PREP2 Algorithm Predictions Are Correct at 2 Years Poststroke for Most Patients

Background. The PREP2 algorithm combines clinical and neurophysiological measures to predict upper-limb (UL) motor outcomes 3 months poststroke, using 4 prediction categories based on Action Research Arm Test (ARAT) scores. The algorithm was accurate at 3 months for 75% of participants in a previous validation study. Objective. This study aimed to evaluate whether PREP2 predictions made at baseline are correct 2 years poststroke. We also assessed whether patients’ UL performance remained stable, improved, or worsened between 3 months and 2 years after stroke. Methods. This is a follow-up study of 192 participants recruited and assessed in the original PREP2 validation study. Participants who completed assessments 3 months poststroke (n = 157) were invited to complete follow-up assessments at 2 years poststroke for the present study. UL outcomes were assessed with the ARAT, upper extremity Fugl-Meyer Scale, and Motor Activity Log. Results. A total of 86 participants completed 2-year follow-up assessments in this study. PREP2 predictions made at baseline were correct for 69/86 (80%) participants 2 years poststroke, and PREP2 UL outcome category was stable between 3 months and 2 years poststroke for 71/86 (83%). There was no difference in age, stroke severity, or comorbidities among patients whose category remained stable, improved, or deteriorated. Conclusions. PREP2 algorithm predictions made within days of stroke are correct at both 3 months and 2 years poststroke for most patients. Further investigation may be useful to identify which patients are likely to improve, remain stable, or deteriorate between 3 months and 2 years

Implementing biomarkers to predict motor recovery after stroke

BACKGROUND: There is growing interest in using biomarkers to predict motor recovery and outcomes after stroke. The PREP2 algorithm combines clinical assessment with biomarkers in an algorithm, to predict upper limb functional outcomes for individual patients. To date, PREP2 is the first algorithm to be tested in clinical practice, and other biomarker-based algorithms are likely to follow. PURPOSE: This review considers how algorithms to predict motor recovery and outcomes after stroke might be implemented in clinical practice. FINDINGS: There are two tasks: first the prediction information needs to be obtained, and then it needs to be used. The barriers and facilitators of implementation are likely to differ for these tasks. We identify specific elements of the Consolidated Framework for Implementation Research that are relevant to each of these two tasks, using the PREP2 algorithm as an example. These include the characteristics of the predictors and algorithm, the clinical setting and its staff, and the healthcare environment. CONCLUSIONS: Active, theoretically underpinned implementation strategies are needed to ensure that biomarkers are successfully used in clinical practice for predicting motor outcomes after stroke, and should be considered in parallel with biomarker developmen

Genetic Diversity of PCR-Positive, Culture-Negative and Culture-Positive Mycobacterium ulcerans Isolated from Buruli Ulcer Patients in Ghana.

Culture of Mycobacterium ulcerans from Buruli ulcer patients has very low sensitivity. Thus confirmation of M. ulcerans infection is primarily based on PCR directed against IS2404. In this study we compare the genotypes obtained by variable number of tandem repeat analysis of DNA from IS2404-PCR positive cultures with that obtained from IS2404 positive, culture-negative tissue. A significantly greater genetic heterogeneity was found among culture-negative samples compared with that found in cultured strains but a single genotype is over-represented in both sample sets. This study provides evidence that both the focal location of bacteria in a lesion as well as differences in the ability to culture a particular genotype may underlie the low sensitivity of culture. Though preliminary, data from this work also suggests that mycobacteria previously associated with fish disease (M. pseudoshottsii) may be pathogenic for humans

Electron transfer ferredoxins with unusual cluster binding motifs support secondary metabolism in many bacteria

The proteins responsible for controlling electron transfer in bacterial secondary metabolism are not always known or characterised. Here we demonstrate that many bacteria contain a set of unfamiliar ferredoxin encoding genes which are associated with those of cytochrome P450 (CYP) monooxygenases and as such are involved in anabolic and catabolic metabolism. The model organism Mycobacterium marinum M contains eleven of these genes which encode [3Fe–4S] or [4Fe–4S] single cluster containing ferredoxins but which have unusual iron–sulfur cluster binding motif sequences, CXX?XXC(X)nCP, where ‘?’ indicates a variable amino acid residue. Rather than a cysteine residue, which is highly conserved in [4Fe–4S] clusters, or alanine or glycine residues, which are common in [3Fe–4S] ferredoxins, these genes encode at this position histidine, asparagine, tyrosine, serine, threonine or phenylalanine. We have purified, characterised and reconstituted the activity of several of these CYP/electron transfer partner systems and show that all those examined contain a [3Fe–4S] cluster. Furthermore, the ferredoxin used and the identity of the variable motif residue in these proteins affects the functionality of the monooxygenase system and has a significant influence on the redox properties of the ferredoxins. Similar ferredoxin encoding genes were identified across Mycobacterium species, including in the pathogenic M. tuberculosis and M. ulcerans, as well as in a wide range of other bacteria such as Rhodococcus and Streptomyces. In the majority of instances these are associated with CYP genes. These ferredoxin systems are important in controlling electron transfer across bacterial secondary metabolite production processes which include antibiotic and pigment formation among others

