2,157 research outputs found

    Phylogenetic Relationship of the Complete Rauscher Murine Leukemia Virus Genome with Other Murine Leukemia Virus Genomes

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    AbstractWe report the complete nucleotide sequence of the genome of Rauscher murine leukemia virus (R-MuLV), the replication-competent helper virus present in the Rauscher virus complex, and its phylogenetic relationship with other murine leukemia virus genomes. An overall sequence identity of 97.6% was found between R-MuLV and the Friend helper virus (F-MuLV), and the two viruses were closely related on the phylogenetic trees constructed from eithergag, pol,orenvsequences. Moloney murine leukemia virus (Mo-MuLV) was the next closest relative to R-MuLV and F-MuLV on all trees, followed by Akv and radiation leukemia virus (RadLV). The most distantly related helper virus was Hortulanus murine leukemia virus (Ho-MuLV). Interestingly, Cas-Br-E branched with Mo-MuLV on thegagandpoltrees, whereas on theenvtree, it revealed the highest degree of relatedness to Ho-MuLV, possibly due to an ancient recombination with an Ho-MuLV ancestor. In summary, a phylogenetic analysis involving various MuLVs has been performed, in which the postulated close relationship between R-MuLV and F-MuLV has been confirmed, consistent with the pathobiology of the two viruses

    Hip abductor moment arm - a mathematical analysis for proximal femoral replacement

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    <p>Abstract</p> <p>Background</p> <p>Patients undergoing proximal femoral replacement for tumor resection often have compromised hip abductor muscles resulting in a Trendelenberg limp and hip instability. Commercially available proximal femoral prostheses offer several designs with varying sites of attachment for the abductor muscles, however, no analyses of these configurations have been performed to determine which design provides the longest moment arm for the hip abductor muscles during normal function.</p> <p>Methods</p> <p>This study analyzed hip abductor moment arm through hip adduction and abduction with a trigonometric mathematical model to evaluate the effects of alterations in anatomy and proximal femoral prosthesis design. Prosthesis dimensions were taken from technical schematics that were obtained from the prosthesis manufacturers. Manufacturers who contributed schematics for this investigation were Stryker Orthopaedics and Biomet.</p> <p>Results</p> <p>Superior and lateral displacement of the greater trochanter increased the hip abductor mechanical advantage for single-leg stance and adduction and preserved moment arm in the setting of Trendelenberg gait. Hip joint medialization resulted in less variance of the abductor moment arm through coronal motion. The Stryker GMRS endoprosthesis provided the longest moment arm in single-leg stance.</p> <p>Conclusions</p> <p>Hip abductor moment arm varies substantially throughout the hip's range of motion in the coronal plane. Selection of a proximal femur endoprosthesis with an abductor muscle insertion that is located superiorly and laterally will optimize hip abductor moment arm in single-leg stance compared to one located inferiorly or medially.</p

    Effects of gamma irradiation on the biomechanical properties of peroneus tendons

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    PURPOSE: This study was designed to investigate the biomechanical properties of nonirradiated (NI) and irradiated (IR) peroneus tendons to determine if they would be suitable allografts, in regards to biomechanical properties, for anterior cruciate ligament reconstruction after a dose of 1.5–2.5 Mrad. METHODS: Seven pairs of peroneus longus (PL) and ten pairs of peroneus brevis (PB) tendons were procured from human cadavers. The diameter of each allograft was measured. The left side of each allograft was IR at 1.5–2.5 Mrad, whereas the right side was kept aseptic and NI. The allografts were thawed, kept wet with saline, and attached in a single-strand fashion to custom freeze grips using liquid nitrogen. A preload of 10 N was then applied and, after it had reached steady state, the allografts were pulled at 4 cm/sec. The parameters recorded were the displacement and force. RESULTS: The elongation at the peak load was 10.3±2.3 mm for the PB NI side and 13.5±3.3 mm for the PB IR side. The elongation at the peak load was 17.4±5.3 mm for the PL NI side and 16.3±2.0 mm for the PL IR side. For PL, the ultimate load was 2,091.6±148.7 N for NI and 2,122.8±380.0 N for IR. The ultimate load for the PB tendons was 1,485.7±209.3 N for NI and 1,318.4±296.9 N for the IR group. The ultimate stress calculations for PL were 90.3±11.3 MPa for NI and 94.8±21.0 MPa for IR. For the PB, the ultimate stress was 82.4±19.0 MPa for NI and 72.5±16.6 MPa for the IR group. The structural stiffness was 216.1±59.0 N/mm for the NI PL and 195.7±51.4 N/mm for the IR side. None of these measures were significantly different between the NI and IR groups. The structural stiffness was 232.1±45.7 N/mm for the NI PB and 161.9±74.0 N/mm for the IR side, and this was the only statistically significant difference found in this study (P=0.034). CONCLUSION: Our statistical comparisons found no significant differences in terms of elongation, ultimate load, or ultimate stress between IR and NI PB and PL tendons. Only the PB structural stiffness was affected by irradiation. Thus, sterilizing allografts at 1.5–2.5 Mrad of gamma irradiation does not cause major alterations in the tendons’ biomechanical properties while still providing a suitable amount of sterilization for anterior cruciate ligament reconstruction

