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Sample records for improve lv function

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

    PubMed

    Liew, Y M; McLaughlin, R A; Chan, B T; Abdul Aziz, Y F; 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. PMID:25768708

  2. 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.

  3. A targeted mutation within the feline leukemia virus (FeLV) envelope protein immunosuppressive domain to improve a canarypox virus-vectored FeLV vaccine.

    PubMed

    Schlecht-Louf, Graldine; Mangeney, Marianne; El-Garch, Hanane; Lacombe, Valrie; Poulet, Herv; Heidmann, Thierry

    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

  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-γ)-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-γ/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. Evaluation of Long Term Effect of RV Apical Pacing on Global LV Function by Echocardiography

    PubMed Central

    Tilkar, Mahendra; Jain, Siddhant; Mondal, Subrata; Sarkar, Piyabi; Modi, Nitin

    2016-01-01

    Introduction We very often face pacemaker implanted patients during follow-up with shortness of breath and effort intolerance inspite of normal clinical parameters. Aim The aim of our study is to evaluate the cause of effort intolerance and probable cause of sub-clinical Congestive Cardiac Failure (CCF) in a case of long term Right Ventricular (RV) apical pacing on global Left Ventricular (LV) function non- invasively by echocardiography. Materials and Methods We studied 54 patients (Male 42, Female 12) of complete heart block (CHB) with RV apical pacing (40 VVI and 14 DCP). Mean duration of pacing was 58+4 months. All patients underwent 24 hours Holter monitoring to determine the percentage of ventricular pacing beats. 2-D Echocardiography was done to assess the regional wall motion of abnormality and global LV ejection fraction by modified Simpson’s rule. These methods were coupled with the Doppler derived Myocardial Performance Index (MPI), tissue Doppler imaging, and mechanical regional dyssynchrony with 3-D Echocardiography. Data were analysed from 54 RV- apical paced patients and compared with age and body surface area of 60 controlled subjects (Male 46, Female 14). Results Evaluation of LV function in 54 patients demonstrated regional wall motion abnormality and Doppler study revealed both LV systolic and diastolic dysfunction compare with control subjects (regional wall motion abnormality 80±6% vs 30±3% with p-value<0.0001) which is proportional to the percentage of ventricular pacing beats (mean paced beat 78%). Global LVEF 50±4% vs 60±2% (p-valve <0.0001) and MPI 0.46 ±0.12 v/s 0.36±0.09 (p-value <0.0001). Conclusion RV–apical pacing induces iatrogenic electrical dyssynchrony which leads to remodeling of LV and produces mechanical dyssynchrony which is responsible for LV dysfunction. Alternate site of RV pacing and/or biventricular pacing should be done to maintain biventricular electrical synchrony which will preserve the LV function. PMID:27134910

  6. Diastolic heart failure and LV dyssynchrony.

    PubMed

    Kasner, Mario; Westermann, Dirk; Schultheiss, Heinz-Peter; Tschöpe, Carsten

    2012-10-01

    Our knowledge of diastolic heart failure (DHF) is still limited with regard to pathophysiology, diagnosis and clinical treatment. Amongst others, LV dyssynchrony was suggested to be an additional factor involved in the pathogenesis of subgroup of patients with DHF. In 20-30% of patients with DHF a systolic LV dyssynchrony could be detected and about 20% DHF patients evidenced a diastolic dyssyncrony. Both systolic and diastolic dyssynchrony may contribute to the impairment of cardiac function and clinical manifestation in DHF. Opposite to the systolic heart failure, wide QRS complex is uncommon which incriminates that dyssynchrony in DHF is rather related to regional disperse in contractility than to electromechanical coupling delay. Asynchronous LV relaxation and impairment of ventricular restoring forces may also impair the LV filing and lead to a diastolic dyssynchrony. Particularly in patients with preserved LV contractility mechanical LV dyssynchrony induces energy wastage and consequently reduces cardiac reserves. However, up to date it is not clear to what degree LV dyssynchrony is involved in the pathomechanisms of this subpopulation of DHF. PMID:22280429

  7. C-Type Natriuretic Peptide Improves Left Ventricular Functional Performance at Rest and Restores Normal Exercise Responses after Heart Failure.

    PubMed

    Li, Tiankai; Cheng, Heng-Jie; Ohte, Nobuyuki; Hasegawa, Hiroshi; Morimoto, Atsushi; Herrington, David M; Little, William C; Li, Weimin; Cheng, Che Ping

    2016-06-01

    In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise. C-type natriuretic peptide (CNP) is elevated in HF; however, its functional effects are unclear. We tested the hypotheses that CNP with vasodilating, natriuretic, and positive inotropic and lusitropic actions may prevent this abnormal exercise response after HF. We determined the effects of CNP (2 μg/kg plus 0.4 μg/kg per minute, i.v., 20 minutes) on plasma levels of cGMP before and after HF and assessed LV dynamics during exercise in 10 chronically instrumented dogs with pacing-induced HF. Compared with the levels before HF, CNP infusion caused significantly greater increases in cGMP levels after HF. After HF, at rest, CNP administration significantly reduced LV end-systolic pressure (PES), arterial elastance (EA), and end-diastolic pressure. The peak mitral flow (dV/dtmax) was also increased owing to decreased minimum LVP (LVPmin) and the time constant of LV relaxation (τ) (P < 0.05). In addition, LV contractility (EES) was increased. The LV-arterial coupling (EES/EA) was improved. The beneficial effects persisted during exercise. Compared with exercise in HF preparation, treatment with CNP caused significantly less important increases in PES but significantly decreased τ (34.2 vs. 42.6 ms) and minimum left ventricular pressure with further augmented dV/dtmax Both EES, EES/EA (0.87 vs. 0.32) were increased. LV mechanical efficiency improved from 0.38 to 0.57 (P < 0.05). After HF, exogenous CNP produces arterial vasodilatation and augments LV contraction, relaxation, diastolic filling, and LV arterial coupling, thus improving LV performance at rest and restoring normal exercise responses after HF. PMID:27026682

  8. A novel functional glucose transporter in the white shrimp Litopenaeus vannamei -LvGLUT2- is up-regulated during hypoxia in hepatopancreas.

    PubMed

    Martínez-Quintana, José A; Kikuta, Shingo; Felix-Portillo, Monserrath; Peregrino-Uriarte, Alma B; Yepiz-Plascencia, Gloria

    2015-12-01

    In hypoxia conditions, the white shrimp Litopenaeus vannamei shifts its energetic metabolism from aerobic to anaerobic, requiring more glucose uptake into the cells by GLUT proteins. We here report a novel glucose transporter in shrimp. The Lvglut2 cDNA is 2473 bp-long containing an ORF of 1458 bp encoding 486 amino acid residues. The deduced protein has the features of a facilitative sugar transporter. The Lvglut2 gene product tagged with GFP was expressed in the cell membrane of Xenopus oocytes. In the same expression system, untagged LvGLUT2 resulted to be a bidirectional glucose transporter that functions moving glucose down its concentration gradient in and out of the cell. Lvglut2 mRNA is expressed in hepatopancreas while in muscle and gills it was not detected. Hypoxia up-regulates the expression of Lvglut2 transcripts in hepatopancreas. These results provide a better understanding of facilitative glucose transporters and gene regulation during hypoxia in crustaceans. PMID:26415036

  9. Vagus Nerve Stimulation Improves Cardiac Function by Preventing Mitochondrial Dysfunction in Obese-Insulin Resistant Rats

    PubMed Central

    Samniang, Bencharunan; Shinlapawittayatorn, Krekwit; Chunchai, Titikorn; Pongkan, Wanpitak; Kumfu, Sirinart; Chattipakorn, Siriporn C.; KenKnight, Bruce H.; Chattipakorn, Nipon

    2016-01-01

    Long-term high-fat diet (HFD) consumption leads to not only obese-insulin resistance, but also impaired left ventricular (LV) function. Vagus nerve stimulation (VNS) has been shown to exert cardioprotection. However, its effects on the heart and metabolic parameters under obese-insulin resistant condition is not known. We determined the effects of VNS on metabolic parameters, heart rate variability (HRV) and LV function in obese-insulin resistant rats. Male Wistar rats were fed with HFD for 12 weeks, and were randomly divided into sham and VNS groups. VNS was applied for the next 12 weeks. Echocardiography, blood pressure and HRV were examined. Blood samples were collected for metabolic parameters. At the end, the heart was removed for determination of apoptosis, inflammation, oxidative stress, and cardiac mitochondrial function. VNS for 12 weeks significantly decreased plasma insulin, HOMA index, total cholesterol, triglyceride, LDL and visceral fat. Serum adiponectin was significantly increased in the VNS group. VNS also significantly decreased blood pressure, improved HRV and LV function, decreased cardiac MDA, TNF-α and Bax levels, and improved cardiac mitochondrial function. VNS improves metabolic and hemodynamic parameters, and the LV function via its ability against apoptosis, inflammation and oxidative stress, and preserved cardiac mitochondrial function in obese-insulin resistant rats. PMID:26830020

  10. 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.

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

    PubMed

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

    2006-04-28

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

  12. Postinfarct Cytokine Therapy Regenerates Cardiac Tissue and Improves Left Ventricular Function

    PubMed Central

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

    2013-01-01

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

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

    NASA Technical Reports Server (NTRS)

    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.

  14. Improvement of left ventricular filling by ivabradine during chronic hypertension: involvement of contraction-relaxation coupling.

    PubMed

    Melka, Jonathan; Rienzo, Mario; Bizé, Alain; Jozwiak, Mathieu; Sambin, Lucien; Hittinger, Luc; Su, Jin Bo; Berdeaux, Alain; Ghaleh, Bijan

    2016-05-01

    Chronic hypertension is associated with left ventricular (LV) hypertrophy and LV diastolic dysfunction with impaired isovolumic relaxation and abnormal LV filling. Increased heart rate (HR) worsens these alterations. We investigated whether the I f channel blocker ivabradine exerts beneficial effects on LV filling dynamic. In this setting, we also evaluated the relationship between LV filling and isovolumic contraction as a consequence of contraction-relaxation coupling. Therefore, hypertension was induced by a continuous infusion of angiotensin II during 28 days in 10 chronically instrumented pigs. LV function was investigated after stopping angiotensin II infusion to offset the changes in loading conditions. In the normal heart, LV relaxation filling, LV early filling, LV peak early filling rate were positively correlated to HR. In contrast, these parameters were significantly reduced at day 28 vs. day 0 (18, 42, and 26 %, respectively) despite the increase in HR (108 ± 6 beats/min vs. 73 ± 2 beats/min, respectively). These abnormalities were corrected by acute administration of ivabradine (1 mg/kg, iv). Ivabradine still exerted these effects when HR was controlled at 150 beats/min by atrial pacing. Interestingly, LV relaxation filling, LV early filling and LV peak early filling were strongly correlated with both isovolumic contraction and relaxation. In conclusion, ivabradine improves LV filling during chronic hypertension. The mechanism involves LV contraction-relaxation coupling through normalization of isovolumic contraction and relaxation as well as HR-independent mechanisms. PMID:27040115

  15. Retraction: 'rhBNP therapy can improve clinical outcomes and reduce in-hospital mortality compared with dobutamine in heart failure patients: a meta-analysis' by Ming-Yi Lv, Shu-Ling Deng and Xiao-Feng Long.

    PubMed

    2016-05-01

    The above article, published online on 28(th) November 2015 in Wiley Online Library (http://onlinelibrary.wiley.com/doi/10.1111/bcp.12788/full), and in volume 81, pp. 174-185, has been retracted by agreement between the authors, the journal Editor in Chief, Professor A Cohen, and John Wiley & Sons Limited. The retraction has been agreed owing to evidence indicating that the peer review of this paper was compromised. The authors were unaware of the actions of the third party responsible for compromising the peer review. Reference Lv M-Y, Deng S-L, Long X-F. rhBNP therapy can improve clinical outcomes and reduce in-hospital mortality compared with dobutamine in heart failure patients: a meta-analysis. Br J Clin Pharmacol 2016; 81: 174-85. doi:10.1111/bcp.12788. PMID:27086732

  16. Renin inhibition improves cardiac function and remodeling after myocardial infarction independent of blood pressure.

    PubMed

    Westermann, Dirk; Riad, Alexander; Lettau, Olga; Roks, Anton; Savvatis, Konstantinos; Becher, Peter Moritz; Escher, Felicitas; Jan Danser, A H; Schultheiss, Heinz-Peter; Tschpe, Carsten

    2008-12-01

    Pharmacological renin inhibition with aliskiren is an effective antihypertensive drug treatment, but it is currently unknown whether aliskiren is able to attenuate cardiac failure independent of its blood pressure-lowering effects. We investigated the effect of aliskiren on cardiac remodeling, apoptosis, and left ventricular (LV) function after experimental myocardial infarction (MI). C57J/bl6 mice were subjected to coronary artery ligation and were treated for 10 days with vehicle or aliskiren (50 mg/kg per day via an SC osmopump), whereas sham-operated animals served as controls. This dose of aliskiren, which did not affect systemic blood pressure, improved systolic and diastolic LV function, as measured by the assessment of pressure-volume loops after MI. Furthermore, after MI LV dilatation, cardiac hypertrophy and lung weights were decreased in mice treated with aliskiren compared with placebo-treated mice after MI. This was associated with a normalization of the mitogen-activated protein kinase P38 and extracellular signal-regulated kinases 1/2, AKT, and the apoptotic markers bax and bcl-2 (all measured by Western blots), as well as the number of TUNEL-positive cells in histology. LV dilatation, as well as the associated upregulation of gene expression (mRNA abundance) and activity (by zymography) of the cardiac metalloproteinase 9 in the placebo group after MI, was also attenuated in the aliskiren-treated group. Aliskiren improved LV dysfunction after MI in a dose that did not affect blood pressure. This was associated with the amelioration of cardiac remodelling, hypertrophy, and apoptosis. PMID:18955663

  17. IMPROVING CARDIAC FUNCTION WITH NEW GENERATION PLASMA VOLUME EXPANDERS

    PubMed Central

    Chatpun, Surapong; Nacharaju, Parimala; Cabrales, Pedro

    2012-01-01

    Background Plasma expander (PE) based on polyethylene glycol (PEG) conjugated to albumin has shown positive results maintaining blood volume (BV) during hemodilution and restoring BV during resuscitation from hemorrhagic shock. PEG conjugation to human serum albumin (HSA), PEG-HSA, increasing size, weigh and colloidal osmotic pressure (COP), with minor effects on solution viscosity. Methods This study was designed to test the hypothesis that PEG-HSA (2 g/dL) produced by direct PEGylation chemistry improves cardiac function during two experimental models, i) moderate hemodilution and ii) resuscitation from hemorrhagic shock, compared to a conventional colloidal plasma expander (dextran 70 kDa, D70, 6 g/dL). Cardiac function was studied using a miniaturized pressure volume (PV) conductance catheter implanted in the left ventricle (LV) and evaluated in terms of cardiac indices derived from the PV measurements. Results PEG-HSA increased cardiac output (CO), stroke volume (SV) and stroke work (SW), and decreased systemic vascular resistance (SVR) compared to D70, in both experimental models. The improvements induced by PEG-HSA in cardiac function were sustained over the observation time. PEG-HSA cardiac mechanoenergetics changes are the result of increased energy transferred per stroke, and decreased resistance of the vasculature connecting the heart. In summary, PEG-HSA decreased LV ejection impedance. Conclusion Ejection of blood diluted with PEG-HSA presented a reduced load to the heart, increased contractile function, and lowered the energy consumed per unit volume compared to D70. Our results emphasize the importance of heart function as a parameter to be included in the evaluation changes induced by new PEs. PMID:22867830

  18. Qishen Yiqi Drop Pill improves cardiac function after myocardial ischemia.

    PubMed

    JianXin, Chen; Xue, Xu; ZhongFeng, Li; Kuo, Gao; FeiLong, Zhang; ZhiHong, Li; Xian, Wang; HongCai, Shang

    2016-01-01

    Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. (1)H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group, and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine. PMID:27075394

  19. Qishen Yiqi Drop Pill improves cardiac function after myocardial ischemia

    PubMed Central

    JianXin, Chen; Xue, Xu; ZhongFeng, Li; Kuo, Gao; FeiLong, Zhang; ZhiHong, Li; Xian, Wang; HongCai, Shang

    2016-01-01

    Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. 1H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group, and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine. PMID:27075394

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

    PubMed

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

    2014-06-01

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

  1. Troglitazone improves cardiac function in patients with congestive heart failure.

    PubMed

    Ogino, Kazuhide; Furuse, Yoshiyuki; Uchida, Kazuhiko; Shimoyama, Masaki; Kinugawa, Toru; Osaki, Shuichi; Kato, Masahiko; Endo, Akihiro; Igawa, Osamu; Hisatome, Ichiro; Ikawa, Shiro; Shigemasa, Chiaki

    2002-05-01

    Troglitazone increased cardiac output and stroke volume, as a result of decreased peripheral resistance, in diabetic patients with normal cardiac function. The cardiovascular effects of troglitazone in patients with heart failure are unknown. The aim of the study was to evaluate the cardiovascular effects of troglitazone in patients with heart failure. Blood pressure and echocardiographic findings were evaluated before and 1, 2, 3 and 4 hours after a single dose of troglitazone (400 mg) or placebo, in eight type II diabetic patients with congestive heart failure. The plasma catecholamines and coefficient of variance of RR intervals (CVRR) were also measured. Neither heart rate nor blood pressure changed after the administration of troglitazone. Left ventricular (LV) end-diastolic dimension did not change either, however, the LV end-systolic dimension significantly decreased compared with its baseline value and with that of the placebo group. On the other hand, the % fractional shortening and the E/A ratio increased significantly after troglitazone. The LV end-diastolic volume did not change, whereas the LV end-systolic volume significantly decreased. The stroke volume and the LV ejection fraction significantly increased compared with its baseline value and with that of the placebo group. The peripheral vascular resistance did not change after the administration of troglitazone, whereas plasma catecholamines significantly decreased, and CVRR remained unchanged in both groups. These hemodynamic changes suggest that a single oral dose of troglitazone induced inotropy without activation of the sympathetic nervous system. PMID:12374899

  2. Recombinant feline leukemia virus (FeLV) variants establish a limited infection with altered cell tropism in specific-pathogen-free cats in the absence of FeLV subgroup A helper virus.

