Physiological reactivity to spontaneously occurring seizure activity in dogs with epilepsy and their carers

There is a complex bidirectional relationship between stress and epilepsy. Stressful stimuli and subsequent cortisol release act as a trigger for seizure activity in some individuals with epilepsy, and seizure activity itself may act as a stressor to the affected individual. Epilepsy is the most common chronic neurological condition in domestic dogs and requires chronic management by their human carers, impacting upon the quality of life of both dog and carer. Seizures occur unpredictably and may be stressful for carers to witness and manage. In the present study we investigated the role of seizure activity as a stressor, measuring the effect of spontaneously occurring seizure activity in dogs with epilepsy upon their own cortisol levels and that of their carers. Furthermore, we tested whether individual differences in HPA reactivity were associated with owner personality characteristics and the quality of the dog carer relationship. Saliva samples were obtained from sixteen dog carer dyads in the home setting 20 and 40 minute post-seizure, and at time-matched points on the following (non-seizure) day. Significant differences in cortisol levels were found in dogs at 40 minute post-seizure (265.1% increase), and at 20 minute post-seizure in their carers (40.5% increase). No associations were found between cortisol reactivity and the strength of the dog-carer bond. Carers with higher neuroticism scores exhibited higher cortisol levels at both post-seizure sampling points. As there was a gender bias in the carer sample (15/16 were female), and there are known sex differences in cortisol reactivity in response to psychological stress, the conclusions of this study may be limited to female carers. These findings are the first to objectively demonstrate the acutely stressful effects of seizures in dogs with epilepsy and their carers

Epilepsy beyond seizures: a review of the impact of epilepsy and its comorbidities on health-related quality of life in dogs

Epilepsy is one of the most common chronic neurological conditions in the dog, estimated to affect 0.6 to 0.75 per cent of dogs. Owners of dogs with epilepsy have previously indicated that their dog's quality of life (QoL) is of greatest importance to them above seizure frequency; however, much of the research into canine epilepsy to date has focussed on seizure frequency, and how to reduce it via antiepileptic drug treatment. In people, the impact of epilepsy upon QoL has been widely studied, exploring not only its impact on physical health, but also the psychological health and cognitive capabilities of affected individuals. This paper reviews the existing literature on canine epilepsy, identifies potential threats to QoL, and draws parallels from human epilepsy research. We suggest that canine epilepsy poses threats to both quality and quantity of life, with treatment interventions posing a fine balance of potential benefits and harms to the patient. At present, little is known about the neurobehavioural, emotional and cognitive effects of epilepsy upon affected dogs. Further studies are needed to establish the extent to which unknown QoL-inhibiting comorbidities exist in the dog, in order to avoid their undertreatment, and to objectively quantify the effects of epilepsy on canine QoL

Clinical reasoning in feline epilepsy: Which combination of clinical information is useful?

We sought to identify the association between clinical risk factors and the diagnosis of idiopathic epilepsy (IE) or structural epilepsy (SE) in cats, using statistical models to identify combinations of discrete parameters from the patient signalment, history and neurological examination findings that could suggest the most likely diagnosis. Data for 138 cats with recurrent seizures were reviewed, of which 110 were valid for inclusion. Seizure aetiology was classified as IE in 57% and SE in 43% of cats. Binomial logistic regression analyses demonstrated that pedigree status, older age at seizure onset (particularly >7 years old), abnormal neurological examinations, and ictal vocalisation were associated with a diagnosis of SE compared to IE, and that ictal salivation was more likely to be associated with a diagnosis of IE than SE. These findings support the importance of considering inter-ictal neurological deficits and seizure history in clinical reasoning

