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Temporomandibular joint (TMJ) ankylosis is defined as fibrous or bony fusion of the mandibular head of the condylar process and the mandibular fossa of the squamous part of the temporal bone. Ankylosis of the TMJ may be intraarticular, extraarticular, or both. The objective of this report is to describe the surgical planning, technique, and outcome of gap arthroplasty for extensive TMJ ankylosis in cats. Client-owned cats (n = 7) were examined clinically and surgical planning included the use of cone-beam computed tomography (CBCT) and tridimensional (3D) printed models. In six of the seven cats, temporary tracheostomy intubation was required. Gap arthroplasty included zygomectomy, coronoidectomy, condylectomy, as well as fossectomy (removal of the mandibular fossa of the temporal bone) and was performed using a piezosurgical unit. In all seven cats, gap arthroplasty was performed without surgical complications. In addition, a clinically acceptable mouth opening was achieved in all cases. However, a noticeable mandibular instability was observed. Medium-term follow-up demonstrated acceptable quality of life with one case of recurrence of ankylosis requiring repeated bilateral surgery, and a second case with recurrence of ankylosis not requiring surgical intervention at the time of manuscript preparation. We concluded that TMJ gap arthroplasty in cats is a salvage procedure indicated in cases of severe intraarticular and extraarticular ankylosis. Diagnostic imaging by means of CBCT and 3D printing are essential for precise surgical planning. The use of a piezosurgical unit allows for safe and precise ostectomy. Clinically, despite the resulting mandibular instability, appropriate prehension of food and water was possible.

Treatment of craniomaxillofacial (CMF) trauma in dogs requires a thorough understanding of the CMF skeletal structures involved. The human medical literature has several examples of CMF trauma and fracture classification, including the classically described Le Fort fractures. The recent classification schemes require large studies using computed tomography (CT). In the veterinary medical literature, such studies are lacking. The aims of part II of this retrospective study were to use a large number of CT studies of dogs evaluated for CMF trauma to determine whether specific fracture locations in the CMF region occur concurrently, and whether trauma etiology influences fracture morphology. This information may then be used to form a fracture classification scheme in the future. The medical records and CT studies of 165 dogs over a 10-year period were evaluated. The skeletal location of CMF fractures as well as the severity of displacement and fragmentation of each fracture was recorded. Dogs' demographic data and trauma etiology were also recorded. Fractured portions of the mandible tended to occur with fractures of adjacent bones, with the major exception of symphyseal separation, which occurred simultaneously with fractures of the cribriform plate. Fractures of the maxillary bone were accompanied by many concurrent fractures affecting the majority of the midface, skull base, and cranial vault. When the zygomatic bone was fractured, the other bones comprising the orbit also tended to fracture. Fractures of the relatively superficially located frontal and nasal bones were often accompanied by fractures of the skull base. Fracture etiology influenced fracture morphology such that vehicular trauma resulted in a relatively higher number of severely displaced and comminuted fractures than did other trauma etiologies. This study provides examples of fractures that, when found, should prompt veterinarians to look for additional injuries in specific locations. In addition, it further highlights the need for thorough CT evaluation of the entire CMF region, even when clinically apparent fractures appear relatively superficial.

Treatment of craniomaxillofacial (CMF) trauma in dogs often requires a multidisciplinary approach and a thorough understanding of the CMF skeletal structures involved. The aim of this retrospective study was to use a large number of CT studies of dogs evaluated for CMF trauma and to describe fracture location and morphology in relation to demographic data and trauma etiology. The medical records and CT studies of 165 dogs over a 10-year period were evaluated. The skeletal location of CMF fractures as well as the severity of displacement and fragmentation of each fracture was recorded. Patient demographic data and trauma etiology were also recorded. Animal bites accounted for the majority of trauma (50%), followed by unknown trauma (15%), vehicular accidents (13%), and blunt force trauma (13%). Small dogs,

BackgroundFeline adipose-derived mesenchymal stem cells (ASCs) have been successfully used in clinical trials for the treatment of immune-mediated diseases with T cell dysregulation. However, the immunomodulatory pathways utilized by feline ASCs to suppress T cell activation have not been fully determined. We investigated the mechanisms used by feline ASCs to inhibit T cell proliferation, including the soluble factors and the cell-cell contact ligands responsible for ASC-T cell interaction.MethodsThe immunomodulatory activity of feline ASCs was evaluated via cell cycle analysis and in vitro mixed leukocyte reaction using specific immunomodulatory inhibitors. Cell-cell interactions were assessed with static adhesion assays, also with inhibitors.ResultsFeline ASCs decrease T cell proliferation by causing cell cycle arrest in G0-G1. Blocking prostaglandin (PGE2), but not IDO, partially restored lymphocyte proliferation. Although PDL-1 and CD137L are both expressed on activated feline ASCs, only the interaction of intercellular adhesion molecule 1 (ICAM-1, CD54) with its ligand, lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18), was responsible for ASC-T cell adhesion. Blocking this interaction reduced cell-cell adhesion and mediator (IFN-γ) secretion and signaling.ConclusionsFeline ASCs utilize PGE2 and ICAM-1/LFA-1 ligand interaction to inhibit T cell proliferation with a resultant cell cycle arrest in G0-G1. These data further elucidate the mechanisms by which feline ASCs interact with T cells, help define appropriate T cell-mediated disease targets in cats that may be amenable to ASC therapy, and may also inform potential translational models for human diseases.

OBJECTIVE:To evaluate and quantify the kinematic behavior of canine mandibles before and after bilateral rostral or unilateral segmental mandibulectomy as well as after mandibular reconstruction with a locking reconstruction plate in ex vivo conditions. SAMPLE:Head specimens from cadavers of 16 dogs (range in body weight, 30 to 35 kg). PROCEDURE:Specimens were assigned to undergo unilateral segmental (n = 8) or bilateral rostral (8) mandibulectomy and then mandibular reconstruction by internal fixation with locking plates. Kinematic markers were attached to each specimen in a custom-built load frame. Markers were tracked in 3-D space during standardized loading conditions, and mandibular motions were quantified. Differences in mandibular range of motion among 3 experimental conditions (before mandibulectomy [ie, with mandibles intact], after mandibulectomy, and after reconstruction) were assessed by means of repeated-measures ANOVA. RESULTS:Both unilateral segmental and bilateral rostral mandibulectomy resulted in significantly greater mandibular motion and instability, compared with results for intact mandibles. No significant differences in motion were detected between mandibles reconstructed after unilateral segmental mandibulectomy and intact mandibles. Similarly, the motion of mandibles reconstructed after rostral mandibulectomy was no different from that of intact mandibles, except in the lateral direction. CONCLUSIONS AND CLINICAL RELEVANCE:Mandibular kinematics in head specimens from canine cadavers were significantly altered after unilateral segmental and bilateral rostral mandibulectomy. These alterations were corrected after mandibular reconstruction with locking reconstruction plates. Findings reinforced the clinical observations of the beneficial effect of reconstruction on mandibular function and the need for reconstructive surgery after mandibulectomy in dogs.