    PubMed

    Bechtel, M K; Hayes, K A; Mathes, L E; Pandey, R; Stromberg, P C; Roy-Burman, P

    1999-03-01

    Feline leukemia virus subgroup B (FeLV-B) is commonly associated with feline lymphosarcoma and arises through recombination between endogenous retroviral elements inherited in the cat genome and corresponding regions of the envelope (env) gene from FeLV subgroup A (FeLV-A). In vivo infectivity for FeLV-B is thought to be inefficient in the absence of FeLV-A. Proposed FeLV-A helper functions include enhanced replication efficiency, immune evasion, and replication rescue for defective FeLV-B virions. In vitro analysis of the recombinant FeLV-B-like viruses (rFeLVs) employed in this study confirmed these viruses were replication competent prior to their use in an in vivo study without FeLV-A helper virus. Eight specific-pathogen-free kittens were inoculated with the rFeLVs alone. Subsequent hematology and histology results were within normal limits, however, in the absence of detectable viremia, virus expression, or significant seroconversion, rFeLV proviral DNA was detected in bone marrow tissue of 4/4 (100%) cats at 45 weeks postinoculation (pi), indicating these rFeLVs established a limited but persistent infection in the absence of FeLV-A. Altered cell tropism was also noted. Focal infection was seen in T-cell areas of the splenic follicles in 3/4 (75%) rFeLV-infected cats analyzed, while an FeLV-A-infected cat showed focal infection in B-cell areas of the splenic follicles. Nucleotide sequence analysis of the surface glycoprotein portion of the rFeLV env gene amplified from bone marrow tissue collected at 45 weeks pi showed no sequence alterations from the original rFeLV inocula. PMID:10098636

  3. LvDJ-1 plays an important role in resistance against Vibrio alginolyticus in Litopenaeus vannamei.

    PubMed

    Huang, Mingzhu; Liu, Yuan; Xie, Chenying; Wang, Wei-Na

    2015-05-01

    DJ-1 was first identified as an oncogene that transformed mouse NIH3T3 cells in cooperation with activated Ras. It has since exhibited a variety of functions in a range of organisms. In this study, the DJ-1 gene in Litopenaeus vannamei (LvDJ-1) was identified and characterized. A recombinant protein LvDJ-1 was produced in Pichia pastoris. LvDJ-1 expression in vivo was knocked down by dsRNA-mediated RNA interference (RNAi), which led to significantly decreased levels of LvDJ-1 mRNA and protein. When the L. vannamei were challenged with RNAi and Vibrio alginolyticus, the transcription and expression of copper zinc superoxide dismutase (LvCZSOD) in the hepatopancreas were dramatically lower in shrimp with knocked down LvDJ-1 than in controls. Transcription and expression of P53 (LvP53) were significantly higher in shrimp lacking LvDJ-1 than in controls. Hepatopancreas samples were analyzed using real time polymerase chain reaction and Western blot. Moreover, blood samples from the shrimp, assessed with flow cytometry, showed significant increases in respiratory burst and apoptosis in those lacking LvDJ-1 compared to the controls. Cumulative mortality in the shrimp lacking LvDJ-1 was significantly different from that in the control group after challenge with V. alginolyticus. Altogether, the results prove that LvDJ-1 regulates apoptosis and antioxidant activity, and that these functions play an important role in L. vannamei resistance against V. alginolyticus. PMID:25703712

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

    PubMed

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

    2012-10-01

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

  6. 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.

  7. Efficacy of an inactivated FeLV vaccine compared to a recombinant FeLV vaccine in minimum age cats following virulent FeLV challenge.

    PubMed

    Stuke, Kristin; King, Vickie; Southwick, Kendra; Stoeva, Mira I; Thomas, Anne; Winkler, M Teresa C

    2014-05-01

    The aim of the study was to determine the efficacy of an inactivated feline leukemia virus (FeLV) vaccine (Versifel(®) FeLV, Zoetis.) compared to a recombinant FeLV vaccine (Purevax(®) FeLV, Merial Animal Health) in young cats, exposed under laboratory conditions to a highly virulent challenge model. The study was designed to be consistent with the general immunogenicity requirements of the European Pharmacopoeia 6.0 Monograph 01/2008:1321-Feline Leukaemia Vaccine (Inactivated) with the exception that commercial-strength vaccines were assessed. Fifty seronegative cats (8-9 weeks old) were vaccinated subcutaneously on two occasions, three weeks apart, with either placebo (treatment group T01), Versifel FeLV Vaccine (treatment group T02), or Purevax FeLV Vaccine (treatment group T03) according to the manufacturer's directions. Cats were challenged three weeks after the second vaccination with a virulent FeLV isolate (61E strain). Persistent FeLV antigenemia was determined from 3 to 15 weeks postchallenge. Bone marrow samples were tested for the presence of FeLV proviral DNA to determine FeLV latent infection. At week 15 after challenge with the virulent FeLV 61E strain, the Versifel FeLV Vaccine conferred 89.5% protection against FeLV persistent antigenemia and 94.7% protection against FeLV proviral DNA integration in bone marrow cells. In comparison, the Purevax FeLV Vaccine conferred 20% protection against FeLV persistent antigenemia and 35% protection against FeLV proviral DNA integration in bone marrow cells following challenge. The data from this study show that the Versifel FeLV Vaccine was efficacious in preventing both FeLV persistent p27 antigenemia and FeLV proviral DNA integration in bone marrow cells of cats challenged with this particular challenge model under laboratory conditions and provided better protection than Purevax FeLV in this experimental challenge model with highly virulent FeLV. PMID:24662705

  8. Improved Function of the Failing Rat Heart by Regulated Expression of Insulin-Like Growth Factor I via Intramuscular Gene Transfer

    PubMed Central

    Lai, N. Chin; Tang, Tong; Gao, Mei Hua; Saito, Miho; Miyanohara, Atsushi

    2012-01-01

    Abstract Current methods of gene transfer for heart disease include injection into heart muscle or intracoronary coronary delivery, approaches that typically provide limited expression and are cumbersome to apply. To circumvent these problems, we selected a transgene, insulin-like growth factor-I (IGF-I), which may, in theory, have favorable effects on heart function when secreted from a remote site. We examined the feasibility and efficacy of skeletal muscle injection of adeno-associated virus 5 encoding IGF-I under Tet regulation (AAV5.IGFI-tet) to treat heart failure. Myocardial infarction (MI) was induced in rats by coronary occlusion; 1 week later, rats with impaired left ventricular (LV) function received 2×1012 genome copies (GC) of AAV5.IGFI-tet in the anterior tibialis muscle, and 4 weeks later, were randomly assigned to receive doxycycline in drinking water to activate IGF-I expression (IGF-On; n=10), or not to receive doxycycline (IGF-Off; n=10). Ten weeks after MI (5 weeks after activation of IGF-I expression), LV size and function were assessed by echocardiography and physiological studies. IGF-On rats showed reduced LV end-systolic dimension (p=0.03) and increased LV ejection fraction (p=0.02). In addition, IGF-On rats showed, before and during dobutamine infusion, increases in cardiac output (p=0.02), stroke work (p=0.0001), LV + dP/dt (p<0.0001), LV relaxation (LV – dP/dt; p=0.03), and systolic arterial blood pressure (p=0.0003). Mean arterial pressure and systemic vascular resistance were unchanged. Activation of IGF-I expression reduced cardiac fibrosis (p=0.048), apoptosis (p<0.0001), and caspase-3/7 activity (p=0.04). Serum IGF-I was increased 5 weeks after transgene activation (p=0.008). These data indicate that skeletal muscle injection of AAV5.IGFI-tet enables tetracycline-activated expression, increases serum IGF-I levels, and improves function of the failing heart. PMID:22017392

  9. The complete nucleotide sequence and genomic organization of Citrus Leprosis associated Virus, Cytoplasmatic type (CiLV-C).

    PubMed

    Pascon, Renata C; Kitajima, João Paulo; Breton, Michèle C; Assumpção, Laura; Greggio, Christian; Zanca, Almir S; Okura, Vagner Katsumi; Alegria, Marcos C; Camargo, Maria E; Silva, Giovana G C; Cardozo, Jussara C; Vallim, Marcelo A; Franco, Sulamita F; Silva, Vitor H; Jordão, Hamilton; Oliveira, Fernanda; Giachetto, Poliana F; Ferrari, Fernanda; Aguilar-Vildoso, Carlos I; Franchiscini, Fabrício J B; Silva, José M F; Arruda, Paulo; Ferro, Jesus A; Reinach, Fernando; da Silva, Ana Cláudia Rasera

    2006-06-01

    The Citrus leprosis disease (CiL) is associated to a virus (CiLV) transmitted by Brevipalpus spp. mites (Acari: Tenuipalpidae). CiL is endemic in Brazil and its recently spreading to Central America represents a threat to citrus industry in the USA. Electron microscopy images show two forms of CiLV: a rare nuclear form, characterized by rod-shaped naked particle (CiLV-N) and a common cytoplasmic form (CiLV-C) associated with bacilliform-enveloped particle and cytoplasmic viroplasm. Due to this morphological feature, CiLV-C has been treated as Rhabdovirus-like. In this paper we present the complete nucleotide sequence and genomic organization of CiLV-C. It is a bipartite virus with sequence similarity to ssRNA positive plant virus. RNA1 encodes a putative replicase polyprotein and an ORF with no known function. RNA2 encodes 4 ORFs. pl5, p24 and p61 have no significant similarity to any known proteins and p32 encodes a protein with similarity to a viral movement protein. The CiLV-C sequences are associated with typical symptoms of CiL by RT-PCR. Phylogenetic analysis suggests that CiLV-C is probably a member of a new family of plant virus evolutionarily related to Tobamovirus. PMID:16732481

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

    PubMed

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

    2005-03-01

    The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair. PMID:15734798

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

    PubMed Central

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

    2005-01-01

    The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair. PMID:15734798

  12. Two cases of FeLV-associated dermatoses.

    PubMed

    Favrot, C; Wilhelm, S; Grest, P; Meli, M L; Hofmann-Lehmann, R; Kipar, A

    2005-12-01

    Two cases of feline leukaemia virus (FeLV)-associated dermatosis are described. The first cat was affected by an ulcerative dermatitis identified as a giant-cell dermatosis. The second case was a cutaneous lymphoma. In both cases, FeLV antigens and FeLV genome were demonstrated in the affected skin immunologically and with polymerase chain reaction, respectively. The first case suggests that, like other retroviruses, at least some strains of FeLV can induce syncytium formation. As FeLV antigens and genome were demonstrated in a serologically negative cat, the second case suggests that focal skin FeLV replication may occur. FeLV-associated dermatoses are rare skin conditions that may be under-diagnosed. PMID:16359309

  13. 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

  14. Higher Fiber Intake May Improve Lung Function

    MedlinePlus

    ... fullstory_156955.html Higher Fiber Intake May Improve Lung Function Best outcomes seen when eating more than ... fiber-rich diet may help protect you against lung disease, a new study suggests. "Lung disease is ...

  15. Advances in Understanding Molecular Determinants in FeLV Pathology

    PubMed Central

    Levy, Laura S.

    2008-01-01

    Feline leukemia virus (FeLV) occurs in nature not as a single genomic species but as a family of closely related viruses. The disease outcome of natural FeLV infection is variable and likely reflects genetic variation both in the virus and the naturally outbreeding host population. A series of studies have been undertaken with the objectives of examining natural FeLV genetic variation, the selective pressures operative in FeLV infection that lead to predominance of natural variants, and the consequences for infection and disease progression. Genetic variation among FeLV isolates was examined in a cohort of naturally infected cats with thymic lymphoma of T-cell origin, non-T-cell multicentric lymphoma, myeloproliferative disorder or anemia. The predominant isolate in the cohort, designated FeLV-945, was identified exclusively in disorders of non-T-cell origin. The FeLV-945 LTR was shown to contain a unique 21-bp repeat element, triplicated in tandem downstream of enhancer. The 21-bp triplication was shown to act as a transcriptional enhancer and to confer a replicative advantage through the assembly of a distinctive transcription factor complex. Oncogene utilization during tumor induction by FeLV-945 was studied using a recombinant Moloney murine leukemia virus containing the FeLV-945 LTR. This approach identified novel loci of common proviral integration in tumors, including the regulatory subunit of PI-3Kgamma. Mutational changes identified in FeLV-945 SU were shown not to alter receptor usage as measured by host range and superinfection interference, but to significantly increase the efficiency of receptor binding. To determine whether the unique sequence elements of FeLV-945 influence the course of infection and disease in vivo, recombinant viruses were constructed in which the FeLV-945 LTR alone, or the FeLV-945 SU gene and LTR were substituted into the prototype isolate FeLV-A/61E. Longitudinal studies of infected animals showed that substitution of the FeLV-945 LTR into FeLV-A/61E resulted in a significantly more rapid disease onset, but did not alter the tumorigenic spectrum. In contrast, substitution of both the FeLV-945 LTR and SU gene changed the disease outcome entirely. Together, these observations indicate that the distinctive LTR and SU gene of FeLV-945 mediate a rapid pathogenesis with distinctive clinical features and oncogenic mechanisms. PMID:18289704

  16. Advances in understanding molecular determinants in FeLV pathology.

    PubMed

    Levy, Laura S

    2008-05-15

    Feline leukemia virus (FeLV) occurs in nature not as a single genomic species but as a family of closely related viruses. The disease outcome of natural FeLV infection is variable and likely reflects genetic variation both in the virus and the naturally outbreeding host population. A series of studies have been undertaken with the objectives of examining natural FeLV genetic variation, the selective pressures operative in FeLV infection that lead to predominance of natural variants, and the consequences for infection and disease progression. Genetic variation among FeLV isolates was examined in a cohort of naturally infected cats with thymic lymphoma of T-cell origin, non-T-cell multicentric lymphoma, myeloproliferative disorder or anemia. The predominant isolate in the cohort, designated FeLV-945, was identified exclusively in disorders of non-T-cell origin. The FeLV-945 LTR was shown to contain a unique 21-bp repeat element, triplicated in tandem downstream of enhancer. The 21-bp triplication was shown to act as a transcriptional enhancer and to confer a replicative advantage through the assembly of a distinctive transcription factor complex. Oncogene utilization during tumor induction by FeLV-945 was studied using a recombinant Moloney murine leukemia virus containing the FeLV-945 LTR. This approach identified novel loci of common proviral integration in tumors, including the regulatory subunit of PI-3Kgamma. Mutational changes identified in FeLV-945 SU were shown not to alter receptor usage as measured by host range and superinfection interference, but to significantly increase the efficiency of receptor binding. To determine whether the unique sequence elements of FeLV-945 influence the course of infection and disease in vivo, recombinant viruses were constructed in which the FeLV-945 LTR alone, or the FeLV-945 SU gene and LTR were substituted into the prototype isolate FeLV-A/61E. Longitudinal studies of infected animals showed that substitution of the FeLV-945 LTR into FeLV-A/61E resulted in a significantly more rapid disease onset, but did not alter the tumorigenic spectrum. In contrast, substitution of both the FeLV-945 LTR and SU gene changed the disease outcome entirely. Together, these observations indicate that the distinctive LTR and SU gene of FeLV-945 mediate a rapid pathogenesis with distinctive clinical features and oncogenic mechanisms. PMID:18289704

  17. The FeLV-945 LTR confers a replicative advantage dependent on the presence of a tandem triplication.

    PubMed

    Prabhu, S; Lobelle-Rich, P A; Levy, L S

    1999-10-25

    Feline leukemia virus (FeLV), like other naturally occurring retroviruses, is characterized by a high degree of genetic diversity. FeLV-945 is a natural isolate derived from non-B-cell non-T-cell lymphomas classified anatomically as multicentric. FeLV-945 exhibits a unique structural motif in the LTR composed of a 21-bp tandem triplication downstream of a single copy of enhancer. The unique FeLV-945 LTR is precisely conserved among eight independent multicentric lymphomas collected in a geographic cluster. Previous studies using reporter gene constructs predict that the FeLV-945 LTR would confer a replicative advantage on the virus that contains it, particularly in primitive hematopoietic cells. Such an advantage may account for the precise conservation of the unique LTR sequence. To test that prediction, a set of recombinant, infectious FeLVs was developed that are isogenic other than the presence of the FeLV-945 LTR or mutations of it. Replication assays show that the FeLV-945 LTR confers a distinct growth advantage in K-562, FEA, and 3201 cells and implicate the 21-bp triplication in that function. Replacement of two copies of the triplicated element with random sequence greatly diminished the replicative capacity, thus implicating the triplicated sequence itself in LTR function. The 21-bp triplication was shown to contain specific nuclear protein binding sites, which may account for the selective pressure to conserve the sequence. PMID:10544118

  18. Recombinant FeLV vaccine: long-term protection and effect on course and outcome of FIV infection.

    PubMed

    Hofmann-Lehmann, R; Holznagel, E; Aubert, A; Ossent, P; Reinacher, M; Lutz, H

    1995-05-01

    The efficacy and the long-term protection of a recombinant feline leukemia virus (FeLV) vaccine were determined in 30 specified pathogen free cats for over 3 years. At the same time, in order to specify the effects of feline immunodeficiency virus (FIV) on the immune system, one half of the cats (n = 15) were previously infected with the Swiss isolate FIV Zurich 2. The second half of the animals (n = 15) served as non-infected controls. Eighteen (nine FIV-negative, nine FIV-positive) vaccinated and 12 (six FIV-negative, six FIV-positive) non-vaccinated cats were intraperitoneally challenged with FeLV A. Seventeen of 18 vaccinated cats were protected against persistent viremia, while ten of 12 non-vaccinated controls became infected. An increase of antibodies against FeLV SU was found in all protected cats after the challenge exposure. No difference in vaccine efficacy was found between FIV-negative and FIV-positive animals. The whole group of cats was observed for over 3 years. There were no further vaccinations during this period. CD4+ and CD8+ cell subsets, clinical outcome and time of survival of the cats were recorded. FIV-negative and FIV-positive animals were kept in two different rooms. However, FeLV-negative and FeLV viremic cats were housed together in both rooms in order to imitate a natural FeLV exposure situation. Anti-recombinant FeLV SU antibodies were measured by enzyme-linked immunosorbent assay. Although a continuous decline of antibodies was found in FeLV vaccinated cats, they remained protected against constant FeLV challenge for over 3 years. FIV infection had a stronger effect on the depression of the CD4+:CD8+ ratio than FeLV infection. Within the group of FIV-positive cats, the FeLV-vaccinated animals had significantly better survival rates as well as better clinical and laboratory parameters. FIV- and FeLV-coinfected cats showed the lowest CD4+:CD8+ ratio, mainly caused by decreased CD4+ lymphocyte counts. CD8+ lymphocytes with strong fluorescence (CD8(high)) disappeared and cells with weak fluorescence (CD8(low)) appeared instead. Prevention of coinfection by immunizing FIV-positive cats against FeLV infection improved the clinical outcome and prolonged the cat's life expectancy. PMID:7618252

  19. [FeLV infection in the cat: clinically relevant aspects].

