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Introduction and objectives: There is great interest in the development of devices for the percutaneous management of mitral regurgitation (MR). For this reason, having an experimental model that reproduces the conditions of the disease is of great importance. Our objective was to validate an experimental model of MR in a porcine model. Methods: For the model creation phase 3, 2-month-old 25 ± 3 kg large white pigs were used. An acute myocardial infarction was caused in the circumflex artery territory that hampered the perfusion of the posteromedial papillary muscle. Then, volume overload was induced in the animal by creating an arteriovenous shunt and connecting the aorta and the pulmonary artery using a Dacron tube. Echocardiography and magnetic resonance imaging were performed before the intervention and on week 8. Afterwards, the animal was euthanized to conduct the pathological study. Results: One out of the 3 pigs died during the intervention due to ventricular fibrillation. The remaining 2 pigs survived the procedure and were euthanized as scheduled on week 8. In both cases a transmural infarction occurred, 1 at lateral level and the other one at posteroinferior level with moderate secondary mitral regurgitation. Ventricular dimensions and volumes increased and the overall contractility was maintained...

© 2020 Published by Elsevier Inc, The modulation of voltage-gated K+ (Kv) channels, involved in cell proliferation, arises as a potential therapeutic approach for the prevention of intimal hyperplasia present in in-stent restenosis (ISR) and allograft vasculopathy (AV). We studied the effect of PAP-1, a selective blocker of Kv1.3 channels, on development of intimal hyperplasia in vitro and in vivo in 2 porcine models of vascular injury. In vitro phenotypic modulation of VSMCs was associated to an increased functional expression of Kv1.3 channels, and only selective Kv1.3 channel blockers were able to inhibit porcine VSMC proliferation. The therapeutic potential of PAP-1 was then evaluated in vivo in swine models of ISR and AV. At 15-days follow-up, morphometric analysis demonstrated a substantial reduction of luminal stenosis in the allografts treated with PAP-1 (autograft 2.72 ± 1.79 vs allograft 10.32 ± 1.92 vs allograft + polymer 13.54 ± 8.59 vs allograft + polymer + PAP-1 3.06 ± 1.08 % of luminal stenosis; P = 0.006) in the swine model of femoral artery transplant. In the pig model of coronary ISR, using a prototype of PAP-1-eluting stent, no differences were observed regarding % of stenosis compared to control stents (31 ± 13 % vs 37 ± 18%, respectively; P = 0.372) at 28-days follow-up. PAP-1 treatment was safe and did not impair vascular healing in terms of delayed endothelialization, inflammation or thrombosis. However, an incomplete release of PAP-1 from stents was documented. We conclude that the use of selective Kv1.3 blockers represents a promising therapeutic approach for the prevention of intimal hyperplasia in AV, although further studies to improve their delivery method are needed to elucidate its potential in ISR., This work was supported by a Translational Research Project on Cardiology (2015) of the Sociedad Española de Cardiología and Fondo de Investigación Sanitario Instituto de Salud Carlos III (PI11/00225) to M. Roqué; BFU2016-75360-R from the Ministerio de Economía y Competitividad (MINECO) to M.T. Pérez-García and J.R. López-López; Junta de Castilla y León Grant VA114P17 to M.T. Pérez-García; and the CERCA Programme of the Generalitat de Catalunya.

16 páginas, 3 tablas, 6 figuras., The COVID-19 pandemic and lockdown brought numerous teaching challenges requiring innovative approaches to teaching and learning, including novel modes of content delivery, virtual classrooms, and online assessment schemes. The aim of this study is to describe and assess the efficacy of the methods implemented at the University of León (Spain) to adapt to lockdowns in the context of the Cytology and Histology (CH) course for veterinary medicine undergraduate students. To evaluate the success of lockdown-adapted methodologies, we used inferential statistical analysis to compare the academic outcomes of two cohorts: 2018–2019 (traditional face-to-face—presential—learning and evaluation) and 2019–2020 (some face-to-face and some online lockdown-adapted learning and online lockdown-adapted evaluation). This analysis considered scores in both theoretical and practical exams and students’ final subject score. We also evaluated the number of logs onto the Moodle platform throughout the 2019–2020 period, as well as performing a student satisfaction survey in both courses. The use of explanatory pre-recorded lectures, continuous online self-assessment tests, and virtual microscopy (VM) may have produced significant improvements in the acquisition of histology competencies among students in the lockdown cohort. However, we need to implement further strategies to improve the assessment of students’ true level of knowledge acquisition. According to the student feedback, VM is a well-accepted resource that is perceived as a flexible and enjoyable tool to use. However, while students found that the resource enhances their ability to learn about microscopic structures, they felt that it should not completely replace optical microscopy., The digital material used for teaching and student assessment was developed thanks to the funding of two grants from the University of León (Spain) from the Teaching Innovation Project Office titled “Introducción en el aula universitaria de una metodología docente virtual para la enseñanza práctica de asignaturas en los Grados en Veterinaria y Biología (PAGID2017)” and “Metodología docente virtual en la enseñanza práctica de asignaturas de los Grados en Veterinaria y Biología. Elaboración de nuevos materiales didácticos digitales (PAGID2018).

