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

A Minimal Model of Metabolism Based Chemotaxis

Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has been predominantly studied as metabolism-independent. All available simulation models of bacterial chemotaxis endorse this assumption. Recent studies have shown, however, that many metabolism-dependent chemotactic patterns occur in bacteria. We hereby present the simplest artificial protocell model capable of performing metabolism-based chemotaxis. The model serves as a proof of concept to show how even the simplest metabolism can sustain chemotactic patterns of varying sophistication. It also reproduces a set of phenomena that have recently attracted attention on bacterial chemotaxis and provides insights about alternative mechanisms that could instantiate them. We conclude that relaxing the metabolism-independent assumption provides important theoretical advances, forces us to rethink some established pre-conceptions and may help us better understand unexplored and poorly understood aspects of bacterial chemotaxis

Patient-Generated Graphs to Measure Pain and Fatigue in Persons with Neuralgic Amyotrophy

Background: Patients with neuralgic amyotrophy (NA) often experience limitations in daily activities because of pain and fatigue. Visual analogue graphs with a 24-hour x-axis can be used to rate pain and fatigue severity during a typical day. This study aimed to investigate the reliability and validity of the visual analogue graphs in patients with NA. Method: Eight patients completed pain and fatigue graphs on three moments to examine inter-rater and test-retest reliability using Intraclass Correlation Coefficients (ICCs). Concurrent validity (n = 47) was tested by determining correlations between mean pain graph scores and numerical rating scale for pain (NRS-pain) and between mean fatigue graph scores and checklist individual strength-subscale fatigue (CIS-fatigue). Results: ICC for test-retest reliability varied from 0.72– 0.93 for pain and 0.67–0.85 for fatigue scores. ICC for inter-rater reliability varied from 0.76–0.97 for pain and 0.47–0.97 for fatigue scores. Correlation between the mean pain graph score and NRS-pain was strong (rs = 0.75, ps = 0.42, p = 0.003). Conclusion: The visual analogue graph for pain appears reliable and valid in patients with NA. Test-retest reliability and concurrent validity for the fatigue graph warrant further research

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

Come for the looks, stay for the personality? A mixed methods investigation of reacquisition and owner recommendation of Bulldogs, French Bulldogs and Pugs

Brachycephalic breeds are proliferating internationally, with dramatic rises in popularity juxtaposed with common and severe breed-related health problems. Physical appearance is as a dominant factor attracting owners to brachycephalic breeds; however, whether these owners will choose their current breed for future ownership and develop 'breed-loyalty' in the face of health problems is not yet known. The aims of this study were (1) to quantify levels of, and explore factors associated with, brachycephalic dog owners' intentions to: (i) reacquire and/or (ii) recommend their current breed to potential first-time dog owners, and (2) to use qualitative methods to explore why brachycephalic dog owners would or would not recommend their current breed. This large mixed methods study reports on 2168 owners of brachycephalic breeds (Pugs: n = 789; French Bulldog: n = 741; Bulldogs: n = 638). Owners were highly likely to want to own their breed again in the future (93.0%) and recommend their breed to other owners (65.5%). Statistical modelling identified that first-time ownership and increased strength of the dog-owner relationship increased the likelihood of reacquisi-tion and/or recommendation. In contrast, an increased number of health problems, positive perception of their dog's health compared with the rest of their breed, and dog behaviour being worse than expected decreased the likelihood of reacquisition and/or recommendation. Thematic analyses constructed three themes describing why owners recommend their breed: positive behavioural attributes for a companion dog, breed suited to a sedentary lifestyle with limited space, and suitability for households with children. Five themes described why owners recommended against their breed: high prevalence of health problems, expense of ownership, ethical and welfare issues associated with breeding brachycephalic dogs, negative effects upon owner lifestyle and negative behavioural attributes. Understanding how breed-loyalty develops, and whether it can be attenuated, will be key to controlling the current population boom in brachycephalic breeds in the long-term

Treatment of atypical central neurocytoma in a child with high dose chemotherapy and autologous stem cell rescue

The authors describe a 9 month old female with recurrent atypical central neurocytoma and leptomeningeal spread treated with high dose chemotherapy, autologous stem cell rescue, and adjuvant therapy. She had a complete response to therapy and was disease free at 4 years of age until a recurrence 6 months later. The use of intensive chemotherapy followed by autologous stem cell rescue for atypical neurocytoma may be considered as an adjunct to surgical therapy in young patients with atypical neurocytoma not amenable to radiation therapy

Surfing a genetic association interaction network to identify modulators of antibody response to smallpox vaccine

The variation in antibody response to vaccination likely involves small contributions of numerous genetic variants, such as single-nucleotide polymorphisms (SNPs), which interact in gene networks and pathways. To accumulate the bits of genetic information relevant to the phenotype that are distributed throughout the interaction network, we develop a network eigenvector centrality algorithm (SNPrank) that is sensitive to the weak main effects, gene–gene interactions and small higher-order interactions through hub effects. Analogous to Google PageRank, we interpret the algorithm as the simulation of a random SNP surfer (RSS) that accumulates bits of information in the network through a dynamic probabilistic Markov chain. The transition matrix for the RSS is based on a data-driven genetic association interaction network (GAIN), the nodes of which are SNPs weighted by the main-effect strength and edges weighted by the gene–gene interaction strength. We apply SNPrank to a GAIN analysis of a candidate-gene association study on human immune response to smallpox vaccine. SNPrank implicates a SNP in the retinoid X receptor α (RXRA) gene through a network interaction effect on antibody response. This vitamin A- and D-signaling mediator has been previously implicated in human immune responses, although it would be neglected in a standard analysis because its significance is unremarkable outside the context of its network centrality. This work suggests SNPrank to be a powerful method for identifying network effects in genetic association data and reveals a potential vitamin regulation network association with antibody response

No effect of 14 day consumption of whole grain diet compared to refined grain diet on antioxidant measures in healthy, young subjects: a pilot study

<p>Abstract</p> <p>Background</p> <p>Epidemiological evidence supports that a diet high in whole grains is associated with lowered risk of chronic diseases included coronary heart disease, obesity, type 2 diabetes, and some types of cancer. One potential mechanism for the protective properties of whole grains is their antioxidant content. The aim of this study was to compare differences in antioxidant measures when subjects consumed either refined or whole grain diets.</p> <p>Methods</p> <p>Twenty healthy subjects took part in a randomized, crossover dietary intervention study. Subjects consumed either a refined grain or whole grain diet for 14 days and then the other diet for the next 14 days. Male subjects consumed 8 servings of grains per day and female subjects consumed 6 servings of grains per day. Blood and urine samples were collected at the end of each diet. Antioxidant measures included oxygen radical absorbance capacity (ORAC) in blood, and isoprostanes and thiobarbituric acid reactive substances (TBARS) in urine.</p> <p>Results</p> <p>The whole grain diet was significantly higher in dietary fiber, vitamin B6, folate, selenium, copper, zinc, iron, magnesium and cystine compared to the refined grain diet. Despite high intakes of whole grains, no significant differences were seen in any of the antioxidant measures between the refined and whole grain diets.</p> <p>Conclusions</p> <p>No differences in antioxidant measures were found when subjects consumed whole grain diets compared to refined grain diets.</p