SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition.

T cell immunity is central for the control of viral infections. To characterize T cell immunity, but also for the development of vaccines, identification of exact viral T cell epitopes is fundamental. Here we identify and characterize multiple dominant and subdominant SARS-CoV-2 HLA class I and HLA-DR peptides as potential T cell epitopes in COVID-19 convalescent and unexposed individuals. SARS-CoV-2-specific peptides enabled detection of post-infectious T cell immunity, even in seronegative convalescent individuals. Cross-reactive SARS-CoV-2 peptides revealed pre-existing T cell responses in 81% of unexposed individuals and validated similarity with common cold coronaviruses, providing a functional basis for heterologous immunity in SARS-CoV-2 infection. Diversity of SARS-CoV-2 T cell responses was associated with mild symptoms of COVID-19, providing evidence that immunity requires recognition of multiple epitopes. Together, the proposed SARS-CoV-2 T cell epitopes enable identification of heterologous and post-infectious T cell immunity and facilitate development of diagnostic, preventive and therapeutic measures for COVID-19.

A structural UGDH variant associated with standard Munchkin cats.

BACKGROUND: Munchkin cats were founded on a naturally occurring mutation segregating into long-legged and short-legged types. Short-legged cats showed disproportionate dwarfism (chondrodysplasia) in which all four legs are short and are referred as standard Munchkin cats. Long-legged animals are referred as non-standard Munchkin cats. A previous study using genome-wide single nucleotide polymorphisms (SNPs) for genome-wide association analysis identified a significantly associated region at 168-184 Mb on feline chromosome (FCA) B1. RESULTS: In this study, we validated the critical region on FCA B1 using a case-control study with 89 cats and 14 FCA B1-SNPs. A structural variant within UGDH (NC_018726.2:g.173294289_173297592delins108, Felis catus 8.0, equivalent to NC_018726.3:g.174882895_174886198delins108, Felis catus 9.0) on FCA B1 was perfectly associated with the phenotype of short-legged standard Munchkin cats. CONCLUSION: This UGDH structural variant very likely causes the chondrodysplastic (standard) phenotype in Munchkin cats. The lack of homozygous mutant phenotypes and reduced litter sizes in standard Munchkin cats suggest an autosomal recessive lethal trait in the homozygote state. We propose an autosomal dominant mode of inheritance for the chondrodysplastic condition in Munchkin cats.

Comparative assessment of left atrial volume in healthy cats by two-dimensional and three-dimensional echocardiography.

BACKGROUND: The left atrium (LA) is an important prognostic parameter in cardiac pathologies of cats. Its size is currently measured in one-dimensional methods, while human medicine considers two- and three-dimensional echocardiography as standard. The objectives of this study were to compare monoplane, biplane, triplane and real-time three dimensional echocardiography for volumetric measurement of the left atrium in healthy cats and establish a reference interval for further studies on cats with heart disease. Additionally, the influence of age, sex and weight on left atrial volume (LAV) was tested. RESULTS: One dimensional monoplane Simpson method of discs (SMOD) in the right parasternal four chamber view (r4) and the left apical 2 chamber view (l2) as well as biplane SMOD had no significant difference for left atrial maximum volume (LAMax). They can be used as equivalent in future studies and one common reference range was set up (1.96 ± 0.54 ml). Those three methods produced significantly higher volumes than triplane echocardiography (RTTPE) and real time three dimensional echocardiography (RT3DE) using TomTec® software. LA volumetry with RTTPE and RT3DE-TomTec™ was more feasible than expected, but low RT3DE image quality was the main reason for excluding patients. Neither age nor weight had an influence on LA volume in healthy cats. Male LAV results were only slightly, but in 2D and RTTPE significantly higher than those of female cats with a range of + 10.46% to + 19.58%. CONCLUSIONS: Monoplane, biplane, triplane and real-time three dimensional echocardiography were feasible for LA volumetry in healthy cats and showed acceptable intra- and interobserver variability. One common LAMax reference range for monoplane r4, l2 and biplane SMOD was set up. Raw data can be used for LA volumes and does not need to be correlated with the cat's weight or age. Male cats have only slightly but significantly larger atria than females in 2D and RTTPE. Therefore, under reservation, also sex related limit values were defined.

