Investigating the potential of the anti-epileptic drug imepitoin as a treatment for co-morbid anxiety in dogs with idiopathic epilepsy

Abstract Background Behavioural changes associated with idiopathic epilepsy (IE) have been identified in dogs, with fear and anxiety-related problems seen in both drug-naïve dogs and dogs treated with anti-epileptic drugs (AEDs). Treating anxiety-related behaviour in dogs with IE may be challenging, as seizures are a contraindication for many conventional anxiolytic drugs. In addition, many dogs with IE are already treated with AEDs to reduce their seizure frequency, which may have negative effects if used in polytherapy. Imepitoin is low-affinity partial agonist at the benzodiazepine (BDZ) site of the GABAA receptor, and has been demonstrated to have both anticonvulsant and anxiolytic effects in laboratory rodents. Imepitoin has been developed for the treatment of IE in dogs, with demonstrated anticonvulsant effects and high tolerability and safety. To date, imepitoin’s potential to reduce anxiety in dogs with IE has not been investigated. An online survey was conducted to investigate the effect of imepitoin on fear and anxiety-related behaviours in dogs with IE. Eighty-five valid responses were received from owners of dogs with IE currently treated with imepitoin. Anxiety-related behaviour was quantified before and during imepitoin treatment using a validated questionnaire tool (C-BARQ). Results No differences were observed in the five fear/anxiety-related measures between the two time periods (before vs. during treatment) for dog directed fear, stranger directed fear, non-social fear, pain sensitivity and separation related behaviour. A median 45% reduction in seizure frequency/month was observed following imepitoin treatment; however, imepitoin did not appear effective in reducing seizure frequency in a minority of cases. Polyphagia was the most common chronic side effect, and more side effects were reported in polytherapy cases. Conclusions Imepitoin does not appear to improve anxiety-related behaviour in dogs with IE treated with this medication for its anti-epileptic effects. Investigating the effects of imepitoin upon the behaviour of dogs with recognised behavioural anxiety-related problems (e.g. specific fears and phobias, separation related behaviours), in both healthy dogs and dogs with epilepsy is required to further explore any potential anxiolytic effects of this medication

What can we learn from the hair of the dog? Complex effects of endogenous and exogenous stressors on canine hair cortisol

Hair is an emerging biological matrix in which to measure chronic HPA axis activity, offering a longer term view into an animal’s life. We explored effects of exogenous (e.g. lifestyle, medications, social environment) and endogenous (e.g. disease, behaviour) stressors on hair cortisol concentration (HCC) in a population of Border Collies (BCs). Owners of BCs were recruited and reported their dog’s lifestyle, clinical history, anxiety-related behaviour, and collected a white hair sample from their dog’s dorsal neck region. HCC was determined using established methods with a commercial cortisol assay kit. Samples from 135 BCs were analysed, with 91 healthy controls and 44 diagnosed with epilepsy as a model disease. Factors associated with higher HCC included psychosocial stressors (living with three or more other dogs) and lifestyle (engaging in competitive flyball); while factors associated with lower HCC included anxiety (stranger-directed and non-social), health (epilepsy diagnosis, with number of seizures to date negatively correlated with HCC) and medication (certain anti-epileptic drugs were associated with elevated or reduced HCC). These novel results highlight the potential of chronic stress with frequent or persisting HPA-axis hyperactivity leading to a state of hypocortisolism, and the need to consider stressor recency and recurrence when interpreting HCC data

