Predictors of peer assessment in junior leader training.

Peer assessments are used in a variety of military contexts. The current study examined factors that may influence how peers assess each other, including age, perceived warmth and competence, locus of control, and physical fitness. Participants in a junior leader training course completed peer assessments at three time points during the course per curriculum requirements. Participants also rated their peers on measures of warmth and competence and responded to a locus of control measure. Course performance metrics, including physical fitness scores were also obtained. Ratings of competence were the only significant predictors of peer assessments over all three time points. The inter-correlations between peer, self, and instructor assessments of leadership and course performance were also examined. The implications of these findings are discussed.

The equine navicular apparatus as a premier enthesis organ: Functional implications.

Navicular syndrome has been traditionally characterized by progressive lameness with chronic degeneration of the navicular bone. Advances in imaging techniques have revealed that its associated soft tissue structures are also affected. This distribution of lesions is explained by conceptualizing the equine navicular apparatus as an enthesis organ that facilitates the dissemination of mechanical stress throughout the tissues of the foot. The navicular apparatus has the same structural adaptations to mechanical stress as the human Achilles tendon complex. These adaptations efficiently dissipate mechanical force away from the tendon's bony attachment site, thereby protecting it from failure. The comparison of these two anatomically distinct structural systems demonstrates their similar adaptations to mechanical forces, and illustrates that important functional insights can be gained from studying anatomic convergences and cross-species comparisons of function. Such a functional conceptualization of the equine navicular apparatus resolves confusion about the diagnosis of navicular syndrome and offers insights for the development of mechanically based therapies. Through comparison with the human Achilles complex, this review (1) re-conceptualizes the equine navicular apparatus as an enthesis organ in which mechanical forces are distributed throughout the structures of the organ; (2) describes the relationship between failure of the navicular enthesis organ and lesions of navicular syndrome; (3) considers the therapeutic implications of navicular enthesis organ degeneration as a form of chronic osteoarthritis; and based upon these implications (4) proposes a focus on whole body posture/motion for the development of prehabilitative and rehabilitative therapies similar to those that have already proven effective in humans.

Canine histiocytic sarcoma presenting as a target lesion on brain magnetic resonance imaging and as a solitary pulmonary mass.

A 6-year-old spayed female miniature schnauzer presented with generalized seizures and progressive multifocal intracranial neurologic disease. Thoracic radiographs and computed tomography (CT) revealed a large solitary pulmonary mass within the right cranial lung lobe. On brain magnetic resonance imaging (MRI), a solitary intraparenchymal mass within the left piriform lobe had a "target" appearance on both pre- and postcontrast sequences. Cerebrospinal fluid was unremarkable and histopathology indicated both masses represented histiocytic sarcoma. This case represents an uncommonly reported MRI appearance of histiocytic sarcoma in the canine brain and a large, solitary-appearing pulmonary histiocytic sarcoma in the same dog.

Brief report: chimeric pigs produced from induced pluripotent stem cells demonstrate germline transmission and no evidence of tumor formation in young pigs.

The recent development of porcine induced pluripotent stem cells (piPSCs) capable of generating chimeric animals, a feat not previously accomplished with embryonic stem cells or iPSCs in a species outside of rodents, has opened the doors for in-depth study of iPSC tumorigenicity, autologous transplantation, and other key aspects to safely move iPSC therapies to the clinic. The study of iPSC tumorigenicity is critical as previous research in the mouse showed that iPSC-derived chimeras possessed large numbers of tumors, rising significant concerns about the safety of iPSC therapies. Additionally, piPSCs capable of generating germline chimeras could revolutionize the transgenic animal field by enabling complex genetic manipulations (e.g., knockout or knockin of genes) to produce biomedically important large animal models or improve livestock production. In this study, we demonstrate for the first time in a nonrodent species germline transmission of iPSCs with the live birth of a transgenic piglet that possessed genome integration of the human POU5F1 and NANOG genes. In addition, gross and histological examination of necropsied porcine chimeras at 2, 7, and 9 months showed that these animals lacked tumor formation and demonstrated normal development. Tissue samples positive for human POU5F1 DNA showed no C-MYC gene expression, further implicating C-MYC as a cause of tumorigenicity. The development of germline-competent porcine iPSCs that do not produce tumors in young chimeric animals presents an attractive and powerful translational model to study the efficacy and safety of stem cell therapies and perhaps to efficiently produce complex transgenic animals.

