Embryologic changes in rabbit lines selected for litter size variability

[EN] A divergent selection experiment on litter size variability was carried out. Correlated response in early embryo survival, embryonic development, size of embryos, and size of embryonic coats after four generations of selection was estimated. A total of 429 embryos from 51 high-line females and 648 embryos from 80 low-line females were used in the experiment. The traits studied were percentage of normal embryos, embryo diameter, zona pellucida thickness, and mucin coat thickness. Traits were measured at 24, 48, and 72 hours postcoitum (hpc); mucin coat thickness was only measured at 48 and 72 hpc. The embryos were classified as zygotes or two-cell embryos at 24 hpc; 16-cell embryos or early morulae at 48 hpc; and early morulae, compacted morulae, or blastocyst at 72 hpc. At 24 hpc, the percentage of normal embryos in the high line was lower than in the low line (-2.5%), and embryos in the high line showed 10% higher zona pellucida thickness than those of the low line. No differences in percentage of zygotes or two-cell embryos were found. At 48 hpc, the high-line embryos were less developed, with a higher percentage of 16-cell embryos (23.4%) and a lower percentage of early morulae (-23.4%). At 72 hpc, high-line embryos continued to be less developed, showing higher percentages of early morulae and compact morulae and lower percentages of blastocyst (-1.8%). No differences in embryo diameter or mucin coat thickness were found at any time. In conclusion, selection for litter size variability has consequences on early embryonic survival and development, with embryos presenting a lower state of development and a lower percentage of normal embryos in the line selected for higher variability. (C) 2016 Elsevier Inc. All rights reserved.This experiment was supported by projects of National Research Plan AGL2011-29831-C03-02 and GVPRE/2008/145.Garcia, M.; Blasco Mateu, A.; Argente, M. (2016). Embryologic changes in rabbit lines selected for litter size variability. Theriogenology. 86(5):1247-1250. https://doi.org/10.1016/j.theriogenology.2016.04.065S1247125086

Litter Survival Differences between Divergently Selected Lines for Environmental Sensitivity in Rabbits

[EN] Simple Summary Two rabbit lines are divergently selected for increasing or decreasing the variability of litter size at birth. Decreasing the litter size variability produces more resilient females with less sensitivity to diseases, being an indirect selection way to improve environmental sensitivity. The kits' survival rate at weaning was higher in the homogeneous line. Moreover, this line led to a greater uniformity of the kits' weight at weaning, although the weight variability at birth was higher, which could be due to a higher lactation capacity of the homogeneous line. A divergent selection experiment on environmental sensitivity was performed in rabbits. The aim was to estimate the correlated response in kit weight and survival, litter weight, and weight distance from birth to weaning. The weight distance was calculated as the absolute value of the differences between the individual value and the mean value of its litter. The relationship between the probability of survival at 4 d of age, and the weight at birth, was studied. Environmental sensitivity was measured as litter size variability. A total of 2484 kits from 127 does from the low line, and 1916 kits of 114 does from the high line of the 12th generation were weighed. Both of the lines showed similar individual and litter weights at birth and weaning, and a similar survival rate at birth, and at 4 d of age. The survival rate at weaning was higher in the low line (0.67 and 0.62; P = 0.93). The weight distance was higher at birth, but lower at weaning in the low line (47.8 g and 54.1 g; P = 0.98). When the weight at birth was high, the kits had a higher survival rate. In conclusion, selection for environmental sensitivity showed a correlated response in the kits' survival, and in the homogeneity of litter weight at weaning.This study is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) with the Projects AGL2017-86083, C2-1-P and C2-2-P.Agea, I.; Garcia, M.; Blasco Mateu, A.; Argente, M. (2019). Litter Survival Differences between Divergently Selected Lines for Environmental Sensitivity in Rabbits. Animals. 