.2016.02.026Pérez-Patiño, C., Parrilla, I., Li, J., Barranco, I., Martínez, E. A., Rodriguez-Martínez, H., & Roca, J. (2019). The Proteome of Pig Spermatozoa Is Remodeled During Ejaculation. Molecular & Cellular Proteomics, 18(1), 41-50. doi:10.1074/mcp.ra118.000840Peralta-Arias, R. D., Vívenes, C. Y., Camejo, M. I., Piñero, S., Proverbio, T., Martínez, E., … Proverbio, F. (2015). ATPases, ion exchangers and human sperm motility. REPRODUCTION, 149(5), 475-484. doi:10.1530/rep-14-0471Piles, M., & Tusell, L. (2011). Genetic correlation between growth and female and male contributions to fertility in rabbit. Journal of Animal Breeding and Genetics, 129(4), 298-305. doi:10.1111/j.1439-0388.2011.00975.xPiles, M., Mocé, M. L., Laborda, P., & Santacreu, M. A. (2013). Feasibility of selection for male contribution to embryo survival as a way of improving male reproductive performance and semen quality in rabbits1. Journal of Animal Science, 91(10), 4654-4658. doi:10.2527/jas.2013-6446Rahman, M. S., Kwon, W.-S., & Pang, M.-G. (2017). Prediction of male fertility using capacitation-associated proteins in spermatozoa. Molecular Reproduction and Development, 84(9), 749-759. doi:10.1002/mrd.22810Roca, J., Martínez, S., Orengo, J., Parrilla, I., Vázquez, J. M., & Martínez, E. A. (2005). Influence of constant long days on ejaculate parameters of rabbits reared under natural environment conditions of Mediterranean area. Livestock Production Science, 94(3), 169-177. doi:10.1016/j.livprodsci.2004.10.011De Rochambeau, H., de la Fuente, L., Rouvier, R., & Ouhayoun, J. (1989). Sélection sur la vitesse de croissance post-sevrage chez le lapin. Genetics Selection Evolution, 21(4), 527. doi:10.1186/1297-9686-21-4-527Saeed, A. I., Sharov, V., White, J., Li, J., Liang, W., Bhagabati, N., … Quackenbush, J. (2003). TM4: A Free, Open-Source System for Microarray Data Management and Analysis. BioTechniques, 34(2), 374-378. doi:10.2144/03342mt01Samanta, L., Parida, R., Dias, T. R., & Agarwal, A. (2018). The enigmatic seminal plasma: a proteomics insight from ejaculation to fertilization. Reproductive Biology and Endocrinology, 16(1). doi:10.1186/s12958-018-0358-6Sabés-Alsina, M., Planell, N., Torres-Mejia, E., Taberner, E., Maya-Soriano, M. J., Tusell, L., … Lopez-Bejar, M. (2015). Daily exposure to summer circadian cycles affects spermatogenesis, but not fertility in an in vivo rabbit model. Theriogenology, 83(2), 246-252. doi:10.1016/j.theriogenology.2014.09.013Shevchenko, A., Jensen, O. N., Podtelejnikov, A. V., Sagliocco, F., Wilm, M., Vorm, O., … Mann, M. (1996). Linking genome and proteome by mass spectrometry: Large-scale identification of yeast proteins from two dimensional gels. Proceedings of the National Academy of Sciences, 93(25), 14440-14445. doi:10.1073/pnas.93.25.14440Shilov, I. V., Seymour, S. L., Patel, A. A., Loboda, A., Tang, W. H., Keating, S. P., … Schaeffer, D. A. (2007). The Paragon Algorithm, a Next Generation Search Engine That Uses Sequence Temperature Values and Feature Probabilities to Identify Peptides from Tandem Mass Spectra. Molecular & Cellular Proteomics, 6(9), 1638-1655. doi:10.1074/mcp.t600050-mcp200Theau-Clément, M., Bolet, G., Sanchez, A., Saleil, G., & Brun, J. M. (2015). Some factors that influence semen characteristics in rabbits. Animal Reproduction Science, 157, 33-38. doi:10.1016/j.anireprosci.2015.03.011Thundathil, J. C., Rajamanickam, G. D., & Kastelic, J. P. (2018). Na/K-ATPase and Regulation of Sperm Function. Animal Reproduction, 15(Suppl. 1), 711-720. doi:10.21451/1984-3143-ar2018-0024Tusell, L., Legarra, A., García-Tomás, M., Rafel, O., Ramon, J., & Piles, M. (2012). Genetic basis of semen traits and their relationship with growth rate in rabbits1. Journal of Animal Science, 90(5), 1385-1397. doi:10.2527/jas.2011-4165Vicente, J. (2004). Study of fertilising capacity of spermatozoa after heterospermic insemination in rabbit using DNA markers. Theriogenology, 61(7-8), 1357-1365. doi:10.1016/j.theriogenology.2003.08.009Vicente, J. S., Llobat, L., Viudes-de-Castro, M. P., Lavara, R., Baselga, M., & Marco-Jiménez, F. (2012). Gestational losses in a rabbit line selected for growth rate. Theriogenology, 77(1), 81-88. doi:10.1016/j.theriogenology.2011.07.019Viudes-de-Castro, M. P., & Vicente, J. S. (1997). Effect of sperm count on the fertility and prolificity rates of meat rabbits. Animal Reproduction Science, 46(3-4), 313-319. doi:10.1016/s0378-4320(96)01628-4Viudes-de-Castro, M. P., Mocé, E., Lavara, R., Marco-Jiménez, F., & Vicente, J. S. (2014). Aminopeptidase activity in seminal plasma and effect of dilution rate on rabbit reproductive performance after insemination with an extender supplemented with buserelin acetate. Theriogenology, 81(9), 1223-1228. doi:10.1016/j.theriogenology.2014.02.003Viudes de Castro, M. P., Casares-Crespo, L., Monserrat-Martínez, A., & Vicente, J. S. (2015). Determination of enzyme activity in rabbit seminal plasma and its relationship with quality semen parameters. World Rabbit Science, 23(4), 247. doi:10.4995/wrs.2015.4064Vizcaíno, J. A., Deutsch, E. W., Wang, R., Csordas, A., Reisinger, F., Ríos, D., … Hermjakob, H. (2014). ProteomeXchange provides globally coordinated proteomics data submission and dissemination. Nature Biotechnology, 32(3), 223-226. doi:10.1038/nbt.2839Wandernoth, P. M., Mannowetz, N., Szczyrba, J., Grannemann, L., Wolf, A., Becker, H. M., … Wennemuth, G. (2015). Normal Fertility Requires the Expression of Carbonic Anhydrases II and IV in Sperm. Journal of Biological Chemistry, 290(49), 29202-29216. doi:10.1074/jbc.m115.698597Weininger, R. B., Fisher, S., Rifkin, J., & Bedford, J. M. (1982). Experimental studies on the passage of specific IgG to the lumen of the rabbit epididymis. Reproduction, 66(1), 251-258. doi:10.1530/jrf.0.0660251Yan, M., Zhang, X., Pu, Q., Huang, T., Xie, Q., Wang, Y., … Gu, J. (2016). Immunoglobulin G Expression in Human Sperm and Possible Functional Significance. Scientific Reports, 6(1). doi:10.1038/srep2016

