Anatomic description of the basivertebral nerve and meningeal branch of the spinal nerve in the dog.

PURPOSE: The existence of the basivertebral nerve and meningeal branch of the spinal nerve has not been proven in dogs to date. The objectives of this study are to 1) determine whether dogs have a meningeal branch of the spinal nerve (MBSN) and a basivertebral nerve (BVN) and to (2) describe anatomical characteristics of these two nerves. Authors also put forward a discussion on the possible clinical relevance of these findings. MATERIAL AND METHODS: Dissections were performed on six embalmed dogs at the Veterinary Faculty of Barcelona with the use of stereomicroscopy and microsurgery equipment. RESULTS: The MBSN (grossly) and BVN (grossly and histologically) were identified in the cervical, thoracic, and lumbar region in all dog specimens. In addition, other small fibers (suspected nerves) entering the vertebral body through small foramina close to the end plates were identified. Histological examination of the tissues confirmed the presence of nerve fibers (myelinated and unmyelinated) in suspected BVN samples. Results of the present study indicated that dogs have BVNs. Also, suspected nerve fibers were identified among the epidural fat, running from the intervertebral foramina, that likely represent the MBSN. CONCLUSION: These findings open up the discussion on extrapolation of treatment options employed in human medicine for "low back pain", such as BVN ablation, which is discussed in this article. Further anatomic and clinical studies of the innervation for the vertebral body, periosteum, vasculature, dorsal longitudinal ligament and anulus fibrosus are necessary to elucidate possible anatomical variants and breed differences as well as potential clinical (e.g., therapeutic) relevance.

Development of polymorphic markers in the immune gene complex loci of cattle.

The addition of cattle health and immunity traits to genomic selection indices holds promise to increase individual animal longevity and productivity, and decrease economic losses from disease. However, highly variable genomic loci that contain multiple immune-related genes were poorly assembled in the first iterations of the cattle reference genome assembly and underrepresented during the development of most commercial genotyping platforms. As a consequence, there is a paucity of genetic markers within these loci that may track haplotypes related to disease susceptibility. By using hierarchical assembly of bacterial artificial chromosome inserts spanning 3 of these immune-related gene regions, we were able to assemble multiple full-length haplotypes of the major histocompatibility complex, the leukocyte receptor complex, and the natural killer cell complex. Using these new assemblies and the recently released ARS-UCD1.2 reference, we aligned whole-genome shotgun reads from 125 sequenced Holstein bulls to discover candidate variants for genetic marker development. We selected 124 SNPs, using heuristic and statistical models to develop a custom genotyping panel. In a proof-of-principle study, we used this custom panel to genotype 1,797 Holstein cows exposed to bovine tuberculosis (bTB) that were the subject of a previous GWAS study using the Illumina BovineHD array. Although we did not identify any significant association of bTB phenotypes with these new genetic markers, 2 markers exhibited substantial effects on bTB phenotypic prediction. The models and parameters trained in this study serve as a guide for future marker discovery surveys particularly in previously unassembled regions of the cattle genome.

Deficits across multiple behavioral domains align with susceptibility to stress in 129S1/SvImJ mice.

Acute physical or psychological stress can elicit adaptive behaviors that allow an organism maintain homeostasis. However, intense and/or prolonged stressors often have the opposite effect, resulting in maladaptive behaviors and curbing goal-directed action; in the extreme, this may contribute to the development of psychiatric conditions like generalized anxiety disorder, major depressive disorder, or post-traumatic stress disorder. While treatment of these disorders generally focuses on reducing reactivity to potentially threatening stimuli, there are in fact impairments across multiple domains including valence, arousal, and cognition. Here, we use the genetically stress-susceptible 129S1 mouse strain to explore the effects of stress across multiple domains. We find that 129S1 mice exhibit a potentiated neuroendocrine response across many environments and paradigms, and that this is associated with reduced exploration, neophobia, decreased novelty- and reward-seeking, and spatial learning and memory impairments. Taken together, our results suggest that the 129S1 strain may provide a useful model for elucidating mechanisms underlying myriad aspects of stress-linked psychiatric disorders as well as potential treatments that may ameliorate symptoms.

Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.

BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.

An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis resistance.

