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Fibroblast growth factor 21 is an endocrine factor, secreted mainly by the liver, that exerts metabolic actions that favour glucose metabolism. Its role in the heart is unknown. Here we show that Fgf21 −/− mice exhibit an increased relative heart weight and develop enhanced signs of dilatation and cardiac dysfunction in response to isoproterenol infusion, indicating eccentric hypertrophy development. In addition, Fgf21 −/− mice exhibit enhanced induction of cardiac hypertrophy markers and pro-inflammatory pathways and show greater repression of fatty acid oxidation. Most of these alterations are already present in Fgf21 −/− neonates, and treatment with fibroblast growth factor 21 reverses them in vivo and in cultured cardiomyocytes. Moreover, fibroblast growth factor 21 is expressed in the heart and is released by cardiomyocytes. Fibroblast growth factor 21 released by cardiomyocytes protects cardiac cells against hypertrophic insults. Therefore, the heart appears to be a target of systemic, and possibly locally generated, fibroblast growth factor 21, which exerts a protective action against cardiac hypertrophy. Fibroblast growth factor 21 (FGF21) regulates energy metabolism in peripheral tissues. Here Planavila and colleagues show that FGF21 also acts directly on cardiomyocytes, thereby protecting mice against cardiac hypertrophy.

It is almost 20 years since the largest observational, multicentre study evaluating the risks of mortality associated with general anaesthesia in horses. We proposed an internet-based method to collect data (cleaned and analysed with R) in a multicentre, cohort, observational, analytical, longitudinal and prospective study to evaluate peri-operative equine mortality. The objective was to report the usefulness of the method, illustrated with the preliminary data, including outcomes for horses seven days after undergoing general anaesthesia and certain procedures using standing sedation. Within six months, data from 6701 procedures under general anaesthesia and 1955 standing sedations from 69 centres were collected. The results showed (i) the utility of the method; also, that (ii) the overall mortality rate for general anaesthesia within the seven-day outcome period was 1.0%. In horses undergoing procedures other than exploratory laparotomy for colic (“noncolics”), the rate was lower, 0.6%, and in “colics” it was higher, at 3.4%. For standing sedations, the overall mortality rate was 0.2%. Finally, (iii) we present some descriptive data that demonstrate new developments since the previous CEPEF2. In conclusion, horses clearly still die unexpectedly when undergoing procedures under general anaesthesia or standing sedation. Our method is suitable for case collection for future studies.

Protein language models have been tested and proved to be reliable when used on curated datasets but have not yet been applied to full proteomes. Accordingly, we tested how two different machine learning-based methods performed when decoding functional information from the proteomes of selected model organisms. We found that protein language models are more precise and informative than deep learning methods for all the species tested and across the three gene ontologies studied, and that they better recover functional information from transcriptomic experiments. The results obtained indicate that these language models are likely to be suitable for large-scale annotation and downstream analyses, and we recommend a guide for their use. Graphical Abstract Graphical Abstract

Background Optimization of an RNA-Sequencing (RNA-Seq) pipeline is critical to maximize power and accuracy to identify genetic variants, including SNPs, which may serve as genetic markers to select for feed efficiency, leading to economic benefits for beef production. This study used RNA-Seq data (GEO Accession ID: PRJEB7696 and PRJEB15314) from muscle and liver tissue, respectively, from 12 Nellore beef steers selected from 585 steers with residual feed intake measures (RFI; n  = 6 low-RFI, n  = 6 high-RFI). Three RNA-Seq pipelines were compared including multi-sample calling from i) non-merged samples; ii) merged samples by RFI group, iii) merged samples by RFI and tissue group. The RNA-Seq reads were aligned against the UMD3.1 bovine reference genome (release 94) assembly using STAR aligner. Variants were called using BCFtools and variant effect prediction (VeP) and functional annotation (ToppGene) analyses were performed. Results On average, total reads detected for Approach i) non-merged samples for liver and muscle, were 18,362,086.3 and 35,645,898.7, respectively. For Approach ii), merging samples by RFI group, total reads detected for each merged group was 162,030,705, and for Approach iii), merging samples by RFI group and tissues, was 324,061,410, revealing the highest read depth for Approach iii). Additionally, Approach iii) merging samples by RFI group and tissues, revealed the highest read depth per variant coverage (572.59 ± 3993.11) and encompassed the majority of localized positional genes detected by each approach. This suggests Approach iii) had optimized detection power, read depth, and accuracy of SNP calling, therefore increasing confidence of variant detection and reducing false positive detection. Approach iii) was then used to detect unique SNPs fixed within low- (12,145) and high-RFI (14,663) groups. Functional annotation of SNPs revealed positional candidate genes, for each RFI group (2886 for low-RFI, 3075 for high-RFI), which were significantly ( P  < 0.05) associated with immune and metabolic pathways. Conclusion The most optimized RNA-Seq pipeline allowed for more accurate identification of SNPs, associated positional candidate genes, and significantly associated metabolic pathways in muscle and liver tissues, providing insight on the underlying genetic architecture of feed efficiency in beef cattle.

