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Mexico is home to 14 species of lagomorphs, 6 of which are endemic. Studies on diseases affecting native lagomorphs are scarce, and in most cases, the impact on their populations remains largely unknown. Rabbit hemorrhagic disease virus (RHDV), especially the RHDV2 variant, causes a serious and extremely contagious disease, resulting in high mortality rates and major declines in wild lagomorph populations. The objectives of this study were to identify disease hotspots and critical biodiversity regions in Mexico through the combined use of disease information and lagomorph distribution maps and to determine the areas of greatest concern. In total, 19 states of Mexico recorded RHDV2 from April 2020 to August 2021, and 12 of them reported the wild species Sylvilagus audubonii, Lepus californicus, and unidentified Leporidae species. The distribution of RHDV2 in Mexico can be closely predicted from climatic variables. RHDV2 hotspots are located in the central-southern area of the Mexican Highlands and the Trans-Mexican Volcanic Belt, where the virus affects multiple species. This knowledge is essential for proposing specific actions to manage and preserve lagomorph populations at risk and address these issues as soon as possible. [ABSTRACT FROM AUTHOR]

A new form of the rabbit haemorrhagic disease virus, RHDV2, first observed in European rabbits, has spread widely among different species of hares in Europe, jackrabbits and cottontails in North America, and hares in southern Africa. However, only limited surveillance studies have been undertaken so far. It is suggested that methods developed for controlling the disease in farmed rabbits in Europe and studying the efficacy of RHDV as a biological control agent in Australia could facilitate epidemiological research on those recently affected lagomorph species. This would enable the assessment of the risk of RHDV2 to native lagomorphs, including endangered species, and the determination of the main host species of RHDV2. Because RHDV2 has not spread equally through all lagomorph species, epidemiological studies could give insights into factors important for determining host susceptibility. [ABSTRACT FROM AUTHOR]

Neuronal ceroid lipofuscinoses (NCL) are among the most prevalent neurodegenerative disorders of early life in humans. Disease‐causing variants have been described for 13 different NCL genes. In this study, a refined pathological characterization of a female rabbit with progressive neurological signs reminiscent of NCL was performed. Cytoplasmic pigment present in neurons was weakly positive with Sudan black B and autofluorescent. Immunohistology revealed astrogliosis, microgliosis and axonal degeneration. During the subsequent genetic investigation, the genome of the affected rabbit was sequenced and examined for private variants in NCL candidate genes. The analysis revealed a homozygous ~10.7 kb genomic duplication on chromosome 15 comprising parts of the MFSD8 gene, NC_013683.1:g.103,727,963_103,738,667dup. The duplication harbors two internal protein coding exons and is predicted to introduce a premature stop codon into the transcript, truncating ~50% of the wild‐type MFSD8 open reading frame encoding the major facilitator superfamily domain containing protein 8, XP_002717309.2:p.(Glu235Leufs*23). Biallelic loss‐of‐function variants in MFSD8 have been described to cause NCL7 in human patients, dogs and a single cat. The available clinical and pathological data, together with current knowledge about MFSD8 variants and their functional impact in other species, point to the MFSD8 duplication as a likely causative defect for the observed phenotype in the affected rabbit. [ABSTRACT FROM AUTHOR]

Trans fatty acids are specific unsaturated fats found in processed foods that undergo hydrogenation, leading to hepatic disorders such as metabolic-associated fatty liver disease (MAFLD) and conditions like CVD and CKD. The effects of different food samples containing trans fatty acids (elaidic and oleic acid) on the liver, heart, and kidney through antioxidant enzyme activity were investigated in animal models. Liver function tests (ALT, ALP, AST, and LDH), heart biomarker levels (CPK, TC, HDL, LDL, and triglycerides), and kidney biomarker levels (serum creatinine, blood urea nitrogen, and serum uric acid) were examined in serum of rabbits and the histopathology of liver tissues. Results showed that these biomarkers were more elevated in the Mujahid Ghee group than in the normal control, oleic acid, and Kausar Ghee groups. The concentration of antioxidant markers such as peroxidase, glutathione, catalase, thiobarbituric acid reactive substances, and superoxide dismutase were lower in the Mujahid Ghee group. HPLC showed that Mujahid Ghee had the highest quantified value of elaidic acid among all selected samples. Overall, this study demonstrated that elaidic acid in its purest form aggravated MAFLD in rabbit livers and provoked CVK and CVD. [ABSTRACT FROM AUTHOR]

Simple Summary: Mammary carcinomas have been diagnosed with increasing frequency in pet rabbits. Prognostic biomarkers are limited, and the only available treatment is surgical excision. Additional treatment options are needed, e.g., for animals in which metastases to internal organs preclude complete tumor removal. Human breast cancer may express the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1), that represents a prognostic biomarker and a possible therapeutic target. Since previous studies revealed similarities between human breast cancer and pet rabbit mammary carcinomas, this study investigated IDO1 immunostaining in 96 mammary carcinomas of 96 pet rabbits with an average age of 5.5 years. All rabbits with reported sex were female. Variable percentages of IDO1-positive tumor cells were detected in 90 (94%) carcinomas. Furthermore, IDO1 immunostaining was observed in the secretory epithelial cells of the adjacent non-neoplastic mammary tissue. This study provides further information on the molecular features of mammary carcinomas in rabbits. It also shows similarities in IDO1 expression between rabbit mammary carcinomas and human breast cancer. These findings can have a mutual benefit. They could lead the development of novel treatment options for rabbits with mammary carcinomas. In addition, they further support the value of rabbits with mammary carcinomas for breast cancer research. For mammary carcinomas in pet rabbits, prognostic biomarkers are poorly defined, and treatment is limited to surgical excision. Additional treatment options are needed for rabbit patients for which surgery is not a suitable option. In human breast cancer, the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) represents a prognostic biomarker and possible therapeutic target. This retrospective immunohistochemical study examined IDO1 in 96 pet rabbit mammary carcinomas with known mitotic count, hormone receptor status, and percentage of stromal tumor infiltrating lymphocytes (TILs). Tumors were obtained from 96 pet rabbits with an average of 5.5 years. All rabbits with reported sex (n = 88) were female or female-spayed. Of the carcinomas, 94% expressed IDO1, and 86% had sparse TILs consistent with cold tumors. Statistically significant correlations existed between a higher percentage of IDO1-positive tumor cells, lower mitotic counts, and increased estrogen receptor expression. The threshold for significance was IDO1 staining in >10% of tumor cells. These results lead to the assumption that IDO1 expression contributes to tumorigenesis and may represent a prognostic biomarker and possible therapeutic target also in pet rabbit mammary carcinomas. They also support the value of rabbits for breast cancer research. [ABSTRACT FROM AUTHOR]

Even among vaccinated rabbits, the virus that causes rabbit viral hemorrhagic disease (RHDV) has been increasing in Egypt recently. So, the current study screened the emergent RHDV of vaccinated and unvaccinated domestic rabbits in some Egyptian provinces between 2022 and 2023. 40 pooled Samples were collected from different rabbit flocks with age range of 2 months up to 4 months with high mortality rates, clinical symptoms, and post-mortem lesions related to RHDV. Hemagglutination (HA) test, reverse transcriptase-polymerase chain reaction (RT-PCR) targeting the partial VP60 and sequencing and phylogenetic analysis were conducted for genotyping of RHDV strains. The results revealed that 16 out of 40 cases that were positive for RHDV and were hemagglutinin-positive, with titer ranging from 2³ to 214 Randomly six isolates were selected for genetic sequence and phylogenetic analysis which revealed their clustering with RHDV2 strains which were detected for the first time in Upper Egypt and submitted on GenBank as (OQ925947 Assiut .vac1 to OQ925952Assiut .vac6). The nucleotide sequence identities of the six isolates were 98.8-100 % compared to each other. The recently isolated strains had nucleotide difference 23, 1 % when compared to commonly vaccinal strain (JQ995154Giza 2006). The inoculated rabbits expressed RHDV-typical signs and postmortem findings and Ninety percent (90 %) mortality rate was recorded within3-6 days post-infection. Microscopic examination revealed that presence of acute necrotizing hepatitis, congestion and widespread hemorrhages in all internal organs; liver, lungs, spleen, kidneys and brain. In conclusion, the presence of RHDV- 2 strains was detected for the first time in some Upper Egypt provinces. [ABSTRACT FROM AUTHOR]

Serological tests for the presence of antibodies to European brown hare syndrome virus and rabbit hemorrhagic disease virus type a and type 2 were performed on 275 samples of blood serum from the European brown hare by hemagglutination inhibition test and enzyme-linked immunosorbent assay. The presence of antibodies against European brown hare syndrome virus was 28% in the Czech Republic while in the Slovak Republic between 9–33%. Furthermore, the results showed the possibility of interspecies transmission, both rabbit hemorrhagic disease virus type a and rabbit hemorrhagic disease virus type 2 on the European brown hare. In case of RHDVa it is the first documented interspecies transmission, which has not yet been described. This study improved our knowledge about circulation of RHDV in Central European ecosystems and its possible ability to cross interspecies barriers. However, from an epizootiological point of view, it is likely European brown hare is not a significant source of RHD infection for domesticated rabbits. [ABSTRACT FROM AUTHOR]

