Rigorous science demands support of transgender scientists.

To build a just, equitable, and diverse academy, scientists and institutions must address systemic barriers that sex and gender minorities face. This Commentary summarizes (1) critical context informing the contemporary oppression of transgender people, (2) how this shapes extant research on sex and gender, and (3) actions to build an inclusive and rigorous academy for all.

Clinical features of idiopathic inflammatory polymyopathy in the Hungarian Vizsla.

BACKGROUND: A retrospective study of the clinicopathological features of presumed and confirmed cases of idiopathic inflammatory polymyopathy in the Hungarian Vizsla dog and guidelines for breeding. RESULTS: 369 medical records were reviewed (1992-2013) and 77 Hungarian Vizslas were identified with a case history consistent with idiopathic inflammatory polymyopathy. Inclusion criteria were: group 1 (confirmed diagnosis); histopathology and clinical findings compatible with an inflammatory polymyopathy and group 2 (probable diagnosis); clinical findings compatible with a polymyopathy including dysphagia, sialorrhea, temporal muscle atrophy, elevated serum creatine kinase (CK) activity, and sufficient clinical history to suggest that other neuromuscular disorders could be ruled out. Some group 2 dogs had muscle biopsy, which suggested muscle disease but did not reveal an inflammatory process. The mean age of onset was 2.4 years; male dogs were slightly overrepresented. Common presenting signs were dysphagia, sialorrhea, masticatory muscle atrophy, and regurgitation. Common muscle histopathological findings included degenerative and regenerative changes, with multifocal mononuclear cell infiltration with lymphoplasmacytic myositis of variable severity. A positive response to immunosuppressive treatment supported an immune-mediated aetiology. The mean age at death and survival time were 6.4 and 3.9 years, respectively. Recurrence of clinical signs and aspiration pneumonia were common reasons for euthanasia. CONCLUSIONS: Diagnosis of Vizsla idiopathic inflammatory polymyopathy can be challenging due to lack of specific tests, however the presence of dysphagia, regurgitation and masticatory muscle atrophy in this breed with negative serological tests for masticatory muscle myositis and myasthenia gravis, along with muscle biopsies suggesting an inflammatory process, support the diagnosis. However, there is an urgent need for a more specific diagnostic test. The average of inbreeding coefficient (CoI) of 16.3% suggests an increased expression of a Dog Leukocyte Antigen Class II haplotype, leading to an increased disease risk. The prognosis remains guarded, as treatment can only manage the disease. Recurrence of clinical signs and perceived poor quality of life are the most common reasons for humane euthanasia.

International veterinary epilepsy task force consensus proposal: outcome of therapeutic interventions in canine and feline epilepsy.

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered.

International veterinary epilepsy task force consensus report on epilepsy definition, classification and terminology in companion animals.

Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, "a common language", for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies.In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders.

International veterinary epilepsy task force consensus proposal: diagnostic approach to epilepsy in dogs.

This article outlines the consensus proposal on diagnosis of epilepsy in dogs by the International Veterinary Epilepsy Task Force. The aim of this consensus proposal is to improve consistency in the diagnosis of epilepsy in the clinical and research settings. The diagnostic approach to the patient presenting with a history of suspected epileptic seizures incorporates two fundamental steps: to establish if the events the animal is demonstrating truly represent epileptic seizures and if so, to identify their underlying cause. Differentiation of epileptic seizures from other non-epileptic episodic paroxysmal events can be challenging. Criteria that can be used to make this differentiation are presented in detail and discussed. Criteria for the diagnosis of idiopathic epilepsy (IE) are described in a three-tier system. Tier I confidence level for the diagnosis of IE is based on a history of two or more unprovoked epileptic seizures occurring at least 24 h apart, age at epileptic seizure onset of between six months and six years, unremarkable inter-ictal physical and neurological examination, and no significant abnormalities on minimum data base blood tests and urinalysis. Tier II confidence level for the diagnosis of IE is based on the factors listed in tier I and unremarkable fasting and post-prandial bile acids, magnetic resonance imaging (MRI) of the brain (based on an epilepsy-specific brain MRI protocol) and cerebrospinal fluid (CSF) analysis. Tier III confidence level for the diagnosis of IE is based on the factors listed in tier I and II and identification of electroencephalographic abnormalities characteristic for seizure disorders. The authors recommend performing MRI of the brain and routine CSF analysis, after exclusion of reactive seizures, in dogs with age at epileptic seizure onset <6 months or >6 years, inter-ictal neurological abnormalities consistent with intracranial neurolocalisation, status epilepticus or cluster seizure at epileptic seizure onset, or a previous presumptive diagnosis of IE and drug-resistance with a single antiepileptic drug titrated to the highest tolerable dose.This consensus article represents the basis for a more standardised diagnostic approach to the seizure patient. These recommendations will evolve over time with advances in neuroimaging, electroencephalography, and molecular genetics of canine epilepsy.

