3,126 research outputs found

    Brain Injury Clubhouses

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    The National Institutes of Health (NIH) reported that the number of people living with permanent disability from brain injury grows annually as medical technology has advanced in life saving techniques. However, community-based programs which enable brain injury survivors to live productive lives throughout the entire course of recovery have not grown proportionately to meet this the need. Brain Injury Clubhouses were developed to address the need for coordinated, long-term, community-based supports for brain survivors in a community-based setting. Brain Injury Clubhouses are designed to improve the lives of persons with ABI and reduce strain on caregivers and healthcare services The information in this research brief is designed to provide funders, administrators, policy makers, and other stakeholders with an overview of Brain Injury Clubhouses. The brief also provides outcomes associated with participation in a Brain Injury Clubhouse from a recent research study to provide stakeholders with a better understanding of Brain Injury Clubhouses

    Multiaxial pulsatile dynamics of the thoracic aorta and impact of thoracic endovascular repair

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    Purpose: The thoracic aorta is a highly mobile organ whose dynamics are altered by thoracic endovascular aorta repair (TEVAR). The aim of this study was to quantify cardiac pulsatility-induced multi-axial deformation of the thoracic aorta before and after descending aortic TEVAR. Methods: Eleven TEVAR patients (8 males and 3 females, age 57–89) underwent retrospective cardiac-gated CT angiography before and after TEVAR. 3D geometric models of the thoracic aorta were constructed, and lumen centerlines, inner and outer surface curves, and cross-sections were extracted to measure aortic arclength, centerline, inner surface, and outer surface longitudinal curvatures, as well as cross-sectional effective diameter and eccentricity for the ascending and stented aortic portions. Results: From pre- to post-TEVAR, arclength deformation was increased at the ascending aorta from 5.9 \ub1 3.1 % to 8.8 \ub1 4.4 % (P < 0.05), and decreased at the stented aorta from 7.5 \ub1 5.1 % to 2.7 \ub1 2.5 % (P < 0.05). Longitudinal curvature and diametric deformations were reduced at the stented aorta. Centerline curvature, inner surface curvature, and cross-sectional eccentricity deformations were increased at the distal ascending aorta. Conclusions: Deformations were reduced in the stented thoracic aorta after TEVAR, but increased in the ascending aorta near the aortic arch, possibly as a compensatory mechanism to maintain overall thoracic compliance in the presence of reduced deformation in the stiffened stented aorta

    Influence of Thoracic Endovascular Aortic Repair on True Lumen Helical Morphology for Stanford Type B Dissections

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    Objective: Thoracic endovascular aortic repair (TEVAR) can change the morphology of the flow lumen in aortic dissections, which may affect aortic hemodynamics and function. This study characterizes how the helical morphology of the true lumen in type B aortic dissections is altered by TEVAR. Methods: Patients with type B aortic dissection who underwent computed tomography angiography before and after TEVAR were retrospectively reviewed. Images were used to construct three-dimensional stereolithographic surface models of the true lumen and whole aorta using custom software. Stereolithographic models were segmented and co-registered to determine helical morphology of the true lumen with respect to the whole aorta. The true lumen region covered by the endograft was defined based on fiducial markers before and after TEVAR. The helical angle, average helical twist, peak helical twist, and cross-sectional eccentricity, area, and circumference were quantified in this region for pre- and post-TEVAR geometries. Results: Sixteen patients (61.3 \ub1 8.0 years; 12.5% female) were treated successfully for type B dissection (5 acute and 11 chronic) with TEVAR and scans before and after TEVAR were retrospectively obtained (follow-up interval 52 \ub1 91 days). From before to after TEVAR, the true lumen helical angle (–70.0 \ub1 71.1 to –64.9 \ub1 75.4\ub0; P =.782), average helical twist (–4.1 \ub1 4.0 to –3.7 \ub1 3.8\ub0/cm; P =.674), and peak helical twist (–13.2 \ub1 15.2 to –15.4 \ub1 14.2\ub0/cm; P =.629) did not change. However, the true lumen helical radius (1.4 \ub1 0.5 to 1.0 \ub1 0.6 cm; P <.05) and eccentricity (0.9 \ub1 0.1 to 0.7 \ub1 0.1; P <.05) decreased, and the cross-sectional area (3.0 \ub1 1.1 to 5.0 \ub1 2.0 cm2; P <.05) and circumference (7.1 \ub1 1.0 to 8.0 \ub1 1.4 cm; P <.05) increased significantly from before to after TEVAR. The distinct bimodal distribution of chiral and achiral native dissections disappeared after TEVAR, and subgroup analyses showed that the true lumen circumference of acute dissections increased with TEVAR, although it did not for chronic dissections. Conclusions: The unchanged helical angle and average and peak helical twists as a result of TEVAR suggest that the angular positions of the true lumen are constrained and that the endografts were helically conformable in the angular direction. The decrease of helical radius indicated a straightening of the corkscrew shape of the true lumen, and in combination with more circular and expanded lumen cross-sections, TEVAR produced luminal morphology that theoretically allows for lower flow resistance through the endografted portion. The impact of TEVAR on dissection flow lumen morphology and the interaction between endografts and aortic tissue can provide insight for improving device design, implantation technique, and long-term clinical outcomes

