Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment, and Prevention

Equine protozoal myeloencephalitis (EPM) remains an important neurologic disease of horses. There are no pathognomonic clinical signs for the disease. Affected horses can have focal or multifocal central nervous system (CNS) disease. EPM can be difficult to diagnose antemortem. It is caused by either of 2 parasites, Sarcocystis neurona and Neospora hughesi, with much less known about N. hughesi. Although risk factors such as transport stress and breed and age correlations have been identified, biologic factors such as genetic predispositions of individual animals, and parasite-specific factors such as strain differences in virulence, remain largely undetermined. This consensus statement update presents current published knowledge of the parasite biology, host immune response, disease pathogenesis, epidemiology, and risk factors. Importantly, the statement provides recommendations for EPM diagnosis, treatment, and prevention

Definitive and adjuvant radiotherapy for sinonasal squamous cell carcinomas: a single institutional experience

Background: The aim of this study was to evaluate the disease outcomes of patients treated with definitive and adjuvant radiotherapy for squamous cell carcinomas of the nasal cavity and paranasal sinuses in a single institution. Methods: Between 2007–2012 patients were retrospectively identified from electronic databases who had undergone surgery and adjuvant radiotherapy or definitive radiotherapy for sinonasal squamous cell carcinomas with curative intent. Results: Fourty three patients with sinonasal squamous cell carcinoma were identified (22 nasal cavity, 21 paranasal sinuses). 31/43 (72 %) had T3 or T4 disease; nodal stage was N0 in 38, N1 in 4, Na/b in 0 and N2c in 1 patient. Median age was 67 years (range 41–86). 18 (42 %) received definitive and 25 (58 %) adjuvant radiotherapy. Radiotherapy was delivered using either conventional radiotherapy (n = 39) or intensity modulated radiotherapy (n = 4). Elective neck radiotherapy was delivered to two patients. Chemotherapy was delivered to 6/43 (14 %) of patients. Two-year local control, regional control, distant metastases free survival, progression free survival, cause specific survival and overall survival were 81 %, 90 %, 95 %, 71 %, 84 % and 80 % respectively. There was no significant difference in outcome comparing patients who underwent surgery and adjuvant radiotherapy with patients receiving definitive radiotherapy (2 year locoregional disease free survival 75 % and 70 % respectively, p = 0.98). Pooly differentiated tumours were significantly associated with inferior disease outcomes. Local, regional, combined local and regional, and distant failure occurred in 7 (16 %), 3 (7 %), 1 (2 %) and 2 (5 %) of patients; all 3 regional recurrences were in patients with nasal cavity squamous cell carcinomas who had not undergone elective neck treatment. Conclusions: Definitive or adjuvant radiotherapy provides an effective treatment for sinonasal malignancies. The main pattern of failure remains local, suggesting the need for investigation of intensified local therapy. Whilst remaining uncommon, the cases of regional failure mean that the merits of elective lymph node treatment should be considered on an individual basis

Bi-Directional Effect of Cholecystokinin Receptor-2 Overexpression on Stress-Triggered Fear Memory and Anxiety in the Mouse

Fear, an emotional response of animals to environmental stress/threats, plays an important role in initiating and driving adaptive response, by which the homeostasis in the body is maintained. Overwhelming/uncontrollable fear, however, represents a core symptom of anxiety disorders, and may disturb the homeostasis. Because to recall or imagine certain cue(s) of stress/threats is a compulsory inducer for the expression of anxiety, it is generally believed that the pathogenesis of anxiety is associated with higher attention (acquisition) selectively to stress or mal-enhanced fear memory, despite that the actual relationship between fear memory and anxiety is not yet really established. In this study, inducible forebrain-specific cholecystokinin receptor-2 transgenic (IF-CCKR-2 tg) mice, different stress paradigms, batteries of behavioral tests, and biochemical assays were used to evaluate how different CCKergic activities drive fear behavior and hormonal reaction in response to stresses with different intensities. We found that in IF-CCKR-2 tg mice, contextual fear was impaired following 1 trial of footshock, while overall fear behavior was enhanced following 36 trials of footshock, compared to their littermate controls. In contrast to a standard Yerkes-Dodson (inverted-U shaped) stress-fear relationship in control mice, a linearized stress-fear curve was observed in CCKR-2 tg mice following gradient stresses. Moreover, compared to 1 trial, 36 trials of footshock in these transgenic mice enhanced anxiety-like behavior in other behavioral tests, impaired spatial and recognition memories, and prolonged the activation of adrenocorticotropic hormone (ACTH) and glucocorticoids (CORT) following new acute stress. Taken together, these results indicate that stress may trigger two distinctive neurobehavioral systems, depending on both of the intensity of stress and the CCKergic tone in the brain. A “threshold theory” for this two-behavior system has been suggested