Identification of altered MicroRNA expression in canine lymphoid cell lines and cases of B- and T-Cell lymphomas.

Canine lymphoma is a common spontaneous tumor with many similarities to human lymphoma, and thus has potential to be an important animal model of lymphomagenesis. This study determined that microRNA (miRNA) expression in canine tumors can be assessed using a commercially available human cancer miRNA qPCR array. miRNA expression in six different canine lymphoid cell lines and in naturally occurring canine B- and T-cell lymphomas was compared using RNA harvested from normal canine peripheral blood mononuclear cells (PBMC) and normal lymph nodes (LN) as controls. We found that false discovery rate (FDR) correction for multiple testing after quantile normalization controlled for variation across arrays and that they were the best methods for normalization and statistical analysis. Increases in miRNAs known to upregulate oncogenes (miR19a+b, miR17-5p) and decreased expression of miRNAs with tumor suppressor functions (miR-203, miR-218, and miR-181a) also seen in human lymphoid malignancies were observed. However, there were few similarities between canine groups. The results of this study indicate that the use of both PBMC and LN cells as controls provides different, but potentially equally important targets for further analysis. Our findings of miRNA dysregulation in canine lymphoid cell lines and clinical cases of lymphoma emphasize the potential of canine lymphoma as an important spontaneous, large animal model of human B- and T-cell lymphomas.

Stems to GEMs: impact of stem cell technology on engineered animal models.

Collectively, these presentations introduced the audience to the roles of ES cells in generating phenotypes of transgenic animals,and they provided examples where the GEMs were used to define molecular mechanisms of disease or where ES cells were used as a therapeutic modality. Points of discussion among audience members reinforced the importance of strain-associated background lesions in animal models, technological advances in imaging functional biology, opportunities for stem cell therapies, and ubiquitination in regulation of cell proliferation. The 2012 American College of Veterinary Pathologists symposium ''Evolutionary Aspects of Animal Models'' will focus on the proper selection of a relevant animal model in biomedical research as critical to investigative success. Recent work characterizing rapid evolutionary changes and differences in physiology between species questions the validity of some comparative models. Dr. Robert Hamlin will be speaking on cardiovascular disease in ''Animals as Models of Human Cardiovascular Disease: Or the Search to Overcome Outdated Evolutionary Homeostatic Mechanisms.'' Dr. Stefan Niewiesk will discuss evolutionary factors that affect modeling the human immune system in ''Of Mice and Men: Evolutionarily, What Are the Best Rodent Models of the Human Immune System for Infectious Disease Research?'' Dr. Steven Austad will consider evolution in ''Evolutionary Aspects of Animal Models of Aging.''Finally, Dr. Elizabeth Uhl will conclude the session with ''Modeling Disease Phenotypes: How an Evolutionary Perspective Enhances the Questions.''

Cardiomyopathy and right-sided congestive heart failure in a red-tailed hawk (Buteo jamaicensis).

A 15-year-old female red-tailed hawk (Buteo jamaicensis) was evaluated because of dyspnea, anorexia, and coelomic distension. Diagnostic imaging results confirmed severe coelomic effusion and revealed a markedly dilated right ventricle. The diagnosis was right-sided congestive heart failure. Results of measurements of vitamin E, selenium, lead, zinc, and cardiac troponin levels were normal or nondiagnostic. The hawk was treated with furosemide, antifungal and antimicrobial agents, and supplemental fluids and oxygen, but euthanasia was elected because of the poor prognosis and the practical difficulties associated with intensive case management. To our knowledge, this is the first described case of cardiomyopathy and congestive heart failure in a captive red-tailed hawk.

Construction of a Realistic, Whole-Body, Three-Dimensional Equine Skeletal Model using Computed Tomography Data.

