Health knowledge and infection control by event horse owners

Infection control and quarantine measures are essential to minimise the impact of equine infectious diseases, but their uptake by equestrians involved with sport horses in the United Kingdom is undocumented. Using a questionnaire, this study aimed to: i) determine the knowledge and practices of eventing equestrians about their horses’ health and the clinical signs of endemic and exotic equine infectious diseases and ii) assess existing infection control and quarantine measures on event horse yards. A questionnaire was designed, piloted and distributed electronically over six weeks. The target respondents were equestrians involved in eventing, including jumping their horses over fences either 100cms. Data were described qualitatively and analysed statistically to identify any relationships between selected parameters. A total of 146 responses were analysed. The majority of respondents were female, involved as amateurs in eventing and their veterinary surgeon was the first choice for advice. To assess temperature,owners often used touch, but rectal temperature was taken rarely. The majority of horses were vaccinated against tetanus and influenza but a minority against EHV-1/-4. Most respondents identified the clinical signs of influenza and Streptococcus equi, but were less certain about EHV-1/-4. Only 30.1% of respondents had access to quarantine facilities, which were significantly more likely to be available in professional yards (p=0.043) and in riders competing above the 100cm level (p=0.0003). Professionals competing their horses above 100cm were significantly more likely to have quarantine facilities (p<0.05). A majority of yards with quarantine facilities isolated new horses for 2-4 weeks. Facilities included a separate stable (81.8%) or field (68.2%), but separate equipment (47.7%) and access to disinfectant (36.4%) were available less frequently. In conclusion, amateur equestrians involved in eventing require better education on the routine use of infection control and quarantine measures to minimise the impact of equine infectious diseases and thus strengthen infection control nationally

Cbx7 represses cancer stem cell phenotype in Tera2 through inhibition of Wnt signaling

Epigenetics has been defined as heritable changes in cell phenotypes and attendant gene expression patterns that do not directly alter the nucleic acid base sequence. Several interdependent processes are currently classified as epigenetic, such as DNA methylation, nuclear positioning and covalent modifications of histone proteins, interaction with non-coding RNA species, and higher order organization of nucleic acid in the nucleus. This thesis centers on the activities of key players in maintenance of epigenetic imposition of gene silencing, the repressive Polycomb group proteins and DNA methylation. Both mechanisms serve as major regulators of normal developmental processes and have interactive roles in cancer as potential mediators of abnormal gene silencing and associated altered DNA methylation of normally unmethylated regions such gene promoter CpG islands. Our lab has previously reported on the polycomb complex, PRC1, and specifically the protein CBX7, and its role in initiating DNA methylation at cancer-specific genes in Tera2 embryonal carcinoma cells. Tera2 has been shown to differentiate to neuronal cells in response to exposure to all-trans retinoic acid (ATRA), but in CBX7-overexpressing Tera2, a small “outgrowth” subpopulation exhibits retinoid resistance after 3 weeks of ATRA exposure. When withdrawn from ATRA exposure and subsequently re-exposed, the majority of Cbx7 outgrowth cells again show sensitivity to the differentiating effects of ATRA, but again forms a retinoid resistant subpopulation. The CBX7 and CBX7 outgrowth populations exhibit reduced tumorigenicity in NOD/SCID mice. We link CBX7 overexpression to suppression of both canonical and non-canonical Wnt signaling pathways, owing in part to transcriptional repression and associated DNA methylation of the LEF1 enhancer protein and cJUN transcription factor. In the above Tera2 model, the unresponsiveness of the Wnt pathway induced by CBX7 may represent an altered epigenetic state associated with a less tumorigenic state with a new pattern of cancer-specific promoter CpG island DNA hypermethylation