9(9):1-9. https://doi.org/10.3390/ani9090603S1999Garcı́a, M. L., & Baselga, M. (2002). Estimation of genetic response to selection in litter size of rabbits using a cryopreserved control population. Livestock Production Science, 74(1), 45-53. doi:10.1016/s0301-6226(01)00280-9Sánchez, J. P., Theilgaard, P., Mínguez, C., & Baselga, M. (2008). Constitution and evaluation of a long-lived productive rabbit line1. Journal of Animal Science, 86(3), 515-525. doi:10.2527/jas.2007-0217Larzul, C., Ducrocq, V., Tudela, F., Juin, H., & Garreau, H. (2014). The length of productive life can be modified through selection: An experimental demonstration in the rabbit1. Journal of Animal Science, 92(6), 2395-2401. doi:10.2527/jas.2013-7216Rauw, W. ., Kanis, E., Noordhuizen-Stassen, E. ., & Grommers, F. . (1998). Undesirable side effects of selection for high production efficiency in farm animals: a review. Livestock Production Science, 56(1), 15-33. doi:10.1016/s0301-6226(98)00147-xBlasco, A., Martínez-Álvaro, M., García, M.-L., Ibáñez-Escriche, N., & Argente, M.-J. (2017). Selection for environmental variance of litter size in rabbits. Genetics Selection Evolution, 49(1). doi:10.1186/s12711-017-0323-4Argente, M. J., García, M. L., Zbyňovská, K., Petruška, P., Capcarová, M., & Blasco, A. (2019). Correlated response to selection for litter size environmental variability in rabbits’ resilience. animal, 13(10), 2348-2355. doi:10.1017/s1751731119000302Bolet, G., Esparbié, J., & Falières, J. (1996). Relations entre le nombre de fœtus par corne utérine, la taille de portée à la naissance et la croissance pondérale des lapereaux. Annales de Zootechnie, 45(2), 185-200. doi:10.1051/animres:19960207Poigner J., Szendrõ Zs., Lévai A., Radnai I., & Biró-Németh E. (2010). EFFECT OF BIRTH WEIGHT AND LITTER SIZE ON GROWTH AND MORTALITY IN RABBITS. World Rabbit Science, 8(1). doi:10.4995/wrs.2000.413TM Threshold Modelhttp://snp.toulouse.inra.fr/~alegarra/manualtm.pdfPeiró, R., Badawy, A. Y., Blasco, A., & Santacreu, M. A. (2019). Correlated responses on growth traits after two-stage selection for ovulation rate and litter size in rabbits. animal, 13(11), 2457-2462. doi:10.1017/s1751731119001423Pascual, J. J., Savietto, D., Cervera, C., & Baselga, M. (2013). Resources allocation in reproductive rabbit does: a review of feeding and genetic strategies for suitable performance. World Rabbit Science, 21(3). doi:10.4995/wrs.2013.1236Bolet, G., Garreau, H., Joly, T., Theau-Clement, M., Falieres, J., Hurtaud, J., & Bodin, L. (2007). Genetic homogenisation of birth weight in rabbits: Indirect selection response for uterine horn characteristics. Livestock Science, 111(1-2), 28-32. doi:10.1016/j.livsci.2006.11.012Garreau, H., Bolet, G., Larzul, C., Robert-Granié, C., Saleil, G., SanCristobal, M., & Bodin, L. (2008). Results of four generations of a canalising selection for rabbit birth weight. Livestock Science, 119(1-3), 55-62. doi:10.1016/j.livsci.2008.02.009Hamilton, H. H., Lukefahr, S. D., & McNitt, J. I. (1997). Maternal nest quality and its influence on litter survival and weaning performance in commercial rabbits. Journal of Animal Science, 75(4), 926. doi:10.2527/1997.754926xVicente, J., García-Ximénez, F., & Viudes-de-Castro, M. (1995). Neonatal performances in 3 lines of rabbit (litter sizes, litter and individual weights). Annales de Zootechnie, 44(3), 255-261. doi:10.1051/animres:19950305Hull, D., & Segall, M. M. (1965). The contribution of brown adipose tissue to heat production in the new-born rabbit. The Journal of Physiology, 181(3), 449-457. doi:10.1113/jphysiol.1965.sp007773Spencer, S. A., & Hull, D. (1984). The effect of over-feeding newborn rabbits on somatic and visceral growth, body composition and long-term growth potential. British Journal of Nutrition, 51(3), 389-402. doi:10.1079/bjn19840045Venge, O. (1963). The influence of nursing behaviour and milk production on early growth in rabbits. Animal