Aims The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment. Methods and results Large-white male pigs (n=40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure [0.45 mg/kg intracoronary (IC) doxorubicin per injection] and follow-up: control (no doxorubicin); single injection and sacrifice either at 48 h (ExPr. 1) or 2 weeks (ExPr. 2); 3 injections 2 weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; five injections 2 weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls. A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (three bi-weekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibres even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime. Conclusion Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects., Graphical Abstract

Aims: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. Methods and results: Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs. Conclusion: In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC. Fil: Galán Arriola, Carlos. Centro de Investigacion Biomedica En Red.; España Fil: Villena Gutiérrez, Rocio. Centro de Investigacion Biomedica En Red.; España Fil: Higuero Verdejo, María I.. Centro Nacional de Investigaciones Cardiovasculares; España Fil: Díaz Rengifo, Iván A.. Centro Nacional de Investigaciones Cardiovasculares; España Fil: Pizarro, Gonzalo. Centro de Investigacion Biomedica En Red.; España Fil: López, Gonzalo J.. Centro Nacional de Investigaciones Cardiovasculares; España Fil: de Molina Iracheta, Antonio. Centro Nacional de Investigaciones Cardiovasculares; España Fil: Pérez Martínez, Claudia. Universidad de Leon. Facultad de Veterinaria; Argentina Fil: García, Rodrigo Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: González Calle, David. Centro de Investigacion Biomedica En Red.; España Fil: Lobo, Manuel. Centro de Investigacion Biomedica En Red.; España Fil: Sánchez, Pedro L.. Centro de Investigacion Biomedica En Red.; España Fil: Oliver, Eduardo. Centro de Investigacion Biomedica En Red.; España Fil: Córdoba, Raúl. Hospital Fundacion Jimenez Diaz; España Fil: Fuster, Valentin. Centro Nacional de Investigaciones Cardiovasculares; España Fil: Sánchez González, Javier. No especifíca; Fil: Ibanez, Borja. Centro de Investigacion Biomedica En Red.; España

Introduction Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect occurring in a significant proportion of patients. Irreversible mitochondrial damage is a central mechanism of AIC. Despite many efforts, there is a lack of therapies able to prevent AIC. Remote ischemic preconditioning (RIPC) could be a promising therapy to prevent AIC due to the scheduled application of chemotherapy in cancer patients. Purpose To evaluate the cardioprotective efficacy of RIPC in large animal model of AIC. Methods Large-White pigs (n=20) underwent a validated protocol of AIC consisting on five intracoronary doxorubicin injections (0.45 mg/kg), on weeks 0, 2, 4, 6, 8 of the study. Pigs were randomized before the initiation of the study to remote ischemic pre-conditioning (RIPC, 3 cycles of 5 min lower limb ischemia followed by 5 min reperfusion) or sham procedure immediately before doxorubicin injections. An additional group of 10 pigs without any exposure to doxorubicin was carried out as controls. Pigs underwent a comprehensive serial cardiac magnetic resonance (CMR) exam baseline, and on weeks 6, 8, 12, and 16. After 16-week CMR, pigs were sacrificed and tissue samples collected. A second group of 10 pigs (randomized 1:1 for RIPC) underwent the same protocol but were sacrificed 2 weeks after the third doxorubicin dose for early evaluation of tissue changes. Primary endpoint of the study was CMR-based left ventricular ejection fraction on week 16. Results Until week 6 (time of fourth doxorubicin injection), LVEF remained unchanged in both groups. From there on, a progressive decline in LVEF was observed. LVEF depression trajectory was blunted in RIPC animals. Compared to controls, pigs undergoing RIPC before each doxorubicin dose had a significantly higher LVEF at week 16: median (IQR) 45% (27–50%) vs 33% (19–47%) in RIPC and controls respectively, p=0.04. Improvement in LVEF was mainly due to a more preserved contractile function, as evidence by smaller LVESV, and better regional contractile function. After 3 doxorubicin doses, a time where global (LVEF) and regional contractile function was still unchanged, transmission electron microscopy (TEM) showed fragmented mitochondria with remodeled cristae only in control pigs. At the end of the 16 weeks, TEM evaluation in control pigs (as compared to RIPC pigs) showed overt cardiomyocyte's mitochondrial fragmentation with overt structural derangement. At this time, RIPC pigs had significantly less interstitial fibrosis on histology. Conclusions In a translatable large animal model of AIC, RIPC applied immediately before each doxorubicin cycle resulted in a preservation of cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented the deleterious effects of doxorubicin on mitochondria since early stages of AIC. RIPC is a promising intervention to be tested in clinical trials to prevent cardiotoxicity. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovaciόn and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505)

New-generation catheters-based renal denervation (RDN) is under investigation for the treatment of uncontrolled hypertension (HTN). We assessed the feasibility of a large animal model of HTN to accommodate the human RDN devices. Ten minipigs were instrumented to measure blood pressure (BP) in an awake-state. HTN was induced with subcutaneous 11-deoxycorticosterone (DOCA, 100 mg/kg) implants. Five months after, the surviving animals underwent RDN with the Symplicity&reg, system. Norepinephrine (NE) renal gradients were determined before and 1 month after RDN. Renal arteries were processed for histological (hematoxylin-eosin, Movat pentachrome) and immunohistochemical (S100, tyrosine-hydroxylase) analyses. BP significantly rose after DOCA implants. Six animals died prematurely, mainly from infectious causes. The surviving animals showed stable BP levels after 5 months. One month after RDN, nerve damage was showed in three animals, with impedance drop &gt, 10%, NE gradient drop and reduction in BP. The fourth animal showed no nerve damage, impedance drop &lt, 10%, NE gradient increase and no change in BP. In conclusion, the minipig model of DOCA-induced HTN is feasible, showing durable effects. High mortality should be addressed in next iterations of this model. RDN may partially offset the DOCA-induced HTN. Impedance drop and NE renal gradient could be markers of RDN success.