Simple Summary: The study focuses on the shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN), which associates with PrP and promotes the progression of prion diseases. While genetic polymorphisms in SPRN are linked to susceptibility in several species, rabbit SPRN gene polymorphisms have not been extensively studied. Through amplicon sequencing, we identified novel single nucleotide polymorphisms (SNPs) in the rabbit SPRN gene and found strong linkage disequilibrium (LD) between them. However, strong LD was not observed between polymorphisms in the prion protein gene (PRNP) and SPRN genes in rabbits. Comparison of amino acid sequences revealed differences in SPRN between rabbits and other species susceptible or resistant to prion diseases. This study represents the first examination of genetic features of the rabbit SPRN gene. Prion disorders are fatal infectious diseases that are caused by a buildup of pathogenic prion protein (PrPSc) in susceptible mammals. According to new findings, the shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) is associated with prion protein (PrP), promoting the progression of prion diseases. Although genetic polymorphisms in SPRN are associated with susceptibility to several prion diseases, genetic polymorphisms in the rabbit SPRN gene have not been investigated in depth. We discovered two novel single nucleotide polymorphisms (SNPs) in the leporine SPRN gene on chromosome 18 and found strong linkage disequilibrium (LD) between them. Additionally, strong LD was not found between the polymorphisms of PRNP and SPRN genes in rabbits. Furthermore, nonsynonymous SNPs that alter the amino acid sequences within the open reading frame (ORF) of SPRN have been observed in prion disease-susceptible animals, but this is the first report in rabbits. As far as we are aware, this study represents the first examination of the genetic features of the rabbit SPRN gene. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, research has shown that animals' gut microbiota can regulate various physiological functions such as nutrition, metabolism, and immunity, and play an indispensable role in maintaining host gut health. At present, there are few reports on the establishment of rabbits' gut microbiota and its relationship with the host. To clarify the colonization of rabbits' gut microbiota, the changes in species during development, and the relationship between gut microbiota and rabbits' growth and development, this study determined the 16s rRNA of gut microbiota in rabbits of different age groups and preliminarily explored the changes in the types of gut microbiota during the colonization process. Six amplicon sequence variants (ASVs) that significantly affect body weight were obtained. The research results provide a firm theoretical basis for maintaining gut health and constructing new methods for rabbit breeding. This study used feces from 0-day-old (36 rabbits), 10-day-old (119 rabbits), and 60-day-old (119 rabbits) offspring rabbits and their corresponding female rabbits (36 rabbits) as experimental materials. Using 16s rRNA sequencing, the study analyzed the types and changes of gut microbiota in rabbits at different growth and development stages, as well as the correlation between gut microbiota composition and the weight of 60-day-old rabbits. All experimental rabbits were placed in the same rabbit shed. Juvenile rabbits were fed solid feed at 18 days of age and weaned at 35 days of age. In addition to identifying the dominant bacterial phyla of gut microbiota in rabbits at different age stages, it was found that the abundance of Clostridium tertium and Clostridium paraputrificum in all suckling rabbits (10-day-old) was significantly higher than that in rabbits fed with whole feed (60-day-old) (p < 0.05), while the abundance of Gram-negative bacterium cTPY13 was significantly lower (p < 0.05). In addition, Fast Expected Maximum Microbial Source Tracing (FEAST) analysis showed that the contribution of female rabbits' gut microbiota to the colonization of offspring rabbits' gut microbiota was significantly higher than that of unrelated rabbits' gut microbiota (p < 0.05). The contribution of female rabbits' gut microbiota to the colonization of gut microbiota in 0-day-old rabbits was significantly higher than that to the colonization of gut microbiota in the 10- and 60-day-old rabbits (p < 0.05). Finally, the correlation between gut microbiota composition and body weight of 60-day-old rabbits was analyzed based on a mixed linear model, and six ASVs significantly affecting body weight were screened. The above results provide important theoretical and practical guidance for maintaining gut health, improving growth and development performance, and feeding formulation in rabbits. [ABSTRACT FROM AUTHOR]

Featured Application: Postbiotic, Mundticin-like substance EM 41/3 looks as a promising additive for health status sustainability in animal husbandry. Nowadays, the use of probiotics, postbiotics, parabiotics and other beneficial natural substances dominate health status sustainability in animals. Mundticin-like substance EM 41/3 (MLS) is a thermo-stable substance of proteinaceous character—a bacteriocin (postbiotic) with a broad antimicrobial (inhibitory) spectrum produced by the horse-derived strain Enterococcus mundtii EM 41/3. The aim of this study was to find if this new one bacteriocin can have an effect and/or a similar effect in rabbits as was achieved previously by using enterocins detected and characterized in our laboratory. In addition, these tests have been conducted to secure the health of rabbits as food-derived animals. Moreover, the aim of this study was also to test the effect of MLS EM 41/3 in broiler rabbits as an animal model before its use in horses. The parameters tested were analyzed by validated methods. Administration of MLS EM 41/3 lead to a significant increase in the non-specific immunity parameter (phagocytic activity, p < 0.05), while microbiota in feces, caecum and appendix were not negatively influenced. However, the total enterococcal count was significantly increased in the EG compared to the CG (p < 0.001). Application of MLS EM 41/3 did not have a negative impact on blood biochemistry. No oxidative stress was noted. However, higher growth parameters were noted and also hydrolytic activity was increased after MLS EM 41/3 application. Finally, to check physico-chemical parameters, no negative influence on rabbit meat quality was noted. Postbiotic MLS EM 41/3 administration seems to be a contributing factor in the feeding strategy for animal health status sustainability. [ABSTRACT FROM AUTHOR]

The article discusses a study conducted by Shah and colleagues on the genetic characteristics and phylogeographic dynamics of lagoviruses. The study aimed to provide an update on the evolutionary history of lagoviruses and their emergence and re-emergence. However, the authors of this response argue that the methodologies used in the analysis were inappropriate and led to incorrect and misleading inferences. They highlight the importance of considering recombination in phylogenetic analysis and criticize the conclusions drawn by Shah et al. They also point out errors in the classification system proposed by Shah et al. and suggest that their analysis will only generate confusion in the already complex classification of lagoviruses. [Extracted from the article]

The article is a response to a comment made by Abrantes et al. on a previously published article about the genetic characteristics and phylogeographic dynamics of lagoviruses. The authors of the response address the questions raised by Abrantes et al. and defend their classification system and methodology. They argue that their classification system is not complicated and that they have used the latest tools and techniques to make it more reliable. They also explain the importance of considering recombination in virus evolution and the need to include full-length genome sequences in their analysis. The authors clarify some misunderstandings and provide additional evidence to support their findings. [Extracted from the article]

Integrated pest management (IPM) is widely recommended for managing invasive pests to maximise effectiveness. However, the extent to which IPM occurs is typically unknown. We used the rabbit in Australia as a case study to investigate whether land managers apply IPM. Using 7415 control records voluntarily submitted to RabbitScan by land managers, we found evidence of IPM in only 39%. The extent to which integration occurred depended on the control method applied [warren ripping, poison baiting, release of rabbit haemorrhagic disease virus (RHDV), warren fumigation]. Two of four major rabbit control methods were frequently integrated with at least one other method; 73% of warren ripping and 55% of poison baiting records were associated with another different control method. In contrast, only 15% of RHDV releases and 35% of warren fumigations were integrated with another different control method. This confirmed reports that land managers view RHDV release as a 'silver bullet' and release it to avoid applying more expensive but more effective control methods. We identified control sequences that were neither biologically appropriate nor cost-efficient. In some situations, where there is a risk to other animals, or land managers lack suitable equipment, it may be difficult to apply IPM in an optimal sequence or at the optimal time. However, a greater level of control and at a proportionally lower cost could result if IPM principals were more rigorously applied, for instance, by focusing on strategic application of control methods in sequences known to be highly effective and cost-efficient. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study is to provide information about the Pasteurella multocida strains that are responsible for pasteurellosis in rabbits. A total of 114 strains responsible for different lesions in rabbits from industrial farms were investigated. In detail, the serogroup belonging to and the presence of 15 virulence-associated genes were investigated using PCR (polymerase chain reaction) protocols. The tested strains belonged to serogroups A, D, and F. Type A was the most frequently identified and it was prevalently found in strains responsible for rhinitis and pneumonia. Type D was the prevalent capsular type of strains responsible for metritis, while F was identified in strains detected from otitis, mastitis, subcutaneous abscesses, and septicaemia. Among the virulence-associated genes, sodC was found in all tested strains. Gene pfhA was more frequently found in strains belonging to type A than in type D and it was prevalently found in strains responsible for respiratory lesions. In addition, it was found in all F strains, suggesting a strong relationship between pfhA and this capsular type. Conversely, gene tadD was rarely found in strains belonging to capsular type F. Gene fur occurred more frequently in strains belonging to type D and involved with rhinitis. Gene hgbB was detected prevalently in strains responsible for metritis. Additionally, based on the results, the presence of more than 8 virulence-associated genes in the strains seems to increase the risk of the occurrence of severe lesions in the affected rabbits. Nevertheless, the detection of some strains responsible only for rhinitis which were equipped with 10 and 11 virulence-associated genes, seems to emphasise the importance of a gene's expression rather than its presence in strains. Pasteurellosis, a disease caused by Pasteurella multocida, is responsible for economic losses in rabbit industrial farms due to rhinitis, conjunctivitis, pneumonia, metritis, mastitis, orchitis, subcutaneous abscesses, otitis, encephalitis, and septicaemic forms. Although the occurrence of the disease is conditioned by predisposing factors that affect the rabbit immune response, the strains of P. multocida involved in the infection may have a different pathogenic ability. Therefore, typing of strains spread among the rabbits is important to assess their pathogenic potential. The aim of this study is to investigate the P. multocida strains responsible for disease in rabbit industrial farms. A total of 114 strains identified from different lesions were serotyped. Additionally, the presence of virulence-associated genes was investigated using three PCR (polymerase chain reaction) protocols. Capsular type A was prevalently found in strains from respiratory lesions while types D and F in those from metritis, mastitis, and other lesions. Different associations between some virulence-associated genes and both capsular type and lesions found in rabbits were detected. The presence of 8 virulence-associated genes seems to increase the occurrence of metritis. In addition, strains belonging to capsular type A and responsible for respiratory disorders especially, were found equipped with 10 and 11 virulence-associated genes. Nevertheless, the presence of strains responsible only for rhinitis was also detected among the latter, suggesting that the pathogenic ability of the bacteria depends on the expression rather than the presence of a gene. [ABSTRACT FROM AUTHOR]

The Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging pathogen of the Orthonairovirus genus that can cause severe and often lethal hemorrhagic diseases in humans. CCHFV has a broad tropism and can infect a variety of species and tissues. Here, by using gene silencing, blocking antibodies or soluble receptor fragments, we identify the low-density lipoprotein receptor (LDL-R) as a CCHFV entry factor. The LDL-R facilitates binding of CCHFV particles but does not allow entry of Hazara virus (HAZV), another member of the genus. In addition, we show that apolipoprotein E (apoE), an exchangeable protein that mediates LDL/LDL-R interaction, is incorporated on CCHFV particles, though not on HAZV particles, and enhances their specific infectivity by promoting an LDL-R dependent entry. Finally, we show that molecules that decrease LDL-R from the surface of target cells could inhibit CCHFV infection. Our study highlights that CCHFV takes advantage of a lipoprotein receptor and recruits its natural ligand to promote entry into cells. This study shows that Crimean-Congo hemorrhagic fever virus (CCHFV) recruits apoE, an exchangeable apolipoprotein that mediates LDL/LDL-R interaction, to promote virion entry via the LDLR. Molecules that down-regulate LDL-R inhibit CCHFV infection. [ABSTRACT FROM AUTHOR]

Rabbit haemorrhagic disease viruses (RHDV) belong to the family Caliciviridae, genus Lagovirus europaeus, genogroup GI, comprising four genotypes GI.1–GI.4, of which the genotypes GI.1 and GI.2 are pathogenic RHD viruses, while the genotypes GI.3 and GI.4 are non-pathogenic RCV (Rabbit calicivirus) viruses. Among the pathogenic genotypes GI.1 and GI.2 of RHD viruses, an antigenic variant of RHDV, named RHDVa—now GI.1a–RHDVa, was distinguished in 1996; and in 2010, a variant of RHDV—named RHDVb, later RHDV2 and now GI.2–RHDV2/b—was described; and recombinants of these viruses were registered. Pathogenic viruses of the genotype GI.1 were the cause of a disease described in 1984 in China in domestic (Oryctolagus (O.) cuniculus domesticus) and wild (O. cuniculus) rabbits, characterised by a very rapid course and a mortality rate of 90–100%, which spread in countries all over the world and which has been defined since 1989 as rabbit haemorrhagic disease. It is now accepted that GI.1–RHDV, including GI.1a–RHDVa, cause the predetermined primary haemorrhagic disease in domestic and wild rabbits, while GI.2–RHDV2/b cause it not only in rabbits, including domestic rabbits' young up to 4 weeks and rabbits immunised with rabbit haemorrhagic disease vaccine, but also in five various species of wild rabbits and seven different species of hares, as well as wild ruminants: mountain muskoxen and European badger. Among these viruses, haemagglutination-positive, doubtful and harmful viruses have been recorded and described and have been shown to form phylogenogroups, immunotypes, haematotypes and pathotypes, which, together with traits that alter and expand their infectious spectrum (rabbit, hare, wild ruminant, badger and various rabbit and hare species), are the determinants of their pathogenicity (infectivity) and immunogenicity and thus shape their virulence. These relationships are the aim of our consideration in this article. [ABSTRACT FROM AUTHOR]

To avoid adverse events in humans, toxicity studies in nonclinical species have been the foundation of safety evaluation in the pharmaceutical industry. However, it is recognized that working with animals in research is a privilege, and conscientious use should always respect the 3Rs: replacement, reduction, and refinement. In the wake of the shortages in routine nonrodent species and considering that nonanimal methods are not yet sufficiently mature, the value of the rabbit as a nonrodent species is worth exploring. Historically used in vaccine, cosmetic, and medical device testing, the rabbit is seldom used today as a second species in pharmaceutical development, except for embryo-fetal development studies, ophthalmic therapeutics, some medical devices and implants, and vaccines. Although several factors affect the decision of species selection, including pharmacological relevance, pharmacokinetics, and ADME considerations, there are no perfect animal models. In this forum article, we bring together experts from veterinary medicine, industry, contract research organizations, and government to explore the pros and cons, residual concerns, and data gaps regarding the use of the rabbit for general toxicity testing. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant form of vascular dysplasia. Genetic diagnosis is made by identifying loss‐of‐function variants in genes, such as ENG and ACVRL1. However, the causal mechanisms of various variants of unknown significance remains unclear. In this study, we analyzed 12 Japanese patients from 11 families who were clinically diagnosed with HHT. Sequencing analysis identified 11 distinct variants in ACVRL1 and ENG. Three of the 11 were truncating variants, leading to a definitive diagnosis, whereas the remaining eight were splice‐site and missense variants that required functional analyses. In silico splicing analyses demonstrated that three variants, c.526‐3C > G and c.598C > G in ACVRL1, and c.690‐1G > A in ENG, caused aberrant splicing, as confirmed by a minigene assay. The five remaining missense variants were p.Arg67Gln, p.Ile256Asn, p.Leu285Pro, and p.Pro424Leu in ACVRL and p.Pro165His in ENG. Nanoluciferase‐based bioluminescence analyses demonstrated that these ACVRL1 variants impaired cell membrane trafficking, resulting in the loss of bone morphogenetic protein 9 (BMP9) signal transduction. In contrast, the ENG mutation impaired BMP9 signaling despite normal cell membrane expression. The updated functional analysis methods performed in this study will facilitate effective genetic testing and appropriate medical care for patients with HHT. [ABSTRACT FROM AUTHOR]

Summary: Prolonged coagulation times, such as activated partial thromboplastin time (APTT) and thrombin time (TT), are common in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV) and have been confirmed to be related to patient's poor outcome by previous studies. To find out the reason for prolonged coagulation time in patients with SFTSV infection, and whether it predicts haemorrhagic risk or not. Seventy‐eight consecutive patients with confirmed SFTSV infection were enrolled in this prospective, single‐centre, observational study. Several global and specific coagulation parameters of these patients on admission were detected, and the haemorrhagic events during hospitalization and their outcomes were recorded. Most of the enrolled patients had prolonged APTT (82.1%) and TT (80.8%), normal prothrombin time (83.3%) and intrinsic coagulation factors above haemostatic levels (97.4%). The heparin‐like effect was confirmed by a protamine neutralization test and anti‐Xa activity detection in most patients. Interestingly, the APTT and TT results were significantly positively correlated with the levels of endothelial markers and viral load, respectively. The APTT was independently associated with the haemorrhage of patients. The prolonged APTT and TT of SFTS patients may mainly be attributed to endogenous heparinoids and are associated with increased haemorrhagic risk. [ABSTRACT FROM AUTHOR]