International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine epilepsy in Europe.

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors' experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible.

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol.

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature.There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6-7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed.

International veterinary epilepsy task force recommendations for systematic sampling and processing of brains from epileptic dogs and cats.

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals.The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures.Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements.The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations.

EARLY POSTOPERATIVE MAGNETIC RESONANCE IMAGING FINDINGS IN FIVE DOGS WITH CONFIRMED AND SUSPECTED BRAIN TUMORS.

Early postoperative neuroimaging has been performed in people for over 20 years to detect residual brain tumor tissue and surgical complications. The purpose of this retrospective study was to describe characteristics observed using early postoperative magnetic resonance imaging in a group of dogs undergoing craniotomy for brain tumor removal. Two independent observers came to a consensus opinion for presence/absence of the following MRI characteristics: residual tumor tissue; hemorrhage and ischemic lesions; abnormal enhancement (including the margins of the resection cavity, choroid plexus, meninges) and signal intensity changes on diffusion-weighted imaging. Five dogs were included in the study, having had preoperative and early postoperative MRI acquired within four days after surgery. The most commonly observed characteristics were abnormal meningeal enhancement, linear enhancement at margins of the resection cavity, hemorrhage, and a thin rim of hyperintensity surrounding the resection cavity on diffusion-weighted imaging. Residual tumor tissue was detected in one case of an enhancing tumor and in one case of a tumor containing areas of hemorrhage preoperatively. Residual tumor tissue was suspected but could not be confirmed when tumors were nonenhancing. Findings supported the use of early postoperative MRI as a method for detecting residual brain tumor tissue in dogs.

Magnetic resonance imaging appearance of hypertensive encephalopathy in a dog.

A 16-year-old female spayed English Staffordshire terrier was presented for evaluation of a 10-month history of intermittent myoclonic episodes, and a one weeks history of short episodes of altered mentation, ataxia and collapse. Magnetic resonance imaging identified subcortical oedema, predominately in the parietal and temporal lobes and multiple cerebral microbleeds. Serum biochemistry, indirect blood pressure measurements and magnetic resonance imaging abnormalities were consistent with hypertensive encephalopathy secondary to chronic kidney disease.

Dynamic contrast enhanced high field magnetic resonance imaging for canine primary intracranial neoplasia.

Introduction: Distinguishing meningiomas from other intracranial neoplasms is clinically relevant as the prognostic and therapeutic implications differ greatly and influence clinical decision making. Dynamic contrast-enhanced MRI (DCE-MRI) is an imaging technique that assists with characterisation of physiologic alterations such as blood flow and tissue vascular permeability. Quantitative pharmacokinetic analysis utilising DCE-MRI has not been studied in canine neuro-oncology. Methods: A retrospective study was performed in canine patients that underwent DCE-MRI with an imaging diagnosis of an intracranial meningioma and surgery for histopathological diagnosis. Kinetic parameters Ktrans and cerebral blood flow were measured and compared to assess whether differences could be identified between meningiomas and other intracranial neoplasms. Results: Six dogs with meningiomas and 3 dogs with other intracranial neoplasms were included for statistical analysis. Cerebral blood flow values were found to be statistically higher within meningiomas compared to other intracranial neoplasms. Ktrans values were higher within meningiomas than in other types of intracranial tumours, however this difference did not reach statistical significance. Discussion: Based on the results of this study cerebral blood flow measurement can be utilised to differentiate canine intracranial meningiomas from other similar appearing intracranial tumours.

Miniature fluorescence sensor for quantitative detection of brain tumour.