8 páginas, 2 figuras, 3 tablas., Sarcoptic mange is caused by the mite Sarcoptes scabiei and has been described in several species of domestic and wild mammals. Macroscopic lesions are predominantly hyperkeratotic (type I hypersensitivity) in fox, chamois and deer, but alopecic (type IV hypersensitivity) in wolf and some fox populations. To begin to understand the immune processes underlying these species differences in lesions, we examined skin biopsies from wolves (Canis lupus), foxes (Vulpes vulpes), chamois (Rupicapra rupicapra) and red deer (Cervus elaphus) naturally infested with S. scabiei. Twenty skin samples from five animals per species were used. Sections were immuno-stained with primary antibodies against Iba1 to detect macrophages, lambda chain to detect plasma cells, CD3 to detect T lymphocytes and CD20 to detect B lymphocytes. Skin lesions contained significantly more inflammatory cells in the fox than in the wolf and chamois. Macrophages were the most abundant inflammatory cells in the lesions of all the species studied, suggesting a predominantly innate, non-specific immune response. Lesions from the wolf contained higher proportions of macrophages than the other species, which may reflect a more effective response, leading to alopecic lesions. In red deer, macrophages were significantly more abundant than plasma cells, T lymphocytes and B lymphocytes, which were similarly abundant. The fox proportion of plasma cells was significantly higher than those of T and B lymphocytes. In chamois, T lymphocytes were more abundant than B lymphocytes and plasma cells, although the differences were significant only in the case of macrophages. These results suggest that all the species examined mount a predominantly innate immune response against S. scabiei infestation, while fox and chamois may also mount substantial humoral and cellular immune responses, respectively, with apparently scarce effectiveness that lead to hyperkeratotic lesions., This work was partially supported by the Principado de Asturias, PCTI 2018–220 (GRUPIN: IDI2018-000237 and FEDER). Ms. Ileana Z. Martínez was supported by a Fundación Carolina PhD scholarship (2017 call).

7 páginas, 2 tablas, 3 figuras., Spanish goat encephalitis virus (SGEV) is a novel tick-borne flavivirus subtype, closely related to the flavivirus louping ill virus (LIV). SGEV caused a severe, acute and mortal neurological disease outbreak in northern Spain in a goat herd. In order to characterize the cell population in lesions and to determine the distribution of the inflammatory cells, central nervous system (CNS) samples of nine female Alpine goats challenged subcutaneously with SGEV over the right thorax behind the elbow were evaluated using immunohistochemistry (microglia-Iba1, T lymphocytes-CD3, B lymphocytes-CD20 and astrocytes-GFAP). The number of microglia (37.8 %) and T lymphocytes (21.5 %) was greater than the number of B lymphocytes (16.8 %). Goats were classified into clusters based on the severity of histological lesions in CNS (A-mild to moderate lesions and B-severe lesions). Microglia was significantly more abundant than T and B lymphocytes in cluster B (severe lesions). The total area occupied by glial foci revealed that medulla oblongata and spinal cord were the most affected tissues. Astrogliosis (GFAP+) was present in the majority of the CNS sections being near to the pial surface. The lesion predominance on the right side of the medulla oblongata, which could be associated to the site of challenge suggestive of neurotropic route was also statistically confirmed. Results suggest that the cellular immune response would be the most important response to the SGEV infection., This work was partially supported by a grant from Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), reference number E- RTA2013-00013-C04-04 (FEDER co-funded) and the Principado de Asturias, PCTI 2018–220 (GRUPIN: IDI2018-000237 and FEDER). Ms. Ileana Z. Martínez was supported by a Fundacion Carolina PhD scholarship (2017 call). We thank Dr. Kevin P. Dalton for critically reviewing this article.

Three recombinant outer membrane proteins (rOmps) from the Haemophilus parasuis Nagasaki strain (serovar 5 reference strain), rOmpP2, rOmpP5 and rOmpD15, which have previously shown protection against H. parasuis infection in mice, were cloned, expressed and evaluated as vaccine antigens in colostrum-deprived pigs. When these animals were immunized with these rOmps and were later challenged intratracheally with 108 CFUs of the Nagasaki strain, no protection was seen in terms of survival, clinical signs, pathological results and recovery of H. parasuis. We hypothesized that a possible explanation for this lack of protection could be the low number of epitopes accessible to the immune system as a consequence of their poor exposure on the bacterial surface so that the immune response would not be able to protect against experimental infection by H. parasuis when a fully susceptible animal model, such as pigs, was used.

Resumen Introduccion y objetivos Los nuevos stents farmacoactivos (SFA), disenados para solventar las limitaciones de los existentes, han de someterse inicialmente al analisis preclinico. El objetivo es analizar la eficacia y la seguridad de nuevos SFA con polimero biodegradable en comparacion con stents convencionales (SC) y SFA comercializados en el modelo de arteria coronaria sana porcina. Metodos Se implantaron aleatoriamente 101 stents (SC y stents liberadores de sirolimus con polimero biodegradable: 3 formulaciones test [BD1, BD2 y BD3], Orsiro, Biomime y Biomatrix) en las arterias coronarias de 34 cerdos domesticos. Se completo estudio angiografico e histomorfometrico al mes (n = 83) y a los 3 meses (n = 18). Resultados Los stents se implantaron en proporcion stent/arteria de 1,31 ± 0,21, sin diferencias entre grupos. Al mes, los nuevos stents (BD1, BD2 y BD3) mostraron menos perdida tardia y reestenosis angiografica, asi como menor area neointimal y reestenosis histologica (p Conclusiones En este modelo preclinico, los nuevos SFA con polimero biodegradable estudiados presentan menos reestenosis que los SC, sin diferencias significativas en seguridad y eficacia respecto a SFA comercializados.