    PubMed

    Boretti, F S; Lutz, H; Hofmann-Lehmann, R

    2011-11-01

    The feline leukemia virus (FeLV) is a retrovirus of the domestic cat that was described almost 50 years ago. The FeLV-infection may lead to fatal diseases in domestic and small wild cats. The use of efficacious diagnostics assays and vaccines led to a reduction of the FeLV prevalence; however, FeLV still poses a problem for the cat presented with the infection. This article aims to describe recent developments in diagnostics and findings in the infection pathogenesis that are clinically relevant. PMID:22045454

  20. Autologous Mesenchymal Stem Cells Produce Concordant Improvements in Regional Function, Tissue Perfusion and Fibrotic Burden when Administered to Patients Undergoing Coronary Artery Bypass Grafting – The PROMETHEUS Trial

    PubMed Central

    Karantalis, Vasileios; DiFede, Darcy L.; Gerstenblith, Gary; Pham, Si; Symes, James; Zambrano, Juan Pablo; Fishman, Joel; Pattany, Pradip; McNiece, Ian; Conte, John; Schulman, Steven; Wu, Katherine; Shah, Ashish; Breton, Elayne; Davis-Sproul, Janice; Schwarz, Richard; Feigenbaum, Gary; Mushtaq, Muzammil; Suncion, Viky Y.; Lardo, Albert C.; Borrello, Ivan; Mendizabal, Adam; Karas, Tomer Z.; Byrnes, John; Lowery, Maureen; Heldman, Alan W.; Hare, Joshua M.

    2014-01-01

    Rationale While accumulating data support the efficacy of intramyocardial cell-based therapy to improve LV function in patients with chronic ischemic cardiomyopathy undergoing CABG, the underlying mechanism and impact of cell injection site remain controversial.Mesenchymal stem cells (MSCs) improve LV structure and function through several effects including: reducing fibrosis, neoangiogenesis and neomyogenesis. Objective To test the hypothesis that the impact on cardiac structure and function following intramyocardial injections of autologous MSCs results from a concordance of pro-recovery phenotypic effects. Methods and Results Six patients were injected with autologous MSCs into akinetic/hypokinetic myocardial territories not receiving bypass graft for clinical reasons. MRI was used to measure scar, perfusion, wall thickness and contractility at baseline, 3, 6 and 18 months and to compare structural and functional recovery in regions that received MSC injections alone, revascularization alone, or neither. A composite score of MRI variables was used to assess concordance of antifibrotic effects, perfusion, and contraction at different regions. After 18 months, subjects receiving MSCs exhibited increased LVEF (+9.4±1.7%, p=0.0002) and decreased scar mass (-47.5±8.1%; p<0.0001) compared to baseline. MSC-injected segments had concordant reduction in scar size, perfusion and contractile improvement (concordant score: 2.93±0.07), whereas revascularized (0.5±0.21) and non-treated segments (-0.07±0.34) demonstrated non-concordant changes (p<0.0001 vs. injected segments). Conclusions Intramyocardial injection of autologous MSCs into akinetic yet non-revascularized segments produces comprehensive regional functional restitution, which in turn drives improvement in global LV function. These findings, although inconclusive due to lack of placebo group, have important therapeutic and mechanistic hypothesis-generating implications. PMID:24565698

  1. Estrogen Therapy, Independent of Timing, Improves Cardiac Structure and Function in Oophorectomized mRen2.Lewis Rats

    PubMed Central

    Jessup, Jewell A.; Wang, Hao; MacNamara, Lindsay M.; Presley, Tennille D.; Kim-Shapiro, Daniel B.; Zhang, Lili; Chen, Alex F.; Groban, Leanne

    2013-01-01

    Objective mRen2.Lewis Rats exhibit exacerbated increases in blood pressure, left ventricular (LV) remodeling, and diastolic impairment following the loss of estrogens. In this same model, depletion of estrogens has marked effects on the cardiac biopterin profile concomitant with suppressed nitric oxide (NO) release. With respect to the establishment of overt systolic hypertension after oophorectomy (OVX), we assessed the effects of timing chronic 17 β-estradiol (E2) therapy on myocardial function, structure, and the cardiac NO system. Methods Oophrectomy (OVX; n=24) or sham-operation (Sham; n=13) was performed in 4-week-old, female mRen2.Lewis rats. Following randomization, OVX rats received E2 immediately (OVX + early E2; n=7), E2 at 11 weeks of age (OVX + late E2 N=8), or no E2 at all (OVX N=9). Results Early E2 was associated with lower body weight, less hypertension-related cardiac remodeling, and decreased LV filling pressure compared to OVX rats without E2 supplementation. Late E2 similarly attenuated the adverse effects of ovarian hormone loss on tissue-Doppler derived LV filling pressures and perivascular fibrosis, and significantly improved myocardial relaxation, or mitral annular velocity (e′). Early and late exposure to E2 decreased dihydrobiopterin, but only late E2 yielded significant increases in cardiac nitrite concentrations. Conclusions Although there were some similarities between early and late E2 treatment on preservation of diastolic function and cardiac structure after OVX, the lusitropic potential of E2 was most consistent with late supplementation. The cardioprotective effects of late E2 were independent of blood pressure and may have occurred through regulation of cardiac biopterins and NO production. PMID:23481117

  2. Rapid Surface Cooling by ThermoSuit System Dramatically Reduces Scar Size, Prevents Post-Infarction Adverse Left Ventricular Remodeling, and Improves Cardiac Function in Rats

    PubMed Central

    Dai, Wangde; Herring, Michael J; Hale, Sharon L; Kloner, Robert A

    2015-01-01

    Background The long-term effects of transient hypothermia by the non-invasive ThermoSuit apparatus on myocardial infarct (MI) scar size, left ventricular (LV) remodeling, and LV function were assessed in rat MI model. Methods and Results Rats were randomized to normothermic or hypothermic groups (n=14 in each group) and subjected to 30 minutes coronary artery occlusion and 6 weeks of reperfusion. For hypothermia therapy, rats were placed into the ThermoSuit apparatus at 2 minutes after the onset of coronary artery occlusion, were taken out of the apparatus when the core body temperature reached 32°C (in ≈8 minutes), and were then allowed to rewarm. After 6 weeks of recovery, rats treated with hypothermia demonstrated markedly reduced scar size (expressed as % of left ventricular area: hypothermia, 6.5±1.1%; normothermia, 19.4±1.7%; P=1.3×10−6); and thicker anterior LV wall (hypothermia, 1.57±0.09 mm; normothermia, 1.07±0.05 mm; P=3.4×10−5); decreased postmortem left ventricular volume (hypothermia, 0.45±0.04 mL; normothermia, 0.6±0.03 mL; P=0.028); and better LV fractional shortening by echocardiography (hypothermia, 37.2±2.8%; normothermia, 18.9±2.3%; P=0.0002) and LV ejection fraction by LV contrast ventriculography (hypothermia, 66.8±2.3%; normothermia, 56.0±2.0%; P=0.0014). Conclusions Rapid, transient non-invasive surface cooling with the ThermoSuit apparatus in the acute phase of MI decreased scar size by 66.5%, attenuated adverse post-infarct left ventricular dilation and remodeling, and improved cardiac function in the chronic phase of experimental MI. PMID:26116692

  3. The surface glycoprotein of a natural feline leukemia virus subgroup A variant, FeLV-945, as a determinant of disease outcome

    PubMed Central

    Bolin, Lisa L.; Ahmad, Shamim; Levy, Laura S.

    2011-01-01

    Feline leukemia virus (FeLV) is a natural retrovirus of domestic cats associated with degenerative, proliferative and malignant diseases. Studies of FeLV infection in a cohort of naturally infected cats were undertaken to examine FeLV variation, the selective pressures operative in FeLV infection that lead to predominance of natural variants, and the consequences for infection and disease progression. A unique variant, designated FeLV-945, was identified as the predominant isolate in the cohort and was associated with non-T-cell diseases including multicentric lymphoma. FeLV-945 was assigned to the FeLV-A subgroup based on sequence analysis and receptor utilization, but was shown to differ in sequence from a prototype member of FeLV-A, designated FeLV-A/61E, in the long terminal repeat (LTR) and the surface glycoprotein gene (SU). A unique sequence motif in the FeLV-945 LTR was shown to function as a transcriptional enhancer and to confer a replicative advantage. The FeLV-945 SU protein was observed to differ in sequence as compared to FeLV-A/61E within functional domains known to determine receptor selection and binding. Experimental infection of newborn cats was performed using wild type FeLV-A/61E or recombinant FeLV-A/61E in which the LTR (61E/945L) or LTR and SU (61E/945SL) were exchanged for that of FeLV-945. Infection with either FeLV-A/61E or 61E/945L resulted in T-cell lymphoma of the thymus, although 61E/945L caused disease significantly more rapidly. In contrast, infection with 61E/945SL resulted in the rapid induction of a multicentric lymphoma of B-cell origin, thus recapitulating the outcome of natural infection and implicating FeLV-945 SU as a determinant of disease outcome. Recombinant FeLV-B was detected infrequently and at low levels in multicentric lymphomas, and was thereby not implicated in disease induction. Preliminary studies of receptor interaction indicated that virus particles bearing FeLV-945 SU bind to the FeLV-A receptor more efficiently than do particles bearing FeLV-A/61E SU, and that soluble SU proteins expressed from the viruses demonstrate the same differential binding phenotype. Preliminary mutational analysis of FeLV-945 was performed by exchanging regions containing either the primary receptor binding determinant, VRA, the secondary determinant, VRB, or a proline-rich region, PRR, with that of FeLV-A/61E. Results implicated a region containing VRA as a minor contributor, while a region containing VRB largely conferred increased binding efficiency. PMID:21764142

  4. The surface glycoprotein of a natural feline leukemia virus subgroup A variant, FeLV-945, as a determinant of disease outcome.

    PubMed

    Bolin, Lisa L; Ahmad, Shamim; Levy, Laura S

    2011-10-15

    Feline leukemia virus (FeLV) is a natural retrovirus of domestic cats associated with degenerative, proliferative and malignant diseases. Studies of FeLV infection in a cohort of naturally infected cats were undertaken to examine FeLV variation, the selective pressures operative in FeLV infection that lead to predominance of natural variants, and the consequences for infection and disease progression. A unique variant, designated FeLV-945, was identified as the predominant isolate in the cohort and was associated with non-T-cell diseases including multicentric lymphoma. FeLV-945 was assigned to the FeLV-A subgroup based on sequence analysis and receptor utilization, but was shown to differ in sequence from a prototype member of FeLV-A, designated FeLV-A/61E, in the long terminal repeat (LTR) and the surface glycoprotein gene (SU). A unique sequence motif in the FeLV-945 LTR was shown to function as a transcriptional enhancer and to confer a replicative advantage. The FeLV-945 SU protein was observed to differ in sequence as compared to FeLV-A/61E within functional domains known to determine receptor selection and binding. Experimental infection of newborn cats was performed using wild type FeLV-A/61E or recombinant FeLV-A/61E in which the LTR (61E/945L) or LTR and SU (61E/945SL) were exchanged for that of FeLV-945. Infection with either FeLV-A/61E or 61E/945L resulted in T-cell lymphoma of the thymus, although 61E/945L caused disease significantly more rapidly. In contrast, infection with 61E/945SL resulted in the rapid induction of a multicentric lymphoma of B-cell origin, thus recapitulating the outcome of natural infection and implicating FeLV-945 SU as a determinant of disease outcome. Recombinant FeLV-B was detected infrequently and at low levels in multicentric lymphomas, and was thereby not implicated in disease induction. Preliminary studies of receptor interaction indicated that virus particles bearing FeLV-945 SU bind to the FeLV-A receptor more efficiently than do particles bearing FeLV-A/61E SU, and that soluble SU proteins expressed from the viruses demonstrate the same differential binding phenotype. Preliminary mutational analysis of FeLV-945 was performed by exchanging regions containing either the primary receptor binding determinant, VRA, the secondary determinant, VRB, or a proline-rich region, PRR, with that of FeLV-A/61E. Results implicated a region containing VRA as a minor contributor, while a region containing VRB largely conferred increased binding efficiency. PMID:21764142

  5. 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-κB) 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-κB 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-κB pathway. PMID:25816098

  6. MRI assessment of LV relaxation by untwisting rate: a new isovolumic phase measure of tau.

    PubMed

    Dong, S J; Hees, P S; Siu, C O; Weiss, J L; Shapiro, E P

    2001-11-01

    Most noninvasive measures of diastolic function are made during left ventricular (LV) filling and are therefore subject to "pseudonormalization," because variation in left atrial (LA) pressure may confound the estimation of relaxation rate. Counterclockwise twist of the LV develops during ejection, but untwisting occurs rapidly during isovolumic relaxation, before mitral opening. We hypothesized that the rate of untwisting might reflect the process of relaxation independent of LA pressure. Recoil rate (RR), the velocity of LV untwisting, was measured by tagged magnetic resonance imaging and regressed against the relaxation time constant (tau), recorded by catheterization, in 10 dogs at baseline and after dobutamine, saline, esmolol, and methoxamine treatment. RR correlated closely (average r = -0.86) with tau and was unaffected by elevated LA pressure. Multiple regression showed that tau, but not LA or aortic pressure, was an independent predictor of RR (P < 0.0001, P = 0.99, and P = 0.18, respectively). The rate of recoil of torsion, determined wholly noninvasively, provides an isovolumic phase, preload-independent assessment of LV relaxation. Use of this novel parameter should allow the detailed study of diastolic function in states known to affect filling rates, such as aging, hypertension, and congestive heart failure. PMID:11668061

  7. 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

  8. Nutraceutical Intervention Improves Older Adults' Cognitive Functioning

    PubMed Central

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

    2014-01-01

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

  9. Virtual reality training improves balance function

    PubMed Central

    Mao, Yurong; Chen, Peiming; Li, Le; Huang, Dongfeng

    2014-01-01

    Virtual reality is a new technology that simulates a three-dimensional virtual world on a computer and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can activate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function. PMID:25368651

  10. Nutraceutical intervention improves older adults' cognitive functioning.

    PubMed

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

    2014-02-01

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

  11. Nutraceutical intervention improves older adults' cognitive functioning.

    TOXLINE Toxicology Bibliographic Information

    Small BJ; Rawson KS; Martin C; Eisel SL; Sanberg CD; McEvoy CL; Sanberg PR; Shytle RD; Tan J; Bickford PC

    2014-02-01

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

  12. Exercise training improves vascular mitochondrial function.

    PubMed

    Park, Song-Young; Rossman, Matthew J; Gifford, Jayson R; Bharath, Leena P; Bauersachs, Johann; Richardson, Russell S; Abel, E Dale; Symons, J David; Riehle, Christian

    2016-04-01

    Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim-trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state 2 respiration) were greater in vessels from EX relative to SED mice, despite similar levels of arterial citrate synthase activity and mitochondrial DNA content. Furthermore, compared with the SED mice, arteries from EX mice displayed elevated transcript levels ofperoxisome proliferative activated receptor-γ coactivator-1αand the downstream targetscytochrome c oxidase subunit IV isoform 1,isocitrate dehydrogenase(Idh)2, andIdh3a, increased manganese superoxide dismutase protein expression, increased endothelial NO synthase phosphorylation (Ser(1177)), and suppressed reactive oxygen species generation (allP< 0.05). Although there were no differences in EX and SED mice concerning endothelium-dependent and endothelium-independent vasorelaxation, phenylephrine-induced vasocontraction was blunted in vessels from EX compared with SED mice, and this effect was normalized by NOS inhibition. These training-induced increases in vascular mitochondrial respiratory capacity and evidence of improved redox balance, which may, at least in part, be attributable to elevated NO bioavailability, have the potential to protect against age- and disease-related challenges to arterial function. PMID:26825520

  13. 3D quantitative visualization of altered LV wall thickening dynamics caused by coronary microembolization

    NASA Astrophysics Data System (ADS)

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

    2001-05-01

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

  14. Lanczos steps to improve variational wave functions

    NASA Astrophysics Data System (ADS)

    Becca, Federico; Hu, Wen-Jun; Iqbal, Yasir; Parola, Alberto; Poilblanc, Didier; Sorella, Sandro

    2015-09-01

    Gutzwiller-projected fermionic states can be efficiently implemented within quantum Monte Carlo calculations to define extremely accurate variational wave functions for Heisenberg models on frustrated two-dimensional lattices, not only for the ground state but also for low-energy excitations. The application of few Lanczos steps on top of these states further improves their accuracy, allowing calculations on large clusters. In addition, by computing both the energy and its variance, it is possible to obtain reliable estimations of exact results. Here, we report the cases of the frustrated Heisenberg models on square and Kagome lattices.

  15. Treatment of hypertension with perindopril reduces plasma atrial natriuretic peptide levels, left ventricular mass, and improves echocardiographic parameters of diastolic function

    NASA Technical Reports Server (NTRS)

    Yalcin, F.; Aksoy, F. G.; Muderrisoglu, H.; Sabah, I.; Garcia, M. J.; Thomas, J. D.

    2000-01-01

    BACKGROUND: Hypertension is a major independent risk factor for cardiac deaths, and diastolic dysfunction is a usual finding during the course of this disease. HYPOTHESIS: This study was designed to investigate the effects of chronic therapy with perindopril on left ventricular (LV) mass, left atrial size, diastolic function, and plasma level of atrial natriuretic peptide (ANP) in patients with hypertension. METHODS: Twenty four patients who had not been previously taking any antihypertensive medication and without prior history of angina pectoris, myocardial infarction, congestive heart failure, dysrhythmias, valvular heart disease, or systemic illnesses received 4-8 mg/day of perindopril orally. Echocardiographic studies were acquired at baseline and 6 months after the initiation of therapy. RESULTS: Systolic and diastolic blood pressure decreased from 174 +/- 19.7 and 107.5 +/- 7.8 mmHg to 134 +/- 10.6 and 82 +/- 6.7 mmHg, respectively (p < 0.001). Left ventricular mass decreased from 252.4 +/- 8.3 to 205.7 +/- 7.08 g and left atrial volume from 20.4 +/- 5.1 to 17.6 +/- 5.2 ml, respectively (p < 0.001). Transmitral Doppler early and atrial filling velocity ratio (E/A) increased from 0.69 +/- 0.06 to 0.92 +/- 0.05 m/s and plasma ANP level decreased from 71.9 +/- 11.7 to 35.3 +/- 7.8 pg/ml (p < 0.001). Reduction of LV mass correlated positively with a reduction in ANP levels (r = 0.66, p < 0.0005). CONCLUSIONS: Perindopril caused a significant reduction of LV mass, left atrial volume, and plasma ANP levels, as well as improvement in Doppler parameters of LV filling in this group of patients with hypertension.