Behaviour, 11(4), 500-506. doi:10.1016/0003-3472(63)90269-0Coureaud, G., Schaal, B., Coudert, P., Rideaud, P., Fortun-Lamothe, L., Hudson, R., & Orgeur, P. (2000). Immediate postnatal sucking in the rabbit: Its influence on pup survival and growth. Reproduction Nutrition Development, 40(1), 19-32. doi:10.1051/rnd:2000117Argente, M. J., Santacreu, M. A., Climent, A., & Blasco, A. (1999). Phenotypic and genetic parameters of birth weight and weaning weight of rabbits born from unilaterally ovariectomized and intact does. Livestock Production Science, 57(2), 159-167. doi:10.1016/s0301-6226(98)00166-3Xiccato, G., Trocino, A., Sartori, A., & Queaque, P. I. (2004). Effect of parity order and litter weaning age on the performance and body energy balance of rabbit does. Livestock Production Science, 85(2-3), 239-251. doi:10.1016/s0301-6226(03)00125-8Rebollar, P. G., Pérez-Cabal, M. A., Pereda, N., Lorenzo, P. L., Arias-Álvarez, M., & García-Rebollar, P. (2009). Effects of parity order and reproductive management on the efficiency of rabbit productive systems. Livestock Science, 121(2-3), 227-233. doi:10.1016/j.livsci.2008.06.01

Correlated response in body condition and energy mobilisation in rabbits selected for litter size variability

[EN] A divergent selection experiment on litter size variability (high and low lines) was performed in rabbits over seven generations. The aim of this study was to evaluate the correlated responses to selection in body condition and fat reserves mobilisation. Litter size variability was estimated as phenotypic variance of litter size within female after correcting for the year-season and the parity-lactation status effects. A total of 226 females were used in this study, of which 158 females were used to measure body condition and energy mobilisation. Body condition was measured as BW and perirenal fat thickness. Females were stimulated with the adrenergic isoproterenol. Mobilisation capacity of fat reserves was measured by the lipolytic potential, defined as the increment in non-esterified fatty acids (NEFA) levels from basal concentration until adrenergic stimulation at mating, delivery and 10 days after delivery of the second reproductive cycle. Females were classified as survivor or non-survivor when they were culled for sanitary reasons or died before the third kindling. Data were analysed using Bayesian methodology. Survivor females presented higher BW than the non-survivor females at delivery (238 g, P=1.00) and 10 days after delivery (276 g, P=1.00). They also showed higher perirenal fat thickness at 10 days after delivery (0.62 mm, P=1.00). At delivery, basal NEFA levels was lower in survivor than non-survivor females (-0.18 mmol/l, P=1.00), but their lipolytic potential ( increment NEFA) was higher (0.08 mmol/l, P=0.94). Body weight was similar between lines in survivor females. Perirenal fat thickness was lower in the high line than in the low line at delivery (-0.23 mm, P=0.90) and 10 days after delivery (-0.28 mm, P=0.92). The high line exhibited higher NEFA (0.10 mmol/l, P=0.93) and lower increment NEFA (-0.08 mmol/l, P=0.92) than the low line at delivery. The low line showed a favourable correlated response to selection on body condition and fat reserves mobilisation. In conclusion, the low line selected for litter size variability seems to adapt better to adverse conditions, as it has a greater capacity to mobilise energy reserves at delivery than the high line. Females that adequately manage their body reserves and perform energy mobilisation correctly have a lower risk of dying or being culled.This study is supported by the Spanish Ministry of Economy and Competitiveness (MINECO), projects AGL2014-55921-C2, P1 and P2.Garcia, M.; Blasco Mateu, A.; Garcia, M.; Argente, M. (2019). Correlated response in body condition and energy mobilisation in rabbits selected for litter size variability. Animal. 