Canine acanthomatous ameloblastomas (CAA), analogs of human ameloblastoma, are oral tumors of odontogenic origin for which the genetic drivers have remained undefined. By whole-exome sequencing, we have now discovered recurrent HRAS and BRAF activating mutations, respectively, in 63% and 8% of CAA. Notably, cell lines derived from CAA with HRAS mutation exhibit marked sensitivity to MAP kinase (MAPK) pathway inhibitors, which constrain cell proliferation and drive ameloblast differentiation. Our findings newly identify a large-animal spontaneous cancer model to study the progression and treatment of RAS-driven cancer. More broadly, our study highlights the translational potential of canine cancer genome sequencing to benefit both humans and their companion animals.

The objective of this study was to evaluate the diagnostic yield of dental radiography (DR) and 3 cone-beam computed tomography (CBCT) software modules for the identification of 32 pre-defined dentoalveolar lesions in cats. For 5 feline cadaver heads and 22 client-owned cats admitted for evaluation and treatment of dental disease, 32 predefined dentoalveolar lesions were evaluated separately and scored by use of dental radiography and 3 CBCT software modules [multiplanar reconstructions (MPR), tridimensional (3-D) rendering, and reconstructed panoramic views]. A qualitative scoring system was used. Dentoalveolar lesions were grouped into 14 categories for statistical analysis. Point of reference for presence or absence of a dentoalveolar lesion was determined as the method that could be used to clearly identify the disorder as being present. Accuracy, sensitivity, specificity, and positive and negative predictive values were calculated with the McNemar χ2 test of marginal homogeneity of paired data. When all 3 CBCT software modules were used in combination, the diagnostic yield of CBCT was significantly higher than that of dental radiography for 4 of 14 categories (missing teeth, horizontal bone loss, loss of tooth integrity, feline resorptive lesions), and higher, although not significantly so, for 9 categories (supernumerary teeth, supernumerary roots, abnormally shaped roots, vertical bone loss, buccal bone expansion, periapical disease, inflammatory root resorption, and external replacement root resorption). In conclusion, we found that CBCT provided more clinically relevant detailed information as compared to dental radiography. Therefore, CBCT should be considered better suited for use in diagnosing dentoalveolar lesions in cats.

The objective of this study was to evaluate the diagnostic yield of dental radiography (DR) and 3 cone-beam computed tomography (CBCT) methods for the identification of predefined anatomic structures in cats. For 5 feline cadaver heads and 22 client-owned cats admitted for evaluation and treatment of dental disease, a total of 22 predefined anatomic structures were evaluated separately by use of the DR method and 3 CBCT software modules [multiplanar reconstructions (MPR), tridimensional (3-D) rendering, and reconstructed panoramic views (Pano)]. A semi quantitative scoring system was used, and mean scores were calculated for each anatomic structure and imaging method. The Friedman test was used to evaluate values for significant differences in diagnostic yield. For values that were significant the Wilcoxon signed rank test was used with the Bonferroni-Holm multiple comparison adjustment to determine significant differences among each of the possible pairs of diagnostic methods. Differences of diagnostic yield among the DR and 3 CBCT methods were significant for 17 of 22 anatomic structures. For these structures, DR scores were significantly higher than scores for Pano views for 2 of 17 structures, but DR scores were significantly lower than scores for Pano views for 6 anatomic structures, tridimensional rendering for 10 anatomic structures, and MPR for 17 anatomic structures. In conclusion, it was found that CBCT methods were better suited than DR for the identification of anatomic structures in cats. Results of this study can serve as a basis for CBCT evaluation of dentoalveolar and other maxillofacial bony lesions in cats.

Spatial visualization ability is defined as the ability to mentally rotate two- and three-dimensional figures. Visual reasoning is the ability to manipulate mental images of an object to reach a certain conclusion and has been linked to spatial ability. There is currently limited information about how entry-level spatial and visual reasoning abilities may be enhanced with progression through the rigorous veterinary medical curriculum. The present study made use of two tests that measure spatial ability and one test that measures non-verbal general reasoning ability in female veterinary students: Guay's Visualization of Views Test, Adapted Version (VVT), Mental Rotations Test (MRT), and Raven's Advanced Progressive Matrices Test, short form (APMT). Tests were given immediately before commencing the integrated veterinary medical curriculum (T0), at week 32 (T1), and at week 64 (T2) into the program. Results showed improved spatial visualization ability as measured by VVT and MRT and improved non-verbal general reasoning ability as measured by APMT at both 32 and 64 weeks. The spatial ability scores measured by VVT and MRT showed a positive correlation with non-verbal general reasoning ability scores (APMT), supporting the idea that these abilities are linked.

Odontodysplasia is an uncommon dental developmental disorder associated with enamel, dentin, pulp abnormalities, and overall tooth morphology. The affected tooth is grossly abnormal in size and contour and is commonly associated with swelling of the affected area and failure of eruption. Histologically, the enamel and dentin are hypoplastic and hypomineralized. Odontodyplasia occurs most commonly in response to direct trauma to the developing tooth bud (enamel organ and dental follicle). Data on the prevalence and features of non-traumatic odontodysplasia are lacking. Medical records of dogs diagnosed with odontodysplasia were reviewed at the William R. Pritchard Veterinary Medical Teaching Hospital (VMTH), University of California, Davis, for 10 years (from 2013 to 2023). Dogs with a known history of facial trauma, persistent deciduous tooth or teeth over the region of odontodysplastic tooth or teeth, and endodontic disease of the persistent deciduous tooth or teeth were excluded from the study. Twenty-eight dogs were included in this retrospective study, representing an incidence of 1.4 per 100 dogs presenting over 10 years. Regional odontodysplasia (RO) was identified in twenty-two dogs, and generalized odontodysplasia (GO) was found in six dogs. Both comprehensive oral examination and diagnostic imaging were essential in diagnosing and assessing the presence of odontodysplasia. Awake oral examination failed to identify odontodysplasia in almost 70% of the RO cases. Secondary diseases or lesions in odontodysplastic teeth, such as periodontal disease, endodontal disease, and perio-endo lesions, were commonly seen and were particularly more frequently identified in strategic teeth (canine and carnassial teeth) than non-strategic ones. Similarities, such as female predilection, maxilla more commonly affected, and clinical signs, were observed between RO in dogs and those reported in people. The exact etiology of non-traumatic odontodysplasia remains elusive, and the condition may be of multifactorial causality. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma is the most common oral cancer in the cat and presents as a locally aggressive lesion for which an effective therapeutic protocol remains elusive. Feline oral squamous cell carcinoma (OSCC) shares many clinical characteristics with human head and neck squamous cell carcinoma (HNSCC). Accordingly, present studies were conducted to determine similarities for immune markers shared by feline OSCC and human HNSCC. Biopsies harvested from a feline patient cohort-1 (n = 12) were analyzed for lymphoid cell infiltrates by immunohistochemistry (IHC). Results revealed unique patterns of T cell infiltration involving both neoplastic epithelium and stroma that were detected in most patient tumor biopsies (92%) examined by IHC staining for CD3. Intratumoral B cell infiltrates were detected within tumor stroma only, based on IHC staining for CD79a and CD20 for all patients within the same cohort-1. Infiltration of tumors by a regulatory CD4 T cell subset (Tregs) defined by expression of the forkhead transcription factor FoxP3, was also detected in biopsies from 57% of patients and involved infiltration of neoplastic epithelium and stroma. Patient biopsies were also examined for expression of immunomodulator cyclooxygenase (COX)-2 and revealed positive but weak staining of neoplastic epithelium in a significant proportion of cases (75%). Interestingly, COX-2 expression was detected in both neoplastic epithelium and stroma. Blood collected from a second cohort of feline OSCC patients (n = 9) revealed an increased frequency of circulating CD4+FoxP3+ T cells when compared to healthy adult controls (n = 7) (P = 0.045), although frequencies of CD4+CD25+FoxP3+ T cells were comparable between patients and healthy pet cat controls. Lastly, biopsies from feline OSCC patients were characterized for histologic subtype using a classification scheme previously described for human HNSCC. This analysis revealed the conventional subtype as the predominant variant (75%) with conventional subtypes split evenly between well differentiated and moderately differentiated carcinomas. Two cases were classified as papillary and one case as basaloid subtypes. Correlations between subtype, immune marker scores or circulating Treg frequencies and clinical characteristics or outcome were not detected, most likely due to small patient numbers within patient cohorts. However, findings from these studies provide a preliminary step in the characterization of immune and histologic markers that will be critical to defining prognostic immune markers for feline OSCC and potential targets for testing of immunotherapeutics also relevant to human HNSCC in future studies.

