542 research outputs found

    Correction: Effect of an Inpatient Rehabilitation Program for Recovery of Deconditioning in Hematologic Cancer Patients After Chemotherapy

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    Objective To investigate the effect of a rehabilitation program in terms of De Morton Mobility Index (DEMMI) score, in hematologic cancer patients after chemotherapy. Methods Hematologic cancer patients admitted for chemotherapy were reviewed. They received a rehabilitation program during their hospital stay. DEMMI score measurement was performed, before and after rehabilitation. Demographics, diagnosis, chemotherapy information, rehabilitation program duration, mortality, body mass index (BMI), and laboratory test results were collected. For analysis, patients were classified according to diagnosis (multiple myeloma, leukemia, and others), mortality, and additional chemotherapy. Results There was statistically significant improvement in DEMMI score of 10.1 points (95% confidence interval, 5.9–14.3) after rehabilitation. It was more evident in the multiple myeloma group, and they revealed less mortality. When patients were divided according to mortality, survivors received the program earlier, and in a shorter period than in mortality cases. Although survivors revealed higher initial DEMMI score, improvement after rehabilitation did not differ significantly. Conclusion In hematologic cancer patients, rehabilitation program was effective for recovery from deconditioning, revealing significant increase in DEMMI score. Multiple myeloma patients may be good candidates for rehabilitation. Rehabilitation could be sustained during chemotherapy and for high-risk patients

    The management of type 2 diabetes with fixed‐ratio combination insulin degludec/liraglutide (IDegLira) versus basal‐bolus therapy (insulin glargine U100 plus insulin aspart): a short‐term cost‐effectiveness analysis in the UK setting

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    Aim: To evaluate the cost‐effectiveness of IDegLira versus basal‐bolus therapy (BBT) with insulin glargine U100 plus up to 4 times daily insulin aspart for the management of type 2 diabetes in the UK. Methods: A Microsoft Excel model was used to evaluate the cost‐utility of IDegLira versus BBT over a 1‐year time horizon. Clinical input data were taken from the treat‐to‐target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (HbA1c <7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar HbA1c reductions. Costs (expressed in GBP) and event‐related disutilities were taken from published sources. Extensive sensitivity analyses were performed. Results: IDegLira was associated with an improvement of 0.05 quality‐adjusted life years (QALYs) versus BBT, due to reductions in non‐severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost‐effectiveness ratio (ICER) of GBP 5924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20 000 per QALY gained across a range of sensitivity analyses. Conclusions: IDegLira is a cost‐effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK

    Electrically Robust Single-Crystalline WTe2 Nanobelts for Nanoscale Electrical Interconnects

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    As the elements of integrated circuits are downsized to the nanoscale, the current Cu-based interconnects are facing limitations due to increased resistivity and decreased current-carrying capacity because of scaling. Here, the bottom-up synthesis of single-crystalline WTe2 nanobelts and low- and high-field electrical characterization of nanoscale interconnect test structures in various ambient conditions are reported. Unlike exfoliated flakes obtained by the top-down approach, the bottom-up growth mode of WTe2 nanobelts allows systemic characterization of the electrical properties of WTe2 single crystals as a function of channel dimensions. Using a 1D heat transport model and a power law, it is determined that the breakdown of WTe2 devices under vacuum and with AlOx capping layer follows an ideal pattern for Joule heating, far from edge scattering. High-field electrical measurements and self-heating modeling demonstrate that the WTe2 nanobelts have a breakdown current density approaching approximate to 100 MA cm(-2), remarkably higher than those of conventional metals and other transition-metal chalcogenides, and sustain the highest electrical power per channel length (approximate to 16.4 W cm(-1)) among the interconnect candidates. The results suggest superior robustness of WTe2 against high-bias sweep and its possible applicability in future nanoelectronics

    Early Motor Balance and Coordination Training Increased Synaptophysin in Subcortical Regions of the Ischemic Rat Brain

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    The aim of this study was to evaluate the effect of early motor balance and coordination training on functional recovery and brain plasticity in an ischemic rat stroke model, compared with simple locomotor exercise. Adult male Sprague-Dawley rats with cortical infarcts were trained under one of four conditions: nontrained control, treadmill training, motor training on the Rota-rod, or both Rota-rod and treadmill training. All types of training were performed from post-operation day 1 to 14. Neurological and behavioral performance was evaluated by Menzies' scale, the prehensile test, and the limb placement test, at post-operation day 1, 7, and 14. Both Rota-rod and treadmill training increased the expression of synaptophysin in subcortical regions of the ischemic hemisphere including the hippocampus, dentate gyrus, and thalamus, but did not affect levels of brain-derived neurotrophic factor or tyrosin kinase receptor B. The Rota-rod training also improved Menzies' scale and limb placement test scores, whereas the simple treadmill training did neither. The control group showed significant change only in Menzies' scale score. This study suggests that early motor balance and coordination training may induce plastic changes in subcortical regions of the ischemic hemisphere after stroke accompanied with the recovery of sensorimotor performance

    Enzyme immobilisation on amino-functionalised multi-walled carbon nanotubes : structural and biocatalytic characterisation

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    BACKGROUND: The aim of this work is to investigate the structure and function of enzymes immobilised on nanomaterials. This work will allow better understanding of enzyme-nanomaterial interactions, as well as designing functional protein-nanomaterial conjugates. METHODOLOGY/PRINCIPAL FINDINGS: Multiwalled carbon nanotubes (MWNTs) were functionalised with amino groups to improve solubility and biocompatibility. The pristine and functionalised forms of MWNTs were characterised with Fourier-transform infrared spectroscopy. Thermogravimetric analysis was done to examine the degree of the functionalisation process. An immobilised biocatalyst was prepared on functionalised nanomaterial by covalent binding. Thermomyces lanuginosus lipase was used as a model enzyme. The structural change of the immobilised and free lipases were characterised with transmission electron Microscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy and Circular dichroism spectroscopy. Biochemical characterisation of immobilised enzyme showed broader pH and thermal optima compared to soluble form. Reusability of the immobilised enzyme for hydrolysis of long chain esters was demonstrated up to ten cycles. CONCLUSION/SIGNIFICANCE: Lipase immobilised on MWNTs has exhibited significantly improved thermal stability. The exploration of advanced nanomaterial for enzyme immobilisation support using sophisticated techniques makes nanobiocatalyst of potential interest for biosensor applications

    The Induction of MicroRNA Targeting IRS-1 Is Involved in the Development of Insulin Resistance under Conditions of Mitochondrial Dysfunction in Hepatocytes

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    BACKGROUND: Mitochondrial dysfunction induces insulin resistance in myocytes via a reduction of insulin receptor substrate-1 (IRS-1) expression. However, the effect of mitochondrial dysfunction on insulin sensitivity is not understood well in hepatocytes. Although research has implicated the translational repression of target genes by endogenous non-coding microRNAs (miRNA) in the pathogenesis of various diseases, the identity and role of the miRNAs that are involved in the development of insulin resistance also remain largely unknown. METHODOLOGY: To determine whether mitochondrial dysfunction induced by genetic or metabolic inhibition causes insulin resistance in hepatocytes, we analyzed the expression and insulin-stimulated phosphorylation of insulin signaling intermediates in SK-Hep1 hepatocytes. We used qRT-PCR to measure cellular levels of selected miRNAs that are thought to target IRS-1 3' untranslated regions (3'UTR). Using overexpression of miR-126, we determined whether IRS-1-targeting miRNA causes insulin resistance in hepatocytes. PRINCIPAL FINDINGS: Mitochondrial dysfunction resulting from genetic (mitochondrial DNA depletion) or metabolic inhibition (Rotenone or Antimycin A) induced insulin resistance in hepatocytes via a reduction in the expression of IRS-1 protein. In addition, we observed a significant up-regulation of several miRNAs presumed to target IRS-1 3'UTR in hepatocytes with mitochondrial dysfunction. Using reporter gene assay we confirmed that miR-126 directly targeted to IRS-1 3'UTR. Furthermore, the overexpression of miR-126 in hepatocytes caused a substantial reduction in IRS-1 protein expression, and a consequent impairment in insulin signaling. CONCLUSIONS/SIGNIFICANCE: We demonstrated that miR-126 was actively involved in the development of insulin resistance induced by mitochondrial dysfunction. These data provide novel insights into the molecular basis of insulin resistance, and implicate miRNA in the development of metabolic disease

    Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

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    We reconstruct the rare decays B+→K+ÎŒ+Ό−B^+ \to K^+\mu^+\mu^-, B0→K∗(892)0ÎŒ+Ό−B^0 \to K^{*}(892)^0\mu^+\mu^-, and Bs0→ϕ(1020)ÎŒ+Ό−B^0_s \to \phi(1020)\mu^+\mu^- in a data sample corresponding to 4.4fb−14.4 {\rm fb^{-1}} collected in ppˉp\bar{p} collisions at s=1.96TeV\sqrt{s}=1.96 {\rm TeV} by the CDF II detector at the Fermilab Tevatron Collider. Using 121±16121 \pm 16 B+→K+ÎŒ+Ό−B^+ \to K^+\mu^+\mu^- and 101±12101 \pm 12 B0→K∗0ÎŒ+Ό−B^0 \to K^{*0}\mu^+\mu^- decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the B+B^+ and B0B^0 decay modes, and the K∗0K^{*0} longitudinal polarization in the B0B^0 decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the Bs0→ϕΌ+Ό−decayandmeasureitsbranchingratioB^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio {\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}using using 27 \pm 6signalevents.Thisiscurrentlythemostrare signal events. This is currently the most rare B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

    The UNC-45 Chaperone Is Critical for Establishing Myosin-Based Myofibrillar Organization and Cardiac Contractility in the Drosophila Heart Model

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    UNC-45 is a UCS (UNC-45/CRO1/She4P) class chaperone necessary for myosin folding and/or accumulation, but its requirement for maintaining cardiac contractility has not been explored. Given the prevalence of myosin mutations in eliciting cardiomyopathy, chaperones like UNC-45 are likely to be equally critical in provoking or modulating myosin-associated cardiomyopathy. Here, we used the Drosophila heart model to examine its role in cardiac physiology, in conjunction with RNAi-mediated gene silencing specifically in the heart in vivo. Analysis of cardiac physiology was carried out using high-speed video recording in conjunction with movement analysis algorithms. unc-45 knockdown resulted in severely compromised cardiac function in adults as evidenced by prolonged diastolic and systolic intervals, and increased incidence of arrhythmias and extreme dilation; the latter was accompanied by a significant reduction in muscle contractility. Structural analysis showed reduced myofibrils, myofibrillar disarray, and greatly decreased cardiac myosin accumulation. Cardiac unc-45 silencing also dramatically reduced life-span. In contrast, third instar larval and young pupal hearts showed mild cardiac abnormalities, as severe cardiac defects only developed during metamorphosis. Furthermore, cardiac unc-45 silencing in the adult heart (after metamorphosis) led to less severe phenotypes. This suggests that UNC-45 is mostly required for myosin accumulation/folding during remodeling of the forming adult heart. The cardiac defects, myosin deficit and decreased life-span in flies upon heart-specific unc-45 knockdown were significantly rescued by UNC-45 over-expression. Our results are the first to demonstrate a cardiac-specific requirement of a chaperone in Drosophila, suggestive of a critical role of UNC-45 in cardiomyopathies, including those associated with unfolded proteins in the failing human heart. The dilated cardiomyopathy phenotype associated with UNC-45 deficiency is mimicked by myosin knockdown suggesting that UNC-45 plays a crucial role in stabilizing myosin and possibly preventing human cardiomyopathies associated with functional deficiencies of myosin

    Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

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    We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure

    Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

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    We present a search for a new heavy charged vector boson Wâ€ČW^\prime decaying to an electron-neutrino pair in ppˉp\bar{p} collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on σ⋅B(Wâ€Č→eÎœ)\sigma\cdot{\cal B}(W^\prime\to e\nu). Assuming standard model couplings to fermions and the neutrino from the Wâ€ČW^\prime boson decay to be light, we exclude a Wâ€ČW^\prime boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR
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