Critical Period After Stroke Study (CPASS): A phase II clinical trial testing an optimal time for motor recovery after stroke in humans

Restoration of human brain function after injury is a signal challenge for translational neuroscience. Rodent stroke recovery studies identify an optimal or sensitive period for intensive motor training after stroke: near-full recovery is attained if task-specific motor training occurs during this sensitive window. We extended these findings to adult humans with stroke in a randomized controlled trial applying the essential elements of rodent motor training paradigms to humans. Stroke patients were adaptively randomized to begin 20 extra hours of self-selected, task-specific motor therapy at ≤30 d (acute), 2 to 3 mo (subacute), or ≥6 mo (chronic) after stroke, compared with controls receiving standard motor rehabilitation. Upper extremity (UE) impairment assessed by the Action Research Arm Test (ARAT) was measured at up to five time points. The primary outcome measure was ARAT recovery over 1 y after stroke. By 1 y we found significantly increased UE motor function in the subacute group compared with controls (ARAT difference = +6.87 ± 2.63, P = 0.009). The acute group compared with controls showed smaller but significant improvement (ARAT difference = +5.25 ± 2.59 points, P = 0.043). The chronic group showed no significant improvement compared with controls (ARAT = +2.41 ± 2.25, P = 0.29). Thus task-specific motor intervention was most effective within the first 2 to 3 mo after stroke. The similarity to rodent model treatment outcomes suggests that other rodent findings may be translatable to human brain recovery. These results provide empirical evidence of a sensitive period for motor recovery in humans

Owning an overweight or underweight body: distinguishing the physical, experienced and virtual body

Our bodies are the most intimately familiar objects we encounter in our perceptual environment. Virtual reality provides a unique method to allow us to experience having a very different body from our own, thereby providing a valuable method to explore the plasticity of body representation. In this paper, we show that women can experience ownership over a whole virtual body that is considerably smaller or larger than their physical body. In order to gain a better understanding of the mechanisms underlying body ownership, we use an embodiment questionnaire, and introduce two new behavioral response measures: an affordance estimation task (indirect measure of body size) and a body size estimation task (direct measure of body size). Interestingly, after viewing the virtual body from first person perspective, both the affordance and the body size estimation tasks indicate a change in the perception of the size of the participant’s experienced body. The change is biased by the size of the virtual body (overweight or underweight). Another novel aspect of our study is that we distinguish between the physical, experienced and virtual bodies, by asking participants to provide affordance and body size estimations for each of the three bodies separately. This methodological point is important for virtual reality experiments investigating body ownership of a virtual body, because it offers a better understanding of which cues (e.g. visual, proprioceptive, memory, or a combination thereof) influence body perception, and whether the impact of these cues can vary between different setups

Trigger finger: etiology, evaluation, and treatment

Trigger finger is a common finger aliment, thought to be caused by inflammation and subsequent narrowing of the A1 pulley, which causes pain, clicking, catching, and loss of motion of the affected finger. Although it can occur in anyone, it is seen more frequently in the diabetic population and in women, typically in the fifth to sixth decade of life. The diagnosis is usually fairly straightforward, as most patients complain of clicking or locking of the finger, but other pathological processes such as fracture, tumor, or other traumatic soft tissue injuries must be excluded. Treatment modalities, including splinting, corticosteroid injection, or surgical release, are very effective and are tailored to the severity and duration of symptoms

A Human-Curated Annotation of the Candida albicans Genome

Recent sequencing and assembly of the genome for the fungal pathogen Candida albicans used simple automated procedures for the identification of putative genes. We have reviewed the entire assembly, both by hand and with additional bioinformatic resources, to accurately map and describe 6,354 genes and to identify 246 genes whose original database entries contained sequencing errors (or possibly mutations) that affect their reading frame. Comparison with other fungal genomes permitted the identification of numerous fungus-specific genes that might be targeted for antifungal therapy. We also observed that, compared to other fungi, the protein-coding sequences in the C. albicans genome are especially rich in short sequence repeats. Finally, our improved annotation permitted a detailed analysis of several multigene families, and comparative genomic studies showed that C. albicans has a far greater catabolic range, encoding respiratory Complex 1, several novel oxidoreductases and ketone body degrading enzymes, malonyl-CoA and enoyl-CoA carriers, several novel amino acid degrading enzymes, a variety of secreted catabolic lipases and proteases, and numerous transporters to assimilate the resulting nutrients. The results of these efforts will ensure that the Candida research community has uniform and comprehensive genomic information for medical research as well as for future diagnostic and therapeutic applications

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Rapid outbreak sequencing of Ebola virus in Sierra Leone identifies transmission chains linked to sporadic cases.

To end the largest known outbreak of Ebola virus disease (EVD) in West Africa and to prevent new transmissions, rapid epidemiological tracing of cases and contacts was required. The ability to quickly identify unknown sources and chains of transmission is key to ending the EVD epidemic and of even greater importance in the context of recent reports of Ebola virus (EBOV) persistence in survivors. Phylogenetic analysis of complete EBOV genomes can provide important information on the source of any new infection. A local deep sequencing facility was established at the Mateneh Ebola Treatment Centre in central Sierra Leone. The facility included all wetlab and computational resources to rapidly process EBOV diagnostic samples into full genome sequences. We produced 554 EBOV genomes from EVD cases across Sierra Leone. These genomes provided a detailed description of EBOV evolution and facilitated phylogenetic tracking of new EVD cases. Importantly, we show that linked genomic and epidemiological data can not only support contact tracing but also identify unconventional transmission chains involving body fluids, including semen. Rapid EBOV genome sequencing, when linked to epidemiological information and a comprehensive database of virus sequences across the outbreak, provided a powerful tool for public health epidemic control efforts