Treatments for temporomandibular joint (TMJ) disc thinning and perforation, conditions prevalent in TMJ pathologies, are palliative but not reparative. To address this, scaffold-free tissue-engineered implants were created using allogeneic, passaged costal chondrocytes. A combination of compressive and bioactive stimulation regimens produced implants with mechanical properties akin to those of the native disc. Efficacy in repairing disc thinning was examined in minipigs. Compared to empty controls, treatment with tissue-engineered implants restored disc integrity by inducing 4.4 times more complete defect closure, formed 3.4-fold stiffer repair tissue, and promoted 3.2-fold stiffer intralaminar fusion. The osteoarthritis score (indicative of degenerative changes) of the untreated group was 3.0-fold of the implant-treated group. This tissue engineering strategy paves the way for developing tissue-engineered implants as clinical treatments for TMJ disc thinning.

There is a paucity of in vivo studies that investigate the safety and efficacy of temporomandibular joint (TMJ) tissue regeneration approaches, in part due to the lack of established animal models. Review of disease models for study of TMJ is presented herein with an attempt to identify relevant preclinical animal models for TMJ tissue engineering, with emphasis on the disc and condyle. Although degenerative joint disease models have been mainly performed on mice, rats, and rabbits, preclinical regeneration approaches must employ larger animal species. There remains controversy regarding the preferred choice of larger animal models between the farm pig, minipig, goat, sheep, and dog. The advantages of the pig and minipig include their well characterized anatomy, physiology, and tissue properties. The advantages of the sheep and goat are their easier surgical access, low cost per animal, and its high tissue availability. The advantage of the dog is that the joint space is confined, so migration of interpositional devices should be less likely. However, each species has limitations as well. For example, the farm pig has continuous growth until about 18 months of age, and difficult surgical access due to the zygomatic arch covering the lateral aspect of joint. The minipig is not widely available and somewhat costly. The sheep and the goat are herbivores, and their TMJs mainly function in translation. The dog is a carnivore, and the TMJ is a hinge joint that can only rotate. Although no species provides the gold standard for all preclinical TMJ tissue engineering approaches, the goat and sheep have emerged as the leading options, with the minipig as the choice when cost is less of a limitation; and with the dog and farm pig serving as acceptable alternatives. Finally, naturally occurring TMJ disorders in domestic species may be harnessed on a preclinical trial basis as a clinically relevant platform for translation.

OBJECTIVE To describe the radiographic outcome of root canal treatment (RCT) of canine teeth of cats. DESIGN Retrospective case series. ANIMALS 32 cats with 37 canine teeth with complicated crown fractures that underwent RCT. PROCEDURES Medical record databases of 5 referral veterinary hospitals were searched to identify cats that underwent RCT between 1998 and 2016. Only cats that had at least 1 follow-up examination during which radiographs were obtained of the treated canine tooth or teeth were included in the study. Dental radiographs obtained before and immediately after RCT and during all follow-up examinations were reviewed. Treatment was considered successful if the periodontal ligament space was within reference limits and preoperative external inflammatory root resorption (EIRR), if present, had stabilized. Treatment was considered to have no evidence of failure if preoperative EIRR had stabilized and preexisting periapical lucency was stable or decreased in size but had not resolved. Treatment was considered to have failed if periapical lucency or EIRR developed subsequent to RCT or preexisting periapical lucency increased in size or preoperative EIRR progressed following RCT. RESULTS Follow-up time after RCT ranged from 3 to 72 months. The RCT was successful for 18 (49%) of the 37 treated teeth, had no evidence of failure for 12 (32%), and failed for 7 (19%). Preexisting EIRR and patient age ≥ 5 years significantly increased the rate of RCT failure. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that RCT was a viable treatment option to salvage endodontically diseased canine teeth in cats.

OBJECTIVE To evaluate the diagnostic yield of dental radiography (Rad method) and cone-beam CT (CBCT) methods for the identification of 31 predefined dental disorders in brachycephalic dogs. ANIMALS 19 client-owned brachycephalic dogs admitted for evaluation and treatment of dental disease. PROCEDURES 31 predefined dental disorders were evaluated separately and scored by use of dental radiography and 3 CBCT software modules (serial CBCT slices and custom cross sections, tridimensional rendering, and reconstructed panoramic views). A qualitative scoring system was used. Dental disorders were grouped into 10 categories for statistical analysis. Point of reference for presence or absence of a dental disorder was determined as the method that could be used to clearly identify the disorder as being present. Accuracy, sensitivity, specificity, and positive and negative predictive values were calculated with the McNemar χ2 test of marginal homogeneity of paired data. RESULTS When all 3 CBCT methods were used in combination, the diagnostic yield of CBCT was significantly higher than that of dental radiography for 4 of 10 categories (abnormal eruption, abnormally shaped roots, periodontitis, and tooth resorption) and higher, although not significantly so, for all categories, except for 1 (loss of tooth integrity). CONCLUSIONS AND CLINICAL RELEVANCE CBCT provided more detailed information than did dental radiography. Therefore, CBCT would be better suited for use in diagnosing dental disorders in brachycephalic dogs.