Preliminary assessment of cognitive impairments in canine idiopathic epilepsy

In humans, epilepsy can induce or accelerate cognitive impairment (CI). There is emerging evidence of CI in dogs with idiopathic epilepsy (IE) from recent epidemiological studies. The aim of our study was to assess CI in dogs with IE using two tests of cognitive dysfunction designed for use in a clinical setting. Dogs with IE (n=17) were compared against controls (n=18) in their performance in two tasks; a spatial working memory task and a problem-solving task. In addition, owners completed the Canine Cognitive Dysfunction Rating (CCDR) scale for their dog. The groups did not differ statistically with respect to age and breed. Dogs with IE performed significantly worse than controls on the spatial working memory task (P=0.016), but not on the problem solving task (P=0.683). CCDR scores were significantly higher in the IE group (P=0.016); however, no dogs reach the recommended threshold score for CCD diagnosis. Our preliminary data suggest that dogs with IE exhibit impairments in a spatial working memory task. Further research is required to explore the effect of IE on other cognitive abilities in dogs with a larger sample, characterising the age of onset, nature and progression of any impairments and the impact of anti-epileptic drugs

Early LQT2 Nonsense Mutation Generates N-Terminally Truncated hERG Channels with Altered Gating Properties by the Reinitiation of Translation

Mutations in the human ether-a-go-go-related gene (hERG) result in long QT syndrome type 2 (LQT2). The hERG gene encodes a K+ channel that contributes to the repolarization of the cardiac action potential. We have previously shown that hERG mRNA transcripts that contain premature termination codon mutations are rapidly degraded by nonsense-mediated mRNA decay (NMD). In this study, we identified a LQT2 nonsense mutation, Q81X, which escapes degradation by the reinitiation of translation and generates N-terminally truncated channels. RNA analysis of hERG minigenes revealed equivalent levels of wild-type and Q81X mRNA while the mRNA expressed from minigenes containing the LQT2 frameshift mutation, P141fs+2X, was significantly reduced by NMD. Western blot analysis revealed that Q81X minigenes expressed truncated channels. Q81X channels exhibited decreased tail current levels and increased deactivation kinetics compared to wild-type channels. These results are consistent with the disruption of the N-terminus, which is known to regulate hERG deactivation. Site-specificmutagenesis studies showed that translation of the Q81X transcript is reinitiated atMet124 following premature termination. Q81X co-assembled with hERG to form heteromeric channels that exhibited increased deactivation rates compared to wild-type channels. Mutant channels also generated less outward current and transferred less charge at late phases of repolarization during ventricular action potential clamp. These results provide new mechanistic insight into the prolongation of the QT interval in LQT2 patients. Our findings indicate that the reinitiation of translation may be an important pathogenic mechanism in patients with nonsense and frameshift LQT2 mutations near the 5′ end of the hERG gene

Visitors’ learning for environmental sustainability: Testing short- and long-term impacts of wildlife tourism experiences using structural equation modelling

Wildlife tourism experiences have the potential to positively impact tourists' awareness, appreciation and actions in relation to the specific wildlife they encounter and the environment in general. This paper investigates the extent of such impact across multiple sites, and uses Structural Equation Modelling to identify factors that best predict positive long-term learning and environmental behaviour change outcomes. Three sets of variables were measured - visitors' entering attributes (including pre-visit environmental orientation and motivation for the visit), salient aspects of the experience, and short- and long-term learning and environmental behaviour change outcomes. Although attributes such as pre-visit commitment and motivation to learn were among the best predictors of the long-term impact of the experience, there was evidence that aspects of the experience were also important. In particular, reflective engagement which involved cognitive and affective processing of the experience was found to be associated with short- and long-term environmental learning outcomes. The implications for wildlife tourism managers are discussed. (C) 2010 Elsevier Ltd. All rights reserved

Institutional affiliation and the role of venture capital: Evidence from initial public offerings in Japan

The presence of venture capital in the ownership structure of U.S. firms going public has been associated with both improved long-term performance and lower underpricing at the time of the IPOs. In Japan, we find the long-run performance of venture capital-backed IPOs to be no better than that of other IPOs, with the exception of firms backed by foreign-owned or independent venture capitalists. Many of the major venture capital firms in Japan are subsidiaries of securities firms that may face a conflict of interest when underwriting the venture capital-backed issue. When venture capital holdings are broken down by their institutional affiliation, we find that firms with venture backing from securities company subsidiaries do not perform significantly worse over a three-year time horizon than other IPOs. On the other hand, we find that IPOs in which the lead venture capitalist is also the lead underwriter have higher initial returns than other venture capital-backed IPOs. The latter result suggests that conflicts of interest influence the initial pricing, but not the long-term performance, of initial public offerings in Japan