Ryanodine-receptor inhibition by dantrolene effectively suppresses ventricular arrhythmias in an ex vivo model of long-QT syndrome.

AIMS: A significant antiarrhythmic potential of ryanodine receptor inhibition was reported in experimental studies. The aim of the present study was to assess potential antiarrhythmic effects of dantrolene in an experimental whole-heart model of drug-induced long-QT syndrome (LQTS). METHODS: In 12 isolated rabbit hearts, long-QT-2-syndrome was simulated by infusion of erythromycin (300 µM). Twelve rabbit hearts were treated with veratridine (0.5 µM) to mimic long-QT-3-syndrome. RESULTS: Monophasic action potentials and ECG showed a significant prolongation of QT-interval (+71 ms, P < 0.01) and action potential duration (APD, +43 ms, P < 0.01) after infusion of erythromycin as compared with baseline. Similar results were obtained in veratridine-treated hearts (QT-interval: +43 ms, P < 0.01; APD: +36 ms, P < 0.01). Both erythromycin (+36 ms, P < 0.05) and veratridine (+38 ms) significantly increased dispersion of repolarization. Additional infusion of dantrolene (20 µM) did not significantly alter QT-interval and APD but resulted in a significant reduction of dispersion of repolarization (erythromycin group: -33 ms, P < 0.05; veratridine group: -29 ms, P < 0.05). Lowering of potassium concentration resulted in the occurrence of early afterdepolarizations (EAD) and polymorphic ventricular tachycardia (VT) in 9 of 12 erythromycin-treated hearts (175 episodes) and 8 of 12 veratridine-treated hearts (66 episodes). Additional infusion of dantrolene significantly reduced occurrence of polymorphic VT and resulted in occurrence of EAD and polymorphic VT in 1 of 12 erythromycin-treated hearts (18 episodes) and 1 of 12 veratridine-treated hearts (3 episodes). CONCLUSION: Inhibition of the ryanodine receptor by dantrolene significantly reduced occurrence of polymorphic VT in drug-induced LQTS. A significant reduction of spatial dispersion of repolarization represents a major antiarrhythmic mechanism. These results imply that dantrolene may represent a promising antiarrhythmic option in drug-induced LQTS.

Antiarrhythmic effect of antazoline in experimental models of acquired short- and long-QT-syndromes.

Aims: Antazoline is a first-generation antihistamine with antiarrhythmic properties. This study examines potential electrophysiological effects of antazoline in short-QT-syndrome (SQTS) and long-QT-syndrome (LQTS). Methods and results: Sixty-five rabbit hearts were Langendorff-perfused. Action potential duration at 90% of repolarization (APD90), QT-interval, spatial dispersion (DISP), and effective refractory period (ERP) were measured. The IK, ATP-opener pinacidil (1 µM, n = 14) reduced APD90 (-14 ms, P < 0.01), QT-interval (-14 ms, P < 0.01), and ERP (-11 ms, P < 0.01), thus simulating acquired SQTS. Additional infusion of 20 µM antazoline prolonged repolarization. Under baseline conditions, ventricular fibrillation (VF) was inducible in 5 of 14 hearts (10 episodes) and in 5 of 14 pinacidil-treated hearts (21 episodes, P = ns). Antazoline significantly reduced induction of VF (0 episodes, P < 0.05 each). Further 17 hearts were perfused with 100 µM sotalol and 17 hearts with 300 µM erythromycin to induce acquired LQTS2. In both groups, prolongation of APD90, QT-interval, and ERP was observed. Spatial dispersion was increased (sotalol: +26 ms, P < 0.01; erythromycin: +31 ms, P < 0.01). Additional infusion of antazoline reduced DISP (sotalol: -22 ms, P < 0.01; erythromycin: -26 ms, P < 0.01). Torsade de pointes (TdP) occurred in 6 of 17 sotalol-treated (22 episodes, P < 0.05 each) and in 8 of 17 erythromycin-treated hearts (96 episodes P < 0.05 each). Additional infusion of antazoline completely suppressed TdP in both groups (P < 0.05 each). Acquired LQTS3 was induced by veratridine (0.5 µM, n = 17) and similar results were obtained (APD90: +24 ms, P < 0.01, QT-interval: +58 ms, P < 0.01, DISP: +38 ms, P < 0.01). Torsade de pointes occurred in 10 of 17 hearts (41 episodes, P < 0.05 each). Antazoline significantly reduced TdP (2 of 17 hearts, 4 episodes, P < 0.05 each). Conclusion: Antazoline significantly reduced induction of VF in an experimental model of acquired SQTS. In three experimental models of acquired LQTS, antazoline effectively suppressed TdP.

