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Lameness in sows is reported as the most frequent cause of early culling from commercial farms and results in reduced productivity, economic losses, and a negative impact on animal welfare. Osteochondrosis was reported as the leading cause of lameness in North American sows and, although more recent European studies report infectious arthritis as the leading cause, lameness in US production facilities using group housing for gestating sows has not yet been evaluated. This study’s aim was to characterize lesions associated with lameness in the appendicular musculoskeletal system of 26 sows euthanized for lameness using pathologic, radiologic, and microbiologic analyses. Of 178 total lesions, infectious lesions were most common (54%), predominated in distal limb segments (ie, at or distal to carpi and tarsi) and more often correlated with the clinically lame limb, whereas osteochondrosis and degenerative osteoarthritis predominated in proximal limb segments (ie, at or proximal to cubital and stifle joints) and rarely correlated with the clinically lame limb. The location and characteristics of infectious lesions, including mixed bacterial growth isolated from 22/22 orthopedic sites representing 19 sows with Trueperella pyogenes isolated in 16/22 (73%) of samples, suggest an etiologic component involving trauma. Radiography had a 70.6% sensitivity and 93.9% specificity for detecting infectious lesions affecting tarsocrural, antebrachiocarpal, and digital (ie, claw) regions combined. The frequency, type, and location of infectious lesions identified in this cohort of sows euthanized for lameness differ from previous reports, indicating the need for further investigation of the etiopathogenesis, earlier detection methods, and prevention.

The intestinal parasite, Cryptosporidium, is a major contributor to global child mortality and causes opportunistic infection in immune deficient individuals. Innate resistance to Cryptosporidium, which specifically invades enterocytes, is dependent on the production of IFN-γ, yet whether enterocytes contribute to parasite control is poorly understood. In this study, utilizing a mouse-adapted strain of C. parvum, we show that epithelial-derived IL-18 synergized with IL-12 to stimulate innate lymphoid cell (ILC) production of IFN-γ required for early parasite control. The loss of IFN-γ-mediated STAT1 signaling in enterocytes, but not dendritic cells or macrophages, antagonized early parasite control. Transcriptional profiling of enterocytes from infected mice identified an IFN-γ signature and enrichment of the anti-microbial effectors IDO, GBP, and IRG. Deletion experiments identified a role for Irgm1/m3 in parasite control. Thus, enterocytes promote ILC production of IFN-γ that acts on enterocytes to restrict the growth of Cryptosporidium.

Signalment and primary tumor characteristics of dogs in the historical control group.

Purpose: Recombinant Listeria vaccines induce tumor-specific T-cell responses that eliminate established tumors and prevent metastatic disease in murine cancer models. We used dogs with HER2/neu+ appendicular osteosarcoma, a well-recognized spontaneous model for pediatric osteosarcoma, to determine whether a highly attenuated, recombinant Listeria monocytogenes expressing a chimeric human HER2/neu fusion protein (ADXS31-164) could safely induce HER2/neu-specific immunity and prevent metastatic disease.Experimental Design: Eighteen dogs that underwent limb amputation or salvage surgery and adjuvant chemotherapy were enrolled in a phase I dose escalation clinical trial and received either 2 × 108, 5 × 108, 1 × 109, or 3.3 × 109 CFU of ADXS31-164 intravenously every 3 weeks for 3 administrations.Results: Only low-grade, transient toxicities were observed. ADXS31-164 broke peripheral tolerance and induced antigen-specific IFNγ responses against the intracellular domain of HER2/neu in 15 of 18 dogs within 6 months of treatment. Furthermore, ADXS31-164 reduced the incidence of metastatic disease and significantly increased duration of survival time and 1-, 2-, and 3-year survival rates when compared with a historical control group with HER2/neu+ appendicular osteosarcoma treated with amputation and chemotherapy alone.Conclusions: These findings demonstrate that ADXS31-164 administered in the setting of minimal residual disease can induce HER2/neu-specific immunity and may reduce the incidence of metastatic disease and prolong overall survival in a clinically relevant, spontaneous, large animal model of cancer. These findings, therefore, have important translational relevance for children with osteosarcoma and adults with other HER2/neu+ cancers. Clin Cancer Res; 22(17); 4380–90. ©2016 AACR.

ADXS31-164 does not adversely affect cardiac function.