New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries.We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later.The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P.0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls.In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES.

BACKGROUND: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. OBJECTIVES: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model. METHODS: Twenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T2 and T1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. RESULTS: The earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage. CONCLUSIONS: T2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy. This study was partially supported by grants from the Ministerio de Ciencia, Innovacion y Universidades through the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (P116/02110), the European Regional Development Fund (SAF2013-49663-EXP), and the Spanish Society of Cardiology (FEC basic science in cardiology grant). This research program is part of an institutional agreement between the CNIC and FIIS-Fundacion Jimenez Diaz. This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare, and is part of a bilateral research program between Hospital de Salamanca Cardiology Department and the CNIC. The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades, and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505). Drs. Galan-Arriola and Villena-Gutierrez are P-FIS fellows (Instituto de Salud Carlos III). Dr. Fernandez-Jimenez has received funding through the European Union Horizon 2020 Research and Innovation program under grant MSCA-IF-GF-707642. Dr. Sanchez -Gonzalez is an employee of Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Sí

In social media users share a lot of content, such as comments, news, photos, videos, etc. This information can be used by automated systems to segment the users to provide them with specific recommendations or focused content. One of the most popular way to segment the users is by age and gender. Nevertheless, such demographic variables are frequently hidden, and thus becomes useful to indirectly infer them. Commonly, these variables are learned using the text comments the users publish, analyzing the style of writing or frequency of words. In this paper, we present a study of several machine learning models that employ user generated images and text trying to exploit both types of information to infer the age and gender for Pinterest users. We experiment with the models using a dataset composed of 548,761 pins, posted by 264 users. Each pin is a combination of an image and a short comment. We transformed the images to a deep visual representation using the pretrained convolutional neural network ResNet-50, and transformed the comments using the tf-idf method. We compare the models among them and between the types of information using different performance metrics. Our experiments show interesting results and the viability of employing the user generated image and text content to characterize users.

Initial preclinical studies are required during the process of improving polymers, platforms, and drug-eluting systems for new coronary stent designs. Our objective was to analyze the efficacy and safety of new drug-eluting stent models compared with a conventional stent and commercialized drug-eluting stents in an experimental model with healthy porcine coronary arteries.Sixty stents (conventional stent, new sirolimus-eluting stents: drug-eluting stents 1, 2 and 3; Cypher(®) and Xience(®)) were randomly placed in the coronary arteries of 20 Large White domestic pigs. Angiographic and histomorphometric studies were done 28 days later.The stents were implanted at a stent/artery ratio of 1.34±0.15, with no significant differences between groups. The new stents showed less late loss and angiographic restenosis than conventional stents (P=.006 and P.001, respectively). Histologically, restenosis and neointimal area were lower with all the new platforms than with the conventional stents (P.001 for each variable), and no differences were found vs the drug-eluting stents on the market. Safety data showed that endothelialization was lower with drug-eluting stents than with conventional stents, except for drug-eluting stent 3 (P=.084). Likewise, inflammation was lower with drug-eluting stent 3 than with other stents.The new drug-eluting stent platforms studied are associated with less restenosis than conventional stents and showed no significant differences in safety or efficacy vs commercialized drug-eluting stents.

Las tutorías son una herramienta útil en el binomioenseñanza-aprendizaje universitario, aunque su desarrollo se ve dificultado enlas aulas masificadas. Con este estudio se ha pretendido potenciar esta funcióntutorial en una asignatura en la que concurre esta circunstancia, con el fin demejorar el rendimiento académico del alumnado. Para ello, se ha realizado el seguimientode la asignatura de “Microbiología e Inmunología” del Grado en Veterinaria dela Universidad de León, mediante la plataforma virtual Moodle. Cuarenta estudiantes se incorporaron voluntariamente (25%de la matrícula total) al proyecto, en menos de un día. Se realizaron trescuestionarios de quince preguntas sobre la materia impartida, con el objetivo defomentar el trabajo del estudiante y su aproximación al profesorado desde losprimeros momentos. Finalizado el periodo de resolución establecido, losestudiantes obtenían automáticamente la calificación y las respuestascorrectas. Posteriormente, se habilitaban tres días para aclarar dudas mediantecorreo electrónico. Además, se realizaron encuestas para conocer el grado desatisfacción. El análisis estadístico reveló que el porcentaje de alumnos tutelados(95,2%) que se presentó al examen final fue significativamente mayor que entrelos no tutelados (74,8%), lo que también se observó en la proporcion deaprobados (60,0% versus 43,1%). Lacalificación numérica fue también mayor entre los participantes y el porcentajede los que obtuvieron la calificación de “sobresaliente” fue el doble que en losnotutelados (2,7% versus 1,1%). El87,5% de los participantes se mostró satisfecho con esta metodología docente.Teniendoen cuenta estos resultados, se aconseja su aplicación en asignaturas con unelevado número de alumnos.