    Cells Isolated from Cadaveric Bone Marrow are Safe for Use in Bone Healing and Effective at Promoting Osteogenic Re-construction

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    The efficacy and immune-modulation of mesenchymal stem cells is well documented. The issue of obtaining mesenchymal stem cells without patient risk, extensive intra-operative procedure, cell manipulation or exposure of cells to harmful reagents remains an issue. This study was designed to test the viability, composition and osteogenic potential of cells derived from cadaveric bone marrow by a new process. Vertebral bone from cadavers was collected within 24 hours of death, processed by a new procedure of tumbling and collection, and evaluated for viability, marker expression, cell composition, and inflammatory properties at various stages of the isolation process and following cryopreservation. Viability was excellent in all fractions and at all stages of the study. Cell staining and microscopic observation showed increased erythrocyte content in the first tumble of bone for marrow extraction, as well as gross observation of debris. Cryopreservation favored the preservation of CD45-/CD105+ and GlycoA-/STRO-1+ mesenchymal stem cells at the expense of platelets, red blood cells, white blood cells and neutrophils. The resulting cell solution contains a percentage of mesenchymal stem cells far above that required for immune modulation. A mixed lymphocyte reaction assay showed no inflammatory response to this cell composition. The cells produced and preserved in this manner are viable, should elicit no immune response, suppress recipient immune responses and osteogenically differentiate

    Leukotriene antagonists as first-line or add-on asthma controller therapy

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    Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS: We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score =6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score =1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS: Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS: Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group

    Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

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    Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

    MRI T2 mapping assessment of T2 relaxation time in desmoid tumors as a quantitative imaging biomarker of tumor response: preliminary results

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    ObjectivesBecause size-based imaging criteria poorly capture biologic response in desmoid-type fibromatosis (DF), changes in MRI T2 signal intensity are frequently used as a response surrogate, but remain qualitative. We hypothesized that absolute quantification of DF T2 relaxation time derived from parametric T2 maps would be a feasible and effective imaging biomarker of disease activity.MethodsThis IRB-approved retrospective study included 11 patients with DF, managed by observation or systemic therapy, assessed by 3T MRI. Tumor maximum diameter, volume, and T2-weighted signal intensity were derived from manual tumor segmentations. Tumor:muscle T2 signal ratios were recorded. Two readers measured tumor T2 relaxation times using a commercial T2 scanning sequence, manual ROI delineation and commercial calculation software enabling estimation of reader reliability. Objective response rates based on RECIST1.1 and best responses were compared between size-based and signal-based parameters.ResultsMedian patient age was 52.6 years; 8 subjects were female (73%). Nine patients with longitudinal assessments were followed for an average of 314 days. Median baseline tumor diameter was 7.2 cm (range 4.4 - 18.2 cm). Median baseline T2 was 65.1 ms (range 40.4 - 94.8 ms, n=11); median at last follow-up was 44.3 ms (-32% from baseline; range 29.3 - 94.7 ms, n=9). T2 relaxation times correlated with tumor:muscle T2 signal ratios, Spearman p=0.78 (p&lt;0.001). T2 mapping showed high inter-reader reliability, ICC=0.84. The best response as a percentage change in T2 values was statistically significant (mean -17.9%, p=0.05, paired t-test) while change in diameter was not (mean -8.9%, p=0.12).ConclusionsAnalysis of T2 relaxation time maps of DF may offer a feasible quantitative biomarker for assessing the extent of response to treatment. This approach may have high inter-reader reliability
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