Spotted Fever Group Rickettsiae in Questing Ticks, Central Spain

These results demonstrate that SFG rickettsiae with public health relevance are found in ticks in central Spain as in other regions in Spain. In central Spain, the widespread distribution of tick vectors and possible wildlife hosts, the presence of persons in tick-infested recreational and hunting areas, and the transstadial and transovarial transmission of the pathogen in ticks may favor transmission to humans.Fil: Fernandez de Mera, Isabel G.. Consejo Superior de Investigaciones Cientificas. Instituto de Investigación en Recursos Cinegéticos; España;Fil: Ruiz-Fons, Francisco. Consejo Superior de Investigaciones Cientificas. Instituto de Investigación en Recursos Cinegéticos; España;Fil: de la Fuente, Gabriela. Consejo Superior de Investigaciones Cientificas. Instituto de Investigación en Recursos Cinegéticos; España;Fil: Mangold, Atilio Jose. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria, Rafaela; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;Fil: Gortázar, Christian. Consejo Superior de Investigaciones Cientificas. Instituto de Investigación en Recursos Cinegéticos; España;Fil: de la Fuente, José. Oklahoma State University; Estados Unidos de América

A duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient Cavalier King Charles Spaniels is amenable to exon 51 skipping

BACKGROUND Duchenne muscular dystrophy (DMD), which afflicts 1 in 3500 boys, is one of the most common genetic disorders of children. This fatal degenerative condition is caused by an absence or deficiency of dystrophin in striated muscle. Most affected patients have inherited or spontaneous deletions in the dystrophin gene that disrupt the reading frame resulting in unstable truncated products. For these patients, restoration of the reading frame via antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach. The major DMD deletion "hot spot" is found between exons 45 and 53, and skipping exon 51 in particular is predicted to ameliorate the dystrophic phenotype in the greatest number of patients. Currently the mdx mouse is the most widely used animal model of DMD, although its mild phenotype limits its suitability in clinical trials. The Golden Retriever muscular dystrophy (GRMD) model has a severe phenotype, but due to its large size, is expensive to use. Both these models have mutations in regions of the dystrophin gene distant from the commonly mutated DMD "hot spot". METHODOLOGY/PRINCIPAL FINDINGS Here we describe the severe phenotype, histopathological findings, and molecular analysis of Cavalier King Charles Spaniels with dystrophin-deficient muscular dystrophy (CKCS-MD). The dogs harbour a missense mutation in the 5' donor splice site of exon 50 that results in deletion of exon 50 in mRNA transcripts and a predicted premature truncation of the translated protein. Antisense oligonucleotide-mediated skipping of exon 51 in cultured myoblasts from an affected dog restored the reading frame and protein expression. CONCLUSIONS/SIGNIFICANCE Given the small size of the breed, the amiable temperament and the nature of the mutation, we propose that CKCS-MD is a valuable new model for clinical trials of antisense oligonucleotide-induced exon skipping and other therapeutic approaches for DMD

Contributions to the morphology and phylogeny of the newly discovered bat tick species, Ixodes ariadnae in comparison with I. vespertilionis and I. simplex

Background: Recently a new hard tick species, Ixodes ariadnae has been discovered, adding to the two known ixodid tick species (I. vespertilionis and I. simplex) of bats in Europe. Findings: Scanning electron microscopic comparison of adult females of these species shows morphological differences concerning the palps, the scutum, the Haller's organ, the coxae, as well as the arrangement and fine structure of setae. Molecular analysis of 10 geographically different isolates revealed 90-95% sequence homology in the 12S and 16S rDNA genes of bat tick species. Based on 12S rDNA sequences, genotypes of I. ariadnae clustered closest to I. simplex, whereas according to their 16S rDNA gene they were closest to I. vespertilionis. The subolesin gene of I. ariadnae had only 91% sequence homology with that of I. ricinus, and is the longest known among hard tick species. Conclusions: The present study illustrates the morphology and clarifies the phylogenetic relationships of the three known bat tick species that occur in Europe. According to its subolesin gene I. ariadnae may have a long evolutionary history