Genetic selection of cattle more resistant to bovine tuberculosis (bTB) may offer a complementary control strategy. Hypothesising underlying non-additive genetic variation, we present an approach using genome-wide high density markers to identify genomic loci with dominance effects on bTB resistance and to test previously published regions with heterozygote advantage in bTB. Our data comprised 1151 Holstein-Friesian cows from Northern Ireland, confirmed bTB cases and controls, genotyped with the 700K Illumina BeadChip. Genome-wide markers were tested for associations between heterozygosity and bTB status using marker-based relationships. Results were tested for robustness against genetic structure, and the genotypic frequencies of a significant locus were tested for departures from Hardy-Weinberg equilibrium. Genomic regions identified in our study and in previous publications were tested for dominance effects. Genotypic effects were estimated through ASReml mixed models. A SNP (rs43032684) on chromosome 6 was significant at the chromosome-wide level, explaining 1.7% of the phenotypic variance. In the controls, there were fewer heterozygotes for rs43032684 (P < 0.01) with the genotypic values suggesting that heterozygosity confers a heterozygote disadvantage. The region surrounding rs43032684 had a significant dominance effect (P < 0.01). SNP rs43032684 resides within a pseudogene with a parental gene involved in macrophage response to infection and within a copy-number-variation region previously associated with nematode resistance. No dominance effect was found for the region on chromosome 11, as indicated by a previous candidate region bTB study. These findings require further validation with large-scale data.

Hemifacial Microsomia in a Cat.

A 7-month-old domestic medium hair cat presented with facial asymmetry affecting the bony and soft tissue structures of the right side of the head including the maxilla, nose, eye and pinna of the ear. Additionally, neurological dysfunction of the facial and vestibulocochlear nerves on the affected side was present. A congenital malformation affecting the first and second embryologic pharyngeal arches was suspected. This is the first case of hemifacial microsomia of likely congenital origin reported in a cat.

Neuroendodermal cyst in the fourth ventricle of a dog.

CASE REPORT: We describe the MRI appearance and surgical outcome of a rare neuroendodermal cyst in the fourth ventricle of a German Shorthaired Pointer. The dog presented with uncoordinated gait and occasional falling that increased when she became excited. The MRI appearance is shown and the surgical treatment described. Recurrence occurred on two occasions and the dog was euthanased. CONCLUSION: Recurrence of these cysts is highly likely unless there is complete surgical resection.

The Scottish enhanced Staphylococcus aureus bacteraemia surveillance programme: the first 18 months of data in adults.

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) is the second most common source of positive blood cultures, after Escherichia coli, reported within NHS Scotland. Laboratory surveillance has been mandatory in Scotland for SAB since 2001. AIM: To gain an understanding of the epidemiology of SAB cases and associated risk factors for healthcare and true community onset. Identification of these factors and the patient populations at greatest risk enables the development of focused improvement plans. METHODS: All NHS boards within NHS Scotland take part in the mandatory enhanced surveillance, with data collected by trained data collectors using nationally agreed definitions. FINDINGS: Between 1st October 2014 and 31st March 2016, 2256 episodes of SAB in adults were identified. The blood cultures were taken in 58 hospitals and across all 15 Scottish health boards. The data demonstrated that approximately one-third of all SAB cases are true community cases. Vascular access devices continue to be the most reported entry point (25.7%) in individuals who receive health care, whereas skin and soft tissue risk factors are present in all origins. A significant risk factor unique to community cases is illicit drug injection. CONCLUSION: Improvement plans for reduction of SAB should be targeted more widely than hospital care settings alone.

Fine-mapping host genetic variation underlying outcomes to Mycobacterium bovis infection in dairy cows.

