Sample records for improve lv function

  1. Motion corrected LV quantification based on 3D modelling for improved functional assessment in cardiac MRI

    NASA Astrophysics Data System (ADS)

    Liew, Y. M.; McLaughlin, R. A.; Chan, B. T.; Aziz, Y. F. Abdul; Chee, K. H.; Ung, N. M.; Tan, L. K.; Lai, K. W.; Ng, S.; Lim, E.

    2015-04-01

    Cine MRI is a clinical reference standard for the quantitative assessment of cardiac function, but reproducibility is confounded by motion artefacts. We explore the feasibility of a motion corrected 3D left ventricle (LV) quantification method, incorporating multislice image registration into the 3D model reconstruction, to improve reproducibility of 3D LV functional quantification. Multi-breath-hold short-axis and radial long-axis images were acquired from 10 patients and 10 healthy subjects. The proposed framework reduced misalignment between slices to subpixel accuracy (2.88 to 1.21?mm), and improved interstudy reproducibility for 5 important clinical functional measures, i.e. end-diastolic volume, end-systolic volume, ejection fraction, myocardial mass and 3D-sphericity index, as reflected in a reduction in the sample size required to detect statistically significant cardiac changes: a reduction of 21–66%. Our investigation on the optimum registration parameters, including both cardiac time frames and number of long-axis (LA) slices, suggested that a single time frame is adequate for motion correction whereas integrating more LA slices can improve registration and model reconstruction accuracy for improved functional quantification especially on datasets with severe motion artefacts.

  2. 4D ultrasound quantification of LV function and valvular pathology

    Microsoft Academic Search

    N. L. Greenberg; S. Fukuda; D. Agler; Y. Matsumura; T. Shiota; J. D. Thomas

    2006-01-01

    Real-time 3D echocardiography is currently limited by factors including accessibility of analysis software to quickly and accurately determine ventricular volumes for assessment of myocardial function. The goal of this study was to examine the capabilities of a 3D system to acquire full 4D echocardiographic datasets and evaluate the ability to obtain both LV function and valvular pathology. 3D exams were

  3. Inhibition of class I histone deacetylase activity represses matrix metalloproteinase-2 and -9 expression and preserves LV function postmyocardial infarction.

    PubMed

    Mani, Santhosh K; Kern, Christine B; Kimbrough, Denise; Addy, Benjamin; Kasiganesan, Harinath; Rivers, William T; Patel, Risha K; Chou, James C; Spinale, Francis G; Mukherjee, Rupak; Menick, Donald R

    2015-06-01

    Left ventricular (LV) remodeling, after myocardial infarction (MI), can result in LV dilation and LV pump dysfunction. Post-MI induction of matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been implicated as causing deleterious effects on LV and extracellular matrix remodeling in the MI region and within the initially unaffected remote zone. Histone deacetylases (HDACs) are a class of enzymes that affect the transcriptional regulation of genes during pathological conditions. We assessed the efficacy of both class I/IIb- and class I-selective HDAC inhibitors on MMP-2 and MMP-9 abundance and determined if treatment resulted in the attenuation of adverse LV and extracellular matrix remodeling and improved LV pump function post-MI. MI was surgically induced in MMP-9 promoter reporter mice and randomized for treatment with a class I/IIb HDAC inhibitor for 7 days post-MI. After MI, LV dilation, LV pump dysfunction, and activation of the MMP-9 gene promoter were significantly attenuated in mice treated with either the class I/IIb HDAC inhibitor tichostatin A or suberanilohydroxamic acid (voronistat) compared with MI-only mice. Immunohistological staining and zymographic levels of MMP-2 and MMP-9 were reduced with either tichostatin A or suberanilohydroxamic acid treatment. Class I HDAC activity was dramatically increased post-MI. Treatment with the selective class I HDAC inhibitor PD-106 reduced post-MI levels of both MMP-2 and MMP-9 and attenuated LV dilation and LV pump dysfunction post-MI, similar to class I/IIb HDAC inhibition. Taken together, these unique findings demonstrate that selective inhibition of class I HDACs may provide a novel therapeutic means to attenuate adverse LV remodeling post-MI. PMID:25795711

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

    PubMed Central

    Schlecht-Louf, Géraldine; Mangeney, Marianne; El-Garch, Hanane; Lacombe, Valérie; Poulet, Hervé

    2014-01-01

    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. PMID:24198407

  5. Left ventricular torsional dynamics post exercise for LV diastolic function assessment

    PubMed Central

    2014-01-01

    Aims 2D speckle tracking echocardiography allows for assessment of left ventricular (LV) torsional deformation as a composite function of the radial, longitudinal and circumferential fibres. We test the hypothesis that post-exercise LV torsional dynamics are more sensitive markers for myocardial dysfunction than resting measures, and better predictors for exercise capacity compared to post-exercise LV diastolic filling pressure (E/e’). Methods We studied 88 patients referred for stress echocardiogram. Treadmill exercise was performed using Bruce protocol, and echo images were acquired using GE Vivid 7. LV rotational dynamics were analysed by speckle tracking method using the GE ECHOPAC software. Tertiles were defined according to exercise capacity measured by the achieved metabolic equivalents (METS) adjusted for age and gender. Comparison was made between LV torsional dynamics and E/e’ to correlate with METS to predict exercise capacity. Results Mean age of the study population was 58 years, 48% females. Patients with systolic dysfunction or evidence of ischaemia were excluded from the analysis. No significant correlation was found between METS and LV torsion measures at rest. There was statistically significant correlation between METS and post-exercise LV torsion (r=0.34, p=0.001), twist velocity increase (r=0.27, p=0.01), and incremental change in torsion (r=0.22, p<0.05). In addition, a correlation was also shown between post-exercise E/e’ and METS (r=-0.33, p=0.002). Conclusion Post-exercise LV torsional dynamics correlate with exercise capacity and may be a useful tool for assessing LV myocardial function in subjects with normal LVEF. PMID:24529199

  6. COMPLETE ASSESSMENT OF LV AND RV FUNCTION AND VOLUME IN A SINGLE BREATHOLD USING REAL-TIME, SPIRAL, STEADY-STATE FREE PRECESSION

    E-print Network

    Southern California, University of

    -space SSFP strategy for the assessment of LV and RV function in heart failure patients. Methods: Twenty heart failure patients (mean age 59 ± 17 yrs, 13 men and 7 women) underwent scanning with the standard, multipleCOMPLETE ASSESSMENT OF LV AND RV FUNCTION AND VOLUME IN A SINGLE BREATHOLD USING REAL-TIME, SPIRAL

  7. A EUKARYOTIC GENE IS FUNCTIONALLY EXPRESSED ri\\i E.COLI Kevin Struhl and Rona1d lV. Davis

    E-print Network

    A EUKARYOTIC GENE IS FUNCTIONALLY EXPRESSED ri\\i E.COLI Kevin Struhl and Rona1d lV. Davis expression of this eukaryotic DNA in E. coli ap- proaches the arnount resulting frorn the analogous E.- goli gene. This cloning of such a eukaryotic gene in E. coli represents a good rnodel systern ior synthesis

  8. Improvement of cardiac function by increasing stimulus strength during left ventricular pacing in cardiac resynchronization therapy.

    PubMed

    Ishibashi, Kohei; Kubo, Takashi; Kitabata, Hironori; Takarada, Shigeho; Shimamura, Kunihiro; Tanimoto, Takashi; Orii, Makoto; Shiono, Yasutsugu; Yamano, Takashi; Ino, Yasushi; Yamaguchi, Tomoyuki; Hirata, Kumiko; Tanaka, Atsushi; Imanishi, Toshio; Akasaka, Takashi

    2015-01-01

    Cardiac resynchronization therapy (CRT) is an established therapy in patients with severe heart failure due to left ventricular (LV) dyssynchrony. Increasing stimulus strength (SS) of LV pacing could capture an enlarged myocardial area and provide rapid electrical conduction. The aim of the present study was to investigate whether increasing SS of LV pacing improves LV mechanical dyssynchrony and cardiac function in patients treated with CRT.We enrolled 26 patients with CRT and changed the SS of LV pacing: 2.5 V (standard SS) and 5 V (high SS). Electrocardiography and echocardiography were performed to assess QRS duration, LV mechanical dyssynchrony, and cardiac function under each condition.The QRS duration (138.6 ± 21.4 ms versus 126.8 ± 23.1 ms, P < 0.001), septal-posterior wall motion delay (126.5 ± 42.7 ms versus 111.4 ± 55.3 ms, P = 0.012), standard deviation of time from QRS (69.6 ± 21.8 ms versus 55.6 ± 19.4 ms, P < 0.001), LV ejection fraction (29.4 ± 10.6% versus 33.4 ± 11.6%, P = 0.005), and LV stroke volume (50.7 ± 15.5 mL versus 63.8 ± 18.3 mL, P < 0.001) improved significantly in high SS compared with standard SS.Increasing SS of LV pacing in CRT improves LV mechanical dyssynchrony and cardiac function. The capture of an enlarged myocardial area by increasing SS of LV pacing might offer an acute hemodynamic benefit to patients treated with CRT. PMID:25503657

  9. Brief reoxygenation episodes during chronic hypoxia enhance posthypoxic recovery of LV function

    Microsoft Academic Search

    Sandrine Morel; Giuseppina Milano; Kathi Mujynya Ludunge; Antonio F. Corno; Michele Samaja; Sylvain Fleury; Christophe Bonny; Lukas Kappenberger; Ludwig K. von Segesser; Giuseppe Vassalli

    2006-01-01

    Children with congenital cyanotic heart defects have worse outcomes after surgical repair of their heart defects compared\\u000a with noncyanotic ones. Institution of extracorporeal circulation in these children exposes the cyanotic heart to reoxygenation\\u000a injury. Mitogen-activated protein kinase (MAPK) signaling cascades are major regulators of cardiomyocyte function in acute\\u000a hypoxia and reoxygenation. However, their roles in chronic hypoxia are incompletely understood.

  10. Methods used for the assessment of LV systolic function: common currency or tower of Babel?

    PubMed

    Marwick, Thomas H

    2013-08-01

    The last decade has produced a proliferation of techniques for the assessment of left ventricular systolic function, and there now seems to be more choice than seems rational for the questions that we need answers to. In some instances, simple estimation is all that is required-the risk stratification process is inexact, as emphasised by the variety of modalities used to characterise ejection fraction (EF) in studies that validated the efficacy of treatments selected on the basis of EF. Nonetheless, while technical advances often cause disruption and confusion, it would be wrong to dismiss them as lacking benefit. The purpose of this review is to try to provide rational grounds for selecting both test modality and physiological parameter in various specific clinical situations. PMID:23376947

  11. Left Ventricular Remodeling and Improvement in Diastolic Function after Balloon Aortic Valvuloplasty for Congenital Aortic Stenosis

    PubMed Central

    Friedman, Kevin G.; McElhinney, Doff B.; Colan, Steven D.; Porras, Diego; Powell, Andrew J.; Lock, James E.; Brown, David W.

    2014-01-01

    Background In congenital aortic stenosis (AS) chronic pressure load has detrimental effects on left ventricular (LV) systolic and diastolic function. Reduction in LV pressure load with balloon aortic valvuloplasty (BAVP) may improve diastolic function. Methods and Results Echocardiographic and catheterization data for 25 consecutive patients undergoing BAVP for congenital AS were retrospectively analyzed. Median age at BAVP was 11.5 years (3.2–40.1). LV end-diastolic pressure (EDP) pressure was elevated (? 15 mm Hg) in 72% of patients with a median of 17 mm Hg (range: 9–24). With BAVP, median AS gradient was reduced from 63 mm Hg (44–105) to 30 mm Hg (10–43). Aortic regurgitation (AR) increased from trivial (none to mild) to mild (trivial - moderate). Pre-BAVP early diastolic mitral inflow velocity/tissue Doppler early diastolic velocity (E/E') correlated with LVEDP (r= 0.52, p=0.007). On follow up echocardiogram (median 11 months post-BAVP), AS gradient was lower (p<0.001) and degree of AR was higher (P=0.01) compared to pre-BAVP echocardiograms. LV end-diastolic volume z-score increased (p=0.02), LV mass was unchanged, and LV mass: volume decreased (p=0.002). Mitral annular and septal E' (p<0.001) were higher and E/E' was lower post-dilation (10.8 vs. 14.2, p<0.001). Lower pre-BAVP E/E' and lower pre-BAVP LV mass z-score were associated with lower post-BAVP E/E'. Conclusions After BAVP, LV remodeling characterized by an increase in EDV and decrease in LV mass: volume occurs and echocardiographic measures of diastolic function and LVEDP improve in most patients. Risk factors for persistent diastolic dysfunction include higher pre-BAVP LV mass z-score and worse pre-BAVP diastolic function. PMID:22739787

  12. 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

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

    2014-01-01

    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. PMID:24919180

  13. Selective inactivation of M-MuLV RT RNase H activity by site-directed PEGylation: an improved ability to synthesize long cDNA molecules.

    PubMed

    Radzvilavicius, Tomas; Lagunavicius, Arunas

    2012-02-15

    Moloney murine leukemia virus reverse transcriptase (M-MuLV RT) is a domain structured enzyme that has the N-terminally located DNA polymerization activity and C-terminally located RNase H activity, which interferes with the efficient synthesis of long cDNA molecules. Here we present the PEGylation as a tool for engineering the M-MuLV RT derivative deficient in RNase H activity. We demonstrate that site-directed chemical modification (SDCM) of the RNase H domain by selectively PEGylating C635, one of the eight cysteine residues present in the reverse transcriptase (RT), specifically inactivated its ribonucleolytic activity. As a consequence, the efficiency of long cDNA molecules synthesis by modified enzyme was greatly increased. PMID:21807127

  14. LV software for supersonic flow analysis

    NASA Technical Reports Server (NTRS)

    Bell, William A.

    1992-01-01

    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.

  15. An Electrically Coupled Tissue Engineered Cardiomyocyte Scaffold Improves Cardiac Function in Rats with Chronic Heart Failure

    PubMed Central

    Lancaster, Jordan J.; Juneman, Elizabeth; Arnce, Sarah A.; Johnson, Nicholle M.; Qin, Yexian; Witte, Russell; Thai, Hoang; Kellar, Robert S.; Vitorin, Jose Ek; Burt, Janis; Gaballa, Mohamed A.; Bahl, Joseph J.; Goldman, Steven

    2014-01-01

    Background Varying strategies are currently being evaluated to develop tissue-engineered constructs for the treatment of ischemic heart disease. This study examines an angiogenic and biodegradable cardiac construct seeded with neonatal cardiomyocytes for the treatment of chronic heart failure (CHF). Methods We evaluated a neonatal cardiomyocyte (NCM)-seeded three-dimensional fibroblast construct (3DFC) in vitro for the presence of functional gap junctions and the potential of the NCM-3DFC to restore left ventricular (LV) function in an in vivo rat model of CHF at 3 weeks after permanent left coronary artery ligation. Results The NCM-3DFC demonstrated extensive cell-to-cell connectivity following dye injection. At 5 days in culture, the patch contracted spontaneously in a rhythmic and directional fashion, at 43±3 beats/min with a mean displacement of 1.3±0.3 mm and contraction velocity of 0.8±0.2 mm/sec. The seeded patch could be electrically paced at near physiological rates (270±30 beats/min) while maintaining coordinated, directional contractions. Three weeks after implantation, the NCM-3DFC improved LV function by increasing (p<0.05) ejection fraction 26%, cardiac index 33%, dP/dt(+) 25%, dP/dt(?) 23%, and peak developed pressure (PDP) 30%, while decreasing (p<0.05) LV end diastolic pressure 38% and the time constant of relaxation (Tau) 16%. Eighteen weeks post implantation, the NCM-3DFC improved LV function by increasing (p<0.05) ejection fraction 54%, mean arterial pressure 20%, dP/dt(+) 16%, dP/dt(?) 34% and PDP 39%. Conclusion This study demonstrates that a multicellular, electromechanically organized, cardiomyocyte scaffold, constructed in vitro by seeding NCM onto 3DFC, can improve LV function long-term when implanted in rats with CHF. PMID:24560982

  16. Functionality Improvements to Overaero

    NASA Technical Reports Server (NTRS)

    Gee, Ken; Rizk, Yehia M.

    2000-01-01

    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.

  17. Antihypertensive treatment improves left ventricular diastolic function in patients with chronic kidney disease

    PubMed Central

    LI, KU-LIN; WANG, RU-XING; DAI, MIN; LU, JUAN; XUE, JING; YANG, XIANG-JUN

    2015-01-01

    In patients with chronic kidney disease (CKD), hypertension (HP) is associated with the development of left ventricular (LV) diastolic dysfunction. However, the impact of antihypertensive treatment on LV diastolic function has not been well studied in CKD patients. Recently, two-dimensional speckle-tracking echocardiography (2DSTE) has emerged as a sensitive and quantitative assessment of LV diastolic function. The present study used 2DSTE to investigate the effects of antihypertensive treatment on LV diastolic function in patients with CKD and untreated HP. The study comprised 134 patients with CKD and untreated HP. The patients received blood pressure (BP)-lowering therapy for six months. The patients were clinically and echocardiographically evaluated at baseline and after 6 months of therapy. It was found that the mean systolic BP (SBP) and diastolic BP (DBP) at baseline were 154.0±7.0 and 92.6±10.2 mmHg, respectively, decreasing to 121.2±7.3 and 74.6±10.4 mmHg, respectively (P<0.05 for both) after the 6-month treatment period. Moreover, the mean peak LV strain rate during the isovolumetric relaxation period (SRIVR) and early diastole (SRE) improved following treatment (from 0.23±0.10 to 0.42±0.10 sec?1 and from 0.58±0.25 to 1.07±0.24 sec?1, respectively; P<0.05 for both). Notably, the patients with CKD stage ?3 were more likely to demonstrate an improvement in diastolic speckle-tracking parameters than those with CKD stage 1 or 2. For the entire population, the change (?) in B-type natriuretic peptide (BNP) level correlated with changes in echocardiographic parameters between baseline and follow-up, among which ?SRIVR presented the highest correlation coefficient (r=-0.73, P<0.01). On multivariate analysis, the independent predictors of ?SRIVR were found to include baseline CKD stage, SBP and SRIVR. This study demonstrated that LV diastolic function was improved in CKD patients following antihypertensive treatment, particularly in patients with CKD stage ?3, higher baseline SBP and worse LV diastolic function. These results highlight the importance of BP reduction in the treatment of CKD. PMID:26136880

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    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.

  19. Nicorandil improves myocardial function by regulating plasma nitric oxide and endothelin-1 in coronary slow flow

    PubMed Central

    Chen, Xiuhua; Li, Shan; Huo, Xuezhen; Fu, Xiuxiu; Dong, Xiaonan

    2015-01-01

    Background Coronary slow flow (CSF) is a special coronary microvascular disorder. The pathogenesis and effective therapeutics of CSF remain unclear. This study aimed to evaluate the global and regional functions of the left ventricle (LV) and investigate the efficacy of nicorandil in patients with CSF. Patients and methods Thirty-six patients with CSF in the left anterior descending (LAD) branch and 20 patients with normal coronary arteries were included. Global and regional functions of the LV supplied by LAD were measured using conventional Doppler echocardiography and two-dimensional speckle tracking echocardiography, respectively, within 24?h after coronary angiography. Concentrations of plasma nitric oxide (NO) and endothelin-1 (ET-1) were detected using colorimetry and radioimmunoassay, respectively. The function of the LV and the levels of NO and ET-1 were also investigated before and 90 days after treatment with 15?mg/day of nicorandil. Results Compared with the control group, the early diastolic peak velocity (E), E/A ratio, and plasma NO levels were lower, whereas the late diastolic peak flow velocity (A) and plasma ET-1 levels were significantly higher in the CSF group (P<0.05). The longitudinal strain rate peak of the LV was reduced significantly in CSF patients (P<0.001). After treatment, 75% (27/36) of CSF patients were free of chest pain. The values of E peak, E/A ratio, longitudinal strain rate peak, and plasma NO level were increased (P<0.001), whereas the ET-1 level was decreased in CSF patients (P<0.001). Conclusion Nicorandil may improve chest pain symptoms and the impaired function of the LV, possibly by increasing plasma NO and reducing ET-1 in CSF. PMID:25325437

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

    PubMed Central

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

    2013-01-01

    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. PMID:23608998

  1. Temporal pattern of left ventricular structural and functional remodeling following reversal of volume overload heart failure.

    PubMed

    Hutchinson, Kirk R; Guggilam, Anuradha; Cismowski, Mary J; Galantowicz, Maarten L; West, Thomas A; Stewart, James A; Zhang, Xiaojin; Lord, Kevin C; Lucchesi, Pamela A

    2011-12-01

    Current surgical management of volume overload-induced heart failure (HF) leads to variable recovery of left ventricular (LV) function despite a return of LV geometry. The mechanisms that prevent restoration of function are unknown but may be related to the timing of intervention and the degree of LV contractile impairment. This study determined whether reduction of aortocaval fistula (ACF)-induced LV volume overload during the compensatory stage of HF results in beneficial LV structural remodeling and restoration of pump function. Rats were subjected to ACF for 4 wk; a subset then received a load-reversal procedure by closing the shunt using a custom-made stent graft approach. Echocardiography or in vivo pressure-volume analysis was used to assess LV morphology and function in sham rats; rats subjected to 4-, 8-, or 15-wk ACF; and rats subjected to 4-wk ACF followed by 4- or 11-wk reversal. Structural and functional changes were correlated to LV collagen content, extracellular matrix (ECM) proteins, and hypertrophic markers. ACF-induced volume overload led to progressive LV chamber dilation and contractile dysfunction. Rats subjected to short-term reversal (4-wk ACF + 4-wk reversal) exhibited improved chamber dimensions (LV diastolic dimension) and LV compliance that were associated with ECM remodeling and normalization of atrial and brain natriuretic peptides. Load-independent parameters indicated LV systolic (preload recruitable stroke work, Ees) and diastolic dysfunction (tau, arterial elastance). These changes were associated with an altered ?/?-myosin heavy chain ratio. However, these changes were normalized to sham levels in long-term reversal rats (4-wk ACF + 11-wk reversal). Acute hemodynamic changes following ACF reversal improve LV geometry, but LV dysfunction persists. Gradual restoration of function was related to normalization of eccentric hypertrophy, LV wall stress, and ECM remodeling. These results suggest that mild to moderate LV systolic dysfunction may be an important indicator of the ability of the myocardium to remodel following the reversal of hemodynamic overload. PMID:21885799

  2. Automatic detection of echocardiographic LV-contours-a new image enhancement and sequential tracking method

    Microsoft Academic Search

    A. P. Monteiro; J. P. Marques de Sa; C. Abreu-Lima

    1988-01-01

    The automatic analysis of 2-D echocardiographic images in order to evaluate the cardiac function quantitatively, detect wall-motion abnormalities, and perform 3-D modeling and simulation of the left ventricle (LV) would constitute a valuable tool for clinical use. All these analyses require the complete and reliable determination of at least the LV endocardial border. The authors describe a method for accurate

  3. Vagus nerve stimulation improves left ventricular function in a canine model of chronic heart failure

    PubMed Central

    Hamann, Jason J.; Ruble, Stephen B.; Stolen, Craig; Wang, Mengjun; Gupta, Ramesh C.; Rastogi, Sharad; Sabbah, Hani N.

    2013-01-01

    Aims Autonomic dysfunction is a feature of chronic heart failure (HF). This study tested the hypothesis that chronic open-loop electrical vagus nerve stimulation (VNS) improves LV structure and function in canines with chronic HF. Methods and results Twenty-six canines with HF (EF ?35%) produced by intracoronary microembolizations were implanted with a bipolar cuff electrode around the right cervical vagus nerve and connected to an implantable pulse generator. The canines were enrolled in Control (n = 7) vs. VNS therapy (n = 7) or a crossover study, with crossovers occurring at 3 months (C × VNS, n = 6; VNS × C, n = 6). After 6 months of VNS, LVEF and LV end-systolic volume (ESV) were significantly improved compared with Control (?EF Control –4.6 ± 0.9% vs. VNS 6.0 ± 1.6%, P < 0.001) and (?ESV Control 8.3 ± 1.8 mL vs. VNS –3.0 ± 2.3 mL, P = 0.002. Plasma and tissue biomarkers were also improved. In the crossover study, VNS also resulted in a significant improvement in EF and ESV compared with Control (?EF Control –2.3 ± 0.65% vs. VNS 6.7 ± 1.1 mL, P < 0.001 and ?ESV Control 3.2 ± 1.2 mL vs. VNS –4.0 ± 0.9 mL, P < 0.001). Initiation of therapy in the Control group at 3 months resulted in a significant improvement in EF (Control –4.7 ± 1.4% vs. VNS 3.7 ± 0.74%, P < 0.001) and ESV (Control 1.5 ± 1.2 mL vs. NS –5.5 ± 1.6 mL, P = 0.003) by 6 months. Conclusions In canines with HF, long-term, open-looped low levels of VNS therapy improves LV systolic function, prevents progressive LV enlargement, and improves biomarkers of HF when compared with control animals that did not receive therapy. PMID:23883651

  4. LV software support for supersonic flow analysis

    NASA Technical Reports Server (NTRS)

    Bell, William A.

    1991-01-01

    During 1991, the software developed allowed an operator to configure and checkout the TSI, Inc. laser velocimeter (LV) system prior to a run. This setup procedure established the operating conditions for the TSI MI-990 multichannel interface and the RMR-1989 rotating machinery resolver. In addition to initializing the instruments, the software package provides a means of specifying LV calibration constants, controlling the sampling process, and identifying the test parameters.

  5. CRNK Gene Transfer Improves Function and Reverses the Myosin Heavy Chain Isoenzyme Switch During Post-Myocardial Infarction Left Ventricular Remodeling

    PubMed Central

    Hart, Davin L.; Heidkamp, Maria C.; Iyengar, Rekha; Vijayan, Kalpana; Szotek, Erika L.; Barakat, John A.; Leya, Marysa; Henze, Marcus; Scrogin, Karie; Henderson, Kyle K.; Samarel, Allen M.

    2008-01-01

    PYK2 is a Ca2+-dependent, nonreceptor protein tyrosine kinase that is involved in the induction of left ventricular hypertrophy (LVH) and its transition to heart failure. We and others have previously investigated PYK2’s function in vitro using cultured neonatal and adult rat ventricular myocytes as model systems. However, the function of PYK2 in the in vivo adult heart remains unclear. Here we evaluate the effect of PYK2 inhibition following myocardial infarction (MI) using adenoviral (Adv) overexpression of the C-terminal domain of PYK2, known as CRNK. First we demonstrate that CRNK functions as a dominant-negative inhibitor of PYK2-dependent signaling, presumably by displacing PYK2 from focal adhesions and costameres. Then, male Sprague-Dawley rats (~300g) underwent permanent left anterior descending coronary artery ligation. One wk post-MI, either Adv-GFP (n=34) or Adv-CRNK (n=28) was administered (1010 pfu, 0.1ml) via catheter-based, Optison®-mediated gene transfer. LV structure and function were evaluated by echocardiography 1 and 3wk after gene transfer, and LV tissue was analyzed by real-time RT-PCR and Western blotting. CRNK overexpression was readily detected by Western blotting 1wk following gene transfer. Adv-CRNK improved overall survival (P=0.03; Logrank Test) and LV fractional shortening (23±2% vs. 31±2% for Adv-GFP vs. Adv-CRNK infected animals, respectively; P<0.05). Whereas MI hearts exhibited increased ?-, and decreased ?-myosin heavy chain (MHC) mRNA expression characteristic of LVH, Adv-CRNK reversed the MHC isoenzyme switch (3.3±1.4 fold increase in ?MHC; 0.4±0.1 fold decrease in ?MHC; P<0.05 for both). In summary, CRNK gene transfer improves survival, increases LV function, and alters MHC gene expression suggesting an attenuation of LV remodeling post-MI. PMID:18495152

  6. Shape coexistence and ?-decay chains of 293Lv

    NASA Astrophysics Data System (ADS)

    Li, Zhao-Xi; Zhang, Zhen-Hua; Zhao, Peng-Wei

    2015-06-01

    Two recently observed 293Lv ( Z = 116) ?-decay chains [ Eur. Phys. J. A 48, 62 (2012)] are investigated in the framework of covariant density functional theory with PC-PK1, where the pairing correlations are treated by the Bardeen-Cooper-Schrieffer method with a density-independent zerorange force. From the calculated potential energy curves, it is found that two minima always occur, with one having an almost spherical shape and the other exhibiting a large deformed prolate shape. Originating from the ground state and the shape-isomeric state of 293Lv, the two observed ?-decay chains are constructed and the calculated Q ? values are found to be in good agreement with the data.

  7. Shape coexistence and ?-decay chains of 293Lv

    NASA Astrophysics Data System (ADS)

    Li, Zhao-Xi; Zhang, Zhen-Hua; Zhao, Peng-Wei

    2015-05-01

    Two recently observed 293Lv (Z = 116) ?;-decay chains [Eur. Phys. J. A 48, 62 (2012)] are investigated in the framework of covariant density functional theory with PC-PK1, where the pairing correlations are treated by the Bardeen-Cooper-Schrieffer method with a density-independent zerorange force. From the calculated potential energy curves, it is found that two minima always occur, with one having an almost spherical shape and the other exhibiting a large deformed prolate shape. Originating from the ground state and the shape-isomeric state of 293Lv, the two observed ?-decay chains are constructed and the calculated Q? values are found to be in good agreement with the data.

  8. Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma

    Microsoft Academic Search

    Yasuhiro Maejima; Hiroyuki Okada; Go Haraguchi; Yasuyuki Onai; Hisanori Kosuge; Jun-ichi Suzuki; Mitsuaki Isobe

    2011-01-01

    Unfavorable left ventricular (LV) remodeling after myocardial infarction (MI) leads to cardiac dysfunction. We examined whether Telmisartan, an angiotensin (Ang) II type I receptor blocker (ARB), could improve the recovery of LV function in a rat model of MI. The effect of Telmisartan as a peroxisome proliferator-activated receptor-? (PPAR-?) agonist was also investigated. After 28 days of MI, a significant

  9. Early and late improvement of global and regional left ventricular function after transcatheter aortic valve implantation in patients with severe aortic stenosis: an echocardiographic study.

    PubMed

    Giannini, Cristina; Petronio, Anna Sonia; Talini, Enrica; De Carlo, Marco; Guarracino, Fabio; Grazia, Maria; Donne, Delle; Nardi, Carmela; Conte, Lorenzo; Barletta, Valentina; Marzilli, Mario; Di Bello, Vitantonio

    2011-01-01

    The recent development of transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) treatment offers a viable option for high-risk patient categories. Our aim is to evaluate whether 2D strain and strain rate can detect subtle improvement in global and regional LV systolic function immediately after TAVI. 2D conventional and 2D strain (speckle analysis) echocardiography was performed before, at discharge and after three months in thirty three patients with severe AS. After TAVI, we assessed by conventional echocardiography an immediate reduction of transaortic peak pressure gradient (p<0.0001), of mean pressure gradient (p<0.0001) and a concomitant increase in aortic valve area (AVA: 1.08±0.31 cm(2)/m(2); p<0.0001). 2D longitudinal systolic strain showed a significant improvement in all patients, both at septal and lateral level, as early as 72 h after procedure (septal: -14.2±5.1 vs -16.7±3.7%, p<0.001; lateral: -9.4±3.9 vs -13.1±4.5%, p<0.001; respectively) and continued at 3 months follow-up (septal: -18.1±4.6%, p<0.0001; lateral: -14.8±4.4%, p<0.0001; respectively). Conventional echocardiography after TAVI proved a significant reduction of LV end-systolic volume and of LV mass with a mild improvement of LV ejection fraction (EF) (51.2±11.8 vs 52.9±6.4%; p<0.02) only after three months. 2D strain seems to be able to detect subtle changes in LV systolic function occurring early and late after TAVI in severe AS, while all conventional echo parameters seem to be less effective for this purpose. Further investigations are needed to prove the real prognostic impact of these echocardiographic findings. PMID:22254204

  10. Early and late improvement of global and regional left ventricular function after transcatheter aortic valve implantation in patients with severe aortic stenosis: an echocardiographic study

    PubMed Central

    Giannini, Cristina; Petronio, Anna Sonia; Talini, Enrica; De Carlo, Marco; Guarracino, Fabio; Grazia, Maria; Donne, Delle; Nardi, Carmela; Conte, Lorenzo; Barletta, Valentina; Marzilli, Mario; Di Bello, Vitantonio

    2011-01-01

    The recent development of transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS) treatment offers a viable option for high-risk patient categories. Our aim is to evaluate whether 2D strain and strain rate can detect subtle improvement in global and regional LV systolic function immediately after TAVI. 2D conventional and 2D strain (speckle analysis) echocardiography was performed before, at discharge and after three months in thirty three patients with severe AS. After TAVI, we assessed by conventional echocardiography an immediate reduction of transaortic peak pressure gradient (p<0.0001), of mean pressure gradient (p<0.0001) and a concomitant increase in aortic valve area (AVA: 1.08±0.31 cm2/m2; p<0.0001). 2D longitudinal systolic strain showed a significant improvement in all patients, both at septal and lateral level, as early as 72 h after procedure (septal: -14.2±5.1 vs -16.7±3.7%, p<0.001; lateral: -9.4±3.9 vs -13.1±4.5%, p<0.001; respectively) and continued at 3 months follow-up (septal: -18.1±4.6%, p<0.0001; lateral: -14.8±4.4%, p<0.0001; respectively). Conventional echocardiography after TAVI proved a significant reduction of LV end-systolic volume and of LV mass with a mild improvement of LV ejection fraction (EF) (51.2±11.8 vs 52.9±6.4%; p<0.02) only after three months. 2D strain seems to be able to detect subtle changes in LV systolic function occurring early and late after TAVI in severe AS, while all conventional echo parameters seem to be less effective for this purpose. Further investigations are needed to prove the real prognostic impact of these echocardiographic findings. PMID:22254204

  11. LV software support for supersonic flow analysis

    NASA Technical Reports Server (NTRS)

    Bell, William A.

    1992-01-01

    The software for configuring a Laser Velocimeter (LV) counter processor system was developed using structured design. The LV system includes up to three counter processors and a rotary encoder. The software for configuring and testing the LV system was developed, tested, and included in an overall software package for data acquisition, analysis, and reduction. Error handling routines respond to both operator and instrument errors which often arise in the course of measuring complex, high-speed flows. The use of networking capabilities greatly facilitates the software development process by allowing software development and testing from a remote site. In addition, high-speed transfers allow graphics files or commands to provide viewing of the data from a remote site. Further advances in data analysis require corresponding advances in procedures for statistical and time series analysis of nonuniformly sampled data.

  12. Left Ventricle: Fully Automated Segmentation Based on Spatiotemporal Continuity and Myocardium Information in Cine Cardiac Magnetic Resonance Imaging (LV-FAST)

    PubMed Central

    Wang, Lijia; Pei, Mengchao; Codella, Noel C. F.; Kochar, Minisha; Weinsaft, Jonathan W.; Li, Jianqi; Prince, Martin R.

    2015-01-01

    CMR quantification of LV chamber volumes typically and manually defines the basal-most LV, which adds processing time and user-dependence. This study developed an LV segmentation method that is fully automated based on the spatiotemporal continuity of the LV (LV-FAST). An iteratively decreasing threshold region growing approach was used first from the midventricle to the apex, until the LV area and shape discontinued, and then from midventricle to the base, until less than 50% of the myocardium circumference was observable. Region growth was constrained by LV spatiotemporal continuity to improve robustness of apical and basal segmentations. The LV-FAST method was compared with manual tracing on cardiac cine MRI data of 45 consecutive patients. Of the 45 patients, LV-FAST and manual selection identified the same apical slices at both ED and ES and the same basal slices at both ED and ES in 38, 38, 38, and 41 cases, respectively, and their measurements agreed within ?1.6 ± 8.7?mL, ?1.4 ± 7.8?mL, and 1.0 ± 5.8% for EDV, ESV, and EF, respectively. LV-FAST allowed LV volume-time course quantitatively measured within 3 seconds on a standard desktop computer, which is fast and accurate for processing the cine volumetric cardiac MRI data, and enables LV filling course quantification over the cardiac cycle. PMID:25738153

  13. Left ventricle: fully automated segmentation based on spatiotemporal continuity and myocardium information in cine cardiac magnetic resonance imaging (LV-FAST).

    PubMed

    Wang, Lijia; Pei, Mengchao; Codella, Noel C F; Kochar, Minisha; Weinsaft, Jonathan W; Li, Jianqi; Prince, Martin R; Wang, Yi

    2015-01-01

    CMR quantification of LV chamber volumes typically and manually defines the basal-most LV, which adds processing time and user-dependence. This study developed an LV segmentation method that is fully automated based on the spatiotemporal continuity of the LV (LV-FAST). An iteratively decreasing threshold region growing approach was used first from the midventricle to the apex, until the LV area and shape discontinued, and then from midventricle to the base, until less than 50% of the myocardium circumference was observable. Region growth was constrained by LV spatiotemporal continuity to improve robustness of apical and basal segmentations. The LV-FAST method was compared with manual tracing on cardiac cine MRI data of 45 consecutive patients. Of the 45 patients, LV-FAST and manual selection identified the same apical slices at both ED and ES and the same basal slices at both ED and ES in 38, 38, 38, and 41 cases, respectively, and their measurements agreed within -1.6 ± 8.7?mL, -1.4 ± 7.8?mL, and 1.0 ± 5.8% for EDV, ESV, and EF, respectively. LV-FAST allowed LV volume-time course quantitatively measured within 3 seconds on a standard desktop computer, which is fast and accurate for processing the cine volumetric cardiac MRI data, and enables LV filling course quantification over the cardiac cycle. PMID:25738153

  14. Interleukin-10 overexpression improves the function of endothelial progenitor cells stimulated with TNF-? through the activation of the STAT3 signaling pathway.

    PubMed

    Wang, Ying; Chen, Qingzhong; Zhang, Zhuhong; Jiang, Feng; Meng, Xiangda; Yan, Hua

    2015-02-01

    Lentivirus vector-interleukin-10 green fluorescent protein (LV-IL-10-GFP) was transfected into endothelial progenitor cells (EPCs) in the present study. The aim was to detect the function of IL?10?modified EPCs and analyze the molecular mechanism. EPCs were cultured and identified by fluorescent labeling with the von Willebrand factor antibody, vascular endothelial growth factor (VEGF) receptor, Ulex europaeus agglutinin-1 and acetylated low?density lipoprotein. Subsequently, EPCs were transfected with LV-IL-10-GFP and lentivirus vector?noncontain?GFP as the control group. Enzyme?linked immunosorbent assay (ELISA) was used to detect the concentrations of cytokines in the supernatant with or without tumor necrosis factor?? (TNF??). All types of cells were assessed by a tube formation assay, adhesion assay and migration assay induced with or without TNF??. Cell cycle was assessed by flow cytometry. Western blot analysis was applied to detect the expression of proteins in the cells. ELISA analysis showed that the levels of TNF?? and IL?8 in the supernatant without TNF?? significantly decreased in EPC?LV?IL?10?GFP (P<0.05 for all). By contrast, the levels of IL?10 and VEGF were contrasting in association with these. The concentrations of cytokines in the supernatant with TNF?? were consistent to the supernatant without TNF??. There was no statistically significant difference in the average number of EPCs undergoing migration, adhesion, total length and cell growth among the EPC, EPC?LV?IL?10?GFP and EPC?LV?NC?GFP groups without TNF??. Further study showed that EPC?LV?IL?10?GFP with TNF?? significantly enhanced EPC migration, adhesion and promoted tube formation (P<0.05 for all). Western blot analysis revealed that the expression of VEGF, matrix metallopeptidase?9 and phosphorylated?signal transducer and activator of transcription 3 (p?STAT3) significantly increased in the EPC?LV?IL?10?GFP group. Conversely, STAT?3 expression decreased in the EPC?LV?IL?10?GFP group. The present study suggested that overexpression of IL?10 had no effect on migration, adhesion, tubule formation and cell growth of EPCs without TNF??. Furthermore, in EPCs stimulated with TNF??, the overexpression of IL?10 improved EPC function, including migration, adhesion and tubule formation by activating the STAT3 signal pathway. PMID:25504316

  15. Longstanding Hyperthyroidism Is Associated with Normal or Enhanced Intrinsic Cardiomyocyte Function despite Decline in Global Cardiac Function

    PubMed Central

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

    Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390

  16. Fasudil improves short-term echocardiographic parameters of diastolic function in patients with type 2 diabetes with preserved left ventricular ejection fraction: a pilot study.

    PubMed

    Guo, Rong; Su, Yang; Yan, Jing; Sun, Hui; Wu, Jiakang; Liu, Weijing; Xu, Yawei

    2015-01-01

    Left ventricular (LV) diastolic dysfunction is observed frequently in patients with type 2 diabetes; however, few studies have focused on the effect of the Rho-associated kinase inhibitor fasudil on cardiac performance in humans. We conducted a prospective pilot study to assess the impact of fasudil on LV diastolic function in patients with diabetes without systolic dysfunction. Two hundred and fifty eligible patients with type 2 diabetes (149 men [61.3 %] and 94 women [38.7 %]) with a mean age of 57.2 years were randomly assigned to fasudil (n = 122, 30 mg intravenously twice a day for 14 days) or placebo (n = 121) groups. Echocardiographic variables were measured at the baseline and 1 month after the intervention. Compared with the placebo group, the fasudil group showed a significant decrease in diastolic blood pressure and in the peak of late diastolic transmitral flow (Am) (P < 0.05 for both). Deceleration time (DT), isovolumic relaxation time (IVRT), the peak of early diastolic annular velocity (e'), the peak of late diastolic annular velocity, and E/e' also exhibited a significant improvement (all, P < 0.05) after fasudil administration. Furthermore, the Em/Am ratio and IVRT, DT, and E/e' values recorded after fasudil treatment in the subgroup with impaired LV relaxation significantly differed from the corresponding values in the subgroup with normal LV relaxation (all, P < 0.05). Fasudil improves short-term echocardiographic parameters of LV diastolic function in patients with type 2 diabetes with preserved left ventricular ejection fraction. PMID:24390764

  17. Introduction to the improved functional epsilon algorithm

    NASA Astrophysics Data System (ADS)

    Thukral, R.

    2002-10-01

    This paper introduces the improved functional epsilon algorithm. We have defined this new method in principle of the modified Aitken [Delta]2 algorithm. Moreover, we have found that the improved functional epsilon algorithm has remarkable precision of the approximation of the exact solution and there exists a relationship with the integral Padé approximant. The use of the improved functional epsilon algorithm for accelerating the convergence of sequence of functions is demonstrated. The relationship of the improved functional epsilon algorithm with the integral Padé approximant is also demonstrated. Moreover, we illustrate the similarity between the integral Padé approximant and the modified Aitken [Delta]2 algorithm; thus we have shown that the integral Padé approximant is a natural generalisation of modified Aitken [Delta]2 algorithm.

  18. Sequential biventricular pacing improves regional contractility, longitudinal function and dyssynchrony in patients with heart failure and prolonged QRS

    PubMed Central

    2010-01-01

    Aims Biventricular pacing (BiP) is an effective treatment in systolic heart failure (HF) patients with prolonged QRS. However, approximately 35% of the patients receiving BiP are classified as non-responders. The aim of this study is to evaluate the acute effects of VV-optimization on systolic heart function. Methods Twenty-one HF patients aged 72 (46-88) years, QRS 154 (120-190) ms, were studied with echocardiography, Tissue Doppler Imaging (TDI) and 3D-echo the first day after receiving a BiP device. TDI was performed; during simultaneous pacing (LV-lead pacing 4 ms before the RV-lead) and during sequential pacing (LV 20 and 40 ms before RV and RV 20 and 40 ms before LV-lead pacing). Systolic heart function was studied by tissue tracking (TT) for longitudinal function and systolic maximal velocity (SMV) for regional contractility and signs of dyssynchrony assessed by time-delays standard deviation of aortic valve opening to SMV, AVO-SMV/SD and tissue synchronization imaging (TSI). Results The TT mean value preoperatively was 4,2 ± 1,5 and increased at simultaneous pacing to 5,0 ± 1,2 mm (p < 0,05), and at best VV-interval to 5,4 ± 1,2 (p < 0,001). Simultaneous pacing achieved better TT distance compared with preoperative in 16 patients (76%). However, it was still higher after VV-optimization in 12 patients 57%. Corresponding figures for SMV were 3,0 ± 0,7, 3,5 ± 0,8 (p < 0,01), and 3,6 ± 0,8 (p < 0,001). Also dyssynchrony improved. Conclusions VV-optimization in the acute phase improves systolic heart function more than simultaneous BiP pacing. Long-term effects should be evaluated in prospective randomized trials. PMID:20384995

  19. Fiber optics transmission of LV signal

    NASA Technical Reports Server (NTRS)

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

    1981-01-01

    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.

  20. Inhibition of Let-7 microRNA attenuates myocardial remodeling and improves cardiac function postinfarction in mice

    PubMed Central

    Tolonen, Anna-Maria; Magga, Johanna; Szabó, Zoltán; Viitala, Pirkko; Gao, Erhe; Moilanen, Anne-Mari; Ohukainen, Pauli; Vainio, Laura; Koch, Walter J; Kerkelä, Risto; Ruskoaho, Heikki; Serpi, Raisa

    2014-01-01

    The members of lethal-7 (Let-7) microRNA (miRNA) family are involved in regulation of cell differentiation and reprogramming of somatic cells into induced pluripotent stem cells. However, their function in the heart is not known. In this study, we examined the effect of inhibiting the function of Let-7c miRNA on the progression of postinfarction left ventricular (LV) remodeling in mice. Myocardial infarction was induced with permanent ligation of left anterior descending coronary artery with a 4-week follow-up period. Let-7c miRNA was inhibited with a specific antagomir administered intravenously. The inhibition of Let-7c miRNA downregulated the levels of mature Let-7c miRNA and its other closely related members of Let-7 family in the heart and resulted in increased expression of pluripotency-associated genes Oct4 and Sox2 in cardiac fibroblasts in vitro and in adult mouse heart in vivo. Importantly, Let-7c inhibitor prevented the deterioration of cardiac function postinfarction, as demonstrated by preserved LV ejection fraction and elevated cardiac output. Improvement in cardiac function by Let-7c inhibitor postinfarction was associated with decreased apoptosis, reduced fibrosis, and reduction in the number of discoidin domain receptor 2–positive fibroblasts, while the number of c-kit+ cardiac stem cells and Ki-67+ proliferating cells remained unaltered. In conclusion, inhibition of Let-7 miRNA may be beneficial for the prevention of postinfarction LV remodeling and progression of heart failure. PMID:25505600

  1. Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment

    PubMed Central

    2013-01-01

    Background Defective copper regulation is implicated as a causative mechanism of organ damage in diabetes. Treatment with trientine, a divalent-copper-selective chelator, improves arterial and renal structure/function in diabetes, wherein it also ameliorates left-ventricular (LV) hypertrophy. However, direct in vivo evidence that trientine can improve cardiac function in heart failure has hitherto been lacking. Methods To determine whether trientine treatment could improve in vivo outcome, we measured cardiac function in groups of trientine-treated diabetic (TETA-DIA), non-drug-treated diabetic (DIA) and sham-treated control (SHAM) rats, by using in vivo high-field cardiac magnetic-resonance imaging (cMRI) and an ex vivo isolated-perfused working heart method. Forty age-matched animals underwent a cMRI scan after which 12 were randomized to the SHAM group and 28 underwent streptozotocin-injection; of these, 25 developed stable diabetes, and 12 were then randomized to receive no treatment for 16 weeks (DIA) and the other 13 to undergo 8-weeks’ untreated diabetes followed by 8-weeks’ drug treatment (TETA-DIA). Animals were studied again by cMRI at 8 and 16 weeks following disease induction, and finally by measurement of ex vivo cardiac function. Results After eight weeks diabetes, rats (DIA/TETA-DIA) had developed significant impairment of LV function, as judged by impairment of ejection fraction (LVEF), cardiac output (CO), and LV mass (LVM)/body-mass (all P?functional indexes. LVEF, CO (both P?improved cardiac function by elevating LVEF and CO (both P?improved in TETA-DIA animals (P?improved cardiac function in diabetic rats with substantive LV impairment. These results implicate impaired copper regulation in the pathogenesis of impaired cardiac function caused by diabetic cardiomyopathy, and support ongoing studies of trientine treatment in patients with heart failure. PMID:23368770

  2. Diacerein Improves Left Ventricular Remodeling and Cardiac Function by Reducing the Inflammatory Response after Myocardial Infarction

    PubMed Central

    Torina, Anali Galluce; Reichert, Karla; Lima, Fany; de Souza Vilarinho, Karlos Alexandre; de Oliveira, Pedro Paulo Martins; do Carmo, Helison Rafael Pereira; de Carvalho, Daniela Diógenes; Saad, Mário José Abdalla; Sposito, Andrei Carvalho; Petrucci, Orlando

    2015-01-01

    Background The inflammatory response has been implicated in the pathogenesis of left ventricular (LV) remodeling after myocardial infarction (MI). An anthraquinone compound with anti-inflammatory properties, diacerein inhibits the synthesis and activity of pro-inflammatory cytokines, such as tumor necrosis factor and interleukins 1 and 6. The purpose of this study was to investigate the effects of diacerein on ventricular remodeling in vivo. Methods and Results Ligation of the left anterior descending artery was used to induce MI in an experimental rat model. Rats were divided into two groups: a control group that received saline solution (n = 16) and a group that received diacerein (80 mg/kg) daily (n = 10). After 4 weeks, the LV volume, cellular signaling, caspase 3 activity, and nuclear factor kappa B (NF-?B) transcription were compared between the two groups. After 4 weeks, end-diastolic and end-systolic LV volumes were reduced in the treatment group compared to the control group (p < .01 and p < .01, respectively). Compared to control rats, diacerein-treated rats exhibited less fibrosis in the LV (14.65%± 7.27% vs. 22.57%± 8.94%; p < .01), lower levels of caspase-3 activity, and lower levels of NF-?B p65 transcription. Conclusions Treatment with diacerein once a day for 4 weeks after MI improved ventricular remodeling by promoting lower end-systolic and end-diastolic LV volumes. Diacerein also reduced fibrosis in the LV. These effects might be associated with partial blockage of the NF-?B pathway. PMID:25816098

  3. Cross-Functional Team Processes and Patient Functional Improvement

    PubMed Central

    Alexander, Jeffrey A; Lichtenstein, Richard; Jinnett, Kimberly; Wells, Rebecca; Zazzali, James; Liu, Dawei

    2005-01-01

    Objective To test the hypothesis that higher levels of participation and functioning in cross-functional psychiatric treatment teams will be related to improved patient outcomes. Data Sources/Study Setting Primary data were collected during the period 1992–1999. The study was conducted in 40 teams within units treating seriously mentally ill patients in 16 Veterans Affairs hospitals across the U.S. Study Design A longitudinal, multilevel analysis assessed the relationship between individual- and team-level variables and patients' ability to perform activities of daily living (ADL) over time. Team data were collected in 1992, 1994, and 1995. The number of times patient data were collected was dependent on the length of time the patient was treated and varied from 1 to 14 between 1992 and 1999. Key variables included: patients' ADL scores (the dependent variable); measures of team participation and team functioning; the number of days from baseline on which a patient's ADLs were assessed; and several control variables. Data Collection Methods Team data were obtained via self-administered questionnaires distributed to staff on the study teams. Additional team data were obtained via questionnaires completed by unit directors contemporaneously with the staff survey. Patient data were collected by trained clinicians at regular intervals using a standard assessment instrument. Principal Findings Results indicated that patients treated in teams with higher levels of staff participation experienced greater improvement in ADL over time. No differences in ADL change were noted for patients treated in teams with higher levels of team functioning. Conclusions Findings support our premise that team process has important implications for patient outcomes. The results suggest that the level of participation by the team as a whole may be a more important process attribute, in terms of patient improvements in ADLs, than the team's smooth functioning. These findings indicate the potential appropriateness of managerial interventions to encourage member investment in team processes. PMID:16174137

  4. Successful weight reduction improves left ventricular diastolic function and physical performance in severe obesity.

    PubMed

    Fenk, Sabine; Fischer, Marcus; Strack, Christina; Schmitz, Gerd; Loew, Thomas; Lahmann, Claas; Baessler, Andrea

    2015-01-01

    Obesity and the metabolic syndrome (MetS) are risk factors for left ventricular diastolic dysfunction (LVDD). However, little is known about the impact of successful weight reduction (WR) on diastolic function and physical performance.Obese subjects (øBMI 40.2 ± 8.6 kg/m(2)) underwent a 1-year WR program comprising diet and lifestyle components. Echocardiography and exercise capacity (6-minute walk) were performed at baseline and after 1 year. The distribution of weight reduction was split at the sample median and subjects were dichotomized in "successful WR" (% WR ? median, corresponding to a weight loss of 8%) and "failed-WR" (% WR < median).From a total of 188 obese subjects, 71 had LVDD at baseline. Obese patients with successful WR improved their MetS alterations, including fasting glucose, insulin, lipids, adipokines, blood pressure levels, and epicardial fat thickness. The same was not true for obesity with failed WR. Subjects with successful WR demonstrated significant improvement in echocardiographic LVDD parameters (median [interquartile range]): ?e' (2,5 [-1.0, 4.7], P < 0.01), ?e'/a' (0.34 [0.07, 079], P < 0.01), ?E/e' (-1.14 [-2.72, -0.54], P < 0.05), ?E/A (0.08 [-0.04, 0.26], P < 0.05), ?Ard-Ad (-28 [-54, -4], P < 0.01), and 6-minute walk distance (65 [19, 135], P < 0.01). Improvement of ? 2 LVDD criteria was accomplished in 30% of subjects with WR versus 10% without (P = 0.009). Using multivariable regression analysis, reduction of epicardial fat thickness was particularly predictive for the improvement of diastolic function.In summary, in severe obesity, successful long-term WR was associated with improved LV diastolic function and exercise capacity. PMID:25740581

  5. Helminthic therapy: improving mucosal barrier function

    PubMed Central

    Wolff, Martin J.; Broadhurst, Mara J.

    2014-01-01

    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. PMID:22464690

  6. Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway

    PubMed Central

    Liu, Zhong-wei; Wang, Jun-kui; Qiu, Chuan; Guan, Gong-chang; Liu, Xin-hong; Li, Shang-jian; Deng, Zheng-rong

    2015-01-01

    Aim: Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Methods: Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg?1·d?1, po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. Results: DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Conclusion: Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway. PMID:25619390

  7. Improving the algebraic immunity of resilient and nonlinear functions and

    E-print Network

    Improving the algebraic immunity of resilient and nonlinear functions and constructing bent functions Claude Carlet Abstract The currently known constructions of Boolean functions with high high algebraic immunities. We introduce a construction of Boolean functions, which builds a new

  8. IMPROVED FUNCTIONALITY AND PERFORMANCE IN PHOTONIC INTEGRATED CIRCUITS

    E-print Network

    Coldren, Larry A.

    IMPROVED FUNCTIONALITY AND PERFORMANCE IN PHOTONIC INTEGRATED CIRCUITS Larry A. Coldren, JamesP-based photonic ICs, improvements in their functionality, performance, and reliability are evolving. High reliability and reduced power dissipation. Increased reliability results from the elimination of possible

  9. Autologous Fat Grafting Improves Facial Nerve Function

    PubMed Central

    Klinger, Marco; Lisa, Andrea; Caviggioli, Fabio; Maione, Luca; Murolo, Matteo; Vinci, Valeriano; Klinger, Francesco Maria

    2015-01-01

    We describe the case of a 45-year-old male patient who presented a retractile and painful scar in the nasolabial fold due to trauma which determined partial motor impairment of the mouth movements. We subsequently treated him with autologous fat grafting according to Coleman's technique. Clinical assessments were performed at 5 and 14 days and 1, 3, and 6 months after surgical procedure and we observed a progressive release of scar retraction together with an important improvement of pain symptoms. A second procedure was performed 6 months after the previous one. We observed total restoration of mimic movements within one-year follow-up. The case described confirms autologous fat grafting regenerative effect on scar tissue enlightening a possible therapeutic effect on peripheral nerve activity, hypothesizing that its entrapment into scar tissue can determine a partial loss of function.

  10. Prevention and reversal of LV remodeling with neurohormonal inhibitors

    Microsoft Academic Search

    Richard D. Patten; Prem Soman

    2004-01-01

    Opinion statement  Left ventricular (LV) remodeling refers to alterations in ventricular mass, chamber size, and shape that result from myocardial\\u000a injury, pressure, or volume overload. Numerous studies have demonstrated that LV remodeling correlates with the incidence\\u000a of heart failure and death, supporting a causative role for remodeling in heart failure progression. Heart failure trials\\u000a have shown that neurohormonal antagonists, including angiotensin-converting

  11. Absence of Type VI Collagen Paradoxically Improves Cardiac Function, Structure and Remodeling Following Myocardial Infarction

    PubMed Central

    Luther, Daniel J.; Thodeti, Charles K.; Shamhart, Patricia E.; Adapala, Ravi K.; Hodnichak, Cheryl; Weihrauch, Dorothee; Bonaldo, Paolo; Chilian, William M.; Meszaros, J. Gary

    2014-01-01

    Rationale We previously reported that type VI collagen deposition increases in the infarcted myocardium in vivo. To date, a specific role for this non-fibrillar collagen has not been explored in the setting of myocardial infarction (MI). Objective To determine whether deletion of type VI collagen in an in vivo model of post-MI wound healing would alter cardiac function and remodeling in the days to weeks after injury. Methods and Results Wild type (WT) and Col6a1-/- mice were subjected to MI followed by serial echocardiographic and histological assessments. At 8 weeks post-MI, infarct size was significantly reduced, ejection fraction was significantly preserved (43.9 ± 3.3% vs. 29.1 ± 4.3% for WT) and left ventricular (LV) chamber dilation was attenuated in the Col6a1-/- MI group (25.8 ± 7.9% increase vs. 62.6 ± 16.5% for WT). The improvement in cardiac remodeling was evident as early as 10 days post-MI in the Col6a1-/- mice. Myocyte apoptosis within the infarcted zones was initially greater in the Col6a1-/- group 3 days post-MI but by day 14 this was significantly reduced. Collagen deposition was also reduced in the infarcted and remote areas of the Col6a1-/- hearts. The reductions in chronic myocyte apoptosis and fibrosis are critical events leading to improved long-term remodeling and functional outcomes. Conclusions These unexpected results demonstrate for the first time that deletion of type VI collagen in this knockout model plays a critical protective role following MI by limiting infarct size, chronic apoptosis, aberrant remodeling and fibrosis leading to preservation of cardiac function. PMID:22343710

  12. Injectable biodegradable hydrogels for embryonic stem cell transplantation: improved cardiac remodelling and function of myocardial infarction

    PubMed Central

    Wang, Haibin; Liu, Zhiqiang; Li, Dexue; Guo, Xuan; Kasper, F Kurtis; Duan, Cuimi; Zhou, Jin; Mikos, Antonios G; Wang, Changyong

    2012-01-01

    Abstract In this study, an injectable, biodegradable hydrogel composite of oligo[poly(ethylene glycol) fumarate] (OPF) was investigated as a carrier of mouse embryonic stem cells (mESCs) for the treatment of myocardial infarction (MI). The OPF hydrogels were used to encapsulate mESCs. The cell differentiation in vitro over 14 days was determined via immunohistochemical examination. Then, mESCs encapsulated in OPF hydrogels were injected into the LV wall of a rat MI model. Detailed histological analysis and echocardiography were used to determine the structural and functional consequences after 4 weeks of transplantation. With ascorbic acid induction, mESCs could differentiate into cardiomyocytes and other cell types in all three lineages in the OPF hydrogel. After transplantation, both the 24-hr cell retention and 4-week graft size were significantly greater in the OPF + ESC group than that of the PBS + ESC group (P < 0.01). Four weeks after transplantation, OPF hydrogel alone significantly reduced the infarct size and collagen deposition and improved the cardiac function. The heart function and revascularization improved significantly, while the infarct size and fibrotic area decreased significantly in the OPF + ESC group compared with that of the PBS + ESC, OPF and PBS groups (P < 0.01). All treatments had significantly reduced MMP2 and MMP9 protein levels compared to the PBS control group, and the OPF + ESC group decreased most by Western blotting. Transplanted mESCs expressed cardiovascular markers. This study suggests the potential of a method for heart regeneration involving OPF hydrogels for stem cell encapsulation and transplantation. PMID:21838774

  13. Improved algorithm for calculating the Chandrasekhar function

    NASA Astrophysics Data System (ADS)

    Jablonski, A.

    2013-02-01

    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

  14. Relation between severity of coronary artery disease, left ventricular function, and myocardial infarction, and influence of the ACE I\\/D gene polymorphism

    Microsoft Academic Search

    François Ledru; Didier Blanchard; Salvatore Battaglia; Xavier Jeunemaitre; Dominique Courbon; Louis Guize; Jean-Léon Guermonprez; Pierre Ducimetière; Benoit Diébold

    1998-01-01

    Left ventricular (LV) systolic function is partly determined by severity of coronary artery disease and is improved by angiotensin-converting enzyme (ACE) inhibition, at least in post-infarct patients. Because the ACE insertion\\/deletion (I\\/D) gene polymorphism is associated with circulating and tissue ACE activity, we sought to evaluate the role of this genetic variant on LV function in patients studied with coronary

  15. Improving Sensorimotor Function Using Stochastic Vestibular Stimulation

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

    Astronauts experience sensorimotor changes during spaceflight, particularly during G-transition phases. Post flight sensorimotor changes may include postural and gait instability, spatial disorientation, and visual performance decrements, all of which can degrade operational capabilities of the astronauts and endanger the crew. Crewmember safety would be improved if these detrimental effects of spaceflight could be mitigated by a sensorimotor countermeasure and even further if adaptation to baseline could be facilitated. The goal of this research is to investigate the potential use of stochastic vestibular stimulation (SVS) as a technology to improve sensorimotor function. We hypothesize that low levels of SVS will improve sensorimotor performance through stochastic resonance (SR). The SR phenomenon 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. Two studies have been initiated to investigate the beneficial effects and potential practical usage of SVS. In both studies, electrical vestibular stimulation is applied via electrodes on the mastoid processes using a constant current stimulator. The first study aims to determine the repeatability of the effect of vestibular stimulation on sensorimotor performance and perception in order to better understand the practical use of SVS. The beneficial effect of low levels of SVS on balance performance has been shown in the past. This research uses the same balance task repeated multiple times within a day and across days to study the repeatability of the stimulation effects. The balance test consists of 50 sec trials in which the subject stands with his or her feet together, arms crossed, and eyes closed on compliant foam. Varying levels of SVS, ranging from 0-700 micro A, are applied across different trials. The subject-specific optimal SVS level is that which results in the best balance performance as measured by inertial measurement units placed on the upper and lower torso of the subjects. Additionally, each individual’s threshold for illusory motion perception of suprasensory electrical vestibular stimulation is measured multiple times within and across days to better understand how multiple SVS test methods compare. The second study aims to demonstrate stochastic resonance in the vestibular system using a perception based motion recognition task. This task measures an individual’s velocity threshold of motion recognition using a 6-degree of freedom Stewart platform and a 3-down/1-up staircase procedure. For this study, thresholds are determined using 150 trials in the upright, head-centered roll tilt motion direction at a 0.2 Hz frequency. We aim to demonstrate the characteristic bell shaped curve associated with stochastic resonance with each subject’s motion recognition thresholds at varying SVS levels ranging from 0 to 1500 micro A. The curve includes the individual’s baseline threshold with no SVS, optimal or minimal threshold at some mid-level of SVS, and finally degraded or increased threshold at a high SVS level. An additional aim is to formally retest each subject at his or her individual optimal SVS level on a different day than the original testing for additional validity. The overall purpose of this research is to further quantify the effects of SVS on various sensorimotor tasks and investigate the practical implications of its use in the context of human space flight so that it may be implemented in the future as a component of a comprehensive countermeasure plan for adaptation to G-transitions.