Health knowledge and infection control by event horse owners

Infection control and quarantine measures are essential to minimise the impact of equine infectious diseases, but their uptake by equestrians involved with sport horses in the United Kingdom is undocumented. Using a questionnaire, this study aimed to: i) determine the knowledge and practices of eventing equestrians about their horses’ health and the clinical signs of endemic and exotic equine infectious diseases and ii) assess existing infection control and quarantine measures on event horse yards. A questionnaire was designed, piloted and distributed electronically over six weeks. The target respondents were equestrians involved in eventing, including jumping their horses over fences either 100cms. Data were described qualitatively and analysed statistically to identify any relationships between selected parameters. A total of 146 responses were analysed. The majority of respondents were female, involved as amateurs in eventing and their veterinary surgeon was the first choice for advice. To assess temperature,owners often used touch, but rectal temperature was taken rarely. The majority of horses were vaccinated against tetanus and influenza but a minority against EHV-1/-4. Most respondents identified the clinical signs of influenza and Streptococcus equi, but were less certain about EHV-1/-4. Only 30.1% of respondents had access to quarantine facilities, which were significantly more likely to be available in professional yards (p=0.043) and in riders competing above the 100cm level (p=0.0003). Professionals competing their horses above 100cm were significantly more likely to have quarantine facilities (p<0.05). A majority of yards with quarantine facilities isolated new horses for 2-4 weeks. Facilities included a separate stable (81.8%) or field (68.2%), but separate equipment (47.7%) and access to disinfectant (36.4%) were available less frequently. In conclusion, amateur equestrians involved in eventing require better education on the routine use of infection control and quarantine measures to minimise the impact of equine infectious diseases and thus strengthen infection control nationally

Polarisation of equine pregnancy outcome associated with a maternal MHC class I allele: preliminary evidence

Identification of risk factors which are associated with severe clinical signs can assist in the management of disease outbreaks and indicate future research areas. Pregnancy loss during late gestation in the mare compromises welfare, reduces fecundity and has financial implications for horse owners. This retrospective study focussed on the identification of risk factors associated with pregnancy loss among 46 Thoroughbred mares on a single British stud farm, with some but not all losses involving equid herpesvirus-1 (EHV-1) infection. In a sub-group of 30 mares, association between pregnancy loss and the presence of five common Thoroughbred horse haplotypes of the equine Major Histocompatibility Complex (MHC) was assessed. This involved development of sequence specific, reverse transcriptase polymerase chain reactions and in several mares, measurement of cytotoxic T lymphocyte activity. Of the 46 mares, 10 suffered late gestation pregnancy loss or neonatal foal death, five of which were EHV-1 positive. Maternal factors including age, parity, number of EHV-1 specific vaccinations and the number of days between final vaccination and foaling or abortion were not significantly associated with pregnancy loss. In contrast, a statistically significant association between the presence of the MHC class I B2 allele and pregnancy loss was identified, regardless of the fetus / foal’s EHV-1 status (p=0.002). In conclusion, this study demonstrated a significantly positive association between pregnancy loss in Thoroughbred mares and a specific MHC class I allele in the mother. This association requires independent validation and further investigation of the mechanism by which the mare’s genetic background contributes to pregnancy outcome

The Effects of Methylphenidate on Cognitive Control in Active Methamphetamine Dependence Using Functional Magnetic Resonance Imaging