Ranolazine Prevents Levosimendan-Induced Atrial Fibrillation.

OBJECTIVES: Levosimendan is a calcium sensitizer that is used as positive inotropic drug in acute decompensated heart failure. An increased incidence of atrial fibrillation after levosimendan-treatment was observed in clinical and experimental studies. Due to the limited range of antiarrhythmic drugs, the aim of the present study was to assess potential antiarrhythmic effects of ranolazine in levosimendan-pretreated isolated rabbit hearts. METHODS: Twelve rabbit hearts were excised and retrogradely perfused employing the Langendorff setup. Left and right atrial catheters were used to record monophasic action potentials and to obtain cycle length-dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). After obtaining baseline data, 0.5 µmol/L levosimendan was infused. Subsequently, 10 µmol/L ranolazine was administered. RESULTS: Infusion of levosimendan led to a reduction of aAPD90 (-9 ms, p < 0.05) and aERP (-13 ms, p < 0.05). Additional treatment with ranolazine prolonged aAPD90 (+23 ms, p < 0.01) and aERP (+30 ms, p < 0.05). Under baseline conditions, a predefined pacing protocol induced 77 episodes of atrial fibrillation. Infusion of levosimendan enhanced the vulnerability to atrial fibrillation (132 episodes, p = 0.14). Further treatment with ranolazine had a significant antiarrhythmic effect (61 episodes, p < 0.05). CONCLUSIONS: In this study, ranolazine seems to prevent atrial fibrillation in levosimendan-pretreated hearts. Underlying mechanism is a prolongation of atrial repolarization and aERP.

Severe Hemorrhagic Shock Leads to a Delayed Fracture Healing and Decreased Bone Callus Strength in a Mouse Model.

BACKGROUND: Multiple trauma is frequently associated with hemorrhagic shock and fractures of the extremities. Clinically, the rate of impaired fracture healing (delayed healing and nonunion) seems to be increased in patients with multiple injuries compared with patients with isolated fractures. As the underlying pathogenesis remains poorly understood, we aimed to analyze the biomechanical properties during fracture healing in a murine model. QUESTIONS: The aim of this study was to determine whether fracture healing after severe hemorrhagic shock results in (1) delayed bridging as determined by macroscopic and radiographic assessment, (2) altered conditions of callus components as determined by µCT, and (3) decreased maximum bending moment measured by a three-point-bending test compared with ordinary fracture healing. METHODS: Male C57BL/6NCrl mice were randomly assigned to five groups and four different times (five to 10 mice per group and time). Only the right femur from each mouse was used for analysis: the trauma hemorrhage (TH) group received a pressure-controlled hemorrhagic shock via catheter; the osteotomy (Fx) group underwent osteotomy and implantation of an external fixator on the right femur; the combined trauma (THFx) group received hemorrhagic shock and an external fixator with osteotomy; the sham group underwent implantation of a catheter and external fixator but had no blood loss or osteotomy, and the control group underwent no interventions. After 2, 3, 4, or 6 weeks, five to 10 animals of each group were sacrificed. Bones were analyzed macroscopically and via radiographs, µCT, and three-point-bending test. Statistical significance was set at a probability less than 0.05. Comparisons were performed using the Mann-Whitney U or the Kruskal-Wallis test. RESULTS: In the Fx group, the osteotomy gap was stable and bridged after 2 weeks in contrast to some bones in the THFx group where stable bridging did not occur. No difference was observed between the groups. µCT analysis showed reduced density of bone including callus (THFx: 1.17 g/cm3; interquartile range [IQR], 0.04 g/cm3; Fx: 1.22 g/cm3; IQR, 0.04 g/cm3; p = 0.002; difference of medians [DM], -0.048; 95% CI, -0.073 to -0.029) and increased share of callus per volume of bone mass (%) after 2 weeks in the THFx group compared with the Fx group (THFx: 44.16%; IQR, 8.66%; Fx: 36.73%; IQR, 4.39%; p = 0.015; DM, 7.634; 95% CI, 2.018-10.577). The three-point-bending test established a decreased maximum bending moment in the THFx group compared with the Fx group 2 weeks after surgery (THFx: 7.10 Nmm; IQR, 11.25 Nmm; Fx: 11.25 Nmm; IQR, 5.70 Nmm; p = 0.026; DM, -5.043; 95% CI, -10.867 to -0.74). No differences were observed between the THFx and Fx groups after more than 2 weeks. CONCLUSION: In this in vivo mouse fracture model, we conclude that hemorrhagic shock retards fracture healing during the early phase of the facture healing process. CLINICAL RELEVANCE: A severe hemorrhagic shock in patients could result in initial delayed fracture healing and needs special attention. We plan to conduct a prospective, observational clinical research study to analyze if delayed fracture healing occurs in patients after severe blood loss.