  16. Predictors of Improvements in Daytime Function Outcomes with CPAP Therapy

    Microsoft Academic Search

    RUTH N. KINGSHOTT; MARJORIE VENNELLE; CAROL J. HOY; HEATHER M. ENGLEMAN; IAN J. DEARY; NEIL J. DOUGLAS

    2000-01-01

    Continuous positive airway pressure (CPAP) therapy improves daytime function in the sleep apnea\\/ hypopnea syndrome (SAHS) but it is unclear which patients benefit and what factors predict this im- provement. To test the hypothesis that brief arousals from sleep predict improvements in daytime functioning with CPAP therapy, we prospectively studied 62 patients with polysomnography-defined SAHS. Each underwent daytime function assessments

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

    PubMed

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

    2013-05-01

    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

  18. Improved association in a classical density functional theory for water

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  19. Improved wave functions for quantum Monte Carlo

    E-print Network

    Seth, Priyanka

    2013-02-05

    similarity- transformed Hamiltonian HTC is not Hermitian. Consequently, interest in the method faded. Following a recent revival, the transcorrelated method has been applied to a variety of systems including solids [15], for which traditional quantum... The antisymmetry of fermionic wave functions requires that they have both positive and negative regions, preventing the wave function from being directly interpreted as a prob- ability distribution. This fundamental property is at the root of the fermion sign...

  20. f"\\ f ,:( '( t'\\ (J!_ .) , L."'v<1

    E-print Network

    Rathbun, Julie A.

    f HO. ATM-903 ltiV. MO. AA I f"\\ f ,:( '( t'\\ (J!_ .) , L."'v DESCRIPTION INCLUDING THE HEAT FLOW EXPERIMENT PAGI OP1 19 DATE 23 October 1970 This ATM provides a brief description of the ALSEP Array AZ system configuration which includes the Heat Flow Experiment. Prepared by: D

  1. Autocorrelation distortion function for improved AR modeling

    Microsoft Academic Search

    V. Jain; B. Xu

    1987-01-01

    For noisy signals it is not enough to achieve a match between the first p+1 correlations of the measured data and that of the AR model. The higher order correlations begin to diverge as the level of data noise increases. In an effort to perform extended correlation matching we have found the need to use an Autocorrelation Distortion Function (ADF),

  2. Activated Protein C Has a Protective Effect against Myocardial I/R Injury by Improvement of Endothelial Function and Activation of AKT1

    PubMed Central

    Maehata, Yoshito; Miyagawa, Shigeru; Sawa, Yoshiki

    2012-01-01

    Objectives Activated protein C (APC) has a protective efficacy against ischemia-reperfusion (I/R) injury in several organs. The objective of this study was to investigate effect of APC in myocardium with possible mechanism. Methods We used regional and global myocardial I/R injury models of rats. They consisted of I/R injuries (1) by ligation of left coronary artery, or (2) using Langendorff apparatus. Langendorff was used to focus the mechanism of APC excluding coagulation cascade in a working heart. Each experiment had an APC group (n?=?10) and a control group with normal saline (n?=?10). Injections of these solutions into rats were performed 30 minutes before the planned-I/R injury. Cardiac performance after the procedure was evaluated by echocardiography or indices with Langendorff apparatus. Coronary flow (CF) was measured in the global I/R injury model. Western blotting was performed to detect the change of AKT1 signal in myocardium after global I/R injury. Results LV function improved significantly in the APC group: %EF at 2 weeks after procedure, 70.8%±4.5% vs. 56.5%±0.7%; APC vs. control; p<0.01. Percent LV development pressure (LVDP) also improved in the APC group significantly, 88.8%±45.3% vs. 28.1%±15.4%; APC vs. control; p<0.01. In APC group, %CF improved significantly, 88.5%±15.8% vs. 65.0%±13.4%; APC vs. control; p<0.01. It was enhanced significantly when acetylcholine was administered; % CF: 103.5%±9.9% vs. 87.0%±12.1%; APC vs. control; p<0.05. Western blotting revealed that APC significantly induced activation of phosphorylated AKT1 in myocardium (p<0.05). Conclusions APC has a novel effect to protect myocardium and cardiac performance against I/R injury through improvement of endothelial function and activation of AKT1. PMID:22916090

  3. Litopenaeus vannamei Sterile-Alpha and Armadillo Motif Containing Protein (LvSARM) Is Involved in Regulation of Penaeidins and antilipopolysaccharide factors

    PubMed Central

    Wang, Pei-Hui; Gu, Zhi-Hua; Wan, Ding-Hui; Zhu, Wei-Bin; Qiu, Wei; Weng, Shao-Ping; Yu, Xiao-Qiang; He, Jian-Guo

    2013-01-01

    The Toll-like receptor (TLR)-mediated NF-?B pathway is tightly controlled because overactivation may result in severe damage to the host, such as in the case of chronic inflammatory diseases and cancer. In mammals, sterile-alpha and armadillo motif-containing protein (SARM) plays an important role in negatively regulating this pathway. While Caenorhabditis elegans SARM is crucial for an efficient immune response against bacterial and fungal infections, it is still unknown whether Drosophila SARM participates in immune responses. Here, Litopenaeus vannamei SARM (LvSARM) was cloned and functionally characterized. LvSARM shared signature domains with and exhibited significant similarities to mammalian SARM. Real-time quantitative PCR analysis indicated that the expression of LvSARM was responsive to Vibrio alginolyticus and white spot syndrome virus (WSSV) infections in the hemocyte, gill, hepatopancreas and intestine. In Drosophila S2 cells, LvSARM was widely distributed in the cytoplasm and could significantly inhibit the promoters of the NF-?B pathway-controlled antimicrobial peptide genes (AMPs). Silencing of LvSARM using dsRNA-mediated RNA interference increased the expression levels of Penaeidins and antilipopolysaccharide factors, which are L.vannamei AMPs, and increased the mortality rate after V. alginolyticus infection. Taken together, our results reveal that LvSARM may be a novel component of the shrimp Toll pathway that negatively regulates shrimp AMPs, particularly Penaeidins and antilipopolysaccharide factors. PMID:23405063

  4. Correcting For Seed-Particle Lag In LV Measurements

    NASA Technical Reports Server (NTRS)

    Jones, Gregory S.; Gartrell, Luther R.; Kamemoto, Derek Y.

    1994-01-01

    Two experiments conducted to evaluate effects of sizes of seed particles on errors in LV measurements of mean flows. Both theoretical and conventional experimental methods used to evaluate errors. First experiment focused on measurement of decelerating stagnation streamline of low-speed flow around circular cylinder with two-dimensional afterbody. Second performed in transonic flow and involved measurement of decelerating stagnation streamline of hemisphere with cylindrical afterbody. Concluded, mean-quantity LV measurements subject to large errors directly attributable to sizes of particles. Predictions of particle-response theory showed good agreement with experimental results, indicating velocity-error-correction technique used in study viable for increasing accuracy of laser velocimetry measurements. Technique simple and useful in any research facility in which flow velocities measured.

  5. LV wall segmentation using the variational level set method (LSM) with additional shape constraint for oedema quantification

    NASA Astrophysics Data System (ADS)

    Kadir, K.; Gao, H.; Payne, A.; Soraghan, J.; Berry, C.

    2012-10-01

    In this paper an automatic algorithm for the left ventricle (LV) wall segmentation and oedema quantification from T2-weighted cardiac magnetic resonance (CMR) images is presented. The extent of myocardial oedema delineates the ischaemic area-at-risk (AAR) after myocardial infarction (MI). Since AAR can be used to estimate the amount of salvageable myocardial post-MI, oedema imaging has potential clinical utility in the management of acute MI patients. This paper presents a new scheme based on the variational level set method (LSM) with additional shape constraint for the segmentation of T2-weighted CMR image. In our approach, shape information of the myocardial wall is utilized to introduce a shape feature of the myocardial wall into the variational level set formulation. The performance of the method is tested using real CMR images (12 patients) and the results of the automatic system are compared to manual segmentation. The mean perpendicular distances between the automatic and manual LV wall boundaries are in the range of 1-2 mm. Bland-Altman analysis on LV wall area indicates there is no consistent bias as a function of LV wall area, with a mean bias of -121 mm2 between individual investigator one (IV1) and LSM, and -122 mm2 between individual investigator two (IV2) and LSM when compared to two investigators. Furthermore, the oedema quantification demonstrates good correlation when compared to an expert with an average error of 9.3% for 69 slices of short axis CMR image from 12 patients.

  6. Improving structure-based function prediction using molecular dynamics

    PubMed Central

    Glazer, Dariya S.; Radmer, Randall J.; Altman, Russ B.

    2009-01-01

    Summary The number of molecules with solved three-dimensional structure but unknown function is increasing rapidly. Particularly problematic are novel folds with little detectable similarity to molecules of known function. Experimental assays can determine the functions of such molecules, but are time-consuming and expensive. Computational approaches can identify potential functional sites; however, these approaches generally rely on single static structures and do not use information about dynamics. In fact, structural dynamics can enhance function prediction: we coupled molecular dynamics simulations with structure-based function prediction algorithms that identify Ca2+ binding sites. When applied to 11 challenging proteins, both methods showed substantial improvement in performance, revealing 22 more sites in one case and 12 more in the other, with a modest increase in apparent false positives. Thus, we show that treating molecules as dynamic entities improves the performance of structure-based function prediction methods. PMID:19604472

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

    PubMed

    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

    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 (15 min, 60 min, 4h, 12h, 24h and 48 h) 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

  8. Experience feedback and maintenance policies of substations and electrical equipment in EDF's distribution MV and LV networks, and RTE's VHV and HV networks

    Microsoft Academic Search

    P. Carer; J. Aupied; G. Malarange; S. Gougeon; C. Spelleman

    2004-01-01

    The aim of this paper is to present aspects of the maintenance policies of substations and electrical equipment, and experience feedback method in the EDF's distribution network (MV and LV) and the RTE's network (VHV, HV). EDF has tested reliability-centered maintenance (RCM), with a view to improving EDF maintenance policies and adapting them to the company's new goals of improving

  9. Astakine LvAST binds to the ? subunit of F1-ATP synthase and likely plays a role in white shrimp Litopeneaus vannamei defense against white spot syndrome virus.

    PubMed

    Liang, Gao-Feng; Liang, Yan; Xue, Qinggang; Lu, Jin-Feng; Cheng, Jun-Jun; Huang, Jie

    2015-03-01

    Cytokines play a critical role in innate and adaptive immunity. Astakines represent a group of invertebrate cytokines that are related to vertebrate prokineticin and function in promoting hematopoiesis in crustaceans. We have identified an astakine from the white shrimp Litopeneaus vannamei and named it LvAST in a previous research. In the present research, we investigated the interactions among LvAST, the envelope protein VP37 of white spot syndrome virus (i.e., WSSV), and the ? subunit of F1-ATP synthase (ATPsyn-?) of the white shrimp (i.e., BP53) using binding assays and co-precipitations. We also examined the effects of LvAST on shrimp susceptibility to WSSV. We found that LvAST and VP37 competitively bound to BP53, but did not bind to each other. Shrimps that had been injected with recombinant LvAST exhibited significantly lower mortality and longer survival time in experimental infections by WSSV. In contrast, shrimps whose LvAST gene expression had been inhibited by RNA interference showed significantly higher WSSV infection intensity and shorter survival time following viral challenges. These results suggested that LvAST and WSSV both likely use ATPsyn-? as a receptor and LvAST plays a role in shrimp defense against WSSV infection. This represented the first research showing the involvement of astakines in host antiviral immunity. PMID:25536411

  10. Cardiac Structure and Function in Cushing's Syndrome: A Cardiac Magnetic Resonance Imaging Study

    PubMed Central

    Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

    2014-01-01

    Background: Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. Objectives: The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Methods: Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2–12 mo) after the treatment of hypercortisolism. Results: Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Conclusion: Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism. PMID:25093618

  11. Why does pulmonary venous pressure rise after onset of LV dysfunction: a theoretical analysis.

    PubMed

    Burkhoff, D; Tyberg, J V

    1993-11-01

    One of the most important consequences of acute left ventricular dysfunction (LVD) is pulmonary edema resulting from a rise in pulmonary venous pressure (PVP). It is generally believed that the PVP rise is a direct hemodynamic consequence of LVD. While this paradigm seems plausible, especially if the LV is viewed as a sump pump, there is no specific evidence to support this simple explanation. A theoretical analysis was performed to assess the hemodynamic mechanisms responsible for the dramatic rise in PVP after acute LVD. The ventricles were modeled as time-varying elastances; pulmonary and systemic vascular systems were modeled as series of resistive and capacitive elements. In response to a 50% decrease in LV contractile strength [end-systolic elastance (Ees)], cardiac output (CO) and mean arterial pressure (MAP) dropped substantially, while PVP increased minimally from its baseline of 12 to approximately 15 mmHg. With LV Ees set at 50% of normal, the effects of sympathetic activation were tested. When heart rate and total peripheral resistance were increased, CO and MAP improved, yet PVP still did not rise. The only intervention that caused a substantial increase in PVP was to simulate the decrease in unstressed volume (VU) of the venous system known to occur with sympathetic activation. When VU was decreased by about 15-20% (comparable to experimentally observed shifts with acute heart failure), PVP increased above 25 mmHg. The effects of pericardial constraints were investigated, and the results suggest a major role of this organ in determining the overall hemodynamic response to acute LVD, sympathetic activation, and explaining the responses to therapy. Thus this analysis suggests that elevations of PVP do not occur simply as a direct hemodynamic consequence of acute LVD. Rather, changes in PVP may be dictated more by sympathetic control on venous capacity. If confirmed, recognition of this as a primary mechanism may prove important in directing development of new therapies and in understanding the mechanisms of disease progression in heart failure. PMID:8238596

  12. [Improving functional outcome of schizophrenia with cognitive remediation].

    PubMed

    Franck, Nicolas; Demily, Caroline

    2015-03-01

    The functional outcome of schizophrenia is partly conditioned by cognitive disorders associated with this disease. The functional outcome of schizophrenia depends not only on psychotropic medications, but also on non-pharmacological measures and in particular on cognitive remediation. All patients suffering from schizophrenia should benefit from a multidisciplinary functional evaluation including neuropsychological assessment. The restitution of the functional evaluation's results values preserved skills rather than deficits. Cognitive remediation should be considered when cognitive disorders have a functional impact. It reduces the impact of the patient's cognitive disorders and improves the success of his/her concrete projects. PMID:25544348

  13. Text Mining Improves Prediction of Protein Functional Sites

    PubMed Central

    Cohn, Judith D.; Ravikumar, Komandur E.

    2012-01-01

    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. PMID:22393388

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

    PubMed

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

    2008-02-01

    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

  15. Will Incremental Hemodialysis Preserve Residual Function and Improve Patient Survival?

    PubMed Central

    Davenport, Andrew

    2015-01-01

    The progressive loss of residual renal function in peritoneal dialysis patients is associated with increased mortality. It has been suggested that incremental dialysis may help preserve residual renal function and improve patient survival. Residual renal function depends upon both patient related and dialysis associated factors. Maintaining patients in an over-hydrated state may be associated with better preservation of residual renal function but any benefit comes with a significant risk of cardiovascular consequences. Notably, it is only observational studies that have reported an association between dialysis patient survival and residual renal function; causality has not been established for dialysis patient survival. The tenuous connections between residual renal function and outcomes and between incremental hemodialysis and residual renal function should temper our enthusiasm for interventions in this area. PMID:25385441

  16. Improved Cost Function in the Design of Boolean Functions Satisfying Multiple Criteria

    Microsoft Academic Search

    Selçuk Kavut; Melek D. Yücel

    2003-01-01

    \\u000a We develop an improved cost function to be used in simulated annealing followed by hill-climbing to find Boolean functions\\u000a satisfying multiple desirable criteria such as high nonlinearity, low autocorrelation, balancedness, and high algebraic degree.\\u000a Using this cost function that does not necessitate experimental search for parameter tuning, the annealing-based algorithm\\u000a reaches the desired function profiles more rapidly. Some Boolean functions

  17. Comparison of left ventricular diastolic function in obstructive hypertrophic cardiomyopathy in patients undergoing percutaneous septal alcohol ablation versus surgical myotomy/myectomy

    NASA Technical Reports Server (NTRS)

    Sitges, Marta; Shiota, Takahiro; Lever, Harry M.; Qin, Jian Xin; Bauer, Fabrice; Drinko, Jeannie K.; Agler, Deborah A.; Martin, Maureen G.; Greenberg, Neil L.; Smedira, Nicholas G.; Lytle, Bruce W.; Tuzcu, E. Murat; Garcia, Mario J.; Thomas, James D.

    2003-01-01

    Both percutaneous transcoronary alcohol septal reduction (ASR) and surgical myectomy are effective treatments to relieve left ventricular (LV) outflow tract obstruction in obstructive hypertrophic cardiomyopathy (HC). LV diastolic function was assessed by echocardiography in 57 patients with obstructive HC at baseline and 5 +/- 4 months after ASR (n = 37) or surgical myectomy (n = 20). LV outflow tract pressure gradient decreased from 65 +/- 40 to 23 +/- 21 mm Hg (p <0.01) after treatment. The ratio of the early-to-late peak diastolic LV inflow velocities, and the ratio of the early peak diastolic LV inflow velocity to the lateral mitral annulus early diastolic velocity determined by tissue Doppler imaging significantly decreased after the procedures (1.6 +/- 1.7 vs 1.0 +/- 0.7 and 15 +/- 8 vs 11 +/- 5, respectively), whereas LV inflow propagation velocity significantly increased (60 +/- 24 vs 71 +/- 36 cm/s). Left atrial size decreased from 29 +/- 7 to 25 +/- 6 cm(2) (p <0.05). Patients had a significant improvement in New York Heart Association functional class and in exercise performance. When comparing ASR with myectomy, no difference was found in the degree of change in any parameter of diastolic function. Thus, diastolic function indexes obtained by echocardiography changed after septal reduction interventions in patients with obstructive HC; this change was similar to that after surgical myectomy and ASR.

  18. Improve vehicle's function safety with an approach investigating vehicle's electromagnetic interference with its function safety

    Microsoft Academic Search

    Shuo Wang

    2011-01-01

    In this paper, an approach to improve vehicle's function safety by integrating the analysis of electromagnetic interference with the analysis of safety function is proposed. It is proposed that vehicle's EMI analysis should be carried out with vehicle's function safety analysis. These two analyses should be carried out together from the beginning of the design of vehicle's electrical and electronic

  19. Peripheral Blood Stem Cell Transplantation Improves Liver Functional Reserve

    PubMed Central

    Cai, Ting; Deng, Qinzhi; Zhang, Shun; Hu, Airong; Gong, Qinghai; Zhang, Xingfen

    2015-01-01

    Background Currently available treatment options for decompensated hepatitis B-induced liver cirrhosis are limited and largely ineffective. Recently, stem cell transplantation has emerged as a promising treatment for cirrhosis. The aim of this study was to determine whether autologous peripheral blood stem cell transplantation can improve liver functional reserve in patients with hepatitis B-induced cirrhosis. Material/Methods In this study, 51 patients with hepatitis B-induced liver cirrhosis were assigned to the treatment group (n=23) or the control group (n=28). The treatment group underwent autologous peripheral blood stem cell transplantation in addition to comprehensive medical treatment, and the control group received comprehensive medical treatment alone. Liver functional reserve was monitored for 48 weeks after autologous peripheral blood stem cell transplantation. Results After transplantation, most patients showed improvements in symptoms such as fatigue, anorexia, and abdominal distension. The retention rate of indocyanine green at 15 minutes, a common indicator of liver functional reserve, declined from 41.99±4.68 at baseline to 37.79±3.75 by 48 weeks after transplantation, showing significant improvement. Conclusions Autologous peripheral blood stem cell transplantation can improve several markers of liver health and liver functional reserve and is a promising prospect for clinical application. PMID:25970080

  20. FAB (Functionally Alert Behavior Strategies) to Improve Self-Control

    ERIC Educational Resources Information Center

    Pagano, John

    2015-01-01

    This paper describes the FAB (Functionally Alert Behavior) Strategies approach to improve behavior in children and adolescents with complex behavioral challenges. FAB Strategies include evidence-based environmental adaptations, sensory modulation, positive behavioral support, and physical self-regulation strategies. FAB Strategies can be used by…

  1. Improving the Strict Avalanche Characteristics of Cryptographic Functions

    E-print Network

    Seberry, Jennifer

    Improving the Strict Avalanche Characteristics of Cryptographic Functions Jennifer Seberry Xian not satisfy the strict avalanche criterion (SAC) into ones that satisfy the criterion. Such a method has in digital systems, strict avalanche criterion (SAC), substitu- tion boxes (S-boxes). 1 The Strict Avalanche

  2. Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca2+-sensitive K+ current in miniature swine with LV hypertrophy

    PubMed Central

    Tharp, Darla L.; Ivey, Jan R.; Ganjam, Venkataseshu K.; Bowles, Douglas K.

    2011-01-01

    Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ETA) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K+ currents (IK+) in coronary smooth muscle cells. Raising internal Ca2+ from 200 to 500 nM increased Ca2+-sensitive K+ current in HF-TR and control, but not HF animals. In conclusion, an ETA-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca2+-sensitive IK+ was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca2+-sensitive IK+, illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy. PMID:21841018

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

    PubMed Central

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

    2008-01-01

    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. PMID:18489766

  4. Training improves visual processing speed and generalizes to untrained functions

    PubMed Central

    Lev, Maria; Ludwig, Karin; Gilaie-Dotan, Sharon; Voss, Stephanie; Sterzer, Philipp; Hesselmann, Guido; Polat, Uri

    2014-01-01

    Studies show that manipulating certain training features in perceptual learning determines the specificity of the improvement. The improvement in abnormal visual processing following training and its generalization to visual acuity, as measured on static clinical charts, can be explained by improved sensitivity or processing speed. Crowding, the inability to recognize objects in a clutter, fundamentally limits conscious visual perception. Although it was largely considered absent in the fovea, earlier studies report foveal crowding upon very brief exposures or following spatial manipulations. Here we used GlassesOff's application for iDevices to train foveal vision of young participants. The training was performed at reading distance based on contrast detection tasks under different spatial and temporal constraints using Gabor patches aimed at testing improvement of processing speed. We found several significant improvements in spatio-temporal visual functions including near and also non-trained far distances. A remarkable transfer to visual acuity measured under crowded conditions resulted in reduced processing time of 81?ms, in order to achieve 6/6 acuity. Despite a subtle change in contrast sensitivity, a robust increase in processing speed was found. Thus, enhanced processing speed may lead to overcoming foveal crowding and might be the enabling factor for generalization to other visual functions. PMID:25431233

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

    PubMed Central

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

    2013-01-01

    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. PMID:23661057

  6. Reconstructive Osteotomy for Ankle Malunion Improves Patient Satisfaction and Function.

    PubMed

    Inori, Fumiaki; Tohyama, Masahiko; Yasuda, Hiroyuki; Konishi, Sadahiko; Waseda, Akeo

    2015-01-01

    Treatment of chronic symptoms caused by a malunion is a difficult problem in orthopedic surgery. We encountered a case of ankle malunion at our hospital about 1 year after the first operation. The patient had been unable to walk with weight-bearing but regained the ability to walk after reconstructive osteotomy of the fibula. Functional scores for the foot and ankle were significantly improved after intervention. Reconstructive osteotomy appears to represent a good option for ankle malunion. PMID:26064743

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

    Microsoft Academic Search

    Ling Ti Kong; Colin Denniston; Martin H. Müser

    2011-01-01

    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 Gamma-point

  8. Reconstructive Osteotomy for Ankle Malunion Improves Patient Satisfaction and Function

    PubMed Central

    Tohyama, Masahiko; Yasuda, Hiroyuki; Konishi, Sadahiko; Waseda, Akeo

    2015-01-01

    Treatment of chronic symptoms caused by a malunion is a difficult problem in orthopedic surgery. We encountered a case of ankle malunion at our hospital about 1 year after the first operation. The patient had been unable to walk with weight-bearing but regained the ability to walk after reconstructive osteotomy of the fibula. Functional scores for the foot and ankle were significantly improved after intervention. Reconstructive osteotomy appears to represent a good option for ankle malunion.

  9. Folic acid improves arterial endothelial function in adults with hyperhomocystinemia

    Microsoft Academic Search

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

    1999-01-01

    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

  10. Activities and Programs That Improve Children’s Executive Functions

    PubMed Central

    Diamond, Adele

    2014-01-01

    Executive functions (EFs; e.g., reasoning, working memory, and self-control) can be improved. Good news indeed, since EFs are critical for school and job success and for mental and physical health. Various activities appear to improve children’s EFs. The best evidence exists for computer-based training, traditional martial arts, and two school curricula. Weaker evidence, though strong enough to pass peer review, exists for aerobics, yoga, mindfulness, and other school curricula. Here I address what can be learned from the research thus far, including that EFs need to be progressively challenged as children improve and that repeated practice is key. Children devote time and effort to activities they love; therefore, EF interventions might use children’s motivation to advantage. Focusing narrowly on EFs or aerobic activity alone appears not to be as efficacious in improving EFs as also addressing children’s emotional, social, and character development (as do martial arts, yoga, and curricula shown to improve EFs). Children with poorer EFs benefit more from training; hence, training might provide them an opportunity to “catch up” with their peers and not be left behind. Remaining questions include how long benefits of EF training last and who benefits most from which activities. PMID:25328287

  11. Assessment of the LV-S2 & LV-S3 Stack Sampling Probe Locations for Compliance with ANSI/HPS N13.1-1999

    SciTech Connect

    Glissmeyer, John A.; Antonio, Ernest J.; Flaherty, Julia E.; Amidan, Brett G.

    2014-09-30

    This document reports on a series of tests conducted to assess the proposed air sampling locations for the Hanford Tank Waste Treatment and Immobilization Plant (WTP) Group 1-2A exhaust stacks with respect to the applicable criteria regarding the placement of an air sampling probe. The LV-C2, LV-S2, and LV-S3 exhaust stacks were tested together as a group (Test Group 1-2A). This report only covers the results of LV-S2 and LV-S3; LV-C2 will be reported on separately. Federal regulations1 require that a sampling probe be located in the exhaust stack according to the criteria established by the American National Standards Institute/Health Physics Society (ANSI/HPS) N13.1-1999, Sampling and Monitoring Releases of Airborne Radioactive Substances from the Stack and Ducts of Nuclear Facilities. 2 These criteria address the capability of the sampling probe to extract a sample that represents the effluent stream.

  12. Functional remediation for patients with bipolar II disorder: improvement of functioning and subsyndromal symptoms.

    PubMed

    Solé, Brisa; Bonnin, C Mar; Mayoral, María; Amann, Benedikt L; Torres, Imma; González-Pinto, Ana; Jimenez, Esther; Crespo, Jose Manuel; Colom, Francesc; Tabarés-Seisdedos, Rafael; Reinares, Maria; Ayuso-Mateos, Jose Luis; Soria, Sara; Garcia-Portilla, M Paz; Ibañez, Ángela; Vieta, Eduard; Martinez-Aran, Anabel; Torrent, Carla

    2015-02-01

    Recently, Functional Remediation (FR) has proven to be effective in improving the functional outcome of euthymic bipolar patients. The aim of this study was to test the efficacy of the FR program in a subsample of euthymic bipolar II patients (BPII). A post-hoc analyses were undertaken using data of 53 BPII outpatients who had participated in a multicenter, rater-blind, randomized, controlled trial exploring the efficacy of FR (n=17) as compared with a Psychoeducation group (PSY) (n=19) and a treatment as usual control group (TAU n=17). The primary outcome variable was the functional improvement defined as the mean change in the Functioning Assessment Short Test (FAST) from baseline to endpoint after the intervention. Regarding the treatment effect, data reveal a significant functional improvement from baseline to endpoint, suggestive for an interaction between program pertinence and time (pre-post). Nevertheless, Tukey?s post-hoc test only revealed a trend in favor of a better outcome for FR when compared to the other two groups. We also found an interaction between program pertinence and time when analysing the subdepressive symptoms, with BPII patients in FR showing a significant reduction when compared to the PSY group. Our results suggest that the FR appears to be effective in improving the overall functional outcome in BPII, as well as in reducing subdepressive symptoms. PMID:24906790

  13. Improving functional disability and cognition in Parkinson disease

    PubMed Central

    Peña, Javier; García-Gorostiaga, Inés; Gomez-Beldarrain, Maria Angeles; Díez-Cirarda, María; Ojeda, Natalia

    2014-01-01

    Objectives: To examine the efficacy of an integrative cognitive training program (REHACOP) to improve cognition, clinical symptoms, and functional disability of patients with Parkinson disease (PD). Methods: Forty-two patients diagnosed with PD in Hoehn & Yahr stages 1 to 3 were randomly assigned to either the cognitive training group (REHACOP) or the control group (occupational activities) for 3 months (3 sessions, 60 min/wk). Primary outcomes were change on processing speed, verbal memory, visual memory, executive functioning, and theory of mind. Secondary outcomes included changes on neuropsychiatric symptoms, depression, apathy, and functional disability. The trial was registered with clinicaltrials.gov (NCT02118480). Results: No baseline group differences were found. Bootstrapped analysis of variance results showed significant differences in the mean change scores between the REHACOP group and control group in processing speed (0.13 [SE = 0.07] vs ?0.15 [SE = 0.09], p = 0.025), visual memory (0.10 [SE = 0.10] vs ?0.24 [SE = 0.09], p = 0.011), theory of mind (1.00 [SE = 0.37] vs ?0.27 [SE = 0.29], p = 0.013), and functional disability (?5.15 [SE = 1.35] vs 0.53 [SE = 1.49], p = 0.012). Conclusions: Patients with PD receiving cognitive training with REHACOP demonstrated statistically significant and clinically meaningful changes in processing speed, visual memory, theory of mind, and functional disability. Future studies should consider the long-term effect of this type of intervention. These findings support the integration of cognitive training into the standard of care for patients with PD. Classification of evidence: This study provides Class II evidence that for patients with PD, an integrative cognitive training program improves processing speed, visual memory, theory of mind, and functional disability. PMID:25361785

  14. Improvement in Midwall Myocardial Shortening With Regression of Left Ventricular Hypertrophy

    Microsoft Academic Search

    Jamil Mayet; Ben Ariff; Balvinder Wasan; Neil Chapman; Manjit Shahi; Neil R. Poulter; Peter S. Sever; Rodney A. Foale

    2010-01-01

    Despite normal indices of left ventricular (LV) chamber function, patients with LV hypertrophy (LVH) due to hypertension are thought to have depressed midwall systolic shortening compared with normotensives. The aims of the present study were (1) to confirm this observation and (2) to assess the effects of antihypertensive therapy that cause regression of LVH on LV systolic function assessed at

  15. Original article Exposure of cats to low doses of FeLV: seroconversion

    E-print Network

    Paris-Sud XI, Université de

    July 2009; accepted 26 October 2009) Abstract ­ In felids, feline leukemia virus (FeLV) infection response was monitored by measuring FeLV whole virus and p45 antibodies; and feline oncornavirus / infection outcome / abortive infection / FOCMA assay 1. INTRODUCTION Feline leukemia virus (Fe

  16. Functional improvements in ?-lactoglobulin by conjugating with soybean soluble polysaccharide.

    PubMed

    Inada, Naoki; Hayashi, Mai; Yoshida, Tadashi; Hattori, Makoto

    2015-01-01

    Soybean soluble polysaccharide (SSPS) was hydrolyzed by autoclaving for 6 and 12 h to obtain SSPS (6 h) and SSPS (12 h). Bovine ?-lactoglobulin (BLG) was conjugated with each SSPS by the Maillard reaction to improve its function. Conjugation between BLG and each SSPS was confirmed by Sodium dodecyl sulfate polyacrylamide gel electrophoresis and isoelectric focusing. BLG-SSPS (6 h) and BLG-SSPS (12 h), respectively, retained approximately 56 and 43% of the retinol-binding activity of BLG. Structural analyses by intrinsic fluorescence and enzyme-linked immunosorbent assay with monoclonal antibodies indicated that the native structure of BLG had almost been maintained in each conjugate and that the surface structure was covered by conjugated SSPS. The emulsifying properties of BLG were improved in each conjugate at pH 3, 5, and 7 in the presence of 0.2 M NaCl. The antibody responses to BLG-SSPS (6 h) and BLG-SSPS (12 h) were considerably reduced in BALB/c mice. We conclude that conjugation with SSPS was very effective for improving the function of BLG and this study would contribute to greater utilization of SSPS. PMID:25315246

  17. Improving nonlinear modeling capabilities of functional link adaptive filters.

    PubMed

    Comminiello, Danilo; Scarpiniti, Michele; Scardapane, Simone; Parisi, Raffaele; Uncini, Aurelio

    2015-09-01

    The functional link adaptive filter (FLAF) represents an effective solution for online nonlinear modeling problems. In this paper, we take into account a FLAF-based architecture, which separates the adaptation of linear and nonlinear elements, and we focus on the nonlinear branch to improve the modeling performance. In particular, we propose a new model that involves an adaptive combination of filters downstream of the nonlinear expansion. Such combination leads to a cooperative behavior of the whole architecture, thus yielding a performance improvement, particularly in the presence of strong nonlinearities. An advanced architecture is also proposed involving the adaptive combination of multiple filters on the nonlinear branch. The proposed models are assessed in different nonlinear modeling problems, in which their effectiveness and capabilities are shown. PMID:26057613

  18. Improving Network Structure can lead to Functional Failures

    PubMed Central

    Pade, Jan Philipp; Pereira, Tiago

    2015-01-01

    In many real-world networks the ability to synchronize is a key property for their performance. Recent work on undirected networks with diffusive interaction revealed that improvements in the network connectivity such as making the network more connected and homogeneous enhances synchronization. However, real-world networks have directed and weighted connections. In such directed networks, understanding the impact of structural changes on the network performance remains a major challenge. Here, we show that improving the structure of a directed network can lead to a failure in the network function. For instance, introducing new links to reduce the minimum distance between nodes can lead to instabilities in the synchronized motion. This effect only occurs in directed networks. Our results allow to identify the dynamical importance of a link and thereby have a major impact on the design and control of directed networks. PMID:25989294

  19. Improving Network Structure can lead to Functional Failures.

    PubMed

    Pade, Jan Philipp; Pereira, Tiago

    2015-01-01

    In many real-world networks the ability to synchronize is a key property for their performance. Recent work on undirected networks with diffusive interaction revealed that improvements in the network connectivity such as making the network more connected and homogeneous enhances synchronization. However, real-world networks have directed and weighted connections. In such directed networks, understanding the impact of structural changes on the network performance remains a major challenge. Here, we show that improving the structure of a directed network can lead to a failure in the network function. For instance, introducing new links to reduce the minimum distance between nodes can lead to instabilities in the synchronized motion. This effect only occurs in directed networks. Our results allow to identify the dynamical importance of a link and thereby have a major impact on the design and control of directed networks. PMID:25989294

  20. Rationale and Design of a Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of B-type Natriuretic Peptide For the Preservation of Left Ventricular Function Post Anterior Myocardial Infarction

    PubMed Central

    Sangaralingham, S. Jeson; Burnett, John C.; McKie, Paul M.; Schirger, John A.; Chen, Horng H.

    2013-01-01

    Background B-type natriuretic peptide (BNP) is a hormone with pleiotropic cardio-protective properties. Previously in our non-placebo controlled, un-blinded pilot study (BELIEVE) in human ST-elevation anterior acute myocardial infarction (AMI), a 72 hour intravenous infusion (IV) of recombinant human BNP (nesiritide) at a dose of 0.006 ug/kg/min suppressed plasma aldosterone and reduced cardiac dilatation while improved left ventricular ejection fraction (LV EF) at 1 month compared to baseline. Methods and Design The BELIEVE II study is a phase II, randomized, double-blind, placebo-controlled, single center clinical trial to assess the efficacy of 72 hour IV infusion of nesiritide therapy (0.006 ug/kg/min), in humans with first time ST-elevation anterior AMI and successful reperfusion, in preventing adverse LV remodeling and preserving LV function. A total of 60 patients will be randomized to placebo or nesiritide therapy. The primary efficacy endpoint is LV end-systolic and end-diastolic dimensions determined by MUGA scan between placebo and nesiritide group at 30 days; secondary endpoints include 30 day LV EF, diastolic function, infarct size, LV mass and combined total mortality and heart failure hospitalization. Conclusion This will be the first randomized, double-blind, placebo-controlled clinical trial that will assess the clinical efficacy of nesiritide in human ST-elevation anterior AMI. PMID:23910581

  1. Note: Work function change measurement via improved Anderson method.

    PubMed

    Sabik, A; Go?ek, F; Antczak, G

    2015-05-01

    We propose the modification to the Anderson method of work function change (??) measurements. In this technique, the kinetic energy of the probing electrons is already low enough for non-destructive investigation of delicate molecular systems. However, in our implementation, all electrodes including filament of the electron gun are polarized positively. As a consequence, electron bombardment of any elements of experimental system is eliminated. Our modification improves cleanliness of the ultra-high vacuum system. As an illustration of the solution capabilities, we present ?? of the Ag(100) surface induced by cobalt phthalocyanine layers. PMID:26026572

  2. Note: Work function change measurement via improved Anderson method

    NASA Astrophysics Data System (ADS)

    Sabik, A.; Go?ek, F.; Antczak, G.

    2015-05-01

    We propose the modification to the Anderson method of work function change (??) measurements. In this technique, the kinetic energy of the probing electrons is already low enough for non-destructive investigation of delicate molecular systems. However, in our implementation, all electrodes including filament of the electron gun are polarized positively. As a consequence, electron bombardment of any elements of experimental system is eliminated. Our modification improves cleanliness of the ultra-high vacuum system. As an illustration of the solution capabilities, we present ?? of the Ag(100) surface induced by cobalt phthalocyanine layers.

  3. 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

    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

    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

  4. Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction

    PubMed Central

    Reil, Jan-Christian; Hohl, Mathias; Reil, Gert-Hinrich; Granzier, Henk L.; Kratz, Mario T.; Kazakov, Andrey; Fries, Peter; Müller, Andreas; Lenski, Matthias; Custodis, Florian; Gräber, Stefan; Fröhlig, Gerd; Steendijk, Paul; Neuberger, Hans-Ruprecht; Böhm, Michael

    2013-01-01

    Aims In diabetes mellitus, heart failure with preserved ejection fraction (HFPEF) is a significant comorbidity. No therapy is available that improves cardiovascular outcomes. The aim of this study was to characterize myocardial function and ventricular-arterial coupling in a mouse model of diabetes and to analyse the effect of selective heart rate (HR) reduction by If-inhibition in this HFPEF-model. Methods and results Control mice, diabetic mice (db/db), and db/db mice treated for 4 weeks with the If-inhibitor ivabradine (db/db-Iva) were compared. Aortic distensibility was measured by magnetic resonance imaging. Left ventricular (LV) pressure–volume analysis was performed in isolated working hearts, with biochemical and histological characterization of the cardiac and aortic phenotype. In db/db aortic stiffness and fibrosis were significantly enhanced compared with controls and were prevented by HR reduction in db/db-Iva. Left ventricular end-systolic elastance (Ees) was increased in db/db compared with controls (6.0 ± 1.3 vs. 3.4 ± 1.2 mmHg/µL, P < 0.01), whereas other contractility markers were reduced. Heart rate reduction in db/db-Iva lowered Ees (4.0 ± 1.1 mmHg/µL, P < 0.01), and improved the other contractility parameters. In db/db active relaxation was prolonged and end-diastolic capacitance was lower compared with controls (28 ± 3 vs. 48 ± 8 ?L, P < 0.01). These parameters were ameliorated by HR reduction. Neither myocardial fibrosis nor hypertrophy were detected in db/db, whereas titin N2B expression was increased and phosphorylation of phospholamban was reduced both being prevented by HR reduction in db/db-Iva. Conclusion In db/db, a model of HFPEF, selective HR reduction by If-inhibition improved vascular stiffness, LV contractility, and diastolic function. Therefore, If-inhibition might be a therapeutic concept for HFPEF, if confirmed in humans. PMID:22833515

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

    Microsoft Academic Search

    April R. Baker; Candace M. Callison

    2007-01-01

    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

  6. Coronary flow reserve improves after aortic valve replacement for aortic stenosis: an adenosine transthoracic echocardiography study

    Microsoft Academic Search

    David J. R Hildick-Smith; Leonard M Shapiro

    2000-01-01

    OBJECTIVESThe goal of this study was to assess coronary flow reserve (CFR) before and after aortic valve replacement (AVR).BACKGROUNDCoronary flow reserve is impaired under conditions of left ventricular (LV) hypertrophy. It is not known whether CFR improves with regression of LV hypertrophy in humans.METHODSWe investigated 35 patients with pure aortic stenosis, LV hypertrophy and normal coronary arteriograms. Patients underwent adenosine

  7. Exercise Training Improves Plantarflexor Muscle Function in mdx Mice

    PubMed Central

    Baltgalvis, Kristen A.; Call, Jarrod A.; Cochrane, Gregory D.; Laker, Rhianna C.; Yan, Zhen; Lowe, Dawn A.

    2012-01-01

    Purpose We tested the hypothesis that low intensity exercise in mdx mice improves plantarflexor muscle contractile function, resistance to fatigue, and mitochondrial adaptations without exacerbating muscular dystrophy. Methods We subjected mdx mice to 12 wk of voluntary, low-resistance wheel running (Run, n=17) or normal cage activities (sedentary; Sed, n=16) followed by in vivo analyses for plantarflexor torque generation and fatigue resistance, or running capacity on a treadmill. Gastrocnemius muscles were further evaluated for exercise-induced mitochondrial adaptations and fiber type distribution and central nuclei. T-tests were used to determine differences between the Sed and Run groups. Results Plantarflexor submaximal isometric torques and maximal isometric torque at multiple ankle joint angles, and resistance to fatigue were greater in Run compared to Sed mdx mice (P<0.05). Citrate synthase and ?-HAD enzyme activities and COX IV protein expression in gastrocnemius muscles were greater in Run than Sed mdx mice (P?0.04), along with a trend of fiber type transformation from type IIb to type 2x fibers. Exercise training in mdx mice did not elevate serum creatine kinase levels, but led to a significant reduction of centrally-nucleated myofibers. Conclusion Voluntary, low-resistance wheel running in mdx mice can result in skeletal muscle adaptation, leading to improved contractile function and reduced fatigability, with no indication that exercise was detrimental. This study supports the need for further investigation of low intensity exercise as an early therapeutic intervention in ambulatory boys with DMD. PMID:22460476

  8. Improved CLARAty Functional-Layer/Decision-Layer Interface

    NASA Technical Reports Server (NTRS)

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

    2008-01-01

    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.

  9. Valuing preferences over stormwater management outcomes including improved hydrologic function

    NASA Astrophysics Data System (ADS)

    LondoñO Cadavid, Catalina; Ando, Amy W.

    2013-07-01

    Stormwater runoff causes environmental problems such as flooding, soil erosion, and water pollution. Conventional stormwater management has focused primarily on flood reduction, while a new generation of decentralized stormwater solutions yields ancillary benefits such as healthier aquatic habitat, improved surface water quality, and increased water table recharge. Previous research has estimated values for flood reduction from stormwater management, but no estimates exist for the willingness to pay (WTP) for some of the other environmental benefits of alternative approaches to stormwater control. This paper uses a choice experiment survey of households in Champaign-Urbana, Illinois, to estimate the values of several attributes of stormwater management outcomes. We analyzed data from 131 surveyed households in randomly selected neighborhoods. We find that people value reduced basement flooding more than reductions in yard or street flooding, but WTP for basement flood reduction in the area only exists if individuals are currently experiencing significant flooding themselves. Citizens value both improved water quality and improved hydrologic function and aquatic habitat from runoff reduction. Thus, widespread investment in low impact development stormwater solutions could have very large total benefits, and stormwater managers should be wary of policies and infrastructure plans that reduce flooding at the expense of water quality and aquatic habitat.

  10. Comparative Efficacy of Feline Leukemia Virus (FeLV) Inactivated Whole-Virus Vaccine and Canarypox Virus-Vectored Vaccine during Virulent FeLV Challenge and Immunosuppression.

    PubMed

    Patel, M; Carritt, K; Lane, J; Jayappa, H; Stahl, M; Bourgeois, M

    2015-07-01

    Four vaccines for feline leukemia virus (FeLV) are available in the United States. This study's purpose was to compare the efficacy of Nobivac feline 2-FeLV (an inactivated, adjuvanted whole-virus vaccine) and PureVax recombinant FeLV (a live, canarypox virus-vectored vaccine) following FeLV challenge. Cats were vaccinated at 9 and 12 weeks with Nobivac feline 2-FeLV (group A, n = 11) or PureVax recombinant FeLV (group B, n = 10). Group C (n = 11) comprised unvaccinated controls. At 3 months postvaccination, cats were immunosuppressed and challenged with FeLV-A/61E. The outcomes measured were persistent antigenemia at 12 weeks postchallenge (PC) and proviral DNA and viral RNA at 3 to 9 weeks PC. Persistent antigenemia was observed in 0 of 11 cats in group A, 5 of 10 cats in group B, and 10 of 11 cats in group C. Group A was significantly protected compared to those in groups B (P < 0.013) and C (P < 0.0001). No difference was found between groups B and C (P > 0.063). The preventable fraction was 100% for group A and 45% for group B. At 9 weeks PC, proviral DNA and viral RNA were detected 1 of 11 cats in group A, 6 of 10 cats in group B, and 9 of 11 cats in group C. Nucleic acid loads were significantly lower in group A than in group C (P < 0.01). Group A had significantly lower proviral DNA loads than group B at weeks 6 to 9 (P < 0.02). The viral RNA loads were significantly lower in group A than in group B at weeks 7 to 9 (P < 0.01). The results demonstrate that Nobivac feline 2-FeLV-vaccinated cats were fully protected against persistent antigenemia and had significantly smaller amounts of proviral DNA and plasma viral RNA loads than PureVax recombinant FeLV-vaccinated cats and unvaccinated controls. PMID:25972402

  11. Schwann Cells Seeded in Acellular Nerve Grafts Improve Functional Recovery

    PubMed Central

    Jesuraj, Nithya J.; Santosa, Katherine B.; MacEwan, Matthew R.; Moore, Amy M.; Kasukurthi, Rahul; Ray, Wilson Z.; Flagg, Eric R.; Hunter, Daniel A.; Borschel, Gregory H.; Johnson, Philip J.; Mackinnon, Susan E.; Sakiyama-Elbert, Shelly E.

    2014-01-01

    Introduction This study evaluated whether Schwann cells (SCs) from different nerve sources transplanted into cold-preserved acellular nerve grafts (CP-ANGs) would improve functional regeneration compared to nerve isografts. Methods SCs isolated and expanded from motor and sensory branches of rat femoral and sciatic nerves were seeded into 14mm CP-ANGs. Growth factor expression, axonal regeneration, and functional recovery were evaluated in a14 mm rat sciatic injury model and compared to isografts. Results At 14 days, motor or sensory-derived SCs increased expression of growth factors in CP-ANGs versus isografts. After 42 days, histomorphometric analysis found CP-ANGs with SCs and isografts had similar numbers of regenerating nerve fibers. At 84 days, muscle force generation was similar for CP-ANGs with SCs and isografts. SC source did not affect nerve fiber counts or muscle force generation. Discussion SCs transplanted into CP-ANGs increase functional regeneration to isograft levels; however SC nerve source did not have an effect. PMID:23625513

  12. OSM Enhances Angiogenesis and Improves Cardiac Function after Myocardial Infarction

    PubMed Central

    Zhang, Xiaotian; Zhu, Di; Wei, Liping; Zhao, Zhijing; Qi, Xin; Li, Zongjin; Sun, Dongdong

    2015-01-01

    Oncostatin M (OSM) has been reported to stimulate angiogenesis by upregulating VEGF and bFGF, implying that it could be a therapeutic strategy in treating ischemic diseases. The present study was aimed at investigating whether OSM could improve cardiac function via prompting angiogenesis following myocardial infarction (MI). Wild type (WT) and O? knock-out (O??/?) mice were, respectively, randomized into sham group, MI?+?vehicle group, and MI?+?OSM group. WT mice displayed significantly impaired cardiac function after MI. OSM treatment attenuated cardiac dysfunction in WT MI mice, while O? deletion abrogated the protective effects. Besides, OSM attenuated heart hypertrophy and pulmonary congestion evidenced by decreased heart weight/body weight and lung weight/body weight ratio. Further, reduction of apoptosis and fibrosis in infarct border zone was observed in OSM treated WT MI mice compared with vehicle. Moreover, in WT mice subjected to MI, OSM treatment significantly increased capillary density along with upregulation of p-Akt and angiogenic factors VEGF and bFGF in comparison with vehicle, and this phenomenon was not found in O??/? mice. In conclusion, OSM treatment preserved cardiac function, inhibited apoptosis and fibrosis, and stimulated angiogenesis via upregulating VEGF and bFGF in infarct border zone of ischemic myocardium, indicating that OSM could be a novel therapeutic target for MI. PMID:26146616

  13. Inhibiting epigenetic enzymes to improve atherogenic macrophage functions.

    PubMed

    Van den Bossche, Jan; Neele, Annette E; Hoeksema, Marten A; de Heij, Femke; Boshuizen, Marieke C S; van der Velden, Saskia; de Boer, Vincent C; Reedquist, Kris A; de Winther, Menno P J

    2014-12-12

    Macrophages determine the outcome of atherosclerosis by propagating inflammatory responses, foam cell formation and eventually necrotic core development. Yet, the pathways that regulate their atherogenic functions remain ill-defined. It is now apparent that chromatin remodeling chromatin modifying enzymes (CME) governs immune responses but it remains unclear to what extent they control atherogenic macrophage functions. We hypothesized that epigenetic mechanisms regulate atherogenic macrophage functions, thereby determining the outcome of atherosclerosis. Therefore, we designed a quantitative semi-high-throughput screening platform and studied whether the inhibition of CME can be applied to improve atherogenic macrophage activities. We found that broad spectrum inhibition of histone deacetylases (HDACs) and histone methyltransferases (HMT) has both pro- and anti-inflammatory effects. The inhibition of HDACs increased histone acetylation and gene expression of the cholesterol efflux regulators ATP-binding cassette transporters ABCA1 and ABCG1, but left foam cell formation unaffected. HDAC inhibition altered macrophage metabolism towards enhanced glycolysis and oxidative phosphorylation and resulted in protection against apoptosis. Finally, we applied inhibitors against specific HDACs and found that HDAC3 inhibition phenocopies the atheroprotective effects of pan-HDAC inhibitors. Based on our data, we propose the inhibition of HDACs, and in particular HDAC3, in macrophages as a novel potential target to treat atherosclerosis. PMID:25446073

  14. Why and how a functional information system improves computerized operations

    SciTech Connect

    Pirus, D. [EDF SEPTEN, Service Etudes et Projets Thermiques et Nucleaires, 12-14, Avenue Dutrievoz, 69628 Villeurbanne Cedex (France)

    2006-07-01

    At the beginning of the eighties, designing a computerized control room was similar to exploring a terra incognita. Some major projects were carried out (N4 project, Kashiwasaki for example) in order to provide initial experience feedback. Today design guidelines and standards exist to help designers and now all projects (for new control rooms or for renovating existing ones) are designed to use computerized operations. Experience feedback on existing projects clearly shows that the computerization of operations significantly improves the overall quality and efficiency of operations. Nevertheless, the computerization of operations introduces new specific problems, the most important being the 'key hole effect' and the lack of global vision. These problems can be directly attributed to the media currently used (the screens) where space is scarce, and to the philosophy used when designing the information system (fundamentally, based on a reproduction of existing piping diagrams with little or no summary information). Yesterday, the challenge was to computerize the control room, today, it is to computerize operations and reduce or eliminate these existing problems. One promising method is to design the HSI using a functional methodology. This paper describes the operators' operational needs and how and why a functional information system can help address those needs. Finally, the paper presents a few proposals on how to design a functional information system. (authors)

  15. HoMuLV: a novel pathogenic ecotropic virus isolated from the European mouse, Mus hortulanus.

    PubMed

    Voytek, P; Kozak, C

    1988-08-01

    We isolated a novel infectious murine leukemia virus (HoMuLV) from the wild mouse Mus hortulanus. HoMuLV has an ecotropic virus host range, but the viral DNA fails to hybridize to viral envelope segments specific for the known inbred and wild mouse ecotropic as well as nonecotropic MuLVs. Despite this difference in its env gene, HoMuLV appears to use the same ecotropic cell-surface receptor since it infects only hamster and mouse somatic cell hybrids which contain the Rec-1 ecotropic virus receptor on chromosome 5. Furthermore, HoMuLV does not infect mice carrying the Fv-4r allele which is thought to prevent ecotropic virus infection through an interference mechanism. HoMuLV is NB-tropic and, unlike other infectious MuLVs, does not grow in cells derived from the wild mouse species. M. dunni. Five to ten months after neonatal inoculation with HoMuLV, 72% of female NIH Swiss mice (8/11) contracted lymphoma or erythroid leukemia, but 33% of the inoculated males (5/15) developed erythroid or myelogenous leukemia within 8-16 months. These data suggest that NIH Swiss males and females differ in their susceptibility to HoMuLV-induced disease. Furthermore, NIH Swiss mice were found to be more susceptible to HoMuLV-induced disease than NFS/N mice. Tumors contained infectious MCF virus, which is consistent with the hypothesis that MCF virus may mediate tumorigenesis by HoMuLV. PMID:2841796

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

    PubMed Central

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

    1997-01-01

    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. PMID:9251199

  17. In vivo MRI-Based 3D FSI RV/LV Models for Human Right Ventricle and Patch Design for Potential Computer-Aided Surgery Optimization

    PubMed Central

    Yang, Chun; Tang, Dalin; Haber, Idith; Geva, Tal; del Nido, Pedro J.

    2009-01-01

    Right ventricular dysfunction is one of the more common causes of heart failure in patients with congenital heart defects. Use of computer-assisted procedures is becoming more popular in clinical decision making process and computer-aided surgeries. A 3D in vivo MRI-based RV/LV combination model with fluid-structure interaction (FSI), RV-LV interaction, and RV-patch interaction was introduced to perform mechanical analysis for human right ventricle with potential clinical applications. Patient-specific RV/LV morphologies were acquired by using planar tagged MRI. The 3D RV/LV FSI model was solved using a commercial finite element package ADINA. Our results indicated that flow and stress/strain distributions in the right ventricle are closely related to RV morphology, material properties and blood pressure conditions. Patches with material properties better matching RV tissue properties and smaller size lead to better RV function recoveries. Computational RV volumes showed very good agreement with MRI data (error < 3%). More patient studies are needed to establish baseline database so that computational simulations can be used to replace empirical and often risky clinical experimentation to examine the efficiency and suitability of various reconstructive procedures in diseased hearts and optimal design can be found. PMID:19809530

  18. Automated classification of LV regional wall motion based on spatio-temporal profiles from cardiac cine magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Mantilla, Juan; Garreau, Mireille; Bellanger, Jean-Jacques; Paredes, José Luis

    2013-11-01

    Assessment of the cardiac Left Ventricle (LV) wall motion is generally based on visual inspection or quantitative analysis of 2D+t sequences acquired in short-axis cardiac cine-Magnetic Resonance Imaging (MRI). Most often, cardiac dynamic is globally analized from two particular phases of the cardiac cycle. In this paper, we propose an automated method to classify regional wall motion in LV function based on spatio-temporal pro les and Support Vector Machines (SVM). This approach allows to obtain a binary classi cation between normal and abnormal motion, without the need of pre-processing and by exploiting all the images of the cardiac cycle. In each short- axis MRI slice level (basal, median, and apical), the spatio-temporal pro les are extracted from the selection of a subset of diametrical lines crossing opposites LV segments. Initialized at end-diastole phase, the pro les are concatenated with their corresponding projections into the succesive temporal phases of the cardiac cycle. These pro les are associated to di erent types of information that derive from the image (gray levels), Fourier, Wavelet or Curvelet domains. The approach has been tested on a set of 14 abnormal and 6 healthy patients by using a leave-one-out cross validation and two kernel functions for SVM classi er. The best classi cation performance is yielded by using four-level db4 wavelet transform and SVM with a linear kernel. At each slice level the results provided a classi cation rate of 87.14% in apical level, 95.48% in median level and 93.65% in basal level.

  19. 42 CFR 493.2001 - Establishment and function of the Clinical Laboratory Improvement Advisory Committee.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...Establishment and function of the Clinical Laboratory Improvement Advisory Committee. 493...CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Consultations § 493...Establishment and function of the Clinical Laboratory Improvement Advisory Committee....

  20. 42 CFR 493.2001 - Establishment and function of the Clinical Laboratory Improvement Advisory Committee.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...Establishment and function of the Clinical Laboratory Improvement Advisory Committee. 493...CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Consultations § 493...Establishment and function of the Clinical Laboratory Improvement Advisory Committee....

  1. 42 CFR 493.2001 - Establishment and function of the Clinical Laboratory Improvement Advisory Committee.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...Establishment and function of the Clinical Laboratory Improvement Advisory Committee. 493...CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Consultations § 493...Establishment and function of the Clinical Laboratory Improvement Advisory Committee....

  2. 42 CFR 493.2001 - Establishment and function of the Clinical Laboratory Improvement Advisory Committee.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...Establishment and function of the Clinical Laboratory Improvement Advisory Committee. 493...CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Consultations § 493...Establishment and function of the Clinical Laboratory Improvement Advisory Committee....

  3. 42 CFR 493.2001 - Establishment and function of the Clinical Laboratory Improvement Advisory Committee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...Establishment and function of the Clinical Laboratory Improvement Advisory Committee. 493...CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Consultations § 493...Establishment and function of the Clinical Laboratory Improvement Advisory Committee....

  4. Improved Fibroblast Functionalities by Microporous Pattern Fabricated by Microelectromechanical Systems

    PubMed Central

    Wei, Hongbo; Zhao, Lingzhou; Chen, Bangdao; Bai, Shizhu; Zhao, Yimin

    2014-01-01

    Fibroblasts, which play an important role in biological seal formation and maintenance, determine the long-term success of percutaneous implants. In this study, well-defined microporous structures with micropore diameters of 10–60 µm were fabricated by microelectromechanical systems and their influence on the fibroblast functionalities was observed. The results show that the microporous structures with micropore diameters of 10–60 µm did not influence the initial adherent fibroblast number; however, those with diameters of 40 and 50 µm improved the spread, actin stress fiber organization, proliferation and fibronectin secretion of the fibroblasts. The microporous structures with micropore diameters of 40–50 µm may be promising for application in the percutaneous part of an implant. PMID:25054322

  5. ATP citrate lyase improves mitochondrial function in skeletal muscle.

    PubMed

    Das, Suman; Morvan, Frederic; Jourde, Benjamin; Meier, Viktor; Kahle, Peter; Brebbia, Pascale; Toussaint, Gauthier; Glass, David J; Fornaro, Mara

    2015-06-01

    Mitochondrial dysfunction is associated with skeletal muscle pathology, including cachexia, sarcopenia, and the muscular dystrophies. ATP citrate lyase (ACL) is a cytosolic enzyme that catalyzes mitochondria-derived citrate into oxaloacetate and acetyl-CoA. Here we report that activation of ACL in skeletal muscle results in improved mitochondrial function. IGF1 induces activation of ACL in an AKT-dependent fashion. This results in an increase in cardiolipin, thus increasing critical mitochondrial complexes and supercomplex activity, and a resultant increase in oxygen consumption and cellular ATP levels. Conversely, knockdown of ACL in myotubes not only reduces mitochondrial complex I, IV, and V activity but also blocks IGF1-induced increases in oxygen consumption. In vivo, ACL activity is associated with increased ATP. Activation of this IGF1/ACL/cardiolipin pathway combines anabolic signaling with induction of mechanisms needed to provide required ATP. PMID:26039450

  6. Improved Functionality and Curation Support in the ADS

    NASA Astrophysics Data System (ADS)

    Accomazzi, Alberto; Kurtz, Michael J.; Henneken, Edwin A.; Grant, Carolyn S.; Thompson, Donna; Chyla, Roman; Holachek, Alexandra; Sudilovsky, Vladimir; Murray, Stephen S.

    2015-01-01

    In this poster we describe the developments of the new ADS platform over the past year, focusing on the functionality which improves its discovery and curation capabilities.The ADS Application Programming Interface (API) is being updated to support authenticated access to the entire suite of ADS services, in addition to the search functionality itself. This allows programmatic access to resources which are specific to a user or class of users.A new interface, built directly on top of the API, now provides a more intuitive search experience and takes into account the best practices in web usability and responsive design. The interface now incorporates in-line views of graphics from the AAS Astroexplorer and the ADS All-Sky Survey image collections.The ADS Private Libraries, first introduced over 10 years ago, are now being enhanced to allow the bookmarking, tagging and annotation of records of interest. In addition, libraries can be shared with one or more ADS users, providing an easy way to collaborate in the curation of lists of papers. A library can also be explicitly made public and shared at large via the publishing of its URL.In collaboration with the AAS, the ADS plans to support the adoption of ORCID identifiers by implementing a plugin which will simplify the import of papers in ORCID via a query to the ADS API. Deeper integration between the two systems will depend on available resources and feedback from the community.

  7. PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.

    PubMed

    Zhang, Hao; Wang, Zheng; Feng, Shou-Jie; Xu, Lei; Shi, He-Xian; Chen, Li-Li; Yuan, Guang-Da; Yan, Wei; Zhuang, Wei; Zhang, Yi-Qian; Zhang, Zhong-Ming; Dong, Hong-Yan

    2015-01-01

    Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPAR?-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size. PMID:25768344

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

    PubMed

    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

    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

  9. Model simulation of a curvature matching algorithm to assess systolic and diastolic LV wall motion

    Microsoft Academic Search

    G. Barletta; M. Baroni; F. Fantini

    1992-01-01

    Curvature-motion (CM) is a method explaining shape analysis to assess left ventricular (LV) wall motion. A model based approach is proposed for validation. Complete contour sequences from end-diastolic LV outlines were generated by applying a locally linear transformation to simulate normal\\/abnormal systolic and diastolic movements. Time trajectories and segmental excursions, as measured by the centerline, radial, and curvature-motion methods, were

  10. Molecular and phylogenetic analyses of a new Amphotropic murine leukemia virus (MuLV-1313)

    Microsoft Academic Search

    Thomas M Howard; Zhijuan Sheng; Mingwu Wang; Yongchun Wu; Suraiya Rasheed

    2006-01-01

    BACKGROUND: The amphotropic murine leukemia viruses (MuLV-A's) are naturally occurring, exogenously acquired gammaretroviruses that are indigenous to the Southern California wild mice. These viruses replicate in a wide range of cell types including human cells in vitro and they can cause both hematological and neurological disorders in feral as well as in the inbred laboratory mice. Since MuLV-A's also exhibit

  11. Relation between severity of coronary artery disease, left ventricular function and myocardial infarction, and influence of the ACE I/D gene polymorphism.