Methamphetamine (MA) dependence is associated with cognitive deficits. Methylphenidate (MPH) has been shown to improve inhibitory control in healthy and cocaine-dependent subjects. This study aimed to understand the neurophysiological effects before and after acute MPH administration in active MA-dependent and control subjects. Fifteen MA-dependent and 18 control subjects aged 18–46 years were scanned using functional magnetic resonance imaging before and after either a single oral dose of MPH (18 mg) or placebo while performing a color-word Stroop task. Baseline accuracy was lower (p = 0.026) and response time (RT) was longer (p < 0.0001) for the incongruent compared to congruent condition, demonstrating the task probed cognitive control. Increased activation of the dorsolateral prefrontal cortex (DLPFC) and parietal cortex during the incongruent and Stroop effect conditions, respectively was observed in MA-dependent compared to control subjects (p < 0.05), suggesting the need to recruit neural resources within these regions for conflict resolution. Post- compared to pre-MPH treatment, increased RT and DLPFC activation for the Stroop effect were observed in MA-dependent subjects (p < 0.05). In comparison to MPH-treated controls and placebo-treated MA-dependent subjects, MPH-treated MA-dependent subjects showed decreased activation of parietal and occipital regions during the incongruent and Stroop effect conditions (p < 0.05). These findings suggest that in MA-dependent subjects, MPH facilitated increased recruitment of the DLPFC for Stroop conflict resolution, and a decreased need for recruitment of neural resources in parietal and occipital regions compared to the other groups, while maintaining a comparable level of task performance to that achieved pre-drug administration. Due to the small sample size, the results from this study are preliminary; however, they inform us about the effects of MPH on the neural correlates of cognitive control in active MA-dependent subjects

Health knowledge and infection control by event horse owners

Infection control and quarantine measures are essential to minimise the impact of equine infectious diseases, but their uptake by equestrians involved with sport horses in the United Kingdom is undocumented. Using a questionnaire, this study aimed to: i) determine the knowledge and practices of eventing equestrians about their horses’ health and the clinical signs of endemic and exotic equine infectious diseases and ii) assess existing infection control and quarantine measures on event horse yards. A questionnaire was designed, piloted and distributed electronically over six weeks. The target respondents were equestrians involved in eventing, including jumping their horses over fences either 100cms. Data were described qualitatively and analysed statistically to identify any relationships between selected parameters. A total of 146 responses were analysed. The majority of respondents were female, involved as amateurs in eventing and their veterinary surgeon was the first choice for advice. To assess temperature,owners often used touch, but rectal temperature was taken rarely. The majority of horses were vaccinated against tetanus and influenza but a minority against EHV-1/-4. Most respondents identified the clinical signs of influenza and Streptococcus equi, but were less certain about EHV-1/-4. Only 30.1% of respondents had access to quarantine facilities, which were significantly more likely to be available in professional yards (p=0.043) and in riders competing above the 100cm level (p=0.0003). Professionals competing their horses above 100cm were significantly more likely to have quarantine facilities (

Disrupted white matter integrity in treatment-resistant schizophrenia

Treatment response in schizophrenia is heterogeneous and has been posited to divide into three distinct subcategories: treatment-responsive (first-line responders; FLR), treatment-resistant (TRS, responding to clozapine), and ultra-treatment-resistant schizophrenia (UTRS, requiring augmented antipsychotic therapy). Previous work suggests that white matter abnormalities drive antipsychotic resistance but little work has been carried out to identify differences between those with TRS and those with UTRS. The current study aimed to establish whether differences in white matter structure are present across both treatment-resistant subtypes of schizophrenia or if UTRS is distinct from TRS. Diffusion-weighted images were acquired for 18 individuals with TRS, 14 with UTRS, 18 FLR and 20 healthy controls. Measures of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and parallel diffusivity (PD) were obtained using tract-based spatial statistics. Analysis of variance (ANOVA) and post-hoc between-groups t-tests interrogating differences were conducted for each white matter measure. Those with TRS had lower FA than healthy controls across widespread regions of the brain, including the superior longitudinal fasciculus, corpus callosum, thalamic radiation, corticospinal tract, internal capsule, corona radiata and fronto-occipital fasciculus (p<.05 FWE-corrected). Lower FA was also observed in those with TRS compared with UTRS in the superior longitudinal fasciculus (p<.05 FWE-corrected). However, post-hoc tests failed to survive corrections for multiple comparisons across the 12 post-hoc contrasts. No differences in MD, PD or RD were observed between groups. These data suggest that TRS is distinct from UTRS and that lower FA could act as a biomarker of treatment resistance in people with schizophrenia