Toll-like receptors 4 and 9 are responsible for the maintenance of the inflammatory reaction in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis

BACKGROUND: Steroid-responsive meningitis-arteritis (SRMA) is a systemic inflammatory disease affecting young adult dogs and a potential large animal model for neutrophilic meningitis. Similarities between SRMA and infectious central nervous system (CNS) diseases in lymphocyte subsets suggest an infectious origin. Toll-like receptors (TLRs) are pattern recognition receptors playing an important role in innate immunity. Due to their ability to recognize both self and non-self antigens, we hypothesize that TLRs are among the key factors for the induction of the inflammatory process in SRMA and provide an indirect hint on the etiology of the disease. METHODS: The expression profile of cell surface TLRs (TLR2, TLR4 and TLR5) and intracellular TLRs (TLR3 and TLR9) of canine leukocytes was analyzed by immunophenotyping and subsequent flow cytometric measurements. Experiments were performed on cerebrospinal fluid (CSF) and peripheral blood (PB) samples of dogs affected with SRMA during the acute phase (n = 14) as well as during treatment (n = 23) and compared with those of dogs with bacterial meningitis (n = 3), meningoencephalitis of unknown etiology (n = 6), neoplasia of the central nervous system (n = 6) and a group of dogs with miscellaneous neurological diseases (n = 9). Two additional control groups consisted of dogs with pyogenic infections (n = 13) and of healthy dogs (n = 6). RESULTS: All examined groups showed a high percentage of TLR2, TLR4 and TLR5 positive PB polymorphonuclear cells (PMNs) in comparison to healthy dogs. Very high values of TLR9 positive PB PMNs were detected in acute SRMA. Only a few similarities were found between SRMA patients and dogs with pyogenic infections, both groups were characterized by high expression of TLR4 positive PB monocytes. Glucocorticosteroid therapy reduced TLR2, TLR4 and TLR9 expression in PB monocytes. CONCLUSIONS: A relatively high expression of TLR4 and TLR9 in acute SRMA suggests that these two receptors might be involved in the inflammatory process in SRMA, enhancing the autoimmune reaction. Systematic CSF cell analysis for TLRs can be performed in future treatment studies in larger animals, such as dogs

Clinical externships within undergraduate studies in veterinary medicine

The purpose of this study was to evaluate the benefits of checklists for clinical practical courses. Clinical externships are a component of the practical part of the veterinary medicine curriculum. The control is under the responsibility of the training centres. Guidelines and checklists for extramural clinical courses were developed in order to facilitate control mechanisms. The analysis of such checklists should give an overview over the actual situation to enable the setting of minimum standards for extramural courses. The guidelines list practical activities carried out by the students in the veterinary practices or clinics. Data of 360 checklists were assessed in this study to evaluate whether checklists constitute a useful tool to control extramural studies

Evaluation of the Canine Intervertebral Disc Structure in Turbo Spin Echo-T2 and Fast Field Echo-T1 Sequences in Magnetic Resonance Imaging

In the current study the hypothesis should be proven that T1 weighted Fast Field Echo (FFE) sequence is a useful method to visualize intervertebral disc degeneration, respectively changes of the expected disc appearance. Medical records of 208 dogs were reviewed and images of 781 intervertebral discs were evaluated by two blinded examiners using a modified Pfirrmann classification system in two MRI sequences: FFE and Turbo-Spin-Echo T2-weighted sequence (T2W). The patients were allocated to three categories based on body conformation: (1) brachycephalic and chondrodystrophic breeds, (2) non-chondrodystrophic and non-brachycephalic breeds with a body weight of < 25 kg, and (3) non-chondrodystrophic and non-brachycephalic breeds with a body weight greater or equal 25 kg. In brachycephalic and chondrodystrophic dogs 340 intervertebral discs were evaluated, the majority of them presented a mild change of the normal disc structure, 53% in the FFE sequence and 41% in T2W images. High discrepancies were observed between mild and moderate degeneration: in the FFE-sequence 15% (n = 50) of the discs had signs of mild degeneration, whereas in T2W the same discs were graded as moderately degenerated. In non-chondrodystrophic and non-brachycephalic breeds under 25 kg body weight 320 intervertebral discs were assessed. In the FFE-sequence 52% (n = 166) of the intervertebral discs were judged as having a mild degeneration. In contrast, these same discs were graded as healthy discs (22%), mildly degenerated (33%), moderately degenerated (37%), and severely degenerated (8%) in T2W. In non-chondrodystrophic and non-brachycephalic breeds greater or equal 25 kg 121 intervertebral discs were assessed. The grading was equal in 43%, but differed in one grade (47%) and in two grades (10%) between the two sequences. In both sequences intervertebral disc herniations were equally well-diagnosed. The Kappa coefficient revealed a high discrepancy between the two MRI-sequences. In conclusion, FFE cannot replace the well-established T2W sequence for grading disc degeneration

Clinical skills of veterinary students - a cross-sectional study of the self-concept and exposure to skills training in Hannover, Germany