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Linguatula serrata can infect most ruminants and cause accidental infections in humans. It is a causative parasite of linguatulosis, a disease that not only produces economic losses in cattle but also represents a public health risk due to its zoonotic nature. This study aimed to explore the clinical and pathological findings of pulmonary linguatulosis in a rabbit. The most striking clinical findings in the deceased rabbits were wheezing and labored breathing. Grossly, the most prominent morphological changes in the lungs were well-circumscribed, flat or slightly raised, solitary grayish-white nodular lesions, and consolidated areas. The characteristically tongue-shaped developmental forms of parasites were observed on the cut surface of the lung. Histopathologically, the most noticeable morphological changes in the lung parenchyma were diffuse thickening of the inter-alveolar septum, fibrinoid necrotic vasculitis, medial smooth muscle cells hypertrophy of the arteries, alveolar emphysema, longitudinal and transverse sections of L. serrata nymphs and extra-medullary hematopoietic foci (megakaryocytes). The morphological appearance of the nymphs showed multiple transverse grooves, saw-like cuticles, peri-buccal hooks and acidophilic glands. In conclusion, these findings reveal the etiopathological diagnosis of linguatulosis and suggest that the lungs might be a target organ in addition to the liver and lymph nodes. [ABSTRACT FROM AUTHOR]

Cysticercus pisiformis is a kind of tapeworm larvae of Taenia pisiformis, which parasitizes the liver envelope, omentum, mesentery, and rectum of rodents such as rabbits. Cysteine protease inhibitors derived from helminth were immunoregulatory molecules of intermediate hosts and had an immunomodulatory function that regulates the production of inflammatory factors. Thus, in the present research, the recombinant Stefin of C. pisiformis was confirmed to have the potential to fight inflammation in LPS-Mediated RAW264.7 murine macrophages. CCK8 test showed that rCpStefin below 50 μg/mL concentration did not affect cellular viability. Moreover, the NO production level determined by the Griess test was decreased. In addition, the secretion levels of IL-1β, IL-6, and TNF-α as measured by ELISA were decreased. Furthermore, it exerted anti-inflammatory activity by decreasing the production of proinflammatory cytokines and proinflammatory mediators, including IL-1β, IL-6, TNF-α, iNOS, and COX-2 at the gene transcription level, as measured by qRT-PCR. Therefore, Type I cystatin derived from C. pisiformis suppresses the LPS-Mediated inflammatory response of the intermediate host and is a potential candidate for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Domestic rabbits (Oryctolagus cuniculus) are the fourth most common species admitted to the British Columbia Society for the Prevention of Cruelty to Animals (BC SPCA) shelter system. However, shelter data analysis has largely focused on cats and dogs and little is known about the population dynamics of rabbits in shelters. We analyzed five years of rabbit records (n = 1567) at the BC SPCA to identify trends in intake and predictors of length of stay (LOS) of rabbits. The majority of rabbits were surrendered by their owners (40.2%), with most rabbits being surrendered for human-related reasons (96.9%). Overall, rabbit intakes decreased over the study period. When analyzing by month of intake, rabbit intakes were found to be the highest in May. Most rabbits in our data were adults (46.7%), non-brachycephalic (66.7%), erect-eared (82.5%), short-furred (76.2%), and subsequently adopted (80.3%). The median LOS of rabbits was 29 days, highlighting the pressing need to improve their time to adoption. A linear model was constructed to identify predictors of LOS of adopted rabbits (n = 1203) and revealed that intake year, intake month, source of intake, age, cephalic type, and breed size significantly predicted time to adoption for rabbits (F(37, 1165) = 7.95, p < 2.2e-16, adjusted R2 = 0.18). These findings help characterize shelter population dynamics for rabbits, shed light on the challenges associated with unwanted rabbits, and offer a foundation for animal shelters to design programs and marketing strategies tailored to reduce LOS of rabbits with particular characteristics. Shelter rabbits represent an understudied population and our study highlights the importance of further research in companion rabbits. [ABSTRACT FROM AUTHOR]

Simple Summary: Domestic rabbits are one of the most commonly kept pets with a hypselodontic type of dentition, possessing teeth that grow throughout the animal's life. These animals often show signs of disease in the stomatognathic system. Dental disease can also affect the function of other organs and systems. The most common clinical signs of dental disease in domestic rabbits are the following: lack of appetite, weight loss, apathy, and difficulty chewing and swallowing food. These clinical signs are non-specific, and, therefore, a definitive diagnosis usually requires additional methods, such as an X-ray examination, a CT scan, MRI, and endoscopic examination. The most common dental disease found in this study's animals was malocclusion secondary to abnormal clinical crown abrasion and abnormal tooth growth. In domestic rabbits, osteomyelitis is a common complication of dental abscesses. Computed tomography is an invaluable diagnostic method in the diagnosis of dental disease and secondary diseases of the head area, such as inflammation of the nasal cavities or otitis media, in pet rabbits. Domestic rabbits have teeth that grow throughout the animal's life and are prone to disease. Clinical signs of dental disease in domestic rabbits are non-specific, and, therefore, a definitive diagnosis usually requires additional methods. This study was carried out on a group of 105 domestic rabbits aged 3 to 9 years. In total, 90 domestic rabbits with dental disease visible on CT images and other secondary diseases of the head area qualified for this study. Malocclusion was found in 57 (63.3%). Retrograde elongation of the tooth apices in the mandible was present in 39 (43.3%), and it was present in the maxilla in 48 (53%). Clinical tooth crowns were overgrown in 39 (43%). Dental abscesses were present in 54 (63%). Secondary to the presence of a dental abscess, osteomyelitis was found in 43 (79% of the animals with a dental abscess). Dental inflammatory resorption was found in 36 (40%). Secondary to dental disease, nasal cavity inflammation was found in 18 (20%). Otitis media was present in six (6.7%). The most common dental disease found in this study's animals was malocclusion secondary to abnormal clinical crown abrasion and abnormal tooth growth. In domestic rabbits, osteomyelitis is a common complication of dental abscesses. Computed tomography is an invaluable diagnostic method in the diagnosis of dental disease and secondary diseases of the head area, such as inflammation of the nasal cavities or otitis media, in pet rabbits. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTIs) in the U.S. as well as more serious invasive diseases, including bacteremia, sepsis, endocarditis, surgical site infections, osteomyelitis, and pneumonia. These infections are exacerbated by the emergence of antibiotic-resistant clinical isolates such as methicillin-resistant S. aureus (MRSA), highlighting the need for alternatives to antibiotics to treat bacterial infections. We have previously developed a multi-component toxoid vaccine (IBT-V02) in a liquid formulation with efficacy against multiple strains of Staphylococcus aureus prevalent in the industrialized world. However, liquid vaccine formulations are not compatible with the paucity of cold chain storage infrastructure in many low-to-middle income countries (LMICs). Furthermore, whether our IBT-V02 vaccine formulations are protective against S. aureus isolates from LMICs is unknown. To overcome these limitations, we developed lyophilized and spray freeze-dried formulations of IBT-V02 vaccine and demonstrated that both formulations had comparable biophysical attributes as the liquid formulation, including similar levels of toxin neutralizing antibodies and protective efficacy against MRSA infections in murine and rabbit models. To enhance the relevancy of our findings, we then performed a multi-dimensional screen of 83 S. aureus clinical isolates from LMICs (e.g., Democratic Republic of Congo, Palestine, and Cambodia) to rationally down-select strains to test in our in vivo models based on broad expression of IBT-V02 targets (i.e., pore-forming toxins and superantigens). IBT-V02 polyclonal antisera effectively neutralized toxins produced by the S. aureus clinical isolates from LMICs. Notably, the lyophilized IBT-V02 formulation exhibited significant in vivo efficacy in various preclinical infection models against the S. aureus clinical isolates from LMICs, which was comparable to our liquid formulation. Collectively, our findings suggested that lyophilization is an effective alternative to liquid vaccine formulations of our IBTV02 vaccine against S. aureus infections, which has important implications for protection from S. aureus isolates from LMICs. [ABSTRACT FROM AUTHOR]

Rabbit hemorrhagic disease virus 2 (RHDV2) emerged in the United States in 2018 and has spread in both domestic and wild rabbits nationwide. The virus has a high mortality rate and can spread rapidly once introduced in a rabbit population. Vaccination against RHDV2 provides the best protection against disease and should be considered by all rabbit owners. Here, we investigate the duration of immunity provided by vaccination with the Medgene Platform conditionally licensed commercial vaccine 6 months following the initial series. Rabbits received either the vaccination or a placebo and were challenged with RHDV2 6 months later. All vaccinated rabbits survived challenge whereas 18/19 non-vaccinated controls succumbed to infection within 10 or fewer days post-challenge. These results demonstrate lasting immunity following vaccination with the Medgene RHDV2 vaccine. [ABSTRACT FROM AUTHOR]