OBJECTIVE To evaluate the diagnostic yield of dental radiography (Rad method) and 3 cone-beam CT (CBCT) methods for the identification of predefined anatomic landmarks in brachycephalic dogs. ANIMALS 19 client-owned brachycephalic dogs admitted for evaluation and treatment of dental disease. PROCEDURES 26 predefined anatomic landmarks were evaluated separately by use of the RAD method and 3 CBCT software modules (serial CBCT slices and custom cross sections, tridimensional rendering, and reconstructed panoramic views). A semiquantitative scoring system was used, and mean scores were calculated for each anatomic landmark and imaging method. The Friedman test was used to evaluate values for significant differences in diagnostic yield. For values that were significant, the Wilcoxon signed rank test was used with the Bonferroni-Holm multiple comparison adjustment to determine significant differences among each of the 6 possible pairs of diagnostic methods. RESULTS Differences of diagnostic yield among the Rad and 3 CBCT methods were significant for 19 of 26 anatomic landmarks. For these landmarks, Rad scores were significantly higher than scores for reconstructed panoramic views for 4 of 19 anatomic landmarks, but Rad scores were significantly lower than scores for reconstructed panoramic views for 8 anatomic landmarks, tridimensional rendering for 18 anatomic landmarks, and serial CBCT slices and custom cross sections for all 19 anatomic landmarks. CONCLUSIONS AND CLINICAL RELEVANCE CBCT methods were better suited than dental radiography for the identification of anatomic landmarks in brachycephalic dogs. Results of this study can serve as a basis for CBCT evaluation of dental disorders in brachycephalic dogs.

Bite force is generated by the interaction of the masticatory muscles, the mandibles and maxillae, the temporomandibular joints (TMJs), and the teeth. Several methods to measure bite forces in dogs and cats have been described. Direct in vivo measurement of a bite in dogs has been done; however, bite forces were highly variable due to animal volition, situation, or specific measurement technique. Bite force has been measured in vivo from anesthetized dogs by electrical stimulation of jaw adductor muscles, but this may not be reflective of volitional bite force during natural activity. In vitro bite forces have been estimated by calculation of the force produced using mechanical equations representing the jaw adductor muscles and of the mandible and skull structure Bite force can be estimated in silico using finite element analysis (FEA) of the computed model of the anatomical structures. FEA can estimate bite force in extinct species; however, estimates may be lower than the measurements in live animals and would have to be validated specifically in domestic dogs and cats to be reliable. The main factors affecting the bite forces in dogs and cats are body weight and the skull's morphology and size. Other factors such as oral pain, TMJ disorders, masticatory muscle atrophy, and malocclusion may also affect bite force. Knowledge of bite forces in dogs and cats is essential for various clinical and research fields such as the development of implants, materials, and surgical techniques as well as for forensic medicine. This paper is a summary of current knowledge of bite forces in dogs and cats, including the effect of measurement methods and of other factors.

The objective of this study is to describe the clinical features and computed tomography (CT) findings of dogs with retrobulbar disease. There are two facets to this study: a retrospective case series in which findings of dogs with primary vs. secondary retrobulbar disease are described, and a retrospective cross-sectional study in which computed tomography findings of dogs with retrobulbar neoplasia vs. infection/inflammation are described and compared. The medical records of 66 client-owned dogs diagnosed with retrobulbar disease between 2006 and 2016 were reviewed. Clinical information including signalment, the specialty service to which the dog was presented, clinical signs, physical examination findings, diagnostic results, treatment, and outcome were documented. Diagnostic imaging and histopathology were reviewed. Forty-one dogs (62.1%) were diagnosed with primary disease of the retrobulbar space; 25 dogs (37.9%) were considered to have secondary retrobulbar disease. Of the 41 dogs with primary retrobulbar disease, 19 were diagnosed with neoplasia, 19 with infectious/inflammatory disease, and 3 suffered traumatic insult to the retrobulbar space. Of the 25 dogs with secondary retrobulbar disease, 21 were diagnosed with neoplasia, 3 with infectious/inflammatory disease, and 1 with a cyst. Dogs had a combination of ocular, oral, and/or nasal clinical signs. CT findings of orbital osteolysis, orbital periosteal reaction, and presence of a retrobulbar mass were significantly associated with neoplasia, while zygomatic salivary gland enlargement, retrobulbar mass effect, and mandibular lymphadenopathy were more often associated with infectious/inflammatory disease. CT findings overlap among different retrobulbar diseases, but new bone formation and lysis are more often associated with neoplasia. Disease originating from the retrobulbar space was equally likely to be infectious/inflammatory (n = 19) or neoplastic (n = 19), based on definitive diagnostic results of dogs with primary retrobulbar disease. Due to the clinical ramifications of these disorders, the diagnosis and treatment of these cases should be managed with a multi-specialty approach.

There is currently limited available information, but growing interest, in possible relationships between spatial visualization skills in medical students and their academic performance in select areas of the curriculum such as radiographic interpretation and anatomy. There is very limited comparable information on how entry-level spatial visualization skills may correlate with macroscopic anatomy performance in veterinary medical students exposed to an integrated curriculum. The present study made use of a battery of two short tests that measure spatial ability: Guay's visualization of views test (VVT) and mental rotation test (MRT) and, one test that measures general non-verbal reasoning abilities: Raven's Advanced Progressive Matrices Test, short form (APMT). Tests were given to 1st-year veterinary medical students (n = 124) immediately before commencing the integrated veterinary medical curriculum. Results show there is a positive correlation between entry-level spatial ability and non-verbal general reasoning scores confirming these abilities are linked (r: +0.22 and +0.3 for VVT/APMT and MRT/APMT respectively). The dispersion and inconsistency of significant positive correlation between anatomy practical exams grade and spatial and general reasoning scores suggest these abilities either do not correlate with anatomy practical exams grade or, are overcome with progression through the anatomy courses. Males scored higher than females in the spatial ability tests: 16.59 vs. 12.06 for VVT (p = 0.01) and 19.0 vs. 14.68 for MRT (p = 0.01). Scores for APMT did not show a significant difference by gender.

BackgroundAdipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs, with an emphasis on their immunomodulatory capacity and transcriptome.MethodsHuman and feline ASCs were evaluated for phenotype, immunomodulatory profile, and transcriptome. Additionally, transwells were used to determine the role of cell-cell contact in ASC-mediated inhibition of lymphocyte proliferation in both humans and cats.ResultsSimilar to human ASCs, feline ASCs were highly proliferative at low passages and fit the minimal criteria of multipotent stem cells including a compatible surface protein phenotype, osteogenic capacity, and normal karyotype. Like ASCs from all species, feline ASCs inhibited mitogen-activated lymphocyte proliferation in vitro, with or without direct ASC-lymphocyte contact. Feline ASCs mimic human ASCs in their mediator secretion pattern, including prostaglandin E2, indoleamine 2,3 dioxygenase, transforming growth factor beta, and interleukin-6, all augmented by interferon gamma secretion by lymphocytes. The transcriptome of three unactivated feline ASC lines were highly similar. Functional analysis of the most highly expressed genes highlighted processes including: 1) the regulation of apoptosis; 2) cell adhesion; 3) response to oxidative stress; and 4) regulation of cell differentiation. Finally, feline ASCs had a similar gene expression profile to noninduced human ASCs.ConclusionsFindings suggest that feline ASCs modulate lymphocyte proliferation using soluble mediators that mirror the human ASC secretion pattern. Uninduced feline ASCs have similar gene expression profiles to uninduced human ASCs, as revealed by transcriptome analysis. These data will help inform clinical trials using cats with naturally occurring diseases as surrogate models for human clinical trials in the regenerative medicine arena.

Frequent involvement of the disc in temporomandibular joint (TMJ) disorders warrants attempts to tissue engineer TMJ disc replacements. Physiologically, a great degree of similarity is seen between humans and farm pigs (FPs), but the pig's rapid growth confers a significant challenge for in vivo experiments. Minipigs have a slower growth rate and are smaller than FPs, but minipig TMJ discs have yet to be fully characterized. The objective of this study was to determine the suitability of the minipig for TMJ studies by extensive structural and functional characterization. The properties of minipig TMJ discs closely reproduced previously reported morphological, biochemical, and biomechanical values of human and FP discs. The width/length dimension ratio of the minipig TMJ disc was 1.95 (1.69 for human and 1.94 for FP). The biochemical evaluation revealed, on average per wet weight, 24.3% collagen (22.8% for human and 24.9% for FP); 0.8% glycosaminoglycan (GAG; 0.5% for human and 0.4% for FP); and 0.03% DNA (0.008% for human and 0.02% for FP). Biomechanical testing revealed, on average, compressive relaxation modulus of 50 kPa (37 kPa for human and 32 kPa for FP), compressive instantaneous modulus of 1121 kPa (1315 kPa for human and 1134 kPa for FP), and coefficient of viscosity of 13 MPa·s (9 MPa·s for human and 3 MPa·s for FP) at 20% strain. These properties also varied topographically in accordance to those of human and FP TMJ discs. Anisotropy, quantified by bidirectional tensile testing and histology, again was analogous among minipig, human, and FP TMJ discs. The minipig TMJ's ginglymoarthrodial nature was verified through cone beam computer tomography. Collectively, the similarities between minipig and human TMJ discs support the use of minipig as a relevant model for TMJ research; considering the practical advantages conferred by its growth rate and size, the minipig may be a preferred model over FP.

ObjectiveTo describe the application of 3-dimensional (3D) printing in advanced oral and maxillofacial surgery (OMFS) and to discuss the benefits of this modality in surgical planning, student and resident training, and client education.Study designRetrospective case series.AnimalsClient-owned dogs (n = 28) and cats (n = 4) with 3D printing models of the skulls.MethodsThe medical records of 32 cases with 3D printing prior to major OMFS were reviewed.ResultsIndications for 3D printing included preoperative planning for mandibular reconstruction after mandibulectomy (n = 12 dogs) or defect nonunion fracture (n = 6 dogs, 2 cats), mapping of ostectomy location for temporomandibular joint ankylosis or pseudoankylosis (n = 4 dogs), assessment of palatal defects (n = 2 dogs, 1 cat), improved understanding of complex anatomy in cases of neoplasia located in challenging locations (n = 2 dogs, 1 cat), and in cases of altered anatomy secondary to trauma (n = 2 dogs).ConclusionIn the authors' experience, 3D printed models serve as excellent tools for OMFS planning and resident training. Furthermore, 3D printed models are a valuable resource to improve clients' understanding of the pet's disorder and the recommended treatment.Clinical relevanceThree-dimensional printed models should be considered viable tools for surgical planning, resident training, and client education in candidates for complex OMFS.

Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune-mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose-derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart. Oral inflammation, blood lymphocyte subsets, anti-fetal bovine serum antibody levels, ASC crossmatching and serum proteins and cytokine concentrations were determined. Four of the 7 cats (57%) responded to treatment [complete clinical remission (n = 2) or substantial clinical improvement (n = 2)]. Three cats were nonresponders. Prior to therapy, most cats had increased circulating CD8+ T cells, decreased CD8lo cells, and a decreased CD4/CD8 ratio, however clinical resolution was not associated with normalization of these parameters. Nonresponders showed more severe systemic inflammation (neutrophilia, hyperglobulinemia and increased interferon gamma and tumor necrosis factor alpha concentration) prior to ASC therapy. Clinical remission took up to 20 months and no clinical relapse has occurred. A higher fraction of radiolabeled ASCs were identified in the oral cavity of FCGS affected cats than the control cat. The administration of fresh, allogenic ASCs appeared to have lower clinical efficacy with a delayed response as compared to the fresh, autologous ASCs. In addition, the mechanism(s) of action for autologous and allogenic ASCs may differ in this model of oral inflammation. Stem Cells Translational Medicine 2017;6:1710-1722.

OBJECTIVE To evaluate biomechanical properties of intact feline mandibles, compared with those for mandibles with an experimentally created osteotomy that was stabilized with 1 of 2 internal fixation configurations. SAMPLE 20 mandibles from 10 adult feline cadavers. PROCEDURES An incomplete block study design was used to assign the mandibles of each cadaver to 2 of 3 groups (locking plate with locking screws [locking construct], locking plate with nonlocking screws [nonlocking construct], or intact). Within each cadaver, mandibles were randomly assigned to the assigned treatments. For mandibles assigned to the locking and nonlocking constructs, a simple transverse osteotomy was created caudal to the mandibular first molar tooth after plate application. All mandibles were loaded in cantilever bending in a single-load-to-failure test while simultaneously recording load and actuator displacement. Mode of failure (bone or plate failure) was recorded, and radiographic evidence of tooth root and mandibular canal damage was evaluated. Mechanical properties were compared among the 3 groups. RESULTS Stiffness, bending moments, and most post-yield energies for mandibles with the locking and nonlocking constructs were significantly lower than those for intact mandibles. Peak bending moment and stiffness for mandibles with the locking construct were significantly greater than those for mandibles with the nonlocking construct. Mode of failure and frequency of screw damage to tooth roots and the mandibular canal did not differ between the locking and nonlocking constructs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both fixation constructs were mechanically inferior to intact mandibles. The locking construct was mechanically stronger than the nonlocking construct.