Calcium Homeostasis in Myogenic Differentiation Factor 1 (MyoD)-Transformed, Virally-Transduced, Skin-Derived Equine Myotubes

Dysfunctional skeletal muscle calcium homeostasis plays a central role in the pathophysiology of several human and animal skeletal muscle disorders, in particular, genetic disorders associated with ryanodine receptor 1 (RYR1) mutations, such as malignant hyperthermia, central core disease, multiminicore disease and certain centronuclear myopathies. In addition, aberrant skeletal muscle calcium handling is believed to play a pivotal role in the highly prevalent disorder of Thoroughbred racehorses, known as Recurrent Exertional Rhabdomyolysis. Traditionally, such defects were studied in human and equine subjects by examining the contractile responses of biopsied muscle strips exposed to caffeine, a potent RYR1 agonist. However, this test is not widely available and, due to its invasive nature, is potentially less suitable for valuable animals in training or in the human paediatric setting. Furthermore, increasingly, RYR1 gene polymorphisms (of unknown pathogenicity and significance) are being identified through next generation sequencing projects. Consequently, we have investigated a less invasive test that can be used to study calcium homeostasis in cultured, skin-derived fibroblasts that are converted to the muscle lineage by viral transduction with a MyoD (myogenic differentiation 1) transgene. Similar models have been utilised to examine calcium homeostasis in human patient cells, however, to date, there has been no detailed assessment of the cells’ calcium homeostasis, and in particular, the responses to agonists and antagonists of RYR1. Here we describe experiments conducted to assess calcium handling of the cells and examine responses to treatment with dantrolene, a drug commonly used for prophylaxis of recurrent exertional rhabdomyolysis in horses and malignant hyperthermia in humans

Proteomics approach to the study of cattle tick adaptation to white tailed deer

Cattle ticks, Rhipicephalus (Boophilus) microplus, are a serious threat to animal health and production. Some ticks feed on a single host species while others such as R. microplus infest multiple hosts. White tailed deer (WTD) play a role in the maintenance and expansion of cattle tick populations. However, cattle ticks fed on WTD show lower weight and reproductive performance when compared to ticks fed on cattle, suggesting the existence of host factors that affect tick feeding and reproduction. To elucidate these factors, a proteomics approach was used to characterize tick and host proteins in R. microplus ticks fed on cattle and WTD. The results showed that R. microplus ticks fed on cattle have overrepresented tick proteins involved in blood digestion and reproduction when compared to ticks fed on WTD, while host proteins were differentially represented in ticks fed on cattle or WTD. Although a direct connection cannot be made between differentially represented tick and host proteins, these results suggested that differentially represented host proteins together with other host factors could be associated with higher R. microplus tick feeding and reproduction observed in ticks fed on cattle.Peer reviewedVeterinary Pathobiolog

Mindfulness-based stress reduction in Parkinson’s disease: a systematic review

Background: Mindfulness based stress reduction (MBSR) is increasingly being used to improve outcomes such as stress and depression in a range of long-term conditions (LTCs). While systematic reviews on MBSR have taken place for a number of conditions there remains limited information on its impact on individuals with Parkinson’s disease (PD). Methods: Medline, Central, Embase, Amed, CINAHAL were searched in March 2016. These databases were searched using a combination of MeSH subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed based on questions from the Cochrane Collaboration risk of bias tool. Results: Two interventions and three papers with a total of 66 participants were included. The interventions were undertaken in Belgium (n = 27) and the USA (n = 39). One study reported significantly increased grey matter density (GMD) in the brains of the MBSR group compared to the usual care group. Significant improvements were reported in one study for a number of outcomes including PD outcomes, depression, mindfulness, and quality of life indicators. Only one intervention was of reasonable quality and both interventions failed to control for potential confounders in the analysis. Adverse events and reasons for drop-outs were not reported. There was also no reporting on the costs/benefits of the intervention or how they affected health service utilisation. Conclusion: This systematic review found limited and inconclusive evidence of the effectiveness of MBSR for PD patients. Both of the included interventions claimed positive effects for PD patients but significant outcomes were often contradicted by other results. Further trials with larger sample sizes, control groups and longer follow-ups are needed before the evidence for MBSR in PD can be conclusively judged

Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms. A substantial placebo response was observed but no significant difference in efficacy between the two arms.</p> <p>Methods</p> <p>A <it>post hoc </it>analysis was conducted on data from 93 participants who completed this previously published study. Variables at baseline were investigated as potential predictors of the response on any of the endpoints of flushing, overall menopausal symptoms and depression. Focused tests were conducted using hierarchical linear regression analyses. Based on these findings, analyses were conducted for both groups separately. These findings are discussed in relation to existing literature on placebo effects.</p> <p>Results</p> <p>Distinct differences in predictors were observed between the placebo and active groups. A significant difference was found for study entry anxiety, and Greene Climacteric Scale (GCS) scores, on all three endpoints. Attitude to menopause was found to differ significantly between the two groups for GCS scores. Examination of the individual arms found anxiety at study entry to predict placebo response on all three outcome measures individually. In contrast, <it>low </it>anxiety was significantly associated with improvement in the active treatment group. None of the variables found to predict the placebo response was relevant to the treatment arm.</p> <p>Conclusion</p> <p>This study was a <it>post hoc </it>analysis of predictors of the placebo versus treatment response. Whilst this study does not explore neurobiological mechanisms, these observations are consistent with the hypotheses that 'drug' effects and placebo effects are not necessarily additive, and that mutually exclusive mechanisms may be operating in the two arms. The need for more research in the area of mechanisms and mediators of placebo versus active responses is supported.</p> <p>Trial Registration</p> <p>International Clinical Trials Registry ISRCTN98972974.</p

Tailoring nanostructured surfaces with plasmonic/magnetic multifunctional response

IIn this work, we present an innovative way to functionalize large surfaces combining both plasmonic and magnetic nanoparticles on a substrate, by the growth of bilayers and a subsequent single annealing. In particular, we show here the formation of Au and gamma- Fe₂O₃ nanoparticles using this route. Thermal treatments promote the nanostructuration of the film plus a partial oxidation of Fe to form ferrimagnetic oxides. For this purpose, annealing conditions and the structure of the bilayer must be selected to achieve an optimal nanostructuration, avoiding the full oxidation of Fe to form antiferromagnetic hematite. Published by AIP Publishing

High degree of mitochondrial gene heterogeneity in the bat tick species Ixodes vespertilionis, I. ariadnae and I. simplex from Eurasia

Background: Phylogeographical studies allow precise genetic comparison of specimens, which were collected over large geographical ranges and belong to the same or closely related animal species. These methods have also been used to compare ticks of veterinary-medical importance. However, relevant data are missing in the case of ixodid ticks of bats, despite (1) the vast geographical range of both Ixodes vespertilionis and Ixodes simplex, and (2) the considerable uncertainty in their taxonomy, which is currently unresolvable by morphological clues. Methods: In the present study 21 ticks were selected from collections or were freshly removed from bats or cave walls in six European and four Asian countries. The DNA was extracted and PCRs were performed to amplify part of the cytochrome oxidase I (COI), 16S and 12S rDNA genes, followed by sequencing for identification and molecular-phylogenetic comparison. Results: No morphological differences were observed between Ixodes vespertilionis specimens from Spain and from other parts of Europe, but corresponding genotypes had only 94.6 % COI sequence identity. An I. vespertilionis specimen collected in Vietnam was different both morphologically and genetically (i.e. with only 84.1 % COI sequence identity in comparison with I. vespertilionis from Europe). Two ticks (collected in Vietnam and in Japan) formed a monophyletic clade and shared morphological features with I. ariadnae, recently described and hitherto only reported in Europe. In addition, two Asiatic specimens of I. simplex were shown to differ markedly from European genotypes of the same species. Phylogenetic relationships of ticks showed similar clustering patterns with those of their associated bat host species. Conclusions: Although all three ixodid bat tick species evaluated in the present study appear to be widespread in Eurasia, they exhibit pronounced genetic differences. Data of this study also reflect that I. vespertilionis may represent a species complex