10 páginas, 4 figuras, 2 tablas., Spanish goat encephalitis virus (SGEV), a novel subtype of tick-borne flavivirus closely related to louping ill virus, causes a neurological disease in experimentally infected goats and lambs. Here, the distribution of microglia, T and B lymphocytes, and astrocytes was determined in the encephalon and spinal cord of eight Assaf lambs subcutaneously infected with SGEV. Cells were identified based on immunohistochemical staining against Iba1 (microglia), CD3 (T lymphocytes), CD20 (B lymphocytes), and glial fibrillary acidic protein (astrocytes). In glial foci and perivascular cuffing areas, microglia were the most abundant cell type (45.4% of immunostained cells), followed by T lymphocytes (18.6%) and B lymphocytes (4.4%). Thalamus, hypothalamus, corpus callosum, and medulla oblongata contained the largest areas occupied by glial foci. Reactive astrogliosis occurred to a greater extent in the lumbosacral spinal cord than in other regions of the central nervous system. Lesions were more frequent on the side of the animal experimentally infected with the virus. Lesions were more severe in lambs than in goats, suggesting that lambs may be more susceptible to SGEV, which may be due to species differences or to interindividual differences in the immune response, rather than to differences in the relative proportions of immune cells. Larger studies that monitor natural or experimental infections may help clarify local immune responses to this flavivirus subtype in the central nervous system., This work was partially supported by a FEDER co-funded grant from the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (E-RTA2013-00013-C04-04), Ministerio de Ciencia, Innovación y Universidades (MCIU) and the Agencia Estatal de Investigación (AEI) reference project RTI2018-096010-B-C21 (FEDER co-funded) and by the Principado de Asturias, PCTI 2018–220 (GRUPIN: IDI2018-000237 and FEDER). Ms. Ileana Z. Martínez was supported by a Fundación Carolina PhD scholarship (2017 call).

Tutoring is a useful tool in the university teaching-learning binomial, although its development is impaired in large classes. Recent improvements in information and communication technologies have made tutoring possible via the Internet. The aim of this study was to evaluate the efficacy of mixed-method academic tutoring in two basic subjects in Veterinary Science studies at the University of León (Spain) to optimize the usefulness of tutoring support in the college environment. This quasi-experimental study was firstly carried out as a pilot study in a small group of tutored students of "Cytology and Histology" (CH) (47/186; 25.3%) and "Veterinary Pharmacology" (VP) (33/141; 23.4%) subjects, and was implemented in a large class of CH the next academic year (150 students) while comparing the results with those obtained in a previous tutorless course (162 students). Tutored students were given access to online questionnaires with electronic feedback on each subject. In addition to traditional tutoring carried out in both tutored and tutorless students, the pilot study included three sessions of face-to-face tutoring in order to monitor the progress of students. Its efficacy was assessed by monitoring students' examination scores and attendance as well as a satisfaction survey.Although the examination attendance rate in the pilot study was not significantly different between tutored and tutorless groups in both subjects, an increase for numerical scores in tutored groups was observed, with a significant higher final score in VP (p = 0.001) and in the CH practice exams (first term, p = 0.009; final, p = 0.023). Good and merit scores were also better in tutored students with significant differences in VP (p = 0.005). Students felt comfortable with the tutoring service (100% in CH; 91.7% in VP). Implementation of this additional support in CH also resulted in a significant increase of attendance at the final exam in tutored courses (87.3% versus 77.2%; p = 0.026), scaled (p = 0.001) and numerical scores (final score, p = 0.001).Online tutoring support, together with conventional teaching methods, may be a useful method to incorporate student-centered learning in basic subjects in Veterinary Science.

Background Tutoring is a useful tool in the university teaching-learning binomial, although its development is impaired in large classes. Recent improvements in information and communication technologies have made tutoring possible via the Internet. The aim of this study was to evaluate the efficacy of mixed-method academic tutoring in two basic subjects in Veterinary Science studies at the University of León (Spain) to optimize the usefulness of tutoring support in the college environment. This quasi-experimental study was firstly carried out as a pilot study in a small group of tutored students of “Cytology and Histology” (CH) (47/186; 25.3%) and “Veterinary Pharmacology” (VP) (33/141; 23.4%) subjects, and was implemented in a large class of CH the next academic year (150 students) while comparing the results with those obtained in a previous tutorless course (162 students). Tutored students were given access to online questionnaires with electronic feedback on each subject. In addition to traditional tutoring carried out in both tutored and tutorless students, the pilot study included three sessions of face-to-face tutoring in order to monitor the progress of students. Its efficacy was assessed by monitoring students’ examination scores and attendance as well as a satisfaction survey. Results Although the examination attendance rate in the pilot study was not significantly different between tutored and tutorless groups in both subjects, an increase for numerical scores in tutored groups was observed, with a significant higher final score in VP (p = 0.001) and in the CH practice exams (first term, p = 0.009; final, p = 0.023). Good and merit scores were also better in tutored students with significant differences in VP (p = 0.005). Students felt comfortable with the tutoring service (100% in CH; 91.7% in VP). Implementation of this additional support in CH also resulted in a significant increase of attendance at the final exam in tutored courses (87.3% versus 77.2%; p = 0.026), scaled (p = 0.001) and numerical scores (final score, p = 0.001). Conclusions Online tutoring support, together with conventional teaching methods, may be a useful method to incorporate student-centered learning in basic subjects in Veterinary Science. Electronic supplementary material The online version of this article (doi: 10.1186/s12917-018-1330-6) contains supplementary material, which is available to authorized users.

Resumen Introduccion y objetivos Los balones liberadores de paclitaxel tienen demostrada eficacia en el tratamiento y la prevencion de la restenosis. Sin embargo, no todos los dispositivos comercializados son igualmente efectivos; por ello es importante comparar los resultados en un modelo preclinico. Nuestro objetivo es analizar la seguridad y la eficacia preclinicas de distintos dispositivos. Metodos En 17 cerdos domesticos (25 ± 3 kg) se implantaron 51 stents metalicos (Architect®, iVascular), uno en cada rama coronaria principal, y se sobredilataron con distintos balones de control (n = 10) o liberadores de paclitaxel: balon liberador de paclitaxel 1 (iVascular) (n = 15); balon liberador de paclitaxel 2 (iVascular) (n = 16) e In.Pact Falcon® (Medtronic) (n = 10). Tras 28 dias, se analizaron los resultados de restenosis (angiografia e histomorfometria) y de reparacion vascular: dano vascular, endotelizacion, persistencia de fibrina e inflamacion. Resultados Los distintos balones liberadores de paclitaxel mostraron valores similares de estenosis en el seguimiento significativamente menores que los controles: angiografia, el 9 ± 12% frente al 34 ± 18% (p Conclusiones En este modelo preclinico, los balones liberadores de paclitaxel analizados mostraron una reduccion significativa de la restenosis. Aunque no se observaron datos de dano vascular o inflamacion persistentes, si se apreciaron los efectos de la accion farmacologica en forma de endotelizacion retrasada y acumulacion de fibrina.

A vertebral mass in a dog with an acute onset paraparesis was identified by magnetic resonance imaging. A poorly differentiated hemangiosarcoma was diagnosed by histopathology and immunohistochemistry. Endothelial nitric oxide synthase could be a new differential marker for poorly differentiated hemangiosarcoma in dogs. Immunohistochemical detection of p53 phosphorylated at Serine392, p53, CD117, and CD44 suggest targets for design of therapeutic strategies.

Preclinical research into all aspects of myocardial ischemia, infarction and reperfusion has made use of a range of models, from ex vivo models of the isolated beating heart to animal models of coronary artery occlusion produced using surgical or endovascular techniques. In the area of cardiac ischemia, such research has led to the development of several forms of treatment that were subsequently found to be effective in patients. The principle tools for reducing the extent of myocardial necrosis, and thereby improving prognosis, comprise different techniques for recanalization of the occluded artery responsible for an infarction, all of which must be implemented as soon as possible (“time is muscle”). However, reperfusion can itself result in injury that exacerbates the effects of an infarction. A number of ways of limiting reperfusion injury have been tested successfully in animal models (e.g. various pharmacological treatments and different forms of myocardial conditioning) but none has proven effective when applied clinically. The recent explosion of interest in regenerative medicine has been particularly important in the area of cardiovascular disease, and future development will require the best possible set of preclinical tests. Animal models continue to be refined, with the ultimate goal being the perfect model that replicates all aspects of human biology and pathology.

In recent years, we have witnessed a revolution in the treatment of coronary artery disease. The development and improvement of drug eluting stents (DES) have lowered the incidence of restenosis to one-digit figures. In the search for a superior efficacy, animal models have played a key role. The classical swine model of coronary stenting remains the preferred model to measure restenosis, although the rabbit iliac artery stenting has become an accepted alternative. After widespread clinical use of DES, an unforeseen complication arose: late stent thrombosis. In a back-to-bench step, some data from animal models helped to explain the phenomenon. A delayed and incomplete vascular healing was detected. Toxic and hypersensitivity reactions to polymers and/or drugs seem to be the underlying causes. So, translational research focused on the safety aspect of these devices: development of better drug carriers as absorbable polymers or fully bioresorbable scaffolds, selection of different drugs and assessment of the re-endothelialization process. We review and evaluate the efficacy and safety of coronary stents in different animal models. Further improvements in this field such as, the selection of better animal models (e.g. hyperlipidemic, diabetic, atherosclerotic) that closely mimic the clinical setting and longer follow-up periods to detect late complications are also discussed.

This study aimed to characterize the type of immune response induced by an experimental vaccine based on a mutant Haemophilus parasuis transferrin binding protein (Tbp) B (Y167A) defective in its ability to bind porcine transferrin. Clinical and pathological signs, bacterial clearance, antibody response and the cytokine profile in alveolar macrophages and spleen after the vaccination and challenge of twenty-two colostrum-deprived pigs with 10(8) CFU of H. parasuis were analysed. Pigs vaccinated with Y167A were compared to those vaccinated with native TbpB (nTbpB), those treated with a commercial bacterin (CB) against Glasser's disease, those unvaccinated challenged (CH) and those unvaccinated unchallenged (UNCH) pigs. The rectal temperatures of Y167A pigs resembled those of UNCH pigs and were significantly lower than those of the nTbpB, CB and CH animals. A major reduction in pathological changes of the challenged pigs was observed in the Y167A group. H. parasuis was cleared from 88.9% of the samples from Y167A pigs versus 60.0% and 55.6% from those of the CB and nTbpB groups, respectively. The antibody response elicited by Y167A by ELISA was notably higher than that observed for nTbpB and CB pigs and was capable of preventing the expression and secretion of IL-8. The expression of IL-4 and IL-5, which were associated with the specific antibody levels, suggests that the main mechanism of protection conferred by Y167A vaccine is based on a strong T-helper 2 response.