Surgical stabilisation of the distal phalanx (DP) is a potential therapeutic strategy for severe acute laminitis.To evaluate the effects of locking compression plate (LCP) fixation of the DP to the dorsal hoof wall.Ex vivo and in vivo experiments.A T-shaped LCP was applied to one limb per pair in six pairs of cadaver forelimbs subjected to a combination of thermally induced lamellar failure and vertical load to simulate severe acute laminitis. Standard radiographic measurements were used to compare DP displacement. The LCP was then applied to one forefoot in 12 healthy Standardbred horses either standing (n = 6) or under general anaesthesia (n = 6). Lameness was evaluated daily, then horses were euthanised (day 8) and lamellar tissue analysed using light microscopy, histomorphometery and molecular markers of apoptosis.In the cadaver limb model, LCP fixation prevented the significant changes in hoof-distal phalanx distance, coronary extensor process distance and sole depth that characterised DP displacement in untreated limbs (p 0.05). Application of the construct in vivo was well tolerated with minimal lameness (10/12 horses were sound at the trot on day 8); however, histology revealed dorsal lamellar pathology consistent with laminitis, but with extensive keratinocyte apoptosis. Adjacent to the LCP, caspase-3 positive cell counts were approximately 20-fold higher than control (p 0.001).Pathology was evaluated at a single time point. Microvascular perfusion was not evaluated.Rigid fixation of the DP to the hoof capsule was achieved with the LCP construct in a cadaver limb laminitis model. In live horses, LCP fixation caused regional lamellar pathology with extensive apoptosis, likely due to disturbed lamellar microvascular perfusion and/or mechanostasis. Understanding these mechanisms is critical for refinement of the technique in order to avoid iatrogenic lamellar damage.Chirurgische Stabilisation der distalen Phalanx (DP) ist eine potenzielle therapeutische Strategie für hochgradig akute Hufrehe.Evaluation einer Locking Compression Plate (LCP) Fixation der DP zur dorsalen Hufwand.Ex vivo und in vivo Experiment.Eine T-förmige LCP wurde in jeweils einem Vorderfuß aus 6 Paaren von Kadaver Vorderbeinen angebracht und mit thermisch induziertem lamellarem Versagen und vertikaler Belastung ausgesetzt, um hochgradig akute Hufrehe zu simulieren. Standard radiologische Messungen wurden für den Vergleich von DP Verlagerung durchgeführt. Die LCP wurde anschließend bei 12 gesunden Standardbred Trabrennpferden in jeweils einem Vorderfuß entweder stehend (n = 6) oder unter Allgemeinanästhesie (n = 6) angebracht. Lahmheit wurde täglich beurteilt, die Pferde wurden anschließend euthanasiert (Tag 8) und das lamellare Gewebe mithilfe von Lichtmikroskopie, Histomorphometrie, und molekularer Marker für Apoptose analysiert.Im Kadavergliedmaßen-Modell verhinderte die Fixation mit LCP die signifikanten Veränderungen in Huf-DP Abstand, Kronrand zu Strecksehnenfortsatz Abstand und Sohlendicke welche DP Verlagerung in unbehandelten Gliedmaßen charakterisierte (p 0.05). Applikation des Konstrukts in vivo wurde gut und mit minimaler Lahmheit toleriert (10/12 Pferde waren lahmfrei im Trab an Tag 8); indessen zeigte Histologie dorsale lamellare Pathologie vereinbar mit Hufrehe, allerdings mit umfangreicher Apoptose der Keratinozyten. Der LCP angrenzend wurde eine ca. 20-fach höhere Caspase-3 positive Zellzahl als in der Kontrollgruppe (p 0.001) nachgewiesen. HAUPTEINSCHRÄNKUNGEN: Pathologie wurde lediglich an einem einzigen Zeitpunkt beurteilt. Mikrovaskuläre Perfusion wurde nicht beurteilt.Rigide Fixation der DP zur Hufkapsel wurde mithilfe des LCP-Konstrukts im Kadavergliedmaßen-Hufrehe-Modell erreicht. In lebenden Pferden verursachte die LCP Fixation regional lamellare Pathologie mit extensiver Apoptose, vermutlich durch gestörte lamellare mikrovaskuläre Perfusion und/oder Mechanostase. Verständnis dieser Mechanismen ist entscheidend für die Verbesserung der Methode um iatrogen lamellare Schäden zu verhindern.

Phlegmonous gastritis was diagnosed in 2 yearling fillies that were presented with a 1-wk history of fever, lethargy, and hypoproteinemia, associated with a previous diagnosis of equine proliferative enteropathy based on clinical signs and PCR assay detection of Lawsonia intracellularis in fecal samples. Abdominal ultrasound revealed enlargement of the stomach and expansion of its submucosal layer with hypoechoic fluid, as well as thickened hypomotile small intestinal segments. Given the poor prognosis and poor response to treatment, both horses were euthanized, one on the day of presentation and the other after 3 wk of intensive medical management including a combination of antimicrobials, analgesics, and intravenous colloids. At autopsy, acute mural gastritis characterized by severe submucosal edema with suppurative inflammation (i.e., phlegmonous gastritis) and necroulcerative enteritis compatible with the necrotizing form of equine proliferative enteropathy were identified in both horses. The gastric inflammation was associated with thrombosis and mixed bacterial populations, including Clostridium perfringens, that were confined to the submucosa without evidence of mucosal involvement; toxin genes compatible with C. perfringens type C were identified in one case. Human phlegmonous gastritis is an uncommon, often-fatal pyogenic infection that is often associated with mucosal injury, bacteremia, or immunocompromise. Our finding of this unusual gastric lesion in 2 horses with similar signalment, clinical disease, and spectrum of postmortem lesions suggests a similar etiopathogenesis that possibly involves local, regional, or distant hematogenous origin, and should be considered a potential complication of gastrointestinal mucosal compromise in horses.

Objective To describe the clinical presentation, treatment, and clinical outcome of horses with ocular disease and evidence of systemic or ocular Lyme disease. Animals studied Five horses met the inclusion criteria of ocular disease with evidence of B burgdorferi present in ocular or CNS tissues. Procedure The goal of this study was to describe the clinical presentation and progression of ocular disease when associated with ocular or CNS B burgdorferi infection in horses. A retrospective review of medical records was performed on horses admitted for ocular disease with evidence of B burgdorferi infection between 1998 and 2015. The diagnosis of B burgdorferi-associated uveitis was based on histopathologic lesions of lymphohistiocytic and suppurative uveitis/endophthalmitis and intralesional argyrophilic spirochetes in either ocular or CNS tissue consistent with Borrelia. Leptospiral uveitis was ruled out by PCR. Results All five horses in the current study had intraocular inflammation at the time of presentation. Medical management with anti-inflammatories was successful in controlling uveitis in the two horses in which treatment of uveitis was attempted. Systemic treatment with oral tetracyclines was unsuccessful in a single case in which treatment of Borrelia was attempted. Four horses were euthanized due to progression of neurologic disease. The surviving horse had an enucleation performed and did not show systemic signs. Conclusions Infection with Borrelia burgdorferi should be considered in endemic areas as a differential for horses with ocular disease, in particular, uveitis. The prognosis for uveitis and neurologic disease associated with Lyme disease was poor in the current study.

The elongated, distally tapered limbs of horses are adapted for high-speed locomotion. Because these traits are artificially selected for in modern racehorses, they operate at a morphological extreme with a high risk of fracture. Racehorses are subject to different training and racing regimes depending on their breed and gait, and are therefore an interesting model to examine bone functional adaptation under variable biomechanically intense conditions. This study compares bone structural properties in the third metacarpal (MCIII) of Thoroughbred (n = 9) and Quarter Horse (n = 11) racehorses, using feral Assateague Island ponies (n = 6) as an untrained/unraced outgroup, to determine whether structural properties reflect variable racing and training regimes. Geometric section properties and bone mineral densities were determined using peripheral quantitative CT at two diaphyseal sites and through the distal epiphysis. Diaphyseal strength of the MCIII in all three breeds does not differ relative to body size, but in the mid-diaphyseal region Thoroughbreds have higher antero-posterior relative to medio-lateral bending strength than Quarter Horses, as well as higher bone mineral densities in left MCIII epiphyses (particularly in the lateral condyle). Interestingly, all breeds have lower bone mineral densities in the lateral versus medial condyle, an inherent structural feature that may influence predisposition to fracture when running around turns. Our results suggest that despite subtle differences in bone structure between different racehorse breeds, basic morphology of the third metacarpus is relatively similar among racing and non-racing horses, possibly reflecting intense selection (natural and artificial) across domestic equids for similar structural features within distal limb elements.