Anaesthesia in dogs carries measurable risk, and whether this varies by breed is uncertain. We analysed a prospective, multicentre cohort of 55,019 canine anaesthetic procedures from premedication to 48 h post-extubation; after excluding euthanasias and non-anaesthetic deaths, 54,542 anaesthetics remained. Mixed-breed dogs served as the benchmark. Unadjusted mortality by breed, Fédération Cynologique Internationale (FCI) groups and sections used Wilson 95% CIs and χ2/Fisher tests; robust Poisson models adjusted for ASA status. Overall mortality was 0.69% (378/54,542; 95% CI 0.62–0.76), with mixed-breed dogs at 0.68% (109/16,129). Unadjusted rates were higher for German Shepherd Dog (1.46%), Chihuahua (1.35%) and Bulldog (1.26%); no FCI group differed, while the Chihuahueno section was higher. Brachycephalic dogs showed higher crude mortality than non-brachycephalics (0.82% vs. 0.65%), but this attenuated with ASA adjustment (RR 1.19, 95% CI 0.96–1.47). MDR1-associated breeds did not differ in crude or adjusted analyses (adjusted RR, 1.14; 95% CI, 0.61–2.14). After ASA adjustment, excess risk persisted for Chihuahua (RR 1.80, 95% CI 1.08–2.99) and Spanish Water Dog (RR 2.72, 95% CI 1.23–6.01), but not for German Shepherd Dog or Bulldog. Anaesthetic mortality was low overall; between-breed differences largely reflected case severity, supporting breed-aware, ASA-centred risk communication and further breed-specific research.

Lumbar and lumbosacral pain in dogs often involves multiple concurrent spinal pathologies, complicating the identification of primary pain generators. This study assessed the associations between MRI-diagnosed spinal pathologies and pain to provide clinically relevant insights for their diagnosis and management. MRI scans and clinical records of 518 client-owned dogs were retrospectively reviewed, documenting demographic data, pain status, and MRI findings. Multivariable logistic regression models evaluated the associations between spinal pathologies and pain, adjusting for age and weight. The intervertebral disc (IVD) extrusion was the primary pathology associated with lumbar pain, while radiculopathy had the strongest association with lumbosacral pain. Additional lumbosacral pathologies, including foraminal stenosis, IVD bulging, and IVD protrusion, were also significantly associated with pain. However, some dogs with MRI-diagnosed abnormalities showed no pain, whereas others with pain had no detectable MRI pathology, underscoring the need to interpret imaging within the clinical context. Pain responses observed during physical examination often overlapped between spinal and hip conditions, complicating diagnostic accuracy. These findings emphasise the importance of integrating imaging, clinical assessment, and targeted diagnostic techniques to improve pain localisation and treatment decisions, providing veterinarians with valuable data to refine the management of lumbar and lumbosacral pain in dogs.

Pimobendan is an inotropic and vasodilator drug with no sympathomimetic effects. This study aimed to evaluate the haemodynamic effects of pimobendan during anaesthesia in healthy senior dogs. A prospective, randomised, triple-blinded, placebo-controlled clinical study was conducted. Thirty-three dogs (median [range]: 9 [7, 12] years) were anaesthetised for surgical procedures. The dogs were randomly allocated into two groups: eighteen dogs received intravenous pimobendan at a dose of 0.15 mg/kg (PIMOBENDAN), and fifteen dogs received intravenous saline solutions at a dose of 0.2 mL/kg (PLACEBO). Data were recorded before, 1 min, 10 min, and 20 min after injection. Velocity-time integral (VTI), peak-velocity (PV), and mean-acceleration (MA) were measured using an oesophageal Doppler monitor (ODM). Heart rate and mean arterial pressure were also registered. The data were analysed using a two-way ANOVA for trimmed means. Statistical differences were considered if p < 0.05. Twenty minutes after injection, the VTI (13.0 cm [10.4, 22.3]), PV (95.0 [83.0, 160] m/s), and MA (12.6 [9.40, 17.0] m/s2) were significantly higher in the PIMOBENDAN group compared to the PLACEBO group (VTI: 10.5 [6.50, 17.4] cm, PV: 80.0 [62.0, 103] m/s and MA: 10.2 [7.00, 16.0] ms2). No significant differences were observed in the rest of the variables. Using pimobendan during anaesthesia increases VTI, PV, and MA, as measured by an ODM.