Resumen Introduccion y objetivos Los stents farmacoactivos son una herramienta util para prevenir la reestenosis, pero los mecanismos involucrados en la respuesta proliferativa tras su implante aun no son conocidos en su totalidad. El objetivo de este estudio es comparar la histomorfometria vascular coronaria tras el implante de stents sin recubrir o stents farmacoactivos en un modelo porcino. Metodos En 20 hembras de cerdos de la raza Large White de 2 meses de edad se implanto de forma aleatoria un total de 60 stents distribuidos en dos grupos: convencionales (n = 20) y farmacoactivos (paclitaxel) (n = 40). A los 28 dias se procedio a eutanasia y analisis histomorfometrico. Se clasifico el grado de dano vascular en funcion de integridad o rotura de la tunica limitante elastica interna. Resultados En el grupo de integridad de lamina elastica interna no se encontraron diferencias significativas entre stents farmacoactivos y stents convencionales para las variables area de neointima y porcentaje de reestenosis (1,3 [1,1-2,2] frente a 2 [1,3-2,5] mm2; p = 0,6; y 14 [12,1-20,8] frente a 22,2 [14,1-23,3] %; p = 0,5). En cambio, en el grupo de rotura de la lamina elastica interna si se encontraron diferencias significativas (area de neointima, 1,2 [0,8-2] frente a 2,9 [2,3-3,7] mm2; p = 0,001 y porcentaje de reestenosis, 16,63 [11,2-23,5] frente a 30,4 [26,4-45,7] %; p = 0,001). Conclusiones En el modelo porcino de coronarias sanas, la integridad de la lamina elastica interna no permite apreciar diferencias en la respuesta proliferativa entre stent farmacoactivo y convencional; la diferencia se establece solo cuando el dano vascular es mas profundo.

Objectives The purpose of this study was to test the ability of insulin-like growth factor (IGF)-1/hepatocyte growth factor (HGF) to activate resident endogenous porcine cardiac stem/progenitor cells (epCSCs) and to promote myocardial repair through a clinically applicable intracoronary injection protocol in a pig model of myocardial infarction (MI) relevant to human disease. Background In rodents, cardiac stem/progenitor cell (CSC) transplantation as well as in situ activation through intramyocardial injection of specific growth factors has been shown to result in myocardial regeneration after acute myocardial infarction (AMI). Methods Acute MI was induced in pigs by a 60-min percutaneous transluminal coronary angiography left anterior descending artery occlusion. The IGF-1 and HGF were co-administered through the infarct-related artery in a single dose (ranging from 0.5 to 2 μg HGF and 2 to 8 μg IGF-1) 30 min after coronary reperfusion. Pigs were sacrificed 21 days later for dose-response relationship evaluation by immunohistopathology or 2 months later for cardiac function evaluation by cardiac magnetic resonance imaging. Results The IGF-1/HGF activated c-kit positive–CD45 negative epCSCs and increased their myogenic differentiation in vitro. The IGF-1/HGF, in a dose-dependent manner, improved cardiomyocyte survival, and reduced fibrosis and cardiomyocyte reactive hypertrophy. It significantly increased c-kit positive–CD45 negative epCSC number and fostered the generation of new myocardium (myocytes and microvasculature) in infarcted and peri-infarct/border regions at 21 and 60 days after AMI. The IGF-1/HGF reduced infarct size and improved left ventricular function at 2 months after AMI. Conclusions In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function.

Late thrombosis of coronary drug-eluting stents is an infrequent but serious complication of percutaneous transluminal coronary angioplasty. The best predictor of this event is the lack of endothelialization of stent struts. The objective of this study is to characterize and quantify the time course of endothelialization of different stents implanted in nonatherosclerotic swine coronary arteries. Thirty-three Carbofilm-coated stents were implanted percutaneously in 11 anesthetized domestic, crossbred pigs (weight 25 ± 3 kg, 2 months old). Each animal received 1 stainless steel stent (SS), 1 cobalt-chromium stent (CCS), and 1 tacrolimus-eluting stent (TES) in each coronary artery. Follow-up periods were 1 day (n = 9 stents), 3 days (n = 9 stents), and 7 days (n = 15 stents). Longitudinal sections of the stented vessels were examined using scanning electron microscopy. At 1 day, there was scarce, patchy endothelialization with areas of fibrin; the endothelialization rate was similar for all the stents (SS, 29% ± 23%; CCS, 29% ± 24%; TES, 31% ± 25%; P = .9). At 3 days, there were more endothelial cells but with immature features and giant cells over fibrin; the endothelialization was greater in SS and CCS than in TES (SS, 79% ± 14%; CCS, 81% ± 17%; TES, 46% ± 9%; P = .007). At 7 days, arteries showed better endothelialization with few giant cells; the endothelialization was greater in SS and CCS than in TES (SS, 95% ± 4%; CCS, 98% ± 4%; TES, 79% ± 9%; P = .01). In conclusion, the described model is useful for the analysis of endothelialization of coronary stents and facilitates measurement of its rate of formation and characterization of the involved cell types.

A tumour located in the pectoral region and the left front flipper was observed in a 29-year-old female California sea lion (Zalophus californianus) that died following signs of respiratory disease and inappetence. Metastases were present in the lung and adrenal gland. The histological pattern of the tumour was variable. In some areas the tumour consisted of pleomorphic fibroblast-like cells arranged in a storiform pattern, while in other areas it comprised oval or polygonal cells with round to oval nuclei and some bizarre cells arranged in an alveolar pattern. Occasionally, multinucleated giant cells were observed. Immunohistochemically, the neoplastic cells only expressed vimentin. On the basis of the microscopical and immunohistochemical features the tumour was diagnosed as an undifferentiated high-grade pleomorphic sarcoma. This type of neoplasm with disseminated involvement of other organs is rare in all species and has never been reported in California sea lions.