OBJECTIVE To compare the application and healing of the zip skin closure system (ZSCS) with sutured closure by use of a split-scar model of ventral midline incisions in horses in a prospective, randomized experimental study. ANIMALS 8 adult horses. PROCEDURES All horses underwent an exploratory ventral midline celiotomy with a standardized 30-cm skin incision. Each horse was randomized to have either the cranial 15 cm closed with suture and caudal 15 cm with the ZSCS or vice versa (split-scar model). Skin closure time was recorded and compared. Photography and skin biopsies were taken preoperatively and 14 days postoperatively. Cosmetic appearance was assessed by use of a proposed equine celiotomy incision score. Healing at 14 days was assessed by histopathology. RESULTS Skin closure times were faster with the ZSCS compared to sutured incisions. At 14 days postoperatively, the cosmetic appearance (equine celiotomy incision scores) for ZSCS incisions were better than sutured closure and histologic healing scores were not different between methods of closure. Subcuticular sutures were associated with deep dermal inflammation and necrosis independent of epidermal closure methods. CLINICAL RELEVANCE While limitations to the utility of the ZSCS are recognized, the potential benefits of expedient closure, good cosmetic outcome, and satisfactory healing make this method viable for closure of linear wounds or incisions in horses.

Cryptosporidiumis a leading cause of severe diarrhea and diarrheal-related death in children worldwide. As an obligate intracellular parasite,Cryptosporidiumrelies on intestinal epithelial cells to provide a niche for its growth and survival, but little is known about the contributions that the infected cell makes to this relationship. Here we conducted a genome wide CRISPR/Cas9 knockout screen to discover host genes required forCryptosporidium parvuminfection and/or host cell survival. Gene enrichment analysis indicated that the host interferon response, glycosaminoglycan (GAG) and glycosylphosphatidylinositol (GPI) anchor biosynthesis are important determinants of susceptibility toC. parvuminfection. Several of these pathways are linked to parasite attachment and invasion and C-type lectins on the surface of the parasite. Evaluation of transcript and protein induction of innate interferons revealed a pronounced type III interferon response toCryptosporidiumin human cells as well as in mice. Treatment of mice with IFNλ reduced infection burden and protected immunocompromised mice from severe outcomes including death, with effects that required STAT1 signaling in the enterocyte. Initiation of this type III interferon response was dependent on sustained intracellular growth and mediated by the pattern recognition receptor TLR3. We conclude that host cell intrinsic recognition ofCryptosporidiumresults in IFNλ production critical to early protection against this infection.Author SummaryCryptosporidiuminfection is an important contributor to global childhood mortality. There are currently no vaccines available, and the only drug has limited efficacy in immunocompromised individuals and malnourished children who need it most. To discover which host proteins are essential forCryptosporidiuminfection, we conducted a genome wide knockout screen in human host cells. Our results confirm the importance of glycosaminoglycans on the surface of epithelial cells for attachment and invasion of the parasite. We also found that host GPI anchor biosynthesis and interferon signaling pathways were enriched by our screen. Examining the role of interferon signaling further we found a type III interferon response, IFNλ, was generated in response to infection and shown to be initiated in the infected cell. Utilizing mouse models of infection, we found that the type III interferon response was important early during infection with its induction likely preceding IFNγ, a key cytokine for the control of this infection. We also determined that TLR3 was the pattern recognition receptor responsible for IFNλ production duringCryptosporidiuminfection. Our work shows that IFNλ acts directly on the enterocyte and its use in treating immunocompromised mice produced striking reductions in infection.

Cryptosporidiumis a leading cause of severe diarrhea and diarrheal-related death in children worldwide. As an obligate intracellular parasite,Cryptosporidiumrelies on intestinal epithelial cells to provide a niche for its growth and survival, but little is known about the contributions that the infected cell makes to this relationship. Here we conducted a genome wide CRISPR/Cas9 knockout screen to discover host genes that influenceCryptosporidium parvuminfection and/or host cell survival. Gene enrichment analysis indicated that the host interferon response, glycosaminoglycan (GAG) and glycosylphosphatidylinositol (GPI) anchor biosynthesis are important determinants of susceptibility toC.parvuminfection and impact on the viability of host cells in the context of parasite infection. Several of these pathways are linked to parasite attachment and invasion and C-type lectins on the surface of the parasite. Evaluation of transcript and protein induction of innate interferons revealed a pronounced type III interferon response toCryptosporidiumin human cells as well as in mice. Treatment of mice with IFNλ reduced infection burden and protected immunocompromised mice from severe outcomes including death, with effects that required STAT1 signaling in the enterocyte. Initiation of this type III interferon response was dependent on sustained intracellular growth and mediated by the pattern recognition receptor TLR3. We conclude that host cell intrinsic recognition ofCryptosporidiumresults in IFNλ production critical to early protection against this infection.

This perspective summarizes the genesis, development, and potential future directions of the multispeciesJOR Spinehistopathology series.