Anaesthetic-related mortality in cats is uncommon, yet concerns persist regarding potential breed predispositions and the influence of brachycephalic conformation. This study evaluated breed-specific peri-anaesthetic death before and after adjustment for American Society of Anesthesiologists (ASA) physical status. It explored whether genomic lineage or brachycephalic phenotype was associated with mortality. A prospective, multicentre cohort of general anaesthetics from 198 centres was analysed. Anaesthetic-related death was defined as death during anaesthesia or within 48 h after extubation, excluding euthanasia and deaths attributed to non-anaesthetic causes. Breeds were grouped into four genomic lineages and three brachycephalic phenotypes. Mortality proportions (Wilson 95% confidence intervals) were calculated, and relative risks (RR) were estimated using Poisson regression with robust standard errors, adjusting for ASA class. Among 14,964 cats, 94 deaths occurred (0.63%; 95% CI 0.51–0.77), with mortality increasing from 0.07% (ASA I) to 33.33% (ASA V). After ASA adjustment, most breeds did not differ from European/Domestic Shorthair cats, but Persians remained at increased risk (RR 2.22; 95% CI 1.11–4.46). Mortality did not differ between genomic lineages. Moderate brachycephaly was not associated with an increased risk, whereas brachycephalic breeds (Persian, Exotic Shorthair, Himalayan) showed a higher adjusted risk (RR = 2.33; 95% CI, 1.17–4.63).

Determining the cause of death in studies assessing mortality during small animal anesthesia poses challenges due to varying definitions of anesthetic death, limited information, and differences in evaluators’ interpretations. This study aims to establish the interobserver agreement in classifying the cause of death in anesthetized animals. The observational, retrospective, multicenter study analyzed 432 deaths (83 cats and 349 dogs). Data were collected from a database of 55,022 anesthetized dogs and 14,962 anesthetized cats, created to investigate anesthetic-related mortality in these species. Three highly qualified veterinary anesthesiologists independently assessed whether the deaths were related to anesthesia, using their professional judgment. Data were collected from questionnaires that included the animal’s signalment, reason for anesthesia, ASA status, drugs, anesthetic procedures, and comments from the submitting veterinarian. Light’s Kappa and the intraclass correlation coefficient (ICC) measured interrater agreement among the three evaluators, while Cohen’s Kappa assessed interrater reliability between pairs of observers ( p  < 0.05). Evaluators A, B, and C classified 296/432 (68.5%), 264/432 (61.1%), and 54/432 (12.5%) of the cases as anesthesia-related deaths, respectively. Agreement among the three evaluators was 128/432 (29.6%) [Light’s Kappa: 0.17, p  = 0.00026; ICC: 0.06, p-value = 0.0167]. The three evaluators agreed on classifying a death as anesthetic-related in 14.1% of cases (50 out of 354 cases where at least one evaluator classified the death as anesthetic-related). Similarly, for non-anesthetic-related deaths, the three evaluators reached an agreement in 20.4% of cases (78 out of 382 cases where at least one evaluator classified the death as non-anesthetic-related). Overall, agreement between two out of three evaluators was 304/432 (70.4%). Evaluators A and B had a 65.7% agreement [Cohen’s Kappa: 0.25, p  < 0.00001], A and C had a 46.6% agreement [Cohen’s Kappa: 0.10, p  < 0.00001], and B and C had a 50.9% agreement [Cohen’s Kappa: 0.16, p  < 0.00001]. In conclusion, the evaluators’ agreement was weak, highlighting the need for a consensus on defining anesthetic mortality in dogs and cats.

Advancements in technology have fostered a continuous evolution of higher education, driving the adoption of innovative tools, including artificial intelligence (AI). This study explores veterinary students' interest in AI, their training and experiences, and their perceptions on AI integration in veterinary medicine. A comprehensive survey was administered to veterinary students at the Faculty of Veterinary Medicine of a single international university in Spain, focusing on their experience with AI, their perception of its integration into veterinary education, and their views on its future role in veterinary medicine. Six hundred and four students of 34 nationalities across all academic years answered the survey. Most students were familiar with AI tools and primarily utilize them in academic settings, recognizing AI as a valuable educational resource. The majority believed universities should encourage and regulate AI use. There was a strong desire to integrate AI-related education into the veterinary curriculum, with students eager to learn more about specific AI applications in various veterinary fields, in particular clinical patient monitoring and veterinary management. The study also highlights the need for training in AI principles and regulation. Likewise, students expressed concerns about ethical and responsible use of AI, as well as the reliability of AI responses. This study underscores the importance of integrating AI training in veterinary education to enhance students' competencies. By providing targeted training and support, universities can help students harness the potential of AI while ensuring its ethical and effective use in their careers. This research emphasizes the need for continuous curriculum adaptation to keep pace with technological advancements and meet the evolving demands of veterinary medicine education.