ObjectivesTo report the use of compression resistant matrix (CRM) infused with recombinant human bone morphogenetic protein (rhBMP-2) prospectively in the healing of nonunion long-bone fractures in dogs.MethodsA longitudinal cohort of dogs that were presented with nonunion fractures were classified and treated with CRM soaked with rhBMP-2 and fracture fixation. They were followed with serial radiographs and evaluated for healing times and complications according to the time frame and definitions previously established for orthopaedic clinical cases.ResultsEleven nonunion fractures in nine dogs were included. Median healing time was 10 weeks (range: 7-20 weeks). Major perioperative complications due to bandage morbidity were encountered in two of 11 limbs and resolved. All other complications were minor. They occurred perioperatively in eight of 11 limbs. Minor follow-up complications included short-term in one of two limbs, mid-term in one of three, and long-term in four of five limbs. Nine limbs returned to full function and two limbs returned to acceptable function at the last follow-up.Clinical significanceNonunion fractures given a poor prognosis via standard-of-care treatment were successfully repaired using CRM with rhBMP-2 accompanying fixation. These dogs, previously at high risk of failure, returned to full or acceptable function.

Domestic rabbits are increasing in popularity as household pets; therefore, veterinarians need to be familiar with the most common diseases afflicting rabbits including dental disease. Current diagnostic approaches include gross oral examination, endoscopic oral examination, skull radiography, and computed tomography (CT). Cone beam computed tomography (CBCT), a new oral and maxillofacial imaging modality that has the capability to produce high-resolution images, has not yet been described for use in evaluating dental disease in rabbits. A total of 15 client-owned rabbits had CBCT, oral examination, dental charting, and dental treatment performed under general anesthesia. Images were evaluated using transverse and custom multiplanar (MPR), 3D, and panoramic reconstructed images. The CBCT findings were grouped into abnormalities that could be detected on conscious oral examination vs. abnormalities that could not be detected by conscious oral examination. Potential associations between the two categories were examined by pairwise Fisher's exact test with statistical significance determined by P

Abundance and accessibility render skin-derived stem cells an attractive cell source for tissue engineering applications. Toward assessing their utility, the variability of constructs engineered from human dermis-isolated adult stem (hDIAS) cells was examined with respect to different anatomical locations (foreskin, breast, and abdominal skin), both in vitro and in a subcutaneous, athymic mouse model. All anatomical locations yielded hDIAS cells with multi-lineage differentiation potentials, though adipogenesis was not seen for foreskin-derived hDIAS cells. Using engineered cartilage as a model, tissue engineered constructs from hDIAS cells were compared. Construct morphology differed by location. The mechanical properties of human foreskin- and abdominal skin-derived constructs were similar at implantation, remaining comparable after 4 additional weeks of culture in vivo. Breast skin-derived constructs were not mechanically testable. For all groups, no signs of abnormality were observed in the host. Addition of aggregate redifferentiation culture prior to construct formation improved chondrogenic differentiation of foreskin-derived hDIAS cells, as evident by increases in glycosaminoglycan and collagen contents. More robust Alcian blue staining and homogeneous cell populations were also observed compared to controls. Human DIAS cells elicited no adverse host responses, reacted positively to chondrogenic regimens, and possessed multi-lineage differentiation potential with the caveat that efficacy may differ by anatomical origin of the skin. Taken together, these results suggest that hDIAS cells hold promise as a potential cell source for a number of tissue engineering applications.

Introduction: Digital tomosynthesis (DT) has emerged as a potential imaging modality for evaluating anatomic structures in veterinary medicine. This study aims to validate the diagnostic yield of DT in identifying predefined anatomic structures in feline cadaver heads, comparing it with conventional intraoral dental radiography (DR). Methods: A total of 16 feline cadaver heads were utilized to evaluate 19 predefined clinically relevant anatomic structures using both DR and DT. A semi-quantitative scoring system was employed to characterize the ability of each imaging method to identify these structures. Results: DT demonstrated a significantly higher diagnostic yield compared to DR for all evaluated anatomic structures. Orthogonal DT imaging identified 13 additional anatomic landmarks compared to a standard 10-view feline set obtained via DR. Moreover, DT achieved statistically significant higher scores for each of these landmarks, indicating improved visualization over DR. Discussion: These findings validate the utility of DT technology in reliably identifying clinically relevant anatomic structures in the cat skull. This validation serves as a foundation for further exploration of DT imaging in detecting dentoalveolar and other maxillofacial bony lesions and pathologies in cats. [ABSTRACT FROM AUTHOR]

Feline chronic gingivostomatitis (FCGS) is a disease characterized by protracted and potentially debilitating oral inflammation in cats, the etiology of which is currently unknown. The purpose of this review is to apply an evidence-based medicine approach to systematically review and critically evaluate the scientific literature reporting the outcome of medical and surgical management of FCGS. Those articles meeting inclusion criteria were reviewed and assigned an "Experimental Design Grade" (EDG) and an "Evidence Grade" (EG) in order to score relative strength of study design and produced data. Studies were evaluated and compared, especially highlighting the treatments, the outcomes, and the therapeutic success rates. This review found a lack of consistency between articles' data, rendering direct comparison of results unreliable. The field of FCGS research, and ultimately patient care, would benefit from standardizing studies by adopting use of a consistent semi-quantitative scoring system and extending follow-up duration. Future researchers should commit to large prospective studies that compare existing treatments and demonstrate the promise of new treatments.

Domestic rabbits (Oryctolagus cuniculus) are increasingly popular as household pets; therefore, veterinarians need to be familiar with the most common diseases afflicting rabbits including dental diseases. Diagnostic approaches for dental disease include gross oral examination, endoscopic oral examination, skull radiography, and computed tomography (CT). CT overcomes many limitations of standard radiography by permitting cross-sectional images of the rabbit head in multiple planes without superimposition of anatomic structures. Cone-beam CT (CBCT) is an oral and maxillofacial imaging modality that produces high-resolution images. The objective of this study was to describe and compare the normal anatomic features of the dentition and surrounding maxillofacial structures in healthy rabbits on CBCT and conventional CT. Ten New Zealand white rabbit cadaver heads were scanned using CBCT and conventional CT. Images were evaluated using Anatomage Invivo 5 software. The maxillofacial anatomy was labeled on CBCT images, and the mean lengths and widths of the teeth were determined. The visibility of relevant dental and anatomic features (pulp cavity, germinal center, tooth outline, periodontal ligament) were scored and compared between conventional CT and CBCT. The thinnest teeth were the maxillary second incisor teeth at 1.29 ± 0.26 mm and the maxillary third molar teeth at 1.04 ± 0.10 mm. In general, it was found that CBCT was superior to conventional CT when imaging the dentition. Importantly, the periodontal ligament was significantly (P