Dronedarone and digitalis: individually reduced post-repolarization refractoriness enhances life-threatening arrhythmias.

AIMS: Interaction between dronedarone and digitalis has been discussed as a possible cause for increased mortality in the presence of dronedarone observed in the PALLAS trial. The aim of this study was to assess possible proarrhythmic effects of dronedarone in combination with digitalis in an experimental whole heart model. METHODS AND RESULTS: Twenty-six female rabbits underwent chronic oral treatment with dronedarone (50 mg/kg/day for 6 weeks). Twenty-four rabbits received placebo. Heart failure was induced by rapid ventricular pacing. Sham-operated rabbits received a right-ventricular pacing lead but were not paced. Thereafter, hearts were isolated and Langendorff-perfused. Monophasic action potentials and a 12 lead electrocardiogram showed a dose-dependent decrease of QT interval, APD90, effective refractory periods, and postrepolarization refractoriness in control hearts and dronedarone-pretreated hearts after application of ouabain (0.1 and 0.2 µM). After acute application of ouabain, ventricular fibrillation (VF) was inducible by programmed ventricular stimulation in 6 of 12 untreated sham hearts (38 episodes) as compared with 7 of 11 dronedarone-pretreated sham hearts (76 episodes). In untreated failing hearts, 6 of 12 hearts were inducible (47 episodes) as compared with 7 of 15 hearts dronedarone-pretreated failing hearts (93 episodes). CONCLUSION: In this study, ouabain treatment resulted in an increased ventricular vulnerability in chronically dronedarone-pretreated control and failing hearts. Ouabain led to a significant abbreviation of ventricular repolarization. This was more marked in dronedarone-pretreated hearts and resulted in an elevated incidence of VF. This may help to interpret the results of the PALLAS trial.

Vernakalant in an experimental model of pacing-induced heart failure: lack of proarrhythmia despite prolongation of repolarization.

BACKGROUND: The present ESC guidelines on atrial fibrillation have introduced vernakalant (VER) for pharmacologic cardioversion of atrial fibrillation. The aim of the present study was to investigate possible proarrhythmic effects of vernakalant in an experimental model of heart failure (HF). METHODS AND RESULTS: In 12 female rabbits, HF was induced with the use of 4 weeks of rapid ventricular pacing. Twelve rabbits were sham operated. Isolated hearts demonstrated a significant prolongation of myocardial repolarization after induction of HF. Vernakalant caused a concentration-dependent (10 µmol/L and 30 µmol/L) increase of action potential duration (APD90) and QT interval without affecting spatial and temporal dispersion of repolarization. The increase in APD90 was accompanied by a greater increase in refractory period resulting in a significant increase in post-repolarization refractoriness. In control conditions, programmed ventricular stimulation and burst pacing led to ventricular fibrillation (VF) in 2 of the 12 sham (4 episodes) and in 3 of the 12 HF (24 episodes) subjects. In the presence of 30 µmol/L vernakalant, VF was no longer inducible in both groups (0 episodes). In the presence of low K+ concentration, neither sham nor HF vernakalant-treated subjects developed early after-depolarizations or ventricular tachyarrhythmias. CONCLUSION: In the present study, application of vernakalant led to a significant prolongation of myocardial repolarization and increased post-repolarization refractoriness but did not induce early after-depolarization and therefore did not cause proarrhythmia in failing hearts.