Rabbit haemorrhage disease virus 2 (RHDV2) is a highly pathogenic lagovirus that causes lethal disease in rabbits and hares (lagomorphs). Since its first detection in Europe in 2010, RHDV2 has spread worldwide and has been detected in over 35 countries so far. Here, we provide the first detailed report of the detection and subsequent circulation of RHDV2 in New Zealand. RHDV2 was first detected in New Zealand in 2018, with positive samples retrospectively identified in December 2017. Subsequent time-resolved phylogenetic analysis suggested a single introduction into the North Island between March and November 2016. Genetic analysis identified a GI.3P-GI.2 variant supporting a non-Australian origin for the incursion; however, more accurate identification of the source of the incursion remains challenging due to the wide global distribution of the GI.3P-GI.2 variant. Furthermore, our analysis suggests the spread of the virus between the North and South Islands of New Zealand at least twice, dated to mid-2017 and around 2018. Further phylogenetic analysis also revealed a strong phylogeographic pattern. So far, no recombination events with endemic benign New Zealand rabbit caliciviruses have been identified. This study highlights the need for further research and surveillance to monitor the distribution and diversity of lagoviruses in New Zealand and to detect incursions of novel variants. [ABSTRACT FROM AUTHOR]

Rabbit hemorrhagic disease (RHD) is an acute fatal disease caused by the rabbit hemorrhagic disease virus (RHDV). Since the first outbreaks of type 2 RHDV (RHDV2) in April 2020 in China, the persistence of this virus in the rabbit population has caused substantial economic losses in rabbit husbandry. Previous failures in preventing RHDV2 prompted us to further investigate the immune mechanisms underlying the virus's pathogenicity, particularly concerning the spleen, a vital component of the mononuclear phagocyte system (MPS). For this, a previous RHDV2 isolate, CHN/SC2020, was utilized to challenge naive adult rabbits. Then, the splenic transcriptome was determined by RNA-Seq. This study showed that the infected adult rabbits had 3148 differentially expressed genes (DEGs), which were associated with disease, signal transduction, cellular processes, and cytokine signaling categories. Of these, 100 upregulated DEGs were involved in inflammatory factors such as IL1α, IL-6, and IL-8. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEGs were significantly enriched in the cytokine–cytokine receptor interaction signaling pathway, which may play a vital role in CHN/SC2020 infection. At the same time, proinflammatory cytokines and chemokines were significantly increased in the spleen at the late stages of infection. These findings suggested that RHDV2 (CHN/SC2020) might induce dysregulation of the cytokine network and compromise splenic immunity against viral infection, which expanded our understanding of RHDV2 pathogenicity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to characterize the bacterial and eukaryotic microbiota of the gastrointestinal (GI) tract in domestic rabbits and to evaluate the effect of different diet characteristics, such as pelleting, extrusion, and hay supplementation. ANIMALS: 30 New Zealand White rabbits (15 male and 15 female; 6 to 7 months old) were fed 1 of 6 diets (5 rabbits per diet) for 30 days after an initial acclimation period. At the end of the trial, samples were collected from the stomach, small intestine, cecum, large intestine, and hard feces. METHODS: The samples were analyzed using 16S rRNA and internal transcribed spacer 1 region-targeted amplicon sequencing. RESULTS: The bacterial microbiota was distinct between the foregut and hindgut. The most abundant bacterial genera included an unclassified genus in the Bacteroidales order and Alistipes. Candida was the most abundant genus in the eukaryotic dataset. In the bacterial dataset, diet No Hay/Pellet E was shown to have lower diversity (Shannon diversity, P < .05) compared to all diet groups except for No Hay/Pellet M. Few significant differences in alpha-diversity indexes between diet groups were detected in the eukaryotic dataset. CLINICAL RELEVANCE: Our findings demonstrated that feeding hay had a significant effect on the beta diversity of the bacterial microbiota. Given the prevalence of gastrointestinal disease in the domestic rabbit population, furthering our understanding of what constitutes a healthy rabbit microbiota and the effects of different diets on the microbial community can help veterinarians implement better intervention strategies and allow pet owners to provide the best level of care. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the diagnostic efficacy of T1ρ dispersion and Gd-EOB-DTPAenhanced T1mapping in the identification of early liver fibrosis (LF) and non-alcoholic steatohepatitis (NASH) in a non-alcoholic fatty liver disease (NAFLD) rabbit model induced by a high-fat diet using histopathological findings as the standard reference. Methods: A total of sixty rabbits were randomly allocated into the standard control group (n = 12) and the NAFLD model groups (8 rabbits per group) corresponding to different high-fat high cholesterol diet feeding weeks. All rabbits underwent noncontrast transverse T1ρ mapping with varying spin-locking frequencies (FSL = 0 Hz and 500 Hz), native T1 mapping, and Gd-EOB-DTPA-enhanced T1 mapping during the hepatobiliary phase. The histopathological findings were assessed based on the NASH CRN Scoring System. Statistical analyses were conducted using the intraclass correlation coefficient, analysis of variance, multiple linear regression, and receiver operating characteristics. Results: Except for native T1, T1ρ, T1ρ dispersion, HBP T1, and △T1 values significantly differed among different liver fibrosis groups (F = 14.414, 18.736, 10.15, and 9.799, respectively; all P < 0.05). T1ρ, T1ρ dispersion, HBP T1, and △T1 values also exhibited significant differences among different NASH groups (F = 4.138, 4.594, 21.868, and 22.678, respectively; all P < 0.05). In the multiple regression analysis, liver fibrosis was the only factor that independently influenced T1ρ dispersion (R2 = 0.746, P = 0.000). Among all metrics, T1ρ dispersion demonstrated the best area under curve (AUC) for identifying early LF (≥ F1 stage) and significant LF (≥ F2 stage) (AUC, 0.849 and 0.916, respectively). The performance of △T1 and HBP T1 (AUC, 0.948 and 0.936, respectively) were better than that of T1ρ and T1ρ dispersion (AUC, 0.762 and 0.769, respectively) for diagnosing NASH. Conclusion: T1⍴ dispersion may be suitable for detecting liver fibrosis in the complex background of NAFLD, while Gd-EOB-DTPA enhanced T1 mapping is superior to nonenhanced T1⍴ mapping (T1⍴ and T1⍴ dispersion) for identifying NASH. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the prevalence and to identify the risk factors of Eimeria spp. and Giardia spp. infection in rabbits from the local population of four localities in northern Algeria. Dung samples were collected from 16 farms, totalling 111 rabbits, and were analysed by the flotation method. Additional, data regarding the farms and management practices were obtained by means of a questionnaire used in the surveys and interviews. The results revealed that the prevalence of Eimeriaspp. contamination was 68.75% (11/16) for farms and 58.56% (65/111) for rabbits, respectively. The prevalence of Giardia spp. was respectively 56.25% (9/16) for farms and 11.7% (13/111) for rabbits. The analyses showed that the prevalence of Eimeria spp. was significantly higher in the farms that did not comply with hygiene and non-conventional feeding and watering. However, the prevalence of Giardia spp. was significant in rabbits kept in poor conditions of rearing. In conclusion, this study showed that the prevalence of these two parasites in rabbits from the local population is relevant and may have important implications for the rabbit industry and public health, especially in rural areas. [ABSTRACT FROM AUTHOR]

keeping rabbits as pets and their use in laboratory research increased the need for studying heart diseases and treatments in rabbits. Pimobendan is one of the most common medications used in cardiac diseases and is anecdotal in rabbits. The first step toward the approval of pimobendan in rabbits is assessing the potential for beneficial effects on cardiac function through echocardiographic functional parameters. This study aimed to determine the effects of pimobendan on echocardiographic parameters. Eleven rabbits were included in this study. Echocardiographic examinations were performed before and after pimobendan administration for each rabbit. The LV morphological and functional parameters were compared between study time points. Pimobendan resulted in changes in several echocardiographic variables in the rabbits, including FS and an increase in EF, SV, LVPWs, and LA end-systolic (p = 0.0001, p = 0.0001, p = 0.0284, p = 0.0272, and p = 0.0007, respectively). Moreover, LVIDs and end-systolic volume decreased (p = 0.0343 and p = 0.038). The changes in some parameters were not significant, such as LVIDd, LVPWd, end-diastolic volume, LA max, Mitral annulus diameter, and LA/Ao. FS, which indicates an increase in the power of heart contraction and consequently an improvement in heart function, increased in this study after pimobendan administration. Therefore, it can be concluded that pimobendan improves cardiac functions. Further studies are required to investigate whether pimobendan has similar effects in rabbits with cardiac diseases. [ABSTRACT FROM AUTHOR]

