47 research outputs found

    Treatment of hallux valgus by modified McBride procedure: a 6-year follow-up

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    PubMed ID: 20505975Background Surgical decision-making was reevaluated by comparison with an algorithm designed to analyze treatment of hallux valgus deformities. Materials and methods A modified McBride procedure was performed on 52 feet of 35 patients with hallux valgusdeformity. From this series, 36 feet of 21 patients were evaluated preoperatively, early postoperatively, and late postoperatively by means of subjective evaluation and clinical and radiological findings. Results The hallux valgus angle preoperatively, early postoperatively, and late postoperatively was 32.7 ± 8.5°, 10.1 ± 6.9°, and 20.6 ± 9.5°, respectively. Hallux valgus recurrence of 72.2% was observed. Subjective results were better and the patients rated their satisfaction with the procedure as excellent or high in 23 cases (63.9%) and moderate, low, or unsatisfactory in 13 cases (36.1%). Conclusions This level of patient satisfaction demonstrates that the McBride procedure is an efficient approach for eliminating pain due to hallux valgus deformity. © The Author(s) 2010

    Treatment of hallux valgus by modified McBride procedure: a 6-year follow-up

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    PubMed ID: 20505975Background Surgical decision-making was reevaluated by comparison with an algorithm designed to analyze treatment of hallux valgus deformities. Materials and methods A modified McBride procedure was performed on 52 feet of 35 patients with hallux valgusdeformity. From this series, 36 feet of 21 patients were evaluated preoperatively, early postoperatively, and late postoperatively by means of subjective evaluation and clinical and radiological findings. Results The hallux valgus angle preoperatively, early postoperatively, and late postoperatively was 32.7 ± 8.5°, 10.1 ± 6.9°, and 20.6 ± 9.5°, respectively. Hallux valgus recurrence of 72.2% was observed. Subjective results were better and the patients rated their satisfaction with the procedure as excellent or high in 23 cases (63.9%) and moderate, low, or unsatisfactory in 13 cases (36.1%). Conclusions This level of patient satisfaction demonstrates that the McBride procedure is an efficient approach for eliminating pain due to hallux valgus deformity. © The Author(s) 2010

    Detailed Regulatory Mechanism of the Interaction between ZO-1 PDZ2 and Connexin43 Revealed by MD Simulations

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    The gap junction protein connexin43 (Cx43) binds to the second PDZ domain of Zonula occludens-1 (ZO-1) through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9) and Ser (-10) of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD) simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9) significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation

    PDZ domains and their binding partners: structure, specificity, and modification

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    PDZ domains are abundant protein interaction modules that often recognize short amino acid motifs at the C-termini of target proteins. They regulate multiple biological processes such as transport, ion channel signaling, and other signal transduction systems. This review discusses the structural characterization of PDZ domains and the use of recently emerging technologies such as proteomic arrays and peptide libraries to study the binding properties of PDZ-mediated interactions. Regulatory mechanisms responsible for PDZ-mediated interactions, such as phosphorylation in the PDZ ligands or PDZ domains, are also discussed. A better understanding of PDZ protein-protein interaction networks and regulatory mechanisms will improve our knowledge of many cellular and biological processes

    Nuclear Factor-Kappa B Family Member RelB Inhibits Human Immunodeficiency Virus-1 Tat-Induced Tumor Necrosis Factor-Alpha Production

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    Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorder (HAND) is likely neuroinflammatory in origin, believed to be triggered by inflammatory and oxidative stress responses to cytokines and HIV protein gene products such as the HIV transactivator of transcription (Tat). Here we demonstrate increased messenger RNA for nuclear factor-kappa B (NF-κB) family member, transcription factor RelB, in the brain of doxycycline-induced Tat transgenic mice, and increased RelB synthesis in Tat-exposed microglial cells. Since genetic ablation of RelB in mice leads to multi-organ inflammation, we hypothesized that Tat-induced, newly synthesized RelB inhibits cytokine production by microglial cells, possibly through the formation of transcriptionally inactive RelB/RelA complexes. Indeed, tumor necrosis factor-alpha (TNFα) production in monocytes isolated from RelB deficient mice was significantly higher than in monocytes isolated from RelB expressing controls. Moreover, RelB overexpression in microglial cells inhibited Tat-induced TNFα synthesis in a manner that involved transcriptional repression of the TNFα promoter, and increased phosphorylation of RelA at serine 276, a prerequisite for increased RelB/RelA protein interactions. The Rel-homology-domain within RelB was necessary for this interaction. Overexpression of RelA itself, in turn, significantly increased TNFα promoter activity, an effect that was completely blocked by RelB overexpression. We conclude that RelB regulates TNFα cytokine synthesis by competitive interference binding with RelA, which leads to downregulation of TNFα production. Moreover, because Tat activates both RelB and TNFα in microglia, and because Tat induces inflammatory TNFα synthesis via NF-κB, we posit that RelB serves as a cryoprotective, anti-inflammatory, counter-regulatory mechanism for pathogenic NF-κB activation. These findings identify a novel regulatory pathway for controlling HIV-induced microglial activation and cytokine production that may have important therapeutic implications for the management of HAND

    Four Regional Marine Biodiversity Studies: Approaches and Contributions to Ecosystem-Based Management

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    We compare objectives and approaches of four regional studies of marine biodiversity: Gulf of Maine Area Census of Marine Life, Baltic Sea History of Marine Animal Populations, Great Barrier Reef Seabed Biodiversity Project, and Gulf of Mexico Biodiversity Project. Each program was designed as an "ecosystem" scale but was created independently and executed differently. Each lasted 8 to 10 years, including several years to refine program objectives, raise funding, and develop research networks. All resulted in improved baseline data and in new, or revised, data systems. Each contributed to the creation or evolution of interdisciplinary teams, and to regional, national, or international science-management linkages. To date, there have been differing extents of delivery and use of scientific information to and by management, with greatest integration by the program designed around specific management questions. We evaluate each research program's relative emphasis on three principal elements of biodiversity organization: composition, structure, and function. This approach is used to analyze existing ecosystem-wide biodiversity knowledge and to assess what is known and where gaps exist. In all four of these systems and studies, there is a relative paucity of investigation on functional elements of biodiversity, when compared with compositional and structural elements. This is symptomatic of the current state of the science. Substantial investment in understanding one or more biodiversity element(s) will allow issues to be addressed in a timely and more integrative fashion. Evaluating research needs and possible approaches across specific elements of biodiversity organization can facilitate planning of future studies and lead to more effective communication between scientists, managers, and stakeholders. Building a general approach that captures how various studies have focused on different biodiversity elements can also contribute to meta-analyses of worldwide experience in scientific research to support ecosystem-based management
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