Therapies based upon whole-body biomechanical assessments are successful for injury prevention and rehabilitation in human athletes. Similar approaches have rarely been used to study equine athletic injury. Degenerative osteoarthritis caused by mechanical stress can originate from chronic postural dysfunction, which, because the primary dysfunction is often distant from the site of tissue injury, is best identified through modeling whole-body biomechanics. To characterize whole-body equine kinematics, a realistic skeletal model of a horse was created from equine computed tomography (CT) data that can be used for functional anatomical and biomechanical modeling. Equine CT data were reconstructed into individual three-dimensional (3D) data sets (i.e., bones) using 3D visualization software and assembled into a complete 3D skeletal model. The model was then rigged and animated using 3D animation and modeling software. The resulting 3D skeletal model can be used to characterize equine postures associated with degenerative tissue changes as well as to identify postures that reduce mechanical stress at the sites of tissue injury. In addition, when animated into 4D, the model can be used to demonstrate unhealthy and healthy skeletal movements and can be used to develop preventative and rehabilitative individualized therapies for horses with degenerative lamenesses. Although the model will soon be available for download, it is currently in a format that requires access to the 3D animation and modeling software, which has quite a learning curve for new users. This protocol will guide users in (1) developing such a model for any organism of interest and (2) using this specific equine model for their own research questions.

Intrapericardial ectopic thyroid carcinoma in a cat.

A 7-year-old spayed female domestic shorthair feline presented with tachycardia and was later euthanized due to a declining condition. On gross examination, the thoracic cavity contained an expansile, multiloculated mass that displaced the lungs dorsocaudally. The mass, within the pericardial sac, compressed adjacent myocardium. Cut surface revealed variably sized, fluid-filled spaces with multiple foci of hemorrhage and necrosis. Histologically, the mass was composed of solid foci of polygonal cells admixed with colloid-containing follicles. Immunohistochemical staining for thyroglobulin was positive, and staining for calcitonin was negative. Grossly, thyroid glands were normal, and serum thyroxine was within reference intervals.

Gingival osteogenic melanoma in two dogs.

Osteogenic melanoma is a rare variant of metaplastic malignant melanoma in human medicine and appears to be a similarly rare variant in dogs. Two dogs with oral malignant melanoma with neoplastic bone formation are reported in this study. Both tumors were characterized by malignant melanocytes that transitioned into neoplastic bone at the deep margins of the neoplasm. Immunohistochemical analysis revealed S100- and Melan-A-positive neoplastic cells adjacent to, and occasionally embedded within, an osteoid and chondroblastic matrix. Scattered clusters of neoplastic cells were also positive for osteocalcin. The findings indicate that in dogs, as in humans, neoplastic melanocytes have metaplastic potential and can be osteogenic.

Clinicopathologic and magnetic resonance imaging characteristics associated with polioencephalomyelopathy in a Shih Tzu.

CASE DESCRIPTION: A 17-month-old 7-kg (15.4-lb) Shih Tzu was evaluated because of progressive thoracic limb weakness of 3 months' duration. CLINICAL FINDINGS: Neuroanatomic diagnosis was consistent with a lesion affecting the cervicothoracic (C6 through T2) spinal cord segments. Electrophysiologic testing revealed abnormal spontaneous activity in the thoracic limbs. Via magnetic resonance (MR) imaging, a lesion in the spinal cord that extended from the C5 through C7 vertebrae was detected, as were symmetric lesions in the cranial portion of the cervical spinal cord, caudal colliculi, and vestibular and cerebellar nuclei. Tests to detect metabolites indicative of inborn errors in metabolism revealed no abnormalities. TREATMENT AND OUTCOME: Prior to undergoing MR imaging, the dog received clindamycin (14 mg/kg [6.4 mg/lb], PO, q 12 h), trimethoprim-sulfadiazine (17 mg/kg [7.7 mg/lb], PO, q 12 h), and prednisone (1 mg/kg [0.45 mg/lb], PO, q 24 h). Because of its deteriorating condition, the dog was euthanized. During necropsy, gross lesions were identified in the cervical spinal cord, caudal colliculi, and vestibular and cerebellar nuclei (corresponding to lesions detected via MR imaging). Microscopic evaluation of the brain and spinal cord revealed polioencephalomyelopathy; there was severe spongiosis of the neuropil with reactive astrocytes (many with high numbers of swollen mitochondria) and preservation of large neurons. CLINICAL RELEVANCE: The form of polioencephalomyelopathy in the Shih Tzu of this report was similar to that described for Australian Cattle dogs; the similarity of findings in dogs with those in humans with Leigh disease is suggestive of a mitochondrial defect.

New world origin of canine distemper: Interdisciplinary insights.