Spanish Consensus Document on the Treatment Algorithm for Rosacea

Recent scientific evidence and the incorporation of new drugs into the therapeutic arsenal against rosacea have made it necessary to review and update treatment criteria and strategies. To this end, a panel of 15 dermatologists, all experts in rosacea, was formed to share experiences and discuss treatment options, response criteria, and changes to treatment. Based on a critical review of the literature and a discussion of the routine practices of Spanish dermatologists, the panel proposed and debated different options, with consideration of the experience of professionals and the preferences of patients or equality criteria. Following validation of the proposals, the final recommendations were formulated and, together with the evidence from the main international guidelines and studies, used to produce this consensus document. The goal of this consensus document is to provide dermatologists with practical recommendations for the management of rosacea. Las últimas evidencias científicas y la incorporación de nuevos fármacos al arsenal terapéutico de la rosácea hacen necesario revisar y actualizar los criterios y estrategias de tratamiento. Con este fin, un grupo de 15 dermatólogos expertos en esta enfermedad aportaron y discutieron acerca de las diferentes terapias y los criterios de respuesta y cambio de tratamiento. Partiendo de la revisión crítica de la bibliografía y de la exposición de los hábitos de los dermatólogos españoles en su práctica clínica, se formularon distintas propuestas que fueron debatidas teniendo en consideración tanto la experiencia profesional como las preferencias de los pacientes o los criterios de equidad. Una vez validadas las propuestas, se formularon las recomendaciones finales que, junto con la evidencia aportada por las principales guías y estudios internacionales, dieron lugar al presente documento. El objetivo de este consenso es ofrecer al dermatólogo un enfoque práctico para abordar la rosácea