13(4):784-789. https://doi.org/10.1017/S1751731118002203S784789134Webster Marketon, J. I., & Glaser, R. (2008). Stress hormones and immune function. Cellular Immunology, 252(1-2), 16-26. doi:10.1016/j.cellimm.2007.09.006Theilgaard, P., Sánchez, J. P., Pascual, J. J., Friggens, N. C., & Baselga, M. (2006). Effect of body fatness and selection for prolificacy on survival of rabbit does assessed using a cryopreserved control population. Livestock Science, 103(1-2), 65-73. doi:10.1016/j.livsci.2006.01.007Theilgaard, P., Baselga, M., Blas, E., Friggens, N. C., Cervera, C., & Pascual, J. J. (2009). Differences in productive robustness in rabbits selected for reproductive longevity or litter size. animal, 3(5), 637-646. doi:10.1017/s1751731109003838Roche, J. R., Friggens, N. C., Kay, J. K., Fisher, M. W., Stafford, K. J., & Berry, D. P. (2009). Invited review: Body condition score and its association with dairy cow productivity, health, and welfare. Journal of Dairy Science, 92(12), 5769-5801. doi:10.3168/jds.2009-2431PILORZ, V., JACKEL, M., KNUDSEN, K., & TRILLMICH, F. (2005). The cost of a specific immune response in young guinea pigs. Physiology & Behavior, 85(2), 205-211. doi:10.1016/j.physbeh.2005.04.008Pascual, J. J., Castella, F., Cervera, C., Blas, E., & Fernández-Carmona, J. (2000). The use of ultrasound measurement of perirenal fat thickness to estimate changes in body condition of young female rabbits. Animal Science, 70(3), 435-442. doi:10.1017/s135772980005178xMartínez-Paredes, E., Ródenas, L., Martínez-Vallespín, B., Cervera, C., Blas, E., Brecchia, G., … Pascual, J. J. (2012). Effects of feeding programme on the performance and energy balance of nulliparous rabbit does. animal, 6(7), 1086-1095. doi:10.1017/s1751731111002643Gellrich, K., Sigl, T., Meyer, H. H. D., & Wiedemann, S. (2015). Cortisol levels in skimmed milk during the first 22 weeks of lactation and response to short-term metabolic stress and lameness in dairy cows. Journal of Animal Science and Biotechnology, 6(1). doi:10.1186/s40104-015-0035-yFortun-Lamothe, L. (2006). Energy balance and reproductive performance in rabbit does. Animal Reproduction Science, 93(1-2), 1-15. doi:10.1016/j.anireprosci.2005.06.009Feugier, A., & Fortun-Lamothe, L. (2006). Extensive reproductive rhythm and early weaning improve body condition and fertility of rabbit does. Animal Research, 55(5), 459-470. doi:10.1051/animres:2006025Blasco, A., Martínez-Álvaro, M., García, M.-L., Ibáñez-Escriche, N., & Argente, M.-J. (2017). Selection for environmental variance of litter size in rabbits. Genetics Selection Evolution, 49(1). doi:10.1186/s12711-017-0323-4Friggens, N. C. (2003). Body lipid reserves and the reproductive cycle: towards a better understanding. Livestock Production Science, 83(2-3), 219-236. doi:10.1016/s0301-6226(03)00111-8Johnson, R. . (1998). Immune and endocrine regulation of food intake in sick animals. Domestic Animal Endocrinology, 15(5), 309-319. doi:10.1016/s0739-7240(98)00031-9Bareille, N., Beaudeau, F., Billon, S., Robert, A., & Faverdin, P. (2003). Effects of health disorders on feed intake and milk production in dairy cows. Livestock Production Science, 83(1), 53-62. doi:10.1016/s0301-6226(03)00040-xBlasco A , Martínez-Álvaro M , Garcia ML , Capcarova M , Zbynovska K , Petruska P , Ibáñez-Escriche N and Argente MJ 2018. Selection for genetic environmental sensitivity of litter size changes resilience in rabbits. In 11th World Congress on Genetics Applied to Livestock Production, 11–16 February 2018, Auckland, New Zealand.Fortun, L., Prunier, A., Étienne, M., & Lebas, F. (1994). Influence of the nutritional deficit of foetal survival and growth and plasma metabolites in rabbit does. Reproduction Nutrition Development, 34(3), 201-211. doi:10.1051/rnd:19940303Rosell, J. M., & de la Fuente, L. F. (2016). Causes of mortality in breeding rabbits. Preventive Veterinary Medicine, 127, 56-63. doi:10.1016/j.prevetmed.2016.03.014Savietto, D., Cervera, C., Blas, E., Baselga, M., Larsen, T., Friggens, N. C., & Pascual, J. J. (2013). Environmental sensitivity differs between rabbit lines selected for reproductive intensity and longevity. animal, 7(12), 1969-1977. doi:10.1017/s175173111300178xGarcía ML , Argente MJ , Muelas R , Birlanga V and Blasco A 2012. Effect of divergent selection for residual variance of litter size on health status and welfare. In Proceedings of the 10th World Rabbit Congress, 3–6 September 2012, Sharm El-Sheikh, Egypt, pp. 103–106.Chilliard, Y. (1993). Dietary Fat and Adipose Tissue Metabolism in Ruminants, Pigs, and Rodents: A Review. Journal of Dairy Science, 76(12), 3897-3931. doi:10.3168/jds.s0022-0302(93)77730-9Blasco, A. (2017). Bayesian Data Analysis for Animal Scientists. doi:10.1007/978-3-319-54274-4Sorensen, D., & Gianola, D. (2002). Likelihood, Bayesian, and MCMC Methods in Quantitative Genetics. Statistics for Biology and Health. doi:10.1007/b98952Rosell, J. M., & de la Fuente, L. F. (2009). Culling and mortality in breeding rabbits. 