Continuous digital hypothermia can prevent the development and progression of laminitis associated with sepsis but its effects on laminitis due to hyperinsulinaemia are unknown.To determine the effects of continuous digital hypothermia on laminitis development in the euglycaemic hyperinsulinaemic clamp model.Randomised, controlled (within subject), blinded, experiment.Eight clinically normal Standardbred horses underwent laminitis induction using the euglycaemic hyperinsulinaemic clamp model (EHC). At initiation of the EHC, one forelimb was continuously cooled (ICE), with the other maintained at ambient temperature (AMB). Dorsal lamellar sections (proximal, middle, distal) were harvested 48 h after initiation of the EHC and were analysed using histological scoring (0-3) and histomorphometry. Cellular proliferation was quantified by counting epidermal cell nuclei staining positive with an immunohistochemical proliferation marker (TPX2).Severe elongation and disruption of SEL with dermo-epidermal separation (score of 3) was observed in all AMB feet at one or more section locations, but was not observed in any ICE sections. Overall 92% of the AMB sections received the most severe histological score (grade 3) and 8% were grade 2, whereas ICE sections were classified as either grade 1 (50%) or grade 2 (50%). Relative to AMB feet, ICE sections were 98% less likely to exhibit grades 2 or 3 (OR: 0.02, 95% CI 0.001, 0.365; P0.01). Histomorphometry measurements of total and nonkeratinised primary epidermal lamellar length were significantly increased (P0.01) in AMB limbs compared with ICE. TPX2 positive cell counts were significantly increased (P0.01) in AMB limbs compared with ICE.Continuous digital hypothermia was initiated before recognition of laminitis and therefore the clinical applicability requires further investigation.Continuous digital hypothermia reduced the severity of laminitis in the EHC model and prevented histological lesions compatible with lamellar structural failure.

Background Laminitis is often associated with endocrinopathies that cause hyperinsulinemia and is also induced experimentally by hyperinsulinemia, suggesting that insulin initiates laminitis pathogenesis. Hyperinsulinemia is expected to activate pro-growth and anabolic signaling pathways. We hypothesize that chronic over-stimulation of these pathways in lamellar tissue results in endoplasmic reticulum stress, contributing to tissue pathology, as it does in human metabolic diseases. We tested this hypothesis by asking whether lamellar tissue from horses with naturally-occurring endocrinopathic laminitis showed expression of protein markers of endoplasmic reticulum stress. Results Three markers of endoplasmic reticulum stress, spliced XBP1, Grp78/BiP and Grp94, were upregulated 2.5–9.5 fold in lamellar tissues of moderately to severely laminitic front limbs (n = 12) compared to levels in controls (n = 6–7) measured by immunoblotting and densitometry. Comparing expression levels between laminitic front limbs and less affected hind limbs from the same horses (paired samples from 7 to 8 individual horses) demonstrated significantly higher expression for both spliced XBP1 and Grp78/BiP in the laminitic front limbs, and a similar trend for Grp94. Expression levels of the 3 markers were minimal in all samples of the control (n = 6–7) or hind limb groups (n = 7–8). Immunofluorescent localizations were used to identify cell types expressing high levels of Grp78/BiP, as an indicator of endoplasmic reticulum stress. Grp78/BiP expression was highly elevated in suprabasal epidermal keratinocytes and only observed in laminitic front limbs (10/12 laminitic samples, compared to 0/7 in sections from the hind limbs and 0/5 of controls). Conclusions These data demonstrate that the endoplasmic reticulum stress pathway is active in naturally occurring cases of laminitis and is most active within a subset of epidermal keratinocytes. These data provide the rationale for further study of endoplasmic reticulum stress in experimental models of laminitis and the links between laminitis and human diseases sharing activation of this stress pathway. Pharmacological options to manipulate the endoplasmic reticulum stress pathway under investigation for human disease could be applicable to laminitis treatment and prevention should this pathway prove to be a driver of disease progression. Electronic supplementary material The online version of this article (10.1186/s12917-018-1748-x) contains supplementary material, which is available to authorized users.

Background The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. Aims The purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model. Materials and Methods The scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra‐class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors. Results The final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus. Discussion Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field. Conclusion This study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing., The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies, and histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. Therefore, the purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model.

Objective To compare end-to-end jejunal anastomoses with a one-layer (Utrecht) and two-layer (simple continuous/Cushing) patterns. Study design Experimental study. Animals Eight healthy adult horses. Methods Jejunal end-to-end anastomoses were performed in randomly assigned one-layer or two-layer patterns. Horses were recovered from surgery and monitored for complications. At 14 days, the opposite pattern was performed (cross-over design) prior to euthanasia. Duration of closures was compared between patterns. Serosal width was measured before harvesting anastomotic sites from the first procedure. Luminal diameter was measured, and sections were collected for histological evaluation of heating after routine and immunohistochemical staining. Results One-layer closure was faster (716 ± 86 s) than two-layer closures (1136 ± 111 s). Postoperative complications were minimal. No difference was detected in lumen size between groups. The lumen was reduced by 18% after one-layer and 15% after two-layer closures (p = .34). Serosal adhesions to the mesentery without clinical evidence of obstruction were observed in two horses with two-layer closure. Histopathological scores for inflammation, infection, and healing did not differ between groups. Conclusion Jejunal anastomosis with one-layer Utrecht technique was about 7 min faster and led to similar luminal reduction and histological healing scores as two-layer jejunojejunostomies. Clinical significance The outcomes of one-layer Utrecht jejunojejunostomies in healthy horses justify clinical evaluation of this technique.

Joint injury can cause posttraumatic inflammation, which if severe enough can lead to posttraumatic osteoarthritis (PTOA), a progressive and debilitating condition. Posttraumatic inflammation is characterized by an influx of T lymphocytes and upregulation of inflammatory cytokines and degradative enzymes by activated chondrocytes and synoviocytes. Intra-articular bone marrow-derived mesenchymal stem cell (BM-MSC) injection for the treatment of osteoarthritis (OA) has been of interest due to the immunomodulatory properties of these cells. Interleukin (IL)-10, a potent immunomodulatory cytokine, has also been investigated as an OA therapeutic. Therefore, the objective of this study was to evaluate the combinatorial effects of BM-MSCs and IL-10 in OA using a gene therapy approach. We hypothesized that BM-MSCs overexpressing IL-10 would have superior immunomodulatory effects leading to increased suppression of T cell proliferation and decreased production of proinflammatory cytokines, providing protection of the extracellular matrix (ECM) in a stimulated, co-culture OA model. Treatment groups included the following: untransduced BM-MSC, adeno-associated virus (AAV)-IL10-transduced BM-MSC, and AAV-null transduced BM-MSC, which were unstimulated or stimulated with IL-1β/tumor necrosis factor-α (TNF-α). T cell proliferation was significantly decreased by the presence of BM-MSCs, especially when these BM-MSCs were AAV transduced. There was no significant difference in T cell suppression when cells were cultured with AAV-IL10-transduced or AAV-null transduced BM-MSCs. AAV transduction itself was associated with decreased synthesis of IL-1β, IL-6, and TNF-α. Expression of IL-1β and MMP13 was downregulated in AAV-transduced BM-MSCs and MMP13 expression was downregulated in cartilage explants co-cultured with AAV-transduced BM-MSCs. Despite mitigation of some proinflammatory cascades, rescue of ECM loss, as determined by glycosaminoglycan quantification and histological evaluation, did not occur in either AAV-IL10-transduced or AAV-null transduced co-cultures. Although IL-10 overexpression may enhance BM-MSC-mediated T cell suppression, we did not observe significant modulation of inflammation-driven cartilage degradation in cultures containing AAV-IL10-transduced BM-MSCs. AAV transduction itself does appear to affect paracrine signaling by BM-MSCs, which warrants further investigation.