    PubMed

    Ledru, F; Blanchard, D; Battaglia, S; Jeunemaitre, X; Courbon, D; Guize, L; Guermonprez, J L; Ducimetière, P; Diébold, B

    1998-07-15

    Left ventricular (LV) systolic function is partly determined by severity of coronary artery disease and is improved by angiotensin-converting enzyme (ACE) inhibition, at least in post-infarct patients. Because the ACE insertion/deletion (I/D) gene polymorphism is associated with circulating and tissue ACE activity, we sought to evaluate the role of this genetic variant on LV function in patients studied with coronary angiography, taking into account coronary vessel anatomy and history of infarction. Coronary artery disease extent scores, coronary artery patency, and LV ejection fraction were assessed in 400 consecutive Caucasian patients referred for established or suspected ischemic heart disease. A previous infarction had occurred in 141 patients an average of 3.7 years before the study. The ACE DD genotype, compared with the ACE ID/II genotype, was associated with a 2.7% higher ejection fraction in noninfarct patients (p = 0.047) but a 5.0% lower ejection fraction in post-infarct patients (p = 0.047). An interaction effect between the ACE I/D gene polymorphism, the infarction status, and LV ejection fraction was observed in the whole population (p = 0.003), in patients with no disease and 1-, 2-, and 3-vessel diseases (p = 0.03 and p = 0.06, respectively), and in those with chronically occluded coronary vessels (p = 0.02). The influence of the ACE I/D gene polymorphism on LV function is modulated by infarction status and coronary anatomy. PMID:9678285

  12. The Rapalogue, CCI-779, Improves Salivary Gland Function following Radiation

    PubMed Central

    Morgan-Bathke, Maria; Harris, Zoey I.; Arnett, Deborah G.; Klein, Rob R.; Burd, Randy; Ann, David K.; Limesand, Kirsten H.

    2014-01-01

    The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5f/f; Aqp5-Cre, Atg5+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side effects in head and neck cancer patients who have completed anti-tumor therapy. PMID:25437438

  13. Genetically enhancing mitochondrial antioxidant activity improves muscle function in aging

    PubMed Central

    Umanskaya, Alisa; Santulli, Gaetano; Andersson, Daniel C.; Reiken, Steven R.; Marks, Andrew R.

    2014-01-01

    Age-related skeletal muscle dysfunction is a leading cause of morbidity that affects up to half the population aged 80 or greater. Here we tested the effects of increased mitochondrial antioxidant activity on age-dependent skeletal muscle dysfunction using transgenic mice with targeted overexpression of the human catalase gene to mitochondria (MCat mice). Aged MCat mice exhibited improved voluntary exercise, increased skeletal muscle specific force and tetanic Ca2+ transients, decreased intracellular Ca2+ leak and increased sarcoplasmic reticulum (SR) Ca2+ load compared with age-matched wild type (WT) littermates. Furthermore, ryanodine receptor 1 (the sarcoplasmic reticulum Ca2+ release channel required for skeletal muscle contraction; RyR1) from aged MCat mice was less oxidized, depleted of the channel stabilizing subunit, calstabin1, and displayed increased single channel open probability (Po). Overall, these data indicate a direct role for mitochondrial free radicals in promoting the pathological intracellular Ca2+ leak that underlies age-dependent loss of skeletal muscle function. This study harbors implications for the development of novel therapeutic strategies, including mitochondria-targeted antioxidants for treatment of mitochondrial myopathies and other healthspan-limiting disorders. PMID:25288763

  14. Improvement of the organic solar cells functional parameters

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

    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.

  15. Effects of a myofilament calcium sensitizer on left ventricular systolic and diastolic function in rats with volume overload heart failure.

    PubMed

    Wilson, Kristin; Guggilam, Anuradha; West, T Aaron; Zhang, Xiaojin; Trask, Aaron J; Cismowski, Mary J; de Tombe, Pieter; Sadayappan, Sakthivel; Lucchesi, Pamela A

    2014-12-01

    Aortocaval fistula (ACF)-induced volume overload (VO) heart failure (HF) results in progressive left ventricular (LV) dysfunction. Hemodynamic load reversal during pre-HF (4 wk post-ACF; REV) results in rapid structural but delayed functional recovery. This study investigated myocyte and myofilament function in ACF and REV and tested the hypothesis that a myofilament Ca(2+) sensitizer would improve VO-induced myofilament dysfunction in ACF and REV. Following the initial sham or ACF surgery in male Sprague-Dawley rats (200-240 g) at week 0, REV surgery and experiments were performed at weeks 4 and 8, respectively. In ACF, decreased LV function is accompanied by impaired sarcomeric shortening and force generation and decreased Ca(2+) sensitivity, whereas, in REV, impaired LV function is accompanied by decreased Ca(2+) sensitivity. Intravenous levosimendan (Levo) elicited the best inotropic and lusitropic responses and was selected for chronic oral studies. Subsets of ACF and REV rats were given vehicle (water) or Levo (1 mg/kg) in drinking water from weeks 4-8. Levo improved systolic (% fractional shortening, end-systolic elastance, and preload-recruitable stroke work) and diastolic (?, dP/dtmin) function in ACF and REV. Levo improved Ca(2+) sensitivity without altering the amplitude and kinetics of the intracellular Ca(2+) transient. In ACF-Levo, increased cMyBP-C Ser-273 and Ser-302 and cardiac troponin I Ser-23/24 phosphorylation correlated with improved diastolic relaxation, whereas, in REV-Levo, increased cMyBP-C Ser-273 phosphorylation and increased ?-to-?-myosin heavy chain correlated with improved diastolic relaxation. We concluded that Levo improves LV function, and myofilament composition and regulatory protein phosphorylation likely play a key role in improving function. PMID:25260618

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  17. MuLV IN Mutants Responsive to HDAC Inhibitors Enhance Transcription from Unintegrated Retroviral DNA

    PubMed Central

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

    2012-01-01

    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

  18. Endothelial function and left ventricular diastolic functional reserve in type 2 diabetes mellitus

    PubMed Central

    Leung, Melissa; Phan, Victoria; Leung, Dominic Y

    2014-01-01

    Background Endothelial dysfunction is an early feature of vascular disease. Left ventricular (LV) diastolic reserve is the ability of the left ventricle to augment diastolic function with exercise and may be impaired in patients with diabetes mellitus (DM). It is unclear if endothelial dysfunction is related to impaired LV diastolic reserve and diminished exercise capacity. Methods 96 patients with type 2 DM and 10 controls had brachial artery reactivity testing, followed by exercise echocardiography. The brachial artery diameter was measured at rest and during reactive hyperaemia. LV diastolic reserve was measured as ?e? with exercise and diastolic reserve index (?e?/rest e?). Exercise capacity was calculated by metabolic equivalents (METs). Results Compared with controls, patients with DM had lower rest e? (7 vs 9?cm/s, p=0.002), lower ?e?(1 vs 4?cm/s, p=0.023), lower ?e?/rest e? (0.20 vs 0.47, p=0.003) and reduced flow mediated dilation (FMD, 5 vs 15%, p<0.001). FMD was correlated with ?e? (r=0.65, p<0.001), diastolic reserve index (r=0.61, p<0.001) and post-exercise septal E/e? (r=?0.50, p<0.001), but not with rest e? (r=0.13, p=0.177). FMD was an independent predictor of ?e? (?=0.002, p<0.001, R2=0.47) and diastolic reserve index (?=0.030, p<0.001, R2=0.41). Younger age (p<0.001), male gender (p=0.014), lower body mass index (p<0.001), lower rest E/e? (p=0.042) and higher FMD (p=0.025) were independent predictors of higher METs (R2=0.52, p<0.001). Conclusions Patients with DM had impaired endothelial function and LV diastolic dysfunction. LV diastolic reserve and exercise capacity are linked to endothelial function. Targeting vascular risk factors to improve endothelial function may improve LV diastolic reserve and exercise capacity. PMID:25332819

  19. Improving protein function prediction methods with integrated literature data

    Microsoft Academic Search

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

    2008-01-01

    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

  20. An Improved Complexity Hierarchy on the Depth of Boolean Functions

    Microsoft Academic Search

    Ingo Wegener

    1981-01-01

    Circuit depth is an important complexity measure for a Boolean function. Let some Boolean function of n variables have depth k according to an arbitrary binary basis O. For each j where [log n]?j?k we prove the existence of a Boolean function f with the following properties. f depends essentially on n variables and the depth of f according to

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

    PubMed Central

    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

    2014-01-01

    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.—Luo, S., Zhangsun, D., Schroeder, C. I., Zhu, X., Hu, Y., Wu, Y., Weltzin, M. M., Eberhard, S., Kaas, Q., Craik, D. J., McIntosh, J. M., Whiteaker, P. A novel ?4/7-conotoxin LvIA from Conus lividus that selectively blocks ?3?2 vs. ?6/?3?2?3 nicotinic acetylcholine receptors. PMID:24398291

  2. Speckle-Tracking and Tissue-Doppler Stress Echocardiography in Arterial Hypertension: A Sensitive Tool for Detection of Subclinical LV Impairment

    PubMed Central

    Hensel, Kai O.; Leischik, Roman

    2014-01-01

    Early diagnosis of cardiac alterations in hypertensive heart disease is still challenging. Since such patients might have depressed global LV systolic strain or strain rate when EF is still normal, speckle-tracking echocardiography (STE) and tissue-Doppler imaging (TDI) combined with stress echocardiography might improve early diagnosis of cardiac alterations. In this prospective study standard 2D Doppler echocardiography, STE, and TDI were performed at rest and during bicycle exercise in 92 consecutive patients—46 hypertensive subjects with normal ejection fraction and 46 healthy controls. STE and TDI were used to measure global peak systolic LV circumferential strain (CS), longitudinal strain (LS), and longitudinal strain rate (SR). Mean arterial blood pressure was significantly higher in hypertensive patients at rest (100.8?mmHg SD 13.5?mmHg; P = 0.002) and during physical exercise testing (124.2?mmHg SD 13.4?mmHg; P = 0.003). Hypertensive patients had significantly reduced values of systolic CS (P = 0.001), LS (P = 0.014), and SR (P < 0.001) at rest as well as during physical exercise—CS (P < 0.001), LS (P < 0.001), and SR (P < 0.001). Using STE and TDI, reduced LV systolic strain and strain rate consistent with early cardiac alterations can be detected in patients with arterial hypertension. These findings were evident at rest and markedly pronounced during exercise echocardiography. PMID:25389528

  3. Combining specificity determining and conserved residues improves functional site prediction

    Microsoft Academic Search

    Olga V. Kalinina; Mikhail S. Gelfand; Robert B. Russell

    2009-01-01

    BACKGROUND: Predicting the location of functionally important sites from protein sequence and\\/or structure is a long-standing problem in computational biology. Most current approaches make use of sequence conservation, assuming that amino acid residues conserved within a protein family are most likely to be functionally important. Most often these approaches do not consider many residues that act to define specific sub-functions

  4. 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 ...

  5. ?3-Adrenergic receptor antagonist improves exercise performance in pacing-induced heart failure.

    PubMed

    Masutani, Satoshi; Cheng, Heng-Jie; Morimoto, Atsushi; Hasegawa, Hiroshi; Han, Qing-Hua; Little, William C; Cheng, Che Ping

    2013-09-15

    In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise. We have previously shown that in HF at rest stimulation of ?3-adrenergic receptors by endogenous catecholamine depresses LV contraction and relaxation. ?3-Adrenergic receptors are activated at higher concentrations of catecholamine. Thus exercise may cause increased stimulation of cardiac ?3-adrenergic receptors and contribute to this abnormal response. We assessed the effect of L-748,337 (50 ?g/kg iv), a selective ?3-adrenergic receptor antagonist (?3-ANT), on LV dynamics during exercise in 12 chronically instrumented dogs with pacing-induced HF. Compared with HF at rest, exercise increased LV end-systolic pressure (PES), minimum LV pressure (LVPmin), and the time constant of LV relaxation (?) with an upward shift of early diastolic portion of LV pressure-volume loop. LV contractility decreased and arterial elastance (EA) increased. LV arterial coupling (EES/EA) (0.40 vs. 0.51) was impaired. Compared with exercise in HF preparation, exercise after ?3-ANT caused similar increases in heart rate and PES but significantly decreased ? (34.9 vs. 38.3 ms) and LVPmin with a downward shift of the early diastolic portion of LV pressure-volume loop and further augmented dV/dtmax. Both EES and EES/EA (0.68 vs. 0.40) were increased. LV mechanical efficiency improved from 0.39 to 0.53. In conclusion, after HF, ?3-ANT improves LV diastolic filling; increases LV contractility, LV arterial coupling, and mechanical efficiency; and improves exercise performance. PMID:23873794

  6. C-peptide improves autonomic nerve function in IDDM patients

    Microsoft Academic Search

    B. L. Johansson; K. Borg; E. Fernqvist-Forbes; T. Odergren; S. Remahl; J. Wahren

    1996-01-01

    Summary  In order to determine the possible influence of C-peptide on nerve function, 12 insulin-dependent diabetic (IDDM) patients with symptoms of diabetic polyneuropathy were studied twice under euglycaemic conditions. Tests of autonomic nerve function (respiratory heart rate variability, acceleration and brake index during tilting), quantitative sensory threshold determinations, nerve conduction studies and clinical neurological examination were carried out before and during

  7. Improvement in respiratory function after vertebroplasty and kyphoplasty

    Microsoft Academic Search

    RenBin Dong; Liang Chen; Yong Gu; GuoSheng Han; HuiLin Yang; TianSi Tang; Chen Xiaoqing

    2009-01-01

    Our objective was to study the changes in respiratory function of patients with osteoporotic vertebral compression fractures\\u000a (OVCFs) after vertebroplasty and kyphoplasty. Thoracic kyphotic angle, local kyphotic angle, pain scores and pulmonary function\\u000a parameters were measured in 38 older women with OVCFs before, three days after and three months after operation. Vital capacity,\\u000a forced vital capacity and maximum voluntary ventilation significantly increased

  8. Improved response functions for gamma-ray skyshine analyses

    Microsoft Academic Search

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

    1992-01-01

    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

  9. GMOS-IFU Spectroscopy of 167-317 (LV2) Proplyd in Orion

    E-print Network

    M. J. Vasconcelos; A. H. Cerqueira; H. Plana; A. C. Raga; C. Morisset

    2005-06-14

    We present high spatial resolution spectroscopic observations of the proplyd 167-317 (LV2) near the Trapezium cluster in the Orion nebula, obtained during the System Verification run of the Gemini Multi Object Spectrograph (GMOS) Integral Field Unit (IFU) at the Gemini South Observatory. We have detected 38 forbidden and permitted emission lines associated with the proplyd and its redshifted jet. We have been able to detect three velocity components in the profiles of some of these lines: a peak with a 28-33 km/s systemic velocity that is associated with the photoevaporated proplyd flow, a highly redshifted component associated with a previously reported jet (which has receding velocities of about 80-120 km/s with respect to the systemic velocity and is spatially distributed to the southeast of the proplyd) and a less obvious, approaching structure, which may possibly be associated with a faint counter-jet with systemic velocity of (-75 +/- 15) km/s. We find evidences that the redshifted jet has a variable velocity, with slow fluctuations as a function of the distance from the proplyd. We present several background subtracted, spatially distributed emission line maps and we use this information to obtain the dynamical characteristics over the observed field. Using a simple model and with the extinction corrected Halpha fluxes, we estimate the mass loss rate for both the proplyd photoevaporated flow and the redshifted microjet, obtaining (6.2 +/- 0.6) x 10^{-7} M_sun/year and (2.0 +/- 0.7) x 10^{-8} M_sun/year, respectively.

  10. Neurofeedback Improves Executive Functioning in Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Kouijzer, Mirjam E. J.; de Moor, Jan M. H.; Gerrits, Berrie J. L.; Congedo, Marco; van Schie, Hein T.

    2009-01-01

    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…

  11. Does psychosocial functioning improve independent of depressive symptoms? a comparison of nefazodone, psychotherapy, and their combination

    Microsoft Academic Search

    Robert M. A Hirschfeld; David L Dunner; Gabor Keitner; Daniel N Klein; Lorrin M Koran; Susan G Kornstein; John C Markowitz; Ivan Miller; Charles B Nemeroff; Philip T Ninan; A. John Rush; Alan F Schatzberg; Michael E Thase; Madhukar H Trivedi; Frances E Borian; Paul Crits-Christoph; Martin B Keller

    2002-01-01

    Background: Although it is known that antidepressant treatment improves psychosocial functioning, whether such changes occur independent of depressive symptoms is not known. This study compared efficacy of nefazodone, psychotherapy, and their combination in improving psychosocial functioning in chronically depressed outpatients.Methods: Patients with chronic forms of major depressive disorder were randomized to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of

  12. Leukocyte depletion results in improved lung function and reduced inflammatory response after cardiac surgery

    Microsoft Academic Search

    Y. J. Gu; A. J. deVries; P. W. Boonstra; W. van Oeveren

    1996-01-01

    Leukocyte depletion during cardiopulmonary bypass has been demonstrated in animal experiments to improve pulmonary function. Conflicting results have been reported, however, with clinical depletion by arterial line filter of leukocytes at the beginning of cardiopulmonary bypass. In this study, we examined whether leukocyte depletion from the residual heart-lung machine blood at the end of cardiopulmonary bypass would improve lung function

  13. High- and Moderate-Intensity Training Normalizes Ventricular Function and Mechanoenergetics in Mice With Diet-Induced Obesity

    PubMed Central

    Hafstad, Anne D.; Lund, Jim; Hadler-Olsen, Elin; Höper, Anje C.; Larsen, Terje S.; Aasum, Ellen

    2013-01-01

    Although exercise reduces several cardiovascular risk factors associated with obesity/diabetes, the metabolic effects of exercise on the heart are not well-known. This study was designed to investigate whether high-intensity interval training (HIT) is superior to moderate-intensity training (MIT) in counteracting obesity-induced impairment of left ventricular (LV) mechanoenergetics and function. C57BL/6J mice with diet-induced obesity (DIO mice) displaying a cardiac phenotype with altered substrate utilization and impaired mechanoenergetics were subjected to a sedentary lifestyle or 8–10 weeks of isocaloric HIT or MIT. Although both modes of exercise equally improved aerobic capacity and reduced obesity, only HIT improved glucose tolerance. Hearts from sedentary DIO mice developed concentric LV remodeling with diastolic and systolic dysfunction, which was prevented by both HIT and MIT. Both modes of exercise also normalized LV mechanical efficiency and mechanoenergetics. These changes were associated with altered myocardial substrate utilization and improved mitochondrial capacity and efficiency, as well as reduced oxidative stress, fibrosis, and intracellular matrix metalloproteinase 2 content. As both modes of exercise equally ameliorated the development of diabetic cardiomyopathy by preventing LV remodeling and mechanoenergetic impairment, this study advocates the therapeutic potential of physical activity in obesity-related cardiac disorders. PMID:23493573

  14. Improving protein function prediction methods with integrated literature data

    PubMed Central

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

    2008-01-01

    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. PMID:18412966

  15. HeAT: A Software Assistant for the Analysis of LV Remodeling after Myocardial Infarction

    E-print Network

    Lübeck, Universität zu

    of left ventricular (LV) remod- eling extracting regional and global parameters in the acute (base- modeling is characterized by wall thinning, chamber dilation and increased end-diastolic and end by hand is time-consuming and in most cases not reproducible. The computer-assisted extraction

  16. Dynamics of two feline retroviruses (FIV and FeLV) within one population of cats

    E-print Network

    Courchamp, Franck

    Dynamics of two feline retroviruses (FIV and FeLV) within one population of cats FRANCK COURCHAMP1 are feline retroviruses, namely Feline Immunodeficiency Virus (FIV) and Feline Leukaemia Virus (Fe population. The host is the domestic cat (Felis catus) and the two pathogens are two feline retroviruses

  17. Theoretical Population Biology 52, 60 70 (1997) Modelling the Feline Leukemia Virus (FeLV) in

    E-print Network

    Courchamp, Franck

    1997-01-01

    Theoretical Population Biology 52, 60 70 (1997) Modelling the Feline Leukemia Virus (Fe and impact of Feline Leukemia Virus (FeLV) in populations of domestic cats. The model was tested with data from a long-term study of several feline populations. The study of stability shows that Fe

  18. LV contour tracking in MRI sequences based on the generalized fuzzy GVF

    Microsoft Academic Search

    Wufan Chen; Shoujun Zhou; Bin Liang

    2004-01-01

    For the segmentation and robust tracking of the cardiac left ventricle (LV) in MRI sequences, an optimized algorithm is presented; it is based on the active contour framework. To use the active contours model (ACM) (Kass, M. et al., Int. J. Comput. Vision, vol.1, p.321-31, 1998) to estimate cardiac motion, a new concept of generalized fuzzy gradient vector flow (GFGVF)

  19. Simulated 3D Ultrasound LV Cardiac Images for Active Shape Model Training

    E-print Network

    Frangi, Alejandro

    Simulated 3D Ultrasound LV Cardiac Images for Active Shape Model Training Constantine Butakoff of 3D ultrasound cardiac segmentation using Active Shape Models (ASM) is presented. The proposed resolution MRI scans and the appearance model obtained from simulated 3D ultrasound images. Usually

  20. Gene cloning: exploring cotton functional genomics and genetic improvement

    Microsoft Academic Search

    Diqiu Liu; Xianlong Zhang

    2008-01-01

    Cotton is the most important natural fiber plant in the world. The genetic improvement of the quality of the cotton fiber\\u000a and agricultural productivity is imperative under the situation of increasing consumption and rapid development of textile\\u000a technology. Recently, the study of cotton molecular biology has progressed greatly. A lot of specifically or preferentially\\u000a expressed cotton fiber genes were cloned

  1. Differential improvement of cognitive functions in recovering alcoholic women

    Microsoft Academic Search

    Marjorie S. Fabian; Oscar A. Parsons

    1983-01-01

    In Study 1, 40 long-term sober alcoholics (mean age 42.15 yrs) performed at or near the level of 40 age-matched short-term sober alcoholics on several perceptuomotor speed tasks, at the level of 70 age-matched nonalcoholic controls on several complex problem-solving measures, and intermediate to the 2 groups on most measures, suggesting a differential improvement in cognitive abilities. In Study 2,

  2. Improved executive functioning following repetitive transcranial magnetic stimulation.

    PubMed

    Moser, D J; Jorge, R E; Manes, F; Paradiso, S; Benjamin, M L; Robinson, R G

    2002-04-23

    The cognitive effects of active and sham repetitive transcranial magnetic stimulation (rTMS) were examined in 19 middle-aged and elderly patients with refractory depression. Patients received either active (n = 9) or sham (n = 10) rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients in the active rTMS group improved significantly on a test of cognitive flexibility and conceptual tracking (Trail Making Test-B). PMID:11971103

  3. Improved siRNA/shRNA Functionality by Mismatched Duplex

    PubMed Central

    Wu, Haoquan; Ma, Hongming; Ye, Chunting; Ramirez, Danielle; Chen, Shuiping; Montoya, Jessica; Shankar, Premlata; Wang, Xiaozhong A.; Manjunath, N.

    2011-01-01

    siRNA (small interfering RNA) and shRNA (small hairpin RNA) are powerful and commonly used tools in biomedical research. Currently, siRNAs are generally designed as two 21 nt strands of RNA that include a 19 nt completely complementary part and a 2 nt overhang. However, since the si/shRNAs use the endogenous miRNA machinery for gene silencing and the miRNAs are generally 22 nt in length and contain multiple internal mismatches, we tested if the functionality can be increased by designing the si/shRNAs to mimic a miRNA structure. We systematically investigated the effect of single or multiple mismatches introduced in the passenger strand at different positions on siRNA functionality. Mismatches at certain positions could significantly increase the functionality of siRNAs and also, in some cases decreased the unwanted passenger strand functionality. The same strategy could also be used to design shRNAs. Finally, we showed that both si and miRNA structured oligos (siRNA with or without mismatches in the passenger strand) can repress targets in all individual Ago containing cells, suggesting that the Ago proteins do not differentiate between si/miRNA-based structure for silencing activity. PMID:22174840

  4. Improved response functions for gamma-ray skyshine analyses

    SciTech Connect

    Shultis, J.K.; Faw, R.E.; Deng, X. (Kansas State Univ., Manhattan, KS (United States). Dept. of Nuclear Engineering)

    1992-09-01

    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 reevaluation 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 compared to previous calculations and benchmark data.

  5. Improved response functions for gamma-ray skyshine analyses

    NASA Astrophysics Data System (ADS)

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

    1992-09-01

    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.

  6. CHEMPS2: Improved DMRG-SCF routine and correlation functions

    NASA Astrophysics Data System (ADS)

    Wouters, Sebastian; Poelmans, Ward; De Baerdemacker, Stijn; Ayers, Paul W.; Van Neck, Dimitri

    2015-06-01

    CHEMPS2, our spin-adapted implementation of the density matrix renormalization group (DMRG) for ab initio quantum chemistry (Wouters et al., 2014), has several new features. A speed-up of the augmented Hessian Newton-Raphson DMRG self-consistent field (DMRG-SCF) routine is achieved with the direct inversion of the iterative subspace (DIIS). For extended molecules, the active space orbitals can be localized by maximizing the Edmiston-Ruedenberg cost function. These localized orbitals can be ordered according to the topology of the molecule by approximately minimizing the bandwidth of the exchange matrix with the Fiedler vector. The electronic structure can be analyzed by means of the two-orbital mutual information, spin, spin-flip, density, and singlet diradical correlation functions.

  7. Zinc sulfate supplementation improves thyroid function in hypozincemic down children

    Microsoft Academic Search

    Ines Bucci; Giorgio Napolitano; Cesidio Giuliani; Serafino Lio; Anita Minnucci; Franco Di Giacomo; Giuseppe Calabrese; Giuseppe Sabatino; Giandomenico Palka; Fabrizio Monaco

    1999-01-01

    In subjects affected by trisomy 21 (Down syndrome), hypothyroidism is the most common endocrinological deficit. Plasma zinc\\u000a levels, which are commonly detected below the normal range in Down patients, are related to some endocrinological and immunological\\u000a functions; in fact, zinc deficiency has been shown to impair immune response and growth rate. Aims of this study were to evaluate\\u000a (1) the

  8. Does obesity surgery improve psychosocial functioning? A systematic review

    Microsoft Academic Search

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

    2003-01-01

    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

  9. Domain Extender for Collision Resistant Hash Functions: Improving Upon Merkle-Damg ard Iteration

    E-print Network

    Domain Extender for Collision Resistant Hash Functions: Improving Upon Merkle-Damg#23;ard Iteration function required by the new algorithm is smaller than the general Merkle-Damg#23;ard algorithm. Lastly, we function are known and these are called variants of the Merkle-Damg#23;ard algorithm [2, 4]. The most

  10. Folate Improves Endothelial Function in Coronary Artery Disease An Effect Mediated by Reduction of Intracellular Superoxide?

    Microsoft Academic Search

    Sagar N. Doshi; Ian F. W. McDowell; Stuart J. Moat; Derek Lang; Robert G. Newcombe; Mahmud B. Kredan; Malcolm J. Lewis; Jonathan Goodfellow

    2001-01-01

    Homocysteine is a risk factor for coronary artery disease (CAD). Folic acid lowers homocysteine and may improve endothelial function in CAD, although the mechanism is unclear. We investigated the effect of folic acid on endothelial function, homocysteine, and oxidative stress in patients with CAD. We also examined the acute effect of 5-methyltetrahydrofolate (5-MTHF), the principal circulating folate, on endothelial function

  11. Improving the algebraic immunity of resilient and nonlinear functions and constructing bent functions

    Microsoft Academic Search

    Claude Carlet

    2004-01-01

    The currently known constructions of Boolean functions with high nonlinearities, high algebraic degrees and high resiliency or- ders do not seem to permit achieving suciently high algebraic immunities. We introduce a construction of Boolean functions, which builds a new function from three known ones. Assuming that the three functions have some resiliency order, nonlinearity and algebraic degree, as well as

  12. Hibiscus sabdariffa extract lowers blood pressure and improves endothelial function.

    PubMed

    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

    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

  13. Functional lipids and lipoplexes for improved gene delivery

    PubMed Central

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

    2013-01-01

    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. PMID:21621581

  14. Improved Memory Function 12 Weeks after Bariatric Surgery

    PubMed Central

    Gunstad, John; Strain, Gladys; Devlin, Michael J.; Wing, Rena; Cohen, Ronald A.; Paul, Robert H.; Crosby, Ross D.; Mitchell, James E.

    2010-01-01

    Background There is growing evidence that obesity is associated with poor neurocognitive outcome. Bariatric surgery is an effective intervention for morbid obesity and improves many comorbid medical conditions that are associated with cognitive dysfunction. The effects of bariatric surgery on cognition are unknown. Methods Prospective study total of 150 individuals (109 bariatric surgery patients enrolled in the Longitudinal Assessment of Bariatric Surgery (LABS) project and 41 obese controls that did not undergo surgery) completed cognitive evaluation at baseline and 12 week follow-up. Demographic, medical, and psychosocial information was also collected to elucidate possible mechanisms of change. Results Many bariatric surgery patients exhibited impaired performance on cognitive testing at baseline (range from 4.6%–23.9%). However, surgery patients were no more likely to exhibit decline on two or more cognitive tests at 12-week follow-up than obese controls [12.84% vs. 23.26%; ?2 (1) = 2.51, p = .11]. Group comparisons using repeated measures MANOVA showed surgery patients had improved memory performance at 12 week follow-up [? = .86, F(4, 147) = 5.88, p<.001], whereas obese controls actually declined. Regression analyses showed surgery patients without hypertension had better short delay recall at 12 weeks than those that did [? = 0.31, p = .005], though other demographic and medical variables were largely unrelated to test performance. Conclusion The current results suggest that cognitive impairment is common in bariatric surgery patients, though these deficits may be at least partly reversible. Future studies are needed to clarify underlying mechanisms, particularly longitudinal studies employing neuroimaging and blood markers. PMID:21145295

  15. Improving Kepler Pipeline Sensitivity with Pixel Response Function Photometry.

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

    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.

  16. Early Intervention to Improve Hand Function in Hemiplegic Cerebral Palsy

    PubMed Central

    Basu, Anna Purna; Pearse, Janice; Kelly, Susan; Wisher, Vicki; Kisler, Jill

    2015-01-01

    Children with hemiplegic cerebral palsy often have marked hand involvement with excessive thumb adduction and flexion and limited active wrist extension from infancy. Post-lesional aberrant plasticity can lead to progressive abnormalities of the developing motor system. Disturbances of somatosensory and visual function and developmental disregard contribute to difficulties with hand use. Progressive soft tissue and bony changes may occur, leading to contractures, which further limit function in a vicious cycle. Early intervention might help to break this cycle, however, the precise nature and appropriateness of the intervention must be carefully considered. Traditional approaches to the hemiplegic upper limb include medications and botulinum toxin injections to manage abnormalities of tone, and surgical interventions. Therapist input, including provision of orthoses, remains a mainstay although many therapies have not been well evaluated. There has been a recent increase in interventions for the hemiplegic upper limb, mostly aimed outside the period of infancy. These include trials of constraint-induced movement therapy (CIMT) and bimanual therapy as well as the use of virtual reality and robot-assisted therapy. In future, non-invasive brain stimulation may be combined with therapy. Interventions under investigation in the infant age group include modified CIMT and action observation therapy. A further approach which may be suited to the infant with thumb-in-palm deformity, but which requires evaluation, is the use of elastic taping. Enhanced cutaneous feedback through mechanical stimulation to the skin provided by the tape during movement has been postulated to modulate ongoing muscle activity. If effective, this would represent a low-cost, safe, widely applicable early intervention. PMID:25610423

  17. Early intervention to improve hand function in hemiplegic cerebral palsy.

    PubMed

    Basu, Anna Purna; Pearse, Janice; Kelly, Susan; Wisher, Vicki; Kisler, Jill

    2014-01-01

    Children with hemiplegic cerebral palsy often have marked hand involvement with excessive thumb adduction and flexion and limited active wrist extension from infancy. Post-lesional aberrant plasticity can lead to progressive abnormalities of the developing motor system. Disturbances of somatosensory and visual function and developmental disregard contribute to difficulties with hand use. Progressive soft tissue and bony changes may occur, leading to contractures, which further limit function in a vicious cycle. Early intervention might help to break this cycle, however, the precise nature and appropriateness of the intervention must be carefully considered. Traditional approaches to the hemiplegic upper limb include medications and botulinum toxin injections to manage abnormalities of tone, and surgical interventions. Therapist input, including provision of orthoses, remains a mainstay although many therapies have not been well evaluated. There has been a recent increase in interventions for the hemiplegic upper limb, mostly aimed outside the period of infancy. These include trials of constraint-induced movement therapy (CIMT) and bimanual therapy as well as the use of virtual reality and robot-assisted therapy. In future, non-invasive brain stimulation may be combined with therapy. Interventions under investigation in the infant age group include modified CIMT and action observation therapy. A further approach which may be suited to the infant with thumb-in-palm deformity, but which requires evaluation, is the use of elastic taping. Enhanced cutaneous feedback through mechanical stimulation to the skin provided by the tape during movement has been postulated to modulate ongoing muscle activity. If effective, this would represent a low-cost, safe, widely applicable early intervention. PMID:25610423

  18. Improved cellular uptake of functionalized single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Antonelli, A.; Serafini, S.; Menotta, M.; Sfara, C.; Pierigé, F.; Giorgi, L.; Ambrosi, G.; Rossi, L.; Magnani, M.

    2010-10-01

    Single-walled carbon nanotubes (SWNTs) due to their unique structural and physicochemical properties, have been proposed as delivery systems for a variety of diagnostic and therapeutic agents. However, SWNTs have proven difficult to solubilize in aqueous solution, limiting their use in biological applications. In an attempt to improve SWNTs' solubility, biocompatibility, and to increase cell penetration we have thoroughly investigated the construction of carbon scaffolds coated with aliphatic carbon chains and phospholipids to obtain micelle-like structures. At first, oxidized SWNTs (2370 ± 30 nmol mg - 1 of SWNTs) were covalently coupled with an alcoholic chain (stearyl alcohol, C18H37OH; 816 nmol mg - 1 of SWNTs). Subsequently, SWNTs-COOC18H37 derivatives were coated with phosphatidylethanolamine (PE) or -serine (PS) phospholipids obtaining micelle-like structures. We found that cellular uptake of these constructs by phagocytic cells occurs via an endocytotic mechanism for constructs larger than 400 nm while occurs via diffusion through the cell membrane for constructs up to 400 nm. The material that enters the cell by phagocytosis is actively internalized by macrophages and localizes inside endocytotic vesicles. In contrast the material that enters the cells by diffusion is found in the cell cytosol. In conclusion, we have realized new biomimetic constructs based on alkylated SWNTs coated with phospholipids that are efficiently internalized by different cell types only if their size is lower than 400 nm. These constructs are not toxic to the cells and could now be explored as delivery systems for non-permeant cargoes.

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

    SciTech Connect

    C. Aubin, K. Orginos

    2011-12-01

    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.

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

    NASA Technical Reports Server (NTRS)

    Ko, William L.; Fleischer, Van Tran

    2012-01-01

    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.

  1. Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

    NASA Astrophysics Data System (ADS)

    Kasten, M. R.; Sunshine, M. D.; Secrist, E. S.; Horner, P. J.; Moritz, C. T.

    2013-08-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation could improve subsequent volitional control of paretic extremities following injury. Approach. We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4-C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main results. Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promoted recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioural tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance. The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

  2. Immunodominant mink cell focus-inducing murine leukemia virus (MuLV)-encoded CTL epitope, identified by its MHC class I-binding motif, explains MuLV-type specificity of MCF-directed cytotoxic T lymphocytes.

    PubMed

    Sijts, A J; Ossendorp, F; Mengedé, E A; van den Elsen, P J; Melief, C J

    1994-01-01

    H-2b mice are immunologic responders to the tumorigenic MCF1233 murine leukemia virus (MuLV), an AKV-related virus derived from endogenous C57BL MuLV. We have identified an immunodominant CTL epitope that is expressed on MCF1233 MuLV-induced lymphomas of H-2b mice. C57BL/10 (B10) mice were immunized with an MCF1233-induced B10 B cell lymphoma, and tumor-specific CTL cultures were generated in vitro. These were tested for recognition of synthetic class I-binding MuLV peptides, selected for class I allele-specific motifs. One of 28 candidate peptides sensitized target cells for CTL recognition. This peptide seems to be an immuno-dominant epitope, because it was recognized by all independent CTL clones, isolated from the tumor-specific bulk culture. The epitope (KSPWFTTL) is derived from the MCF1233 MuLV envelope (env)-p15E region and is shared by all endogenous AKV types of MuLV. It has an optimal length of eight amino acids and is presented by the Kb H-2 class I molecule. Interestingly, Friend, Moloney, and Rauscher (FMR) types of MuLV are not recognized by MCF MuLV-directed CTL. The FMR env-p15E proteins have a single amino acid difference at the first position of the MCF1233 MuLV epitope (RSPWFTTL instead of KSPWFTTL). The corresponding FMR-encoded peptide bound class I H-2 Kb equally well as the MCF peptide, but it was poorly recognized by MCF1233 MuLV-specific CTL. Moreover, in the Rauscher MuLV-induced cell line RMA the FMr peptide seems not to be processed for recognition by CTL, which was illustrated by experiments with CTL elicited against this peptide. Altered TCR interaction as well as lack of processing thus may explain the type specificity of MCF1233 MuLV-directed CTL. PMID:8254184

  3. Comprehensive Annular and Subvalvular Repair of Chronic Ischemic Mitral Regurgitation Improves Long-Term Results With the Least Ventricular Remodeling

    PubMed Central

    Szymanski, Catherine; Bel, Alain; Cohen, Iris; Touchot, Bernard; Handschumacher, Mark D.; Desnos, Michel; Carpentier, Alain; Menasché, Philippe; Hagège, Albert A.; Levine, Robert A.; Messas, Emmanuel

    2012-01-01

    Background Undersized ring annuloplasty for ischemic mitral regurgitation (MR) is associated with variable results and >30% MR recurrence. We tested whether subvalvular repair by severing second-order mitral chordae can improve annuloplasty by reducing papillary muscle tethering. Methods and Results Posterolateral myocardial infarction known to produce chronic remodeling and MR was created in 28 sheep. At 3 months, sheep were randomized to sham surgery versus isolated undersized annuloplasty versus isolated bileaflet chordal cutting versus the combined therapy (n=7 each). At baseline, chronic myocardial infarction (3 months), and euthanasia (6.6 months), we measured left ventricular (LV) volumes and ejection fraction, wall motion score index, MR regurgitation fraction and vena contracta, mitral annulus area, and posterior leaflet restriction angle (posterior leaflet to mitral annulus area) by 2-dimensional and 3-dimensional echocardiography. All groups were comparable at baseline and chronic myocardial infarction, with mild to moderate MR (MR vena contracta, 4.6±0.1 mm; MR regurgitation fraction, 24.2±2.9%) and mitral annulus dilatation (P<0.01). At euthanasia, MR progressed to moderate to severe in controls but decreased to trace with ring plus chordal cutting versus trace to mild with chordal cutting alone versus mild to moderate with ring alone (MR vena contracta, 5.9±1.1 mm in controls, 0.5±0.08 with both, 1.0±0.9 with chordal cutting alone, 2.0±0.7 with ring alone; P<0.01). In addition, LV end-systolic volume increased by 108% in controls versus 28% with ring plus chordal cutting, less than with each intervention alone (P<0.01). In multivariate analysis, LV end-systolic volume and mitral annulus area most strongly predicted MR (r2=0.82, P<0.01). Conclusions Comprehensive annular and subvalvular repair improves long-term reduction of both chronic ischemic MR and LV remodeling without decreasing global or segmental LV function at follow-up. PMID:23139296

  4. Physical resistance training for women with PCOS may improve sexual function.

    PubMed

    2015-06-01

    Women with polycystic ovary syndrome (PCOS) who participate in physical resistance training may experience considerable improvements in sexual function as well as decreases in anxiety and depression, suggests a study in Brazil. PMID:26036378

  5. Improving Fluorescence Lifetime Imaging Microscopy Deconvolution Using Constrained Laguerre Basis Functions 

    E-print Network

    Khatkhatay, Mohammed M

    2014-04-25

    global optimization. Therefore, the IRFs do not necessarily mimic exponential time decays, or monotonically decreasing functions. On the other hand, applying a constraint to the LBFs using the Active Set Nonnegative Least Squares (NNLS) method improves...

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

    E-print Network

    Dunfield, Derek

    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 ...

  7. Identification of LTR-specific small non-coding RNA in FeLV infected cells

    PubMed Central

    Forman, Lora W.; Pal-Ghosh, Ruma; Spanjaard, Remco A.; Faller, Douglas V.; Ghosh, Sajal K.

    2013-01-01

    The U3-LTR region of leukemia viruses transactivates cancer-related signaling pathways through the production of a non-coding RNA transcript although the role of this transcript in virus infection remains unknown. In this study we demonstrate for the first time that an LTR-specific small non-coding RNA is produced from a FeLV-infected feline cell line. RNA cloning identified this as a 104 base transcript that originates from the U3-LTR region. We also demonstrate that in in vitro assays this LTR RNA transcript activates NF?B signaling. Taken together, our findings suggest a possible role for this LTR transcript in FeLV pathogenesis. PMID:19336234

  8. Effect of endovascular stenting of aortic coarctation on biventricular function in adults

    PubMed Central

    Lam, Yat?Yin; Kaya, Mehmet G; Li, Wei; Mahadevan, Vaikom S; Khan, Arif A; Henein, Michael Y; Mullen, Michael

    2007-01-01

    Objective To investigate the effect of endovascular stenting of aortic coarctation on biventricular function in adults during intermediate?term follow?up. Methods 21 patients (age 34 (10)?years) were studied prospectively before and 14 (2)?months after coarctation stenting from year 2002 to 2005. Biventricular function and blood pressure measurements were made. The post?stenting results were compared with pre?stenting values (group 1), with 22 age? and sex?matched post?surgical repair patients (group 2) and 30 normal controls (group 3). Results The peak systolic gradient across the coarctation site fell (55 (15)?mm Hg to 18 (8)?mm Hg, p<0.001). Systolic, mean blood pressure and left ventricular (LV) mass dropped after stenting (p<0.05 for all). LV long?axis function improved at intermediate?term follow?up (tissue Doppler imaging lateral and septal systolic and diastolic velocities and E/Em ratios: LSm, 6.5 (1.4)?cm/s to 7.9 (1.7)?cm/s; SSm, 5.8 (1.2)?cm/s to 7.3 (1.6)?cm/s; LEm, 8.1 (1.3) to 9.4 (2.3)?cm/s; SEm, 6.7 (1.5)?cm/s to 7.8 (1.9)?cm/s; LE/Em, 11.2 (2.7) to 9.8 (2.8); SE/Em, 14.8 (5.3) to 11.8 (3.9); p<0.05 for all). No significant difference in LV ejection fraction, conventional LV diastolic measurements (E, A, E/A ratio, IVRT and DT) was found after stenting. No significant deterioration of right ventricular function was seen in stented patients. Both post?stenting and post?surgical repair patients had poorer LV long?axis function than controls (p<0.01 for all). Conclusions Endovascular stenting of aortic coarctation resulted in medium?term LV mass regression and long?axis function improvement that may provide insight into long?term outcome of the stented patients. The results support aortic stenting in patients with anatomically suitable defects, given the additional benefit of avoiding cardiopulmonary bypass. The clinical significance of subclinical myocardial dysfunction in patients with stented or repaired coarctation warrants further studies. PMID:17575331

  9. Improving the Consumer Protection Function in Postsecondary Education. Executive Summary, Planning/Evaluation Study.

    ERIC Educational Resources Information Center

    Office of Education (DHEW), Washington, DC. Office of Planning, Budgeting, and Evaluation.

    This study on the consumer protection function in postsecondary education was designed to provide the following: (1) improved consumer protection strategies that would stress approaches to presenting or controlling conditions, policies, and practices categorized as consumer abuses; and (2) a nonregulatory strategy detailing ways to improve the…

  10. School Improvement: A Functional View of Enabling Equity of Opportunity. A Center Policy & Practice Brief

    ERIC Educational Resources Information Center

    Center for Mental Health in Schools at UCLA, 2011

    2011-01-01

    The ongoing dilemma for those expected to improve schools is how to meet our society's basic aims for public education in ways that level the playing field. The dilemma is exacerbated by the need to do more with less. This brief approaches these matters in the context of three direct functions that are essential to school improvement: (1)…

  11. Left Ventricular Diastolic Function in Hypertension: Methodological Considerations and Clinical Implications

    PubMed Central

    Palmiero, Pasquale; Zito, Annapaola; Maiello, Maria; Cameli, Matteo; Modesti, Pietro Amedeo; Muiesan, Maria Lorenza; Novo, Salvatore; Saba, Pier Sergio; Scicchitano, Pietro; Pedrinelli, Roberto; Ciccone, Marco Matteo

    2015-01-01

    The assessment of left ventricular (LV) diastolic function should be an integral part of a routine examination of hypertensive patient; indeed when LV diastolic function is impaired, it is possible to have heart failure even with preserved LV ejection fraction. Left ventricular diastolic dysfunction (LVDD) occurs frequently and is associated to heart disease. Doppler echocardiography is the best tool for early LVDD diagnosis. Hypertension affects LV relaxation and when left ventricular hypertrophy (LVH) occurs, it decreases compliance too, so it is important to calculate Doppler echocardiography parameters, for diastolic function evaluation, in all hypertensive patients. The purpose of our review was to discuss about the strong relationship between LVDD and hypertension, and their relationship with LV systolic function. Furthermore, we aimed to assess the relationship between the arterial stiffness and LV structure and function in hypertensive patients. PMID:25584097

  12. Comparative effects of propranolol and verapamil alone and in combination on left ventricular function and volumes in patients with chronic exertional angina: a double-blind, placebo-controlled, randomized, crossover study with radionuclide ventriculography

    SciTech Connect

    Johnston, D.L.; Gebhardt, V.A.; Donald, A.; Kostuk, W.J.

    1983-12-01

    With the use of equilibrium radionuclide ventriculography the effects on left ventricular (LV) function of 160 mg oral propranolol daily and 360 mg verapamil daily alone and in combination were compared in 18 patients with chronic exertional angina. A randomized, double-blind, placebo-controlled, crossover protocol was used. The reduction in exercise rate-pressure product induced by the combination (118 +/- 28 mm Hg/min) was significantly greater than that by propranolol (135 +/- 27 mm Hg/min) or verapamil alone (163 +/- 28 mm Hg/min). In patients at rest, neither single nor combined therapy altered global or regional left ventricular ejection fractions (EFs). Verapamil, but not propranolol, increased cardiac volumes of resting subjects; used in combination, no further increase in LV volume occurred. With placebo, exercise global EF did not decrease from the level at rest and therefore no drug effect could be demonstrated for this parameter of LV function. By an evaluation of normalized regional EF measurements the combination was shown to reduce exercise-induced hypokinesis (placebo 52 +/- 20%, combination 61 +/- 23%. No significant improvement was noted with propranolol or verapamil alone; only the combination prevented a significant increase in end-systolic and end-diastolic volumes during exercise. Thus, propranolol and verapamil, used alone in moderate doses, exert no beneficial effect on exercise LV function as measured by EF and volume changes, and resting function deteriorates slightly with verapamil.

  13. Domain Extender for Collision Resistant Hash Functions: Improving Upon Merkle-Damgard Iteration

    E-print Network

    Domain Extender for Collision Resistant Hash Functions: Improving Upon Merkle-Damg°ard Iteration function required by the new algorithm is smaller than the general Merkle-Damg°ard algorithm. Lastly, we are known and these are called variants of the Merkle-Damg°ard algorithm [2, 4]. The most general

  14. A Personalization Framework to Improve Quality of Experience for DVD-like Functions

    E-print Network

    Zhou, Yuanyuan

    A Personalization Framework to Improve Quality of Experience for DVD-like Functions in P2P Vo, Germany Abstract The requirement for supporting DVD-like functions raises new challenges to the design of P2P VoD systems. The uncertainty of frequent user DVD-like interactivity makes it difficult

  15. APEX: A Personalization Framework to Improve Quality of Experience for DVD-like Functions

    E-print Network

    Zhou, Yuanyuan

    APEX: A Personalization Framework to Improve Quality of Experience for DVD-like Functions in P2P Vo for supporting DVD-like functions raises new challenges to the design of P2P VoD systems. The uncertainty of frequent user DVD-like interactivity makes it difficult to ensure user perceived Quality of Experience (Qo

  16. NEW FUNCTIONAL FOOD INGREDIENTS FOR IMPROVING THE HEALTH BENEFITS OF ASIAN FOODS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to utilize new functional food ingredients containing soluble betaglucan fiber that could be used to improve the heatlh qualities of Asian foods. These functional food fibers were studied as replacements for coconut milk, butter, or saturated fat shortenings that are w...

  17. NEW FUNCTIONAL FOOD INGREDIENTS FOR IMPROVING THE HEALTH BENEFITS OF ASIAN FOODS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to utilize new functional food ingredients containing soluble beta-glucan fiber that could be used to improve the health qualities of Asian foods. These functional food fibers were studied as replacements for coconut milk, butter, or saturated fat shortenings that are ...

  18. TELEMEDICINE TO ASSIST PATIENT UNDERSTANDING OF ATMOSPHERIC INFLUENCE ON LUNG FUNCTION AND IMPROVE

    E-print Network

    McSharry, Patrick E.

    TELEMEDICINE TO ASSIST PATIENT UNDERSTANDING OF ATMOSPHERIC INFLUENCE ON LUNG FUNCTION AND IMPROVE-time generic telemedicine system is presented. It is discussed in the context of self- management for people as influencing lung function, we have used data collected during a feasibility study of the telemedicine system

  19. Improvement in gonadal function through modification of negative feed-back

    E-print Network

    Paris-Sud XI, Université de

    Improvement in gonadal function through modification of negative feed-back R. B. LAND ARC, Animal to negative feed- back. Changes in ovarian function following unilateral ovariectomy, treatment with oestro indicate that the ovulation rate can be changed by modifying « negative feed- back » without a change

  20. Improving Functional Skills Using Behavioral Procedures in a Child with Anoxia.

    ERIC Educational Resources Information Center

    Silver, Bernard; And Others

    A behavioral treatment program was used to improve the functional skills of a 12-year-old anoxic child. Neuropsychological test results indicated marked amnesia and global cognitive deficits. Functionally, self-care tasks could be performed, but only with verbal and physical prompting. Introduction of a monetary reward system significantly reduced…

  1. Echocardiographic evaluation of mitral geometry in functional mitral regurgitation

    Microsoft Academic Search

    Anita Sadeghpour; Firoozeh Abtahi; Majid Kiavar; Maryam Esmaeilzadeh; Niloofar Samiei; Seyedeh Zahra Ojaghi; Hooman Bakhshandeh; Majid Maleki; Feridoun Noohi; Ahmad Mohebbi

    2008-01-01

    OBJECTIVES: We sought to evaluate the geometric changes of the mitral leaflets, local and global LV remodeling in patients with left ventricular dysfunction and varying degrees of Functional mitral regurgitation (FMR). BACKGROUND: Functional mitral regurgitation (FMR) occurs as a consequence of systolic left ventricular (LV) dysfunction caused by ischemic or nonischemic cardiomyopathy. Mitral valve repair in ischemic MR is one

  2. Functionalized self-assembling peptide improves INS-1 ?-cell function and proliferation via the integrin/FAK/ERK/cyclin pathway

    PubMed Central

    Liu, Jingping; Liu, Shuyun; Chen, Younan; Zhao, Xiaojun; Lu, Yanrong; Cheng, Jingqiu

    2015-01-01

    Islet transplantation is considered to be a curative treatment for type 1 diabetes mellitus. However, disruption of the extracellular matrix (ECM) leads to ?-cell destruction and graft dysfunction. In this study, we developed a functionalized self-assembling peptide, KLD-F, with ECM mimic motifs derived from fibronectin and collagen IV, and evaluated its effect on ?-cell function and proliferation. Atomic force microscopy and rheological results showed that KLD-F could self-assemble into a nanofibrous scaffold and change into a hydrogel in physiological saline condition. In a three-dimensional cell culture model, KLD-F improved ECM remodeling and cell-cell adhesion of INS-1 ?-cells by upregulation of E-cadherin, fibronectin, and collagen IV. KLD-F also enhanced glucose-stimulated insulin secretion and expression of ?-cell function genes, including Glut2, Ins1, MafA, and Pdx-1 in INS-1 cells. Moreover, KLD-F promoted proliferation of INS-1 ?-cells and upregulated Ki67 expression by mediating cell cycle progression. In addition, KLD-F improved ?-cell function and proliferation via an integrin/focal adhesion kinase/extracellular signal-regulated kinase/cyclin D pathway. This study highlights the fact that the ?-cell-ECM interaction reestablished with this functionalized self-assembling peptide is a promising method to improve the therapeutic efficacy of islet transplantation. PMID:25999715

  3. The FEATURE framework for protein function annotation: modeling new functions, improving performance, and extending to novel applications

    PubMed Central

    Halperin, Inbal; Glazer, Dariya S; Wu, Shirley; Altman, Russ B

    2008-01-01

    Structural genomics efforts contribute new protein structures that often lack significant sequence and fold similarity to known proteins. Traditional sequence and structure-based methods may not be sufficient to annotate the molecular functions of these structures. Techniques that combine structural and functional modeling can be valuable for functional annotation. FEATURE is a flexible framework for modeling and recognition of functional sites in macromolecular structures. Here, we present an overview of the main components of the FEATURE framework, and describe the recent developments in its use. These include automating training sets selection to increase functional coverage, coupling FEATURE to structural diversity generating methods such as molecular dynamics simulations and loop modeling methods to improve performance, and using FEATURE in large-scale modeling and structure determination efforts. PMID:18831785

  4. Novel Online Dimensionality Reduction Method with Improved Topology Representing and Radial Basis Function Networks

    PubMed Central

    Ni, Shengqiao; Lv, Jiancheng; Cheng, Zhehao; Li, Mao

    2015-01-01

    This paper presents improvements to the conventional Topology Representing Network to build more appropriate topology relationships. Based on this improved Topology Representing Network, we propose a novel method for online dimensionality reduction that integrates the improved Topology Representing Network and Radial Basis Function Network. This method can find meaningful low-dimensional feature structures embedded in high-dimensional original data space, process nonlinear embedded manifolds, and map the new data online. Furthermore, this method can deal with large datasets for the benefit of improved Topology Representing Network. Experiments illustrate the effectiveness of the proposed method. PMID:26161960

  5. Improved Description of Electron-Plasmon Coupling In Green's Function Calculations

    NASA Astrophysics Data System (ADS)

    Zhou, Jianqiang; Reining, Lucia

    2015-03-01

    Green's function (GF) methods have been very successful for describing one- or two-particle excitations in solids. The GW approximation is a well established approach for describing quasi-particle peaks in the spectral function. Beyond GW, the cumulant expansion, which is based on a hole-boson coupling model, gives a better description of plasmon satellites. However, this traditional time-ordered cumulant (TOC) is only valid far from the Fermi level. Recent development of a generalized cumulant (GC) improves the spectral function close to the Fermi level, but a framework for systematically improving is still missing. Here we show how GW, TOC and GC can be derived as a successive series of approximations in a unified way, and how one can go beyond today's state-of-the-art methods. Results for spectral functions and total energies of an exactly solvable model show that systematic improvement is obtained. Work supported by FP7/ERC Grant Agreement No. 320971.

  6. Naloxone improves functional recovery of myocardial stunning in conscious dogs through its action on the central nervous system.

    PubMed

    Weber, T P; Stypmann, J; Meissner, A; Hartlage, M G; Van Aken, H; Rolf, N

    2001-04-01

    This study tests the hypothesis that naloxone, but not its quarternary salt, naloxone methiodide (which does not enter the central nervous system), improves recovery from myocardial stunning in conscious dogs. Twenty dogs were chronically instrumented for measurement of heart rate, left atrial, aortic and left ventricular pressure (LVP), LV dP x dtmax(-1) and myocardial wall thickening fraction (WTF). Regional myocardial blood flow was determined with coloured microspheres. Occluder around the left anterior descending artery (LAD) allowed induction of reversible LAD ischaemia. Each of the 20 dogs underwent two LAD ischaemic challenges. Experiments (performed on separate days, in crossover fashion) were: (i) 10 min of LAD occlusion after application of naloxone 63 microg kg(-1) or naloxone methiodide 63 microg kg(-1) and (ii) occlusion without naloxone or naloxone methiodide. WTF was measured at baseline and until complete recovery occurred. LAD ischaemia significantly reduced LAD WTF with (mean (SD) 54 (15)% lower than baseline) and without naloxone (55 (16)% lower than baseline), without significant haemodynamic differences. Between I to 30 min of reperfusion, WTF was significantly higher with naloxone (P < 0.05). There was no difference in WTF with or without naloxone methiodide. We conclude that naloxone improved recovery from myocardial stunning in conscious dogs, and that this was centrally mediated. PMID:11573630

  7. Differences in somatosensory and motor improvement during temporary functional deafferentation in stroke patients and healthy subjects.

    PubMed

    Sens, Elisabeth; Knorr, Christin; Preul, Christoph; Meissner, Winfried; Witte, Otto W; Miltner, Wolfgang H R; Weiss, Thomas

    2013-09-01

    Temporary functional deafferentation is of interest to become an additional tool in neurorehabilitative treatments. Temporary functional deafferentation is known to improve sensory and motor outcomes in chronic stroke patients and healthy subjects. The present study soughts to indicate differences in the efficiency of pharmacologically induced temporary functional deafferentation between chronic stroke patients and matched healthy subjects. 46 chronic stroke patients and 20 age- and gender-matched healthy subjects were deafferented on one forearm by an anesthetic cream. Somatosensory performance was assessed using von-Frey Hair testing and Grating orientation task; motor performance was assessed by means of a shape-sorter-drum task. Grating orientation task and shape-sorter-drum task were significantly improved during temporary functional deafferentation in stroke patients but not in healthy subjects. Von-Frey Hair testing revealed no improvement of absolute tactile thresholds during temporary functional deafferentation in both groups. Furthermore, the stroke patients showed deficits at baseline measurement in all assessments except the von-Frey Hair test. Temporary functional deafferentation of a forearm by an anesthetic cream results in improvements of motor performance and somatosensory discrimination in stroke patients but not in healthy subjects. Therefore, it is reasonable to test in a next step whether temporary functional deafferentation might become an additional tool in motor rehabilitation of post stroke patients. PMID:23735321

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

    PubMed Central

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

    2014-01-01

    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

  9. A Novel and Efficient Gene Transfer Strategy Reduces Glial Reactivity and Improves Neuronal Survival and Axonal Growth In Vitro

    PubMed Central

    Desclaux, Mathieu; Teigell, Marisa; Amar, Lahouari; Vogel, Roland; Gimenez y Ribotta, Minerva; Privat, Alain; Mallet, Jacques

    2009-01-01

    Background The lack of axonal regeneration in the central nervous system is attributed among other factors to the formation of a glial scar. This cellular structure is mainly composed of reactive astrocytes that overexpress two intermediate filament proteins, the glial fibrillary acidic protein (GFAP) and vimentin. Indeed, in vitro, astrocytes lacking GFAP or both GFAP and vimentin were shown to be the substrate for increased neuronal plasticity. Moreover, double knockout mice lacking both GFAP and vimentin presented lower levels of glial reactivity in vivo, significant axonal regrowth and improved functional recovery in comparison with wild-type mice after spinal cord hemisection. From these results, our objective was to develop a novel therapeutic strategy for axonal regeneration, based on the targeted suppression of astroglial reactivity and scarring by lentiviral-mediated RNA-interference (RNAi). Methods and Findings In this study, we constructed two lentiviral vectors, Lv-shGFAP and Lv-shVIM, which allow efficient and stable RNAi-mediated silencing of endogenous GFAP or vimentin in vitro. In cultured cortical and spinal reactive astrocytes, the use of these vectors resulted in a specific, stable and highly significant decrease in the corresponding protein levels. In a second model — scratched primary cultured astrocytes — Lv-shGFAP, alone or associated with Lv-shVIM, decreased astrocytic reactivity and glial scarring. Finally, in a heterotopic coculture model, cortical neurons displayed higher survival rates and increased neurite growth when cultured with astrocytes in which GFAP and vimentin had been invalidated by lentiviral-mediated RNAi. Conclusions Lentiviral-mediated knockdown of GFAP and vimentin in astrocytes show that GFAP is a key target for modulating reactive gliosis and monitoring neuron/glia interactions. Thus, manipulation of reactive astrocytes with the Lv-shGFAP vector constitutes a promising therapeutic strategy for increasing glial permissiveness and permitting axonal regeneration after central nervous system lesions. PMID:19597552

  10. Biventricular Pacing in End-Stage Heart Failure Improves Functional Capacity and Left Ventricular Function

    Microsoft Academic Search

    Patricia F. Bakker; Huub W. Meijburg; Jaap W. de Vries; Morton M. Mower; Andra C. Thomas; Michael L. Hull; Etienne O. Robles de Medina; Johan J. Bredée

    2000-01-01

    Background Asynchronous patterns of contraction and relaxation may contribute to hemodynamic and functional impairment in heart failure. In 1993, we introduced biventricular pacing as a novel method to treat heart failure by synchronous stimulation of the right and left ventricles after an appropriate atrioventricular delay. The objectives of this study were to assess the early and long-term effects of this

  11. Direct evidence of lymphatic function improvement after advanced pneumatic compression device treatment of lymphedema.

    PubMed

    Adams, Kristen E; Rasmussen, John C; Darne, Chinmay; Tan, I-Chih; Aldrich, Melissa B; Marshall, Milton V; Fife, Caroline E; Maus, Erik A; Smith, Latisha A; Guilloid, Renie; Hoy, Sunday; Sevick-Muraca, Eva M

    2010-01-01

    Lymphedema affects up to 50% of all breast cancer survivors. Management with pneumatic compression devices (PCDs) is controversial, owing to the lack of methods to directly assess benefit. This pilot study employed an investigational, near-infrared (NIR) fluorescence imaging technique to evaluate lymphatic response to PCD therapy in normal control and breast cancer-related lymphedema (BCRL) subjects. Lymphatic propulsion rate, apparent lymph velocity, and lymphatic vessel recruitment were measured before, during, and after advanced PCD therapy. Lymphatic function improved in all control subjects and all asymptomatic arms of BCRL subjects. Lymphatic function improved in 4 of 6 BCRL affected arms, improvement defined as proximal movement of dye after therapy. NIR fluorescence lymphatic imaging may be useful to directly evaluate lymphatic response to therapy. These results suggest that PCDs can stimulate lymphatic function and may be an effective method to manage BCRL, warranting future clinical trials. PMID:21258451

  12. Impact of psychosocial factors on functional improvement in Latino older adults after Tai Chi exercise.

    PubMed

    Siu, Ka-Chun; Rajaram, Shireen S; Padilla, Carolina

    2015-01-01

    Increasing evidence underscores the health benefits of Tai Chi (TC), although there is limited evidence of benefits among racial and ethnic minorities. This study investigated the impact of psychosocial status on balance among 23 Latino seniors after a twice-a-week, 12-week TC exercise program. Functional status was measured at baseline, immediately after, and three months following the TC exercise program, using the Timed Up and Go Test and Tinetti Falls Efficacy Scale. Psychosocial status was measured at baseline by the Center for Epidemiologic Studies Depression Scale and Norbeck Social Support Questionnaire. Both measures of functional status improved and were sustained after three months of TC. Greater improvement was significantly related to a higher level of baseline social support. More depressed seniors reported less fear of falling after TC. Depression and social support are important moderators of functional improvement after TC among Latino seniors. PMID:24451550

  13. COMPASS server for homology detection: improved statistical accuracy, speed and functionality

    Microsoft Academic Search

    Ruslan Sadreyev; Ming Tang; Bong-hyun Kim; Nick V. Grishin

    2009-01-01

    COMPASS is a profile-based method for the detection of remote sequence similarity and the prediction of protein structure. Here we describe a recently improved public web server of COMPASS, http:\\/\\/prodata.swmed.edu\\/compass. The server features three major developments: (i) improved sta- tistical accuracy; (ii) increased speed from parallel implementation; and (iii) new functional features facilitating structure prediction. These features include visualization tools

  14. The effectiveness of proprioceptive training for improving motor function: a systematic review

    PubMed Central

    Aman, Joshua E.; Elangovan, Naveen; Yeh, I-Ling; Konczak, Jürgen

    2015-01-01

    Objective: Numerous reports advocate that training of the proprioceptive sense is a viable behavioral therapy for improving impaired motor function. However, there is little agreement of what constitutes proprioceptive training and how effective it is. We therefore conducted a comprehensive, systematic review of the available literature in order to provide clarity to the notion of training the proprioceptive system. Methods: Four major scientific databases were searched. The following criteria were subsequently applied: (1) A quantified pre- and post-treatment measure of proprioceptive function. (2) An intervention or training program believed to influence or enhance proprioceptive function. (3) Contained at least one form of treatment or outcome measure that is indicative of somatosensory function. From a total of 1284 articles, 51 studies fulfilled all criteria and were selected for further review. Results: Overall, proprioceptive training resulted in an average improvement of 52% across all outcome measures. Applying muscle vibration above 30 Hz for longer durations (i.e., min vs. s) induced outcome improvements of up to 60%. Joint position and target reaching training consistently enhanced joint position sense (up to 109%) showing an average improvement of 48%. Cortical stroke was the most studied disease entity but no clear evidence indicated that proprioceptive training is differentially beneficial across the reported diseases. Conclusions: There is converging evidence that proprioceptive training can yield meaningful improvements in somatosensory and sensorimotor function. However, there is a clear need for further work. Those forms of training utilizing both passive and active movements with and without visual feedback tended to be most beneficial. There is also initial evidence suggesting that proprioceptive training induces cortical reorganization, reinforcing the notion that proprioceptive training is a viable method for improving sensorimotor function. PMID:25674059

  15. Quantifying coronary sinus flow and global LV perfusion at 3T

    PubMed Central

    2009-01-01

    Background Despite the large availability of 3T MR scanners and the potential of high field imaging, this technical platform has yet to prove its usefulness in the cardiac MR setting, where 1.5T remains the established standard. Global perfusion of the left ventricle, as well as the coronary flow reserve (CFR), can provide relevant diagnostic information, and MR measurements of these parameters may benefit from increased field strength. Quantitative flow measurements in the coronary sinus (CS) provide one method to investigate these parameters. However, the ability of newly developed faster MR sequences to measure coronary flow during a breath-hold at 3T has not been evaluated. Methods The aim of this work was to measure CS flow using segmented phase contrast MR (PC MR) on a clinical 3T MR scanner. Parallel imaging was employed to reduce the total acquisition time. Global LV perfusion was calculated by dividing CS flow with left ventricular (LV) mass. The repeatability of the method was investigated by measuring the flow three times in each of the twelve volunteers. Phantom experiments were performed to investigate potential error sources. Results The average CS flow was determined to 88 ± 33 ml/min and the deduced LV perfusion was 0.60 ± 0.22 ml/min·g, in agreement with published values. The repeatability (1-error) of the three repeated measurements in each subject was on average 84%. Conclusion This work demonstrates that the combination of high field strength (3T), parallel imaging and segmented gradient echo sequences allow for quantification of the CS flow and global perfusion within a breath-hold. PMID:19519892

  16. Clustering PPI data based on improved functional-flow model through quantum-behaved PSO.

    PubMed

    Lei, Xiujuan; Huang, Xu; Shi, Lei; Zhang, Aidong

    2012-01-01

    Clustering Protein-Protein Interaction (PPI) data is a difficult problem due to its small world and scale-free characteristics. Existing clustering methods could not perform well. This paper proposes an improved functional-flow based approach through Quantum-behaved Particle Swarm Optimisation (QPSO) algorithm, which can find the optimum threshold automatically when calculating the lowest similarity between modules. We also take bridging nodes into account to improve the clustering result. The experiments on Munich Information Center for Protein Sequences (MIPS) PPI data sets show that the algorithm has better performance than functional flow method in terms of accuracy and number of matched clusters. PMID:22479818

  17. How does the motor relearning program improve neurological function of brain ischemia monkeys??

    PubMed Central

    Yin, Yong; Gu, Zhen; Pan, Lei; Gan, Lu; Qin, Dongdong; Yang, Bo; Guo, Jin; Hu, Xintian; Wang, Tinghua; Feng, Zhongtang

    2013-01-01

    The motor relearning program can significantly improve various functional disturbance induced by ischemic cerebrovascular diseases. However, its mechanism of action remains poorly understood. In injured brain tissues, glial fibrillary acidic protein and neurofilament protein changes can reflect the condition of injured neurons and astrocytes, while vascular endothelial growth factor and basic fibroblast growth factor changes can indicate angiogenesis. In the present study, we induced ischemic brain injury in the rhesus macaque by electrocoagulation of the M1 segment of the right middle cerebral artery. The motor relearning program was conducted for 60 days from the third day after model establishment. Immunohistochemistry and single-photon emission CT showed that the numbers of glial fibrillary acidic protein-, neurofilament protein-, vascular endothelial growth factor- and basic fibroblast growth factor-positive cells were significantly increased in the infarcted side compared with the contralateral hemisphere following the motor relearning program. Moreover, cerebral blood flow in the infarcted side was significantly improved. The clinical rating scale for stroke was used to assess neurological function changes in the rhesus macaque following the motor relearning program. Results showed that motor function was improved, and problems with consciousness, self-care ability and balance function were significantly ameliorated. These findings indicate that the motor relearning program significantly promoted neuronal regeneration, repair and angiogenesis in the surroundings of the infarcted hemisphere, and improve neurological function in the rhesus macaque following brain ischemia. PMID:25206440

  18. Improved constraint satisfaction in a simple generalized gradient approximation exchange functional

    NASA Astrophysics Data System (ADS)

    Vela, Alberto; Pacheco-Kato, Juan C.; Gázquez, José L.; del Campo, Jorge M.; Trickey, S. B.

    2012-04-01

    Though there is fevered effort on orbital-dependent approximate exchange-correlation functionals, generalized gradient approximations, especially the Perdew-Burke-Ernzerhof (PBE) form, remain the overwhelming choice in calculations. A simple generalized gradient approximation (GGA) exchange functional [A. Vela, V. Medel, and S. B. Trickey, J. Chem. Phys. 130, 244103 (2009), 10.1063/1.3152713] was developed that improves substantially over PBE in energetics (on a typical test set) while being almost as simple in form. The improvement came from constraining the exchange enhancement factor to be below the Lieb-Oxford bound for all but one value of the exchange dimensionless gradient, s, and to go to the uniform electron gas limit at both s = 0 and s ? ?. Here we discuss the issue of asymptotic constraints for GGAs and show that imposition of the large s constraint, {lim }nolimits_{s to infty } s^{1/2} F_{xc} (n,s) < infty, where Fxc(n, s) is the enhancement factor and n is the electron density, upon the Vela-Medel-Trickey (VMT) exchange functional yields modest further improvement. The resulting exchange functional, denoted VT{8,4}, is only slightly more complicated than VMT and easy to program. Additional improvement is obtained by combining VT{8,4} or VMT exchange with the Lee-Yang-Parr correlation functional. Extensive computational results on several datasets are provided as verification of the overall performance gains of both versions.

  19. Improved constraint satisfaction in a simple generalized gradient approximation exchange functional.

    PubMed

    Vela, Alberto; Pacheco-Kato, Juan C; Gázquez, José L; del Campo, Jorge M; Trickey, S B

    2012-04-14

    Though there is fevered effort on orbital-dependent approximate exchange-correlation functionals, generalized gradient approximations, especially the Perdew-Burke-Ernzerhof (PBE) form, remain the overwhelming choice in calculations. A simple generalized gradient approximation (GGA) exchange functional [A. Vela, V. Medel, and S. B. Trickey, J. Chem. Phys. 130, 244103 (2009)] was developed that improves substantially over PBE in energetics (on a typical test set) while being almost as simple in form. The improvement came from constraining the exchange enhancement factor to be below the Lieb-Oxford bound for all but one value of the exchange dimensionless gradient, s, and to go to the uniform electron gas limit at both s = 0 and s ? ?. Here we discuss the issue of asymptotic constraints for GGAs and show that imposition of the large s constraint, lim(s??)s(1/2)F(xc)(n,s)functional yields modest further improvement. The resulting exchange functional, denoted VT{8,4}, is only slightly more complicated than VMT and easy to program. Additional improvement is obtained by combining VT{8,4} or VMT exchange with the Lee-Yang-Parr correlation functional. Extensive computational results on several datasets are provided as verification of the overall performance gains of both versions. PMID:22502509

  20. Acetyl-L-Carnitine Treatment Following Spinal Cord Injury Improves Mitochondrial Function Correlated with Remarkable Tissue Sparing and Functional Recovery

    PubMed Central

    Patel, Samir P.; Sullivan, Patrick G.; Lyttle, Travis S.; Magnuson, David S. K.; Rabchevsky, Alexander G.

    2012-01-01

    We have recently documented that treatment with the alternative biofuel, acetyl-l-carnitine (ALC, 300 mg/kg), as late as 1 hr after T10 contusion spinal cord injury (SCI), significantly maintained mitochondrial function 24 hrs after injury. Here we report that following 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 hindlimb function. While control-injured rats were only able to achieve slight movements of hindlimb joints, ALC-treated animals produced consistent weight-supported plantar steps one 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

  1. G(ERLD): A CELL SURFACE ANTIGEN OF THE MOUSE RELATED TO XENOTROPIC MuLV DEFINED BY NATURALLY OCCURRING ANTIBODY AND MONOCLONAL ANTIBODY Relation to GLX, GW, ADAll, G~AmSL2) Systems of MuLV-related Antigens

    Microsoft Academic Search

    YUICHI OBATA; ELISABETH STOCKERT; ALBERT B. DELEO; PAUL V. O'DONNELL; HARRY W. SNYDER; LLOYD J. OLD

    Structural antigens related to endogenous murine leukemia viruses (MuLV) 1 are prominent components of the cell surface in many strains of mice. In some strains, expression of these antigens is associated with synthesis of complete infectious virus, but in others no replicating MuLV can be detected. Genes encoding these MuLV- related antigens are presumably derived from MuLV genetic information that

  2. Contribution of cross-functional teams to the improvement in operational performance

    Microsoft Academic Search

    Ricardo Santa; Mario Ferrer; Phil Bretherton; Paul Hyland

    2010-01-01

    Purpose – The purpose of this paper is to explore the role of cross-functional teams in the alignment between system effectiveness and operational effectiveness after the implementation of enterprise information systems (EIS). In addition, it aims to explore the contribution of cross-functional teams to improvement in operational performance. Design\\/methodology\\/approach – The research uses a combination of qualitative and quantitative methods,

  3. Improved Serum Leptin and Ghrelin Following Bariatric Surgery Predict Better Postoperative Cognitive Function

    PubMed Central

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

    2015-01-01

    Background and Purpose Bariatric surgery is associated with improved cognitive function, but the mechanisms underlying these gains remain poorly understood. Disturbed leptin and ghrelin systems are common in obese individuals and are associated with impaired cognitive function in other samples. Bariatric surgery has been shown to improve serum leptin and ghrelin levels, and these changes may underlie postoperative cognitive improvements. Methods Eighty-four patients completed a computerized cognitive test battery prior to bariatric surgery and at 12 months postoperatively. Participants also submitted to an 8-hour fasting blood draw to quantify serum leptin and ghrelin concentrations at these same time points. Results Baseline cognitive impairments and disturbed leptin and ghrelin levels improved at the 12-month follow-up compared to presurgery. Higher leptin levels were associated with worse attention/executive function at baseline; no such findings emerged for ghrelin. Regression analyses controlling for baseline factors and demographic characteristics showed that both decreased leptin and increased ghrelin following surgery was associated with better attention/executive function at the 12-month follow-up. These effects diminished after controlling for the postoperative change in body mass index (BMI); however, BMI change did not predict 12-month cognitive function. Conclusions Improvements in leptin and ghrelin levels following bariatric surgery appear to contribute to postoperative cognitive benefits. These gains may involve multiple mechanisms, such as reduced inflammation and improved glycemic control. Future studies that employ neuroimaging are needed to clarify the underlying mechanisms and determine whether the effects of bariatric surgery on leptin and ghrelin levels can attenuate adverse brain changes and/or risk of dementia in severely obese individuals. PMID:25628737

  4. Influence of Vascular Function and Pulsatile Hemodynamics on Cardiac Function.

    PubMed

    Bell, Vanessa; Mitchell, Gary F

    2015-09-01

    Interactions between cardiac and vascular structure and function normally are optimized to ensure delivery of cardiac output with modest pulsatile hemodynamic overhead. Aortic stiffening with age or disease impairs optimal ventricular-vascular coupling, increases pulsatile load, and contributes to left ventricular (LV) hypertrophy, reduced systolic function, and impaired diastolic relaxation. Aortic pulse pressure and timing of peak systolic pressure are well-known measures of hemodynamic ventricular-vascular interaction. Recent work has elucidated the importance of direct, mechanical coupling between the aorta and the heart. LV systolic contraction results in displacement of aortic and mitral annuli, thereby producing longitudinal stretch in the ascending aorta and left atrium, respectively. Force associated with longitudinal stretch increases systolic load on the LV. However, the resulting energy stored in the elastic elements of the proximal aorta during systole facilitates early diastolic LV recoil and rapid filling. This review discusses current views on hemodynamics and mechanics of ventricular-vascular coupling. PMID:26164466

  5. Improvements in neurocognitive function and mood following adjunctive treatment with mifepristone (RU-486) in bipolar disorder.

    PubMed

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

    2004-08-01

    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 mifepristone (RU-486) or placebo for 1 week in a double-blind crossover design. Over the total 6 weeks of the study, neurocognitive and neuroendocrine function were evaluated at baseline, days 21 and 42. Mood symptoms were evaluated weekly. Nineteen subjects completed the protocol; there were no drop-outs due to adverse events. Following treatment with mifepristone, selective improvement in neurocognitive functioning was observed. Spatial working memory performance was significantly improved compared to placebo (19.8% improvement over placebo). Measures of verbal fluency and spatial recognition memory were also improved after mifepristone. Beneficial effects on mood were found; Hamilton Depression Rating Scale scores were significantly reduced compared to baseline (mean reduction of 5.1 points) as were Montgomery-Asberg Depression Rating Scale scores (mean reduction of 6.05 points). No significant change occurred after placebo. These data require replication but provide preliminary evidence that glucocorticoid receptor antagonists may have useful cognitive-enhancing and possibly antidepressant properties in bipolar disorder. PMID:15127079

  6. Prefrontal activation predicts social functioning improvement after initial treatment in late-onset depression.

    PubMed

    Pu, Shenghong; Nakagome, Kazuyuki; Yamada, Takeshi; Yokoyama, Katsutoshi; Matsumura, Hiroshi; Nagata, Izumi; Kaneko, Koichi

    2015-03-01

    The activation of oxygenated hemoglobin (oxy-Hb) has been shown to be lacking in the prefrontal cortex (PFC) of patients with late-onset depression (LOD), in verbal fluency task (VFT)-related near-infrared spectroscopy (NIRS). In our previous studies, we have emphasized the connection between the lack of activation in the frontopolar cortex and social functioning disorder in patients with LOD. In this study, we investigated whether the responsiveness to medical treatment of untreated patients with LOD, particularly social functioning improvements, could be predicted by NIRS findings at the initial examination. The subjects were 29 patients with LOD who were diagnosed with major depression at 65 years or older at the initial examination (mean age ± standard deviation, 72.4 ± 5.71 years). We measured the changes in hemoglobin concentration in the prefrontal and temporal cortex regions during a VFT by using 52-channel NIRS. In addition, depression status and social functioning were evaluated with the Hamilton Depression Rating Scale and the Social Adaptation Self-evaluation Scale, respectively, at the initial examination and 8 weeks after the treatment. A negative correlation was found between the NIRS activation in the right ventrolateral PFC region before treatment and the improvement in social functioning. These results suggested that the social functioning improvements were greater in LOD with initially lower NIRS activation in the right ventrolateral PFC region. NIRS is a simple technique that can be used before treatment to evaluate the social functioning levels of patients with LOD, and predict social functioning improvement after treatment. PMID:25659188

  7. Electrical brain stimulation improves cognitive performance by modulating functional connectivity and task-specific activation.

    PubMed

    Meinzer, Marcus; Antonenko, Daria; Lindenberg, Robert; Hetzer, Stefan; Ulm, Lena; Avirame, Keren; Flaisch, Tobias; Flöel, Agnes

    2012-02-01

    Excitatory anodal transcranial direct current stimulation (atDCS) can improve human cognitive functions, but neural underpinnings of its mode of action remain elusive. In a cross-over placebo ("sham") controlled study we used functional magnetic resonance imaging (fMRI) to investigate neurofunctional correlates of improved language functions induced by atDCS over a core language area, the left inferior frontal gyrus (IFG). Intrascanner transcranial direct current stimulation-induced changes in overt semantic word generation assessed behavioral modulation; task-related and task-independent (resting-state) fMRI characterized language network changes. Improved word-retrieval during atDCS was paralleled by selectively reduced task-related activation in the left ventral IFG, an area specifically implicated in semantic retrieval processes. Under atDCS, resting-state fMRI revealed increased connectivity of the left IFG and additional major hubs overlapping with the language network. In conclusion, atDCS modulates endogenous low-frequency oscillations in a distributed set of functionally connected brain areas, possibly inducing more efficient processing in critical task-relevant areas and improved behavioral performance. PMID:22302824

  8. Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Only few hours of formula feeding may induce proinflammatory responses and predispose to necrotizing enterocolitis (NEC) in preterm pigs. We hypothesized that bovine colostrum, rich in bioactive factors, would improve intestinal function in preterm pigs following an initial exposure to formula feedi...

  9. Improving the environmental performance of the fishing fleet by use of Quality Function Deployment (QFD)

    Microsoft Academic Search

    Ingrid Bouwer Utne

    2009-01-01

    This article introduces Quality Function Deployment (QFD) as a method for improving the environmental performance of the Norwegian fishing fleet. Systems engineering has been introduced as a feasible process for handling sustainability issues in the fisheries, because it contains methods for general system design, operation, and support in a life-cycle perspective. QFD is related to systems engineering as a method

  10. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study

    Microsoft Academic Search

    Yoichi Matsui; Junya Uhara; Sohei Satoi; Masaki Kaibori; Hitoshi Yamada; Hiroaki Kitade; Atsusi Imamura; Soichiro Takai; Yusai Kawaguchi; A-Hon Kwon; Yasuo Kamiyama

    2002-01-01

    Background\\/Aims: Active hexose correlated compound (AHCC) is a newly developed functional food. In vitro experiments have shown that AHCC enhances natural killer cell activity, and may be considered a potent biological response modifier in the treatment of cancer patients. However, the effects of AHCC in a clinical setting have not been reported. We seek to determine whether AHCC can improve

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

    Microsoft Academic Search

    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

    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

  12. Endurance exercises versus treadmill training in improving muscle strength and functional activities in hemiparetic cerebral palsy

    Microsoft Academic Search

    Khaled A. Olama

    Weakness of the sound side in hemiparetic cerebral palsy is one of the serious complications which affect these children. Many children with hemiparetic cerebral palsy have diminished muscle power in the neglected sound side, and the application of strengthening exercises aim to improve the muscle strength and function activities and so may be helpful in the management of such cases.

  13. Speed Sensorless Control of PMSM Using An Improved Sliding Mode Observer With Sigmoid Function

    Microsoft Academic Search

    Kittithuch Paponpen; Mongkol Konghirun

    2006-01-01

    An improved sliding mode observer is presented to estimate the rotor position of the permanent mag- net synchronous motors (PMSMs). In this observer, the discontinuous control is replaced by using the sig- moid function in order to reduce the chattering prob- lem commonly found in the conventional sliding mode observer. When the chattering is reduced, the back emf can be

  14. Structure-function strategies to improve the pharmacological value of animal toxins

    E-print Network

    Paris-Sud XI, Université de

    Structure-function strategies to improve the pharmacological value of animal toxins Michel De sources of bioactive compounds that possess obvious pharmacological, therapeutic, and/or biotechnological, identification of actual target(s) is generally a difficult task. Pharmacological profiling using well defined

  15. Improved MDA compression for accelerated linear system solutions and monopolar basis functions for accurate MFIE formulations

    Microsoft Academic Search

    E. Ubeda; A. Heldring; Juan M. Rius; H. Espinosa; J. M. Tamayo; J. Parron

    2007-01-01

    We present some of the recent advances in computational electromagnetics developed at AntennaLab, UPC. The paper focuses on two research lines: Firstly, an improved version of the multilevel matrix decomposition algorithm (MLMDA) is presented. This new approach lends itself to both traditional iterative and direct solutions of the linear system. Secondly, the monopolar basis functions, a new highly accurate set

  16. Sensorimotor Training in a Virtual Reality Environment: Does It Improve Functional

    E-print Network

    New Jersey, University of Medicine and Dentistry of

    Sensorimotor Training in a Virtual Reality Environment: Does It Improve Functional Recovery the effectiveness of computerized virtual reality (VR) training of the hemiparetic hand of patients poststroke using. Key Words: Stroke--Rehabilitation--Recovery--Virtual reality-- Motor learning--Haptics. I

  17. Neutron monitor yield function: New improved computations A. L. Mishev,1,3

    E-print Network

    Usoskin, Ilya G.

    Neutron monitor yield function: New improved computations A. L. Mishev,1,3 I. G. Usoskin,1,2 and G June 2013. [1] A ground-based neutron monitor (NM) is a standard tool to measure cosmic ray (CR experimental data. Citation: Mishev, A. L., I. G. Usoskin, and G. A. Kovaltsov (2013), Neutron monitor yield

  18. IMPROVED CAFFARELLI-KOHN-NIRENBERG AND TRACE INEQUALITIES FOR RADIAL FUNCTIONS

    E-print Network

    Duran, Ricardo

    IMPROVED CAFFARELLI-KOHN-NIRENBERG AND TRACE INEQUALITIES FOR RADIAL FUNCTIONS PABLO L. DE N´APOLI, IRENE DRELICHMAN, AND RICARDO G. DUR´AN Abstract. We show that Caffarelli-Kohn-Nirenberg first order of this paper is to show that inequalities of Caffarelli-Kohn-Nirenberg type hold for a wider class of exponents

  19. proteinsSTRUCTURE O FUNCTION O BIOINFORMATICS Improving taxonomy-based protein fold

    E-print Network

    Chen, Xin

    proteinsSTRUCTURE O FUNCTION O BIOINFORMATICS Improving taxonomy-based protein fold recognition methods can be broadly classified into two categories, that is, template-based1­6 and taxonomy- based.7­13 In recent years, the taxonomy-based method has attracted great attention due to its encouraging performance

  20. Rg3-enriched Korean Red Ginseng improves vascular function in spontaneously hypertensive rats

    PubMed Central

    Park, Jung-Bum; Kwon, Sun Kwan; Nagar, Harsha; Jung, Saet-byel; Jeon, Byeong Hwa; Kim, Chang Sup; Oh, Jin-Hwan; Song, Hee-Jung; Kim, Cuk-Seong

    2014-01-01

    Background Panax ginseng has distinct and impressive health benefits, such as improved blood pressure and immune system functioning. Rg3-enriched Korean Red Ginseng (REKRG) isolated from Korean Red Ginseng contains a high percentage of Rg3. Methods In this study, we examined the effects of REKRG on endothelial cell nitric oxide synthase (eNOS) activation and adhesion molecules in endothelial cells and vascular function in rats. Results REKRG dose-dependently increased eNOS phosphorylation and nitric oxide (NO) production in endothelial cells. In addition, REKRG markedly inhibited the tumor necrosis factor-? (TNF-?)-mediated induction of intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expressions in endothelial cells. REKRG improved endothelium-dependent vasorelaxation in the Wistar-Kyoto (WKY) rat and spontaneously hypertensive rats (SHRs) compared with controls. Furthermore, REKRG treatment for 6 weeks increased serum NO levels and reduced the mean aortic intima-media thickness compared with controls. Conclusion Taken together, these results suggest that REKRG increased vascular function and improved immune system functioning. Therefore, REKRG is a very useful food for preventing or improving various cardiovascular diseases. PMID:25379003

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

    ERIC Educational Resources Information Center

    Zimmerman, Toni Schindler; Fetsch, Robert J.

    1994-01-01

    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…

  2. A finite element inverse analysis to assess functional improvement during the fracture healing process

    E-print Network

    Miga, Michael I.

    ; Marsh, 1998). In long-bones, fracture healing proceeds through the formation of a cartilaginous template annual bone fractures result in non-unions, causing significant morbidity and mortality (Einhorn, 1995A finite element inverse analysis to assess functional improvement during the fracture healing

  3. Improving Global System Development and Collaboration across Functions: Experiences from Industry

    Microsoft Academic Search

    P. Fassbinder; V. Henz

    2009-01-01

    In large and complex organizations efficient collaboration across different locations (e.g. global system development) and different functions within the product lifecycle (e.g. sales, development, production) are key success factors in system and software engineering. As a global expert department for process consulting within the Siemens AG, we developed approaches to analyze and improve collaboration in these two scenarios and have

  4. Inhaled L-Arginine Improves Exhaled Nitric Oxide and Pulmonary Function in Patients with Cystic Fibrosis

    Microsoft Academic Search

    Hartmut Grasemann; Fionn Kurtz; Felix Ratjen

    2006-01-01

    Rationale: Nitric oxide formation is deficient in airways of patients with cystic fibrosis (CF). Since nitric oxide has bronchodilatory ef- fects, nitric oxide deficiency may contribute to airway obstruction in CF. Objectives: We reasoned that inhalation of L-arginine, the precursor of enzymatic nitric oxide formation, could improve airway nitric oxide formation and pulmonary function in patients with CF. Measurements: Exhaled

  5. Selegiline attenuates cardiac oxidative stress and apoptosis in heart failure: association with improvement of cardiac function

    Microsoft Academic Search

    Fuzhong Qin; Junya Shite; Weike Mao; Chang-seng Liang

    2003-01-01

    We have shown recently that selegiline exerts a cardiac neuroprotective effect in chronic heart failure. Since selegiline has an antioxidant antiapoptotic effect, we proposed to determine whether selegiline attenuates cardiac oxidative stress and myocyte apoptosis in chronic heart failure by modulating Bcl-2 and Bax protein expression, and whether the effects are associated with the improvement of cardiac function. Rabbits with

  6. An Improved Particle Swarm Optimization Algorithm Mimicking Territorial Dispute Between Groups for Multimodal Function Optimization Problems

    Microsoft Academic Search

    Jang-Ho Seo; Chang-Hwan Im; Sang-Yeop Kwak; Cheol-Gyun Lee; Hyun-Kyo Jung

    2008-01-01

    In the present paper, an improved particle swarm optimization (PSO) algorithm for multimodal function optimization is proposed. The new algorithm, named auto-tuning multigrouped PSO (AT-MGPSO) algorithm mimics natural phenomena in ecosystem such as territorial dispute between different group members and immigration of weak groups, resulting in automatic determination of the size of each group's territory and robust convergence. The usefulness

  7. Plasma gelsolin improves lung host defense against pneumonia by enhancing macrophage NOS3 function.

    PubMed

    Yang, Zhiping; Chiou, Terry Ting-Yu; Stossel, Thomas P; Kobzik, Lester

    2015-07-01

    Plasma gelsolin (pGSN) functions as part of the "extracellular actin-scavenging system," but its potential to improve host defense against infection has not been studied. In a mouse model of primary pneumococcal pneumonia, recombinant human pGSN (rhu-pGSN) caused enhanced bacterial clearance, reduced acute inflammation, and improved survival. In vitro, rhu-pGSN rapidly improved lung macrophage uptake and killing of bacteria (Streptococcus pneumoniae, Escherichia coli, and Francisella tularensis). pGSN triggers activating phosphorylation (Ser(1177)) of macrophage nitric oxide synthase type III (NOS3), an enzyme with important bactericidal functions in lung macrophages. rhu-pGSN failed to enhance bacterial killing by NOS3(-/-) macrophages in vitro or bacterial clearance in NOS3(-/-) mice in vivo. Prophylaxis with immunomodulators may be especially relevant for patients at risk for secondary bacterial pneumonia, e.g., after influenza. Treatment of mice with pGSN challenged with pneumococci on postinfluenza day 7 (the peak of enhanced susceptibility to secondary infection) caused a ?15-fold improvement in bacterial clearance, reduced acute neutrophilic inflammation, and markedly improved survival, even without antibiotic therapy. pGSN is a potential immunomodulator for improving lung host defense against primary and secondary bacterial pneumonia. PMID:25957291

  8. PRL_2nd_revise_3 -WWW--07/06/021 Improving the performance of radial basis function classifiers in

    E-print Network

    Pont, Michael J.

    PRL_2nd_revise_3 - WWW--07/06/021 Improving the performance of radial basis function classifiers Basis Function (RBF) classifier. Results from two experiments demonstrate that this method can be used to improve the performance of RBF classifiers in practical applications. Keywords: Radial basis function

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

    PubMed Central

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

    2013-01-01

    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. PMID:23894342

  10. [Echopolycardiographic evaluation of left ventricular function after hemodialysis].

    PubMed

    Vancheri, F; Barberi, O; Cammalleri, G; Gruttadauria, G; Macaluso, M R; Torregrossa, R; Vinciguerra, S; Amico, C

    1985-07-01

    The acute effects of haemodialysis on left ventricular (LV) function were studied by echocardiography and systolic time intervals in 19 patients maintained on long-term haemodialysis. Dialysis resulted in a significant reduction in body weight, an increase in heart rate and a small reduction in systolic blood pressure. A significant decrease was observed in LV diastolic and systolic dimensions, with an increase in the mean rate of circumferential shortening (mean VCF). The LV ejection time (LVET) decreased significantly, while changes in the pre-ejection period (PEP) were insignificant. The PEP/LVET ratio increased in all patients. Haemodialysis reduced the serum potassium levels; an increase was noted in the serum calcium concentrations, with a significant, although small, correction of blood pH. The major haemodynamic change induced by dialysis was a decrease in blood volume with a reduction in LV pre-load. These changes are suggested by the reduction in body weight and by the shortening in LV end-diastolic dimension and LVET. There was also a reduction in after-load, as expressed by the shortening in LV systolic diameter and by the decrease in systolic blood pressure. It should be emphasized that the study of LV function in patients on chronic dialysis is greatly influenced by the loading conditions. In such patients the assessment of LV function by echocardiography and systolic time intervals provides information regarding the haemodynamic changes induced by dialysis; however, no direct evidence can be derived about the functional state of the left ventricle. PMID:4076699

  11. Treating Insomnia Improves Mood State, Sleep, and Functioning in Bipolar Disorder: A Pilot Randomized Controlled Trial

    PubMed Central

    Harvey, Allison G.; Soehner, Adriane M.; Kaplan, Kate A.; Hein, Kerrie; Lee, Jason; Kanady, Jennifer; Rabe-Hesketh, Sophia; Neylan, Thomas C.; Li, Descartes; Ketter, Terence A.; Buysse, Daniel J.

    2015-01-01

    Objective To determine if a treatment for interepisode bipolar disorder I patients with insomnia improves mood state, sleep, and functioning. Method Alongside psychiatric care, interepisode bipolar disorder I participants with insomnia were randomly allocated to a bipolar disorder–specific modification of cognitive behavior therapy for insomnia (CBTI-BP; n = 30) or psychoeducation (PE; n = 28) as a comparison condition. Outcomes were assessed at baseline, the end of 8 sessions of treatment, and 6 months later. This pilot was conducted to determine initial feasibility and generate effect size estimates. Results During the 6-month follow-up, the CBTI-BP group had fewer days in a bipolar episode relative to the PE group (3.3 days vs. 25.5 days). The CBTI-BP group also experienced a significantly lower hypomania/mania relapse rate (4.6% vs. 31.6%) and a marginally lower overall mood episode relapse rate (13.6% vs. 42.1%) compared with the PE group. Relative to PE, CBTI-BP reduced insomnia severity and led to higher rates of insomnia remission at posttreatment and marginally higher rates at 6 months. Both CBTI-BP and PE showed statistically significant improvement on selected sleep and functional impairment measures. The effects of treatment were well sustained through follow-up for most outcomes, although some decline on secondary sleep benefits was observed. Conclusions CBTI-BP was associated with reduced risk of mood episode relapse and improved sleep and functioning on certain outcomes in bipolar disorder. Hence, sleep disturbance appears to be an important pathway contributing to bipolar disorder. The need to develop bipolar disorder–specific sleep diary scoring standards is highlighted. Public Health Significance This study suggests that an intervention to improve sleep and circadian functioning reduces risk of relapse and improves sleep and overall functioning among individuals who meet diagnostic criteria for bipolar disorder. PMID:25622197

  12. N-acetylcysteineamide Preserves Mitochondrial Bioenergetics and Improves Functional Recovery Following Spinal Trauma

    PubMed Central

    Patel, Samir P.; Sullivan, Patrick G.; Pandya, Jignesh D.; Goldstein, Glenn A.; VanRooyen, Jenna L.; Yonutas, Heather M.; Eldahan, Khalid C.; Morehouse, Johnny; Magnuson, David S. K.; Rabchevsky, Alexander G.

    2014-01-01

    Mitochondrial dysfunction is becoming a pivotal target for neuroprotective strategies following contusion spinal cord injury (SCI) and the pharmacological compounds that maintain mitochondrial function confer neuroprotection and improve long-term hindlimb function after injury. In the current study we evaluated the efficacy of cell-permeating thiol, N-acetylcysteineamide (NACA), a precursor of endogenous antioxidant glutathione (GSH), on mitochondrial function acutely, and long-term tissue sparing and hindlimb locomotor recovery following upper lumbar contusion SCI. Some designated injured adult female Sprague-Dawley rats (n=120) received either Vehicle or NACA (75, 150, 300 or 600 mg/kg) at 15min and 6hrs post-injury. After 24hr the total, synaptic, and non-synaptic mitochondrial populations were isolated from a single 1.5cm spinal cord segment (centered at injury site) and assessed for mitochondrial bioenergetics. Results showed compromised total mitochondrial bioenergetics following acute SCI that was significantly improved with NACA treatment in a dose-dependent manner, with maximum effects at 300 mg/kg (n=4/group). For synaptic and non-synaptic mitochondria, only 300 mg/kg NACA dosage showed efficacy. Similar dosage (300mg/kg) also maintained mitochondrial GSH near normal levels. Other designated injured rats (n=21) received continuous NACA (150 or 300mg/kg/day) treatment starting at 15min post-injury for one week to assess long-term functional recovery over 6 weeks post-injury. Locomotor testing and novel gait analyses showed significantly improved hindlimb function with NACA that were associated with increased tissue sparing at the injury site. Overall, NACA treatment significantly maintained acute mitochondrial bioenergetics and normalized GSH levels following SCI, and prolonged delivery resulted in significant tissue sparing and improved recovery of hindlimb function. PMID:24805071

  13. Effects of isoproterenol on regional myocardial function, electrogram, and blood flow in conscious dogs with myocardial ischemia.

    PubMed Central

    Vatner, S F; Millard, R W; Patrick, T A; Heyndrickx, G R

    1976-01-01

    The effects of coronary occlusion and of subsequent isoproterenol infusion were examined in conscious dogs. Left ventricular (LV) function was assessed by measurements of LV diameter, pressure, velocity and dP/dt/P, and regional myocardial function was assessed by measurements of segment length (SL) and velocity of SL shortening in normal, border, and ischemic zones. Regional myocardial function was measured from the same sites, along with intramyocardial electrograms and regional myocardial blood flow as determined by radioactive microspheres. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reductions and graded increases in ST segment elevation. Isoproterenol improved overall LV function, and function in the normal zone. Isoproterenol also improved function in 19 of 21 border-zone segments and in all moderately ischemic segments, while elevating further the ST segments. These changes were accompanied by increases in myocardial blood flow. In contrast, in severely ischemic segments, isoproterenol resulted in a deterioration of function, in that paradoxical motion occurred in segments previously akinetic during systole, while paradoxical motion was intensified in those segments in which it was already present. These changes were accompanied by further ST segment elevation but not by concurrent increases in blood flow. In addition, in 2 of 21 border zone segments, myocardial blood flow fell and these segments responded to isoproterenol with complete loss of function; paradoxical motion developed. Thus, in the conscious dog, a strong inotropic agent can improve function, even in the ischemic myocardium, as long as the required additional blood flow can be provided wither through primary or collateral channels. PMID:1262470

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

    PubMed Central

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

    2014-01-01

    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. PMID:24771695

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

    PubMed Central

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

    2007-01-01

    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. PMID:17912365

  16. Evaluation of the Effect of Mega MSM on Improving Joint Function in Populations Experiencing Joint Degeneration

    PubMed Central

    Xu, Gang; Zhou, Tian; Gu, Yaqin; Wang, Qinping; Shariff, Mina; Gu, Pingping; Nguyen, Tuong; Shi, Rong; Rao, Jianyu

    2015-01-01

    Joint degeneration has become a commonplace problem in aging populations. The main clinical manifestations include joint pain, joint stiffness and joint swelling with functional disorder. Mega MSM is a nutritional supplement that may provide potential relief for joint problems associated with joint degeneration. The current experiment performed was a 12-week, randomized, double-blind, controlled study conducted on populations in China experiencing joint degeneration. The objective of the study was to determine whether the daily use of Mega MSM capsules could improve joint function, relieve symptoms of joint degeneration and improve the quality of life in aging populations. A total of 100 male and female participants over 50 years old who had at least one of the related symptoms of joint degeneration (joint pain, joint stiffness, joint swelling, difficulty walking, difficulty getting up from bed and difficulty going down stairs) were recruited and their symptoms of joint degeneration before and after the intervention were recorded. In this study, Mega MSM shows positive effects in improving joint function, relieving symptoms associated with joint degeneration and improving the quality of life in aging populations. PMID:26199577

  17. An Alternative to Current Therapies of Functional Dyspepsia: Self-Administrated Transcutaneous Electroacupuncture Improves Dyspeptic Symptoms

    PubMed Central

    Ji, Ting; Li, Xueliang; Lin, Lin; Jiang, Liuqin; Wang, Meifeng; Zhou, Xiaopin; Zhang, Ranran; Chen, Jiande DZ

    2014-01-01

    Functional dyspepsia is of high prevalence with little treatment options. The aim of this study was to develop a new treatment method using self-management transcutaneous electroacupuncture (TEA) for functional dyspepsia (FD). Twenty-eight patients with FD were enrolled and underwent a crossover clinical trial with 2-week TEA at ST36 and PC6 and 2-week sham-TEA at nonacupuncture sham-points. Questionnaires were used to assess symptoms of dyspepsia and quality of life. Physiological testing included gastric emptying and electrogastrography. It was found that (1) TEA but not sham-TEA significantly improved dyspeptic symptoms and 4 domains in quality of life; improvement was also noted in self-rated anxiety and depression scores; (2) gastric emptying was significantly and substantially increased with 2-week TEA but not sham-TEA; and (3) gastric accommodation was also improved with TEA but not sham-TEA, reflected as increased ingested nutrient volumes at the levels of satiety and maximum tolerance. These findings suggest a therapeutic potential of self-administrated TEA method for functional dyspepsia, possibly attributed to improvement in gastric motility. PMID:25530791

  18. Reverse cardiac remodelling and renal functional improvement following bilateral renal artery stenting for flash pulmonary oedema.

    PubMed

    Chrysochou, Constantina; Schmitt, Matthias; Siddals, Kirk; Hudson, Julie; Fitchet, Alan; Kalra, Philip A

    2013-02-01

    Acute flash pulmonary oedema (AFPO) is a life-threatening syndrome almost unique to patients with atheromatous renovascular disease (ARVD). Although recurrent AFPO is a widely accepted indication to consider renal revascularization, this is based on a number of case reports/series describing a successful outcome post-procedure. There is limited literature on the pathophysiological mechanisms and treatment effects of revascularization to support this clinical decision making. We report the case of a 65-year-old lady who presented with three episodes of AFPO. Investigations revealed severe bilateral renal artery stenosis. Post-revascularization, she experienced substantial improvement in energy levels and New York Heart Association class, with improvement in her blood pressure and renal function. Post-procedure, there were dramatic improvements in her cardiac morphology and function that were sustained at 1 year (ejection fraction improved from 39 to 65%, left ventricular mass decreased from 161 to 116 g) as well as renal function (isotopic glomerular filtration rate increased from 22.4 to 34.2 mL/min). This report provides new insights into the pathophysiological relationships between renal and cardiac changes in AFPO; the extent of the cardiac morphological changes was striking and unexpected. PMID:22262735

  19. PROGENITOR CELL RELEASE PLUS EXERCISE TO IMPROVE FUNCTIONAL PERFORMANCE IN PERIPHERAL ARTERY DISEASE: THE PROPEL STUDY

    PubMed Central

    Domanchuk, Kathryn; Ferrucci, Luigi; Guralnik, Jack M.; Criqui, Michael H.; Tian, Lu; Liu, Kiang; Losordo, Douglas; Stein, James; Green, David; Kibbe, Melina; Zhao, Lihui; Annex, Brian; Perlman, Harris; Lloyd-Jones, Donald; Pearce, William; Taylor, Doris; McDermott, Mary M.

    2013-01-01

    Functional impairment, functional decline, and mobility loss are major public health problems in people with lower extremity peripheral artery disease (PAD). Few medical therapies significantly improve walking performance in PAD. We describe methods for the PROgenitor cell release Plus Exercise to improve functionaL performance in PAD (PROPEL) Study, a randomized controlled clinical trial designed to determine whether granulocyte-macrophage colony stimulating factor (GM-CSF) combined with supervised treadmill walking exercise improves six-minute walk distance more than GM-CSF alone, more than supervised treadmill exercise alone, and more than placebo plus attention control in participants with PAD, respectively. PROPEL Study participants are randomized to one of four arms in a 2 by 2 factorial design. The four study arms are GM-CSF plus supervised treadmill exercise, GM-CSF plus attention control, placebo plus supervised exercise therapy, or placebo plus attention control. The primary outcome is change in six-minute walk distance at 12-week follow-up. Secondary outcomes include change in brachial artery flow-mediated dilation (FMD), change in maximal treadmill walking time, and change in circulating CD34+ cells at 12-week follow-up. Outcomes are also measured at six-week and six-month follow-up. Results of the PROPEL Study will have important implications for understanding mechanisms of improving walking performance and preventing mobility loss in the large and growing number of men and women with PAD. PMID:24080099

  20. Restoring endoplasmic reticulum homeostasis improves functional recovery after spinal cord injury.

    PubMed

    Ohri, Sujata Saraswat; Hetman, Michal; Whittemore, Scott R

    2013-10-01

    The endoplasmic reticulum (ER) stress response (ERSR) is activated to maintain protein homeostasis or induce apoptosis in the ER in response to distinct cellular insults including hypoxia, inflammation, and oxidative damage. Recently, we showed ERSR activation in a mouse model of a contusive spinal cord injury (SCI) and an improved hindlimb locomotor function following SCI when the pro-apoptotic arm of ERSR was genetically inhibited. The objective of the current study was to explore if the pharmacological enhancement of the homeostatic arm of the ERSR pathway can improve the functional outcome after SCI. Salubrinal enhances the homeostatic arm of the ERSR by increasing phosphorylation of eIF2?. Salubrinal significantly enhanced the levels of phosphorylated eIF2? protein and modulated the downstream ERSR effectors assessed at the lesion epicenter 6h post-SCI. Hindlimb locomotion showed significant improvement in animals treated with salubrinal. Treadmill-based-gait assessment showed a significant increase in maximum speed of coordinated walking and a decrease in rear stance time and stride length in salubrinal-treated animals. This improved functional recovery corresponded with increased white matter sparing and decreased oligodendrocyte apoptosis. In addition, salubrinal protected cultured mouse oligodendrocyte progenitor cells against the ER stress-inducing toxin tunicamycin. These data suggest that boosting the homeostatic arm of the ERSR reduces oligodendrocyte loss after traumatic SCI and support the contention that pharmacological targeting of the ERSR after CNS trauma is a therapeutically viable approach. PMID:23659896

  1. Declining ambient air pollution and lung function improvement in Austrian children

    NASA Astrophysics Data System (ADS)

    Neuberger, Manfred; Moshammer, Hanns; Kundi, Michael

    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.

  2. Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents.

    PubMed

    Zhou, June; Keenan, Michael J; Fernandez-Kim, Sun Ok; Pistell, Paul J; Ingram, Donald K; Li, Bing; Raggio, Anne M; Shen, Li; Zhang, Hanjie; McCutcheon, Kathleen L; Tulley, Richard T; Blackman, Marc R; Keller, Jeffrey N; Martin, Roy J

    2013-11-01

    Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (i) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (ii) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (iii) a higher serum active glucagon-like peptide-1 (GLP-1). Then, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (i) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and (ii) GLP-1 is important in the optimal feeding response to a fast. PMID:23818307

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

    PubMed

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

    2014-05-01

    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

  4. Molecular cloning of a C-type lectin (LvLT) from the shrimp Litopenaeus vannamei: Early gene down-regulation after WSSV infection

    Microsoft Academic Search

    Tracy Hoi Tung Ma; Shirley Hiu Kwan Tiu; Jian-Guo He; Siu-Ming Chan

    2007-01-01

    C-type lectin is one of the pattern-recognition proteins of the non-self innate immune system in the invertebrates. In this study, a lectin-like cDNA (LvLT) of Litopenaeus vannamei was cloned and characterized. LvLT cDNA consists of 1035 nt encoding for a protein with 345 amino acid residues. The deduced LvLT consists of two putative carbohydrate-recognition domains (CRDs) as found in most

  5. Improving Function in Age-Related Macular Degeneration: A Randomized Clinical Trial

    PubMed Central

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

    2013-01-01

    Purpose To compare the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) to improve Targeted Vision Function in Age-Related Macular Degeneration (AMD). Design Single-masked, attention controlled randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). Participants Patients with AMD (N = 241) attending retina practices. Interventions PST uses a structured problem-solving approach to reduce vision-related task difficulty. ST is a standardized attention control treatment. Main Outcome Measures Targeted Vision Function (TVF); National Eye Institute Vision Function Questionnaire - 25 plus Supplement (NEI VFQ); Activities Inventory (AI); and Vision-Related Quality of Life. Results There were no significant between-group differences in TVF scores at 3 months (p = 0.47) or 6 months (p = 0.62). For PST subjects, mean [standard deviation (SD)] TVF scores improved from 2.71 (0.52) at baseline to 2.18 (0.88) at 3 months (p = 0.001) and were 2.18 (0.95) at 6 months (change from 3 to 6 months, p = .74). For ST subjects, TVF scores improved from 2.73 (0.52) at baseline to 2.14 (0.96) at 3 months (p = 0.001) and were 2.15 (0.96) at 6 months (change from 3 to 6 months, p = .85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs. 78.6%, respectively; p = 0.83) and 6 months (76.2% vs. 79.1%, respectively; p = 0.61). There were no significant changes in the NEI VFQ or AI. Vision-related quality-of-life improved for PST relative to ST subjects at 3 months [F (4,192) = 2.46; p = 0.05] and 6 months [F (4,178) = 2.55; p = 0.05)]. PST subjects also developed more adaptive coping strategies than ST subjects. Conclusions We found that PST was not superior to ST at improving vision function in patients with AMD but PST improved their vision-related quality of life. Despite the benefits of anti-vascular endothelial growth factor (anti-VEGF) treatments, AMD remains associated with disability, depression, and diminished quality of life. This clinical reality necessitates new rehabilitative interventions to improve the vision function and quality of life of older persons with AMD. PMID:23642378

  6. Myocardial function and geometry in hypertensive subjects with low levels of afterload

    Microsoft Academic Search

    Gerard P. Aurigemma; Richard B. Devereux; Giovanni de Simone; Mary J. Roman; Michael J. O'Grady; Michael Koren; Michael Alderman; John Laragh

    2002-01-01

    Background It has been hypothesized that the level of end-systolic wall stress (?m) is a feedback signal that regulates the level of hypertrophy. Thus, low levels of ?m may signify inappropriate hypertrophy. Methods To characterize left ventricular (LV) structure and systolic function in hypertensive subjects with low levels of ?m, we studied 763 patients. LV function was studied by midwall

  7. Basic Res Cardiol . Author manuscript Impaired left ventricular function in the presence of preserved ejection in

    E-print Network

    Paris-Sud XI, Université de

    ventricle as a muscular pump, we explored LV function during chronic hypertension independently from was preserved. Most of these studies analyzed[ ] [ ] LV function as a hydraulic input-output system as opposed to a muscular pump perspective 7, 23, 38 .[ ] In this setting and considering the heart as a muscular pump, we

  8. Impaired Left Ventricular Function in the Presence of Preserved Ejection in Chronic Hypertensive Conscious Pigs.

    E-print Network

    Paris-Sud XI, Université de

    input-output system as opposed to a muscular pump perspective [7, 23, 38]. In this setting. Considering the left ventricle as a muscular pump, we explored LV function during chronic hypertension and considering the heart as a muscular pump, we aimed at investigating LV function during chronic hypertension

  9. Physical improvements to the solar wind reconnection control function for the Earth's magnetosphere

    NASA Astrophysics Data System (ADS)

    Borovsky, Joseph E.

    2013-05-01

    In a 2008 publication a first principles calculation of the dayside reconnection rate expressed in terms of upstream-solar wind parameters led to a rudimentary solar wind coupling function R1 for the Earth's magnetosphere. Four improvements to that derivation are added in the present paper, resulting in a more correct solar wind control function describing the rate at which solar wind magnetic field lines connect into the Earth's magnetosphere. The first is the inclusion of the effect of ?-dependent plasma compressibility on the reconnection rate. The second is a corrected calculation of the inflow of magnetic field lines into the reconnection X-line. The third is a more accurate estimate of the orientation of the reconnection X-line for asymmetric reconnection. The fourth correction accounts for the compression ratio of the Earth's bow shock for arbitrary orientation of the solar wind magnetic field. Two solar wind control functions result: one function, R2CS, is based on the Cassak-Shay equation and another function, R2CSB, is based on the Cassak-Shay-Birn equation. The control functions are tested using solar wind measurements and geomagnetic indices from 1980 to 2012, and some improved correlation coefficients over the rudimentary function R1 are found. Simplified approximations to the new control functions are supplied: one is R2CS-approx = 1.68 × 10-2 sin2(?/2)no1/2vo2MA-0.3044exp(-[MA/3.18]1/2), where the subscript "o" denotes the solar wind upstream of the bow shock and MA is the solar wind Alfvén Mach number.

  10. Fish oil selectively improves heart function in a mouse model of lipid-induced cardiomyopathy

    PubMed Central

    Khan, Raffay S.; Chokshi, Aalap; Drosatos, Konstantinos; Jiang, Hongfeng; Yu, Shuiqing; Harris, Collette R.; Schulze, P. Christian; Homma, Shunichi; Blaner, William S.; Shulman, Gerald I.; Huang, Li-Shin; Goldberg, Ira J.

    2013-01-01

    Fish oil (FO) supplementation may improve cardiac function in some patients with heart failure, especially those with diabetes. To determine why this occurs, we studied the effects of FO in mice with heart failure due either to transgenic expression of the lipid uptake protein, acyl CoA synthetase 1 (ACS1) or overexpression of the transcription factor peroxisomal proliferator activated receptor (PPAR)? via the cardiac specific myosin heavy chain (MHC) promoter. ACS1 mice and control littermates were fed three diets containing low or high-dose FO or non-purified diet (NPD) for 6 weeks. MHC-PPAR? mice were fed low-dose FO or NPD. Compared to control mice fed NPD, ACS1 and MHC-PPAR? mice fed NPD had reduced cardiac function and survival with cardiac fibrosis. In contrast, ACS1 mice fed high-dose FO had better cardiac function, survival and less myocardial fibrosis. FO increased eicosapentaenoic and docosahexaenoic acids and reduced saturated fatty acids in cardiac diacylglycerols. This was associated with reduced PKC alpha and beta activation. In contrast, low-dose FO reduced MHC-PPAR? mice survival with no change in PKC activation or cardiac function. Thus, dietary FO reverses fibrosis and improves cardiac function and survival of ACS1 mice, but does not benefit all forms of lipid-mediated cardiomyopathy. PMID:23567901

  11. Effects of Acute Increases in Left Ventricular Preload on Indices of Myocardial Function in Conscious, Unrestrained and Intact, Tranquilized Baboons

    PubMed Central

    Zimpfer, Michael; Vatner, Stephen F.

    1981-01-01

    The effects of acute volume loading were examined on indices of left ventricular (LV) function in conscious, unrestrained and intact, tranquilized baboons. Experiments were conducted 1-3 mo after implantation of ultrasonic transducers to measure LV internal diameter and wall thickness, and miniature LV pressure gauges and aortic and left atrial catheters. In 10 intact, tranquilized baboons, rapid volume loading with saline increased LV end-diastolic pressure by 23.7±2.6 mm Hg, LV end-diastolic diameter by 7.8±1.5%, LV stroke work by 37.5±7.8%, while mean arterial pressure and peak LV wall stress did not change significantly. Despite the increase in preload and activation of the Frank-Starling mechanism, LV dP/dtmax and the maximum velocity of myocardial fiber shortening (LV dD/dtmax) did not change. Volume loading after ?-adrenergic or combined ?-adrenergic and cholinergic blockades or volume loading with blood instead of saline also failed to augment LV dP/dtmax and LV dD/dtmax despite the increase in preload. In order to volume load the baboons in the conscious state, a radiofrequency (RF) interrogator system was devised, which upon receipt of a radio command, activated a battery operated pump to infuse 1,000 ml of saline i.v. to the baboons. In these experiments, preload rose, i.e., LV end-diastolic diameter increased by 13.9±2.1% and the Frank-Starling mechanism could be demonstrated, i.e., stroke work rose by 42.8±7.4%, but LV dP/dtmax and LV dD/dtmax did not change. After preload was depressed by hemorrhage, the rapid infusion of either blood or saline increased LV dP/dtmax by 92.7±18.5% and LV dD/dtmax by 64.3±10.1%. Thus, acute volume loading in the conscious baboons increased LV end-diastolic size and even stroke work substantially. However, preload dependency of LV dP/dtmax and the maximum velocity of myocardial fiber shortening was only encountered at low levels of LV preload. Images PMID:7462425

  12. Avocado Oil Improves Mitochondrial Function and Decreases Oxidative Stress in Brain of Diabetic Rats

    PubMed Central

    Ortiz-Avila, Omar; Esquivel-Martínez, Mauricio; Olmos-Orizaba, Berenice Eridani; Saavedra-Molina, Alfredo; Rodriguez-Orozco, Alain R.; Cortés-Rojo, Christian

    2015-01-01

    Diabetic encephalopathy is a diabetic complication related to the metabolic alterations featuring diabetes. Diabetes is characterized by increased lipid peroxidation, altered glutathione redox status, exacerbated levels of ROS, and mitochondrial dysfunction. Although the pathophysiology of diabetic encephalopathy remains to be clarified, oxidative stress and mitochondrial dysfunction play a crucial role in the pathogenesis of chronic diabetic complications. Taking this into consideration, the aim of this work was to evaluate the effects of 90-day avocado oil intake in brain mitochondrial function and oxidative status in streptozotocin-induced diabetic rats (STZ rats). Avocado oil improves brain mitochondrial function in diabetic rats preventing impairment of mitochondrial respiration and mitochondrial membrane potential (??m), besides increasing complex III activity. Avocado oil also decreased ROS levels and lipid peroxidation and improved the GSH/GSSG ratio as well. These results demonstrate that avocado oil supplementation prevents brain mitochondrial dysfunction induced by diabetes in association with decreased oxidative stress.

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

    Microsoft Academic Search

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

    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

  14. ATP synthase subunit alpha and LV mass in ischaemic human hearts

    PubMed Central

    Roselló-Lletí, Esther; Tarazón, Estefanía; Barderas, María G; Ortega, Ana; Molina-Navarro, Maria Micaela; Martínez, Alba; Lago, Francisca; Martínez-Dolz, Luis; González-Juanatey, Jose Ramón; Salvador, Antonio; Portolés, Manuel; Rivera, Miguel

    2015-01-01

    Mitochondrial dysfunction plays a critical role in the development of ischaemic cardiomyopathy (ICM). In this study, the mitochondrial proteome in the cardiac tissue of ICM patients was analysed by quantitative differential electrophoresis (2D-DIGE) and mass spectrometry (MS) for the first time to provide new insights into cardiac dysfunction in this cardiomyopathy. We isolated mitochondria from LV samples of explanted hearts of ICM patients (n = 8) and control donors (n = 8) and used a proteomic approach to investigate the variations in mitochondrial protein expression. We found that most of the altered proteins were involved in cardiac energy metabolism (82%). We focused on ATPA, which is involved in energy production, and dihydrolipoyl dehydrogenase, implicated in substrate utilization, and observed that these molecules were overexpressed and that the changes detected in the processes mediated by these proteins were closely related. Notably, we found that ATPA overexpression was associated with reduction in LV mass (r = ?0.74, P < 0.01). We also found a substantial increase in the expression of elongation factor Tu, a molecule implicated in protein synthesis, and PRDX3, involved in the stress response. All of these changes were validated using classical techniques and by using novel and precise selected reaction monitoring analysis and an RNA sequencing approach, with the total heart samples being increased to 24. This study provides key insights that enhance our understanding of the cellular mechanisms related to the pathophysiology of ICM and could lead to the development of aetiology-specific heart failure therapies. ATPA could serve as a molecular target suitable for new therapeutic interventions. PMID:25382018

  15. Feline upper respiratory tract lymphoma: site, cyto-histology, phenotype, FeLV expression, and prognosis.

    PubMed

    Santagostino, S F; Mortellaro, C M; Boracchi, P; Avallone, G; Caniatti, M; Forlani, A; Roccabianca, P

    2015-03-01

    Lymphoma is the most common feline upper respiratory tract (URT) tumor. Primary nasal and nasopharyngeal lymphomas have been evaluated as distinct pathological entities; however, data on their differing clinical behavior are missing. A total of 164 endoscopic- guided URT pinch biopsies were formalin fixed and routinely processed. Imprint cytological specimens were stained with May Grünwald-Giemsa. Immunohistochemistry for anti-CD20, CD3, FeLVp27, and FeLVgp70 was performed. Prognostic significance of clinicopathological variables was investigated by univariate and multivariate analysis. Lymphoma was diagnosed in 39 cats (24%). Most cats with lymphoma were domestic shorthair (32 [82%]), were male (F/M = 0.56), and had a mean age of 10.3 years (range, 1-16 years). Lymphomas were primary nasal in 26 cats (67%), nasopharyngeal in 6 (15%), and in both locations (combined lymphomas) in 7 cats (18%). Neoplastic growth pattern was diffuse in 35 cases (90%) and nodular in 4 (10%). Epitheliotropism was observed in 10 cases (26%). Tumor cells were large in 15 cases, were small and medium in 11 cases each, and 2 had mixed cell size. Submucosal lymphoplasmacytic inflammation was observed in 23 cases (59%). Cytology was diagnostic for lymphoma in 12 of 25 cases (48%). A B-cell origin prevailed (34 [87%]). Feline leukemia virus (FeLV) p27 or gp70 antigen was detected in 21 lymphomas (54%). URT lymphomas were aggressive, with survival varying from 0 to 301 days (mean, 53 days). Epitheliotropism in 8 B-cell lymphomas (80%) and in 2 T-cell lymphomas (20%) correlated with prolonged survival. Age younger or older than 10 years had a negative prognostic value. Lymphoplasmacytic inflammation and FeLV infection may represent favoring factors for URT lymphoma development. PMID:24903757

  16. Functional improvement after motor training is correlated with synaptic plasticity in rat thalamus.

    PubMed

    Ding, Yuchuan; Li, Jie; Lai, Qin; Azam, Salman; Rafols, José A; Diaz, Fernando G

    2002-12-01

    The goals of this study were to determine whether functional outcome after motor training in rats was linked to synaptic plasticity in thalamus, and whether the Rota-rod apparatus, widely used to test motor function, could be used as an easy and quantitative motor skill training procedure. Adult female Sprague-Dawley rats (n = 39) were evaluated under three training conditions: 1. Movement requiring balance and coordination skills on Rota-rod; 2. simple exercise on treadmill; 3. nontrained controls. Motor function was evaluated by a series of motor tests (foot fault placing, parallel bar crossing, rope and ladder climbing) before and 14 or 28 days after training procedure. Synaptic strength in brain was assessed by synaptophysin immunocytochemistry. After 14 days of training, Rota-rod-trained animals significantly (p < 0.01) improved motor performance, compared to treadmill and nontrained animals. Animals with up to 28 days of simple exercises on the treadmill did not show a significantly improved performance on most motor tasks, except for an improvement in foot fault placing. Intensive synaptophysin immunoreactivity was present in the right but not the left mediodorsal and ventromedial nuclei of thalamus in Rota-rod-trained rats at 14 and 28 days, and in treadmill-trained rats at 28 days. The data suggested that functional outcome is effectively improved by motor skill training rather than by simple exercises, and this may be related, at least partially, to uniquely lateralized synaptogenesis in the thalamus. Both Rota-rod and treadmill could be quantitatively used in rats for motor training of different complexity. PMID:12500709

  17. Longer term improvement in neurocognitive functioning and affective distress among methamphetamine users who achieve stable abstinence.

    PubMed

    Iudicello, Jennifer E; Woods, Steven P; Vigil, Ofilio; Scott, J Cobb; Cherner, Mariana; Heaton, Robert K; Atkinson, J Hampton; Grant, Igor

    2010-08-01

    Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little in the way of 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. A total of 38 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 MA 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 than 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. PMID:20198527

  18. Improving the Robustness of a Parallel Robot Using Predictive Functional Control (PFC) Tools

    Microsoft Academic Search

    Aline I. Maalouf; Manchester Grand Hyatt Hotel

    2006-01-01

    Heuristically, it was claimed in the literature that increasing the time-constant 'Tref' of the reference trajectory in predictive functional control (PFC) improves the closed-loop stability because the controller will be able to tolerate model mismatch which is difficult for a zero time-constant reference trajectory (a pure set-point) to tolerate. On the other hand, PFC uses 'Tref' as the main tuning

  19. Molecular mechanisms that could contribute to prolonged effectiveness of PDE5 inhibitors to improve erectile function

    Microsoft Academic Search

    S H Francis; G Z Morris; J D Corbin

    2008-01-01

    Cyclic guanosine monophosphate (cGMP) in penile vascular smooth muscle cells (VSMC) plays a key role in promoting penile erection. Phosphodiesterase-5 (PDE5) in VSMC breaks down cGMP to counter this effect. Sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis), treatments for erectile dysfunction, inhibit PDE5 action. Many men with erectile dysfunction have improved erectile function after plasma inhibitor concentration falls below therapeutic

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

    PubMed Central

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

    2010-01-01

    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. PMID:20198527

  1. Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering

    Microsoft Academic Search

    Sagar N. Doshi; Ian F. W. McDowell; Stuart J. Moat; Nicola Payne

    2002-01-01

    Background—Homocysteine is a risk factor for coronary artery disease (CAD), although a causal relation remains to be proven. The importance of determining direct causality rests in the fact that plasma homocysteine can be safely and inexpensively reduced by 25% with folic acid. This reduction is maximally achieved by doses of 0.4 mg\\/d. High-dose folic acid (5 mg\\/d) improves endothelial function

  2. A quality function deployment approach for improving technical library and information services: a case study

    Microsoft Academic Search

    Kwai-Sang Chin; Kit-Fai Pun; W. M. Leung; Henry Lau

    2001-01-01

    Quality function deployment (QFD) stresses customer-driven planning, continuous improvement and people participation. This paper elaborates a six-stage QFD approach based on an empirical study of the provision of the library and information services (LIS) in a technical organisation in Hong Kong. Customer requirements are identified through the focus-group brainstorming and critical-incident interviews with users. The study identified 45 critical incidents,

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

    PubMed Central

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

    2014-01-01

    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. PMID:24773463

  4. Improvement of myocardial function and metabolism in diabetic rats by the carnitine palmitoyl transferase inhibitor Etomoxir.

    PubMed

    Schmitz, F J; Rösen, P; Reinauer, H

    1995-12-01

    The effect of Etomoxir as a carnitine palmitoyl transferase I-inhibitor was investigated in normal and chronic diabetic rats. Etomoxir (18 mg/kg) was given daily for 8 days by intraperitoneal injection in order to inhibit the oxidation of fatty acids and to increase the metabolism of glucose. This carnitine palmitoyl transferase I-inhibitor significantly improved and almost normalized the decreased heart function in chronic diabetic rats. Additionally to the improvement of ventricular heart function, alterations in the conducting system of the diabetic heart were significantly ameliorated. The serum concentrations of glucose, glycerol, cholesterol, tricylglycerol, phospholipids, and beta-hydroxybutyrate were significantly lower in comparison to untreated diabetic animals, while the serum concentration of free fatty acids markedly increased. In addition to the improvement of ventricular heart function, the carnitine content of heart and liver increased in the Etomoxir-treated rats. On the other hand, the lipid content of heart and liver increased in the Etomoxir-treated rats. On the other hand, the lipid content of heart and liver increased significantly. Thus, Etomoxir may be valuable not only as a potential anti-diabetic drug but also as a lipid-lowering agent for the treatment of diabetic related dyslipoproteinaemias and, in addition, as an agent in the treatment of diabetic cardiomyopathy. However, a long-term evaluation of the metabolic consequences of the blocked carnitine palmitoyltransferase I is necessary. PMID:8750778

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

    PubMed Central

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

    2012-01-01

    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. PMID:21715240

  6. Importance of specificity, amount, and intensity of locomotor training to improve ambulatory function in patients poststroke.

    PubMed

    Hornby, T George; Straube, Donald S; Kinnaird, Catherine R; Holleran, Carey L; Echauz, Anthony J; Rodriguez, Kelly S; Wagner, Eric J; Narducci, Elizabeth A

    2011-01-01

    The majority of individuals poststroke recover the ability to walk overground, although residual impairments contribute to reduced walking speed, spatiotemporal asymmetries, inefficient gait, and limited walking activity in the home and community. A substantial number of studies have investigated the effects of various interventions on locomotor function in individuals poststroke; these studies vary widely in types of tasks practiced, the amount of practiced activities, and the intensity or workload during the intervention. In contrast, basic and applied studies have identified specific parameters of training that could be applied towards treatment of patients poststroke. More directly, the specificity, amount, and intensity of walking practice are thought to be critical variables of rehabilitation interventions that can facilitate plasticity of neuromuscular and cardiopulmonary systems and result in improved locomotor function. In the present commentary, we delineate the evidence and physiological rationale for providing large amounts of high-intensity locomotor training to improve ambulatory function in individuals poststroke. Additional evidence is presented to indicate that improvements in non-walking tasks, such as static balance and performance of transfers, may also occur following locomotor training. We further evaluate previous and more recent studies in the context of these parameters and provide suggestions for providing locomotor training for patients with stroke in the clinical setting. PMID:21914594

  7. Traditional Chinese Medicine Tongxinluo Improves Cardiac Function of Rats with Dilated Cardiomyopathy

    PubMed Central

    Shen, Fang-Fang; Jiang, Ting-Hui; Jiang, Jin-Qi; Lou, Ying; Hou, Xu-Min

    2014-01-01

    The study aimed at testing the hypothesis that tongxinluo capsule might exert its cardioprotective effect by preventing ventricular remodeling and improving coronary microvascular function in a rat model of doxorubicin-induced dilated cardiomyopathy (DCM). Rats that survived DCM induction were randomly divided into three groups to be given 1.5 g·kg?1·day?1 (TXL-H, n = 9) or 0.15 g·kg?1·day?1 (TXL-L, n = 10) of tongxinluo, or normal saline at the same volume (DCM-C, n = 10) intragastrically. Age matched normal rats treated with normal saline were used as normal controls (NOR-C, n = 9). After four weeks of treatment, the DCM-C, TXL-H, and TXL-L groups exhibited significant cardiac dysfunction, left ventricular remodeling, and coronary microvascular dysfunction, compared with the NOR-C rats. However, myocardial functional parameters were significantly improved and microvascular density (MVD) increased in the TXL-H group compared with the DCM-C group (all P < 0.01). Left ventricular remodeling was prevented. There were close linear relationships between CVF and LVEF (r = ?0.683, P < 0.05), MVD and LVEF (r = 0.895, P < 0.05), and MVD and CVF (r = ?0.798, P < 0.05). It was indicated that high-dose tongxinluo effectively improved cardiac function in rat model of DCM. PMID:25614749

  8. Exenatide Pretreatment Improved Graft Function in Nonhuman Primate Islet Recipients Compared to Treatment after Transplant Only

    PubMed Central

    Buss, Jill L.; Rajab, Amer; Essig, Elizabeth D.; Bergdall, Valerie K.; Wang, Jie; Osei, Kwame

    2012-01-01

    The GLP-1 receptor agonist, exenatide, has previously been shown to improve insulin secretion, protect beta cells from apoptosis, and promote beta cell regeneration. We propose that pretreatment with exenatide will promote islet graft survival and improve graft function. Pancreatectomized cynomolgus monkeys underwent islet allotransplantation and were treated with exenatide beginning on day 0 or day ?2. A third group of animals was treated with an immunosuppressive regimen while a fourth group remained untreated. Fasting blood glucose (FBG) was used to evaluate graft function along with intravenous glucose tolerance tests (IVGTTs) performed at study endpoint (day 10 for untreated and posttransplant exenatide or day 90 for pretreatment exenatide and immunosuppression). The average FBG for pre-treated animals day 5 following transplant was 52.7 ± 14.8?mg/dl, compared to 154.3 ± 105.5?mg/dl for animals treated only following transplant, 59.4?mg/dl ±12.1 for animals treated with immunosuppression, and 265.5 ± 172.3?mg/dl for untreated animals. IVGTTs performed at study endpoint showed normal glucose and insulin curves in the pre-treated exenatide and immunosuppression groups only, with beta cell function actually improving after transplant in the pre-treated group. We conclude, therefore, that exenatide pre-treatment can successfully maintain islet graft survival in nonhuman primates. PMID:23056916

  9. Effects of extract derived from Eriobotrya japonica on liver function improvement in rats.

    PubMed

    Nishioka, Yutaka; Yoshioka, Saburo; Kusunose, Masahiko; Cui, Tailin; Hamada, Atuhide; Ono, Masahide; Miyamura, Mituhiko; Kyotani, Shojiro

    2002-08-01

    Eriobotrya japonica is considered a medicinal plant, and its leaves (Eriobotrya folia) have been used to treat skin diseases, as well as to relieve inflammation, pain, coughing, and sputa. In our evaluation of the pharmacological efficacy of the seed extracts, constituents of the seeds were found to contain the unsaturated fatty acids linolenic and linoleic acids and the sterol beta-sitosterol in the 70% EtOH and the MeOH extracts. The seed extracts were orally administered to rats with dimethylnitrosamine-induced hepatopathy, and blood L-asparate aminotransferase (AST) and L-alanine aminotransferase (ALT) levels, liver retinoid level, and hydroxyproline level were measured. Liver fibrosis rates calculated after Azan-Mallory staining and evaluation of the liver function-improving effects of extracts were showed that AST, ALT, and hydroxyproline levels and liver fibrosis rates were significantly lower, and retinoid levels were significantly higher in hepatopathic rats treated with 70% EtOH and MeOH extracts of the seed than in water-treated control rats. This suggests that the positive effect on liver function of the extracts varies depending on the extracting solvent used. 70% EtOH and MeOH extract of the seeds inhibited the development of liver fibrosis in hepatopathic rats, thus exhibiting potent improvement. The unsaturated linolenic and linoleic acids and the sterol beta-sitosterol contained in these extracts may also contribute to the improvement of liver function. PMID:12186409

  10. Early improvement of functional mitral regurgitation in patients with idiopathic dilated cardiomyopathy.

    PubMed

    Stolfo, Davide; Merlo, Marco; Pinamonti, Bruno; Poli, Stefano; Gigli, Marta; Barbati, Giulia; Fabris, Enrico; Di Lenarda, Andrea; Sinagra, Gianfranco

    2015-04-15

    The aim of the study was to assess the clinical and prognostic impact of early functional mitral regurgitation (FMR) improvement on the outcome of patients with idiopathic dilated cardiomyopathy (IDC). The prevalence and prognostic role of FMR improvement, particularly at early follow-up, in patients with IDC are still unclear. From 1988 to 2009, we enrolled 470 patients with IDC with available FMR data at baseline and after 6 ± 2 months. According to the evolution of FMR, patients were classified into 3 groups: stable absent-mild FMR, early FMR improvement (downgrading from moderate-severe to absent-mild), and persistence/early development of moderate-severe FMR. At baseline, 177 of 470 patients (38%) had moderate-severe FMR. Patients with early FMR improvement had significantly better survival rate-free from heart transplant with respect to those with persistence/early development of moderate-severe FMR (93%, 81%, and 66% vs 91%, 64%, and 52% at 1, 6, and 12 years, respectively; p = 0.044). At 6-month follow-up multivariate analysis, FMR improvement was associated with better prognosis (hazard ratio 0.78, 95% confidence interval [CI] 0.64 to 0.96, p = 0.02); the other independent predictors were male gender, heart failure duration, and early re-evaluation of the New York Heart Association class and left ventricle systolic function. This model provided more accurate risk stratification compared with the baseline model (Net Reclassification Index 80% at 12 months and 41% at 72 months). In conclusion, in a large cohort of patients with IDC receiving optimal medical treatment, early improvement of FMR was frequent (53%) and emerged as a favorable independent prognostic factor with an incremental short- and long-term power compared with the baseline evaluation. PMID:25721482

  11. Improvement of functional properties of ?-lactoglobulin glycated through the Maillard reaction is related to the nature of the sugar

    Microsoft Academic Search

    François Chevalier; Jean-Marc Chobert; Yves Popineau; Marie Georgette Nicolas; Thomas Haertlé

    2001-01-01

    The improvement of functional properties of proteins available in large quantity using non-toxic chemical modifications is of a great interest for the food industry. In this study, the Maillard reaction was used to improve the functional properties (solubility, heat stability, emulsifying and foaming properties) of ?-lactoglobulin (BLG) glycated with several sugars (arabinose, galactose, glucose, lactose, rhamnose or ribose). Protein samples

  12. Modified ultrafiltration improves global left ventricular systolic function after open-heart surgery in infants and children

    Microsoft Academic Search

    Rajiv R. Chaturvedi; Darryl F. Shore; Paul A. White; Michael H. Scallan; W. W. Gothard; Andrew N. Redington; Christopher Lincoln

    2010-01-01

    Abstract Objectives: Modified ultrafiltration increases blood pressure and cardiac index following open-heart surgery in children, but it is unclear if this is secondary to an improvement,in global left ventricular function. A previous report has suggested that left ventricular systolic function as assessed in a single chord is improved by ultrafiltration (Davies MJ, Nguyen K, Gaynor JW, Elliott MJ. Modified ultrafiltration

  13. Modified ultrafiltration improves global left ventricular systolic function after open-heart surgery in infants and children

    Microsoft Academic Search

    Rajiv R. Chaturvedi; Darryl F. Shore; Paul A. White; Michael H. Scallan; John W. W. Gothard; Andrew N. Redington; Christopher Lincoln

    1999-01-01

    Objectives: Modified ultrafiltration increases blood pressure and cardiac index following open-heart surgery in children, but it is unclear if this is secondary to an improvement in global left ventricular function. A previous report has suggested that left ventricular systolic function as assessed in a single chord is improved by ultrafiltration (Davies MJ, Nguyen K, Gaynor JW, Elliott MJ. Modified ultrafiltration

  14. Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke

    PubMed Central

    Ruscher, Karsten; Kuric, Enida; Liu, Yawei; Walter, Helene L; Issazadeh-Navikas, Shohreh; Englund, Elisabet; Wieloch, Tadeusz

    2013-01-01

    After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclo-tetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3+) and CD3+/CD4+ T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke. PMID:23632969

  15. Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans.

    PubMed

    Kobayakawa, Kazu; Kumamaru, Hiromi; Saiwai, Hirokazu; Kubota, Kensuke; Ohkawa, Yasuyuki; Kishimoto, Junji; Yokota, Kazuya; Ideta, Ryosuke; Shiba, Keiichiro; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Iwamoto, Yukihide; Okada, Seiji

    2014-10-01

    Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor ?B (NF-?B) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson ?(2) analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration ?126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, -1.37; 95% confidence interval, -2.65 to -0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes. Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury. PMID:25273098

  16. An Improved Instrument Table for Use in Functional Endoscopic Sinus Surgery

    PubMed Central

    Schmitz, Pia M.; Gollnick, Iris; Modemann, Susanne; Rothe, Anja; Niegsch, Ralf; Strauss, Gero

    2015-01-01

    Background The clinical motivation for the current study was that various instrument tables are located far away from the patient’s head, and the only way for the surgeon to access an instrument is via a scrub nurse. Thus, the idea for this study was the development and evaluation of an improved and conveniently positioned instrument table. Material/Methods An improved instrument table (IT) was designed, built, and tested. We assessed its use in 150 surgeries from 1 October 2013 to 30 June 2014 (group A), and another 150 surgeries without use of the IT from 1 February 2013 to 31 October 2014 as a control group (group B). Results With use of the improved IT during functional endoscopic sinus surgery (FESS), preparation-time was extended by 0.1 min and the SLOT-time was reduced by 19.6%. The number of different instruments (35.3%) used was reduced, as well as the number of manual interactions with instruments (7.8%) and the number of manual interactions with the scrub nurse (66.1%). In addition, the ergonomics with use of the IT improved by 40.0%. The only potential disadvantage was a reduction of working space and thereby a constraint of the scope. Compared to the benefits, this problem is minor. Conclusions Conclusively, the improved IT is of value for everyday use in surgery and offers a great benefit for FESS, and may be useful in other kinds of surgery (e.g., duraplasty). PMID:26098739

  17. Levodopa does not improve function in individuals with dystonic cerebral palsy.

    PubMed

    Pozin, Inna; Bdolah-Abram, Tali; Ben-Pazi, Hilla

    2014-04-01

    Although levodopa is the main treatment for dystonia, its role in cerebral palsy has not been assessed. We hypothesized that levodopa will improve upper limb function in individuals with cerebral palsy. Nine participants (age 16.8 ± 5.6 years) with quadriplegic cerebral palsy and upper limb dystonia were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Function was assessed before and after 2 weeks of treatment of levodopa and placebo using box-and-blocks, 9-hole pegs, dynamometer recordings, and Quality of Upper Extremity Skills Test. No benefits for upper limb functional performance were found following levodopa (6.65 ± 1.66 mg/kg/d) treatment compared to placebo. No side effects were reported. PMID:23349519

  18. Integrated strategy for improving functional connectivity mapping using multiecho fMRI

    PubMed Central

    Kundu, Prantik; Brenowitz, Noah D.; Voon, Valerie; Worbe, Yulia; Vértes, Petra E.; Inati, Souheil J.; Saad, Ziad S.; Bandettini, Peter A.; Bullmore, Edward T.

    2013-01-01

    Functional connectivity analysis of resting state blood oxygen level–dependent (BOLD) functional MRI is widely used for noninvasively studying brain functional networks. Recent findings have indicated, however, that even small (?1 mm) amounts of head movement during scanning can disproportionately bias connectivity estimates, despite various preprocessing efforts. Further complications for interregional connectivity estimation from time domain signals include the unaccounted reduction in BOLD degrees of freedom related to sensitivity losses from high subject motion. To address these issues, we describe an integrated strategy for data acquisition, denoising, and connectivity estimation. This strategy builds on our previously published technique combining data acquisition with multiecho (ME) echo planar imaging and analysis with spatial independent component analysis (ICA), called ME-ICA, which distinguishes BOLD (neuronal) and non-BOLD (artifactual) components based on linear echo-time dependence of signals—a characteristic property of BOLD signal changes. Here we show for 32 control subjects that this method provides a physically principled and nearly operator-independent way of removing complex artifacts such as motion from resting state data. We then describe a robust estimator of functional connectivity based on interregional correlation of BOLD-independent component coefficients. This estimator, called independent components regression, considerably simplifies statistical inference for functional connectivity because degrees of freedom equals the number of independent coefficients. Compared with traditional connectivity estimation methods, the proposed strategy results in fourfold improvements in signal-to-noise ratio, functional connectivity analysis with improved specificity, and valid statistical inference with nominal control of type 1 error in contrasts of connectivity between groups with different levels of subject motion. PMID:24038744

  19. An integrin inhibiting molecule decreases oxidative damage and improves neurological function after spinal cord injury.

    PubMed

    Bao, Feng; Chen, Yuhua; Schneider, Kara A; Weaver, Lynne C

    2008-12-01

    Our previous studies have shown that treatment with an alpha4beta1 integrin blocking antibody after spinal cord injury (SCI) in rats decreases intraspinal inflammation and oxidative damage, improving neurological function. Here, we studied effects of a high affinity small molecule alpha4beta1 inhibitor, BIO5192. First, rats were treated intravenously with BIO5192 (10 mg/kg) or with vehicle (controls) to assess effects of integrin blockade for 24 h or 72 h after thoracic clip-compression SCI. BIO5192 treatment significantly decreased the MPO enzymatic activity (neutrophil infiltration) and ED-1 expression (macrophage density) by 40% and 38% at 24 h and by 52% and 25% at 72 h post injury, respectively. In cord homogenates, BIO5192 treatment decreased expression of the oxidative enzymes gp91(phox), inducible nitric oxide and cyclooxygenase-2 by approximately 40% at both times of analysis. Free radical concentration decreased by 30% and lipid peroxidation decreased by 34% and 46%, respectively, at 24 h and 72 h after SCI. Next, after blockade by BIO5192 for 72 h, neurological outcomes were analyzed for 1-6 weeks after SCI. Motor function significantly improved when assessed by an open-field test. Treated rats planter placed their hind paws and/or dorsal stepped, with weight support, whereas controls only swept their hindlimbs. BIO5192 treatment also decreased mechanical allodynia elicited from the trunk and hind paw by up to 35%. This improved function correlated with decreased lesion size and spared myelin-containing white matter. The neurological improvement offered by this neuroprotective strategy supports the potential for an anti-integrin treatment for SCI. PMID:18926823

  20. Modulating molecular chaperones improves sensory fiber recovery and mitochondrial function in diabetic peripheral neuropathy.

    PubMed

    Urban, Michael J; Pan, Pan; Farmer, Kevin L; Zhao, Huiping; Blagg, Brian S J; Dobrowsky, Rick T

    2012-05-01

    Quantification of intra-epidermal nerve fibers (iENFs) is an important approach to stage diabetic peripheral neuropathy (DPN) and is a promising clinical endpoint for identifying beneficial therapeutics. Mechanistically, diabetes decreases neuronal mitochondrial function and enhancing mitochondrial respiratory capacity may aid neuronal recovery from glucotoxic insults. We have proposed that modulating the activity and expression of heat shock proteins (Hsp) may be of benefit in treating DPN. KU-32 is a C-terminal Hsp90 inhibitor that improved thermal hypoalgesia in diabetic C57Bl/6 mice but it was not determined if this was associated with an increase in iENF density and mitochondrial function. After 16 weeks of diabetes, Swiss Webster mice showed decreased electrophysiological and psychosensory responses and a >30% loss of iENFs. Treatment of the mice with ten weekly doses of 20mg/kg KU-32 significantly reversed pre-existing deficits in nerve conduction velocity and responses to mechanical and thermal stimuli. KU-32 therapy significantly reversed the pre-existing loss of iENFs despite the identification of a sub-group of drug-treated diabetic mice that showed improved thermal sensitivity but no increase in iENF density. To determine if the improved clinical indices correlated with enhanced mitochondrial activity, sensory neurons were isolated and mitochondrial bioenergetics assessed ex vivo using extracellular flux technology. Diabetes decreased maximal respiratory capacity in sensory neurons and this deficit was improved following KU-32 treatment. In conclusion, KU-32 improved physiological and morphologic markers of degenerative neuropathy and drug efficacy may be related to enhanced mitochondrial bioenergetics in sensory neurons. PMID:22465570

  1. Analysis on the expression and function of syndecan in the Pacific white shrimp Litopenaeus vannamei.

    PubMed

    Yang, Hui; Li, Shihao; Li, Fuhua; Wen, Rong; Xiang, Jianhai

    2015-08-01

    Syndecan is considered to be a multifunctional protein which functions as a cell surface receptor involved in cell adhesion, migration, cytoskeleton organization and differentiation. Previous bioinformatic analysis has revealed that syndecan in shrimp might interact with white spot syndrome virus (WSSV). In the present study, we experimentally studied the function of syndecan in shrimp immunity. The syndecan from Litopenaeus vannamei (LvSDC) was cloned and analyzed. The full-length cDNA of LvSDC was 1005?bp, consisting of 59?bp 5'-UTR, 253?bp 3'-UTR, and 693?bp open reading frame encoding 230 amino acids. LvSDC consisted of an extracellular domain (ED), a transmembrane domain (TM) and a cytoplasmic domain (CD). TM and CD shared high similarities with those of syndecan proteins from other species. LvSDC was ubiquitously expressed in all tested tissues, with the highest level in Oka. After WSSV challenge, the transcription level of LvSDC in Oka was apparently up-regulated. Recombinant LvSDC protein and its rabbit polyclonal antibody were prepared for detecting the location of LvSDC in hemocytes using immunocytochemistry approach. Data showed that LvSDC mainly located at the cell membrane and the cytoplasm of hemocytes. After silencing of LvSDC with siRNA, the WSSV copy numbers and mortality of shrimp after WSSV infection were both significantly decreased. These data provide useful information for understanding the immune mechanism of shrimp to WSSV infection. PMID:25847874

  2. On the effects on MV\\/LV component expected life of slow voltage variations and harmonic distortion

    Microsoft Academic Search

    D. Gallo; R. Langella; A. Testa

    2002-01-01

    The effects of electrical stress on MV\\/LV component expected life due to slow voltage variations and harmonic distortion are considered in a realistic scenario characterized by multimodal distributions and the presence of correlations. A simplified approach based on peak voltage mean value, recently proposed, and a new proposal are tested with reference to case studies and field measurements. The slow

  3. Post-Injury Estrogen Treatment of Chronic Spinal Cord Injury Improves Locomotor Function in Rats

    PubMed Central

    Sribnick, Eric A.; Samantaray, Supriti; Das, Arabinda; Smith, Joshua; Matzelle, D. Denise; Ray, Swapan K.; Banik, Naren L.

    2011-01-01

    Spinal cord injury (SCI) causes loss of neurological function and, depending on serverity, may cause paralysis. The only recommended pharmacotherapy for the treatment of SCI is high-dose methylprednisolone and its use is controversial. We have previously shown that estrogen treatment attenuated cell death, axonal and myelin damage, calpain and caspase activities, and inflammation in acute SCI. The aim of this study was to examine whether post-treatment of SCI with estrogen would improve locomotor function by protecting cells and axons and reducing inflammation during chronic phase following injury. Moderately severe injury (40 g.cm force) was induced in male Sprague-Dawley rats following laminectomy at T10. Three groups of animals were used: sham (laminectomy only), vehicle (dimethyl sulfoxide or DMSO) treated injury group, and estrogen treated injury group. Animals were treated with 4 mg/kg estrogen at 15 min and 24 h post-injury followed by 2 mg/kg estrogen daily for the next 5 days. Following treatment, animals were sacrificed at the end of 6 weeks following injury, and 1-cm segments of spinal cord (lesion, rostral to lesion, and caudal to lesion) were removed for biochemical analyses. Estrogen treatment reduced COX-2 activity, blocked NF-?B translocation, prevented glial reactivity, attenuated neuron death, inhibited activation and activity of calpain and caspase-3, decreased axonal damage, reduced myelin loss in the lesion and penumbra, and improved locomotor function when compared with vehicle treated animals. These findings suggest that estrogen may be useful as a promising therapeutic agent for prevention of damage and improvement of locomotor function in chronic SCI. PMID:20091771

  4. Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in rats.

    PubMed

    Sribnick, Eric A; Samantaray, Supriti; Das, Arabinda; Smith, Joshua; Matzelle, D Denise; Ray, Swapan K; Banik, Naren L

    2010-06-01

    Spinal cord injury (SCI) causes loss of neurological function and, depending on serverity, may cause paralysis. The only recommended pharmacotherapy for the treatment of SCI is high-dose methylprednisolone, and its use is controversial. We have previously shown that estrogen treatment attenuated cell death, axonal and myelin damage, calpain and caspase activities, and inflammation in acute SCI. The aim of this study was to examine whether posttreatment of SCI with estrogen would improve locomotor function by protecting cells and axons and reducing inflammation during the chronic phase following injury. Moderately severe injury (40 g . cm force) was induced in male Sprague-Dawley rats following laminectomy at T10. Three groups of animals were used: sham (laminectomy only), vehicle (dimethyl sulfoxide; DMSO)-treated injury group, and estrogen-treated injury group. Animals were treated with 4 mg/kg estrogen at 15 min and 24 hr postnjury, followed by 2 mg/kg estrogen daily for the next 5 days. After treatment, animals were sacrificed at the end of 6 weeks following injury, and 1-cm segments of spinal cord (lesion, rostral to lesion, and caudal to lesion) were removed for biochemical analyses. Estrogen treatment reduced COX-2 activity, blocked nuclear factor-kappaB translocation, prevented glial reactivity, attenuated neuron death, inhibited activation and activity of calpain and caspase-3, decreased axonal damage, reduced myelin loss in the lesion and penumbra, and improved locomotor function compared with vehicle-treated animals. These findings suggest that estrogen may be useful as a promising therapeutic agent for prevention of damage and improvement of locomotor function in chronic SCI. (c) 2010 Wiley-Liss, Inc. PMID:20091771

  5. Delayed administration of a PTEN inhibitor BPV improves functional recovery after experimental stroke.

    PubMed

    Mao, L; Jia, J; Zhou, X; Xiao, Y; Wang, Y; Mao, X; Zhen, X; Guan, Y; Alkayed, N J; Cheng, J

    2013-02-12

    Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors administered prior to or immediately after experimental stroke confer acute neuroprotection. However, it remains unclear if delayed treatment with a PTEN inhibitor improves long-term functional recovery after stroke. We addressed the issue in this study. Adult male mice were subjected to 1h of middle cerebral artery occlusion (MCAO) followed by treatment with a well-established PTEN inhibitor BPV or saline daily for 14 days, starting at 24h after MCAO. Functional recovery was assessed with behavioral tests and acute infarct volumes were analyzed histologically. Delayed BPV treatment did not reduce infarction during the acute phase, but significantly improved long-term functional recovery after MCAO. Since PTEN is a critical intrinsic inhibitory factor in axonal regeneration, we further examined BPV effects on axonal densities following MCAO using bielschowsky silver staining and immunohistochemistry with antibodies against myelin basic protein. Delayed BPV treatment significantly increased axon densities in the ischemic brain at 14 days after MCAO. Moreover, PTEN expression persistently remained high in the ischemic brain over 14 days after MCAO, and BPV treatment increased post-ischemic activation of Akt and mTOR in the ischemic brain. Akt and mTOR activation are the well-established cascades downstream to PTEN inhibition and have been shown to contribute to post-injury axonal regrowth in response to PTEN inhibition. Consistently, in an in vitro neuronal ischemia model, BPV enhanced axonal outgrowth of primary cortical neurons after oxygen-glucose deprivation and the enhancing effects were abolished by Akt/mTOR inhibition. In conclusion, delayed BPV treatment improved functional recovery from experimental stroke possibly via enhancing axonal growth and Akt/mTOR activation contributed to BPV-enhanced post-stroke axon growth. PMID:23219909

  6. Tpd, a damped predominant period function with improvements for magnitude estimation

    NASA Astrophysics Data System (ADS)

    Rietbrock, A.; Hildyard, M.

    2009-12-01

    Quantifying the Magnitude of an earthquake has been a fundamental endeavour in seismology since its beginnings as a science. Nevertheless, it can sometimes be hours before traditional methods of calculating magnitudes reach a robust value. It is now recognised, whether for early warning measures and planning civil response, or simply for public interest, that it is useful to have the earliest possible measures of earthquake magnitudes after the occurrence of large earthquakes. Clearly, such methods must concentrate on information in the first P-wave arrivals, rather than waiting for later seismic phases. In recent years, a great deal of interest has been stimulated by attempts to use a time-domain estimate of the predominant period of a waveform, to estimate seismic magnitude from the very first P-wave arrivals in seismograms. We use an aftershock dataset of over 1500 events (ML = 0.7-5.8), to study the relationship between magnitude, and the predominant period calculated from the initial P-wave arrival. We calculate TpMax (Nakamura, 1988; Allen and Kanamori, 2003), and find that there is a trend between TpMax and magnitude, as reported by previous authors. However, the trend is weaker than expected. We calculate an alternative predominant period function, ?c (Kanamori, 2005), and find virtually no relationship to magnitude for this data. We therefore implement a modified, damped version of the Tp function, which we term Tpd. The Tpd function introduces an additional term, Ds, aimed at stabilising the predominant period function in the transition between noise and signal. We show that TpdMax has an improved relationship to magnitude, with the average coefficient of determination (R2) increasing from 0.15 for TpMax to 0.5 for TpdMax. This improvement is consistent for all stations. We then apply the Tpd function to the displacement waveforms, calling the associated function Tpd_D. The trend in the Tpd_DMax vs. magnitude relationship is superior to that of ?c. Analysing the Tpd function, we conclude that improvements result from damping large values in the noise region, or reducing spikes during the noise-to-signal transition, thus preventing incorrect maxima being selected. We conclude that the performance of TpdMax is superior to TpMax and ?c, and should be considered for real-time magnitude estimation.

  7. Left ventricular diastolic function after anthracycline chemotherapy in childhood: relation with systolic function, symptoms, and pathophysiology

    Microsoft Academic Search

    F. A. BuLock; M. G. Mott; A. Oakhill; R. P. Martin

    1995-01-01

    OBJECTIVES--To examine left ventricular (LV) diastolic function in patients previously treated with anthracycline drugs for childhood malignancy. To consider clinical relevance, relations with systolic dysfunction, and the pathophysiology of anthracycline cardiotoxicity. DESIGN--Cross sectional echocardiographic study of LV function. SETTING--Supraregional centre for paediatric cardiology, principal centre for the treatment of childhood malignancy in southwest England. PATIENTS--226 of 236 patients surviving between

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

    PubMed Central

    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

    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. PMID:23527037

  9. Increased LV apical untwist during preload reduction in healthy humans: an echocardiographic speckle tracking study during lower body negative pressure.

    PubMed

    Hodt, Anders; Hisdal, Jonny; Stugaard, Marie; Stranden, Einar; Atar, Dan; Steine, Kjetil

    2015-03-01

    We sought to investigate the effect of reduced preload on left ventricle (LV) untwist and early diastolic filling in healthy individuals. Twelve healthy men, 22 (22, 23) years of age, were examined at rest and during applied lower body negative pressure (LBNP) of -20 mmHg and -40 mmHg, respectively. Regional untwist and untwist rate during IVRT were calculated at LV basal, papillary, subpapillary, and apical short axis levels by two dimensional speckle tracking echocardiography. Left ventricle early diastolic filling was assessed by transmitral E-wave (E) peak velocity by pulsed Doppler and flow propagation velocity (Vp) by color M-mode Doppler and early diastolic pulsed Doppler tissue velocities (E') from septal and lateral mitral annulus. From rest to LBNP -40 mmHg, the LV untwist and untwist rate at subpapillary level increased from 2.3 (1.4, 3.5) to 4.5 (3.1, 7.6) degrees and from -36 (-51, -25) to -69 (-127, -42) °/s (P < 0.001, P = 0.003), respectively, while apical untwist and untwist rate increased from 3.9 (2.3, 4.3) to 7.6 (6.4, 10.5) degrees and from -51 (-69, -40) to -118 (-170, -84) °/s (P < 0.001, P < 0.001), respectively. Since untwist and untwist rate at the basal level were unchanged, this created markedly larger base to apical untwist and untwist rate gradients from rest to LBNP -40 mmHg. E, Vp, and E' were reduced by 34, 32, and 39%, respectively. LV untwist and untwist rate during IVRT were increased at apical levels, which might be a physiological mechanism to minimize the impairment in LV early diastolic filling during preload reduction. PMID:25802362

  10. Ketogenic Diet Improves Forelimb Motor Function after Spinal Cord Injury in Rodents

    PubMed Central

    Streijger, Femke; Plunet, Ward T.; Lee, Jae H. T.; Liu, Jie; Lam, Clarrie K.; Park, Soeyun; Hilton, Brett J.; Fransen, Bas L.; Matheson, Keely A. J.; Assinck, Peggy; Kwon, Brian K.; Tetzlaff, Wolfram

    2013-01-01

    High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (?-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited. PMID:24223849

  11. Enriched environment induces angiogenesis and improves neural function outcomes in rat stroke model.

    PubMed

    Yu, Kewei; Wu, Yi; Zhang, Qi; Xie, Hongyu; Liu, Gang; Guo, Zhenzhen; Li, Fang; Jia, Jie; Kuang, Shenyi; Hu, Ruiping

    2014-12-15

    Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury has neuroprotective benefits in animal models, including enhancing functional recovery after ischemic stroke. However, the mechanism underlying this effect remains unclear. To clarify this critical issue, the current study investigated the effects of EE on the improvement of damaged neural function and the induction of angiogenesis. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion followed by reperfusion. Neurological status scores were used to evaluate neural function on postoperative days 2, 7, and 14. A beam-walking task was used to test the recovery of motor behavior on postoperative days 2, 5, 10, and 15. We also used a Morris water maze task to examine whether EE protected learning and memory performance. The specific marker of angiogenesis of CD31 was examined by western blot. Angiogenesis around the peri-infarction region was assayed by laser scanning confocal microscopy (LSCM) after 14 days of EE exposure starting 24h after ischemia. Neurological status scores of animals in the EE group were significantly higher than those in the standard housing condition (SC) control group from the seventh day after ischemic. EE accelerated the recovery of motor coordination and integration and also improved learning and memory performance after cerebral ischemia. Furthermore, EE increased CD31 levels and promoted angiogenesis of cortex in the peri-infarction region compared to the SC group. Neural function outcomes are positively correlated with post-ischemia angiogenesis. These findings suggest that EE plays an important role in the recovery of damaged neural function via regulation of angiogenesis after ischemia. PMID:25455300

  12. Combination treatment of experimental stroke with Niaspan and Simvastatin, reduces axonal damage and improves functional outcome.

    PubMed

    Shehadah, Amjad; Chen, Jieli; Cui, Xu; Roberts, Cynthia; Lu, Mei; Chopp, Michael

    2010-07-15

    In this study we examined the effect of combination treatment of experimental stroke with Niaspan, a prolonged-release formulation of Niacin (vitamin B3), and Simvastatin, a cholesterol-lowering drug, on functional outcome, axonal damage, axonal density and the of Iba-1 immunoreactive microglia expression in the ischemic brain of rats. Adult male rats were subjected to 2 h middle cerebral artery occlusion (MCAo) and treated with or without Niaspan alone, Simvastatin alone and combination Niaspan and Simvastatin starting 24 h after MCAo and daily for 14 days. Neurological functional tests were performed. Axonal damage and density were evaluated by Amyloid Precursor Protein (APP) and Bielschowsky silver, respectively. Nogo66 Receptor (NgR) expression and immunoreactive microglia (Iba-1) were also measured in the ischemic brain. Niaspan and Simvastatin monotherapy and combination treatment significantly promote functional outcome after stroke (p<0.05) compared to MCAo control animals. Combination treatment with Niaspan and Simvastatin induces additive but not synergetic effects when compared to Niaspan or Simvastatin monotherapy groups. Combination treatment significantly decreased APP expression and increased Bielschowsky silver expression. NGR and Iba-1 expression were significantly decreased in the ischemic brain. These data suggest that treatment of experimental stroke with combination of Niaspan and Simvastatin significantly improves functional outcome, reduces axonal damage and increases axonal density. Decreased expression of the NGR and reduced activated microglia may contribute to functional recovery after stroke. PMID:20451219

  13. Pulsed electromagnetic field improves cardiac function in response to myocardial infarction

    PubMed Central

    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

    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

  14. Pulsed electromagnetic field improves cardiac function in response to myocardial infarction.

    PubMed

    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

    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

  15. FTY720 is Neuroprotective and Improves Functional Outcomes After Intracerebral Hemorrhage in Mice

    PubMed Central

    Rolland, William B.; Manaenko, Anatol; Lekic, Tim; Hasegawa, Yu; Ostrowski, Robert; Tang, Jiping

    2013-01-01

    Intracerebral hemorrhage (ICH) accounts for 20% of all strokes and is the most devastating form across all stroke types. Lymphocytes have been shown to potentiate cerebral inflammation and brain injury after stroke. FTY720 (Fingolimod) is an immune-modulating drug that prevents the egress of peripheral lymphocytes from peripheral stores. We hypothesized that FTY720 would reduce peripheral circulating lymphocytes, resulting in reduced brain injury and improved functional outcomes. CD-1 mice were anesthetized and then injected with collagenase into the right basal ganglia. Animals were divided into three groups: sham, ICH + Vehicle, and ICH + FTY720, by the intra-peritoneal route at 1 h after ICH induction. Brain water content was measured at 24 and 72 h. Neurobehavioral tests included corner test, forelimb use asymmetry, paw placement, wire-hang test, beam balance test, and a Neuroscore. FTY720 significantly reduced brain edema and improved neurological function at all time points tested. Lymphocyte modulation with FTY720 is an effective neuroprotective strategy to reduce brain injury and promote functional recovery after ICH. PMID:21725758

  16. Active surface model improvement by energy function optimization for 3D segmentation.

    PubMed

    Azimifar, Zohreh; Mohaddesi, Mahsa

    2015-04-01

    This paper proposes an optimized and efficient active surface model by improving the energy functions, searching method, neighborhood definition and resampling criterion. Extracting an accurate surface of the desired object from a number of 3D images using active surface and deformable models plays an important role in computer vision especially medical image processing. Different powerful segmentation algorithms have been suggested to address the limitations associated with the model initialization, poor convergence to surface concavities and slow convergence rate. This paper proposes a method to improve one of the strongest and recent segmentation algorithms, namely the Decoupled Active Surface (DAS) method. We consider a gradient of wavelet edge extracted image and local phase coherence as external energy to extract more information from images and we use curvature integral as internal energy to focus on high curvature region extraction. Similarly, we use resampling of points and a line search for point selection to improve the accuracy of the algorithm. We further employ an estimation of the desired object as an initialization for the active surface model. A number of tests and experiments have been done and the results show the improvements with regards to the extracted surface accuracy and computational time of the presented algorithm compared with the best and recent active surface models. PMID:25700271

  17. Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.

    PubMed

    Thoonen, Robrecht; Ernande, Laura; Cheng, Juan; Nagasaka, Yasuko; Yao, Vincent; Miranda-Bezerra, Alexandre; Chen, Chan; Chao, Wei; Panagia, Marcello; Sosnovik, David E; Puppala, Dheeraj; Armoundas, Antonis A; Hindle, Allyson; Bloch, Kenneth D; Buys, Emmanuel S; Scherrer-Crosbie, Marielle

    2015-07-01

    Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-) BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release. After 3days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1(-/-) mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy. PMID:25968336

  18. Right Ventricular Function Quantification in Takotsubo Cardiomyopathy Using Two-Dimensional Strain Echocardiography

    PubMed Central

    Brade, Joachim; Streitner, Florian; Doesch, Christina; Papavassiliu, Theano; Borggrefe, Martin; Haghi, Dariusch

    2014-01-01

    Aims This study sought to characterize global and regional right ventricular (RV) myocardial function in patients with Takotsubo cardiomyopathy (TC) using 2D strain imaging. Methods We compared various parameters of RV and left ventricular (LV) systolic function between 2 groups of consecutive patients with TC at initial presentation and upon follow-up. Group 1 had RV involvement and group 2 did not have RV involvement. Results At initial presentation, RV peak systolic longitudinal strain (RVPSS) and RV fractional area change (RVFAC) were significantly lower in group 1 (?13.2±8.6% vs. ?21.8±5.4%, p?=?0.001; 30.7±9.3% vs. 43.5±6.3%, p?=?0.001) and improved significantly upon follow-up. Tricuspid annular plane systolic excursion (TAPSE) did not differ significantly at initial presentation between both groups (14.8±4.1 mm vs. 17.9±3.5 mm, p?=?0.050). Differences in regional systolic RV strain were only observed in the mid and apical segments. LV ejection fraction (LVEF) and LV global strain were significantly lower in group 1 (36±8% vs. 46±10%, p?=?0.006 and ?5.5±4.8% vs. ?10.2±6.2%, p?=?0.040) at initial presentation. None of the parameters were significantly different between the 2 groups upon follow-up. A RVPSS cut-off value of >?19.1% had a sensitivity of 85% and a specificity of 71% to discriminate between the 2 groups. Conclusion In TC, RVFAC, RVPSS, LVEF and LV global strain differed significantly between patients with and without RV dysfunction, whereas TAPSE did not. 2 D strain imaging was feasible for the assessment of RV dysfunction in TC and could discriminate between patients with and without RV involvement in a clinically meaningful way. PMID:25089702

  19. Effects of Everolimus-Eluting Stents on the Left Ventricular Systolic and Diastolic Functions

    PubMed Central

    Parsaee, Mohammad Sadegh; Nabati, Maryam; Saffar, Naser; Taghavi, Morteza

    2015-01-01

    Background: The drug-eluting stent (DES) decreases the rate of coronary restenosis and re-obstruction. The aim of this study was to assess prospectively the effectiveness of the new generation DES on the left ventricular (LV) systolic and diastolic functions in patients with isolated severe proximal left anterior descending (LAD) coronary artery stenosis. Methods: A prospective study was conducted on 50 patients with isolated severe proximal LAD stenosis. Successful percutaneous coronary intervention (PCI) with Everolimus-eluting stents was performed for the whole study population. All the patients underwent transthoracic echocardiography within 24 hours before and one month after PCI, and LV systolic and diastolic parameters were compared before and after PCI using the paired samples t-test. Results: The mean age of the study population was 57.68 ± 8.82 years. Within the study population, 26 (52%) patients were male and 24 (48%) were female. There was a significant 10.6% and 5.2% increase in the early diastolic mitral annular motion (e') and the LV ejection fraction following PCI, respectively (p value = 0.005 and p value = 0.044, respectively). Before PCI, wall motion abnormality was seen in 2.21 ± 2.91 segments, which significantly decreased to 1.49 ± 2.58 segments (p value = 0.04) after the procedure. Also, the wall motion score index was 1.18 ± 0.26 before PCI, which significantly decreased to 1.13 ± 0.23 after PCI (p value < 0.001). Also, there was a trend toward a higher ratio of transmitral peak early diastolic velocity to peak late diastolic velocity after PCI (p value = 0.068). Conclusion: Our study showed that the use of the Everolimus-eluting stents improved the LV systolic and diastolic functions in patients with isolated severe LAD stenosis.

  20. The function and response of an improved stratospheric condensation nucleus counter

    NASA Technical Reports Server (NTRS)

    Wilson, J. C.; Hyun, J. H.; Blackshear, E. D.

    1983-01-01

    An improved condensation nucleus counter (CNC) for use in the stratosphere is described. The University of Minnesota CNC (UMCNC) has a sequential saturator and condenser and uses n-butyl alcohol as the working fluid. The use of a coaxial saturator flow, with aerosol in the center and filtered, alcohol-laden air around it, speeds the response of this instrument and improves its stability as pressure changes. The counting efficiency has been studied as a function of particle size and pressure. The UMCNC provides an accurate measure of submicron aerosol concentration as long as the number distribution is not dominated by sub-0.02 micron diameter aerosol. The response of the UMCNC is compared with that of other stratospheric condensation nucleus counters, and the results of a (near) comparison with a balloon-borne condensation nucleus counter are presented. The UMCNC has operated 14 times on a NASA U-2 aircraft at altitudes from 8 to 21.5 km.

  1. Functional module search in protein networks based on semantic similarity improves the analysis of proteomics data.

    PubMed

    Boyanova, Desislava; Nilla, Santosh; Klau, Gunnar W; Dandekar, Thomas; Müller, Tobias; Dittrich, Marcus

    2014-07-01

    The continuously evolving field of proteomics produces increasing amounts of data while improving the quality of protein identifications. Albeit quantitative measurements are becoming more popular, many proteomic studies are still based on non-quantitative methods for protein identification. These studies result in potentially large sets of identified proteins, where the biological interpretation of proteins can be challenging. Systems biology develops innovative network-based methods, which allow an integrated analysis of these data. Here we present a novel approach, which combines prior knowledge of protein-protein interactions (PPI) with proteomics data using functional similarity measurements of interacting proteins. This integrated network analysis exactly identifies network modules with a maximal consistent functional similarity reflecting biological processes of the investigated cells. We validated our approach on small (H9N2 virus-infected gastric cells) and large (blood constituents) proteomic data sets. Using this novel algorithm, we identified characteristic functional modules in virus-infected cells, comprising key signaling proteins (e.g. the stress-related kinase RAF1) and demonstrate that this method allows a module-based functional characterization of cell types. Analysis of a large proteome data set of blood constituents resulted in clear separation of blood cells according to their developmental origin. A detailed investigation of the T-cell proteome further illustrates how the algorithm partitions large networks into functional subnetworks each representing specific cellular functions. These results demonstrate that the integrated network approach not only allows a detailed analysis of proteome networks but also yields a functional decomposition of complex proteomic data sets and thereby provides deeper insights into the underlying cellular processes of the investigated system. PMID:24807868

  2. c-Cbl Inhibition Improves Cardiac function and Survival in Response to Myocardial Ischemia

    PubMed Central

    Rafiq, Khadija; Kolpakov, Mikhail A; Seqqat, Rachid; Guo, Jianfen; Guo, Xinji; Qi, Zhao; Yu, Daohai; Mohapatra, Bhopal; Zutshi, Neha; An, Wei; Band, Hamid; Sanjay, Archana; Houser, Steven R; Sabri, Abdelkarim

    2014-01-01

    Background The proto-oncogene Casitas b-lineage lymphoma (c-Cbl) is an adaptor protein with an intrinsic E3 ubiquitin ligase activity that targets receptor and non-receptor tyrosine kinases, resulting in their ubiquitination and down-regulation. However, the function of c-Cbl in the control of cardiac function is currently unknown. In this study, we examined the role of c-Cbl in myocyte death and cardiac function after myocardial ischemia. Methods and Results We show increased c-Cbl expression in human ischemic and dilated cardiomyopathy hearts and in response to pathological stress stimuli in mice. c-Cbl deficient mice demonstrated a more robust functional recovery after myocardial ischemia reperfusion injury, as well as significantly reduced myocyte apoptosis and improved cardiac function. Ubiquitination and downregulation of key survival c-Cbl targets, epidermal growth factor receptors and focal adhesion kinase, were significantly reduced in c-Cbl knockout mice. Inhibition of c-Cbl expression or its ubiquitin ligase activity in cardiac myocytes offered protection against H2O2 stress. Interestingly, c-Cbl deletion reduced the risk of death and increased cardiac functional recovery after chronic myocardial ischemia. This beneficial effect of c-Cbl deletion was associated with enhanced neoangiogenesis and increased expression of vascular endothelial growth factor (VEGF)-a and VEGF receptor type 2 in the infarcted region. Conclusions c-Cbl activation promotes myocyte apoptosis, inhibits angiogenesis and causes adverse cardiac remodeling after myocardial infarction. These findings point to c-Cbl as a potential therapeutic target for the maintenance of cardiac function and remodeling after myocardial ischemia. PMID:24583314

  3. Six-Week Gait Retraining Program Reduces Knee Adduction Moment, Reduces Pain, and Improves Function for Individuals with Medial

    E-print Network

    Delp, Scott

    pain and function were approximately 75% larger than the expected placebo effect (p Six-Week Gait Retraining Program Reduces Knee Adduction Moment, Reduces Pain, and Improves Function retraining program on the knee adduction moment (KAM) and knee pain and function. Ten subjects with medial

  4. Platelet gene therapy improves hemostatic function for integrin ?IIb?3-deficient dogs

    PubMed Central

    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

    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. PMID:21606353

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

    PubMed Central

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

    2014-01-01

    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. PMID:24440365

  6. Fucosyltransferase VII improves the function of selectin ligands on cord blood hematopoietic stem cells

    PubMed Central

    Wan, Xiang; Sato, Hidetaka; Miyaji, Hiromasa; McDaniel, J Michael; Wang, Yuesi; Kaneko, Etsuji; Gibson, BreeAnna; Mehta-D'Souza, Padmaja; Chen, Yiyuan; Dozmorov, Mikhail; Miller, Leonard P; Goodman, Jean; Sun, Zimin; Xia, Lijun

    2013-01-01

    Selectins and their carbohydrate ligands mediate the homing of hematopoietic stem/progenitor cells (HSPCs) to the bone marrow. We have previously shown that ex vivo fucosylation of selectin ligands on HSPCs by ?1,3 fucosyltransferase VI (FUT6) leads to improved human cord blood (CB)-HSPC engraftment in non-obese diabetic (NOD)/severe combined immune deficient (SCID) mice. In the present study, we determined whether surface fucosylation with ?1,3 fucosyltransferase VII (FUT7), which is primarily expressed by hematopoietic cells, improves the function of selectin ligands on CB-HSPCs in comparison with FUT6. A saturating amount of either FUT6 or FUT7, which generates comparable levels of expression of fucosylated epitopes on CB CD34+ cells, was used for these experiments. In vitro, FUT7-treated CB CD34+ cells exhibited greater binding to P- or E-selectin than that of FUT6-treated CB CD34+ cells under static or physiological flow conditions. In vivo, FUT7 treatment, like FUT6, improved the early engraftment of CB CD34+ cells in the bone marrow of sublethally irradiated NOD/SCID interleukin (IL)-2R?null (NSG) mice. FUT7 also exhibited marginally—yet statistically significant—increased engraftment at 4 and 6 weeks after transplantation. In addition, FUT7-treated CB CD34+ cells exhibited increased homing to the bone marrow of irradiated NSG mice relative to sham-treated cells. These data indicate that FUT7 is effective at improving the function of selectin ligands on CB-HSPCs in vitro and enhancing early engraftment of treated CB-HSPCs in the bone marrow of recipients. PMID:23899669

  7. Consumption of cocoa flavanols results in an acute improvement in visual and cognitive functions.

    PubMed

    Field, David T; Williams, Claire M; Butler, Laurie T

    2011-06-01

    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

  8. The chirally rotated Schrödinger functional with Wilson fermions and automatic O(a) improvement

    E-print Network

    Stefan Sint

    2011-02-03

    A modified formulation of the Schr\\"odinger functional (SF) is proposed. In the continuum it is related to the standard SF by a non-singlet chiral field rotation and therefore referred to as the chirally rotated SF ($\\chi$SF). On the lattice with Wilson fermions the relation is not exact, suggesting some interesting tests of universality. The main advantage of the $\\chi$SF consists in its compatibility with the mechanism of automatic O($a$) improvement. In this paper the basic set-up is introduced and discussed. Chirally rotated SF boundary conditions are implemented on the lattice using an orbifold construction. The lattice symmetries imply a list of counterterms, which determine how the action and the basic fermionic two-point functions are renormalised and O($a$) improved. As with the standard SF, a logarithmically divergent boundary counterterm leads to a multiplicative renormalisation of the fermionic boundary fields. In addition, a finite dimension 3 boundary counterterm must be tuned in order to preserve the chirally rotated boundary conditions in the interacting theory. Once this is achieved, O($a$) effects originating from the bulk action or from insertions of composite operators in the bulk can be avoided by the mechanism of automatic O($a$) improvement. The remaining O($a$) effects arise from the boundaries and can be cancelled by tuning a couple of O($a$) boundary counterterms. The general results are illustrated in the free theory where the Sheikholeslami-Wohlert term is shown to affect correlation functions only at O($a^2$), irrespective of its coefficient.

  9. Sigma-1R agonist improves motor function and motoneuron survival in ALS mice.

    PubMed

    Mancuso, Renzo; Oliván, Sara; Rando, Amaya; Casas, Caty; Osta, Rosario; Navarro, Xavier

    2012-10-01

    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

  10. Progressive resistance strength training for improving physical function in older adults

    PubMed Central

    Liu, Chiung-ju; Latham, Nancy K

    2014-01-01

    Background Muscle weakness in old age is associated with physical function decline. Progressive resistance strength training (PRT) exercises are designed to increase strength. Objectives To assess the effects of PRT on older people and identify adverse events. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialized Register (to March 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2007, Issue 2), MEDLINE (1966 to May 01, 2008), EMBASE (1980 to February 06 2007), CINAHL (1982 to July 01 2007) and two other electronic databases. We also searched reference lists of articles, reviewed conference abstracts and contacted authors. Selection criteria Randomised controlled trials reporting physical outcomes of PRT for older people were included. Data collection and analysis Two review authors independently selected trials, assessed trial quality and extracted data. Data were pooled where appropriate. Main results One hundred and twenty one trials with 6700 participants were included. In most trials, PRT was performed two to three times per week and at a high intensity. PRT resulted in a small but significant improvement in physical ability (33 trials, 2172 participants; SMD 0.14, 95% CI 0.05 to 0.22). Functional limitation measures also showed improvements: e.g. there was a modest improvement in gait speed (24 trials, 1179 participants, MD 0.08 m/s, 95% CI 0.04 to 0.12); and a moderate to large effect for getting out of a chair (11 trials, 384 participants, SMD -0.94, 95% CI -1.49 to -0.38). PRT had a large positive effect on muscle strength (73 trials, 3059 participants, SMD 0.84, 95% CI 0.67 to 1.00). Participants with osteoarthritis reported a reduction in pain following PRT (6 trials, 503 participants, SMD -0.30, 95% CI -0.48 to -0.13). There was no evidence from 10 other trials (587 participants) that PRT had an effect on bodily pain. Adverse events were poorly recorded but adverse events related to musculoskeletal complaints, such as joint pain and muscle soreness, were reported in many of the studies that prospectively defined and monitored these events. Serious adverse events were rare, and no serious events were reported to be directly related to the exercise programme. Authors' conclusions This review provides evidence that PRT is an effective intervention for improving physical functioning in older people, including improving strength and the performance of some simple and complex activities. However, some caution is needed with transferring these exercises for use with clinical populations because adverse events are not adequately reported. PMID:19588334

  11. A Novel Dehydroepiandrosterone Analog Improves Functional Recovery in a Rat Traumatic Brain Injury Model

    PubMed Central

    MALIK, AMIR S.; NARAYAN, RAJ K.; WENDLING, WOODROW W.; COLE, RUSSELL W.; PASHKO, LAURA L.; SCHWARTZ, ARTHUR G.

    2006-01-01

    The purpose of this study was to investigate the efficacy of a novel steroid, fluasterone (DHEF, a dehydroepiandrosterone (DHEA) analog), at improving functional recovery in a rat model of traumatic brain injury (TBI). The lateral cortical impact model was utilized in two studies of efficacy and therapeutic window. DHEF was given (25 mg/kg, intraperitoneally) at the initial time point and once a day for 2 more days. Study A included four groups: sham injury, vehicle treated (n = 22); injured, vehicle treated (n = 30); injured, pretreated (5–10 min prior to injury, n = 24); and injured, posttreated (initial dose 30 min postinjury, n = 15). Study B (therapeutic window) included five groups: sham injury, vehicle treated (n = 17); injured, vehicle treated (n = 26); and three posttreatment groups: initial dose at 30 min (n = 18), 2 h (n = 23), or 12 h (n = 16) postinjury. Three criteria were used to grade functional recovery. In study A, DHEF improved beam walk performance both with pretreatment (79%) and 30-min posttreatment group (54%; p < 0.01, Dunnett vs. injured vehicle). In study B, the 12-h posttreatment group showed a 97% improvement in beam walk perfomance (p < 0.01, Dunnett). The 30-min and 12-h posttreatment groups showed a decreased incidence of falls from the beam, which reached statistical significance (p < 0.05, Dunnett). Tests of memory (Morris water maze) and neurological reflexes both revealed significant improvements in all DHEF treatment groups. In cultured rat mesangial cells, DHEF (and DHEA) potently inhibited interleukin-1?–induced cyclooxygenase-2 (COX2) mRNA and prostaglandin (PGE2) production. In contrast, DHEF treatment did not alter injury-induced COX2 mRNA levels in the cortex or hippocampus. However, DHEF (and DHEA) relaxed ex vivo bovine middle cerebral artery preparations by about 30%, with an IC50 ? 40 ?M. This was a direct effect on the vascular smooth muscle, independent of the endothelial cell layer. Fluasterone (DHEF) treatments improved functional recovery in a rat TBI model. Possible mechanisms of action for this novel DHEA analog are discussed. These findings suggest an exciting potential use for this agent in the clinical treatment of traumatic brain injury. PMID:12803978

  12. Improving functional annotation for industrial microbes: a case study with Pichia pastoris

    PubMed Central

    Dikicioglu, Duygu; Wood, Valerie; Rutherford, Kim M.; McDowall, Mark D.; Oliver, Stephen G.

    2014-01-01

    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. PMID:24929579

  13. Cholesterol Reduction Rapidly Improves Endothelial Function After Acute Coronary Syndromes The RECIFE (Reduction of Cholesterol in Ischemia and Function of the Endothelium) Trial

    Microsoft Academic Search

    Jocelyn Dupuis; Jean-Claude Tardif; Peter Cernacek; Pierre Theroux

    2010-01-01

    Background—Cholesterol lowering reduces coronary events. One mechanism could be improvement of endothelial function. In line with this hypothesis, this study investigates whether cholesterol reduction can result in rapid improvement of endothelial function after acute coronary syndromes. Methods and Results—Patients with acute myocardial infarction or unstable angina and total cholesterol levels at admission $5.2 mmol\\/L or LDL $3.4 mmol\\/L were randomized

  14. Cervical spinal cord injury: tailoring clinical trial endpoints to reflect meaningful functional improvements

    PubMed Central

    Bond, Lisa M.; McKerracher, Lisa

    2014-01-01

    Cervical spinal cord injury (SCI) results in partial to full paralysis of the upper and lower extremities. Traditional primary endpoints for acute SCI clinical trials are too broad to assess functional recovery in cervical subjects, raising the possibility of false positive outcomes in trials for cervical SCI. Endpoints focused on the recovery of hand and arm control (e.g., upper extremity motor score, motor level change) show the most potential for use as primary outcomes in upcoming trials of cervical SCI. As the field moves forward, the most reliable way to ensure meaningful clinical testing in cervical subjects may be the development of a composite primary endpoint that measures both neurological recovery and functional improvement. PMID:25317162

  15. Teaching others rule-use improves executive function and prefrontal activations in young children

    PubMed Central

    Moriguchi, Yusuke; Sakata, Yoko; Ishibashi, Mikako; Ishikawa, Yusuke

    2015-01-01

    Intervention of executive function during early childhood is an important research topic. This study examined the effect of a child-friendly intervention program, where children interacted with a doll or a puppet. Children were presented with cognitive shifting tasks before and after an intervention. In the intervention, children interacted with a doll or a puppet, and taught rules of the cognitive shifting tasks to the object. As the results, 3- to 5-year-old children significantly improved the performances and strengthened activations in the lateral prefrontal regions as measured by near-infrared spectroscopy. The results suggest that interaction with a doll or a puppet may have a significant impact on the development of executive function. PMID:26175706

  16. Growth hormone improves growth rate and preserves renal function in Dent disease.

    PubMed

    Sheffer-Babila, Sharone; Chandra, Manju; Speiser, Phyllis W

    2008-03-01

    Dent disease, an X-linked recessive renal tubular disease, results from loss-of-function mutations in the CLCN5 chloride channel gene. The effects of Dent disease on growth have not been described. We report siblings who presented with proteinuria, calciuria, and phosphaturia and growth failure who responded to growth hormone (GH) treatment. Genotyping revealed a novel c.2179delG frameshift mutation at codon 727, exon 12 of the CLCNS gene. Two years after initial presentation, linear growth had slowed, and evaluation revealed isolated GH deficiency. GH therapy resulted in more than two-fold increases in height velocity and serum IGF-I levels. There was no net change in estimated glomerular filtration rate, proteinuria or calciuria in response to GH therapy, but there was a delayed improvement in phosphaturia. These cases provide insight into the effects of GH on growth and renal function in Dent disease. Furthermore, we have reported a novel CLCN5 mutation. PMID:18540256

  17. Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

    NASA Astrophysics Data System (ADS)

    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

    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.

  18. Contrast and harmonic imaging improves accuracy and efficiency of novice readers for dobutamine stress echocardiography

    NASA Technical Reports Server (NTRS)

    Vlassak, Irmien; Rubin, David N.; Odabashian, Jill A.; Garcia, Mario J.; King, Lisa M.; Lin, Steve S.; Drinko, Jeanne K.; Morehead, Annitta J.; Prior, David L.; Asher, Craig R.; Klein, Allan L.; Thomas, James D.

    2002-01-01

    BACKGROUND: Newer contrast agents as well as tissue harmonic imaging enhance left ventricular (LV) endocardial border delineation, and therefore, improve LV wall-motion analysis. Interpretation of dobutamine stress echocardiography is observer-dependent and requires experience. This study was performed to evaluate whether these new imaging modalities would improve endocardial visualization and enhance accuracy and efficiency of the inexperienced reader interpreting dobutamine stress echocardiography. METHODS AND RESULTS: Twenty-nine consecutive patients with known or suspected coronary artery disease underwent dobutamine stress echocardiography. Both fundamental (2.5 MHZ) and harmonic (1.7 and 3.5 MHZ) mode images were obtained in four standard views at rest and at peak stress during a standard dobutamine infusion stress protocol. Following the noncontrast images, Optison was administered intravenously in bolus (0.5-3.0 ml), and fundamental and harmonic images were obtained. The dobutamine echocardiography studies were reviewed by one experienced and one inexperienced echocardiographer. LV segments were graded for image quality and function. Time for interpretation also was recorded. Contrast with harmonic imaging improved the diagnostic concordance of the novice reader to the expert reader by 7.1%, 7.5%, and 12.6% (P < 0.001) as compared with harmonic imaging, fundamental imaging, and fundamental imaging with contrast, respectively. For the novice reader, reading time was reduced by 47%, 55%, and 58% (P < 0.005) as compared with the time needed for fundamental, fundamental contrast, and harmonic modes, respectively. With harmonic imaging, the image quality score was 4.6% higher (P < 0.001) than for fundamental imaging. Image quality scores were not significantly different for noncontrast and contrast images. CONCLUSION: Harmonic imaging with contrast significantly improves the accuracy and efficiency of the novice dobutamine stress echocardiography reader. The use of harmonic imaging reduces the frequency of nondiagnostic wall segments.

  19. Improving microbial fitness in the mammalian gut by in vivo temporal functional metagenomics

    PubMed Central

    Yaung, Stephanie J; Deng, Luxue; Li, Ning; Braff, Jonathan L; Church, George M; Bry, Lynn; Wang, Harris H; Gerber, Georg K

    2015-01-01

    Elucidating functions of commensal microbial genes in the mammalian gut is challenging because many commensals are recalcitrant to laboratory cultivation and genetic manipulation. We present Temporal FUnctional Metagenomics sequencing (TFUMseq), a platform to functionally mine bacterial genomes for genes that contribute to fitness of commensal bacteria in vivo. Our approach uses metagenomic DNA to construct large-scale heterologous expression libraries that are tracked over time in vivo by deep sequencing and computational methods. To demonstrate our approach, we built a TFUMseq plasmid library using the gut commensal Bacteroides thetaiotaomicron (Bt) and introduced Escherichia coli carrying this library into germfree mice. Population dynamics of library clones revealed Bt genes conferring significant fitness advantages in E. coli over time, including carbohydrate utilization genes, with a Bt galactokinase central to early colonization, and subsequent dominance by a Bt glycoside hydrolase enabling sucrose metabolism coupled with co-evolution of the plasmid library and E. coli genome driving increased galactose utilization. Our findings highlight the utility of functional metagenomics for engineering commensal bacteria with improved properties, including expanded colonization capabilities in vivo. PMID:25762151

  20. An improved model for the rate-level functions of auditory-nerve fibers.

    PubMed

    Heil, Peter; Neubauer, Heinrich; Irvine, Dexter R F

    2011-10-26

    Acoustic information is conveyed to the brain by the spike patterns in auditory-nerve fibers (ANFs). In mammals, each ANF is excited via a single ribbon synapse in a single inner hair cell (IHC), and the spike patterns therefore also provide valuable information about those intriguing synapses. Here we reexamine and model a key property of ANFs, the dependence of their spike rates on the sound pressure level of acoustic stimuli (rate-level functions). We build upon the seminal model of Sachs and Abbas (1974), which provides good fits to experimental data but has limited utility for defining physiological mechanisms. We present an improved, physiologically plausible model according to which the spike rate follows a Hill equation and spontaneous activity and its experimentally observed tight correlation with ANF sensitivity are emergent properties. We apply it to 156 cat ANF rate-level functions using frequencies where the mechanics are linear and find that a single Hill coefficient of 3 can account for the population of functions. We also demonstrate a tight correspondence between ANF rate-level functions and the Ca(2+) dependence of exocytosis from IHCs, and derive estimates of the effective intracellular Ca(2+) concentrations at the individual active zones of IHCs. We argue that the Hill coefficient might reflect the intrinsic, biochemical Ca(2+) cooperativity of the Ca(2+) sensor involved in exocytosis from the IHC. The model also links ANF properties with properties of psychophysical absolute thresholds. PMID:22031889

  1. Improving microbial fitness in the mammalian gut by in vivo temporal functional metagenomics.

    PubMed

    Yaung, Stephanie J; Deng, Luxue; Li, Ning; Braff, Jonathan L; Church, George M; Bry, Lynn; Wang, Harris H; Gerber, Georg K

    2015-01-01

    Elucidating functions of commensal microbial genes in the mammalian gut is challenging because many commensals are recalcitrant to laboratory cultivation and genetic manipulation. We present Temporal FUnctional Metagenomics sequencing (TFUMseq), a platform to functionally mine bacterial genomes for genes that contribute to fitness of commensal bacteria in vivo. Our approach uses metagenomic DNA to construct large-scale heterologous expression libraries that are tracked over time in vivo by deep sequencing and computational methods. To demonstrate our approach, we built a TFUMseq plasmid library using the gut commensal Bacteroides thetaiotaomicron (Bt) and introduced Escherichia coli carrying this library into germfree mice. Population dynamics of library clones revealed Bt genes conferring significant fitness advantages in E. coli over time, including carbohydrate utilization genes, with a Bt galactokinase central to early colonization, and subsequent dominance by a Bt glycoside hydrolase enabling sucrose metabolism coupled with co-evolution of the plasmid library and E. coli genome driving increased galactose utilization. Our findings highlight the utility of functional metagenomics for engineering commensal bacteria with improved properties, including expanded colonization capabilities in vivo. PMID:25762151

  2. Analysis of variability among endogenous ecotropic MuLV loci in laboratory mice.

    PubMed

    Nouvel, P; Philippe, H; Condamine, H; Panthier, J J

    1993-03-01

    We have isolated a molecular clone of an ecotropic murine leukemia virus from the ovaries of an SWR/J x RF/J hybrid female. The molecularly cloned virus, named pSR3, was demonstrated to induce virus production upon transfection into SWR/J immortalized fibroblasts and to promote germ line integration of proviruses in a fraction of the offspring germline when inoculated to neonate SWR/J females. Sequence analysis reveals that pSR3 is closely related to p623, a plasmid derived from Emv-11 (also referred to as AKV-1). Alignment of the pSR3 sequence with the partial nucleotide sequence of Emv-11 (an endogenous virus carried by BALB/c and C3H/He mice) together with p623 then allows a comparison between three viral sequences. Analysis of these data gives (a) an estimation of the natural divergence rate of MuLV genomes in the course of viral replication (1-5 x 10(-5) mutations per cycle and per nucleotide) and (b) molecular evidence for a recent origin through germ line infection of endogenous loci. From additional clues, Emv-11 appears to be the probable ancestor of at least some of these loci. PMID:8382408

  3. Impact of Diabetes on Cardiac Structure and Function The Strong Heart Study

    Microsoft Academic Search

    Richard B. Devereux; Mary J. Roman; Mary Paranicas; Michael J. O'Grady; Elisa T. Lee; Thomas K. Welty; Richard R. Fabsitz; David Robbins; Everett R. Rhoades; Barbara V. Howard

    2010-01-01

    Background—Whether diabetes mellitus (DM) adversely affects left ventricular (LV) structure and function independently of increases in body mass index (BMI) and blood pressure is controversial. Methods and Results—Echocardiography was used in the Strong Heart Study, a study of cardiovascular disease in American Indians, to compare LV measurements between 1810 participants with DM and 944 with normal glucose tolerance. Participants with

  4. Improvement of immune cell functions in aged mice treated for five weeks with soybean isoflavones.

    PubMed

    Baeza, Isabel; de Castro, Nuria M; Alvarado, Carmen; Alvarez, Pedro; Arranz, Lorena; Bayón, Julián; de la Fuente, Mónica

    2007-04-01

    Aging is associated with an impaired immune system as well as with a decline of several hormones, such as estrogens. Dietary phytoestrogens have been proposed as an alternative to hormone replacement therapy. The beneficial action of soybean compounds is probably due to isoflavones, whose role as immunomodulators has been investigated with increasing interest. The aim of the present work was to study whether a 5-week administration of a diet enriched in soybean isoflavones and green tea could influence the immune function of mice that were sham-operated or ovariectomized. Natural killer activity (NK) and lymphoproliferation in response to the mitogens concanavaline A (Con A) and lipopolysaccharide (LPS), were studied in peritoneal leukocytes. Both treatments with soybean or green tea plus soybean were highly effective in improving these immune parameters with respect to control groups. Since the immune system is a marker of health and a predictor of longevity, an adequate treatment with isoflavones could be useful in slowing down the effects of the aging process through an improvement in the two relevant immune functions studied. PMID:17460214

  5. Arm weight support training improves functional motor outcome and movement smoothness after stroke

    PubMed Central

    Bartolo, Michelangelo; De Nunzio, Alessandro Marco; Sebastiano, Fabio; Spicciato, Francesca; Tortola, Paolo; Nilsson, Jan; Pierelli, Francesco

    2014-01-01

    Summary The aim of this study was to compare the effectiveness in acute stroke patients of a rehabilitation program performed with or without an arm weight support device. Twenty-eight acute, first-ever unilateral stroke patients were enrolled in a single-blind, randomized controlled trial. Clinical evaluation included Fugl-Mayer Assessment, Functional Independence Measure and kinematic analysis [maximum and mean hand velocity, maximum range of motion (Max RoM), normalized jerk (NJ)]. Patients received 12 daily 30-minute sessions (6/week) of additional upper limb therapy performed using an arm weight support device (study group) or additional traditional physiotherapy (control group). The patients were evaluated on admission and at the end of the rehabilitation intervention. The two groups were clinically comparable on admission (p>0.05). Both groups showed significant improvements in clinical scale scores and in Max RoM in flexion-extension, while only the study group showed improvements in NJ and in Max RoM in adduction-abduction. Rehabilitation training using an arm weight support device appears to be a useful method to supplement conventional therapy in acute stroke patients, increasing smoothness of movement and motor function. PMID:25014045

  6. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy

    PubMed Central

    Kelly, K. J.; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Dominguez, Jesus H.

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA. PMID:26136112

  7. Long-term, regular remote ischemic preconditioning improves endothelial function in patients with coronary heart disease

    PubMed Central

    Liang, Y.; Li, Y.P.; He, F.; Liu, X.Q.; Zhang, J.Y.

    2015-01-01

    Remote ischemic preconditioning (RIPre) can prevent myocardial injury. The purpose of this study was to assess the beneficial effects of long-term regular RIPre on human arteries. Forty patients scheduled for coronary artery bypass graft (CABG) surgery were assigned randomly to a RIPre group (n=20) or coronary heart disease (CHD) group (n=20). Twenty patients scheduled for mastectomy were enrolled as a control group. RIPre was achieved by occluding arterial blood flow 5 min with a mercury sphygmomanometer followed by a 5-min reperfusion period, and this was repeated 4 times. The RIPre procedure was repeated 3 times a day for 20 days. In all patients, arterial fragments discarded during surgery were collected to evaluate endothelial function by flow-mediated dilation (FMD), CD34+ monocyte count, and endothelial nitric oxide synthase (eNOS expression). Phosphorylation levels of STAT-3 and Akt were also assayed to explore the underlying mechanisms. Compared with the CHD group, long-term regular RIPre significantly improved FMD after 20 days (8.5±2.4 vs 4.9±4.2%, P<0.05) and significantly reduced troponin after CABG surgery (0.72±0.31 and 1.64±0.19, P<0.05). RIPre activated STAT-3 and increased CD34+ endothelial progenitor cell counts found in arteries. Long-term, regular RIPre improved endothelial function in patients with CHD, possibly due to STAT-3 activation, and this may have led to an increase in endothelial progenitor cells. PMID:25923462

  8. Improvement/rehabilitation of memory functioning with neurotherapy/QEEG biofeedback.

    PubMed

    Thornton, K

    2000-12-01

    This article presents a new approach to the remediation of memory deficits by studying the electrophysiological functioning involved in memory and applying biofeedback techniques. A Quantitative EEG (QEEG) activation database was obtained with 59 right-handed subjects during two auditory memory tasks (prose passages and word lists). Memory performance was correlated with the QEEG variables. Clinical cases were administered the same QEEG activation study to determine their deviations from the values that predicted success for the reference group. EEG biofeedback interventions were designed to increase the value (to normal levels) of the specific electrophysiological variable that was related to successful memory function and deviant in the subject. Case examples are presented that indicate the successful use of this intervention style in normal subjects and in subjects with brain injury; improvement cannot be fully explained by spontaneous recovery, given the time postinjury. Five cases (two normal, two subjects with brain injury, and one subject who had stereotactic surgery of the hippocampus for seizure control) are presented. Improvements ranged from 68% to 181% in the group of patients with brain injury, as a result of the interventions. PMID:11056409

  9. Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery.

    PubMed

    Fukuda, Andrew M; Adami, Arash; Pop, Viorela; Bellone, John A; Coats, Jacqueline S; Hartman, Richard E; Ashwal, Stephen; Obenaus, Andre; Badaut, Jerome

    2013-10-01

    Traumatic brain injury (TBI) is common in young children and adolescents and is associated with long-term disability and mortality. The neuropathologic sequelae that result from juvenile TBI are a complex cascade of events that include edema formation and brain swelling. Brain aquaporin-4 (AQP4) has a key role in edema formation. Thus, development of novel treatments targeting AQP4 to reduce edema could lessen the neuropathologic sequelae. We hypothesized that inhibiting AQP4 expression by injection of small-interfering RNA (siRNA) targeting AQP4 (siAQP4) after juvenile TBI would decrease edema formation, neuroinflammation, neuronal cell death, and improve neurologic outcomes. The siAQP4 or a RNA-induced silencing complex (RISC)-free control siRNA (siGLO) was injected lateral to the trauma site after controlled cortical impact in postnatal day 17 rats. Magnetic resonance imaging, neurologic testing, and immunohistochemistry were performed to assess outcomes. Pups treated with siAQP4 showed acute (3 days after injury) improvements in motor function and in spatial memory at long term (60 days after injury) compared with siGLO-treated animals. These improvements were associated with decreased edema formation, increased microglial activation, decreased blood-brain barrier disruption, reduced astrogliosis and neuronal cell death. The effectiveness of our treatment paradigm was associated with a 30% decrease in AQP4 expression at the injection site. PMID:23899928

  10. Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery

    PubMed Central

    Fukuda, Andrew M; Adami, Arash; Pop, Viorela; Bellone, John A; Coats, Jacqueline S; Hartman, Richard E; Ashwal, Stephen; Obenaus, Andre; Badaut, Jerome

    2013-01-01

    Traumatic brain injury (TBI) is common in young children and adolescents and is associated with long-term disability and mortality. The neuropathologic sequelae that result from juvenile TBI are a complex cascade of events that include edema formation and brain swelling. Brain aquaporin-4 (AQP4) has a key role in edema formation. Thus, development of novel treatments targeting AQP4 to reduce edema could lessen the neuropathologic sequelae. We hypothesized that inhibiting AQP4 expression by injection of small-interfering RNA (siRNA) targeting AQP4 (siAQP4) after juvenile TBI would decrease edema formation, neuroinflammation, neuronal cell death, and improve neurologic outcomes. The siAQP4 or a RNA-induced silencing complex (RISC)-free control siRNA (siGLO) was injected lateral to the trauma site after controlled cortical impact in postnatal day 17 rats. Magnetic resonance imaging, neurologic testing, and immunohistochemistry were performed to assess outcomes. Pups treated with siAQP4 showed acute (3 days after injury) improvements in motor function and in spatial memory at long term (60 days after injury) compared with siGLO-treated animals. These improvements were associated with decreased edema formation, increased microglial activation, decreased blood–brain barrier disruption, reduced astrogliosis and neuronal cell death. The effectiveness of our treatment paradigm was associated with a 30% decrease in AQP4 expression at the injection site. PMID:23899928

  11. Morpholino Treatment Improves Muscle Function and Pathology of Pitx1 Transgenic Mice

    PubMed Central

    Pandey, Sachchida Nand; Lee, Yi-Chien; Yokota, Toshifumi; Chen, Yi-Wen

    2014-01-01

    Paired-like homeodomain transcription factor 1 (PITX1) was proposed to be part of the disease mechanisms of facioscapulohumeral muscular dystrophy (FSHD). We generated a tet-repressible muscle-specific Pitx1 transgenic mouse model which develops phenotypes of muscular dystrophy after the PITX1 expression is induced. In this study, we attempted to block the translation of PITX1 protein using morpholinos. Three groups of the transgenic mice received intravenous injections of phosphorodiamidate morpholino oligomers (PMO) (100?mg/kg), octaguanidinium dendrimer-conjugated morpholino (vivo-morpholino) (10?mg/kg), or phosphate-buffered saline (PBS) after the PITX1 expression was induced. Immunoblotting data showed that PITX1 expression in the triceps and quadriceps was significantly reduced 70% and 63% by the vivo-morpholino treatment, respectively. Muscle pathology of the mice treated with the vivo-morpholino was improved by showing 44% fewer angular-shaped atrophic myofibers. Muscle function determined by grip strength was significantly improved by the vivo-morpholino treatment. The study showed that systemic delivery of the vivo-morpholino reduced the PITX1 expression and improved the muscle phenotypes. Aberrant expression of DUX4 from the last unit of the D4Z4 array has been proposed to be the cause of FSHD. The findings of this study suggest that the same principle may be applied to suppress the aberrantly expressed DUX4 in FSHD. PMID:24232919

  12. Improvement in renal function and its impact on survival in patients with newly diagnosed multiple myeloma

    PubMed Central

    Gonsalves, W I; Leung, N; Rajkumar, S V; Dispenzieri, A; Lacy, M Q; Hayman, S R; Buadi, F K; Dingli, D; Kapoor, P; Go, R S; Lin, Y; Russell, S J; Lust, J A; Zeldenrust, S; Kyle, R A; Gertz, M A; Kumar, S K

    2015-01-01

    Renal impairment (RI) is seen in over a quarter of patients with newly diagnosed multiple myeloma (NDMM). It is not clear if reversal of RI improves the outcome to that expected for NDMM patients without RI. We evaluated 1135 consecutive patients with NDMM seen at the Mayo Clinic between January 2003 and December 2012. RI was defined as having a creatinine clearance (CrCl) <40ml/min. The median overall survival (OS) for patients with RI at diagnosis receiving and not receiving novel agent induction therapy was not reached vs 46 months (P<0.001). The median OS for patients with CrCl ?40?ml/min at diagnosis, CrCl <40?ml/min at diagnosis but improved to ?40?ml/min and CrCl <40?ml/min at diagnosis and remained <40?ml/min, were 112, 56 and 33 months, respectively (P<0.001). The complete renal response rate for patients with RI at diagnosis receiving novel agent induction therapy compared to the rest was 40 vs 16% (P<0.001). In conclusion, patients with reversal of RI have improved outcomes, but it remains inferior to patients with normal renal function at diagnosis. These results have implications for identifying early treatment strategies for patients at risk of developing renal insufficiency. PMID:25794132

  13. Urocortins improve dystrophic skeletal muscle structure and function through both PKA- and Epac-dependent pathways.

    PubMed

    Reutenauer-Patte, Julie; Boittin, François-Xavier; Patthey-Vuadens, Ophélie; Ruegg, Urs T; Dorchies, Olivier M

    2012-02-01

    In Duchenne muscular dystrophy, the absence of dystrophin causes progressive muscle wasting and premature death. Excessive calcium influx is thought to initiate the pathogenic cascade, resulting in muscle cell death. Urocortins (Ucns) have protected muscle in several experimental paradigms. Herein, we demonstrate that daily s.c. injections of either Ucn 1 or Ucn 2 to 3-week-old dystrophic mdx(5Cv) mice for 2 weeks increased skeletal muscle mass and normalized plasma creatine kinase activity. Histological examination showed that Ucns remarkably reduced necrosis in the diaphragm and slow- and fast-twitch muscles. Ucns improved muscle resistance to mechanical stress provoked by repetitive tetanizations. Ucn 2 treatment resulted in faster kinetics of contraction and relaxation and a rightward shift of the force-frequency curve, suggesting improved calcium homeostasis. Ucn 2 decreased calcium influx into freshly isolated dystrophic muscles. Pharmacological manipulation demonstrated that the mechanism involved the corticotropin-releasing factor type 2 receptor, cAMP elevation, and activation of both protein kinase A and the cAMP-binding protein Epac. Moreover, both STIM1, the calcium sensor that initiates the assembly of store-operated channels, and the calcium-independent phospholipase A(2) that activates these channels were reduced in dystrophic muscle by Ucn 2. Altogether, our results demonstrate the high potency of Ucns for improving dystrophic muscle structure and function, suggesting that these peptides may be considered for treatment of Duchenne muscular dystrophy. PMID:22192627

  14. Functional Cardiac Magnetic Resonance Imaging (MRI) in the Assessment of Myocardial Viability and Perfusion

    PubMed Central

    2003-01-01

    Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness safety and cost-effectiveness of using functional cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability and perfusion in patients with coronary artery disease and left ventricular dysfunction. Results Functional MRI has become increasingly investigated as a noninvasive method for assessing myocardial viability and perfusion. Most patients in the published literature have mild to moderate impaired LV function. It is possible that the severity of LV dysfunction may be an important factor that can alter the diagnostic accuracy of imaging techniques. There is some evidence of comparable or better performance of functional cardiac MRI for the assessment of myocardial viability and perfusion compared with other imaging techniques. However limitations to most of the studies included: Functional cardiac MRI studies that assess myocardial viability and perfusion have had small sample sizes. Some studies assessed myocardial viability/perfusion in patients who had already undergone revascularization, or excluded patients with a prior MI (Schwitter et al., 2001). Lack of explicit detail of patient recruitment. Patients with LVEF >35%. Interstudy variability in post MI imaging time(including acute or chronic MI), when patients with a prior MI were included. Poor interobserver agreement (kappa statistic) in the interpretation of the results. Traditionally, 0.80 is considered “good”. Cardiac MRI measurement of myocardial perfusion to as an adjunct tool to help diagnose CAD (prior to a definitive coronary angiography) has also been examined in some studies, with methodological limitations, yielding comparable results. Many studies examining myocardial viability and perfusion report on the accuracy of imaging methods with limited data on long-term patient outcome and management. Kim et al. (2000) revealed that the transmural extent of hyperenhancement was significantly related to the likelihood of improvement in contractility after revascularization. However, the LVEF in the patient population was 43% prior to revascularization. It is important to know whether the technique has the same degree of accuracy in patients who have more severe LV dysfunction and who would most benefit from an assessment of myocardial viability. “Substantial” viability used as a measure of a patient’s ability to recover after revascularization has not been definitively reported (how much viability is enough?). Patients with severe LV dysfunction are more likely to have mixtures of surviving myocardium, including normal, infarcted, stunned and hibernating myocardium (Cowley et al., 1999). This may lead to a lack of homogeneity of response to testing and to revascularization and contribute to inter- and intra-study differences. There is a need for a large prospective study with adequate follow-up time for patients with CAD and LV dysfunction (LVEF<35%) comparing MRI and an alternate imaging technique. There is some evidence that MRI has comparable sensitivity, specificity and accuracy to PET for determining myocardial viability. However, there is a lack of evidence comparing the accuracy of these two techniques to predict LV function recovery. In addition, some studies refer to PET as the gold standard for the assessment of myocardial viability. Therefore, PET may be an ideal noninvasive imaging comparator to MRI for a prospective study with follow-up. To date, there is a lack of cost-effectiveness analyses (or any economic analyses) of functional cardiac MRI versus an alternate noninvasive imaging method for the assessment of myocardial viability/perfusion. Conclusion There is some evidence that the accuracy of functional cardiac MRI compares favourably with alternate imaging techniques for the assessment of myocardial viability and perfusion. There is insufficient evidence whether functional cardiac MRI can better select which patients [who have CAD and severe LV dysfuncti

  15. Method of Improving a Digital Image as a Function of its Dynamic Range

    NASA Technical Reports Server (NTRS)

    Woodell, Glenn (Inventor); Jobson, Daniel J. (Inventor); Rahman, Zia-ur (Inventor)

    2004-01-01

    The present invention is a method of processing a digital image that is initially represented by digital data indexed to represent position on a display. The digital data is indicative of an intensity value I(sub i)(x,y) for each position (x,y) in each i-th spectral band. A classification of the image based on its dynamic range is then defined in each of the image's S spectral bands. The intensity value for each position in each i-th spectral band is adjusted to generate an adjusted intensity value for each position in each i-th spectral band in accordance with SIGMA (sup n)(sub n=1) W(sub n)(log I (sub i)(x,y) - log[I(sub i)(x,y)*F(sub n)(x,y)]), i=1,...,S where W(sub n) is a weighting factor, "*" is the convolution operator and S is the total number of unique spectral bands. For each n, the function F(sub n)(x,y) is a unique surround function applied to each position (x,y) and N is the total number of unique surround functions. Each unique surround function is scaled to improve some aspect of the digital image, e.g., dynamic range compression, color constancy, and lightness rendition. The adjusted intensity value to each position in each i-th spectral band of the image is then filtered with a filter function that is based on the dynamic range classification of the image.

  16. Inhibition of matrix metalloproteinase-2 improves endothelial function and prevents hypertension in insulin-resistant rats

    PubMed Central

    Nagareddy, PR; Rajput, PS; Vasudevan, H; McClure, B; Kumar, U; MacLeod, KM; McNeill, JH

    2012-01-01

    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. PMID:21740410

  17. Functional Improvement of Regulatory T Cells from Rheumatoid Arthritis Subjects Induced by Capsular Polysaccharide Glucuronoxylomannogalactan

    PubMed Central

    Alunno, Alessia; Bartoloni Bocci, Elena; Perito, Stefano; Chow, Siu-Kei; Cenci, Elio; Casadevall, Arturo; Gerli, Roberto; Vecchiarelli, Anna

    2014-01-01

    Objective Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal). Methods Flow cytometry and western blot analysis were used to investigate the frequency, function and properties of Treg cells. Results GXMGal was able to: i) induce strong increase of FOXP3 on CD4+ T cells without affecting the number of CD4+CD25+FOXP3+ Treg cells with parallel increase in the percentage of non-conventional CD4+CD25?FOXP3+ Treg cells; ii) increase intracellular levels of TGF-?1 in CD4+CD25?FOXP3+ Treg cells and of IL-10 in both CD4+CD25+FOXP3+ and CD4+CD25?FOXP3+ Treg cells; iii) enhance the suppressive activity of CD4+CD25+FOXP3+ and CD4+CD25?FOXP3+ Treg cells in terms of inhibition of effector T cell activity and increased secretion of IL-10; iv) decrease Th1 response as demonstrated by inhibition of T-bet activation and down-regulation of IFN-? and IL-12p70 production; v) decrease Th17 differentiation by down-regulating pSTAT3 activation and IL-17A, IL-23, IL-21, IL-22 and IL-6 production. Conclusion These data show that GXMGal improves Treg functions and increases the number and function of CD4+CD25?FOXP3+ Treg cells of RA patients. It is suggested that GXMGal may be potentially useful for restoring impaired Treg functions in autoimmune disorders and for developing Treg cell-based strategies for the treatment of these diseases. PMID:25338013

  18. A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury.

    PubMed

    Peterson, Todd C; Hoane, Michael R; McConomy, Keith S; Farin, Fred M; Bammler, Theo K; MacDonald, James W; Kantor, Eric D; Anderson, Gail D

    2015-06-01

    Neuroprotection, recovery of function, and gene expression were evaluated in an animal model of traumatic brain injury (TBI) after a combination treatment of nicotinamide (NAM) and progesterone (Prog). Animals received a cortical contusion injury over the sensorimotor cortex, and were treated with either Vehicle, NAM, Prog, or a NAM/Prog combination for 72?h and compared with a craniotomy only (Sham) group. Animals were assessed in a battery of behavioral, sensory, and both fine and gross motor tasks, and given histological assessments at 24?h post-injury to determine lesion cavity size, degenerating neurons, and reactive astrocytes. Microarray-based transcriptional profiling was used to determine treatment-specific changes on gene expression. Our results confirm the beneficial effects of treatment with either NAM or Prog, demonstrating significant improvements in recovery of function and a reduction in lesion cavitation, degenerating neurons, and reactive astrocytes 24?h post-injury. The combination treatment of NAM and Prog led to a significant improvement in both neuroprotection at 24?h post-injury and recovery of function in sensorimotor related tasks when compared with individual treatments. The NAM/Prog-treated group was the only treatment group to show a significant reduction of cortical loss 24?h post-injury. The combination appears to affect inflammatory and immune processes, reducing expression of a significant number of genes in both pathways. Further preclinical trials using NAM and Prog as a combination treatment should be conducted to identify the window of opportunity, determine the optimal duration of treatment, and evaluate the combination in other pre-clinical models of TBI. PMID:25313690

  19. Burn-Induced Organ Dysfunction: Vagus Nerve Stimulation Improves Cardiac Function

    PubMed Central

    Niederbichler, Andreas D.; Papst, Stephan; Claassen, Leif; Jokuszies, Andreas; Ipaktchi, Kyros; Reimers, Kerstin; Hirsch, Tobias; Steinstraesser, Lars; Kraft, Theresia; Vogt, Peter M.

    2010-01-01

    Introduction: Many studies have demonstrated the existence of an anti-inflammatory, parasympathetic pathway, termed as the inflammatory reflex. Burn-induced heart failure has been investigated in many previous studies. Proinflammatory cytokines, such as TNF-?, IL-1?, and IL-6, have been shown to play a key pathogenetic role and vagus nerve stimulation attenuates proinflammatory cytokine production. This study was designed to evaluate postburn alterations of cardiac functional parameters after vagal electrostimulation. Material and Methods: A 30% total body surface area standardized, full-thickness rat burn model was used. Electric stimulation of the vagus nerve was performed. The following functional cardiac parameters were measured by ventricular microcatheterization: Maximal and minimal left ventricular pressure, mean left ventricular pressure, end-diastolic pressure (EDP), positive and negative pressure rise and fall (±dP/dt), cardiac contractility index, and assessment of the heart rate. Results: Vagus nerve stimulation improved maximal and minimal left ventricular pressure values compared with burn-only animals. End-diastolic pressure was elevated significantly in stimulated animals; however, EDP values were comparable with those in sham-injured animals. Analyzing positive and negative pressure development, ±dP/dt was restored to levels measured in sham-injured animals but not to control animal levels. No variations in heart rate were found. Conclusion: We as well as others have shown that inflammation after burn injury is a key pathogenetic element, and this study provides new evidence that cardiac function is also improved by vagus nerve stimulation. These results lead us to consider novel therapeutic options for the treatment of postburn cardiac dysfunction. PMID:20596235

  20. Testosterone suppresses ventricular remodeling and improves left ventricular function in rats following myocardial infarction

    PubMed Central

    WANG, XIAO-FEI; QU, XING-QIAN; ZHANG, TIAN-TIAN; ZHANG, JUN-FENG

    2015-01-01

    Men with congestive heart failure (CHF) have relatively low testosterone levels. Several studies demonstrated that testosterone treatment increases cardiac output and reduces peripheral vascular resistance. However, the effects of testosterone on heart function, cardiomyocyte apoptosis and ventricular remodeling have not been fully elucidated. This study was conducted to investigate the effects of testosterone on heart function, cardiomyocyte apoptosis and ventricular remodeling in male rats post-myocardial infarction. A total of 86 male rats were randomly assigned to undergo ligation of the coronary artery (n=70) or pseudosurgery (n=16). After 6 weeks, a left ventricular ejection fraction (LVEF) of ?45% was defined as a successful model of CHF. The model rats were randomly assigned to 3 groups, namely low-dose testosterone (TU), high-dose TU and placebo (PL) groups. After treatment for 12 weeks, the expression of several mRNA transcripts in myocardial tissue was measured by quantitative polymerase chain reaction. Immunofluorescence was used to measure myocardial caspase-3 expression. Compared to the PL group, LVEF was significantly improved in the TU treatment groups. Moreover, the mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, matrix metalloproteinase-2 and sarcoendoplasmic reticulum Ca2+-ATPase 2a was significantly reduced, while the mRNA expression of glycogen synthase kinase 3? and tissue inhibitor of metalloproteinase-2 was markedly increased in the TU groups. TU treatment also significantly reduced caspase-3 expression. Therefore, different doses of TU suppressed ventricular remodeling and improved left ventricular function, reduced apoptosis and prevented mortality in a CHF rat model. PMID:25780423

  1. Flexor digitorum superficialis opposition tendon transfer improves hand function in children with Charcot-Marie-Tooth disease: Case series

    PubMed Central

    Estilow, T.; Kozin, S.H.; Glanzman, A.M.; Burns, J.; Finkel, R.S.

    2013-01-01

    Charcot-Marie-Tooth disease limits hand function. Tendon transfer has not been reported in pediatric CMT. We report two severely affected children following long finger flexor digitorum superficialis opposition tendon transfer. Improvement was noted in palmar abduction, (30°/40°), opposition, (thumb to all digits), and acquisition of pincer, palmar, and lateral pinch with measureable force (1 lb). Dexterity testing improved on the 9 Hole Peg Test (1.03 s/77 s, 22 s) and Functional Dexterity Test (13 s/33 s, 88 s). Functional improvements were observed in self feeding, clothing management, and play. These cases support flexor digitorum superficialis opposition tendon transfer surgery to improve hand function in children with CMT. PMID:22944171

  2. Pulsed LLLT improves tendon healing in rats: a biochemical, organizational, and functional evaluation.

    PubMed

    Guerra, Flávia Da Ré; Vieira, Cristiano Pedrozo; dos Santos de Almeida, Marcos; Oliveira, Letícia Prado; Claro, Ana Carolina Ferreira; Simões, Gustavo Ferreira; de Oliveira, Alexandre Leite Rodrigues; Pimentel, Edson Rosa

    2014-03-01

    In the last decades, the tendon injuries have increased substantially. Previous results suggested that low-level laser treatment (LLLT) promotes synthesis of extracellular matrix and improves the functional properties of the tendon. The aim of this study was to evaluate the effects of different protocols of LLLT on partially tenotomized tendons. Adult male rats were divided into the following: G1-intact, G2-injured, G3-injured?+?LLLT (4 J/cm(2) continuous), G4-injured?+?LLLT (4 J/cm(2) at 20 Hz). G2, G3, and G4 were euthanized 8 days after injury. G5-injured, G6-injured?+?LLLT (4 J/cm(2) continuous), and G7-injured?+?LLL (4 J/cm(2) at 20 Hz until the seventh day and 2 kHz from 8 to 14 days). G5, G6, and G7 were euthanized on the 15th day. Glycosaminoglycan (GAG) level was quantified by dimethylmethylene blue method and analyzed on agarose gel. Toluidine blue (TB) stain was used to observe metachromasy. CatWalk system was used to evaluate gait recovery. Collagen organization was analyzed by polarization microscopy. The GAG level increased in all transected groups, except G5. In G6 and G7, there was a significant increase in GAG in relation to G5. In G3 and G4, the presence of dermatan sulfate band was more prominent than G2. TB stains showed intense metachromasy in the treated groups. Birefringence analysis showed improvement in collagen organization in G7. The gait was significantly improved in G7. In conclusion, pulsed LLLT leads to increased organization of collagen bundles and improved gait recovery. PMID:23982719

  3. Cognitive Training Improves Sleep Quality and Cognitive Function among Older Adults with Insomnia

    PubMed Central

    Haimov, Iris; Shatil, Evelyn

    2013-01-01

    Study Objectives To investigate the effect of an eight-week, home-based, personalized, computerized cognitive training program on sleep quality and cognitive performance among older adults with insomnia. Design Participants (n?=?51) were randomly allocated to a cognitive training group (n?=?34) or to an active control group (n?=?17). The participants in the cognitive training group completed an eight-week, home-based, personalized, computerized cognitive training program, while the participants in the active control group completed an eight-week, home-based program involving computerized tasks that do not engage high-level cognitive functioning. Before and after training, all participants' sleep was monitored for one week by an actigraph and their cognitive performance was evaluated. Setting Community setting: residential sleep/performance testing facility. Participants Fifty-one older adults with insomnia (aged 65–85). Interventions Eight weeks of computerized cognitive training for older adults with insomnia. Results Mixed models for repeated measures analysis showed between-group improvements for the cognitive training group on both sleep quality (sleep onset latency and sleep efficiency) and cognitive performance (avoiding distractions, working memory, visual memory, general memory and naming). Hierarchical linear regressions analysis in the cognitive training group indicated that improved visual scanning is associated with earlier advent of sleep, while improved naming is associated with the reduction in wake after sleep onset and with the reduction in number of awakenings. Likewise the results indicate that improved “avoiding distractions” is associated with an increase in the duration of sleep. Moreover, the results indicate that in the active control group cognitive decline observed in working memory is associated with an increase in the time required to fall asleep. Conclusions New learning is instrumental in promoting initiation and maintenance of sleep in older adults with insomnia. Lasting and personalized cognitive training is particularly indicated to generate the type of learning necessary for combined cognitive and sleep enhancements in this population. Trial Registration ClinicalTrials.gov NCT00901641 PMID:23577218

  4. Improving optical contact for functional near?infrared brain spectroscopy and imaging with brush optodes

    PubMed Central

    Khan, Bilal; Wildey, Chester; Francis, Robert; Tian, Fenghua; Delgado, Mauricio R.; Liu, Hanli; MacFarlane, Duncan; Alexandrakis, George

    2012-01-01

    A novel brush optode was designed and demonstrated to overcome poor optical contact with the scalp that can occur during functional near infrared spectroscopy (fNIRS) and imaging due to light obstruction by hair. The brush optodes were implemented as an attachment to existing commercial flat-faced (conventional) fiber bundle optodes. The goal was that the brush optodes would thread through hair and improve optical contact on subjects with dense hair. Simulations and experiments were performed to assess the magnitude of these improvements. FNIRS measurements on 17 subjects with varying hair colors (blonde, brown, and black) and hair densities (0–2.96 hairs/mm2) were performed during a finger tapping protocol for both flat and brush optodes. In addition to reaching a study success rate of almost 100% when using the brush optode extensions, the measurement setup times were reduced by a factor of three. Furthermore, the brush optodes enabled improvements in the activation signal-to-noise ratio (SNR) by up to a factor of ten as well as significant (p < 0.05) increases in the detected area of activation (dAoA). The measured improvements in SNR were matched by Monte Carlo (MC) simulations of photon propagation through scalp and hair. In addition, an analytical model was derived to mathematically estimate the observed light power losses due to different hair colors and hair densities. Interestingly, the derived analytical formula produced excellent estimates of the experimental data and MC simulation results despite several simplifying assumptions. The analytical model enables researchers to readily estimate the light power losses due to obstruction by hair for both flat-faced fiber bundles and individual fibers for a given subject. PMID:22567582

  5. Ketoprofen combined with artery graft entubulization improves functional recovery of transected peripheral nerves.

    PubMed

    Mohammadi, Rahim; Mehrtash, Moein; Nikonam, Nima; Mehrtash, Moied; Amini, Keyvan

    2014-12-01

    The objective was to assess the local effect of ketoprofen on sciatic nerve regeneration and functional recovery. Eighty healthy male white Wistar rats were randomized into four experimental groups of 20 animals each: In the transected group (TC), the left sciatic nerve was transected and nerve cut ends were fixed in the adjacent muscle. In the treatment group the defect was bridged using an artery graft (AG/Keto) filled with 10 microliter ketoprofen (0.1 mg/kg). In the artery graft group (AG), the graft was filled with phosphated-buffer saline alone. In the sham-operated group (SHAM), the sciatic nerve was exposed and manipulated. Each group was subdivided into four subgroups of five animals each and regenerated nerve fibres were studied at 4, 8, 12 and 16 weeks post operation. Behavioural testing, sciatic nerve functional study, gastrocnemius muscle mass and morphometric indices showed earlier regeneration of axons in AG/Keto than in AG group (p < 0.05). Immunohistochemical study clearly showed more positive location of reactions to S-100 in AG/Keto than in AG group. When loaded in an artery graft, ketoprofen improved functional recovery and morphometric indices of the sciatic nerve. Local usage of this easily accessible therapeutic medicine is cost saving and avoids the problems associated with systemic administration. PMID:23932540

  6. Electronic structures and optical properties of TiO2: Improved density-functional-theory investigation

    NASA Astrophysics Data System (ADS)

    Gong, Sai; Liu, Bang-Gui

    2012-05-01

    TiO2 has been recently used to realize high-temperature ferromagnetic semiconductors. In fact, it has been widely used for a long time as white pigment and sunscreen because of its whiteness, high refractive index, and excellent optical properties. However, its electronic structures and the related properties have not been satisfactorily understood. Here, we use Tran and Blaha's modified Becke-Johnson (TB-mBJ) exchange potential (plus a local density approximation correlation potential) within the density functional theory to investigate electronic structures and optical properties of rutile and anatase TiO2. Our comparative calculations show that the energy gaps obtained from mBJ method agree better with the experimental results than that obtained from local density approximation (LDA) and generalized gradient approximation (GGA), in contrast with substantially overestimated values from many-body perturbation (GW) calculations. As for optical dielectric functions (both real and imaginary parts), refractive index, and extinction coefficients as functions of photon energy, our mBJ calculated results are in excellent agreement with the experimental curves. Our further analysis reveals that these excellent improvements are achieved because mBJ potential describes accurately the energy levels of Ti 3d states. These results should be helpful to understand the high temperature ferromagnetism in doped TiO2. This approach can be used as a standard to understand electronic structures and the related properties of such materials as TiO2.

  7. Functionalized carbon nanotubes as a filler for dielectric elastomer composites with improved actuation performance

    NASA Astrophysics Data System (ADS)

    Galantini, Fabia; Bianchi, Sabrina; Castelvetro, Valter; Gallone, Giuseppe

    2013-05-01

    Among the broad class of electro-active polymers, dielectric elastomer actuators represent a rapidly growing technology for electromechanical transduction. In order to further develop this applied science, the high driving voltages currently needed must be reduced. For this purpose, one of the most widely considered approaches is based on making elastomeric composites with highly polarizable fillers in order to increase the dielectric constant while maintaining both low dielectric losses and high-mechanical compliance. In this work, multi-wall carbon nanotubes were first functionalized by grafting either acrylonitrile or diurethane monoacrylate oligomers, and then dispersed into a polyurethane matrix to make dielectric elastomer composites. The procedures for the chemical functionalization of carbon nanotubes and proper characterizations of the obtained products are provided in detail. The consequences of the use of chemically modified carbon nanotubes as a filler, in comparison to using unmodified ones, were studied in terms of dielectric, mechanical and electromechanical response. In particular, an increment of the dielectric constant was observed for all composites throughout the investigated frequency spectrum, but only in the cases of modified carbon nanotubes did the loss factor remain almost unchanged with respect to the simple matrix, indicating that conductive percolation paths did not arise in such systems. An effective improvement in the actuation strain was observed for samples loaded with functionalized carbon nanotubes.

  8. Can prevention classification be improved by considering the function of prevention?

    PubMed

    Foxcroft, David R

    2014-12-01

    Universal, selective and indicated forms of prevention have been adopted as improvements on previous notions of primary and secondary prevention. However, some conceptual confusion remains concerning the placing of environmental, community-based or mass media preventive interventions within this typology. It is suggested that a new dimension of functional types of prevention, namely environmental, developmental and informational prevention should be specified alongside the forms of prevention in a taxonomy matrix. The main advantage of this new taxonomy is that a matrix combining the form and function dimensions of prevention can be used to identify and map out prevention strategies, to consider where research evidence is present and where more is needed, and to evaluate the relative effectiveness of different categories and components of prevention for specific health and social issues. Such evaluations would provide empirical evidence as to whether the different categories of prevention are related to outcomes or processes of prevention in ways that suggest the value of the taxonomy for understanding and increasing the impact of prevention science. This new prevention taxonomy has been useful for conceptualising and planning prevention activities in a case study involving the Swedish National Institute for Public Health. Future work should assess (1) the robustness of this new taxonomy and (2) the theoretical and empirical basis for profiling prevention investments across the various forms and functions of prevention. PMID:24052320

  9. Pomegranate juice is potentially better than apple juice in improving antioxidant function in elderly subjects.

    PubMed

    Guo, Changjiang; Wei, Jingyu; Yang, Jijun; Xu, Jing; Pang, Wei; Jiang, Yugang

    2008-02-01

    In the present study, 26 elderly subjects were recruited and randomly divided into 2 groups, that is, apple (low in antioxidant capacity) and pomegranate (high in antioxidant capacity) groups, and 250 mL of juice was consumed daily for 4 weeks. Changes in plasma antioxidant capacity, activity of antioxidant enzymes, contents of ascorbic acid, vitamin E, reduced glutathione, malondialdehyde, oxidized low-density lipoprotein and carbonyls, and the degree of DNA damage in mononuclear blood cells were measured. Urine samples were collected for determination of 8-hydroxy-2'-deoxyguanosine content. Increased plasma antioxidant capacity and decreased plasma carbonyl content were demonstrated after daily consumption of pomegranate juice. In comparison, apple juice consumption presented a less significant effect on antioxidant function in elderly subjects. It is concluded that daily consumption of pomegranate juices is potentially better than apple juice in improving antioxidant function in the elderly. Because the plasma ascorbic acid, vitamin E, and reduced glutathione contents did not differ significantly between the 2 groups in this study, the phenolics may be the functional components contained in pomegranate juice that accounted for the observations. PMID:19083391

  10. Gastric bypass and banding equally improve insulin sensitivity and ? cell function

    PubMed Central

    Bradley, David; Conte, Caterina; Mittendorfer, Bettina; Eagon, J. Christopher; Varela, J. Esteban; Fabbrini, Elisa; Gastaldelli, Amalia; Chambers, Kari T.; Su, Xiong; Okunade, Adewole; Patterson, Bruce W.; Klein, Samuel

    2012-01-01

    Bariatric surgery in obese patients is a highly effective method of preventing or resolving type 2 diabetes mellitus (T2DM); however, the remission rate is not the same among different surgical procedures. We compared the effects of 20% weight loss induced by laparoscopic adjustable gastric banding (LAGB) or Roux-en-Y gastric bypass (RYGB) surgery on the metabolic response to a mixed meal, insulin sensitivity, and ? cell function in nondiabetic obese adults. The metabolic response to meal ingestion was markedly different after RYGB than after LAGB surgery, manifested by rapid delivery of ingested glucose into the systemic circulation, by an increase in the dynamic insulin secretion rate, and by large, early postprandial increases in plasma glucose, insulin, and glucagon-like peptide–1 concentrations in the RYGB group. However, the improvement in oral glucose tolerance, insulin sensitivity, and overall ? cell function after weight loss were not different between surgical groups. Additionally, both surgical procedures resulted in a similar decrease in adipose tissue markers of inflammation. We conclude that marked weight loss itself is primarily responsible for the therapeutic effects of RYGB and LAGB on insulin sensitivity, ? cell function, and oral glucose tolerance in nondiabetic obese adults. PMID:23187122

  11. New knowledge about the function of the human middle ear: development of an improved analog model.

    PubMed

    Goode, R L; Killion, M; Nakamura, K; Nishihara, S

    1994-03-01

    Conventional teaching regarding the acoustic function of the human middle ear is that it serves as an impedance matching system to offset the loss that occurs when sound passes from the low-impedance sound field to the high-impedance cochlear fluid. A transformer analogy is often used with the pressure transformation produced by the eardrum; footplate area ratio and the lever ratio considered to be approximately 27 dB. Recent data on middle ear function has shown this to be only partially correct. A transformer analogy is not appropriate since the pressure gain of the middle ear decreases above 1000 Hz and does not depend on the cochlear load at all frequencies. Experiments are described of umbo, malleus short process, and stapes displacement in human temporal bones using a laser Doppler measuring system (LDS). The measurements support previous studies that indicate that in addition to a roll-off in tympanic membrane function above 1000 Hz, there is slippage in the ossicular lever system that causes an increasing "lever ratio" above 1000 Hz, thought to be caused by translational movement of the ossicular rotation axis near the short process. An improved analog circuit model of the external and middle ear has been developed that produces results equivalent to those found in the temporal bones. PMID:8172293

  12. Prostaglandin E1 improves pulsatile preservation characteristics and early graft function in expanded criteria donor kidneys.

    PubMed

    Polyak, M M; Arrington, B O; Stubenbord, W T; Kinkhabwala, M

    1998-01-01

    Unlike simple cold storage, machine preservation allows dynamic assessment and manipulation of the donor organ before transplantation. The effects of four pharmacologic agents added to the perfusate during machine preservation of expanded criteria donor (ECD) kidneys were prospectively compared to 1) describe their influence on perfusion parameters and 2) determine their influence on early graft outcome. Between 1 January 1995 and 1 October 1997, 125 consecutive ECD kidneys were preserved in the authors' laboratory. A definition of ECD was assigned to kidneys requiring pretransplant biopsy. The ECD kidneys were randomized to receive prostaglandin E1 (PGE1), trifluoperazine (TFP), verapamil (VER), mannitol (MAN), or no intervention (control) during machine preservation. All kidneys were preserved by continuous hypothermic pulsatile perfusion (CHPP) using Belzer II solution, and perfusion parameters were measured every 2 hours during pulsatile perfusion. The addition of PGE1 to the perfusate increased renal flow and decreased renal resistance. Moreover, the PGE1 treated group was associated with improved early graft function when compared with all other groups. The addition of VER, TFP, and MAN influenced neither the perfusion characteristics nor the incidence of early graft function. Treatment with PGE1 during machine preservation enhances hydrostatic perfusion parameters (renal flow and renal resistance) and reduces the incidence of delayed graft function in ECD kidneys. PMID:9804507

  13. AmIRTEM: a functional model for training of aerobic endurance for health improvement.

    PubMed

    Gaeta, Eugenio; Cea, Gloria; Arredondo, Maria T; Leuteritz, Jan P

    2012-11-01

    In a nonstrenuous exercise, the heart rate (HR) shows a linear relationship with the maximum volume of oxygen consumption VO(2Max) and serves as an indicator of performance of the cardiovascular system. The HR replaces the %VO(2Max) in exercise program prescription to improve aerobic endurance. In order to achieve an optimal effect in an endurance training, the athlete needs to work out at an HR high enough to trigger the aerobic metabolism, while avoiding the very high HRs that bring along significant risks of myocardial infarction. The minimal and optimal base training programs, followed by stretching exercises to prevent injuries, are adequate programs to maximize benefits and minimize health risks for the cardiovascular system during single session training. In this paper, we have defined a functional model for an ambient intelligence system that monitors, evaluates, and trains the aerobic endurance. It is based on the Android operating system and the Gow Running smart shirt. The system has been evaluated during functional assessment stress testing of aerobic endurance in the Stress Physiology Laboratory (SPL) of the Technical University of Madrid. Furthermore, a voice system designed to guide the user through minimal and optimal base training programs has been evaluated. The results obtained fully confirm the model with a high correlation between the data collected by the system and the by SPL. There is also a high hit rate between training sessions of the users and the objective training functions defined in the training programs. PMID:22801486

  14. Chronic intermittent fasting improves cognitive functions and brain structures in mice.

    PubMed

    Li, Liaoliao; Wang, Zhi; Zuo, Zhiyi

    2013-01-01

    Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day) fasting or high fat diet (45% caloric supplied by fat) for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice). Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals. PMID:23755298

  15. Improving adsorption and activation of the lipase immobilized in amino-functionalized ordered mesoporous SBA-15

    NASA Astrophysics Data System (ADS)

    Xu, Yun-qiang; Zhou, Guo-wei; Wu, Cui-cui; Li, Tian-duo; Song, Hong-bin

    2011-05-01

    Ordered mesoporous SBA-15 was prepared by hydrothermal process and was functionalized with(3-aminopropyl) triethoxysilane (APTES) by post-synthesis-grafting method. The materials were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive spectrometer (EDS), small-angle X-ray powder diffraction (SAXRD), N 2 adsorption-desorption and Fourier transform infrared spectroscopy (FT-IR). The results indicated that SBA-15 had a 2-dimensional hexagonal p6 mm mesoscopic structure and the mesoscopic structure was remained after the functionalization procedure. The activities of porcine pancreatic lipase (PPL) immobilized in SBA-15 by physical adsorption and in APTES functionalized SBA-15 by chemical adsorption were studied by hydrolysis of triacetin. Chemically adsorbed PPL showed higher loading amount and catalytic activity comparing with physically adsorbed PPL. The stability of immobilized PPL against thermal and pH of reaction medium was significantly improved. Recycling experiments showed that chemically adsorbed PPL exhibited better reusability than physically adsorbed PPL.

  16. Effect of Smaller Left Ventricular Capture Threshold Safety Margins to Improve Device Longevity in Recipients of Cardiac Resynchronization-Defibrillation Therapy

    PubMed Central

    Steinhaus, Daniel A.; Waks, Jonathan W.; Collins, Robert; Kleckner, Karen; Kramer, Daniel B.; Zimetbaum, Peter J.

    2015-01-01

    Device longevity in cardiac resynchronization therapy (CRT) is affected by the pacing capture threshold (PCT) and programmed pacing amplitude of the left ventricular (LV) pacing lead. The aims of this study were to evaluate the stability of LV pacing thresholds in a nationwide sample of CRT defibrillator recipients and to determine potential longevity improvements associated with a decrease in the LV safety margin while maintaining effective delivery of CRT. CRT defibrillator patients in the Medtronic CareLink database were eligible for inclusion. LV PCT stability was evaluated using ?2 measurements over a 14-day period. Separately, a random sample of 7,250 patients with programmed right atrial and right ventricular amplitudes ?2.5 V, LV thresholds ? 2.5 V, and LV pacing ?90% were evaluated to estimate theoretical battery longevity improvement using LV safety margins of 0.5 and 1.5 V. Threshold stability analysis in 43,256 patients demonstrated LV PCT stability of <0.5 V in 77% of patients and <1 V in 95%. Device longevity analysis showed that the use of a 0.5-V safety margin increased average battery longevity by 0.62 years (95% confidence interval 0.61 to 0.63) compared with a safety margin of 1.5 V. Patients with LV PCTs >1 V had the greatest increases in battery life (mean increase 0.86 years, 95% confidence interval 0.85 to 0.87). In conclusion, nearly all CRT defibrillator patients had LV PCT stability <1.0 V. Decreasing the LV safety margin from 1.5 to 0.5 V provided consistent delivery of CRT for most patients and significantly improved battery longevity. PMID:25933732

  17. Effect of Smaller Left Ventricular Capture Threshold Safety Margins to Improve Device Longevity in Recipients of Cardiac Resynchronization-Defibrillation Therapy.

    PubMed

    Steinhaus, Daniel A; Waks, Jonathan W; Collins, Robert; Kleckner, Karen; Kramer, Daniel B; Zimetbaum, Peter J

    2015-07-01

    Device longevity in cardiac resynchronization therapy (CRT) is affected by the pacing capture threshold (PCT) and programmed pacing amplitude of the left ventricular (LV) pacing lead. The aims of this study were to evaluate the stability of LV pacing thresholds in a nationwide sample of CRT defibrillator recipients and to determine potential longevity improvements associated with a decrease in the LV safety margin while maintaining effective delivery of CRT. CRT defibrillator patients in the Medtronic CareLink database were eligible for inclusion. LV PCT stability was evaluated using ?2 measurements over a 14-day period. Separately, a random sample of 7,250 patients with programmed right atrial and right ventricular amplitudes ?2.5 V, LV thresholds ? 2.5 V, and LV pacing ?90% were evaluated to estimate theoretical battery longevity improvement using LV safety margins of 0.5 and 1.5 V. Threshold stability analysis in 43,256 patients demonstrated LV PCT stability of <0.5 V in 77% of patients and <1 V in 95%. Device longevity analysis showed that the use of a 0.5-V safety margin increased average battery longevity by 0.62 years (95% confidence interval 0.61 to 0.63) compared with a safety margin of 1.5 V. Patients with LV PCTs >1 V had the greatest increases in battery life (mean increase 0.86 years, 95% confidence interval 0.85 to 0.87). In conclusion, nearly all CRT defibrillator patients had LV PCT stability <1.0 V. Decreasing the LV safety margin from 1.5 to 0.5 V provided consistent delivery of CRT for most patients and significantly improved battery longevity. PMID:25933732

  18. Recognizing the fingerprints of the Galactic bar: a quantitative approach to comparing model (l,v) distributions to observation

    E-print Network

    Sormani, Mattia C

    2014-01-01

    We present a new method for fitting simple hydrodynamical models to the (l,v) distribution of atomic and molecular gas observed in the Milky Way. The method works by matching features found in models and observations. It is based on the assumption that the large-scale features seen in (l,v) plots, such as ridgelines and the terminal velocity curve, are influenced primarily by the underlying large-scale Galactic potential and are only weakly dependent on local ISM heating and cooling processes. In our scheme one first identifies by hand the features in the observations: this only has to be done once. We describe a procedure for automatically extracting similar features from simple hydrodynamical models and quantifying the "distance" between each model's features and the observations. Application to models of the Galactic Bar region (|l|<30deg) shows that our feature-fitting method performs better than \\chi^2 or envelope distances at identifying the correct underlying galaxy model.

  19. Improved deposition and deprotection of silane tethered 3,4 hydroxypyridinone (HOPO) ligands on functionalized nanoporous silica

    SciTech Connect

    Davidson, Joseph D.; Wiacek, Robert J.; Burton, Sarah D.; Li, Xiaohong S.; Fryxell, Glen E.; Addleman, Raymond S.; Yantasee, Wasanna; Sangvanich, Thanapon; Pattamakomsan, Kanda

    2012-04-01

    An improved synthesis of a 3,4 hydroxypyridinone (HOPO) functionalized mesoporous silica is described. Higher 3,4-HOPO monolayer ligand loadings have been achieved, resulting in better performance. Performance improvements were demonstrated with the capture of U(VI) from human blood, plasma and filtered river water.

  20. Intensive lifestyle intervention improves physical function among obese adults with knee pain: Findings from the Look AHEAD trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lifestyle interventions causing weight loss or improved physical fitness in obese individuals may lead to improved physical function. This study involved participants in the Action for Health in Diabetes (Look AHEAD) trial who reported knee pain at baseline (n = 2,203). The purposes of this study we...

  1. Effective RNA-silencing strategy of Lv-MSTN/GDF11 gene and its effects on the growth in shrimp, Litopenaeus vannamei.

    PubMed

    Lee, Ji-Hyun; Momani, Jalal; Kim, Young Mog; Kang, Chang-Keun; Choi, Jung-Hwa; Baek, Hae-Ja; Kim, Hyun-Woo

    2015-01-01

    Myostatin (MSTN), also known as GDF8, is a member of the transforming growth factor-? (TGF-?) superfamily and plays an important role in muscle growth, development, and differentiation. Recently, Lv-MSTN/GDF11, the primitive isoform of MSTN and GDF11, was identified from the shrimp Litopenaeus vannamei. The major production site for Lv-MSTN/GDF11 is in the heart, not the tail muscle, which differs from MSTNs in mammals. Among the three injected RNAs, long dsRNA was the most effective for Lv-MSTN/GDF11 knockdown and transcripts of Lv-MSTN/GDF11 decreased in both the heart (88.85%) and skeletal muscles (43.36%) 72h after injection of 10pmol of long dsRNA. We also found that higher doses of dsRNA did not lead to greater decreases in Lv-MSTN/GDF11 transcripts for amounts between 1pmol and 100pmol. Injection of Lv-MSTN/GDF11 dsRNA did not affect the upregulation of the skeletal actin gene (Lv-ACTINSK) in the tail muscle, but the expression of cytoplasmic and cardiac actins were upregulated in both the heart and tail muscle. Over the course of 8weeks of dsRNA injection, considerably higher mortality (~71%) was seen in the dsRNA-injected group compared to the control group (40%). Surviving shrimp in the dsRNA injected group had a lower growth rate due to the adverse effects of Lv-MSTN/GDF11 knockdown. Lv-MSTN/GDF11 appears to be involved in muscular or neuronal development, but not in doubling muscle fibers, as is the case with mammalian MSTN. PMID:25246367

  2. Anti-lipopolysaccharide factor in Litopenaeus vannamei (LvALF): a broad spectrum antimicrobial peptide essential for shrimp immunity against bacterial and fungal infection.

    PubMed

    de la Vega, Enrique; O'Leary, Nuala A; Shockey, Jessica E; Robalino, Javier; Payne, Caroline; Browdy, Craig L; Warr, Gregory W; Gross, Paul S

    2008-04-01

    Antimicrobial peptides are an essential component of the innate immune system of most organisms. Expressed sequence tag analysis from various shrimp (Litopenaeus vannamei) tissues revealed transcripts corresponding to two distinct sequences (LvALF1 and LvALF2) with strong sequence similarity to anti-lipopolysaccharide factor (ALF), an antimicrobial peptide originally isolated from the horseshoe crab Limulus polyphemus. Full-length clones contained a 528bp transcript with a predicted open reading frame coding for 120 amino acids in LvALF1, and a 623bp transcript with a predicted open reading frame coding for 93 amino acids in LvALF2. A reverse genetic approach was implemented to study the in vivo role of LvALF1 in protecting shrimp from bacterial, fungal and viral infections. Injection of double-stranded RNA (dsRNA) corresponding to the LvALF1 message resulted in a significant reduction of LvALF1 mRNA transcript abundance as determined by qPCR. Following knockdown, shrimp were challenged with low pathogenic doses of Vibrio penaeicida, Fusarium oxysporum or white spot syndrome virus (WSSV) and the resulting mortality curves were compared with controls. A significant increase of mortality in the LvALF1 knockdown shrimp was observed in the V. penaeicida and F. oxysporum infections when compared to controls, showing that this gene has a role in protecting shrimp from both bacterial and fungal infections. In contrast, LvALF1 dsRNA activated the sequence-independent innate anti-viral immune response giving increased protection from WSSV infection. PMID:18078996

  3. Race–Ethnic and Sex Differences in Left Ventricular Structure and Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

    PubMed Central

    Kishi, Satoru; Reis, Jared P.; Venkatesh, Bharath A.; Gidding, Samuel S.; Armstrong, Anderson C.; Jacobs, David R.; Sidney, Stephen; Wu, Colin O.; Cook, Nakela L.; Lewis, Cora E.; Schreiner, Pamela J.; Isogawa, Akihiro; Liu, Kiang; Lima, João A. C.