BACKGROUND: Susceptibility to Mycobacterium bovis infection in cattle is governed in part by host genetics. However, cattle diagnosed as infected with M. bovis display varying signs of pathology. The variation in host response to infection could represent a continuum since time of exposure or distinct outcomes due to differing pathogen handling. The relationships between host genetics and variation in host response and pathological sequelae following M. bovis infection were explored by genotyping 1966 Holstein-Friesian dairy cows at 538,231 SNPs with three distinct phenotypes. These were: single intradermal cervical comparative tuberculin (SICCT) test positives with visible lesions (VLs), SICCT-positives with undetected visible lesions (NVLs) and matched controls SICCT-negative on multiple occasions. RESULTS: Regional heritability mapping identified three loci associated with the NVL phenotype on chromosomes 17, 22 and 23, distinct to the region on chromosome 13 associated with the VL phenotype. The region on chromosome 23 was at genome-wide significance and candidate genes overlapping the mapped window included members of the bovine leukocyte antigen class IIb region, a complex known for its role in immunity and disease resistance. Chromosome heritability analysis attributed variance to six and thirteen chromosomes for the VL and NVL phenotypes, respectively, and four of these chromosomes were found to explain a proportion of the phenotypic variation for both the VL and NVL phenotype. By grouping the M. bovis outcomes (VLs and NVLs) variance was attributed to nine chromosomes. When contrasting the two M. bovis infection outcomes (VLs vs NVLs) nine chromosomes were found to harbour heritable variation. Regardless of the case phenotype under investigation, chromosome heritability did not exceed 8% indicating that the genetic control of bTB resistance consists of variants of small to moderate effect situated across many chromosomes of the bovine genome. CONCLUSIONS: These findings suggest the host genetics of M. bovis infection outcomes is governed by distinct and overlapping genetic variants. Thus, variation in the pathology of M. bovis infected cattle may be partly genetically determined and indicative of different host responses or pathogen handling. There may be at least three distinct outcomes following M. bovis exposure in dairy cattle: resistance to infection, infection resulting in pathology or no detectable pathology.

The Scottish enhanced Staphylococcus aureus bacteraemia surveillance programme: the first 18 months of data in children.

BACKGROUND: National enhanced surveillance of Staphylococcus aureus bacteraemia (SAB) commenced on 1st October 2014 to gain a more in-depth understanding of the epidemiology of SAB in Scotland. Children under 16 years of age were analysed separately from adults because previous studies had demonstrated epidemiological differences. AIM: To identify risk factors and patient populations at greatest risk to enable the development of focused improvement plans. METHODS: All National Health Service (NHS) boards within NHS Scotland take part in the mandatory enhanced surveillance, with data collected by trained data collectors using nationally agreed definitions. FINDINGS: Analysis of the first 18 months of data showed that hospital-acquired SAB was mostly associated with neonates with device risk factors, whereas community-associated SAB was found in older children who had few, if any, risk factors and most presented with a bone or joint infection. CONCLUSION: The enhanced SAB data highlighted the difference in risk factors and entry points for the acquisition of SAB within the paediatric population.

Surgical removal of a choroid plexus oncocytoma in an adult cat.

An 11-year-old male castrated domestic shorthair cat presented with left central vestibular dysfunction. Magnetic resonance imaging of the brain revealed a large, extra-parenchymal, strongly contrast-enhancing mass at the level of the left cerebellopontine angle and compressing the cerebellum and brainstem. The mass was surgically excised via left rostral and sub-tentorial craniectomies and histopathology revealed an epithelial neoplasm composed of anastomosing cords of neoplastic cells that contained large amounts of finely granular hypereosinophilic cytoplasm and round nuclei. The cytoplasmic granules were variably positive with periodic acid-Schiff and modified Gomori trichrome. Immunohistochemical staining with anti-cytokeratin AE1/AE3 was diffusely positive. Electron microscopy revealed neoplastic cells that were full of electron-dense organelles consistent with mitochondria. This is the first case of a choroid plexus oncocytoma in the central nervous system of any domestic animal species and highlights the role of successful surgical intervention in extra-parenchymal neoplasia in the central nervous system.

Hydrocephalus secondary to obstruction of the lateral apertures in two dogs.

BACKGROUND: Traditionally, hydrocephalus is divided into communicating or non-communicating (obstructive) based on the identification of a blockage of cerebrospinal fluid (CSF) flow through the ventricular system. Hydrocephalus ex vacuo refers to ventricular enlargement as a consequence of neuroparenchymal loss. Hydrocephalus related to obstruction of the lateral apertures of the fourth ventricles has rarely been described. CASE REPORT: The clinicopathologic findings in two dogs with hydrocephalus secondary to obstruction of the lateral apertures of the fourth ventricle are reported. Signs were associated with a caudal cervical spinal cord lesion in one dog and a caudal brain stem lesion in the other dog. Magnetic resonance imaging (MRI) disclosed dilation of the ventricular system, including the lateral recesses of the fourth ventricle. In one dog, postmortem ventriculography confirmed obstruction of the lateral apertures. Microscopic changes were identified in the choroid plexus in both dogs, yet a definitive cause of the obstructions was not identified. The MRI findings in both dogs are similar to membranous occlusion of the lateral and median apertures in human patients. CONCLUSION: MRI detection of dilation of the entire ventricular system in the absence of an identifiable cause should prompt consideration of an obstruction of the lateral apertures. In future cases, therapeutic interventions aimed at re-establishing CSF flow or ventriculoperitoneal catheterisation should be considered.