Transcutaneous electromagnetic induction heating of an intramedullary nickel-titanium shape memory implant.

PURPOSE: Inadequate mechanical stimuli are a major cause for nonunions following surgery for femoral and tibial shaft fractures. Adapting fixation rigidity during the course of fracture healing requires additional surgery. Nickel-titanium (NiTi) implants can change shape and rigidity by employing a temperature-dependent shape-memory effect. As a first step in the development of advanced intramedullary (IM) NiTi devices for fracture healing, this study aimed to test the feasibility and safety of transcutaneous electromagnetic induction heating of an IM NiTi implant in a rat model. METHODS: In 51 rats, NiTi implants were introduced into the left distal femur. Forty-four animals were transferred to an induction coil, and the implant was electromagnetically heated to temperatures between 40° and 60 °C Blood samples were drawn before and four hours after the procedure. Interleukin (IL)-1, IL-4, IL-10, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) were measured. Animals were sacrificed at three weeks. Histological specimens from the hind leg and liver were retrieved and examined for inflammatory changes, necrosis or corrosion pits. RESULTS: All animals successfully underwent the surgical procedure. Following transcutaneous induction heating, target temperature was confirmed in 37/44 rats. Postoperative controls showed no signs of undue limitations. Neither cytokine measurements nor histological specimens showed any significant differences between groups. There were no corrosion pits or necrosis. CONCLUSION: We conclude that electromagnetic induction heating of IM NiTi implants is feasible and safe in a rat femur model. These findings reflect a further step in the development of novel concepts for IM fracture fixation that might lead to better fracture healing, less patient discomfort and less need for surgical interventions.

Correction: Gross anatomy, histology and blood vessel topography of the alimentary canal of the Inland Bearded Dragon (Pogona vitticeps).

[This corrects the article DOI: 10.1371/journal.pone.0234736.].

Ectoparasites of European hedgehogs (Erinaceus europaeus) in Germany and their health impact.

BACKGROUND: The European hedgehog (Erinaceus europaeus) is known for high levels of ectoparasitism that not only represents a health risk for the animals themselves, but also for pet animals and humans as hedgehogs are frequently taken into human care. In the present study, patterns of ectoparasite infestation were assessed in hedgehogs taken into care at northern German animal rehabilitation centres. METHODS: Ectoparasites (ticks, fleas and mites) of 498 hedgehogs were collected over a period of 3 years from July 2018 to May 2021. Species were identified based on morphological characteristics and also via amplification and sequencing of the partial cytochrome c oxidase subunit 2 (COX-2) gene for fleas of the family Ceratophyllidae. Seasonal changes in infestation patterns as well as correlations with animal age, body weight and health status were assessed using generalised linear models. RESULTS: Infestation with ticks, fleas and mites occurred throughout the year. Overall, 86.5% (431/498) of the examined hedgehogs were infested with ticks, 91.4% (455/498) with fleas and 17.7% (88/498) with mites. Ixodes ricinus and Ixodes hexagonus/Ixodes canisuga were the most common tick species detected, with the additional occurrence of one Ixodes frontalis. Significant seasonal changes were observed for I. ricinus, but not for I. hexagonus/I. canisuga. Additionally, I. ricinus nymph prevalence declined significantly as of 2020, probably as a consequence of the climate change-related drought as of 2018. In hedgehogs with flea infestations, Archaeopsylla erinacei, Ceratophyllus sciurorum, Nosopsyllus fasciatus and Ctenocephalides felis were identified. In all cases of mite infestation, Caparinia tripilis was detected, in addition to specimens of the family Macronyssidae and free-living mites of the family Acaridae. Statistical analyses showed correlations regarding the factors month, year, body weight and age, but no correlation was evident regarding the health status of the animals. CONCLUSIONS: With a detected infestation rate of 98.6%, almost all of the examined hedgehogs were infested with at least one ectoparasite species. The seasonal activity patterns of the different ectoparasite species together with the complex annual cycle of hedgehogs lead to different seasonal patterns in ectoparasite prevalence and infestation intensities. Due to the risk of transmission of zoonotic pathogens as well as the possible negative impact on the host itself, hedgehogs should be treated against ectoparasites when taken into care facilities.