OBJECTIVE To describe the bactericidal and fungicidal properties of a 0.0005% chlorhexidine (CHD) solution potentiated with EDTA-Tris buffers (CHD-EDTA-Tris) and evaluate the safety of 0.0005% CHD-EDTA-Tris in the upper respiratory tract (URT) of normal horses. STUDY DESIGN Clinical, prospective study. ANIMALS Eight healthy, skeletally mature horses. METHODS In vitro-serial dilutions of CHD-EDTA-Tris and EDTA-Tris alone were evaluated for bactericidal and fungicidal activity against Aspergillus fumigatus, Escherichia coli, Staphylococcus aureus, Streptococcus equi subspecies ssp. equi, Streptococcus equi ssp. zooepidemicus, and Pseudomonas aeruginosa. In vivo-eight healthy horses were topically treated twice with 30 ml of 0.0005% CHD-EDTA-Tris. Mucosal samples from each location were evaluated for the presence of inflammation or pathologic lesions. RESULTS Solutions containing CHD were superior in fungal and bacterial killing to those without. In vitro-a 0.005% CHD-EDTA-Tris was 100% effective against all bacterial and fungal species evaluated, while a 0.0005% CHD-EDTA-Tris was less efficacious against A. fumigatus and S. equi ssp. equi. In vivo-a 0.0005% CHD-EDTA-Tris did not cause any clinical, gross, or histologic abnormalities when topically applied to the equine URT. CONCLUSIONS A 0.0005% CHD-EDTA-Tris was highly effective for killing of common bacterial and fungal isolates in the equine upper respiratory tract. Short-term topical treatment of the equine URT with dilute CHD did not cause gross or histological inflammation in the tissue. CLINICAL SIGNIFICANCE A 0.0005% CHD solution with EDTA-Tris should be considered for treatment of clinically relevant inflammatory or infectious conditions or in the URT of the horse.

The apicomplexan parasite Cryptosporidium infects the intestinal epithelium. While infection is widespread around the world, children in resource-poor settings suffer a disproportionate disease burden. Cryptosporidiosis is a leading cause of diarrheal disease, responsible for mortality and stunted growth in children. CD4 T cells are required to resolve this infection, but powerful innate mechanisms control the parasite prior to the onset of adaptive immunity. Here, we use the natural mouse pathogen Cryptosporidium tyzzeri to demonstrate that the inflammasome plays a critical role in initiating this early response. Mice lacking core inflammasome components, including caspase-1 and apoptosis-associated speck-like protein, show increased parasite burden and caspase 1 deletion solely in enterocytes phenocopies whole-body knockout (KO). This response was fully functional in germfree mice and sufficient to control Cryptosporidium infection. Inflammasome activation leads to the release of IL-18, and mice that lack IL-18 are more susceptible to infection. Treatment of infected caspase 1 KO mice with recombinant IL-18 is remarkably efficient in rescuing parasite control. Notably, NOD-like receptor family pyrin domain containing 6 (NLRP6) was the only NLR required for innate parasite control. Taken together, these data support a model of innate recognition of Cryptosporidium infection through an NLRP6-dependent and enterocyte-intrinsic inflammasome that leads to the release of IL-18 required for parasite control.

Equine infectious disease outbreaks may have profound economic impact, resulting in losses of millions of dollars of revenue as a result of horse loss, quarantine, and cancelled events. Early and accurate diagnosis is essential to limit the spread of infectious diseases. However, laboratory detection of infectious agents, especially the simultaneous detection of multiple agents, can be challenging to the clinician and diagnostic laboratory. Next-generation sequencing (NGS), which allows millions of DNA templates to be sequenced simultaneously in a single reaction, is an ideal technology for comprehensive testing. We conducted a proof-of-concept study of targeted NGS to detect 62 common equine bacterial, viral, and parasitic pathogens in clinical samples. We designed 264 primers and constructed a bioinformatics tool for the detection of targeted pathogens. The designed primers were able to specifically detect the intended pathogens. Results of testing 27 clinical samples with our targeted NGS assay compared with results of routine tests (assessed as a group) yielded positive percent agreement of 81% and negative percent agreement of 83%, overall agreement of 81%, and kappa of 0.56 (moderate agreement). This moderate agreement was likely the result of low sensitivity of some primers. However, our NGS assay successfully detected multiple pathogens in the clinical samples, including some pathogens missed by routine techniques.

The horse is uniquely adapted for hindgut fermentation, and the microbiota within the hindgut contribute to immune system stimulation, protection against harmful pathogens and toxins, and regulation of gene expression within the host. Many factors, such as dietary changes, antimicrobials, pathogens, and changes in management, can perturb the microbial communities leading to gastrointestinal complications such as colitis and colic in horses. With advances in genomic tools to characterize microbiota, efforts to expand the body of knowledge on the community structure and function of equine gut microbiota in health and disease are increasing within the equine research community. Colic is an important equine disease. While epidemiological studies have identified risk factors for colic, and intestinal inflammation may play a role in some horses with recurrent colic, there are very few studies investigating the role of the intestinal microbiota in colic. We compared the microbial communities of horses admitted to the hospital for colic to those of horses admitted for an elective procedure. We found a significant difference at the community level (alpha and beta diversity) and also between individual bacterial populations. Furthermore, we also found that location of lesions in the GI tract, duration of colic (acute vs. chronic), and other factors altered the microbial ecology of the equine gut microbiota. Notably, we also investigated whether the changes in microbiota induced by colic were confounded by withholding feed. We found that withholding feed from horses for 24 h induced a significant shift in the microbiota, which reverted to normal within 12 h after the horses gained access to feed. From our experiments, it is becoming increasingly clear that colic in horses induces changes in specific bacterial populations along with generalized changes that are confounded with many other factors. Further research is needed particularly in horses with recurrent colic to determine the association between the intestinal microbiota, diet and management factors, and inflammation.