A novel variant of rabbit haemorrhagic disease virus, designated RHDV2/b/GI.2, was first discovered in France in 2010. Subsequently, RHDV2 rapidly spread to Africa, North America, Australia, and Asia. RHDV2 outbreaks have resulted in significant economic losses in the global rabbit industry and disrupted the balance of natural ecosystems. Our study investigated the seasonal characteristics of RHDV2 outbreaks using seasonal indices. RHDV2 is prone to causing significant outbreaks within domestic and wild rabbit populations during the spring season and is more likely to induce outbreaks within wild rabbit populations during late autumn in the Southern Hemisphere. Furthermore, based on outbreak data for domestic and wild rabbits and environmental variables, our study established two MaxEnt models to explore the relationship between RHDV2 outbreaks and the environmental factors and conducted outbreak risk predictions for RHDV2 in global domestic and wild rabbit populations. Both models demonstrated good predictive performance, with AUC values of 0.960 and 0.974, respectively. Road density, isothermality, and population density were identified as important variables in the outbreak of RHDV2 in domestic rabbits, while road density, normalized difference vegetation index, and mean annual solar radiation were considered key variables in the outbreak of RHDV2 in wild rabbits. The environmental factors associated with RHDV2 outbreaks identified in our study and the outbreak risk prediction maps generated in our study will aid in the formulation of appropriate RHDV2 control measures to reduce the risk of morbidity in domestic and wild rabbits. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) are a group of small, 17–25 nucleotide, non-coding RNA that regulate gene expression at the post-transcriptional level. To date, little is known about the molecular signatures of regulatory interactions between miRs and apoptosis and oxidative stress in viral diseases. Lagovirus europaeus is a virus that causes severe disease in rabbits (Oryctolagus cuniculus) called Rabbit Hemorrhagic Disease (RHD) and belongs to the Caliciviridae family, Lagovirus genus. Within Lagovirus europaeus associated with RHD, two genotypes (GI.1 and GI.2) have been distinguished, and the GI.1 genotype includes four variants (GI.1a, GI.1b, GI.1c, and GI.1d). The study aimed to assess the expression of miRs and their target genes involved in apoptosis and oxidative stress, as well as their potential impact on the pathways during Lagovirus europaeus—two genotypes (GI.1 and GI.2) infection of different virulences in four tissues (liver, lung, kidneys, and spleen). The expression of miRs and target genes related to apoptosis and oxidative stress was determined using quantitative real-time PCR (qPCR). In this study, we evaluated the expression of miR-21 (PTEN, PDCD4), miR-16b (Bcl-2, CXCL10), miR-34a (p53, SIRT1), and miRs—related to oxidative stress—miR122 (Bach1) and miR-132 (Nfr-2). We also examined the biomarkers of both processes (Bax, Bax/Bcl-2 ratio, Caspase-3, PARP) and HO-I as biomarkers of oxidative stress. Our report is the first to present the regulatory effects of miRs on apoptosis and oxidative stress genes in rabbit infection with Lagovirus europaeus—two genotypes (GI.1 and GI.2) in four tissues (liver, lungs, kidneys, and spleen). The regulatory effect of miRs indicates that, on the one hand, miRs can intensify apoptosis (miR-16b, miR-34a) in the examined organs in response to a viral stimulus and, on the other hand, inhibit (miR-21), which in both cases may be a determinant of the pathogenesis of RHD and tissue damage. Biomarkers of the Bax and Bax/Bcl-2 ratio promote more intense apoptosis after infection with the Lagovirus europaeus GI.2 genotype. Our findings demonstrate that miR-122 and miR-132 regulate oxidative stress in the pathogenesis of RHD, which is associated with tissue damage. The HO-1 biomarker in the course of rabbit hemorrhagic disease indicates oxidative tissue damage. Our findings show that miR-21, miR-16b, and miR-34a regulate three apoptosis pathways. Meanwhile, miR-122 and miR-132 are involved in two oxidative stress pathways. [ABSTRACT FROM AUTHOR]

Tularemia is a vector-borne disease caused by the Gram-negative bacterium Francisella tularensis. Known hosts and vectors in Europe are hare and ticks. F. tularensis is transmitted from ticks and animals, but also from the hydrotelluric environment and the consumption of contaminated water or food. A changing climate expands the range in which ticks can live and consequently might contribute to increasing case numbers of tularemia. Two subspecies of F. tularensis are human pathogenic. Francisella tularensis tularensis (Ftt) is endemic in North America, while Francisella tularensis holarctica (Fth) is the only subspecies causing tularemia in Europe. Ft is classified as a category A bioterrorism agent due to its low infectious dose, multiple modes of transmission, high infectivity and potential for airborne transmission and has become a global public health concern. In line with the European survey and previous phylogenetic studies, Switzerland shows the co-distribution of B.6 and B.12 strains with different geographical distribution and prevalence within the country. To establish itself in different host environments of ticks and mammals, F. tularensis presumably undergoes substantial changes on the transcriptomics and proteomic level. Here we investigate the transcriptomic and proteomic differences of five strains of Fth upon infection of rabbit macrophages and tick cells. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection (CDI) is a serious healthcare-associated disease, causing symptoms such as diarrhea and pseudomembranous colitis. The major virulence factors responsible for the disease symptoms are two secreted cytotoxic proteins, TcdA and TcdB. A parenteral vaccine based on formaldehyde-inactivated TcdA and TcdB supplemented with alum adjuvant, has previously been investigated in humans but resulted in an insufficient immune response. In search for an improved response, we investigated a novel toxin inactivation method and a novel, potent adjuvant. Inactivation of toxins by metal-catalyzed oxidation (MCO) was previously shown to preserve neutralizing epitopes and to annihilate reversion to toxicity. The immunogenicity and safety of TcdA and TcdB inactivated by MCO and combined with a novel carbohydrate fatty acid monosulphate ester-based (CMS) adjuvant were investigated in rabbits. Two or three intramuscular immunizations generated high serum IgG and neutralizing antibody titers against both toxins. The CMS adjuvant increased antibody responses to both toxins while an alum adjuvant control was effective only against TcdA. Systemic safety was evaluated by monitoring body weight, body temperature, and analysis of red and white blood cell counts shortly after immunization. Local safety was assessed by histopathologic examination of the injection site at the end of the study. Body weight gain was constant in all groups. Body temperature increased up to 1 ˚C one day after the first immunization but less after the second or third immunization. White blood cell counts, and percentage of neutrophils increased one day after immunization with CMS-adjuvanted vaccines, but not with alum. Histopathology of the injection sites 42 days after the last injection did not reveal any abnormal tissue reactions. From this study, we conclude that TcdA and TcdB inactivated by MCO and combined with CMS adjuvant demonstrated promising immunogenicity and safety in rabbits and could be a candidate for a vaccine against CDI. [ABSTRACT FROM AUTHOR]

Background: To observe the occurrence of related complications after self-expandable metallic (SEM) airway stents implantation with different diameters at different time points, and to provide theoretical basis for the optimal chioce of existing airway stents in clinical practice. Methods: Healthy New Zealand white rabbits were used to establish benign tracheal stenosis models after chest CT examination. Forty-fivemodel rabbits with more than 50% of airway stenosis were divided into two groups. Small-diameter SEM stents (The ratio of stent diameter to airway diameter is nearly 1.0) were implanted in Group A in 21 rabbits, and large-diameter tracheal stents (The ratio of stent diameter to airway diameter is more than 1.2) were implanted in Group B in 24 rabbits. Stent-related complications were observed after stent implantation in 2nd,4th,8th, and 12th week by bronchoscopygross anatomy, pathological and the expressions of IL-1RA, IL-8 and MMP9 in involved tracheal. Results: The incidence rate of tracheomalacia of stent was significantly higher in group B (24/24 100%) than that in group A (1 /21,4.8%) (P < 0.05). The incidence rate of scar contracture at both ends of stent was significantly higher than in group B (11 / 24,45.8%) that in group A (2 /21, 9.5%) (P < 0.05). The pathological results of both A and B showed that the columnar epithelium of bronchial mucosa began to damage and detach, inflammatory cells infiltrated after 2nd and 4th week of stenting, The epithelium was repaired, the lamina propria glands almost disappeared, collagen fiber proliferation was obvious, and scars were formed after 8th and 12th week of stenting. ELISA results revealed that the expressions of IL-1RA, IL-8, and MMP9 were increased in the stent group than in model rabbit with benign tracheal stenosis. IL-1RA and MMP9 increased at different periods in group B, but the expression of IL-1RA and MMP9 showed a tread of increasing in the early stage and then decreasing in group A. Conclusion: Metal stents can cause different degrees of stent-related complications in rabbits with benign tracheal stenosis. The incidence of stent-induced tracheomalacia and scar contracture were higher in Group B than that in Group A. IL-1RA, IL-8 and MMP9 may be involved in the development of complications after stentimplantation and peak value of group B movered backward. ing. [ABSTRACT FROM AUTHOR]

Several conventional and recently available tools are available for an integrated control of European rabbits in Australia. We quantified the impact of the release of rabbit haemorrhagic disease virus K5 (RHDV K5, hereafter K5) and pindone (2‐pivalyl‐1,3‐indandione) baiting at 13 sites within Cudlee Creek fire scar in the Adelaide Hills, South Australia. K5 release was followed by pindone baiting between December 2021 and March 2022; the application of both control methods followed industry best practice. We counted rabbits using spotlights before and after the application of both control methods. Fly samples and livers from dead rabbits were collected to track K5 transmission within and between sites, and to detect the natural circulation of rabbit haemorrhagic disease virus 2 (RHDV2). K5 release had minimal impact on rabbit populations, with treated populations increasing by a mean of 65.5% at 14 days post‐release and 27.9% at 77 days post‐K5 release across all sites, comparable to the changes at control sites. K5 detection in flies up to 77 days post its release, and its detection in rabbit livers, demonstrates that it can survive and transmit in the environment for prolonged periods and that it can lethally infect some rabbits. This limited impact of K5 is consistent with previous studies and may be explained by pre‐existing RHDV/RHDV2 immunity in the target populations or the presence of young rabbits with natural innate RHDV immunity. The detection of K5 in flies from control sites demonstrates that it was vectored beyond its release location. A reduction in rabbit counts post‐pindone baiting was observed at most treatment sites, with a mean population reduction of 36.6% across all sites. Landholders need to carefully and strategically plan their integrated rabbit control programmes. Not all combinations of controls, even if theoretically logical, achieve meaningful outcomes for rabbit management. [ABSTRACT FROM AUTHOR]