UnlabelledMesenchymal stem cells (MSCs) are a promising therapy for immune-mediated and inflammatory disorders, because of their potent immunomodulatory properties. In this study, we investigated the use of fresh, autologous, adipose-derived MSCs (ASCs) for feline chronic gingivostomatitis (FCGS), a chronic, debilitating, idiopathic, oral mucosal inflammatory disease. Nine cats with refractory FCGS were enrolled in this pilot study. Each cat received 2 intravenous injections of 20 million autologous ASCs, 1 month apart. Oral biopsies were taken before and at 6 months after the first ASC injection. Blood immune cell subsets, serum protein, and cytokine levels were measured at 0, 1, 3, and 6 months after treatment to assess immunomodulatory effects. Seven of the 9 cats completed the study. Five cats responded to treatment by either complete clinical remission (n=3) or substantial clinical improvement (n=2). Two cats were nonresponders. Cats that responded to treatment also exhibited systemic immunomodulation demonstrated by decreased numbers of circulating CD8+ T cells, a normalization of the CD4/CD8 ratio, decreased neutrophil counts, and interferon-γ and interleukin (IL)-1β concentration, and a temporary increase in serum IL-6 and tumor necrosis factor-α concentration. No clinical recurrence has occurred following complete clinical remission (follow-up of 6-24 months). In this study, cats with 15% CD8lo cells were nonresponders. The relative absence of CD8lo cells may be a biomarker to predict response to ASC therapy, and may shed light on pathogenesis of FCGS and mechanisms by which ASCs decrease oral inflammation and affect T-cell phenotype.SignificanceThis study is the first to demonstrate the safety and efficacy of fresh, autologous, adipose-derived stem cell systemic therapy for a naturally occurring, chronic inflammatory disease in cats. The findings demonstrate that this therapy resulted in complete clinical and histological resolution or reduction in clinical disease severity and immune modulation in most cats. This study also identified a potentially useful biomarker that could dictate patient enrollment and shed light on immune modulation mechanism. As a naturally occurring animal model, FCGS also provides a strategic platform for potentially translatable therapy for the treatment of human oral inflammatory disease.

Knowledge and resources derived from veterinary medicine represent an underused resource that could serve as a bridge between data obtained from diseases models in laboratory animals and human clinical trials. Naturally occurring disease in companion animals that display the defining attributes of similar, if not identical, diseases in humans hold promise for providing predictive proof of concept in the evaluation of new therapeutics and devices. Here we outline comparative aspects of naturally occurring diseases in companion animals and discuss their current uses in translational medicine, benefits, and shortcomings. Last, we envision how these natural models of disease might ultimately decrease the failure rate in human clinical trials and accelerate the delivery of effective treatments to the human clinical market.

UnlabelledThe exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering.SignificanceAutologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides analysis of the current state-of-the-art regenerative approaches using human-derived dermal stem cells, with consideration of current guidelines, to assist translation toward therapeutic use.

ObjectiveTo describe a surgical technique using a regenerative approach and internal fixation for immediate reconstruction of critical size bone defects after segmental mandibulectomy in dogs.Study designProspective case series.AnimalsDogs (n = 4) that had reconstruction after segmental mandibulectomy for treatment of malignant or benign tumors.MethodsUsing a combination of extraoral and intraoral approaches, a locking titanium plate was contoured to match the native mandible. After segmental mandibulectomy, the plate was secured and a compression resistant matrix (CRM) infused with rhBMP-2, implanted in the defect. The implant was then covered with a soft tissue envelope followed by intraoral and extraoral closure.ResultsAll dogs that had mandibular reconstruction healed with intact gingival covering over the mandibular defect and had immediate return to normal function and occlusion. Mineralized tissue formation was observed clinically within 2 weeks and solid cortical bone formation within 3 months. CT findings at 3 months showed that the newly regenerated mandibular bone had ∼50% of the bone density and porosity compared to the contralateral side. No significant complications occurred.ConclusionMandibular reconstruction using internal fixation and CRM infused with rhBMP-2 is an excellent solution for immediate reconstruction of segmental mandibulectomy defects in dogs.

ObjectiveTo describe a surgical technique using a regenerative approach and internal fixation for reconstruction of critical size bone defect non-union mandibular fractures.Study designCase series.AnimalsDogs (n = 6) that had internal fixation of defect non-union mandibular fracture.MethodsIn 5 dogs, the repair was staged and extraction of teeth performed during the initial procedure. After 21-98 days (mean, 27 days) pharyngotomy intubation and temporary maxillomandibular fixation were performed. Using an extraoral approach, a locking titanium miniplate was contoured and secured to the mandible. A compression resistant matrix (CRM) infused with rhBMP-2 was implanted in the defect. The implant was then covered with a soft tissue envelope followed by surgical wound closure.ResultsAll dogs healed with intact gingival covering over the mandibular fracture site defect and had immediate return to normal function and correct occlusion. Hard-tissue formation was observed clinically within 2 weeks and solid cortical bone formation within 3 months. CT findings in 1 dog at 3 months postoperatively demonstrated that the newly regenerated mandibular bone had 92% of the bone density and porosity compared to the contralateral side. Long-term follow-up revealed excellent outcome.ConclusionMandibular reconstruction using internal fixation and CRM infused with rhBMP-2 is an excellent solution for the treatment of critical size defect non-union fractures in dogs.

Mesenchymal stem cells (MSCs) are a promising therapeutic option for various immune-mediated and inflammatory disorders due to their potent immunomodulatory and trophic properties. Naturally occurring diseases in large animal species may serve as surrogate animal models of human disease, as they may better reflect the complex genetic, environmental, and physiologic variation present in outbred populations. We work with naturally occurring diseases in large animal species to better understand how MSCs work and to facilitate optimal translation of MSC-based therapies. We are investigating the use of MSC therapy for a chronic oral inflammatory disease in cats. During our efforts to expand fat-derived feline MSCs (fMSCs), we observed that∼50% of the cell lines developed giant foamy multinucleated cells in later passages. These morphologic alterations were associated with proliferation arrest. We hypothesized that the cytopathic effects were caused by infection with a retrovirus, feline foamy virus (FFV). Using transmission electron microscopy, polymerase chain reaction, and in vitro assays, we determined that syncytial cell formation and proliferation arrest in fMSCs were caused by FFV strains that were highly homologous to previously reported FFV strains. We determined that the antiretroviral drug, tenofovir, may be used to support ex vivo expansion and salvage of FFV-infected fMSC lines. MSC lines derived from specific pathogen-free cats do not appear to be infected with FFV and may be a source of allogeneic fMSCs for clinical application. FFV infection of fMSC lines may hinder large-scale expansion of autologous MSC for therapeutic use in feline patients.