    Definition of Tubular Anatomic Structures from Arbitrary Stereo Lithographic Surface

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    An accurate description of anatomies and dynamics of vessels is crucial to understand their characteristics and improve surgical techniques, thus it is the basis, in addition to surgeon experience, on which stent design and operation procedures rely. The process of producing this description is user intensive, and recent improvement in image processing of medical3D imaging allows for a more automated workflow. However, there is a need to bridge the gap from a processed geometry to a robust mathematical computational grid. By sequentially segmenting a tubular anatomic structure, here defined by a stereo lithographic (STL) surface, an initial centerline is formed by connecting centroids of orthogonal cross-sectional contours along the length of the structure. Relying on the initial centerline, a set of non-overlapping 2D cross sectional contours are defined along the centerline, a centerline which is updated after the 2D contours are produced. After a second iteration of producing 2D contours and updating the centerline, a full description of the structure is created. Our method for describing vessel geometry shows good coherence to existing method. The main advantages of our method include the possibility of having arbitrary triangulated STL surface input, automated centerline definition, safety against intersecting cross-sectional contours and automatic clean-up of local kinks and wrinkles

    Mechanism of Ad5 Vaccine Immunity and Toxicity: Fiber Shaft Targeting of Dendritic Cells

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    Recombinant adenoviral (rAd) vectors elicit potent cellular and humoral immune responses and show promise as vaccines for HIV-1, Ebola virus, tuberculosis, malaria, and other infections. These vectors are now widely used and have been generally well tolerated in vaccine and gene therapy clinical trials, with many thousands of people exposed. At the same time, dose-limiting adverse responses have been observed, including transient low-grade fevers and a prior human gene therapy fatality, after systemic high-dose recombinant adenovirus serotype 5 (rAd5) vector administration in a human gene therapy trial. The mechanism responsible for these effects is poorly understood. Here, we define the mechanism by which Ad5 targets immune cells that stimulate adaptive immunity. rAd5 tropism for dendritic cells (DCs) was independent of the coxsackievirus and adenovirus receptor (CAR), its primary receptor or the secondary integrin RGD receptor, and was mediated instead by a heparin-sensitive receptor recognized by a distinct segment of the Ad5 fiber, the shaft. rAd vectors with CAR and RGD mutations did not infect a variety of epithelial and fibroblast cell types but retained their ability to transfect several DC types and stimulated adaptive immune responses in mice. Notably, the pyrogenic response to the administration of rAd5 also localized to the shaft region, suggesting that this interaction elicits both protective immunity and vector-induced fevers. The ability of replication-defective rAd5 viruses to elicit potent immune responses is mediated by a heparin-sensitive receptor that interacts with the Ad5 fiber shaft. Mutant CAR and RGD rAd vectors target several DC and mononuclear subsets and induce both adaptive immunity and toxicity. Understanding of these interactions facilitates the development of vectors that target DCs through alternative receptors that can improve safety while retaining the immunogenicity of rAd vaccines

    Structural probing of the HIV-1 polypurine tract RNA:DNA hybrid using classic nucleic acid ligands

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    The interactions of archetypical nucleic acid ligands with the HIV-1 polypurine tract (PPT) RNA:DNA hybrid, as well as analogous DNA:DNA, RNA:RNA and swapped hybrid substrates, were used to probe structural features of the PPT that contribute to its specific recognition and processing by reverse transcriptase (RT). Results from intercalative and groove-binding ligands indicate that the wild-type PPT hybrid does not contain any strikingly unique groove geometries and/or stacking arrangements that might contribute to the specificity of its interaction with RT. In contrast, neomycin bound preferentially and selectively to the PPT near the 5′(rA)4:(dT)4 tract and the 3′ PPT-U3 junction. Nuclear magnetic resonance data from a complex between HIV-1 RT and the PPT indicate RT contacts within the same regions highlighted on the PPT by neomycin. These observations, together with the fact that the sites are correctly spaced to allow interaction with residues in the ribonuclease H (RNase H) active site and thumb subdomain of the p66 RT subunit, suggest that despite the long cleft employed by RT to make contact with nucleic acids substrates, these sites provide discrete binding units working in concert to determine not only specific PPT recognition, but also its orientation on the hybrid structure

    Exploring structural variation and gene family architecture with De Novo assemblies of 15 Medicago genomes