Fluorescence-guided surgery has emerged as a vital tool for tumour resection procedures. As well as intraoperative tumour visualisation, 5-ALA-induced PpIX provides an avenue for quantitative tumour identification based on ratiometric fluorescence measurement. To this end, fluorescence imaging and fibre-based probes have enabled more precise demarcation between the cancerous and healthy tissues. These sensing approaches, which rely on collecting the fluorescence light from the tumour resection site and its "remote" spectral sensing, introduce challenges associated with optical losses. In this work, we demonstrate the viability of tumour detection at the resection site using a miniature fluorescence measurement system. Unlike the current bulky systems, which necessitate remote measurement, we have adopted a millimetre-sized spectral sensor chip for quantitative fluorescence measurements. A reliable measurement at the resection site requires a stable optical window between the tissue and the optoelectronic system. This is achieved using an antifouling diamond window, which provides stable optical transparency. The system achieved a sensitivity of 92.3% and specificity of 98.3% in detecting a surrogate tumour at a resolution of 1 × 1 mm2. As well as addressing losses associated with collecting and coupling fluorescence light in the current 'remote' sensing approaches, the small size of the system introduced in this work paves the way for its direct integration with the tumour resection tools with the aim of more accurate interoperative tumour identification.

Case report: A case of tetanus in a dog: cranial nerve involvement and imaging findings.

An 11 years old male Labrador cross presented with unilateral vestibular signs, ipsilateral facial paresis, moderate obtundation, ptyalism, and paraparesis. MRI of the brain revealed diffuse, multifocal T2/FLAIR hyperintense changes throughout various regions of the brain including the medulla, midbrain, pons, thalamus and right cerebral hemisphere with mild multifocal contrast enhancement. The patient progressed to trismus with generalized increased extensor tone and risus sardonicus. A diagnosis of generalized tetanus was made and the patient was started on antibiotics, skeletal muscle relaxants and tetanus antitoxin and made a full recovery. To the best of the authors' knowledge, this is the first reported case of canine tetanus in which the presenting signs involved cranial nerve dysfunction as well as the first report describing MRI changes in canine tetanus within the central nervous system.

Case report: Atlantoaxial instability and subluxation in a dog with Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome is a rare, heritable connective tissue disorder characterized by soft, hyperextensible skin, joint hypermobility, and tissue fragility, the severity of which can range from mild to severe. A 9-month-old male entire miniature Dachshund was presented following peracute tetraparesis. Neurological examination was suggestive of intracranial vestibular disease or high cervical myelopathy. MRI revealed atlantoaxial instability and subluxation, resulting in marked spinal cord compression at C1-C2, which was surgically stabilized. On discharge from the hospital, skin fragility was noted as the result of skin tearing during tape removal. A piece of full-thickness antebrachial skin was submitted for histopathology which showed changes consistent with Ehlers-Danlos syndrome. This case report describes the first case of atlantoaxial instability and subluxation in a dog as the result of a confirmed underlying collagenopathy.

Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis.

Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine SOD1 gene. SOD1 was considered a regional candidate gene because mutations in human SOD1 can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of SOD1 in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi, Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS.

Another case of canine amoebic meningoencephalitis--the challenges of reaching a rapid diagnosis.

A case of granulomatous amoebic meningoencephalitis in a previously healthy, mature, apparently immunocompetent dog, with a history of exposure to stagnant water, is reported. The case presented with ataxia and a tendency to fall to the left side. A computed tomography (CT) showed a ring-enhancing lesion within the cerebellum; an examination of cerebrospinal fluid (CSF) revealed nonspecific mixed-cell pleocytosis. Despite antibiotic and anti-inflammatory therapy, clinical signs progressed rapidly to decerebellate rigidity over 4 days, and the dog was euthanased. Significant post-mortem findings were restricted to the brain, with a localised lytic lesion in the deep cerebellar white matter. Histopathological examination of the brain showed focally extensive cavitation of the white matter and communication of the lesion with the fourth ventricle. The affected area contained structures consistent with amoebae and was infiltrated by neutrophils mixed with lower numbers of macrophages, plasma cells and lymphocytes. The amoebae were identified as Balamuthia mandrillaris, based on specific immunofluorescence detection. Amoebic meningoencephalitis should be considered in dogs with evidence of focal cavitary lesions in the brain, particularly in cases with a history of swimming in stagnant water.

Multifocal oligodendroglioma in three dogs.