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: Part 2 (treatment)

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP

Vitamin D effects on human colon normal and tumour organoids

Trabajo presentado en FEBS Open Bio, celebrado en Lisboa (Portugal) del 09 al 14 de julio de 2022.Many studies indicate an association between vitamin D deficiency and increased colorectal cancer risk and, specially, mortality. Accordingly, the active vitamin D metabolite 1a,25-dihydroxyvitamin D3 (calcitriol) inhibits the proliferation and promotes the differentiation of colon carcinoma cells and of other tumour cell types, and also has antitumour effects in animal models of colon cancer. These results prompted us to analyse the effects of calcitriol on human colon normal and cancer stem cells. To this end, we established a living biobank of patient-derived colon organoids generated from the tumour mass and from the adjacent healthy tissue obtained from surgical biopsies. Organoids are a three-dimensional culture system of normal or cancer stem cells and their progeny with a self-organized multicellular structure. By immunohistochemistry and RNAscope in situ hybridization, we found that vitamin D receptor is expressed in LGR5+ colon stem cells in human tissue and in normal and tumour organoid cultures. RNA-sequencing assays showed that both organoid types respond differentially to calcitriol with profound and contrasting changes in their transcriptomic profiles. This was confirmed in an independent series of patient-derived organoids by RT-qPCR assays. In normal organoids, calcitriol upregulates stemness-related genes and inhibits cell proliferation. In contrast, in tumour organoids calcitriol has little effect on stemnessrelated genes, while it induces differentiation-associated genes, and variably reduces cell proliferation. Concordantly, electron microscopy analyses showed that calcitriol does not affect the blastic cell phenotype in normal organoids, but it induces a series of differentiated features in tumour organoids. These results indicate that calcitriol maintains the undifferentiated phenotype of human normal colon stem cells (homeostatic action), while it promotes the differentiation of colon cancer stem cells (anticancer action).

SN 2011fu: a type IIb supernova with a luminous double-peaked light curve

We present optical and near-infrared observations of the type IIb supernova (SN) 2011fu from a few days to ∼300 d after explosion. The SN presents a double-peaked light curve (LC) similar to that of SN 1993J, although more luminous and with a longer cooling phase after the primary peak. The spectral evolution is also similar to SN 1993J’s, with hydrogen dominating the spectra to ∼40 d, then helium gaining strength, and nebular emission lines appearing from ∼60 d post-explosion. The velocities derived from the P-Cygni absorptions are overall similar to those of other type IIb SNe. We have found a strong similarity between the oxygen and magnesium line profiles at late times, which suggests that these lines are forming at the same location within the ejecta. The hydrodynamical modelling of the pseudo-bolometric LC and the observed photospheric velocities suggest that SN 2011fu was the explosion of an extended star (R ∼ 450 R☉), in which 1.3 × 1051 erg of kinetic energy were released and 0.15 M of 56Ni were synthesized. In addition, a better reproduction of the observed early pseudo-bolometric LC is achieved if a more massive H-rich envelope than for other type IIb SNe is considered (0.3 M☉). The hydrodynamical modelling of the LC and the comparison of our late-time spectra with nebular spectral models for type IIb SNe, point to a progenitor for SN 2011fu with a Zero Age Main Sequence (ZAMS) mass of 13–18 M☉.Facultad de Ciencias Astronómicas y GeofísicasInstituto de Astrofísica de La Plat