Pathogenic lagoviruses (Rabbit hemorrhagic disease virus, RHDV) are widely spread across the world and are used in Australia and New Zealand to control populations of feral European rabbits. The spread of the non-pathogenic lagoviruses, e.g., rabbit calicivirus (RCV), is less well studied as the infection results in no clinical signs. Nonetheless, RCV has important implications for the spread of RHDV and rabbit biocontrol as it can provide varying levels of cross-protection against fatal infection with pathogenic lagoviruses. In Chile, where European rabbits are also an introduced species, myxoma virus was used for localised biocontrol of rabbits in the 1950s. To date, there have been no studies investigating the presence of lagoviruses in the Chilean feral rabbit population. In this study, liver and duodenum rabbit samples from central Chile were tested for the presence of lagoviruses and positive samples were subject to whole RNA sequencing and subsequent data analysis. Phylogenetic analysis revealed a novel RCV variant in duodenal samples that likely originated from European RCVs. Sequencing analysis also detected the presence of a rabbit astrovirus in one of the lagovirus-positive samples. [ABSTRACT FROM AUTHOR]

Simple Summary: Rabbits' participation in Animal-Assisted Interventions is increasing. Rabbits are loveable animals, their handling is quick to learn, their body language is simple to read and they can be easily transported into several institutions from kindergarten to palliative care homes. While the positive impact of interventions on humans is indisputable, there is little available information about the effects on animals themselves. Regularly transporting the rabbits to the place of the intervention can be a source of stress, but we assume that they can be trained, and animals can get used to it by offering feed (hay, carrot and apple) and providing appropriate circumstances. Cortisol hormone secretion is initiated as the response to stress and metabolites of cortisol can be isolated in feces samples by laboratory analysis. Using this method we can obtain adequate information about the experienced stress caused the transportation, without disturbing the animals. According to our results, based on the laboratory analysis, repeated transportation causes a significant rise in stress hormone metabolite levels in feces samples regardless of the offered treats during the transport. Those owners who use rabbits for Animal-Assisted Intervention purposes need to take into account that transportation itself is a stressful experience for the animals. (1) Background: the popularity of rabbits has increased during the last decade and become the third most common companion animal in the EU. Rabbits' participation in Animal-Assisted Interventions (AAIs) is growing. It is highly important to ensure the well-being of the animals in AAIs. Whereas the needs and the advantages of people involved in AAI are becoming more and more evident, the needs of animals are not clearly defined, therefore, it is a great field of inquiry. Animals who are used for AAI need to be transported regularly, which itself might be a source of stress. (2) Methods: the stress of rabbits—caused by transportation—was measured in a non-invasive way: cortisol levels were determined from feces, based on their breakdown products. Eighteen animals were involved in the study. Rabbits experienced a 30 min transportation every second day for two weeks (altogether six times) while 126 samples were collected. (3) Results: rabbits could handle the transportation procedure the first time but subsequently the stress hormone metabolites in feces samples increased regardless of the offered treatments (hay, carrot and apple) during the carriage. (4) Conclusions: those owners who use rabbits for Animal-Assisted Interventions need to take into account that transportation itself is a stressful experience for the animals. [ABSTRACT FROM AUTHOR]

Hereditary hemorrhagic telangiectasia (HHT), also called Rendu–Osler syndrome, is a group of rare genetic diseases characterized by autosomal dominance, multisystemic vascular dysplasia, and age-related penetrance. This includes arteriovenous malformations (AVMs) in the skin, brain, lung, liver, and mucous membranes. The correlations between the phenotype and genotype for HHT are not clear. An HHT Chinese pedigree was recruited. Whole exome sequencing (WES) analysis, Sanger verification, and co-segregation were conducted. Western blotting was performed for monitoring ENG/VEGFα signaling. As a result, a nonsense, heterozygous variant for ENG/CD105: c.G1169A:p. Trp390Ter of the proband with hereditary hemorrhagic telangiectasia type 1 (HHT1) was identified, which co-segregated with the disease in the M666 pedigree. Western blotting found that, compared with the normal levels associated with non-carrier family members, the ENG protein levels in the proband showed approximately a one-half decrease (47.4% decrease), while levels of the VEGFα protein, in the proband, showed approximately a one-quarter decrease (25.6% decrease), implying that ENG haploinsufficiency, displayed in the carrier of this variant, may affect VEGFα expression downregulation. Pearson and Spearman correlation analyses further supported TGFβ/ENG/VEGFα signaling, implying ENG regulation in the blood vessels. Thus, next-generation sequencing including WES should provide an accurate strategy for gene diagnosis, therapy, genetic counseling, and clinical management for rare genetic diseases including that in HHT1 patients. [ABSTRACT FROM AUTHOR]

Background: Rabbits are extremely sensitive to pain. There is evidence on whether non‐steroidal anti‐inflammatory medication should be administered before or after surgery in rabbits. Objectives: In this study, we compared the pain scores and behaviours of rabbits administered meloxicam before or after routine castration. Methods: Forty‐two healthy rabbits undergoing castration were randomly assigned to receive meloxicam (1 mg/kg SC) 1 h before or upon recovery from anaesthesia. Several parameters were recorded, including the occurrence of eating, defecating and pain scores postoperatively and change in heart rate intraoperatively. Results: At 4 h after surgery, eating was observed in 43% (9/21) of rabbits that received meloxicam before neutering and in 29% (6/21) of rabbits that received meloxicam after. The morning after the surgery, eating was observed in 62% (13/21) of rabbits that received meloxicam before neutering and in 57% (12/21) of rabbits that received meloxicam after. The odds of not eating increased by 1.16 times (1.03–1.29; p = 0.01) per month of age, whereas there was no significant association between eating and administration of meloxicam before or after surgery, body weight and time. Similarly, defecation, pain score and change in heart rate did not differ in animals receiving meloxicam before or after surgery. Conclusions: Administration of meloxicam in rabbits undergoing castration before or after surgery does not have a relevant effect on eating, defecating or pain score. Younger rabbits show less obvious signs of pain and are more likely to resume eating habits sooner after surgery compared to older rabbits. [ABSTRACT FROM AUTHOR]

Since lagoviruses cannot be cultivated in vitro, using expression systems is an alternative and promising way of producing diagnostic viral antigens. It opens up their use as active immunogens for vaccine production. Virus-like particles (VLPs) were produced in a baculovirus expression system in Spodoptera frugiperda 9 (Sf9) insect cells based on wild-type and mutated variants of the virus capsid VP60 protein from a Polish strain of European brown hare syndrome virus (EBHSV) and wild-type and mutated versions of this protein from a Polish strain of rabbit haemorrhagic disease virus 2 (RHDV2). The mutations were the substitution of an arginylglycylaspartic acid (Arg-Gly-Asp/RGD) motif in the P2 subdomain and, in the S or P2 domain, the substitution of three lysines. The VLPs were purified with sucrose gradient ultracentrifugation. Protein production was confirmed by Western blot analysis using rabbit or hare sera and ELISA tests with different types of monoclonal antibody. The haemagglutination properties of some VLPs were also evaluated. Electron microscopy of wild-type EBHSV, wild-type RHDV2 and the four VP60 variants produced in this experiment revealed the formation of characteristic VLP structures. For the first time, mutated VLPs of RHDV2 with an RGD motif in the VP60 sequence were obtained, which could potentially be used to deliver cargo to eukaryotic cells. Virus-like particles based on the VP60 proteins of EBHSV and RHDV with a three-lysine substitution in the S or P2 domains were also obtained. Potential exists for VLPs of EBHSV and RHDV2 as vaccine candidates. [ABSTRACT FROM AUTHOR]

A 4‐year‐old lionhead rabbit with an acute onset of abnormal hindlimb gait was presented. L4–S3 neurolocalisation was determined based on clinical findings of paraparesis, bilateral proprioceptive positioning deficits, left pelvic limb hyporeflexia and discomfort during lumbar spine manipulation. The magnetic resonance imaging (MRI) revealed an intervertebral disc extrusion (IVDE) at L4–L5, with mild spinal cord compression. The condition was treated conservatively, with cage rest and non‐steroidal anti‐inflammatory drugs. The rabbit was fully normal after 1 month. Two months later, a relapse of clinical signs was observed. A new MRI study revealed a L5–L6 IVDE with mild spinal cord compression. Conservative treatment was repeated and full recovery was confirmed at 4‐month follow‐ups associated with MRI follow‐up study. To the authors' knowledge, this is the first case report of spontaneous IVDEs in a rabbit, where MRI was used to monitor the effectiveness of the conservative management of the disease in a rabbit. [ABSTRACT FROM AUTHOR]