OBJECTIVE: Canine distemper virus (CDV), human measles virus (HMV), and rinderpest virus (RPV) of cattle are morbilliviruses that have caused devastating outbreaks for centuries. This paper seeks to reconstruct the evolutionary history of CDV. MATERIALS AND METHODS: An interdisciplinary approach is adopted, synthesizing paleopathological analysis of 96 Pre-Columbian dogs (750-1470 CE) from the Weyanoke Old Town, Virginia site, with historical reports, molecular analysis and morbilliviral epidemiology. RESULTS: Both measles (c.900CE) and rinderpest (c. 376 BCE) were first reported in Eurasia, while canine distemper was initially described in South America much later (1735 CE); there are no paleopathological indications of CDV in Weyanoke Old Town dogs. Molecularly, CDV is closely related to HMV, while viral codon usage indicates CDV may have previously infected humans; South American measles epidemics occurred prior to the emergence of canine distemper and would have facilitated HMV transmission and adaptation to dogs. CONCLUSIONS: The measles epidemics that decimated indigenous South American populations in the 1500-1700 s likely facilitated the establishment of CDV as a canine pathogen, which eventually spread to Europe and beyond. SIGNIFICANCE: Understanding the historical and environmental conditions that have driven morbilliviral evolution provides important insights into potential future threats of animal/human cross-species infections. LIMITATIONS: Interpreting historical disease descriptions is difficult and the archaeological specimens are limited. Molecular sequence data and codon usage analyses rely on modern viruses. SUGGESTIONS FOR FURTHER RESEARCH: Interdisciplinary approaches are increasingly needed to understand diseases of the past and present, as critical information and knowledge is scattered in different disciplines.

Advances in FIV vaccine technology.

Advances in vaccine technology are occurring in the molecular techniques used to develop vaccines and in the assessment of vaccine efficacy, allowing more complete characterization of vaccine-induced immunity correlating to protection. FIV vaccine development has closely mirrored and occasionally surpassed the development of HIV-1 vaccine, leading to first licensed technology. This review will discuss technological advances in vaccine designs, challenge infection assessment, and characterization of vaccine immunity in the context of the protection detected with prototype and commercial dual-subtype FIV vaccines and in relation to HIV-1.

Prevalence of cryptosporidium infection and characteristics of oocyst shedding in a breeding colony of leopard geckos (Eublepharis macularius).

Cryptosporidiosis is an emerging problem in reptile medicine and has been associated with a wasting syndrome in leopard geckos (Eublepharis macularius). This study determined the prevalence of infection in a breeding colony of leopard geckos to be 9.8%. Two groups of 20 geckos, one that was fecal positive for oocysts of Cryptosporidium sp., and one, whose individuals were fecal negative at the inception of the study, were followed for 2 mo. Fecal samples were tested for oocysts every 2 wk, body weights were measured, and a body condition score was assigned for each gecko. Selected geckos from these two groups were euthanized and necropsied. There were statistically significant differences (P < 0.05) between the two groups for mean body weight, mean body condition score, and prevalence of infection. Cryptosporidium sp. infection is endemic in this breeding colony, and there were a large number of geckos with a subclinical or carrier state of infection. These animals continued to be infected with Cryptosporidium sp. but gained weight and remained in good body condition. Only one gecko in the entire group of 40 was confirmed to be negative for oocysts or developmental stages by repeated fecal exams and histopathology. An additional 37 severely emaciated geckos from the breeding colony were euthanized, and all were positive for Cryptosporidium sp. on histopathologic examination of the gastrointestinal tract. The results of this study indicate that although some animals can recover from a clinical infection, if a gecko is severely wasted, it should be euthanized because of the poor prognosis and possible source of infection to other geckos.

The pathology of vitamin D deficiency in domesticated animals: An evolutionary and comparative overview.

Although vitamin D is critical to calcium/phosphorus homeostasis, bone formation and remodeling, there is evolution-based variation between species in vitamin D metabolism and susceptibility to rickets and osteomalacia. Most herbivores produce vitamin D3 in response to sunlight, but dogs and cats have generally lost the ability as carnivore diets are rich in vitamin D. Nutritional deficiencies and/or poor exposure to sunlight can induce rickets in birds, swine, cattle and sheep, but horses are less susceptible as they have evolved a calcium homeostasis that is quite different than other animals. Adaptations to specific environments also affect disease incidence: llamas/alpacas out of their natural high altitude intense solar radiation environments are highly susceptible to vitamin D deficiency. The pathology of rickets/osteomalacia is similar across species, however fibrous osteodystrophy is more common and may also be present. Rickets/osteomalacia were likely more common in animals before the advent of commercial diets, but can be difficult to definitively diagnose especially in single archeological specimens. Consideration of species susceptibility, location - especially in terms of latitude, and any available information on diet, season of occurrence, husbandry practices or descriptions of affected animals can support the diagnosis of metabolic bone disease in animals.