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

    PubMed

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

    2004-01-01

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

  17. Acute monoblastic leukemia in a FeLV-positive cat

    PubMed Central

    Narkkong, Nual-Anong; Apibal, Suntaree

    2008-01-01

    A 1.6-year-old male domestic short hair cat was brought to the Veterinary Medical Teaching Hospital, Kasetsart University, with signs of severe anemia, depression, and general lymph node enlargement. Complete blood count revealed leukocytosis and massive undifferentiated blasts. Testing for antibodies specific to feline leukemia virus (FeLV) was positive, and FeLV nucleic acid was confirmed by nested polymerase chain reaction. Base on cytochemistry and ultrastructure, the cat was diagnosed with acute monoblastic leukemia. PMID:18296895

  18. Acute monoblastic leukemia in a FeLV-positive cat.

    PubMed

    Prihirunkit, Kreangsak; Narkkong, Nual Anong; Apibal, Suntaree

    2008-03-01

    A 1.6-year-old male domestic short hair cat was brought to the Veterinary Medical Teaching Hospital, Kasetsart University, with signs of severe anemia, depression, and general lymph node enlargement. Complete blood count revealed leukocytosis and massive undifferentiated blasts. Testing for antibodies specific to feline leukemia virus (FeLV) was positive, and FeLV nucleic acid was confirmed by nested polymerase chain reaction. Base on cytochemistry and ultrastructure, the cat was diagnosed with acute monoblastic leukemia. PMID:18296895

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

    PubMed Central

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

    2013-01-01

    Objectives This study sought to demonstrate that short-term cardiac unloading with a left ventricular (LV) assist device (LVAD) after acute myocardial infarction (MI) can conserve calcium cycling and improve heart function. Background Heart failure secondary to MI remains a major source of morbidity and mortality. Alterations in calcium cycling are linked to cardiac dysfunction in the failing heart. Methods Adult Dorsett hybrid sheep underwent acute MI and were mechanically unloaded with an axial-flow LVAD (Impella 5.0) for 2 weeks (n = 6). Six sheep with MI only and 4 sham sheep were used as controls. All animals were followed for 12 weeks post-MI. Regional strains in the LV were measured by sonomicrometry. Major calcium-handling proteins (CHPs), including sarco-/endoplasmic reticulum calcium ATPase-2α (SERCA-2α), Na+-Ca2+ exchanger-1, and phospholamban, and Ca2+-ATPase activity were investigated. The electrophysiological calcium cycling in single isolated cardiomyocytes was measured with the patch-clamp technique. The related ultrastructures were studied with electron microscopy. Results LVAD unloading alleviated LV dilation and improved global cardiac function and regional contractility compared with the MI group. The regional myocardial strain (stretch) was minimized during the unloading period and even attenuated compared with the MI group at 12 weeks. Impaired calcium cycling was evident in the adjacent noninfarcted zone in the MI group, whereas CHP expression was normalized and Ca2+-ATPase activity was preserved in the LVAD unloading group. The electrophysiological calcium cycling was also conserved, and the ultrastructural damage was ameliorated in the unloaded animals. Conclusions Short-term LVAD unloading may conserve calcium cycling and improve heart function during the post-infarct period. PMID:23523452

  20. Macrophage tropism of feline leukemia virus (FeLV) of subgroup-C and increased production of tumor necrosis factor-alpha by FeLV-infected macrophages.

    PubMed

    Khan, K N; Kociba, G J; Wellman, M L

    1993-05-15

    Erythroid aplasia is induced in cats by feline leukemia virus (FeLV) of subgroup C but not by FeLV of subgroup A. In an investigation of the role of macrophages in FeLV-C-induced diseases, the concentrations of FeLV and tumor necrosis factor-alpha (TNF-alpha) were compared between feline peritoneal macrophages incubated with FeLV of subgroup A or C. FeLV of both subgroups infected macrophages, but expression of FeLV-C was 21-fold higher than FeLV-A in peritoneal macrophages (P = .004). The supernatants of FeLV-C-inoculated macrophage cultures contained significantly higher levels of TNF-alpha (70 +/- 14 U/mL) at 72 hours postincubation compared with FeLV-A-inoculated (38 +/- 8 U/mL) and uninoculated (31 +/- 8 U/mL) cultures. Moreover, a positive correlation was shown between cell-associated FeLV surface glycoprotein gp70 and TNF-alpha expression in FeLV-C-infected macrophages by immunofluorescence (r = .6; P = .001), measured with a computer-assisted, laser-based digital imaging system. The addition of TNF-alpha to a uniform population of FeLV-infected cells (feline embryonic fibroblasts) caused an enhancement of viral expression (P < .05). These results indicate that FeLV-C has tropism for macrophages, FeLV expression is positively correlated with TNF-alpha expression in macrophages, and TNF-alpha enhances FeLV replication in fibroblasts. We suggest that FeLV-C infection of macrophages and secretion of TNF-alpha may be important in hematopoietic suppression in FeLV-C-infected cats. PMID:8387834

  1. Comparison of the safety and efficacy of a recombinant feline leukemia virus (FeLV) vaccine delivered transdermally and an inactivated FeLV vaccine delivered subcutaneously.

    PubMed

    Grosenbaugh, D A; Leard, T; Pardo, M C; Motes-Kreimeyer, L; Royston, M

    2004-01-01

    The efficacy of a new recombinant FeLV vaccine (rFeLV), delivered transdermally via a needle-free delivery device was compared to that of an inactivated FeLV vaccine (FeLV-k), administered subcutaneously, with a conventional needle and syringe. Kittens were immunized with either rFeLV (0.25 ml, transdermal) or FeLV-k (1 ml, subcutaneous); or they were sham-vaccinated with physiologic saline (0.25 ml, transdermal). Two vaccinations were administered 21 days apart. Injection sites were monitored for any acute or subacute reactions relative to vaccine administration. Four weeks following the final vaccination, all cats were subject to oro-nasal FeLV challenge. Blood was collected for determination of FeLV antigenemia (p27) at weekly intervals beginning three weeks post-challenge. All of the vaccinated cats from both groups resisted FeLV challenge; and 90% of the control cats developed persistent FeLV antigenemia in response to challenge. No acute or persistent injection site reactions were observed. The rFeLV, delivered transdermally, provides protection against persistent FeLV antigenemia following a robust challenge that is equivalent to that of FeLV-k. PMID:15719325

  2. Functional dysphonia: strategies to improve patient outcomes.

    PubMed

    Behlau, Mara; Madazio, Glaucya; Oliveira, Gisele

    2015-01-01

    Functional dysphonia (FD) refers to a voice problem in the absence of a physical condition. It is a multifaceted voice disorder. There is no consensus with regard to its definition and inclusion criteria for diagnosis. FD has many predisposing and precipitating factors, which may include genetic susceptibility, psychological traits, and the vocal behavior itself. The assessment of voice disorders should be multidimensional. In addition to the clinical examination, auditory-perceptual, acoustic, and self-assessment analyses are very important. Self-assessment was introduced in the field of voice 25 years ago and has produced a major impact in the clinical and scientific scenario. The choice of treatment for FD is vocal rehabilitation by means of direct therapy; however, compliance has been an issue, except for cases of functional aphonia or when an intensive training is administered. Nevertheless, there are currently no controlled studies that have explored the different options of treatment regimens for these patients. Strategies to improve patient outcome involve proper multidisciplinary diagnosis in order to exclude neurological and psychiatric disorders, careful voice documentation with quantitative measurement and qualitative description of the vocal deviation for comparison after treatment, acoustic evaluation to gather data on the mechanism involved in voice production, self-assessment questionnaires to map the impact of the voice problem on the basis of the patient's perspective, referral to psychological evaluation in cases of suspected clinical anxiety and/or depression, identification of dysfunctional coping strategies, self-regulation data to assist patients with their vocal load, and direct and intensive vocal rehabilitation to reduce psychological resistance and to reassure patient's recovery. An international multicentric effort, involving a large population of voice-disordered patients with no physical pathology, could produce enough data for achieving a consensus regarding this complex problem. PMID:26664248

  3. Functional dysphonia: strategies to improve patient outcomes

    PubMed Central

    Behlau, Mara; Madazio, Glaucya; Oliveira, Gisele

    2015-01-01

    Functional dysphonia (FD) refers to a voice problem in the absence of a physical condition. It is a multifaceted voice disorder. There is no consensus with regard to its definition and inclusion criteria for diagnosis. FD has many predisposing and precipitating factors, which may include genetic susceptibility, psychological traits, and the vocal behavior itself. The assessment of voice disorders should be multidimensional. In addition to the clinical examination, auditory-perceptual, acoustic, and self-assessment analyses are very important. Self-assessment was introduced in the field of voice 25 years ago and has produced a major impact in the clinical and scientific scenario. The choice of treatment for FD is vocal rehabilitation by means of direct therapy; however, compliance has been an issue, except for cases of functional aphonia or when an intensive training is administered. Nevertheless, there are currently no controlled studies that have explored the different options of treatment regimens for these patients. Strategies to improve patient outcome involve proper multidisciplinary diagnosis in order to exclude neurological and psychiatric disorders, careful voice documentation with quantitative measurement and qualitative description of the vocal deviation for comparison after treatment, acoustic evaluation to gather data on the mechanism involved in voice production, self-assessment questionnaires to map the impact of the voice problem on the basis of the patient’s perspective, referral to psychological evaluation in cases of suspected clinical anxiety and/or depression, identification of dysfunctional coping strategies, self-regulation data to assist patients with their vocal load, and direct and intensive vocal rehabilitation to reduce psychological resistance and to reassure patient’s recovery. An international multicentric effort, involving a large population of voice-disordered patients with no physical pathology, could produce enough data for achieving a consensus regarding this complex problem. PMID:26664248

  4. Treatment of feline leukemia virus (FeLV) infection.

    PubMed

    Hartmann, K; Block, A; Ferk, G; Beer, B; Vollmar, A; Lutz, H

    1999-09-01

    FeLV infection is still considered to account for most disease-related deaths in pet cats. Different treatment attempts with various drugs were performed in the past but none resulted in healing or complete virus elimination. Therefore, it caused a sensation when Horber and Mayr [Horber, D., Mayr, B., 1991. Prax. 19, 311-314; Horber, D., Schnabl, W., Mayr, B., 1992. Tierarztl. Umschau 47, 556-560; Mayr, B., Horber, D., 1992. Kleintierprax. 37, 515-518] published that they were able to cure 80 to 100% FeLV-infected cats from viremia by using an immunomodulating compound. Articles in cat breeder and cat owner journals appeared assuming that obviously there is a rescue for FeLV-infected cats suffering from this deadly infection. The immunomodulator [Buttner, M., 1993. Comp. Immun. Microbiol. Infect. Dis. 18, 1-10] used in those studies was the so-called 'paramunity inducer' PIND-ORF (Baypamun, Bayer, Leverkusen, Germany) consisting of inactivated parapox ovis virus. Since that time, Baypamun is the most commonly used drug for treatment of FeLV infection in Germany and other European countries. Four placebo-controlled double-blind trials were performed to determine the therapeutic efficacy of Baypamun and other compounds in naturally FeLV-infected cats under controlled conditions. PMID:10515279

  5. 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 Davidović 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 (Ref. [5], pp. 183-184) and rechecked. No errors or misprints were found. (2) In the integral representation of the H function derived by Davidović et al. [3], the positive root ν0 of the so-called dispersion function needs to be calculated with accuracy of at least 10 decimal places (see. Ref [6], pp. 61-64 and Ref. [1], Eqs. (5) and (29)). For small values of the argument omega and values of omega close to unity, the nonlinear equation in one unknown, ν0, can be solved analytically. New simple analytical expressions were derived here that can be efficiently used in calculations of the root. (3) The above modifications of the code considerably decreased the time of calculation of both algorithms A and B. The results are summarized in Fig. 1. The time of calculations is in fact the CPU time in microseconds for a computer equipped with an Inter Xeon processor (3.46 GHz) using Lahey-Fujitsu Fortran v. 7.2. Time of calculations of the H(x,omega) function averaged over different pairs of arguments x and omega. (a) 400 pairs uniformly distributed in the ranges 0<=x<=0.05 and 0<=omega<=1; (b) 400 pairs uniformly distributed in the ranges 0.05<=x<=1 and 0<=omega<=1. The shortest execution time averaged over values of the argument x exceeding 0.05 has been observed for algorithm B and Gauss-Legendre quadrature with the number of abscissas equal to 64 (23.2 μs). As compared with Romberg quadrature, the execution time was shortened by a factor of 22.5. For small x values, below 0.05, both algorithms A and B are considerably faster if Gauss-Legendre quadrature is used. For N=64, the average time of execution of algorithm B is decreased with respect to Romberg quadrature by a factor close to 30. However, in that range of argument x, algorithm A exhibits much faster performance. Furthermore, the average execution time of algorithm A, equal to about 100 μs, is practically independent of the number of abscissas N. (4) For Romberg quadrature, to optimize the performance, the mixed algorithm C was proposed in which algorithm A is used for argument x smaller than or equal to x0=0.4, while algorithm B is used for x larger than 0.4 [1]. For Gauss-Legendre quadrature, the limit x0 was found to depend on the number of abscissas N. For each value of N considered, the time of calculations of the H function was determined for pairs of arguments uniformly distributed in the ranges 0<=x<=0.05 and 0<=omega<=1, and for pairs of arguments uniformly distributed in the ranges 0.05<=x<=1 and 0<=omega<=1. As shown in Fig. 2 for N=64, algorithm A is faster than algorithm B for x smaller than or equal to 0.0225. Comparison of the running times of algorithms A and B. Open circles: algorithm B is faster than the algorithm A; full circles: algorithm A is faster than algorithm B. Thus, the value of x0=0.0225 is proposed for the mixed algorithm C when Gauss-Legendere quadrature with N=64 is used. Similar computer experiments performed for other values of N are summarized below. L N0 1 16 0.25 2 20 0.15 3 24 0.10 4 32 0.050 5 40 0.030 6 48 0.045 7 64 0.0225-Recommended 8 80 0.0125 9 96 0.020 The flag L is one of the input parameters for the subroutine GAUSS. In the programs implementing algorithms A, B, and C (CHANDRA, CHANDRB, and CHANDRC), Gauss-Legendre quadrature with N=64 is currently set. As follows from Fig. 1, algorithm B (and consequently algorithm C) is the fastest in that case. It is still possible to change the number of abscissas; the flag L then has to be modified in lines 165, 169, 185, 189, and 304 of program CHANDRAS_v2, and the value of x0 in line 111 has to be adjusted according to the table above. (5) The above modifications of the code did not affect the accuracy of the calculated Chandrasekhar function, as compared to the original code [1]. For the pairs of arguments shown in Fig. 2, the accuracy of the H function, calculated from algorithms A and B, reached at least 12 decimal digits; however, in the majority of cases, the accuracy is equal to 13 decimal digits. Restrictions: Two input parameters for the Chandrasekhar function, x and omega, are restricted to the ranges 0<=x<=1 and 0<=omega<=1, which is sufficient in numerous applications. Running time: between 15 and 100 μs for one pair of arguments of the Chandrasekhar function.

  6. Comparison of image quality, myocardial perfusion, and LV function between standard imaging and single-injection ultra-low-dose imaging using a high-efficiency SPECT camera: the MILLISIEVERT study

    PubMed Central

    Einstein, Andrew J.; Blankstein, Ron; Andrews, Howard; Fish, Mathews; Padgett, Richard; Hayes, Sean W.; Friedman, John D.; Qureshi, Mehreen; Rakotoarivelo, Harivony; Slomka, Piotr; Nakazato, Ryo; Bokhari, Sabahat; Di Carli, Marcello; Berman, Daniel S.

    2015-01-01

    SPECT myocardial perfusion imaging (MPI) plays a central role in coronary artery disease diagnosis; but concerns exist regarding its radiation burden. Compared to standard Anger-SPECT (A-SPECT) cameras, new high-efficiency (HE) cameras with specialized collimators and solid-state cadmium-zinc-telluride detectors offer potential to maintain image quality (IQ), while reducing administered activity and thus radiation dose to patients. No previous study has compared IQ, interpretation, total perfusion deficit (TPD), or ejection fraction (EF) in patients receiving both ultra-low-dose (ULD) imaging on a HE-SPECT camera and standard low-dose (SLD) A-SPECT imaging. Methods We compared ULD-HE-SPECT to SLD-A-SPECT imaging by dividing the rest dose in 101 patients at 3 sites scheduled to undergo clinical A-SPECT MPI using a same day rest/stress Tc-99m protocol. Patients received HE-SPECT imaging following an initial ~130 MBq (3.5mCi) dose, and SLD-A-SPECT imaging following the remainder of the planned dose. Images were scored visually by 2 blinded readers for IQ and summed rest score (SRS). TPD and EF were assessed quantitatively. Results Mean activity was 134 MBq (3.62 mCi) for ULD-HE-SPECT (effective dose 1.15 mSv) and 278 MBq (7.50 mCi, 2.39 mSv) for SLD-A-SPECT. Overall IQ was superior for ULD-HE-SPECT (p<0.0001), with twice as many studies graded excellent quality. Extracardiac activity and overall perfusion assessment were similar. Between-method correlations were high for SRS (r=0.87), TPD (r=0.91), and EF (r=0.88). Conclusion ULD-HE-SPECT rest imaging correlates highly with SLD-A-SPECT. It has improved image quality, comparable extracardiac activity, and achieves radiation dose reduction to 1 mSv for a single injection. PMID:24982439

  7. 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.

  8. 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

  9. Improved initial osteoblast functions on amino-functionalized titanium surfaces.

    PubMed

    Nebe, Barbara; Finke, Birgit; Lthen, Frank; Bergemann, Claudia; Schrder, Karsten; Rychly, Joachim; Liefeith, Klaus; Ohl, Andreas

    2007-11-01

    Adhesion and spreading of cells on biomaterials are integrin-mediated processes. But recent findings indicate a key role of the cell membrane associated matrix substance hyaluronan (HA) in interface interactions. Because HA is a negatively charged molecule we assume that a biomaterial surface with an opposed charge could boost the first contact of the cell to the surface. Polished cp titanium (R(a)=0.19 microm) was coated with an amino-group containing plasma polymer (Ti PPA). For this purpose, a microwave excited, pulsed, low-pressure plasma was used. Additionally, collagen was immobilized on Ti PPA with polyethylene glycol diacid (PEG-DA), catalyzed by carbodiimide (CDI). The physico-chemical surface analytical techniques like XPS, FT-IR, water contact angle and zeta-potential verified the retention of the allylamine precursor structure. Human osteoblasts were cultured in serum-free Dulbecco's modified Eagle medium (DMEM). Adhesion and cell cycle phases were calculated by flow cytometry. Spreading and actin cytoskeleton were visualized by confocal microscopy. Gene expression of osteogenic markers was detected by real-time RT-PCR. Ti PPA is significantly advantageous concerning initial adhesion and spreading during the first hours of the cell contact to the surface. The proliferation of osteoblasts is positively influenced. Gene expression of the differentiation marker bone sialoprotein was upregulated after 24h. Our results demonstrate that functionalization of titanium with positively charged amino-groups is sufficiently enough to significantly improve initial steps of the cellular contact to the material surface. PMID:17825608

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

    PubMed Central

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

    2013-01-01

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

  11. Insertional mutagenesis of flvi-2 in tumors induced by infection with LC-FeLV, a myc-containing strain of feline leukemia virus.