Digestive problems, both those with a clear pathogenic origin (e.g., Escherichia coli) and those without obvious pathogen involvement [e.g., syndromes like epizootic rabbit enteropathy (ERE)], are common in production rabbits and account for the majority of losses in meat rabbit production. A multitude of nutritional, genetic and housing factors have been found to play a role in the occurrence of digestive problems. However, the exact early pathophysiological mechanism, including the links between aforementioned risk factors and subsequent development and expression of gastrointestinal disease, is less clear, especially in non-specific enteropathies without obvious pathogen involvement. In this review, we aim to shed more light on the derailment of the normal gastrointestinal functioning in rabbits. We discuss a conceptual integrated view of this derailment, based on an "overload" pathway and a "chymus jam" pathway, which may occur simultaneously and interact. The "overload" pathway centers around exposure to excess amounts of easily fermentable substrate (e.g., starch and protein) that might be incompletely digested prior to entering the caecum. Once there, hyperfermentationmay result in changes in caecal pH and inhibition of the normal microflora. The second pathway centers around a chymus jam resulting froma compromised passage rate. Here, reduced hindgutmotility (e.g., resulting from stress or limited fiber supply) leads to reduced flow of digesta and increased caecal retention times, which might lead to the production of abnormal caecal fermentation products and subsequent inhibition of the normal microflora. A central role in the presumed mechanism is attributed to the fusus coli. We discuss the suggested mechanisms behind both pathways, as well as the empirical substantiation and alignment between theoretical concepts and observations in practice. The proposed hypotheses may explain the effect of time-based restriction to prevent ERE, which is widely applied in practice but to date not really understood, and suggest that the particle size of fibermay be a key point in the normal functioning of the colon and fusus coli. Further insight into the circumstances leading to the derailment of physiological processes in the rabbit hindgut could provide a meaningful starting point to help improve their gastrointestinal resilience. [ABSTRACT FROM AUTHOR]

Rabbit Haemorrhagic Disease (RHD) is a severe disease caused by Lagovirus europaeus/GI.1 and GI.2. Immunological processes such as apoptosis are important factors involved in the pathogenesis of Rabbit Haemorrhagic Disease (RHD). The process of programmed cell death has been quite well characterized in infection with GI.1 strains, but apoptosis in infection with GI.2 strains has not been widely studied. This is particularly important as several studies have shown that significant differences in the host immune response are observed during infection with different strains of Lagovirus europaeus. In this study, we analyzed the gene expression, protein levels and activity of key apoptotic cell death factors in the spleen, kidney, lung, and heart of rabbits. As a result, we showed that there is a significant increase in caspase-3, Bax, Bcl2 and Bax/Bcl2 mRNA gene expression ratio in organs of infected animals. Our results show also increased levels of cleaved caspase-3, caspase-6 and PARP. Moreover, significant activity of caspase-3 was also detected. Our results indicate that caspase-3, caspase-6 and genes coding Bcl2 family proteins play a key role in the apoptotic response in Lagovirus europaeus/GI.2 infection in organs that are not the target of virus replication. [ABSTRACT FROM AUTHOR]

Rabbit hemorrhagic disease virus 2 (RHDV2), recently detected in the western United States, has the potential to cause mass mortality events in wild rabbit and hare populations. Currently, few management strategies exist other than vaccination. We developed a spatially explicit model of RHDV2 for a population of riparian brush rabbits (Sylvilagus bachmani riparius), a subspecies of brush rabbit classified as endangered in the United States, on a subsection of the San Joaquin River National Wildlife Refuge. The goal of our model was to provide guidance regarding vaccination strategies for an endangered rabbit species. Our model predicts that increased interactions between rabbits (a proxy for landscape connectivity) and disease transmission rates among susceptible hosts (individual brush rabbits and conspecifics) have the greatest influence on the outcome of a potential vaccination campaign. Our model projects that across a range of parameter estimates (given an RHDV2 incursion), the median estimated population size with a 0%–10% vaccination rate after 1 year is 538 rabbits (95% Confidence Interval [C.I.] 69–1235), approximately 36% of the expected size of the study population of 1470 rabbits without an RHDV2 introduction. With a 10%–20%, 20%–30%, or 30%–40% vaccination rate, the median estimated population size increased to 628 rabbits (95% C.I. 130–1298), 723 rabbits (95% C.I. 198–1317), and 774 rabbits (95% C.I. 228–1410), respectively. These estimates represent 43%, 49%, and 53% of the expected population size without an RHDV2 introduction. Overall, a 1% increase in vaccination rate was associated with a six rabbit (95% C.I. 5–7) increase in total remaining population size. This result is dependent on assumptions regarding environmental transmission, home range size (and contact rates of rabbits). Given the relatively short lifespan of rabbits and the potential need for boosters, vaccination programs are most likely to be successful for small target populations where relatively high vaccination rates can be maintained. [ABSTRACT FROM AUTHOR]

Background: Infestation of the mite Sarcoptes scabiei var. cuniculi is one of the most frequent skin diseases in rabbits all over the world. Disease is characterized by intense pruritus, alopecia, erythema, scales and crusts around the head, neck, trunk, feet, ears, nose and genitals, resulting in hypertensive reactions, considerable losses in body weight and productivity causing significant economic losses in rabbit production. Methods: This study is aimed to evaluate the efficacy of Nerium oleander extract against S. scabiei var. cuniculi mite in vitro. Acaricidal bioassay, a dipping method was conducted on mites isolated from naturally infested rabbits. PBS and ivermectin were used as the negative and positive controls, respectively. In addition, three different concentrations of extract (100, 200 and 400 µg/ml) weretested at different periods and changes over time in the viability of mites were registered for (0.5, 1, 2, 4 and 8 hours). A chemical assay was performed via GC-MS to investigate the presence of several anticipated active chemical compounds in Nerium oleander leaf extract. Result: The results showed that the extract had high efficacy in killing mites at 100%, 78% and 49% and ivermectin 91%, respectively, for 8 hours. The results indicate that Nerium oleander possesses effective compounds as a valuable therapeutic method for treating scabies. Further studies are needed to determine the precise active chemicals present in Nerium oleander leaf extract and their modes of action and application in vivo. [ABSTRACT FROM AUTHOR]

Canine parvovirus type-2 (CPV-2) is one of the most common diseases affecting dogs. The disease has been reported worldwide including Egypt causing both acute hemorrhagic enteritis and myocarditis in the infected dogs. Two distinct parvoviruses are incriminated in the disease occurrence CPV-1 and CPV-2. However, the CPV-2 is the most pathogenic and includes three antigenic variants namely, CPV2a, CPV2b and CPV2c. Since the molecular characterization of CPV is critical for future disease prevention and control, the current study aimed to determine the prevalence of CPV-2 in dogs in Giza governorate, Egypt, and molecular characterization of circulating CPV-2. A total of 300 stool samples were collected from dogs with clinical signs suggestive of canine parvovirus from different veterinary hospitals and clinics in Giza governorate, during the period from January 2022 to December 2022. The overall prevalence of CPV-2 in dogs was 72.67% and it was significantly associated with breed, sex and age of examine dogs. In addition, the sequencing and phylogenetic analysis of circulating CPV-2 based on VP2 gene revealed that the circulating strain is CPV-2c. The present findings suggest that the failure of vaccination may be attributed to the use of CPV-2b commercial vaccines in areas where CPV-2c is prevalent. [ABSTRACT FROM AUTHOR]

Lagovirus europaeus/GI.2 causes severe and highly fatal Rabbit Hemorrhagic Disease (RHD). Because of its characteristics, this infection is used as an animal model for acute liver failure (ALF). Apoptosis is one of the key processes underlying ALF and has been described as one of the mechanisms of RHD pathogenesis. Apoptotic cell death has been quite well characterized in infection with different variants of GI.1 strains, but so far, the GI.2 genotype has not been widely studied. In this study, we performed an evaluation of apoptotic cell death in hepatocytes of rabbits infected with Lagovirus europaeus/GI.2. We analyzed the expression of genes involved in apoptotic cell death by real-time PCR and performed immunohistochemical (IHC) assays. We showed a significant increase in the expression of caspase-3 and the proapoptotic Bax and anti-apoptotic Bcl-2 in infected animals. In addition, we recorded increased Bax/Bcl-2 ratios. IHC analyses showed the presence of morphological signs of apoptosis in the hepatocytes of infected rabbits. Our results indicate that caspase-3 and proteins from the Bcl-2 families play a key role in apoptosis induced by Lagovirus europaeus/GI.2 infection. [ABSTRACT FROM AUTHOR]