Late production of CXCL8 in ruminant oro-nasal turbinate cells in response to Chlamydia abortus infection.

Chlamydia abortus is an obligate intracellular bacterium that is an important cause of ovine abortion worldwide. There are reports of abortions in cattle, but these are very rare compared to the reported incidence in sheep. The bacterium is transmitted oro-nasally and can establish a sub-clinical infection until pregnancy, when it can invade the placenta and induce an inflammatory cascade leading to placentitis and abortion. Early host-pathogen interactions could explain differential pathogenesis and subsequent disease outcome in ruminant species. In this study, we assessed the ability of sheep and cattle oro-nasal turbinate cells to sense and respond to C. abortus infection. The cells expressed toll like receptor (TLR) 2, TLR4, nucleotide oligomerization domain (NOD) 1 and NOD-like receptor pyrin domain containing 3 (NLRP3) mRNA. In response to C. abortus infection, both ovine and bovine turbinate cells produce CXCL8 mRNA and protein late in the bacterial developmental cycle, but do not produce IL-1ß or TNF-α. The UV-inactivated bacteria did not elicit a CXCL8 response, suggesting that intracellular multiplication of the bacteria is important for activating the signalling pathways. The production of innate immune cytokines from cattle and sheep turbinate cells in response to C. abortus infection was found to be largely similar.

Magnetic resonance imaging and computed tomography findings of Dyke-Davidoff-Masson-like syndrome in a cat.

CASE REPORT: A 3.5-year-old spayed female Domestic Shorthair cat was evaluated for new onset seizures and lateralising signs indicative of a lesion in the right prosencephalon. Magnetic resonance imaging and computed tomography of the head revealed hypoplasia of the right cerebral hemisphere and changes in the overlying cranium, including hyperostosis and expansion of the diploic space, resulting in an increased pneumatisation of the rostral bones of the cranium. A congenital injury to the cerebral hemisphere and secondary changes of the cranium in response to the decreased brain parenchyma was presumed. Similar changes have been previously recognised in human patients with unilateral anomalies of the cerebral hemispheres, termed Dyke-Davidoff-Masson syndrome (DDMS). CONCLUSION: The case presented is the first clinical and imaging description of a cat with a syndrome that closely resembles DDMS in humans. The description of the syndrome allows recognition of an additional differential for seizures in a young patient and informs the clinician of the imaging characteristics of the cranium seen with early loss of brain parenchyma.

Clinical, magnetic resonance imaging, and histopathologic findings in 6 dogs with surgically resected extraparenchymal spinal cord hematomas.

BACKGROUND: Extraparenchymal spinal cord hematoma has been described in veterinary medicine in association with neoplasia, intervertebral disk disease, and snake envenomation. There are rare reports of spontaneous extraparenchymal spinal cord hematoma formation with no known cause in human medicine. Multiple cases of spontaneous extraparenchymal spinal cord hematoma have not been described previously in veterinary medicine. OBJECTIVES: To describe the signalment, clinical findings, magnetic resonance imaging (MRI) features, and surgical outcomes in histopathologically confirmed extraparenchymal spinal cord hematomas in dogs with no identified underlying etiology. ANIMALS: Six dogs had MRI of the spinal cord, decompressive spinal surgery, and histopathologic confirmation of extraparenchymal spinal cord hematoma not associated with an underlying cause. METHODS: Multi-institutional retrospective study. RESULTS: Six patients had spontaneous extraparenchymal spinal cord hematoma formation. MRI showed normal signal within the spinal cord parenchyma in all patients. All hematomas had T2-weighted hyperintensity and the majority (5/6) had no contrast enhancement. All dogs underwent surgical decompression and most patients (5/6) returned to normal or near normal neurologic function postoperatively. Follow-up of the patients (ranging between 921 and 1,446 days) showed no progression of neurologic clinical signs or any conditions associated with increased bleeding tendency. CONCLUSIONS AND CLINICAL IMPORTANCE: Before surgery and histopathology confirming extraparenchymal hematoma, the primary differential in most cases was neoplasia, based on the MRI findings. This retrospective study reminds clinicians of the importance of the combination of advanced imaging combined with histopathologic diagnosis. The prognosis for spontaneous spinal cord extraparenchymal hematoma with surgical decompression appears to be favorable in most cases.