    PubMed Central

    Levy, L S; Lobelle-Rich, P A

    1992-01-01

    LC-FeLV is a myc-containing strain of feline leukemia virus (FeLV) which exhibits only partial transforming activity in vitro and in vivo. LC-FeLV infection in kittens may induce, but does not necessarily induce, thymic lymphosarcoma in viremic animals after a short latency. These observations suggest that infection with LC-FeLV is not sufficient to induce complete transformation and that another genetic event(s) is required. One possibility for such an event is that the integrating provirus acts as an insertional mutagen and thereby disrupts the structure or function of another proto-oncogene. Using a strategy of transposon tagging, this possibility was examined in eight feline T-cell lymphosarcomas, including four induced by experimental infection with LC-FeLV, three induced by natural infection with FeLV, and one FeLV-negative tumor. The analysis demonstrated one locus, termed flvi-2, to be structurally altered in six of the tumors examined, including three induced by LC-FeLV and three in which no activated myc oncogene is apparent. Inverse polymerase chain reaction was used to demonstrate the presence and transcriptional orientation of proviruses integrated at flvi-2 in five of these tumors. The flvi-2 locus does not hybridize to cloned probes representing 21 previously identified proto-oncogenes or common domains of retroviral integration. Thus, the data suggest that interruption of the flvi-2 locus cooperates with the myc oncogene in the induction of T-cell lymphomas by LC-FeLV; indeed, the observations indicate that the insertional mutagenesis of flvi-2 plays a role in T-cell lymphomagenesis even in the absence of feline v-myc. Images PMID:1313907

  12. 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

  13. In vitro comparison tests of three LV vent valves.

    PubMed

    Lewis, G S; Czaplicka, C

    1990-01-01

    Many surgical teams employ a sump pump to vent the left ventricle (LV). The problems associated with this technique are related to safety and convenience. If the flow is accidentally reversed in the LV vent line, air embolism accidents and subsequent litigation may be the result. If the cannula is occluded, it is inconvenient to juggle pump speed to prevent the line from collapsing while maintaining gentle but adequate suction. In this study we in vitro tested three commercially available LV vent valves (RLV-2100 "B," VRV-200 B, H-130) (GLV did not wish to send samples for comparison at the time of this study). Each valve was designed to: regulate suction in the LV vent line; prevent the flow of air towards the heart; and vent downstream pressure to the atmosphere. Each valve was tested for suction at various flow rates, pressure heads, and for the presence of air leakage during reversed flow conditions. The results of pressure and suction tests during normal flow and occluded line conditions have been tabulated. We found the RLV-2100 "B" offers the safest combination of suction control and pressure relief. The most astonishing fact learned was the RLV-2100 "B" was the only valve which prevented the flow of air towards the heart during reversed flow. As a result, we elected to use only this valve in our clinical practice. PMID:10149013

  14. Functionally Organized Grammars Can Improve Language Learning.

    ERIC Educational Resources Information Center

    Sanchez, Karin Vilar

    2001-01-01

    Compares the treatment of one specific communicative function--the expression of concessive relation--in six recent grammar books of German as a foreign language. Shows that the presentation of grammar in these books is deficient, because in each of them only a part of the existing means for the realization of this function is commented on. (VWL)

  15. Functional significance of the discordance between transcriptional profile and left ventricular structure/function during reverse remodeling

    PubMed Central

    Topkara, Veli K.; Chambers, Kari T.; Yang, Kai-Chien; Tzeng, Huei-Ping; Evans, Sarah; Weinheimer, Carla; Kovacs, Attila; Robbins, Jeffrey; Barger, Philip; Mann, Douglas L.

    2016-01-01

    To elucidate the mechanisms for reverse LV remodeling, we generated a conditional (doxycycline [dox] off) transgenic mouse tetracycline transactivating factor–TRAF2 (tTA-TRAF2) that develops a dilated heart failure (HF) phenotype upon expression of a proinflammatory transgene, TNF receptor–associated factor 2 (TRAF2), and complete normalization of LV structure and function when the transgene is suppressed. tTA-TRAF2 mice developed a significant increase in LV dimension with decreased contractile function, which was completely normalized in the tTA-TRAF2 mice fed dox for 4 weeks (tTA-TRAF2dox4W). Normalization of LV structure and function was accompanied by partial normalization (~60%) of gene expression associated with incident HF. Similar findings were observed in patients with dilated cardiomyopathy who underwent reverse LV remodeling following mechanical circulatory support. Persistence of the HF gene program was associated with an exaggerated hypertrophic response and increased mortality in tTA-TRAF2dox4W mice following transaortic constriction (TAC). These effects were no longer observed following TAC in tTA-TRAF2dox8W, wherein there was a more complete (88%) reversal of the incident HF genes. These results demonstrate that reverse LV remodeling is associated with improvements in cardiac myocyte biology; however, the persistence of the abnormal HF gene program may be maladaptive following perturbations in hemodynamic loading conditions. PMID:27158672

  16. Dietary approaches to improving atheroprotective HDL functions.

    PubMed

    Andersen, Catherine J; Fernandez, Maria Luz

    2013-09-01

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

  17. Psychosocial functioning improves following adolescent bariatric surgery.

    PubMed

    Zeller, Meg H; Modi, Avani C; Noll, Jennie G; Long, Jeffrey D; Inge, Thomas H

    2009-05-01

    The aims of the present study were to examine changes in health-related quality of life (HRQOL) and depressive symptoms in adolescents with extreme obesity undergoing Roux-en-Y gastric bypass (RYGBP) across the first postoperative year. A prospective longitudinal observational study of 31 adolescent patients undergoing RYGBP at a pediatric medical center (mean = 16.4 years; 64.5% females, mean BMI 63.5; 97% of study eligible and consecutive patients) was conducted. Participants completed two adolescent HRQOL measures, the PedsQL (generic) and the IWQOL-Kids (weight-related), the Beck Depression Inventory (BDI), and height and weight were measured at three time points: baseline, and 6 and 12 months following RYGBP. Prior to RYGBP, significant impairments in HRQOL were documented and 38.7% reported depressive symptomatology in the clinical range. As expected, BMI and depressive symptoms decreased and HRQOL improved from baseline to 12 months post-RYGBP. Linear mixed modeling analyses detected several nonlinear slopes in BMI, depressive symptoms, and the majority of HRQOL domains over time with deceleration in these postoperative changes beginning at the 6th month time point. In contrast, the rate of change in weight-related social relations was linear (e.g., no deceleration), indicating continued improvement across the first postoperative year. Adolescent RYGBP results in significant improvement in HRQOL and depressive symptomatology over the first postoperative year. Longer-term follow-up will be critical to determine adolescent weight and psychosocial trajectories, their interrelations, and what role psychosocial status plays in continued weight loss, maintenance, and regain. PMID:19165158

  18. Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction

    PubMed Central

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

    2011-01-01

    Abstract Adult bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) exhibit a Sca-1+/Lin–/CD45– phenotype and can differentiate into various cell types, including cardiomyocytes and endothelial cells. We have previously reported that transplantation of a small number (1 × 106) of freshly isolated, non-expanded VSEL-SCs into infarcted mouse hearts resulted in improved left ventricular (LV) function and anatomy. Clinical translation, however, will require large numbers of cells. Because the frequency of VSEL-SCs in the marrow is very low, we examined whether VSEL-SCs can be expanded in culture without loss of therapeutic efficacy. Mice underwent a 30 min. coronary occlusion followed by reperfusion and, 48 hrs later, received an intramyocardial injection of vehicle (group I, n= 11), 1 × 105 enhanced green fluorescent protein (EGFP)-labelled expanded untreated VSEL-SCs (group II, n= 7), or 1 × 105 EGFP-labelled expanded VSEL-SCs pre-incubated in a cardiogenic medium (group III, n= 8). At 35 days after myocardial infarction (MI), mice treated with pre-incubated VSEL-SCs exhibited better global and regional LV systolic function and less LV hypertrophy compared with vehicle-treated controls. In contrast, transplantation of expanded but untreated VSEL-SCs did not produce appreciable reparative benefits. Scattered EGFP+ cells expressing α-sarcomeric actin, platelet endothelial cell adhesion molecule (PECAM)-1, or von Willebrand factor were present in VSEL-SC-treated mice, but their numbers were very small. No tumour formation was observed. We conclude that VSEL-SCs expanded in culture retain the ability to alleviate LV dysfunction and remodelling after a reperfused MI provided that they are exposed to a combination of cardiomyogenic growth factors and cytokines prior to transplantation. Counter intuitively, the mechanism whereby such pre-incubation confers therapeutic efficacy does not involve differentiation into new cardiac cells. These results support the potential therapeutic utility of VSEL-SCs for cardiac repair. PMID:20629987

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

    PubMed

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

    2014-03-28

    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. PMID:24697459

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

    SciTech Connect

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

    2014-03-28

    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.

  1. Caffeine improves barrier function in male skin.

    PubMed

    Brandner, J M; Behne, M J; Huesing, B; Moll, I

    2006-10-01

    The influence of androgens, especially testosterone and its effector dihydrotestosterone, results in a constitutive disadvantage for male skin, e.g. reduced viability of hair at the scalp and reduced epidermal permeability barrier repair capacity. Dihydrotestosterone can act, among others, as an adenyl cyclase inhibitor. Caffeine on the other hand is an inexpensive and (in regular doses) harmless substance used in various cosmetic products, which can act as a phosphodiesterase inhibitor. To prove the hypothesis that caffeine as a phosphodiesterase inhibitor is able to override testosterone-induced effects on barrier function, we performed a double-blind placebo controlled study with healthy volunteers. In this study, 0.5% caffeine in a hydroxyethylcellulose gel preparation (HEC) was applied on one forearm, HEC without caffeine on the other forearm of male and female volunteers for 7 days and transepidermal water loss (TEWL) was measured before and at the end of the treatment period. Basal TEWL did not differ significantly between male and female subjects but the application of caffeine significantly reduced TEWL in male skin compared with female skin. We conclude that caffeine is beneficial for barrier function in male skin. PMID:18489298

  2. 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.

  3. Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure.

    PubMed

    Yuniadi, Yoga; Kusnadi, Yuyus; Sandhow, Lakshmi; Erika, Rendra; Hanafy, Dicky A; Sardjono, Caroline; Kaligis, R W M; Kasim, Manoefris; Harimurti, Ganesja M

    2016-01-01

    Background. Proangiogenic Hematopoietic Cells (PHC) which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4 ± 7.40 yo) preimplant NT proBNP level is 5124.5 ± 4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87 ± 0.41, 0.63 ± 0.66, 99.00 ± 2.60, and 3.22 ± 3.79%, respectively. LVEF was improved (22 ± 5.68 versus 26.8 ± 7.93, p < 0.001) during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity. PMID:27148465

  4. Progenitor Hematopoietic Cells Implantation Improves Functional Capacity of End Stage Coronary Artery Disease Patients with Advanced Heart Failure

    PubMed Central

    Yuniadi, Yoga; Kusnadi, Yuyus; Sandhow, Lakshmi; Erika, Rendra; Hanafy, Dicky A.; Sardjono, Caroline; Kaligis, R. W. M.; Kasim, Manoefris; Harimurti, Ganesja M.

    2016-01-01

    Background. Proangiogenic Hematopoietic Cells (PHC) which comprise diverse mixture of cell types are able to secrete proangiogenic factors and interesting candidate for cell therapy. The aim of this study was to seek for benefit in implantation of PHC on functional improvement in end stage coronary artery disease patients with advanced heart failure. Methods. Patients with symptomatic heart failure despite guideline directed medical therapy and LVEF less than 35% were included. Peripheral blood mononuclear cells were isolated, cultivated for 5 days, and then harvested. Flow cytometry and cell surface markers were used to characterize PHC. The PHC were delivered retrogradely via sinus coronarius. Echocardiography, myocardial perfusion, and clinical and functional data were analyzed up to 1-year observation. Results. Of 30 patients (56.4 ± 7.40 yo) preimplant NT proBNP level is 5124.5 ± 4682.50 pmol/L. Harvested cells characterized with CD133, CD34, CD45, and KDR showed 0.87 ± 0.41, 0.63 ± 0.66, 99.00 ± 2.60, and 3.22 ± 3.79%, respectively. LVEF was improved (22 ± 5.68 versus 26.8 ± 7.93, p < 0.001) during short and long term observation. Myocardial perfusion significantly improved 6 months after treatment. NYHA Class and six-minute walk test are improved during short term and long term follow-up. Conclusion. Expanded peripheral blood PHC implantation using retrograde delivery approach improved LV systolic function, myocardial perfusion, and functional capacity. PMID:27148465

  5. Sulforaphane is anticonvulsant and improves mitochondrial function.

    PubMed

    Carrasco-Pozo, Catalina; Tan, Kah Ni; Borges, Karin

    2015-12-01

    The nuclear factor erythroid 2-related factor 2 pathway (Nrf2) has been previously identified to protect the brain against various impacts. Here, we investigated the effect of the Nrf2 activator sulforaphane in various seizure models and hippocampal mitochondrial bioenergetics. We found that daily injections of sulforaphane for 5 days elevated the seizure thresholds to 6 Hz stimulation and fluorothyl-, but not pentylenetetrazole-induced tonic seizures and protected mice against pilocarpine-induced status epilepticus (SE). Also, sulforaphane increased the antioxidant defences within hippocampal formations and blood plasma. In addition, sulforaphane treatment reduced the extent of hippocampal lipid peroxidation 24 h post-SE and protected hippocampal mitochondria against SE-induced reduction in state 2 and uncoupler-stimulated state 3 respiration. SE-mediated partial loss of rotenone-sensitive and complex II-driven respiration was reduced, consistent with the enhanced activities of complexes I and II in sulforaphane-treated SE mice. In mitochondria isolated from both no SE and SE mice, sulforaphane increased state 3 respiration and respiration linked to ATP synthesis, which may contribute to its anticonvulsant and antioxidant effects by providing more ATP for cellular vital and protective functions. However, sulforaphane did not prevent SE-induced hippocampal cell death. In conclusion, sulforaphane and/or Nrf2 activation are viable anticonvulsant strategies, which are antioxidant and enhance mitochondrial function, especially the ability to produce ATP. Sulforaphane was anticonvulsant in two acute mouse models of epilepsy and protected mice against pilocarpine-induced status epilepticus (SE). We also found antioxidant effects of sulforaphane in mouse plasma and hippocampal formations, exhibited by increased catalase and superoxide dismutase (SOD) activity, as well as increased abilities of hippocampal mitochondria to produce ATP. These effects likely underlie sulforaphane's anticonvulsant mechanisms of action. PMID:26365487

  6. 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-κB 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-κB 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

  7. Litopenaeus vannamei sterile-alpha and armadillo motif containing protein (LvSARM) is involved in regulation of Penaeidins and antilipopolysaccharide factors.

    PubMed

    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-κB 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-κB 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

  8. 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.

  9. Panleukopenia-like syndrome of FeLV caused by co-infection with FeLV and feline panleukopenia virus.

    PubMed

    Lutz, H; Castelli, I; Ehrensperger, F; Pospischil, A; Rosskopf, M; Siegl, G; Grob, M; Martinod, S

    1995-05-01

    To study the effect of interferon on feline leukemia virus (FeLV) infection, 30 specific pathogen free (SPF) cats were infected with the apathogenic FeLV A Glasgow. Unexpectedly, between 5 and 8 weeks after FeLV infection, all 19 cats with persistent FeLV infection but not the FeLV-negative cats died from a panleukopenia-like syndrome. No feline panleukopenia virus (FPLV) antigen was found in feces by latex agglutination, enzyme-linked immunosorbent assay (ELISA) or immunoelectron microscopy. No enteropathogenic bacteria were found. Histopathology revealed changes resembling those of FPLV infection such as destruction of crypts and pancytopenia of bone marrow. Neither clinical signs nor seroconversion to FPLV could be induced by transmitting intestinal extracts to two SPF cats. However, FPLV antigen was demonstrated by immunofluorescence assay in intestinal cryostat sections of diseased animals. FPLV could also be demonstrated in intestinal extracts by immunoelectron microscopy, by latex agglutination and ELISA after anti-FPLV antibodies were removed from immune-complexed FPLV by ultracentrifugation over a CsCl gradient at pH 2.0. From these experiments it was concluded that the panleukopenia-like syndrome of FeLV may not be caused by FeLV alone but at least in some cases by co-infection with FeLV and FPLV. In addition, some form of 'cooperation' between FeLV and FPLV must be postulated because neither virus alone induced symptoms. PMID:7618258

  10. 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

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

    PubMed Central

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

    2010-01-01

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

  12. From young massive star cluster to old globular: the LV-σ0 relationship as a diagnostic tool

    NASA Astrophysics Data System (ADS)

    de Grijs, Richard; Wilkinson, Mark I.; Tadhunter, Clive N.

    2005-07-01

    We present a new analysis of the properties of the young massive star clusters (YMCs) forming profusely in intense starburst environments, which demonstrates that these objects are plausible progenitors of the old globular clusters (GCs) seen abundantly in the Local Group. The method is based on the tight relationship for old GCs between their V-band luminosities, LV, and (central) velocity dispersions, σ0. We improve the significance of the relationship by increasing the GC sample size and find that its functional form, LV/Lsolar~σ1.57+/-0.100 (km s-1), is fully consistent with previous determinations for smaller Galactic and M31 GC samples. The tightness of the relationship for a GC sample drawn from environments as diverse as those found in the Local Group implies that its origin must be sought in intrinsic properties of the GC formation process itself. We evolve the luminosities of those YMCs in the local Universe which have velocity dispersion measurements to an age of 12 Gyr, adopting a variety of initial mass function (IMF) descriptions, and find that most YMCs will evolve to loci close to, or to slightly fainter luminosities than the improved GC relationship. In the absence of significant external disturbances, this implies that these objects may potentially survive to become old GC-type objects over a Hubble time. The main advantage of our new method is its simplicity. Whereas alternative methods, based on dynamical mass estimates, require one to obtain accurate size estimates and to make further assumptions, the only observables required here are the system's velocity dispersion and luminosity. The most important factor affecting the robustness of our conclusions is the adopted form of the IMF. We use the results of N-body simulations to confirm that dynamical evolution of the clusters does not significantly alter our conclusions about the likelihood of individual clusters surviving to late times. Finally, we find that our youngest observed clusters are consistent with having evolved from a relation of the form . This relation may actually correspond to the origin of the GC fundamental plane.

  13. Astakine LvAST binds to the β 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 β subunit of F1-ATP synthase (ATPsyn-β) 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-β 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

  14. A Simulation of Human Heart Function

    PubMed Central

    Hanna, W. T.