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Relationship between body condition and energy mobilization in rabbit does

[EN] The present work was performed to examine the relationships between measures of body condition and energy mobilization in rabbit does. The variables studied were body weight (BW), perirenal fat thickness (PFT), basal non-esterified fatty acid concentration (NEFAb) and non-esterified fatty acids after lipolysis stimulation by isoproterenol (NEFAr). The effect of time of measuring (at mating, delivery and 10 d after delivery) was estimated in 157 primiparous does. Correlations between body condition components were estimated and a principal component analysis performed. The does decreased BW (6%) and PFT (3%), and increased NEFAb (25%) and NEFAr (16%) from mating to delivery. Later, NEFAb and NEFAr decreased around 20% from delivery to 10 d after delivery without changing perirenal fat thickness. All BW and PFT lay in the first principal component, and all NEFA traits lay in the second component, showing low correlations with body condition measurements. Both NEFA traits showed high positive correlations when measured at the same time (0.65, 0.72 and 0.69), but low correlations when measured at different times (0.09, to 0.20). We conclude that although body weight and perirenal fat thickness are good predictors of body condition, NEFA should be used when an accurate measurement of energetic mobilization is needed, due to their low correlation.This experiment was supported by projects AGL2011-29831-C03-02 and AGL2014-55921-C2-2-P of the National Research Plan. Eddy W. Calle was supported by a research grant from Erasmus Mundi (Programme Babel). We are especially grateful to reviewer A for her detailed comments and useful suggestions.Calle, E.; García, M.; Blasco Mateu, A.; Argente, M. (2017). Relationship between body condition and energy mobilization in rabbit does. World Rabbit Science. 25(1):37-41. https://doi.org/10.4995/wrs.2017.5674SWORD374125

Correlated response to selection for litter size environmental variability in rabbits' resilience

[EN] Resilience is the ability of an animal to return soon to its initial productivity after facing diverse environmental challenges. This trait is directly related to animal welfare and it plays a key role in fluctuations of livestock productivity. A divergent selection experiment for environmental variance of litter size has been performed successfully in rabbits over ten generations. The objective of this study was to analyse resilience indicators of stress and disease in the divergent lines of this experiment. The high line showed a lower survival rate at birth than the low line (-4.1%). After correcting by litter size, the difference was -3.2%. Involuntary culling rate was higher in the high than in the low line (+12.4%). Before vaccination against viral haemorrhagic disease or myxomatosis, concentration of lymphocytes, C-reactive protein (CRP), complement C3, serum bilirubin, triglycerides and cholesterol were higher in the high line than in the low line (difference between lines +4.5%, +5.6 mu g/ml, +4.6 mg/ml, +7.9 mmol/l, +0.3 mmol/l and +0.4 mmol/l). Immunological and biochemical responses to the two vaccines were similar. After vaccination, the percentage of lymphocytes and CRP concentration were higher in the low line than in the high one (difference between lines +4.0% and +13.1 mu g/ml). The low line also showed a higher increment in bilirubin and triglycerides than the high line (+14.2 v. +8.7 mmol/l for bilirubin and +0.11 v. +0.01 mmol/l for triglycerides); these results would agree with the protective role of bilirubin and triglycerides against the larger inflammatory response found in this line. In relation to stress, the high line had higher basal concentration of cortisol than the low line (+0.2ng/ml); the difference between lines increased more than threefold after the injection of ACTH 1 to 24, the increase being greater in the high line (+0.9 ng/ml) than in the low line (+0.4 ng/ml). Selection for divergent environmental variability of litter size leads to dams with different culling rate for reproductive causes and different kits' neonatal survival. These associations suggest that the observed fitness differences are related to differences in the inflammatory response and the corticotrope response to stress, which are two important components of physiological adaptation to environmental aggressions.This study is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) with the Projects AGL2014-55921, C2-1-P and C2-2-P, and AGL2017-86083, C2-1-P and C2-2-P.Argente, M.; Garcia, M.; Zbynovska, K.; Petruska, P.; Capcarova, M.; Blasco Mateu, A. (2019). Correlated response to selection for litter size environmental variability in rabbits' resilience. Animal. 13(10):2348-2355. https://doi.org/10.1017/S1751731119000302S234823551310Glaser, R., & Kiecolt-Glaser, J. K. (2005). Stress-induced immune dysfunction: implications for health. Nature Reviews Immunology, 5(3), 243-251. doi:10.1038/nri1571Markanday, A. (2015). Acute Phase Reactants in Infections: Evidence-Based Review and a Guide for Clinicians. Open Forum Infectious Diseases, 2(3). doi:10.1093/ofid/ofv098Rauw, W. ., Kanis, E., Noordhuizen-Stassen, E. ., & Grommers, F. . (1998). Undesirable side effects of selection for high production efficiency in farm animals: a review. Livestock Production Science, 56(1), 15-33. doi:10.1016/s0301-6226(98)00147-xPiles, M., García, M. L., Rafel, O., Ramon, J., & Baselga, M. (2006). Genetics of litter size in three maternal lines of rabbits: Repeatability versus multiple-trait models. 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Non-alcoholic fatty liver in hereditary fructose intolerance

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation affecting >5% of the liver volume that is not explained by alcohol abuse. It is known that fructose gives rise to NAFLD and it has been recently described that the ingestion of fructose in low amounts in aldolase B deficient mice is associated with the development of fatty liver. Therefore, it is reasonable that patients with HFI (Hereditary Fructose Intolerance) present fatty liver at diagnosis, but its prevalence in patients treated and with adequate follow-up is not well documented in the literature. The aim of this study is to analyze the association between HFI and NAFLD in treated patients. Methods: A cross-sectional observational study was conducted. The population comprised 16 genetically diagnosed HFI patients aged from 3 years to 48 and in dietary treatment of fructose, sorbitol and sacarose exclusion at least for two years. Blood samples were obtained for analytical studies and anthropometric measurements of each patient were performed. Results: Patients presented a Body Mass Index (BMI) of 17.9 ± 2.9 kg/m 2 . The HOMA index and Quick index were in normal range for our population. The S-adenosyl-methionine (SAM)/S-adenosyl-L-homocysteine (SAH) ratio was increased in the patients in whom this analysis was performed. By imaging techniques it was observed that 9 of the 16 patients presented fatty liver (7 by hepatic MRI). Of these 9 patients, only 3 presented hepatomegaly. 7 of 9 patients affected by the c.448G > C mutation had fatty infiltration, of which three of them presented in addition hepatomegaly. Conclusions: There is a high prevalence of fatty liver in HFI patients and it is not related to obesity and insulin resistance. The diagnosis of fatty liver in HFI patients and, above all, the identification of new therapeutic approaches, can positively impact the quality of life of these patients

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions