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1

Chymase Inhibition Prevents Fibronectin and Myofibrillar Loss and Improves Cardiomyocyte Function and LV Torsion Angle in Dogs with Isolated Mitral Regurgitation  

PubMed Central

Background The LV dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix (ECM). In addition to pro-fibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases (MMP) and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate ECM loss and LV remodeling in MR. Methods and Results We studied dogs with four months of untreated MR (MR, n=9) or treated with CI (MR+CI, n=8). Cine magnetic resonance imaging (MRI) demonstrated a >40% increase in LV end-diastolic volume in both groups, consistent with a failure of CI to improve a 25% decrease in interstitial collagen in MR. However, LV cardiomyocyte fractional shortening was decreased in MR vs. normals (3.71 ± 0.24% vs. 4.81 ± 0.31%, P<0.05) and normalized in MR+CI dogs (4.85 ± 0.44%). MRI with tissue tagging demonstrated an increase in LV torsion angle in MR+CI vs. MR dogs. CI normalized the significant decrease in fibronectin and FAK phosphorylation, and prevented cardiomyocyte myofibrillar degeneration in MR dogs. In addition, total titin and its stiffer isoform were increased in the LV epicardium and paralleled the changes in fibronectin and FAK phosphorylation in MR+CI dogs. Conclusions These results suggest that chymase disrupts cell surface-fibronectin connections and FAK phosphorylation that can adversely affect cardiomyocyte myofibrillar structure and function. The greater effect of CI on epicardial vs. endocardial titin and non collagen cell surface proteins may be responsible for the increase in torsion angle in chronic MR.

Pat, Betty; Chen, Yuanwen; Killingsworth, Cheryl; Gladden, James D; Shi, Ke; Zheng, Junying; Powell, Pamela C; Walcott, Greg; Ahmed, Mustafa I; Gupta, Himanshu; Desai, Ravi; Wei, Chih-Chang; Hase, Naoki; Kobayashi, Tsunefumi; Sabri, Abdelkarim; Granzier, Henk; Denney, Thomas; Tillson, Michael; Dillon, A Ray; Husain, Ahsan; Dell'Italia, Louis J

2011-01-01

2

A Targeted Mutation within the Feline Leukemia Virus (FeLV) Envelope Protein Immunosuppressive Domain To Improve a Canarypox Virus-Vectored FeLV Vaccine  

PubMed Central

We previously delineated a highly conserved immunosuppressive (IS) domain within murine and primate retroviral envelope proteins that is critical for virus propagation in vivo. The envelope-mediated immunosuppression was assessed by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. Using this approach, we identified key residues whose mutation (i) specifically abolishes immunosuppressive activity without affecting the “mechanical” function of the envelope protein and (ii) significantly enhances humoral and cellular immune responses elicited against the virus. The objective of this work was to study the immunosuppressive activity of the envelope protein (p15E) of feline leukemia virus (FeLV) and evaluate the effect of its abolition on the efficacy of a vaccine against FeLV. Here we demonstrate that the FeLV envelope protein is immunosuppressive in vivo and that this immunosuppressive activity can be “switched off” by targeted mutation of a specific amino acid. As a result of the introduction of the mutated envelope sequence into a previously well characterized canarypox virus-vectored vaccine (ALVAC-FeLV), the frequency of vaccine-induced FeLV-specific gamma interferon (IFN-?)-producing cells was increased, whereas conversely, the frequency of vaccine-induced FeLV-specific interleukin-10 (IL-10)-producing cells was reduced. This shift in the IFN-?/IL-10 response was associated with a higher efficacy of ALVAC-FeLV against FeLV infection. This study demonstrates that FeLV p15E is immunosuppressive in vivo, that the immunosuppressive domain of p15E can modulate the FeLV-specific immune response, and that the efficacy of FeLV vaccines can be enhanced by inhibiting the immunosuppressive activity of the IS domain through an appropriate mutation.

Schlecht-Louf, Geraldine; Mangeney, Marianne; El-Garch, Hanane; Lacombe, Valerie; Poulet, Herve

2014-01-01

3

Systolic left ventricular function improves more by beta-blokade than losartan: the life study  

Microsoft Academic Search

Systolic left ventricular (LV) function is a predictor of cardiovascular morbidity and mortality and improvement of systolic LV function improves survival. However, it is unclear how to best improve systolic function.A total of 960 prospectively identified patients with essential hypertension and evidence of LV hypertrophy on a screening electrocardiogram underwent echocardiography at enrolment in the Losartan Intervention For Endpoint prevention

Kristian Wachtell; Eva Gerdts; Vittorio Palmieri; Kurt Boman; Björn Dahlöf; Markku S. Nieminen; Vasilios Papademetriou; Richard B. Devereux

2003-01-01

4

Limitations of quantitative phase analysis for detection of coronary artery disease in patients with impaired LV-function  

SciTech Connect

Phase analysis of radionuclide ventriculograms is used for identifying ischemic wall motion abnormalities. Myocardial segments with an abnormal phase and the synchronicity of LV wall motion can be assessed from a histogram of LV phase distribution. We examined in this study the sensitivity of SDP-LV for identifying coronary artery disease and its specificity in patients with normal and various degrees of left ventricular impairment. A total of 84 patients were studied. In severe left ventricular impairment, phase analysis did not aid in distinguishing coronary artery disease from other causes of ventricular dysfunction. By contrast, phase analysis was highly sensitive and specific for coronary artery disease in patients with normal or moderately depressed left ventricular function.

Schwaiger, M.; Ratib, O.; Hanze, E.; Schelbert, H.R.

1983-01-01

5

Rest and redistribution thallium-201 myocardial scintigraphy to predict improvement in left ventricular function after coronary arterial bypass grafting  

SciTech Connect

To examine the value of rest and redistribution thallium-201 imaging in predicting improvement in left ventricular (LV) ejection fraction (EF) after coronary artery bypass grafting (CABG), 26 patients with coronary artery disease (CAD) and abnormal LV function were studied. Nineteen patients had pathologic Q waves preoperatively. Rest and redistribution thallium-201 images and radionuclide ventriculograms were obtained before and after CABG, and the thallium scintigrams were evaluated both quantitatively and qualitatively. The patients were divided according to the preoperative thallium scintigrams into 2 groups: Group I (16 patients) had either normal resting thallium-201 images or reversible resting perfusion defects, and Group II (10 patients) had fixed resting perfusion defects. The resting EF was less than 50% preoperatively in all patients. Fourteen patients (54%) showed improvement in EF postoperatively. Three patients (2 in Group I and 1 in Group II) showed new postoperative perfusion defects, and none of the 3 showed improvement in LV function. Of the remaining 14 patients in Group I, 12 (86%) showed improvement in LV function, compared with 2 of 9 patients in Group II (p less than 0.01). Improvement in LV function was observed in 8 of the 19 patients (42%) with abnormal Q waves. Nitroglycerin intervention radionuclide ventriculograms were obtained in 20 patients before CABG. Of the 6 patients who showed improvement in LV function with nitroglycerin, 4 also showed improvement postoperatively. Postoperative improvement in LV function was also observed in 6 of the 14 patients who did not improve with nitroglycerin.

Iskandrian, A.S.; Hakki, A.H.; Kane, S.A.; Goel, I.P.; Mundth, E.D.; Hakki, A.H.; Segal, B.L.

1983-05-01

6

Intra-Myocardial Injection of Both Growth Factors and Heart Derived Sca-1+/CD31? Cells Attenuates Post-MI LV Remodeling More Than Does Cell Transplantation Alone: Neither Intervention Enhances Functionally Significant Cardiomyocyte Regeneration  

PubMed Central

Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are two potent cell survival and regenerative factors in response to myocardial injury (MI). We hypothesized that simultaneous delivery of IGF+HGF combined with Sca-1+/CD31? cells would improve the outcome of transplantation therapy in response to the altered hostile microenvironment post MI. One million adenovirus nuclear LacZ-labeled Sca-1+/CD31? cells were injected into the peri-infarction area after left anterior descending coronary artery (LAD) ligation in mice. Recombinant mouse IGF-1+HGF was added to the cell suspension prior to the injection. The left ventricular (LV) function was assessed by echocardiography 4 weeks after the transplantation. The cell engraftment, differentiation and cardiomyocyte regeneration were evaluated by histological analysis. Sca-1+/CD31? cells formed viable grafts and improved LV ejection fraction (EF) (Control, 54.5+/?2.4; MI, 17.6+/?3.1; Cell, 28.2+/?4.2, n?=?9, P<0.01). IGF+HGF significantly enhanced the benefits of cell transplantation as evidenced by increased EF (38.8+/?2.2; n?=?9, P<0.01) and attenuated adverse structural remodeling. Furthermore, IGF+HGF supplementation increased the cell engraftment rate, promoted the transplanted cell survival, enhanced angiogenesis, and minimally stimulated endogenous cardiomyocyte regeneration in vivo. The in vitro experiments showed that IGF+HGF treatment stimulated Sca-1+/CD31? cell proliferation and inhibited serum free medium induced apoptosis. Supperarray profiling of Sca-1+/CD31? cells revealed that Sca-1+/CD31? cells highly expressed various trophic factor mRNAs and IGF+HGF treatment altered the mRNAs expression patterns of these cells. These data indicate that IGF-1+HGF could serve as an adjuvant to cell transplantation for myocardial repair by stimulating donor cell and endogenous cardiac stem cell survival, regeneration and promoting angiogenesis.

Wang, Xiaohong; Li, Qinglu; Hu, Qingsong; Suntharalingam, Piradeep; From, Arthur H. L.; Zhang, Jianyi

2014-01-01

7

LV software for supersonic flow analysis  

NASA Technical Reports Server (NTRS)

The NASA Lewis Research Center (LeRC) maintains a leadership position in research into advanced aerospace propulsion systems. For the next generation of aircraft, engine designs continue to involve complex, high-speed flows. Performing the detailed flow diagnostics to properly evaluate these designs requires advanced instrumentation to probe these highly turbulent flows. The hostile flow environment often requires nonintrusive measurement techniques such as the laser velocimeter (LV). Since the LV is a proven instrument for nonintrusive flow measurement, it can provide quantitative velocity data with minimal interference to the flow. Based on anticipated flow conditions, laser velocimeter systems were procured from TSI, Inc. The initial system utilized counter processor technology, but later procurements this past year include a more advanced, correlator-based processor, which significantly improves the overall LV performance. To meet the needs of advanced research into propulsion, this instrument must be integrated into an existing VAX/VMS computer system for data acquisition, processing, and presentation. The work done under this grant before this period concentrated on developing the software required to setup and acquire data from the TSI MI-990 multichannel interface, and the RMR 1989 rotating machinery resolver. With the basis established for controlling the operation of the LV system, software development this past year shifted in emphasis from instrumentation control and data acquisition to data analysis and presentation. The progress of the program is reported.

Bell, William A.

1992-01-01

8

Simultaneous variation of ventricular pacing site and timing with biventricular pacing in acute ventricular failure improves function by interventricular assist  

PubMed Central

The goal of this work was to investigate the hemodynamic effects of simultaneous left ventricular (LV) pacing site (LVPS) and interventricular pacing delay (VVD) variation with biventricular pacing (BiVP) during acute LV failure. Simultaneously varying LVPS and VVD with BiVP has been shown to improve hemodynamics during acute right ventricular (RV) failure. However, effects during acute LV failure have not been reported. In six open-chest pigs, acute LV volume overload was induced by regurgitant flow via an aortic-LV conduit. Epicardial BiVP was implemented with right atrial and ventricular leads and a custom LV pacing array. Fifty-four LVPS-VVD combinations were tested in random order. Cardiac output was evaluated by aortic flow probe, ventricular systolic function by maximum rate of ventricular pressure change, and mechanical interventricular synchrony by normalized RV-LV pressure diagram area. Simultaneous LVPS-VVD variation improved all measures of cardiac function. The observed effect was different for each functional index, with evidence of LVPS-VVD interaction. Compared with effects of LVPS-VVD variation in a model of acute RV failure, hemodynamic changes were markedly different. However, in both models, maximum rate of ventricular pressure change of the failing ventricle was improved with synchronous interventricular contraction, suggesting that, in acute ventricular failure, BiVP can recruit the unstressed ventricle to support systolic function of the failing one. Thus simultaneously varying LVPS and VVD with BiVP during acute ventricular failure can improve cardiac function by “interventricular assist”, with hemodynamic effects dependent on the type of failure. This supports the potential utility of temporary BiVP for the treatment of acute ventricular failure commonly seen after cardiac surgery.

Cabreriza, Santos E.; Richmond, Marc E.; Weinberg, Alan D.; Holmes, Jeffrey W.; Spotnitz, Henry M.

2009-01-01

9

Postinfarct cytokine therapy regenerates cardiac tissue and improves left ventricular function.  

PubMed

We systematically investigated the comparative efficacy of three different cytokine regimens, administered after a reperfused myocardial infarction, in regenerating cardiac tissue and improving left ventricular (LV) function. Wild-type (WT) mice underwent a 30-minute coronary occlusion followed by reperfusion and received vehicle, granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL), G-CSF+stem cell factor (SCF), or G-CSF alone starting 4 hours after reperfusion. In separate experiments, chimeric mice generated by reconstitution of radioablated WT mice with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice underwent identical protocols. Mice were euthanized 5 weeks later. Echocardiographically, LV function was improved in G-CSF+FL- and G-CSF+SCF-treated but not in G-CSF-treated mice, whereas LV end-diastolic dimensions were smaller in all three groups. Morphometrically, cytokine-treated hearts had smaller LV diameter and volume. Numerous EGFP-positive cardiomyocytes, capillaries, and arterioles were noted in the infarcted region in cytokine-treated chimeric mice treated with G-CSF+FL or G-CSF+SCF, but the numbers were much smaller in G-CSF-treated mice. G-CSF+FL therapy mobilized bone marrow-derived cells exhibiting increased expression of surface antigens (CD62L and CD11a) that facilitate homing. We conclude that postinfarct cytokine therapy with G-CSF+FL or G-CSF+SCF limits adverse LV remodeling and improves LV performance by promoting cardiac regeneration and probably also by exerting other beneficial actions unrelated to regeneration, and that G-CSF alone is less effective. PMID:16556872

Dawn, Buddhadeb; Guo, Yiru; Rezazadeh, Arash; Huang, Yiming; Stein, Adam B; Hunt, Greg; Tiwari, Sumit; Varma, Jai; Gu, Yan; Prabhu, Sumanth D; Kajstura, Jan; Anversa, Piero; Ildstad, Suzanne T; Bolli, Roberto

2006-04-28

10

Postinfarct Cytokine Therapy Regenerates Cardiac Tissue and Improves Left Ventricular Function  

PubMed Central

We systematically investigated the comparative efficacy of three different cytokine regimens, administered after a reperfused myocardial infarction, in regenerating cardiac tissue and improving left ventricular (LV) function. Wild-type (WT) mice underwent a 30-minute coronary occlusion followed by reperfusion and received vehicle, granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL), G-CSF+stem cell factor (SCF), or G-CSF alone starting 4 hours after reperfusion. In separate experiments, chimeric mice generated by reconstitution of radioablated WT mice with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice underwent identical protocols. Mice were euthanized 5 weeks later. Echocardiographically, LV function was improved in G-CSF+FL– and G-CSF+SCF–treated but not in G-CSF–treated mice, whereas LV end-diastolic dimensions were smaller in all three groups. Morphometrically, cytokine-treated hearts had smaller LV diameter and volume. Numerous EGFP-positive cardiomyocytes, capillaries, and arterioles were noted in the infarcted region in cytokine-treated chimeric mice treated with G-CSF+FL or G-CSF+SCF, but the numbers were much smaller in G-CSF–treated mice. G-CSF+FL therapy mobilized bone marrow–derived cells exhibiting increased expression of surface antigens (CD62L and CD11a) that facilitate homing. We conclude that postinfarct cytokine therapy with G-CSF+FL or G-CSF+SCF limits adverse LV remodeling and improves LV performance by promoting cardiac regeneration and probably also by exerting other beneficial actions unrelated to regeneration, and that G-CSF alone is less effective.

Dawn, Buddhadeb; Guo, Yiru; Rezazadeh, Arash; Huang, Yiming; Stein, Adam B.; Hunt, Greg; Tiwari, Sumit; Varma, Jai; Gu, Yan; Prabhu, Sumanth D.; Kajstura, Jan; Anversa, Piero; Ildstad, Suzanne T.; Bolli, Roberto

2013-01-01

11

Functionality Improvements to Overaero  

NASA Technical Reports Server (NTRS)

The functionality of the overset, static aeroelasticity, Navier-Stokes flow solver OVERAERO was increased by adding capability to the flow solver and enhancing code performance. Improvements were made to the fluids/structure interface, an MLP version of the parallel OVERAERO code was developed, and the OVERAERO-MPI code was ported to the Cray T3E. The OVERFLOW-MPI and OVERAERO-MPI codes were tested successfully on the IPG testbed and a means of reducing communication overhead within OVERFLOW-MPI was investigated. To solve an aeroelastic problem computationally, a structures grid surface definition and a fluids grid surface definition are required. Typically, the structures grid surface has a lower fidelity than the fluids grid surface. Thus, the methods developed to transfer data between the two grid systems are vital to the accuracy and efficiency of the aeroelasticity code. The fluids/structures interface developed for the OVERAERO code was improved to more accurately treat fluids surfaces that bridge between two different structural surfaces. For example, the method allowed the forward portion of a flap track fairing to deform with the wing and the aft end of the fairing to deform with the flap. A tightly-coupled version of the code based on OVERFLOW-MLP was developed to improve code performance on the SGI Origin 2000. This required a new parallelization strategy to couple the fluids and structures codes. The OVERAERO-MPI code was ported to the Cray T3E to extend the usability of the code. The port required extensive use of dynamic memory management techniques to fit large problems within the memory limitations of the T3E. The OVERFLOW-MPI and OVERAERO-MPI codes were tested on the IPG testbed being developed within NASA. For small problems with minimal data transfer between grids, there was little to no performance penalty spreading the computation across two machines. For very large problems, methods were developed to minimize intermachine communication via the grid partitioning scheme. By minimizing the intermachine communication requirements of the problem, it may still be beneficial to run a tightly-coupled flow solver across two machines within the IPG.

Gee, Ken; Rizk, Yehia M.

2000-01-01

12

Atorvastatin enhances interleukin-10 levels and improves cardiac function in rats after acute myocardial infarction.  

PubMed

LV (left ventricular) remodelling is the basic mechanism of HF (heart failure) following MI (myocardial infarction). Although there is evidence that pro-inflammatory cytokines [including TNF-alpha (tumour necrosis factor-alpha) and IL-6 (interleukin-6)] are involved in the remodelling process, only little is known about the role of anti-inflammatory cytokines, such as IL-10. As accumulating evidence has revealed that statins possess anti-inflammatory properties, the aim of the present study was to elucidate the effect of atorvastatin on the modulation of the anti-inflammatory cytokine IL-10 and its effect on LV function in rats with HF subsequent to MI. Rats with MI, induced by permanent LAD (left anterior descending) branch coronary artery ligation, were treated for 4 weeks with atorvastatin (10 mg x kg(-1) of body weight x day(-1) via oral gavage) starting on the first day after induction of MI. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10 protein, the TNF-alpha/IL-10 ratio, serum levels of MCP-1 (monocyte chemoattractant protein-1) as well as myocardial macrophage infiltration were analysed. Treatment with atorvastatin significantly improved post-MI LV function (fractional shortening, +120%; dP/dt(max), +147%; and LV end-diastolic pressure, -27%). Furthermore atorvastatin treatment markedly decreased the levels of TNF-alpha, IL-6 and MCP-1, reduced myocardial infiltration of macrophages and significantly increased myocardial and serum levels of the anti-inflammatory cytokine IL-10. Thus the balance between pro-inflammatory and anti-inflammatory cytokines was shifted in the anti-inflammatory direction, as shown by a significantly decreased TNF-alpha/IL-10 ratio. Atorvastatin ameliorated early LV remodelling and improved LV function in rats with HF subsequent to MI. Our study suggests that the modulation of the balance between pro- and anti-inflammatory cytokines towards the anti-inflammatory cytokine IL-10 is one salutary mechanism underlying how atorvastatin influences post-MI remodelling and thus improves LV function. PMID:18459941

Stumpf, Christian; Petzi, Sebastian; Seybold, Katrin; Wasmeier, Gerald; Arnold, Martin; Raaz, Dorette; Yilmaz, Atilla; Daniel, Werner G; Garlichs, Christoph D

2009-01-01

13

Relationship between early diastolic intraventricular pressure gradients, an index of elastic recoil, and improvements in systolic and diastolic function  

NASA Technical Reports Server (NTRS)

BACKGROUND: Early diastolic intraventricular pressure gradients (IVPGs) have been proposed to relate to left ventricular (LV) elastic recoil and early ventricular "suction." Animal studies have demonstrated relationships between IVPGs and systolic and diastolic indices during acute ischemia. However, data on the effects of improvements in LV function in humans and the relationship to IVPGs are lacking. METHODS AND RESULTS: Eight patients undergoing CABG and/or infarct exclusion surgery had a triple-sensor high-fidelity catheter placed across the mitral valve intraoperatively for simultaneous recording of left atrial (LA), basal LV, and apical LV pressures. Hemodynamic data obtained before bypass were compared with those with similar LA pressures and heart rates obtained after bypass. From each LV waveform, the time constant of LV relaxation (tau), +dP/dt(max), and -dP/dt(max) were determined. Transesophageal echocardiography was used to determined end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fractions (EF). At similar LA pressures and heart rates, IVPG increased after bypass (before bypass 1.64+/-0.79 mm Hg; after bypass 2.67+/-1.25 mm Hg; P<0.01). Significant improvements were observed in ESV, as well as in apical and basal +dP/dt(max), -dP/dt(max), and tau (each P<0.05). Overall, IVPGs correlated inversely with both ESV (IVPG=-0.027[ESV]+3.46, r=-0.64) and EDV (IVPG=-0.027[EDV]+4.30, r=-0.70). Improvements in IVPGs correlated with improvements in apical tau (Deltatau =5.93[DeltaIVPG]+4.76, r=0.91) and basal tau (Deltatau =2.41[DeltaIVPG]+5.13, r=-0.67). Relative changes in IVPGs correlated with changes in ESV (DeltaESV=-0.97[%DeltaIVPG]+23.34, r=-0.79), EDV (DeltaEDV=-1.16[%DeltaIVPG]+34.92, r=-0.84), and EF (DeltaEF=0.38[%DeltaIVPG]-8.39, r=0.85). CONCLUSIONS: Improvements in LV function also increase IVPGs. These changes in IVPGs, suggestive of increases in LV suction and elastic recoil, correlate directly with improvements in LV relaxation and ESV.

Firstenberg, M. S.; Smedira, N. G.; Greenberg, N. L.; Prior, D. L.; McCarthy, P. M.; Garcia, M. J.; Thomas, J. D.

2001-01-01

14

Reduction in Left Ventricular Wall Stress and Improvement in Function in Failing Hearts using Algisyl-LVR  

PubMed Central

Injection of Algisyl-LVR, a treatment under clinical development, is intended to treat patients with dilated cardiomyopathy. This treatment was recently used for the first time in patients who had symptomatic heart failure. In all patients, cardiac function of the left ventricle (LV) improved significantly, as manifested by consistent reduction of the LV volume and wall stress. Here we describe this novel treatment procedure and the methods used to quantify its effects on LV wall stress and function. Algisyl-LVR is a biopolymer gel consisting of Na+-Alginate and Ca2+-Alginate. The treatment procedure was carried out by mixing these two components and then combining them into one syringe for intramyocardial injections. This mixture was injected at 10 to 19 locations mid-way between the base and apex of the LV free wall in patients. Magnetic resonance imaging (MRI), together with mathematical modeling, was used to quantify the effects of this treatment in patients before treatment and at various time points during recovery. The epicardial and endocardial surfaces were first digitized from the MR images to reconstruct the LV geometry at end-systole and at end-diastole. Left ventricular cavity volumes were then measured from these reconstructed surfaces. Mathematical models of the LV were created from these MRI-reconstructed surfaces to calculate regional myofiber stress. Each LV model was constructed so that 1) it deforms according to a previously validated stress-strain relationship of the myocardium, and 2) the predicted LV cavity volume from these models matches the corresponding MRI-measured volume at end-diastole and end-systole. Diastolic filling was simulated by loading the LV endocardial surface with a prescribed end-diastolic pressure. Systolic contraction was simulated by concurrently loading the endocardial surface with a prescribed end-systolic pressure and adding active contraction in the myofiber direction. Regional myofiber stress at end-diastole and end-systole was computed from the deformed LV based on the stress-strain relationship.

Lee, Lik Chuan; Zhihong, Zhang; Hinson, Andrew; Guccione, Julius M.

2013-01-01

15

Reduction in left ventricular wall stress and improvement in function in failing hearts using Algisyl-LVR.  

PubMed

Injection of Algisyl-LVR, a treatment under clinical development, is intended to treat patients with dilated cardiomyopathy. This treatment was recently used for the first time in patients who had symptomatic heart failure. In all patients, cardiac function of the left ventricle (LV) improved significantly, as manifested by consistent reduction of the LV volume and wall stress. Here we describe this novel treatment procedure and the methods used to quantify its effects on LV wall stress and function. Algisyl-LVR is a biopolymer gel consisting of Na(+)-Alginate and Ca(2+)-Alginate. The treatment procedure was carried out by mixing these two components and then combining them into one syringe for intramyocardial injections. This mixture was injected at 10 to 19 locations mid-way between the base and apex of the LV free wall in patients. Magnetic resonance imaging (MRI), together with mathematical modeling, was used to quantify the effects of this treatment in patients before treatment and at various time points during recovery. The epicardial and endocardial surfaces were first digitized from the MR images to reconstruct the LV geometry at end-systole and at end-diastole. Left ventricular cavity volumes were then measured from these reconstructed surfaces. Mathematical models of the LV were created from these MRI-reconstructed surfaces to calculate regional myofiber stress. Each LV model was constructed so that 1) it deforms according to a previously validated stress-strain relationship of the myocardium, and 2) the predicted LV cavity volume from these models matches the corresponding MRI-measured volume at end-diastole and end-systole. Diastolic filling was simulated by loading the LV endocardial surface with a prescribed end-diastolic pressure. Systolic contraction was simulated by concurrently loading the endocardial surface with a prescribed end-systolic pressure and adding active contraction in the myofiber direction. Regional myofiber stress at end-diastole and end-systole was computed from the deformed LV based on the stress-strain relationship. PMID:23608998

Lee, Lik Chuan; Zhihong, Zhang; Hinson, Andrew; Guccione, Julius M

2013-01-01

16

A PC based frequency domain LV processor  

SciTech Connect

A PC based laser Doppler velocimeter (LV) data system was developed. The data system uses frequency domain processing for multiple component LV individual signal realization. The system is based on a standard add in board for IBM PC's which has a transient digitizer and programmable digital signal processor (DSP) on board. Custom software written for both the general purpose DSP and the PC is described. The DSP is programmed to implement the frequency domain LV signal processor and the PC is programmed to provide a user interface and data archiving capability. The resulting data system is a low cost alternative to dedicated commercial velocimeter signal processors. Furthermore, the general purpose utility of the PC is still available when LV signal acquisition and processing is not active. Typical optical signal data processing is presented to illustrate data system performance. 5 refs., 7 figs.

Layne, T.C.; Giel, T.V. Jr.; Clippard, R.L.

1991-01-01

17

An automatic alignment tool to improve repeatability of left ventricular function and dyssynchrony parameters in serial gated myocardial perfusion SPECT studies  

PubMed Central

Objective Left ventricular (LV) function and dyssynchrony parameters measured from serial gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using blinded processing had a poorer repeatability than when manual side-by-side processing was used. The objective of this study was to validate whether an automatic alignment tool can reduce the variability of LV function and dyssynchrony parameters in serial gated SPECT MPI. Methods Thirty patients who had undergone serial gated SPECT MPI were prospectively enrolled in this study. Thirty minutes after the first acquisition, each patient was repositioned and a gated SPECT MPI image was reacquired. The two data sets were first processed blinded from each other by the same technologist in different weeks. These processed data were then realigned by the automatic tool, and manual side-by-side processing was carried out. All processing methods used standard iterative reconstruction and Butterworth filtering. The Emory Cardiac Toolbox was used to measure the LV function and dyssynchrony parameters. Results The automatic tool failed in one patient, who had a large, severe scar in the inferobasal wall. In the remaining 29 patients, the repeatability of the LV function and dyssynchrony parameters after automatic alignment was significantly improved from blinded processing and was comparable to manual side-by-side processing. Conclusion The automatic alignment tool can be an alternative method to manual side-by-side processing to improve the repeatability of LV function and dyssynchrony measurements by serial gated SPECT MPI.

Zhou, Yanli; Faber, Tracy L.; Patel, Zenic; Folks, Russell D.; Cheung, Alice A.; Garcia, Ernest V.; Soman, Prem; Li, Dianfu; Cao, Kejiang; Chen, Ji

2013-01-01

18

Olfactory function improves following hemodialysis.  

PubMed

Olfactory function has been shown to be affected in chronic kidney disease; however, studies are contradictory and little is known on the effects of dialysis. To resolve these issues we tested olfactory function in 24 healthy controls and in 28 patients with chronic kidney disease receiving hemodialysis (20 patients) or peritoneal dialysis (the other 8). As assays for olfactory function we measured smell identification, n-butanol and acetic acid thresholds, Kt/V urea, percentage reduced urea, and weights before and after dialysis. Olfactory function was also self-rated by the participants. Compared to healthy controls, predialysis olfactory function was moderately but significantly decreased in the two dialysis groups, with hemodialysis patients being more affected. Patients self-rated olfactory function similar to that of healthy controls, suggesting that patients are unaware of the olfactory decrease. Olfactory function was significantly improved by one hemodialysis session. Neither body mass index, total volume loss, nor any other dialysis parameter correlated with olfactory function or its restitution following hemodialysis. The observed pattern of improvement suggests underlying mixed peripheral and central mechanisms. Thus, olfactory dysfunction in patients with chronic kidney disease is readily reversible by hemodialysis. PMID:21697812

Landis, Basile N; Marangon, Nicola; Saudan, Patrick; Hugentobler, Marianne; Giger, Roland; Martin, Pierre-Yves; Lacroix, Jean-Silvain

2011-10-01

19

Stem cell-loaded nanofibrous patch promotes the regeneration of infarcted myocardium with functional improvement in rat model.  

PubMed

Myocardial infarction (MI) leads to the loss of cardiomyocytes, followed by left ventricular (LV) remodeling and cardiac dysfunction. The authors hypothesize that an elastic, biodegradable nanofibrous cardiac patch loaded with mesenchymal stem cells (MSC) could restrain LV remodeling and improve cardiac function after MI. Poly(?-caprolactone)/gelatin (PG) nanofibers were fabricated by electrospinning, and the nanofibers displayed a porous and uniform nanofibrous structure with a diameter of 244±51nm. An MI model was established by ligation of the left anterior descending coronary artery of female Sprague-Dawley rats. The PG nanofibrous patch seeded with MSC, isolated from rat bone marrow, was implanted on the epicardium of the infarcted region of the LV wall of the heart. After transplantation, the PG-cell patch restricted the expansion of the LV wall effectively and reduced the scar size, and the density of the microvessels increased. Cells within the patch were able to migrate towards the scar tissue, and promoted new blood vessel formation at the infarct site. Angiogenesis and the cardiac functions improved significantly after 4weeks of implantation. The MSC-seeded PG nanofibrous patches are demonstrated to provide sufficient mechanical support, to induce angiogenesis and to accelerate cardiac repair in a rat model of MI. The study highlights the positive impact of implantation of an MSC-seeded PG nanofibrous patch as a novel constituent for MI repair. PMID:24576580

Kai, Dan; Wang, Qiang-Li; Wang, Hai-Jie; Prabhakaran, Molamma P; Zhang, Yanzhong; Tan, Yu-Zhen; Ramakrishna, Seeram

2014-06-01

20

Skin Substitutes with Improved Barrier Function.  

National Technical Information Service (NTIS)

The present invention relates to in vitro cultured skin substitutes, and in particular to in vitro cultured skin substitutes that have improved barrier function. In some embodiments, improved barrier function is a result of improved culture conditions, wh...

A. Comer L. A. Hoffmann M. Hoffmann

2005-01-01

21

Fiber optics transmission of LV signal  

NASA Technical Reports Server (NTRS)

The first use of a long optical fiber for transmitting megahertz frequencies in a laser velocimeter (LV) receiver system is reported. The fiber comprises a 600-micron diameter fused silica core, a silicon polymer cladding and a plastic jacket. The fiber numerical aperture is 0.22, corresponding to a maximum entrance half-angle of 0.22 rad. The 10-m length used results in a 5.6% attenuation loss. The fiber is found to transmit an 80-MHz signal with excellent resolution. It is established that an LV receiver using fiber optics sends a clean signal in electronically noisy and high-pressure environments and allows velocity measurements in places too small for a photomultiplier tube.

Young, A. D.; Gunter, W. D., Jr.

1981-01-01

22

Trimetazidine improves right ventricular function by increasing miR-21 expression.  

PubMed

Trimetazidine (TMZ) improves left ventricular (LV) function and alleviates angina. TMZ is a metabolism-related drug, but its molecular actions and non-metabolic effects have not yet been elucidated. In this study, we investigated whether TMZ improves right ventricular (RV) function and decreases apoptosis in RV myocardial cells (RVMCs) by regulating miRNA-21 (miR-21) expression in vitro and in vivo. We used cultivated RVMCs and LV myocardial cells (LVMCs) and provided hypoxic stimulation for 24 h to induce MC apoptosis. RVMCs showed more severe apoptosis as indicated by terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) staining and caspase-3 protein and activity assays. The decrease in miR-21 expression was more dramatic in RVMCs. Subsequently, TMZ (10 µM) was added to the RVMCs prior to hypoxic stimulation. The TMZ-treated RVMCs showed less apoptosis and an increased expression of miR-21. The transfection of RVMCs with a miR-21-specific inhibitor weakened the protective effects of TMZ. To evaluate TMZ effectiveness in right heart failure, we used a combination treatment of hypoxia and the vascular endothelial growth factor receptor blocker, Su5416, to construct a stable model, and administered TMZ. TMZ improved RV function (as indicated by an increase in tricuspid annular plane systolic excursion), and inhibited fibrosis. TMZ also protects RVMCs againts apoptosis and increases miR-21 expression. PMID:22842854

Liu, Fang; Yin, Li; Zhang, Lulu; Liu, Wenhua; Liu, Jingjin; Wang, Yongshun; Yu, Bo

2012-10-01

23

Myocardial Scar Identified by Magnetic Resonance Imaging Can Predict Left Ventricular Functional Improvement after Coronary Artery Bypass Grafting  

PubMed Central

Background Previous studies have shown that viable myocardium predicts recovery of left ventricular (LV) dysfunction after revascularization. Our aim was to evaluate the prognostic value of myocardial scar assessed by late gadolinium-enhanced cardiovascular magnetic resonance imaging (LGE-CMR) on functional recovery in patients undergoing coronary artery bypass grafting (CABG). Methods From November 2009 to September 2012, 63 patients with reduced left ventricular ejection fraction (LVEF) referred for first-time isolated CABG were prospectively enrolled, 52 were included in final analysis. LV functional parameters and scar tissue were assessed by LGE-CMR at baseline and 6 months after surgery. Patency of grafts was evaluated by computed tomography angiography (CTA) 6 months post-CABG. Predictors for global functional recovery were analyzed. Results The baseline LVEF was 32.7±9.2%, which improved to 41.6±11.0% 6 months later and 32/52 patients improved LVEF by ?5%. Multivariate logistic regression analysis showed that the most significant negative predictor for global functional recovery was the number of scar segments (Odds ratio 2.864, 95% Confidence Interval 1.172–6.996, p?=?0.021). Receiver-Operator-Characteristic (ROC) analysis demonstrated that ?4 scar segments predicted global functional recovery with a sensitivity and specificity of 85.0% and 87.5%, respectively (AUC?=?0.91, p<0.001). Comparison of ROC curves also indicated that scar tissue was superior to viable myocardium in predicting cardiac functional recovery (p<0.001). Conclusions Our findings indicated that scar tissue on LGE-CMR is an independent negative predictor of cardiac functional recovery in patients with impaired LV function undergoing CABG. These observations may be helpful for clinicians and cardiovascular surgeons to determine which patients are most likely to benefit from surgical revascularization.

Sun, Han-Song; Tang, Yue; Pan, Shi-Wei; Zhao, Shi-Hua

2013-01-01

24

Interleukin-10 improves left ventricular function in rats with heart failure subsequent to myocardial infarction.  

PubMed

Evidence has shown that pro-inflammatory cytokines, especially TNF-alpha, are involved in the inflammatory response in the remodelling process after myocardial infarction (MI). Although IL-10, an anti-inflammatory cytokine, has been shown to antagonize some of the deleterious effects of TNF-alpha, little is known about its role in post-MI left ventricular (LV) dysfunction. The aim of the present study was to investigate whether a therapy with rhIL-10 could be beneficial in an animal model of post-MI heart failure (HF). Rats with experimental MI were treated with rhIL-10 (75 microg/kg/d sc) starting directly after MI induction, and continuing for 4 weeks. Controls were untreated MI and sham-operated rats. Cardiac function was assessed by echocardiography and cardiac catheterization 4 weeks after MI induction. Membrane-bound and soluble fractions of TNF-alpha, IL-6 and IL-10, the ratio of TNF-alpha to IL-10, serum levels of MCP-1 as well as myocardial macrophage infiltration, were analyzed. Treatment with rhIL-10 significantly improved post-MI LV function (FS +127%;, dP/dt(max) +131%; LVEDP -36%). This effect was associated with a significant decrease in pro-inflammatory cytokine and chemokine levels (TNF-alpha, IL-6, MCP-1) and furthermore resulted in a reduced myocardial infiltration of macrophages. PMID:18599346

Stumpf, Christian; Seybold, Katrin; Petzi, Sebastian; Wasmeier, Gerald; Raaz, Dorette; Yilmaz, Atilla; Anger, Thomas; Daniel, Werner G; Garlichs, Christoph D

2008-08-01

25

Telmisartan improves survival and ventricular function in SHR rats with extensive cardiovascular damage induced by dietary salt excess.  

PubMed

Excessive dietary salt intake induces extensive cardiovascular and renal damage in spontaneously hypertensive rats (SHR) that may be prevented by antihypertensive agents. This study examines whether salt-induced cardiac damage may be reversed by angiotensin II (type 1) receptor blockade (telmisartan). Eight-week-old male SHRs were divided into four groups; Group 1 (NS) was fed regular rat chow, and Group 2 (HS) received high-salt diet (HS; 8% NaCl). After 8 weeks on their respective diets, systemic hemodynamics and indices of left ventricular (LV) function were determined. Group 3 (HSnoT) was given HS for 8 weeks and then switched to a regular chow (0.6% NaCl) diet with no other treatment, and Group 4 (HSArb) received HS for 8 weeks and was then given regular diet plus telmisartan. Rats from these latter two groups were monitored for the ensuing 30 days. Compared with the NS group, rats in the HS group exhibited increased mean arterial pressure (161 ± 7 vs 184 ± 8 mm Hg) and LV diastolic dysfunction, as evidenced by a decreased rate of LV pressure decline (-8754 ± 747 vs -4234 ± 754 mmHg/sec) at the end of the 8 weeks of their respective treatment. After switching to regular chow, only one of 11 rats in the HSnoT group survived for the 30 days, whereas 10 died within 18 days; in the HSArb group only one of nine rats died; eight survived 30 days (P < .01). Telmisartan significantly improved LV function and survival in those SHR rats having extensive cardiovascular damage induced by dietary salt excess. PMID:24726099

Susic, Dinko; Frohlich, Edward D

2014-05-01

26

Clustered PV inverters in LV networks: An overview of impacts and comparison of voltage control strategies  

Microsoft Academic Search

High penetration of photovoltaic (PV) inverters in low voltage (LV) distribution network challenges the voltage stability due to interaction between multiple inverters and grid. As the main objective is to provide more power injection from VSC-based PV inverters, grid stability, reliability and power quality must be maintained or improved by adding cooperative control features to the grid-connected inverters. This paper

Erhan Demirok; Dezso Sera; Remus Teodorescu; P. Rodriguez; U. Borup

2009-01-01

27

Improving functional value of meat products.  

PubMed

In recent years, much attention has been paid to develop meat and meat products with physiological functions to promote health conditions and prevent the risk of diseases. This review focuses on strategies to improve the functional value of meat and meat products. Value improvement can be realized by adding functional compounds including conjugated linoneleic acid, vitamin E, n3 fatty acids and selenium in animal diets to improve animal production, carcass composition and fresh meat quality. In addition, functional ingredients such as vegetable proteins, dietary fibers, herbs and spices, and lactic acid bacteria can be directly incorporated into meat products during processing to improve their functional value for consumers. Functional compounds, especially peptides, can also be generated from meat and meat products during processing such as fermentation, curing and aging, and enzymatic hydrolysis. This review further discusses the current status, consumer acceptance, and market for functional foods from the global viewpoints. Future prospects for functional meat and meat products are also discussed. PMID:20537806

Zhang, Wangang; Xiao, Shan; Samaraweera, Himali; Lee, Eun Joo; Ahn, Dong U

2010-09-01

28

Reduced Ca2+-calmodulin-dependent protein kinase activity and expression in LV myocardium of dogs with heart failure.  

PubMed

Studies on the status of multifunctional Ca(2+)-calmodulin (CaM)-dependent protein kinase-II (CaMKII) in failing hearts are limited and controversial. The study was performed in the left ventricular (LV) myocardium of six dogs with heart failure (HF) (LV ejection fraction, 23 +/- 2%) and six normal (NL) dogs. In the LV homogenate, CaMKII activity and its protein level were determined by using the CaMKII peptide and antibody, respectively. Furthermore, the protein level of CaM and phosphorylated phospholamban (PLB) at threonine-17 (PLB-Thr(17)) and serine-16 (PLB-Ser(16)) were also determined in the LV homogenate using a specific antibody. In addition, the level of zinc, which inhibits protein kinase A activity, was determined in the LV tissue by inductively coupled plasma mass spectrometry. CaMKII activity and phosphorylated PLB-Thr(17) and PLB-Ser(16) levels, but not CaM and Zn levels, were significantly reduced in the LV homogenate of dogs with HF compared with NL dogs. These results suggest that CaMKII activity is reduced in the failing LV myocardium, and this abnormality is associated with reduced protein expression level of the enzyme but not due to changes in CaM and zinc levels. In conclusion, reduced CaMKII activity and phosphorylated PLB level may be partly responsible for impaired sarcoplasmic reticulum function in HF. PMID:12424092

Mishra, Sudhish; Sabbah, Hani N; Jain, Jinesh C; Gupta, Ramesh C

2003-03-01

29

Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function  

PubMed Central

The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.

Dawn, Buddhadeb; Stein, Adam B.; Urbanek, Konrad; Rota, Marcello; Whang, Brian; Rastaldo, Raffaella; Torella, Daniele; Tang, Xian-Liang; Rezazadeh, Arash; Kajstura, Jan; Leri, Annarosa; Hunt, Greg; Varma, Jai; Prabhu, Sumanth D.; Anversa, Piero; Bolli, Roberto

2005-01-01

30

Autologous Cardiomyotissue Implant Promotes Myocardial Regeneration, Decreases Infarct Size and Improves Left Ventricular Function  

PubMed Central

Background Cell therapy for myocardial infarction (MI) may be limited by poor cell survival and lack of transdifferentiation. We report a novel technique of implanting whole autologous myocardial tissue from preserved myocardial regions into infarcted regions. Methods and Results Fourteen rats were used to optimize cardiomyotissue size using peritoneal wall implantation (300?M identified as optimal size). Thirty-nine pigs were used to investigate cardiomyotissue implantation in MI induced by LAD balloon occlusion [10 animals died, male to female transplantation for tracking with ISH for Y chromosome, n=4 (2-donors and 2-MI animals), acute MI implant cohort at 1 hour, n=13, and healed MI implant at 2 weeks, n=12]. Assessment included echocardiography, MRI, hemodynamics, TTC staining, histological, and molecular analysis. Tracking studies demonstrated viable implants with donor cells interspersed in the adjacent myocardium with gap junctions and desmosomes. In the acute MI cohort, treated animals compared to controls had improved perfusion by MRI (1.2±0.01 vs. 0.86±0.05,p<0.01), decreased MI size (MRI:%LV:2.2±0.5 vs. 5.4±1.5,p=0.04, TTC: %Anterior wall: 10.3±4.6 vs. 28.9±5.8,p<0.03), improved contractility (+dP/dt:1235±215 vs. 817±817,p<0.05). In healed MI cohort, treated animals had less decline in EF between 2 and 4 week assessment (-3±4% vs. -13±-4%,p<0.05), less decline in +/-dP/dt, and smaller MI (TTC: 21±11% vs. 3±8%,p=0.006) than control animals. Infarcts in the treated animals contained more mdr-1+ cells and fewer c-kit+ cells with a trend for decreased expression of MMP-2 and increased expression of TIMP-2. Conclusion Autologous cardiomyotissue implanted in myocardial infarction area remains viable, exhibits electromechanical coupling, decreases infarct size and improves LV function.

Wykrzykowska, Joanna J.; Rosinberg, Audrey; Lee, Seung U.; Voisine, Pierre; Wu, Guifu; Appelbaum, Evan; Boodhwani, Munir; Sellke, Frank W.; Laham, Roger J.

2011-01-01

31

Biofeedback improves functional outcome after sphincteroplasty  

Microsoft Academic Search

The primary treatment for obstetric sphincter injury is overlapping sphincteroplasty. However, despite restoration of the anatomy, only 65 percent of patients are fully continent. PURPOSE: This study was undertaken to determine if postoperative biofeedback improved continence in patients with poor functional outcomes after sphincteroplasty. METHOD: Outcomes of 28 patients who underwent electromyographic biofeedback training after sphincteroplasty for obstetric sphincter injury

L. L. Jensen; A. C. Lowry

1997-01-01

32

Revealing Domain Structure through Linker-Scanning Analysis of the Murine Leukemia Virus (MuLV) RNase H and MuLV and Human Immunodeficiency Virus Type 1 Integrase Proteins  

PubMed Central

Linker-scanning libraries were generated within the 3? terminus of the Moloney murine leukemia virus (M-MuLV) pol gene encoding the connection-RNase H domains of reverse transcriptase (RT) as well as the structurally related M-MuLV and human immunodeficiency virus type 1 (HIV-1) integrase (IN) proteins. Mutations within the M-MuLV proviral vectors were Tn7 based and resulted in 15-bp insertions. Mutations within an HIV-1 IN bacterial expression vector were based on Tn5 and resulted in 57-bp insertions. The effects of the insertions were examined in vivo (M-MuLV) and in vitro (HIV-1). A total of 178 individual M-MuLV constructs were analyzed; 40 in-frame insertions within RT connection-RNase H, 108 in-frame insertions within IN, 13 insertions encoding stop codons within RNase H, and 17 insertions encoding stop codons within IN. For HIV-1 IN, 56 mutants were analyzed. In both M-MuLV and HIV-1 IN, regions are identified which functionally tolerate multiple-linker insertions. For MuLV, these correspond to the RT-IN proteolytic junction, the junction between the IN core and C terminus, and the C terminus of IN. For HIV-1 IN, in addition to the junction between the IN core and C terminus and the C terminus of IN, insertions between the N terminus and core domains maintained integration and disintegration activity. Of the 40 in-frame insertions within the M-MuLV RT connection-RNase H domains, only the three C-terminal insertions mapping to the RT-IN proteolytic junction were viable. These results correlate with deletion studies mapping the domain and subdomain boundaries of RT and IN. Importantly, these genetic footprints provide a means to identify nonessential regions within RT and IN for targeted gene therapy applications.

Puglia, Jennifer; Wang, Tan; Smith-Snyder, Christine; Cote, Marie; Scher, Michael; Pelletier, Joelle N.; John, Sinu; Jonsson, Colleen B.; Roth, Monica J.

2006-01-01

33

3D quantitative visualization of altered LV wall thickening dynamics caused by coronary microembolization  

NASA Astrophysics Data System (ADS)

Regional heart wall dynamics has been shown to be a sensitive indicator of LV wall ischemia. Rates of local LV wall thickening during a cardiac cycle can be measured and illustrated using functional parametric mappings. This display conveys the spatial distribution of dynamic strain in the myocardium and thereby provides a rapid qualitative appreciation of the severity and extent of the ischemic region. 3D reconstructions were obtained in an anesthetized pig from 8 adjacent, shortaxis, slices of the left ventricle imaged with an Electron Beam Computer Tomograph at 11 time points through one complete cardiac cycle. The 3D reconstructions were obtained before and after injection of 100 micrometer microspheres into the Left Anterior Descending (LAD) coronary artery. This injection causes microembolization of LAD artery branches within the heart wall. The image processing involved radially dividing the tomographic images of the myocardium into small subdivisions with color encoding of the local magnitude of regional thickness or regional velocities of LV wall thickening throughout the cardiac cycle. We compared the effectiveness of animation of wall thickness encoded in color versus a static image of computed rate of wall thickness change in color. The location, extent and severity of regional wall akinesis or dyskinesis, as determined from these displays, can then be compared to the region of embolization as indicated by the distribution of altered LV wall perfusion.

Eusemann, Christian D.; Mohlenkamp, Stefan; Ritman, Erik L.; Robb, Richard A.

2001-05-01

34

Automatic cardiac LV boundary detection and tracking using hybrid fuzzy temporal and fuzzy multiscale edge detection.  

PubMed

This paper describes a new fully automatic fuzzy multiresolution-based algorithm for cardiac left ventricular (LV) epicardial and endocardial boundary detection and tracking on a sequence of short axis (SA) echocardiographic images of a complete cardiac cycle. This is a necessary step for automatic quantification of cardiac function using echo images. The proposed method is a "center-based" approach in which epicardial and endocardial boundary edge points are searched for on radial lines emanating from the LV center point. The central point of the LV cavity is estimated using a fuzzy-based technique in which the "uncertain" spatial, morphological, and intensity information of the image are represented as fuzzy sets and then combined by fuzzy operators. Edge-detection stage uses multiscale spatial and temporal information in a fuzzy multiresolution framework to identify a single moving edge point for each one of the epicardial and endocardial boundaries over the M radii in the N frames of a complete cardiac cycle. The raw extracted edge points are then processed in the wavelet domain to reduce the effects of noise from the boundaries and papillary muscles from the endocardial boundary extraction process. Finally, a uniform cubic B-spline approximation method is used to define the closed LV boundaries. Experiments with simulated and real echocardiographic images are presented. PMID:10582422

Kamaledin Setarehdan, S; Soraghan, J J

1999-11-01

35

Helminthic therapy: improving mucosal barrier function  

PubMed Central

The epidemiology of autoimmune diseases and helminth infections led to suggestions that helminths could improve inflammatory conditions, which was then tested using animal models. This has translated to clinical investigations aimed at the safe and controlled reintroduction of helminthic exposure to patients suffering from autoimmune diseases (so-called “helminthic therapy”) in an effort to mitigate the inflammatory response. In this review, we will summarize the results of recent clinical trials of helminthic therapy, with particular attention to mechanisms of action. Whereas previous reviews have emphasized immune regulatory mechanisms activated by helminths, we propose that enhancement of mucosal barrier function may have an equally important role in improving conditions of inflammatory bowel diseases.

Wolff, Martin J.; Broadhurst, Mara J.

2014-01-01

36

Therapeutic effects of recombinant feline interferon-omega on feline leukemia virus (FeLV)-infected and FeLV/feline immunodeficiency virus (FIV)-coinfected symptomatic cats.  

PubMed

The clinical efficacy of a recombinant feline interferon, rFeIFN-omega, was evaluated for the treatment of cats presented with clinical signs associated with feline leukemia virus (FeLV) infection and FeLV/feline immunodeficiency virus (FIV) coinfection in the field. In this multicentric, double-blind, placebo-controlled trial, 81 cats meeting the inclusion criteria were randomly placed into 2 groups and treated subcutaneously with rFelFN-omega (1 million [M]U/kg per day) or placebo once daily for 5 consecutive days in 3 series (day 0, 14, 60). The cats were monitored for up to 1 year for clinical signs and mortality. During the initial 4-month period, interferon (IFN)-treated cats (n = 39) had significantly reduced clinical scores compared with placebo (n = 42), with all cats having received concomitant supportive therapies. Compared with the control, the IFN-treated group showed significantly lower rates of mortality: 39% versus 59% (1.7-fold higher risk of death for controls) at the 9-month time point and 47% versus 59% (1.4-fold higher risk of death for controls) at the 12-month time point. The IFN treatment was associated with minor but consistent improvement in abnormal hematologic parameters (red blood cell count, packed cell volume, and white blood cell count), apparently underlying the positive effects of IFN on clinical parameters. These data demonstrate that rFeIFN-omega initially has statistically significant therapeutic effects on clinical signs and later on survival of cats with clinical signs associated with FeLV infection and FeLV/FIV coinfection. PMID:15320583

de Mari, Karine; Maynard, Laurence; Sanquer, Annaelle; Lebreux, Bernard; Eun, Hyone-Myong

2004-01-01

37

Inhibition of Collagen Synthesis With Prolyl 4Hydroxylase Inhibitor Improves Left Ventricular Function and Alters the Pattern of Left Ventricular Dilatation After Myocardial Infarction  

Microsoft Academic Search

Background—Left ventricular (LV) remodeling after myocardial infarction (MI) is associated with fibrosis, dilatation, and dysfunction. We postulated that prevention of fibrosis after MI with a prolyl 4-hydroxylase inhibitor (P4HI) would preserve LV function and attenuate LV enlargement. Methods and Results—Adult female rats (200 to 250 g) had experimental MI and were then randomized to treatment with P4HI (MI-FG041, n529) or

John I. Nwogu; David Geenen; Maurice Bean; Mitchell C. Brenner; Xinfan Huang; Peter M. Buttrick

2010-01-01

38

Methods and compositions for improving cognitive function  

US Patent & Trademark Office Database

This invention relates to treating age-related cognitive impairment. This invention in particular relates to the use of inhibitors of synaptic vesicle protein 2A (SV2A), such as levetiracetam, seletracetam, and brivaracetam, in improving cognitive function in subjects that exhibit age-related cognitive impairment or are at risk thereof, including, without limitation, subjects having or at risk for Mild Cognitive Impairment (MCI), Age-related Cognitive Decline (ARCD) or Age-Associated Memory Impairment (AAMI).

2013-12-10

39

Regression of left ventricular hypertrophy and improvement of diastolic function in hypertensive patients treated with telmisartan  

Microsoft Academic Search

Objectives: The study was designed to test whether or not the angiotensin II receptor blocker telmisartan brings about regression of left ventricular (LV) concentric hypertrophy and whether or not these changes are associated with improved diastolic filling. Methods: An echocardiographic follow-up study was performed in 85 hypertensive patients (systolic blood pressure [SBP] >140 mm Hg, diastolic blood pressure [DBP] >90

A. V. Mattioli; M. Zennaro; S. Bonatti; L. Bonetti; G. Mattioli

2004-01-01

40

Nutraceutical intervention improves older adults' cognitive functioning.  

PubMed

Interventions to improve the cognitive health of older adults are of critical importance. In the current study, we conducted a double-blind, placebo-controlled clinical trial using a pill-based nutraceutical (NT-020) that contained a proprietary formulation of blueberry, carnosine, green tea, vitamin D3, and Biovin to evaluate the impact on changes in multiple domains of cognitive functioning. One hundred and five cognitively intact adults aged 65-85 years of age (M=73.6 years) were randomized to receive NT-020 (n=52) or a placebo (n=53). Participants were tested with a battery of cognitive performance tests that were classified into six broad domains--episodic memory, processing speed, verbal ability, working memory, executive functioning, and complex speed at baseline and 2 months later. The results indicated that persons taking NT-020 improved significantly on two measures of processing speed across the 2-month test period in contrast to persons on the placebo whose performance did not change. None of the other cognitive ability measures were related to intervention group. The results also indicated that the NT-020 was well tolerated by older adults, and the presence of adverse events or symptoms did not differ between the NT-020 and placebo groups. Overall, the results of the current study were promising and suggest the potential for interventions like these to improve the cognitive health of older adults. PMID:24134194

Small, Brent J; Rawson, Kerri S; Martin, Christina; Eisel, Sarah L; Sanberg, Cyndy D; McEvoy, Cathy L; Sanberg, Paul R; Shytle, R Douglas; Tan, Jun; Bickford, Paula C

2014-02-01

41

Umbilical-cord-blood-derived mesenchymal stem cells seeded onto fibronectin-immobilized polycaprolactone nanofiber improve cardiac function.  

PubMed

Stem cells seeded onto biofunctional materials have greater potency for therapeutic applications. We investigated whether umbilical-cord-blood-derived mesenchymal stem cell (UCB-MSC)-seeded fibronectin (FN)-immobilized polycaprolactone (PCL) nanofibers could improve cardiac function and inhibit left ventricle (LV) remodeling in a rat model of myocardial infarction (MI). Aligned nanofibers were uniformly coated with poly(glycidyl methacrylate) by initiated chemical vapor deposition followed by covalent immobilization of FN proteins. The degree of cell elongation and adhesion efficacy were improved by FN immobilization. Furthermore, genes related to angiogenesis and mesenchymal differentiations were up-regulated in the FN-immobilized PCL nanofibers in comparison to control PCL nanofibers in vitro. 4weeks after the transplantation in the rat MI model, the echocardiogram showed that the UCB-MSC-seeded FN-immobilized PCL nanofiber group increased LV ejection fraction and fraction shortening as compared to the non-treated control and acellular FN-immobilized PCL nanofiber groups. Histological analysis indicated that the implantation of UCB-MSCs with FN-immobilized PCL nanofibers induced a decrease in MI size and fibrosis, and an increase in scar thickness. This study indicates that FN-immobilized biofunctional PCL nanofibers could be an effective carrier for UCB-MSC transplantation for the treatment of MI. PMID:24657671

Kang, Byung-Jae; Kim, Hwan; Lee, Seul Ki; Kim, Joohyun; Shen, Yiming; Jung, Sunyoung; Kang, Kyung-Sun; Im, Sung Gap; Lee, So Yeong; Choi, Mincheol; Hwang, Nathaniel S; Cho, Je-Yoel

2014-07-01

42

Modeling Vectorcardiograms Based on LV Papillary Muscle Position  

PubMed Central

Background Vectorcardiographic QRS loops illustrate the electrical activation of the left ventricle (LV) in three dimensional space; however, the individual variability in these loops is not well understood. The left bundle branch fan distributes the initial activation to the LV and has been shown to distribute its fascicles between the LV papillary muscles. Computer models of LV activation utilizing papillary muscle as the initial electrical activation points accurately predict QRS duration and frontal plane axis. Methods 12 healthy adults received standard 12-lead ECGs and 1.5 T cardiac MRI. Software developed by ECG-TECH Corp generated 3 dimensional QRS vector loops for each subject. Short and long axis papillary muscle positions were measured for each subject using cardiac MRI images. A theoretical plane equidistant from the endocardial origins of each papillary muscle was constructed. Vectors perpendicular to the QRS vector loop and the theoretical plane termed the “plane identifier” were used for comparison. Spearman-rank correlation was used to compare the azimuth and elevation of the “plane identifiers” of the QRS vector loop and the theoretical plane. Results No correlation was found between the azimuth or elevation of the theoretical plane and the QRS vector loops with Spearman-rank correlation coefficients of ? = 0.11 (p=0.71) and ? = 0.22 (p=0.49) respectively. Subgroup analysis by QRS vector loop morphology (planar vs. non-planar; narrow vs. wide) also demonstrated no correlation. Conclusions Modeling the activation of the LV based on papillary muscle position alone may be overly simplistic. Better understanding of what other factors contribute to individual variation in LV activation will help develop a more useful theoretical model.

Loring, Zak; Olson, Charles W.; Maynard, Charles; Hakacova, Nina

2011-01-01

43

Inhibition of nitric oxide synthase uncoupling by sepiapterin improves left ventricular function in streptozotocin-induced diabetic mice.  

PubMed

1. Uncoupling of nitric oxide synthase (NOS) has been implicated in the pathogenesis of left ventricular (LV) dysfunction in diabetes mellitus. In the present study, we investigated the role of NOS uncoupling in oxidative/nitrosative stress and LV dysfunction in the diabetic mouse heart. 2. Diabetes was induced in wild-type (WT), endothelial (e) NOS knockout (eNOS(-/-)), inducible (i) NOS knockout (iNOS(-/-)) and neuronal (n) NOS knockout (nNOS(-/-)) mice by streptozotocin (STZ) treatment. 3. In the diabetic heart, iNOS, but not eNOS or nNOS, expression was increased. Levels of malondialdehyde (MDA), 4-hydroxy-noneal (HNE) and nitrotyrosine (NT), as markers of oxidative/nitrosative stress, were increased in the diabetic mouse heart, but the increase in oxidative/nitrosative stress was significantly repressed in the iNOS(-/-) diabetic mouse heart. Levels of nitrite and nitrate (NO(x)), as an index of nitric oxide, bioavailability were significantly decreased in the iNOS(-/-) diabetic mouse heart. 4. Oral administration of sepiapterin (10 mg/kg per day), a precursor of tetrahydrobiopterin (BH(4)), significantly increased BH(4) and the BH(4)/BH(2) ratio in diabetic mouse heart. Similarly, sepiapterin inhibited the formation of HNE, MDA and NT in diabetic hearts from all three genotypes, but the increase in NO(x) following sepiapterin treatment was significantly attenuated in the iNOS(-/-) diabetic mouse heart. Percentage fractional shortening (FS), evaluated by echocardiography, decreased significantly in all genotypes of diabetic mice. Sepiapterin significantly increased percentage FS in diabetic mice, except in iNOS(-/-) mice. 5. These results suggest that sepiapterin inhibits uncoupling of NOS and improves LV function presumably by increasing iNOS-derived nitric oxide in the diabetic heart. PMID:21554376

Jo, Hiromi; Otani, Hajime; Jo, Fusakazu; Shimazu, Takayuki; Okazaki, Toru; Yoshioka, Kei; Fujita, Masanori; Kosaki, Atsushi; Iwasaka, Toshiji

2011-08-01

44

TRANSPLANTATION OF EXPANDED BONE MARROW-DERIVED VERY SMALL EMBRYONIC-LIKE STEM CELLS (VSEL-SCs) IMPROVES LEFT VENTRICULAR FUNCTION AND REMODELING AFTER MYOCARDIAL INFARCTION  

PubMed Central

Adult bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) exhibit a Sca-1+/Lin-/CD45- phenotype and can differentiate into various cell types, including cardiomyocytes and endothelial cells. We have previously reported that transplantation of a small number (1×106) of freshly isolated, non-expanded VSEL-SCs into infarcted mouse hearts resulted in improved left ventricular (LV) function and anatomy. Clinical translation, however, will require large numbers of cells. Because the frequency of VSEL-SCs in the marrow is very low, we examined whether VSEL-SCs can be expanded in culture without loss of therapeutic efficacy. Mice underwent a 30-min coronary occlusion followed by reperfusion and, 48 h later, received an intramyocardial injection of vehicle (group I, n=11), 1×105 EGFP-labeled expanded untreated VSEL-SCs (group II, n=7), or 1×105 EGFP-labeled expanded VSEL-SCs preincubated in a cardiogenic medium (group III, n=8). At 35 d after MI, mice treated with preincubated VSEL-SCs exhibited better global and regional LV systolic function and less LV hypertrophy compared with vehicle-treated controls. In contrast, transplantation of expanded but untreated VSEL-SCs did not produce appreciable reparative benefits. Scattered EGFP+ cells expressing ?-sarcomeric actin, PECAM-1, or von Willebrand factor were present in VSEL-SC-treated mice, but their numbers were very small. No tumor formation was observed. We conclude that VSEL-SCs expanded in culture retain the ability to alleviate LV dysfunction and remodeling after a reperfused MI provided that they are exposed to a combination of cardiomyogenic growth factors and cytokines prior to transplantation. Counter intuitively, the mechanism whereby such preincubation confers therapeutic efficacy does not involve differentiation into new cardiac cells. These results support the potential therapeutic utility of VSEL-SCs for cardiac repair.

Zuba-Surma, Ewa K.; Guo, Yiru; Taher, Hisham; Sanganalmath, Santosh K.; Hunt, Greg; Vincent, Robert J.; Kucia, Magda; Abdel-Latif, Ahmed; Tang, Xian-Liang; Ratajczak, Mariusz Z.; Dawn, Buddhadeb; Bolli, Roberto

2010-01-01

45

Implantable cardioverter-defibrillators improve survival after coronary artery bypass grafting in patients with severely impaired left ventricular function  

PubMed Central

Objective Patients with severe left ventricular (LV) dysfunction have a poor long term survival despite complete surgical revascularization. Recent data suggests that the use of Implantable Cardioverter-Defibrillator (ICD) improves survival in patients with severe LV dysfunction. We compared the survival impact of ICD implantation in patients with severe LV dysfunction who underwent CABG. Methods Between January 1996 and August 2004, 305 patients with LV ejection fraction (EF) ?25% had CABG surgery at our institution. Demographics of patients who had received an ICD (ICD+) in the post -operative period was compared to those without ICD (ICD-). Survival was evaluated by the Kaplan-Meier method. Results Of the entire group, 35 (11.5%) patients received an ICD with a median of 2 (+/-2) years after CABG. Indication for ICD implantation was clinical evidence of non sustained ventricular tachycardia (NSVT). There were no differences between the 2 groups with respect to age, gender, NYHA classification, number of bypasses, or other co-morbidities. Survival at 1, 3 and 5 years was 88%, 79%, and 67% for the ICD- group compared to 94%, 89% and 83% for the ICD+ group, respectively (figure, p < 0.05). Conclusion Implantation of ICD after CABG confers improved short and long term survival benefit to patients with severe LV dysfunction. Prophylactic ICD implantation in the setting of severe LV dysfunction and CABG surgery should be considered.

Al-Dadah, Ashraf S; Voeller, Rochus K; Rahgozar, Paymon; Lawton, Jennifer S; Moon, Marc R; Pasque, Michael K; Damiano, Ralph J; Moazami, Nader

2007-01-01

46

The novel two-dimensional strain reflects improvement and remodeling of left-ventricular function better than conventional echocardiographic parameters after aortic valve repair in pediatric patients.  

PubMed

We aimed to evaluate the outcome and regional and global left-ventricular (LV) function after aortic valve repair in children with congenital aortic valve disease. Thirty-two consecutive patients with a mean age of 12.62 years (4 months to 18 years) undergoing aortic valve repair due to valve stenosis (AS group, n = 21) or aortic regurgitation (AR group, n = 11) were studied during a follow-up period of 12 months regarding change and adaptation of myocardial function using conventional and novel echocardiographic methods, including two-dimensional (2D) strain echocardiogram. Conventional and 2D strain echocardiographic studies were performed and analyzed off-line using commercially available software (EchoPac 6.1.0, GE). Peak aortic valve gradient decreased from 62.04 ± 30.34 mmHg before surgery to 22.80 ± 14.13 mmHg 2 weeks after surgery and to 35.73 ± 22.11 mmHg 12 months after surgery (p = 0.01). The degree of AR decreased significantly to grade 0 in 20 children and to grade I in 12. There was a significant decrease of thickness of the interventricular septum (IVS) and posterior wall resulting in improvement of LV mass index (p = 0.007, p = 0.043, and p = 0.001, respectively). Significant decrease of myocardial thickness was found, especially in the IVS, in the AS group (p = 0.008), and a significant decrease in LV end-diastolic dimension (EDD) was found in the AR group (p = 0.007). 2D strain analysis showed that global peak strain, global systolic strain rate, and global early diastolic strain rates improved significantly for all patients during the study period after aortic valve repair (p < 0.001, p = 0.037, and p = 0.018, respectively). The global strain and strain rates correlated significantly to IVS thickness (r = 0.002 and r = 0.003, respectively), LV mass index (r = 0.02 and r = 0.015, respectively), and EDD (r = 0.26 and r = 0.005, respectively). Aortic valve repair surgery in pediatric patients results in improvement of global and regional systolic and diastolic LV parameters, which was better shown by 2D strain parameters rather than conventional echocardiographic parameters. PMID:22660481

Mi, Yaping; Rädle-Hurst, Tanja; Rentzsch, Axel; Aicher, Diana; Schäfers, Hans Joachim; Abdul-Khaliq, Hashim

2013-01-01

47

Xanthine oxidase inhibition preserves left ventricular systolic but not diastolic function in cardiac volume overload.  

PubMed

Xanthine oxidase (XO) is increased in human and rat left ventricular (LV) myocytes with volume overload (VO) of mitral regurgitation and aortocaval fistula (ACF). In the setting of increased ATP demand, XO-mediated ROS can decrease mitochondrial respiration and contractile function. Thus, we tested the hypothesis that XO inhibition improves cardiomyocyte bioenergetics and LV function in chronic ACF in the rat. Sprague-Dawley rats were randomized to either sham or ACF ± allopurinol (100 mg·kg(-1)·day(-1), n ?7 rats/group). Echocardiography at 8 wk demonstrated a similar 37% increase in LV end-diastolic dimension (P < 0.001), a twofold increase in LV end-diastolic pressure/wall stress (P < 0.05), and a twofold increase in lung weight (P < 0.05) in treated and untreated ACF groups versus the sham group. LV ejection fraction, velocity of circumferential shortening, maximal systolic elastance, and contractile efficiency were significantly depressed in ACF and significantly improved in ACF + allopurinol rats, all of which occurred in the absence of changes in the maximum O2 consumption rate measured in isolated cardiomyocytes using the extracellular flux analyzer. However, the improvement in contractile function is not paralleled by any attenuation in LV dilatation, LV end-diastolic pressure/wall stress, and lung weight. In conclusion, allopurinol improves LV contractile function and efficiency possibly by diminishing the known XO-mediated ROS effects on myofilament Ca(2+) sensitivity. However, LV remodeling and diastolic properties are not improved, which may explain the failure of XO inhibition to improve symptoms and hospitalizations in patients with severe heart failure. PMID:24014679

Gladden, James D; Zelickson, Blake R; Guichard, Jason L; Ahmed, Mustafa I; Yancey, Danielle M; Ballinger, Scott; Shanmugam, Mayilvahanan; Babu, Gopal J; Johnson, Michelle S; Darley-Usmar, Victor; Dell'Italia, Louis J

2013-11-15

48

Short-Term Mechanical Unloading With Left Ventricular Assist Devices After Acute Myocardial Infarction Conserves Calcium Cycling and Improves Heart Function  

PubMed Central

Objectives This study sought to demonstrate that short-term cardiac unloading with a left ventricular (LV) assist device (LVAD) after acute myocardial infarction (MI) can conserve calcium cycling and improve heart function. Background Heart failure secondary to MI remains a major source of morbidity and mortality. Alterations in calcium cycling are linked to cardiac dysfunction in the failing heart. Methods Adult Dorsett hybrid sheep underwent acute MI and were mechanically unloaded with an axial-flow LVAD (Impella 5.0) for 2 weeks (n = 6). Six sheep with MI only and 4 sham sheep were used as controls. All animals were followed for 12 weeks post-MI. Regional strains in the LV were measured by sonomicrometry. Major calcium-handling proteins (CHPs), including sarco-/endoplasmic reticulum calcium ATPase-2? (SERCA-2?), Na+-Ca2+ exchanger-1, and phospholamban, and Ca2+-ATPase activity were investigated. The electrophysiological calcium cycling in single isolated cardiomyocytes was measured with the patch-clamp technique. The related ultrastructures were studied with electron microscopy. Results LVAD unloading alleviated LV dilation and improved global cardiac function and regional contractility compared with the MI group. The regional myocardial strain (stretch) was minimized during the unloading period and even attenuated compared with the MI group at 12 weeks. Impaired calcium cycling was evident in the adjacent noninfarcted zone in the MI group, whereas CHP expression was normalized and Ca2+-ATPase activity was preserved in the LVAD unloading group. The electrophysiological calcium cycling was also conserved, and the ultrastructural damage was ameliorated in the unloaded animals. Conclusions Short-term LVAD unloading may conserve calcium cycling and improve heart function during the post-infarct period.

Wei, Xufeng; Li, Tieluo; Hagen, Brian; Zhang, Pei; Sanchez, Pablo G.; Williams, Katrina; Li, Shuying; Bianchi, Giacomo; Son, Ho Sung; Wu, Changfu; DeFilippi, Christopher; Xu, Kai; Lederer, William J.; Wu, Zhongjun J.; Griffith, Bartley P.

2013-01-01

49

Induction, structural characterization, and genome sequence of Lv1, a prophage from a human vaginal Lactobacillus jensenii strain.  

PubMed

The prophage Lv1, harbored by a vaginal Lactobacillus jensenii isolate, was induced by several different anticancer, antimicrobial, and antiseptic agents, suggesting that they contribute to the adverse vaginal effects associated with their therapeutic use. Of special interest with respect to its novelty was the inducing effect of nonoxynol-9, a non-ionic detergent commonly used as a spermicide. The Lv1 genome consists of a 38,934-bp dsDNA molecule with cohesive ends, in which 48 ORFs were recognized, and is organized into functional modules. Lv1 belongs to the family Siphoviridae and, more precisely, to the proposed Sfi21-like genus. The capsid-tail junction of the Lv1 virions is fragile such that most particles become disrupted, suggesting that the virus is defective and thus unable to generate fertile progeny. However, genome analysis did not provide evidence of the defective nature of the prophage, other than the finding that its genome is shorter than those of other, related, phages. Further analysis indicated that prophage Lv1 suffered deletions in its right half to the extent that it no longer fulfill the minimum packaging limits, thereby generating the observed unstable particles. PMID:20890845

Martín, Rebeca; Escobedo, Susana; Suárez, Juan E

2010-09-01

50

Magnetic resonance imaging in coronary artery bypass surgery - improvement of global and segmental function in patients with severely compromized left ventricular function  

PubMed Central

Objectives In the present study, patients with severely compromized left ventricular function underwent magnetic resonance imaging (MRI) before and after coronary artery bypass grafting (CABG). Although improvement of global myocardial contractile function has been shown before, we sought to evaluate whether a functional contractile improvement may be determinable on a myocardial segmental basis after CABG surgery. Methods Thirty-three CABG patients with left ventricular ejection fraction (LVEF) ?30% prospectively underwent MRI to compare pre- and postoperative functional data. At follow-up, all survivors underwent clinical assessment. In 16 patients (three patients died perioperatively, 13 could were lost to MRI follow-up because of cardiac resynchronization therapy and other reasons) postoperative MRI scanning was performed. Results In-hospital mortality was 9%. At 20 ± 2 months after surgery, New York Heart Association class improved from 3.0 ± 0.1 to 2.2 ± 0.2 (p < 0.01). Left ventricular end-diastolic volumes decreased significantly from 229 ± 14 mL to 189 ± 19 mL (p < 0.05). LV end-systolic volumes decreased significantly from 163 ± 13 mL to 126 ± 17 mL (p < 0.05). LVEF improved from 30 ± 2% to 36 ± 3% (p < 0.05). On a segmental basis, 42 out of 875 segments (4.8%) had normal function before surgery, at follow-up, 177 segments (20.4%) had normal regional function (p < 0.05). Conclusions Patients who undergo CABG surgery with severely compromized left ventricular function, postoperative MRI shows improved global and segmental cardiac function at mid-term follow-up. At the same time there is considerable clinical improvement.

Thielmann, Matthias; Hunold, Peter; Bohm, Claudia; Massoudy, Parwis; Jakob, Heinz

2007-01-01

51

Improved algorithm for calculating the Chandrasekhar function  

NASA Astrophysics Data System (ADS)

Theoretical models of electron transport in condensed matter require an effective source of the Chandrasekhar H(x,omega) function. A code providing the H(x,omega) function has to be both accurate and very fast. The current revision of the code published earlier [A. Jablonski, Comput. Phys. Commun. 183 (2012) 1773] decreased the running time, averaged over different pairs of arguments x and omega, by a factor of more than 20. The decrease of the running time in the range of small values of the argument x, less than 0.05, is even more pronounced, reaching a factor of 30. The accuracy of the current code is not affected, and is typically better than 12 decimal places. New version program summaryProgram title: CHANDRAS_v2 Catalogue identifier: AEMC_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEMC_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC license, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 976 No. of bytes in distributed program, including test data, etc.: 11416 Distribution format: tar.gz Programming language: Fortran 90 Computer: Any computer with a Fortran 90 compiler Operating system: Windows 7, Windows XP, Unix/Linux RAM: 0.7 MB Classification: 2.4, 7.2 Catalogue identifier of previous version: AEMC_v1_0 Journal reference of previous version: Comput. Phys. Commun. 183 (2012) 1773 Does the new version supersede the old program: Yes Nature of problem: An attempt has been made to develop a subroutine that calculates the Chandrasekhar function with high accuracy, of at least 10 decimal places. Simultaneously, this subroutine should be very fast. Both requirements stem from the theory of electron transport in condensed matter. Solution method: Two algorithms were developed, each based on a different integral representation of the Chandrasekhar function. The final algorithm is edited by mixing these two algorithms by selecting ranges of the argument omega in which the performance is the fastest. Reasons for the new version: Some of the theoretical models describing electron transport in condensed matter need a source of the Chandrasekhar H function values with an accuracy of at least 10 decimal places. Additionally, calculations of this function should be as fast as possible since frequent calls to a subroutine providing this function are made (e.g., numerical evaluation of a double integral with a complicated integrand containing the H function). Both conditions were satisfied in the algorithm previously published [1]. However, it has been found that a proper selection of the quadrature in an integral representation of the Chandrasekhar function may considerably decrease the running time. By suitable selection of the number of abscissas in Gauss-Legendre quadrature, the execution time was decreased by a factor of more than 20. Simultaneously, the accuracy of results has not been affected. Summary of revisions: (1) As in previous work [1], two integral representations of the Chandrasekhar function, H(x,omega), were considered: the expression published by Dudarev and Whelan [2] and the expression published by Davidovi? et al. [3]. The algorithms implementing these representations were designated A and B, respectively. All integrals in these implementations were previously calculated using Romberg quadrature. It has been found, however, that the use of Gauss-Legendre quadrature considerably improved the performance of both algorithms. Two conditions have to be satisfied. (i) The number of abscissas, N, has to be rather large, and (ii) the abscissas and corresponding weights should be determined with accuracy as high as possible. The abscissas and weights are available for N=16, 20, 24, 32, 40, 48, 64, 80, and 96 with accuracy of 20 decimal places [4], and all these values were introduced into a new procedure GAUSS replacing procedure ROMBERG. Due to the fact that the implemented tables are rather extensive, they were recalculated using the Rybicki algorithm (Re

Jablonski, A.

2013-02-01

52

Electric drives on the LV100 gas turbine engine  

SciTech Connect

The LV100 gas turbine engine is being developed for US Army ground vehicle use. A unique approach for controls and accessories is being used whereby the engine has no accessory gearbox. Instead a high-speed starter/generator is mounted directly on the compressor shaft and powers all engine accessories as well as supplies the basic electrical power needs of the vehicle. This paper discusses the evolution of the electrically driven LV100 accessory system starting with the Advanced Integrated Propulsion System (AIPS) demonstrator program, through the current system to future possibilities with electric vehicle propulsion. Issues in electrical vehicle propulsion are discussed including machine type, electrical power type, and operation with a gas turbine.

Jones, W.D.; Fletcher, A.R. Jr. (General Electric Aircraft Engines, Lynn, MA (United States))

1994-04-01

53

Electric drives on the LV100 gas turbine engine  

NASA Astrophysics Data System (ADS)

The LV100 gas turbine engine is being developed for U.S. Army ground vehicle use. A unique approach for controls and accessories is being used whereby the engine has no accessory gearbox. Instead a high-speed starter/generator is mounted directly on the compressor shaft and powers all engine accessories as well as supplies the basic electrical power needs of the vehicle. This paper discusses the evolution of the electrically driven LV100 accessory system starting with the Advanced Integrated Propulsion System (AIPS) demonstrator program, through the current system to future possibilities with electric vehicle propulsion. Issues in electrical vehicle propulsion are discussed including machine type, electrical power type, and operation with a gas turbine.

Jones, W. D.; Fletcher, A. R., Jr.

1994-04-01

54

Loss or Inhibition of uPA or MMP-9 Attenuates LV Remodeling and Dysfunction after Acute Pressure Overload in Mice  

PubMed Central

Left ventricular (LV) hypertrophy is a natural response of the heart to increased pressure loading, but accompanying fibrosis and dilatation may result in irreversible life-threatening heart failure. Matrix metalloproteinases (MMPs) have been invoked in various cardiac diseases, however, direct genetic evidence for a role of the plasminogen activator (PA) and MMP systems in pressure overload-induced LV hypertrophy and in heart failure is lacking. Therefore, the consequences of transverse aortic banding (TAB) were analyzed in mice lacking tissue-type PA (t-PA?/?), urokinase-type PA (u-PA?/?), or gelatinase-B (MMP-9?/?), and in wild-type (WT) mice after adenoviral gene transfer of the PA-inhibitor PAI-1 or the MMP-inhibitor TIMP-1. TAB elevated LV pressure comparably in all genotypes. In WT and t-PA?/? mice, cardiomyocyte hypertrophy was associated with myocardial fibrosis, LV dilatation and dysfunction, and pump failure after 7 weeks. In contrast, in u-PA?/? mice or in WT mice after PAI-1- and TIMP-1-gene transfer, cardiomyocyte hypertrophy was moderate and only minimally associated with cardiac fibrosis and LV dilatation, resulting in better preservation of pump function. Deficiency of MMP-9 had an intermediate effect. These findings suggest that the use of u-PA- or MMP-inhibitors might preserve cardiac pump function in LV pressure overloading.

Heymans, Stephane; Lupu, Florea; Terclavers, Sven; Vanwetswinkel, Bjorn; Herbert, Jean-Marc; Baker, Andrew; Collen, Desire; Carmeliet, Peter; Moons, Lieve

2005-01-01

55

Bioinformatics analysis of time series gene expression in left ventricle (LV) with acute myocardial infarction (AMI).  

PubMed

This study is to investigate the key genes and their possible function in acute myocardial infarction (AMI). The data of GSE4648 downloaded from the Gene Expression Omnibus (GEO) database include 6 time points (15min, 60min, 4h, 12h, 24h and 48h) of 12 left ventricle (LV) samples, 12 surviving LV free wall (FW) samples, 12 inter-ventricular septum (IVS) samples after AMI operation and corresponding sham-operated samples. The data of each sample were analyzed with Affy and Bioconductor packages, and differentially expressed genes (DEGs) were screened out using BETR package with false discovery rate (FDR)<0.01. Then, functional enrichment analysis for DEGs was conducted with Database for Annotation, Visualization and Integrated Discovery (DAVID). Totally 194 DEGs were identified in LV, and only the gene tubulin beta 2a (Tubb2a) and natriuretic peptide B (Nppb) were respectively up-regulated in surviving FW tissue and IVS tissue. The biological process response to wounding and inflammatory response were significantly enriched, as well as leukocyte transendothelial migration pathway. Besides, the expression pattern analysis showed the DEGs mostly up-regulated at 4h after AMI, and these genes were mainly associated with immunity. Additionally, in transcriptional regulatory network, early growth response 1 (Egr1), activating transcription factor 3 (Atf3), Atf4, Myc and Fos were considered as the key transcription factors related to immune response. The key transcription factors and potential target genes might provide new information for the development of AMI, and leukocyte transendothelial migration pathway might play a vital role in AMI. PMID:24704022

Zhang, Tong; Zhao, Li-Li; Cao, Xue; Qi, Li-Chun; Wei, Guo-Qian; Liu, Jun-Yan; Yan, Shu-Jun; Liu, Jin-Gang; Li, Xue-Qi

2014-06-15

56

Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy.  

PubMed

Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n = 8; 0.5, 0.3, 0.1 ?g g(-1)) or D with vitamins C and E (DCE; n = 8; 200 and 100 mg kg(-1), respectively) on postnatal days 1-3 (P1-3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n = 8). A fourth group received vitamins alone (CCE; n = 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 ?M), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (cardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min(-1)) or afterload (cardiac output: -5.3 ± 2.0 vs.1.4 ± 1.2 ml min(-1)); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes cardiac dysfunction at adulthood. Combined neonatal treatment with antioxidant vitamins is an effective intervention. PMID:23940378

Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

2013-10-15

57

Role of HIV-2 envelope in Lv2-mediated restriction  

SciTech Connect

We have characterized envelope protein pseudotyped HIV-2 particles derived from two HIV-2 isolates termed prCBL23 and CBL23 in order to define the role of the envelope protein for the Lv2-mediated restriction to infection. Previously, it has been described that the primary isolate prCBL23 is restricted to infection of several human cell types, whereas the T cell line adapted isolate CBL23 is not restricted in these cell types. Molecular cloning of the two isolates revealed that the env and the gag gene are responsible for the observed phenotype and that this restriction is mediated by Lv2, which is distinct from Ref1/Lv1 (Schmitz, C., Marchant, D., Neil, S.J., Aubin, K., Reuter, S., Dittmar, M.T., McKnight, A., Kizhatil, K., Albritton, L.M., 2004. Lv2, a novel postentry restriction, is mediated by both capsid and envelope. J. Virol. 78 (4), 2006-2016). We generated pseudotyped viruses consisting of HIV-2 (ROD-A{delta}env-GFP, ROD-A{delta}env-RFP, or ROD-A{delta}env-REN) and the prCBL23 or CBL23 envelope proteins as well as chimeric proteins between these envelopes. We demonstrate that a single amino acid exchange at position 74 in the surface unit of CBL23-Env confers restriction to infection. This single point mutation causes tighter CD4 binding, resulting in a less efficient fusion into the cytosol of the restricted cell line. Prevention of endosome formation and prevention of endosome acidification enhance infectivity of the restricted particles for GHOST/X4 cells indicating a degradative lysosomal pathway as a cause for the reduced cytosolic entry. The described restriction to infection of the primary isolate prCBL23 is therefore largely caused by an entry defect. A remaining restriction to infection (19-fold) is preserved when endosomal acidification is prevented. This restriction to infection is also dependent on the presence of the point mutation at position 74 (G74E)

Reuter, Sandra [Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg (Germany); Kaumanns, Patrick [Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg (Germany); Buschhorn, Sabine B. [Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg (Germany); Dittmar, Matthias T. [Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg (Germany)]. E-mail: Matthias_Dittmar@med.uni-heidelberg.de

2005-02-05

58

Improvement of Left Ventricular Function under Cardiac Resynchronization Therapy Goes along with a Reduced Incidence of Ventricular Arrhythmia  

PubMed Central

Objectives The beneficial effects of cardiac resynchronization therapy (CRT) are thought to result from favorable left ventricular (LV) reverse remodeling, however CRT is only successful in about 70% of patients. Whether response to CRT is associated with a decrease in ventricular arrhythmias (VA) is still discussed controversially. Therefore, we investigated the incidence of VA in CRT responders in comparison with non-responders. Methods In this nonrandomized, two-center, observational study patients with moderate-to-severe heart failure, LV ejection fraction (LVEF) ?35%, and QRS duration >120 ms undergoing CRT were included. After 6 months patients were classified as CRT responders or non-responders. Incidence of VA was compared between both groups by Kaplan-Meier analysis and Cox regression analysis. ROC analysis was performed to determine the aptitude of LVEF cut-off values to predict VA. Results In total 126 consecutive patients (64±11years; 67%male) were included, 74 were classified as responders and 52 as non-responders. While the mean LVEF at baseline was comparable in both groups (25±7% vs. 24±8%; P?=?0.4583) only the responder group showed an improvement of LVEF (36±6% vs. 24±7; p<0.0001) under CRT. In total in 56 patients VA were observed during a mean follow-up of 28±14 months, with CRT responders experiencing fewer VA than non-responders (35% vs. 58%, p<0.0061). Secondary preventive CRT implantation was associated with a higher likelihood of VA. As determined by ROC analysis an increase of LVEF by >7% was found to be a predictor of a significantly lower incidence of VA (AUC?=?0.606). Conclusions Improvement of left ventricular function under cardiac resynchronization therapy goes along with a reduced incidence of ventricular arrhythmia.

Eickholt, Christian; Siekiera, Marcus; Kirmanoglou, Kiriakos; Rodenbeck, Astrid; Heussen, Nicole; Schauerte, Patrick; Lichtenberg, Artur; Balzer, Jan; Rassaf, Tienush; Perings, Stefan; Kelm, Malte; Shin, Dong-In; Meyer, Christian

2012-01-01

59

Tissue kallikrein-modified human endothelial progenitor cell implantation improves cardiac function via enhanced activation of akt and increased angiogenesis.  

PubMed

Endothelial progenitor cells (EPCs) have been shown to enhance angiogenesis not only by incorporating into the vasculature but also by secreting cytokines, thereby serving as an ideal vehicle for gene transfer. As tissue kallikrein (TK) has pleiotropic effects in inhibiting apoptosis and oxidative stress, and promoting angiogenesis, we evaluated the salutary potential of kallikrein-modified human EPCs (hEPCs; Ad.hTK-hEPCs) after acute myocardial infarction (MI). We genetically modified hEPCs with a TK gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a nude mouse left anterior descending ligation model. hEPCs were manipulated to overexpress the TK gene. In vitro, the antiapoptotic and paracrine effects were assessed under oxidative stress. TK protects hEPCs from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and -9, induction of Akt phosphorylation, and secretion of vascular endothelial growth factor. In vivo, the Ad.hTK-hEPCs were transplanted after MI via intracardiac injection. The surviving cells were tracked after transplantation using near-infrared optical imaging. Left ventricular (LV) function was evaluated by transthoracic echocardiography. Capillary density was quantified using immunohistochemical staining. Engrafted Ad.hTK-hEPCs exhibited advanced protection against ischemia by increasing LV ejection fraction. Compared with Ad.Null-hEPCs, transplantation with Ad.hTK-hEPCs significantly decreased cardiomyocyte apoptosis in association with increased retention of transplanted EPCs in the myocardium. Capillary density and arteriolar density in the infarct border zone was significantly higher in Ad.hTK-hEPC-transplanted mice than in Ad.Null-hEPC-treated mice. Transplanted hEPCs were clearly incorporated into CD31(+) capillaries. These results indicate that implantation of kallikrein-modified EPCs in the heart provides advanced benefits in protection against ischemia-induced MI by enhanced angiogenesis and reducing apoptosis. PMID:23508045

Yao, Yuyu; Sheng, Zulong; Li, YeFei; Fu, Cong; Ma, Genshan; Liu, Naifeng; Chao, Julie; Chao, Lee

2013-05-01

60

Tissue Kallikrein-Modified Human Endothelial Progenitor Cell Implantation Improves Cardiac Function via Enhanced Activation of Akt and Increased Angiogenesis  

PubMed Central

Endothelial progenitor cells (EPCs) have been shown to enhance angiogenesis not only by incorporating into the vasculature but also by secreting cytokines, thereby serving as an ideal vehicle for gene transfer. As tissue kallikrein (TK) has pleiotropic effects in inhibiting apoptosis and oxidative stress, and promoting angiogenesis, we evaluated the salutary potential of kallikrein-modified human EPCs (Ad.hTK-hEPCs) after acute myocardial infarction (MI). We genetically modified hEPCs with a TK gene and evaluated cell survival, engraftment, revascularization, and functional improvement in a nude mouse left anterior descending ligation model. hEPCs were manipulated to overexpress the TK gene. In-vitro, the antiapoptotic and paracrine effects were assessed under oxidative stress. TK protects hEPCs from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and 9, induction of Akt phosphorylation, and secretion of vascular endothelial growth factor. In vivo, the Ad.hTK-hEPCs were transplanted after MI via intracardiac injection. The surviving cells were tracked after transplantation using near-infrared optical imaging. Left ventricular (LV) function was evaluated by transthoracic echocardiography. Capillary density was quantified using immunohistochemical staining. Engrafted Ad.hTK-hEPCs exhibited advanced protection against ischemia by increasing LV ejection fraction. Compared with Ad.Null-hEPCs, transplantation with Ad.hTK-hEPCs significantly decreased cardiomyocyte apoptosis in association with increased retention of transplanted EPCs in the myocardium. Capillary density and arteriolar density in the infarct border zone was significantly higher in Ad.hTK-hEPCs transplanted mice than in Ad.Null-hEPCs treated mice. Transplanted hEPCs were clearly incorporated into CD31+ capillaries. These results indicate that implantation of kallikrein-modified EPCs in the heart provides advanced benefits in protection against ischemia-induced MI by enhanced angiogenesis and reducing apoptosis.

Yao, Yuyu; Sheng, Zulong; Li, Yefei; Fu, Cong; Ma, Genshan; Liu, Naifeng; Chao, Julie; Chao, Lee

2014-01-01

61

Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in Dukes' C colon cancer: the X-ACT trial  

PubMed Central

Oral capecitabine (Xeloda®) is an effective drug with favourable safety in adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming standard for Dukes' C colon cancer in patients suitable for combination therapy, but is not yet approved by the UK National Institute for Health and Clinical Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in relapse-free survival and a trend towards improved disease-free and overall survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer (UK National Health Service (NHS)) and societal perspectives. We used clinical trial data and published sources to estimate incremental direct and societal costs and gains in quality-adjusted life months (QALMs). Acquisition costs were higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5-FU/LV-associated adverse events required fewer medications and hospitalisations (cost savings £3653). Societal costs, including patient travel/time costs, were reduced by >75% with capecitabine vs 5-FU/LV (cost savings £1318), with lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society. Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost savings and better outcomes make capecitabine a preferred adjuvant therapy for Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.

Cassidy, J; Douillard, J-Y; Twelves, C; McKendrick, J J; Scheithauer, W; Bustova, I; Johnston, P G; Lesniewski-Kmak, K; Jelic, S; Fountzilas, G; Coxon, F; Diaz-Rubio, E; Maughan, T S; Malzyner, A; Bertetto, O; Beham, A; Figer, A; Dufour, P; Patel, K K; Cowell, W; Garrison, L P

2006-01-01

62

Functional tasks exercise improves daily function in older women  

Microsoft Academic Search

Ageing is characterised by a reduction in physical reserve, the physiological capacity in excess of that needed for daily activities, that provides a margin of safety that absorbs age- or disease-related changes without a loss in function. When physical capacity falls below the ability required for the performance of daily tasks, functional limitations and a loss of independence may occur.

P. L. de Vreede

2006-01-01

63

Dietary approaches to improving atheroprotective HDL functions.  

PubMed

High-density lipoproteins (HDL) are known to protect against cardiovascular disease (CVD). In addition to facilitating reverse cholesterol transport to remove excess lipids from the body - including atherosclerotic plaques - HDL exhibits antioxidant, anti-inflammatory, vasodilatory, and antithrombotic activities. Together, these properties contribute to the overall atheroprotective nature of HDL. However, similar to many other physiological pathways, these HDL parameters are known to become dysregulated in conditions of metabolic disease. Further, research suggests these alternative HDL properties may be regulated independently of blood HDL-cholesterol (HDL-C) levels, and must therefore be considered when designing HDL-targeted therapies. To date, a number of dietary strategies have been investigated to assess the effect of dietary components on functional properties of HDL beyond HDL-C. This review will highlight the bioactive nutrients, functional foods, and dietary programs known to modulate HDL function as a means of reducing CVD. PMID:23921436

Andersen, Catherine J; Fernandez, Maria Luz

2013-09-01

64

A model to determine the effect of collagen fiber alignment on heart function post myocardial infarction  

PubMed Central

Background Adverse remodeling of the left ventricle (LV) following myocardial infarction (MI) leads to heart failure. Recent studies have shown that scar anisotropy is a determinant of cardiac function post-MI, however it remains unclear how changes in extracellular matrix (ECM) organization and structure contribute to changes in LV function. The objective of this study is to develop a model to identify potential mechanisms by which collagen structure and organization affect LV function post-MI. Methods A four-region, multi-scale, cylindrical model of the post-MI LV was developed. The mechanical properties of the infarct region are governed by a constitutive equation based on the uncrimping of collagen fibers. The parameters of this constitutive equation include collagen orientation, angular dispersion, fiber stiffness, crimp angle, and density. Parametric variation of these parameters was used to elucidate the relationship between collagen properties and LV function. Results The mathematical model of the LV revealed several factors that influenced cardiac function post-MI. LV function was maximized when collagen fibers were aligned longitudinally. Increased collagen density was also found to improve stroke volume for longitudinal alignments while increased fiber stiffness decreased stroke volume for circumferential alignments. Conclusions The results suggest that cardiac function post-MI is best preserved through increased circumferential compliance. Further, this study identifies several collagen fiber-level mechanisms that could potentially regulate both infarct level and organ level mechanics. Improved understanding of the multi-scale relationships between the ECM and LV function will be beneficial in the design of new diagnostic and therapeutic technologies.

2014-01-01

65

Improved coil design for functional magnetic stimulation of expiratory muscles  

Microsoft Academic Search

The authors' studies have demonstrated effective stimulation of the expiratory muscles in patients with spinal cord injury (SCI) using functional magnetic stimulation (FMS). The observed contraction of the expiratory muscles and functional improvement of the pulmonary functions make functional magnetic stimulation an appropriate tool for expiratory muscle training. To fully capitalize on the benefits of FMS for expiratory muscle training,

Ian N. Hsiao; Vernon Weh-Hau Lin

2001-01-01

66

Improved association in a classical density functional theory for water  

NASA Astrophysics Data System (ADS)

We present a modification to our recently published statistical associating fluid theory-based classical density functional theory for water. We have recently developed and tested a functional for the averaged radial distribution function at contact of the hard-sphere fluid that is dramatically more accurate at interfaces than earlier approximations. We now incorporate this improved functional into the association term of our free energy functional for water, improving its description of hydrogen bonding. We examine the effect of this improvement by studying two hard solutes (a hard hydrophobic rod and a hard sphere) and a Lennard-Jones approximation of a krypton atom solute. The improved functional leads to a moderate change in the density profile and a large decrease in the number of hydrogen bonds broken in the vicinity of the hard solutes. We find an improvement of the partial radial distribution for a krypton atom in water when compared with experiment.

Krebs, Eric J.; Schulte, Jeff B.; Roundy, David

2014-03-01

67

Using membership functions to improve multiclass SVM  

Microsoft Academic Search

Support vector machine is originally designed for binary classification. One-against-one method is commonly used in multiclass classification. Based on the analysis of the decision process of max wins used in one-against-one method, new membership functions are introduced to resolve the possibly existed unclassifiable regions and a fuzzy SVM multiclass classification algorithm FSVM is proposed. Classification experiments result proves the effectiveness

Wang Xiaodan; Wu Chongming

2004-01-01

68

?3 adrenergic receptor selective stimulation during ischemia/reperfusion improves cardiac function in translational models through inhibition of mPTP opening in cardiomyocytes.  

PubMed

Selective stimulation of ?3 adrenergic-receptor (?3AR) has been shown to reduce infarct size in a mouse model of myocardial ischemia/reperfusion. However, its functional long-term effect and the cardioprotective mechanisms at the level of cardiomyocytes have not been elucidated, and the impact of ?3AR stimulation has not been evaluated in a more translational large animal model. This study aimed at evaluating pre-perfusion administration of BRL37344 both in small and large animal models of myocardial ischemia/reperfusion. Pre-reperfusion administration of the ?3AR agonist BRL37344 (5 ?g/kg) reduced infarct size at 2-and 24-h reperfusion in wild-type mice. Long-term (12-weeks) left ventricular (LV) function assessed by echocardiography and cardiac magnetic resonance (CMR) was significantly improved in ?3AR agonist-treated mice. Incubation with ?3AR agonist (BRL37344, 7 ?mol/L) significantly reduced cell death in isolated adult mouse cardiomyocytes during hypoxia/reoxygenation and decreased susceptibility to deleterious opening of the mitochondrial permeability transition pore (mPTP), via a mechanism dependent on the Akt-NO signaling pathway. Pre-reperfusion BRL37344 administration had no effect on infarct size in cyclophilin-D KO mice, further implicating mPTP in the mechanism of protection. Large-white pigs underwent percutaneous coronary ischemia/reperfusion and 3-T CMR at 7 and 45 days post-infarction. Pre-perfusion administration of BRL37344 (5 ?g/kg) decreased infarct size and improved long-term LV contractile function. A single-dose administration of ?3AR agonist before reperfusion decreased infarct size and resulted in a consistent and long-term improvement in cardiac function, both in small and large animal models of myocardial ischemia/reperfusion. This protection appears to be executed through inhibition of mPTP opening in cardiomyocytes. PMID:24951958

García-Prieto, Jaime; García-Ruiz, Jose Manuel; Sanz-Rosa, David; Pun, Andrés; García-Alvarez, Ana; Davidson, Sean M; Fernández-Friera, Leticia; Nuno-Ayala, Mario; Fernández-Jiménez, Rodrigo; Bernal, Juan A; Izquierdo-Garcia, José Luis; Jimenez-Borreguero, Jesús; Pizarro, Gonzalo; Ruiz-Cabello, Jesús; Macaya, Carlos; Fuster, Valentín; Yellon, Derek M; Ibanez, Borja

2014-07-01

69

Does repair of pectus excavatum improve cardiopulmonary function?  

PubMed Central

A best evidence topic was written according to a structured protocol. The question addressed was ‘Does repair of pectus excavatum (PE) improve cardiopulmonary function?’ One hundred and sixty-eight papers were found using the reported search, 19 level III evidence papers and three meta-analyses were relevant. Studies were divided into four groups based on the surgical technique applied and pulmonary and cardiac functions in these groups were analysed. The meta-analyses show conflicting results for improvements in pulmonary and cardiac functions when comparing surgical techniques, while four more recent studies show improved long-term results using the Nuss technique. The best evidence of papers studying the PE repair using the minimally invasive Nuss technique demonstrates a decrease in pulmonary function during the early postoperative period, however, there is a small but significant improvement during the late postoperative period and after bar removal. The best evidence for cardiac function in this group suggests an early improvement that is sustained during further follow-up. The best evidence of papers studying the PE repair using the Ravitch technique shows that pulmonary function decreased during the early postoperative period, however, there is a small but significant improvement during the late postoperative period. The best evidence for cardiac function in this group suggests an early improvement that is sustained during further follow-up. The best evidence of papers studying the PE repair using other techniques (modified Daniel's technique, modified Baronofsky's technique, sterno-costal turn-over technique and sterno-costal elevation technique) or where surgical techniques used were not described (preceding year 1985) suggests that there is no improvement in pulmonary function after surgery. There is some evidence that certain aspects of cardiac function improved after surgery in this group.

Jayaramakrishnan, Kumara; Wotton, Robin; Bradley, Amy; Naidu, Babu

2013-01-01

70

Characterization of the putative farnesoic acid O-methyltransferase (LvFAMeT) cDNA from white shrimp, Litopenaeus vannamei: Evidence for its role in molting.  

PubMed

Methyl farnesoate (MF) is the crustacean homolog of the insect juvenile hormone and is believed to regulate growth and reproduction in crustaceans. Farnesoic acid O-methyltransferase (FAMeT) catalyzes the conversion of farnesoic acid (FA) to MF. Here we report the cloning and characterization of two forms of FAMeTs (i.e. LvFAMeT-S and LvFAMeT-L) from the shrimp Litopenaeus vannamei. LvFAMeT transcript has a wide tissue distribution pattern in L. vannamei and is also expressed in nauplius, zoea, mysis, post-larval stages and adults. Unlike FAMeTs reported in other decapods, transcripts of two different sizes were detected in L. vannamei. We postulate that the wide distribution of LvFAMeT expression may be related to its role in growth and regulation of molting. To study the functions of LvFAMeT in molting, the RNA interference (RNAi) technique was used. Injection of double stranded RNA (dsRNA) for LvFAMeT knocked down the expression of LvFAMeT in shrimp for at least 3 days and the shrimp did not advance to the final stage of molt cycle. Furthermore, the expression of the molt-related genes encoding cathepsin-L and the hemocyanin gene was disturbed. Subsequently, 100% mortality of the shrimp was observed in the LvFAMeT dsRNA-injected shrimp. In contrast, control shrimp completed their molt and proceeded to the next molt cycle. We postulate that, as an important enzyme for the conversion of FA to MF, RNAi injection knocked down the expression of LvFAMeT which could potentially result in a decrease in the production of MF and subsequently, could affect the molting process. The newly identified LvFAMeT may be involved in the control of molting in shrimp. The results of this study demonstrate the potential use of the RNA interference technique to study other putative genes identified in crustaceans. PMID:18226425

Hui, Jerome Ho Lam; Tobe, Stephen S; Chan, Siu-Ming

2008-02-01

71

Exogenously administered secreted frizzled related protein 2 (Sfrp2) reduces fibrosis and improves cardiac function in a rat model of myocardial infarction.  

PubMed

Secreted frizzled related protein 2 (Sfrp2) is known as an inhibitor for the Wnt signaling. In recent studies, Sfrp2 has been reported to inhibit the activity of Xenopus homolog of mammalian Tolloid-like 1 metalloproteinase. Bone morphogenic protein 1 (Bmp1)/Tolloid-like metalloproteinase plays a key role in the regulation of collagen biosynthesis and maturation after tissue injury. Here, we showed both endogenous Sfrp2 and Bmp1 protein expressions were up-regulated in rat heart after myocardial infarction (MI). We hypothesize that Sfrp2 could inhibit mammalian Bmp1 activity and, hence, the exogenous administration of Sfrp2 after MI would inhibit the deposition of mature collagen and improve heart function. Using recombinant proteins, we demonstrated that Sfrp2, but not Sfrp1 or Sfrp3, inhibited Bmp1 activity in vitro as measured by a fluorogenic peptide based procollagen C-proteinase activity assay. We also demonstrated that Sfrp2 at high concentration inhibited human and rat type I procollagen processing by Bmp1 in vitro. We further showed that exogenously added Sfrp2 inhibited type I procollagen maturation in primary cardiac fibroblasts. Two days after direct injection into the rat infarcted myocardium, Sfrp2 inhibited MI-induced type I collagen deposition. As early as 2 wk after injection, Sfrp2 significantly reduced left ventricular (LV) fibrosis as shown by trichrome staining. Four weeks after injection, Sfrp2 prevented the anterior wall thinning and significantly improved cardiac function as revealed by histological analysis and echocardiographic measurement. Our study demonstrates Sfrp2 at therapeutic doses can inhibit fibrosis and improve LV function at a later stage after MI. PMID:21078975

He, Wei; Zhang, Lunan; Ni, Aiguo; Zhang, Zhiping; Mirotsou, Maria; Mao, Lan; Pratt, Richard E; Dzau, Victor J

2010-12-01

72

Neurofeedback improves executive functioning in children with autism spectrum disorders  

Microsoft Academic Search

Seven autistic children diagnosed with autism spectrum disorders (ASD) received a neurofeedback treatment that aimed to improve their level of executive control. Neurofeedback successfully reduced children's heightened theta\\/beta ratio by inhibiting theta activation and enhancing beta activation over sessions. Following treatment, children's executive capacities were found to have improved greatly relative to pre-treatment assessment on a range of executive function

Mirjam E. J. Kouijzer; Berrie J. L. Gerrits; Marco Congedo; Hein T. van Schie

2008-01-01

73

Effects of Acute Intravenous Infusion of Apelin on Left Ventricular Function in Dogs with Advanced Heart Failure  

PubMed Central

Background Apelin-13 (APLN) through apelin receptor (APJ) exerts peripheral vasodilatory and potent positive inotropic effects. We examined the effects of exogenous intravenous infusion of APLN on left ventricular (LV) systolic function in dogs with heart failure (HF, LV ejection fraction, EF~30%). Methods and Results Studies were performed in 7 dogs with microembolization-induced HF. Each dog received an intravenous infusion of low dose and high dose APLN followed by washout period. LV end-diastolic volume (EDV), end-systolic volume (ESV) and LV EF were measured at specified time points. APLN protein level was determined in plasma at all time points. mRNA and protein levels of APLN and APJ in LV tissue were also measured in 7 normal (NL) and 7 heart failure (HF) dogs. APLN reduced EDV only at the high dose, significantly reduced ESV and increased EF with both doses. In plasma of HF dogs, APLN levels were reduced significantly compared to NL dogs. APLN treatment in HF dogs significantly increased the plasma APLN levels at both low and high doses. Expression of APLN, but not of APJ, was reduced in LV tissue of HF dogs compared to NL. Conclusion Exogenous administration of APLN improved LV systolic function in dogs with advanced HF.

Wang, Mengjun; Gupta, Ramesh C.; Rastogi, Sharad; Kohli, Smita; Sabbah, Michael S.; Zhang, Kefei; Mohyi, Paula; Hogie, Manuela; Fischer, Yvan; Sabbah, Hani N.

2013-01-01

74

Effects of propranolol treatment on left ventricular function and intracellular calcium regulation in rats with postinfarction heart failure  

PubMed Central

Chronic treatment with beta-adrenergic blocking agents can improve survival in patients with heart failure. The mechanisms underlying the beneficial effects and whether these effects are generalizable to ischaemic heart failure are unresolved.We performed echocardiographic-Doppler examinations in rats (n=28) 1 and 6 weeks after myocardial infarction (MI) or sham surgery. Rats were randomized to no treatment or propranolol (500?mg/l in drinking water) after the first echocardiogram. Isometric contractions and intracellular Ca transients were recorded simultaneously in noninfarcted left ventricular (LV) papillary muscles.Untreated MI rats had significant LV dilatation (10.6±0.4* vs 8.9±0.3?mm, MI vs control), impaired systolic function (fractional shortening=11±2* vs 38±2%), and a restrictive LV diastolic filling pattern. MI rats receiving propranolol had similar LV chamber sizes (10.6±0.5?mm) and systolic function (13±2%). The propranolol treated animals had higher LV end-diastolic pressures (27±2* vs 20±3?mmHg) and a more restricted LV diastolic filling pattern (increased ratio of early to late filling velocities and more rapid E wave deceleration rate). Contractility of papillary muscles from untreated MI rats was depressed (1.6±0.3 vs 2.4±0.5?g?mm?2). In addition, Ca transients were prolonged and the inotropic response to isoproterenol was blunted. Propranolol treatment did not improve force development (1.6±0.3?g?mm?2) or the duration of Ca transients during isoproterenol stimulation.Chronic propranolol treatment in rats with postinfarction heart failure did not improve LV remodeling or systolic function. LV diastolic pressures and filling patterns were worsened by propranolol. Treatment also did not produce appreciable improvement in contractility, intracellular Ca regulation or beta-adrenergic responsiveness in the noninfarcted myocardium.

Litwin, Sheldon E; Katz, Sarah E; Morgan, James P; Douglas, Pamela S

1999-01-01

75

Improved synthesis of functionalized molecular platforms related to marine cyclopeptides  

Microsoft Academic Search

We report an improved synthesis of new molecular platforms, functionalized for studies in molecular recognition and combinatorial chemistry. Their structures are related to naturally occurring marine cyclopeptides such as the Dolostatins and Dendroamides that feature side chain functionality positioned on the same face of a rigid platform. Incorporation of methyl substituted oxazole and thiazole rings into the platforms enhances the

László Somogyi; Gebhard Haberhauer; Julius Rebek

2001-01-01

76

Learning evaluation functions to improve optimization by local search  

Microsoft Academic Search

This paper describes algorithms that learn to improve search performance on large-scale optimization tasks. The main algorithm, STAGE, works by learning an evaluation function that predicts the outcome of a local search algorithm, such as hillclimbing or Walksat, from features of states visited during search. The learned evaluation function is then used to bias future search trajectories toward better optima

Justin Boyan; Andrew W. Moore

2001-01-01

77

Learning Evaluation Functions to Improve Optimization by Local Search  

Microsoft Academic Search

This paper describes algorithms that learn to improve search performance on largescale optimization tasks. The main algorithm, Stage, works by learning an evaluation function that predicts the outcome of a local search algorithm, such as hillclimbing or Walksat, from features of states visited during search. The learned evaluation function is then used to bias future search trajectories toward better optima

Justin A. Boyan; Andrew W. Moore

2000-01-01

78

Improved pair-potential function for diatomic systems  

NASA Astrophysics Data System (ADS)

A three-parameter pair-potential model recently constructed is improved in the short- and long-range interaction regions. We demonstrate that this improved potential function is able to accurately describe the entire potentials of the ground-state van der Waals systems such as rare-gas, triplet H2, Alkali-helium, Alkaline-earth, and group 12 diatomic systems. All these systems show a single binding-energy relation in the attractive region. The improved function suggests a unique form for describing the potentials of diatomic systems ranging from strongly-bound to weakly-bound diatomic systems.

Xie, Jianing Colin; Kar, Tapas; Mishra, Sudhanshu K.; Xie, Rui-Hua

2014-02-01

79

Statin therapy improves brachial artery endothelial function in nephrotic syndrome  

Microsoft Academic Search

Statin therapy improves brachial artery endothelial function in nephrotic syndrome.Background:Patients with nephrotic syndrome have impaired endothelial function probably related to dyslipidemia. This study evaluated the effects of statin therapy on dyslipidemia and endothelial function in patients with nephrotic syndrome.Methods:A sequential, open-label study of the effects of statins on endothelial dysfunction in 10 nephrotic patients treated with an angiotensin-converting enzyme (ACE)

Gursharan K Dogra; Gerald F Watts; Susan Herrmann; Mark A B Thomas; Ashley B Irish

2002-01-01

80

Viral DNA tethering domains complement replication-defective mutations in the p12 protein of MuLV Gag  

PubMed Central

The p12 protein of murine leukemia virus (MuLV) group-specific antigen (Gag) is associated with the preintegration complex, and mutants of p12 (PM14) show defects in nuclear entry or retention. Here we show that p12 proteins engineered to encode peptide sequences derived from known viral tethering proteins can direct chromatin binding during the early phase of viral replication and rescue a lethal p12-PM14 mutant. Peptides studied included segments of Kaposi sarcoma herpesvirus latency-associated nuclear antigen (LANA)1–23, human papillomavirus 8 E2, and prototype foamy virus chromatin-binding sequences. Amino acid substitutions in Kaposi sarcoma herpesvirus LANA and prototype foamy virus chromatin-binding sequences that blocked nucleosome association failed to rescue MuLV p12-PM14. Rescue by a larger LANA peptide, LANA1–32, required second-site mutations that are predicted to reduce peptide binding affinity to chromosomes, suggesting that excessively high binding affinity interfered with Gag/p12 function. This is supported by confocal microscopy of chimeric p12-GFP fusion constructs showing the reverted proteins had weaker association to condensed mitotic chromosomes. Analysis of the integration-site selection of these chimeric viruses showed no significant change in integration profile compared with wild-type MuLV, suggesting release of the tethered p12 post mitosis, before viral integration.

Schneider, William M.; Brzezinski, Jonathon D.; Aiyer, Sriram; Malani, Nirav; Gyuricza, Mercedes; Bushman, Frederic D.; Roth, Monica J.

2013-01-01

81

Inhibiting TGF-? activity improves respiratory function in mdx mice.  

PubMed

Respiratory function is the main cause of mortality in patients with Duchenne muscular dystrophy (DMD). Elevated levels of TGF-? play a key role in the pathophysiology of DMD. To determine whether therapeutic attenuation of TGF-? signaling improves respiratory function, mdx mice were treated from 2 weeks of age to 2 months or 9 months of age with either 1D11 (a neutralizing antibody to all three isoforms of TGF-?), losartan (an angiotensin receptor antagonist), or a combination of the two agents. Respiratory function was measured in nonanesthetized mice by plethysmography. The 9-month-old mdx mice had elevated Penh values and decreased breathing frequency, due primarily to decreased inspiratory flow rate. All treatments normalized Penh values and increased peak inspiratory flow, leading to decreased inspiration times and breathing frequency. Additionally, forelimb grip strength was improved after 1D11 treatment at both 2 and 9 months of age, whereas, losartan improved grip strength only at 2 months. Decreased serum creatine kinase levels (significant improvement for all groups), increased diaphragm muscle fiber density, and decreased hydroxyproline levels (significant improvement for 1D11 only) also suggested improved muscle function after treatment. For all endpoints, 1D11 was equivalent or superior to losartan; coadministration of the two agents was not superior to 1D11 alone. In conclusion, TGF-? antagonism may be a useful therapeutic approach for treating DMD patients. PMID:21641384

Nelson, Carol A; Hunter, R Bridge; Quigley, Lindsay A; Girgenrath, Stefan; Weber, William D; McCullough, Jennifer A; Dinardo, Carol J; Keefe, Kelly A; Ceci, Lorena; Clayton, Nicholas P; McVie-Wylie, Alison; Cheng, Seng H; Leonard, John P; Wentworth, Bruce M

2011-06-01

82

Text Mining Improves Prediction of Protein Functional Sites  

PubMed Central

We present an approach that integrates protein structure analysis and text mining for protein functional site prediction, called LEAP-FS (Literature Enhanced Automated Prediction of Functional Sites). The structure analysis was carried out using Dynamics Perturbation Analysis (DPA), which predicts functional sites at control points where interactions greatly perturb protein vibrations. The text mining extracts mentions of residues in the literature, and predicts that residues mentioned are functionally important. We assessed the significance of each of these methods by analyzing their performance in finding known functional sites (specifically, small-molecule binding sites and catalytic sites) in about 100,000 publicly available protein structures. The DPA predictions recapitulated many of the functional site annotations and preferentially recovered binding sites annotated as biologically relevant vs. those annotated as potentially spurious. The text-based predictions were also substantially supported by the functional site annotations: compared to other residues, residues mentioned in text were roughly six times more likely to be found in a functional site. The overlap of predictions with annotations improved when the text-based and structure-based methods agreed. Our analysis also yielded new high-quality predictions of many functional site residues that were not catalogued in the curated data sources we inspected. We conclude that both DPA and text mining independently provide valuable high-throughput protein functional site predictions, and that integrating the two methods using LEAP-FS further improves the quality of these predictions.

Cohn, Judith D.; Ravikumar, Komandur E.

2012-01-01

83

Does interferon-  improve pulmonary function in idiopathic pulmonary fibrosis?  

Microsoft Academic Search

Does interferon-c improve pulmonary function in idiopathic pulmonary fibrosis? A. Prasse, K-M.Muller, C. Kurz, H. Hamm, J.C. Virchow Jr. #ERS Journals Ltd 2003. ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a disease with progressive and devastating deterioration of lung function and a fatal prognosis, despite aggressive therapeutic attempts, which, in the majority of cases are futile. Recently, a preliminary study of

A. Prasse; K. M. Muller; C. Kurz; H. Hammz; J. C. Virchow Jr

2003-01-01

84

The Na+/Ca2+ exchange inhibitor SEA0400 limits intracellular Ca2+ accumulation and improves recovery of ventricular function when added to cardioplegia  

PubMed Central

Background The Na+/Ca2+ exchange inhibitor SEA0400 prevents myocardial injury in models of global ischemia and reperfusion. We therefore evaluated its potential as a cardioplegia additive. Methods Isolated rat cardiomyocytes were exposed to hypoxia (45 min) followed by reperfusion. During hypoxia, cells were protected using cardioplegia with (n?=?25) or without (n?=?24) SEA0400 (1 ?M), or were not protected with cardioplegia (hypoxic control, n?=?8). Intracellular Ca2+ levels were measured using Ca2+ sensitive dye (fura-2 AM). Isolated rat hearts were arrested using cardioplegia with (n?=?7) or without (n?=?6) SEA0400 (1 ?M) then reperfused after 45 min of ischemia. Left ventricular (LV) function, troponin release, and mitochondrial morphology were evaluated. Results Cardiomyocytes exposed to hypoxia without cardioplegia had poor survival (13%). Survival was significantly improved when cells were protected with cardioplegia containing SEA0400 (68%, p?=?0.009); cardioplegia without SEA0400 was associated with intermediate survival (42%). Cardiomyocytes exposed to hypoxia alone had a rapid increase in intracellular Ca2+ (305?±?123 nM after 20 minutes of ischemia). Increases in intracellular Ca2+ were reduced in cells arrested with cardioplegia without SEA0400; however cardioplegia containing SEA0400 was associated with the lowest intracellular Ca2+ levels (110?±?17 vs. 156?±?42 nM after 45 minutes of ischemia, p?=?0.004). Hearts arrested with cardioplegia containing SEA0400 had better recovery of LV work compared to cardioplegia without SEA0400 (23140?±?2264 vs. 7750?±?929 mmHg.?l, p?=?0.0001). Troponin release during reperfusion was lower (0.6?±?0.2 vs. 2.4?±?0.5 ng/mL, p?=?0.0026), and there were more intact (41?±?3 vs. 22?±?5%, p?improves recovery of LV function in isolated hearts.

2014-01-01

85

Impact of a systolic parameter, defined as the ratio of right brachial pre-ejection period to ejection time, on the relationship between brachial-ankle pulse wave velocity and left ventricular diastolic function  

Microsoft Academic Search

Arterial stiffness is correlated with left ventricular (LV) diastolic function as well as susceptibility to LV systolic function. Therefore, if LV systolic function is not known, the relationship between arterial stiffness and LV diastolic function is difficult to determine. A total of 260 patients were included in the study. The brachial-ankle pulse wave velocity (baPWV) and the ratio of right

Po-Chao Hsu; Tsung-Hsien Lin; Chee-Siong Lee; Chun-Yuan Chu; Ho-Ming Su; Wen-Chol Voon; Wen-Ter Lai; Sheng-Hsiung Sheu; H-M Su

2011-01-01

86

Improvement to the averaging method using the Jacobian elliptic function  

Microsoft Academic Search

The averaging method was improved by using the Jacobian elliptic sine (sn), cosine (cn) and delta (dn) functions as generating solutions in order to obtain a highly accurate periodic solution for a strongly nonlinear dynamical system. The proposed method can be applied to a relatively general nonlinear system based on the single degree-of-freedom Duffing equation. Two methods of stability analysis

T. Okabe; T. Kondou

2009-01-01

87

Improvement of functional magnetic resonance images by pretreatment of data  

Microsoft Academic Search

Functional magnetic resonance images of the brains of subjects performing the finger-tapping paradigm were made using a conventional technique. Two threshold values for the pixels were obtained by analysing pixel by pixel the distributions of the means and variances of each subject's images for 20 consecutive scans, both while performing the task and while at rest. Considerable signal improvement in

Manuel Cortijo; Carmen Santisteban; Beatriz Carrero-González; Jesus Alvarado; Jesus Ruiz-Cabello

1996-01-01

88

Dichloroacetate improves postischemic function of hypertrophied rat hearts  

Microsoft Academic Search

OBJECTIVESWe sought to determine whether improving coupling between glucose oxidation and glycolysis by stimulating glucose oxidation during reperfusion enhances postischemic recovery of hypertrophied hearts.BACKGROUNDLow rates of glucose oxidation and high glycolytic rates are associated with greater postischemic dysfunction of hypertrophied as compared with nonhypertrophied hearts.METHODSHeart function, glycolysis and glucose oxidation were measured in isolated working control and hypertrophied rat hearts

Richard B Wambolt; Gary D Lopaschuk; Roger W Brownsey; Michael F Allard

2000-01-01

89

Maca (L. meyenii) for improving sexual function: a systematic review  

Microsoft Academic Search

BACKGROUND: Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. METHODS: We searched 17 databases from their inception to April

Byung-Cheul Shin; Myeong Soo Lee; Eun Jin Yang; Hyun-Suk Lim; Edzard Ernst

2010-01-01

90

Functional and pathological improvements of the hearts in diabetes model by the combined therapy of bFGF-loaded nanoparticles with ultrasound-targeted microbubble destruction.  

PubMed

Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality among the diabetic patients and currently there is no effective means to reverse its pathological progress. Basic fibroblast growth factor (bFGF) has shown promise as a molecular therapy for DCM, but its delivery is inefficient and non-specific. In the present study, a therapy combining nanoparticle (NP) carrier and ultrasound-targeted microbubble destruction (UTMD) was reported the first time for bFGF delivery to the heart of diabetic rats. bFGF-loaded NP (bFGF-NP) were prepared with Poloxamer 188-grafted heparin copolymer using water-in-water technique, and the morphology, encapsulation efficiency, and bioactivity of bFGF-NP were studied. The cellular uptake and cytotoxicity of bFGF-NP were evaluated with primary cultures of the left ventricular (LV) cardiomyocytes in vitro. Therapeutic effects of bFGF-NP/UTMD on the heart of DCM rats were studied by measuring LV systolic and diastolic functions, hemodynamic characteristics and indicators of cardiac remodeling including myocardial collagen volume fraction and capillary density. Results demonstrated that bFGF-NP showed good round morphology, efficient bFGF encapsulation and stable bioactivity of bFGF in vitro. bFGF-NP/UTMD combined treatment significantly enhanced the efficiency of bFGF cellular uptake (P<0.05) without obvious cytotoxicity. Significant improvements (P<0.05) in both cardiac functions and tissue morphology in the DCM rats were observed in bFGF-NP/UTMD group. These were not achievable using free bFGF, bFGF-NP or UTMD treatment alone. Our results show that combining a non-viral vector with UTMD technique is an effective strategy to deliver bFGF to the heart, and the resulting growth factor therapy has demonstrated potential to reverse the progress of DCM by restoring the cardiac functions and even the structure of damaged cardiac tissues. PMID:24815422

Zhao, Ying-Zheng; Tian, Xin-Qiao; Zhang, Ming; Cai, Lu; Ru, Ao; Shen, Xiao-Tong; Jiang, Xi; Jin, Rong-Rong; Zheng, Lei; Hawkins, Kyle; Charkrabarti, Subrata; Li, Xiao-Kun; Lin, Qian; Yu, Wen-Ze; Ge, Shuping; Lu, Cui-Tao; Wong, Ho Lun

2014-07-28

91

Characterization of Thiobacillus thioparus LV43 and its distribution in a chemoautotrophically based groundwater ecosystem.  

PubMed Central

Bacterial strain LV43 was previously isolated from a floating microbial mat located in Movile Cave, the access point to a chemoautotrophically based groundwater ecosystem in southern Romania. This gram-negative, rod-shaped organism grows autotrophically through the oxidation of thiosulfate and sulfide, but it does not grow heterotrophically. Strain LV43 grows over a pH range of 5.0 to 9.0, with an optimum near 7.5 at 28 degrees C. The pH of the medium decreased from 7.5 to 6.5 during growth on thiosulfate. Carbon isotope fractionation values for strain LV43 were within the previously reported range of fractionation values for the overall floating microbial mat in Movile Cave and were similar to values reported for chemoautotrophic sulfur-oxidizing strains of Thiobacillus neapolitanus and Thiomicrospira sp. The 16S rRNA gene sequence of strain LV43 was determined, and phylogenetic analysis indicated that strain LV43 was most closely related to Thiobacillus thioparus and the uncultured bacterial strain Strip2, which is represented by a 16S rRNA clone obtained by direct PCR from the Stripa research mine in Sweden. This identification of strain LV43 is supported by its G+C content of 62%, which is within the range reported for strains of T. thioparus. Fluorescently labeled polyclonal antibodies specific for strain LV43 were used to locate and enumerate this strain at different locations in Movile Cave and in nearby surface-water and groundwater sources. Strain LV43 was found only at aerobic, neutral-pH sites within the cave. Strain LV43 was also found outside Movile Cave in surface waters and in groundwater believed to intercept the same sulfurous aquifer as Movile Cave.

Vlasceanu, L; Popa, R; Kinkle, B K

1997-01-01

92

In Hypertrophic Cardiomyopathy Reduction of Relative Resting Myocardial Blood Flow Is Related to Late Enhancement, T2-Signal and LV Wall Thickness  

PubMed Central

Objectives To quantify resting myocardial blood flow (MBF) in the left ventricular (LV) wall of HCM patients and to determine the relationship to important parameters of disease: LV wall thickness, late gadolinium enhancement (LGE), T2-signal abnormalities (dark and bright signal), LV outflow tract obstruction and age. Materials and Methods Seventy patients with proven HCM underwent cardiac MRI. Absolute and relative resting MBF were calculated from cardiac perfusion MRI by using the Fermi function model. The relationship between relative MBF and LV wall thickness, T2-signal abnormalities (T2 dark and T2 bright signal), LGE, age and LV outflow gradient as determined by echocardiography was determined using simple and multiple linear regression analysis. Categories of reduced and elevated perfusion in relation to non- or mildly affected reference segments were defined, and T2-signal characteristics and extent as well as pattern of LGE were examined. Statistical testing included linear and logistic regression analysis, unpaired t-test, odds ratios, and Fisher’s exact test. Results 804 segments in 70 patients were included in the analysis. In a simple linear regression model LV wall thickness (p<0.001), extent of LGE (p<0.001), presence of edema, defined as focal T2 bright signal (p<0.001), T2 dark signal (p<0.001) and age (p?=?0.032) correlated inversely with relative resting MBF. The LV outflow gradient did not show any effect on resting perfusion (p?=?0.901). Multiple linear regression analysis revealed that LGE (p<0.001), edema (p?=?0.026) and T2 dark signal (p?=?0.019) were independent predictors of relative resting MBF. Segments with reduced resting perfusion demonstrated different LGE patterns compared to segments with elevated resting perfusion. Conclusion In HCM resting MBF is significantly reduced depending on LV wall thickness, extent of LGE, focal T2 signal abnormalities and age. Furthermore, different patterns of perfusion in HCM patients have been defined, which may represent different stages of disease.

Hueper, Katja; Zapf, Antonia; Skrok, Jan; Pinheiro, Aurelio; Goldstein, Thomas A.; Zheng, Jie; Zimmerman, Stefan L.; Kamel, Ihab R.; Abraham, Roselle; Wacker, Frank; Bluemke, David A.; Abraham, Theodore; Vogel-Claussen, Jens

2012-01-01

93

Arylsulfatase B improves locomotor function after mouse spinal cord injury.  

PubMed

Bacterial chondroitinase ABC (ChaseABC) has been used to remove the inhibitory chondroitin sulfate chains from chondroitin sulfate proteoglycans to improve regeneration after rodent spinal cord injury. We hypothesized that the mammalian enzyme arylsulfatase B (ARSB) would also enhance recovery after mouse spinal cord injury. Application of the mammalian enzyme would be an attractive alternative to ChaseABC because of its more robust chemical stability and reduced immunogenicity. A one-time injection of human ARSB into injured mouse spinal cord eliminated immunoreactivity for chondroitin sulfates within five days, and up to 9 weeks after injury. After a moderate spinal cord injury, we observed improvements of locomotor recovery assessed by the Basso Mouse Scale (BMS) in ARSB treated mice, compared to the buffer-treated control group, at 6 weeks after injection. After a severe spinal cord injury, mice injected with equivalent units of ARSB or ChaseABC improved similarly and both groups achieved significantly more locomotor recovery than the buffer-treated control mice. Serotonin and tyrosine hydroxylase immunoreactive axons were more extensively present in mouse spinal cords treated with ARSB and ChaseABC, and the immunoreactive axons penetrated further beyond the injury site in ARSB or ChaseABC treated mice than in control mice. These results indicate that mammalian ARSB improves functional recovery after CNS injury. The structural/molecular mechanisms underlying the observed functional improvement remain to be elucidated. PMID:23520469

Yoo, Myungsik; Khaled, Muntasir; Gibbs, Kurt M; Kim, Jonghun; Kowalewski, Björn; Dierks, Thomas; Schachner, Melitta

2013-01-01

94

Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury  

PubMed Central

Bacterial chondroitinase ABC (ChaseABC) has been used to remove the inhibitory chondroitin sulfate chains from chondroitin sulfate proteoglycans to improve regeneration after rodent spinal cord injury. We hypothesized that the mammalian enzyme arylsulfatase B (ARSB) would also enhance recovery after mouse spinal cord injury. Application of the mammalian enzyme would be an attractive alternative to ChaseABC because of its more robust chemical stability and reduced immunogenicity. A one-time injection of human ARSB into injured mouse spinal cord eliminated immunoreactivity for chondroitin sulfates within five days, and up to 9 weeks after injury. After a moderate spinal cord injury, we observed improvements of locomotor recovery assessed by the Basso Mouse Scale (BMS) in ARSB treated mice, compared to the buffer-treated control group, at 6 weeks after injection. After a severe spinal cord injury, mice injected with equivalent units of ARSB or ChaseABC improved similarly and both groups achieved significantly more locomotor recovery than the buffer-treated control mice. Serotonin and tyrosine hydroxylase immunoreactive axons were more extensively present in mouse spinal cords treated with ARSB and ChaseABC, and the immunoreactive axons penetrated further beyond the injury site in ARSB or ChaseABC treated mice than in control mice. These results indicate that mammalian ARSB improves functional recovery after CNS injury. The structural/molecular mechanisms underlying the observed functional improvement remain to be elucidated.

Yoo, Myungsik; Khaled, Muntasir; Gibbs, Kurt M.; Kim, Jonghun; Kowalewski, Bjorn; Dierks, Thomas; Schachner, Melitta

2013-01-01

95

Fast and automatic LV mass calculation from echocardiographic images via B-spline snake model and markov random fields  

Microsoft Academic Search

Left ventricular (LV) mass has several important diagnostic and indicative implications. In this paper, a fast and accurate technique for detection of inner and outer boundaries of LV and, consequently, calculation of LV mass from apical 4-chamber echocardiographic images is presented. For detection of the inner boundary, a modified B-spline snake is proposed, which relies merely on image intensity and

Mahdi Marsousi; Armin Eftekhari; Javad Alirezaie; Armen Kocharian; E. Sharifahmadian

2009-01-01

96

Operative treatment improves patient function in recalcitrant medial epicondylitis.  

PubMed

The purpose of this retrospective study was to assess the outcome of open surgery for patients with recalcitrant medial epicondylitis following failed conservative management. The clinical results are presented for 15 patients (17 elbows) who were reviewed at a mean follow-up of 66 months. Operative treatment improved patient function significantly with a mean increase in grip strength of 10kg and a mean decrease (improvement) in DASH (Disabilities of the Arm, Shoulder and Hand) score of 25.7. All but one patient experienced little or no residual elbow discomfort and had excellent Mayo elbow performance scores postoperatively. Eleven of the twelve patients who were previously in employment were able to return to work within eight weeks of surgery. This study demonstrates that operative treatment for recalcitrant medial epicondylitis is effective in restoring patient function and strength. PMID:24112494

Shahid, M; Wu, F; Deshmukh, S C

2013-10-01

97

Surgical procedures for functional improvement of the velum  

Microsoft Academic Search

The velopharyngoplasty, developed by the author (1966) usually results in lengthening of the palatal roof and improving the tensor function. When needed, it can be performed in conjunction with any of the three following procedures:1.A Levatorplasty, where a new levator sling is formed by a muscle transposition from the M. Pterygoideus medialis.2.An Arcus palatopharyngoplasty, where a bulkier vault is obtained.3.An

Otto Neuner

1972-01-01

98

Folic acid improves arterial endothelial function in adults with hyperhomocystinemia  

Microsoft Academic Search

OBJECTIVESTo evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia.BACKGROUNDHyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known.METHODSAdults subjects were recruited from a community-based atherosclerosis

Kam S Woo; Ping Chook; Yvette I Lolin; John E Sanderson; Con Metreweli; David S Celermajer

1999-01-01

99

FBSIM/Lv. Anvaendarhandledning och Referensmanual foer SUN Sparc Arbetsstation (FBSIM/Lv. User's Guide and Reference Manual for Sun Sparc Workstation).  

National Technical Information Service (NTIS)

The software package FBSIM/Lv is used to study the duel between air defense and ground attack aircraft. The simulation software is adapted to the requirements given by the Army Air Defense Centre. The User's manual describes how to get started with the FB...

M. Nilsson

1996-01-01

100

Modification of biochar for functionality improvement in soils  

NASA Astrophysics Data System (ADS)

Application of biochar to soils is generally considered and practiced in order to improve specific soil functions such as CEC, moisture and nutrient retention and providing additional habitat for micro-organisms. Improvement of these soil functions should lead to a higher crop yield. This would be added value to the long term sequestration of carbon in soils and contribution to renewable energy from producing and using biochar. The concept of using biochar for soil amendment is predicated on biochar behaving in a similar manner as soil organic matter (SOM) does. However, if one critically compares the properties of biochar with the properties of SOM, it is evident that biochar is rather different from SOM [Zwart, 2013 ;Zwart & Kuikman, 2013]. We have has produced a range of biochar from different feedstock using pyrolysis, gasification and hydrothermal carbonisation resulting in chars with significantly different properties. The project also investigates and tested several possibilities for improving the functionality of biochar in soils by either(i) selection of feedstock, (ii), selection of processing conditions and (iii) chemical and physical modification of biochar during and after the production process. Post modification includes the chemical treatment of biochars with either H2O2, KOH, H2SO4 and transitional metals such as Fe and investigates their effect on surface functionality, porosity, surface area, CEC and phosphate sorption. The influence of the addition of chemical modifiers and oxidants during pyrolysis and gasification has also been investigated and their effect on surface functionality determined using similar techniques. The influence of the original biomass structure on the morphology of the resultant biochars has been investigated using scanning electron microscopy.

Zwart, Kor; Kuikman, Peter; Ross, Anrew; Takaya, Chibi; Singh, Surjit; Kocaturk, Pelin; Visser, Rian

2014-05-01

101

Relation of Left Ventricular Midwall Function to Cardiovascular Risk Factors and Arterial Structure and Function  

Microsoft Academic Search

Left ventricular (LV) midwall shortening (MWS) is subnormal in relation to LV circumferential end-systolic stress (ESS) (ESS-corrected MWS) in many hypertensive patients with normal LV chamber function and predicts subsequent morbidity and mortality. However, little is known of the relations of LV midwall function to demographic and metabolic variables or to arterial geometry. Asymptomatic, unmedicated normotensive (n5366) or hypertensive (n5282)

Richard B. Devereux; Giovanni de Simone; Thomas G. Pickering; Joseph E. Schwartz; Mary J. Roman

102

Rosuvastatin improves pulse wave reflection by restoring endothelial function.  

PubMed

One of the major indicators of intact endothelial function is basal nitric oxide (NO) activity. Further, it seems to be likely that statin therapy exerts beneficial effects on vascular function, at least in part via an improvement of NO bioavailability. In the present double-blind crossover study 29 hypercholesterolemic patients were randomly assigned to receive rosuvastatin and placebo for 42days. Pulse wave analysis was assessed after 30min of rest (baseline) and after infusion of N(G)-monomethyl-l-arginine (l-NMMA) at the end of 42days treatment period. The magnitude of the increase in central augmentation index (cAIx) in response to inhibition of NO synthase (NOS) by l-NMMA is indicative of basal NO activity. CAIx was significantly lower (18.3±10 versus 21.9±12%, p=0.027) with rosuvastatin compared to placebo. There was no increment of cAIx in response to l-NMMA in placebo group. In contrast, cAIx increased significantly in response to l-NMMA (20.5±11 versus 25.7±10mm Hg, p=0.001) in rosuvastatin group. The percentage of increase of cAIx tended to be more pronounced after treatment with rosuvastatin compared to placebo (53.7±92 versus 14.1±36%, p=0.087). Pulse pressure amplification (PPA) improved (1.31±0.2 versus 1.26±0.2%, p=0.016) after rosuvastatin compared to placebo. Regression analyses revealed that both LDL-cholesterol and CRP-levels are independent determinants of basal NO activity improvement, which itself is an independent determinant of vascular function, expressed by an improvement of pulse wave reflection and PPA. In this placebo controlled study, treatment with rosuvastatin improved vascular and endothelial function. Determinants for improved NO production in patients with hypercholesterolemia were the achieved levels of LDL-cholesterol and CRP. Overall, in patients without CV disease, rosuvastatin exerted beneficially effect on vascular dysfunction, one of the earliest manifestation of atherosclerosis. PMID:22484031

Ott, C; Schneider, M P; Schlaich, M P; Schmieder, R E

2012-07-01

103

Efficacy of 5-FU/LV plus CPT-11 as first-line adjuvant chemotherapy for stage IIIa colorectal cancer.  

PubMed

The aim of this study was to retrospectively evaluate the effect of adding CPT-11 to postoperative chemotherapy for stage III colorectal cancer. The subjects were 94 patients, including 60 in stage IIIa (or=4 positive nodes), who underwent curative resection. The clinical outcome was compared between patients receiving 5-FU/LV plus CPT-11 (FLC group) and patients receiving 5-FU/LV alone (FL group). The FLC group (54 patients) had a 3-year relapse-free survival (3Y-RFS) of 68.7%, a 5Y-RFS of 68.7% and a 5Y-OS of 67.1%, while the FL group (40 patients) had a 3Y-RFS of 67.5% (n.s.), a 5Y-RFS of 64.9% (n.s.), and a 5Y-OS of 77.3% (n.s.). There were no significant differences of these parameters between the two groups. For stage IIIa patients, the corresponding survival rates were 92.4, 92.4 and 90.9% in the FLC group (29 patients) vs. 64.5% (p=0.024), 61.1% (p=0.018), and 77.1% (n.s.) in the FL group (31 patients). For stage IIIb patients, the rates were 36.6, 36.6 and 24.8% in the FLC group (25 patients) vs. 77.8% (n.s.), 77.8% (n.s.), and 77.8% (n.s.) in the FL group (9 patients). These results suggest that the 3Y-RFS and 5Y-RFS of patients with stage IIIa colorectal cancer were significantly improved by adjuvant chemotherapy with 5-FU/LV plus CPT-11. PMID:19639213

Mukai, Masaya; Okada, Kazutake; Fukumitsu, Hiroshi; Yazawa, Naoki; Hoshikawa, Tatsuhiko; Tajima, Takayuki; Hirakawa, Hitoshi; Ogoshi, Kyouji; Makuuchi, Hiroyasu

2009-09-01

104

A dual propagation contours technique for semi-automated assessment of systolic and diastolic cardiac function by CMR  

Microsoft Academic Search

BACKGROUND: Although cardiovascular magnetic resonance (CMR) is frequently performed to measure accurate LV volumes and ejection fractions, LV volume-time curves (VTC) derived ejection and filling rates are not routinely calculated due to lack of robust LV segmentation techniques. VTC derived peak filling rates can be used to accurately assess LV diastolic function, an important clinical parameter. We developed a novel

Wei Feng; Hosakote Nagaraj; Himanshu Gupta; Steven G Lloyd; Inmaculada Aban; Gilbert J Perry; David A Calhoun; Louis J Dell'Italia; Thomas S Denney Jr

2009-01-01

105

Kidney Function Can Improve in Patients with Hypertensive CKD  

PubMed Central

The typical assumption is that patients with CKD will have progressive nephropathy. Methodological issues, such as measurement error and regression to the mean, have made it difficult to document whether kidney function might improve in some patients. Here, we used data from 12 years of follow-up in the African American Study of Kidney Disease and Hypertension to determine whether some patients with CKD can experience a sustained improvement in GFR. We calculated estimated GFR (eGFR) based on serum creatinine measurements during both the trial and cohort phases. We defined clearly improved patients as those with positive eGFR slopes that we could not explain by random measurement variation under Bayesian mixed-effects models. Of 949 patients with at least three follow-up eGFR measurements, 31 (3.3%) demonstrated clearly positive eGFR slopes. The mean slope among these patients was +1.06 (0.12) ml/min per 1.73 m2 per yr, compared with ?2.45 (0.07) ml/min per 1.73 m2 per yr among the remaining patients. During the trial phase, 24 (77%) of these 31 patients also had clearly positive slopes of 125I-iothalamate–measured GFR during the trial phase. Low levels of proteinuria at baseline and randomization to the lower BP goal (mean arterial pressure ?92 mmHg) associated with improved eGFR. In conclusion, the extended follow-up from this study provides strong evidence that kidney function can improve in some patients with hypertensive CKD.

Gadegbeku, Crystal; Lipkowitz, Michael S.; Rostand, Stephen; Lewis, Julia; Wright, Jackson T.; Appel, Lawrence J.; Greene, Tom; Gassman, Jennifer; Astor, Brad C.

2012-01-01

106

Ranolazine improves diastolic function in spontaneously hypertensive rats.  

PubMed

Diastolic dysfunction can lead to heart failure with preserved ejection fraction, for which there is no effective therapeutic. Ranolazine has been reported to reduce diastolic dysfunction, but the specific mechanisms of action are unclear. The effect of ranolazine on diastolic function was examined in spontaneously hypertensive rats (SHRs), where left ventricular relaxation is impaired and stiffness increased. The objective of this study was to determine whether ranolazine improves diastolic function in SHRs and identify the mechanism(s) by which improvement is achieved. Specifically, to test the hypothesis that ranolazine, by inhibiting late sodium current, reduces Ca(2+) overload and promotes ventricular relaxation and reduction in diastolic stiffness, the effects of ranolazine or vehicle on heart function and the response to dobutamine challenge were evaluated in aged male SHRs and Wistar-Kyoto rats by echocardiography and pressure-volume loop analysis. The effects of ranolazine and the more specific sodium channel inhibitor tetrodotoxin were determined on the late sodium current, sarcomere length, and intracellular calcium in isolated cardiomyocytes. Ranolazine reduced the end-diastolic pressure-volume relationship slope and improved diastolic function during dobutamine challenge in the SHR. Ranolazine and tetrodotoxin also enhanced cardiomyocyte relaxation and reduced myoplasmic free Ca(2+) during diastole at high-stimulus rates in the SHR. The density of the late sodium current was elevated in SHRs. In conclusion, ranolazine was effective in reducing diastolic dysfunction in the SHR. Its mechanism of action, at least in part, is consistent with inhibition of the increased late sodium current in the SHR leading to reduced Ca(2+) overload. PMID:24464752

Williams, Sarah; Pourrier, Marc; McAfee, Donald; Lin, Shunping; Fedida, David

2014-03-01

107

Improved Memory Function Two Years After Bariatric Surgery  

PubMed Central

Objective Obesity is as an independent risk factor for poor neurocognitive outcomes, including Alzheimer’s disease. Bariatric surgery has recently been shown to result in improved memory at 12-weeks post-operatively. However, the long-term effects of bariatric surgery on cognitive function remain unclear. Design and Methods 86 individuals (63 bariatric surgery patients, 23 obese controls) were recruited from a prospective study examining the neurocognitive effects of bariatric surgery. All participants completed self-report measurements and a computerized cognitive test battery prior to surgery and at 12-week and 24-month follow-up; obese controls completed measures at equivalent time points. Results Bariatric surgery patients exhibited high rates of pre-operative cognitive impairments in attention, executive function, memory, and language. Relative to obese controls, repeated measures ANOVA showed improvements in memory from baseline to 12-weeks and 24-months post-operatively (p < .05). Regression analyses controlling for baseline factors revealed that a lower BMI at 24-months demonstrated a trend toward significance for improved memory (? = -.30, p = .075). Conclusion These findings suggest that cognitive benefits of bariatric surgery may extend to 24-months post-operatively. Larger prospective studies with extended follow-up periods are needed to elucidate whether bariatric surgery decreases risk for cognitive decline and possibly the development of dementia.

Alosco, Michael L.; Spitznagel, Mary Beth; Strain, Gladys; Devlin, Michael; Cohen, Ronald; Paul, Robert; Crosby, Ross D.; Mitchell, James E.; Gunstad, John

2014-01-01

108

Oral zinc supplementation may improve cognitive function in schoolchildren.  

PubMed

Zinc is an important micronutrient for humans, and zinc deficiency among schoolchildren is deleterious to growth and development, immune competence, and cognitive function. However, the effect of zinc supplementation on cognitive function remains poorly understood. The purpose of our study was to evaluate the effect of oral zinc supplementation (5 mg Zn/day for 3 months) on the Full Scale Intelligence Quotient (FSIQ), Verbal Intelligence Quotient (VIQ), and Performance Intelligence Quotient (PIQ) using a Wechsler Intelligence Scale for Children (WISC-III). We studied 36 schoolchildren aged 6 to 9 years (7.8 ± 1.1) using a nonprobability sampling method. The baseline serum zinc concentrations increased significantly after zinc supplementation (p < 0.0001), with no difference between sexes. Tests were administered under basal conditions before and after zinc supplementation, and there was no difference in FSIQ according to gender or age. The results demonstrated that zinc improved the VIQ only in the Information Subtest (p = 0.009), although the supplementation effects were more significant in relation to the PIQ, as these scores improved for the Picture Completion, Picture Arrangement, Block Design, and Object Assembly Subtests (p = 0.0001, for all subtests). In conclusion, zinc supplementation improved specific cognitive abilities, thereby positively influencing the academic performance of schoolchildren, even those without marginal zinc deficiency. PMID:23892699

de Moura, José Edson; de Moura, Edna Nubia Oliveira; Alves, Camila Xavier; Vale, Sancha Helena de Lima; Dantas, Márcia Marília Gomes; Silva, Alfredo de Araújo; Almeida, Maria das Graças; Leite, Lúcia Dantas; Brandão-Neto, José

2013-10-01

109

Selective Endothelin-1 Receptor type-A Inhibition in Cardiac Surgery Subjects with Pre-Existing LV Dysfunction: Influence on Early Post-Operative Hemodynamics  

PubMed Central

Background and Objective A robust release of endothelin-1-1 (ET) with subsequent ETA subtype receptor (ET-AR) activation occurs in patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Increased ET-AR activation has been identified in patients with poor LV function (reduced ejection fraction; EF). Accordingly, this study tested the hypothesis that a selective ET-AR antagonist (ET-ARA) administered peri-operatively would favorably affect post-CPB hemodynamic profiles in patients with a pre-existing poor LVEF. Methods and Results Patients (n=29; 66±2 yrs) with a reduced LVEF (37±2%) were prospectively randomized, in a blinded fashion, at the time of elective coronary revascularization and/or valve replacement requiring CPB, to infusion of the highly-selective and potent ET-ARA, sitaxsentan at 1 or 2 mg/kg (IV bolus; n=9, 10 respectively) or vehicle (saline; n=10). Infusion of the ET-ARA/vehicle was performed immediately prior to separation from CPB and again at 12 hrs post-CPB. ET and hemodynamic measurements were performed at baseline, at separation from CPB (Time 0) and at 0.5, 6, 12, 24 hrs post-CPB. Baseline plasma ET (4.0±0.3 fmol/mL) was identical across all 3 groups, but when compared to pre-operative, baseline values obtained from age matched subjects with a normal LVEF (n=37;LVEF>50%), were significantly increased (2.9±0.2 fmol/mL, p<0.05) Baseline systemic (SVR; 1358±83 d·s·cm-5) and pulmonary (PVR; 180±23 d·s·cm-5) vascular resistance were equivalent in all 3 groups. As a function of Time 0, SVR changed in an equivalent fashion in the post-CPB period, but a significant ET-ARA effect was observed for PVR (ANOVA; p<0.05). For example at 24 hrs post-CPB, PVR increased by 40 d.scm-5 in the vehicle group, but directionally decreased by over 40 d·s·cm-5 in the 2 mg/kg ETARA group (p<0.05). Total adverse events were equivalently distributed across the ET-ARA/placebo groups. Conclusions These unique findings demonstrated that infusion of an ET-ARA in high risk cardiac surgery patients was not associated with significant hemodynamic compromise. Moreover, ET-ARA favorably affected PVR in the early post-operative period. Thus, the ET-AR serves as a potential pharmacological target for improving outcomes following cardiac surgery in patients with compromised LV function.

Toole, John M.; Ikonomidis, John S.; Szeto, Wilson Y.; Zellner, James L.; Mulcahy, John; Deardorff, Rachael L.; Spinale, Francis G.

2010-01-01

110

Erythropoietin improves functional and histological outcome in neonatal stroke.  

PubMed

Neonatal stroke is a condition that leads to disability in later life, and as yet there is no effective treatment. Recently, erythropoietin (EPO) has been shown to be cytoprotective following brain injury and may promote neurogenesis. However, the effect of EPO on functional outcome and on morphologic changes in neonatal subventricular zone (SVZ) following experimental neonatal stroke has not been described. We used a transient focal model of neonatal stroke in P10 rat. Injury was documented by diffusion weighted MRI during occlusion. Immediately upon reperfusion, either EPO (5U/gm) or vehicle was administered intraperitoneally and animals were allowed to grow for 2 wk. Sensorimotor function was assessed using the cylinder rearing test and then brains were processed for volumetric analysis of the SVZ. Stroke induced SVZ expansion proportional to hemispheric volume loss. EPO treatment markedly preserved hemispheric volume and decreased the expansion of SVZ unilaterally. Furthermore, EPO treatment significantly improved the asymmetry of forelimb use following neonatal stroke. This functional improvement directly correlated with the amount of preserved hemispheric volume. These results suggest EPO may be a candidate in the treatment of neonatal stroke. PMID:15879287

Chang, Yun Sil; Mu, Dezhi; Wendland, Michael; Sheldon, R Ann; Vexler, Zinaida S; McQuillen, Patrick S; Ferriero, Donna M

2005-07-01

111

Left Ventricular Functional Analysis Using 64Slice Multidetector Row Computed Tomography: Comparison with Left Ventriculography and Cardiovascular Magnetic Resonance  

Microsoft Academic Search

Objective: The progress in computed tomography (CT) has improved temporal resolution and shortened the acquisition time. We compared cardiac function using 64-slice CT with left ventriculography (LVG) and cardiovascular magnetic resonance (CMR). Methods: A head-to-head comparison between CT, LVG and CMR was performed in 41 patients. In global LV function, CMR served as the reference. Regional wall motion was compared

Yen-Wen Wu; Eiji Tadamura; Shotaro Kanao; Masaki Yamamuro; Satoshi Okayama; Neiko Ozasa; Masanao Toma; Takeshi Kimura; Toru Kita; Akira Marui; Masashi Komeda; Kaori Togashi

2008-01-01

112

Molecular Characterizations of a Novel Putative DNA-Binding Protein LvDBP23 in Marine Shrimp L. vannamei Tissues and Molting Stages  

PubMed Central

Background Litopenaeus Vannamei, well known as pacific white shrimp, is the most popular shrimp in the world shrimp market. Identification and characterization of shrimp muscle regulatory genes are not only important for shrimp genetic improvement, but also facilitate comparative genomic tools for understanding of muscle development and regeneration. Methodology/Principal Findings A novel mRNA encoding for a putative DNA-binding protein LvDBP23 was identified from Litopenaeus vannamei abdominal muscle cDNA library. The LvDBP23 cDNA contains 639 nucleotides of protein-coding sequence with deduced 212 amino acids of predicted molecular mass 23.32 kDa with glycine-rich domain at amino acid position 94–130. The mRNA sequence is successfully used for producing LvDBP23 recombinant protein in sf9 insect cell expression system. The expression of LvDBP23 mRNA is presented in abdominal muscle and swimming leg muscle, as well as other tissues including intestine, lymphoid and gill. The mRNA expression has the highest level in abdominal muscle in all tested tissues. LVDBP23 transcript during the molt cycle is highly expressed in the intermolt stage. In vitro nucleic acid-binding assays reveal that LvDBP23 protein can bind to both ssDNA and dsDNA, indicating its possible role of regulation of gene transcription. Conclusions/Significance We are the first to report a DNA-binding protein identified from the abdominal muscle tissue of marine shrimp L. Vannamei. Its high-level specific expression during the intermot stage suggests its role in the regulation of muscle buildup during the growth phase of shrimp molt cycle.

Laoong-u-thai, Yanisa; Zhao, Baoping; Phongdara, Amornrat; Yang, Jinzeng

2011-01-01

113

Improved ambient noise correlation functions using Welch's method  

NASA Astrophysics Data System (ADS)

Here, we evaluate the improvement in noise correlation functions (NCFs) gained by dividing ambient seismic records into shorter, overlapping time windows before correlation and stacking (Welch's method). We compare waveform convergence of short duration NCF stacks (e.g. 2, 5, 15 and 50 d stacks) towards the long-term (365 d) NCF stack. We observe short duration NCF improvement when applying Welch's method for non-pre-processed and running normalized time-series and short duration NCF degradation when applied to a 'one-bit' normalized time-series. Surprisingly, non-pre-processed time-series provides the quickest convergence to a robust (year-long) NCF. Because of the simplicity of Welch's method, the improved NCF convergence and a minimal increase in computation, we recommend applying Welch's method for future ambient seismic field analyses. Using this approach will likely improve future NCF analyses, particularly for studies with limited duration recordings, high levels of intermittent local or site noise and studies attempting to evaluate temporal variations in subsurface structure.

Seats, Kevin J.; Lawrence, Jesse F.; Prieto, German A.

2012-02-01

114

Improved gene transfer with histidine-functionalized mesoporous silica nanoparticles.  

PubMed

Mesoporous silica nanoparticles (MSN) were functionalized with aminopropyltriethoxysilane (MSN-NH2) then l-histidine (MSN-His) for pDNA delivery in cells and in vivo. The complexation of pDNA with MSN-NH2 and MSN-His was first studied with gel shift assay. pDNA complexed with MSN-His was better protected from DNase degradation than with MSN-NH2. An improvement of the transfection efficiency in cells was observed with MSN-His/pDNA compared to MSN-NH2/pDNA, which could be explained by a better internalization of MSN-His. The improvement of the transfection efficiency with MSN-His was also observed for gene transfer in Achilles tendons in vivo. PMID:24853464

Brevet, David; Hocine, Ouahiba; Delalande, Anthony; Raehm, Laurence; Charnay, Clarence; Midoux, Patrick; Durand, Jean-Olivier; Pichon, Chantal

2014-08-25

115

Active robotic training improves locomotor function in a stroke survivor  

PubMed Central

Background Clinical outcomes after robotic training are often not superior to conventional therapy. One key factor responsible for this is the use of control strategies that provide substantial guidance. This strategy not only leads to a reduction in volitional physical effort, but also interferes with motor relearning. Methods We tested the feasibility of a novel training approach (active robotic training) using a powered gait orthosis (Lokomat) in mitigating post-stroke gait impairments of a 52-year-old male stroke survivor. This gait training paradigm combined patient-cooperative robot-aided walking with a target-tracking task. The training lasted for 4-weeks (12 visits, 3?×?per week). The subject’s neuromotor performance and recovery were evaluated using biomechanical, neuromuscular and clinical measures recorded at various time-points (pre-training, post-training, and 6-weeks after training). Results Active robotic training resulted in considerable increase in target-tracking accuracy and reduction in the kinematic variability of ankle trajectory during robot-aided treadmill walking. These improvements also transferred to overground walking as characterized by larger propulsive forces and more symmetric ground reaction forces (GRFs). Training also resulted in improvements in muscle coordination, which resembled patterns observed in healthy controls. These changes were accompanied by a reduction in motor cortical excitability (MCE) of the vastus medialis, medial hamstrings, and gluteus medius muscles during treadmill walking. Importantly, active robotic training resulted in substantial improvements in several standard clinical and functional parameters. These improvements persisted during the follow-up evaluation at 6?weeks. Conclusions The results indicate that active robotic training appears to be a promising way of facilitating gait and physical function in moderately impaired stroke survivors.

2012-01-01

116

Improvement of right ventricular function with transcatheter aortic valve implantation.  

PubMed

Abstract Background and aim. It has been demonstrated that right ventricular systolic dysfunction develops soon after surgical aortic valve replacement (s-AVR). While the impact of s-AVR or TAVI on the function of the left ventricle has been studied with various imaging modalities, little is known about the impact on right ventricular function (RVF). In the current study, we evaluated the impact of TAVI on RVF using conventional echocardiography parameters. Methods and results. Echocardiography was performed prior to 24 h, 1 month and 6 months after TAVI. RVF was assessed using (1) tricuspid annular plane systolic excursion (TAPSE); (2) RV Tissue Doppler Imaging (S'); (3) right ventricular systolic pressure (RVSP); (4) Fractional area change (FAC); and (5) RV ejection fraction (RVEF). TAVI was performed through the subclavian artery in two patients and femoral artery in 48 patients with an Edwards Sapien XT valve. TAVI was performed on 50 patients between the dates of December 2012 and June 2013. After TAVI, a statistically significant improvement was observed for all parameters related to RVF (RVSP, RVEF, TAPSE, FAC, RVTDI S'). During the 1st and 6th months this statistically significant improvement continued in TAPSE and FAC, and there was no deterioration in RVSP, RVEF, and RVTDI S during the 1st month but a statistically significant improvement continued in the 6th month. Conclusion. RVF assessed by conventional echocardiography did not deteriorate after TAVI in early and midterm follow-up. Further, TAVI provides improvement of RVF and can safely and efficiently be performed in patients with impaired RVF. PMID:24491180

Ayhan, Hüseyin; Durmaz, Tahir; Kele?, Telat; Sari, Cenk; Aslan, Abdullah Nabi; Kasapkara, Haci Ahmet; Bozkurt, Engin

2014-06-01

117

A model-based time-reversal of left ventricular motion improves cardiac motion analysis using tagged MRI data  

PubMed Central

Background Myocardial motion is an important observable for the assessment of heart condition. Accurate estimates of ventricular (LV) wall motion are required for quantifying myocardial deformation and assessing local tissue function and viability. Harmonic Phase (HARP) analysis was developed for measuring regional LV motion using tagged magnetic resonance imaging (tMRI) data. With current computer-aided postprocessing tools including HARP analysis, large motions experienced by myocardial tissue are, however, often intractable to measure. This paper addresses this issue and provides a solution to make such measurements possible. Methods To improve the estimation performance of large cardiac motions while analyzing tMRI data sets, we propose a two-step solution. The first step involves constructing a model to describe average systolic motion of the LV wall within a subject group. The second step involves time-reversal of the model applied as a spatial coordinate transformation to digitally relax the contracted LV wall in the experimental data of a single subject to the beginning of systole. Cardiac tMRI scans were performed on four healthy rats and used for developing the forward LV model. Algorithms were implemented for preprocessing the tMRI data, optimizing the model parameters and performing the HARP analysis. Slices from the midventricular level were then analyzed for all systolic phases. Results The time-reversal operation derived from the LV model accounted for the bulk portion of the myocardial motion, which was the average motion experienced within the overall subject population. In analyzing the individual tMRI data sets, removing this average with the time-reversal operation left small magnitude residual motion unique to the case. This remaining residual portion of the motion was estimated robustly using the HARP analysis. Conclusion Utilizing a combination of the forward LV model and its time reversal improves the performance of motion estimation in evaluating the cardiac function.

Alrefae, Tareq; Smirnova, Irina V; Cook, Larry T; Bilgen, Mehmet

2008-01-01

118

Intravenous Glial Growth Factor 2 (GGF2) Isoform of Neuregulin-1? Improves Left Ventricular Function, Gene and Protein Expression in Rats after Myocardial Infarction  

PubMed Central

Aims Recombinant Neuregulin (NRG)-1? has multiple beneficial effects on cardiac myocytes in culture, and has potential as a clinical therapy for heart failure (HF). A number of factors may influence the effect of NRG-1? on cardiac function via ErbB receptor coupling and expression. We examined the effect of the NRG-1? isoform, glial growth factor 2 (GGF2), in rats with myocardial infarction (MI) and determined the impact of high-fat diet as well as chronicity of disease on GGF2 induced improvement in left ventricular systolic function. Potential mechanisms for GGF2 effects on the remote myocardium were explored using microarray and proteomic analysis. Methods and Results Rats with MI were randomized to receive vehicle, 0.625 mg/kg, or 3.25 mg/kg GGF2 in the presence and absence of high-fat feeding beginning at day 7 post-MI and continuing for 4 weeks. Residual left ventricular (LV) function was improved in both of the GGF2 treatment groups compared with the vehicle treated MI group at 4 weeks of treatment as assessed by echocardiography. High-fat diet did not prevent the effects of high dose GGF2. In experiments where treatment was delayed until 8 weeks after MI, high but not low dose GGF2 treatment was associated with improved systolic function. mRNA and protein expression analysis of remote left ventricular tissue revealed a number of changes in myocardial gene and protein expression altered by MI that were normalized by GGF2 treatment, many of which are involved in energy production. Conclusions This study demonstrates that in rats with MI induced systolic dysfunction, GGF2 treatment improves cardiac function. There are differences in sensitivity of the myocardium to GGF2 effects when administered early vs. late post-MI that may be important to consider in the development of GGF2 in humans.

Murphy, Abigail; Smith, Holly M.; Galindo, Cristi L.; Pentassuglia, Laura; Peng, Xuyang; Lenneman, Carrie G.; Odiete, Oghenerukevwe; Friedman, David B.; Kronenberg, Marvin W.; Zheng, Siyuen; Zhao, Zhongming; Song, Yanna; Harrell, Frank E.; Srinivas, Maya; Ganguly, Anindita; Iaci, Jennifer; Parry, Tom J.; Caggiano, Anthony O.; Sawyer, Douglas B.

2013-01-01

119

A novel ?4/7-conotoxin LvIA from Conus lividus that selectively blocks ?3?2 vs. ?6/?3?2?3 nicotinic acetylcholine receptors.  

PubMed

This study was performed to discover and characterize the first potent ?3?2-subtype-selective nicotinic acetylcholine receptor (nAChR) ligand. A novel ?4/7-conotoxin, ?-CTxLvIA, was cloned from Conus lividus. Its pharmacological profile at Xenopus laevis oocyte-expressed rat nAChR subtypes was determined by 2-electrode voltage-clamp electrophysiology, and its 3-dimensional (3D) structure was determined by NMR spectroscopy. ?-CTx LvIA is a 16-aa C-terminally-amidated peptide with 2-disulfide bridges. Using rat subunits expressed in Xenopus oocytes, we found the highest affinity of ?-CTxLvIA was for ?3?2 nAChRs (IC50 8.7 nM), where blockade was reversible within 2 min. IC50 values were >100 nM at ?6/?3?2?3, ?6/?3?4, and ?3?4 nAChRs, and ?3 ?M at all other subtypes tested. ?3?2 vs. ?6?2 subtype selectivity was confirmed for human-subunit nAChRs with much greater preference (300-fold) for ?3?2 over ?6?2 nAChRs. This is the first ?-CTx reported to show high selectivity for human ?3?2 vs. ?6?2 nAChRs. ?-CTxLvIA adopts two similarly populated conformations water: one (assumed to be bioactive) is highly structured, whereas the other is mostly random coil in nature. Selectivity differences with the similarly potent, but less selective, ?3?2 nAChR antagonist ?-CTx PeIA probably reside within the three residues, which differ in loop 2, given their otherwise similar 3D structures. ?4/7-CTx LvIA is a new, potent, selective ?3?2 nAChR antagonist, which will enable detailed studies of ?3?2 nAChR structure, function, and physiological roles. PMID:24398291

Luo, Sulan; Zhangsun, Dongting; Schroeder, Christina I; Zhu, Xiaopeng; Hu, Yuanyan; Wu, Yong; Weltzin, Maegan M; Eberhard, Spencer; Kaas, Quentin; Craik, David J; McIntosh, J Michael; Whiteaker, Paul

2014-04-01

120

MuLV IN mutants responsive to HDAC inhibitors enhance transcription from unintegrated retroviral DNA.  

PubMed

For Moloney murine leukemia virus (M-MuLV), sustained viral infections require expression from an integrated provirus. For many applications, non-integrating retroviral vectors have been utilized to avoid the unwanted effects of integration, however, the level of expression from unintegrated DNA is significantly less than that of integrated provirus. We find that unintegrated DNA expression can be increased in the presence of HDAC inhibitors, such as TSA, when applied in combination with integrase (IN) mutations. These mutants include an active site mutation as well as catalytically active INs bearing mutations of K376 in the MuLV C-terminal domain of IN. MuLV IN K376 is homologous to K266 in HIV-1 IN, a known substrate for acetylation. The MuLV IN protein is acetylated by p300 in vitro, however, the effect of HDAC inhibitors on gene expression from unintegrated DNA is not dependent on the acetylation state of MuLV IN K376. PMID:22365328

Schneider, William M; Wu, Dai-tze; Amin, Vaibhav; Aiyer, Sriram; Roth, Monica J

2012-05-10

121

Are Clinicians' Assessments of Improvements in Children's Functioning "Global"?  

PubMed Central

In this study, the authors examined the relations among clinician ratings of treatment improvement and discrepancies between parent and blinded laboratory rater reports of child social functioning administered before and after treatment for social anxiety disorder. Participants included a clinic sample of 101 children (7–16 years old [M = 11.67, SD = 2.57]; 51 girls; 81% Caucasian) receiving treatment as part of a two site controlled trial. Overall, clinician ratings reflected lack of improvement when parents reported persistent (i.e., pre-to-posttreament) social functioning deficits not reported by blinded raters. However, when blinded raters reported persistent social skill deficits not reported by parents, we did not observe the same effect on clinician ratings as we did when the direction of discrepant reports was reversed. We replicated these observations in a subset of participants (n = 81) providing parent and child pre-post reports of social anxiety symptoms. These findings have implications for the interpretations of clinical ratings as “primary outcome measures” within controlled trials.

De Los Reyes, Andres; Alfano, Candice A.; Beidel, Deborah C.

2011-01-01

122

Improved CLARAty Functional-Layer/Decision-Layer Interface  

NASA Technical Reports Server (NTRS)

Improved interface software for communication between the CLARAty Decision and Functional layers has been developed. [The Coupled Layer Architecture for Robotics Autonomy (CLARAty) was described in Coupled-Layer Robotics Architecture for Autonomy (NPO-21218), NASA Tech Briefs, Vol. 26, No. 12 (December 2002), page 48. To recapitulate: the CLARAty architecture was developed to improve the modularity of robotic software while tightening coupling between planning/execution and basic control subsystems. Whereas prior robotic software architectures typically contained three layers, the CLARAty contains two layers: a decision layer (DL) and a functional layer (FL).] Types of communication supported by the present software include sending commands from DL modules to FL modules and sending data updates from FL modules to DL modules. The present software supplants prior interface software that had little error-checking capability, supported data parameters in string form only, supported commanding at only one level of the FL, and supported only limited updates of the state of the robot. The present software offers strong error checking, and supports complex data structures and commanding at multiple levels of the FL, and relative to the prior software, offers a much wider spectrum of state-update capabilities.

Estlin, Tara; Rabideau, Gregg; Gaines, Daniel; Johnston, Mark; Chouinard, Caroline; Nessnas, Issa; Shu, I-Hsiang

2008-01-01

123

Does L-carnitine improve endothelial function in hemodialysis patients?  

PubMed Central

Background: Atherosclerosis is the leading cause of death in hemodialysis patients. These patients are also very prone to L-carnitine deficiency due to kidney disease. In this clinical trial, we investigated the effect of oral L-carnitine on endothelial function of these patients. Materials ans Methods: We studied 31 adult chronic hemodialysis patients in our center and divided them into two groups. The first group (n = 20) received 1500 mg/dialysis interval (every other day) oral L-carnitine. The control group (n = 11) received placebo for one month. Ultrasonographic measurements of flow mediated dilation and carotid intima-media thickness were performed before and after one month of L-carnitine and placebo therapy. Results: This study showed that after one month of L-carnitine or placebo therapy there was no significant improvement in flow mediated dilation (p = 0.80 and p = 0.59, respectively) or decrease in carotid intima-media thickness (p = 0.12 and p = 0.50, respectively). Conclusions: Our study revealed that one month of oral L-carnitine therapy did not improve endothelial function in hemodialysis patients. Long-term studies with large sample size using intravenous form and higher doses of the drug are required to clarify the questionable role of L-carnitine in hemodialysis patients.

Sabri, Mohammad Reza; Fahimi, Farnaz; Hajialiasgar, Soheila; Etminan, Abbas; Nazemi, Sarir; Salehi, Farzaneh

2012-01-01

124

The Use of Functional Electrical Stimulation to Improve Function in People with Spinal Cord Injury  

Microsoft Academic Search

1. Clinical Bottom Line: Currently there is no evidence to support the notion that in people with spinal cord injury, the use of FES as a physical therapy intervention results in improved functional outcomes. All of the articles we critically analyzed had significant threats to internal validity preventing us from generalizing the results to our clinical scenarios. Higher quality research

April R. Baker; Candace M. Callison

2007-01-01

125

Exendin-4 improves ?-cell function in autophagy-deficient ?-cells.  

PubMed

Autophagy is cellular machinery for maintenance of ?-cell function and mass. The implication of autophagy failure in ?-cells on the pathophysiology of type 2 diabetes and its relation to the effect of treatment of diabetes remains elusive. Here, we found increased expression of p62 in islets of db/db mice and patients with type 2 diabetes mellitus. Treatment with exendin-4, a glucagon like peptide-1 receptor agonist, improved glucose tolerance in db/db mice without significant changes in p62 expression in ?-cells. Also in ?-cell-specific Atg7-deficient mice, exendin-4 efficiently improved blood glucose level and glucose tolerance mainly by enhanced insulin secretion. In addition, we found that exendin-4 reduced apoptotic cell death and increased proliferating cells in the Atg7-deficient islets, and that exendin-4 counteracted thapsigargin-induced cell death of isolated islets augmented by autophagy deficiency. Our results suggest the potential involvement of reduced autophagy in ?-cell dysfunction in type 2 diabetes. Without altering the autophagic state in ?-cells, exendin-4 improves glucose tolerance associated with autophagy deficiency in ?-cells. This is mainly achieved through augmentation of insulin secretion. In addition, exendin-4 prevents apoptosis and increases the proliferation of ?-cells associated with autophagy deficiency, also without altering the autophagic machinery in ?-cells. PMID:24105478

Abe, Hiroko; Uchida, Toyoyoshi; Hara, Akemi; Mizukami, Hiroki; Komiya, Koji; Koike, Masato; Shigihara, Nayumi; Toyofuku, Yukiko; Ogihara, Takeshi; Uchiyama, Yasuo; Yagihashi, Soroku; Fujitani, Yoshio; Watada, Hirotaka

2013-12-01

126

Naringenin chalcone improves adipocyte functions by enhancing adiponectin production.  

PubMed

Naringenin chalcone is a flavonoid contained in tomato peel. In this study, we investigated its effects on adipocyte functions related to metabolic processes, including adipocytokine production. Naringenin chalcone promoted the gene expression (8.0-fold, p<0.001) and protein secretion (2.2-fold, p<0.001) of adiponectin from 3T3-L1 adipocytes. Reporter gene assays revealed that naringenin enhanced the activity of peroxisome proliferator-activated receptor gamma. DNA microarray experiments and Gene Ontology analysis revealed that naringenin chalcone also up-regulated the genes associated with mitochondrial energy metabolism, reflecting its insulin-sensitizing effects. Conversely, genes in categories such as those for cell adhesion were down-regulated. The expression of one adiponectin receptor, AdipoR2, was also increased (1.8-fold, p<0.01), suggesting that naringenin chalcone could activate the adiponectin pathway through the elevation of both the ligand and its receptor. These results indicate that naringenin chalcone is a potent tomato flavonoid that improves adipocyte metabolic functions and exerts insulin-sensitizing effects by activating an adiponectin-related pathway. PMID:20363289

Horiba, Taro; Nishimura, Ikuko; Nakai, Yuji; Abe, Keiko; Sato, Ryuichiro

2010-07-29

127

?-Opioid Receptor Stimulation Improves Endothelial Function in Hypoxic Pulmonary Hypertension  

PubMed Central

The present study was designed to investigate the effect of ?-opioid receptor stimulation with U50,488H on endothelial function and underlying mechanism in rats with hypoxic pulmonary hypertension (HPH). Chronic hypoxia-induced HPH was simulated by exposing the rats to 10% oxygen for 2 wk. After hypoxia, mean pulmonary arterial pressure (mPAP), right ventricular pressure (RVP) and right ventricular hypertrophy index (RVHI) were measured. Relaxation of pulmonary artery in response to acetylcholine (ACh) was determined. Expression and activity of endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) with NO production, total antioxidant capacity (T-AOC), gp91phox expression and nitrotyrosine content were measured. The effect of U50,488H administration during chronic hypoxia was investigated. Administration of U50,488H significantly decreased mPAP and right ventricular hypertrophy as evidenced by reduction in RVP and RVHI. These effects were mediated by ?-opioid receptor. In the meantime, treatment with U50,488H significantly improved endothelial function as evidenced by enhanced relaxation in response to ACh. Moreover, U50,488H resulted in a significant increase in eNOS phosphorylation, NO content in serum, and T-AOC in pulmonary artery of HPH rats. In addition, the activity of eNOS was enhanced, but the activity of iNOS was attenuated in the pulmonary artery of chronic hypoxic rats treated with U50,488H. On the other hand, U50,488H markedly blunted HPH-induced elevation of gp91phox expression and nitrotyrosine content in pulmonary artery, and these effects were blocked by nor-BNI, a selective ?-opioid receptor antagonist. These data suggest that ?-opioid receptor stimulation with U50,488H improves endothelial function in rats with HPH. The mechanism of action might be attributed to the preservation of eNOS activity, enhancement of eNOS phosphorylation, downregulation of iNOS activity and its antioxidative/nitrative effect.

Zhou, Peng; Wang, Qiu-Lin; Zhao, Lei; Fan, Rong; Wang, Yue-Min; Xu, Xue-Zeng; Yi, Ding-Hua; Yu, Shi-Qiang; Pei, Jian-Ming

2013-01-01

128

Lady Prelox® improves sexual function in post-menopausal women.  

PubMed

AIM:he aim of this pilot, single-blinded study was to evaluate the efficacy of a proprietary, dietary supplement Lady Prelox® for supporting and improving sexual function in generally healthy, post-menopausal women. METHODS: The Lady Prelox® and placebo control groups were comparable at inclusion with regard to the total Female Sexual Function Index (FSFI) score, as well as for the six individual FSFI domains, with 40 women (50.1±3.1 years) and 43 women (51.2±2.3 years), respectively. RESULTS:At baseline the women in the verum group presented with a mean total FSFI score of 44.6±24.1 which increased significantly already after four weeks treatment with Lady Prelox® to 70.9±18.5 and further increased to 71.7±23.9 after completion of the eight-week trial period. In the control group the mean total FSFI was 44.1±22.8 at inclusion and non-significantly increased to 45±21.4 after four weeks and 47.4±21.8 after eight weeks, respectively. The treatment with Lady Prelox® was comparatively significantly more effective than placebo after both four and eight weeks of treatment (P<0.05). The individual six FSFI domains related to desire, arousal, lubrication, orgasm, satisfaction and pain did all respond favourably to treatment with Lady Prelox®; however, with only marginable higher scores in the placebo group. Four women in each group dropped out because of inabilities to attend scheduled check-ups. No adverse effects were reported. CONCLUSION: This study opens an interesting perspective for women experiencing moderate sexual function impairment and suggests a promising new treatment option. Further studies with larger numbers of women, including also premenopausal and perimenopausal women are warranted. PMID:23138717

Bottari, A; Belcaro, G; Ledda, A; Cesarone, M R; Vinciguerra, G; Di Renzo, A; Stuard, S; Dugall, M; Pellegrini, L; Errichi, S; Gizzi, G; Ippolito, E; Ricci, A; Cacchio, M; Ruffini, I; Fano, F; Hosoi, M

2012-11-01

129

Cardiac assist with a twist: apical torsion as a means to improve failing heart function.  

PubMed

Changes in muscle fiber orientation across the wall of the left ventricle (LV) cause the apex of the heart to turn 10-15 deg in opposition to its base during systole and are believed to increase stroke volume and lower wall stress in healthy hearts. Studies show that cardiac torsion is sensitive to various disease states, which suggests that it may be an important aspect of cardiac function. Modern imaging techniques have sparked renewed interest in cardiac torsion dynamics, but no work has been done to determine whether mechanically augmented apical torsion can be used to restore function to failing hearts. In this report, we discuss the potential advantages of this approach and present evidence that turning the cardiac apex by mechanical means can displace a clinically significant volume of blood from failing hearts. Computational models of normal and reduced-function LVs were created to predict the effects of applied apical torsion on ventricular stroke work and wall stress. These same conditions were reproduced in anesthetized pigs with drug-induced heart failure using a custom apical torsion device programmed to rotate over various angles during cardiac systole. Simulations of applied 90 deg torsion in a prolate spheroidal computational model of a reduced-function pig heart produced significant increases in stroke work (25%) and stroke volume with reduced fiber stress in the epicardial region. These calculations were in substantial agreement with corresponding in vivo measurements. Specifically, the computer model predicted torsion-induced stroke volume increases from 13.1 to 14.4 mL (9.9%) while actual stroke volume in a pig heart of similar size and degree of dysfunction increased from 11.1 to 13.0 mL (17.1%). Likewise, peak LV pressures in the computer model rose from 85 to 95 mm Hg (11.7%) with torsion while maximum ventricular pressures in vivo increased in similar proportion, from 55 to 61 mm Hg (10.9%). These data suggest that: (a) the computer model of apical torsion developed for this work is a fair and accurate predictor of experimental outcomes, and (b) supra-physiologic apical torsion may be a viable means to boost cardiac output while avoiding blood contact that occurs with other assist methods. PMID:22070328

Trumble, Dennnis R; McGregor, Walter E; Kerckhoffs, Roy C P; Waldman, Lewis K

2011-10-01

130

Iloprost improves ventricular function in the hypertrophic and functionally impaired right heart by direct stimulation  

PubMed Central

Abstract Right heart function is an important predictor of morbidity and mortality in patients suffering from pulmonary arterial hypertension and congenital heart diseases. We investigated whether the prostacyclin analog iloprost has a direct inotropic effect in the pressure-overloaded hypertrophic and dysfunctional right ventricle (RV). Rats were randomized to monocrotaline injection (60 mg/kg; ), pulmonary trunk banding (PTB; ), or a sham operation (). RV function was evaluated with magnetic resonance imaging, echocardiography, and invasive pressure measurements at baseline, after intravenous administration of placebo, iloprost 10 ng/kg/min, or iloprost 100 ng/kg/min (Ilo100). Infusion of Ilo100 induced a () increase in stroke volume in the sham group and a () increase in the PTB group. RV was elevated by () in the sham group and by () in the PTB group. An elevation in cardiac output of () and an () increase in RV systolic pressure were found in the PTB group. Iloprost caused a decrease in mean arterial blood pressure (MAP) in all groups of animals. An equal reduction in MAP induced by the arterial vasodilator nitroprusside did not improve any of the measured parameters of RV function. We conclude that iloprost has inotropic properties directly improving ventricular function in the hypertrophic and dysfunctional right heart of the rat.

2013-01-01

131

Cost Savings Associated with the LV 100-5 Tank Engine.  

National Technical Information Service (NTIS)

The LV 100-5 turbine engine is the replacement for the AGT 1500 engine in the Abrams Main Battle Tank. The AGT 1500, produced with the Abrams in 1980, has now aged to the point where the engine costs exceed 60% of the total operations and support costs fo...

K. M. Nash

2002-01-01

132

Effects of verapamil and propranolol on left ventricular systolic function and diastolic filling in patients with coronary artery disease: radionuclide angiographic studies at rest and during exercise  

SciTech Connect

To determine the effects of verapamil on left ventricular (LV) systolic function and diastolic filling in patients with coronary artery disease (CAD), researchers performed gated radionuclide angiography at rest and during exercise in 16 symptomatic patients before and during oral verapamil therapy (480 mg/day). Twelve patients were also studied during oral propranolol. LV ejection fraction at rest was normal in 13 patients, but abnormal diastolic filling at rest, defined as peak filling rate (PFR) less than 2.5 end-diastolic volumes (EDV)/sec or time to PFR greater than 180 msec, was present in 15. During verapamil, resting ejection fraction decreased, but resting diastolic filling improved: PFR increased and time to PFR decreased. Exercise ejection fraction did not change during verapamil, but exercise PFR increased, and exercise time to PFR decreased. In contrast, propranolol did not alter ejection fraction, PFR, or time to PFR at rest or during exercise. Thus, LV ejection fraction is decreased by verapamil at rest but is unchanged during exercise. While LV systolic function is not improved by verapamil, LV diastolic filling is enhanced by verapamil, both at rest and during exercise. These mechanisms may account in part for the symptomatic improvement in many patients during verapamil therapy.

Bonow, R.O.; Leon, M.B.; Rosing, D.R.; Kent, K.M.; Lipson, L.C.; Bacharach, S.L.; Green, M.V.; Epstein, S.E.

1982-06-01

133

Cardiomyocyte-specific expression of CRNK, the C-terminal domain of PYK2, maintains ventricular function and slows ventricular remodeling in a mouse model of dilated cardiomyopathy.  

PubMed

Up-regulation and activation of PYK2, a member of the FAK family of protein tyrosine kinases, is involved in the pathogenesis of left ventricular (LV) remodeling and heart failure (HF). PYK2 activation can be prevented by CRNK, the C-terminal domain of PYK2. We previously demonstrated that adenoviral-mediated CRNK gene transfer improved survival and LV function, and slowed LV remodeling in a rat model of coronary artery ligation-induced HF. We now interrogate whether cardiomyocyte-specific, transgenic CRNK expression prevents LV remodeling and HF in a mouse model of dilated cardiomyopathy (DCM) caused by constitutively active Protein Kinase C? (caPKC?). Transgenic (TG; FVB/N background) mice were engineered to express rat CRNK under control of the ?-myosin heavy chain promoter, and crossed with FVB/N mice with cardiomyocyte-specific expression of caPKC? to create double TG mice. LV structure, function, and gene expression were evaluated in all 4 groups (nonTG FVB/N; caPKC?(+/-); CRNK(+/-); and caPKC?×CRNK (PXC) double TG mice) at 1, 3, 6, 9 and 12mo of age. CRNK expression followed a Mendelian distribution, and CRNK mice developed and survived normally through 12mo. Cardiac structure, function and selected gene expression of CRNK mice were similar to nonTG littermates. CRNK had no effect on caPKC? expression and vice versa. PYK2 was up-regulated ~6-fold in caPKC? mice, who developed a non-hypertrophic, progressive DCM with reduced systolic (Contractility Index=151±5 vs. 90±4s(-1)) and diastolic (Tau=7.5±0.5 vs. 14.7±1.3ms) function, and LV dilatation (LV Remodeling Index (LVRI)=4.2±0.1 vs. 6.0±0.3 for FVB/N vs. caPKC? mice, respectively; P<0.05 for each at 12mo). In double TG PXC mice, CRNK expression significantly prolonged survival, improved contractile function (Contractile Index=115±8s(-1); Tau=9.5±1.0ms), and reduced LV remodeling (LVRI=4.9±0.1). Cardiomyocyte-specific expression of CRNK improves contractile function and slows LV remodeling in a mouse model of DCM. PMID:24713463

Koshman, Yevgeniya E; Chu, Miensheng; Kim, Taehoon; Kalmanson, Olivia; Farjah, Mariam; Kumar, Mohit; Lewis, William; Geenen, David L; de Tombe, Pieter; Goldspink, Paul H; Solaro, R John; Samarel, Allen M

2014-07-01

134

May pentoxifylline improve lung function after one-lung flooding?  

PubMed

One-lung flooding makes the intraoperative sonography of round pulmonary lesions possible. During the flooded phase, the flooded lung suffers a significant reduction in perfusion. After ischemia and reperfusion, neutrophil granulocytes lead to further tissue injuries. A study was made on four animals to determine whether administration of pentoxifylline--a potent inhibitor of granulocyte adhesion to the endothelium--improves lung function after one-lung flooding. Two animals were subjected to thoracotomy with extended hemodynamic monitoring. Thoracoscopy was performed on two other animals, which were extubated after the flooding liquid was drained and survived for 24 degrees h. A bolus of 1 mg/kg of pentoxifylline was administered at the time of thoracotomy/thoracoscopy. followed by continuous infusion of pentoxifylline at a rate of 1.5 mg/kg per hour until 30 degrees min after reventilation (thoracotomy), or until extubation, respectively. The control group consisted of animals employed in previous experiments. Except for pentoxifylline administration, they were subjected to identical experimental conditions. The control group for the thoracotomy experiment comprised 14 animals, that for the thoracoscopy experiment three animals. The experiments proved that 30 degrees min after the draining of the flooding liquid and reventilation, all four pentoxifylline-treated animals had a higher partial arterial oxygen pressure and a lower pulmonary shunt volume compared with the control animals. In the two animals that survived, a positive effect on lung function was no longer detectable 24 degrees h after extubation. The administration did not lead to a drop in the pulmonary arterial pressure and did not cause any hemodynamic changes other than a moderate tachycardia. PMID:11271514

Klinzing, S; Lesser, T; Schubert, H; Bartel, M; Klein, U

2001-01-01

135

Improvement of the organic solar cells functional parameters  

NASA Astrophysics Data System (ADS)

By changing the concentration ratio (zinc-phthalocyanine-ZnPhTc:Fullerene-C60 from ZnPhTc:C60 = 1:0 through ZnPhTc:C60 = 1:1, to 1 C60: ZnPhTc = 1:0) in the active layer, as well as the architecture of the organic solar cells (OSC), a substanial increase of their short-circuit current is achieved. We suggest that the blurred interlayer boundaries lead to an enhanced motion of the holes and the electrons to the electrodes – ITO and Al respectively. Regardless of the shorter distances between the places of excitons creation, the excitons have enough "life-time" for diffusion to the suitable places where their decomposition to the charge carriers – holes and electrons, takes place. This is one of the well-known approaches to achieve a higher efficiency of the OSCs. We thus suggest that the possible interactions and processes discussed are obviously essential prerequisites for improving the functional parameters of the OSCs.

Dimov, D.; Spassova, I.; Danev, G.; Zhivkov, I.; Assa, J.

2014-05-01

136

Bioactive rosette nanotube-hydroxyapatite nanocomposites improve osteoblast functions.  

PubMed

Inspired from biological systems, small synthetic organic molecules expressing the hydrogen bonding arrays of the DNA bases guanine and cytosine were prepared, and their self-assembly into rosette nanotubes (RNTs) was investigated. Due to their unique biological, physicochemical, and mechanical properties, RNTs could serve as the next generation of injectable orthopedic materials. In this study, a self-assembling module (termed twin base linkers or TBL) was synthesized, and the corresponding RNTs were used as bioactive components in composites of poly (2-hydroxyethyl methacrylate) (pHEMA) and hydroxyapatite (HA) nanoparticles (termed TBL/HA/pHEMA). The properties of these composites were characterized for solidification time, surface morphology, mechanical properties, and cytocompatibility. The experimental conditions were optimized to achieve solidification within 2-40 min, offering a range of properties for orthopedic applications. Composites with 20 wt% HA nanoparticles had a compressive strength (37.1 MPa) and an ultimate tensile stress (14.7 MPa) similar to that of a natural vertebral disc (5-30 MPa). Specifically, the TBL (0.01 mg/mL)/HA(20 wt%)/pHEMA composites improved long-term functions of osteoblasts (or bone-forming cells) in terms of collagen synthesis, alkaline phosphatase activity, and calcium deposition. Moreover, this composite inhibited fibroblast adhesion, thus decreasing the potential for undesirable fibrous tissue formation. In summary, this in vitro study provided evidence that TBL/HA/pHEMA composites are promising injectable orthopedic implant materials that warrant further mechanistic and in vivo studies. PMID:22530958

Sun, Linlin; Zhang, Lijie; Hemraz, Usha D; Fenniri, Hicham; Webster, Thomas J

2012-09-01

137

Using SVD for improved interferometric Green's function retrieval  

NASA Astrophysics Data System (ADS)

Seismic interferometry (SI) is a technique used to estimate the Green's function (GF) between two receiver locations, as if there were a source at one of the receiver locations. However, in many applications, the requirements to recover the exact GF are not satisfied and SI yields a poor estimate of the GF. For these non-ideal cases, we improve the interferometric GFs, by applying singular value decomposition (SVD) to the cross-correlations before stacking. The SVD approach preserves energy that is stationary in the cross-correlations, which is the energy that contributes most to the GF recovery, and attenuates non-stationary energy, which leads to artefacts in the interferometric GF. We apply this method to construct virtual shot gathers (for both synthetic and field data) and demonstrate how using SVD enhances physical arrivals in these gathers. We also find that SVD is robust with respect to weakly correlated random noise, allowing a better recovery of events from noisy data, in some cases recovering energy that would otherwise be completely lost in the noise and that the standard SI technique fails to recover.

Melo, Gabriela; Malcolm, Alison; Mikesell, Dylan; van Wijk, Kasper

2013-09-01

138

Improved echo volumar imaging (EVI) for functional MRI.  

PubMed

Echo volumar imaging (EVI) is a 3D modification of echo-planar imaging (EPI) that allows data from an entire volume to be acquired following a single RF excitation. EVI provides a high rate of volumar data acquisition, which is advantageous for functional MRI (fMRI). However, few studies to date have applied EVI to fMRI, since because of gradient hardware limitations EVI generally has to be used with long sampling times, resulting in high sensitivity to susceptibility-induced distortions. In this study we modified the EVI sequence to improve its suitability for fMRI. The sampling time is reduced by the use of a high gradient-switching frequency, a small number of echoes, and outer volume suppression (OVS); rewind gradients ameliorate Nyquist ghosting; and phase correction via a calibration scan reduces ghosting and distortion. It is shown that the modified EVI sequence allows fMRI data to be acquired with a temporal resolution of 167 ms. PMID:17089364

van der Zwaag, Wietske; Francis, Susan; Bowtell, Richard

2006-12-01

139

Stimulus Characteristics for Vestibular Stochastic Resonance to Improve Balance Function  

NASA Technical Reports Server (NTRS)

Stochastic resonance (SR) is a mechanism by which noise can enhance the response of neural systems to relevant sensory signals. Studies have shown that imperceptible stochastic vestibular electrical stimulation, when applied to normal young and elderly subjects, significantly improved their ocular stabilization reflexes in response to whole-body tilt as well as balance performance during postural disturbances. The goal of this study was to optimize the amplitude characteristics of the stochastic vestibular signals for balance performance during standing on an unstable surface. Subjects performed a standard balance task of standing on a block of foam with their eyes closed. Bipolar stochastic electrical stimulation was applied to the vestibular system using constant current stimulation through electrodes placed over the mastoid process behind the ears. Amplitude of the signals varied in the range of 0-700 microamperes. Balance performance was measured using a force plate under the foam block, and inertial motion sensors were placed on the torso and head. Balance performance with stimulation was significantly greater (10%-25%) than with no stimulation. The signal amplitude at which performance was maximized was in the range of 100-300 microamperes. Optimization of the amplitude of the stochastic signals for maximizing balance performance will have a significant impact on development of vestibular SR as a unique system to aid recovery of function in astronauts after long-duration space flight or in patients with balance disorders.

Mulavara, Ajitkumar; Fiedler, Matthew; Kofman, Igor; Peters, Brian; Wood, Scott; Serrado, Jorge; Cohen, Helen; Reschke, Millard; Bloomberg, Jacob

2010-01-01

140

Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats  

PubMed Central

Background Left ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear. Methods MI was produced in adult female Sprague–Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study. Results T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 ?m) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to ?4 expression was also observed in T4 treated MI rats. Conclusions These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area.

2013-01-01

141

Detection of antibodies to the feline leukemia Virus (FeLV) transmembrane protein p15E: an alternative approach for serological FeLV detection based on antibodies to p15E.  

PubMed

The aim of this report was to investigate whether the diagnosis of feline leukemia virus (FeLV) infection by serology might be feasible and useful. Among the various viral proteins, the FeLV env-gene product (SU) and the envelope transmembrane protein p15E were considered promising candidates for the serological diagnosis of FeLV infection. Thus, we evaluated p15E and three other FeLV antigens, namely, a recombinant env-gene product, whole FeLV, and a short peptide from the FeLV transmembrane protein, for their potential to detect FeLV infection. To evaluate possible exposure of cats to FeLV, we tested serum and plasma samples from experimentally and naturally infected and vaccinated cats for the presence of antibodies to these antigens by enzyme-linked immunosorbent assays (ELISAs). The serological results were compared with the p27 and proviral real-time PCR results. We found that p15E displayed a diagnostic sensitivity of 95.7% and a specificity of 100% in experimentally infected cats. In naturally infected cats, p15E showed a diagnostic sensitivity of 77.1% and a specificity of 85.6%. Vaccinated cats displayed minimal antibody levels to p15E, suggesting that anti-p15E antibodies indicate infection rather than vaccination. The other antigens turned out to be too unspecific. The lower specificity in cats exposed to FeLV under field conditions may be explained by the fact that some cats become infected and seroconvert in the absence of detectable viral nucleic acids in plasma. We conclude that p15E serology may become a valuable tool for diagnosing FeLV infection; in some cases, it may replace PCR. PMID:24696026

Boenzli, Eva; Hadorn, Maik; Hartnack, Sonja; Huder, Jon; Hofmann-Lehmann, Regina; Lutz, Hans

2014-06-01

142

Strategies for improving the functionality of an affinity bioreactor.  

PubMed

Heparin employed in extracorporeal blood circulation (ECBC) procedures (e.g. open heart operations) often leads to a high incidence of bleeding complications. Protamine employed in heparin neutralization, on the other hand, can cause severe adverse reactions. We previously developed an approach that could prevent both heparin- and protamine-induced toxic side effects concomitantly. This approach consisted of placing a hollow fiber-based bioreactor device containing immobilized protamine (termed a "protamine bioreactor") at the distal end of the ECBC procedure. This protamine bioreactor would remove heparin after heparin served its anticoagulant purpose in the ECBC device, thereby eliminating heparin-induced bleeding risks. In addition, this protamine bioreactor would prevent protamine from entering the patients, thereby aborting any protamine-induced toxic effects. Both in vitro and in vivo studies have successfully demonstrated the feasibility of this approach. Despite promises, early findings also revealed two shortcomings that must be overcome for the protamine bioreactor to be applied clinically. The first drawback was that the cyanate ester linkages, involved in conjugating protamine to the bioreactor device, were unstable and prone to hydrolysis, resulting in the leakage of a significant amount of protamine into circulation during application of the protamine bioreactor. The second deficiency was that the capacity of the protamine bioreactor in heparin removal was rather low, owing to the limited surface area of the hollow fibers for protamine immobilization and subsequently heparin adsorption. In this paper, we present novel strategies to overcome these two limitations. A new conjugation method based on the use of 4-(oxyacetyl)phenoxyacetic acid (OAPA) as the activating reagent was employed to yield stable linkages, via the abundant arginine residues of protamine, onto the hollow fibers. Results showed that while the amount of protamine immobilized on each gram of fibers was relatively comparable between the OAPA and the previous CNBr activation methods (7.45 mg/g versus 7.69 mg/g fibers), there was virtually no detectable leaching of immobilized protamine from the bioreactor by the OAPA method, comparing to 35% leaching of protamine by the previous CNBr method following 72 h of storage of the bioreactor in PBS buffer at 37 degrees C. To improve the capacity and functionality of the protamine bioreactor, two novel approaches were adopted. Long chain and high molecular weight poly-lysine was linked to the hollow fibers, prior to protamine coupling, to create multiple layers of immobilized protamine for subsequent heparin adsorption. In addition, a poly(ethylene glycol) (PEG) chain was inserted between protamine and the hollow fibers to yield a three-dimensional, free dynamic motion for immobilized protamine. Preliminary observations indicated that a four- to five-fold enhancement in heparin adsorption was attained by utilizing each of these new approaches. Aside from their current use, these new strategies can also be employed generically to improve the functionality of any affinity-type bioreactor. Indeed, efforts have been made recently in utilizing these approaches to develop a clinically usable GPIIb/IIIa bioreactor for the treatment of immune thrombocytopenic purpura (ITP)-an autoimmune disease. PMID:16246511

Wang, Tanya; Yang, Zhiqiang; Emregul, Emel; David, Allan; Balthasar, Joseph P; Liang, Junfeng; Yang, Victor C

2005-12-01

143

An improved version of the Green's function molecular dynamics method  

NASA Astrophysics Data System (ADS)

This work presents an improved version of the Green's function molecular dynamics method (Kong et al., 2009; Campañá and Müser, 2004 [1,2]), which enables one to study the elastic response of a three-dimensional solid to an external stress field by taking into consideration only atoms near the surface. In the previous implementation, the effective elastic coefficients measured at the ?-point were altered to reduce finite size effects: their eigenvalues corresponding to the acoustic modes were set to zero. This scheme was found to work well for simple Bravais lattices as long as only atoms within the last layer were treated as Green's function atoms. However, it failed to function as expected in all other cases. It turns out that a violation of the acoustic sum rule for the effective elastic coefficients at ? (Kong, 2010 [3]) was responsible for this behavior. In the new version, the acoustic sum rule is enforced by adopting an iterative procedure, which is found to be physically more meaningful than the previous one. In addition, the new algorithm allows one to treat lattices with bases and the Green's function slab is no longer confined to one layer. New version program summaryProgram title: FixGFC/FixGFMD v1.12 Catalogue identifier: AECW_v1_1 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AECW_v1_1.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 206 436 No. of bytes in distributed program, including test data, etc.: 4 314 850 Distribution format: tar.gz Programming language: C++ Computer: All Operating system: Linux Has the code been vectorized or parallelized?: Yes. Code has been parallelized using MPI directives. RAM: Depends on the problem Classification: 7.7 External routines: LAMMPS ( http://lammps.sandia.gov/), MPI ( http://www.mcs.anl.gov/research/projects/mpi/), FFT ( http://www.fftw.org/) Catalogue identifier of previous version: AECW_v1_0 Journal reference of previous version: Comput. Phys. Comm. 180 (2009) 1004 Does the new version supersede the previous version?: Yes Nature of problem: Green's function molecular dynamics (GFMD) is a coarse-graining method that enables one to investigate the full elastic response of an interface between a semi-infinite solid and a contact while taking only the surface atoms in the solid into consideration. The effect of long-range elastic deformations on the surface atoms from the semi-infinite solid is replaced by effective elastic interactions, thus reducing the problem from three dimensions to two dimensions without compromising the physical essence of the problem. Solution method: See "Nature of problem". Reasons for new version: The basic theory underlying the new version is essentially the same as the previous one, while the special treatment to reduce the finite size effect on effective elastic coefficients at the ?-point is now realized in a physically meaningful manner. Finite size effects are an important issue in molecular dynamics simulations, particularly for GFMD, they result in a violation of the acoustic sum rule (ASR) for the effective elastic coefficients measured at the ?-point ( ?). In the previous implementation, the effective elastic coefficients measured at the ?-point were altered by setting their eigenvalues corresponding to the acoustic modes to zero. This scheme was found to work well for simple Bravais lattices as long as only atoms within the last layer were treated as Green's function atoms. However, it failed to function as expected in all other cases. We therefore adopt a new algorithm to enforce the ASR for ? (Kong, 2010 [3]) which is implemented in this revision. Summary of revisions: Assuming the lattice under study consists of surface unit cells with n basis atoms labeled by k=1,2,…,n. When all atoms in the lattice are moved by the same amount, i.e., the crystal is rigidly translated, the force on any atom must be zero

Kong, Ling Ti; Denniston, Colin; Müser, Martin H.

2011-02-01

144

Development and evaluation of a semiautomatic segmentation method for the estimation of LV parameters on cine MR images  

NASA Astrophysics Data System (ADS)

The purpose of this study was to develop and evaluate a semiautomatic method for left ventricular (LV) segmentation on cine MR images and subsequent estimation of cardiac parameters. The study group comprised cardiac MR examinations of 18 consecutive patients with known or suspected coronary artery disease. The new method allowed the automatic detection of the LV endocardial and epicardial boundaries on each short-axis cine MR image using a Bayesian flooding segmentation algorithm and weighted least-squares B-splines minimization. Manual editing of the automatic contours could be performed for unsatisfactory segmentation results. The end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and LV mass estimated by the new method were compared with the reference values obtained by manually tracing the LV cavity borders. The reproducibility of the new method was determined using data from two independent observers. The mean number of endocardial and epicardial outlines not requiring any manual adjustment was more than 80% and 76% of the total contour number per study, respectively. The mean segmentation time including the required manual corrections was 2.3 ± 0.7 min per patient. LV volumes estimated by the semiautomatic method were significantly lower than those by manual tracing (P < 0.05), whereas no difference was found for EF and LV mass (P > 0.05). LV indices estimated by the two methods were well correlated (r >= 0.80). The mean difference between manual and semiautomatic method for estimating EDV, ESV, EF and LV mass was 6.1 ± 7.2 ml, 3.0 ± 5.2 ml, -0.6 ± 4.3% and -6.2 ± 12.2 g, respectively. The intraobserver and interobserver variability associated with the semiautomatic determination of LV indices was 0.5-1.2% and 0.8-3.9%, respectively. The estimation of LV parameters with the new semiautomatic segmentation method is technically feasible, highly reproducible and time effective.

Mazonakis, Michalis; Grinias, Elias; Pagonidis, Konstantin; Tziritas, George; Damilakis, John

2010-02-01

145

Cardiac function assessed by attenuation-corrected radionuclide pressure-volume indices  

SciTech Connect

Using attenuation-corrected radionuclide volumes and arm-cuff peak systolic pressures, the authors established the mean value for the ratio of left ventricular (LV) peak systolic pressure/end systolic volume at rest for 15 healthy persons. In 43 patients with coronary disease, this ratio was more sensitive as an indicator of abnormal LV function and for predicting coronary artery disease than the resting ejection fraction. The slope of an end systolic pressure-volume line was also calculated from data obtained under three loading conditions: at rest, during isometric handgrip testing, and after the sublingual administration of nitroglycerin. These results represent an improvement over previous radionuclide pressure-volume measurements that have not used attenuation correction and show the need for accurate, nongeometric measurements of the LV end systolic volume.

Maurer, A.H.; Siegel, J.A.; Blasius, K.M.; Deneberg, B.S.; Spann, J.F.; Malmud, L.S.

1985-07-01

146

Improving Sensorimotor Function and Adaptation using Stochastic Vestibular Stimulation  

NASA Technical Reports Server (NTRS)

Astronauts experience sensorimotor changes during adaption to G-transitions that occur when entering and exiting microgravity. Post space flight, these sensorimotor disturbances can include postural and gait instability, visual performance changes, manual control disruptions, spatial disorientation, and motion sickness, all of which can hinder the operational capabilities of the astronauts. Crewmember safety would be significantly increased if sensorimotor changes brought on by gravitational changes could be mitigated and adaptation could be facilitated. The goal of this research is to investigate and develop the use of electrical stochastic vestibular stimulation (SVS) as a countermeasure to augment sensorimotor function and facilitate adaptation. For this project, SVS will be applied via electrodes on the mastoid processes at imperceptible amplitude levels. We hypothesize that SVS will improve sensorimotor performance through the phenomena of stochastic resonance, which occurs when the response of a nonlinear system to a weak input signal is optimized by the application of a particular nonzero level of noise. In line with the theory of stochastic resonance, a specific optimal level of SVS will be found and tested for each subject [1]. Three experiments are planned to investigate the use of SVS in sensory-dependent tasks and performance. The first experiment will aim to demonstrate stochastic resonance in the vestibular system through perception based motion recognition thresholds obtained using a 6-degree of freedom Stewart platform in the Jenks Vestibular Laboratory at Massachusetts Eye and Ear Infirmary. A range of SVS amplitudes will be applied to each subject and the subjectspecific optimal SVS level will be identified as that which results in the lowest motion recognition threshold, through previously established, well developed methods [2,3,4]. The second experiment will investigate the use of optimal SVS in facilitating sensorimotor adaptation to system disturbances. Subjects will adapt to wearing minifying glasses, resulting in decreased vestibular ocular reflex (VOR) gain. The VOR gain will then be intermittently measured while the subject readapts to normal vision, with and without optimal SVS. We expect that optimal SVS will cause a steepening of the adaptation curve. The third experiment will test the use of optimal SVS in an operationally relevant aerospace task, using the tilt translation sled at NASA Johnson Space Center, a test platform capable of recreating the tilt-gain and tilt-translation illusions associated with landing of a spacecraft post-space flight. In this experiment, a perception based manual control measure will be used to compare performance with and without optimal SVS. We expect performance to improve in this task when optimal SVS is applied. The ultimate goal of this work is to systematically investigate and further understand the potential benefits of stochastic vestibular stimulation in the context of human space flight so that it may be used in the future as a component of a comprehensive countermeasure plan for adaptation to G-transitions.

Galvan, R. C.; Bloomberg, J. J.; Mulavara, A. P.; Clark, T. K.; Merfeld, D. M.; Oman, C. M.

2014-01-01

147

On the Interpretation of the l-v Features in the Milky Way Galaxy  

Microsoft Academic Search

We modeled the gas dynamics of barred galaxies using a three-dimensional, high-resolution, N-body + hydrodynamical simulation, and applied it to the Milky Way in an attempt to reproduce both the large-scale structure and the clumpy morphology observed in galactic HI and CO l-v diagrams. Owing to including of the multi-phase interstellar medium, self-gravity, star-formation, and supernovae feedback, the clumpy morphology,

Junichi Baba; Takayuki R. Saitoh; Keiichi Wada

2010-01-01

148

On the role of the spleen in Friend virus (F-MuLV-P) erythroleukemia.  

PubMed

About 30% of Friend virus (F-MuLV-P)-infected C57BL/6 mice became leukemic more than ten weeks after virus infection. This late leukemia development could not be essentially influenced by drug treatment, such as injection of hydroxyurea (2 X 500 mg/kg), actinomycin D (3 X 120 micrograms/kg), phenylhydrazine (3 X 60 mg/kg), or 30 micrograms endotoxin or by bone marrow transplantation following lethal irradiation. Endotoxin (30 micrograms) given prior to virus caused the loss of resistance to F-MuLV-P, but it had only a slight effect if applied one or three months after virus infection. Leukemia development has never been observed in C57BL/6 mice after splenectomy. In DBA/2 mice, highly susceptible to F-MuLV-P, leukemia development was markedly impaired if the mice were splenectomized. These results clearly indicate that the spleen plays a crucial role in the mechanism of susceptibility or resistance to the Friend virus. PMID:3861325

Kreja, L; Seidel, H J

1985-08-01

149

Fixed-Bearing Total Ankle Replacement (TAR) Improves Gait Function  

MedlinePLUS

... positive short-term results A study of gait mechanics in patients who underwent total ankle replacement (TAR) ... improvement in nearly all measured parameters of gait mechanics (measured preoperatively, 1 year postoperative, and 2 years ...

150

Improving Cognition and Function Through Exercise Intervention in Alzheimer's Disease  

Microsoft Academic Search

Purpose: To analyze the effects of cognition on function and to explore the potential of aerobic exercise for promoting cognitive and functional capacities. Design: Integrative review of literature. Methods: Studies were selected based on an extensive search of electronic databases and man- ual cross-referencing for 1980 to 2006, using the combination of key words: Alzheimer's disease (AD), dementia, or cognitive

Fang Yu; Ann M. Kolanowski; Neville E. Strumpf; Paul J. Eslinger

2006-01-01

151

Functional Structure for Performance Improvement of Time Overcurrent Relays  

Microsoft Academic Search

In this article, we recommend a functional structure for time overcurrent relays. This type of relay has a higher sensitivity and reduced back-up times compared to other types of relay using only the information available at the relay's site. We describe the functional structure of time overcurrent adaptive relays for phase protection. The results obtained from time overcurrent adaptive relays

A. Conde; E. Vázquez

2007-01-01

152

Improvement of skin barrier function during treatment of atopic dermatitis  

Microsoft Academic Search

Background: Active dermatitis causes a disturbance in skin barrier function. This can be evaluated by the measurement of transepidermal water loss (TEWL) and percutaneous absorption of hydrocortisone.Objective: The study objective was to evaluate changes in skin barrier function during treatment of atopic dermatitis.Methods: Nine patients with widespread atopic dermatitis were studied longitudinally by measuring the severity of the dermatitis and

Kristiina Aalto-Korte

1995-01-01

153

Cardiovascular magnetic resonance assessment of ventricular function and myocardial scarring before and early after repair of anomalous left coronary artery from the pulmonary artery  

PubMed Central

Background In patients with anomalous left coronary artery from the pulmonary artery (ALCAPA) left ventricular (LV) dilatation and dysfunction evolves due to diminished myocardial perfusion caused by coronary steal phenomenon. Using late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) imaging, myocardial scarring has been shown in ALCAPA patients late after repair, however the incidence of scarring before surgery and its impact on postoperative course after surgical repair remained unknown. Methods 8 ALCAPA-patients (mean age 10.0?±?5.8 months) underwent CMR before and early after (mean 4.9?±?2.5 months) coronary reimplantation procedures. CMR included functional analysis and LGE for detection of myocardial scars. Results LV dilatation (mean LVEDVI 171?±?94 ml/m2) and dysfunction (mean LV-EF 22?±?10 %) was present in all patients and improved significantly after surgery (mean LVEDV 68?±?42 ml/m2, p?=?0.02; mean LV-EF 58?±?19 %, p?LV function while myocardial scarring was still present in both patients. In two patients new-onset transmural scarring was found, although functional recovery after operation was sufficient. One of them showed a stenosis of the left coronary artery and required resurgery. Conclusions Despite diminished myocardial perfusion and severely compromised LV function, myocardial scarring was preoperatively only infrequently present. Improvement of myocardial function was independent of new-onset scarring while the impact of preoperative scarring still needs to be defined.

2014-01-01

154

Improved WKB radial wave functions in several bases  

SciTech Connect

We develop approximate WKB-like solutions to the radial Schroedinger equation for problems with an angular momentum barrier using Riccati-Bessel, Coulomb, and harmonic-oscillator functions as basis functions. The solutions treat the angular momentum singularity near the origin more accurately in leading approximation than the standard WKB solutions based on sine waves. The solutions based on Riccati-Bessel and free Coulomb wave functions continue smoothly through the inner turning point and are appropriate for scattering problems. The solutions based on oscillator and bound Coulomb wave functions incorporate both turning points smoothly and are particularly appropriate for bound-state problems; no matching of piecewise solutions using Airy functions is necessary.

Durand, B.; Durand, L.

1986-05-01

155

Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy  

NASA Technical Reports Server (NTRS)

BACKGROUND: Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. METHODS AND RESULTS: Thirty patients who underwent IE (mean age 61+/-8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42+/-67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99+/-40, 67+/-26, and 71+/-31 mL/m(2), respectively; ESVI 72+/-37, 40+/-21, and 42+/-22 mL/m(2), respectively; P:<0.05). LV ejection fraction increased significantly and remained higher (0.29+/-0.11, 0.43+/-0.13, and 0.42+/-0.09, respectively, P:<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22+/-12, 53+/-24, and 58+/-21 mL, respectively, P:<0.005). New York Heart Association functional class at an average 285+/-144 days of clinical follow-up significantly improved from 3.0+/-0.8 to 1.8+/-0.8 (P:<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman's rho=0.58 and 0.60, respectively). CONCLUSIONS: RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.

Qin, J. X.; Shiota, T.; McCarthy, P. M.; Firstenberg, M. S.; Greenberg, N. L.; Tsujino, H.; Bauer, F.; Travaglini, A.; Hoercher, K. J.; Buda, T.; Smedira, N. G.; Thomas, J. D.

2000-01-01

156

The process of performance improvement: preserving myocardial function.  

PubMed

In today's healthcare environment, the continual assessment of processes is necessary to provide the best patient care. Ongoing process improvement also is helpful in organizations' remaining both competitive and fiscally viable. Because of the increasing concern about mortality rates from acute myocardial infarction (AMI), the Johnson City Medical Center chose to evaluate the care of patients with AMI. This article describes the first of three phases of the hospital's efforts to examine and improve the process of caring for patients with AMI to achieve positive patient outcomes. PMID:11565169

Washington, G T

2001-01-01

157

Isolated soy protein improves endothelial function in postmenopausal hypercholesterolemic women  

Microsoft Academic Search

Background: Postmenopausia and hypercholesterolemia are related to endothelial dysfunction, a pathogenic event in atherosclerosis. Soy protein reduces plasma cholesterol, but there is scanty information about its effect on endothelial function.Objective: To evaluate the effect of isolated soy protein compared to caseinate on plasma lipoproteins and endothelial function in postmenopausal hypercholesterolemic women.Design: Randomized, double-blind, cross-over trial.Setting: Outpatient clinic of the Catholic

A M Cuevas; V L Irribarra; O A Castillo; M D Yañez; A M Germain

2003-01-01

158

Structural and functional cardiac adaptations to 6?months of football training in untrained hypertensive men.  

PubMed

We investigated the effects of 3 and 6 months of regular football training on cardiac structure and function in hypertensive men. Thirty-one untrained males with mild-to-moderate hypertension were randomized 2:1 to a football training group (n?=?20) and a control group receiving traditional recommendations on healthy lifestyle (n?=?11). Cardiac measures were evaluated by echocardiography. The football group exhibited significant (P?function after just 3 months: Left ventricular (LV) end-diastolic volume increased from 104?±?25 to 117?±?29?mL. LV diastolic function improved measured as E/A ratio (1.15?±?0.32 to 1.54?±?0.38), early diastolic velocity, E' (11.0?±?2.5 to 11.9?±?2.6?cm/s), and isovolumetric relaxation time (74?±?13 to 62?±?13?ms). LV systolic function improved measured as longitudinal displacement (10.7?±?2.1 to 12.1?±?2.3?mm). Right ventricular function improved with respect to tricuspid annular plane systolic excursion (21.8?±?3.2 to 24.5?±?3.7?mm). Arterial blood pressure decreased in both groups, but significantly more in the football training group. No significant changes were observed in the control group. In conclusion, short-term football training improves LV diastolic function in untrained men with mild-to-moderate arterial hypertension. Furthermore, it may improve longitudinal systolic function of both ventricles. The results suggest that football training has favorable effects on cardiac function in hypertensive men. PMID:24903081

Andersen, L J; Randers, M B; Hansen, P R; Hornstrup, T; Schmidt, J F; Dvorak, J; Søgaard, P; Krustrup, P; Bangsbo, J

2014-08-01

159

Improving protein function prediction methods with integrated literature data  

PubMed Central

Background Determining the function of uncharacterized proteins is a major challenge in the post-genomic era due to the problem's complexity and scale. Identifying a protein's function contributes to an understanding of its role in the involved pathways, its suitability as a drug target, and its potential for protein modifications. Several graph-theoretic approaches predict unidentified functions of proteins by using the functional annotations of better-characterized proteins in protein-protein interaction networks. We systematically consider the use of literature co-occurrence data, introduce a new method for quantifying the reliability of co-occurrence and test how performance differs across species. We also quantify changes in performance as the prediction algorithms annotate with increased specificity. Results We find that including information on the co-occurrence of proteins within an abstract greatly boosts performance in the Functional Flow graph-theoretic function prediction algorithm in yeast, fly and worm. This increase in performance is not simply due to the presence of additional edges since supplementing protein-protein interactions with co-occurrence data outperforms supplementing with a comparably-sized genetic interaction dataset. Through the combination of protein-protein interactions and co-occurrence data, the neighborhood around unknown proteins is quickly connected to well-characterized nodes which global prediction algorithms can exploit. Our method for quantifying co-occurrence reliability shows superior performance to the other methods, particularly at threshold values around 10% which yield the best trade off between coverage and accuracy. In contrast, the traditional way of asserting co-occurrence when at least one abstract mentions both proteins proves to be the worst method for generating co-occurrence data, introducing too many false positives. Annotating the functions with greater specificity is harder, but co-occurrence data still proves beneficial. Conclusion Co-occurrence data is a valuable supplemental source for graph-theoretic function prediction algorithms. A rapidly growing literature corpus ensures that co-occurrence data is a readily-available resource for nearly every studied organism, particularly those with small protein interaction databases. Though arguably biased toward known genes, co-occurrence data provides critical additional links to well-studied regions in the interaction network that graph-theoretic function prediction algorithms can exploit.

Gabow, Aaron P; Leach, Sonia M; Baumgartner, William A; Hunter, Lawrence E; Goldberg, Debra S

2008-01-01

160

Recent improvements of the parameterization of Bragg peak profile functions  

SciTech Connect

The Jorgensen'' profile function conventionally used to describe the shape of observed Bragg peaks in time-of-flight powder neutron diffraction fits individual peaks very well. However, the wavelength or plane spacing variation of the parameters of the components of this function, as they are conventionally represented in Rietveld analysis, is inappropriate for fitting data extending over a wide range of plane spacings, d. We have developed a new representation of the d-dependence of the profile parameters which are generalizations of Pade' approximants, have built-in physically realistic large- and small-d limiting behavior, and provide better fits to parameters derived from individual peak fits than the conventional forms. We report the results of tests of the new parameterization of the profile functions. 3 refs., 5 figs.

Carpenter, J.M.; Dimm, W.C.; Rotella, F.J.

1990-01-01

161

Improving balance function using vestibular stochastic resonance: optimizing stimulus characteristics  

Microsoft Academic Search

Stochastic resonance (SR) is a phenomenon whereby the response of a non-linear system to a weak periodic input signal is optimized\\u000a by the presence of a particular non-zero level of noise. Stochastic resonance using imperceptible stochastic vestibular electrical\\u000a stimulation, when applied to normal young and elderly subjects, has been shown to significantly improve ocular stabilization\\u000a reflexes in response to whole-body

Ajitkumar P. Mulavara; Matthew J. Fiedler; Igor S. Kofman; Scott J. Wood; Jorge M. Serrador; Brian Peters; Helen S. Cohen; Millard F. Reschke; Jacob J. Bloomberg

2011-01-01

162

Effects of ivabradine on allograft function and exercise performance in heart transplant recipients with permanent sinus tachycardia.  

PubMed

Aim of this retrospective analysis was to evaluate the effects of ivabradine given primarily as a heart rate-lowering agent on allograft function and cardiopulmonary performance in heart transplant recipients with permanent sinus tachycardia. Starting May 2006, 26 heart transplant recipients with permanent sinus tachycardia received ivabradine (5 mg bid). It was discontinued early in 3 patients (11.5%) due to adverse events. In the remaining 23 patients, resting heart rate (HR) was significantly lowered from 106.3 +/- 9.1 to 82.2 +/- 6.3 bpm after 3 weeks of treatment. The effect remained constant during the remaining treatment period, whereas resting blood pressure was not affected. After 12 weeks of ivabradine treatment, the corrected QT interval was significantly reduced into the range seen in normal individuals. Left ventricular (LV) end-diastolic posterior wall thickness, LV mass and LV mass index were also found to have decreased significantly. There was a trend to improvement of cardiopulmonary performance and LV ejection fraction, both of which did not reach statistical significance, however. It may be concluded that ivabradine successfully reduced the resting HR of heart transplant recipients with sinus tachycardia without negatively influencing the blood pressure. The definitive impact of ivabradine on LV mass regression and cardiopulmonary performance require further prospective, randomized and controlled trials. PMID:18648727

Zhang, R; Haverich, A; Strüber, M; Simon, A; Pichlmaier, M; Bara, Christoph

2008-11-01

163

Terminal Warm Blood Cardioplegia Improves Cardiac Function Through Microtubule Repolymerization  

Microsoft Academic Search

Background. To elucidate the mechanisms responsible for the beneficial effects of terminal warm blood cardioplegia, we studied dynamic change in microtubules induced by cold cardioplegia followed by rewarming. Further, we investigated the relationship between cardiac function and morphologic changes in microtubules caused by hyperkalemic, hypocalcemic warm cardioplegia during initial reperfusion.Methods. In protocol 1 isolated rat hearts were perfused at 37°C

Hironori Tenpaku; Koji Onoda; Kyoko Imanaka-Yoshida; Toshimichi Yoshida; Takatsugu Shimono; Hideto Shimpo; Isao Yada

1998-01-01

164

Insulin Infusion Improves Neutrophil Function in Diabetic Cardiac Surgery Patients  

Microsoft Academic Search

Diabetic patients are at increased risk of wound infec- tion after major surgery, but the effect of perioperative glucose control on postoperative wound infection rates after surgery is uncertain. We tested the effect of an in- sulin infusion on perioperative neutrophil function in diabetic patients scheduled for coronary artery bypass surgery. Participants (n 5 26) were randomly allocated to receive

Athos J. Rassias; Charles A. S. Marrin; Janice Arruda; Patricia Kate Whalen; Michael Beach; Mark P. Yeager

1999-01-01

165

Improved estimation of discrete probability density functions using multirate models  

Microsoft Academic Search

For many decades, the problem of estimating a pdf based on measurements has been of interest to many researchers. Even though much work has been done in the area of pdf estimation, most of it was focused on the continuous case. In this paper, we propose a new model based approach for estimating a discrete probability density function. This approach

Byung-Jun Yoon; P. P. Vaidyanathan

2003-01-01

166

Improving Joint Function Using Photochemical Hydrogels for Articular Surface Repair.  

National Technical Information Service (NTIS)

The goal of our research is to introduce a novel means to regenerate the articular cartilage and restore normal function of the joint. A strategy that can generate durable hyaline articular cartilage, which will be predominantly type II collagen, and is c...

T. J. Gill

2013-01-01

167

Improved Likelihood Function in Particle-based IR Eye Tracking  

Microsoft Academic Search

In this paper we propose a log likelihood-ratio function of foreground and background models used in a particle filter to track the eye region in dark-bright pupil image sequences. This model fuses information from both dark and bright pupil images and their difference image into one model. Our enhanced tracker overcomes the issues of prior selection of static thresholds during

Dan Witzner Hansen; R. Satria; J. Sorensen; R. Hammoud

2005-01-01

168

Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function  

Microsoft Academic Search

Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers

K. SantaCruz; J. Lewis; T. Spires; J. Paulson; L. Kotilinek; M. Ingelsson; A. Guimaraes; M. DeTure; M. Ramsden; E. McGowan; C. Forster; M. Yue; J. Orne; C. Janus; A. Mariash; M. Kuskowski; B. Hyman; M. Hutton; K. H. Ashe

2005-01-01

169

Improved response functions for gamma-ray skyshine analyses  

NASA Astrophysics Data System (ADS)

A computationally simple method, based on line-beam response functions, is refined for estimating gamma skyshine dose rates. Critical to this method is the availability of an accurate approximation for the line-beam response function (LBRF). In this study, the LBRF is evaluated accurately with the point-kernel technique using recent photon interaction data. Various approximations to the LBRF are considered, and a three parameter formula is selected as the most practical approximation. By fitting the approximating formula to point-kernel results, a set of parameters is obtained that allows the LBRF to be quickly and accurately evaluated for energies between 0.01 and 15 MeV, for source-to-detector distances from 1 to 3000 m, and for beam angles from 0 to 180 degrees. This re-evaluation of the approximate LBRF gives better accuracy, especially at low energies, over a greater source-to-detector range than do previous LBRF approximations. A conical beam response function is also introduced for application to skyshine sources that are azimuthally symmetric about a vertical axis. The new response functions are then applied to three simple skyshine geometries (an open silo geometry, an infinite wall, and a rectangular four-wall building) and the results are compared to previous calculations and benchmark data.

Shultis, J. K.; Faw, R. E.; Deng, X.

1992-09-01

170

Cellular entry via an actin and clathrin-dependent route is required for Lv2 restriction of HIV-2  

SciTech Connect

Lv2 is a human factor that restricts infection of some HIV-2 viruses after entry into particular target cells. HIV-2 MCR is highly susceptible to Lv2 whereas HIV-2 MCN is not. The block is after reverse transcription but prior to nuclear entry. The viral determinants for this restriction have been mapped to the HIV-2 envelope and the capsid genes. Our model of Lv2 restriction suggests that the route taken into a cell is important in determining whether a productive infection occurs. Here we characterised the infectious routes used by MCN and MCR using chemical compounds and molecular techniques to distinguish between potential pathways. Our results suggest that susceptible MCR can enter restrictive HeLa{sup CD4} cells via two pathways; a clathrin/AP2 mediated endocytic route that is sensitive to Lv2 restriction and an alternative, non-clathrin mediated route, which results in more efficient infection.

Harrison, I.P., E-mail: ian.harrison@medsch.ucl.ac.uk [Queen Mary, University of London, Whitechapel, London (United Kingdom); School of Medicine and Dentistry, Centre for Immunology and Infectious Disease, Blizard Institute for Cell and Molecular Science, 4 Newark Street, Whitechapel, London E1 2AT (United Kingdom); McKnight, A., E-mail: a.mcknight@qmul.ac.uk [Queen Mary, University of London, Whitechapel, London (United Kingdom)

2011-06-20

171

Pressure overload-dependent membrane type 1-matrix metalloproteinase induction: relationship to LV remodeling and fibrosis  

PubMed Central

Increased myocardial extracellular matrix collagen represents an important structural milestone during the development of left ventricular (LV) pressure overload (PO); however, the proteolytic pathways that contribute to this process are not fully understood. This study tested the hypothesis that membrane type 1-matrix metalloproteinase (MT1-MMP) is directly induced at the transcriptional level in vivo during PO and is related to changes in LV collagen content. PO was induced in vivo by transverse aortic constriction in transgenic mice containing the full length human MT1-MMP promoter region ligated to luciferase (MT1-MMP Prom mice). MT1-MMP promoter activation (luciferase expression), expression, and activity; collagen volume fraction (CVF); and left atrial dimension were measured at 1 (n = 8), 2 (n = 12), and 4 (n = 17) wk following PO. Non-PO mice (n = 10) served as controls. Luciferase expression increased by fivefold at 1 wk, fell at 2 wk, and increased again by ninefold at 4 wk of PO (P < 0.05). MT1-MMP expression and activity increased at 1 wk, fell at 2 wk, and increased again at 4 wk after PO. CVF increased at 1 wk, remained unchanged at 2 wk, and increased by threefold at 4 wk of PO (P < 0.05). There was a strong positive correlation between CVF and MT1-MMP activity (r = 0.80, P < 0.05). Left atrial dimension remained unchanged at 1 and 2 wk but increased by 25% at 4 wk of PO. When a mechanical load was applied in vitro to LV papillary muscles isolated from MT1-MMP Prom mice, increased load caused MT1-MMP promoter activation to increase by twofold and MT1-MMP expression to increase by fivefold (P < 0.05). These findings challenge the canonical belief that PO suppresses overall matrix proteolytic activity, but rather supports the concept that certain proteases, such as MT1-MMP, play a pivotal role in PO-induced matrix remodeling and fibrosis.

Baicu, Catalin F.; Stroud, Robert E.; Van Laer, An; Arroyo, Jazmine; Mukherjee, Rupak; Jones, Jeffrey A.; Spinale, Francis G.

2012-01-01

172

Specific identification of Lachesis muta muta snake venom using antibodies against the plasminogen activator enzyme, LV-PA  

Microsoft Academic Search

Sandwich-type Enzyme linked immunosorbent assays (ELISA) were developed to detect Lachesis muta muta (bushmaster) snake venom using antibodies against the plasminogen activator enzyme (LV-PA). Antibodies to LV-PA were obtained by immunization of one rabbit with the purified enzyme. The IgG fraction was purified from rabbit blood in a single step on a column of Sepharose-L. m. muta venom and used

Liza F. Felicori; Carlos Chávez-Olórtegui; Eladio F. Sánchez

2005-01-01

173

Nanoparticle Surface Functionalization for Improved Dispersion in Network Composites  

NASA Astrophysics Data System (ADS)

Incorporation of inorganic nanoparticles into crosslinked networks has resulted in greater toughening behavior with lower filler content compared to traditional composites. The characteristics that provide these desirable qualities are also responsible for their poor dispersion and, consequently, limiting wide commercial use. This work aims to demonstrate how excellent dispersion can be obtained easily and efficiently in different networks through nanoparticle surface modification. Both epoxy/Jeffamine and thiol-ene based networks were examined with differing molecular weight and chemical functionality tethers. The aggregation behavior of nanocomposite samples were monitored optically and using TEM. Thermomechanical properties were studied using DSC, DMA and MTS. The Tg was dependent on both nanoparticle incorporation and functionality. Toughening was observed in some, but not all, cases.

Richardson, Adam; McNair, Olivia; Strange, Gregory; Early, Mark; Savin, Daniel

2011-03-01

174

Improved measurement of camera response function and its performance evaluation.  

PubMed

Estimation of camera response function (CRF) has become important in the field of computer graphics and radiance measurement to achieve accurate modeling and high dynamic range imaging. A method is proposed to provide accurate radiance for direct measurement of the CRF in this paper by using a polariscope. The experimental results indicate that the accuracy of the estimated CRF obtained by the new approach is about 5% better than that of the previous method. PMID:24513993

Chang, Shih-Hsin; Wu, Hsien-Huang P

2014-01-01

175

Improved synthesis of DCDHF fluorophores with maleimide functional groups  

PubMed Central

A group of dicyanodihydrofuran (DCDHF) fluorophores with thiol-reactive maleimide functionality has been synthesized. One of the methods involves aromatic nucleophilic substitution reaction between an arylfluoride containing DCDHF and an amine containing protected maleimide. An alternative and generally useful method involves combination of the Mitsunobu reaction of a DCDHF-OH with a furan or 2-methylfuran protected maleimide and then subsequent retro Diels–Alder reaction.

Lu, Zhikuan; Weber, Ryan; Twieg, Robert J.

2008-01-01

176

Does obesity surgery improve psychosocial functioning? A systematic review  

Microsoft Academic Search

OBJECTIVE: The objective of this study is to present a review of the psychosocial outcome of bariatric surgery with special consideration of psychiatric comorbidity, psychopathology, psychosocial functioning, econometric data, and general quality of life (QoL).PURPOSE: A review of all (non-) controlled trials of the last two decades both with a retrospective and prospective design and a follow-up period of at

S Herpertz; R Kielmann; A M Wolf; M Langkafel; W Senf; J Hebebrand; S Herpertz

2003-01-01

177

Novel MRI-derived quantitative biomarker for cardiac function applied to classifying ischemic cardiomyopathy within a Bayesian rule learning framework  

NASA Astrophysics Data System (ADS)

Characterization of regional left ventricular (LV) function may have application in prognosticating timely response and informing choice therapy in patients with ischemic cardiomyopathy. The purpose of this study is to characterize LV function through a systematic analysis of 4D (3D + time) endocardial motion over the cardiac cycle in an effort to define objective, clinically useful metrics of pathological remodeling and declining cardiac performance, using standard cardiac MRI data for two distinct patient cohorts accessed from CardiacAtlas.org: a) MESA - a cohort of asymptomatic patients; and b) DETERMINE - a cohort of symptomatic patients with a history of ischemic heart disease (IHD) or myocardial infarction. The LV endocardium was segmented and a signed phase-to-phase Hausdorff distance (HD) was computed at 3D uniformly spaced points tracked on segmented endocardial surface contours, over the cardiac cycle. An LV-averaged index of phase-to-phase endocardial displacement (P2PD) time-histories was computed at each tracked point, using the HD computed between consecutive cardiac phases. Average and standard deviation in P2PD over the cardiac cycle was used to prepare characteristic curves for the asymptomatic and IHD cohort. A novel biomarker of RMS error between mean patient-specific characteristic P2PD over the cardiac cycle for each individual patient and the cumulative P2PD characteristic of a cohort of asymptomatic patients was established as the RMS-P2PD marker. The novel RMS-P2PD marker was tested as a cardiac function based feature for automatic patient classification using a Bayesian Rule Learning (BRL) framework. The RMS-P2PD biomarker indices were significantly different for the symptomatic patient and asymptomatic control cohorts (p<0.001). BRL accurately classified 83.8% of patients correctly from the patient and control populations, with leave-one-out cross validation, using standard indices of LV ejection fraction (LV-EF) and LV end-systolic volume index (LV-ESVI). This improved to 91.9% with inclusion of the RMS-P2PD biomarker and was congruent with improvements in both sensitivity for classifying patients and specificity for identifying asymptomatic controls from 82.6% up to 95.7%. RMS-P2PD, when contrasted against a collective normal reference, is a promising biomarker to investigate further in its utility for identifying quantitative signs of pathological endocardial function which may boost standard image makers as precursors of declining cardiac performance.

Menon, Prahlad G.; Morris, Lailonny; Staines, Mara; Lima, Joao; Lee, Daniel C.; Gopalakrishnan, Vanathi

2014-03-01

178

Dual-functionalized mesoporous TiO2 hollow nanospheres for improved CO2 separation membranes.  

PubMed

Simultaneous improvement in CO2 permeability and CO2/N2 selectivity was obtained from mixed matrix membranes (MMMs) containing dual-functionalized mesoporous TiO2 hollow nanospheres (f-MTHS). Dual functionality resulted in the increased CO2 affinity and improved interfacial properties between inorganic nanofillers and the polymer matrix. PMID:24733026

Roh, Dong Kyu; Kim, Sang Jin; Chi, Won Seok; Kim, Jin Kyu; Kim, Jong Hak

2014-06-01

179

Course of functional improvement after stroke, spinal cord injury, and traumatic brain injury  

Microsoft Academic Search

Bode RK, Heinemann AW. Course of functional improvement after stroke, spinal cord injury, and traumatic brain injury. Arch Phys Med Rehabil 2002;83:100-6. Objective: To examine functional improvement patterns of persons with stroke, traumatic brain injury (TBI), and spinal cord injury (SCI). Design: Statistical analysis of data from a multisite study evaluating rehabilitation outcomes. Setting: Eight inpatient rehabilitation facilities. Participants: A

Rita K. Bode; Allen W. Heinemann

2002-01-01

180

Functional lipids and lipoplexes for improved gene delivery  

PubMed Central

Cationic lipids are the most common non-viral vectors used in gene delivery with a few currently being investigated in clinical trials. However, like most other synthetic vectors, these vectors suffer from low transfection efficiencies. Among the various approaches to address this challenge, functional lipids (i.e., lipids responding to a stimuli) offer a myriad of opportunities for basic studies of nucleic acid–lipid interactions and for in vitro and in vivo delivery of nucleic acid for a specific biological/medical application. This manuscript reviews recent advances in pH, redox, and charge-reversal sensitive lipids.

Zhang, Xiao-Xiang; McIntosh, Thomas J.; Grinstaff, Mark W.

2013-01-01

181

Curcumin improves early functional results after experimental spinal cord injury  

Microsoft Academic Search

Background  Curcumin is a polyphenol extracted from the rhizome of Curcuma longa and well known as a multifunctional drug with anti-oxidative, anticancerous, and anti-inflammatory activities. The aim of\\u000a the study was to evaluate and compare the effects of the use of the curcumin and the methylprednisolone sodium succinate (MPSS)\\u000a functionally, biochemically, and pathologically after experimental spinal cord injury (SCI).\\u000a \\u000a \\u000a \\u000a \\u000a Method  Forty rats

Berker Cemil; Kivanc Topuz; Mehmet Nusret Demircan; Gokhan Kurt; Kagan Tun; Murat Kutlay; Osman Ipcioglu; Zafer Kucukodaci

2010-01-01

182

Hibiscus sabdariffa extract lowers blood pressure and improves endothelial function.  

PubMed

Polyphenols from Hibiscus sabdariffa calices were administered to patients with metabolic syndrome (125 mg/kg/day for 4 wk, n = 31) and spontaneously hypertensive rats (125 or 60 mg/kg in a single dose or daily for 1 wk, n = 8 for each experimental group). The H. sabdariffa extract improved metabolism, displayed potent anti-inflammatory and antioxidant activities, and significantly reduced blood pressure in both humans and rats. Diuresis and inhibition of the angiotensin I-converting enzyme were found to be less important mechanisms than those related to the antioxidant, anti-inflammatory, and endothelium-dependent effects to explain the beneficial actions. Notably, polyphenols induced a favorable endothelial response that should be considered in the management of metabolic cardiovascular risks. PMID:24668839

Joven, Jorge; March, Isabel; Espinel, Eugenia; Fernández-Arroyo, Salvador; Rodríguez-Gallego, Esther; Aragonès, Gerard; Beltrán-Debón, Raúl; Alonso-Villaverde, Carlos; Rios, Lidia; Martin-Paredero, Vicente; Menendez, Javier A; Micol, Vicente; Segura-Carretero, Antonio; Camps, Jordi

2014-06-01

183

Improving Kepler Pipeline Sensitivity with Pixel Response Function Photometry.  

NASA Astrophysics Data System (ADS)

We present the results of our investigation into the feasibility and expected benefits of implementing PRF-fitting photometry in the Kepler Science Processing Pipeline. The Kepler Pixel Response Function (PRF) describes the expected system response to a point source at infinity and includes the effects of the optical point spread function, the CCD detector responsivity function, and spacecraft pointing jitter. Planet detection in the Kepler pipeline is currently based on simple aperture photometry (SAP), which is most effective when applied to uncrowded bright stars. Its effectiveness diminishes rapidly as target brightness decreases relative to the effects of noise sources such as detector electronics, background stars, and image motion. In contrast, PRF photometry is based on fitting an explicit model of image formation to the data and naturally accounts for image motion and contributions of background stars. The key to obtaining high-quality photometry from PRF fitting is a high-quality model of the system's PRF, while the key to efficiently processing the large number of Kepler targets is an accurate catalog and accurate mapping of celestial coordinates onto the focal plane. If the CCD coordinates of stellar centroids are known a priori then the problem of PRF fitting becomes linear. A model of the Kepler PRF was constructed at the time of spacecraft commissioning by fitting piecewise polynomial surfaces to data from dithered full frame images. While this model accurately captured the initial state of the system, the PRF has evolved dynamically since then and has been seen to deviate significantly from the initial (static) model. We construct a dynamic PRF model which is then used to recover photometry for all targets of interest. Both simulation tests and results from Kepler flight data demonstrate the effectiveness of our approach. Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA’s Science Mission Directorate.Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA’s Science Mission Directorate.

Morris, Robert L.; Bryson, Steve; Jenkins, Jon Michael; Smith, Jeffrey C

2014-06-01

184

Midwall Mechanics Are Improved After Regression of Hypertensive Left Ventricular Hypertrophy and Normalization of Chamber Geometry  

Microsoft Academic Search

Background—It is still unclear whether substantial regression of hypertensive left ventricular hypertrophy (LVH) and normalization of chamber geometry are associated with improved left ventricular (LV) myocardial function. Methods and Results—Midwall mechanics were evaluated in 152 patients undergoing 1 year of effective antihypertensive treatment. Two-dimensionally directed M-mode echocardiography was performed as follows: (1) after a 4-week placebo \\

Stefano Perlini; Maria Lorenza Muiesan; Cesare Cuspidi; Lorena Sampieri; Bruno Trimarco; Gerard P. Aurigemma; Enrico Agabiti-Rosei; Giuseppe Mancia

185

Functionally gradient hard carbon composites for improved adhesion and wear  

NASA Astrophysics Data System (ADS)

A new approach is proposed for fabricating biomedical devices that last longer and are more biocompatible than those presently available. In this approach, a bulk material is chosen that has desirable mechanical properties (low modulus, high strength, high ductility and high fatigue strength). This material is coated with corrosion-resistant, wear-resistant, hard, and biocompatible hard carbon films. One of the many forms of carbon, tetrahedral amorphous carbon, consists mainly of sp3-bonded atoms. Tetrahedral amorphous carbon possesses properties close to diamond in terms of hardness, atomic smoothness, and inertness. Tetrahedral amorphous carbon and diamond films usually contain large amounts of compressive and sometimes tensile stresses; adhesive failure from these stresses has limited widespread use of these materials. This research involves processing, characterization and modeling of functionally gradient tetrahedral amorphous carbon and diamond composite films on metals (cobalt-chromium and titanium alloys) and polymers (polymethylmethacrylate and polyethylene) used in biomedical applications. Multilayer discontinuous thin films of titanium carbide, titanium nitride, aluminum nitride, and tungsten carbide have been developed to control stresses and graphitization in diamond films. A morphology of randomly interconnected micron sized diamond crystallites provides increased toughness and stress reduction. Internal stresses in tetrahedral amorphous carbon were reduced via incorporation of carbide forming elements (silicon and titanium) and noncarbide forming elements (copper, platinum, and silver). These materials were produced using a novel target design during pulsed laser deposition. These alloying atoms reduce hardness and sp3-bonded carbon content, but increase adhesion and wear resistance. Silver and platinum provide the films with antimicrobial properties, and silicon provides bioactivity and aids bone formation. Bilayer coatings were created that couple the adherence, biocompatibility, erosion resistance, and long term release of functional elements from hard carbon coatings with bioactive properties of nanocrystalline hydroxyapatite and short term drug release properties of resorbable poly (D,L) lactide-based materials. Finally, these hard carbon coatings have a variety of non-medical applications, including use in microelectronics packaging, sensors, flat panel displays, photodiodes, cutting tools, optical switches, and wear-resistant magnetic disks.

Narayan, Roger Jagdish

186

Prospects for improving brain function in individuals with Down syndrome.  

PubMed

Down syndrome (DS), which results from an extra copy of chromosome 21 (trisomy 21), is the most common genetically defined cause of intellectual disability. Although no pharmacotherapy aimed at counteracting the cognitive and adaptive deficits associated with this genetic disorder has been approved at present, there have been several new promising studies on pharmacological agents capable of rescuing learning/memory deficits seen in mouse models of DS. Here, we will review the available mouse models for DS and provide a comprehensive, albeit not exhaustive review of the following preclinical research strategies: (1) SOD1 and antioxidant agents; (2) APP and ?-secretase inhibitors; (3) DYRK1A and the polyphenol epigallocatechin gallate (EGCG); (4) GIRK2 and fluoxetine; (5) adrenergic receptor agonists; (6) modulation of GABAA and GABAB receptors; (7) agonism of the hedgehog signaling pathway; (8) nerve growth factor (NGF) and other neurotrophic factors; (9) anticholinesterase (AChE) agents; and (10) antagonism of NMDA receptors. Finally, we will review briefly five different strategies in DS that have led to clinical studies that either have been concluded or are currently underway: (1) antioxidant therapy; (2) AChE therapy; (3) green tea extract therapy; (4) RG1662 therapy; and (5) memantine therapy. These are exciting times in DS research. Within a decade or so, it is well into the realm of possibility that new forms of pharmacotherapies might become valuable tools in the armamentarium of developmental clinicians, as adjutants to more traditional and proven forms of habilitative interventions aimed at improving the quality of life of individuals with DS. PMID:23821040

Costa, Alberto C S; Scott-McKean, Jonah J

2013-09-01

187

Silymarin improves vascular function of aged ovariectomized rats.  

PubMed

Both aging and estrogen depletion lead to endothelial dysfunction, which is the main reason of many cardiovascular diseases. Previous reports have shown that cell protective effect of silymarin (SM) depends on its antioxidant and phytoestrogenic properties. We investigated the effect of SM on vascular stiffness of aged menopausal rats and the involvement of estrogenic activity in this effect. Isolated rat aortas were obtained from 22-month-old rats, after 18?months of ovariectomy (OVX) follow-up. Each ring was incubated in tissue bath either with SM (50?mg/L) and 17?-estradiol (10??M, E2) or in the presence of SM/fulvestrant (50?mg/L, 10 ?M). Endothelium-intact rings were precontracted with phenylephrine (0.001-30??M) or high potassium (40?mM); endothelium-dependent/independent relaxant responses were obtained using acetylcholine (0.001-30??M) and sodium nitroprusside (0.0001-3??M), respectively. While phenylephrine sensitivity was significantly increased in OVX rats, relaxations were significantly less in aged OVX rats compared with young rats. In spite of the presence of estrogen antagonist, immediate SM treatment restored the endothelial function and vascular tone better than estrogen replacement. Additionally, as a complementary and alternative medicine, it does not cause estrogenic side effects when taken acutely. Copyright © 2013 John Wiley & Sons, Ltd. PMID:24123505

Demirci, Buket; Dost, Turhan; Gokalp, Filiz; Birincioglu, Mustafa

2014-06-01

188

Seismic Station Functionality Improvements of Seismic Network of Slovenia  

NASA Astrophysics Data System (ADS)

The Environmental Agency of the Republic of Slovenia, the Office of Seismology and Geology is responsible for the fast and reliable information about earthquakes, originating in the area of Slovenia and nearby. The Seismic Network of Slovenia, which covers the entire Slovenian territory, involving an area of 20,256 km2, consists of 26 seismic stations equipped with broadband seismometers (CMG-40T, CMG-3ESPC, CMG-3T and STS2) and Quanterra Q730 data loggers. The seismic data is transmitted in real-time to the Data Center in Ljubljana (DCL). Leased lines, xDSL and satellite communication are used for data transfer from stations to DCL. When an event occurs main earthquake parameters (magnitude and the location of the epicenter) can be evaluated at sufficient accuracy only if data from several seismic stations is available. In case of temporary communication failure loss of important seismic data can occur. The duration of communication failure, which exceeds 2 hours can cause data loss. This is due to low memory storage of Quanterra Q730 acquisition unit. In this paper our solution for extending storage capabilities of particular seismic station to several months is presented (momentarily the storage capabilities of particular seismic station lies between 1 and 2 hours). To extend storage capabilities we used a special Industrial Computer (JetBox 8100), which runs on Linux. To collect seismic data from the Q730 unit the acquisition software SeiComP is used. The combination of Q730 and JetBox 8100 assures that in case of temporary communication failure there will be no data loss. Seismic data is simply retrieved from JetBox 8100 (from ring buffer that is generated by SeiComP acquisition software) after communication is once again established. Moreover, an advanced state of health system was build and installed on JetBox 8100, that makes identifying, predicting and solving of different problems quick and effective. With combining Q730 data logger and JetBox 8100 we did not only significantly improved the local storage capabilities but also made the whole seismic system more flexible and reliable.

Sincic, Peter; Tasic, Izidor; Mali, Marko; Pancur, Luka; Vidrih, Renato

2010-05-01

189

Functional improvement and correlations with symptomatic improvement in adults with attention deficit hyperactivity disorder receiving long-acting methylphenidate  

PubMed Central

Background Data on the relationship between core symptoms and daily functioning in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily functioning was assessed as part of an open-label extension, and associations with symptom scores were evaluated. Method After a 5-week double-blind study with adults with ADHD receiving osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were eligible for a 7-week open-label extension in which all patients received OROS MPH. Data for the Conners' Adult ADHD Rating Scale – Observer: Screening Version (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary endpoints included the observer self-reported short version of the CAARS (CAARS-S:S) and the Clinical Global Impressions – Severity Scale (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in subgroups. Relationships between symptom and functional outcomes were evaluated in a multivariate regression analysis. Results A total of 370 patients entered the open-label extension. Significant improvements from baseline in CAARS-O:SV were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co-morbidity. Significant improvements from double-blind baseline were also seen for the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV Hyperactivity/Impulsivity subscale were associated with improvements in SDS total and subscale scores, and in the Q-LES-Q score at open-label endpoint. Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not significantly associated with functional changes. Conclusions Improvements in ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS MPH are associated with improvements in daily functioning and quality of life.

Buitelaar, J. K.; Casas, M.; Philipsen, A.; Kooij, J. J. S.; Ramos-Quiroga, J. A.; Dejonckheere, J.; van Oene, J. C.; Schauble, B.

2012-01-01

190

An improved method for extracting matrix elements from lattice three-point functions  

SciTech Connect

The extraction of matrix elements from baryon three-point functions is complicated by the fact that the signal-to-noise drops rapidly as a function of time. Using a previously discussed method to improve the signal-to-noise for lattice two-point functions, we use this technique to do so for lattice three-point functions, using electromagnetic form factors for the nucleon and Delta as an example.

C. Aubin, K. Orginos

2011-12-01

191

Improvements in Physical Activity and Functioning After Undergoing Midurethral Sling Procedure for Urinary Incontinence  

PubMed Central

Objectives To estimate the effect of midurethral sling on improving leisure physical activity levels and physical functioning in women with stress urinary incontinence (SUI). Our secondary objective was to identify possible risk factors for postoperative insufficient physical activity. Methods We conducted a prospective, observational study of women undergoing outpatient midurethral sling for SUI. Women completed validated questionnaires for incontinence, leisure physical activity, and physical functioning at baseline and 6 months postoperative. The primary outcome was leisure physical activity level. We used multiple logistic and linear regression to estimate the effect of improvements in urinary symptoms and life effect on physical activity levels and physical functioning scores. Results Ninety women underwent surgery and 85 returned for follow-up. At baseline, 38% had sedentary, 18% had moderate, and 44% had sufficient leisure physical activity levels. Postoperatively, this modestly improved to 26% sedentary, 20% moderate, and 54% sufficient levels. The median leisure physical activity energy expenditure increased from 396 to 693 metabolic equivalent-minutes/week (P=.04). Physical functioning scores also significantly improved (mean score 44 vs 55 points, P<.001). On multiple logistic regression, improvements in incontinence life effect were associated with increased odds of leisure physical activity improvement (AOR 1.66; 95% CI 1.08–2.54). On multiple linear regression, improvements in both urinary incontinence severity and effect were associated with improvements in physical functioning scores (P<.01 for both). Factors associated with insufficient postoperative physical activity included low baseline physical activity levels, and smaller improvements in urinary effect scores. Conclusions Midurethral sling and subsequent improvements in urinary incontinence are associated with improved leisure physical activity levels and physical functioning.

Sung, Vivian W.; Kassis, Nadine; Raker, Christina A.

2012-01-01

192

Improved Displacement Transfer Functions for Structure Deformed Shape Predictions Using Discretely Distributed Surface Strains  

NASA Technical Reports Server (NTRS)

In the formulations of earlier Displacement Transfer Functions for structure shape predictions, the surface strain distributions, along a strain-sensing line, were represented with piecewise linear functions. To improve the shape-prediction accuracies, Improved Displacement Transfer Functions were formulated using piecewise nonlinear strain representations. Through discretization of an embedded beam (depth-wise cross section of a structure along a strain-sensing line) into multiple small domains, piecewise nonlinear functions were used to describe the surface strain distributions along the discretized embedded beam. Such piecewise approach enabled the piecewise integrations of the embedded beam curvature equations to yield slope and deflection equations in recursive forms. The resulting Improved Displacement Transfer Functions, written in summation forms, were expressed in terms of beam geometrical parameters and surface strains along the strain-sensing line. By feeding the surface strains into the Improved Displacement Transfer Functions, structural deflections could be calculated at multiple points for mapping out the overall structural deformed shapes for visual display. The shape-prediction accuracies of the Improved Displacement Transfer Functions were then examined in view of finite-element-calculated deflections using different tapered cantilever tubular beams. It was found that by using the piecewise nonlinear strain representations, the shape-prediction accuracies could be greatly improved, especially for highly-tapered cantilever tubular beams.

Ko, William L.; Fleischer, Van Tran

2012-01-01

193

Changes in rest and exercise myocardial perfusion and left ventricular function 3 to 26 weeks after clinically uncomplicated acute myocardial infarction: effects of exercise training  

SciTech Connect

The effects of exercise training on exercise myocardial perfusion and left ventricular (LV) function in the first 6 months after clinically uncomplicated acute myocardial infarction (AMI) were assessed in 53 consecutive men aged 55 +/- 9 years. Symptom-limited treadmill exercise with thallium myocardial perfusion scintigraphy and symptom-limited upright bicycle ergometry with equilibrium gated radionuclide ventriculography were performed 3, 11 and 26 weeks after AMI by 23 men randomized to training and 30 randomized to no training. Peak cycle capacity increased in both groups between 3 and 26 weeks (p less than 0.01), but reached higher levels in trained than in untrained patients (803 +/- 149 vs 648 +/- 182 kg-m/min, p less than 0.01). Reversible thallium perfusion defects were significantly more frequent at 3 than at 26 weeks: 59% and 36% of patients, respectively (p less than 0.05), without significant inter-group differences. Values of LV ejection fraction at rest, submaximal and peak exercise did not change significantly in either group. The increase in functional capacity, i.e., peak treadmill or bicycle workload, that occurred 3 to 26 weeks after infarction was significantly correlated with the increase in peak exercise heart rate (p less than 0.001), but not with changes in myocardial perfusion or LV function determined by radionuclide techniques. Changes in myocardial perfusion or LV function do not appear to account for the improvement in peak functional capacity that occurs within the first 6 months after clinically uncomplicated AMI.

Hung, J.; Gordon, E.P.; Houston, N.; Haskell, W.L.; Goris, M.L.; DeBusk, R.F.

1984-11-01

194

Levosimendan improves cardiac function and survival in rats with angiotensin II-induced hypertensive heart failure  

Microsoft Academic Search

Calcium-sensitizing agents improve cardiac function in acute heart failure; however, their long-term effects on cardiovascular mortality are unknown. We tested the hypothesis that levosimendan, an inodilator that acts through calcium sensitization, opening of ATP-dependent potassium channels and phosphodiesterase III inhibition, improves cardiac function and survival in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs), a model of angiotensin

Agnieszka Biala; Essi Martonen; Petri Kaheinen; Jouko Levijoki; Piet Finckenberg; Saara Merasto; Marjut Louhelainen; Dominik N Muller; Friedrich C Luft; Eero Mervaala

2010-01-01

195

Repeated thermal therapy improves impaired vascular endothelial function in patients with coronary risk factors  

Microsoft Academic Search

OBJECTIVESWe sought to determine whether sauna therapy, a thermal vasodilation therapy, improves endothelial function in patients with coronary risk factors such as hypercholesterolemia, hypertension, diabetes mellitus and smoking.BACKGROUNDExposure to heat is widely used as a traditional therapy in many different cultures. We have recently found that repeated sauna therapy improves endothelial and cardiac function in patients with chronic heart failure.METHODSTwenty-five

Masakazu Imamura; Sadatoshi Biro; Takashi Kihara; Shiro Yoshifuku; Kunitsugu Takasaki; Yutaka Otsuji; Shinichi Minagoe; Yoshifumi Toyama; Chuwa Tei

2001-01-01

196

EFFECT OF SEIZURE CONTROL ON IMPROVEMENT OF COGNITIVE FUNCTIONS IN EPILEPTIC PATIENTS  

PubMed Central

SUMMARY A group of fifty epileptic patients were tested with neuropsychological tools for cognitive functions like memory, intelligence, visuomotor coordination, spatial perception and body schema perception. Patients were on carbamazepine and were tested after three months. Seizure improvement was shown to have different effects on different cognitive functions. Memory and intellectual deficits improved, while no difference was observed in visuomotor coordination, spatial and personal perception.

Nainian, M.R.; Behere, P.B.; Mohanti, S.

1993-01-01

197

Evolutionary fuzzy system models with improved fuzzy functions and its application to industrial process  

Microsoft Academic Search

This paper presents a new evolutionary fuzzy system modeling strategy alternative to fuzzy rule bases, and does not entail if...then rule base structure. The new approach, which is based on improved fuzzy functions with genetic algorithms, is proposed to reduce complexity of earlier fuzzy system models and improve modeling accuracy. Structure identification of the new approach is based on a

Asli Çelikyilmaz; I. Burhan Türksen

2007-01-01

198

Chronic Treatment with Tadalafil Improves Endothelial Function in Men with Increased Cardiovascular Risk  

Microsoft Academic Search

Objective:Erectile dysfunction (ED) is often associated with a cluster of risk factors for coronary artery disease and reduced endothelial function. Acute and chronic administration of oral sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, improves endothelial function in patients with ED. Tadalafil (TAD) is a new PDE5 inhibitor with a long half life that allows alternate day administration. Aim of the

Giuseppe M. C. Rosano; Antonio Aversa; Cristiana Vitale; Andrea Fabbri; Massimo Fini; Giovanni Spera

2005-01-01

199

Pilot Study of Pioglitazone and Exercise Training Effects on Basal Myocardial Substrate Metabolism and Left Ventricular Function in HIV-Positive Individuals with Metabolic Complications  

PubMed Central

Background Individuals with HIV infection and peripheral metabolic complications have impaired basal myocardial insulin sensitivity that is related to left ventricular (LV) diastolic dysfunction. It is unknown whether interventions shown to be effective in improving peripheral insulin sensitivity can improve basal myocardial insulin sensitivity and diastolic function in people with HIV and peripheral metabolic complications. Objective In a pilot study, we evaluated whether the peroxisome proliferator–activated receptor-gamma (PPAR-?) agonist pioglitazone or combined endurance and resistance exercise training improves basal myocardial insulin sensitivity and diastolic function in HIV+ adults with peripheral metabolic complications. Design Twenty-four HIV+ adults with metabolic complications including peripheral insulin resistance were randomly assigned to 4 months of pioglitazone (PIO; 30 mg/d) or supervised, progressive endurance and resistance exercise training (EXS; 90–120 min/d, 3 d/wk). Basal myocardial substrate metabolism was quantified by radioisotope tracer methodology and positron emission tomography (PET) imaging, and LV function was measured by echocardiography. Results Twenty participants completed the study. Neither PIO nor EXS resulted in a detectable improvement in basal myocardial insulin sensitivity or diastolic function. Post hoc analyses revealed sample sizes of more than 100 participants are needed to detect significant effects of these interventions on basal myocardial insulin sensitivity and function. Conclusions PIO or EXS alone did not significantly increase basal myocardial insulin sensitivity or LV diastolic function in HIV+ individuals with peripheral metabolic complications.

Cade, W. Todd; Reeds, Dominic N.; Overton, E. Turner; Herrero, Pilar; Waggoner, Alan D.; Laciny, Erin; Bopp, Coco; Lassa-Claxton, Sherry; Gropler, Robert J.; Peterson, Linda R.; Yarasheski, Kevin E.

2014-01-01

200

Improvement of cardiac function by short-term enzyme replacement therapy in a murine model of cardiomyopathy associated with Hunter syndrome evaluated by serial echocardiography with speckle tracking 2-D strain analysis.  

PubMed

Cardiac systolic function is significantly decreased in a proportion of patients with Hunter syndrome. This study was performed to evaluate the change in myocardial function associated with enzyme replacement therapy (ERT) in a mouse model of cardiomyopathy associated with Hunter syndrome. Thirty 9-week-old iduronate-2-sulfatase (IDS) knockout mice received either intravenous injection of human recombinant IDS (ERT group, N=15) or saline (control group, N=15) for 5weeks. Echocardiography was performed at baseline and after treatment. Echocardiographic parameters of left ventricular (LV) systolic function and 2-dimensional radial and circumferential strain were assessed. At follow-up, there was a significant increase in LV fractional shortening and radial and circumferential strain in the ERT group only. Notable myocardial fibrosis was observed in the control group only. In the murine model of Hunter syndrome, ERT exerts beneficial effects on cardiac function, which can be evaluated by serial echocardiographic evaluation including 2-dimensional strain analysis. PMID:24836711

Lee, Sang-Chol; Lee, Jieun; Jin, Dong-Kyu; Kim, Jung-Sun; Jeon, Eun-Seok; Kwun, Young Hee; Chang, Mi Sun; Ko, Ah-Ra; Yook, Yeon Joo; Sohn, Young Bae

2014-07-01

201

Comparison of gated single-photon emission computed tomography with magnetic resonance imaging for evaluation of left ventricular function in ischemic cardiomyopathy  

Microsoft Academic Search

To perform a head-to-head comparison between magnetic resonance imaging (MRI) and gated single-photon emission computed tomography (SPECT) for the evaluation of left ventricular (LV) function (LV ejection fraction [LVEF], LV volumes, and regional wall motion) in patients with ischemic cardiomyopathy, we studied 22 patients with chronic coronary artery disease and LV dysfunction. Multislice, multiphase echoplanar MRI was performed with Philips

Jeroen J Bax; Hildo Lamb; Petra Dibbets; Harold Pelikan; Eric Boersma; Eric P Viergever; Guido Germano; Hubert W Vliegen; Albert de Roos; Ernest K. J Pauwels; Ernst E Van der Wall

2000-01-01

202

Weight loss improves endothelial function independently of ADMA reduction in severe obesity.  

PubMed

This prospective study was performed in order to establish whether improvement of endothelial function after weight reduction can be explained by a decrease of elevated asymmetric dimethyl arginine (ADMA), an inhibitor of endogenous NO-synthase (eNOS). Therefore, 21 obese subjects (BMI: 41.1±6.4?kg/m(2)) were studied at baseline and after 12 weeks of weight reduction with a very low calorie diet. Biochemical and clinical parameters of endothelial function were assessed before and after weight loss. Biochemical parameters were determined by measurement of ADMA and soluble intercellular adhesion molecule (sICAM). Clinical parameters were assessed by pulse wave analysis (PWA). Weight intervention resulted in a 21.4±6.8 kg reduction of body weight from 119.7±12.8 kg at study start to 98.3±11.6 kg at study end (p<0.001). Accordingly, biochemical markers improved under weight reduction (ADMA from 0.47±0.07 mmol/l to 0.42±0.08 mmol/l; p=0.002; ICAM from 276±42 ng/ml to 236±29 ng/ml; p<0.001). Further, clinical parameters of functional endothelial function improved with an increase of deltaRI after salbutamol inhalation from -1% before to -9% after weight reduction (p=0.02). Interestingly, improvement of endothelial function correlated with improved HOMA index only (r=-0.60, p=0.04) but not with reduced ADMA levels, improved hypertension or reduced body weight. In conclusion, weight reduction with a very low calorie diet improves endothelial function measured by pulse wave velocity. The missing correlation with ADMA suggests possible further mechanisms underlying this observed effect, for example, improvement of insulin resistance. PMID:21365529

Rudofsky, G; Roeder, E; Merle, T; Hildebrand, M; Nawroth, P P; Wolfrum, C

2011-05-01

203

Developing models of how cognitive improvements change functioning: Mediation, moderation and moderated mediation  

PubMed Central

Background Cognitive remediation (CRT) affects functioning but the extent and type of cognitive improvements necessary are unknown. Aim To develop and test models of how cognitive improvement transfers to work behaviour using the data from a current service. Method Participants (N49) with a support worker and a paid or voluntary job were offered CRT in a Phase 2 single group design with three assessments: baseline, post therapy and follow-up. Working memory, cognitive flexibility, planning and work outcomes were assessed. Results Three models were tested (mediation — cognitive improvements drive functioning improvement; moderation — post treatment cognitive level affects the impact of CRT on functioning; moderated mediation — cognition drives functioning improvements only after a certain level is achieved). There was evidence of mediation (planning improvement associated with improved work quality). There was no evidence that cognitive flexibility (total Wisconsin Card Sorting Test errors) and working memory (Wechsler Adult Intelligence Scale III digit span) mediated work functioning despite significant effects. There was some evidence of moderated mediation for planning improvement if participants had poorer memory and/or made fewer WCST errors. The total CRT effect on work quality was d = 0.55, but the indirect (planning-mediated CRT effect) was d = 0.082 Conclusion Planning improvements led to better work quality but only accounted for a small proportion of the total effect on work outcome. Other specific and non-specific effects of CRT and the work programme are likely to account for some of the remaining effect. This is the first time complex models have been tested and future Phase 3 studies need to further test mediation and moderated mediation models.

Wykes, Til; Reeder, Clare; Huddy, Vyv; Taylor, Rumina; Wood, Helen; Ghirasim, Natalia; Kontis, Dimitrios; Landau, Sabine

2012-01-01

204

Do stimulants improve functioning in adults with ADHD? A review of the literature.  

PubMed

ADHD is prevalent in adulthood and stimulant pharmacotherapy is the primary treatment for uncomplicated presentations. ADHD is associated with significant functional impairment in major life roles. Measurement of the efficacy of stimulant treatment for adult ADHD therefore should include assessment of improvement in role function. A literature search was conducted to identify studies that measured change in function with stimulant treatment in adult ADHD using measures other than global clinical impression or global assessment of function ratings. Five studies were identified that met our search criteria. Evidence of functional improvement with stimulant treatment was found with the following validated self-report measures of functional wellbeing employed across these studies: the Medical Outcome Study 36-item Short Form Health Survey; ADHD Impact Module for Adults; Quality of Life Enjoyment and Satisfaction scale-Short Form; Sheehan Disability Scale, and Social Adjustment Scale-Self-Report. We conclude that investigations using self-report scales provide evidence that stimulant treatment translates into measurable improvement in daily function for adults with ADHD. Further investigation could better characterize the mediators and moderators of individual improvement, an important step towards the personalization of treatment for ADHD in adulthood. PMID:23391411

Surman, Craig B H; Hammerness, Paul G; Pion, Katie; Faraone, Stephen V

2013-06-01

205

Relationship between left ventricular diastolic function and atrial natriuretic factor in never-treated mild hypertensives.  

PubMed

Using digitized M-mode echocardiograms, we evaluated the relationship between plasma atrial natriuretic factor (ANF) and morphofunctional characteristics of the left ventricle (LV) in 24 mild hypertensive men, never treated, with normal renal function. For each subject we collected a blood sample for plasma ANF evaluation and, immediately after, we recorded the LV echocardiogram. All the patients had normal LV diastolic diameter and systolic function; LV hypertrophy was present in 10 patients, 7 of whom had left atrial enlargement, and 13 patients had impaired LV diastolic function. ANF was similar between patients with and without LV hypertrophy, as well as between patients with and without left atrial enlargement, whereas ANF was significantly (P < .01) higher in patients with LV diastolic dysfunction than in patients with normal diastolic function. ANF was inversely correlated with both indices of diastolic function (peak lengthening rate and peak wall thinning rate), whereas it did not correlate with blood pressure, heart rate, end-systolic wall stress, and other LV parameters. In conclusion, from our results, ANF level in never-treated mild hypertensives is related neither to the degree of LV hypertrophy nor to the afterload, expressed as blood pressure or end-systolic wall stress, whereas it is mainly influenced by LV diastolic function: the diastolic impairment induces an increase in ANF level, probably through an increased atrial stretch. PMID:9270092

Grandi, A M; Zanzi, P; Ceriani, L; Gaudio, G; Bertolini, A; Giovanella, L; Guasti, L; Roncari, G; Venco, A

1997-08-01

206

Improving Balance Function Using Low Levels of Electrical Stimulation of the Balance Organs  

NASA Technical Reports Server (NTRS)

Crewmembers returning from long-duration space flight face significant challenges due to the microgravity-induced inappropriate adaptations in balance/ sensorimotor function. The Neuroscience Laboratory at JSC is developing a method based on stochastic resonance to enhance the brain s ability to detect signals from the balance organs of the inner ear and use them for rapid improvement in balance skill, especially when combined with balance training exercises. This method involves a stimulus delivery system that is wearable/portable providing imperceptible electrical stimulation to the balance organs of the human body. Stochastic resonance (SR) is a phenomenon whereby the response of a nonlinear system to a weak periodic input signal is optimized by the presence of a particular non-zero level of noise. This phenomenon of SR is based on the concept of maximizing the flow of information through a system by a non-zero level of noise. Application of imperceptible SR noise coupled with sensory input in humans has been shown to improve motor, cardiovascular, visual, hearing, and balance functions. SR increases contrast sensitivity and luminance detection; lowers the absolute threshold for tone detection in normal hearing individuals; improves homeostatic function in the human blood pressure regulatory system; improves noise-enhanced muscle spindle function; and improves detection of weak tactile stimuli using mechanical or electrical stimulation. SR noise has been shown to improve postural control when applied as mechanical noise to the soles of the feet, or when applied as electrical noise at the knee and to the back muscles.

Bloomberg, Jacob; Reschke, Millard; Mulavara, Ajitkumar; Wood, Scott; Serrador, Jorge; Fiedler, Matthew; Kofman, Igor; Peters, Brian T.; Cohen, Helen

2012-01-01

207

High Intensity Training Improves Health and Physical Function in Middle Aged Adults  

PubMed Central

High intensity training (HIT) is effective at improving health; however, it is unknown whether HIT also improves physical function. This study aimed to determine whether HIT improves metabolic health and physical function in untrained middle aged individuals. Fourteen (three male and eleven female) untrained individuals were recruited (control group n = 6: age 42 ± 8 y, weight 64 ± 10 kg, BMI 24 ± 2 kg·m?2 or HIT group n = 8: age 43 ± 8 y, weight 80 ± 8 kg, BMI 29 ± 5 kg·m?2). Training was performed twice weekly, consisting of 10 × 6-second sprints with a one minute recovery between each sprint. Metabolic health (oral glucose tolerance test), aerobic capacity (incremental time to exhaustion on a cycle ergometer) and physical function (get up and go test, sit to stand test and loaded 50 m walk) were determined before and after training. Following eight weeks of HIT there was a significant improvement in aerobic capacity (8% increase in VO2 peak; p < 0.001), physical function (11%–27% respectively; p < 0.05) and a reduction in blood glucose area under the curve (6% reduction; p < 0.05). This study demonstrates for the first time the potential of HIT as a training intervention to improve skeletal muscle function and glucose clearance as we age.

Adamson, Simon; Lorimer, Ross; Cobley, James N.; Lloyd, Ray; Babraj, John

2014-01-01

208

High intensity training improves health and physical function in middle aged adults.  

PubMed

High intensity training (HIT) is effective at improving health; however, it is unknown whether HIT also improves physical function. This study aimed to determine whether HIT improves metabolic health and physical function in untrained middle aged individuals. Fourteen (three male and eleven female) untrained individuals were recruited (control group n = 6: age 42 ± 8 y, weight 64 ± 10 kg, BMI 24 ± 2 kg·m-2 or HIT group n = 8: age 43 ± 8 y, weight 80 ± 8 kg, BMI 29 ± 5 kg·m-2). Training was performed twice weekly, consisting of 10 × 6-second sprints with a one minute recovery between each sprint. Metabolic health (oral glucose tolerance test), aerobic capacity (incremental time to exhaustion on a cycle ergometer) and physical function (get up and go test, sit to stand test and loaded 50 m walk) were determined before and after training. Following eight weeks of HIT there was a significant improvement in aerobic capacity (8% increase in VO2 peak; p < 0.001), physical function (11%-27% respectively; p < 0.05) and a reduction in blood glucose area under the curve (6% reduction; p < 0.05). This study demonstrates for the first time the potential of HIT as a training intervention to improve skeletal muscle function and glucose clearance as we age. PMID:24833513

Adamson, Simon; Lorimer, Ross; Cobley, James N; Lloyd, Ray; Babraj, John

2014-01-01

209

Does natural erectile function improve following intracavernous injections of vasoactive drugs?  

PubMed

Improvement in natural erections has been reported in approximately 9% of impotent men using intracavernous injections of vasoactive drugs for erection induction. The mechanisms which may account for this improvement are psychogenic, improved cavernous hemodynamics, prostaglandin-induced angiogenesis, improved cavernous oxygenation, cavernous smooth muscle hypertrophy and/or normal episodic fluctuations in erectile function. A review of the basic science literature on this subject reveals several theoretical explanations for this phenomenon but a review of the clinical literature reveals little convincing evidence that physiologic and/or pharmacologic factors are responsible for improvement in natural erections with intracavernous injection therapy. Furthermore, the prevalence of a placebo effect from impotence therapy exceeds the reported rate of improvement in natural or spontaneous erections. The most plausible explanations for spontaneous improvement in erections during or after intracavernous injection therapy are psychogenic and episodic variations in erectile function, rather than physiologic or pharmacologic factors. However, intracavernous injection therapy started soon after radical prostatectomy may have a protective effect in preserving normal cavernous physiology and erectile function in men being treated for prostate cancer. PMID:9442416

Sharlip, I D

1997-12-01

210

Mechanical fault diagnosis for LV circuit breakers based on energy spectrum entropy of wavelet packet and Naive Bayesian classifier  

Microsoft Academic Search

The paper has extracted the energy spectrum entropy of wavelet packet as the eigen vector of fault patterns, through analyzing the vibration signal in the decomposition of wavelet packet when Low-Voltage (LV) Circuit Breaker broke down. Based on the concept of Clustering Center, a Nai?ve Bayesian classifier has been constructed. By using the weight of probability measure, the correlations between

Jiao-Min Liu; Jian-Li Zhao; Li Li; Ya-Ning Wang

2010-01-01

211

Pelvic Floor Rehabilitation to Improve Functional Outcome After a Low Anterior Resection: A Systematic Review  

PubMed Central

Purpose Impaired functional outcome is common after a low anterior resection (LAR). Pelvic floor rehabilitation (PFR) might improve functional outcome after a LAR. The aim of this systematic review is to evaluate the effectiveness of PFR in improving functional outcome. Methods PubMed, Embase, and the Cochrane Library were searched using the terms fecal incontinence, colorectal neoplasm/surgery, LAR, rectal cancer, anterior resection syndrome, bowel habit, pelvic floor, training, therapy, physical therapy, rehabilitation and biofeedback. Of the 125 identified records, 5 articles were included. Results The 5 included studies reported on 321 patients, of which 286 patients (89%) underwent pelvic floor training. Three studies included patients with anterior resection syndrome after a LAR while the remaining studies included a series of patients after a LAR. Functional outcome was mostly assessed by using the Wexner incontinence scale. Quality of life was assessed in one study, and in three studies, rectal manometry was performed. After PFR, the functional outcome was improved in four studies, as was the quality of life. Conclusion This systematic review demonstrated that PFR is useful for improving the functional outcome after a LAR. The data are extracted from studies of limited quality, but the available evidence points to the effectiveness of the procedure.

Visser, Wilhelmina S; te Riele, Wouter W; Boerma, Djamila; van Ramshorst, Bert

2014-01-01

212

Association of N-terminal pro-B-type natriuretic peptide with left ventricular structure and function in chronic kidney disease (from the Chronic Renal Insufficiency Cohort [CRIC]).  

PubMed

We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease without clinical heart failure, the Chronic Renal Insufficiency Cohort (n = 3,232). The associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated using multivariate logistic and linear regression models. Reclassification of participants' predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement index that compared a clinical model with and without NT-proBNP. The median NT-proBNP was 126.6 pg/ml (interquartile range 55.5 to 303.7). The greatest quartile of NT-proBNP was associated with a nearly threefold odds of LVH (odds ratio 2.7, 95% confidence interval [CI] 1.8 to 4.0) and LV systolic dysfunction (odds ratio 2.7, 95% CI 1.7 to 4.5) and a twofold odds of diastolic dysfunction (odds ratio 2.0, 95% CI 1.3 to 2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve 0.66) and LV systolic dysfunction (area under the curve 0.62) and poorly for the detection of diastolic dysfunction (area under the curve 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants' likelihood of having LVH (net reclassification improvement 0.14, 95% CI 0.13-0.15; p <0.001) and LV systolic dysfunction (net reclassification improvement 0.28, 95% CI 0.27 to 0.30; p <0.001) but not diastolic dysfunction (net reclassification improvement 0.10, 95% CI 0.10 to 0.11; p = 0.07). In conclusion, in this large chronic kidney disease cohort without heart failure, NT-proBNP had strong associations with prevalent LVH and LV systolic dysfunction. PMID:23178053

Mishra, Rakesh K; Li, Yongmei; Ricardo, Ana C; Yang, Wei; Keane, Martin; Cuevas, Magdalena; Christenson, Robert; deFilippi, Christopher; Chen, Jing; He, Jiang; Kallem, Radhakrishna R; Raj, Dominic S; Schelling, Jeffrey R; Wright, Jackson; Go, Alan S; Shlipak, Michael G

2013-02-01

213

Optimization of exit pupil function: improvement on the OTF of full parallax holographic stereograms  

NASA Astrophysics Data System (ADS)

The wavefront reconstructed errors of full parallax holographic stereograms are analysed. The optical transfer function (OTF) is simulated to investigate frequency response and imaging quality of holographic stereogram systems. The behaviour of the OTF with respect to slit size and spatial frequency in different aberrations is described and used to optimize the exit pupil function. The shaped window function (Gaussian and Blackman) is proposed to be used as the exit pupil function of holographic systems, and the influence of different exit pupil functions on the OTF is investigated in detail. The calculated results show that the shaped exit pupil function with optimized slit size can improve the imaging quality of full parallax holographic stereogram systems effectively. The design criterion of the exit pupil function is also discussed.

Jiang, Xiaoyu; Pei, Chuang; Yan, Xingpeng; Liu, Junhui; Zhao, Kai

2013-12-01

214

Improved Constraint-based GGA Functionals in Extended Systems and Molecules  

NASA Astrophysics Data System (ADS)

Despite wide-spread interest in explicitly orbitally-dependent exchange-correlation functionals, there is aimed at the basic vision of Density Functional Theory, orbital-free implementation. Here we report on further development of our non-empirical X functionals. We give results for the VMT functional (J. Chem. Phys. 130 244103 (2009)) combined with the PBE C functional on simple solids and ultra-thin films. We also give results for molecules for a more sophisticated family of functionals, VPTmn, which satisfy more constraints than VMT. VMT11 with PBE C tested on a widely used 20 molecule set shows essentially no change in atomization energies compared to VMT, an illustration that enforcing more constraints does not necessarily improve outcomes. We also consider VMT11 in extended systems and in combination with both the LYP and rev-TCA correlation functionals on molecules.

Trickey, Sam; Vela, A.; Pacheco Kato, Juan

2010-03-01

215

Restriction of multiple divergent retroviruses by Lv1 and Ref1  

PubMed Central

The mouse gene Fv1 encodes a saturable restriction factor that selectively blocks infection by N-tropic or B-tropic murine leukemia virus (MLV) strains. Despite the absence of an Fv1 gene, a similar activity is present in humans that blocks N-MLV infection (Ref1). Moreover, some non-human primate cell lines express a potentially related inhibitor of HIV-1 and/or SIVmac infection (Lv1). Here, we examine the spectrum of retrovirus-restricting activities expressed by human and African green monkey cell lines. Human cells restrict N-MLV and equine infectious anemia virus (EIAV), but not HIV-1, HIV-2, SIVmac or SIVagm, whilst AGM cells restrict N-MLV, EIAV, HIV-1, HIV-2 and SIVmac. Remarkably, in each example examined, restriction of infection by a given retrovirus can be abrogated at least partially by saturation with another retrovirus, provided that it is also restricted but regardless of whether it is closely related. These data suggest that restriction factors in human and non-human primate cells are able to recognize and block infection by multiple, widely divergent retroviruses and that the factors themselves may be related.

Hatziioannou, Theodora; Cowan, Simone; Goff, Stephen P.; Bieniasz, Paul D.; Towers, Greg J.

2003-01-01

216

Left atrial pressure-clamp servomechanism demonstrates LV suction in canine hearts with normal mitral valves.  

PubMed

A novel technique is presented to study suction of the in situ left ventricle in open-chest experimental animals without requiring cardiopulmonary bypass or disturbing the native mitral valvular apparatus. In 17 dogs, left ventricular pressure (LVP) and left atrial pressure (LAP) were measured, the left atrium was cannulated and connected to a servo pump, and LAP was controlled to a setpoint near 0 mmHg by withdrawing blood from the left atrium. Heart rate [103 +/- 17 (SD) min-1], peak pressure (100 +/- 13 mmHg), minimum pressure (1.4 +/- 0.8 mmHg), and maximum rate of change of pressure with respect to time during isovolumic contraction and relaxation (2,506 +/- 775 and -1,761 +/- 855 mmHg/s, respectively) were normal. Servo control of LAP was possible to +/- 1 mmHg. LV suction was demonstrated in each heart (mean negative LVP -2.3 +/- 1.1 mmHg; P < 0.0001). This new technique demonstrates that the left ventricle can generate negative diastolic suction pressures when examined in vivo and in situ with an undisturbed mitral valve and physiologically normal preload and afterload. This adds to a growing body of evidence that, under appropriate circumstances, the heart can suck blood into itself and thereby aid in its own filling. PMID:8048601

Ingels, N B; Daughters, G T; Nikolic, S D; DeAnda, A; Moon, M R; Bolger, A F; Komeda, M; Derby, G C; Yellin, E L; Miller, D C

1994-07-01

217

Further improvement in the variational many-body wave functions for light nuclei  

NASA Astrophysics Data System (ADS)

An improved variational ansatz is proposed and implemented for variational many-body wave functions for light nuclei with nucleons interacting through Argonne (AV18) and Urbana IX (UIX) three-nucleon interactions. The new ansatz is based upon variationally distinguishing between the various components of the two-body Jastrow and operatorial correlations, which are operated upon by three-body and spin-orbit correlations. We obtain noticeable improvement in the quality of the wave function and lowering of the energies compared to earlier results. The new energies are -8.38(1), -28.07(1), and -29.90(1) MeV for 3H, 4He, and 6Li, respectively. Though, the present improved ansatz still fails to stabilize the 6Li nucleus against a breakup into an ? particle and a deuteron by 390 KeV; nonetheless, it is an improvement over previous studies.

Usmani, Q. N.; Anwar, K.; Abdullah, Nooraihan

2012-09-01

218

Increased Cardiac Myocyte PDE5 Levels in Human and Murine Pressure Overload Hypertrophy Contribute to Adverse LV Remodeling  

PubMed Central

Background The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC). Methodology/Principal Findings In patients with severe aortic stenosis (AS) undergoing valve replacement, we detected greater myocardial PDE5 expression than in control hearts. We observed robust expression in scattered cardiac myocytes of those AS patients with higher LV filling pressures and BNP serum levels. Following TAC, we detected similar, focal PDE5 expression in cardiac myocytes of C57BL/6NTac mice exhibiting the most pronounced LV remodeling. To examine the effect of cell-specific PDE5 expression, we subjected transgenic mice with cardiac myocyte-specific PDE5 overexpression (PDE5-TG) to TAC. LV hypertrophy and fibrosis were similar as in WT, but PDE5-TG had increased cardiac dimensions, and decreased dP/dtmax and dP/dtmin with prolonged tau (P<0.05 for all). Greater cardiac dysfunction in PDE5-TG was associated with reduced myocardial cGMP and SERCA2 levels, and higher passive force in cardiac myocytes in vitro. Conclusions/Significance Myocardial PDE5 expression is increased in the hearts of humans and mice with chronic pressure overload. Increased cardiac myocyte-specific PDE5 expression is a molecular hallmark in hypertrophic hearts with contractile failure, and represents an important therapeutic target.

Vandenwijngaert, Sara; Pokreisz, Peter; Hermans, Hadewich; Gillijns, Hilde; Pellens, Marijke; Bax, Noortje A. M.; Coppiello, Giulia; Oosterlinck, Wouter; Balogh, Agnes; Papp, Zoltan; Bouten, Carlijn V. C.; Bartunek, Jozef; D'hooge, Jan; Luttun, Aernout; Verbeken, Erik; Herregods, Marie Christine; Herijgers, Paul; Bloch, Kenneth D.; Janssens, Stefan

2013-01-01

219

Daily use of sildenafil improves endothelial function in men with type 2 diabetes.  

PubMed

Diminished vascular endothelial function results in decreased vasodilator capacity and is associated with erectile dysfunction (ED) in patients afflicted with type 2 diabetes. The current study was designed to evaluate whether daily use of sildenafil could alter endothelial function and improve penile rigidity in a group of patients with diabetic ED. A double-blind, placebo-controlled, prospective trial was conducted with 24 men with type 2 diabetes who were randomized into 2 groups: one receiving daily sildenafil (50 mg, n = 12) and the other placebo (n = 12) for 10 weeks. Erectile function was captured subjectively using the International Index of Erectile Function (IIEF-5), and endothelial function was objectively monitored via brachial artery flow-mediated dilation. Among the placebo and sildenafil groups, there were no significant differences in average patient age, time from type 2 diabetes diagnosis, duration of ED, or baseline IIEF-5 scores. Past medical histories, including smoking, alcohol consumption, hypertension, and hyperlipidemia, were also similar. At the conclusion of the 10-week trial, patients who received daily sildenafil had significantly improved erectile rigidity as captured by IIEF-5 (P < .001) and increased endothelial function via brachial artery flow-mediated dilation (P < .01). Endothelial function in men with type 2 diabetes was enhanced with daily sildenafil. Improved erectile rigidity and enhanced vascular circulation was noted after 10 weeks of daily sildenafil use. PMID:21680809

Deyoung, Ling; Chung, Eric; Kovac, Jason R; Romano, Walter; Brock, Gerald B

2012-01-01

220

Acetyl-L-carnitine treatment following spinal cord injury improves mitochondrial function correlated with remarkable tissue sparing and functional recovery.  

PubMed

We have recently documented that treatment with the alternative biofuel, acetyl-L-carnitine (ALC, 300 mg/kg), as late as 1 h after T10 contusion spinal cord injury (SCI), significantly maintained mitochondrial function 24 h after injury. Here we report that after more severe contusion SCI centered on the L1/L2 segments that are postulated to contain lamina X neurons critical for locomotion (the "central pattern generator"), ALC treatment resulted in significant improvements in acute mitochondrial bioenergetics and long-term hind limb function. Although control-injured rats were only able to achieve slight movements of hind limb joints, ALC-treated animals produced consistent weight-supported plantar steps 1 month after injury. Such landmark behavioral improvements were significantly correlated with increased tissue sparing of both gray and white matter proximal to the injury, as well as preservation of choline acetyltransferase (ChAT)-positive neurons in lamina X rostral to the injury site. These findings signify that functional improvements with ALC treatment are mediated, in part, by preserved locomotor circuitry rostral to upper lumbar contusion SCI. Based on beneficial effects of ALC on mitochondrial bioenergetics after injury, our collective evidence demonstrate that preventing mitochondrial dysfunction acutely "promotes" neuroprotection that may be associated with the milestone recovery of plantar, weight-supported stepping. PMID:22445934

Patel, S P; Sullivan, P G; Lyttle, T S; Magnuson, D S K; Rabchevsky, A G

2012-05-17

221

Time-dependent improvement in functional outcome following Oxford medial unicompartmental knee arthroplasty  

PubMed Central

Background and purpose 10-year survival rates after unicompartmental knee replacement (UKR) have been up to 97% in single-center studies, but they have been as low as 80% in studies from arthroplasty registers. Few studies have evaluated short-term functional outcome and its improvement with time. We determined the time course of functional outcome as evaluated by the knee injury and osteoarthritis outcome score (KOOS) over the first 2 years after Oxford medial UKR. Patients and methods In a prospective multicenter study, we included 99 unselected knees (96 patients, mean age 65 (51–80) years, 57 women) operated with Oxford medial UKR at 3 hospitals in the southeast of Norway between November 2003 and October 2006. Data were collected by independent investigators preoperatively and at 6 weeks, 3 months, 6 months, 1 year, and 2 years postoperatively. KOOS and range of motion (ROM) were determined at all follow-ups. Results Mean KOOS values for pain and activities of daily living were improved already after 6 weeks, and increased between each time point up to 2 years postoperatively. However, no statistically significant improvements were seen after 6 months. Mean active and passive ROM gradually improved up to 2 years after UKR, and were then better than before surgery. Interpretation Most of the expected improvements in pain and function after UKR are achieved within 6 months of surgery. Only minimal improvement can be expected beyond this time.

2012-01-01

222

Eucalyptus increases ceramide levels in keratinocytes and improves stratum corneum function.  

PubMed

The objectives of this study were to identify a plant extract that would improve stratum corneum functions and to elucidate the mechanism(s) involved. Based on the information that stratum corneum functions depend on the level of ceramide in the stratum corneum, we identified a Eucalyptus extract that was able to increase the level of ceramide in human keratinocytes in culture and in human stratum corneum and that improves the stratum corneum water holding and barrier functions. Addition of the Eucalyptus extract to human keratinocytes in culture increased the level of ceramide in a dose-dependent manner and also increased the biosynthesis of ceramide, glucosylceramide and sphingomyelin. Topical application of the Eucalyptus extract on the dry skin of human subjects induced by acetone and diethylether treatment resulted in a significant increase in ceramide level in the stratum corneum, a significant improvement in its water-holding function and an improvement in its barrier function. The addition of macrocarpal A, one of the main components of the Eucalyptus extract, to human keratinocytes in culture increased the level of ceramide and the mRNA expression of serine palmitoyltransferase, acid sphingomyelinase, neutral sphingomyelinase, glucosylceramide synthase and glucocerebrosidase in a dose-dependent manner. Our results indicate that the increased content of ceramides in the stratum corneum may underlie the therapeutic effect of the Eucalyptus extract. Our results also indicate the possibility that macrocarpal A is the key component that stimulates the synthesis of ceramide in the stratum corneum. PMID:21696405

Ishikawa, J; Shimotoyodome, Y; Chen, S; Ohkubo, K; Takagi, Y; Fujimura, T; Kitahara, T; Takema, Y

2012-02-01

223

Rehabilitation and improvement of Guilin urban water environment: function-oriented management.  

PubMed

Economic development and population growth have deeply damaged the urban water environment of Guilin City, China. Main problems involved structural damage and functional deterioration of the urban waters. An integrated technical scheme was developed to rehabilitate the urban water environment and to enhance the waters' functions during 1998-2008. Improvement of waters' functions included water system reconstruction, water pollution control, water safety assurance, and aquatic ecological restoration. The water system was reconstructed to connect different waters and clean water supplies to the lakes. Moreover, water pollution was controlled to improve water quality by endogenous pollutant elimination and extraneous pollutant interception. In addition, ecological measures put in place serve to enhance water system functions and better benefit both nature and humans. The project has brought about sound ecological, economic and social benefits in Guilin City, which can potentially be extended to similar cities. PMID:24218862

Pei, Yuansheng; Zuo, Hua; Luan, Zhaokun; Gao, Sijia

2013-07-01

224

Normal Left and Right Ventricular Volume and Function  

Microsoft Academic Search

In patients with heart disease, quantification of left ventricular (LV) function and mass is important for prognosis (1,2). Cardiac magnetic resonance imaging (MRI) measurements of LV function have already been helpful in the prognostic assessment\\u000a of patients (3).

Ralf Wassmuth; Jeanette Schulz-Menger

225

A decentralized mechanism for improving the functional robustness of distribution networks.  

PubMed

Most real-world distribution systems can be modeled as distribution networks, where a commodity can flow from source nodes to sink nodes through junction nodes. One of the fundamental characteristics of distribution networks is the functional robustness, which reflects the ability of maintaining its function in the face of internal or external disruptions. In view of the fact that most distribution networks do not have any centralized control mechanisms, we consider the problem of how to improve the functional robustness in a decentralized way. To achieve this goal, we study two important problems: 1) how to formally measure the functional robustness, and 2) how to improve the functional robustness of a network based on the local interaction of its nodes. First, we derive a utility function in terms of network entropy to characterize the functional robustness of a distribution network. Second, we propose a decentralized network pricing mechanism, where each node need only communicate with its distribution neighbors by sending a "price" signal to its upstream neighbors and receiving "price" signals from its downstream neighbors. By doing so, each node can determine its outflows by maximizing its own payoff function. Our mathematical analysis shows that the decentralized pricing mechanism can produce results equivalent to those of an ideal centralized maximization with complete information. Finally, to demonstrate the properties of our mechanism, we carry out a case study on the U.S. natural gas distribution network. The results validate the convergence and effectiveness of our mechanism when comparing it with an existing algorithm. PMID:22547458

Shi, Benyun; Liu, Jiming

2012-10-01

226

Ventricular Reconstruction Results in Improved Left Ventricular Function and Amelioration of Mitral Insufficiency  

PubMed Central

Introduction Surgical restoration of the left ventricular wall (Dor procedure) has been advocated as a therapy for left ventricular dysfunction due to ischemic cardiomyopathy. This procedure involves placement of an endoventricular patch through a ventriculotomy. Methods We reviewed our series of patients that underwent the Dor procedure within the past 4 years and examined their pre and postoperative ventricular function and mitral valve function. Pre and postoperative ejection fraction and degree of mitral regurgitation were analyzed using the paired Student t-test. We hypothesized that this procedure would result in improved ventricular function and that it would also help improve mitral valve function. Results Thirty-four patients underwent this procedure, with one death. Of these, 30 patients underwent concomitant coronary artery bypass grafting and 8 patients had mitral intervention (seven had an Alfieri repair of the mitral valve, and one had mitral valve annuloplasty). The average preoperative ejection fraction among these patients was 26.8% (range 10–45%). The postoperative ejection fraction was significantly higher at 35.4% (range 25–52%) (P < .001). We noted an improvement in ejection fraction in 27 patients (82%). We also noted that 21 of 33 patients (64%) had improvement in the degree of mitral regurgitation based on echocardiography data (P < .001). Conclusions We conclude that the Dor procedure results in improvement in the left ventricular function. Furthermore, we also note that this procedure ameliorates mitral regurgitation in a majority of these patients even in the absence of associated mitral valve procedures, probably due to reduction in the size of the ventricle and improved orientation of the papillary muscles.

Kaza, Aditya K.; Patel, Mayank R.; Fiser, Steven M.; Long, Stewart M.; Kern, John A.; Tribble, Curtis G.; Kron, Irving L.

2002-01-01

227

Improvement in cognitive and psychosocial functioning and self image among adolescent inpatient suicide attempters  

PubMed Central

Background Psychiatric treatment of suicidal youths is often difficult and non-compliance in treatment is a significant problem. This prospective study compared characteristics and changes in cognitive functioning, self image and psychosocial functioning among 13 to 18 year-old adolescent psychiatric inpatients with suicide attempts (n = 16) and with no suicidality (n = 39) Methods The two-group pre-post test prospective study design included assessments by a psychiatrist, a psychologist and medical staff members as well as self-rated measures. DSM-III-R diagnoses were assigned using the SCID and thereafter transformed to DSM-IV diagnoses. Staff members assessed psychosocial functioning using the Global Assessment Scale (GAS). Cognitive performance was assessed using the Wechsler Adult Intelligence Scale, while the Offer Self-Image Questionnaire (OSIQ) was used to assess the subjects' self-image. ANCOVA with repeated measures was used to test changes from entry to discharge among the suicide attempters and non suicidal patients. Logistic regression modeling was used to assess variables associated with an improvement of 10 points or more in the GAS score. Results Among suicide attempter patients, psychosocial functioning, cognitive performance and both the psychological self and body-image improved during treatment and their treatment compliance and outcome were as good as that of the non-suicidal patients. Suicidal ideation and hopelessness declined, and psychosocial functioning improved. Changes in verbal cognitive performance were more pronounced among the suicide attempters. Having an improved body-image associated with a higher probability of improvement in psychosocial functioning while higher GAS score at entry was associated with lower probability of functional improvement in both patient groups. Conclusion These findings illustrate that a multimodal treatment program seems to improve psychosocial functioning and self-image among severely disordered suicidal adolescent inpatients. There were no changes in familial relationships, possibly indicating a need for more intensive family interventions when treating suicidal youths. Multimodal inpatient treatment including an individual therapeutic relationship seems recommendable for severely impaired psychiatric inpatients tailored to the suicidal adolescent's needs.

Hintikka, Ulla; Marttunen, Mauri; Pelkonen, Mirjami; Laukkanen, Eila; Viinamaki, Heimo; Lehtonen, Johannes

2006-01-01

228

Improvement of Eustachian Tube Function by Tissue-Engineered Regeneration of Mastoid Air Cells  

PubMed Central

Objectives/Hypothesis Most cases of chronic otitis media (OMC) are associated with poor development of the mastoid air cells (MACs) and poor Eustachian tube (ET) function. We have previously reported that MAC regeneration can effectively eliminate intractable OMC. In this study, we assessed the ability of regenerated MACs to restore normal gas exchange function and contribute to improved ET function. Study Design Clinical trial with control. Setting General hospitals. Materials and Methods Seventy-six patients with OMC, including cholesteatoma and adhesive otitis media, received tympanoplasty and MAC regeneration therapy. At the first-stage of tympanoplasty, artificial pneumatic bones and/or autologous bone fragments were implanted into the opened mastoid cavity. At the 2nd-stage operation, a nitrous oxide (N2O) gas study was performed in 10 patients to measure middle ear pressure (MEP). For the control group, MEP was measured in five patients with good MAC development during cochlear implantation or facial nerve decompression. ET function was measured twice in each patient, once before the 1st operation and 6 months after the second operation. Results At the 2nd-stage operation, in all cases with regenerated MACs and in the normal control group, MEP changed after administration of N2O. In contrast, no change in MEP was observed in cases with unregenerated MACs. In 70% (n = 37/53) of the regenerated MAC group, ET function was improved, whereas improvement of ET function was observed in only 13% (n = 3/23) of the unregenerated MAC group. Conclusions Tissue-engineered regeneration of MACs improves ET function and gas exchange in the middle ear. Laryngoscope, 2012 Level of Evidence 3b

Kanemaru, Shin-ichi; Umeda, Hiroo; Yamashita, Masaru; Hiraumi, Harukazu; Hirano, Shigeru; Nakamura, Tatsuo; Ito, Juichi

2013-01-01

229

Weak Convergence and Banach Space-Valued Functions: Improving the Stability Theory of Feynman's Operational Calculi  

NASA Astrophysics Data System (ADS)

In this paper we investigate the relation between weak convergence of a sequence left\\{ ?nright\\} of probability measures on a Polish space S converging weakly to the probability measure ? and continuous, norm-bounded functions into a Banach space X. We show that, given a norm-bounded continuous function f: S? X, it follows that lim_{ntoinfty}intSf d?n=intSf d?—the limit one has for bounded and continuous real (or complex)—valued functions on S. This result is then applied to the stability theory of Feynman's operational calculus where it is shown that the theory can be significantly improved over previous results.

Nielsen, Lance

2011-12-01

230

CUDA implementation of histogram stretching function for improving X-ray image.  

PubMed

This paper presents a method to improve the contrast of digital X-ray image using CUDA program on a GPU. The histogram is commonly used to get the statistical distribution of the contrast in image processing. To increase the visibility of the image in real time, we use the histogram stretching function. It is difficult to implement the function on a GPU because the CUDA program is due to handle the complex process to transfer the source data and the processed results between the memory of GPU and the host system. As a result, we show to operate the histogram stretching function quickly on GPU by the CUDA program. PMID:23920761

Lee, Yong H; Kim, Kwan W; Kim, Soon S

2013-01-01

231

Ingestion of Broccoli Sprouts Does Not Improve Endothelial Function in Humans with Hypertension  

Microsoft Academic Search

Ingestion of glucosinolates has previously been reported to improve endothelial function in spontaneously hypertensive rats, possibly because of an increase in NO availability in the endothelium due to an attenuation of oxidative stress; in our study we tried to see if this also would be the case in humans suffering from essential hypertension.Methods40 hypertensive individuals without diabetes and with normal

Buris Christiansen; Natalia Bellostas Muguerza; Atheline Major Petersen; Britt Kveiborg; Christian Rask Madsen; Hermann Thomas; Nikolaj Ihlemann; Jens Christian Sørensen; Lars Køber; Hilmer Sørensen; Christian Torp-Pedersen; Helena Domínguez

2010-01-01

232

Perfluorocarbon Improves Post-Transplant Survival and Early Kidney Function following Prolonged Cold Ischemia  

Microsoft Academic Search

Background: The two-layer organ preservation method (TLM) based on oxygenated perfluorocarbon overlaid with University of Wisconsin (UW) solution has been successfully used in clinical islet and experimental heart and intestine transplantation. We tested whether this technique would prevent tissue damage and improve kidney function in a model of syngeneic kidney transplantation with prolonged ischemia time. Methods: Kidneys were stored for

T. Marada; K. Zacharovova; F. Saudek

2010-01-01

233

Improvements in Neurocognitive Function and Mood Following Adjunctive Treatment with Mifepristone (RU486) in Bipolar Disorder  

Microsoft Academic Search

High cortisol levels are found in severe mood disorders, particularly bipolar disorder. Hypercortisolaemia may cause or exacerbate both neurocognitive impairment and depressive symptoms. We hypothesized that antiglucocorticoid treatments, particularly corticosteroid receptor antagonists, would improve neurocognitive functioning and attenuate depressive symptoms in this disorder. To test this hypothesis, 20 bipolar patients were treated with 600 mg\\/day of the corticosteroid receptor antagonist

Allan H Young; Peter Gallagher; Stuart Watson; Dolores Del-Estal; Bruce M Owen; I Nicol Ferrier

2004-01-01

234

Family Ranching and Farming: A Consensus Management Model to Improve Family Functioning and Decrease Work Stress.  

ERIC Educational Resources Information Center

Notes that internal and external threats could squeeze ranch and farm families out of business. Offers six-step Consensus Management Model that combines strategic planning with psychoeducation/family therapy. Describes pilot test with intergenerational ranch family that indicated improvements in family functioning, including reduced stress and…

Zimmerman, Toni Schindler; Fetsch, Robert J.

1994-01-01

235

New application of Exp-function method for improved Boussinesq equation  

Microsoft Academic Search

The Exp-function method is used to obtain generalized solitary solutions and periodic solutions for nonlinear evolution equations arising in mathematical physics with the aid of symbolic computation method, namely, the improved Boussinesq equation. The method is straightforward and concise, and its applications is promising for other nonlinear evolution equations in mathematical physics.

M. A. Abdou; A. A. Soliman; S. T. El-Basyony

2007-01-01

236

A new approach to improve functionality for cost reduction in construction project  

Microsoft Academic Search

This paper summarized and reviewed the current main strategies for cost reduction in construction projects. According to the feedback from ten experienced construction managers, we analyzed the implementation of the current main strategies and nine possible factors (reasons) that should influence these strategies. Then a new approach is introduced to improve functionality for cost reduction in construction projects.

Shujing Li

2010-01-01

237

Transdermal Testosterone Gel Improves Sexual Function, Mood, Muscle Strength, and Body Composition Parameters in Hypogonadal Men  

Microsoft Academic Search

Testosterone (T) therapy for hypogonadal men should correct the clinical abnormalities of T deficiency, including improvement of sex- ual function, increase in muscle mass and strength, and decrease in fat mass, with minimal adverse effects. We have shown that admin- istration of a new transdermal T gel formulation to hypogonadal men provided dose proportional increases in serum T levels to

CHRISTINA WANG; RONALD S. SWERDLOFF; ALI IRANMANESH; ADRIAN DOBS; PETER J. SNYDER; GLENN CUNNINGHAM; ALVIN M. MATSUMOTO

2007-01-01

238

A Study of Improving Sight and Functional Vocabulary Development and Comprehension.  

ERIC Educational Resources Information Center

This report describes a program to increase sight/functional vocabulary to improve reading comprehension. The targeted population consisted of one 2nd-3rd grade and one 6th-8th grade cross-categorical self-contained class, located in an elementary school and a middle school. The schools were located in a northeast suburb of a major city in the…

Henning, Diane; Pickett, Anita

239

Enriched Rehabilitative Training Promotes Improved Forelimb Motor Function and Enhanced Dendritic Growth after Focal Ischemic Injury  

Microsoft Academic Search

Chronic impairment of forelimb and digit movement is a com- mon problem after stroke that is resistant to therapy. Previous studies have demonstrated that enrichment improves behav- ioral outcome after focal ischemia; however, postischemic en- richment alone is not capable of enhancing fine digit and forelimb function. Therefore, we combined environmental en- richment with daily skilled-reach training to assess the

Jeff Biernaskie; Dale Corbett

2001-01-01

240

0++ glueball wave function for improved SU(2) lattice gauge theory in (2+1) dimensions  

NASA Astrophysics Data System (ADS)

Using the improved lattice gauge field Hamiltonian and the truncated eigenvalue equation method, we compute the 0++ glueball wave function of (2+1)-dimensional SU(2) gauge field theory. The result shows a good scaling behavior in the weak coupling region 3?1/g2?6.

Jiang, Jun-Qin

2012-08-01

241

Playing Piano Can Improve Upper Extremity Function after Stroke: Case Studies  

PubMed Central

Music-supported therapy (MST) is an innovative approach that was shown to improve manual dexterity in acute stroke survivors. The feasibility of such intervention in chronic stroke survivors and its longer-term benefits, however, remain unknown. The objective of this pilot study was to estimate the short- and long-term effects of a 3-week piano training program on upper extremity function in persons with chronic stroke. A multiple pre-post sequential design was used, with measurements taken at baseline (week0, week3), prior to (week6) and after the intervention (week9), and at 3-week follow-up (week12). Three persons with stroke participated in the 3-week piano training program that combined structured piano lessons to home practice program. The songs, played on an electronic keyboard, involved all 5 digits of the affected hand and were displayed using a user-friendly MIDI program. After intervention, all the three participants showed improvements in their fine (nine hole peg test) and gross (box and block test) manual dexterity, as well as in the functional use of the upper extremity (Jebsen hand function test). Improvements were maintained at follow-up. These preliminary results support the feasibility of using an MST approach that combines structured lessons to home practice to improve upper extremity function in chronic stroke.

Villeneuve, Myriam; Lamontagne, Anouk

2013-01-01

242

Chemical abundances in the protoplanetary disc LV 2 (Orion) - II. High-dispersion VLT observations and microjet properties  

NASA Astrophysics Data System (ADS)

Integral field spectroscopy of the LV 2 proplyd is presented taken with the Very Large Telescope (VLT)/FLAMES Argus array at an angular resolution of 0.31 × 0.31 arcsec2 and velocity resolutions down to 2 km s-1 pixel-1. Following subtraction of the local M42 emission, the spectrum of LV 2 is isolated from the surrounding nebula. We measured the heliocentric velocities and widths of a number of lines detected in the intrinsic spectrum of the proplyd, as well as in the adjacent Orion nebula falling within a 6.6 × 4.2 arcsec2 field of view. It is found that far-ultraviolet to optical collisional lines with critical densities, Ncr, ranging from 103 to 109 cm-3 suffer collisional de-excitation near the rest velocity of the proplyd correlating tightly with their critical densities. Lines of low Ncr are suppressed the most. The bipolar jet arising from LV 2 is spectrally and spatially well detected in several emission lines. We compute the [O III] electron temperature profile across LV 2 in velocity space and measure steep temperature variations associated with the red-shifted lobe of the jet, possibly being due to a shock discontinuity. From the velocity-resolved analysis the ionized gas near the rest frame of LV 2 has Te= 9200 ± 800 K and Ne˜ 106 cm-3, while the red-shifted jet lobe has Te? 9000-104 K and Ne˜ 106-107 cm-3. The jet flow is highly ionized but contains dense semineutral clumps emitting neutral oxygen lines. The abundances of N+, O2 +, Ne2 +, Fe2 +, S+and S2 +are measured for the strong red-shifted jet lobe. Iron in the core of LV 2 is depleted by 2.54 dex with respect to solar as a result of sedimentation on dust, whereas the efficient destruction of dust grains in the fast microjet raises its Fe abundance to at least 30 per cent solar. Sulphur does not show evidence of significant depletion on dust, but its abundance both in the core and the jet is only about half solar. Based on observations made with ESO telescopes at the Paranal Observatory under programme 078.C-0247(A).

Tsamis, Y. G.; Walsh, J. R.

2011-11-01

243

Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation.  

PubMed

Protein functional sites control most biological processes and are important targets for drug design and protein engineering. To characterize them, the evolutionary trace (ET) ranks the relative importance of residues according to their evolutionary variations. Generally, top-ranked residues cluster spatially to define evolutionary hotspots that predict functional sites in structures. Here, various functions that measure the physical continuity of ET ranks among neighboring residues in the structure, or in the sequence, are shown to inform sequence selection and to improve functional site resolution. This is shown first, in 110 proteins, for which the overlap between top-ranked residues and actual functional sites rose by 8% in significance. Then, on a structural proteomic scale, optimized ET led to better 3D structure-function motifs (3D templates) and, in turn, to enzyme function prediction by the Evolutionary Trace Annotation (ETA) method with better sensitivity of (40% to 53%) and positive predictive value (93% to 94%). This suggests that the similarity of evolutionary importance among neighboring residues in the sequence and in the structure is a universal feature of protein evolution. In practice, this yields a tool for optimizing sequence selections for comparative analysis and, via ET, for better predictions of functional site and function. This should prove useful for the efficient mutational redesign of protein function and for pharmaceutical targeting. PMID:20506260

Wilkins, A D; Lua, R; Erdin, S; Ward, R M; Lichtarge, O

2010-07-01

244

A Bayesian Method to Incorporate Hundreds of Functional Characteristics with Association Evidence to Improve Variant Prioritization  

PubMed Central

The increasing quantity and quality of functional genomic information motivate the assessment and integration of these data with association data, including data originating from genome-wide association studies (GWAS). We used previously described GWAS signals (“hits”) to train a regularized logistic model in order to predict SNP causality on the basis of a large multivariate functional dataset. We show how this model can be used to derive Bayes factors for integrating functional and association data into a combined Bayesian analysis. Functional characteristics were obtained from the Encyclopedia of DNA Elements (ENCODE), from published expression quantitative trait loci (eQTL), and from other sources of genome-wide characteristics. We trained the model using all GWAS signals combined, and also using phenotype specific signals for autoimmune, brain-related, cancer, and cardiovascular disorders. The non-phenotype specific and the autoimmune GWAS signals gave the most reliable results. We found SNPs with higher probabilities of causality from functional characteristics showed an enrichment of more significant p-values compared to all GWAS SNPs in three large GWAS studies of complex traits. We investigated the ability of our Bayesian method to improve the identification of true causal signals in a psoriasis GWAS dataset and found that combining functional data with association data improves the ability to prioritise novel hits. We used the predictions from the penalized logistic regression model to calculate Bayes factors relating to functional characteristics and supply these online alongside resources to integrate these data with association data.

Gagliano, Sarah A.; Barnes, Michael R.

2014-01-01

245

Bone Marrow-Derived CXCR4+ Cells Mobilized by Macrophage Colony-Stimulating Factor Participate in the Reduction of Infarct Area and Improvement of Cardiac Remodeling after Myocardial Infarction in Mice  

PubMed Central

The monocyte/macrophage lineage might affect the healing process after myocardial infarction (MI). Because macrophage colony-stimulating factor (M-CSF) stimulates differentiation and proliferation of this lineage, we examined the effect of M-CSF treatment on infarct size and left ventricular (LV) remodeling after MI. MI was induced in C57BL/6J mice by ligation of the left coronary artery. Either recombinant human M-CSF or saline was administered for 5 consecutive days after MI induction. M-CSF treatment significantly reduced the infarct size (P < 0.05) and scar formation (P < 0.05) and improved the LV dysfunction (percent fractional shortening, P < 0.001) after the MI. Immunohistochemistry revealed that M-CSF increased macrophage infiltration (F4/80) and neovascularization (CD31) of the infarct myocardium but did not increase myofibroblast accumulation (?-smooth muscle actin). M-CSF mobilized CXCR4+ cells into peripheral circulation, and the mobilized CXCR4+ cells were then recruited into the infarct area in which SDF-1 showed marked expression. The CXCR4 antagonist AMD3100 deteriorated the infarction and LV function after the MI in the M-CSF-treated mice. In conclusion, M-CSF reduced infarct area and improved LV remodeling after MI through the recruitment of CXCR4+ cells into the infarct myocardium by the SDF-1-CXCR4 axis activation; this suggests that the SDF-1-CXCR4 axis is as a potential target for the treatment of MI.

Morimoto, Hajime; Takahashi, Masafumi; Shiba, Yuji; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hatake, Kiyohiko; Motoyoshi, Kazuo; Ikeda, Uichi

2007-01-01

246

PACAP improves functional outcome in excitotoxic retinal lesion: an electroretinographic study.  

PubMed

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors occur throughout the nervous system, including the retina. PACAP exerts diverse actions in the eye: it influences ocular blood flow, contraction of the ciliary muscle, and has retinoprotective effects. This has been proven in different models of retinal degeneration. The in vivo protective effects of PACAP have been shown in retinal degeneration induced by kainic acid, optic nerve transection and ischemia. We have previously shown by morphological, morphometrical and immunohistochemical analyses that intravitreal PACAP administration protects against monosodium glutamate (MSG)-induced damage in neonatal rats. The question was raised whether these apparent morphological improvements by PACAP administration also lead to functional amelioration in MSG-induced retinal damage. The aim of the present study was to investigate the functional consequences of MSG treatment and the subsequent PACAP administration using electroretinographic measurements. The histological and morphometrical analyses supported the earlier findings that PACAP protected the retina in MSG-induced excitotoxicity. ERG recordings revealed a marked decrease in both the b- and a-wave values, reflecting the function of the inner retinal layers and the photoreceptors, respectively. In retinas receiving intravitreal PACAP treatment, these values were significantly increased. Thus, the functional outcome, although not parallel with the morphology, was significantly improved after PACAP treatment. The present observations are important from the clinical point of view showing, for the first time, that PACAP treatment is able to improve the functional properties of the retina in excitotoxic damage. PMID:20567936

Varga, Balazs; Szabadfi, Krisztina; Kiss, Peter; Fabian, Eszter; Tamas, Andrea; Griecs, Monika; Gabriel, Robert; Reglodi, Dora; Kemeny-Beke, Adam; Pamer, Zsuzsanna; Biro, Zsolt; Tosaki, Arpad; Atlasz, Tamas; Juhasz, Bela

2011-01-01

247

Improving Function in Age-Related Macular Degeneration: Design and Methods of a Randomized Clinical Trial  

PubMed Central

Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD’s prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population.

Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Tasman, William S.

2010-01-01

248

Improving Correlation Function Fitting with Ridge Regression: Application to Cross-correlation Reconstruction  

NASA Astrophysics Data System (ADS)

Cross-correlation techniques provide a promising avenue for calibrating photometric redshifts and determining redshift distributions using spectroscopy which is systematically incomplete (e.g., current deep spectroscopic surveys fail to obtain secure redshifts for 30%-50% or more of the galaxies targeted). In this paper, we improve on the redshift distribution reconstruction methods from our previous work by incorporating full covariance information into our correlation function fits. Correlation function measurements are strongly covariant between angular or spatial bins, and accounting for this in fitting can yield substantial reduction in errors. However, frequently the covariance matrices used in these calculations are determined from a relatively small set (dozens rather than hundreds) of subsamples or mock catalogs, resulting in noisy covariance matrices whose inversion is ill-conditioned and numerically unstable. We present here a method of conditioning the covariance matrix known as ridge regression which results in a more well behaved inversion than other techniques common in large-scale structure studies. We demonstrate that ridge regression significantly improves the determination of correlation function parameters. We then apply these improved techniques to the problem of reconstructing redshift distributions. By incorporating full covariance information, applying ridge regression, and changing the weighting of fields in obtaining average correlation functions, we obtain reductions in the mean redshift distribution reconstruction error of as much as ~40% compared to previous methods. We provide a description of POWERFIT, an IDL code for performing power-law fits to correlation functions with ridge regression conditioning that we are making publicly available.

Matthews, Daniel J.; Newman, Jeffrey A.

2012-02-01

249

Plasma Midregional Pro-Adrenomedullin Improves Prediction of Functional Outcome in Ischemic Stroke  

PubMed Central

Background To evaluate if plasma levels of midregional pro-adrenomedullin (MR-proADM) improve prediction of functional outcome in ischemic stroke. Methods In 168 consecutive ischemic stroke patients, plasma levels of MR-proADM were measured within 24 hours from symptom onset. Functional outcome was assessed by the modified Rankin Scale (mRS) at 90 days following stroke. Logistic regression, receiver operating characteristics (ROC) curve analysis, net reclassification improvement (NRI), and Kaplan-Meier survival analysis were applied. Results Plasma MR-proADM levels were found significantly higher in patients with unfavourable (mRS 3–6) compared to favourable (mRS 0–2) outcomes. MR-proADM levels were entered into a predictive model including the patients' age, National Institutes of Health Stroke Scale (NIHSS), and the use of recanalization therapy. The area under the ROC curve did not increase significantly. However, category-free NRI of 0.577 (p<0.001) indicated a significant improvement in reclassification of patients. Furthermore, MR-proADM levels significantly improved reclassification of patients in the prediction of outcome by the Stroke Prognostication using Age and NIHSS-100 (SPAN-100; NRI?=?0.175; p?=?0.04). Kaplan-Meier survival analysis showed a rising risk of death with increasing MR-proADM quintiles. Conclusions Plasma MR-proADM levels improve prediction of functional outcome in ischemic stroke when added to the patients' age, NIHSS on admission, and the use of recanalization therapy. Levels of MR-proADM in peripheral blood improve reclassification of patients when the SPAN-100 is used to predict the patients' functional outcome.

Gattringer, Thomas; Simmet, Nicole E.; Scharnagl, Hubert; Bocksrucker, Christoph; Lampl, Christian; Storch, Maria K.; Stojakovic, Tatjana; Fazekas, Franz

2013-01-01

250

COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia.  

PubMed

Preliminary evidence suggests that a single nucleotide polymorphism (SNP), the val108/158met SNP, within the gene that codes for catechol-O-methyltransferase (COMT), a key enzyme involved in regulating dopamine (DA) transmission within the prefrontal cortex (PFC), is related to cognitive function in schizophrenia and cognitive improvement with atypical antipsychotic drugs (APDs). Specifically, several studies have identified an association between working memory and executive functions, and COMT val108/158met genotype in schizophrenia; although there have been several negative findings that are likely related to small sample sizes and, possibly, medication status of patients at the time of testing. The association between COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine was investigated in a relatively large prospective sample of patients with schizophrenia, most of whom were unmedicated at baseline. Patients were genotyped for the COMT val108/158met SNP after completing a cognitive battery consisting of tests of attention, working memory, verbal learning and memory, executive function, and verbal fluency at baseline and after 6 weeks and 6 months of treatment with clozapine. Consistent with several previous studies, an association between COMT genotype and tests of executive function and working memory was identified at baseline. In addition, a novel interaction between genotype and improvement on tests of attention and verbal fluency was identified. Specifically, met homozygous and val/met heterozygous patients demonstrated significantly greater improvement than val homozygous patients following 6 months of treatment with clozapine. The results are discussed in relation to previous cross-sectional studies and prospective investigations of the associations between COMT genotype, cognition, and cognitive improvement with atypical APDs in schizophrenia. PMID:17123785

Woodward, Neil D; Jayathilake, Karu; Meltzer, Herbert Y

2007-02-01

251

Analysis and improvement of a chaos-based Hash function construction  

NASA Astrophysics Data System (ADS)

The construction of a new Hash function attracts much attention recently. In Kwok and Tang (2005) [Kwok HS, Tang WKS. A chaos-based cryptographic Hash function for message authentication. Int J Bifurcat Chaos 2005;15:4043-50], a chaos-based Hash function has been proposed. In this paper, the potential flaws in the original algorithm are analyzed in detail, and then the corresponding improving measures are proposed. We enhance the influence that each bit of the final Hash value is closely related to all the bits of the message or key and a single bit change in message or key results in great changes in the final Hash value. Simulation results show that the proposed improving algorithm has strong diffusion and confusion capability, good collision resistance, extreme sensitivity to message and secret key.

Deng, Shaojiang; Li, Yantao; Xiao, Di

2010-05-01

252

Second Preimage Attack on a Chaos-Based Hash Function Construction and Its Improvement  

NASA Astrophysics Data System (ADS)

Hash functions play an important role in cryptography. Recently, Hash functions based on chaotic map are attracting more and more attention. In 2005, Kwok and Tang proposed a chaos-based cryptographic hash function. Five years later, Deng and Xiao showed that this algorithm has low collision resistance and it does not have good diffusion and confusion property. Then, based on the weakness of this algorithm, they improved it and introduced the second version of the original algorithm. In this paper, we show that both algorithms: the first algorithm and the second version of the algorithm have the same weaknesses and they are not second preimage resistance. Then, we improve the second version of the algorithm and show that this algorithm has good confusion and diffusion property such as the second version of the original algorithm.

Hajibabaei, Zahra; Dakhilalian, Mohammad

253

Rationale for Combined Exercise and Cognition-Focused Interventions to Improve Functional Independence in People with Dementia  

Microsoft Academic Search

Evidence suggests that exercise and some cognition-focused intervention approaches can be used to elicit functional improvements in older people and, to some degree, those diagnosed with dementia. Independently, the two intervention types have been found to improve functional performance in people with dementia. The mechanisms underpinning these improvements come from comparable and diverse pathways. This suggests that it may be

Jeanette M. Thom; Linda Clare

2011-01-01

254

Recent trends in robot-assisted therapy environments to improve real-life functional performance after stroke  

Microsoft Academic Search

Upper and lower limb robotic tools for neuro-rehabilitation are effective in reducing motor impairment but they are limited in their ability to improve real world function. There is a need to improve functional outcomes after robot-assisted therapy. Improvements in the effectiveness of these environments may be achieved by incorporating into their design and control strategies important elements key to inducing

Michelle J Johnson; Clement J. Zablocki

2006-01-01

255

Brain Training Game Improves Executive Functions and Processing Speed in the Elderly: A Randomized Controlled Trial  

PubMed Central

Background The beneficial effects of brain training games are expected to transfer to other cognitive functions, but these beneficial effects are poorly understood. Here we investigate the impact of the brain training game (Brain Age) on cognitive functions in the elderly. Methods and Results Thirty-two elderly volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). This study was completed by 14 of the 16 members in the Brain Age group and 14 of the 16 members in the Tetris group. To maximize the benefit of the interventions, all participants were non-gamers who reported playing less than one hour of video games per week over the past 2 years. Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Each group played for a total of about 20 days. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into four categories (global cognitive status, executive functions, attention, and processing speed). Results showed that the effects of the brain training game were transferred to executive functions and to processing speed. However, the brain training game showed no transfer effect on any global cognitive status nor attention. Conclusions Our results showed that playing Brain Age for 4 weeks could lead to improve cognitive functions (executive functions and processing speed) in the elderly. This result indicated that there is a possibility which the elderly could improve executive functions and processing speed in short term training. The results need replication in large samples. Long-term effects and relevance for every-day functioning remain uncertain as yet. Trial Registration UMIN Clinical Trial Registry 000002825

Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Akitsuki, Yuko; Shigemune, Yayoi; Sekiguchi, Atsushi; Kotozaki, Yuka; Tsukiura, Takashi; Yomogida, Yukihito; Kawashima, Ryuta

2012-01-01

256

The Surface Glycoprotein of Feline Leukemia Virus Isolate FeLV-945 Is a Determinant of Altered Pathogenesis in the Presence or Absence of the Unique Viral Long Terminal Repeat  

PubMed Central

Feline leukemia virus (FeLV) is a naturally transmitted gammaretrovirus that infects domestic cats. FeLV-945, the predominant isolate associated with non-T-cell disease in a natural cohort, is a member of FeLV subgroup A but differs in sequence from the FeLV-A prototype, FeLV-A/61E, in the surface glycoprotein (SU) and long terminal repeat (LTR). Substitution of the FeLV-945 LTR into FeLV-A/61E resulted in pathogenesis indistinguishable from that of FeLV-A/61E, namely, thymic lymphoma of T-cell origin. In contrast, substitution of both FeLV-945 LTR and SU into FeLV-A/61E resulted in multicentric lymphoma of non-T-cell origin. These results implicated the FeLV-945 SU as a determinant of pathogenic spectrum. The present study was undertaken to test the hypothesis that FeLV-945 SU can act in the absence of other unique sequence elements of FeLV-945 to determine the disease spectrum. Substitution of FeLV-A/61E SU with that of FeLV-945 altered the clinical presentation and resulted in tumors that demonstrated expression of CD45R in the presence or absence of CD3. Despite the evident expression of CD45R, a typical B-cell marker, T-cell receptor beta (TCR?) gene rearrangement indicated a T-cell origin. Tumor cells were detectable in bone marrow and blood at earlier times during the disease process, and the predominant SU genes from proviruses integrated in tumor DNA carried markers of genetic recombination. The findings demonstrate that FeLV-945 SU alters pathogenesis, although incompletely, in the absence of FeLV-945 LTR. Evidence demonstrates that FeLV-945 SU and LTR are required together to fully recapitulate the distinctive non-T-cell disease outcome seen in the natural cohort.

Bolin, Lisa L.; Ahmad, Shamim; Lobelle-Rich, Patricia A.; Ooms, Tara G.; Alvarez-Hernandez, Xavier; Didier, Peter J.

2013-01-01

257

Improving Balance Function Using Low Levels of Electrical Stimulation of the Balance Organs  

NASA Technical Reports Server (NTRS)

Crewmembers returning from long-duration space flight face significant challenges due to the microgravity-induced inappropriate adaptations in balance/sensorimotor function. The Neuroscience Laboratory at JSC is developing a method based on stochastic resonance to enhance the brain's ability to detect signals from the balance organs of the inner ear and use them for rapid improvement in balance skill, especially when combined with balance training exercises. This method involves a stimulus delivery system that is wearable/portable and provides imperceptible electrical stimulation to the balance organs of the human body. Stochastic resonance (SR) is a phenomenon whereby the response of a nonlinear system to a weak periodic input signal is optimized by the presence of a particular non-zero level of noise. This phenomenon of SR is based on the concept of maximizing the flow of information through a system by a non-zero level of noise. Application of imperceptible SR noise coupled with sensory input in humans has been shown to improve motor, cardiovascular, visual, hearing, and balance functions. SR increases contrast sensitivity and luminance detection; lowers the absolute threshold for tone detection in normal hearing individuals; improves homeostatic function in the human blood pressure regulatory system; improves noise-enhanced muscle spindle function; and improves detection of weak tactile stimuli using mechanical or electrical stimulation. SR noise has been shown to improve postural control when applied as mechanical noise to the soles of the feet, or when applied as electrical noise at the knee and to the back muscles. SR using imperceptible stochastic electrical stimulation of the vestibular system (stochastic vestibular stimulation, SVS) applied to normal subjects has shown to improve the degree of association between the weak input periodic signals introduced via venous blood pressure receptors and the heart-rate responses. Also, application of SVS over 24 hours improves the long-term heart-rate dynamics and motor responsiveness as indicated by daytime trunk activity measurements in patients with multi-system atrophy, Parkinson s disease, or both, including patients who were unresponsive to standard therapy for Parkinson s disease. Recent studies conducted at the NASA JSC Neurosciences Laboratories showed that imperceptible SVS, when applied to normal young healthy subjects, leads to significantly improved balance performance during postural disturbances on unstable compliant surfaces. These studies have shown the benefit of SR noise characteristic optimization with imperceptible SVS in the frequency range of 0-30 Hz, and amplitudes of stimulation have ranged from 100 to 400 microamperes.

Bloomberg, Jacob; Reschke, Millard; Mulavara, Ajitkumar; Wood, Scott; Serrador, Jorge; Fiedler, Matthew; Kofman, Igor; Peters, Brian T.; Cohen, Helen

2012-01-01

258

Effect of Intracoronary Delivery of Autolologous Bone Marrow Mononuclear Cells Two to Three Weeks Following Acute Myocardial Infarction on Left-Ventricular Function: The LateTIME Randomized Trial  

PubMed Central

Context Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, since a substantial number of patients may not present for early cell delivery, we investigated the efficacy of autologous BMC delivery 2–3 weeks post-MI. Objective To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2–3 weeks following first MI. Design, Setting, and Patients LateTIME is a randomized, double-blind, placebo-controlled trial of the National Heart, Lung, and Blood Institute - sponsored Cardiovascular Cell Therapy Research Network (CCTRN) of 87 patients with significant LV dysfunction (LVEF ? 45%) following successful primary percutaneous coronary intervention (PCI). Interventions Intracoronary infusion of 150 × 106 autologous BMCs (total nucleated cells) or placebo (2:1 BMC:placebo) was performed within 12 hours of bone marrow aspiration after local automated cell processing. Main Outcome Measures The primary endpoints were changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone from baseline to 6 months as measured by cardiac MRI at a core lab blinded to treatment assignment Secondary endpoints included changes in LV volumes and infarct size. Results 87 patients were randomized between July 2008 and February 2011: mean age = 57 ± 11 yrs, 83% male. Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible and safe. The change from baseline to six months in the BMC group, when compared to the placebo group, for LVEF (48.7 to 49.2% vs. 45.3 to 48.8%; Difference = ?3.0, 95% CI ?7.0 to 0.9), wall motion in the infarct zone (6.2 to 6.5 vs. 4.9 to 5.9 mm; Difference = ?0.7, 95% CI ?2.8 to 1.3), and wall motion in the border zone (16.0 to 16.6 mm vs. 16.1 to 19.3 mm; Difference = ?2.6; 95% CI ?6.0 to 0.8) were not statistically significant. There was no significant change in LV volumes and infarct volumes decreased by a similar amount in both groups at 6 months compared to baseline. Conclusions Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs compared to intracoronary placebo infusion, 2–3 weeks after PCI did not improve global or regional function at 6 months.

Traverse, Jay H.; Henry, Timothy D.; Ellis, Stephen G.; Pepine, Carl J.; Willerson, James T.; Zhao, David X.M.; Forder, John R.; Byrne, Barry J.; Hatzopoulos, Antonis K.; Penn, Marc S.; Perin, Emerson C.; Baran, Kenneth W.; Chambers, Jeffrey; Lambert, Charles; Raveendran, Ganesh; Simon, Daniel I.; Vaughan, Douglas E.; Simpson, Lara M.; Gee, Adrian P.; Taylor, Doris A.; Cogle, Christopher R.; Thomas, James D.; Silva, Guilherme V.; Jorgenson, Beth C.; Olson, Rachel E.; Bowman, Sherry; Francescon, Judy; Geither, Carrie; Handberg, Eileen; Smith, Deirdre X.; Baraniuk, Sarah; Piller, Linda B.; Loghin, Catalin; Aguilar, David; Richman, Sara; Zierold, Claudia; Bettencourt, Judy; Sayre, Shelly L.; Vojvodic, Rachel W.; Skarlatos, Sonia I.; Gordon, David J.; Ebert, Ray F.; Kwak, Minjung; Moye, Lemuel A.; Simari, Robert D.

2013-01-01

259

An Improved, Bias-Reduced Probabilistic Functional Gene Network of Baker's Yeast, Saccharomyces cerevisiae  

PubMed Central

Background Probabilistic functional gene networks are powerful theoretical frameworks for integrating heterogeneous functional genomics and proteomics data into objective models of cellular systems. Such networks provide syntheses of millions of discrete experimental observations, spanning DNA microarray experiments, physical protein interactions, genetic interactions, and comparative genomics; the resulting networks can then be easily applied to generate testable hypotheses regarding specific gene functions and associations. Methodology/Principal Findings We report a significantly improved version (v. 2) of a probabilistic functional gene network [1] of the baker's yeast, Saccharomyces cerevisiae. We describe our optimization methods and illustrate their effects in three major areas: the reduction of functional bias in network training reference sets, the application of a probabilistic model for calculating confidences in pair-wise protein physical or genetic interactions, and the introduction of simple thresholds that eliminate many false positive mRNA co-expression relationships. Using the network, we predict and experimentally verify the function of the yeast RNA binding protein Puf6 in 60S ribosomal subunit biogenesis. Conclusions/Significance YeastNet v. 2, constructed using these optimizations together with additional data, shows significant reduction in bias and improvements in precision and recall, in total covering 102,803 linkages among 5,483 yeast proteins (95% of the validated proteome). YeastNet is available from http://www.yeastnet.org.

Lee, Insuk; Li, Zhihua; Marcotte, Edward M.

2007-01-01

260

Tiotropium Respimat(R) improves physical functioning in chronic obstructive pulmonary disease  

PubMed Central

Aim: This observational study with tiotropium Respimat® was performed in a real-life setting to investigate its effectiveness with regard to physical functioning and tolerability. Methods: Patients with chronic obstructive pulmonary disease (COPD; n = 1,230; mean age, 65.5 years) received tiotropium 5 ?g once daily via Respimat® Soft Inhaler for 6 weeks in an open-label observational study. At baseline and week 6, patients completed the Physical Function subdomain [PF-10] of the Short Form (SF) 36 questionnaire. Results: Improvement in standardized PF-10 score of ?10 points was achieved by 61.5% of patients. Mean (SD) standardized PF-10 scores improved by 13.4 (15.9) points, from 49.0 (24.5) to 62.3 points (23.5; P < 0.001). Results in smokers (n = 435) were not significantly different to those in nonsmokers. The general condition of patients improved during treatment. Adverse events were reported by 4.0% of patients and were chiefly respiratory symptoms and dry mouth. Conclusion: In COPD patients receiving tiotropium Respimat® in daily practice, physical function improved rapidly within 6 weeks of treatment, irrespective of smoking status.

Rau-Berger, Heike; Mitfessel, Harald; Glaab, Thomas

2010-01-01

261

Definition of a 4D continuous polar transformation for the tracking and the analysis of LV motion  

Microsoft Academic Search

A 4D polar transformation is defined to describe the left ventricle (LV) motion and a method is presented to estimate it from sequences of 3D images. The transformation is defined in 3D-planispheric coordinates by a small number of parameters involved in a set of simple linear equations. It is continuous and regular in time and space, periodicity in time can

Jérôme Declerck; Jacques Feldmar; Nicholas Ayache

1997-01-01

262

Declining ambient air pollution and lung function improvement in Austrian children  

NASA Astrophysics Data System (ADS)

Three thousand four hundred fifty-one Austrian elementary school children were examined (between 2 and 8 times) by spirometry by standardized methods, over a 5 yr period. The districts where they lived were grouped into those where NO 2 declined during this period (by at least 30 ?g/m 3 measured as half year means) and those with less or no decline in ambient NO 2. In both groups of districts, SO 2 and TSP fell by similar amounts over this period. A continuous improvement of MEF25 (maximum exspiratory flow rate at 25% vital capacity) was found in districts with declining ambient NO 2. Populations did not differ in respect of anthropometric factors, passive smoking or socioeconomic status. A birth cohort from this study population which was followed up to age 18 confirmed the improved growth of MEF25 with decline in NO 2, while the improved growth of forced vital capacity was more related to decline in SO 2. This study provides the first evidence that improvements in the outdoor air quality during the 1980s are correlated with health benefits, and suggest that adverse effects on lung function related to ambient air pollution are reversible before adulthood. Improvement of small airway functions appeared to be more dependent on reductions of NO 2 than reduction in SO 2 and TSP.

Neuberger, Manfred; Moshammer, Hanns; Kundi, Michael

263

Arginine improves peroxisome functioning in cells from patients with a mild peroxisome biogenesis disorder  

PubMed Central

Background Zellweger spectrum disorders (ZSDs) are multisystem genetic disorders caused by a lack of functional peroxisomes, due to mutations in one of the PEX genes, encoding proteins involved in peroxisome biogenesis. The phenotypic spectrum of ZSDs ranges from an early lethal form to much milder presentations. In cultured skin fibroblasts from mildly affected patients, peroxisome biogenesis can be partially impaired which results in a mosaic catalase immunofluorescence pattern. This peroxisomal mosaicism has been described for specific missense mutations in various PEX genes. In cell lines displaying peroxisomal mosaicism, peroxisome biogenesis can be improved when these are cultured at 30°C. This suggests that these missense mutations affect the folding and/or stability of the encoded protein. We have studied if the function of mutant PEX1, PEX6 and PEX12 can be improved by promoting protein folding using the chemical chaperone arginine. Methods Fibroblasts from three PEX1 patients, one PEX6 and one PEX12 patient were cultured in the presence of different concentrations of arginine. To determine the effect on peroxisome biogenesis we studied the following parameters: number of peroxisome-positive cells, levels of PEX1 protein and processed thiolase, and the capacity to ?-oxidize very long chain fatty acids and pristanic acid. Results Peroxisome biogenesis and function in fibroblasts with mild missense mutations in PEX1, 6 and 12 can be improved by arginine. Conclusion Arginine may be an interesting compound to promote peroxisome function in patients with a mild peroxisome biogenesis disorder.

2013-01-01

264

Progress in TILLING as a tool for functional genomics and improvement of crops.  

PubMed

Food security is a global concern and substantial yield increases in crops are required to feed the growing world population. Mutagenesis is an important tool in crop improvement and is free of the regulatory restrictions imposed on genetically modified organisms. Targeting Induced Local Lesions in Genomes (TILLING), which combines traditional chemical mutagenesis with high-throughput genome-wide screening for point mutations in desired genes, offers a powerful way to create novel mutant alleles for both functional genomics and improvement of crops. TILLING is generally applicable to genomes whether small or large, diploid or even allohexaploid, and shows great potential to address the major challenge of linking sequence information to the function of genes and to modulate key traits for plant breeding. TILLING has been successfully applied in many crop species and recent progress in TILLING is summarized below, especially on the developments in mutation detection technology, application of TILLING in gene functional studies and crop breeding. The potential of TILLING/EcoTILLING for functional genetics and crop improvement is also discussed. Furthermore, a small-scale forward strategy including backcross and selfing was conducted to release the potential mutant phenotypes masked in M2 (or?M3) plants. PMID:24618006

Chen, Liang; Hao, Liugen; Parry, Martin A J; Phillips, Andrew L; Hu, Yin-Gang

2014-05-01

265

Dejian Mind-Body Intervention Improves the Cognitive Functions of a Child with Autism  

PubMed Central

There has been increasing empirical evidence for the enhancing effects of Dejian Mind-Body Intervention (DMBI), a traditional Chinese Shaolin healing approach, on human frontal brain activity/functions, including patients with autism who are well documented to have frontal lobe problems. This study aims to compare the effects of DMBI with a conventional behavioural/cognitive intervention (CI) on enhancing the executive functions and memory of a nine-year-old boy with low-functioning autism (KY) and to explore possible underlying neural mechanism using EEG theta cordance. At post-one-month DMBI, KY's inhibitory control, cognitive flexibility, and memory functioning have significantly improved from “severely-to-moderately impaired” to “within-normal” range. This improvement was not observed from previous 12-month CI. Furthermore, KY showed increased cordance gradually extending from the anterior to the posterior brain region, suggesting possible neural mechanism underlying his cognitive improvement. These findings have implicated potential applicability of DMBI as a rehabilitation program for patients with severe frontal lobe and/or memory disorders.

Chan, Agnes S.; Sze, Sophia L.; Cheung, Mei-Chun; Han, Yvonne M. Y.; Leung, Winnie W. M.; Shi, Dejian

2011-01-01

266

Chronic activation of a designer Gq-coupled receptor improves ? cell function  

PubMed Central

Type 2 diabetes (T2D) has emerged as a major threat to human health in most parts of the world. Therapeutic strategies aimed at improving pancreatic ? cell function are predicted to prove beneficial for the treatment of T2D. In the present study, we demonstrate that drug-mediated, chronic, and selective activation of ? cell Gq signaling greatly improve ? cell function and glucose homeostasis in mice. These beneficial metabolic effects were accompanied by the enhanced expression of many genes critical for ? cell function, maintenance, and differentiation. By employing a combination of in vivo and in vitro approaches, we identified a novel ? cell pathway through which receptor-activated Gq leads to the sequential activation of ERK1/2 and IRS2 signaling, thus triggering a series of events that greatly improve ? cell function. Importantly, we found that chronic stimulation of a designer Gq-coupled receptor selectively expressed in ? cells prevented both streptozotocin-induced diabetes and the metabolic deficits associated with the consumption of a high-fat diet in mice. Since ? cells are endowed with numerous receptors that mediate their cellular effects via activation of Gq-type G proteins, our findings provide a rational basis for the development of novel antidiabetic drugs targeting this class of receptors.

Jain, Shalini; de Azua, Inigo Ruiz; Lu, Huiyan; White, Morris F.; Guettier, Jean-Marc; Wess, Jurgen

2013-01-01

267

Resveratrol, an activator of SIRT1, upregulates AMPK and improves cardiac function in heart failure.  

PubMed

Reduced AMP-activated protein kinase (AMPK) expression has been shown to play a significant role in the cardiac dysfunction in heart failure. This study was designed to examine the effect of resveratrol, a potent activator of silent information regulator (SIRT1), on cardiac function and AMPK expression in heart failure. Adult male rat left anterior descending arteries were ligated, and they were fed with either a regular diet or a diet enriched with resveratrol. Heart failure was produced by myocardial infarction, and was associated with markedly increased AMPK and SIRT1 protein levels. Resveratrol treatment had a tremendous beneficial effect, both in terms of improving AMPK expression and on cardiac function. Decreased cardiac function and AMPK expression were also found in SIRT1 knockout (+/-) mice. In cultured cardiomyocytes, resveratrol increased AMPK and SIRT1 expressions, and overexpression of SIRT1 was found to be sufficient to activate AMPK in H9c2 cells. In contrast, pretreatment of cardiomyocytes with an SIRT1 antagonist, nicotinamide, blocked these beneficial effects of resveratrol. Therefore, the protective effects of resveratrol were found to be dependent on its ability to activate SIRT1 and improve AMPK expression. These results demonstrated that in heart failure, the enzymatic activity of cardiac SIRT1 is increased, which contributes to increased expression of AMPK, and resveratrol enhances the expression of AMPK and improves cardiac function through the activation of SIRT1. PMID:24535859

Gu, X S; Wang, Z B; Ye, Z; Lei, J P; Li, L; Su, D F; Zheng, X

2014-01-01

268

Selective GABAA ?5 Positive Allosteric Modulators Improve Cognitive Function in Aged Rats with Memory Impairment  

PubMed Central

A condition of excess activity in the hippocampal formation is observed in the aging brain and in conditions that confer additional risk during aging for Alzheimer’s disease. Compounds that act as positive allosteric modulators at GABAA ?5 receptors might be useful in targeting this condition because GABAA ?5 receptors mediate tonic inhibition of principal neurons in the affected network. While agents to improve cognitive function in the past focused on inverse agonists, which are negative allosteric modulators at GABAA ?5 receptors, research supporting that approach used only young animals and predated current evidence for excessive hippocampal activity in age-related conditions of cognitive impairment. Here, we used two compounds, Compound 44 [6,6-dimethyl-3-(3-hydroxypropyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one] and Compound 6 [methyl 3,5-diphenylpyridazine-4-carboxylate], with functional activity as potentiators of ?-aminobutyric acid at GABAA ?5 receptors, to test their ability to improve hippocampal-dependent memory in aged rats with identified cognitive impairment. Improvement was obtained in aged rats across protocols differing in motivational and performance demands and across varying retention intervals. Significant memory improvement occurred after either intracereboventricular infusion with Compound 44 (100 ?g) in a water maze task or systemic administration with Compound 6 (3 mg/kg) in a radial arm maze task. Furthermore, systemic administration improved behavioral performance at dosing shown to provide drug exposure in the brain and in vivo receptor occupancy in the hippocampus. These data suggest a novel approach to improve neural network function in clinical conditions of excess hippocampal activity.

Koh, Ming Teng; Rosenzweig-Lipson, Sharon; Gallagher, Michela

2012-01-01

269

HIGH RESOLUTION H{alpha} IMAGES OF THE BINARY LOW-MASS PROPLYD LV 1 WITH THE MAGELLAN AO SYSTEM  

SciTech Connect

We utilize the new Magellan adaptive optics system (MagAO) to image the binary proplyd LV 1 in the Orion Trapezium at H{alpha}. This is among the first AO results in visible wavelengths. The H{alpha} image clearly shows the ionization fronts, the interproplyd shell, and the cometary tails. Our astrometric measurements find no significant relative motion between components over {approx}18 yr, implying that LV 1 is a low-mass system. We also analyze Large Binocular Telescope AO observations, and find a point source which may be the embedded protostar's photosphere in the continuum. Converting the H magnitudes to mass, we show that the LV 1 binary may consist of one very-low-mass star with a likely brown dwarf secondary, or even plausibly a double brown dwarf. Finally, the magnetopause of the minor proplyd is estimated to have a radius of 110 AU, consistent with the location of the bow shock seen in H{alpha}.

Wu, Y.-L.; Close, L. M.; Males, J. R.; Follette, K.; Morzinski, K.; Kopon, D.; Rodigas, T. J.; Hinz, P. [Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States); Puglisi, A.; Esposito, S.; Pinna, E.; Riccardi, A.; Xompero, M.; Briguglio, R., E-mail: yalinwu@email.arizona.edu [INAF-Osservatorio Astrofisico di Arcetri, Largo E. Fermi 5, I-50125 Firenze (Italy)

2013-09-01

270

The Natural-Fit Handrim: Factors Related to Improvement in Symptoms and Function in Wheelchair Users  

PubMed Central

Background/Objective: People with spinal cord injury (SCI) may spend several decades using a wheelchair as their primary means of mobility. Secondary injury and a decline in independence over time are common with manual wheelchair users who, in turn, may require increased assistance as time passes. The Natural-Fit contoured handrim has been shown to improve symptoms and function in people with SCI who use manual wheelchairs and who have experienced upper extremity pain. The objective of this study was to determine the factors associated with improved symptoms and functions. Participants: 87 people who purchased the ergonomic wheelchair handrims. Participants were predominately men, with a median age of 51 to 55 years, median level of injury T10 to T12, median time in a wheelchair of 15 years, and they had used the contoured rims for 1 to 2 years. Methods: This was a mail survey of 217 people who purchased the rims. The survey was mailed out from the manufacturer and was anonymously returned to the physical therapy department of a university. A $10 incentive was offered for returning the survey. Results: The majority of participants reported improvements in upper extremity symptoms, ease of wheelchair propulsion, and functional status. Longer use of the rims was associated with reported improvement in ease of wheelchair propulsion and reduction in pain in hands and wrists. Conclusion: If a simple modification of the wheelchair can help bring about significant changes in the users' symptoms and function, this modification should be incorporated by people who use manual wheelchairs before decline in function begins. Proactive intervention may alleviate symptoms, help the person maintain maximal independence, and prolong the length of time the individual remains independent.

Dieruf, Kathy; Ewer, Lynette; Boninger, David

2008-01-01

271

Functional improvements desired by patients before and in the first year after total hip arthroplasty  

PubMed Central

Background In the field of rehabilitation, patients are supposed to be experts on their own lives, but the patient’s own desires in this respect are often not reported. Our objectives were to describe the patients’ desires regarding functional improvements before and after total hip arthroplasty (THA). Methods Sixty-four patients, 34 women and 30 men, with a mean age of 65 years, were asked to describe in free text which physical functions they desired to improve. They were asked before surgery and at three and 12 months after surgery. Each response signified one desired improvement. The responses were coded according to the International Classification of Functioning, Disability and Health (ICF) to the 1st, 2nd and 3rd category levels. The frequency of the codes was calculated as a percentage of the total number of responses of all assessments times and in percentage of each time of assessment. Results A total of 333 responses were classified under Part 1 of the ICF, Functioning and Disability, and 88% of the responses fell into the Activities and Participation component. The numbers of responses classified into the Activities and Participation component were decreasing over time (p < 0.001). The categories of Walking (d450), Moving around (d455), and Recreation and leisure (d920) included more than half of the responses at all the assessment times. At three months after surgery, there was a trend that fewer responses were classified into the Recreation and leisure category, while more responses were classified into the category of Dressing (d540). Conclusions The number of functional improvements desired by the patients decreased during the first postoperative year, while the content of the desires before and one year after THA were rather consistent over time and mainly concerned with the ability to walk and participate in recreation and leisure activities. At three months, however, there was a tendency that the patients were more concerned about the immediate problems with putting on socks and shoes.

2013-01-01

272

Sleep Extension Improves Neurocognitive Functions in Chronically Sleep-Deprived Obese Individuals  

PubMed Central

Background Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals. Objective To characterize neurocognitive functions and assess its reversibility. Design Prospective cohort study. Setting Tertiary Referral Research Clinical Center. Patients A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m2) men and pre-menopausal women. Intervention Sleep extension (468±88 days) with life-style modifications. Measurements Neurocognitive functions, sleep quality and sleep duration. Results At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p?=?0.02), and lower urinary dopamine levels (p?=?0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N?=?74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p?=?0.04), and daytime sleepiness tended to improve (p?=?0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p?=?0.001), and memory and executive functions tended to improve (p?=?0.07 and p?=?0.06). Serum cortisol increased by 17% (p?=?0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function. Limitations Drop-out rate. Conclusions Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population. Trail registration www.ClinicalTrials.gov NCT00261898. NIDDK protocol 06-DK-0036

Lucassen, Eliane A.; Piaggi, Paolo; Dsurney, John; de Jonge, Lilian; Zhao, Xiong-ce; Mattingly, Megan S.; Ramer, Angela; Gershengorn, Janet; Csako, Gyorgy; Cizza, Giovanni

2014-01-01

273

Improvement of neuropsychological function in cognitively impaired multiple sclerosis patients treated with natalizumab: a preliminary study.  

PubMed

Treatment with natalizumab has been shown to reduce physical disability in people with multiple sclerosis (MS). However, its effect on neuropsychological dysfunction is not well understood. A single-center, open-label, retrospective study was conducted to evaluate the effect of natalizumab treatment on neuropsychological function in individuals with relapsing-remitting multiple sclerosis (RRMS) who had a measurable neuropsychological deficit prior to natalizumab treatment. A total of 40 MS patients (mean age, 48.5 years; 77.5% female) were evaluated on a neuropsychological battery of nine tests designed for MS patients before and after 6 or more months of treatment with natalizumab. Posttreatment neuropsychological testing results were compared to baseline results. The mean baseline Neuropsychological Impairment Index was 0.49, which improved to 0.41 after treatment (P = .0002) as analyzed using the Wilcoxon signed rank test. The mean Beck Depression Inventory-II (BDI-II) score improved by 2.45 points (P = .001). The mean Expanded Disability Status Scale (EDSS) score improved by 0.30 (P = .02). A total of 52.5% of patients showed neuropsychological improvement, while 30.0% showed no change and 17.5% had worsening. Magnetic resonance imaging showed no changes. The specific prior disease-modifying therapy had no influence on the results for natalizumab effect. The results of this study show that natalizumab can stabilize or improve neuropsychological function in RRMS patients. The improvement was consistent with, but apparently independent of, improvement in depression and physical disability. PMID:24453740

Edwards, Keith R; Goodman, William A; Ma, Carl Y

2012-01-01

274

Functional Complementation of a Model Target to Study Vpu Sensitivity  

PubMed Central

HIV-1 forms infectious particles with Murine Leukemia virus (MLV) Env, but not with the closely related Gibbon ape Leukemia Virus (GaLV) Env. We have determined that the incompatibility between HIV-1 and GaLV Env is primarily caused by the HIV-1 accessory protein Vpu, which prevents GaLV Env from being incorporated into particles. We have characterized the ‘Vpu sensitivity sequence’ in the cytoplasmic tail domain (CTD) of GaLV Env using a chimeric MLV Env with the GaLV Env CTD (MLV/GaLV Env). Vpu sensitivity is dependent on an alpha helix with a positively charged face containing at least one Lysine. In the present study, we utilized functional complementation to address whether all the three helices in the CTD of an Env trimer have to contain the Vpu sensitivity motif for the trimer to be modulated by Vpu. Taking advantage of the functional complementation of the binding defective (D84K) and fusion defective (L493V) MLV and MLV/GaLV Env mutants, we were able to assay the activity of mixed trimers containing both MLV and GaLV CTDs. Mixed trimers containing both MLV and GaLV CTDs were functionally active and remained sensitive to Vpu. However, trimers containing an Env with the GaLV CTD and an Env with no CTD remained functional but were resistant to Vpu. Together these data suggest that the presence of at least one GaLV CTD is sufficient to make an Env trimer sensitive to Vpu, but only if it is part of a trimeric CTD complex.

Janaka, Sanath Kumar; Faurot, Jared; Johnson, Marc C.

2013-01-01

275

Prognostic significance of left ventricular diastolic function in burn patients.  

PubMed

Severe inflammation leads to cardiac diastolic dysfunction, an independent prognostic marker for the mortality of critically ill patients. We investigated the possible molecular mechanism from inflammatory cytokines (tumor necrosis factor ? [TNF-?] and interleukin 6 [IL-6]) causing left ventricular (LV) diastolic dysfunction in critically burned patients. We consecutively enrolled 56 critically burned patients who were admitted to the intensive care unit and performed transthoracic echocardiography to evaluate LV diastolic function. Sarcoplasmic reticulum Ca²?-ATPase 2 (SERCA2) gene expression in HL-1 cardiomyocytes was used as a molecular phenotype of diastolic heart failure. Soluble plasma levels of TNF-? and IL-6 were measured in all subjects. The effect of serum from the burned patients on SERCA2 gene expression of HL-1 cardiomyocytes was investigated. The total body surface area of burned patients was proportional to serum level of IL-6 and TNF-? (P < 0.001 for each). Significant correlations were found for TNF-? and decelerating time, E/A, and E/Em (r² = 0.59, 0.45, and 0.52; P <0.001 for each) and for IL-6 and decelerating time, E/A, and E/Em (r² = 0.63, 0.60, and 0.62; P < 0.001 for each). Diastolic function improved significantly in association with decrease in cytokines after burned patients were transferred to general ward (P < 0.001). Tumor necrosis factor ?, IL-6, and sera from critically burned patients downregulated the expression of the SERCA2 gene in HL-1 cardiomyocytes. There was a significant correlation between LV diastolic dysfunction and in-hospital mortality in critically burned patients (hazard ratio, 3.92; P = 0.034) after risk factors were adjusted. Inflammatory cytokines may be associated with cardiac diastolic, which could be an independent prognostic factor in burn patients. Novel therapeutic strategies may be applied in critically burned patients with LV diastolic dysfunction by modulating inflammatory reactions. PMID:22508290

Lin, Chih-Yun; Wu, Cho-Kai; Yeong, Eng-Kean; Lin, Heng-Hsu; Huang, Yin-Tsen; Lee, Jen-Kuang; Lin, Yu-Hsun; Chiang, Fu-Tien; Tang, Yueh-Bih; Tsai, Chia-Ti

2012-05-01

276

Improving 3D active appearance model segmentation of the left ventricle with Jacobian tuning  

NASA Astrophysics Data System (ADS)

Automated image processing techniques may prove invaluable in the examination of real-time three-dimensional echocardiograms, by providing quantitative and objective measurements of functional parameters such as left ventricular (LV) volume and ejection fraction. In this study, we investigate the use of active appearance models (AAMs) for automatic detection of left ventricular endocardial contours. AAMs are especially useful in segmenting ultrasound images, due to their ability to model the typical LV appearance. However, since only a limited number of images is available for training, the model may be incapable of capturing the large variability in ultrasound image appearance. This may cause standard AAM matching procedures to fail if the model and image are significantly different. Recently, a Jacobian-tuning method for AAM matching was proposed, which allowed the model's training matrix to adapt to the new, unseen image. This may potentially result in a more robust matching. To compare both matching methods, AAMs were built with end-diastolic images from 54 patients. Larger capture ranges and higher accuracy were obtained when the new method was used. In conclusion, this method has great potential for segmentation in echocardiograms and will improve the assessment of LV functional parameters.

Leung, K. Y. E.; van Stralen, M.; Voormolen, M. M.; de Jong, N.; van der Steen, A. F. W.; Reiber, J. H. C.; Bosch, J. G.

2008-04-01

277

Regulation of the immediate-early genes of white spot syndrome virus by Litopenaeus vannamei kruppel-like factor (LvKLF).  

PubMed

Kruppel-like factors (KLFs) belong to a subclass of Cys2/His2 zinc-finger DNA-binding proteins, and act as important regulators with diverse roles in cell growth, proliferation, differentiation, apoptosis and tumorigenesis. Our previous research showed that PmKLF from Penaeus monodon is crucial for white spot syndrome virus (WSSV) infection, yet the mechanisms by which PmKLF influences WSSV infection remain unclear. This study cloned KLF from Litopenaeus vannamei (LvKLF), which had 93% similarity with PmKLF. LvKLF formed a dimer via the C-terminal zinc-finger motif. Knockdown of LvKLF expression by dsRNA injection in WSSV-challenged shrimps was found to significantly inhibit the transcription of two important immediate-early (IE) genes, IE1 and WSSV304, and also reduced WSSV copy numbers. Moreover, reporter assays revealed that the promoter activities of these two WSSV IE genes were substantially enhanced by LvKLF. Mutations introduced in the promoter sequences of IE1 and WSSV304 were shown to abolish LvKLF activation of promoter activities; and an electrophoretic mobility shift assay demonstrated that LvKLF binds to putative KLF-response elements (KRE) in the promoters. Taken together, these results indicate that LvKLF transcriptional regulation of key IE genes is critical to WSSV replication. PMID:24881625

Huang, Ping-Han; Lu, Shao-Chia; Yang, Shu-Han; Cai, Pei-Si; Lo, Chu-Fang; Chang, Li-Kwan

2014-10-01

278

Improvement of the poly-3-hexylthiophene transistor performance using small molecule contact functionalization  

NASA Astrophysics Data System (ADS)

We demonstrate an approach to improve poly-3-hexylthiophene field effect transistors by modifying the gold contacts with monolayer thick pentacenequinone (PQ) or naphthalene (NL). The effective contact resistance is reduced by a factor of two and sixteen for interlayers of PQ and NL, respectively. The observation is attributed to different injection barriers at the metal-organic interface caused by the functionalization and to an additional tunneling barrier enhancing the on/off ratios. This barrier yields to activation energies of 37 meV (NL) and 104 meV (PQ) below 190 K, which are smaller than without functionalization, 117 meV.

Winter, Rebecca; Hammer, Maria S.; Deibel, Carsten; Pflaum, Jens

2009-12-01

279

Lateral Unicompartmental Knee Arthroplasty Relieves Pain and Improves Function in Posttraumatic Osteoarthritis  

Microsoft Academic Search

Background  Posttraumatic arthritis secondary to lateral tibial plateau fracture malunion causes pain and limited function for patients.\\u000a It is sometimes technically challenging to correct malalignment in these patients with advanced arthritis using osteotomies.\\u000a Lateral unicompartmental knee arthroplasty (UKA) may be an option to treat such patients.\\u000a \\u000a \\u000a \\u000a \\u000a Questions\\/purposes  We asked whether UKA for lateral posttraumatic osteoarthritis (1) reliably alleviates pain and improve function,

Sebastien Lustig; Sebastien Parratte; Robert A. Magnussen; Jean-Noel Argenson; Philippe Neyret

280

Improving gross motor function and postural control with hippotherapy in children with Down syndrome: case reports.  

PubMed

The purpose of this case report is to describe the impact of an 11-week hippotherapy program on the gross motor functions of two children (respectively 28 and 37 months old) diagnosed with Down syndrome. Hippotherapy is a strategy that uses the horse's motion to stimulate and enhance muscle contraction and postural control. The children were assessed by the Gross Motor Function Measure (GMFM) and accelerometry. The results indicate that both children improved on many dimensions of the GMFM. Power spectral analysis of the acceleration signals showed improvement in postural control of either the head or trunk, because the children adopted two different adaptative strategies to perturbation induced by the moving horse. PMID:20673078

Champagne, Danielle; Dugas, Claude

2010-11-01

281

Increasing MuSK Activity Delays Denervation and Improves Motor Function in ALS Mice  

PubMed Central

Summary ALS is a devastating disease, progressing from detachment of motor nerve terminals to complete muscle paralysis and lethal respiratory failure within five years of diagnosis. Genetic studies have linked mutations in several genes to ALS, and mice bearing mutations in SOD1 recapitulate hallmark features of the disease. We have taken a novel approach to ALS by targeting and co-opting the normal retrograde signaling pathway that promotes attachment of nerve terminals to muscle. We crossed SOD1G93A mice with transgenic mice that express MuSK, a receptor tyrosine kinase required for retrograde signaling, and we used histological and behavioral assays to assess motor innervation and behavior. A threefold increase in MuSK expression delayed the onset and reduced the extent of muscle denervation, improving motor function for more than a month, without altering survival. These findings suggest that increasing MuSK activity by pharmacological means has the potential to improve motor function in ALS.

Perez-Garcia, Maria J.; Burden, Steven J.

2012-01-01

282

Stratum corneum drying drives vertical compression and lipid organization and improves barrier function in vitro.  

PubMed

The stratum corneum dehydrates after exogenous hydration due to skincare or bathing. In this study, sheets of stratum corneum were isolated from reconstructed human epidermis and the barrier function and structure of these sheets were assessed during drying with the aim of improving our understanding of skincare. Water diffusion through the sheets of stratum corneum decreased with drying, accompanied by decreased thickness and increased visible light transmission through the sheets. Electron paramagnetic resonance revealed that the order parameter values of stratum corneum lipids increased with drying. X-ray diffraction analysis revealed increases in the diffraction intensity of lamellar structures, with an 11-12 nm periodicity and spacing of 0.42 nm for lattice structures with drying. These results suggest that the drying process improves the barrier function of the stratum corneum by organizing the intercellular lipids in a vertically compressed arrangement. PMID:23165657

Iwai, Ichiro; Kunizawa, Naomi; Yagi, Eiichiro; Hirao, Tetsuji; Hatta, Ichiro

2013-03-27

283

Does an exercise aimed at improving swallow function have an effect on vocal function in the healthy elderly?  

PubMed

Age-related sarcopenia or muscle wasting contributes to changes in the ability to perform activities of daily living, changes in deglutition, and changes in vocal function. The Shaker Exercise, an isometric and isokinetic exercise, has been shown to strengthen suprahyoid muscles and increase deglutitive anteroposterior (AP) upper esophageal sphincter (UES) opening diameter. The aim of this study was to determine if this exercise has an effect on the age-related changes in vocal function and deglutition in healthy older adults. Eleven females and 10 males, aged 65-78 years (mean = 70 +/- 4 years) and with a negative history for dysphagia and voice disorders, participated by exercising three times per day for 6 weeks. Five age-matched controls did not perform the exercise. Acoustic analysis of voice and biomechanical analysis of deglutition were performed before and after 6 weeks of exercise. Controls participated in voice analysis only. Dysphonia Severity Index (DSI), a multivariate voice index, was used to compare voice production initially and after 6 weeks. Deglutitive biomechanical measures increased and DSI scores improved in 10 of 21 participants following 6 weeks of the exercise. DSI for controls did not change over the 6-week period. Ten of 21 exercise participants experienced improved deglutitive biomechanics and DSI scores. Accuracy of exercise performance, compliance, and/or disclosed alterations in health status may contribute to the lack of deglutitive and DSI change in the participants who did not experience change in function. A large randomized control study, including periodic monitoring of health status, exercise performance accuracy, and compliance, is warranted to evaluate the affect of this exercise on deglutition as well as voice. The Shaker Exercise could be recommended as a preventative measure to diminish the effect of sarcopenia on the muscles used in deglutition and voice and alter the progression of the characteristic senescent voice and swallow changes. PMID:18437461

Easterling, Caryn

2008-09-01

284

Directed Epicardial Assistance in Ischemic Cardiomyopathy: Flow and Function Using Cardiac Magnetic Resonance Imaging  

PubMed Central

Background Heart failure after myocardial infarction (MI) is a result of increased myocardial workload, adverse left ventricular (LV) geometric remodeling, and less efficient LV fluid movement. In this study we utilize cardiac magnetic resonance imaging to evaluate ventricular function and flow after placement of a novel directed epicardial assist device. Methods Five swine underwent posterolateral MI and were allowed to remodel for 12 weeks. An inflatable bladder was positioned centrally within the infarct and secured with mesh. The device was connected to an external gas exchange pump, which inflated and deflated in synchrony with the cardiac cycle. Animals then underwent cardiac magnetic resonance imaging during active epicardial assistance and with no assistance. Results Active epicardial assistance of the infarct showed immediate improvement in LV function and intraventricular flow. Ejection fraction significantly improved from 26.0% ± 4.9% to 37.3% ± 4.5% (p < 0.01). End-systolic volume (85.5 ± 12.7 mL versus 70.1 ± 11.9 mL, p < 0.01) and stroke volume (28.5 ± 4.4 mL versus 39.9 ± 3.1 mL, p = 0.03) were also improved with assistance. End-diastolic volume and regurgitant fraction did not change with treatment. Regional LV flow improved both qualitatively and quantitatively during assistance. Unassisted infarct regional flow showed highly dis-coordinate blood movement with very slow egress from the posterolateral wall. Large areas of stagnant flow were also identified. With assistance, posterolateral wall blood velocities improved significantly during both systole (26.4% ± 3.2% versus 12.6% ± 1.2% maximum velocity; p < 0.001) and diastole (54.3% ± 9.3% versus 24.2% ± 2.5% maximum velocity; p < 0.01). Conclusions Directed epicardial assistance can improve LV function and flow in ischemic cardiomyopathy. This novel device may provide a valuable alternative to currently available heart failure therapies.

McGarvey, Jeremy R.; Kondo, Norihiro; Takebe, Manabu; Koomalsingh, Kevin J.; Witschey, Walter R.T.; Barker, Alex J.; Markl, Michael; Takebayashi, Satoshi; Shimaoka, Toru; Gorman, Joseph H.; Gorman, Robert C.; Pilla, James J.

2013-01-01

285

Parametric Bayesian priors and better choice of negative examples improve protein function prediction  

PubMed Central

Motivation: Computational biologists have demonstrated the utility of using machine learning methods to predict protein function from an integration of multiple genome-wide data types. Yet, even the best performing function prediction algorithms rely on heuristics for important components of the algorithm, such as choosing negative examples (proteins without a given function) or determining key parameters. The improper choice of negative examples, in particular, can hamper the accuracy of protein function prediction. Results: We present a novel approach for choosing negative examples, using a parameterizable Bayesian prior computed from all observed annotation data, which also generates priors used during function prediction. We incorporate this new method into the GeneMANIA function prediction algorithm and demonstrate improved accuracy of our algorithm over current top-performing function prediction methods on the yeast and mouse proteomes across all metrics tested. Availability: Code and Data are available at: http://bonneaulab.bio.nyu.edu/funcprop.html Contact: shasha@courant.nyu.edu or bonneau@cs.nyu.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Youngs, Noah; Penfold-Brown, Duncan; Drew, Kevin; Shasha, Dennis; Bonneau, Richard

2013-01-01

286

Acute inhibition of Rho-kinase improves cardiac contractile function in streptozotocin-diabetic rats  

Microsoft Academic Search

Objective: The purpose of the present study was to determine whether increased activation of the RhoA\\/Rho-kinase (ROCK) pathway occurs in diabetic cardiomyopathy and whether acute inhibition of this pathway improves contractile function of the diabetic heart. Methods: Male Wistar rats were made diabetic with streptozotocin. Twelve to fourteen weeks later, the effects of acute administration of the ROCK inhibitors Y-27632

Guorong Lin; Graham P. Craig; Lili Zhang; Violet G. Yuen; Michael Allard; John H. McNeill; Kathleen M. MacLeod

2007-01-01

287

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin  

Microsoft Academic Search

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective\\/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle

H Ehrenreich; D Hinze-Selch; S Stawicki; C Aust; S Knolle-Veentjer; S Wilms; G Heinz; S Erdag; H Jahn; D Degner; M Ritzen; A Mohr; M Wagner; U Schneider; M Bohn; M Huber; A Czernik; T Pollmächer; W Maier; A-L Sirén; J Klosterkötter; P Falkai; E Rüther; J B Aldenhoff; H Krampe

2007-01-01

288

Long-term Successful Weight Loss Improves Vascular Endothelial Function in Severely Obese Individuals  

Microsoft Academic Search

Obesity is associated with increased cardiovascular risk. Although short-term weight loss improves vascular endothelial function, longer term outcomes have not been widely investigated. We examined brachial artery endothelium-dependent vasodilation and metabolic parameters in 29 severely obese subjects who lost ?10% body weight (age 45 ± 13 years; BMI 48 ± 9 kg\\/m2) at baseline and after 12 months of dietary

Sherman J. Bigornia; Melanie M. Mott; Donald T. Hess; Caroline M. Apovian; Marie E. McDonnell; Mai-Ann Duess; Matthew A. Kluge; Antonino J. Fiscale; Joseph A. Vita; Noyan Gokce

2010-01-01

289

Longer Term Improvement in Neurocognitive Functioning and Affective Distress Among Methamphetamine Users Who Achieve Stable Abstinence  

PubMed Central

Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little data is available on the possible added benefits of long-term sobriety. To address this, we performed detailed neuropsychological and affective evaluations in 83 MA-dependent individuals at a baseline visit and following an average one-year interval period. Among the 83 MA-dependent participants, 25 remained abstinent and 58 used MA at least once during the interval period. Thirty-eight non-MA-addicted, demographically matched healthy comparison (i.e., HC) participants were also examined. At baseline, both MA-dependent participants who were able to maintain abstinence and those who were not performed significantly worse than the healthy comparison subjects on global neuropsychological functioning and were significantly more distressed. At the one-year follow-up, both the long term abstainers and healthy comparison groups showed comparable global neuropsychological performance and affective distress levels, whereas the MA-dependent group who continued to use were worse than the comparison participants in terms of global neuropsychological functioning and affective distress. An interaction was observed between neuropsychological impairment at baseline, MA abstinence, and cognitive improvement, with abstinent MA-dependent participants who were neuropsychologically impaired at baseline demonstrating significantly and disproportionately greater improvement in processing speed and slightly greater improvement in motor abilities relative to the other participants. These results suggest partial recovery of neuropsychological functioning and improvement in affective distress upon sustained abstinence from MA that may extend beyond a year or more.

IUDICELLO, JENNIFER E.; WOODS, STEVEN PAUL; VIGIL, OFILIO; SCOTT, J. COBB; CHERNER, MARIANA; HEATON, ROBERT K.; ATKINSON, J. HAMPTON; GRANT, IGOR

2010-01-01

290

RESISTANCE TRAINING IMPROVES METABOLIC ECONOMY DURING FUNCTIONAL TASKS IN OLDER ADULTS  

Microsoft Academic Search

Hartman, M.J., D.A. Fields, N.M. Byrne, and G.R. Hunter. Resistance training improves metabolic economy during functional tasks in older adults. J. Strength Cond. Res. 21(1):91- 95. 2007.—The purpose of this study was to determine the effect resistance training has on metabolic economy during typical ac- tivities of daily living in a geriatric population. Twenty-nine men and women (age: 66.7 4.4

MICHAEL J. HARTMAN; DAVID A. FIELDS; NUALA M. BYRNE; GARY R. HUNTER

2007-01-01

291

A pilot study of an acupuncture protocol to improve visual function in retinitis pigmentosa patients  

PubMed Central

Background Patients with retinitis pigmentosa are motivated to try complementary or integrative therapies to slow disease progression. Basic science, clinical research and retinitis pigmentosa patients' self-reports support the hypothesis that acupuncture may improve visual function. Methods A prospective, case series, pilot study enrolled 12 adult patients with RP treated at an academic medical centre with a standardised protocol that combined electroacupuncture to the forehead and below the eyes and acupuncture to the body, at 10 half-hour sessions over two weeks. Pre- and post-treatment tests included Early Treatment Diabetic Retinopathy Study visual acuity (VA), Pelli-Robson contrast sensitivity (CS), Goldmann visual fields, and dark-adapted full-field stimulus threshold (FST)(n = 9). Scotopic Sensitivity Tester-1 (SST-1) dark-adaptometry was performed on the last two subjects. Results Six of 12 subjects had measurable, significant visual function improvements after treatment. Three of nine subjects tested with the FST had a significant 10.3 to 17.5 dB (that is, 13- to 53-fold) improvement in both eyes at one week after acupuncture, maintained for at least 10 to 12 months, which was well outside typical test-retest variability (95% CI: 3–3.5 dB) previously found in retinitis pigmentosa. SST-1 dark-adaptation was shortened in both subjects tested on average by 48.5 per cent at one week (range 36 to 62 per cent across 10 to 30 dB), which was outside typical coefficients of variation of less than 30 per cent previously determined in patients with retinitis pigmentosa and normals. Four of the five subjects with psychophysically measured scotopic sensitivity improvements reported subjective improvements in vision at night or in dark environments. One subject had 0.2 logMAR improvement in VA; another had 0.55 logCS improvement. Another subject developed more than 20 per cent improvement in the area of the Goldmann visual fields. The acupuncture protocol was completed and well tolerated by all, without adverse events or visual loss. Conclusions Acupuncture entails minimal risk, if administered by a well-trained acupuncturist and may have significant, measurable benefits on residual visual function in patients with retinitis pigmentosa, in particular scotopic sensitivity, which had not previously been studied. These preliminary findings support the need for future controlled studies of potential mechanisms.

Bittner, Ava K; Gould, Jeffrey M; Rosenfarb, Andy; Rozanski, Collin; Dagnelie, Gislin

2014-01-01

292

Folic Acid Supplementation Improves Vascular Function in Professional Dancers With Endothelial Dysfunction  

PubMed Central

Objective To determine if folic acid supplementation improves vascular function (brachial artery flow-mediated dilation [FMD]) in professional dancers with known endothelial dysfunction. Design Prospective cross-sectional study. Setting Academic institution in the Midwestern United States. Subjects Twenty-two professional ballet dancers volunteered for this study. Main Outcome Measures Subjects completed a 3-day food record to determine caloric and micronutrient intake. Menstrual status was determined by interview and questionnaire. Endothelial function was determined as flow-induced vasodilation measured by high-frequency ultrasound of the brachial artery. A change in brachial diameter of <5% to hyperemic flow stimulus was defined a priori as endothelial dysfunction. Subjects with abnormal FMD took 10 mg of folic acid daily for 4 weeks, and FMD testing was then repeated. Serum whole blood was measured for folic acid levels before and after supplementation. Results Sixty-four percent of dancers (n = 14) had abnormal brachial artery FMD (<5%) (mean ± standard deviation, 2.9% ± 1.5%). After 4 weeks of folic acid supplementation (10 mg/day), FMD improved in all the subjects (7.1% ± 2.3%; P < .0001). Conclusions This study reveals that vascular endothelial function improves in dancers after supplementation with folic acid (10 mg/day) for at least 4 weeks. This finding may have clinically important implications for future cardiovascular disease risk prevention.

Hoch, Anne Z.; Papanek, Paula; Szabo, Aniko; Widlansky, Michael E.; Gutterman, David D.

2012-01-01

293

Robotic Resistance/Assistance Training Improves Locomotor Function in Individuals Poststroke: A Randomized Controlled Study  

PubMed Central

Objective To determine whether providing a controlled resistance versus assistance to the paretic leg at the ankle during treadmill training will improve walking function in individuals poststroke. Design Repeated assessment of the same patients with parallel design and randomized controlled study between 2 groups. Setting Research units of rehabilitation hospitals. Participants Patients (N=30) with chronic stroke. Intervention Subjects were stratified based on self-selected walking speed and were randomly assigned to the resistance or assistance training group. For the resistance group, a controlled resistance load was applied to the paretic leg at the ankle to resist leg swing during treadmill walking. For the assistance group, a load that assists swing was applied. Main Outcome Measures Primary outcome measures were walking speed and 6-minute walking distance. Secondary measures included clinical assessments of balance, muscle tone, and quality of life. Outcome measures were evaluated before and after 6 weeks of training and at 8 weeks’ follow-up, and compared within group and between the 2 groups. Results After 6 weeks of robotic training, walking speed significantly increased for both groups, with no significant differences in walking speed gains observed between the 2 groups. In addition, 6-minute walking distance and balance significantly improved for the assistance group but not for the resistance group. Conclusions Applying a controlled resistance or an assistance load to the paretic leg during treadmill training may induce improvements in walking speed in individuals poststroke. Resistance training was not superior to assistance training in improving locomotor function in individuals poststroke.

Wu, Ming; Landry, Jill M.; Kim, Janis; Schmit, Brian D.; Yen, Sheng-Che; MacDonald, Jillian

2014-01-01

294

Functional Impairment in Peripheral Artery Disease and How to Improve It in 2013  

PubMed Central

Lower extremity peripheral artery disease (PAD) affects eight million men and women in the United States and will be increasingly common as the U.S. population lives longer with chronic disease. People with PAD have poorer walking endurance, slower walking velocity, and poorer balance, compared to individuals without PAD. People with PAD may reduce their walking activity to avoid leg symptoms. Thus, clinicians should not equate stabilization or improvement in exertional leg symptoms with stabilization or improvement in walking performance in PAD. Additionally, even asymptomatic PAD patients have greater functional impairment and faster functional decline than individuals without PAD. Of the two FDA-approved medications for treating claudication symptoms, pentoxifylline may not be more efficacious than placebo, while cilostazol confers a modest improvement in treadmill walking performance. Supervised treadmill walking exercise is associated with substantial improvement in walking endurance, but many PAD patients do not have access to supervised exercise programs. Unsupervised walking exercise programs may be beneficial in PAD, but data are mixed.

2013-01-01

295

Effects of short-term exercise training on tissue Doppler indices of left ventricular diastolic function in overweight and obese individuals.  

PubMed

Although exercise training is unable to improve obesity-associated decreases in left ventricular (LV) diastolic function, as assessed using chamber function measurements, the effects on LV diastolic myocardial function, as assessed using tissue Doppler imaging (TDI), are uncertain. In 32 overweight (n = 11) or obese (n = 21), sedentary or recreationally active men and women (30-57 years), we assessed the effects of 6 weeks of exercise training either preceded (n = 16) or followed (n = 16) by a 6-week control period on TDI indices of LV diastolic function (e', e'/a' and E/e') (echocardiography). Diastolic function at baseline was comparable to that noted in overweight and obese participants from a community sample (n = 245), and 56% (n = 18) had e' values below the lower 95% CI of a lean and healthy cohort (n = 60) of the community sample. Exercise training increased peak oxygen consumption (27.4 ± 4.9 to 29.4 ± 5.8 mL · kg(-1) · min(-1), P = 0.0001), but had no effect on body mass index (P = 0.99). No changes in TDI indices of diastolic function were observed after exercise training in all the participants (e': P = 0.74, a': P = 0.98, e'/a': P = 0.85, E/e': P = 0.26), participants with abnormal e' values (n = 18)(e': P = 0.99, a': P = 0.96, e'/a': P = 0.91, E/e': P = 0.97) or obese participants (n = 21)(e': P = 0.67, a': P = 1.00, e'/a': P = 0.78, E/e': P = 0.11). In conclusion, exercise training, despite increasing cardiorespiratory fitness, is unable to improve obesity-associated decreases in LV diastolic myocardial function. PMID:24050712

Millen, Aletta; Norton, Gavin; Avidon, Ingrid; Woodiwiss, Angela

2014-01-01

296

ORIGINAL RESEARCH Restored Activation of Primary Motor Area from Motor Reorganization and Improved Motor Function after Brain Tumor Resection  

Microsoft Academic Search

BACKGROUND AND PURPOSE: Reorganization of brain function may result in preservation of motor function in patients with brain tumors. The goal of the present study was to investigate whether function of the primary motor area (M1) was restored and whether motor function improved after brain tumor resection. METHODS: Five patients with metastatic brain tumors located within or near M1 underwent

N. Shinoura; Y. Suzuki; R. Yamada; T. Kodama; M. Takahashi; K. Yagi

297

Sustained improvement of cardiac function and prevention of cardiac remodeling after long-term dual ECE-NEP inhibition in rats with congestive heart failure.  

PubMed

Acute inhibition of endothelin converting enzyme (ECE) and neutral endopeptidase (NEP) exerts beneficial hemodynamic effects in chronic heart failure (CHF). However, the long-term effects of dual ECE-NEP inhibition are unknown. We evaluated, in rats with CHF, the long-term effects of the dual ECE-NEP inhibitor CGS 26303 (10 mg.kg(-1).day(-1)) on systemic and left ventricular (LV) hemodynamics and LV remodeling, and compared them to those induced by the selective NEP inhibitor CGS 24592 (10 mg.kg(-1).day(-1)), both administered subcutaneously by mini-pump for 30 days starting 7 days after left coronary artery ligation. After 30 days, CGS 26303, but not CGS 24592, reduced systolic blood pressure, while both drugs never affected heart rate. Echocardiographic studies showed that only CGS 26303 diminished LV end-diastolic and systolic diameters and increased LV fractional shortening and cardiac output. Moreover, CGS 26303, but not CGS 24592, reduced LV end-diastolic pressure, while LV dP/dtmax/min was not affected. Both drugs reduced collagen accumulation in the 'viable' part of the LV, but only CGS 26303 reduced LV weight. Thus, long-term treatment with CGS 26303 decreases both preload and afterload, increases cardiac output, and diminishes LV hypertrophy, dilatation, and cardiac fibrosis, suggesting that dual ECE-NEP inhibition might be beneficial in human CHF. PMID:15085059

Mulder, Paul; Barbier, Stephane; Monteil, Christelle; Jeng, Arco Y; Henry, Jean Paul; Renet, Sylvanie; Thuillez, Christian

2004-04-01

298

Adipose-derived stem cells improved mouse ovary function after chemotherapy-induced ovary failure  

PubMed Central

Introduction Young patients receiving chemotherapy occasionally face infertility and premature ovarian failure (POF). Numerous investigations reported that adipose-derived stem cells (ADSCs) transplantation could ameliorate the structure and function of injured tissues. The aim of this study was to explore the therapeutic efficacy of ADSC transplantation for chemotherapy-induced ovarian damage. Methods Female mice were injected intraperitoneally with 50 mg/kg cyclophosphamide (CTX). After 15 consecutive days of injection, ADSCs were transplanted either directly into bilateral ovaries or via intravenous injection, and the ovaries were excised after either 1 week or 1 month of treatment. The follicles were counted and categorized, and ovarian histologic sections were stained for TUNEL. Ovarian function was evaluated by monitoring ovulation. ADSC tracking, microarray analyses, and real-time polymerase chain reaction (PCR) were used to assess the inner mechanism of injury and repair. Results The ovarian function of mice exposed to CTX injection improved after ADSC transplantation. The population of follicles at different stages and ovulation significantly increased after the treatment. Immunofluorescence revealed reduced TUNEL staining. The tracking of ADSCs revealed that these cells did not directly differentiate into the follicle component. Microarray analyses indicated that changes in different groups of genes might affect follicle formation or ovulation. Conclusions ADSC transplantation improved ovarian function. Our results suggest a potential mechanism for ADSC therapy.

2013-01-01

299

Improved global and regional left ventricular function after angioplasty for chronic coronary occlusion.  

PubMed

Percutaneous transluminal coronary angioplasty can be performed safely and effectively in patients with chronic total coronary occlusion. To investigate the effect on left ventricular function, global and regional left ventricular ejection fraction were analyzed by contrast angiography in 49 patients before and 10 +/- 6 weeks after successful recanalization. Coronary angiography at follow-up showed reocclusion in 12 patients (24%). In 37 patients with patent arteries global ejection fraction increased from 55.8 +/- 7.1% at baseline to 62.5 +/- 11.3% at follow-up (P < 0.001), and regional wall motion assessed by the centerline method improved from -1.7 +/- 1.0 to -0.6 +/- 1.5 standard deviations/chord (P < 0.001). In contrast, in patients with reocclusion neither global ejection fraction nor regional wall motion were significantly different at follow-up compared with baseline. Changes in global or regional left ventricular function after coronary recanalization were unrelated to other parameters such as severity of angina, duration of occlusion, history of myocardial infarction, presence or absence of visible collaterals, or baseline left ventricular function. Thus in patients with primarily successful recanalization of chronically occluded coronary arteries persistent vessel patency is the major determinant of global and regional improvement of left ventricular function. PMID:7950155

Engelstein, E; Terres, W; Hofmann, D; Hansen, L; Hamm, C W

1994-06-01

300

Cortical Depth Dependent Functional Responses in Humans at 7T: Improved Specificity with 3D GRASE  

PubMed Central

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE.

Muckli, Lars; Ugurbil, Kamil; Yacoub, Essa; Goebel, Rainer

2013-01-01

301

Transplantation of Induced Pluripotent Stem Cells Improves Functional Recovery in Huntington's Disease Rat Model  

PubMed Central

The purpose of this study was to determine the functional recovery of the transplanted induced pluripotent stem cells in a rat model of Huntington's disease with use of 18F-FDG microPET/CT imaging. Methods In a quinolinic acid-induced rat model of striatal degeneration, induced pluripotent stem cells were transplanted into the ipsilateral lateral ventricle ten days after the quinolinic acid injection. The response to the treatment was evaluated by serial 18F-FDG PET/CT scans and Morris water maze test. Histological analyses and Western blotting were performed six weeks after stem cell transplantation. Results After induced pluripotent stem cells transplantation, higher 18F-FDG accumulation in the injured striatum was observed during the 4 to 6-weeks period compared with the quinolinic acid-injected group, suggesting the metabolic recovery of injured striatum. The induced pluripotent stem cells transplantation improved learning and memory function (and striatal atrophy) of the rat in six week in the comparison with the quinolinic acid-treated controls. In addition, immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated into the lesioned area in striatum, and most of the stem cells expressed protein markers of neurons and glial cells. Conclusion Our findings show that induced pluripotent stem cells can survive, differentiate to functional neurons and improve partial striatal function and metabolism after implantation in a rat Huntington's disease model.

Zhou, Guangqian; Peng, Wenda; He, Zhendan; Zhao, Zhenfu; Mo, CuiPing; Qu, Junle; Zhang, Jian

2014-01-01

302

Kyphoplasty Increases Vertebral Height, Decreases Both Pain Score and Opiate Requirements While Improving Functional Status  

PubMed Central

Vertebral compression fractures can result from advanced osteoporosis, or less commonly from metastatic or traumatic insults to the vertebral column, and result in disabling pain and decreased functional capacity. Various vertebral augmentation options including kyphoplasty aim at preventing the sequelae of pain and immobility that can develop as the result of the vertebral fractures. The mechanism for pain relief following kyphoplasty is not entirely understood, and the restoration of a portion of the lost vertebral height is a subject of debate. We retrospectively reviewed radiographic imaging, pain relief, analgesic intake and functional outcomes in 67 consecutive patients who underwent single- or multilevel kyphoplasty with the primary goal of quantifying the restoration of lost vertebral height. We observed a mean of 45% of the lost vertebral height restored postprocedurally. Secondarily, kyphoplasty was associated with significant decreases in pain scores, daily morphine consumption and improvement in patient-reported functional measures.

Tolba, Reda; Bolash, Robert B.; Shroll, Joshua; Costandi, Shrif; Dalton, Jarrod E.; Sanghvi, Chirag; Mekhail, Nagy

2014-01-01

303

Functional Clustering Drives Encoding Improvement in a Developing Brain Network during Awake Visual Learning  

PubMed Central

Sensory experience drives dramatic structural and functional plasticity in developing neurons. However, for single-neuron plasticity to optimally improve whole-network encoding of sensory information, changes must be coordinated between neurons to ensure a full range of stimuli is efficiently represented. Using two-photon calcium imaging to monitor evoked activity in over 100 neurons simultaneously, we investigate network-level changes in the developing Xenopus laevis tectum during visual training with motion stimuli. Training causes stimulus-specific changes in neuronal responses and interactions, resulting in improved population encoding. This plasticity is spatially structured, increasing tuning curve similarity and interactions among nearby neurons, and decreasing interactions among distant neurons. Training does not improve encoding by single clusters of similarly responding neurons, but improves encoding across clusters, indicating coordinated plasticity across the network. NMDA receptor blockade prevents coordinated plasticity, reduces clustering, and abolishes whole-network encoding improvement. We conclude that NMDA receptors support experience-dependent network self-organization, allowing efficient population coding of a diverse range of stimuli.

Haas, Kurt

2012-01-01

304

Dual-functionalized PAMAM dendrimers with improved P-glycoprotein inhibition and tight junction modulating effect.  

PubMed

This study aims to surface modify poly(amido amine) or PAMAM dendrimers by sequentially grafting poly(ethylene glycol) or PEG and 4-thiobutylamidine (TBA) so as to reduce PAMAM cytotoxicity while improving the ability of PAMAM to modulate P-glycoprotein (P-gp) efflux and tight junction integrity. Conjugation of functional groups was determined by NMR spectroscopy, FT-IR, thiol group quantification and molecular weight estimation. The yield of the dual-functionalized dendrimers was >80%. The dual-functionalized dendrimer could significantly reduce PAMAM cytotoxicity to <15% as reflected by LDH release in Caco-2 and MDCK/MDR1 cells after 72 h of exposure. Thiolated dendrimers could increase cellular accumulation and permeation of the P-gp substrate R-123, and such effect could be affected by the extent of PEGylation of the dendrimer. Surface-modified PAMAM dendrimers, either by single or dual functionalization, could better modulate tight junction integrity in comparison with unmodified PAMAM, as demonstrated through immunostaining of the tight junction marker ZO-1, permeation of the model compound Lucifer Yellow (LY) and transepithelial electrical resistance (TEER). Of importance, reversible tight junction modulating effect was only observed in the dual-functionalized dendrimers. Collectively, dual functionalization with PEG and TBA represented a promising approach in altering PAMAM dendrimer surface for potential application in oral drug delivery. PMID:24219381

Liu, Yuanjie; Chiu, Gigi N C

2013-12-01

305

A Bayesian statistical approach of improving knowledge-based scoring functions for protein-ligand interactions.  

PubMed

Knowledge-based scoring functions are widely used for assessing putative complexes in protein-ligand and protein-protein docking and for structure prediction. Even with large training sets, knowledge-based scoring functions face the inevitable problem of sparse data. Here, we have developed a novel approach for handling the sparse data problem that is based on estimating the inaccuracies in knowledge-based scoring functions. This inaccuracy estimation is used to automatically weight the knowledge-based scoring function with an alternative, force-field-based potential (FFP) that does not rely on training data and can, therefore, provide an improved approximation of the interactions between rare chemical groups. The current version of STScore, a protein-ligand scoring function using our method, achieves a binding mode prediction success rate of 91% on the set of 100 complexes by Wang et al., and a binding affinity correlation of 0.514 with the experimentally determined affinities in PDBbind. The method presented here may be used with other FFPs and other knowledge-based scoring functions and can also be applied to protein-protein docking and protein structure prediction. © 2014 Wiley Periodicals, Inc. PMID:24623011

Grinter, Sam Z; Zou, Xiaoqin

2014-05-01

306

Cyclosporine A Attenuates Mitochondrial Permeability Transition and Improves Mitochondrial Respiratory Function in Cardiomyocytes Isolated from Dogs With Heart Failure  

PubMed Central

Objective We used isolated cardiomyocytes to investigate a possible role of mitochondrial permeability transition pore in mitochondrial abnormalities associated with heart failure. Methods Cardiomyocytes were isolated from LV myocardium of normal control dogs and dogs with heart failure produced by intracoronary microembolizations. Mitochondrial permeability transition was measured in isolated cardiomyocytes with intact sarcolemma with and without 0.2 ?M Cyclosporin A using calcein AM and the fluorometer. State-3 mitochondrial respiration was also measured with the Clark electrode. Mitochondrial membrane potential was measured with JC-1 probe using the fluorometer. Propidium iodide was used to ensure sarcolemma integrity. Results 200 minutes after loading with calcein AM, mitochondria of failing cardiomyocytes showed only 50% of maximal level of calcein fluorescence while it remained unchanged in normal cells. The mitochondrial membrane potential in failing cardiomyocytes was significantly decreased by 38% compared to normal cardiomyocytes. Cyclosporine A significantly slowed the exit of calcein from mitochondria of failing cardiomyocytes and increased mitochondrial membrane potential by 29%. State-3 respiration was not affected with Cyclosporine A in normal cardiomyocytes while it was significantly increased in failing cardiomyocytes by 20%. Conclusions Exit of calcein (m.w. 1.0 kDa) from mitochondria of viable failing cardiomyocytes with intact sarcolemma suggests an existence of a reversible transitory permeability transition opening in high conductance mode. Attenuation of calcein exit, ??m and improvement of state-3 respiration achieved with CsA (0.2 ?M) show that permeability transition opening could be a cause of mitochondrial dysfunction described in the failing heart.

Sharov, Victor G.; Todor, Anastassia; Khanal, Sanjaya; Imai, Makoto; Sabbah, Hani N.

2009-01-01

307

Intravenous immunoglobulins improve the function and ameliorate joint involvement in systemic sclerosis: a pilot study  

PubMed Central

Background In systemic sclerosis (SSc), joint involvement may reduce the functional capacity of the hands. Intravenous immunoglobulins have previously been shown to benefit patients with SSc. Aim To verify the efficacy of intravenous immunoglobulins on joint involvement and function in SSc. Patients and methods 7 women with SSc, 5 with limited and 2 with diffuse SSc, with a severe and refractory joint involvement were enrolled in the study. Methotrexate and cyclophosphamide pulse therapy did not ameliorate joint symptoms. Hence, intravenous immunoglobulins therapy was prescribed at a dosage of 2?g/kg body weight during 4?days/month for six consecutive courses. The presence of joint tenderness and swelling, and articular deformities (due to primary joint involvement and not due to skin and subcutaneous changes) were evaluated. Before and after 6?months of treatment, patients were subjected to (1) Ritchie Index (RI) evaluation of joint involvement; (2) Dreiser Algo?Functional Index (IAFD) evaluation of hand joint function; (3) pain visual analogue scale (VAS) to measure joint pain; (4) Health Assessment Questionnaire (HAQ) to evaluate the limitations in everyday living and physical disability; and (5) modified Rodnan Skin Score for skin involvement. Results After 6?months of intravenous immunoglobulins therapy, joint pain and tenderness, measured with the VAS, decreased significantly (p<0.03), and hand function (IAFD) improved significantly (p<0.02), together with the quality of life (HAQ; p<0.03). All patients significantly improved, except for one. The skin score after 6?months of intravenous immunoglobulins therapy was significantly reduced (p<0.003). Conclusion This pilot study suggests that intravenous immunoglobulins may reduce joint pain and tenderness, with a significant recovery of joint function in patients with SSc with severe and refractory joint involvement. The cost of intravenous immunoglobulins might limit their use only to patients who failed disease?modifying antirheumatic drugs.

Nacci, F; Righi, A; Conforti, M L; Miniati, I; Fiori, G; Martinovic, D; Melchiorre, D; Sapir, T; Blank, M; Shoenfeld, Y; Pignone, A Moggi; Cerinic, M Matucci

2007-01-01

308

Intracoronary endothelin receptor blockade improves endothelial function in patients with coronary artery disease.  

PubMed

Endothelin (ET)-1 receptor blockade improves endothelial function in the forearm of patients with atherosclerosis. The aim was to investigate whether intracoronary ET receptor blockade improves coronary endothelial function and increases blood flow in patients with coronary artery disease. Ten patients received a 60-minute infusion of either the selective ETA receptor antagonist BQ123 (40 nmol/min, n = 6) or BQ123 + the ETB receptor antagonist BQ788 (40 nmol/min, n = 4). In all patients, substance P, an endothelium-dependent vasodilator, did not increase baseline coronary flow reserve with thermodilution (CFRThermo) (0.71 +/- 0.14 s during NaCl versus 0.59 +/- 0.14 s during substance P) or baseline quantitative coronary angiography (QCA) (2.74 +/- 0.16 mm versus 2.83 +/- 0.20 mm). After ET receptor blockade, however, the response to substance P was significantly improved as determined both by CFRThermo (0.62 +/- 0.14 s during NaCl versus 0.48 +/- 0.10 s during substance P, p < 0.05) and by QCA (2.70 +/- 0.18 mm versus 2.85 +/- 0.19 mm, p < 0.05). In addition, ET blockade increased blood flow in all patients by 16% +/- 10% (n = 10, p < 0.05) and in the BQ123 group by 22% +/- 16% (n = 6, p < 0.05). Furthermore, ETA blockade increased blood flow significantly more than did dual ETA/ETB blockade (p < 0.05). These findings indicate that ET receptor blockade may be a new therapeutic strategy to improve coronary vascular function in patients with coronary artery disease. PMID:19011669

Böhm, Felix; Jensen, Jens; Svane, Bertil; Settergren, Magnus; Pernow, John

2008-11-01

309

Improvement of attentional function with antagonism of nicotinic receptors in female rats  

PubMed Central

Nicotinic agonists have been shown in a variety of studies to improve cognitive function. Since nicotinic receptors are easily desensitized by agonists, it is not completely clear to what degree receptor desensitization or receptor activation are responsible for nicotinic agonist-induced cognitive improvement. In the current study, the effect of the neuronal nicotinic cholinergic ?4?2 receptor antagonist dihydro-?-erythroidine (DH?E) and the ?7 nicotinic receptor antagonist methyllycaconitine (MLA) on attentional function was determined. Adult female Sprague-Dawley rats were trained on the visual signal detection task. They were required to discriminate whether or not a light signal occurred on a trial and respond with a lever press on one side after a signal and the opposite side after the absence of a signal in order to receive a food pellet reinforcer. Acute administration of the ?4?2 antagonist DH?E improved attentional function either alone or in reversing the attentional impairment caused by the NMDA glutamate antagonist dizocilpine (MK-801). Acute administration of MLA also significantly attenuated the dizocilpine-induced attentional impairment. In previous research we have shown that the ?4?2 nicotinic desensitizing agent and partial agonist sazetidine-A also was effective in reversing dizocilpine-induced attentional impairments on the signal detection task and that low doses of the general nicotinic antagonist mecamylamine improved learning and memory. The current studies indicate that blockade of nicotinic receptors can effectively attenuate attentional impairments. Development of drugs that provide a net decrease in nicotinic receptor activity either through antagonism or desensitization could be worth exploring for beneficial effects for treating cognitive impairments.

Levin, Edward D.; Cauley, Marty; Rezvani, Amir H.

2013-01-01

310

Improvement of attentional function with antagonism of nicotinic receptors in female rats.  

PubMed

Nicotinic agonists have been shown in a variety of studies to improve cognitive function. Since nicotinic receptors are easily desensitized by agonists, it is not completely clear to what degree receptor desensitization or receptor activation are responsible for nicotinic agonist-induced cognitive improvement. In the current study, the effect of the neuronal nicotinic cholinergic ?4?2 receptor antagonist dihydro-?-erythroidine (DH?E) and the ?7 nicotinic receptor antagonist methyllycaconitine (MLA) on attentional function was determined. Adult female Sprague-Dawley rats were trained on the visual signal detection task. They were required to discriminate whether or not a light signal occurred on a trial and respond with a lever press on one side after a signal and the opposite side after the absence of a signal in order to receive a food pellet reinforcer. Acute administration of the ?4?2 antagonist DH?E improved attentional function either alone or in reversing the attentional impairment caused by the NMDA glutamate antagonist dizocilpine (MK-801). Acute administration of MLA also significantly attenuated the dizocilpine-induced attentional impairment. In previous research we have shown that the ?4?2 nicotinic desensitizing agent and partial agonist sazetidine-A also was effective in reversing dizocilpine-induced attentional impairments on the signal detection task and that low doses of the general nicotinic antagonist mecamylamine improved learning and memory. The current studies indicate that blockade of nicotinic receptors can effectively attenuate attentional impairments. Development of drugs that provide a net decrease in nicotinic receptor activity either through antagonism or desensitization could be worth exploring for beneficial effects for treating cognitive impairments. PMID:23399762

Levin, Edward D; Cauley, Marty; Rezvani, Amir H

2013-02-28

311

Functional improvement of jeopardized myocardium following intracoronary streptokinase infusion in acute myocardial infarction.  

PubMed Central

The effect of reperfusion on regional left ventricular performance following acute myocardial infarction in man was determined. Intracoronary streptokinase was administered in 24 patients within 6 h of the onset of symptoms. 15 patients (62%) were successfully recanalized during the initial study. Mean percent radial shortening (%RS) in both the jeopardized and compensatory regions were determined using 23 radii from the centroid of diastolic and systolic angiographic silhouettes. Sequential measurements were obtained during repeat cardiac catheterization studies at 24 h in 19 patients and before discharge from the hospital (16 +/- 11 d) in 15 patients. At the time of the predischarge study, each acutely reperfused patient showed improvement in %RS in the jeopardized region (P = 0.01) with 56% returning to the normal range. Despite the uniform improvement in the contractile function of the jeopardized region in each reperfused patient, the global ejection fraction showed no improvement or a decrease at the time of the chronic study in 44%. This was due to a decrease in the compensatory wall motion in the uninvolved segments between the acute and chronic study in each case. Neither the %RS nor the ejection fraction changed significantly at the time of the chronic study in the patients who could not be acutely recanalized. These data indicate (a) significant salvage of jeopardized myocardium associated with recovery of contractile function in patients reperfused during the first 6 h of chest pain following acute myocardial infarction; (b) no improvement in regional or global left ventricular performance in patients who could not be reperfused acutely; and (c) the ejection fraction is strongly influenced by changes in the compensatory wall motion of the uninvolved segments and does not accurately reflect changes in the contractile function of the jeopardized myocardium.

Stack, R S; Phillips, H R; Grierson, D S; Behar, V S; Kong, Y; Peter, R H; Swain, J L; Greenfield, J C

1983-01-01

312

At least four non- env factors that reside in the LTR, in the 5?-non-coding region, in gag and in part of pol affect neuropathogenicity of PVC441 murine leukemia virus (MuLV)  

Microsoft Academic Search

PVC-441 murine leukemia virus (MuLV) is neuropathogenic in F344 rats. Recently, an infectious DNA clone was isolated and its nucleotide sequence was determined (J. Virol. 72: 3423–3426. 1998). To identify the viral determinants of neuropathogenicity of the molecularly cloned PVC-441 MuLV, chimeras were constructed between PVC-441 MuLV and F-MuLV clones at appropriate restriction enzyme sites that divide the viral genome

Atsushi Tanaka; Kyoko Saida; Masako Andoh; Ken Maeda; Kazushige Kai

2000-01-01

313

The impact of obesity and hypoxia on left ventricular function and glycolytic metabolism  

PubMed Central

Abstract We have previously reported that 4 weeks of intermittent hypoxia (IH) exposure, mimicking the hypoxic stress of obstructive sleep apnea, produces compensatory increases in left ventricular (LV) contractility in lean C57BL/6J mice. In this study we compared the effects of 4 weeks IH to 4 weeks of sustained hypoxia (SH) on LV function and cardiac glycolysis in lean C57BL/6J mice and obese ob/ob mice at 10–12 weeks of age. The four exposure conditions were IH (nadir O2 [5–6%] at 60 cycles/h during the 12 h light period), SH (24 h inspired O2 [10%]), and control groups of intermittent air (IA) or room air. Cardiac function was assessed under isoflurane anesthesia (1–2%) by echocardiography and pressure–volume loop analysis and myocardial glycolytic rates were determined ex vivo using radiolabeled 3H?glucose. Lean mice exposed to IH exhibited increases in contractile parameters which were associated with elevated glycolytic rates (3.4 vs. 5.7 ?g/?L·g; P < 0.05). Ob/ob mice did not show any improvements in contractility after IH. Moreover, cardiac glycolytic rates and LV systolic and diastolic function did not differ from IA ob/ob controls. Following SH exposure, lean mice exhibited increased contractility and glycolytic rates (3.8 vs. 5.7 ?g/?L·g; P < 0.05), however, LV lumen dimensions were reduced. In contrast, ob/ob mice exposed to SH show compromised systolic and diastolic function associated with unchanging glycolytic rates. These findings demonstrate that, in a murine model of obesity, an inability to increase glycolysis is associated with an absence of an adaptive cardiac response to IH and marked systolic and diastolic dysfunction in response to SH.

Rodriguez, Rosa H.; Bickta, Janelle L.; Murawski, Patrick; O'Donnell, Christopher P.

2014-01-01

314

Gastric Bypass Improves ?-Cell Function and Increases ?-Cell Mass in a Porcine Model.  

PubMed

The most frequently used and effective treatment for morbid obesity is Roux-en-Y gastric bypass surgery (RYGB), which results in rapid remission of type 2 diabetes in most cases. To what extent this is accounted for by weight loss or other factors remains elusive. To gain insight into these mechanisms, we investigated the effects of RYGB on ?-cell function and ?-cell mass in the pig, a species highly reminiscent of the human. RYGB was performed using linear staplers during open surgery. Sham-operated pigs were used as controls. Both groups were fed a low-calorie diet for 3 weeks after surgery. Intravenous glucose tolerance tests were performed 2 weeks after surgery. Body weight in RYGB pigs and sham-operated, pair-fed control pigs developed similarly. RYGB pigs displayed improved glycemic control, which was attributed to increases in ?-cell mass, islet number, and number of extraislet ?-cells. Pancreatic expression of insulin and glucagon was elevated, and cells expressing the glucagon-like peptide 1 receptor were more abundant in RYGB pigs. Our data from a pig model of RYGB emphasize the key role of improved ?-cell function and ?-cell mass to explain the improved glucose tolerance after RYGB as food intake and body weight remained identical. PMID:24487021

Lindqvist, Andreas; Spégel, Peter; Ekelund, Mikael; Garcia Vaz, Eliana; Pierzynowski, Stefan; Gomez, Maria F; Mulder, Hindrik; Hedenbro, Jan; Groop, Leif; Wierup, Nils

2014-05-01

315

The Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Improves Vascular Endothelial Function in Type 2 Diabetes  

PubMed Central

The vascular endothelial function is impaired in the very early stage of atherosclerosis in diabetic patients. The goal of this study was to identify the mechanism underlying the improvement in vascular endothelial function by sitagliptin in type 2 diabetes mellitus patients. This study was an open-labeled prospective observational single arm trial. Forty patients were treated with 50 mg of sitagliptin once daily for 12-weeks. The flow-mediated dilation (FMD) and plasma adiponectin were measured at baseline and 12 weeks after initiating treatment. The %FMD was significantly increased after treatment (4.13 ± 1.59 vs 5.12 ± 1.55, P < 0.001), whereas the nitroglycerin-mediated dilation (NMD) did not change. The plasma adiponectin levels significantly increased (13.0 ± 11.3 vs 14.3 ± 12.8, P < 0.001). The changes in the FMD were significantly correlated with those of the plasma adiponectin (r = 0.322, P < 0.05). A multivariate linear regression analysis demonstrated that the improvement in the FMD is associated with the plasma adiponectin (P < 0.05). The treatment of type 2 diabetes mellitus patients with sitagliptin reverses vascular endothelial dysfunction, as evidenced by increase in the FMD, and improvement of the adiponectin levels (UMIN Clinical Trials Registry System as trial ID UMIN000004236).

Kubota, Yoshiaki; Takagi, Gen; Ikeda, Takeshi; Kirinoki-Ichikawa, Sonoko; Tanaka, Kotoko; Mizuno, Kyoichi

2012-01-01

316

Chronic vagal nerve stimulation improves baroreflex neural arc function in heart failure rats.  

PubMed

We tested whether 6-wk vagal stimulation (VS) treatment improved open-loop baroreflex function in rats after myocardial infarction (MI). The following three groups of Sprague-Dawley rats were examined: normal control (NC, n = 9), MI with no treatment (MI-NT, n = 8), and MI treated with VS (MI-VS, n = 7). Under anesthesia, a stepwise input ranging from 60 to 180 mmHg was imposed on isolated carotid sinus baroreceptor regions, while the responses in splanchnic sympathetic nerve activity (SNA) and arterial pressure (AP) were measured. The response range of percent SNA was greater in the MI-VS than in the MI-NT group (63.8 ± 4.9% vs. 33.1 ± 3.8%, P < 0.01). The slope of the AP response to percent SNA was not different between the MI-VS and MI-NT groups (0.611 ± 0.076 vs. 0.781 ± 0.057 mmHg/%). The difference in the response range of AP between the MI-VS and MI-NT groups did not reach statistical significance (40.7 ± 6.2 vs. 26.4 ± 3.5 mmHg). In conclusion, the 6-wk VS treatment significantly improved the baroreflex control of SNA, but the effect was limited for the baroreflex total-loop function due to the lack of significant improvement in the AP response to percent SNA. PMID:24674859

Kawada, Toru; Li, Meihua; Zheng, Can; Shimizu, Shuji; Uemura, Kazunori; Turner, Michael J; Yamamoto, Hiromi; Sugimachi, Masaru

2014-05-15

317

Neovascularization of ischemic myocardium by newly isolated tannins prevents cardiomyocyte apoptosis and improves cardiac function.  

PubMed

During remodeling progress post myocardial infarction, the contribution of neoangiogenesis to the infarct-bed capillary is insufficient to support the greater demands of the hypertrophied but viable myocardium resulting in further ischemic injury to the viable cardiomyocytes at risk. Here we reported the bio-assay-guided identification and isolation of angiogenic tannins (angio-T) from Geum japonicum that induced rapid revascularization of infarcted myocardium and promoted survival potential of the viable cardiomyocytes at risk after myocardial infarction. Our results demonstrated that angio-T displayed potent dual effects on up-regulating expression of angiogenic factors, which would contribute to the early revascularization and protection of the cardiomyocytes against further ischemic injury, and inducing antiapoptotic protein expression, which inhibited apoptotic death of cardiomyocytes in the infarcted hearts and limited infarct size. Echocardiographic studies demonstrated that angio-T-induced therapeutic effects on acute infarcted myocardium were accompanied by significant functional improvement by 2 days after infarction. This improvement was sustained for 14 days. These therapeutic properties of angio-T to induce early reconstitution of a blood supply network, prevent apoptotic death of cardiomyocytes at risk, and improve heart function post infarction appear entirely novel and may provide a new dimension for therapeutic angiogenesis medicine for the treatment of ischemic heart diseases. PMID:17380192

Gu, Xuemei; Cheng, Lei; Chueng, Winghong L; Yao, Xinsheng; Liu, Hongwei; Qi, Guoqing; Li, Ming

2006-01-01

318

Improved Description of Stereoelectronic Effects Using Semi-local Density Functional Theory  

NASA Astrophysics Data System (ADS)

Proper description of stereoelectronic (SE) effects is desirable for any theoretical method to be used in organic chemistry. The SE design rules are frequently used in synthetic organic chemistry to design and explain new reactions by electron donating and withdrawing effects or steric interactions. These effects are often poorly described by standard generalized gradient approximations for exchange and correlation. Many popular exchange-correlation functionals are biased toward the correct description of free atoms and fail to improve upon LSDA for solids. Changing two parameters within the PBE form to satisfy different constraints leads to a new non-empirical GGA, PBEsol [1], that performs well for solids and improves the description of large organic systems and reactions. We present examples where this new non-empirical functional provides considerable improvements for molecules. [1] J.P. Perdew, A. Ruzsinszky, G.I. Csonka, O.A. Vydrov, G.E. Scuseria, L.A. Constantin, X. Zhou, and K. Burke, http://arxiv.org/abs/0711.0156

Csonka, Gabor I.; Perdew, John P.; Ruzsinszky, Adrienn

2008-03-01

319

Targeting oxidized LDL improves insulin sensitivity and immune cell function in obese Rhesus macaques?  

PubMed Central

Oxidation of LDL (oxLDL) is a crucial step in the development of cardiovascular disease. Treatment with antibodies directed against oxLDL can reduce atherosclerosis in rodent models through unknown mechanisms. We demonstrate that through a novel mechanism of immune complex formation and Fc-? receptor (Fc?R) engagement, antibodies targeting oxLDL (MLDL1278a) are anti-inflammatory on innate immune cells via modulation of Syk, p38 MAPK phosphorylation and NF?B activity. Subsequent administration of MLDL1278a in diet-induced obese (DIO) nonhuman primates (NHP) resulted in a significant decrease in pro-inflammatory cytokines and improved overall immune cell function. Importantly, MLDL1278a treatment improved insulin sensitivity independent of body weight change. This study demonstrates a novel mechanism by which an anti-oxLDL antibody improves immune function and insulin sensitivity independent of internalization of oxLDL. This identifies MLDL1278a as a potential therapy for reducing vascular inflammation in diabetic conditions.

Li, Shijie; Kievit, Paul; Robertson, Anna-Karin; Kolumam, Ganesh; Li, Xiumin; von Wachenfeldt, Karin; Valfridsson, Christine; Bullens, Sherry; Messaoudi, Ilhem; Bader, Lindsay; Cowan, Kyra J.; Kamath, Amrita; van Bruggen, Nicholas; Bunting, Stuart; Frendeus, Bjorn; Grove, Kevin L.

2013-01-01

320

A Novel Cable-Driven Robotic Training Improves Locomotor Function in Individuals Post-Stroke  

PubMed Central

A novel cable-driven robotic gait training system has been tested to improve the locomotor function in individuals post stroke. Seven subjects with chronic stroke were recruited to participate in this 6 weeks robot-assisted treadmill training paradigm. A controlled assistance force was applied to the paretic leg at the ankle through a cable-driven robotic system. The force was applied from late stance to mid-swing during treadmill training. Body weight support was provided as necessary to prevent knee buckling or toe drag. Subjects were trained 3 times a week for 6 weeks. Overground gait speed, 6 minute walking distance, and balance were evaluated at pre, post 6 weeks robotic training, and at 8 weeks follow up. Significant improvements in gait speed and 6 minute walking distance were obtained following robotic treadmill training through a cable-driven robotic system. Results from this study indicate that it is feasible to improve the locomotor function in individuals post stroke through a flexible cable-driven robot.

Landry, Jill M.; Yen, Sheng-Che; Schmit, Brian D.; Hornby, T. George; Rafferty, Miriam

2013-01-01

321

Can Functional Magnetic Resonance Imaging Improve Success Rates in CNS Drug Discovery?  

PubMed Central

Introduction The bar for developing new treatments for CNS disease is getting progressively higher and fewer novel mechanisms are being discovered, validated and developed. The high costs of drug discovery necessitate early decisions to ensure the best molecules and hypotheses are tested in expensive late stage clinical trials. The discovery of brain imaging biomarkers that can bridge preclinical to clinical CNS drug discovery and provide a ‘language of translation’ affords the opportunity to improve the objectivity of decision-making. Areas Covered This review discusses the benefits, challenges and potential issues of using a science based biomarker strategy to change the paradigm of CNS drug development and increase success rates in the discovery of new medicines. The authors have summarized PubMed and Google Scholar based publication searches to identify recent advances in functional, structural and chemical brain imaging and have discussed how these techniques may be useful in defining CNS disease state and drug effects during drug development. Expert opinion The use of novel brain imaging biomarkers holds the bold promise of making neuroscience drug discovery smarter by increasing the objectivity of decision making thereby improving the probability of success of identifying useful drugs to treat CNS diseases. Functional imaging holds the promise to: (1) define pharmacodynamic markers as an index of target engagement (2) improve translational medicine paradigms to predict efficacy; (3) evaluate CNS efficacy and safety based on brain activation; (4) determine brain activity drug dose-response relationships and (5) provide an objective evaluation of symptom response and disease modification.

Borsook, David; Hargreaves, Richard; Becerra, Lino

2011-01-01

322

Cardiac responses to left ventricular pacing in hearts with normal electrical conduction: beneficial effect of improved filling is counteracted by dyssynchrony.  

PubMed

Cardiac resynchronization therapy (CRT) has been proposed in heart failure patients with narrow QRS, but the mechanism of a potential beneficial effect is unknown. The present study investigated the hypothesis that left ventricular (LV) pacing increases LV end-diastolic volume (LVEDV) by allowing the LV to start filling before the right ventricle (RV) during narrow QRS in an experimental model. LV and biventricular pacing were studied in six anesthetized dogs before and after the induction of LV failure. Function was evaluated by pressures and dimensions, and dyssynchrony was evaluated by electromyograms and deformation. In the nonfailing heart, LV pacing gave the LV a head start in filling relative to the RV (P < 0.05) and increased LVEDV (P < 0.05). The response was similar during LV failure when RV diastolic pressure was elevated. The pacing-induced increase in LVEDV was attributed to a rightward shift of the septum (P < 0.01) due to an increased left-to-right transseptal pressure gradient (P < 0.05). LV pacing, however, also induced dyssynchrony (P < 0.05) and therefore reduced LV stroke work (P < 0.05) during baseline, and similar results were seen in failing hearts. Biventricular pacing did not change LVEDV, but systolic function was impaired. This effect was less marked than with LV pacing. In conclusion, pacing of the LV lateral wall increased LVEDV by displacing the septum rightward, suggesting a mechanism for a favorable effect of CRT in narrow QRS. The pacing, however, induced dyssynchrony and therefore reduced LV systolic function. These observations suggest that detrimental effects should be considered when applying CRT in patients with narrow QRS. PMID:24906920

Boe, Espen; Russell, Kristoffer; Remme, Espen W; Gjesdal, Ola; Smiseth, Otto A; Skulstad, Helge

2014-08-01

323

Left ventricular diastolic function and characteristics in fetal aortic stenosis.  

PubMed

Fetal aortic balloon valvuloplasty (FAV) has shown promise in averting progression of midgestation aortic stenosis (AS) to hypoplastic left heart syndrome in a subset of patients. Patients who achieve biventricular circulation after FAV frequently have left ventricular (LV) diastolic dysfunction (DD). This study evaluates DD in fetuses with AS by comparing echocardiographic indices of LV diastolic function in fetuses underwent FAV (n = 20) with controls (n = 40) and evaluates for LV factors associated with DD in patients with FAV. We also compared pre-FAV and post-FAV DD variables (n = 16). Median gestational age (24 weeks, range 18 to 29 weeks) and fetal heart rate were similar between FAV and controls. Compared with controls, patients with FAV had universally abnormal LV diastolic parameters including fused mitral inflow E and A waves (p = 0.008), higher E velocity (p <0.001), shorter mitral inflow time (p = 0.001), lower LV lateral annulus E' (p <0.001), septal E' (p = 0.003), and higher E/E' (p <0.001) than controls. Patients with FAV had abnormal right ventricular mechanics with higher tricuspid inflow E velocity (p <0.001) and shorter tricuspid inflow time (p = 0.03). Worse LV diastolic function (lower LV E') was associated with higher endocardial fibroelastosis grade (r = 0.74, p <0.001), large LV volume (r = 0.55, p = 0.013), and sphericity (r = 0.58, p = 0.009) and with lower LV pressure by mitral regurgitation jet (r = -0.68, p <0.001). Post-FAV, fewer patients had fused mitral inflow E and A than pre-FAV (p = 0.05) and septal E' was higher (=0.04). In conclusion, fetuses with midgestation AS have evidence of marked DD. Worse DD is associated with larger, more spherical LV, with more extensive endocardial fibroelastosis and lower LV pressure. PMID:24819899

Friedman, Kevin G; Schidlow, David; Freud, Lindsay; Escobar-Diaz, Maria; Tworetzky, Wayne

2014-07-01

324

Global profiling of Shewanella oneidensis MR-1: Expression of hypothetical genes and improved functional annotations  

PubMed Central

The ?-proteobacterium Shewanella oneidensis strain MR-1 is a metabolically versatile organism that can reduce a wide range of organic compounds, metal ions, and radionuclides. Similar to most other sequenced organisms, ?40% of the predicted ORFs in the S. oneidensis genome were annotated as uncharacterized “hypothetical” genes. We implemented an integrative approach by using experimental and computational analyses to provide more detailed insight into gene function. Global expression profiles were determined for cells after UV irradiation and under aerobic and suboxic growth conditions. Transcriptomic and proteomic analyses confidently identified 538 hypothetical genes as expressed in S. oneidensis cells both as mRNAs and proteins (33% of all predicted hypothetical proteins). Publicly available analysis tools and databases and the expression data were applied to improve the annotation of these genes. The annotation results were scored by using a seven-category schema that ranked both confidence and precision of the functional assignment. We were able to identify homologs for nearly all of these hypothetical proteins (97%), but could confidently assign exact biochemical functions for only 16 proteins (category 1; 3%). Altogether, computational and experimental evidence provided functional assignments or insights for 240 more genes (categories 2–5; 45%). These functional annotations advance our understanding of genes involved in vital cellular processes, including energy conversion, ion transport, secondary metabolism, and signal transduction. We propose that this integrative approach offers a valuable means to undertake the enormous challenge of characterizing the rapidly growing number of hypothetical proteins with each newly sequenced genome.

Kolker, Eugene; Picone, Alex F.; Galperin, Michael Y.; Romine, Margaret F.; Higdon, Roger; Makarova, Kira S.; Kolker, Natali; Anderson, Gordon A.; Qiu, Xiaoyun; Auberry, Kenneth J.; Babnigg, Gyorgy; Beliaev, Alex S.; Edlefsen, Paul; Elias, Dwayne A.; Gorby, Yuri A.; Holzman, Ted; Klappenbach, Joel A.; Konstantinidis, Konstantinos T.; Land, Miriam L.; Lipton, Mary S.; McCue, Lee-Ann; Monroe, Matthew; Pasa-Tolic, Ljiljana; Pinchuk, Grigoriy; Purvine, Samuel; Serres, Margrethe H.; Tsapin, Sasha; Zakrajsek, Brian A.; Zhu, Wenhong; Zhou, Jizhong; Larimer, Frank W.; Lawrence, Charles E.; Riley, Monica; Collart, Frank R.; Yates, John R.; Smith, Richard D.; Giometti, Carol S.; Nealson, Kenneth H.; Fredrickson, James K.; Tiedje, James M.

2005-01-01

325

Inhibition of matrix metalloproteinase-2 improves endothelial function and prevents hypertension in insulin-resistant rats  

PubMed Central

BACKGROUND AND PURPOSE Insulin resistance is often found to be associated with high blood pressure. We propose that in insulin-resistant hypertension, endothelial dysfunction is the consequence of increased activity of vascular MMP-2. As MMP-2 proteolytically cleaves a number of extracellular matrix proteins, we hypothesized that MMP-2 impairs endothelial function by proteolytic degradation of endothelial NOS (eNOS) or its cofactor, heat shock protein 90 (HSP90). EXPERIMENTAL APPROACH We tested our hypothesis in bovine coronary artery endothelial cells and fructose-fed hypertensive rats (FHR), a model of acquired systolic hypertension and insulin resistance. KEY RESULTS Treatment of FHRs with the MMP inhibitor doxycycline, preserved endothelial function as well as prevented the development of hypertension, suggesting that MMPs impair endothelial function. Furthermore, incubating endothelial cells in vitro with a recombinant MMP-2 decreased NO production in a dose-dependent manner. Using substrate cleavage assays and immunofluorescence microscopy studies, we found that MMP-2 not only cleaves and degrades HSP90, an eNOS cofactor but also co-localizes with both eNOS and HSP90 in endothelial cells, suggesting that MMPs functionally interact with the eNOS system. Treatment of FHRs with doxycycline attenuated the decrease in eNOS and HSP90 expression but did not improve insulin sensitivity. CONCLUSIONS AND IMPLICATIONS Our data suggest that increased activity of MMP-2 in FHRs impairs endothelial function and promotes hypertension. Inhibition of MMP-2 could be a potential therapeutic strategy for the management of hypertension.

Nagareddy, PR; Rajput, PS; Vasudevan, H; McClure, B; Kumar, U; MacLeod, KM; McNeill, JH

2012-01-01

326

Uniform approximation of wave functions with improved semiclassical transformation amplitudes and Gram-Schmidt orthogonalization  

SciTech Connect

Semiclassical transformation theory implies an integral representation for stationary-state wave functions {psi}{sub m}(q) in terms of angle-action variables ({theta},J). It is a particular solution of Schroedinger's time-independent equation when terms of order ({Dirac_h}/2{pi}){sup 2} and higher are omitted, but the preexponential factor A(q,{theta}) in the integrand of this integral representation does not possess the correct dependence on q. The origin of the problem is identified: the standard unitarity condition invoked in semiclassical transformation theory does not fix adequately in A(q,{theta}) a factor which is a function of the action J written in terms of q and {theta}. A prescription for an improved choice of this factor, based on successfully reproducing the leading behavior of wave functions in the vicinity of potential minima, is outlined. Exact evaluation of the modified integral representation via the residue theorem is possible. It yields wave functions which are not, in general, orthogonal. However, closed-form results obtained after Gram-Schmidt orthogonalization bear a striking resemblance to the exact analytical expressions for the stationary-state wave functions of the various potential models considered (namely, a Poeschl-Teller oscillator and the Morse oscillator)

Davis, Edward D. [Department of Physics, Kuwait University, P.O. Box 5969, Safat (Kuwait)

2004-09-01

327

Quenched Lieb-Oxford Satisfaction and Improved Performance for PBE-type Functionals  

NASA Astrophysics Data System (ADS)

Success for the orbital-free DFT approach to Born-Oppenheimer forces for first-principles molecular dynamics requires progress on orbital-free exchange-correlation (XC) functionals to go along with newly developed orbital-free kinetic energy functionals [V.V. Karasiev et al.,rXiv 0809.4798, J. Comput.-Aided Mat.Des. 13, 111 (2006)]. We report on development and testing of a non-empirical X functional which generalizes PBE X. It satisfies a reduced Lieb-Oxford bound by quenching to homogeneous electron gas behavior for large values of the inhomogeneity s |?n|/n^4/3 on the grounds that large s often corresponds (counter-intuitively) to small, smooth density. Used with the PBE C functional, our X functional reduces mean absolute errors for small molecules by 20% or more with respect to conventional PBE XC. Used with LYP C (a semi-empirical combination), the performance also is improved relative to PBE-LYP.

Trickey, S. B.; Medel, V.; Vela, A.

2009-03-01

328

Prehabilitation Improves Physical Function of Individuals with Severe Disability from Hip or Knee Osteoarthritis  

PubMed Central

ABSTRACT Purpose: To evaluate the effects of prehabilitation (enhancing physical capacity before total hip or knee joint arthroplasty) on pain and physical function of adults with severe hip and knee osteoarthritis (OA). Methods: Consecutive patients (n=650) from 2006 to 2008 with hip or knee OA awaiting total joint arthroplasty (TJA) attended a hospital outpatient clinic for a prehabilitation assessment. All participants completed self-report (Lower Extremity Functional Scale [LEFS] and visual analogue scale for pain [VAS]) and functional performance measures (self-paced walk [SPW], timed stair, and timed up-and-go [TUG] tests). A subset of 28 participants with severe disability participated in a structured outpatient prehabilitation programme. Between-group differences were assessed via independent t-tests; paired Student's t-tests and Wilcoxon signed rank tests were used to compare changes in pain and function following the prehabilitation programme. Results: A total of 28 individuals (16 female) with mean age 67 (SD 10) years and BMI 33 (8) kg/m2 awaiting TJA (10 hips, 18 knees) participated in a prehabilitation programme of 9 (6) weeks' duration. Relative to baseline, there was significant improvement in LEFS score (mean change 7.6; 95% CI, 1.7–13.5; p=0.013), SPW (mean change 0.17 m/s; 95% CI, 0.07–0.26; p=0.001), TUG (mean change 4.2 s; 95% CI, 2.0–6.4; p<0.001), and stair test performance (mean change 3.8 s [SD 14.6]; p=0.005) following prehabilitation. Conclusion: This study presents preliminary evidence that prehabilitation improves physical function even in the most severely compromised patients with OA awaiting TJA.

Desmeules, Francois; Hall, Jayne

2013-01-01

329

Pulsed electromagnetic field improves cardiac function in response to myocardial infarction.  

PubMed

Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to improve regeneration in various ischemic episodes. Here, we examined whether PEMF therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the cellular/molecular mechanisms underlying PEMF-related therapy was further investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8 minutes/cycle, 30 ± 3 Hz, 5 mT) after MI induction. The data demonstrated that PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac systolic function. Moreover, PEMF treatment increased capillary density, the levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor-1? in infarct border zone. Furthermore, the number and function of circulating endothelial progenitor cells were advanced in PEMF treating rats. In vitro, PEMF induced the degree of human umbilical venous endothelial cells tubulization and increased soluble pro-angiogenic factor secretion (VEGF and nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function, inhibits apoptosis and trigger postnatal neovascularization in ischemic myocardium. PMID:24936220

Hao, Chang-Ning; Huang, Jing-Juan; Shi, Yi-Qin; Cheng, Xian-Wu; Li, Hao-Yun; Zhou, Lin; Guo, Xin-Gui; Li, Rui-Lin; Lu, Wei; Zhu, Yi-Zhun; Duan, Jun-Li

2014-01-01

330

Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement.  

PubMed

To examine the influence of chronic mechanical stretch on functional behavior of cardiac myocytes, we reconstituted embryonic chick or neonatal rat cardiac myocytes to a 3-dimensional engineered heart tissue (EHT) by mixing freshly isolated cells with neutralized collagen I and culturing them between two Velcro-coated silicone tubes, held at a fixed distance with a metal spacer. After 4 days, EHTs were subjected to a phasic unidirectional stretch for 6 days in serum-containing medium. Compared to unstretched controls, RNA/DNA and protein/cell ratios increased by 100% and 50%, respectively. ANF mRNA and alpha-sarcomeric actin increased by 98% and 40%, respectively. Morphologically, stretched EHTs exhibited improved organization of cardiac myocytes into parallel arrays of rod-shaped cells, increased cell length and width, longer myofilaments, and increased mitochondrial density. Thus, stretch induced phenotypic changes, generally referred to as hypertrophy. Concomitantly, force of contraction was two- to fourfold higher both under basal conditions and after stimulation with calcium or the beta-adrenergic agonist isoprenaline. Contraction kinetics were accelerated with a 14-44% decrease in twitch duration under all those conditions. In summary, we have developed a new in vitro model that allows morphological, molecular, and functional consequences of stretch to be studied under defined conditions. The main finding was that stretch of EHTs induced cardiac myocyte hypertrophy, which was accompanied by marked improvement of contractile function. PMID:10744624

Fink, C; Ergün, S; Kralisch, D; Remmers, U; Weil, J; Eschenhagen, T

2000-04-01

331

An appraisal of rehabilitation regimes used for improving functional outcome after total hip replacement surgery.  

PubMed

This study aimed to systematically review the literature with regards to studies of rehabilitation programmes that have tried to improve function after total hip replacement (THR) surgery. 15 randomised controlled trials were identified of which 11 were centre-based, 2 were home based and 2 were trials comparing home and centre based interventions. The use of a progressive resistance training (PRT) programme led to significant improvement in muscle strength and function if the intervention was carried out early (< 1 month following surgery) in a centre (6/11 centre-based studies used PRT), or late (> 1 month following surgery) in a home based setting (2/2 home based studies used PRT). In direct comparison, there was no difference in functional measures between home and centre based programmes (2 studies), with PRT not included in the regimes prescribed. A limitation of the majority of these intervention studies was the short period of follow up. Centre based program delivery is expensive as high costs are associated with supervision, facility provision, and transport of patients. Early interventions are important to counteract the deficit in muscle strength in the affected limb, as well as persistent atrophy that exists around the affected hip at 2 years post-operatively. Studies of early home-based regimes featuring PRT with long term follow up are needed to address the problems currently associated with rehabilitation following THR. PMID:22313723

Okoro, Tosan; Lemmey, Andrew B; Maddison, Peter; Andrew, John G

2012-01-01

332

Perturbative renormalization functions of local operators for staggered fermions with stout improvement  

NASA Astrophysics Data System (ADS)

In this paper we present the perturbative computation of the renormalization functions for the quark field and for a complete set of ultralocal fermion bilinears. The computation of the relevant Green’s functions are carried out at one-loop level for the staggered action using massive fermions. The gluon links which appear both in the fermion action and in the definition of the bilinears are improved by applying a stout smearing procedure up to two times, iteratively. In the gluon sector we employ the Symanzik improved gauge action for different sets of values of the Symanzik coefficients. The renormalization functions are presented in (two variants of) the RI' and in the MS¯ renormalization scheme; the dependence on all stout parameters, as well as on the fermion mass, the gauge fixing parameter, and the renormalization scale, is shown explicitly. This work is related to our recent paper [Phys. Rev. D 86, 094512 (2012)]. To make our results easily accessible to the reader, we include them in the distribution package of this paper as a Mathematica input file, “Staggered.m.”

Constantinou, M.; Costa, M.; Panagopoulos, H.

2013-08-01

333

Embryonic Stem Cell-Based Cardiopatches Improve Cardiac Function in Infarcted Rats  

PubMed Central

Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.

Vallee, Jean-Paul; Hauwel, Mathieu; Lepetit-Coiffe, Matthieu; Bei, Wang; Montet-Abou, Karin; Meda, Paolo; Gardier, Stephany; Zammaretti, Prisca; Kraehenbuehl, Thomas P.; Herrmann, Francois; Hubbell, Jeffrey A.

2012-01-01

334

Pulsed electromagnetic field improves cardiac function in response to myocardial infarction  

PubMed Central

Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to improve regeneration in various ischemic episodes. Here, we examined whether PEMF therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the cellular/molecular mechanisms underlying PEMF-related therapy was further investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8 minutes/cycle, 30 ± 3 Hz, 5 mT) after MI induction. The data demonstrated that PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac systolic function. Moreover, PEMF treatment increased capillary density, the levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor-1? in infarct border zone. Furthermore, the number and function of circulating endothelial progenitor cells were advanced in PEMF treating rats. In vitro, PEMF induced the degree of human umbilical venous endothelial cells tubulization and increased soluble pro-angiogenic factor secretion (VEGF and nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function, inhibits apoptosis and trigger postnatal neovascularization in ischemic myocardium.

Hao, Chang-Ning; Huang, Jing-Juan; Shi, Yi-Qin; Cheng, Xian-Wu; Li, Hao-Yun; Zhou, Lin; Guo, Xin-Gui; Li, Rui-Lin; Lu, Wei; Zhu, Yi-Zhun; Duan, Jun-Li

2014-01-01

335

Lv1 Inhibition of Human Immunodeficiency Virus Type 1 Is Counteracted by Factors That Stimulate Synthesis or Nuclear Translocation of Viral cDNA  

Microsoft Academic Search

Human immunodeficiency virus type 1 (HIV-1) cDNA synthesis is inhibited in cells from some nonhuman primates by an activity called Lv1. Sensitivity to restriction by Lv1 maps to a region of the HIV-1 CA required for interaction with the cellular protein cyclophilin A. A similar antiviral activity in mammalian cells, Ref1, inhibits reverse transcription of murine leukemia virus (MLV), but

Lionel Berthoux; Sarah Sebastian; Elena Sokolskaja; Jeremy Luban

2004-01-01

336

Mitral annular descent velocity by tissue Doppler echocardiography as an index of global left ventricular function  

Microsoft Academic Search

Mitral annular descent has been described as an index of left ventricular (LV) systolic function, which is independent of endocardial definition. Echocardiographic tissue Doppler imaging is a new technique that calculates and displays color-coded cardiac tissue velocities on-line. To evaluate mitral annular descent velocity as a rapid index of global LV function, we performed tissue Doppler imaging studies in 55

Vijay K. Gulati; William E. Katz; William P. Follansbee; John Gorcsan

1996-01-01

337

Treatment of functional mitral regurgitation by percutaneous annuloplasty: results of the TITAN Trial  

PubMed Central

Aims Functional mitral regurgitation (FMR) contributes to morbidity and mortality in heart failure (HF) patients. The aim of this study was to determine whether percutaneous mitral annuloplasty could safely and effectively reduce FMR and yield durable long-term clinical benefit. Methods and results The impact of mitral annuloplasty (Carillon Mitral Contour System) was evaluated in HF patients with at least moderate FMR. Patients in whom the device was placed then acutely recaptured for clinical reasons served as a comparator group. Quantitative measures of FMR, left ventricular (LV) dimensions, New York Heart Association (NYHA) class, 6 min walk distance (6MWD), and quality of life were assessed in both groups up to 12 months. Safety and key functional data were assessed in the implanted cohort up to 24 months. Thirty-six patients received a permanent implant; 17 had the device recaptured. The 30-day major adverse event rate was 1.9%. In contrast to the comparison group, the implanted cohort demonstrated significant reductions in FMR as represented by regurgitant volume [baseline 34.5 ±11.5 mL to 17.4 ±12.4 mL at 12 months (P < 0.001)]. There was a corresponding reduction in LV diastolic volume [baseline 208.5 ±62.0 mL to 178.9 ±48.0 mL at 12 months (P =0.015)] and systolic volume [baseline 151.8 ±57.1 mL to 120.7 ±43.2 mL at 12 months (P =0.015)], compared with progressive LV dilation in the comparator. The 6MWD markedly improved for the implanted patients by 102.5 ±164 m at 12 months (P =0.014) and 131.9 ±80 m at 24 months (P < 0.001). Conclusion Percutaneous reduction of FMR using a coronary sinus approach is associated with reverse LV remodelling. Significant clinical improvements persisted up to 24 months.

Siminiak, Tomasz; Wu, Justina C.; Haude, Michael; Hoppe, Uta C.; Sadowski, Jerzy; Lipiecki, Janusz; Fajadet, Jean; Shah, Amil M.; Feldman, Ted; Kaye, David M.; Goldberg, Steven L.; Levy, Wayne C.; Solomon, Scott D.; Reuter, David G.

2012-01-01

338

Sampling Multiple Scoring Functions Can Improve Protein Loop Structure Prediction Accuracy  

PubMed Central

Accurately predicting loop structures is important for understanding functions of many proteins. In order to obtain loop models with high accuracy, efficiently sampling the loop conformation space to discover reasonable structures is a critical step. In loop conformation sampling, coarse-grain energy (scoring) functions coupling with reduced protein representations are often used to reduce the number of degrees of freedom as well as sampling computational time. However, due to implicitly considering many factors by reduced representations, the coarse-grain scoring functions may have potential insensitivity and inaccuracy, which can mislead the sampling process and consequently ignore important loop conformations. In this paper, we present a new computational sampling approach to obtain reasonable loop backbone models, so-called the Pareto Optimal Sampling (POS) method. The rationale of the POS method is to sample the function space of multiple, carefully-selected scoring functions to discover an ensemble of diversified structures yielding Pareto optimality to all sampled conformations. POS method can efficiently tolerate insensitivity and inaccuracy in individual scoring functions and thereby lead to significant accuracy improvement in loop structure prediction. We apply the POS method to a set of 4- to 12-residue loop targets using a function space composed of backbone-only Rosetta, DFIRE, and a triplet backbone dihedral potential developed in our lab. Our computational results show that in 501 out of 502 targets, the model sets generated by POS contain structure models are within subangstrom resolution. Moreover, the top-ranked models have Root Mean Square Deviation (RMSD) less than 1A in 96.8%, 84.1%, and 72.2% of the short (4~6 residues), medium (7~9 residues), and long (10~12) targets, respectively, when the all-atom models are generated by local optimization from the backbone models and are ranked by our recently developed Pareto Optimal Consensus (POC) method. Similar sampling effectiveness can also be found in a set of 13-residue loop targets.

Rata, Ionel; Jakobsson, Eric

2011-01-01

339

Jatropha curcas, a biofuel crop: Functional genomics for understanding metabolic pathways and genetic improvement  

PubMed Central

Jatropha curcas is currently attracting much attention as an oilseed crop for biofuel, as Jatropha can grow under climate and soil conditions that are unsuitable for food production. However, little is known about Jatropha, and there are a number of challenges to be overcome. In fact, Jatropha has not really been domesticated; most of the Jatropha accessions are toxic, which renders the seedcake unsuitable for use as animal feed. The seeds of Jatropha contain high levels of polyunsaturated fatty acids, which negatively impact the biofuel quality. Fruiting of Jatropha is fairly continuous, thus increasing costs of harvesting. Therefore, before starting any improvement program using conventional or molecular breeding techniques, understanding gene function and the genome scale of Jatropha are prerequisites. This review presents currently available and relevant information on the latest technologies (genomics, transcriptomics, proteomics and metabolomics) to decipher important metabolic pathways within Jatropha, such as oil and toxin synthesis. Further, it discusses future directions for biotechnological approaches in Jatropha breeding and improvement.

Maghuly, Fatemeh; Laimer, Margit

2013-01-01

340

Dor procedure for dyskinetic anteroapical myocardial infarction fails to improve contractility in the borderzone  

PubMed Central

Background Endoventricular patch plasty (Dor) is used to reduce left ventricular (LV) volume after myocardial infarction (MI) and subsequent LV remodeling. Methods and Results End-diastolic and end-systolic pressure volume and Starling relationships were measured and magnetic resonance (MRI) images with non-invasive tags used to calculate 3D myocardial strain in six sheep 2 weeks before, and 2 and 6 weeks after the Dor procedure. These experimental results were previously reported. The imaging data from one sheep was incomplete. Animal specific finite element (FE) models were created from the remaining five animals using MRI images and LV pressure obtained at early diastolic filling. FE models were optimized using 3D strain and used to determine systolic material properties, Tmax,skinned-fiber, and diastolic and systolic stress in remote myocardium and borderzone (BZ). Six weeks after Dor procedure, end-diastolic and end-systolic stress in the BZ were substantially reduced. However, although there was a slight increase in Tmax,skinned-fiber in the BZ near the MI at 6 weeks, the change was not significant. Conclusions The Dor procedure decreases end-diastolic and end-systolic stress but fails to improve contractility in the infarct BZ. Future work should focus on measures that will enhance BZ function alone or in combination with surgical remodeling.

Sun, Kay; Zhang, Zhihong; Suzuki, Takamaro; Wenk, Jonathan; Stander, Nielen; Einstein, Daniel R.; Saloner, David A.; Wallace, Arthur W.; Guccione, Julius M.; Ratcliffe, Mark B.

2009-01-01

341

Body adiposity dictates different mechanisms of increased coronary reactivity related to improved in vivo cardiac function  

PubMed Central

Background Saturated fatty acid-rich high fat (HF) diets trigger abdominal adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. This study was aimed at evaluating the effects of nascent obesity on the cardiac function of animals fed a high-fat diet and at analyzing the mechanisms by which these alterations occurred at the level of coronary reserve. Materials and methods Rats were fed a control (C) or a HF diet containing high proportions of saturated fatty acids for 3 months. Thereafter, their cardiac function was evaluated in vivo using a pressure probe inserted into the cavity of the left ventricle. Their heart was isolated, perfused iso-volumetrically according to the Langendorff mode and the coronary reserve was evaluated by determining the endothelial-dependent (EDV) and endothelial-independent (EIV) vasodilatations in the absence and presence of endothelial nitric oxide synthase and cyclooxygenase inhibitors (L-NAME and indomethacin). The fatty acid composition of cardiac phospholipids was then evaluated. Results Although all the HF-fed rats increased their abdominal adiposity, some of them did not gain body weight (HF- group) compared to the C group whereas other ones had a higher body weight (HF+). All HF rats displayed a higher in vivo cardiac activity associated with an increased EDV. In the HF- group, the improved EDV was due to an increase in the endothelial cell vasodilatation activity whereas in the HF+?group, the enhanced EDV resulted from an improved sensitivity of coronary smooth muscle cells to nitric oxide. Furthermore, in the HF- group the main pathway implicated in the EDV was the NOS pathway while in the HF+?group the COX pathway. Conclusions Nascent obesity-induced improvement of cardiac function may be supported by an enhanced coronary reserve occurring via different mechanisms. These mechanisms implicate either the endothelial cells activity or the smooth muscle cells sensitivity depending on the body adiposity of the animals.

2014-01-01

342

Time for Bed: Parent-Set Bedtimes Associated with Improved Sleep and Daytime Functioning in Adolescents  

PubMed Central

Study Objectives: To determine the proportion of adolescents whose bedtime is set by their parents and to evaluate whether parent-set bedtimes are associated with earlier bedtimes, more sleep, and better daytime functioning. Participants: 385 adolescents aged 13-18 years (mean = 15.6, SD = 0.95; 60% male) from 8 socioeconomically diverse schools in South Australia. Measurements & Methods: Adolescents completed the School Sleep Habits Survey during class time and then completed an 8-day Sleep Diary. The Flinders Fatigue Scale was completed on the final day of the study. Results: 17.5% of adolescents reported a parent-set bedtime as the main factor determining their bedtime on school nights. Compared to adolescents without parent-set bedtimes, those with parent-set bedtimes had earlier bedtimes, obtained more sleep, and experienced improved daytime wakefulness and less fatigue. They did not differ significantly in terms of time taken to fall asleep. When parent-set bedtimes were removed on weekends, sleep patterns did not significantly differ between groups. Conclusions: Significant personal and public health issues, such as depression and accidental injury and mortality, are associated with insufficient sleep. Converging biological and psychosocial factors mean that adolescence is a period of heightened risk. Parent-set bedtimes offer promise as a simple and easily translatable means for parents to improve the sleep and daytime functioning of their teens. Citation: Short MA; Gradisar M; Wright H; Lack LC; Dohnt H; Carskadon MA. Time for bed: parent-set bedtimes associated with improved sleep and daytime functioning in adolescents. SLEEP 2011;34(6):797-800.

Short, Michelle A.; Gradisar, Michael; Wright, Helen; Lack, Leon C.; Dohnt, Hayley; Carskadon, Mary A.

2011-01-01

343

Consumption of cocoa flavanols results in an acute improvement in visual and cognitive functions.  

PubMed

Cocoa flavanols (CF) influence physiological processes in ways that suggest their consumption may improve aspects of neural function, and previous studies have found positive influences of CF on cognitive performance. In this preliminary study we investigated whether visual, as well as cognitive, function is influenced by an acute dose of CF in young adults. We employed a randomized, single-blinded, order counterbalanced, crossover design in which 30 healthy adults consumed both dark chocolate containing 720mg CF and a matched quantity of white chocolate, with a one week interval between testing sessions. Visual contrast sensitivity was assessed by reading numbers that became progressively more similar in luminance to their background. Motion sensitivity was assessed firstly by measuring the threshold proportion of coherently moving signal dots that could be detected against a background of random motion, and secondly by determining the minimum time required to detect motion direction in a display containing a high proportion of coherent motion. Cognitive performance was assessed using a visual spatial working memory for location task and a choice reaction time task designed to engage processes of sustained attention and inhibition. Relative to the control condition, CF improved visual contrast sensitivity and reduced the time required to detect motion direction, but had no statistically reliable effect on the minimum proportion of coherent motion that could be detected. In terms of cognitive performance, CF improved spatial memory and performance on some aspects of the choice reaction time task. As well as extending the range of cognitive tasks that are known to be influenced by CF consumption, this is the first report of acute effects of CF on the efficiency of visual function. These acute effects can be explained by increased cerebral blood flow caused by CF, although in the case of contrast sensitivity there may be an additional contribution from CF induced retinal blood flow changes. PMID:21324330

Field, David T; Williams, Claire M; Butler, Laurie T

2011-06-01

344

Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer The designer peptide LRKKLGKA could self-assemble into nanofibers. Black-Right-Pointing-Pointer Injection of LRKKLGKA peptides could promote the sustained delivery of VEGF. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides lead to sufficient angiogenesis. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides improves heart function. -- Abstract: Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. This designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.

Guo, Hai-dong [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China)] [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Cui, Guo-hong; Yang, Jia-jun [Department of Neurology, Shanghai No. 6 People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233 (China)] [Department of Neurology, Shanghai No. 6 People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233 (China); Wang, Cun [Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China)] [Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Zhu, Jing; Zhang, Li-sheng; Jiang, Jun [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China)] [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Shao, Shui-jin, E-mail: shaoshuijin@163.com [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China)] [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China)

2012-07-20

345

Sigma-1R agonist improves motor function and motoneuron survival in ALS mice.  

PubMed

Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive weakness, muscle atrophy, and paralysis due to the loss of upper and lower motoneurons (MNs). Sigma-1 receptor (sigma-1R) activation promotes neuroprotection after ischemic and traumatic injuries to the central nervous system. We recently reported that sigma-1R agonist (PRE-084) improves the survival of MNs after root avulsion injury in rats. Moreover, a mutation of the sigma-1R leading to frontotemporal lobar degeneration/amyotrophic lateral sclerosis (ALS) was recently described in human patients. In the present study, we analyzed the potential therapeutic effect of the sigma-1R agonist (PRE-084) in the SOD1(G93A) mouse model of ALS. Mice were daily administered with PRE-084 (0.25 mg/kg) from 8 to 16 weeks of age. Functional outcome was assessed by electrophysiological tests and computerized analysis of locomotion. Histological, immunohistochemical analyses and Western blot of the spinal cord were performed. PRE-084 administration from 8 weeks of age improved the function of MNs, which was manifested by maintenance of the amplitude of muscle action potentials and locomotor behavior, and preserved neuromuscular connections and MNs in the spinal cord. Moreover, it extended survival in both female and male mice by more than 15 %. Delayed administration of PRE-084 from 12 weeks of age also significantly improved functional outcome and preservation of the MNs. There was an induction of protein kinase C-specific phosphorylation of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor in SOD1(G93A) animals, and a reduction of the microglial reactivity compared with untreated mice. PRE-084 exerts a dual therapeutic contribution, modulating NMDA Ca(2+) influx to protect MNs, and the microglial reactivity to ameliorate the MN environment. In conclusion, sigma-1R agonists, such as PRE-084, may be promising candidates for a therapeutical strategy of ALS. PMID:22935988

Mancuso, Renzo; Oliván, Sara; Rando, Amaya; Casas, Caty; Osta, Rosario; Navarro, Xavier

2012-10-01

346

Platelet gene therapy improves hemostatic function for integrin ?IIb?3-deficient dogs  

PubMed Central

Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ?1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin ?IIb?3. Transfusion therapy is frequently inadequate because patients often generate antibodies to ?IIb?3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 ?IIb?3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to ?IIb?3’s major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ?135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to ?IIb?3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects.

Fang, Juan; Jensen, Eric S.; Boudreaux, Mary K.; Du, Lily M.; Hawkins, Troy B.; Koukouritaki, Sevasti B.; Cornetta, Kenneth; Wilcox, David A.

2011-01-01

347

Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia  

Microsoft Academic Search

OBJECTIVEThis work was undertaken to determine whether dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia.BACKGROUNDMarine omega-3 fatty acids improve vascular function, but the underlying mechanism(s) are unclear. We studied the effects of marine omega-3 fatty acids on large artery endothelial function in subjects with hypercholesterolemia.METHODSHypercholesterolemic subjects with no other known cause

Jonathan Goodfellow; Michael F Bellamy; Mark W Ramsey; Christopher J. H Jones; Malcolm J Lewis

2000-01-01

348

Reflex conditioning: A new strategy for improving motor function after spinal cord injury  

PubMed Central

Spinal reflex conditioning changes reflex size, induces spinal cord plasticity, and modifies locomotion. Appropriate reflex conditioning can improve walking in rats after spinal cord injury (SCI). Reflex conditioning offers a new therapeutic strategy for restoring function in people with SCI. This approach can address the specific deficits of individuals with SCI by targeting specific reflex pathways for increased or decreased responsiveness. In addition, once clinically significant regeneration can be achieved, reflex conditioning could provide a means of re-educating the newly (and probably imperfectly) reconnected spinal cord.

Chen, Xiang Yang; Chen, Yi; Wang, Yu; Thompson, Aiko; Carp, Jonathan S.; Segal, Richard L.; Wolpaw, Jonathan R.

2010-01-01

349

Improving functional annotation for industrial microbes: a case study with Pichia pastoris  

PubMed Central

The research communities studying microbial model organisms, such as Escherichia coli or Saccharomyces cerevisiae, are well served by model organism databases that have extensive functional annotation. However, this is not true of many industrial microbes that are used widely in biotechnology. In this Opinion piece, we use Pichia (Komagataella) pastoris to illustrate the limitations of the available annotation. We consider the resources that can be implemented in the short term both to improve Gene Ontology (GO) annotation coverage based on annotation transfer, and to establish curation pipelines for the literature corpus of this organism.

Dikicioglu, Duygu; Wood, Valerie; Rutherford, Kim M.; McDowall, Mark D.; Oliver, Stephen G.

2014-01-01

350

Improving Performance of the System Safety Function at Marshall Space Flight Center  

NASA Technical Reports Server (NTRS)

The Columbia Accident Investigation Board (CAIB) determined that organizational and management issues were significant contributors to the loss of Space Shuttle Columbia. In addition, the CAIB observed similarities between the organizational and management climate that preceded the Challenger accident and the climate that preceded the Columbia accident. To prevent recurrence of adverse organizational and management climates, effective implementation of the system safety function is suggested. Attributes of an effective system safety program are presented. The Marshall Space Flight Center (MSFC) system safety program is analyzed using the attributes. Conclusions and recommendations for improving the MSFC system safety program are offered in this case study.

Kiessling, Ed; Tippett, Donald D.; Shivers, Herb

2004-01-01

351

Rational identification of diet-derived postbiotics for improving intestinal microbiota function.  

PubMed

The intestinal microbiota plays an important role in a wide range of functions and whole body homeostasis. Recent advances have linked microbiota dysbiosis to conditions ranging from Crohn's disease to cancer. The restoration or strengthening of the intestinal microbiota through diet-based approaches such as probiotics and prebiotics has been proposed for combating the onset or progression of these diseases. In this review, we highlight the importance of postbiotics for the manipulation of the intestinal microbiota, with special emphasis on systems biology computational tools and targeted metabolomics for the rational discovery and identification of these bioactive molecules. The identification of novel postbiotics and the pathways responsible for their production should lead to improved mechanistic understanding of the role that specific probiotics, prebiotics, and postbiotics have in restoring intestinal microbiota composition and function. PMID:24679263

Klemashevich, Cory; Wu, Charmian; Howsmon, Daniel; Alaniz, Robert C; Lee, Kyongbum; Jayaraman, Arul

2014-04-01

352

Improved partition-expansion of two-center distributions involving Slater functions.  

PubMed

The calculation of the electronic structure of large systems is facilitated by the substitution of the two-center distributions by their projections on auxiliary basis sets of one-center functions. An alternative is the partition-expansion method in which one first decides what part of the distribution is assigned to each center, and next expands each part in spherical harmonics times radial factors. The method is exact, requires neither auxiliary basis sets nor projections, and can be applied to Gaussian and Slater basis sets. Two improvements in the partition-expansion method for Slater functions are reported: general expressions valid for arbitrary quantum numbers are derived and the efficiency of the procedure is increased giving analytical solutions to integrals previously computed by numerical quadrature. The efficiency of the new version is assessed in several molecules and the advantages over the projection methods are pointed out. PMID:23702966

López, Rafael; Ramírez, Guillermo; Ema, Ignacio; Fernández Rico, Jaime

2013-08-01

353

Engineering the heart: evaluation of conductive nanomaterials for improving implant integration and cardiac function.  

PubMed

Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction. PMID:24429673

Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; Mengqiu Xing, Malcolm; Wang, Changyong

2014-01-01

354

Resveratrol improves the mitochondrial function and fertilization outcome of bovine oocytes.  

PubMed

The aim of the present study was to address the effect of resveratrol-mediated upregulation of sirtuin 1 (SIRT1) during oocyte maturation on mitochondrial function, the developmental ability of oocytes and on mechanisms responsible for blockage of polyspermic fertilization. Oocytes collected from slaughterhouse-derived ovaries were cultured in TCM-199 medium supplemented with 10% FCS and 0 or 20 µM resveratrol (Res). We examined the effect of Res on SIRT1 expression in in vitro-matured oocytes (Exp 1); fertilization and developmental ability (Exp 2); mitochondrial DNA copy number (Mt number), ATP content and mitochondrial membrane potential in matured oocytes (Exp 3); and the time required for proteinase to dissolve the zona pellucida following in vitro fertilization (as a marker of zona pellucida hardening), as well as on the distribution of cortical granules before and after fertilization (Exp 4). In Exp 1, the 20 µM Res treatment upregulated protein expression of SIRT1 in oocytes. In Exp 2, Res treatment improved the ratio of normal fertilization and the total cell number of blastocysts. In Exp 3, Res treatment significantly increased the ATP content in matured oocytes. Additionally, Res increased the overall Mt number and mitochondrial membrane potential, but the effect was donor-dependent. In Exp 4, Res-induced zona hardening improved the distribution and exocytosis of cortical granules after in vitro fertilization. In conclusion, Res improved the quality of oocytes by improving mitochondrial quantity and quality. In addition, Res added to the maturation medium enhanced SIRT1 protein expression in oocytes and improved fertilization via reinforcement of the mechanisms responsible for blockage of polyspermic fertilization. PMID:24390595

Takeo, Shun; Sato, Daichi; Kimura, Koji; Monji, Yasunori; Kuwayama, Takehito; Kawahara-Miki, Ryoka; Iwata, Hisataka

2014-04-24

355

Resveratrol Improves the Mitochondrial Function and Fertilization Outcome of Bovine Oocytes  

PubMed Central

The aim of the present study was to address the effect of resveratrol-mediated upregulation of sirtuin 1 (SIRT1) during oocyte maturation on mitochondrial function, the developmental ability of oocytes and on mechanisms responsible for blockage of polyspermic fertilization. Oocytes collected from slaughterhouse-derived ovaries were cultured in TCM-199 medium supplemented with 10% FCS and 0 or 20 µM resveratrol (Res). We examined the effect of Res on SIRT1 expression in in vitro-matured oocytes (Exp 1); fertilization and developmental ability (Exp 2); mitochondrial DNA copy number (Mt number), ATP content and mitochondrial membrane potential in matured oocytes (Exp 3); and the time required for proteinase to dissolve the zona pellucida following in vitro fertilization (as a marker of zona pellucida hardening), as well as on the distribution of cortical granules before and after fertilization (Exp 4). In Exp 1, the 20 µM Res treatment upregulated protein expression of SIRT1 in oocytes. In Exp 2, Res treatment improved the ratio of normal fertilization and the total cell number of blastocysts. In Exp 3, Res treatment significantly increased the ATP content in matured oocytes. Additionally, Res increased the overall Mt number and mitochondrial membrane potential, but the effect was donor-dependent. In Exp 4, Res-induced zona hardening improved the distribution and exocytosis of cortical granules after in vitro fertilization. In conclusion, Res improved the quality of oocytes by improving mitochondrial quantity and quality. In addition, Res added to the maturation medium enhanced SIRT1 protein expression in oocytes and improved fertilization via reinforcement of the mechanisms responsible for blockage of polyspermic fertilization.

TAKEO, Shun; SATO, Daichi; KIMURA, Koji; MONJI, Yasunori; KUWAYAMA, Takehito; KAWAHARA-MIKI, Ryoka; IWATA, Hisataka

2013-01-01

356

Improving protein function prediction using domain and protein complexes in PPI networks  

PubMed Central

Background Characterization of unknown proteins through computational approaches is one of the most challenging problems in silico biology, which has attracted world-wide interests and great efforts. There have been some computational methods proposed to address this problem, which are either based on homology mapping or in the context of protein interaction networks. Results In this paper, two algorithms are proposed by integrating the protein-protein interaction (PPI) network, proteins’ domain information and protein complexes. The one is domain combination similarity (DCS), which combines the domain compositions of both proteins and their neighbors. The other is domain combination similarity in context of protein complexes (DSCP), which extends the protein functional similarity definition of DCS by combining the domain compositions of both proteins and the complexes including them. The new algorithms are tested on networks of the model species of Saccharomyces cerevisiae to predict functions of unknown proteins using cross validations. Comparing with other several existing algorithms, the results have demonstrated the effectiveness of our proposed methods in protein function prediction. Furthermore, the algorithm DSCP using experimental determined complex data is robust when a large percentage of the proteins in the network is unknown, and it outperforms DCS and other several existing algorithms. Conclusions The accuracy of predicting protein function can be improved by integrating the protein-protein interaction (PPI) network, proteins’ domain information and protein complexes.

2014-01-01

357

Strategies for improving early detection of glaucoma: the combined structure-function index  

PubMed Central

The early detection of glaucoma is important in order to enable appropriate monitoring and treatment, and to minimize the risk of irreversible visual field loss. Although advances in ocular imaging offer the potential for earlier diagnosis, the best method is likely to involve a combination of information from structural and functional tests. Recent studies have shown it is possible to estimate the number of retinal ganglion cells from optical coherence tomography and standard automated perimetry, and to then pool the results to produce a combined structure–function index (CSFI). The CSFI represents the estimated percentage of retinal ganglion cells lost compared to an age-matched healthy eye. Previous studies have suggested that the CSFI is better able to detect glaucoma than isolated measures of structure and function, and that it performs well even in preperimetric glaucoma. The purpose of this review is to describe new strategies, such as the CSFI, that have the potential to improve the early detection of glaucoma. We also describe how our ability to detect early glaucoma may be further enhanced by incorporating demographic risk factors, clinical examination findings, and imaging and functional test results into intuitive models that provide estimates of disease probability.

Tatham, Andrew J; Weinreb, Robert N; Medeiros, Felipe A

2014-01-01

358

Pharmacological inhibition of DDAH1 improves survival, haemodynamics and organ function in experimental septic shock.  

PubMed

The aim of the present study was to investigate the therapeutic effects of pharmacological inhibition of DDAH1 (dimethylarginine dimethylaminohydrolase 1), an enzyme that metabolizes endogenously produced nitric oxide synthase inhibitors, principally ADMA (asymmetric dimethylarginine). The present study employs a series of rodent models to evaluate the effectiveness a DDAH1-selective inhibitor (L-257). Short-term models involved the development of endotoxaemia using lipopolysaccharide and long-term models involved the intraperitoneal administration of faecal slurry. In order to generate the most relevant model possible, following induction of severe sepsis, animals received appropriate fluid resuscitation and in some models vasopressor therapy. The effects of L-257 on survival, haemodynamics and organ function were subsequently assessed. Survival was significantly longer in all L-257 treatment groups (P<0.01) and no adverse effects on haemodynamics and organ function were observed following L-257 administration to either animals with sepsis or naïve animals. Haemodynamic performance was preserved and the noradrenaline dose required to maintain target blood pressure was reduced in the treated animals (P<0.01). Animals receiving L-257 had significantly increased plasma ADMA concentrations. Plasma nitrite/nitrate was reduced as was severity of sepsis-associated renal dysfunction. The degree of tachycardia was improved as were indices of tissue and microvascular perfusion. The results of the present study show that the selective DDAH-1 inhibitor L-257 improved haemodynamics, provided catecholamine sparing and prolonged survival in experimental sepsis. Further studies will determine its potential utility in human septic shock. PMID:24611830

Wang, Zhen; Lambden, Simon; Taylor, Valerie; Sujkovic, Elizabeth; Nandi, Manasi; Tomlinson, James; Dyson, Alex; McDonald, Neil; Caddick, Stephen; Singer, Mervyn; Leiper, James

2014-06-01

359

Functional improvements after orthodontic-surgical reconstruction in a patient with multiple maxillofacial fractures.  

PubMed

Patients with multiple craniofacial fractures often suffer from stomatognathic problems after their primary treatment, because administering emergency care is the clinician's highest priority. Therefore, optimal bone repositioning is sometimes difficult because bone fixation is delayed. Moreover, neither an adequate radiographic examination nor an evaluation of pri