    2015-01-01

    Background We investigated race–ethnic and sex?specific relationships of left ventricular (LV) structure and LV function in African American and white men and women at 43 to 55 years of age. Methods and Results The Coronary Artery Risk Development in Young Adults (CARDIA) Study enrolled African American and white adults, age 18 to 30 years, from 4 US field centers in 1985–1986 (Year?0) who have been followed prospectively. We included participants with echocardiographic assessment at the Year?25 examination (n=3320; 44% men, 46% African American). The end points of LV structure and function were assessed using conventional echocardiography and speckle?tracking echocardiography. In the multivariable models, we used, in addition to race–ethnic and gender terms, demographic (age, physical activity, and educational level) and cardiovascular risk variables (body mass index, systolic blood pressure, diastolic blood pressure, heart rate, presence of diabetes, use of antihypertensive medications, number of cigarettes/day) at Year?0 and ?25 examinations as independent predictors of echocardiographic outcomes at the Year?25 examination (LV end?diastolic volume [LVEDV]/height, LV end?systolic volume [LVESV]/height, LV mass [LVM]/height, and LVM/LVEDV ratio for LV structural indices; LV ejection fraction [LVEF], Ell, and Ecc for systolic indices; and early diastolic and atrial ratio, mitral annulus early peak velocity, ratio of mitral early peak velocity/mitral annulus early peak velocity; ratio, left atrial volume/height, longitudinal peak early diastolic strain rate, and circumferential peak early diastolic strain rate for diastolic indices). Compared with women, African American and white men had greater LV volume and LV mass (P<0.05). For LV systolic function, African American men had the lowest LVEF as well as longitudinal (Ell) and circumferential (Ecc) strain indices among the 4 sex/race–ethnic groups (P<0.05). For LV diastolic function, African American men and women had larger left atrial volumes; African American men had the lowest values of Ell and Ecc for diastolic strain rate (P<0.05). These race/sex differences in LV structure and LV function persisted after adjustment. Conclusions African American men have greater LV size and lower LV systolic and diastolic function compared to African American women and to white men and women. The reasons for these racial?ethnic differences are partially but not completely explained by established cardiovascular risk factors. PMID:25770024

  4. Illuminance of the image in the ultraspeed cameras SFR, ZhLV-2 and ZhFR-3

    Microsoft Academic Search

    A. S. Dubovik; Iu. A. Zatsepin; A. O. Daragan; N. M. Sitsinskaia

    1976-01-01

    On the basis of the structural characteristics of their optical schemes, formulas are derived for the illuminance of the image in the streak camera (SFR), the high-speed slave-type camera ZhLV-2, and the slave photographic detector ZhFR-3, in both photographic detector and high-speed slow-motion variants. The SFR contains two lenses, the first of which is the Industar-51 lens with a focal

  5. Improvement in protein functional site prediction by distinguishing structural and functional constraints on protein family evolution using computational design

    Microsoft Academic Search

    Gong Cheng; Bin Qian; Ram Samudrala; David Baker

    2005-01-01

    The prediction of functional sites in newly solved protein structures is a challenge for computational structural biology. Most methods for approaching this problem use evolutionary conservation as the primary indicator of the location of functional sites. However, sequence conservation reflects not only evolutionary selection at functional sites to main- tain protein function, but also selection throughout the protein to maintain

  6. Ecosystem function in waste stabilisation ponds: Improving water quality through a better understanding of biophysical coupling

    NASA Astrophysics Data System (ADS)

    Ghadouani, Anas; Reichwaldt, Elke S.; Coggins, Liah X.; Ivey, Gregory N.; Ghisalberti, Marco; Zhou, Wenxu; Laurion, Isabelle; Chua, Andrew

    2014-05-01

    Wastewater stabilisation ponds (WSPs) are highly productive systems designed to treat wastewater using only natural biological and chemical processes. Phytoplankton, microbial communities and hydraulics play important roles for ecosystem functionality of these pond systems. Although WSPs have been used for many decades, they are still considered as 'black box' systems as very little is known about the fundamental ecological processes which occur within them. However, a better understanding of how these highly productive ecosystems function is particularly important for hydrological processes, as treated wastewater is commonly discharged into streams, rivers, and oceans, and subject to strict water quality guidelines. WSPs are known to operate at different levels of efficiency, and treatment efficiency of WSPs is dependent on physical (flow characteristics and sludge accumulation and distribution) and biological (microbial and phytoplankton communities) characteristics. Thus, it is important to gain a better understanding of the role and influence of pond hydraulics and vital microbial communities on pond performance and WSP functional stability. The main aim of this study is to investigate the processes leading to differences in treatment performance of WSPs. This study uses a novel and innovative approach to understand these factors by combining flow cytometry and metabolomics to investigate various biochemical characteristics, including the metabolite composition and microbial community within WSPs. The results of these analyses will then be combined with results from the characterisation of pond hydrodynamics and hydraulic performance, which will be performed using advanced hydrodynamic modelling and advanced sludge profiling technology. By understanding how hydrodynamic and biological processes influence each other and ecosystem function and stability in WSPs, we will be able to propose ways to improve the quality of the treatment using natural processes, with less reliance on chemical treatment. This will in turn contribute to the reduction in the cost of operation, but more importantly reduce the impact on the environment (i.e., discharge, GHGs), and increase water quality and the potential for water reuse worldwide.

  7. Sodium nitrite supplementation improves motor function and skeletal muscle inflammatory profile in old male mice.

    PubMed

    Justice, Jamie N; Gioscia-Ryan, Rachel A; Johnson, Lawrence C; Battson, Micah L; de Picciotto, Natalie E; Beck, Hannah J; Jiang, Hong; Sindler, Amy L; Bryan, Nathan S; Enoka, Roger M; Seals, Douglas R

    2015-01-15

    Aging is associated with motor declines that lead to functional limitations and disability, necessitating the development of therapies to slow or reverse these events. We tested the hypothesis that sodium nitrite supplementation attenuates declines in motor function in older C57BL/6 mice. Motor function was assessed using a battery of tests (grip strength, open-field distance, rota-rod endurance) in old animals (age 20-24 mo) at baseline and after 8 wk of sodium nitrite (old nitrite, n = 22, 50 mg/liter) or no treatment (old control, n = 40), and in young reference animals (3 mo, n = 87). Eight weeks of sodium nitrite supplementation improved grip strength (old nitrite, +12.0 ± 14.9% vs. old control, +1.5 ± 15.2%, P < 0.05) and open field distance (old nitrite, +9.5 ± 7.7%, P < 0.01 vs. old control, -28.1 ± 2.0%) and completely restored rota-rod endurance-run time (old nitrite, +3.2 ± 7.1%, P < 0.01 vs. old control, -21.5 ± 7.2%; old nitrite after treatment P > 0.05 vs. young reference). Inflammatory cytokines were markedly increased in quadriceps of old compared with young reference animals (by ELISA, interleukin-1? [IL-1?] 3.86 ± 2.34 vs. 1.11 ± 0.74, P < 0.05; interferon-gamma [INF-?] 8.31 ± 1.59 vs. 3.99 ± 2.59, P < 0.01; tumor necrosis factor-alpha [TNF-?] 1.69 ± 0.44 vs. 0.76 ± 0.30 pg/ml, P < 0.01), but were reduced to young reference levels after treatment (old nitrite, IL-1? 0.67 ± 0.95; INF-? 5.22 ± 2.01, TNF-? 1.21 ± 0.39 pg/ml, P < 0.05 vs. old control, P > 0.05 vs. young reference). Cytokine expression and treatment (old nitrite vs. old control) predicted strength (R(2) = 0.822, P < 0.001, IL-1?, INF-?, group), open field distance (R(2) = 0.574, P < 0.01, IL-1?, group) and endurance run time (R(2) = 0.477, P < 0.05, INF-?). Our results suggest that sodium nitrite improves motor function in old mice, in part by reducing low-grade inflammation in muscle. PMID:25377884

  8. Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy.

    PubMed

    Englander, Zoë A; Sun, Jessica; Laura Case; Mikati, Mohamad A; Kurtzberg, Joanne; Song, Allen W

    2015-01-01

    Cerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study. PMID:25610796

  9. Deep Inelastic Scattering in Improved Lattice QCD. I. The first moment of structure functions

    E-print Network

    Stefano Capitani; Giancarlo Rossi

    1994-07-04

    We present the complete 1-loop perturbative computation of the renormalization constants and mixing coefficients of the operators that measure the first moment of deep inelastic scattering structure functions, employing the nearest neighbor improved lattice QCD action. The interest of using this action in Monte Carlo simulations lies in the fact that all terms which in the continuum limit are effectively of order $a$ ($a$ being the lattice spacing) have been proven to be absent from on-shell hadronic lattice matrix elements. Because of the complexity of the calculations, we have checked the analytical expression of all Feynman diagrams using Schoonschip. To this end we have developed a suitable code designed to automatically carry out all the necessary lattice algebraic manipulations, starting from the elementary building blocks of each diagram. We have found discrepancies with some of the published numbers, but we are in agreement with the known results on the energy-momentum tensor.

  10. A dynamic FRET reporter of gene expression improved by functional screening.

    PubMed

    Schifferer, Martina; Griesbeck, Oliver

    2012-09-19

    Here, we describe a reporter system that consists of a FRET biosensor and its corresponding aptamer. The FRET biosensor employs the synthetic aptamer binding peptide Rsg1.2 sandwiched between mutants of the Green Fluorescent Protein and undergoes FRET when binding its corresponding Rev Responsive Element (RRE) RNA aptamer. We developed a novel approach to engineer FRET biosensors by linker extension and screening to improve signal strength of the biosensor which we called VAmPIRe (Viral Aptamer binding Peptide based Indicator for RNA detection). We demonstrate that the system is quantitative, reversible and works with high specificity in vitro and in vivo in living bacteria and mammalian cells. Thus, VAmPIRe may become valuable for RNA localizations and as a dynamic RNA-based reporter for live cell imaging. Moreover, functional screening of large libraries as demonstrated here may become applicable to optimize some of the many FRET biosensors of cellular signaling. PMID:22946509

  11. Solution of an optimal control lifting body entry problem by an improved method of perturbation functions

    NASA Technical Reports Server (NTRS)

    Garcia, F., Jr.

    1975-01-01

    This paper presents a solution to a complex lifting reentry three-degree-of-freedom problem by using the calculus of variations to minimize the integral of the sum of the aerodynamics loads and heat rate input to the vehicle. The entry problem considered does not have state and/or control constraints along the trajectory. The calculus of variations method applied to this problem gives rise to a set of necessary conditions which are used to formulate a two point boundary value (TPBV) problem. This TPBV problem is then numerically solved by an improved method of perturbation functions (IMPF) using several starting co-state vectors. These vectors were chosen so that each one had a larger norm with respect to show how the envelope of convergence is significantly increased using this method and cases are presented to point this out.

  12. G-CSF does not improve systolic function in a rat model of acute myocardial infarction

    Microsoft Academic Search

    João Pedro S. Werneck-de-Castro; Ricardo Henrique Costa-e-Sousa; Patricia Fidelis de Oliveira; Vanessa Pinho-Ribeiro; Débora B. Mello; Ramon Peçanha; Elisabete Mattos; Emerson L. Olivares; Anna Carolina V. Maia; José Geraldo Mill; Regina Coeli dos Santos Goldenberg; Antônio Carlos Campos-de-Carvalho

    2006-01-01

    \\u000a Abstract\\u000a \\u000a \\u000a Objective\\u000a   Granulocyte colony-stimulating factor (G-CSF) has been reported to improve cardiac performance by increasing the number of\\u000a bone marrow stem cell in the peripheral circulation. The aim of this study was to investigate the impact of G-CSF administration\\u000a on cardiac function in a rat model of acute myocardial infarction.\\u000a \\u000a \\u000a \\u000a \\u000a Methods\\u000a   Recombinant human G-CSF (Filgrastim, 100 ?g\\/kg, sc) twice a day

  13. A new meta-GGA exchange functional based on an improved constraint-based GGA

    NASA Astrophysics Data System (ADS)

    del Campo, Jorge M.; Gázquez, José L.; Trickey, S. B.; Vela, Alberto

    2012-08-01

    We report the performance of a non-empirical meta-GGA that comes from converting our simple VT{8,4} GGA. That GGA satisfies the large dimensionless reduced gradient limit, obeys the Lieb-Oxford bound, and reduces to the exact second-order gradient expansion approximation in the slowly varying limit. Validation studies of meta-VT{8,4} for several properties using well-known test sets shows a modest improvement with respect to revTPSS. Compared with the heavily parameterized M06-L, the heats of formation of meta-VT{8,4} are substantially better but reaction barrier heights are considerably worse. This suggests the opportunity for additional constraints and the need for better correlation functionals.

  14. Improving the Description of Nonmagnetic and Magnetic Molecular Crystals via the van der Waals Density Functional

    E-print Network

    Obata, Masao; Hamada, Ikutaro; Oda, Tatsuki

    2015-01-01

    We have derived and implemented a stress tensor formulation for the van derWaals density functional (vdW-DF) with spin-polarization-dependent gradient correction (GC) recently proposed by the authors [J. Phys. Soc. Jpn. 82, 093701 (2013)] and applied it to nonmagnetic and magnetic molecular crystals under ambient condition. We found that the cell parameters of the molecular crystals obtained with vdW-DF show an overall improvement compared with those obtained using local density and generalized gradient approximations. In particular, the original vdW-DF with GC gives the equilibrium structural parameters of solid oxygen in the {\\alpha}-phase, which are in good agreement with the experiment.

  15. Cranial electrical stimulation improves symptoms and functional status in individuals with fibromyalgia.

    PubMed

    Taylor, Ann Gill; Anderson, Joel G; Riedel, Shannon L; Lewis, Janet E; Kinser, Patricia A; Bourguignon, Cheryl

    2013-12-01

    To investigate the effects of microcurrent cranial electrical stimulation (CES) therapy on reducing pain and its associated symptoms in fibromyalgia (FM), we conducted a randomized, controlled, three-group (active CES device, sham device, and usual care alone [UC]), double-blind study to determine the potential benefit of CES therapy for symptom management in FM. Those individuals using the active CES device had a greater decrease in average pain (p = .023), fatigue (p = .071), and sleep disturbance (p = .001) than individuals using the sham device or those receiving usual care alone over time. Additionally, individuals using the active CES device had improved functional status versus the sham device and UC groups over time (p = .028). PMID:24315255

  16. An improved model function method for choosing regularization parameters in linear inverse problems

    NASA Astrophysics Data System (ADS)

    Xie, Jianli; Zou, Jun

    2002-06-01

    This paper proposes a new model function iterative method, that improves our earlier work (Kunisch K and Zou J 1998 Inverse Problems 14 1247-64), on finding some reasonable regularization parameters in the widely used output least squares formulations of linear inverse problems, based on the Morozov and damped Morozov principles. The new algorithm updates the model parameters in a computationally more stable manner. In addition, the method can be rigorously shown to have global convergence, in particular, its convergence is carried on strictly monotone decreasingly. This property seems especially useful and important in real applications as it enables us to start with some larger regularization parameters, and thus with more stable least squares problems. Numerical experiments for one-and two-dimensional elliptic inverse problems and an inverse integral problem are presented to illustrate the efficiency of the proposed algorithm.

  17. Improving the Description of Nonmagnetic and Magnetic Molecular Crystals via the van der Waals Density Functional

    NASA Astrophysics Data System (ADS)

    Obata, Masao; Nakamura, Makoto; Hamada, Ikutaro; Oda, Tatsuki

    2015-02-01

    We have derived and implemented a stress tensor formulation for the van der Waals density functional (vdW-DF) with spin-polarization-dependent gradient correction (GC) recently proposed by the authors [J. Phys. Soc. Jpn. 82, 093701 (2013)] and applied it to nonmagnetic and magnetic molecular crystals under ambient condition. We found that the cell parameters of the molecular crystals obtained with vdW-DF show an overall improvement compared with those obtained using local density and generalized gradient approximations. In particular, the original vdW-DF with GC gives the equilibrium structural parameters of solid oxygen in the ?-phase, which are in good agreement with the experiment.

  18. Regulation of Isotopic Composition of Water - way of Improvement of Cosmonauts Drinking Water Functional Properties

    NASA Astrophysics Data System (ADS)

    Kulikova, Ekaterina; Utina, Dina; Vorozhtsova, Svetlana; Severyuhin, Yuri; Abrosimova, Anna; Sinyak, Yuri; Ivanov, Alexander

    The problem in providing drinking water to cosmonauts is solved - at this moment there is a task to improve the functional properties of the water. One of the perspectives of this trend is the use of light isotopic water. The animal studies have shown that long-term consumption of water with a depletion of deuterium and oxygen heavy isotopes accelerates the rise of mass non-irradiated mice, the phase fluctuations reducing or increasing hematological parameters were having adaptive nature. These fluctuations didn’t overcome values beyond the physiological norm of this type of animal. It is established that the therapeutic use of light isotopic water with 35 - 90 ppm in deuterium increases the survival of irradiated mice by an average of 30%, contributes to the preservation of irradiated animals body weight. Treatment of acute radiation sickness with light isotopic water stimulates hematopoietic recovery. At the same time, keeping mice drinking light isotopic water for 7 - 8 days before the irradiation (from 4 to 8.5 Gr) has no effect on the level of radio resistance. Longer keeping mice on light isotopic water, for 14 -21 days - reduction in life expectancy, animal mass, bone marrow cellularity and the level of white blood cells in irradiated animals is noted. It was established that keeping mice on light isotopic water for 14 days before exposure in experimental animals causes an increase in the mitotic index and the frequency of formation of aberrant mitosis after 24 hours of Co(60) gamma radiation in doses of 1 , 2, and 4 Gr. Thus, it is clear that the regulation of the isotopic composition of drinking water - way to improve its functional properties.

  19. Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep.

    PubMed

    Torres, Flavio; González-Candia, Alejandro; Montt, Camilo; Ebensperger, Germán; Chubretovic, Magdalena; Serón-Ferré, María; Reyes, Roberto V; Llanos, Aníbal J; Herrera, Emilio A

    2015-04-01

    Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial- and muscular-dependent pathways. This was associated with an enhanced nitric oxide-dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN. PMID:25736256

  20. Telbivudine is associated with improvement of renal function in patients transplanted for HBV liver disease.

    PubMed

    Cholongitas, E; Vasiliadis, T; Goulis, I; Fouzas, I; Antoniadis, N; Papanikolaou, V; Akriviadis, E

    2015-07-01

    Recent studies showed that telbivudine in patients with hepatitis B virus (HBV) infection improved their glomerular filtration rate (GFR), but data regarding its impact on renal function in liver transplant (LT) recipients are very limited. We evaluated 17 consecutive recipients who received at baseline nucleos(t)ide analogue(s) (NAs) other than telbivudine for 12 months, and then they were switched to telbivudine prophylaxis for another 12 months. In each patient, laboratory data including evaluation of GFR (using MDRD and CKD-EPI) were prospectively recorded. The changes in GFR (?GFR) between baseline and after 12 months (1st period) and between telbivudine initiation and 24 months (2nd period) were evaluated. All patients remained serum HBsAg and HBV-DNA negative. GFR-MDRD at baseline, 12 months and 24 months were 72 ± 18, 67.8 ± 16 and 70.3 ± 12mL/min, respectively, (P = 0.025 for comparison between 12 months and 24 months). ?GFR at the 1st period was significantly lower, compared with ?GFR at the 2nd period [mean ?GFR-MDRD: -4.2 (range: -24-9) vs 2.5 (range: -7-22) mL/min, P = 0.013; mean ?GFR-CKD-EPI: -4.2 (range: -19-10) vs 4.0 (range: -7-23) mL/min, P = 0.004], although the serum levels of calcineurin inhibitors were similar between the two periods. A second group of recipients (n = 17) who remained under the same nontelbivudine NA(s) for 24 months had a decline in the mean eGFR during the total follow-up period. In conclusion, we showed that telbivudine administration in LT recipients for HBV cirrhosis was effective and it was associated with significant improvement in renal function, but this remains to be confirmed in larger well-designed studies. PMID:25385239

  1. Improvements to executive function during exercise training predict maintenance of physical activity over the following year

    PubMed Central

    Best, John R.; Nagamatsu, Lindsay S.; Liu-Ambrose, Teresa

    2014-01-01

    Previous studies have shown that exercise training benefits cognitive, neural, and physical health markers in older adults. It is likely that these positive effects will diminish if participants return to sedentary lifestyles following training cessation. Theory posits that that the neurocognitive processes underlying self-regulation, namely executive function (EF), are important to maintaining positive health behaviors. Therefore, we examined whether better EF performance in older women would predict greater adherence to routine physical activity (PA) over 1 year following a 12-month resistance exercise training randomized controlled trial. The study sample consisted of 125 community-dwelling women aged 65–75 years old. Our primary outcome measure was self-reported PA, as measured by the Physical Activity Scale for the Elderly (PASE), assessed on a monthly basis from month 13 to month 25. Executive function was assessed using the Stroop Test at baseline (month 0) and post-training (month 12). Latent growth curve analyses showed that, on average, PA decreased during the follow-up period but at a decelerating rate. Women who made greater improvements to EF during the training period showed better adherence to PA during the 1-year follow-up period (? = ?0.36, p < 0.05); this association was unmitigated by the addition of covariates (? = ?0.44, p < 0.05). As expected, EF did not predict changes in PA during the training period (p > 0.10). Overall, these findings suggest that improving EF plays an important role in whether older women maintain higher levels of PA following exercise training and that this association is only apparent after training when environmental support for PA is low. PMID:24904387

  2. Resistance Training Improves Hemodynamic Function, Collagen Deposition and Inflammatory Profiles: Experimental Model of Heart Failure

    PubMed Central

    Alves, Jadson P.; Nunes, Ramiro B.; Stefani, Giuseppe P.; Dal Lago, Pedro

    2014-01-01

    The role of resistance training on collagen deposition, the inflammatory profile and muscle weakness in heart failure remains unclear. Therefore, this study evaluated the influence of a resistance training program on hemodynamic function, maximum strength gain, collagen deposition and inflammatory profile in chronic heart failure rats. Thirty-two male Wistar rats submitted to myocardial infarction by coronary artery ligation or sham surgery were assigned into four groups: sedentary sham (S-Sham, n?=?8); trained sham (T-Sham, n?=?8); sedentary chronic heart failure (S-CHF, n?=?8) and trained chronic heart failure (T-CHF, n?=?8). The maximum strength capacity was evaluated by the one maximum repetition test. Trained groups were submitted to an 8-week resistance training program (4 days/week, 4 sets of 10–12 repetitions/session, at 65% to 75% of one maximum repetition). After 8 weeks of the resistance training program, the T-CHF group showed lower left ventricular end diastolic pressure (P<0.001), higher left ventricular systolic pressure (P<0.05), higher systolic blood pressure (P<0.05), an improvement in the maximal positive derivative of ventricular pressure (P<0.05) and maximal negative derivative of ventricular pressure (P<0.05) when compared to the S-CHF group; no differences were observed when compared to Sham groups. In addition, resistance training was able to reduce myocardial hypertrophy (P<0.05), left ventricular total collagen volume fraction (P<0.01), IL-6 (P<0.05), and TNF-?/IL-10 ratio (P<0.05), as well as increasing IL-10 (P<0.05) in chronic heart failure rats when compared to the S-CHF group. Eight weeks of resistance training promotes an improvement of cardiac function, strength gain, collagen deposition and inflammatory profile in chronic heart failure rats. PMID:25340545

  3. Functional Gastrointestinal Disorders in Canada: First Population-Based Survey Using Rome II Criteria with Suggestions for Improving the Questionnaire

    Microsoft Academic Search

    W. G. Thompson; E. J. Irvine; P. Pare; S. Ferrazzi; L. Rance

    2002-01-01

    The Rome II criteria and questionnaires developed to identify functional gastrointestinal disorders have not been evaluated. Our objectives were to determine the prevalence of functional gastrointestinal disorders in Canada, compare our results with data from other published studies, assess concordance of Rome I and Rome II criteria for irritable bowel syndrome, and suggest improvements in the Rome II questionnaire. An

  4. A differential equation for the zeros of bessel functions

    Microsoft Academic Search

    E. K. Ifantis; P. D. Siafarikas

    1985-01-01

    Let ?(v) be a positive zero of the ordinary Bessel function Jv(z) of order v. It is shown that for every v in the interval -1>v>? the function ?(v) satisfies the differential equation ?(v)=?(vv)(LvX(v)) where Lv is the diagonal operator LVen=1\\/n+en on an abstract Hilbert space H with the oYtRonormal basis en=1,2,… and x(v) is a normalized element in H.

  5. Engineering Upper Hinge Improves Stability and Effector Function of a Human IgG1

    PubMed Central

    Yan, Boxu; Boyd, Daniel; Kaschak, Timothy; Tsukuda, Joni; Shen, Amy; Lin, Yuwen; Chung, Shan; Gupta, Priyanka; Kamath, Amrita; Wong, Anne; Vernes, Jean-Michel; Meng, Gloria Y.; Totpal, Klara; Schaefer, Gabriele; Jiang, Guoying; Nogal, Bartek; Emery, Craig; Vanderlaan, Martin; Carter, Paul; Harris, Reed; Amanullah, Ashraf

    2012-01-01

    Upper hinge is vulnerable to radical attacks that result in breakage of the heavy-light chain linkage and cleavage of the hinge of an IgG1. To further explore mechanisms responsible for the radical induced hinge degradation, nine mutants were designed to determine the roles that the upper hinge Asp and His play in the radical reactions. The observation that none of these substitutions could inhibit the breakage of the heavy-light chain linkage suggests that the breakage may result from electron transfer from Cys231 directly to the heavy-light chain linkage upon radical attacks, and implies a pathway separate from His229-mediated hinge cleavage. On the other hand, the substitution of His229 with Tyr showed promising advantages over the native antibody and other substitutions in improving the stability and function of the IgG1. This substitution inhibited the hinge cleavage by 98% and suggests that the redox active nature of Tyr did not enable it to replicate the ability of His to facilitate radical induced degradation. We propose that the lower redox potential of Tyr, a residue that may be the ultimate sink for oxidizing equivalents in proteins, is responsible for the inhibition. More importantly, the substitution increased the antibody's binding to Fc?RIII receptors by 2–3-fold, and improved ADCC activity by 2-fold, while maintaining a similar pharmacokinetic profile with respect to the wild type. Implications of these observations for antibody engineering and development are discussed. PMID:22203673

  6. Glycosaminoglycan mimetic improves enrichment and cell functions of human endothelial progenitor cell colonies.

    PubMed

    Chevalier, Fabien; Lavergne, Mélanie; Negroni, Elisa; Ferratge, Ségolène; Carpentier, Gilles; Gilbert-Sirieix, Marie; Siñeriz, Fernando; Uzan, Georges; Albanese, Patricia

    2014-05-01

    Human circulating endothelial progenitor cells isolated from peripheral blood generate in culture cells with features of endothelial cells named late-outgrowth endothelial colony-forming cells (ECFC). In adult blood, ECFC display a constant quantitative and qualitative decline during life span. Even after expansion, it is difficult to reach the cell dose required for cell therapy of vascular diseases, thus limiting the clinical use of these cells. Glycosaminoglycans (GAG) are components from the extracellular matrix (ECM) that are able to interact and potentiate heparin binding growth factor (HBGF) activities. According to these relevant biological properties of GAG, we designed a GAG mimetic having the capacity to increase the yield of ECFC production from blood and to improve functionality of their endothelial outgrowth. We demonstrate that the addition of [OTR(4131)] mimetic during the isolation process of ECFC from Cord Blood induces a 3 fold increase in the number of colonies. Moreover, addition of [OTR(4131)] to cell culture media improves adhesion, proliferation, migration and self-renewal of ECFC. We provide evidence showing that GAG mimetics may have great interest for cell therapy applied to vascular regeneration therapy and represent an alternative to exogenous growth factor treatments to optimize potential therapeutic properties of ECFC. PMID:24681520

  7. Novel television-based cognitive training improves working memory and executive function.

    PubMed

    Shatil, Evelyn; Mikulecká, Jaroslava; Bellotti, Francesco; Bureš, Vladimír

    2014-01-01

    The main study objective was to investigate the effect of interactive television-based cognitive training on cognitive performance of 119 healthy older adults, aged 60-87 years. Participants were randomly allocated to a cognitive training group or to an active control group in a single-blind controlled two-group design. Before and after training interactive television cognitive performance was assessed on well validated tests of fluid, higher-order ability, and system usability was evaluated. The participants in the cognitive training group completed a television-based cognitive training programme, while the participants in the active control group completed a TV-based programme of personally benefiting activities. Significant improvements were observed in well validated working memory and executive function tasks in the cognitive training but not in the control group. None of the groups showed statistically significant improvement in life satisfaction score. Participants' reports of "adequate" to "high" system usability testify to the successful development and implementation of the interactive television-based system and compliant cognitive training contents. The study demonstrates that cognitive training delivered by means of an interactive television system can generate genuine cognitive benefits in users and these are measurable using well-validated cognitive tests. Thus, older adults who cannot use or afford a computer can easily use digital interactive television to benefit from advanced software applications designed to train cognition. PMID:24992187

  8. Novel Television-Based Cognitive Training Improves Working Memory and Executive Function

    PubMed Central

    Shatil, Evelyn; Mikulecká, Jaroslava; Bellotti, Francesco; Bureš, Vladimír

    2014-01-01

    The main study objective was to investigate the effect of interactive television-based cognitive training on cognitive performance of 119 healthy older adults, aged 60–87 years. Participants were randomly allocated to a cognitive training group or to an active control group in a single-blind controlled two-group design. Before and after training interactive television cognitive performance was assessed on well validated tests of fluid, higher-order ability, and system usability was evaluated. The participants in the cognitive training group completed a television-based cognitive training programme, while the participants in the active control group completed a TV-based programme of personally benefiting activities. Significant improvements were observed in well validated working memory and executive function tasks in the cognitive training but not in the control group. None of the groups showed statistically significant improvement in life satisfaction score. Participants' reports of “adequate” to “high” system usability testify to the successful development and implementation of the interactive television-based system and compliant cognitive training contents. The study demonstrates that cognitive training delivered by means of an interactive television system can generate genuine cognitive benefits in users and these are measurable using well-validated cognitive tests. Thus, older adults who cannot use or afford a computer can easily use digital interactive television to benefit from advanced software applications designed to train cognition. PMID:24992187

  9. Inspiratory flow resistive loading improves respiratory muscle function and endurance capacity in recreational runners.

    PubMed

    Mickleborough, T D; Nichols, T; Lindley, M R; Chatham, K; Ionescu, A A

    2010-06-01

    The purpose of this study was to assess the efficacy of inspiratory flow resistive loading (IFRL) on respiratory muscle function, exercise performance and cardiopulmonary and metabolic responses to exercise. Twenty-four recreational road runners (12 male) were randomly assigned from each gender into an IFRL group (n=8) and sham-IFRL group (n=8), which performed IFRL for 6 weeks, or a control group (n=8). Strength (+43.9%Delta), endurance (+26.6%Delta), maximum power output (+41.9%Delta) and work capacity (+38.5%Delta) of the inspiratory muscles were significantly increased (P<0.05) at rest following the study period in IFRL group only. In addition, ventilation (-25.7%Delta), oxygen consumption (-13.3%Delta), breathing frequency (-11.9%Delta), tidal volume (-16.0%Delta), heart rate (HR) (-13.1%Delta), blood lactate concentration (-38.9%Delta) and the perceptual response (-33.5%Delta) to constant workload exercise were significantly attenuated (P<0.05), concomitant with a significant improvement (P<0.05) in endurance exercise capacity (+16.4%Delta) during a treadmill run set at 80% VO2max in IFRL group only. These data suggest that IFRL can alter breathing mechanics, attenuate the oxygen cost, ventilation, HR, blood lactate and the perceptual response during constant workload exercise and improve endurance exercise performance in recreational runners. PMID:19558387

  10. Islet Xenotransplantation Using Gal-deficient Neonatal Donors Improves Engraftment and Function

    PubMed Central

    Thompson, P; Badell, IR; Lowe, M; Cano, J; Song, M; Leopardi, F; Avila, J; Ruhil, R; Strobert, E; Korbutt, G; Rayat, G; Rajotte, R; Iwakoshi, N; Larsen, CP; Kirk, AD

    2011-01-01

    Significant deficiencies in understanding of xenospecific immunity have impeded the success of preclinical trials in xenoislet transplantation. While galactose-?1,3-galactose, the gal epitope, has emerged as the principal target of rejection in pig-to-primate models of solid organ transplant, the importance of gal-specific immunity in islet xenotransplant models has yet to be clearly demonstrated. Here we directly compare the immunogenicity, survival and function of neonatal porcine islets (NPIs) from gal-expressing wild-type (WT) or gal-deficient galactosyl transferase knock-out (GTKO) donors. Paired diabetic rhesus macaques were transplanted with either WT (n=5) or GTKO (n=5) NPIs. Recipient blood glucose, transaminase, and serum xenoantibody levels were used to monitor response to transplant. Four of 5 GTKO versus 1 of 5 WT recipients achieved insulin-independent normoglycemia; transplantation of WT islets resulted in significantly greater transaminitis. WT NPIs were more susceptible to antibody and complement binding and destruction in vitro. Our results confirm that gal is an important variable in xenoislet transplantation. GTKO NPI recipients have improved rates of normoglycemia, likely due to decreased susceptibility of xenografts to innate immunity mediated by complement and preformed xenoantibody. Therefore, the use of GTKO donors is an important step towards improved consistency and interpretability of results in future xenoislet studies. PMID:21883917

  11. Inhibitory effect of bisphosphonate on osteoclast function contributes to improved skeletal pain in ovariectomized mice.

    PubMed

    Abe, Yasuhisa; Iba, Kousuke; Sasaki, Koichi; Chiba, Hironori; Kanaya, Kumiko; Kawamata, Tomoyuki; Oda, Kimimitsu; Amizuka, Norio; Sasaki, Muneteru; Yamashita, Toshihiko

    2015-03-01

    The aim of this study was to evaluate skeletal pain associated with osteoporosis and to examine the inhibitory effect of bisphosphonate (BP) on pain in an ovariectomized (OVX) mouse model. We evaluated skeletal pain in OVX mice through an examination of pain-like behavior as well as immunohistochemical findings. In addition, we assessed the effects of alendronate (ALN), a potent osteoclast inhibitor, on those parameters. The OVX mice showed a decrease in the pain threshold value, and an increase in the number of c-Fos immunoreactive neurons in laminae I-II of the dorsal horn of the spinal cord. Alendronate caused an increase in the pain threshold value and inhibited c-Fos expression. The serum level of tartrate-resistant acid phosphatase 5b, a marker of osteoclast activity, was significantly negatively correlated with the pain threshold value. Furthermore, we found that an antagonist of the transient receptor potential channel vanilloid subfamily member 1, which is an acid-sensing nociceptor, improved pain-like behavior in OVX mice. These results indicated that the inhibitory effect of BP on osteoclast function might contribute to an improvement in skeletal pain in osteoporosis patients. PMID:24633536

  12. Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke

    PubMed Central

    Zhang, Chunling; Chopp, Michael; Cui, Yisheng; Wang, Lei; Zhang, Ruilan; Zhang, Li; Lu, Mei; Szalad, Alexandra; Doppler, Edith; Hitzl, Monika; Zhang, Zheng Gang

    2011-01-01

    Cerebrolysin is a peptide preparation mimicking the action of neurotrophic factors and has beneficial effects on neurodegenerative diseases and stroke. The present study investigated the effect of Cerebrolysin on neurogenesis in a rat model of embolic middle cerebral artery occlusion (MCAo). Treatment with Cerebrolysin at doses of 2.5 and 5 ml/kg significantly increased the number of bromodeoxyuridine positive (BrdU+) subventricular zone (SVZ) neural progenitor cells and doublecortin (DCX) immunoreactivity (migrating neuroblasts) in the ipsilateral SVZ and striatal ischemic boundary 28 days after stroke when the treatment was initiated 24h after stroke. The treatment also reduced TUNEL+ cells by ~50% in the ischemic boundary. However, treatment with Cerebrolysin at a dose of 2.5 ml/kg initiated at 24 and 48h did not significantly reduce infarct volume, but substantially improved neurological outcomes measured by an array of behavioral tests 21 and 28 days after stroke. Incubation of SVZ neural progenitor cells from ischemic rats with Cerebrolysin dose dependently augmented BrdU+ cells and increased the number of Tuj1+ cells (a marker of immature neurons). Blockage of the PI3K/Akt pathway abolished Cerebrolysin-increased BrdU+ cells. Moreover, Cerebrolysin treatment promoted neural progenitor cell migration. Collectively, these data indicate that Cerebrolysin treatment when initiated 24 and 48h after stroke enhances neurogenesis in the ischemic brain and improves functional outcome and that Cerebrolysin-augmented proliferation, differentiation, and migration of adult SVZ neural progenitor cells contribute to Cerebrolysin-induced neurogenesis, which may be related to improvement of neurological outcome. The PI3K/Akt pathway mediates Cerebrolysin-induced progenitor cell proliferation. PMID:20857512

  13. Cerebrolysin enhances neurogenesis in the ischemic brain and improves functional outcome after stroke.

    PubMed

    Zhang, Chunling; Chopp, Michael; Cui, Yisheng; Wang, Lei; Zhang, Ruilan; Zhang, Li; Lu, Mei; Szalad, Alexandra; Doppler, Edith; Hitzl, Monika; Zhang, Zheng Gang

    2010-11-15

    Cerebrolysin is a peptide preparation mimicking the action of neurotrophic factors and has beneficial effects on neurodegenerative diseases and stroke. The present study investigated the effect of Cerebrolysin on neurogenesis in a rat model of embolic middle cerebral artery occlusion (MCAo). Treatment with Cerebrolysin at doses of 2.5 and 5 ml/kg significantly increased the number of bromodeoxyuridine-positive (BrdU(+)) subventricular zone (SVZ) neural progenitor cells and doublecortin (DCX) immunoreactivity (migrating neuroblasts) in the ipsilateral SVZ and striatal ischemic boundary 28 days after stroke when the treatment was initiated 24 hr after stroke. The treatment also reduced TUNEL(+) cells by ?50% in the ischemic boundary. However, treatment with Cerebrolysin at a dose of 2.5 ml/kg initiated at 24 and 48 hr did not significantly reduce infarct volume but substantially improved neurological outcomes measured by an array of behavioral tests 21 and 28 days after stroke. Incubation of SVZ neural progenitor cells from ischemic rats with Cerebrolysin dose dependently augmented BrdU(+) cells and increased the number of Tuj1(+) cells (a marker of immature neurons). Blockage of the PI3K/Akt pathway abolished Cerebrolysin-increased BrdU(+) cells. Moreover, Cerebrolysin treatment promoted neural progenitor cell migration. Collectively, these data indicate that Cerebrolysin treatment when initiated 24 and 48 hr after stroke enhances neurogenesis in the ischemic brain and improves functional outcome and that Cerebrolysin-augmented proliferation, differentiation, and migration of adult SVZ neural progenitor cells contribute to Cerebrolysin-induced neurogenesis, which may be related to improvement of neurological outcome. The PI3K/Akt pathway mediates Cerebrolysin-induced progenitor cell proliferation. PMID:20857512

  14. THE PEROXYNITRITE CATALYST WW-85 IMPROVES PULMONARY FUNCTION IN OVINE SEPTIC SHOCK

    PubMed Central

    Maybauer, Dirk M.; Maybauer, Marc O.; Szabó, Csaba; Cox, Robert A.; Westphal, Martin; Kiss, Levente; Horvath, Eszter M.; Traber, Lillian D.; Hawkins, Hal K.; Salzman, Andrew L.; Southan, Garry J.; Herndon, David N.; Traber, Daniel L.

    2013-01-01

    Systemic inflammatory response syndrome (SIRS) is associated with excessive production of nitric oxide (NO•) and superoxide (O2?), forming peroxynitrite (ONOO?), which in turn, acts as a terminal mediator of cellular injury by producing cell necrosis and apoptosis. We examined the effect of the ONOO? decomposition catalyst WW-85 in a sheep model of acute lung injury (ALI) and septic shock. Eighteen sheep were operatively prepared and randomly allocated, either to the sham, control, or WW-85 group (n=6 each). Following a tracheotomy, ALI was produced in the control and WW-85 group by insufflation of four sets of 12 breaths of cotton smoke. Then, a 30 mL suspension of live Pseudomonas aeruginosa bacteria (containing 2–5×1011 cfu) was instilled into the lungs according to an established protocol. The sham group received only the vehicle (30 mL saline). The sheep were studied in awake state for 24 hrs and ventilated with 100% oxygen. WW-85 was administered 1 h post injury as bolus infusion (0.1 mg/kg), followed by a continuous infusion of 0.02 mg•kg?1•h?1 until the end of the 24-h experimental period. Compared to injured but untreated controls, WW-85-treated animals had significantly improved gas exchange, reductions in airway obstruction, shunt formation, lung myeloperoxidase-, lung malondialdehyde-, lung 3-nitrotyrosine concentrations, and plasma nitrate-to-nitrite (NOx) levels. Animals treated with WW-85 exhibited less microvascular leakage and improvements in pulmonary function. These results provide evidence that blockade of the nitric oxide - peroxynitrite pathway improves disturbances from septic shock, as demonstrated in a clinically relevant ovine experimental model. PMID:20577150

  15. Ingestion of sodium plus water improves cardiovascular function and performance during dehydrating cycling in the heat.

    PubMed

    Hamouti, N; Fernández-Elías, V E; Ortega, J F; Mora-Rodriguez, R

    2014-06-01

    We studied if salt and water ingestion alleviates the physiological strain caused by dehydrating exercise in the heat. Ten trained male cyclists (VO2max?: 60 ± 7 mL/kg/min) completed three randomized trials in a hot-dry environment (33 °C, 30% rh, 2.5 m/s airflow). Ninety minutes before the exercise, participants ingested 10 mL of water/kg body mass either alone (CON trial) or with salt to result in concentrations of 82 or 164 mM Na(+) (ModNa(+) or HighNa(+) trial, respectively). Then, participants cycled at 63% of VO2 m ? a x for 120 min immediately followed by a time-trial. After 120 min of exercise, the reduction in plasma volume was lessened with ModNa(+) and HighNa(+) trials (-11.9 ± 2.1 and -9.8 ± 4.2%) in comparison with CON (-16.4 ± 3.2%; P < 0.05). However, heat accumulation or dissipation (forearm skin blood flow and sweat rate) were not improved by salt ingestion. In contrast, both salt trials maintained cardiac output (? 1.3 ± 1.4 L/min; P < 0.05) and stroke volume (? 10 ± 11 mL/beat; P < 0.05) above CON after 120 min of exercise. Furthermore, the salt trials equally improved time-trial performance by 7.4% above CON (? 289 ± 42 vs 269 ± 50 W, respectively; P < 0.05). Our data suggest that pre-exercise ingestion of salt plus water maintains higher plasma volume during dehydrating exercise in the heat without thermoregulatory effects. However, it maintains cardiovascular function and improves cycling performance. PMID:23253191

  16. Effects of thrombin and thrombin receptor activation on cardiac function after acute myocardial infarction

    PubMed Central

    Gu, Xinyuan; Zhang, Xiaorong; Lu, Guihua; Li, Yanhui; Li, Xiujuan; Huang, He; Zeng, Jianping; Tang, Lilong

    2015-01-01

    Thrombin and thrombin receptor activation impact cardiomyocyte contraction and ventricular remodeling. However, there is some controversy regarding their effects in cardiac function, especially in cardiac dysfunction after acute myocardial infarction (AMI). A rat AMI model was created by left coronary artery ligation (LCA). Cardiac functional parameters, including the maximum left ventricular (LV) systolic pressure (LVSPmax), LV end-diastolic pressure (LVEDP), and the rise and fall rates in LV pressure (dp/dt max and dp/dt min, respectively), were measured. Hirudin decreased cardiac function within 120 minutes after AMI, whereas treatment with thrombin receptor-activating peptide (TRAP) reversed this hirudin-induced decrease in cardiac function. The mRNA and protein expression levels of inositol 1,4,5-trisphosphate receptor (IP3R) subtypes in infarct area tissues were analyzed by reverse transcription-polymerase chain reaction and immunoreaction. Hirudin decreased the expression levels of IP3R-1, -2, and -3 in the infarct area for up to 40 minutes after AMI, whereas TRAP treatment reversed these hirudin-induced effects. Treatment with the IP3R antagonist 2-aminoethoxydiphenyl borate (2.5 mg/kg) eliminated the effect of TRAP on the hirudin-induced decrease in cardiac function after AMI. Finally, TRAP increased the maximum binding capacity of the three IP3R subtypes, but only enhanced the affinity of IP3R-2. Thrombin and thrombin receptor activation improved cardiac function after AMI by an IP3R-mediated pathway, probably through the IP3R-2 subtype.

  17. Immediate and long-term changes in corticomotor output in response to rehabilitation: correlation with functional improvements in chronic stroke.

    PubMed

    Koski, Lisa; Mernar, Thomas J; Dobkin, Bruce H

    2004-12-01

    The goal of this study was to determine whether transcranial magnetic stimulation (TMS) measures of the corticomotor pathways might reflect and predict functional improvements during rehabilitation of a hemiparetic upper extremity. Ten patients with variable levels of functional impairment in upper extremity use were enrolled at least 3 months after a stroke. TMS was used to obtain serial measures of motor thresholds and motor-evoked potential (MEP) size for a muscle from both hands before and after each session of an intervention aimed at improving functional motor control. Functional ability and cortical map area and volume were measured before each therapy session. At intake, all TMS measures from the affected side were impaired compared with the unaffected side but they did not reliably predict the level of functional improvement. Motor thresholds decreased, whereas MEP amplitude and map size increased with treatment. The amount of change in affected side measures was correlated with the amount of improvement in hand/arm function. Normalization of MEP amplitude asymmetry in response to the 1st 2 therapy sessions predicted long-term improvement in Fugl-Meyer motor score. Within limits, TMS appears to be useful in both moderate and more impaired patients as a physiological assay of treatment-induced plasticity and behavioral gains. Methodological differences in the literature, however, currently obscure a full understanding of the potential contributions of TMS to rehabilitation research. PMID:15537994

  18. Determine Optimal Stimulus Amplitude for Using Vestibular Stochastic Stimulation to Improve Balance Function

    NASA Technical Reports Server (NTRS)

    Goel, R.; Kofman, I.; DeDios, Y. E.; Jeevarajan, J.; Stepanyan, V.; Nair, M.; Congdon, S.; Fregia, M.; Cohen, H.; Bloomberg, J.J.; Mulavara, A.P.

    2015-01-01

    Sensorimotor changes such as postural and gait instabilities can affect the functional performance of astronauts when they transition across different gravity environments. We are developing a method, based on stochastic resonance (SR), to enhance information transfer by applying non-zero levels of external noise on the vestibular system (vestibular stochastic resonance, VSR). Our previous work has shown the advantageous effects of VSR in a balance task of standing on an unstable surface [1]. This technique to improve detection of vestibular signals uses a stimulus delivery system that provides imperceptibly low levels of white noise-based binaural bipolar electrical stimulation of the vestibular system. The goal of this project is to determine optimal levels of stimulation for SR applications by using a defined vestibular threshold of motion detection. A series of experiments were carried out to determine a robust paradigm to identify a vestibular threshold that can then be used to recommend optimal stimulation levels for sensorimotor adaptability (SA) training applications customized to each crewmember. The amplitude of stimulation to be used in the VSR application has varied across studies in the literature such as 60% of nociceptive stimulus thresholds [2]. We compared subjects' perceptual threshold with that obtained from two measures of body sway. Each test session was 463s long and consisted of several 15s long sinusoidal stimuli, at different current amplitudes (0-2 mA), interspersed with 20-20.5s periods of no stimulation. Subjects sat on a chair with their eyes closed and had to report their perception of motion through a joystick. A force plate underneath the chair recorded medio-lateral shear forces and roll moments. Comparison of threshold of motion detection obtained from joystick data versus body sway suggests that perceptual thresholds were significantly lower. In the balance task, subjects stood on an unstable surface and had to maintain balance, and the stimulation was administered from 20-400% of subjects' vestibular threshold. Optimal stimulation amplitude was determined at which the balance performance was best compared to control (no stimulation). Preliminary results show that, in general, using stimulation amplitudes at 40-60% of perceptual motion threshold significantly improved the balance performance. We hypothesize that VSR stimulation will act synergistically with SA training to improve adaptability by increasing utilization of vestibular information and therefore will help us to optimize and personalize a SA countermeasure prescription. This combination may help to significantly reduce the number of days required to recover functional performance to preflight levels after long-duration spaceflight.

  19. Functional and Morphological Improvement of Dystrophic Muscle by Interleukin 6 Receptor Blockade

    PubMed Central

    Pelosi, Laura; Berardinelli, Maria Grazia; De Pasquale, Loredana; Nicoletti, Carmine; D'Amico, Adele; Carvello, Francesco; Moneta, Gian Marco; Catizone, Angela; Bertini, Enrico; De Benedetti, Fabrizio; Musarò, Antonio

    2015-01-01

    The anti-inflammatory agents glucocorticoids (GC) are the only available treatment for Duchenne muscular dystrophy (DMD). However, long-term GC treatment causes muscle atrophy and wasting. Thus, targeting specific mediator of inflammatory response may be more specific, more efficacious, and with fewer side effects. The pro-inflammatory cytokine interleukin (IL) 6 is overproduced in patients with DMD and in the muscle of mdx, the animal model for human DMD. We tested the ability of inhibition of IL6 activity, using an interleukin-6 receptor (Il6r) neutralizing antibody, to ameliorate the dystrophic phenotype. Blockade of endogenous Il6r conferred on dystrophic muscle resistance to degeneration and alleviated both morphological and functional consequences of the primary genetic defect. Pharmacological inhibition of IL6 activity leaded to changes in the dystrophic muscle environment, favoring anti-inflammatory responses and improvement in muscle repair. This resulted in a functional homeostatic maintenance of dystrophic muscle. These data provide an alternative pharmacological strategy for treatment of DMD and circumvent the major problems associated with conventional therapy.

  20. An Improved Method for oriT-Directed Cloning and Functionalization of Large Bacterial Genomic Regions

    PubMed Central

    Kvitko, Brian H.; McMillan, Ian A.

    2013-01-01

    We have made significant improvements to a broad-host-range system for the cloning and manipulation of large bacterial genomic regions based on site-specific recombination between directly repeated oriT sites during conjugation. Using two suicide capture vectors carrying flanking homology regions, oriT sites are recombined on either side of the target region. Using a broad-host-range conjugation helper plasmid, the region between the oriT sites is conjugated into an Escherichia coli recipient strain, where it is circularized and maintained as a chimeric mini-F vector. The cloned target region is functionalized in multiple ways to accommodate downstream manipulation. The target region is flanked with Gateway attB sites for recombination into other vectors and by rare 18-bp I-SceI restriction sites for subcloning. The Tn7-functionalized target can also be inserted at a naturally occurring chromosomal attTn7 site(s) or maintained as a broad-host-range plasmid for complementation or heterologous expression studies. We have used the oriTn7 capture technique to clone and complement Burkholderia pseudomallei genomic regions up to 140 kb in size and have created isogenic Burkholderia strains with various combinations of genomic islands. We believe this system will greatly aid the cloning and genetic analysis of genomic islands, biosynthetic gene clusters, and large open reading frames. PMID:23747708

  1. Tai chi improves cognitive and physical function in the elderly: a randomized controlled trial

    PubMed Central

    Sun, Jiao; Kanagawa, Katsuko; Sasaki, Junko; Ooki, Syuichi; Xu, Huali; Wang, Li

    2015-01-01

    [Purpose] To investigate the effect of Tai Chi on cognitive and physical function in the elderly. [Subjects and Methods] A randomized trial design was used. A total 150 subjects were enrolled and were divided into Tai Chi and control groups. Subjects in the Tai Chi group participated Tai Chi for 6 months, and subjects in the control group participated in other non-athletic activities. [Results] There were no differences between the groups in the one leg standing time with eyes open, left grip strength, or the Frontal Assessment Battery at bedside after 3 and 6 months of intervention. The Mini-Mental State Examination scores after 3 and 6 months were higher in the Tai Chi group than in the control group. The right grip strength after 3 months increased more in the Tai Chi group than in the control group. Both the 5-m high walking speed and 10-m normal walking speed were significantly lower after 3 and 6 months of Tai Chi practice. [Conclusion] These results suggest that regular Tai Chi practice may improve cognitive and physical function in the elderly. PMID:26157242

  2. Local delivery of FTY720 in PCL membrane improves SCI functional recovery by reducing reactive astrogliosis.

    PubMed

    Wang, Junjuan; Wang, Jiaqiu; Lu, Ping; Cai, Youzhi; Wang, Yafei; Hong, Lan; Ren, Hao; Heng, Boon Chin; Liu, Hua; Zhou, Jing; Ouyang, Hongwei

    2015-09-01

    FTY720 has recently been approved as an oral drug for treating relapsing forms of multiple sclerosis, and exerts its therapeutic effect by acting as an immunological inhibitor targeting the sphingosine-1-phosphate (S1P) receptor subtype (S1P1) of T cells. Recently studies demonstrated positive efficacy of this drug on spinal cord injury (SCI) in animal models after systemic administration, albeit with significant adverse side effects. We hereby hypothesize that localized delivery of FTY720 can promote SCI recovery by reducing pathological astrogliosis. The mechanistic functions of FTY720 were investigated in vitro and in vivo utilizing immunofluorescence, histology, MRI and behavioral analysis. The in vitro study showed that FTY720 can reduce astrocyte migration and proliferation activated by S1P. FTY720 can prolong internalization of S1P1 and exert antagonistic effects on S1P1. In vivo study of SCI animal models demonstrated that local delivery of FTY720 with polycaprolactone (PCL) membrane significantly decreased S1P1 expression and glial scarring compared with the control group. Furthermore, FTY720-treated groups exhibited less cavitation volume and neuron loss, which significantly improved recovery of motor function. These findings demonstrated that localized delivery of FTY720 can promote SCI recovery by targeting the S1P1 receptor of astrocytes, provide a new therapeutic strategy for SCI treatment. PMID:26036174

  3. Hydrolysis enhances bioavailability of proanthocyanidin-derived metabolites and improves ?-cell function in glucose intolerant rats.

    PubMed

    Yang, Kaiyuan; Hashemi, Zohre; Han, Wei; Jin, Alena; Yang, Han; Ozga, Jocelyn; Li, Liang; Chan, Catherine B

    2015-08-01

    Proanthocyanidins (PAC) are a highly consumed class of flavonoids and their consumption has been linked to beneficial effects in type 2 diabetes. However, limited gastrointestinal absorption occurs due to the polymeric structure of PAC. We hypothesized that hydrolysis of the PAC polymer would increase bioavailability, thus leading to enhanced beneficial effects on glucose homeostasis and pancreatic ?-cell function. PAC-rich pea seed coats (PSC) were supplemented to a high-fat diet (HFD) either in native (PAC) or hydrolyzed (HPAC) form fed to rats for 4 weeks. HFD or low-fat diet groups were controls. PAC-derived compounds were characterized in both PSC and serum. Glucose and insulin tolerance tests were conducted. Pancreatic ?-cell and ?-cell areas and glucose-stimulated insulin secretion (GSIS) from isolated islets were measured. Increased PAC-derived metabolites were detected in the serum of HPAC-fed rats compared to PAC-fed rats, suggesting hydrolysis of PSC-enhanced PAC bioavailability. This was associated with ~18% less (P<.05) weight gain compared to HFD without affecting food intake, as well as improvement in glucose disposal in vivo. There was a 2-fold decrease of ?/?-cell area ratio and a 2.5-fold increase in GSIS from isolated islets of HPAC-fed rats. These results demonstrate that hydrolysis of PSC-derived PAC increased the bioavailability of PAC-derived products, which is critical for enhancing beneficial effects on glucose homeostasis and pancreatic ?-cell function. PMID:25987165

  4. Improving effector functions of antibodies for cancer treatment: Enhancing ADCC and CDC

    PubMed Central

    Natsume, Akito; Niwa, Rinpei; Satoh, Mitsuo

    2009-01-01

    As platforms for therapeutic agents, monoclonal antibodies (MAbs) have already been approved, and several MAbs have demonstrated clinical effectiveness in a variety of malignancies. However, several issues have also been emerging in antibody therapy, such as high cost and insufficient drug action. Recently, to improve MAb activity in humans, effector functions have been subjects of focus, especially antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Extensive efforts have been made to enhance these effector functions of MAbs, and successful approaches have been reported by us and others, wherein the binding activity of MAbs to Fc?RIIIa or C1q is increased by introducing amino acid mutations into heavy chain constant regions or through glyco-modification of Fc-linked oligosaccharides. In addition, one of the next approaches to optimizing therapeutic antibodies would be to combine multiple enhancing modifications into a single antibody platform to overcome the diverse mechanisms of clinical resistance of tumor cells. For this aim, we have recently developed a successful combination composed of ADCC-enhancing modification by the fucose depletion from Fc-linked oligosaccharides and CDC-enhancing modification by IgG1 and IgG3 isotype shuffling in heavy chains, which could be of great value for the development of third-generation antibody therapeutics. PMID:19920917

  5. Improving skin function with CM-glucan, a biological response modifier from yeast.

    PubMed

    Zulli, F; Suter, F; Biltz, H; Nissen, H P

    1998-04-01

    Preparations from yeast have been used for a long time for cosmetic and pharmaceutical purposes. Studies have identified glucan from the cell wall of baker's yeast as an immunologically active agent. Glucan is a poly beta-( 1-3)-linked glucopyranose of high molecular weight and belongs to the class of compounds known as biological response modifiers. Glucan preparations are involved in the activation of the body's natural defence mechanisms and in the acceleration of the skin's wound healing processes. In the skin, Langerhans' cells and keratinocytes are the immunologically competent cells. Recent studies indicate that UV irradiation can deplete the number and viability of these cells (immunosuppression). The use of non-specific immune-stimulators, such as glucan, is a new approach for improving the function of stressed skin. We have developed a process to modify pure glucan from baker's yeast to carboxymethyl glucan (CM-glucan), a water soluble product suitable for topical formulations. The functional properties of this new compound have been investigated in vitro and in vivo. Cell culture experiments showed that CM-glucan protects skin cells against the depletion of antioxidant molecules upon UV-A irradiation and promotes the growth of keratinocytes. In placebo controlled studies with healthy volunteers, the pretreatment of skin with CM-glucan offered substantial protection against skin damage caused by a detergent challenge or UV-A irradiation. In addition, CM-glucan enhanced the renewal rate of the stratum corneum. PMID:18505493

  6. Brain sigma-1 receptor stimulation improves mental disorder and cardiac function in mice with myocardial infarction.

    PubMed

    Ito, Koji; Hirooka, Yoshitaka; Sunagawa, Kenji

    2013-08-01

    Mental disorder after myocardial infarction (MI) is reported by many epidemiological studies and is associated with a poor prognosis. The reduction of brain sigma-1 receptor (S1R) plays an important role in the pathogenesis of mental disorder, and we recently demonstrated that the reduction of brain S1R causes sympathoexcitation. However, the role of brain S1R in the association between MI and mental disorder, such as depression or cognitive impairment, remains unclear. To investigate this, we performed left coronary artery ligation on mice to produce an MI model (MI-mice). Compared with sham-operated controls (Sham-mice), MI-mice showed augmented sympathetic activity, decreased cardiac function, and lower S1R expression in both the hypothalamus and hippocampus. Furthermore, MI-mice displayed decreased Y-maze spontaneous alternation (a maker of spatial working memory), decreased circadian variation in locomotor activity, and increased immobility time in the tail suspension test (markers of depression-like behavior). Intracerebroventricular infusion of the S1R agonist PRE084 in MI-mice improved both mental disorder and cardiac function with lowered sympathetic activity and the recovery of the S1R expression in both the hypothalamus and hippocampus. These results indicate that brain S1R is decreased in MI-mice and that this plays an important role in the coexistence of increased heart failure via sympathoexcitation and mental disorders, such as depression or cognitive impairment. PMID:23615161

  7. The improvement in functional characteristics of eco-friendly composites made of natural rubber and cellulose

    NASA Astrophysics Data System (ADS)

    Araki, Kunihiro; Kaneko, Shonosuke; Matsumoto, Koki; Nagatani, Asahiro; Tanaka, Tatsuya; Arao, Yoshihiko

    2015-05-01

    We investigated the efficient use of cellulose to resolve the problem of the depletion of fossil resources. In this study, as the biomass material, the green composite based on natural rubber (NR) and the flake-shaped cellulose particles (FSCP) was produced. In order to further improvement of functional characteristics, epoxidized natural rubber (ENR) was also used instead of NR. The FSCP were produced by mechanical milling in a planetary ball mill with a grinding aid as a cellulose aggregation inhibitor. Moreover, talc and mica particles were used to compare with FSCP. NR and ENR was mixed with vulcanizing agents and then each filler was added to NR compound in an internal mixer. The vulcanizing agents are as follows: stearic acid, zinc oxide, sulfur, and vulcanization accelerator. The functionalities of the composites were evaluated by a vibration-damping experiment and a gas permeability experiment. As a result, we found that FSCP filler has effects similar to (or more than) inorganic filler in vibration-damping and O2 barrier properties. And then, vibration- damping and O2 barrier properties of the composite including FSCP was increased with use of ENR. In particular, we found that ENR-50 composite containing 50 phr FSCP has three times as high vibration-damping property as ENR-50 without FSCP.