    1973-01-01

    A simulation of the function of the human heart and heart muscle has been developed in the form of a digital computer code. For a given set of values for the input variables, realistic values of the cardiac output variables are predicted. A detailed discussion of the simulation and some results obtained from its application are presented. This simulation represents a unique combination of what was known in muscle mechanics, muscle thermodynamics, and of the structure, size, and shape of the heart, into an engineering model to improve the understanding of human heart muscle function. The left ventricle (LV) is treated as a thick-walled sphere whose wall is composed entirely of muscle fibers. Force-length velocity relationships are used to determine the tension in each fiber. The pressure in the LV is computed from fiber tension and fiber structure in the LV. A lumped-parameter simulation of the arterial tree provides a load impedance for the LV. Results are presented for simulation of normal human LV performance. PMID:4715580

  15. Role of HIV-2 envelope in Lv2-mediated restriction

    SciTech Connect

    Reuter, Sandra; Kaumanns, Patrick; Buschhorn, Sabine B.; Dittmar, Matthias T. . E-mail: Matthias_Dittmar@med.uni-heidelberg.de

    2005-02-05

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

  16. Effect of Paricalcitol on Left Ventricular Mass and Function in CKD—The OPERA Trial

    PubMed Central

    Fang, Fang; Chan, John; Wen, Yue-Yi; Qing, Shang; Chan, Iris Hiu-Shuen; Lo, Gladys; Lai, Kar-Neng; Lo, Wai-Kei; Lam, Christopher Wai-Kei; Yu, Cheuk-Man

    2014-01-01

    Vitamin D seems to protect against cardiovascular disease, but the reported effects of vitamin D on patient outcomes in CKD are controversial. We conducted a prospective, double blind, randomized, placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular (LV) mass in patients with stages 3–5 CKD with LV hypertrophy. Subjects with echocardiographic criteria of LV hypertrophy were randomly assigned to receive either oral paricalcitol (1 μg) one time daily (n=30) or matching placebo (n=30) for 52 weeks. The primary end point was change in LV mass index over 52 weeks, which was measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volume, echocardiographic measures of systolic and diastolic function, biochemical parameters of mineral bone disease, and measures of renal function. Change in LV mass index did not differ significantly between groups (median [interquartile range], −2.59 [−6.13 to 0.32] g/m2 with paricalcitol versus −4.85 [−9.89 to 1.10] g/m2 with placebo). Changes in LV volume, ejection fraction, tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities, and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups. However, paricalcitol treatment significantly reduced intact parathyroid hormone (P<0.001) and alkaline phosphatase (P=0.001) levels as well as the number of cardiovascular-related hospitalizations compared with placebo. In conclusion, 52 weeks of treatment with oral paricalcitol (1 μg one time daily) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD. PMID:24052631

  17. 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

  18. Cloning and characterization of a novel hemocyanin variant LvHMCV4 from shrimp Litopenaeus vannamei.

    PubMed

    Lu, Xin; Lu, Hui; Guo, Lingling; Zhang, Zehui; Zhao, Xianliang; Zhong, Mingqi; Li, Shengkang; Zhang, Yueling

    2015-10-01

    Recently, we found 3 variants of hemocyanin subunit with higher molecular weight in shrimp Litopenaeus vannamei (Named as LvHMCV1-3). In this study, a novel L. vannamei hemocyanin variant (Named as LvHMCV4) was further cloned and characterized. Bioinformatic analysis predicted that LvHMCV4 contains one open reading frame of 2137 bp and encodes a polypeptide of 678 amino acids. It shares 84-99% cDNA sequences identity to that of the classical form of L. vannamei hemocyanin (LvHMC, AJ250830.1) and LvHMCV1-3. LvHMCV4 possesses a conserved structure characteristic of the hemocyanin family and can be clustered into one branch along with other arthropod hemocyanins in a phylogenetic tree. Further, the full-length DNA of LvHMCV4 contains 2660 bp and two introns, which are located at the 80-538 bp and 2063-2227 bp regions, respectively. In addition, the mRNA transcript of LvHMCV4 was expressed highly in the hepatopancreas, lymphoid, brain and hemocytes, and weakly in the heart, intestine and gill, while no expression was found in the muscle, stomach and gut. Infection by Escherichia coli K12, Vibrio parahaemolyticus, Vibrio alginolyticus, Vibrio fluvialis, Streptococcus pyogenes or Staphylococcus aureus up-regulated significantly LvHMCV4 mRNA expression in the hepatopancreas. Furthermore, the recombinant protein of LvHMCV4 (rLvHMCV4) was prepared, which showed agglutination activities against six pathogenic bacteria at concentrations ranging from 15.6 to 125 μg/ml. When co-injected with V. parahaemolyticus in L.vannamei, rLvHMCV4 significantly increased the survival rate after 48 h injection. Together, these studies suggested that hemocyanin variant, LvHMCV4, might be involved in shrimp resistance to pathogenic infection. PMID:26115633

  19. Surface glycosaminoglycans mediate adherence between HeLa cells and Lactobacillus salivarius Lv72

    PubMed Central

    2013-01-01

    Background The adhesion of lactobacilli to the vaginal surface is of paramount importance to develop their probiotic functions. For this reason, the role of HeLa cell surface proteoglycans in the attachment of Lactobacillus salivarius Lv72, a mutualistic strain of vaginal origin, was investigated. Results Incubation of cultures with a variety of glycosaminoglycans (chondroitin sulfate A and C, heparin and heparan sulfate) resulted in marked binding interference. However, no single glycosaminoglycan was able to completely abolish cell binding, the sum of all having an additive effect that suggests cooperation between them and recognition of specific adhesins on the bacterial surface. In contrast, chondroitin sulfate B enhanced cell to cell attachment, showing the relevance of the stereochemistry of the uronic acid and the sulfation pattern on binding. Elimination of the HeLa surface glycosaminoglycans with lyases also resulted in severe adherence impairment. Advantage was taken of the Lactobacillus-glycosaminoglycans interaction to identify an adhesin from the bacterial surface. This protein, identify as a soluble binding protein of an ABC transporter system (OppA) by MALDI-TOF/(MS), was overproduced in Escherichia coli, purified and shown to interfere with L. salivarius Lv72 adhesion to HeLa cells. Conclusions These data suggest that glycosaminoglycans play a fundamental role in attachment of mutualistic bacteria to the epithelium that lines the cavities where the normal microbiota thrives, OppA being a bacterial adhesin involved in the process. PMID:24044741

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

    PubMed

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

    2014-07-28

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

  1. How molecular methods change our views of FeLV infection and vaccination.

    PubMed

    Hofmann-Lehmann, Regina; Cattori, Valentino; Tandon, Ravi; Boretti, Felicitas S; Meli, Marina L; Riond, Barbara; Lutz, Hans

    2008-05-15

    FeLV was discovered 40 years ago and vaccines have been commercially available for almost two decades. So far, most FeLV pathogenesis and vaccine studies were conducted assaying parameters, such as virus isolation and antigen detection. Accordingly, regressive infection was characterized by transient or undetectable viremia, while persistent viremia is typically observed in cats with progressive infection. Using real-time polymerase chain reaction assays, the spectrum of host response categories to FeLV infection was recently refined by investigating proviral and plasma viral RNA loads. Cats believed to be immune to FeLV infection were found to turn provirus-positive after virus exposure. Moreover, efficacious FeLV vaccines were found unable to prevent provirus-integration and minimal viral replication. Remarkably, no difference was found in initial proviral and plasma viral RNA loads between cats with different infection outcomes. Only subsequently, the infection outcome is associated with FeLV loads. FeLV provirus was found to persist for years; reoccurrence of viremia and disease development was observed in some cats. Thus, aviremic provirus-positive cats are FeLV carriers and, following reactivation, may act as an infection source. However, integrated viral DNA may also be essential for solid protection and long-lasting maintenance of protective immunity. In conclusion, real-time TaqMan PCR and RT-PCR assays are highly sensitive and specific. They yield a more sensitive measure for FeLV exposure than antigen detection, virus isolation or immunofluoresence assays. We recommend the use of real-time PCR assays to identify FeLV exposed cats, particularly in catteries, and investigate obscure clinical cases that may be FeLV-associated. The use of sensitive molecular methods will contribute to a more in-depth understanding of the FeLV pathogenesis. PMID:18295346

  2. 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.

  3. Intracoronary Transplantation of Mesenchymal Stem Cells with Overexpressed Integrin-Linked Kinase Improves Cardiac Function in Porcine Myocardial Infarction

    PubMed Central

    Mu, Dan; Zhang, Xin-Lin; Xie, Jun; Yuan, Hui-Hua; Wang, Kun; Huang, Wei; Li, Guan-Nan; Lu, Jian-Rong; Mao, Li-Juan; Wang, Lian; Cheng, Le; Mai, Xiao-Li; Yang, Jun; Tian, Chuan-Shuai; Kang, Li-Na; Gu, Rong; Zhu, Bin; Xu, Biao

    2016-01-01

    The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK), a pleiotropic protein critically regulating cell survival, proliferation, differentiation, and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL), and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronary transplantation of allogeneic ILK-MSCs, but not vector-MSCs, significantly enhanced global left ventricular ejection fraction (LVEF) by 7.8% compared with baseline, by 10.3% compared with vehicles, and inhibited myocardial remodeling compared with vehicles at 15-day follow-up. Compared with vector-MSCs, ILK-MSCs significantly improved regional LV contractile function, reduced scar size, fibrosis, cell apoptosis, and increased regional myocardial perfusion and cell proliferation. This preclinical study indicates that ILK-engineered MSCs might promote the clinical translation of MSC-based therapy in post-MI patients, and provides evidence that ferumoxytol labeling of cells combined with PLL is feasible in in vivo cell tracking. PMID:26750752

  4. Intracoronary Transplantation of Mesenchymal Stem Cells with Overexpressed Integrin-Linked Kinase Improves Cardiac Function in Porcine Myocardial Infarction.

    PubMed

    Mu, Dan; Zhang, Xin-Lin; Xie, Jun; Yuan, Hui-Hua; Wang, Kun; Huang, Wei; Li, Guan-Nan; Lu, Jian-Rong; Mao, Li-Juan; Wang, Lian; Cheng, Le; Mai, Xiao-Li; Yang, Jun; Tian, Chuan-Shuai; Kang, Li-Na; Gu, Rong; Zhu, Bin; Xu, Biao

    2016-01-01

    The effect of mesenchymal stem cell (MSCs)-based therapy on treating acute myocardial infarction (MI) is limited due to poor engraftment and limited regenerative potential. Here we engineered MSCs with integrin-linked kinase (ILK), a pleiotropic protein critically regulating cell survival, proliferation, differentiation, and angiogenesis. We firstly combined ferumoxytol with poly-L-lysine (PLL), and found this combination promisingly enabled MRI visualization of MSCs in vitro and in vivo with good safety. We provided visually direct evidence that intracoronary ILK-MSCs had substantially enhanced homing capacity to infarct myocardium in porcine following cardiac catheterization induced MI. Intracoronary transplantation of allogeneic ILK-MSCs, but not vector-MSCs, significantly enhanced global left ventricular ejection fraction (LVEF) by 7.8% compared with baseline, by 10.3% compared with vehicles, and inhibited myocardial remodeling compared with vehicles at 15-day follow-up. Compared with vector-MSCs, ILK-MSCs significantly improved regional LV contractile function, reduced scar size, fibrosis, cell apoptosis, and increased regional myocardial perfusion and cell proliferation. This preclinical study indicates that ILK-engineered MSCs might promote the clinical translation of MSC-based therapy in post-MI patients, and provides evidence that ferumoxytol labeling of cells combined with PLL is feasible in in vivo cell tracking. PMID:26750752

  5. Improvements of Functional Validation by Analysis of Operational Problems

    NASA Astrophysics Data System (ADS)

    Di Nisio, Nicola; Reggestad, Vemund; Fuchs, Joachim

    2015-09-01

    As part of the TRP study “Improvements of Functional Validation by Analysis of Operational Problems”, we will explore the possibility of feeding the experience gained in the operational phase of a space mission into the design, development and verification phase of future missions. This paper will present the background of the problem and provide possible solutions that will be taken into account for the study. Also, a few examples of operational problems that could be used to improve the functional validation of future missions will be provided.

  6. 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

  7. 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…

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

    ERIC Educational Resources Information Center

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

    2011-01-01

    In this study, the authors examined the relations among clinician ratings of treatment improvement and discrepancies between parent and blinded laboratory rater reports of child social functioning administered before and after treatment for social anxiety disorder. Participants included a clinic sample of 101 children (7-16 years old; M = 11.67,…

  9. Using Quality Function Deployment To Improve Academic Advising Processes.

    ERIC Educational Resources Information Center

    Barrows, Richard; Murray, Bruce

    1997-01-01

    Quality Function Deployment, a set of concepts and tools used in manufacturing engineering to link consumer needs with product design, can also improve academic advising systems and processes. The technique promotes structured, logical examination of students' advising needs and their relationship to advising system design, processes, methods,…

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

    ERIC Educational Resources Information Center

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

    2011-01-01

    In this study, the authors examined the relations among clinician ratings of treatment improvement and discrepancies between parent and blinded laboratory rater reports of child social functioning administered before and after treatment for social anxiety disorder. Participants included a clinic sample of 101 children (7-16 years old; M = 11.67,

  11. The putative invertebrate adaptive immune protein Litopenaeus vannamei Dscam (LvDscam) is the first reported Dscam to lack a transmembrane domain and cytoplasmic tail.

    PubMed

    Chou, Pin-Hsiang; Chang, Hao-Shuo; Chen, I-Tung; Lin, Han-You; Chen, Yi-Min; Yang, Huey-Lang; Wang, K C Han-Ching

    2009-12-01

    It has recently been suggested that Dscam (Down syndrome cell adhesion molecule), a member of the immunoglobulin superfamily (IgSF), plays an essential role in the alternative adaptive immune system of invertebrates. Here, we isolated and characterized the first shrimp Dscam from Litopenaeus vannamei. The LvDscam protein had an extracellular domain but lacked the expected transmembrane domain and cytoplasmic tail, both of which are found in all other members of the Dscam family (and may also be found in other L. vannamei Dscams that have not yet been isolated). In nervous tissue, expression levels of LvDscam were unexpectedly low. Phylogenetic analysis suggests that LvDscam is far from the Dscams found in other invertebrates. Nevertheless, the domain architecture of the extracellular region of LvDscam is similar to other invertebrate Dscams, and it exhibits the typical configuration of 10 immunoglobulin (Ig) domains, 6 fibronectin type 3 domains (FNIII) and one cell attachment sequence (RGD). Cloning and characterization of a total of 62 cDNAs from hemocytes collected from WSSV-free, WSSV-persistent and WSSV-acute-infected shrimp revealed 23 alternative amino acid sequences in the N-terminal of Ig2, 30 in the N-terminal of Ig3 and 13 in the Ig7 domain. This implies that LvDscam can potentially encode at least 8970 unique isoforms. Further analysis suggested that the LvDscam Ig2 and Ig3 regions are more functionally important than Ig7 in the shrimp's specific immune response against WSSV. We discuss how this tail-less, soluble Dscam can still play an active role in alternative adaptive immune response even while its axonal guidance functionality may be impaired. PMID:19635499

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

    PubMed

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

    2013-06-01

    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, LANA(1-32), 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

  13. Effects of septal myectomy on left ventricular diastolic function and left atrial volume in patients with hypertrophic cardiomyopathy.

    PubMed

    Tower-Rader, Albree; Furiasse, Nicholas; Puthumana, Jyothy J; Kruse, Jane; Li, Zhi; Andrei, Adin-Cristian; Rigolin, Vera; Bonow, Robert O; McCarthy, Patrick M; Choudhury, Lubna

    2014-11-15

    Ventricular septal myectomy in patients with obstructive hypertrophic cardiomyopathy (HC) has been shown to reduce left ventricular (LV) outflow tract (LVOT) gradient and improve symptoms, although little data exist regarding changes in left atrial (LA) volume and LV diastolic function after myectomy. We investigated changes in LA size and LV diastolic function in patients with HC after septal myectomy from 2004 to 2011. We studied 25 patients (age 49.2 ± 13.1 years, 48% women) followed for a mean of 527 days after surgery who had serial echocardiography at baseline and at most recent follow-up, at least 6 months after myectomy. In addition to myectomy, 3 patients (12%) underwent Maze surgery and 13 (52%) underwent mitral valve surgery, of whom 5 had a mitral valve replacement or mitral annuloplasty. Patients with mitral valve replacement or mitral annuloplasty were excluded from LV diastolic function analysis. LA volume index decreased (from 47.2 ± 17.6 to 35.9 ± 17.0 ml/m(2), p = 0.001) and LV diastolic function improved with an increase in lateral e' velocity (from 7.3 ± 2.9 to 9.8 ± 3.1 cm/sec, p = 0.01) and a decrease in E/e' (from 14.8 ± 6.3 to 11.7 ± 5.5, p = 0.051). Ventricular septal thickness and LVOT gradient decreased, and symptoms of dyspnea and heart failure improved, with reduction in the New York Heart Association functional class III/IV symptoms from 21 (84%) to 1 (4%). In conclusion, relief of LVOT obstruction in HC by septal myectomy results in improved LV diastolic function and reduction in LA volume with improved symptoms. PMID:25260948

  14. 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.