Mycobacterium ulcerans in Mosquitoes Captured during Outbreak of Buruli Ulcer, Southeastern Australia

Mosquitoes positive for M. ulcerans were linked to outbreaks of Buruli ulcer in humans

Aproximaciones metodológicas a la investigación en artes

La ciencia, entendida como saber científico, puede definirse como una forma de llegar al conocimiento. Pero ¿qué es realmente y cómo iniciarse en esta forma de trabajo? Este artículo expone algunas estrategias y orientaciones sobre cómo elaborar y planificar una investigación en artes, atendiendo a las actividades y conocimientos necesarios para desarrollarla. El objetivo principal es ayudar al estudiante que se dispone a dar sus primeros pasos en el camino de la investigación, por lo que se abordan algunas de las cuestiones más comunes entre los investigadores nóveles y que, con frecuencia, presentan dificultades notables, tales como: cuáles son los tipos de investigaciones en este ámbito, el posicionamiento teórico a adoptar por parte del investigador; la elección de una metodología o el procedimiento para recogida y análisis de datos, entre otras. Science, as a scientific knowledge, can be defined as a means to reach knowledge. Nevertheless, what is it actually and how can I get started with this work method? This article shows some strategies and orientations about elaborating and planning art investigations by paying attention to those activities and knowledge that are necessary to develop it. The main scope is helping the student who is trying to take their first steps in the investigation field; thus, some of the most frequent questions among novel investigators will be approached. In many occasions, these issues cause difficulties, such as: the type of investigations that can be found in this field; the theoretical position to be adopted by the investigator; or the selection of a method or a procedure to collect and analyse data, among many other

Single Nucleotide Polymorphism Typing of Mycobacterium ulcerans Reveals Focal Transmission of Buruli Ulcer in a Highly Endemic Region of Ghana

Buruli ulcer (BU) is an emerging necrotizing disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. While proximity to stagnant or slow flowing water bodies is a risk factor for acquiring BU, the epidemiology and mode of M. ulcerans transmission is poorly understood. Here we have used high-throughput DNA sequencing and comparisons of the genomes of seven M. ulcerans isolates that appeared monomorphic by existing typing methods. We identified a limited number of single nucleotide polymorphisms (SNPs) and developed a real-time PCR SNP typing method based on these differences. We then investigated clinical isolates of M. ulcerans on which we had detailed information concerning patient location and time of diagnosis. Within the Densu river basin of Ghana we observed dominance of one clonal complex and local clustering of some of the variants belonging to this complex. These results reveal focal transmission and demonstrate, that micro-epidemiological analyses by SNP typing has great potential to help us understand how M. ulcerans is transmitted

Task-Dependent Interaction between Parietal and Contralateral Primary Motor Cortex during Explicit versus Implicit Motor Imagery

Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks

Evolution of two distinct phylogenetic lineages of the emerging human pathogen Mycobacterium ulcerans

<p>Abstract</p> <p>Background</p> <p>Comparative genomics has greatly improved our understanding of the evolution of pathogenic mycobacteria such as <it>Mycobacterium tuberculosis</it>. Here we have used data from a genome microarray analysis to explore insertion-deletion (InDel) polymorphism among a diverse strain collection of <it>Mycobacterium ulcerans</it>, the causative agent of the devastating skin disease, Buruli ulcer. Detailed analysis of large sequence polymorphisms in twelve regions of difference (RDs), comprising irreversible genetic markers, enabled us to refine the phylogenetic succession within <it>M. ulcerans</it>, to define features of a hypothetical <it>M. ulcerans </it>most recent common ancestor and to confirm its origin from <it>Mycobacterium marinum</it>.</p> <p>Results</p> <p><it> M. ulcerans </it>has evolved into five InDel haplotypes that separate into two distinct lineages: (i) the "classical" lineage including the most pathogenic genotypes – those that come from Africa, Australia and South East Asia; and (ii) an "ancestral" <it>M. ulcerans </it>lineage comprising strains from Asia (China/Japan), South America and Mexico. The ancestral lineage is genetically closer to the progenitor <it>M. marinum </it>in both RD composition and DNA sequence identity, whereas the classical lineage has undergone major genomic rearrangements.</p> <p>Conclusion</p> <p>Results of the InDel analysis are in complete accord with recent multi-locus sequence analysis and indicate that <it>M. ulcerans </it>has passed through at least two major evolutionary bottlenecks since divergence from <it>M. marinum</it>. The classical lineage shows more pronounced reductive evolution than the ancestral lineage, suggesting that there may be differences in the ecology between the two lineages. These findings improve the understanding of the adaptive evolution and virulence of <it>M. ulcerans </it>and pathogenic mycobacteria in general and will facilitate the development of new tools for improved diagnostics and molecular epidemiology.</p