BACKGROUND Previous studies have identified alterations in the faecal microbiota of horses with colic; however, further work is needed to interpret these findings. OBJECTIVES To compare the faecal microbiota of horses presenting for colic at hospital admission, day 1 and day 3/discharge and with different colic duration and lesion locations. STUDY DESIGN Prospective observational clinical study. METHODS Faecal samples were collected from 17 colic cases at hospital admission, on day 1 and on day 3 post-admission or at the time of hospital discharge if prior to 72 hours. Faecal samples were extracted for genomic DNA, PCR-amplified, sequenced and analysed using QIIME. Species richness and Shannon diversity (alpha diversity) were estimated. The extent of the relationship between bacterial communities (beta diversity) was quantified using pairwise UniFrac distances, visualised using principal coordinate analysis (PCoA) and statistically analysed using permutational multivariate analysis of variance (PERMANOVA). The relative abundance of bacterial populations at the different time points and in different types of colic was compared using ANCOM. RESULTS There was a decrease in species richness from admission to day 3/hospital discharge (P

Supporting limb laminitis (SLL) is suspected to be caused by lamellar ischaemia as a consequence of increased mechanical load.Examine the effects of prolonged preferential weight bearing (PWB) on lamellar perfusion and metabolism.In vivo experiment.Microdialysis probes were inserted in the lamellar and sublamellar dermis of one forelimb in 13 Standardbred horses. In six horses, a platform shoe (contralateral forelimb) was used to induce increased load on the microdialysis-instrumented forelimb (PWB). The remaining seven horses were controls (CON). All horses were housed in stocks with limb weight distribution logged continuously for 92 hours. Microdialysate was collected and analysed every 4 hours for glucose, lactate, pyruvate, and lactate to pyruvate ratio (L:P). Microdialysis urea clearance was used to estimate lamellar perfusion. Data were analysed using a mixed-effects linear regression model.Median [IQR] load on the microdialysis-instrumented limb was equivalent to 38.7% bwt. [37.3-40.3] in PWB and 27.3% bwt. [26.6-28] in CON. Limb offloading frequency increased in CON (P .001) but not PWB (P = .2). Lamellar microdialysate glucose decreased in PWB (P .001) and CON (P = .004), however, the rate of decrease was higher in PWB (P = .007). Lamellar L:P increased in PWB (P .001) and peaked at 196 [79-656], whereas L:P did not change over time in CON (P = .6) and peaked at 42 [41-49]. Lamellar urea clearance decreased in PWB (P .001) but not in CON (P = .3). Sublamellar L:P and urea clearance did not change over time in either group (P .05).The PWB model may not be representative of naturally occurring SLL.Evidence of lamellar ischaemia (increased L:P and decreased urea clearance) was detected exclusively in the lamellar dermis of PWB feet subjected to persistently increased load. Lamellar ischaemia is a consequence of increased mechanical load and likely contributes to the development of SLL.

Background Strangulating small intestinal lesions in the horse have increased morbidity and mortality compared to nonstrangulating obstructions due to mucosal barrier disruption and subsequent endotoxaemia. Objectives To investigate protective effects of dexmedetomidine on small intestinal ischaemia-reperfusion injury in the horse. Study design Randomised, controlled, experimental study. Methods Eighteen systemically healthy horses were randomly assigned to three groups: control, preconditioning, and post-conditioning. During isoflurane anaesthesia, complete ischaemia was induced in a 1-m segment of jejunum for 90 minutes. Horses in the preconditioning and post-conditioning groups received dexmedetomidine (3.5 µg/kg followed by 7 µg/kg/h) before (preconditioning) or after beginning ischaemia (post-conditioning), and during reperfusion. Jejunal biopsies were collected before ischaemia (baseline-1), at the end of the ischaemic period (ischaemia), and 30 minutes after reperfusion (reperfusion-1). Additional biopsies were taken 24 hours after reperfusion from ischaemia-reperfusion-injured jejunum (reperfusion-2). Epithelial injury was scored histologically, and morphometric analyses were used to calculate villus surface area (VSA) denuded of epithelium. Data were analysed using analysis of variance, Kruskal-Wallis and Wilcoxon two-sample tests. Results In the control group, epithelial injury scores and percentage of VSA denudation for ischaemia-reperfusion-injured jejunum were higher compared to baseline-1 at all time points. The ischaemia and both reperfusion samples from the pre- and post-conditioning groups had lower epithelial injury scores and percentage of VSA epithelial denudation compared to the control group, with no difference from baseline-1 at any time point for the preconditioning group. Main limitations Preconditioning has limited application in the clinical setting with naturally occurring strangulating small intestinal lesions. Conclusions Dexmedetomidine was protective for small intestinal ischaemia-reperfusion injury in the horse when administered before or during ischaemia.

Supporting Limb Laminitis (SLL) is a painful and crippling secondary complication of orthopedic injuries and infections in horses, often resulting in euthanasia. Due to altered weight bearing, SLL causes structural alternations and inflammation of the interdigitating layers of specialized epidermal and dermal tissues, the lamellae, which suspend the equine distal phalanx from the hoof capsule. Activation of the interleukin-17 (IL-17)-dependent inflammatory pathway is an epidermal stress response that contributes to physiologic cutaneous wound healing as well as pathological skin conditions. To test the hypothesis that IL-17 pathway activation is involved in equine epidermal lamellae in SLL, we analyzed the expression of the IL-17 receptor subunit A and 11 genes upregulated by IL-17 in lamellar tissue isolated from Thoroughbreds euthanized due to naturally occurring SLL and in age and breed matched non-laminitic controls. The IL-17 Receptor A subunit was expressed in both non-laminitic and laminitic tissues. In severe acute SLL (n=7) compared to non-laminitic controls (n=8), quantitative PCR demonstrated ∼20-100 fold upregulation of ß defensin 4 (E. caballus gene DEFB4B) and S100A9 genes. DEFB4B was also upregulated in developmental (n=8), moderate acute (n=7), and severe chronic (n=5) samples. By RT-PCR, S100A8, MMP9, and PTSG2 (COX2) expression was upregulated in most or all severe acute SLL samples, whereas several other genes, CCL2, CxCL8, TNFα, IL6 and MMP1 were detected in some, but not all, severe acute samples. PTGS2, CCL2, TNFα and IL6 were also expressed in some, but not all, developmental and moderate acute disease stages. Moreover, expression of DEFB4 by in situ hybridization and calprotectin (S100A9/S100A8) protein by immunofluorescence was detected in keratinocytes, primarily in suprabasal cell layers, from SLL samples. These data support the hypothesis that the IL-17 inflammatory pathway is active in equine SLL, and that similarities exist between equine and human epidermal tissue responses to stresses and/or damage.

Background A novel equine parvovirus (EqPV-H) was recently discovered in the equine liver with Theiler's disease. Objectives To determine the prevalence of EqPV-H infection in naturally occurring Theiler's disease cases and in-contact horses in the absence of historical equine biologic product administration. Animals Ten cases of Theiler's disease from 6 separate properties were included in the study, based on the criteria of acute onset of clinical signs of liver failure with laboratory or histopathologic findings characteristic of Theiler's disease and no history of receiving an equine biologic product within the preceding 4 months. In addition, 37 in-contact horses from 4 of the 6 properties were screened for EqPV-H infection and hepatitis. Methods In prospective case series, cases were diagnosed with Theiler's disease by the attending veterinarian and were tested for EqPV-H by PCR of liver or serum. In-contact horses were assessed via serum chemistry and PCR at the attending veterinarian's discretion. Hepatitis was defined as serum gamma-glutamyltransferase activity above reference interval. The association of EqPV-H with hepatitis was determined by Fisher's exact test. Results Nine of 10 (90%) Theiler's disease cases and 54% of tested in-contact horses were EqPV-H positive. Hepatitis was significantly associated with EqPV-H infection (P = .036). Conclusions and clinical importance Although further study is required to identify EqPV-H as the causative agent of Theiler's disease, EqPV-H appears strongly associated with cases of fatal Theiler's disease and subclinical hepatitis in horses in contact with those cases. The prevalence of EqPV-H infection on affected properties can be high.

BACKGROUND The faecal microbiota is emerging as potentially important in intestinal disease. More research is needed to characterise the faecal microbiota from horses with colic. OBJECTIVES To compare the relative abundance of bacterial populations comprising the faecal microbiota in horses presenting for colic compared with an elective surgical procedure. STUDY DESIGN Prospective observational clinical study. METHODS Admission faecal samples were collected from horses presenting for colic and elective surgical procedures. Faecal samples were extracted for genomic DNA, PCR- amplified, sequenced and analysed using QIIME. Species richness and Shannon diversity were estimated for each faecal sample. The extent of the relationship between bacterial communities (beta diversity) was quantified using pairwise UniFrac distances, visualised using principal coordinate analysis (PCoA) and statistically analysed using PERMANOVA. The relative abundance of bacterial populations between the two treatment groups were compared using ANCOM. RESULTS Faecal bacterial communities in horses presenting for colic had fewer species (P

OBJECTIVE To describe gastrointestinal histologic findings for horses with recurrent colic and evaluate possible associations between initial clinical signs, biopsy method, histologic diagnosis, and outcome 1 year after hospital discharge. DESIGN Retrospective case series. ANIMALS 66 horses with a history of recurrent colic for which gastrointestinal specimens had been submitted for histologic examination. PROCEDURES Histologic diagnosis was categorized as inflammatory, neoplastic, ischemic, other, and undiagnosed. Relationships among initial clinical features, biopsy method, histologic diagnosis, and outcome 1 year after hospital discharge (ie, alive vs dead and persistent recurrent colic [yes vs no]) and between corticosteroid treatment and outcome were investigated. Odds ratios and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. RESULTS Inflammatory disease (36/66 [55%]) was the most common histologic diagnosis. Horses undergoing rectal biopsy alone were significantly (OR, 14.4; 95% Cl, 2.7 to 76.1) more likely to not have a histologic diagnosis than were horses in which other biopsy methods were used. In multivariable modelling, persistence of recurrent colic (HR, 15.2; 95% Cl, 1.9 to 121.2) and a history of weight loss (HR, 4.9; 95% Cl, 1.4 to 16.5) were significantly associated with outcome (alive vs dead) 1 year after surgery. Corticosteroid treatment was not significantly associated with either outcome. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that a high proportion (36/66 [55%]) of horses with recurrent colic had inflammatory gastrointestinal disease. Use of rectal biopsy alone to obtain biopsy specimens was more likely to result in no histologic diagnosis. Use of corticosteroids in horses with inflammatory gastrointestinal disease was not associated with outcome but warrants further investigation.