Blood Vessel Topography of the Feet in Selected Species of Birds of Prey and Owls.

Birds of prey and owls are susceptible to diseases of and traumatic injuries to their feet, which regularly require surgical intervention. A precise knowledge of the blood vessel topography is essential for a targeted therapy. Therefore, the metatarsal and digital vasculature was examined in eight species of birds of prey and owls. The study included contrast micro-computed tomography scans and anatomical dissections after intravascular injection of colored latex. In all examined species, the dorsal metatarsal arteries provided the main supply to the foot and their branching pattern and number differed between species. They continued distally as digital arteries. All examined species showed a basic pattern of four collaterally located digital blood vessels per toe: a prominent artery and small vein on one side and a small artery and prominent vein on the other side. Digital veins united to form common digital veins, most of which joined into a superficial, medially located metatarsal vein. This vein provided the main drainage of the foot. The detailed visualization of the topography of pedal blood vessels will help veterinary surgeons during surgical procedures. In addition, differences in the plantar arterial arch between hawks and falcons were discussed regarding their possible influence on the prevalence of pododermatitis (bumblefoot).

Potential drivers of vector-borne pathogens in urban environments: European hedgehogs (Erinaceus europaeus) in the spotlight.

Vector-borne diseases (VBDs) are considered as (re-)emerging, but information on the transmission cycles and wildlife reservoirs is often incomplete, particularly with regard to urban areas. The present study investigated blood samples from European hedgehogs (Erinaceus europaeus) presented at wildlife rehabilitation centres in the region of Hanover. Past exposure to B. burgdorferi sensu lato (s.l.) and tick-borne encephalitis virus (TBEV) was assessed by serological detection of antibodies, while current infections with Borrelia spp., Anaplasma phagocytophilum, Rickettsia spp., Neoehrlichia mikurensis, Bartonella spp., Babesia spp. and Spiroplasma ixodetis were investigated by (q)PCR. Of 539 hedgehogs tested for anti-Borrelia antibodies, 84.8% (457/539) were seropositive, with a higher seropositivity rate in adult than subadult animals, while anti-TBEV antibodies were detected in one animal only (0.2%; 1/526). By qPCR, 31.2% (168/539) of hedgehog blood samples were positive for Borrelia spp., 49.7% (261/525) for A. phagocytophilum, 13.0% (68/525) for Bartonella spp., 8.2% for S. ixodetis (43/525), 8.0% (42/525) for Rickettsia spp. and 1.3% (7/525) for Babesia spp., while N. mikurensis was not detected. While further differentiation of Borrelia spp. infections was not successful, 63.2% of the A. phagocytophilum infections were assigned to the zoonotic ecotype I and among Rickettsia spp. infections, 50.0% to R. helvetica by ecotype- or species-specific qPCR, respectively. Sequencing revealed the presence of a Rickettsia sp. closely related to Rickettsia felis in addition to a Bartonella sp. previously described from hedgehogs, as well as Babesia microti and Babesia venatorum. These findings show that hedgehogs from rehabilitation centres are valuable sources to identify One Health pathogens in urban areas. The hedgehogs are not only exposed to pathogens from fleas and ticks in urban areas, but they also act as potent amplifiers for these vectors and their pathogens, relevant for citizens and their pets.

Surgical Stabilisation of a Coxofemoral Luxation in a Northern Goshawk (Accipter gentilis) with Transarticular Pinning.

A 3-year-old male northern goshawk (Accipiter gentilis) used in falconry for hunting was diagnosed with a craniodorsal coxofemoral luxation of the left leg after an unsuccessful hunting flight. Closed reduction in the dislocation was unsuccessful and the hip joint reluxed again with slight abduction of the limb. An open surgical reduction with a transarticular stabilization using a normogradely inserted Kirschner wire was performed. The implant was removed surgically after five weeks. After about seven weeks, the owner saw no abnormalities in the loading of the limbs, and the goshawk was successfully used for hunting after nine months in the next hunting season.