High field (4.7 T) magnetic resonance imaging of feline hip joints.

Magnetic resonance imaging (MRI) is a non-invasive technique widely used to investigate degenerative joint disease (DJD). In this study, we obtained magnetic resonance images of feline hip joints, using a high magnetic field MRI unit (4.7 tesla) with proton density (PD)-weighted and T2-weighted fast spin-echo (FSE). PD-weighted FSE provided detailed anatomical images of feline hip joints with superb depiction of subchondral bones of the femoral head and acetabulum. Articular cartilage (AC) was also visualized with PD-weighted and T2-weighted FSE; however, mild AC lesions noted on gross examination were not detectable with these sequences.

Three-dimensional culture of feline articular chondrocytes in alginate microspheres.

Chondrocytes isolated from proximal femoral articular cartilage from 3 adult cat cadavers were expanded in monolayer culture and subsequently cultured in alginate microspheres for 24 days. Cell proliferation and production of proteoglycans in alginate microspheres were observed during day 18 and 24. Quantification of chondroitin sulfates (CS) by capillary electrophoresis revealed that cultured chondrocytes synthesized CS6 but not CS4. Three-dimensional culture using alginate microspheres is a useful in vitro technique to study proliferation and metabolism of chondrocytes; however, further modifications are needed to apply the technique to feline articular chondrocytes.

Comparison of NIRS, serum biomarkers, and muscle damage in a porcine balloon compression model of acute compartment syndrome.

BACKGROUND: Near-infrared spectroscopy (NIRS) has been shown to aid in the diagnosis of extremity acute compartment syndrome (ACS), offering continuous real-time capability to monitor perfusion in extremities. Porcine models of ACS have been developed to attempt to aid in the understanding of the development of ACS and provide better methods of diagnosing ACS. The objective of the present study was to assess and correlate NIRS, tibial intracompartmental pressure (TICP), tibial intracompartmental perfusion pressure (TIPP), serum markers of inflammation and muscle injury in a balloon compression model of ACS. METHODS: Six swine were used. Balloon catheters were inflated below the cranial tibial muscle. Systolic, diastolic, and mean arterial pressures; compartmental pressures; and oximetry were measured before, during, and after balloon inflation/deflation. Cranial tibial muscle was collected for muscle damage scoring. Serum creatine kinase, myoglobin, tumor necrosis factor α, IL-1ß, and IL-6 were measured. Data analysis included comparing differences in TICP, NIRS, and TIPP measurements as well as creatine kinase, myoglobin, tumor necrosis factor α, IL-1ß, and IL-6 levels between time points. Pearson correlations were calculated for muscle degeneration and edema and NIRS. RESULTS: Increases in TICP and decreases in TIPP were found. Near-infrared spectroscopy detected significant changes in tissue oxygenation at all the same time points. Myoglobin significantly increased from 45.7 ± 13.0 ng/mL (baseline) to 219.5 ± 57.3-ng/mL (balloon deflation) and continued to increase over the duration of the study. Creatine kinase significantly increased 2 hours after balloon deflation. Cranial tibial muscle degeneration, necrosis, and edema scores were higher in the test than the control legs. CONCLUSIONS: Near-infrared spectroscopy of the compartment provided a reliable, sensitive measure of both an increase and decrease in TICP and TIPP in this porcine balloon model of ACS. Creatine kinase and myoglobin significantly increased following balloon removal. Significant correlations between muscle degeneration, edema, hemorrhage, and NIRS were found.

Mouse Models as Predictors of Human Responses: Evolutionary Medicine.

Mice offer a number of advantages and are extensively used to model human diseases and drug responses. Selective breeding and genetic manipulation of mice have made many different genotypes and phenotypes available for research. However, in many cases, mouse models have failed to be predictive. Important sources of the prediction problem have been the failure to consider the evolutionary basis for species differences, especially in drug metabolism, and disease definitions that do not reflect the complexity of gene expression underlying disease phenotypes. Incorporating evolutionary insights into mouse models allow for unique opportunities to characterize the effects of diet, different gene expression profiles, and microbiomics underlying human drug responses and disease phenotypes.