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    Abstract Background Previous studies exploring sequence variation in the model legume, Medicago truncatula, relied on mapping short reads to a single reference. However, read-mapping approaches are inadequate to examine large, diverse gene families or to probe variation in repeat-rich or highly divergent genome regions. De novo sequencing and assembly of M. truncatula genomes enables near-comprehensive discovery of structural variants (SVs), analysis of rapidly evolving gene families, and ultimately, construction of a pan-genome. Results Genome-wide synteny based on 15 de novo M. truncatula assemblies effectively detected different types of SVs indicating that as much as 22% of the genome is involved in large structural changes, altogether affecting 28% of gene models. A total of 63 million base pairs (Mbp) of novel sequence was discovered, expanding the reference genome space for Medicago by 16%. Pan-genome analysis revealed that 42% (180 Mbp) of genomic sequences is missing in one or more accession, while examination of de novo annotated genes identified 67% (50,700) of all ortholog groups as dispensable – estimates comparable to recent studies in rice, maize and soybean. Rapidly evolving gene families typically associated with biotic interactions and stress response were found to be enriched in the accession-specific gene pool. The nucleotide-binding site leucine-rich repeat (NBS-LRR) family, in particular, harbors the highest level of nucleotide diversity, large effect single nucleotide change, protein diversity, and presence/absence variation. However, the leucine-rich repeat (LRR) and heat shock gene families are disproportionately affected by large effect single nucleotide changes and even higher levels of copy number variation. Conclusions Analysis of multiple M. truncatula genomes illustrates the value of de novo assemblies to discover and describe structural variation, something that is often under-estimated when using read-mapping approaches. Comparisons among the de novo assemblies also indicate that different large gene families differ in the architecture of their structural variation

    Constraints on Type Ib/c and GRB Progenitors

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    Although there is strong support for the collapsar engine as the power source of long-duration gamma-ray bursts (GRBs), we still do not definitively know the progenitor of these explosions. Here we review the current set of progenitor scenarios for long-duration GRBs and the observational constraints on these scenarios. Examining these, we find that single-star models cannot be the only progenitor for long-duration GRBs. Several binary progenitors can match the solid observational constraints and also have the potential to match the trends we are currently seeing in the observations. Type Ib/c supernovae are also likely to be produced primarily in binaries; we discuss the relationship between the progenitors of these explosions and those of the long-duration GRBs.Comment: 36 pages, 6 figure

    CAHM, a long non-coding RNA gene hypermethylated in colorectal neoplasia

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    Copyright © 2014 Landes Bioscience This is an open-access article licensed under a Creative Commons Attribution 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. Permission is granted subject to the terms of the License under which the work was published. Please check the License conditions for the work which you wish to reuse. Full and appropriate attribution must be given. This permission does not cover any third party copyrighted material which may appear in the work requested.The CAHM gene (Colorectal Adenocarcinoma HyperMethylated), previously LOC 100526820, is located on chromosome 6, hg19 chr6:163 834 097–163 834 982. It lacks introns, encodes a long non-coding RNA (lncRNA) and is located adjacent to the gene QKI, which encodes an RNA binding protein. Deep bisulphite sequencing of ten colorectal cancer (CRC ) and matched normal tissues demonstrated frequent hypermethylation within the CAHM gene in cancer. A quantitative methylation-specific PCR (qMSP ) was used to characterize additional tissue samples. With a threshold of 5% methylation, the CAHM assay was positive in 2/26 normal colorectal tissues (8%), 17/21 adenomas (81%), and 56/79 CRC samples (71%). A reverse transcriptase-qPCR assay showed that CAHM RNA levels correlated negatively with CAHM % methylation, and therefore CAHM gene expression is typically decreased in CRC . The CAHM qMSP assay was applied to DNA isolated from plasma specimens from 220 colonoscopy-examined patients. Using a threshold of 3 pg methylated genomic DNA per mL plasma, methylated CAHM sequences were detected in the plasma DNA of 40/73 (55%) of CRC patients compared with 3/73 (4%) from subjects with adenomas and 5/74 (7%) from subjects without neoplasia. Both the frequency of detection and the amount of methylated CAHM DNA released into plasma increased with increasing cancer stage. Methylated CAHM DNA shows promise as a plasma biomarker for use in screening for CRC

    A genetically modified adenoviral vector with a phage display-derived peptide incorporated into fiber fibritin chimera prolongs survival in experimental glioma

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    The dismal clinical context of advanced-grade glioma demands the development of novel therapeutic strategies with direct patient impact. Adenovirus-mediated virotherapy represents a potentially effective approach for glioma therapy. In this research, we generated a novel glioma-specific adenovirus by instituting more advanced genetic modifications that can maximize the efficiency and safety of therapeutic adenoviral vectors. In this regard, a glioma-specific targeted fiber was developed through the incorporation of previously published glioma-specific, phage-panned peptide (VWT peptide) on a fiber fibritin-based chimeric fiber, designated as “GliomaFF.” We showed that the entry of this virus was highly restricted to glioma cells, supporting the specificity imparted by the phage-panned peptide. In addition, the stability of the targeting moiety presented by fiber fibritin structure permitted greatly enhanced infectivity. Furthermore, the replication of this virus was restricted in glioma cells by controlling expression of the E1 gene under the activity of the tumor-specific survivin promoter. Using this approach, we were able to explore the combinatorial efficacy of various adenoviral modifications that could amplify the specificity, infectivity, and exclusive replication of this therapeutic adenovirus in glioma. Finally, virotherapy with this modified virus resulted in up to 70% extended survival in an in vivo murine glioma model. These data demonstrate that this novel adenoviral vector is a safe and efficient treatment for this difficult malignancy
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