Surgical removal of an atypical histiocytic cell proliferation in a bearded dragon (Pogona vitticeps).

A 4-year-old female bearded dragon (Pogona vitticeps) was referred to the Clinic for Small Mammals, Reptiles and Birds of the University of Veterinary Medicine, Hannover, Germany for diagnostics and treatment of a growing mass in the right cervical region. The owner reported that the mass had grown over the past 4 weeks with only little alteration in the lizard´s behavior when the animal started rubbing its neck against the cage equipment. Physical examination as well as ultrasonographic and computed tomographic diagnostics revealed a highly vascularized mass, which allowed for the hypothesis of an aneurysm or a neoplasia. Complete surgical resection of the mass could be performed uneventfully. The bearded dragon recovered well from anesthesia and the surgical procedure. The microbiological sample of the excised mass revealed Group F-67 Salmonella. Histopathological examination of the excised mass revealed a histiocytic cell proliferation with centrally located blood filled cavities, hemorrhages and granulation tissue resembling features of a pseudoaneurysm. This report describes the diagnosis of an atypical growing mass in a bearded dragon and its successful removal.

Treatment options, complications and long-term outcomes for limb fractures in pet rabbits.

BACKGROUND: Limb fractures represent the most common orthopaedic disease in pet rabbits. However, only a few studies have evaluated therapeutic details of limb fractures. There are no data available for long-term outcomes of limb fracture treatment. METHODS: The medical records of six institutions were reviewed retrospectively to identify cases of traumatic limb bone fractures in pet rabbits between 1999 and 2020. The medical records (n = 387) were analysed for details of fracture prevalence, aetiology, therapy protocols, treatment complications, outcome and long-term effects. In addition to the retrospective data evaluation, 13 rabbits were re-evaluated in person in recent clinical analyses, including orthopaedic examination, radiography and computed-tomographic imaging. Details of long-term effects of fracture treatment were requested over the telephone for a further 232 animals using a standardised questionnaire. RESULTS: Long bone fractures accounted for the majority of all fractures (296/387; 76.5%). Hindlimb fractures (301/387; 77.7%) were more common than forelimb fractures (86/387; 22.2%), and tibial fractures and combined fractures of the tibia and fibula (119/387; 30.8%) were observed most frequently. Most fracture treatments were based on osteosynthesis procedures (243/328; 74.1%). Treatment complications occurred in 130 out of 328 (39.6%) cases. A high bodyweight (p = 0.047) and an older age (p = 0.01) were found to be significant risk factors for the emergence of therapy complications. Overall, 75.4% of animals (175/232) had a satisfactory long-term outcome. Limb posture anomalies were evaluated in 61 cases (26.3%). LIMITATIONS: The multi-centre approach led to the inclusion of various institutions, veterinarians, treatment protocols and rabbit populations that might have influenced the results. The medical records were reviewed retrospectively, so there were some data that were lacking or could not be collected in a standardised manner. Furthermore, rabbit owners' evaluation of long-term outcomes might be prone to error, despite the use of a standardised interview questionnaire. CONCLUSION: Limb fractures are a common orthopaedic issue in pet rabbits. The patient's bodyweight and age are significant risk factors for the emergence of complications during the fracture treatment process. Long-term orthopaedic effects, such as abnormal limb posture and permanent lameness of the affected limb, were observed regularly.