  15. Lentivirus-mediated Inhibition of Tumour Necrosis Factor-α improves motor function associated with PRDX6 in spinal cord contusion rats

    PubMed Central

    Zhang, Xiao; Shi, Lan-lan; Gao, Xia; Jiang, Di; Zhong, Zhan-qiong; Zeng, Xi; Rao, Ying; Hu, Xi; Li, Tian-zhi; Li, Xiu-juan; Li, Lei; Chen, Jian-min; Xia, Qingjie; Wang, Ting-hua

    2015-01-01

    The recovery of motor function in rats is inhibited following contusion spinal cord injury (cSCI). However, the mechanism of tumour necrosis factor α (TNF-α) in motor function after cSCI associated with peroxiredoxin 6 (PRDX6) remains unknown. We randomly divided rats into four groups: sham, cSCI, vector and lentivirus mediating TNF-α RNA interference (TNF-α-RNAi-LV) group. The Basso, Beattie, Bresnahan (BBB) scale was used to evaluate motor function. Real-time quantitative PCR (qRT-PCR) and western blotting were used to detect the expression of TNF-α and PRDX6, which were located in neurons using immunohistochemistry (IHC) and immunofluorescence. Subsequently, lentiviral-mediated TNF-α was used to determine the role of TNF-αand the relationship of PRDX6 and TNF-α in cSCI. After cSCI, the motor capability of hind limbs disappeared and was followed by recovery of function. IHC analysis indicated that TNF-α and PRDX6 were primarily located in spinal cord neurons. TNF-α interference significantly improved neural behaviour and increased expression of PRDX6. Our study suggests that inhibition of TNF-α can promote the recovery of motor function. The underlying mechanism of TNF-α-promoted motor function may be connected with the up-regulation of PRDX6. This provides a new strategy or target for the clinical treatment of SCI in future. PMID:25686213

  16. Improved Functional Characteristics of Whey Protein Hydrolysates in Food Industry.

    PubMed

    Jeewanthi, Renda Kankanamge Chaturika; Lee, Na-Kyoung; Paik, Hyun-Dong

    2015-01-01

    This review focuses on the enhanced functional characteristics of enzymatic hydrolysates of whey proteins (WPHs) in food applications compared to intact whey proteins (WPs). WPs are applied in foods as whey protein concentrates (WPCs), whey protein isolates (WPIs), and WPHs. WPs are byproducts of cheese production, used in a wide range of food applications due to their nutritional validity, functional activities, and cost effectiveness. Enzymatic hydrolysis yields improved functional and nutritional benefits in contrast to heat denaturation or native applications. WPHs improve solubility over a wide range of pH, create viscosity through water binding, and promote cohesion, adhesion, and elasticity. WPHs form stronger but more flexible edible films than WPC or WPI. WPHs enhance emulsification, bind fat, and facilitate whipping, compared to intact WPs. Extensive hydrolyzed WPHs with proper heat applications are the best emulsifiers and addition of polysaccharides improves the emulsification ability of WPHs. Also, WPHs improve the sensorial properties like color, flavor, and texture but impart a bitter taste in case where extensive hydrolysis (degree of hydrolysis greater than 8%). It is important to consider the type of enzyme, hydrolysis conditions, and WPHs production method based on the nature of food application. PMID:26761849

  17. Improved Functional Characteristics of Whey Protein Hydrolysates in Food Industry

    PubMed Central

    Jeewanthi, Renda Kankanamge Chaturika; Lee, Na-Kyoung; Paik, Hyun-Dong

    2015-01-01

    This review focuses on the enhanced functional characteristics of enzymatic hydrolysates of whey proteins (WPHs) in food applications compared to intact whey proteins (WPs). WPs are applied in foods as whey protein concentrates (WPCs), whey protein isolates (WPIs), and WPHs. WPs are byproducts of cheese production, used in a wide range of food applications due to their nutritional validity, functional activities, and cost effectiveness. Enzymatic hydrolysis yields improved functional and nutritional benefits in contrast to heat denaturation or native applications. WPHs improve solubility over a wide range of pH, create viscosity through water binding, and promote cohesion, adhesion, and elasticity. WPHs form stronger but more flexible edible films than WPC or WPI. WPHs enhance emulsification, bind fat, and facilitate whipping, compared to intact WPs. Extensive hydrolyzed WPHs with proper heat applications are the best emulsifiers and addition of polysaccharides improves the emulsification ability of WPHs. Also, WPHs improve the sensorial properties like color, flavor, and texture but impart a bitter taste in case where extensive hydrolysis (degree of hydrolysis greater than 8%). It is important to consider the type of enzyme, hydrolysis conditions, and WPHs production method based on the nature of food application. PMID:26761849

  18. 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

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

    PubMed

    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

  20. ANGIOTENSIN-CONVERTING ENZYME 2 ACTIVATION IMPROVES ENDOTHELIAL FUNCTION

    PubMed Central

    Fraga-Silva, Rodrigo A.; Costa-Fraga, Fabiana P.; Murça, Tatiane M.; Moraes, Patrícia L.; Lima, Augusto Martins; Lautner, Roberto Q.; Castro, Carlos H.; Soares, Célia Maria A.; Borges, Clayton L.; Nadu, Ana Paula; Oliveira, Marilene L.; Shenoy, Vinayak; Katovich, Michael J.; Santos, Robson A.S.; Raizada, Mohan K.; Ferreira, Anderson J.

    2013-01-01

    Diminished release and function of endothelium-derived nitric oxide (NO) coupled with increases in reactive oxygen species (ROS) production is critical in endothelial dysfunction. Recent evidences have shown that activation of the protective axis of the renin-angiotensin system composed by angiotensin-converting enzyme2 (ACE2), Angiotensin-(1-7) [Ang-(1-7)] and Mas receptor promotes many beneficial vascular effects. This has led us to postulate that activation of intrinsic ACE2 would improve endothelial function by decreasing the ROS production. In the present study, we tested 1-[[2-(dimetilamino)etil]amino]-4-(hidroximetil)-7-[[(4-metilfenil)sulfonil]oxi]-9H-xantona-9 (XNT), a small molecule ACE2 activator, on endothelial function to validate this hypothesis. In vivo treatment with XNT (1mg/kg/day for 4 weeks) improved the endothelial function of spontaneously hypertensive rats and of streptozotocin-induced diabetic rats when evaluated through the vasorelaxant responses to acetylcholine/sodium nitroprusside. Acute in vitro incubation with XNT caused endothelial-dependent vasorelaxation in aortic rings of rats. This vasorelaxation effect was attenuated by the Mas antagonist D-pro7-Ang-(1-7) and it was reduced in Mas knockout mice. These effects were associated with reduction in ROS production. In addition, Ang II-induced ROS production in human aortic endothelial cells was attenuated by pre-incubation with XNT. These results showed that chronic XNT administration improves the endothelial function of hypertensive and diabetic rat vessels by attenuation of the oxidative stress. Moreover, XNT elicits an endothelial-dependent vasorelaxation response, which was mediated by Mas. Thus, this study indicated that ACE2 activation promotes beneficial effects on the endothelial function and it is a potential target for treating cardiovascular disease. PMID:23608648

  1. Berberine Improves Kidney Function in Diabetic Mice via AMPK Activation

    PubMed Central

    Zhao, Long; Sun, Li-Na; Nie, Hui-Bin; Wang, Xue-Ling; Guan, Guang-Ju

    2014-01-01

    Diabetic nephropathy is a major cause of morbidity and mortality in diabetic patients. Effective therapies to prevent the development of this disease are required. Berberine (BBR) has several preventive effects on diabetes and its complications. However, the molecular mechanism of BBR on kidney function in diabetes is not well defined. Here, we reported that activation of AMP-activated protein kinase (AMPK) is required for BBR-induced improvement of kidney function in vivo. AMPK phosphorylation and activity, productions of reactive oxygen species (ROS), kidney function including serum blood urea nitrogen (BUN), creatinine clearance (Ccr), and urinary protein excretion, morphology of glomerulus were determined in vitro or in vivo. Exposure of cultured human glomerulus mesangial cells (HGMCs) to BBR time- or dose-dependently activates AMPK by increasing the thr172 phosphorylation and its activities. Inhibition of LKB1 by siRNA or mutant abolished BBR-induced AMPK activation. Incubation of cells with high glucose (HG, 30 mM) markedly induced the oxidative stress of HGMCs, which were abolished by 5-aminoimidazole-4-carboxamide ribonucleoside, AMPK gene overexpression or BBR. Importantly, the effects induced by BBR were bypassed by AMPK siRNA transfection in HG-treated HGMCs. In animal studies, streptozotocin-induced hyperglycemia dramatically promoted glomerulosclerosis and impaired kidney function by increasing serum BUN, urinary protein excretion, and decreasing Ccr, as well as increased oxidative stress. Administration of BBR remarkably improved kidney function in wildtype mice but not in AMPKα2-deficient mice. We conclude that AMPK activation is required for BBR to improve kidney function in diabetic mice. PMID:25409232

  2. Structural and functional adaptation in the rat myocardium and coronary vascular bed caused by changes in pressure and volume load.

    PubMed

    Friberg, P

    1985-01-01

    The structural and functional characteristics of the myocardium and coronary vessels are major determinants of cardiac function. Both can be influenced by long-term hemodynamic changes, such as sustained alterations of pressure and/or volume load on the heart. The diastolic pressure-volume relationship of the left ventricle (LV) was evaluated in arrested isolated hearts from spontaneously hypertensive rats (SHR), Wistar Kyoto normotensive rats (WKY), pregnant and hyperthyroid SHR and WKY. Such measurements of the LV dimensions were also performed after antihypertensive therapy by hydralazine, felodipine, metoprolol and alpha-methyldopa. Cardiac function was studied in a perfusion system in which external work could be measured at various pre- and afterloads. Coronary flow and O2-extraction could also be determined. LV function was examined in young and aged SHR and WKY, in metoprolol-felodipine treated SHR and in two-kidney, one clip hypertension before and after its reversal by renal artery unclipping. The SHR LV in early established primary hypertension mainly showed eccentric hypertrophy, with increased LV enddiastolic volume for a given filling pressure and a marginal reduction of wall to lumen ratio (w/ri). Hence, a higher stroke volume could be delivered for a given myocardial fibre shortening. Nevertheless, when challenged by high afterloads, LV function in SHR was considerably augmented compared with WKY. The antihypertensive drugs used reduce arterial pressure in different ways, which may differently affect cardiac design. Generally, the results suggest that wall thickness was structurally adapted to keep w/ri balanced to the prevailing blood pressure, while internal radius was adapted to long-term changes in diastolic filling. Thus sympatholytic drugs which lowered arterial pressure by reducing cardiac output, induced a reduction of wall thickness at a minor change of internal radius, while drugs which reduced pressure by systemic vasodilation increased internal radius, thus reducing w/ri. Further, the results stress the importance also to consider the type of load which causes LV hypertrophy, and how rapidly it is imposed. Thus, renal hypertension was associated with reduced LV performance, despite considerable hypertrophy. However, on reversal of renal hypertension by unclipping, cardiac function was soon enhanced to match the degree of LV hypertrophy as in SHR. This suggests that the renal hypertensive state per se adds some cardio-depressive influence, possibly by inducing reversible changes of cardiac myosin isoenzymes, which tends to offset the improved ventricular performance inherent in LV hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3161269

  3. Recombinant Expression and Characterization of α-Conotoxin LvIA in Escherichia coli.

    PubMed

    Zhu, Xiaopeng; Bi, Jianpeng; Yu, Jinpeng; Li, Xiaodan; Zhang, Yaning; Zhangsun, Dongting; Luo, Sulan

    2016-01-01

    α-Conotoxin LvIA is derived from Conus lividus, native to Hainan, and is the most selective inhibitor of α3β2 nicotinic acetylcholine receptors (nAChRs) known to date. In this study, an efficient approach for the production of recombinant α-Conotoxin LvIA is described. Tandem repeats of a LvIA gene fragment were constructed and fused with a KSI gene and a His₆ tag in a Escherichia coli (E. coli) expression vector pET-31b(+). The recombinant plasmids were transformed into E. coli and were found to express well. The KSI-(LvIA)n-His₆ fusion protein was purified by metal affinity chromatography and then cleaved with CNBr to release recombinant LvIA (rLvIA). High yields of fusion protein ranging from 100 to 500 mg/L culture were obtained. The pharmacological profile of rLvIA was determined by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing rat nAChR subtypes. The rLvIA antagonized the α3β2 nAChR subtype selectively with a nano-molar IC50. The rLvIA was analgesic in a mouse hot-plate test model of pain. Overall, this study provides an effective method to synthesize α-conotoxin LvIA in an E. coli recombinant expression system, and this approach could be useful to obtain active conopeptides in large quantity and at low cost. PMID:26742048

  4. Recombinant Expression and Characterization of α-Conotoxin LvIA in Escherichia coli

    PubMed Central

    Zhu, Xiaopeng; Bi, Jianpeng; Yu, Jinpeng; Li, Xiaodan; Zhang, Yaning; Zhangsun, Dongting; Luo, Sulan

    2016-01-01

    α-Conotoxin LvIA is derived from Conus lividus, native to Hainan, and is the most selective inhibitor of α3β2 nicotinic acetylcholine receptors (nAChRs) known to date. In this study, an efficient approach for the production of recombinant α-Conotoxin LvIA is described. Tandem repeats of a LvIA gene fragment were constructed and fused with a KSI gene and a His6 tag in a Escherichia coli (E. coli) expression vector pET-31b(+). The recombinant plasmids were transformed into E. coli and were found to express well. The KSI-(LvIA)n-His6 fusion protein was purified by metal affinity chromatography and then cleaved with CNBr to release recombinant LvIA (rLvIA). High yields of fusion protein ranging from 100 to 500 mg/L culture were obtained. The pharmacological profile of rLvIA was determined by two-electrode voltage-clamp electrophysiology in Xenopus laevis oocytes expressing rat nAChR subtypes. The rLvIA antagonized the α3β2 nAChR subtype selectively with a nano-molar IC50. The rLvIA was analgesic in a mouse hot-plate test model of pain. Overall, this study provides an effective method to synthesize α-conotoxin LvIA in an E. coli recombinant expression system, and this approach could be useful to obtain active conopeptides in large quantity and at low cost. PMID:26742048

  5. 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. PMID:26064743

  6. Targeted therapies to improve CFTR function in cystic fibrosis.

    PubMed

    Brodlie, Malcolm; Haq, Iram J; Roberts, Katie; Elborn, J Stuart

    2015-01-01

    Cystic fibrosis is the most common genetically determined, life-limiting disorder in populations of European ancestry. The genetic basis of cystic fibrosis is well established to be mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that codes for an apical membrane chloride channel principally expressed by epithelial cells. Conventional approaches to cystic fibrosis care involve a heavy daily burden of supportive treatments to combat lung infection, help clear airway secretions and maintain nutritional status. In 2012, a new era of precision medicine in cystic fibrosis therapeutics began with the licensing of a small molecule, ivacaftor, which successfully targets the underlying defect and improves CFTR function in a subgroup of patients in a genotype-specific manner. Here, we review the three main targeted approaches that have been adopted to improve CFTR function: potentiators, which recover the function of CFTR at the apical surface of epithelial cells that is disrupted in class III and IV genetic mutations; correctors, which improve intracellular processing of CFTR, increasing surface expression, in class II mutations; and production correctors or read-through agents, which promote transcription of CFTR in class I mutations. The further development of such approaches offers great promise for future therapeutic strategies in cystic fibrosis. PMID:26403534

  7. Which Factors Influence Functional Patients Improvements During Rehabilitation?

    PubMed Central

    Gabriele, Messina; Lorena, Rasimelli; Chiara, Bonavita; Emma, Ceriale; Cecilia, Quercioli; Nicola, Nante

    2014-01-01

    Background: Rehabilitation in patients with disabilities is an important aspect of tertiary prevention. Severity of disability, evaluated by global measures of autonomy, is essential for functional outcome evaluation. Aim: To determine the effectiveness of a rehabilitation programme in terms of percentage functional improvement (PFI); to verify the role of gender, age and length of stay (LOS), by motor and cognitive domains, on PFI. Design: Longitudinal study. Setting: An intensive rehabilitation hospital. Population: 305 inpatients. Methods: The disability has been investigated using the Functional Independence Measure (FIM). Percentage differences between discharge and admission were calculated for FIM score. Wilcoxon matched pair test for the six areas and the two domains of the FIM score were calculated. The effect of LOS, gender and age on PFI were studied with Robust regression. Results: Neurological and Orthopaedic patients had improvements on Motor and Cognitive domains. The greatest gains were in the Self Care, Sphintere Control, Transfer and Locomotion Areas (p=<0.001). LOS was associated (p<0.001) with PFI while age resulted borderline significant (p=0.049) in the cognitive domain in Neurological patients. Conclusion: The rehabilitation improved the overall conditions of neurological and orthopaedic patients. LOS emerged as the most important determinant in PFI. PMID:24762348

  8. Modification of biochar for functionality improvement in soils

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  9. Defensive functioning predicts improvement in major depressive episodes.

    PubMed

    Høglend, P; Perry, J C

    1998-04-01

    We investigated the predictive effect of psychological defenses on the course of major depression in a subsample of psychiatric patients from a larger study. We tested the hypothesis that a group of eight defenses, associated with depression in previous research, would predict, outcome of major depression. After an intake interview, 37 patients were rated on all DSM-III-R Axes, the SCL-90-R, and 28 defenses, using the Defense Mechanism Rating Scales. At 6-month follow-up interview, SCL-90-R and Global Assessment and Functioning (GAF) were redetermined on 34 (92%), 16 of whom had major depression at intake. Overall Defensive Functioning (ODF) significantly predicted GAF at 6-month follow-up over and above initial level of global functioning and presence of a personality disorder. The group of eight defenses were identified more often (p = .068) in depressed patients who improved less than predicted by their initial functional status. The high adaptive level defense, self-observation, was identified more often in those who improved more than predicted by their initial status. Our findings support the theory of a hierarchy of defenses, and the mediating effects of specific low and high adaptive level defenses on the course of a major depressive episode. Further research should examine passive aggression, acting out, help-rejecting complaining, splitting of self-images, splitting of others' images, projective identification, projection, and devaluation in relationship to the onset, course, and treatment response of depressive disorders. PMID:9569892

  10. Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates

    PubMed Central

    Huang, Ruiqi; Hippauf, Frank; Rohrbeck, Diana; Haustein, Maria; Wenke, Katrin; Feike, Janie; Sorrelle, Noah; Piechulla, Birgit; Barkman, Todd J.

    2012-01-01

    In this study, we investigated the role for ancestral functional variation that may be selected upon to generate protein functional shifts using ancestral protein resurrection, statistical tests for positive selection, forward and reverse evolutionary genetics, and enzyme functional assays. Data are presented for three instances of protein functional change in the salicylic acid/benzoic acid/theobromine (SABATH) lineage of plant secondary metabolite-producing enzymes. In each case, we demonstrate that ancestral nonpreferred activities were improved upon in a daughter enzyme after gene duplication, and that these functional shifts were likely coincident with positive selection. Both forward and reverse mutagenesis studies validate the impact of one or a few sites toward increasing activity with ancestrally nonpreferred substrates. In one case, we document the occurrence of an evolutionary reversal of an active site residue that reversed enzyme properties. Furthermore, these studies show that functionally important amino acid replacements result in substrate discrimination as reflected in evolutionary changes in the specificity constant (kcat/KM) for competing substrates, even though adaptive substitutions may affect KM and kcat separately. In total, these results indicate that nonpreferred, or even latent, ancestral protein activities may be coopted at later times to become the primary or preferred protein activities. PMID:22315396

  11. 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

  12. Activities and Programs That Improve Children's Executive Functions.

    PubMed

    Diamond, Adele

    2012-10-01

    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

  13. 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

  14. 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

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

    PubMed Central

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

    2015-01-01

    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

  16. 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

  17. Lymphadiposal Flaps and Lymphaticovenular Anastomoses for Severe Leg Edema: Functional Reconstruction for Lymph Drainage System.