This report describes the clinical, histopathologic, and imaging findings of multifocal oligodendrogliomas from three canine patients. Clinical history varied but included seizure activity and behavior changes. Neurologic examination abnormalities included ataxia, proprioceptive deficits, cranial nerve deficits, and changes in mentation. MRI in one patient revealed multifocal brain lesions; however, the MRI was normal in another one of the patients. Histopathologic evaluation identified multifocal neoplastic infiltrates in all three patients involving the cerebral cortex, brainstem, and spinal cord, with leptomeningeal extension in two of the three patients. All three patients were euthanized due to progression of their neurologic condition and/or complications due to aspiration pneumonia. Oligodendrogliomas should be considered a differential diagnosis for patients with multifocal brain disease.

Surgical stabilization of an occipitoatlantoaxial malformation in an adult dog.

OBJECTIVE: To report surgical planning, technique, and outcome of stabilization surgery in an adult dog with occipitoatlantoaxial malformation (OAAM). STUDY DESIGN: Clinical report. ANIMAL: A 19-month-old, 25.5 kg, male castrated, Shiba Inu. METHODS: Radiographic and magnetic resonance imaging were used to identify and characterize OAAM. Using a ventral approach to the cranial cervical region 2 cortical bone screws were inserted from the axis into the malformed atlas and occiput. RESULTS: Ambulation was conserved postoperatively. Within 4 weeks, neurologic examination was mostly normal except for decreased proprioception in the right pelvic limb. At 9 months, the dog retained an extended neck posture, but had no neurologic abnormalities. CONCLUSION: OAAM should be considered as a differential diagnosis in an adult dog with cervical myelopathy. Surgical fixation with cortical bone screws using a ventral approach can be successful.

Protein disulphide isomerase is associated with mutant SOD1 in canine degenerative myelopathy.

Canine degenerative myelopathy (DM) is a fatal neurodegenerative disorder prevalent in the canine population. It may represent a unique, naturally occurring disease model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs and association with superoxide dismutase 1 gene (SOD1) mutations. Misfolded SOD1 aggregates and endoplasmic reticulum (ER) stress are major pathophysiological features associated with ALS. Interestingly, an ER foldase, protein disulphide isomerase (PDI) is upregulated during ALS and it co-localizes with SOD1 inclusions in ALS patient tissues. Furthermore, mutations in the gene encoding PDI were recently associated with ALS. Given the genetic similarity between DM and ALS, we investigated whether ER stress and PDI were associated with DM. Protein extracts from spinal cord tissue of DM-affected dogs bearing a SOD1 mutation were examined for ER stress by western blotting. Immunohistochemical staining was also carried out to examine co-localization between endogenous PDI and SOD1 inclusions in spinal cord tissues of dogs affected with DM. PDI and CHOP, the proapoptotic protein induced during ER stress, were significantly upregulated in DM-affected dogs compared with controls. Furthermore, PDI co-localized with intracellular SOD1 aggregates in DM-affected dogs in all motor neurons examined, indicating that PDI may be a cellular defence mechanism against SOD1 misfolding in DM. Our results imply that ER stress is induced in DM-affected dogs; hence, it is a common pathological mechanism associated with both ALS and DM. The possibility that PDI may be a therapeutic target to inhibit SOD1 aggregation in DM dogs is also raised by this study.

Vascular endothelial growth factor expression in canine intracranial meningiomas and association with patient survival.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis and vascular permeability. In human patients with meningiomas, increased VEGF expression is predictive of postsurgical recurrence. The objectives of this study were to evaluate VEGF expression in canine intracranial meningiomas and to determine whether an association between VEGF expression and patient survival existed. METHODOLOGY: Tumor tissue from 17 dogs with histologically confirmed intracranial meningiomas was obtained surgically. All dogs then were treated with radiotherapy. Immunohistochemistry was performed on 5-microm sections of paraffin-embedded tumor tissue with rabbit anti-human VEGF polyclonal antibody. The extent, intensity, and distribution of VEGF staining for each section were assessed with light microscopy by means of a semiquantitative scale. Survival was analyzed by the Kaplan-Meier procedure. Survival rates among groups were compared by log-rank tests with the significance set at P < or = .05. FINDINGS: VEGF expression was detected in all tumors, with >50% of cells staining positively in tissues from 15/17 dogs. Shorter survival times were associated with greater VEGF expression (P = .01). CONCLUSIONS: VEGF expression can be measured in canine intracranial meningiomas and may be associated with poor outcome. SIGNIFICANCE: The extent of VEGF expression in canine intracranial meningiomas may be used as a prognostic marker and suggests a potential future target for therapy.