SN 2011fu: a type IIb supernova with a luminous double-peaked light curve

We present optical and near-infrared observations of the type IIb supernova (SN) 2011fu from a few days to ∼300 d after explosion. The SN presents a double-peaked light curve (LC) similar to that of SN 1993J, although more luminous and with a longer cooling phase after the primary peak. The spectral evolution is also similar to SN 1993J’s, with hydrogen dominating the spectra to ∼40 d, then helium gaining strength, and nebular emission lines appearing from ∼60 d post-explosion. The velocities derived from the P-Cygni absorptions are overall similar to those of other type IIb SNe. We have found a strong similarity between the oxygen and magnesium line profiles at late times, which suggests that these lines are forming at the same location within the ejecta. The hydrodynamical modelling of the pseudo-bolometric LC and the observed photospheric velocities suggest that SN 2011fu was the explosion of an extended star (R ∼ 450 R☉), in which 1.3 × 1051 erg of kinetic energy were released and 0.15 M of 56Ni were synthesized. In addition, a better reproduction of the observed early pseudo-bolometric LC is achieved if a more massive H-rich envelope than for other type IIb SNe is considered (0.3 M☉). The hydrodynamical modelling of the LC and the comparison of our late-time spectra with nebular spectral models for type IIb SNe, point to a progenitor for SN 2011fu with a Zero Age Main Sequence (ZAMS) mass of 13–18 M☉.Facultad de Ciencias Astronómicas y GeofísicasInstituto de Astrofísica de La Plat

The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: Part 1 (diagnosis)

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-fac

Extra-uterine (abdominal) full term foetus in a 15-day pregnant rabbit

[EN] Background: While ectopic pregnancies account for 1-2% of all pregnancies, abdominal pregnancy is extremely rare, accounting for approximately 1% of ectopic pregnancies. Extrauterine abdominal pregnancy is defined as the implantation and development of an embryo in the peritoneal cavity. The present report is the first of an incidental case of abdominal pregnancy within four full-term foetus simultaneously with 2 weeks of physiological gestation in a healthy doe rabbit. Case presentation: The doe was born on November 3, 2014 and the first partum took place on May 18, 2015. The doe had previously delivered and weaned an average of 12.0 +/- 1.41 live kits at birth (no stillbirths were recorded) during 5 consecutive pregnancies. The last mating was on December 18, 2015 and the detection of pregnancy failure post breeding (by abdominal palpation) on December 31, 2015. Then, the doe was artificially inseminated on January 27, 2016, diagnosed pregnant on February 11, 2016 and subsequently euthanized to recover the foetus. A ventral midline incision revealed a reproductive tract with 12 implantation sites with 15 days old foetus and 4 term foetus in abdominal cavity. There were two foetus floating on either side of the abdominal cavity and two suspended near the greater curvature of the stomach. They were attached to internal organs by means of one or 2 thread-like blood vessels that linked them to the abdominal surfaces. Conclusions: In our opinion a systematic monitoring of rabbit breeding should be included to fully understand and enhance current knowledge of this phenomenon of abdominal pregnancy.This work was supported by Spanish Research Project AGL2014-53405-C2-1-P (Interministerial Commission on Science and Technology).Marco-Jiménez, F.; Garcia-Dominguez, X.; Valdes-Hernández, J.; Vicente Antón, JS. (2017). 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Vet Rec. 1998;142:176.Glišić A, Radunović N, Atanacković J. Methotrexate and fallopian tubes in ectopic pregnancy. Acta veterinaria. 2006;56:375–82.Nwobodo EI. Abdominal pregnancy. A case report. Ann Afr Med. 2004;3:195–6.Nassali MN, Benti TM, Bandani-Ntsabele M, Musinguzi E. A case report of an asymptomatic late term abdominal pregnancy with a live birth at 41 weeks of gestation. BMC Res Notes. 2016;9:31.Baffoe P, Fofie C, Gandau BN. Term abdominal pregnancy with healthy new-born: a case report. Ghana Med J. 2011;45:81–3.Eleje GU, Adewae O, Osuagwu IK, Obianika CE. Post-date extra-uterine abdominal pregnancy in a rhesus negative Nullipara with successful outcome: a case report. J Women's Health. 2013;6:2.Hong CC, Armstrong ML. Ectopic pregnancy in 2 guinea-pigs. Lab Anim. 1978;12:243–4.Peters LJ. Abdominal pregnancy in a golden hamster (Mesocricetus Auratus). Lab Anim Sci. 1982;32:392–3.Xiccato G, Trocino A, Boiti C, Brecchia G. Reproductive rhythm and litter weaning age as they affect rabbit doe performance and body energy balance. Anim Sci. 2005;81:289–96.Fortun-Lamothe L, De Rochambeau H, Lebas F, Tudela F. Influence of the number of suckling young on reproductive performance in intensively reared rabbits does. In: Blasco A, editor. Proceedings of the 7th world rabbit congress; 2002. p. 125–32