Awareness and implementation of the regional animal welfare strategy for the Americas: a questionnaire.

The World Organisation for Animal Health (OIE) is the global standard-setting organisation for animal health and these standards are references for the World Trade Organization legal framework. In 2002, noting the relationship between animal health and welfare, the OIE accepted the mandate to develop animal welfare standards. These standards were subsequently adopted by Member Countries and have been included in the TerrestrialAnimal Health Code and the Aquatic Animal Health Code. The implementation of the OIE standards by Member Countries is continually promoted. National OIE Delegates are encouraged to nominate National Focal Points for key topics, including animal welfare. In 2012, the OIE Regional Commission of the Americas adopted a Regional Animal Welfare Strategy (Regional Strategy) to promote a coordinated approach to the implementation of the OIE animal welfare standards by the 29 Member Countries in the region. In February 2015, the OIE Regional Representation for the Americas distributed a questionnaire to determine the level of awareness and implementation of the Regional Strategy. This paper presents the results of the questionnaire. With a few exceptions, veterinary officials and stakeholders are only just becoming aware of the strategy and implementation is at an early stage. To promote the implementation of the Regional Strategy, it will be.necessary to continue building the capacity of the national Veterinary Services, strengthening public-private partnerships, modernising legislation and promoting veterinary involvement in animal welfare. Through the implementation of the Regional Strategy, the OIE will provide support to countries in establishing animal welfare standards, in line with government priorities and consumer concerns.

Severity of spinal cord dysfunction and pain associated with hydrated nucleus pulposus extrusion in dogs.

OBJECTIVE: To identify the severity of neurological deficits, presence of signs of cervical pain, and the site of intervertebral disc space extrusion in 21 dogs diagnosed via magnetic resonance imaging (MRI) with a hydrated nucleus pulposus extrusion (HNPE) and compare those findings to dogs with other compressive cervical myelopathies. METHODS: Medical records and MRI findings were reviewed in dogs that were presented to two veterinary hospitals between 2006 and 2012 and subsequently diagnosed by MRI to have a HNPE (n = 21) or other compressive cervical myelopathies originating from the intervertebral disc (n = 174). Information obtained included signalment, severity of neurological deficits, presence of signs of neck pain, and site of HNPE. The severity of clinical neurological spinal cord dysfunction was determined for each dog in both groups using the Frankel scoring system (0-4). The MRI were reviewed for confirmation of diagnosis and site of HNPE. An ANOVA was used to compare age between groups and a Mann-Whitney test for pairwise comparisons of the Frankel score between groups. Values of p <0.05 were considered statistically significant. RESULTS: Significantly more severe Frankel scores and less severe signs of cervical pain detected on palpation were observed in dogs with a HNPE as compared to dogs with other compressive myelopathies. The sites of HNPE were C3-C4 (8/21), C4-C5 (12/21), and C5-C6 (1/21). CLINICAL SIGNIFICANCE: Dogs affected with HNPE have more severe clinical neurological deficits and less severe signs of cervical pain as compared to dogs with other compressive cervical myelopathies.

Late-onset cerebellar abiotrophy in a Labrador Retriever.

CASE REPORT: A 5-year-old female spayed Labrador Retriever was examined for a hindlimb gait abnormality. Initial neurological examination was consistent with vestibular dysfunction. Over the course of 1 year, signs progressed to reflect cerebellar ataxia, vertical nystagmus and delayed postural reactions in all limbs. At the initial examination, subjective evaluation of magnetic resonance imaging scan of the brain was considered normal. Repeat imaging at 1 year after initial examination revealed a reduction in the size of the cerebellum. Retrospectively, the size of the cerebellum on the initial MRI was small when assessed using an objective measurement algorithm. Postmortem histopathological evaluation of the brain showed diffuse degeneration of Purkinje cell neurones with secondary granule cell loss in the cerebellum, in addition to pigment inclusions in brainstem neurones. CONCLUSION: The clinical history and clinicopathological data are consistent with late-onset cerebellar abiotrophy, which has not previously been described in this breed.