Mesenchymal stem cells (MSCs) are a promising therapeutic option for various immune-mediated and inflammatory disorders due to their potent immunomodulatory and trophic properties. Naturally occurring diseases in large animal species may serve as surrogate animal models of human disease, as they may better reflect the complex genetic, environmental, and physiologic variation present in outbred populations. We work with naturally occurring diseases in large animal species to better understand how MSCs work and to facilitate optimal translation of MSC-based therapies. We are investigating the use of MSC therapy for a chronic oral inflammatory disease in cats. During our efforts to expand fat-derived feline MSCs (fMSCs), we observed that∼50% of the cell lines developed giant foamy multinucleated cells in later passages. These morphologic alterations were associated with proliferation arrest. We hypothesized that the cytopathic effects were caused by infection with a retrovirus, feline foamy virus (FFV). Using transmission electron microscopy, polymerase chain reaction, and in vitro assays, we determined that syncytial cell formation and proliferation arrest in fMSCs were caused by FFV strains that were highly homologous to previously reported FFV strains. We determined that the antiretroviral drug, tenofovir, may be used to support ex vivo expansion and salvage of FFV-infected fMSC lines. MSC lines derived from specific pathogen-free cats do not appear to be infected with FFV and may be a source of allogeneic fMSCs for clinical application. FFV infection of fMSC lines may hinder large-scale expansion of autologous MSC for therapeutic use in feline patients.

Cleft lip with or without cleft palate (CL/P) is the most commonly occurring craniofacial birth defect. We provide insight into the genetic etiology of this birth defect by performing genome-wide association studies in two species: dogs and humans. In the dog, a genome-wide association study of 7 CL/P cases and 112 controls from the Nova Scotia Duck Tolling Retriever (NSDTR) breed identified a significantly associated region on canine chromosome 27 (unadjusted p=1.1 x 10(-13); adjusted p= 2.2 x 10(-3)). Further analysis in NSDTR families and additional full sibling cases identified a 1.44 Mb homozygous haplotype (chromosome 27: 9.29 - 10.73 Mb) segregating with a more complex phenotype of cleft lip, cleft palate, and syndactyly (CLPS) in 13 cases. Whole-genome sequencing of 3 CLPS cases and 4 controls at 15X coverage led to the discovery of a frameshift mutation within ADAMTS20 (c.1360_1361delAA (p.Lys453Ilefs*3)), which segregated concordant with the phenotype. In a parallel study in humans, a family-based association analysis (DFAM) of 125 CL/P cases, 420 unaffected relatives, and 392 controls from a Guatemalan cohort, identified a suggestive association (rs10785430; p =2.67 x 10-6) with the same gene, ADAMTS20. Sequencing of cases from the Guatemalan cohort was unable to identify a causative mutation within the coding region of ADAMTS20, but four coding variants were found in additional cases of CL/P. In summary, this study provides genetic evidence for a role of ADAMTS20 in CL/P development in dogs and as a candidate gene for CL/P development in humans.

Integration of engineered musculoskeletal tissues with adjacent native tissues presents a significant challenge to the field. Specifically, the avascularity and low cellularity of cartilage elicit the need for additional efforts in improving integration of neocartilage within native cartilage. Self-assembled neocartilage holds significant potential in replacing degenerated cartilage, though its stabilization and integration in native cartilage require further efforts. Physical and enzymatic stabilization methods were investigated in an in vitro model for temporomandibular joint (TMJ) disc degeneration. First, in phase 1, suture, glue and press-fit constructs were compared in TMJ disc intermediate zone defects. In phase 1, suturing enhanced interfacial shear stiffness and strength immediately; after four weeks, a 15-fold increase in stiffness and a ninefold increase in strength persisted over press-fit. Neither suture nor glue significantly altered neocartilage properties. In phase 2, the effects of the enzymatic stabilization regimen composed of lysyl oxidase, CuSO4 and hydroxylysine were investigated. A full factorial design was employed, carrying forward the best physical method from phase 1, suturing. Enzymatic stabilization significantly increased interfacial shear stiffness after eight weeks. Combined enzymatic stabilization and suturing led to a fourfold increase in shear stiffness and threefold increase in strength over press-fit. Histological analysis confirmed the presence of a collagen-rich interface. Enzymatic treatment additionally enhanced neocartilage mechanical properties, yielding a tensile modulus over 6 MPa and compressive instantaneous modulus over 1200 kPa at eight weeks. Suturing enhances stabilization of neocartilage, and enzymatic treatment enhances functional properties and integration of neocartilage in the TMJ disc. Methods developed here are applicable to other orthopaedic soft tissues, including knee meniscus and hyaline articular cartilage.

The aim of this report was to characterize osteonecrosis of the jaws (ONJ) in previously irradiated fields in dogs that underwent radiotherapy (RT) for oral tumors. Osteoradionecrosis of the jaw (ORNJ) was further defined as osteonecrosis in a previously irradiated field in the absence of a tumor. Thirteen dogs clinically diagnosed with 15 ONJ lesions were included in this retrospective case series. Medical records were reviewed for: breed, sex, weight, and age of the patient, tumor type, location in the oral cavity and size, location of the ONJ, time from RT to ONJ onset, known duration of the ONJ, and tumor presence. Where available, histological assessment of tissues obtained from the primary tumor, and tissues obtained from the ONJ lesion, was performed, and computed tomographic (CT) images and dental radiographs were reviewed. RT and other treatment details were also reviewed. Twelve dogs developed ONJ in the area of the previously irradiated tumor or the jaw closest to the irradiated mucosal tumor. Recurrence of neoplasia was evident at the time of ONJ diagnosis in five dogs. Time from RT start to ONJ onset varied from 2 to 44 months. In three cases, ORNJ developed after dental extractions in the irradiated field. Dental radiographs mostly revealed a moth-eaten pattern of bone loss, CT mostly revealed osteolysis, and histopathology was consistent with osteonecrosis. To conclude, development of ONJ/ORNJ following RT is a rare, but potentially fatal complication. Patients undergoing RT may benefit from a comprehensive oral and dental examination and treatment prior to RT.

Osteonecrosis of the jaws (ONJ) is an entity of major clinical impact characterized by chronically exposed necrotic mandibular or maxillary bone. Its clinicopathological characteristics and possible inciting or risk factors are well described in humans but only anecdotally reported in dogs. Treatment modalities and outcome vary depending on the inciting factors involved and the extent and severity of the lesions. The objectives of this study were to retrospectively describe the clinicopathological features of non-radiation-related ONJ in a series of 14 dogs, identify possible inciting or risk factors, and report on the surgical treatment and outcome. For all patients, the medical records were used to collect information regarding signalment, clinical signs, characteristics of the oral, jaw and dental lesions, diagnostic imaging findings, histopathological and microbiological analysis, treatment performed, and outcome. The data collected showed that non-radiation-related ONJ appears to be an infrequent clinical entity but of significant impact in dogs; that a history of systemic antibiotics and dental disease is common among affected dogs; that previous dental extractions are commonly associated with ONJ sites; that using a systematic diagnostic approach is essential for diagnosis; and that thorough surgical debridement combined with a course of oral antibiotics was effective in the described dogs affected by advanced non-radiation-related ONJ.