  8. Bone Marrow Mesenchymal Cells Improve Muscle Function in a Skeletal Muscle Re-Injury Model

    PubMed Central

    Ribeiro, Karla C.; Porto, Anderson; Peçanha, Ramon; Fortes, Fabio S. A.; Zapata-Sudo, Gisele; Campos-de-Carvalho, Antonio C.; Goldenberg, Regina C. S.; Werneck-de-Castro, João Pedro

    2015-01-01

    Skeletal muscle injury is the most common problem in orthopedic and sports medicine, and severe injury leads to fibrosis and muscle dysfunction. Conventional treatment for successive muscle injury is currently controversial, although new therapies, like cell therapy, seem to be promise. We developed a model of successive injuries in rat to evaluate the therapeutic potential of bone marrow mesenchymal cells (BMMC) injected directly into the injured muscle. Functional and histological assays were performed 14 and 28 days after the injury protocol by isometric tension recording and picrosirius/Hematoxilin & Eosin staining, respectively. We also evaluated the presence and the fate of BMMC on treated muscles; and muscle fiber regeneration. BMMC treatment increased maximal skeletal muscle contraction 14 and 28 days after muscle injury compared to non-treated group (4.5 ± 1.7 vs 2.5 ± 0.98 N/cm2, p<0.05 and 8.4 ± 2.3 vs. 5.7 ± 1.3 N/cm2, p<0.05 respectively). Furthermore, BMMC treatment increased muscle fiber cross-sectional area and the presence of mature muscle fiber 28 days after muscle injury. However, there was no difference in collagen deposition between groups. Immunoassays for cytoskeleton markers of skeletal and smooth muscle cells revealed an apparent integration of the BMMC within the muscle. These data suggest that BMMC transplantation accelerates and improves muscle function recovery in our extensive muscle re-injury model. PMID:26039243

  9. Improved endothelialization of NiTi alloy by VEGF functionalized nanocoating.

    PubMed

    Shen, Weixing; Cai, Kaiyong; Yang, Zaixiang; Yan, Ying; Yang, Weihu; Liu, Peng

    2012-06-01

    To improve surface endothelialization of NiTi alloy substrate, a nano-structured coating functionalized with vascular endothelial growth factor (VEGF) was fabricated via polydopamine (PDOP) as intermediate layer. The successful preparation of VEGF conjugated nanocoating was demonstrated by X-ray diffraction (XRD), atomic force microscope (AFM), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS), respectively. Inductively coupled plasma mass spectrometry (ICP-MS) test showed that the formed nanocoating significantly reduced the release of Ni ion from NiTi alloy in simulated body fluid. The biological behaviors of endothelial cells adhered to modified NiTi alloy substrates, including cell proliferation, cell spreading and production of nitric oxide and prostacyclin were investigated in vitro. The results suggest that surface functionalization of NiTi alloy substrate with VEGF is beneficial for cell growth. The approach presented here affords an alternative for surface modification of NiTi implants applied as heart and vascular implant devices. PMID:22387019

  10. Tai chi improves cognitive and physical function in the elderly: a randomized controlled trial.

    PubMed

    Sun, Jiao; Kanagawa, Katsuko; Sasaki, Junko; Ooki, Syuichi; Xu, Huali; Wang, Li

    2015-05-01

    [Purpose] To investigate the effect of Tai Chi on cognitive and physical function in the elderly. [Subjects and Methods] A randomized trial design was used. A total 150 subjects were enrolled and were divided into Tai Chi and control groups. Subjects in the Tai Chi group participated Tai Chi for 6 months, and subjects in the control group participated in other non-athletic activities. [Results] There were no differences between the groups in the one leg standing time with eyes open, left grip strength, or the Frontal Assessment Battery at bedside after 3 and 6 months of intervention. The Mini-Mental State Examination scores after 3 and 6 months were higher in the Tai Chi group than in the control group. The right grip strength after 3 months increased more in the Tai Chi group than in the control group. Both the 5-m high walking speed and 10-m normal walking speed were significantly lower after 3 and 6 months of Tai Chi practice. [Conclusion] These results suggest that regular Tai Chi practice may improve cognitive and physical function in the elderly. PMID:26157242

  11. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    PubMed Central

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  12. Bovine Milk as a Source of Functional Oligosaccharides for Improving Human Health12

    PubMed Central

    Zivkovic, Angela M.; Barile, Daniela

    2011-01-01

    Human milk oligosaccharides are complex sugars that function as selective growth substrates for specific beneficial bacteria in the gastrointestinal system. Bovine milk is a potentially excellent source of commercially viable analogs of these unique molecules. However, bovine milk has a much lower concentration of these oligosaccharides than human milk, and the majority of the molecules are simpler in structure than those found in human milk. Specific structural characteristics of milk-derived oligosaccharides are crucial to their ability to selectively enrich beneficial bacteria while inhibiting or being less than ideal substrates for undesirable and pathogenic bacteria. Thus, if bovine milk products are to provide human milk–like benefits, it is important to identify specific dairy streams that can be processed commercially and cost-effectively and that can yield specific oligosaccharide compositions that will be beneficial as new food ingredients or supplements to improve human health. Whey streams have the potential to be commercially viable sources of complex oligosaccharides that have the structural resemblance and diversity of the bioactive oligosaccharides in human milk. With further refinements to dairy stream processing techniques and functional testing to identify streams that are particularly suitable for enriching beneficial intestinal bacteria, the future of oligosaccharides isolated from dairy streams as a food category with substantiated health claims is promising. PMID:22332060

  13. Thoracic epidural anesthesia improves functional recovery from myocardial stunning in conscious dogs.

    PubMed

    Rolf, N; Van de Velde, M; Wouters, P F; Möllhoff, T; Weber, T P; Van Aken, H K

    1996-11-01

    The effects of thoracic epidural anesthesia (TEA) on the contractile performance of ischemic and postischemic myocardium have not been well investigated. The purpose of this investigation was to examine the effects of TEA on severity and duration of myocardial stunning in an experimental model for sublethal acute myocardial ischemia. Seven dogs were chronically instrumented for measurement of heart rate (HR), left atrial (LAP), aortic and left ventricular pressure (LVP), LV dP/dtmax' and myocardial wall-thickening fraction (WTF). An occluder around the left anterior descending artery (LAD) allowed induction of reversible LAD ischemia. TEA was performed with lidocaine 4 mg/kg through a chronically implanted epidural catheter at the second thoracic level. Regional myocardial blood flow was determined with colored microspheres. Two experiments were performed in a cross-over design on separate days: Experiment 1, induction of 10 min of LAD ischemia without TEA; and Experiment 2, induction of 10 min of LAD ischemia with TEA. WTF was measured at baseline (BL) and predetermined time points until complete recovery from ischemic dysfunction occurred. LAD ischemia caused a significant decrease of LAD-WTF with (-28% +/- 5.1% versus BL) and without TEA (-15.5% +/- 5.3% versus BL). After 3 h of reperfusion, WTF as percent of BL values was significantly higher with TEA (P < 0.001). BL values of WTF were reached after 24 h with TEA and after more than 48 h without TEA (P < 0.05). There were no significant differences for mean arterial pressure (MAP), heart rate (HR), LVP, LAP, and LVdP/dtmax between the groups during ischemia and reperfusion. In nonischemic myocardium TEA caused an increase of subendocardial blood flow. During ischemia neither the subendocardial/subepicardial nor the occluded/ normal zone blood flow was affected by TEA. TEA attenuates myocardial stunning in conscious dogs. This finding is consistent with data regarding a reduction of infarct size due to TEA. PMID:8895266

  14. Endothelial progenitor cells in diabetic patients with myocardial infarction - can statins improve their function?

    PubMed

    António, Natália; Soares, Ana; Fernandes, Rosa; Soares, Francisco; Lopes, Ana; Carvalheiro, Tiago; Paiva, Artur; Providência, Luís A; Gonçalves, Lino; Fontes Ribeiro, Carlos

    2014-10-15

    The effect of statins on endothelial progenitor cells (EPCs) function derived from diabetic patients (DMpts) with acute myocardial infarction (AMI) is unknown. In this study we assess the response of early and late EPCs from diabetic versus non-diabetic patients (NDMpts) with AMI to statins. EPCs were obtained from 10 diabetic and 10 age-matched non-diabetic male patients with AMI. For each patient, cultures of early and late EPCs were performed under 4 different conditions: normal glucose concentration (control); high glucose concentration; normal glucose concentration with atorvastatin supplementation and normal glucose concentration with pravastatin supplementation. To compare the effect of these treatments on EPC function in DMpts versus NDMpts, we performed in vitro: EPC colony-forming units (CFU) assay; cell cycle analysis; viability assessment and expression of the surface markers CXCR4, CD133, CD34 and KDR. Under control conditions, CFU numbers were reduced in DMpts-derived EPCs when compared to those of NDMpts (1.4±0.8 vs 2.6±1.2 CFU/well, P=0.021). When early EPCs from DMpts were cultured in the presence of statins, CFU capacity was restored, surmounting that of NDMpts under control conditions. Statins significantly improved viability of early EPCs and delayed the onset of late EPCs senescence, even in cells from DMpts. In addition, statins induced approximately a 2-fold increase in the proportion of late EPCs in S-phase of the cell cycle (P<0.05). Statins have a beneficial effect on both early and late EPCs from DMpts with AMI. Despite the functional impairment of EPCs from DMpts, they exhibit similar responsiveness to statins as equivalent cells from NDMpts. PMID:25066111

  15. The W-shaped pupil in cuttlefish (Sepia officinalis): functions for improving horizontal vision.

    PubMed

    Mäthger, Lydia M; Hanlon, Roger T; Håkansson, Jonas; Nilsson, Dan-Eric

    2013-05-01

    The eyes of cuttlefish (Sepia officinalis) have a modified horizontal slit-pupil with a distinctive W-shape in bright light, while in darkness the pupil is circular. Two suggestions have previously been made for a function of the W-shape: (1) camouflaging the eye; (2) providing distance information. Since neither of these suggestions can fully explain the function of this pupil across the entire visual field, particularly the frontal and caudal periphery, we re-addressed the question of its functional significance. We took infra-red images of the eyes of live S. officinalis at different light intensities and from different viewing angles. This allowed us to determine the shape and light-admitting area of the pupil for different parts of the visual field. Our data show that the W-shaped pupil projects a blurred "W" directly onto the retina and that it effectively operates as vertical slits for the frontal and caudal parts of the visual field. We also took images of the natural habitat of S. officinalis and calculated the average vertical brightness distribution in the visual habitat. Computing a retinal illumination map shows that the W-shaped pupil is effective in balancing a vertically uneven light field: The constricted pupil reduces light from the dorsal part of the visual field significantly more than it reduces light from the horizontal band. This will cut the amount of direct sunlight that is scattered by the lens and ocular media, and thus improve image contrast particularly for the dimmer parts of the scene. We also conclude that the pupil provides even attenuation along the horizontal band, whereas a circular pupil would attenuate the image relatively more in the important frontal and caudal periphery of the visual field. PMID:23474299

  16. Short-term strength training improves muscle quality and functional capacity of elderly women.

    PubMed

    Pinto, Ronei Silveira; Correa, Cleiton Silva; Radaelli, Regis; Cadore, Eduardo Lusa; Brown, Lee E; Bottaro, Martim

    2014-02-01

    To assess effects of a short-term strength training (ST) program on muscle quality (MQ) and functional capacity, 36 sedentary elderly women (age = 66.0 ± 8 year, height = 159.1 ± 9.2 cm, body mass = 68.3 ± 12.1 kg, body fat = 37.0 ± 4.2 %) were randomly divided into an experimental group (EG; n = 19) or a control group (CG; n = 17). The EG performed two to three sets of 12-15 repeats of leg press, knee extension, and knee flexion exercises, 2 days/week for 6 weeks. Before and after training, lower body one repetition maximum (1RM), functional performance tests, quadriceps femoris muscle thickness (MT), and muscle quality (MQ) (1RM and quadriceps MT quotient) were assessed. After training, only the EG showed significant improvements in 1RM (p < 0.05), 30-s sit-to-stand (p < 0.001), and 8 foot up-and-go (p < 0.001). In addition, only in the EG, significant increases in all quadriceps femoris MT measurements (vastus lateralis, vastus medialis, vastus intermedius, and rectus femoris) (p ? 0.05), and MQ (p < 0.001) were demonstrated. No changes were observed in the CG. Furthermore, there were significant associations between individual changes in MQ and corresponding changes in 30-s sit-to-stand (r = 0.62, p < 0.001), and 8 foot up-and-go (r = -0.71, p < 0.001). In conclusion, a ST program of only 6 weeks was sufficient to enhance MQ of the knee extensors in elderly women, which resulted in beneficial changes in functional capacity. PMID:23881608

  17. Insight into the mechanism by which metoclopramide improves immune functions after trauma-hemorrhage.

    PubMed

    Knöferl, M W; Angele, M K; Ayala, A; Cioffi, W G; Bland, K I; Chaudry, I H

    2000-07-01

    Although studies have shown that prolactin (Prl) and metoclopramide (Mcp) administration restores the depressed cell-mediated immune functions after hemorrhage, the underlying mechanism responsible for the immunostimulatory effects of Mcp remains unknown. We hypothesized that Mcp improves immune responses by upregulating the secretion of Prl. To test this hypothesis, male C3H/HeN mice were subjected to sham operation or laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (Hem; 35 +/- 5 mmHg for 90 min) and then resuscitated. Plasma Prl levels were determined 30 min after Mcp (1 microgram/g body wt sc at end of Hem) or vehicle (Veh) treatment in sham and Hem mice. The results indicate that plasma Prl levels increased significantly in Mcp-treated mice (sham-Veh 249.9 +/- 5.3, Hem-Veh 229.9 +/- 7.6, Hem-Mcp 596.9 +/- 73.1 ng/ml, one-way ANOVA, P < 0.05 vs. Veh). To determine whether Mcp produces its salutary effects directly or indirectly via increased Prl secretion, splenocyte proliferation and splenocyte interleukin (IL)-2 and IL-3 release from untreated sham or Hem mice were determined in the presence of increasing concentrations of mouse Prl or Mcp. The addition of Mcp had no effect on splenocyte immune functions in vitro. However, the addition of Prl restored the hemorrhage-induced depressed splenocyte proliferation as well as splenocyte IL-2 and IL-3 release in vitro in a dose-dependent manner. Thus the beneficial effects of Mcp on immune functions after Hem appear to be mediated by Prl. Because Mcp increases plasma levels of the immunoenhancing hormone Prl, this agent should be considered a useful adjunct for the treatment of immunodepression in trauma victims. PMID:10898718

  18. Adipose stromal vascular fraction improves cardiac function in chronic myocardial infarction through differentiation and paracrine activity.

    PubMed

    Mazo, Manuel; Cemborain, Arantxa; Gavira, Juan José; Abizanda, Gloria; Araña, Miriam; Casado, Mayte; Soriano, Mario; Hernández, Salomón; Moreno, Cristina; Ecay, Margarita; Albiasu, Edurne; Belzunce, Miriam; Orbe, Josune; Páramo, José Antonio; Merino, Juana; Peñuelas, Iván; Verdugo, José Manuel García; Pelacho, Beatriz; Prosper, Felipe

    2012-01-01

    Fresh adipose-derived cells have been shown to be effective in the treatment of acute myocardial infarction (MI), but their role in the chronic setting is unknown. We sought to determine the long-term effect of the adipose derived-stromal vascular fraction (SVF) cell transplantation in a rat model of chronic MI. MI was induced in 82 rats by permanent coronary artery ligation and 5 weeks later rats were allocated to receive an intramyocardial injection of 10(7) GFP-expressing fresh SVF cells or culture media as control. Heart function and tissue metabolism were determined by echocardiography and (18)F-FDG-microPET, respectively, and histological studies were performed for up to 3 months after transplantation. SVF induced a statistically significant long-lasting (3 months) improvement in cardiac function and tissue metabolism that was associated with increased revascularization and positive heart remodeling, with a significantly smaller infarct size, thicker infarct wall, lower scar fibrosis, and lower cardiac hypertrophy. Importantly, injected cells engrafted and were detected in the treated hearts for at least 3 months, directly contributing to the vasculature and myofibroblasts and at negligible levels to cardiomyocytes. Furthermore, SVF release of angiogenic (VEGF and HGF) and proinflammatory (MCP-1) cytokines, as well as TIMP1 and TIMP4, was demonstrated in vitro and in vivo, strongly suggesting that they have a trophic effect. These results show the potential of SVF to contribute to the regeneration of ischemic tissue and to provide a long-term functional benefit in a rat model of chronic MI, by both direct and indirect mechanisms. PMID:22305117

  19. Improvements in Speed and Functionality of a 670-GHz Imaging Radar

    NASA Technical Reports Server (NTRS)

    Dengler, Robert J.; Cooper, Ken B.; Mehdi, Imran; Siegel, Peter H.; Tarsala, Jan A.; Bryllert, Thomas E.

    2011-01-01

    Significant improvements have been made in the instrument originally described in a prior NASA Tech Briefs article: Improved Speed and Functionality of a 580-GHz Imaging Radar (NPO-45156), Vol. 34, No. 7 (July 2010), p. 51. First, the wideband YIG oscillator has been replaced with a JPL-designed and built phase-locked, low-noise chirp source. Second, further refinements to the data acquisition and signal processing software have been performed by moving critical code sections to C code, and compiling those sections to Windows DLLs, which are then invoked from the main LabVIEW executive. This system is an active, single-pixel scanned imager operating at 670 GHz. The actual chirp signals for the RF and LO chains were generated by a pair of MITEQ 2.5 3.3 GHz chirp sources. Agilent benchtop synthesizers operating at fixed frequencies around 13 GHz were then used to up-convert the chirp sources to 15.5 16.3 GHz. The resulting signals were then multiplied 36 times by a combination of off-the-shelf millimeter- wave components, and JPL-built 200- GHz doublers and 300- and 600-GHz triplers. The power required to drive the submillimeter-wave multipliers was provided by JPL-built W-band amplifiers. The receive and transmit signal paths were combined using a thin, high-resistivity silicon wafer as a beam splitter. While the results at present are encouraging, the system still lacks sufficient speed to be usable for practical applications in a contraband detection. Ideally, an image acquisition speed of ten seconds, or a factor of 30 improvement, is desired. However, the system improvements to date have resulted in a factor of five increase in signal acquisition speed, as well as enhanced signal processing algorithms, permitting clearer imaging of contraband objects hidden underneath clothing. In particular, advances in three distinct areas have enabled these performance enhancements: base source phase noise reduction, chirp rate, and signal processing. Additionally, a second pixel was added, automatically reducing the imaging time by a factor of two. Although adding a second pixel to the system doubles the amount of submillimeter components required, some savings in microwave hardware can be realized by using a common low-noise source.

  20. Percutaneous transvenous intracardiac ultrasound imaging in dogs: a new approach to monitor left ventricular function.

    PubMed Central

    Jiang, L.; Weissman, N. J.; Guerrero, J. L.; He, J.; Weyman, A. E.; Levine, R. A.; Picard, M. H.

    1996-01-01

    OBJECTIVE: To evaluate the feasibility and ability of percutaneous transvenous intracardiac echocardiography (ICE) to image the left ventricle (LV) and monitor its function from the right ventricular (RV) cavity. METHODS: A 10 MHz catheter was advanced into the RV from the jugular vein and positioned along the septum at the LV papillary muscle level in five dogs. The catheter was manipulated until a stable catheter position along the septum, which provided on-axis images of LV, was obtained. Different states of LV size and systolic function (n = 80) were created with dobutamine or esmolol, both in the presence and absence of coronary stenoses. LV stroke area (cm2) obtained by ICE was measured at the mid-ventricular level and compared with stroke volume (cm3) obtained simultaneously with a transaortic flow probe. LV end diastolic, end systolic, and stroke areas obtained by ICE were also compared with those obtained by short-axis epicardial echocardiography. RESULTS: In 96% of the stages, short axis images of the LV could be obtained and measured by ICE. LV end diastolic, end systolic, and stroke areas measured by ICE were not significantly different from epicardial echocardiographic values. Stroke area correlated with stroke volume in each dog (mean correlation coefficient 0.79 (SEE 0.19) cm2) (P < 0.001). CONCLUSIONS: Percutaneous intracardiac ultrasound imaging allows monitoring of LV function from the RV with an accuracy comparable to a short-axis epicardial echocardiogram. The present device can be used in closed chest experimental studies. With the development of lower frequency devices, this technique may be valuable for continuous monitoring of LV function in patients in the intensive care unit or operating room. Images PMID:8944593

  1. Arachidonic acid-enriched triacylglycerol improves cognitive function in elderly with low serum levels of arachidonic acid.

    PubMed

    Tokuda, Hisanori; Kontani, Masanori; Kawashima, Hiroshi; Akimoto, Kengo; Kusumoto, Aki; Kiso, Yoshinobu; Koga, Yoshihiko; Shibata, Hiroshi

    2014-01-01

    Arachidonic acid (ARA) is an n-6 PUFA and is thought to have an important role in various physiological and psychological functions. Recently, supplementation with ARA-enriched TAG was shown to improve age-related decreases in cognitive function in healthy elderly men. To investigate the influence of baseline serum ARA status on cognitive function and its improvement, we analyzed cognitive function stratified by serum ARA level. The stratified analysis was also conducted for the effects of ARA-enriched TAG supplementation on cognitive improvement. Cognitive function was evaluated by measuring event-related potentials (ERPs), including P300 latency and amplitude. When participants were stratified by baseline serum ARA level, P300 latency was significantly longer and P300 amplitude was generally lower in the low-ARA group than in the high-ARA group. No significant difference in P300 components was observed when participants were stratified by serum levels of any other fatty acid. ARA-enriched TAG supplementation significantly shortened P300 latency and increased P300 amplitude in the low-ARA group, although no significant differences were observed in the high-ARA group. These findings suggest that lower serum ARA levels were associated with cognitive function in elderly men and that ARA-enriched TAG supplementation is more effective in improving cognitive function in healthy elderly men with low serum ARA levels than in those with high serum ARA levels. PMID:24521845

  2. High- and low-leukemogenic variants of the radiation leukemia virus (RadLV) differ in ability to induce tumor-specific immune suppression.

    PubMed

    Yefenof, E; Zilcha, D

    1982-09-15

    Adult C57BL/6 mice inoculated intrathymically (i.t.) with the highly leukemogenic variant of the radiation leukemia virus (A-RadLV) develop suppressor cells capable of specifically abrogating a potential anti-tumor cytotoxic response in vitro. Suppressor cells were generated directly by the virus, independently of an initiation of a leukemogenic process. Inoculation of C57BL/6 animals with the low leukemogenic D-RadLV variant did not result in suppressor cell generation. It is proposed that induction of tumor-specific immune suppression by A-RadLV is essential for tumor progression, and the leukemogenic activity of D-RadLV is attributed to its inability to recruit suppressor cells. PMID:6215365

  3. Anti-lipopolysaccharide factor in Litopenaeus vannamei ( LvALF): A broad spectrum antimicrobial peptide essential for shrimp immunity against bacterial and fungal infection

    Microsoft Academic Search

    Enrique de la Vega; Nuala A. O’Leary; Jessica E. Shockey; Javier Robalino; Caroline Payne; Craig L. Browdy; Gregory W. Warr; Paul S. Gross

    2008-01-01

    Antimicrobial peptides are an essential component of the innate immune system of most organisms. Expressed sequence tag analysis from various shrimp (Litopenaeus vannamei) tissues revealed transcripts corresponding to two distinct sequences (LvALF1 and LvALF2) with strong sequence similarity to anti-lipopolysaccharide factor (ALF), an antimicrobial peptide originally isolated from the horseshoe crab Limulus polyphemus. Full-length clones contained a 528bp transcript with

  4. Patients Undergoing Subacute Physical Rehabilitation following an Acute Hospital Admission Demonstrated Improvement in Cognitive Functional Task Independence

    PubMed Central

    McPhail, Steven M.; Varghese, Paul N.; Kuys, Suzanne S.

    2014-01-01

    Objective. This study investigated cognitive functioning among older adults with physical debility not attributable to an acute injury or neurological condition who were receiving subacute inpatient physical rehabilitation. Design. A cohort investigation with assessments at admission and discharge. Setting. Three geriatric rehabilitation hospital wards. Participants. Consecutive rehabilitation admissions (n = 814) following acute hospitalization (study criteria excluded orthopaedic, neurological, or amputation admissions). Intervention. Usual rehabilitation care. Measurements. The Functional Independence Measure (FIM) Cognitive and Motor items. Results. A total of 704 (86.5%) participants (mean age = 76.5 years) completed both assessments. Significant improvement in FIM Cognitive items (Z-score range 3.93–8.74, all P < 0.001) and FIM Cognitive total score (Z-score = 9.12, P < 0.001) occurred, in addition to improvement in FIM Motor performance. A moderate positive correlation existed between change in Motor and Cognitive scores (Spearman's rho = 0.41). Generalized linear modelling indicated that better cognition at admission (coefficient = 0.398, P < 0.001) and younger age (coefficient = ?0.280, P < 0.001) were predictive of improvement in Motor performance. Younger age (coefficient = ?0.049, P < 0.001) was predictive of improvement in FIM Cognitive score. Conclusions. Improvement in cognitive functioning was observed in addition to motor function improvement among this population. Causal links cannot be drawn without further research. PMID:25544961

  5. Regional assessment of LV wall in infarcted heart using tagged MRI and cardiac modelling

    NASA Astrophysics Data System (ADS)

    Jahanzad, Zeinab; Miin Liew, Yih; Bilgen, Mehmet; McLaughlin, Robert A.; Onn Leong, Chen; Chee, Kok Han; Aziz, Yang Faridah Abdul; Ung, Ngie Min; Lai, Khin Wee; Ng, Siew-Cheok; Lim, Einly

    2015-05-01

    A segmental two-parameter empirical deformable model is proposed for evaluating regional motion abnormality of the left ventricle. Short-axis tagged MRI scans were acquired from 10 healthy subjects and 10 postinfarct patients. Two motion parameters, contraction and rotation, were quantified for each cardiac segment by fitting the proposed model using a non-rigid registration algorithm. The accuracy in motion estimation was compared to a global model approach. Motion parameters extracted from patients were correlated to infarct transmurality assessed with delayed-contrast-enhanced MRI. The proposed segmental model allows markedly improved accuracy in regional motion analysis as compared to the global model for both subject groups (1.22–1.40?mm versus 2.31–2.55?mm error). By end-systole, all healthy segments experienced radial displacement by ~25–35% of the epicardial radius, whereas the 3 short-axis planes rotated differently (basal: 3.3° mid:???1° and apical:???4.6°) to create a twisting motion. While systolic contraction showed clear correspondence to infarct transmurality, rotation was nonspecific to either infarct location or transmurality but could indicate the presence of functional abnormality. Regional contraction and rotation derived using this model could potentially aid in the assessment of severity of regional dysfunction of infarcted myocardium.

  6. Hemodynamic flow improves rat hepatocyte morphology, function, and metabolic activity in vitro.

    PubMed

    Dash, A; Simmers, M B; Deering, T G; Berry, D J; Feaver, R E; Hastings, N E; Pruett, T L; LeCluyse, E L; Blackman, B R; Wamhoff, B R

    2013-06-01

    In vitro primary hepatocyte systems typically elicit drug induction and toxicity responses at concentrations much higher than corresponding in vivo or clinical plasma C(max) levels, contributing to poor in vitro-in vivo correlations. This may be partly due to the absence of physiological parameters that maintain metabolic phenotype in vivo. We hypothesized that restoring hemodynamics and media transport would improve hepatocyte architecture and metabolic function in vitro compared with nonflow cultures. Rat hepatocytes were cultured for 2 wk either in nonflow collagen gel sandwiches with 48-h media changes or under controlled hemodynamics mimicking sinusoidal circulation within a perfused Transwell device. Phenotypic, functional, and metabolic parameters were assessed at multiple times. Hepatocytes in the devices exhibited polarized morphology, retention of differentiation markers [E-cadherin and hepatocyte nuclear factor-4? (HNF-4?)], the canalicular transporter [multidrug-resistant protein-2 (Mrp-2)], and significantly higher levels of liver function compared with nonflow cultures over 2 wk (albumin ~4-fold and urea ~5-fold). Gene expression of cytochrome P450 (CYP) enzymes was significantly higher (fold increase over nonflow: CYP1A1: 53.5 ± 10.3; CYP1A2: 64.0 ± 15.1; CYP2B1: 15.2 ± 2.9; CYP2B2: 2.7 ± 0.8; CYP3A2: 4.0 ± 1.4) and translated to significantly higher basal enzyme activity (device vs. nonflow: CYP1A: 6.26 ± 2.41 vs. 0.42 ± 0.015; CYP1B: 3.47 ± 1.66 vs. 0.4 ± 0.09; CYP3A: 11.65 ± 4.70 vs. 2.43 ± 0.56) while retaining inducibility by 3-methylcholanthrene and dexamethasone (fold increase over DMSO: CYP1A = 27.33 and CYP3A = 4.94). These responses were observed at concentrations closer to plasma levels documented in vivo in rats. The retention of in vivo-like hepatocyte phenotype and metabolic function coupled with drug response at more physiological concentrations emphasizes the importance of restoring in vivo physiological transport parameters in vitro. PMID:23485712

  7. Effect of spironolactone on left ventricular systolic and diastolic function in patients with early stage chronic kidney disease.

    PubMed

    Edwards, Nicola C; Ferro, Charles J; Kirkwood, Helen; Chue, Colin D; Young, Alistair A; Stewart, Paul M; Steeds, Richard P; Townend, Jonathan N

    2010-11-15

    Patients with early chronic kidney disease (CKD) have an increased risk for cardiovascular disease. Aldosterone levels are elevated and might impair ventricular function through adverse myocardial and vascular proinflammatory and fibrotic effects. In the Chronic Renal Impairment in Birmingham II (CRIB II) study, it was hypothesized that mineralocorticoid receptor blockade with spironolactone in addition to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers would improve left ventricular (LV) function and markers of inflammation, ventricular stretch, and collagen turnover in early CKD. A total of 112 patients with early CKD were randomized to spironolactone 25 mg/day or placebo for 40 weeks. Ventricular function was assessed by echocardiography and cardiac magnetic resonance imaging tagging. High-sensitivity C-reactive protein, N-terminal-pro-B-type natriuretic peptide, and aminoterminal propeptide of type III procollagen were measured. Spironolactone improved LV long-axis systolic function (Sm 8.2 ± 1.4 vs 7.7 ± 1.3 cm/s, p <0.05), torsion (7.77 ± 1.61° vs 6.77 ± 1.48°, p <0.05), and myocardial deformation (strain rate -1.14 ± 0.24 vs -1.09 ± 0.20 s(-1), p <0.05) compared to placebo, without a change in the ejection fraction. Markers of LV relaxation (E/e' ratio 7.2 ± 2.3 vs 8.5 ± 2.3, p <0.05) and suction (M-mode propagation velocity 56 ± 12 vs 50 ± 12 cm/s, p <0.05) were also improved. Spironolactone reduced N-terminal-pro-B-type natriuretic peptide (24.8 pmol/L [range 0.4 to 122.4] vs 39.4 pmol/L [range 10.8 to 102.4], p <0.01) and attenuated an increase in aminoterminal propeptide of type III procollagen observed with placebo. In conclusion, spironolactone improves markers of regional LV systolic and diastolic function in early CKD. PMID:21059444

  8. Hollow Fiber Membrane Modification with Functional Zwitterionic Macromolecules for Improved Thromboresistance in Artificial Lungs

    PubMed Central

    Ye, Sang-Ho; Arazawa, David T.; Zhu, Yang; Shankarraman, Venkat; Malkin, Alexander D.; Kimmel, Jeremy D.; Gamble, Lara J.; Ishihara, Kazuhiko; Federspiel, William J.; Wagner, William R.

    2015-01-01

    Respiratory assist devices seek optimized performance in terms of gas transfer efficiency and thromboresistance to minimize device size and reduce complications associated with inadequate blood biocompatibility. The exchange of gas with blood occurs at the surface of the hollow fiber membranes (HFMs) used in these devices. In this study, three zwitterionic macromolecules were attached to HFM surfaces to putatively improve thromboresistance: (1) carboxyl-functionalized zwitterionic phosphorylcholine (PC) and (2) sulfobetaine (SB) macromolecules (mPC or mSB-COOH) prepared by a simple thiol-ene radical polymerization and (3) a low-molecular weight sulfobetaine (SB)-co-methacrylic acid (MA) block copolymer (SBMAb-COOH) prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. Each macromolecule type was covalently immobilized on an aminated commercial HFM (Celg-A) by a condensation reaction, and HFM surface composition changes were analyzed by X-ray photoelectron spectroscopy. Thrombotic deposition on the HFMs was investigated after contact with ovine blood in vitro. The removal of CO2 by the HFMs was also evaluated using a model respiratory assistance device. The HFMs conjugated with zwitterionic macromolecules (Celg-mPC, Celg-mSB, and Celg-SBMAb) showed expected increases in phosphorus or sulfur surface content. Celg-mPC and Celg-SBMAb experienced rates of platelet deposition significantly lower than those of unmodified (Celg-A, >95% reduction) and heparin-coated (>88% reduction) control HFMs. Smaller reductions were seen with Celg-mSB. The CO2 removal rate for Celg-SBMAb HFMs remained comparable to that of Celg-A. In contrast, the rate of removal of CO2 for heparin-coated HFMs was significantly reduced. The results demonstrate a promising approach to modifying HFMs using zwitterionic macromolecules for artificial lung devices with improved thromboresistance without degradation of gas transfer. PMID:25669307

  9. Transplantation of human fetal-derived neural stem cells improves cognitive function following cranial irradiation.

    PubMed

    Acharya, Munjal M; Christie, Lori-Ann; Hazel, Thomas G; Johe, Karl K; Limoli, Charles L

    2014-01-01

    Treatment of central nervous system (CNS) malignancies typically involves radiotherapy to forestall tumor growth and recurrence following surgical resection. Despite the many benefits of cranial radiotherapy, survivors often suffer from a wide range of debilitating and progressive cognitive deficits. Thus, while patients afflicted with primary and secondary malignancies of the CNS now experience longer local regional control and progression-free survival, there remains no clinical recourse for the unintended neurocognitive sequelae associated with their cancer treatments. Multiple mechanisms contribute to disrupted cognition following irradiation, including the depletion of radiosensitive populations of stem and progenitor cells in the hippocampus. We have explored the potential of using intrahippocampal transplantation of human stem cells to ameliorate radiation-induced cognitive dysfunction. Past studies demonstrated the capability of cranially transplanted human embryonic (hESCs) and neural (hNSCs) stem cells to functionally restore cognition in rats 1 and 4 months after cranial irradiation. The present study employed an FDA-approved fetal-derived hNSC line capable of large scale-up under good manufacturing practice (GMP). Animals receiving cranial transplantation of these cells 1 month following irradiation showed improved hippocampal spatial memory and contextual fear conditioning performance compared to irradiated, sham surgery controls. Significant newly born (doublecortin positive) neurons and a smaller fraction of glial subtypes were observed within and nearby the transplantation core. Engrafted cells migrated and differentiated into neuronal and glial subtypes throughout the CA1 and CA3 subfields of the host hippocampus. These studies expand our prior findings to demonstrate that transplantation of fetal-derived hNSCs improves cognitive deficits in irradiated animals, as assessed by two separate cognitive tasks. PMID:23866792

  10. Short-term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats

    PubMed Central

    LI, YAN; XUAN, YAN-HUA; LIU, SHUANG-SHUANG; DONG, JING; LUO, JIA-YING; SUN, ZHI-JUN

    2015-01-01

    Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86±9.73, vs. 45.60±5.51%; P=0.025) and left ventricular fractional shortening (25.31±6.30, vs. 15.42±8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07±2.63, vs. 19.95±5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11±0.50, vs. 1.54±0.57 cm3; P=0.032) and left ventricular end systolic volume (0.50±0.28, vs. 0.87±0.36 cm3; P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. PMID:25873055

  11. Collagen Scaffold Supplementation does not Improve the Functional Properties of the Repaired Anterior Cruciate Ligament

    PubMed Central

    Fleming, Braden C.; Magarian, Elise M.; Harrison, Sophia L.; Paller, David J.; Murray, Martha M.

    2009-01-01

    Primary suture ACL repair was abandoned in favor of reconstruction due to a high rate of clinical failures. However, the insertion of a collagen scaffold loaded with platelets into the wound at the time of suture repair (“enhanced primary repair”) has been shown to improve functional healing in animal models. Our objectives were to determine if using a collagen scaffold alone (without platelets) would be sufficient to increase the structural properties of the repaired ACL and decrease postoperative knee laxity compared to suture repair without the scaffold. Eight Yucatan minipigs underwent bilateral ACL transection and suture repair. In one knee, the repair was augmented with a collagen scaffold (SCAFFOLD group) while the other had suture alone (SUTURE group). After thirteen weeks of healing, knee joint laxity and the structural properties of the ACL were measured. The addition of the collagen scaffold to suture repair of a transected ACL did not significantly improve the mean anteroposterior knee laxity [SCAFFOLD vs SUTURE: 6.1±1.4 vs 4.4±2.0 mm (p=0.07), 8.1±2.0 vs 7.6±2.0 mm (p=0.66), and 6.2±1.2 vs 6.1±1.8 mm (p=0.85) at 30°, 60°, and 90° flexion, respectively]. Likewise, there were no significant differences in the structural properties [SCAFFOLD vs SUTURE: 367±185.9 vs 322±122.0 N (p=0.66) and 90.7±29.5 vs 85.0±30.3 N/mm (p=0.74) for the yield load and linear stiffness, respectively]. The use of a collagen scaffold alone to enhance suture repair of the ACL was ineffective in this animal model. Future work will be directed at stimulating biological activity in the scaffold. PMID:20058276

  12. Short?term vagal nerve stimulation improves left ventricular function following chronic heart failure in rats.

    PubMed

    Li, Yan; Xuan, Yan-Hua; Liu, Shuang-Shuang; Dong, Jing; Luo, Jia-Ying; Sun, Zhi-Jun

    2015-08-01

    Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long?term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short?term VNS on the hemodynamics of cardiac remodeling and cardiac excitation?contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham?stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86±9.73, vs. 45.60±5.51%; P=0.025) and left ventricular fractional shortening (25.31±6.30, vs. 15.42±8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07±2.63, vs. 19.95±5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11±0.50, vs. 1.54±0.57 cm3; P=0.032) and left ventricular end systolic volume (0.50±0.28, vs. 0.87±0.36 cm3; P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. PMID:25873055

  13. Inhibition of Taura syndrome virus replication in Litopenaeus vannamei through silencing the LvRab7 gene using double-stranded RNA.

    PubMed

    Ongvarrasopone, Chalermporn; Saejia, Pipop; Chanasakulniyom, Mayuree; Panyim, Sakol

    2011-07-01

    Taura syndrome virus (TSV) is a major cause of high mortality in Pacific white shrimp (Litopenaeus vannamei, Lv). Previously, silencing of Penaeus monodon Rab7 (PmRab7) by injecting double-stranded RNA corresponding to PmRab7 (dsRNA-PmRab7) prevented white spot syndrome virus or yellow head virus infection. Rab7 is proposed to be involved in intracellular trafficking of the viruses. This study aimed to investigate whether knockdown of Rab7 in L. vannamei by dsRNA-PmRab7 could inhibit replication of TSV. RNA interference (RNAi) technology using dsRNA targeting the LvRab7 gene was used to silence the mRNA expression of LvRab7. The silencing of the LvRab7 gene inhibited TSV replication dramatically when compared to groups receiving dsRNA-GFP or NaCl. This is the first demonstration that dsRNA targeting the endogenous shrimp gene LvRab7 strongly reduces TSV replication. It provides further evidence that LvRab7 is involved in the endosomal trafficking pathway of viruses infecting penaeid shrimp. PMID:21347841

  14. Research on biochemical spectrum denoising based on a novel wavelet threshold function and an improved translation-invariance method

    NASA Astrophysics Data System (ADS)

    Ren, Zhong; Liu, Guodong; Zeng, Lvming; Huang, Zhen; Huang, Shuanggen

    2008-12-01

    In this paper, an improved wavelet threshold denoising with combined translation invariance(TI)method is adopted to remove noises existed in the bio-chemical spectrum. Meanwhile, a novel wavelet threshold function and an optimal threshold determination algorithm are proposed. The new function is continuous and high-order derivable, it can overcome the vibration phenomena generated by the classical threshold function and decrease the error of reconstructed spectrum. So, it is superior to the frequency-domain filtering methods, the soft- and hard-threshold function proposed by D.L. Donoho and the semisoft-threshold function proposed by Gao, etc. The experimental results show that the improved TI wavelet threshold(TI-WT) denoising method can availably eliminate the Pseudo-Gibbs phenomena generated by the traditional wavelet thresholding method. At the same time, the improved wavelet threshold function and the TI-WT method present lower root mean-square-error (RMSE) and higher signal-to-noise ratio(SNR) than the frequency-domain filtering, classical soft and hard-threshold denoising The SNR increasing from 17.3200 to 32.5609, the RMSE decreasing from 4.0244 to 0.6257. Otherwise, The improved denoising method not only makes the spectrum smooth, but also effectively preserves the edge characteristics of the original spectrum.

  15. A diet based on multiple functional concepts improves cognitive performance in healthy subjects

    PubMed Central

    2013-01-01

    Background Disorders such as the metabolic syndrome (MetS), impaired glucose tolerance and diabetes, are associated with increased risk of cognitive decline. Also several of the individual key features that define the MetS, e.g. hypertension, impaired glucose regulation, dyslipidemia, obesity, and inflammation, are related to an increased risk of cognitive decline. Consequently, a diet that prevents metabolic disorders might be expected to prevent cognitive decline. The purpose of the present study was to, in overweight but otherwise healthy subjects, investigate effects on cognitive functions of a dietary regime combining multiple functional concepts potentially beneficial to risk markers associated with MetS. The purpose was in addition to evaluate cognitive performance in relation to results on cardiometabolic risk variables (BMI, blood pressure, glucose, insulin, cholesterol, triglycerides, free fatty acids, lipoprotein A-1 and B, hs-CRP, HbA1c, interleukin-6, TNF-?, and PAI-1). Methods Fourty-four healthy women and men (50–73 years, BMI 25–33, fasting glycemia???6.1 mmol/L) participated in a randomized, controlled crossover intervention, comparing a multifunctional diet (active diet (AD)) including foods with a potential anti-inflammatory action, with a control diet (CD) devoid of the “active” components. Both diets were composed in close agreement with the Nordic dietary recommendations. Each diet was consumed during 4 wk, separated by a 4 wk washout period. Cognitive tests were performed at fasting and in the postprandial period after a standardized breakfast, after each diet period. Results In comparison with the CD, the AD improved performance in the Rey Auditory-Verbal Learning test (recognition test, p?improved performance in test of selective attention, which also included aspects of working memory (p?

  16. A diet based on multiple functional concepts improves cardiometabolic risk parameters in healthy subjects

    PubMed Central

    2012-01-01

    Background Different foods can modulate cardiometabolic risk factors in persons already affected by metabolic alterations. The objective of this study was to assess, in healthy overweight individuals, the impact of a diet combining multiple functional concepts on risk markers associated with cardiometabolic diseases (CMD). Methods Fourty-four healthy women and men (50-73 y.o, BMI 25-33, fasting glycemia ? 6.1 mmol/L) participated in a randomized crossover intervention comparing a multifunctional (active) diet (AD) with a control diet (CD) devoid of the "active" components. Each diet was consumed during 4 wk with a 4 wk washout period. AD included the following functional concepts: low glycemic impact meals, antioxidant-rich foods, oily fish as source of long-chain omega-3 fatty acids, viscous dietary fibers, soybean and whole barley kernel products, almonds, stanols and a probiotic strain (Lactobacillus plantarum Heal19/DSM15313). Results Although the aim was to improve metabolic markers without promoting body weight loss, minor weight reductions were observed with both diets (0.9-1.8 ± 0.2%; P < 0.05). CD did not modify the metabolic variables measured. AD promoted significant changes in total serum cholesterol (-26 ± 1% vs baseline; P < 0.0001), LDL-cholesterol (-34 ± 1%; P < 0.0001), triglycerides (-19 ± 3%; P = 0.0056), LDL/HDL (-27 ± 2%; P < 0.0001), apoB/apoA1 (-10 ± 2%; P < 0.0001), HbA1c (-2 ± 0.4%; P = 0.0013), hs-CRP (-29 ± 9%; P = 0.0497) and systolic blood pressure (-8 ± 1%¸ P = 0.0123). The differences remained significant after adjustment for weight change. After AD, the Framingham cardiovascular risk estimate was 30 ± 4% (P < 0.0001) lower and the Reynolds cardiovascular risk score, which considers CRP values, decreased by 35 ± 3% (P < 0.0001). Conclusion The improved biomarker levels recorded in healthy individuals following the multifunctional regime suggest preventive potential of this dietary approach against CMD. PMID:22472183

  17. Heme Oxygenase-1 Induction Improves Cardiac Function following Myocardial Ischemia by Reducing Oxidative Stress

    PubMed Central

    Issan, Yossi; Kornowski, Ran; Aravot, Dan; Shainberg, Asher; Laniado-Schwartzman, Michal; Sodhi, Komal; Abraham, Nader G.; Hochhauser, Edith

    2014-01-01

    Background Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05). CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01), reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNF? levels (p<0.05). The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05). CoPP significantly increased the expression levels of pAKT and pGSK3? (p<0.05) in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects. Conclusions HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by the increased levels of pAKT with a concomitant inhibition of pGSK3? leading to preserved mitochondrial membrane potential. PMID:24658657

  18. Psychological and metabolic improvement after an outpatient teaching program for functional intensified insulin therapy (FIT).

    PubMed

    Langewitz, W; Wössmer, B; Iseli, J; Berger, W

    1997-09-01

    To be the master of their disease and not its slave is the ultimate goal of many patients with diabetes. Intensified functional insulin therapy (FIT) helps to establish this goal by an intensive patient education: each patient learns in five small-group sessions how s/he reacts to standardized challenges of glucose homeostasis (e.g. 24 h fasting; physical exercise; various carbohydrate loads). We investigated in 43 patients with long-standing diabetes type 1 (mean age: 33 +/- 10 years; mean duration of diabetes: 15 +/- 10 years) whether FIT improves quality of life, influences metabolic control and doctor-patient relationship. The following instruments were used: diabetes specific quality of life questionnaire (DQOL), hierarchical distance and cohesion between doctor and patient (FAST), anxiety and depression (HAD). Pre and post intervention values were compared with paired t-tests. HbA1c and number of hypoglycaemic episodes were also assessed 1 year after FIT and 1 year prior to FIT. Metabolic control was improved: HbA1c in the year before FIT: 6.72 +/- 1.35; 4 months before FIT: 6.61 +/- 1.46; 4 months after FIT: 6.29 +/- 1.09 (P < 0.05 compared to 4 months before FIT); 1 year after FIT: 6.46 +/- 1.12 (n.s. compared to 1 year before FIT). Dissatisfaction with life decreases from 33.3 +/- 8.0 to 28.5 +/- 7.7 (P < 0.001). Moments free of disease-specific strain increase from 74.3 +/- 13.9 to 78.1 +/- 16.1 (P = 0.07). Hierarchical distance between doctor and patient decreases from 1.1 +/- to 0.6 +/- 0.8 (P < 0.001), cohesion increases from 9.3 +/- 1.5 to 9.9 +/- 1.1 (P < 0.001). Anxiety and depression both decreases significantly: anxiety, 6.5 +/- 3.3-->4.6 +/- 3.2 (P < 0.001); depression, 2.7 +/- 2.5-->1.5 +/- 1.6 (P < 0.001). The number of patients with severe hypoglycaemic episodes (level 4) decreases from five (11.6%) to one (2.3%) after intervention (P < 0.05). In conclusion, FIT enhances quality of life in diabetic individuals. It helps to establish a less hierarchical and closer relationship between patient and doctor as revealed by the FAST data. It should be emphasized that the psychological improvements are not achieved at the expense of less strict metabolic control. PMID:9306036

  19. Estradiol improves cardiovascular function through up-regulation of SOD2 on vascular wall

    PubMed Central

    Liu, Zhaoyu; Gou, Yulan; Zhang, Hongyu; Zuo, Houjuan; Zhang, Haimou; Liu, Zhengxiang; Yao, Dachun

    2014-01-01

    Epidemiological studies have shown that estrogens have protective effects in cardiovascular diseases, even though the results from human clinical trials remain controversial, while most of the animal experiments confirmed this effect, but the detailed mechanism remains unclear. In this study, we found that estradiol (E2) treatment significantly increases the expression of mitochondrial superoxide dismutase (SOD2) in mice and in vitro in human aorta endothelial cells. Further investigation shows that E2 up-regulates SOD2 through tethering of estrogen receptor (ER) to Sp1 and the increased binding of Sp1 to GC-box on the SOD2 promoter, where ER? responses E2-mediated gene activation, and ER? maintains basal gene expression level. The E2/ER-mediated SOD2 up-regulation results in minimized ROS generation, which highly favors healthy cardiovascular function. Gene therapy through lentivirus-carried endothelium-specific delivery to the vascular wall in high-fat diet (HFT) mice shows that the SOD2 expression in endothelial cells normalizes E2 deficiency-induced ROS generation with ameliorated mitochondrial dysfunction and vascular damage, while SOD2 knockdown worsens the problem despite the presence of E2, indicating that E2-induced SOD2 expression plays an important vasculoprotective role. To our knowledge, this is the first report for the mechanism by which E2 improves cardiovascular function through up-regulation of SOD2 in endothelial cells. In turn, this suggests a novel gene therapy through lentivirus-carried gene delivery to vascular wall for E2 deficiency-induced cardiovascular damage in postmenopausal women. PMID:25462070

  20. Eprosartan improves cardiac function in swine working heart model of ischemia-reperfusion injury

    PubMed Central

    Weymann, Alexander; Sabashnikov, Anton; Patil, Nikhil P.; Konertz, Wolfgang; Modersohn, Diethelm; Dohmen, Pascal M.

    2014-01-01

    Background Eprosartan is an angiotensin II receptor antagonist used as an antihypertensive. We sought to evaluate the regional effect of Eprosartan on postinfarct ventricular remodeling and myocardial function in an isolated swine working heart model of ischemia-reperfusion injury. Material/Methods 22 swine hearts were perfused with the Langendorff perfusion apparatus under standard experimental conditions. Myocardial ischemia was induced by a 10-min left anterior descending artery ligation. Hearts were reperfused with either saline (control group, n=11), or Eprosartan (treatment group, n=11). Left ventricular pressure (LVP) and regional heart parameters such as intramyocardial pressure (IMP), wall thickening rate (WTh), and pressure-length-loops (PLL) were measured at baseline and after 30 min of reperfusion. Results Measured parameters were statistically similar between the 2 groups at baseline. The administration of Eprosartan led to a significantly better recovery of IMP and WTh: 44.4±2.5 mmHg vs. 51.2±3.3 mmHg, p<0.001 and 3.8±0.4 ?m vs. 4.4±0.3 ?m, p=0.001, respectively. PLL were also significantly higher in the treatment group following reperfusion (21694±3259 units vs. 31267±3429 units, p<0.01). There was no difference in the LVP response to Eprosartan versus controls (63.6±3.0 mmHg vs. 62.5±3.1 mmHg, p=0.400). Conclusions Pre-treatment with Eprosartan is associated with a significant improvement in regional cardiac function under ischemic conditions. Pharmacological treatment with eprosartan may exert a direct cardioprotective effect on ischemic myocardium. PMID:24762635

  1. Aerobic exercise training improves whole muscle and single myofiber size and function in older women

    PubMed Central

    Konopka, Adam R.; Douglass, Matthew D.; Minchev, Kiril; Kaminsky, Leonard A.; Trappe, Todd A.; Trappe, Scott

    2009-01-01

    To comprehensively assess the influence of aerobic training on muscle size and function, we examined seven older women (71 ± 2 yr) before and after 12 wk of cycle ergometer training. The training program increased (P < 0.05) aerobic capacity by 30 ± 6%. Quadriceps muscle volume, determined by magnetic resonance imaging (MRI), was 12 ± 2% greater (P < 0.05) after training and knee extensor power increased 55 ± 7% (P < 0.05). Muscle biopsies were obtained from the vastus lateralis to determine size and contractile properties of individual slow (MHC I) and fast (MHC IIa) myofibers, myosin light chain (MLC) composition, and muscle protein concentration. Aerobic training increased (P < 0.05) MHC I fiber size 16 ± 5%, while MHC IIa fiber size was unchanged. MHC I peak power was elevated 21 ± 8% (P < 0.05) after training, while MHC IIa peak power was unaltered. Peak force (Po) was unchanged in both fiber types, while normalized force (Po/cross-sectional area) was 10% lower (P < 0.05) for both MHC I and MHC IIa fibers after training. The decrease in normalized force was likely related to a reduction (P < 0.05) in myofibrillar protein concentration after training. In the absence of an increase in Po, the increase in MHC I peak power was mediated through an increased (P < 0.05) maximum contraction velocity (Vo) of MHC I fibers only. The relative proportion of MLC1s (Pre: 0.62 ± 0.01; Post: 0.58 ± 0.01) was lower (P < 0.05) in MHC I myofibers after training, while no differences were present for MLC2s and MLC3f isoforms. These data indicate that aerobic exercise training improves muscle function through remodeling the contractile properties at the myofiber level, in addition to pronounced muscle hypertrophy. Progressive aerobic exercise training should be considered a viable exercise modality to combat sarcopenia in the elderly population. PMID:19692660

  2. Hydrologic-Process-Based Soil Texture Classifications for Improved Visualization of Landscape Function.

    PubMed

    Groenendyk, Derek G; Ferré, Ty P A; Thorp, Kelly R; Rice, Amy K

    2015-01-01

    Soils lie at the interface between the atmosphere and the subsurface and are a key component that control ecosystem services, food production, and many other processes at the Earth's surface. There is a long-established convention for identifying and mapping soils by texture. These readily available, georeferenced soil maps and databases are used widely in environmental sciences. Here, we show that these traditional soil classifications can be inappropriate, contributing to bias and uncertainty in applications from slope stability to water resource management. We suggest a new approach to soil classification, with a detailed example from the science of hydrology. Hydrologic simulations based on common meteorological conditions were performed using HYDRUS-1D, spanning textures identified by the United States Department of Agriculture soil texture triangle. We consider these common conditions to be: drainage from saturation, infiltration onto a drained soil, and combined infiltration and drainage events. Using a k-means clustering algorithm, we created soil classifications based on the modeled hydrologic responses of these soils. The hydrologic-process-based classifications were compared to those based on soil texture and a single hydraulic property, Ks. Differences in classifications based on hydrologic response versus soil texture demonstrate that traditional soil texture classification is a poor predictor of hydrologic response. We then developed a QGIS plugin to construct soil maps combining a classification with georeferenced soil data from the Natural Resource Conservation Service. The spatial patterns of hydrologic response were more immediately informative, much simpler, and less ambiguous, for use in applications ranging from trafficability to irrigation management to flood control. The ease with which hydrologic-process-based classifications can be made, along with the improved quantitative predictions of soil responses and visualization of landscape function, suggest that hydrologic-process-based classifications should be incorporated into environmental process models and can be used to define application-specific maps of hydrologic function. PMID:26121466

  3. Proteasome inhibition slightly improves cardiac function in mice with hypertrophic cardiomyopathy

    PubMed Central

    Schlossarek, Saskia; Singh, Sonia R.; Geertz, Birgit; Schulz, Herbert; Reischmann, Silke; Hübner, Norbert; Carrier, Lucie

    2014-01-01

    A growing line of evidence indicates a dysfunctional ubiquitin-proteasome system (UPS) in cardiac diseases. Anti-hypertrophic effects and improved cardiac function have been reported after treatment with proteasome inhibitors in experimental models of cardiac hypertrophy. Here we tested whether proteasome inhibition could also reverse the disease phenotype in a genetically-modified mouse model of hypertrophic cardiomyopathy (HCM), which carries a mutation in Mybpc3, encoding the myofilament protein cardiac myosin-binding protein C. At 7 weeks of age, homozygous mutant mice (KI) have 39% higher left ventricular mass-to-body-weight ratio and 29% lower fractional area shortening (FAS) than wild-type (WT) mice. Both groups were treated with epoxomicin (0.5 mg/kg/day) or vehicle for 1 week via osmotic minipumps. Epoxomicin inhibited the chymotrypsin-like activity by ~50% in both groups. All parameters of cardiac hypertrophy (including the fetal gene program) were not affected by epoxomicin treatment in both groups. In contrast, FAS was 12% and 35% higher in epoxomicin-treated than vehicle-treated WT and KI mice, respectively. To identify which genes or pathways could be involved in this positive effect, we performed a transcriptome analysis in KI and WT neonatal cardiac myocytes, treated or not with the proteasome inhibitor MG132 (1 ?M, 24 h). This revealed 103 genes (four-fold difference; 5% FDR) which are commonly regulated in both KI and WT cardiac myocytes. Thus, even in genetically-modified mice with manifest HCM, proteasome inhibition showed beneficial effects, at least with regard to cardiac function. Targeting the UPS in cardiac diseases remains therefore a therapeutic option. PMID:25566086

  4. Inhibition of connexin43 improves functional recovery after ischemic brain injury in neonatal rats.

    PubMed

    Li, Xiaojing; Zhao, Heqing; Tan, Xianxing; Kostrzewa, Richard M; Du, Gang; Chen, Yuanyuan; Zhu, Jiangtao; Miao, Zhigang; Yu, Hailong; Kong, Jiming; Xu, Xingshun

    2015-09-01

    Connexin43 (Cx43) is one of the most abundant gap junction proteins in the central nervous system. Abnormal opening of Cx43 hemichannels after ischemic insults causes apoptotic cell death. In this study, we found persistently increased expression of Cx43 8 h to 7 d after hypoxia/ischemia (HI) injury in neonatal rats. Pre-treatment with Gap26 and Gap27, two Cx43 mimetic peptides, significantly reduced cerebral infarct volume. Gap26 treatment at 24 h after ischemia improved functional recovery on muscle strength, motor coordination, and spatial memory abilities. Further, Gap26 inhibited Cx43 expression and reduced active astrogliosis. Gap26 interacted and co-localized with Cx43 together in brain tissues and cultured astrocytes. After oxygen glucose deprivation, Gap26 treatment reduced the total Cx43 level in cultured astrocytes; but Cx43 level in the plasma membrane was increased. Degradation of Cx43 in the cytoplasm was mainly via the ubiquitin proteasome pathway. Concurrently, phosphorylated Akt, which phosphorylates Cx43 on Serine(373) and facilitates the forward transport of Cx43 to the plasma membrane, was increased by Gap26 treatment. Microdialysis showed that increased membranous Cx43 causes glutamate release by opening Cx43 hemichannels. Extracellular glutamate concentration was significantly decreased by Gap26 treatment in vivo. Finally, we found that cleaved caspase-3, an apoptosis marker, was attenuated after HI injury by Gap26 treatment. Effects of Gap27 were analogous to those of Gap26. In summary, our findings demonstrate that modulation of Cx43 expression and astroglial function is a potential therapeutic strategy for ischemic brain injury. GLIA 2015;63:1553-1567. PMID:25988944

  5. Hydrologic-Process-Based Soil Texture Classifications for Improved Visualization of Landscape Function

    PubMed Central

    Groenendyk, Derek G.; Ferré, Ty P.A.; Thorp, Kelly R.; Rice, Amy K.

    2015-01-01

    Soils lie at the interface between the atmosphere and the subsurface and are a key component that control ecosystem services, food production, and many other processes at the Earth’s surface. There is a long-established convention for identifying and mapping soils by texture. These readily available, georeferenced soil maps and databases are used widely in environmental sciences. Here, we show that these traditional soil classifications can be inappropriate, contributing to bias and uncertainty in applications from slope stability to water resource management. We suggest a new approach to soil classification, with a detailed example from the science of hydrology. Hydrologic simulations based on common meteorological conditions were performed using HYDRUS-1D, spanning textures identified by the United States Department of Agriculture soil texture triangle. We consider these common conditions to be: drainage from saturation, infiltration onto a drained soil, and combined infiltration and drainage events. Using a k-means clustering algorithm, we created soil classifications based on the modeled hydrologic responses of these soils. The hydrologic-process-based classifications were compared to those based on soil texture and a single hydraulic property, Ks. Differences in classifications based on hydrologic response versus soil texture demonstrate that traditional soil texture classification is a poor predictor of hydrologic response. We then developed a QGIS plugin to construct soil maps combining a classification with georeferenced soil data from the Natural Resource Conservation Service. The spatial patterns of hydrologic response were more immediately informative, much simpler, and less ambiguous, for use in applications ranging from trafficability to irrigation management to flood control. The ease with which hydrologic-process-based classifications can be made, along with the improved quantitative predictions of soil responses and visualization of landscape function, suggest that hydrologic-process-based classifications should be incorporated into environmental process models and can be used to define application-specific maps of hydrologic function. PMID:26121466

  6. D-Cycloserine improves functional outcome after traumatic brain injury with wide therapeutic window

    SciTech Connect

    Adeleye, A.; Biegon, A.; Adeleye, A.; Shohami, E.; Nachman, D.; Alexandrovich, A.; Trembovler, V.; Yaka, R.; Shoshan, Y.; Dhawan, J.; Biegon, A.

    2009-12-01

    It has been long thought that hyperactivation of N-methyl-D-aspartate (NMDA) receptors underlies neurological decline after traumatic brain injury. However, all clinical trials with NMDA receptor antagonists failed. Since NMDA receptors are down-regulated from 4 h to 2 weeks after brain injury, activation at 24 h, rather than inhibition, of these receptors, was previously shown to be beneficial in mice. Here, we tested the therapeutic window, dose regimen and mechanism of action of the NMDA receptor partial agonist d-cycloserine (DCS) in traumatic brain injury. Male mice were subjected to trauma using a weight-drop model, and administered 10 mg/kg (i.p.) DCS or vehicle once (8, 16, 24, or 72 h) twice (24 and 48 h) or three times (24, 48 and 72 h). Functional recovery was assessed for up to 60 days, using a Neurological Severity Score that measures neurobehavioral parameters. In all groups in which treatment was begun at 24 or 72 h neurobehavioral function was significantly better than in the vehicle-treated groups. Additional doses, on days 2 and 3 did not further improve recovery. Mice treated at 8 h or 16 h post injury did not differ from the vehicle-treated controls. Co-administration of the NMDA receptor antagonist MK-801 completely blocked the protective effect of DCS given at 24 h. Infarct volume measured by 2,3,5-triphenyltetrazolium chloride staining at 48 h or by cresyl violet at 28 days was not affected by DCS treatment. Since DCS is used clinically for other indications, the present study offers a novel approach for treating human traumatic brain injury with a therapeutic window of at least 24 h.

  7. Environmental enrichment attenuates hippocampal neuroinflammation and improves cognitive function during influenza infection.

    PubMed

    Jurgens, Heidi A; Johnson, Rodney W

    2012-08-01

    Recent findings from our lab have shown that peripheral infection of adult mice with influenza A/PR/8/34 (H1N1) virus induces a neuroinflammatory response that is paralleled by loss of neurotrophic and glial regulatory factors in the hippocampus, and deficits in cognitive function. Environmental enrichment has been shown to exert beneficial effects on the brain and behavior in many central nervous system (CNS) disorders, but its therapeutic potential during peripheral viral infection remains unknown. Therefore, the objective of the present study was to determine if long-term continuous exposure to environmental enrichment could prevent and/or attenuate the negative effects of influenza infection on the hippocampus and spatial cognition. Mice were housed in enriched or standard conditions for 4 months, and continued to live in their respective environments throughout influenza infection. Cognitive function was assessed in a reversal learning version of the Morris water maze, and changes in hippocampal expression of proinflammatory cytokines (IL-1?, IL-6, TNF-?, IFN-?), neurotrophic (BDNF, NGF), and immunomodulatory (CD200, CX3CL1) factors were determined. We found that environmental enrichment reduced neuroinflammation and helped prevent the influenza-induced reduction in hippocampal CD200. These changes were paralleled by improved cognitive performance of enriched mice infected with influenza when compared to infected mice in standard housing conditions. Collectively, these data are the first to demonstrate the positive impact of environmental enrichment on the brain and cognition during peripheral viral infection, and suggest that enhanced modulation of the neuroimmune response may underlie these beneficial effects. PMID:22687335

  8. Intensive lifestyle intervention improves physical function among obese adults with knee pain: findings from the Look AHEAD trial.

    PubMed

    Foy, Capri G; Lewis, Cora E; Hairston, Kristen G; Miller, Gary D; Lang, Wei; Jakicic, John M; Rejeski, W Jack; Ribisl, Paul M; Walkup, Michael P; Wagenknecht, Lynne E

    2011-01-01

    Lifestyle interventions have resulted in weight loss or improved physical fitness among individuals with obesity, which may lead to improved physical function. This prospective investigation involved participants in the Action for Health in Diabetes (Look AHEAD) trial who reported knee pain at baseline (n = 2,203). The purposes of this investigation were to determine whether an Intensive Lifestyle Intervention (ILI) condition resulted in improvement in self-reported physical function from baseline to 12 months vs. a Diabetes Support and Education (DSE) condition, and whether changes in weight or fitness mediated the effect of the ILI. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and physical function subscales, and WOMAC summary score. ILI participants exhibited greater adjusted mean weight loss (s.e.) vs. DSE participants (-9.02 kg (0.48) vs. -0.78 kg (0.49); P < 0.001)). ILI participants also demonstrated more favorable change in WOMAC summary scores vs. DSE participants (? (s.e.) = -1.81 (0.63); P = 0.004). Multiple regression mediation analyses revealed that weight loss was a mediator of the effect of the ILI intervention on change in WOMAC pain, function, and summary scores (P < 0.001). In separate analyses, increased fitness also mediated the effect of the ILI intervention upon WOMAC summary score (P < 0.001). The ILI condition resulted in significant improvement in physical function among overweight and obese adults with diabetes and knee pain. The ILI condition also resulted in significant weight loss and improved fitness, which are possible mechanisms through which the ILI condition improved physical function. PMID:20559303

  9. Intensive Lifestyle Intervention Improves Physical Function Among Obese Adults With Knee Pain: Findings From the Look AHEAD Trial

    PubMed Central

    Foy, Capri G.; Lewis, Cora E.; Hairston, Kristen G.; Miller, Gary D.; Lang, Wei; Jakicic, John M.; Rejeski, W. Jack; Ribisl, Paul M.; Walkup, Michael P.; Wagenknecht, Lynne E.

    2011-01-01

    Lifestyle interventions have resulted in weight loss or improved physical fitness among individuals with obesity, which may lead to improved physical function. This prospective investigation involved participants in the Action for Health in Diabetes (Look AHEAD) trial who reported knee pain at baseline (n = 2,203). The purposes of this investigation were to determine whether an Intensive Lifestyle Intervention (ILI) condition resulted in improvement in self-reported physical function from baseline to 12 months vs. a Diabetes Support and Education (DSE) condition, and whether changes in weight or fitness mediated the effect of the ILI. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and physical function subscales, and WOMAC summary score. ILI participants exhibited greater adjusted mean weight loss (s.e.) vs. DSE participants (?9.02 kg (0.48) vs. ?0.78 kg (0.49); P < 0.001)). ILI participants also demonstrated more favorable change in WOMAC summary scores vs. DSE participants (? (s.e.) = ?1.81 (0.63); P = 0.004). Multiple regression mediation analyses revealed that weight loss was a mediator of the effect of the ILI intervention on change in WOMAC pain, function, and summary scores (P < 0.001). In separate analyses, increased fitness also mediated the effect of the ILI intervention upon WOMAC summary score (P < 0.001). The ILI condition resulted in significant improvement in physical function among overweight and obese adults with diabetes and knee pain. The ILI condition also resulted in significant weight loss and improved fitness, which are possible mechanisms through which the ILI condition improved physical function. PMID:20559303