BACKGROUND CONTEXT Intervertebral disc (IVD) degeneration (IVDD) is implicated as a cause of low back pain. The earliest degenerative changes typically occur in the central nucleus pulposus (NP), where progressive loss of proteoglycans and associated hydration compromise tissue mechanical function. PURPOSE We developed a noncrosslinked injectable hydrogel for NP replacement and augmentation together with its percutaneous delivery method and instrument assembly. We then evaluated the short- and long-term performance of this hydrogel in a goat model of moderate IVDD. Methods Six goats underwent two percutaneous procedures: one to induce degeneration in 3 lumbar IVDs via injection of 1U C-ABC and, 2 weeks later, a second procedure for the delivery of hydrogel at 2 levels with the third remaining untreated. Animals were euthanized at 6 weeks (n=2) and 12 weeks (n=1); three animals are currently enrolled for long-term survival. Disc height index (DHI) was measured from monthly lateral radiographs in the standing animal. Postmortem, motion segments were imaged using microcomputed tomography (µCT) to assess hydrogel distribution and bone volume fraction values (BV/TV) for cranial and caudal endplates. Volumetric analysis and compression testing were performed on explanted gels. Samples were dried to determine polymer and water content. Explant characteristics were compared to nonimplanted gels. Histology was performed to assess glycosaminoglycans and collagen content, cellularity, and disc morphology. Significant changes in DHI were established using Wilcoxon matched-pairs signed ranks tests and differences in histological grades were established using Kruskal-Wallis test with post-hoc Dunn's tests (p Results Animals recovered uneventfully from surgical procedures. Extrusion of hydrogel into the spinal canal during delivery occurred in two animals without major clinical repercussions. At 2 weeks after C-ABC injection, DHI was ∼80% of pre-C-ABC levels. For IVDs treated with hydrogel, DHI improved while untreated IVDs continued to degenerate. The hydrogel presents radiographically unremarkable for up to 2 years post nucleoplasty. µCT imaging demonstrated that the majority of hydrogel was localized to the central NP. BV/TV ratio of treated levels at 6-week and 12-week endpoint were similar to controls. Explant analyses showed higher elastic moduli and polymer content compared to nonimplanted gels. Treated IVDs exhibited an overall improved histological grade compared to positive controls. Conclusions The results of this work illustrate the practical utility of an injectable hydrogel being effective in normalizing the mechanical function of the degenerating IVD in a clinically relevant animal model. The implant showed successful retention without extrusion following delivery. A critical benchmark for the success of any injectable implant to treat IVDD is the normalization of mechanical properties. We demonstrate through long-term in vivo follow up studies that hydrogel injected into degenerating goat discs can preserve the spine motion segment. There is a critical need for new therapies for patients with symptomatic disc degeneration that preserve joint mobility. A minimally invasive injectable therapy mitigates anulus fibrosus trauma during nucleoplasty and may restore the biomechanics of the motion segment. Moreover, successful biomechanical restoration of the affected motion segment may slow or prevent further IVDD. Motion preservation therapies may also help mitigate adjacent level IVDD in these patient cohorts. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Objective To determine the characteristics of and prognosis for ocular and periocular hemangiosarcoma in horses. Animal studied Six horses treated for ocular or periocular hemangiosarcoma. Procedure A retrospective review of medical records from 2007 to 2015 was performed to identify horses with a histologic diagnosis of ocular or periocular hemangiosarcoma. Signalment (age, sex, breed), duration of clinical signs, prior treatment, tumor size and location, medical and surgical treatment including postoperative chemotherapy, follow-up time, and outcome were obtained from medical records. Histopathology was reviewed by a board-certified pathologist. Results In six horses diagnosed with ocular or periocular hemangiosarcoma, no breed, age, or sex was overrepresented. Sites included the temporal limbus (3), third eyelid (2), and uvea (1). With the exception of one horse with uveal hemangiosarcoma, 5/6 horses had lightly pigmented periocular haircoat. Histologic features of ocular hemangiosarcoma in 6/6 cases included high cellularity, nuclear pleomorphism, and inflammation with a mitotic index ranging from 0 to 8 mitoses per 10 consecutive 400× fields. Five of six tumors displayed solar elastosis, indicating ultraviolet light-induced damage to sub-epithelial collagen. Treatment included surgical excision in all cases and was not associated with recurrence in 4/6. Three cases that received ancillary treatment with topical mitomycin C had no postoperative recurrence. Two cases with postexcisional recurrence had histologic evidence of incomplete excision. Conclusions Complete surgical excision may be associated with resolution of periocular and ocular hemangiosarcoma in horses. Etiopathogenesis may include exposure to ultraviolet light.

Equine catastrophic skeletal breakdown injury is a serious issue within the racing industry, given the impact on equine and human health. The metacarpo- and metatarso-phalangeal (fetlock) joints are common sites of catastrophic injury. However, lesions involving articular cartilage, subchondral bone, and synovium are commonly identified within the fetlock of the contralateral limb; hence, it is imperative that lesions in both limbs are evaluated and characterized during postmortem examination. Bone and articular cartilage changes typically occur in specific locations, related to cyclic fetlock load and overextension during high-speed exercise. Associations between preexisting degenerative fetlock lesions and catastrophic injury are a focus of continued research. These lesions often occur because of adaptive failure related to cumulative damage. Further investigation of these lesions is imperative to determine their impact on equine performance or injury. Ultimately, consistent documentation of catastrophic versus non-catastrophic osteochondral lesions provided by pathologists, in the context of training history, diagnostic imaging, and the presence or absence of catastrophic injury, will contribute to further understanding of skeletal responses associated with catastrophic failure.

As a pathologist, postmortem examination of the equine carpus can be daunting. The anatomy is complex and oftentimes, small or subtle lesions have significant impact on lameness and secondary lesions such as catastrophic musculoskeletal fractures and other injuries. In performance horses, particularly racehorses, the carpus is a common site of injury and source of lameness. Given the predisposition of racehorses to developing carpal disease, familiarity with clinically relevant anatomy and common developmental, degenerative, traumatic, and inflammatory processes are imperative for thorough postmortem examination. Our aim is (1) to provide a concise summary of clinically relevant anatomy and function that serves as a guide for postmortem evaluation of the equine carpus, and (2) to review common carpal injuries and diseases in actively training, racing, or retired racehorses, including developmental lesions (incomplete ossification, osteochondromata), infectious and inflammatory lesions (septic arthritis and tenosynovitis), and degenerative and traumatic lesions (degenerative and traumatic osteoarthritis, osteochondral fragmentation, and polyostotic catastrophic “breakdown” fractures). Representative gross and histologic images are presented along with corresponding antemortem and postmortem diagnostic images, and a review of current scientific literature pertaining to the pathogenesis of these equine carpal lesions.

There are reports of horses with acute onset acquired cervical scoliosis and cutaneous analgesia. The underlying dorsal gray column myelitis that produces these neurologic signs has been only presumptively attributed to migration of Parelaphostrongylus tenuis within the spinal cord. Despite previous confirmation brain by polymerase chain reaction testing, of P. tenuis within the brain of horses by polymerase chain reaction testing, genetic testing has failed to definitively identify the presence of this parasite in cases of equine myelitis. This case report provides molecular confirmation via polymerase chain reaction of P. tenuis within the cervical spinal cord of a horse with scoliosis and cutaneous analgesia.