A missense mutation in the SERPINH1 gene in Dachshunds with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a hereditary disease occurring in humans and dogs. It is characterized by extremely fragile bones and teeth. Most human and some canine OI cases are caused by mutations in the COL1A1 and COL1A2 genes encoding the subunits of collagen I. Recently, mutations in the CRTAP and LEPRE1 genes were found to cause some rare forms of human OI. Many OI cases exist where the causative mutation has not yet been found. We investigated Dachshunds with an autosomal recessive form of OI. Genotyping only five affected dogs on the 50 k canine SNP chip allowed us to localize the causative mutation to a 5.82 Mb interval on chromosome 21 by homozygosity mapping. Haplotype analysis of five additional carriers narrowed the interval further down to 4.74 Mb. The SERPINH1 gene is located within this interval and encodes an essential chaperone involved in the correct folding of the collagen triple helix. Therefore, we considered SERPINH1 a positional and functional candidate gene and performed mutation analysis in affected and control Dachshunds. A missense mutation (c.977C>T, p.L326P) located in an evolutionary conserved domain was perfectly associated with the OI phenotype. We thus have identified a candidate causative mutation for OI in Dachshunds and identified a fifth OI gene.

[Studies on the use of iodine-containing contrast agent diatrizoate in rabbits (Oryctolagus cuniculus)]. / Untersuchungen zum Einsatz des jodhaltigen Kontrastmittels Amidotrizoesäure beim Kaninchen (Oryctolagus cuniculus).

OBJECTIVE: The use of the iodine-containing contrast agent diatrizoate was investigated in healthy rabbits and in rabbits with gastric dilatation and intestinal obstruction. For this purpose, transit times through the gastrointestinal tract and clinical use were investigated during a one year period. In addition, a possible influence on thyroid hormone levels was evaluated. MATERIAL AND METHODS: Transit times of contrast agent through the different intestinal sections were examined radiographically in 14 healthy rabbits. For this purpose, 7 ml/kg of a 300 mg iodine/ml and 600 mg diatrizoate/ml containing solution were administered. Radiographs were obtained at different time intervals. Three different doses (D1 2 ml/kg, D2 7 ml/kg, D3 10 ml/kg) were administered, and blood samples were collected at two time points (60 min, 24 h) to analyze thyroid hormone levels (TT4, fT4, TSH). In addition, 70 rabbits that had received the contrast agent diatrizoate because of gastric dilatation and suspected intestinal obstruction were retrospectively evaluated during a period of one year. Focus was placed on arrival of the contrast agent in the cecum, laboratory changes, and mortalities. RESULTS: In all healthy rabbits, contrast medium was detectable in the cecum after a mean of 45-60 min. In the animals suffering from gastrointestinal obstruction, this was delayed to a mean of 121.2 min. These animals showed hypothermia in 92.4 % and hyperglycemia in 45.9 %. 56.1 % exhibited an increase in urea and 33.9 % an increase in creatinine. In 71.4 % of cases, medical treatment was possible, however 12 % of these individuals succumbed to the disease. 28.6 % of the cases were managed surgically which was associated with a mortality of 50 %. TT4, fT4, and TSH levels displayed significant alterations among the three contrast agent doses (p < 0.05). These changes were found to be transient when follow-up was performed two weeks later. CONCLUSION AND CLINICAL RELEVANCE: When ileus is suspected in rabbits, diatrizoate may be helpful in evaluating the progression of the disease in addition to the use of native radiographs. Sufficient hydration and monitoring of renal function are advisable. Transient changes in thyroid hormones were evident but lacked clinical relevance.

Analysis of the B-Type Natriuretic Peptide and the Aminoterminal-Pro-B-Type Natriuretic Peptide in Different Parrot, Raptor and Owl Species.

The B-type natriuretic peptide (BNP), a member of the natriuretic peptide family and a cardiac hormone, is produced mainly in the ventricular myocytes and released into the circulation due to mechanical stimuli during an increasing cardiac wall stretch. BNP has a significant role in the regulation of the cardiovascular system and body fluid. The concentration of this hormone and of the biologically inactive amino-terminal-prohormone in the blood plasma is a helpful diagnostic tool for detecting cardiovascular diseases in human medicine and can be used as a prognostic marker for the risk of mortality, whilst such a tool does not exist for avian medicine. To date, the amino acid sequence of BNP is not known for many of the species commonly presented in avian consultation. In this study, the amino acid sequence of BNP and the prepropeptide was described for 12 parrot species as well as 3 raptor and 3 owl species by polymerase chain reaction (PCR) after RNA isolation from the heart. The results showed a high similarity between the amino acid sequences in the mature peptide region of the BNP. The prepropeptide showed several differences between the examined species, some of them shared by closely related species.