Background: Students of veterinary medicine should achieve basic professional competences required to practise their profession. A main focus of veterinary education is on developing clinical skills. The present study used the guidelines of the "Day-One Skills" list of European Association of Establishments for Veterinary Education (EAEVE) to create an online questionnaire for assessing the skills acquired by students at the University of Veterinary Medicine Hannover (TiHo). The theoretical and practical veterinary knowledge levels of the students and postgraduates are determined and compared. Results: In two batches, 607 people responded (response batch 1, 23.78%; response batch 2, 23.83%). From 49 defined skills, 28 are actually practised during training at the university and 21 activities are known only theoretically. Furthermore, the students showed great willingness to use simulators and models in a clinical skills lab. Conclusions: The results of this survey highlight that the opening of a clinical skills lab at the University of Veterinary Medicine Hannover and its incorporation into the study programme are ideal tools to promote practical competences and foster the motivation to learn

Evaluation of the eOSCE for testing clinical skills

The OSCE is a proven instrument for testing practical skills of students, not only in the (veterinary) medical field. At the University of Veterinary Medicine Hannover, Foundation (TiHo), students must complete a 10-week rotation in one of the university’s own clinics during the practical year in the 9th and 10th semesters in addition to other practical training. Within this framework, the first training for acquiring clinical practical skills with a formative examination (OSCE; Objective Structured Clinical Examination) was developed in the Clinical Skills Lab (CSL) in 2014. Since 2018, the TiHo has been the first veterinary medical training institution in Germany to conduct electronic OSCEs (eOSCEs). In the future, eOSCEs will also be introduced as a summative examination at the TiHo. For this reason, students in the practical year of the winter semester 2021/2022 and summer semester 2022 as well as former and current examiners were surveyed regarding their satisfaction with the eOSCE examination format as part of this study. The 175 analyzed questionnaires from students and 27 analyzed questionnaires from examiners showed a high level of satisfaction with the eOSCE overall, but at the same time indicated problems that should be ironed out before it is introduced as a summative examination in the state examination. In addition to its standardization and objectivity, the examination format also convinced with its quality-assurance review procedure and the direct feedback possibility with regard to the students’ performance

Generalized myoclonic epilepsy with photosensitivity in juvenile dogs caused by a defective DIRAS family GTPase 1

The clinical and electroencephalographic features of a canine generalized myoclonic epilepsy with photosensitivity and onset in young Rhodesian Ridgeback dogs (6 wk to 18 mo) are described. A fully penetrant recessive 4-bp deletion was identified in the DIRAS family GTPase 1 (DIRAS1) gene with an altered expression pattern of DIRAS1 protein in the affected brain. This neuronal DIRAS1 gene with a proposed role in cholinergic transmission provides not only a candidate for human myoclonic epilepsy but also insights into the disease etiology, while establishing a spontaneous model for future intervention studies and functional characterization

Molecular alterations of the TLR4-signaling cascade in canine epilepsy

Background: Cumulating evidence from rodent models points to a pathophysiological role of inflammatory signaling in the epileptic brain with Toll-like receptor-4 signaling acting as one key factor. However, there is an apparent lack of information about expression alterations affecting this pathway in canine patients with epilepsy. Therefore, we have analyzed the expression pattern of Toll-like receptor 4 and its ligands in brain tissue of canine patients with structural or idiopathic epilepsy in comparison with tissue from laboratory dogs or from owner-kept dogs without neurological diseases. Results: The analysis revealed an overexpression of Toll-like receptor-4 in the CA3 region of dogs with structural epilepsy. Further analysis provided evidence for an upregulation of Toll-like receptor-4 ligands with high mobility group box-1 exhibiting increased expression levels in the CA1 region of dogs with idiopathic and structural epilepsy, and heat shock protein 70 exhibiting increased expression levels in the piriform lobe of dogs with idiopathic epilepsy. In further brain regions, receptor and ligand expression rates proved to be either in the control range or reduced below control levels. Conclusions: Our study reveals complex molecular alterations affecting the Toll-like receptor signaling cascade, which differ between epilepsy types and between brain regions. Taken together, the data indicate that multi-targeting approaches modulating Toll-like receptor-4 signaling might be of interest for management of canine epilepsy. Further studies are recommended to explore respective molecular alterations in more detail in dogs with different etiologies and to confirm the role of the pro-inflammatory signaling cascade as a putative target

Concomitant necrotizing encephalitis and granulomatous meningoencephalitis in four toy breed dogs.

The term "meningoencephalitis of unknown origin" (MUO) describes a group of different encephalitides in dogs in which no infectious agent can be identified and a multifactorial etiology is suspected. Among others, genetic factors and unknown triggers seem to be involved. Included are necrotizing leukoencephalitis (NLE), necrotizing meningoencephalitis (NME), and granulomatous meningoencephalitis (GME). In this case series, we describe the histopathological findings of four toy breed dogs with focal or multifocal necrotizing encephalitis and mainly lymphocytic perivascular infiltrates on histopathological examination. At the same time, however, in all dogs, focal or multifocal high-grade angiocentric granulomatous inflammatory lesions were evident with focal histiocytic perivascular infiltrates in the brain. The former changes are typical for NLE and NME. In contrast, the latter changes are indicative of GME. This case series shows that the boundaries between the necrotizing and granulomatous variants of MUO might be smooth and suggests that NLE, NME, and GME are not as distinct as previously described. This finding could be a crucial piece of the puzzle in the study of the pathogenesis of MUO as individual susceptibility and specific triggers could be responsible for the manifestation of the different MUO subtypes