Comparison of embedded and added motor imagery training in patients after stroke: Study protocol of a randomised controlled pilot trial using a mixed methods approach

Copyright @ 2009 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Two different approaches have been adopted when applying motor imagery (MI) to stroke patients. MI can be conducted either added to conventional physiotherapy or integrated within therapy sessions. The proposed study aims to compare the efficacy of embedded MI to an added MI intervention. Evidence from pilot studies reported in the literature suggests that both approaches can improve performance of a complex motor skill involving whole body movements, however, it remains to be demonstrated, which is the more effective one.Methods/Design: A single blinded, randomised controlled trial (RCT) with a pre-post intervention design will be carried out. The study design includes two experimental groups and a control group (CG). Both experimental groups (EG1, EG2) will receive physical practice of a clinical relevant motor task ('Going down, laying on the floor, and getting up again') over a two week intervention period: EG1 with embedded MI training, EG2 with MI training added after physiotherapy. The CG will receive standard physiotherapy intervention and an additional control intervention not related to MI.The primary study outcome is the time difference to perform the task from pre to post-intervention. Secondary outcomes include level of help needed, stages of motor task completion, degree of motor impairment, balance ability, fear of falling measure, motivation score, and motor imagery ability score. Four data collection points are proposed: twice during baseline phase, once following the intervention period, and once after a two week follow up. A nested qualitative part should add an important insight into patients' experience and attitudes towards MI. Semi-structured interviews of six to ten patients, who participate in the RCT, will be conducted to investigate patients' previous experience with MI and their expectations towards the MI intervention in the study. Patients will be interviewed prior and after the intervention period.Discussion: Results will determine whether embedded MI is superior to added MI. Findings of the semi-structured interviews will help to integrate patient's expectations of MI interventions in the design of research studies to improve practical applicability using MI as an adjunct therapy technique

Anthromes dispaying evidence of weekly cycles in active fire data cover 70% of the global land surface

Across the globe, human activities have been gaining importance relatively to climate and ecology as the main controls on fire regimes and consequently human activity became an important driver of the frequency, extent and intensity of vegetation burning worldwide. Our objective in the present study is to look for weekly cycles in vegetation fire activity at global scale as evidence of human agency, relying on the original MODIS active fire detections at 1 km spatial resolution (MCD14ML) and using novel statistical methodologies to detect significant periodicities in time series data. We tested the hypotheses that global fire activity displays weekly cycles and that the weekday with the fewest fires is Sunday. We also assessed the effect of land use and land cover on weekly fire cycle significance by testing those hypotheses separately for the Villages, Settlements, Croplands, Rangelands, Seminatural, and Wildlands anthromes. Based on a preliminary data analysis of the daily global active fire counts periodogram, we developed an harmonic regression model for the mean function of daily fire activity and assumed a linear model for the de-seasonalized time series. For inference purposes, we used a Bayesian methodology and constructed a simultaneous 95% credible band for the mean function. The hypothesis of a Sunday weekly minimum was directly investigated by computing the probabilities that the mean functions of every weekday (Monday to Saturday) are inside the credible band corresponding to mean Sunday fire activity. Since these probabilities are small, there is statistical evidence of significantly fewer fires on Sunday than on the other days of the week. Cropland, rangeland, and seminatural anthromes, which cover 70% of the global land area and account for 94% of the active fires analysed, display weekly cycles in fire activity. Due to lower land management intensity and less strict control over fire size and duration, weekly cycles in Rangelands and Seminatural anthromes, which jointly account for 53.46% of all fires, although statistically significant are weaker than those detected in Croplandsinfo:eu-repo/semantics/publishedVersio

Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

EMSY overexpression disrupts the BRCA2/RAD51 pathway in the DNA-damage response: implications for chromosomal instability/recombination syndromes as checkpoint diseases

EMSY links the BRCA2 pathway to sporadic breast/ovarian cancer. It encodes a nuclear protein that binds to the BRCA2 N-terminal domain implicated in chromatin/transcription regulation, but when sporadically amplified/overexpressed, increased EMSY level represses BRCA2 transactivation potential and induces chromosomal instability, mimicking the activity of BRCA2 mutations in the development of hereditary breast/ovarian cancer. In addition to chromatin/transcription regulation, EMSY may also play a role in the DNA-damage response, suggested by its ability to localize at chromatin sites of DNA damage/repair. This implies that EMSY overexpression may also repress BRCA2 in DNA-damage replication/checkpoint and recombination/repair, coordinated processes that also require its interacting proteins: PALB2, the partner and localizer of BRCA2; RPA, replication/checkpoint protein A; and RAD51, the inseparable recombination/repair enzyme. Here, using a well-characterized recombination/repair assay system, we demonstrate that a slight increase in EMSY level can indeed repress these two processes independently of transcriptional interference/repression. Since EMSY, RPA and PALB2 all bind to the same BRCA2 region, these findings further support a scenario wherein: (a) EMSY amplification may mimic BRCA2 deficiency, at least by overriding RPA and PALB2, crippling the BRCA2/RAD51 complex at DNA-damage and replication/transcription sites; and (b) BRCA2/RAD51 may coordinate these processes by employing at least EMSY, PALB2 and RPA. We extensively discuss the molecular details of how this can happen to ascertain its implications for a novel recombination mechanism apparently conceived as checkpoint rather than a DNA repair system for cell division, survival, death, and human diseases, including the tissue specificity of cancer predisposition, which may renew our thinking about targeted therapy and prevention