Haemophilus parasuis is the agent responsible for causing Glässer's disease, which is characterized by fibrinous polyserositis, polyarthritis, and meningitis in pigs. In this study, we have characterized native outer membrane proteins with affinity to porcine transferrin (NPAPT) from H. parasuis serovar 5, Nagasaki strain. This pool of proteins was used as antigen to developed two vaccine formulations: one was adjuvanted with a mineral oil (Montanide IMS 2215 VG PR), while the other was potentiated with a bacterial neuraminidase from Clostridium perfringens . The potential protective effect conferred by these two vaccines was compared to that afforded by two other vaccines, consisting of recombinant transferrin-binding protein (rTbp) A or B fragments from H. parasuis , Nagasaki strain, and by a commercially available inactivated vaccine. Five groups of colostrum-deprived piglets immunized with the vaccines described above, one group per each vaccine, and a group of nonvaccinated control animals were challenged intratracheally with a lethal dose (3 × 10 8 CFU) of H. parasuis , Nagasaki strain. The two vaccines containing rTbps yielded similar results with minimal protection against death, clinical signs, gross and microscopic lesions, and H. parasuis invasion. In contrast, the two vaccines composed of NPAPT antigen and commercial bacterin resulted in a strong protection against challenge (without deaths and clinical signs), mild histopathological changes, and no recovery of H. parasuis , thus suggesting their effectiveness in preventing Glässer's disease outbreaks caused by serovar 5.

Introduction Progress in cardiovascular regenerative medicine research requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to assess the validity of a porcine endovascular model of myocardial infarction and reperfusion. Methods Fifteen domestic pigs (Large White race) were anesthetized and pre-medicated with amiodarone. Endovascular fluoroscopy-guided coronary procedures were performed to occlude the mid-left anterior descending artery using a coronary angioplasty balloon. Occlusion was confirmed by angiography and electrocardiography. After 75 min the balloon catheter system was withdrawn and the presence of reperfusion flow was verified. The animals were sacrificed after 1 and 2 weeks of follow-up, the hearts were explanted, and the extent of myocardial infarction with respect to the left ventricle was quantified. Results Overall survival rate was 67%. Five animals died prematurely: 3 showing signs of heart failure, 1 had reperfusion failure (final TIMI flow grade 1) and 1 succumbed to acute stress. The most common adverse event was ventricular fibrillation (87% of the animals) and defibrillation was effective in all affected animals. The extent of myocardial infarct in the animals followed-up for 1 and 2 weeks was similar (20.4 ± 4.3% vs. 20.9 ± 2.8%, respectively; p = 0.8) but was significantly greater in the animals that died prematurely (29.5 ± 3.6%, p = 0.02). Conclusions The endovascular porcine model we have explored constitutes a feasible and reproducible alternative for the evaluation of human myocardial infarction and reperfusion.

Adult Naval Medical Research Institute (NMRI) mice, after prenatal exposure to retinoic acid (RA), were treated with a standard two-stage skin carcinogenesis regime to characterize hyperplastic epidermal foci that precede the appearance of cutaneous papillomas, and to investigate the in vivo long-term action of RA on adult mouse skin treated with DMBA (7,12 dimethyl benz[a]anthracene) and TPA (12-O-tetradecanoylphorbol 13-acetate). The results demonstrate that RA administered to pregnant mice had a long-term inhibitory action on the cell differentiation and development of hyperplastic lesions occurring prior to cancer on the adult skin of their offspring as well as a stimulatory effect on cell proliferation of these hyperplastic lesions.

[ES] La tutoría es una herramienta útil en el proceso de enseñanza-aprendizaje universitario, aunque su desarrollo se ve dificultado en las aulas masificadas. Con este estudio se ha pretendido potenciar esta función tutorial en una asignatura en la que concurre esta circunstancia, con el fin de mejorar el rendimiento académico del alumnado. Para ello, se ha implementado un programa de tutorías en línea en la asignatura de “Microbiología e Inmunología” del Grado en Veterinaria de la Universidad de León, mediante la plataforma virtual Moodle. Cuarenta estudiantes se incorporaron voluntariamente (25% de la matrícula) al estudio, en menos de un día. Se elaboraron tres cuestionarios de quince preguntas sobre la materia impartida, con el objetivo de fomentar el trabajo del estudiante. Finalizado el periodo de resolución establecido, los estudiantes obtenían automáticamente la calificación y las respuestas correctas. Posteriormente, se habilitaban tres días pa, [EN] Tutoring is a useful tool in the university teaching-learning process, although its development is impaired in overcrowded classrooms. In this study, we have tried to strengthen the tutoring function, which is complex in subjects with high number of students, in order to improve academic efficiency. For this purpose, on-line tutoring have been implemented in the subject “Microbiology and Immunology”, belonging to Veterinary Degree at the University of León, by means of Moodle. Forty students who registered voluntarily were accepted (25% of the students enrolled). They filled these places in less than one day. Three on-line questionnaires with fifteen questions each about the subject taught were carried out, in order to promote the student work. Once the time given for their reply had finished, students automatically got the answers and their marks. Then, they had three days to clarify any doubts by e-mail. In addition, satisfaction surveys were made among stud, La realización de este estudio ha sido posible gracias a la concesión de un Proyecto de Ayuda a la Innovación Docente (PAID), denominado “La tutoría presencial y on line como herramienta para la adaptación y mejora en el rendimiento académico de asignaturas básicas en el Grado en Veterinaria (TUBAVET)”, concedido por la Universidad de León en su convocatoria de 2013. Este proyecto forma parte de un trabajo coordinado por dos departamentos de la Universidad de León (Ciencias Biomédicas y Sanidad Animal), que fue galardonado con el primer premio al mejor trabajo presentado en el “I Congreso de Docencia Veterinaria”, celebrado en Lugo en septiembre de 2014, organizado por la “Asociación Española de Veterinarios Docentes (VetDoc)”.