Percutaneous revascularization for the treatment of refractory digital ischemia in systemic sclerosis

OBJECTIVE: The objective of this study is to explore the role of adjunctive percutaneous revascularization of the hand in the management of patients with systemic sclerosis-associated refractory digital ischemia. METHODS: We present our initial experience of using percutaneous upper extremity interventions to treat patients with systemic sclerosis and symptomatic Raynaud\u27s phenomenon who presented with either refractory digital ischemia or non-healing ulcers. We discuss patient characteristics, procedural findings, and short-term clinical outcomes of these interventions. RESULTS: We performed 14 interventions in 6 patients with non-healing digital ulcers or refractory ischemia secondary to systemic sclerosis. Angioplasty was performed at or below the wrist in conjunction with intravenous prostaglandin therapy, started prior to or immediately after the revascularization procedure. All patients experienced symptomatic relief and demonstrated accelerated wound healing. Two patients required an additional procedure to treat recurrent ischemia (without new ulceration) in the treated digit. Three of the patients underwent multiple procedures during the study period to treat new ischemic lesions or Raynaud\u27s phenomenon symptoms, highlighting the progressive nature of the vascular occlusions in systemic sclerosis. There were no adverse events related to the interventions. CONCLUSIONS: Our retrospective analysis suggests that percutaneous revascularization in combination with vasodilator therapy in systemic sclerosis-associated digital ischemia is safe and can facilitate the healing of long-standing ulcers. Its role in the management of refractory digital ischemia in patients with systemic sclerosis should be explored further

Are Split Tablet Keyboards Better? A Study of Soft Keyboard Layout and Hand Posture

acceptedVersio

Mas-related G-protein–coupled receptors inhibit pathological pain in mice

An important objective of pain research is to identify novel drug targets for the treatment of pathological persistent pain states, such as inflammatory and neuropathic pain. Mas-related G-protein–coupled receptors (Mrgprs) represent a large family of orphan receptors specifically expressed in small-diameter nociceptive primary sensory neurons. To determine the roles of Mrgprs in persistent pathological pain states, we exploited a mouse line in which a chromosomal locus spanning 12 Mrgpr genes was deleted (KO). Initial studies indicated that these KO mice show prolonged mechanical- and thermal-pain hypersensitivity after hind-paw inflammation compared with wild-type littermates. Here, we show that this mutation also enhances the windup response of dorsal-horn wide dynamic-range neurons, an electrophysiological model for the triggering of central pain sensitization. Deletion of the Mrgpr cluster also blocked the analgesic effect of intrathecally applied bovine adrenal medulla peptide 8–22 (BAM 8–22), an MrgprC11 agonist, on both inflammatory heat hyperalgesia and neuropathic mechanical allodynia. Spinal application of bovine adrenal medulla peptide 8–22 also significantly attenuated windup in wild-type mice, an effect eliminated in KO mice. These data suggest that members of the Mrgpr family, in particular MrgprC11, may constitute an endogenous inhibitory mechanism for regulating persistent pain in mice. Agonists for these receptors may, therefore, represent a class of antihyperalgesics for treating persistent pain with minimal side effects because of the highly specific expression of their targets

Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements

Physical interactions between genetic elements located throughout the genome play important roles in gene regulation and can be identified with the Chromosome Conformation Capture (3C) methodology. 3C converts physical chromatin interactions into specific ligation products, which are quantified individually by PCR. Here we present a high-throughput 3C approach, 3C-Carbon Copy (5C), that employs microarrays or quantitative DNA sequencing using 454-technology as detection methods. We applied 5C to analyze a 400-kb region containing the human beta-globin locus and a 100-kb conserved gene desert region. We validated 5C by detection of several previously identified looping interactions in the beta-globin locus. We also identified a new looping interaction in K562 cells between the beta-globin Locus Control Region and the gamma-beta-globin intergenic region. Interestingly, this region has been implicated in the control of developmental globin gene switching. 5C should be widely applicable for large-scale mapping of cis- and trans- interaction networks of genomic elements and for the study of higher-order chromosome structure

Investigating student teachers’ presentations of literacy and literacy pedagogy in a complex context

The field of literacy and primary literacy education is patterned by multiple discourses and this raises challenges for those educating the next generation of primary literacy teachers. In England, the last 15 years have seen considerable levels of prescription in the primary literacy curriculum and compliance by the school and teacher education sectors has been enforced through demanding accountability regimes. In this paper, the authors draw on findings of a small-scale interview study to consider how understandings of literacies associated with different contexts may or may not inflect student teachers’ orientations towards literacy provision in school. The authors explore how five student teachers presented their experiences of literacy within and beyond the classroom and how they seemed to position themselves in relation to literacy pedagogy. The authors focus particularly on continuities and discontinuities between literacies in the student teachers’ personal and professional lives, and on tensions they identified between the teachers they felt they wanted to, and were expected to, become. Reflecting on this work, the authors consider how they can best equip pre-service primary and early years teachers to develop as critical reflective literacy practitioners in the current context

Genome-Wide Analysis of Subependymomas Shows Underlying Chromosomal Copy Number Changes Involving Chromosomes 6, 7, 8 and 14 in a Proportion of Cases

Subependymomas (SE) are slow-growing brain tumors that tend to occur within the ventricles of middle-aged and elderly adults. The World Health Organization classifies these tumors within the ependymoma group. Previous limited analysis of this tumor type had not revealed significant underlying cytogenetic abnormalities

A Dutch validation study of the Multiple Sclerosis Work difficulties questionnaire in relapsing remitting multiple sclerosis

Health and self-regulatio

High-Resolution Description of Antibody Heavy-Chain Repertoires in Humans

Antibodies' protective, pathological, and therapeutic properties result from their considerable diversity. This diversity is almost limitless in potential, but actual diversity is still poorly understood. Here we use deep sequencing to characterize the diversity of the heavy-chain CDR3 region, the most important contributor to antibody binding specificity, and the constituent V, D, and J segments that comprise it. We find that, during the stepwise D-J and then V-DJ recombination events, the choice of D and J segments exert some bias on each other; however, we find the choice of the V segment is essentially independent of both. V, D, and J segments are utilized with different frequencies, resulting in a highly skewed representation of VDJ combinations in the repertoire. Nevertheless, the pattern of segment usage was almost identical between two different individuals. The pattern of V, D, and J segment usage and recombination was insufficient to explain overlap that was observed between the two individuals' CDR3 repertoires. Finally, we find that while there are a near-infinite number of heavy-chain CDR3s in principle, there are about 3–9 million in the blood of an adult human being