Impact of canine epilepsy on judgement and attention biases

Idiopathic epilepsy (IE) is the most common chronic neurological condition in dogs, characterised by recurrent seizure activity and associated with negative behavioural and cognitive changes. We hypothesised that IE would negatively impact putative affective state, with dogs with IE exhibiting a more pessimistic judgement bias and more negative attention bias than controls. Dogs were tested in a previously-validated spatial judgement bias task, and a novel auditory attention bias task testing attention to sounds with different valence or salience (neutral, novel pre-habituated, threatening). Sixty-eight dogs (IE = 33, Control = 35) were tested, of which n = 37 acquired the spatial discrimination and responses to judgement bias probes were tested (IE = 19, Control = 18), and n = 36 were tested for responses to sounds (IE = 20, Control = 16). Study groups did not significantly differ by age, sex, breed or neuter-status (p > 0.05). Main effects of study group were not significant in judgement bias (F1,102 = 0.20, p = 0.658) or attention bias tasks (F3,102 = 1.64, p = 0.184). In contrast with our hypotheses, there was no evidence that IE altered cognitive biases in this study population; however, dogs with IE were significantly more likely to be unable to learn the spatial discrimination task (p = 0.019), which may reflect IE-related cognitive deficits. Developing methods to test affective state without excluding cognitively impaired individuals is a future challenge for animal welfare science

A Formal Framework for Modeling Trust and Reputation in Collective Adaptive Systems

Trust and reputation models for distributed, collaborative systems have been studied and applied in several domains, in order to stimulate cooperation while preventing selfish and malicious behaviors. Nonetheless, such models have received less attention in the process of specifying and analyzing formally the functionalities of the systems mentioned above. The objective of this paper is to define a process algebraic framework for the modeling of systems that use (i) trust and reputation to govern the interactions among nodes, and (ii) communication models characterized by a high level of adaptiveness and flexibility. Hence, we propose a formalism for verifying, through model checking techniques, the robustness of these systems with respect to the typical attacks conducted against webs of trust.Comment: In Proceedings FORECAST 2016, arXiv:1607.0200

GlycoDigest: a tool for the targeted use of exoglycosidase digestions in glycan structure determination

Summary: Sequencing oligosaccharides by exoglycosidases, either sequentially or in an array format, is a powerful tool to unambiguously determine the structure of complex N- and O-link glycans. Here, we introduce GlycoDigest, a tool that simulates exoglycosidase digestion, based on controlled rules acquired from expert knowledge and experimental evidence available in GlycoBase. The tool allows the targeted design of glycosidase enzyme mixtures by allowing researchers to model the action of exoglycosidases, thereby validating and improving the efficiency and accuracy of glycan analysis. Availability and implementation: http://www.glycodigest.org. Contact: [email protected] or [email protected]

Inter-observer agreement of canine and feline paroxysmal event semiology and classification by veterinary neurology specialists and non-specialists

Background: Advances in mobile technology mean vets are now commonly presented with videos of paroxysmal events by clients, but the consistency of the interpretation of these videos has not been investigated. The objective of this study was to investigate the level of agreement between vets (both neurology specialists and non-specialists) on the description and classification of videos depicting paroxysmal events, without knowing any results of diagnostic workup. An online questionnaire study was conducted, where participants watched 100 videos of dogs and cats exhibiting paroxysmal events and answered questions regarding: epileptic seizure presence (yes/ no), seizure type, consciousness status, and the presence of motor, autonomic and neurobehavioural signs. Agreement statistics (percentage agreement and kappa) calculated for each variable, with prevalence indices calculated to aid their interpretation. Results: Only a fair level of agreement (kappa = 0.40) was found for epileptic seizure presence. Overall agreement of seizure type was moderate (kappa = 0.44), with primary generalised seizures showing the highest level of agreement (kappa = 0.60), and focal the lowest (kappa = 0.31). Fair agreement was found for consciousness status and the presence of autonomic signs (kappa = 0.21-0.40), but poor agreement for neurobehavioral signs (kappa = 0.16). Agreement for motor signs ranged from poor (kappa = <= 0.20) to moderate (kappa = 0.41-0.60). Differences between specialists and non-specialists were identified. Conclusions: The relatively low levels of agreement described here highlight the need for further discussions between neurology experts regarding classifying and describing epileptic seizures, and additional training of non-specialists to facilitate accurate diagnosis. There is a need for diagnostic tools (e.g. electroencephalogram) able to differentiate between epileptic and non-epileptic paroxysms