Evolutionary history of the OmpR/IIIA family of signal transduction two component systems in Lactobacillaceae and Leuconostocaceae

<p>Abstract</p> <p>Background</p> <p>Two component systems (TCS) are signal transduction pathways which typically consist of a sensor histidine kinase (HK) and a response regulator (RR). In this study, we have analyzed the evolution of TCS of the OmpR/IIIA family in <it>Lactobacillaceae </it>and <it>Leuconostocaceae</it>, two families belonging to the group of lactic acid bacteria (LAB). LAB colonize nutrient-rich environments such as foodstuffs, plant materials and the gastrointestinal tract of animals thus driving the study of this group of both basic and applied interest.</p> <p>Results</p> <p>The genomes of 19 strains belonging to 16 different species have been analyzed. The number of TCS encoded by the strains considered in this study varied between 4 in <it>Lactobacillus helveticus </it>and 17 in <it>Lactobacillus casei</it>. The OmpR/IIIA family was the most prevalent in <it>Lactobacillaceae </it>accounting for 71% of the TCS present in this group. The phylogenetic analysis shows that no new TCS of this family has recently evolved in these <it>Lactobacillaceae </it>by either lineage-specific gene expansion or domain shuffling. Furthermore, no clear evidence of non-orthologous replacements of either RR or HK partners has been obtained, thus indicating that coevolution of cognate RR and HKs has been prevalent in <it>Lactobacillaceae</it>.</p> <p>Conclusions</p> <p>The results obtained suggest that vertical inheritance of TCS present in the last common ancestor and lineage-specific gene losses appear as the main evolutionary forces involved in their evolution in <it>Lactobacillaceae</it>, although some HGT events cannot be ruled out. This would agree with the genomic analyses of <it>Lactobacillales </it>which show that gene losses have been a major trend in the evolution of this group.</p

Biapenem Inactivation by B2 Metallo β-Lactamases: Energy Landscape of the Post-Hydrolysis Reactions

<div><h3>Background</h3><p>The first line of defense by bacteria against <em>β</em>-lactam antibiotics is the expression of β-lactamases, which cleave the amide bond of the β-lactam ring. In the reaction of biapenem inactivation by B2 metallo β-lactamases (MβLs), after the β-lactam ring is opened, the carboxyl group generated by the hydrolytic process and the hydroxyethyl group (common to all carbapenems) rotate around the C5–C6 bond, assuming a new position that allows a proton transfer from the hydroxyethyl group to C2, and a nucleophilic attack on C3 by the oxygen atom of the same side-chain. This process leads to the formation of a bicyclic compound, as originally observed in the X-ray structure of the metallo β-lactamase CphA in complex with product.</p> <h3>Methodology/Principal Findings</h3><p>QM/MM and metadynamics simulations of the post-hydrolysis steps in solution and in the enzyme reveal that while the rotation of the hydroxyethyl group can occur in solution or in the enzyme active site, formation of the bicyclic compound occurs primarily in solution, after which the final product binds back to the enzyme. The calculations also suggest that the rotation and cyclization steps can occur at a rate comparable to that observed experimentally for the enzymatic inactivation of biapenem only if the hydrolysis reaction leaves the N4 nitrogen of the β-lactam ring unprotonated.</p> <h3>Conclusions/Significance</h3><p>The calculations support the existence of a common mechanism (in which ionized N4 is the leaving group) for carbapenems hydrolysis in all MβLs, and suggest a possible revision of mechanisms for B2 MβLs in which the cleavage of the β-lactam ring is associated with or immediately followed by protonation of N4. The study also indicates that the bicyclic derivative of biapenem has significant affinity for B2 MβLs, and that it may be possible to obtain clinically effective inhibitors of these enzymes by modification of this lead compound.</p> </div

Sequential Bottlenecks Drive Viral Evolution in Early Acute Hepatitis C Virus Infection

Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS) and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection