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 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

Improving the cost-effectiveness of visual devices for the control of Riverine tsetse flies, the major vectors of Human African Trypanosomiasis

Control of the Riverine (Palpalis) group of tsetse flies is normally achieved with stationary artificial devices such as traps or insecticide-treated targets. The efficiency of biconical traps (the standard control device), 161 m black targets and small 25625 cm targets with flanking nets was compared using electrocuting sampling methods. The work was done on Glossina tachinoides and G. palpalis gambiensis (Burkina Faso), G. fuscipes quanzensis (Democratic Republic of Congo), G. f. martinii (Tanzania) and G. f. fuscipes (Kenya). The killing effectiveness (measured as the catch per m2 of cloth) for small targets plus flanking nets is 5.5–15X greater than for 1 m2 targets and 8.6–37.5X greater than for biconical traps. This has important implications for the costs of control of the Riverine group of tsetse vectors of sleeping sickness

How do tsetse recognise their hosts? The role of shape in the responses of tsetse (Glossina fuscipes and G. palpalis) to artificial hosts

Palpalis-group tsetse, particularly the subspecies of Glossina palpalis and G. fuscipes, are the most important transmitters of human African trypanomiasis (HAT), transmitting .95% of cases. Traps and insecticide-treated targets are used to control tsetse but more cost-effective baits might be developed through a better understanding of the fly’s host-seeking behaviour.Electrocuting grids were used to assess the numbers of G. palpalis palpalis and G. fuscipes quanzensis attracted to and landing on square or oblong targets of black cloth varying in size from 0.01 m2 to 1.0 m2. For both species, increasing the size of a square target from 0.01 m2 (dimensions = 0.1 x 0.1 m) to 1.0 m2 (1.0 x 1.0 m) increased the catch ,4x however the numbers of tsetse killed per unit area of target declined with target size suggesting that the most cost efficient targets are not the largest. For G. f. quanzensis, horizontal oblongs, (1 m wide x 0.5 m high) caught, 1.8x more tsetse than vertical ones (0.5 m wide x 1.0 m high) but the opposite applied for G. p. palpalis. Shape preference was consistent over the range of target sizes. For G. p. palpalis square targets caught as many tsetse as the oblong; while the evidence is less strong the same appears to apply to G. f. quanzensis. The results suggest that targets used to control G. p. palpalis and G. f. quanzensis should be square, and that the most cost-effective designs, as judged by the numbers of tsetse caught per area of target, are likely to be in the region of 0.25 x 0.25 m2. The preference of G. p. palpalis for vertical oblongs is unique amongst tsetse species, and it is suggested that this response might be related to its anthropophagic behaviour and hence importance as a vector of HAT

A novel approach to improve cardiac performance: cardiac myosin activators

Decreased systolic function is a central factor in the pathogenesis of heart failure, yet there are no safe medical therapies to improve cardiac function in patients. Currently available inotropes, such as dobutamine and milrinone, increase cardiac contractility at the expense of increased intracellular concentrations of calcium and cAMP, contributing to increased heart rate, hypotension, arrhythmias, and mortality. These adverse effects are inextricably linked to their inotropic mechanism of action. A new class of pharmacologic agents, cardiac myosin activators, directly targets the kinetics of the myosin head. In vitro studies have demonstrated that these agents increase the rate of effective myosin cross-bridge formation, increasing the duration and amount of myocyte contraction, and inhibit non-productive consumption of ATP, potentially improving myocyte energy utilization, with no effect on intracellular calcium or cAMP. Animal models have shown that this novel mechanism increases the systolic ejection time, resulting in improved stroke volume, fractional shortening, and hemodynamics with no effect on myocardial oxygen demand, culminating in significant increases in cardiac efficiency. A first-in-human study in healthy volunteers with the lead cardiac myosin activator, CK-1827452, as well as preliminary results from a study in patients with stable chronic heart failure, have extended these findings to humans, demonstrating significant increases in systolic ejection time, fractional shortening, stroke volume, and cardiac output. These studies suggest that cardiac myosin activators offer the promise of a safe and effective treatment for heart failure. A program of clinical studies are being planned to test whether CK-1827452 will fulfill that promise

Prospects for the development of odour baits to control the tsetse flies Glossina tachinoides and G. palpalis s.l.

Field studies were done of the responses of Glossina palpalis palpalis in Côte d'Ivoire, and G. p. gambiensis and G. tachinoides in Burkina Faso, to odours from humans, cattle and pigs. Responses were measured either by baiting (1.) biconical traps or (2.) electrocuting black targets with natural host odours. The catch of G. tachinoides from traps was significantly enhanced (~5×) by odour from cattle but not humans. In contrast, catches from electric targets showed inconsistent results. For G. p. gambiensis both human and cattle odour increased (>2×) the trap catch significantly but not the catch from electric targets. For G. p. palpalis, odours from pigs and humans increased (~5×) the numbers of tsetse attracted to the vicinity of the odour source but had little effect on landing or trap-entry. For G. tachinoides a blend of POCA (P = 3-n-propylphenol; O = 1-octen-3-ol; C = 4-methylphenol; A = acetone) alone or synthetic cattle odour (acetone, 1-octen-3-ol, 4-methylphenol and 3-n-propylphenol with carbon dioxide) consistently caught more tsetse than natural cattle odour. For G. p. gambiensis, POCA consistently increased catches from both traps and targets. For G. p. palpalis, doses of carbon dioxide similar to those produced by a host resulted in similar increases in attraction. Baiting traps with super-normal (~500 mg/h) doses of acetone also consistently produced significant but slight (~1.6×) increases in catches of male flies. The results suggest that odour-baited traps and insecticide-treated targets could assist the AU-Pan African Tsetse and Trypanosomiasis Eradication Campaign (PATTEC) in its current efforts to monitor and control Palpalis group tsetse in West Africa. For all three species, only ~50% of the flies attracted to the vicinity of the trap were actually caught by it, suggesting that better traps might be developed by an analysis of the visual responses and identification of any semiochemicals involved in short-range interaction

Improving the Cost-Effectiveness of Artificial Visual Baits for Controlling the Tsetse Fly Glossina fuscipes fuscipes

Tsetse flies, which transmit sleeping sickness to humans and nagana to cattle, are commonly controlled by stationary artificial baits consisting of traps or insecticide-treated screens known as targets. In Kenya the use of electrocuting sampling devices showed that the numbers of Glossina fuscipes fuscipes (Newstead) visiting a biconical trap were nearly double those visiting a black target of 100 cm×100 cm. However, only 40% of the males and 21% of the females entered the trap, whereas 71% and 34%, respectively, alighted on the target. The greater number visiting the trap appeared to be due to its being largely blue, rather than being three-dimensional or raised above the ground. Through a series of variations of target design we show that a blue-and-black panel of cloth (0.06 m2) flanked by a panel (0.06 m2) of fine black netting, placed at ground level, would be about ten times more cost-effective than traps or large targets in control campaigns. This finding has important implications for controlling all subspecies of G. fuscipes, which are currently responsible for more than 90% of sleeping sickness cases

From rehabilitation to recovery: protocol for a randomised controlled trial evaluating a goal-based intervention to reduce depression and facilitate participation post-stroke

<p>Abstract</p> <p>Background</p> <p>There is much discourse in healthcare about the importance of client-centred rehabilitation, however in the realm of community-based therapy post-stroke there has been little investigation into the efficacy of goal-directed practice that reflects patients' valued activities. In addition, the effect of active involvement of carers in such a rehabilitation process and their subsequent contribution to functional and emotional recovery post-stroke is unclear. In community based rehabilitation, interventions based on patients' perceived needs may be more likely to alter such outcomes. In this paper, we describe the methodology of a randomised controlled trial of an integrated approach to facilitating patient goal achievement in the first year post-stroke. The effectiveness of this intervention in reducing the severity of post-stroke depression, improving participation status and health-related quality of life is examined. The impact on carers is also examined.</p> <p>Methods/Design</p> <p>Patients (and their primary carers, if available) are randomly allocated to an intervention or control arm of the study. The intervention is multimodal and aims to screen for adverse stroke sequelae and address ways to enhance participation in patient-valued activities. Intervention methods include: telephone contacts, written information provision, home visitation, and contact with treating health professionals, with further relevant health service referrals as required. The control involves treatment as usual, as determined by inpatient and community rehabilitation treating teams. Formal blinded assessments are conducted at discharge from inpatient rehabilitation, and at six and twelve months post-stroke. The primary outcome is depression. Secondary outcome measures include participation and activity status, health-related quality of life, and self-efficacy.</p> <p>Discussion</p> <p>The results of this trial will assist with the development of a model for community-based rehabilitation management for stroke patients and their carers, with emphasis on goal-directed practice to enhance home and community participation status. Facilitation of participation in valued activities may be effective in reducing the incidence or severity of post-stroke depression, as well as enhancing the individual's perception of their health-related quality of life. The engagement of carers in the rehabilitation process will enable review of the influence of the broader social context on recovery.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12608000042347.aspx">ACTRN12608000042347</a></p

Lions and Prions and Deer Demise

Background: Contagious prion diseases – scrapie of sheep and chronic wasting disease of several species in the deer family – give rise to epidemics that seem capable of compromising host population viability. Despite this prospect, the ecological consequences of prion disease epidemics in natural populations have received little consideration. Methodology/Principal Findings: Using a cohort study design, we found that prion infection dramatically lowered survival of free-ranging adult (.2-year-old) mule deer (Odocoileus hemionus): estimated average life expectancy was 5.2 additional years for uninfected deer but only 1.6 additional years for infected deer. Prion infection also increased nearly fourfold the rate of mountain lions (Puma concolor) preying on deer, suggesting that epidemics may alter predator–prey dynamics by facilitating hunting success. Despite selective predation, about one fourth of the adult deer we sampled were infected. High prevalence and low survival of infected deer provided a plausible explanation for the marked decline in this deer population since the 1980s. Conclusion: Remarkably high infection rates sustained in the face of intense predation show that even seemingly complete ecosystems may offer little resistance to the spread and persistence of contagious prion diseases. Moreover, the depression of infected populations may lead to local imbalances in food webs and nutrient cycling in ecosystems in which deer ar