    PubMed

    Koshima, Isao; Narushima, Mitsunaga; Mihara, Makoto; Yamamoto, Takumi; Hara, Hisako; Ohshima, Azusa; Kikuchi, Kazuki; Todokoro, Ken; Seki, Yukio; Iida, Takuya; Nakagawa, Masahiro

    2016-01-01

    Background Collecting lymphatics have lymph-drainage function with contraction of smooth muscle cells. Patients with edema have lost this drainage function due to degeneration of smooth muscle cells. Lymphaticovenular (LV) anastomosis salvages smooth muscle cells from reversible degeneration (mild edema), but muscle cells cannot be recovered from irreversible degeneration (severe edema). Therefore, in severe edema, LV anastomoses cannot reestablish the drainage function of the lymphatic system.To overcome this weakness of LV bypass methods for severe edema, new methods were instituted for repair of this missing drainage function using a lymphadiposal flap from the contralateral foot for hemilateral edema, or transfer of lateral thoracic lymph nodes for bilateral edema. Methods A total of 13 cases were repaired with lymphadiposal flaps and additional LV anastomoses. These cases have frequent phlegmon or cellulitis or resisted to previous LV anastomoses and/or compression therapy. The ages ranged from 15 to 75 years. There were four cases of primary edema and nine cases of secondary edema. Results Regarding the lymphadiposal flap (n = 8), three cases showed an excellent response (37.5%; no need for compression therapy), four cases had a good response (50%; improvement with compression), one case showed no change (12.5%; no improvement), and there were no cases of deterioration. Regarding the lateral thoracic lymph nodes transfer (n = 5), two cases had a good response (40%), three showed no improvement (60%), and there were no cases of deterioration. Conclusion It is concluded that lymphadiposal flap or lymph nodes transfer is suitable for severe edema having frequent cellulitis in unilateral or bilateral lower extremities resisting previous LV anastomoses and/or compression therapy. PMID:26258914

  18. Left ventricular systolic function following alcohol septal ablation for symptomatic hypertrophic cardiomyopathy.

    PubMed

    Moss, Travis J; Krantz, Mori J; Zipse, Matthew M; Quaife, Robert A; Sauer, William H; Messenger, John C; Groves, Bertron M; Salcedo, Ernesto E; Schuller, Joseph L

    2014-04-15

    Because alcohol septal ablation (ASA) for the treatment of symptomatic hypertrophic cardiomyopathy (HC) with left ventricular (LV) outflow tract (LVOT) obstruction results in a myocardial infarct of up to 10% of ventricular mass, LV systolic function could decline over time. We evaluated LV function during longitudinal follow-up in a cohort of patients who underwent ASA. We studied 145 consecutive patients with HC that underwent 167 ASA procedures from 2002 to 2011. Echocardiographic follow-up was available in 139 patients (96%). Echocardiographic indexes included LV ejection fraction (LVEF), mitral regurgitation severity, systolic anterior motion of the anterior mitral leaflet, and resting and provoked LVOT gradients. All patients had a baseline LVEF of >55%. LVEF was preserved in 97.1% of patients over a mean follow-up time of 3.1±2.3 years (maximum 9.7). Mild LV systolic dysfunction was observed (LVEF range 44% to 54%) in only 4 patients. Mitral regurgitation severity improved in 67% (n=112 of 138 with complete data). Resting LVOT gradient declined from a mean of 75 to 19 mm Hg (p<0.001), and provoked gradient declined from a mean of 101 to 33 mm Hg (p<0.001). New York Heart Association class improved from a mean of 2.9±0.4 to 1.3±0.5 (p<0.001). In conclusion, LV systolic function is only mildly reduced in a minority of patients after ASA for symptomatic HC; other echocardiographic and functional measures were significantly improved. PMID:24576545

  19. [The significance of FeLV infection for diseases in necropsied cats].

    PubMed

    Reinacher, M; Wittmer, G; Koberstein, H; Failing, K

    1995-02-01

    Persistent FeLV infection was demonstrated in more than 3000 necropsied cats by an immunohistological method. The findings were associated with the diagnoses established by means of post-mortem examination, histopathological, bacteriological, virological, and parasitological investigations. Statistically significant differences between FeLV-positive and FeLV-negative cats in the relative risk for certain lesions could be demonstrated for the first time. As a consequence, the importance of FeLV infection for the development of certain lesions in cats is to be seen under new aspects for some diagnoses. The relative risk for development of anemia, e.g., is only slightly increased in FeLV-positive animals whereas the relative risk for focal myocardial necrosis and coccidiosis is elevated tremendously in these cats. The relative risk for some lesions and diagnoses is much higher in FeLV-negative cats than in FeLV-positive animals. This is true, e.g., for myocardiopathy and hemorrhagic cystitis. PMID:7786279

  20. Analysis of FeLV-FAIDS provirus burden and productive infection in lymphocyte subsets in vivo.

    PubMed

    Quackenbush, S L; Dean, G A; Mullins, J I; Hoover, E A

    1996-09-01

    To help elucidate the immunopathogenesis of feline leukemia virus (FeLV)-induced immunodeficiency we studied the tropism of viruses derived from the FeLV-FAIDS isolate for lymphocyte subpopulations in cats. FeLV-FAIDS is composed of a replication-competent virus typical of subgroup A FeLV (prototype, clone 61E) and a family of replication-defective but immunopathogenic variant viruses (prototype, clone 61C). We sorted CD4+, CD8+, and IgG+ lymphocytes to > or = 97% purity and analyzed viral load in each cell population via genome-specific semiquantitative PCR. Both the 61E and 61C viruses were tropic for CD4+ and CD8+ T cells as well as IgG+ B lymphocytes in blood and lymph node. High provirus burden were established for both virus genomes-ranging from 0.3 to > 2 copies/cell. To identify the fraction of circulating cells which expressed viral antigen in vivo, we developed a flow cytometric method to simultaneously label blood leukocytes for surface immunophenotype and intracytoplasmic FeLV CA (p27 Gag). These experiments established that 20 to 60% of CD4+, CD8+, and IgG+ lymphocytes and > 85% of monocytes and granulocytes expressed FeLV p27 intracellularly. Thus the in vivo target cells for FeLV-FAIDS infection are manifold and include CD4+ and CD8+ T cells, B cells, and myeloid cells. PMID:8806534

  1. Diazoxide accelerates wound healing by improving EPC function.

    PubMed

    Li, Zhang-Peng; Xin, Ru-Juan; Yang, Hong; Jiang, Guo-Jun; Deng, Ya-Ping; Li, Dong-Jie; Shen, Fu-Ming

    2016-01-01

    Endothelial cell dysfunction is the primary cause of microvascular complications in diabetes. Diazoxide enables beta cells to rest by reversibly suppressing glucose-induced insulin secretion by opening ATP-sensitive K+ channels in the beta cells. This study investigated the role of diazoxide in wound healing in mice with streptozotocin (STZ)-induced diabetes and explored the possible mechanisms of its effect. Compared to the controls, mice with STZ-induced diabetes exhibited significantly impaired wound healing. Diazoxide treatment (30 mg/kg/d, intragastrically) for 28 days accelerated wound closure and stimulated angiogenesis in the diabetic mice. Circulating endothelial progenitor cells (EPCs) increased significantly in the diazoxide-treated diabetic mice. The adhesion, migration, and tube formation abilities of bone marrow (BM)-EPCs were impaired by diabetes, and these impairments were improved by diazoxide treatment. The expression of both p53 and TSP-1 increased in diabetic mice compared to that in the controls, and these increases were inhibited significantly by diazoxide treatment. In vitro, diazoxide treatment improved the impaired BM-EPC function and diminished the increased expression of p53 and TSP-1 in cultured BM-EPCs caused by high glucose levels. We conclude that diazoxide improved BM-EPC function in mice with STZ-induced diabetes, possibly via a p53- and TSP-1-dependent pathway. PMID:27100489

  2. Adaptive servoventilation improves cardiac function and respiratory stability

    PubMed Central

    Bitter, Thomas; Lehmann, Roman; Korte, Stefan; Dimitriadis, Zisis; Faber, Lothar; Schmidt, Anke; Westerheide, Nina; Horstkotte, Dieter

    2010-01-01

    Cheyne–Stokes respiration (CSR) in patients with chronic heart failure (CHF) is of major prognostic impact and expresses respiratory instability. Other parameters are daytime pCO2, VE/VCO2-slope during exercise, exertional oscillatory ventilation (EOV), and increased sensitivity of central CO2 receptors. Adaptive servoventilation (ASV) was introduced to specifically treat CSR in CHF. Aim of this study was to investigate ASV effects on CSR, cardiac function, and respiratory stability. A total of 105 patients with CHF (NYHA ≥ II, left ventricular ejection fraction (EF) ≤ 40%) and CSR (apnoea–hypopnoea index ≥ 15/h) met inclusion criteria. According to adherence to ASV treatment (follow-up of 6.7 ± 3.2 months) this group was divided into controls (rejection of ASV treatment or usage <50% of nights possible and/or <4 h/night; n = 59) and ASV (n = 56) adhered patients. In the ASV group, ventilator therapy was able to effectively treat CSR. In contrast to controls, NYHA class, EF, oxygen uptake, 6-min walking distance, and NT-proBNP improved significantly. Moreover, exclusively in these patients pCO2, VE/VCO2-slope during exercise, EOV, and central CO2 receptor sensitivity improved. In CHF patients with CSR, ASV might be able to improve parameters of SDB, cardiac function, and respiratory stability. PMID:20835903

  3. Phosphonic Acid-Functionalized Polyurethane Dispersions with Improved Adhesion Properties.

    PubMed

    Breucker, Laura; Landfester, Katharina; Taden, Andreas

    2015-11-11

    A facile route to phosphorus-functionalized polyurethane dispersions (P-PUDs) with improved adhesion properties is presented. (Bis)phosphonic acid moieties serve as adhesion promoting sites that are covalently attached via an end-capping reaction to isocyanate-reactive polyurethane particles under aqueous conditions. The synthetic approach circumvents solubility issues, offers great flexibility in terms of polyurethane composition, and allows for the synthesis of semicrystalline systems with thermomechanical response due to reversible physical cross-linking. Differential scanning calorimetry (DSC) is used to investigate the effect of functionalization on the semicrystallinity. The end-capping conversion was determined via inductively-coupled plasma optical emission spectroscopy (ICP-OES) and was surprisingly found to be almost independent of the stoichiometry of reaction, suggesting an adsorption-dominated process. Particle charge detection (PCD) experiments reveal that a dense surface coverage of phosphonic acid groups can be attained and that, at high functionalization degrees, the phosphonic adhesion moieties are partially dragged inside the colloidal P-PUD particle. Quartz crystal microbalance with dissipation (QCMD) investigations conducted with hydroxyapatite (HAP) and stainless steel sensors as model surfaces show a greatly enhanced affinity of the aqueous P-PUDs and furthermore indicate polymer chain rearrangements and autonomous film formation under wet conditions. Due to their facile synthesis, significantly improved adhesion, and variable film properties, P-PUD systems such as the one described here are believed to be of great interest for multiple applications, e.g., adhesives, paints, anticorrosion, or dentistry. PMID:26491881

  4. FeLV envelope protein (gp70) variable region 5 causes alterations in calcium homeostasis and toxicity of neurons.

    PubMed

    Mitchell, T W; Rojko, J L; Hartke, J R; Mihajlov, A R; Kasameyer, G A; Gasper, P W; Whalen, L R

    1997-04-01

    In humans and animals, retroviruses have been implicated in nervous system disease. Our objective was to characterize the neurotoxicity of a peptide sequence derived from an animal retrovirus, the feline leukemia virus (FeLV). Using a peptide sequence from the subtype FeLV-C envelope protein variable region 5 (VR5), cytotoxicity was demonstrated in studies that evaluated neuronal survival, neurite outgrowth, and alterations in intracellular calcium ion concentration. The FeLV subtype isolate FeLV-CSarma possesses an envelope protein VR5 amino acid sequence that varies by four amino acids from the VR5 amino acid sequence of subtype FeLV-AGlasgow. The polypeptide representing the VR5 of FeLV-CSarma (FeLV-CVR5) is significantly more neurotoxic than the polypeptide sequence representing the VR5 of FeLV-AGlasgow (FeLV-AVR5). FeLV-CVR5 (> or = 3 microM) exposure resulted in significant dose-dependent neurotoxicity. Antibodies to FeLV-CVR5 blocked this effect. Neurite outgrowth was significantly reduced at all tested concentrations (3-12 microM) of FeLV-CVR5, with a 92% reduction in neurite length at 12 microM. FeLV-AVR5 was significantly less neurotoxic with respect to neurite outgrowth than was FeLV-CVR5. The significant reduction in neurotoxicity for FeLV-AVR5 illustrates the importance of the 4-amino-acid difference between it and FeLV-CVR5. Alterations in intracellular calcium ion concentration were associated with this neurotoxicity. PMID:9111472

  5. Improvement of digital photoelasticity based on camera response function.

    PubMed

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

    2011-09-20

    Studies on photoelasticity have been conducted by many researchers in recent years, and many equations for photoelastic analysis based on digital images were proposed. While these equations were all presented by the light intensity emitted from the analyzer, pixel values of the digital image were actually used in the real calculations. In this paper, a proposal of using relative light intensity obtained by the camera response function to replace the pixel value for photoelastic analysis was investigated. Generation of isochromatic images based on relative light intensity and pixel value were compared to evaluate the effectiveness of the new approach. The results showed that when relative light intensity was used, the quality of an isochromatic image can be greatly improved both visually and quantitatively. We believe that the technique proposed in this paper can also be used to improve the performance for the other types of photoelastic analysis using digital images. PMID:21947044

  6. A Short Executive Function Training Program Improves Preschoolers’ Working Memory

    PubMed Central

    Blakey, Emma; Carroll, Daniel J.

    2015-01-01

    Cognitive training has been shown to improve executive functions (EFs) in middle childhood and adulthood. However, fewer studies have targeted the preschool years—a time when EFs undergo rapid development. The present study tested the effects of a short four session EF training program in 54 four-year-olds. The training group significantly improved their working memory from pre-training relative to an active control group. Notably, this effect extended to a task sharing few surface features with the trained tasks, and continued to be apparent 3 months later. In addition, the benefits of training extended to a measure of mathematical reasoning 3 months later, indicating that training EFs during the preschool years has the potential to convey benefits that are both long-lasting and wide-ranging. PMID:26635710

  7. 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

  8. Mesenchymal Stromal Cells Improve Renovascular Function in Polycystic Kidney Disease.

    PubMed

    Franchi, Federico; Peterson, Karen M; Xu, Rende; Miller, Brent; Psaltis, Peter J; Harris, Peter C; Lerman, Lilach O; Rodriguez-Porcel, Martin

    2015-01-01

    Polycystic kidney disease (PKD) is a common cause of end-stage renal failure, for which there is no accepted treatment. Progenitor and stem cells have been shown to restore renal function in a model of renovascular disease, a disease that shares many features with PKD. The objective of this study was to examine the potential of adult stem cells to restore renal structure and function in PKD. Bone marrow-derived mesenchymal stromal cells (MSCs, 2.5 × 10(5)) were intrarenally infused in 6-week-old PCK rats. At 10 weeks of age, PCK rats had an increase in systolic blood pressure (SBP) versus controls (126.22 ± 2.74 vs. 116.45 ± 3.53 mmHg, p < 0.05) and decreased creatinine clearance (3.76 ± 0.31 vs. 6.10 ± 0.48 µl/min/g, p < 0.01), which were improved in PKD animals that received MSCs (SBP: 114.67 ± 1.34 mmHg, and creatinine clearance: 4.82 ± 0.24 µl/min/g, p = 0.001 and p = 0.003 vs. PKD, respectively). MSCs preserved vascular density and glomeruli diameter, measured using microcomputed tomography. PCK animals had increased urine osmolality (843.9 ± 54.95 vs. 605.6 ± 45.34 mOsm, p < 0.01 vs. control), which was improved after MSC infusion and not different from control (723.75 ± 56.6 mOsm, p = 0.13 vs. control). Furthermore, MSCs reduced fibrosis and preserved the expression of proangiogenic molecules, while cyst size and number were unaltered by MSCs. Delivery of exogenous MSCs improved vascular density and renal function in PCK animals, and the benefit was observed up to 4 weeks after a single infusion. Cell-based therapy constitutes a novel approach in PKD. PMID:25290249

  9. Modelling the feline leukemia virus (FeLV) in natural populations of cats (Felis catus).

    PubMed

    Fromont, E; Artois, M; Langlais, M; Courchamp, F; Pontier, D

    1997-08-01

    A compartmental model was built in order to study the circulation 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 FeLV is maintained in the population with a stable equilibrium and a slight reduction of population size. Estimation of the transmission rate allows us to make a comparison with the values previously estimated in the literature. We compare the impact of mass vaccination or removal programmes in controlling FeLV infection, and conclude that vaccination is more efficient. PMID:9345792

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

    PubMed

    Sabik, A; Gołek, F; Antczak, G

    2015-05-01

    We propose the modification to the Anderson method of work function change (Δϕ) 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 Δϕ of the Ag(100) surface induced by cobalt phthalocyanine layers. PMID:26026572

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

    SciTech Connect

    Sabik, A. Gołek, F.; Antczak, G.

    2015-05-15

    We propose the modification to the Anderson method of work function change (Δϕ) 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 Δϕ of the Ag(100) surface induced by cobalt phthalocyanine layers.

  12. Astym therapy improves function and range of motion following mastectomy

    PubMed Central

    Davies, Claire C; Brockopp, Dorothy; Moe, Krista

    2016-01-01

    Hypersensitive scar tissue formation along the incision line and drain site is a common side effect following mastectomy. If this scar tissue is not addressed, it can lead to decreased flexibility and function in the involved upper quadrant. Astym® treatment is a new approach to soft tissue injuries, and is evidenced in animal studies to promote the healing and regeneration of soft tissues. It has also been found to reduce pain and increase function in people with soft tissue dysfunction. The aim of Astym treatment is to engage the regenerative mechanisms of the body in order to resorb scar tissue, stimulate tissue turnover, and regenerate soft tissues. Handheld instrumentation is applied topically to locate and treat the underlying dysfunctional soft tissue through specific protocols for the application of particular pressures and shear forces. The purpose of this study was to examine the effects of Astym treatment on activities of daily living in women who had undergone a mastectomy following a diagnosis of breast cancer. A quasi-experiment involving 40 women, following a mastectomy, evaluated five outcome measures pre- and post-Astym treatment. All five measurement scores: Disabilities of the Arm, Shoulder, and Hand Outcome Measure; a clothing questionnaire on their ability to wear a bra; Patient-Specific Functional Scale; active range of motion of shoulder flexion; and active range of motion of abduction were also measured and all demonstrated significant changes. In this study, Astym treatment improved active range of motion in the involved quadrant and also improved function in patients following a mastectomy. PMID:27022302

  13. Oral magnesium supplementation improves vascular function in elderly diabetic patients.

    PubMed

    Barbagallo, Mario; Dominguez, Ligia J; Galioto, Antonio; Pineo, Antonella; Belvedere, Mario

    2010-09-01

    Magnesium (Mg) ions directly influence vascular tone and responsiveness and are cofactors for acetylcholine-induced endothelium-dependent relaxation. Alterations in extracellular Mg are able to modify the formation and release of nitric oxide (NO), altering arterial smooth muscle tone. Previous in vivo studies in humans have shown that parenteral or oral Mg supplementation increase endothelial-dependent vasodilation. The aim of the present study was to evaluate the effects of Mg oral supplementation on endothelial function in elderly diabetic and hypertensive subjects. Sixty elderly (≥ 65 years) diabetic patients were recruited (mean age: 71.1 ± 6.1 years; M/F: 35/25). Endothelial function, evaluated by non-invasive flow-mediated dilatation of the brachial artery, as well as anthropometric and laboratory data, including ionized Mg (Mg-ion), were measured in all patients before and after one-month. Thirty patients underwent oral Mg supplementation with 4.5 g/day of Mg pidolate (368 mg/day of Mg ion), while the rest were used as a control group. The usual management of diabetes and hypertension was not changed during the month of study participation for all the patients. In the group of patients that underwent Mg supplementation, Mg-ion concentration significantly increased from 0.42 ± 0.05 mmol/L to 0.49 ± 0.06 mmol/L; p < 0.05. Mg intervention resulted in a significant improvement of the post-ischemic endothelial-dependent flow-mediated dilation (from 3.3 ± 3.6% to 8.4 ± 3.9%; p < 0.05). No significant differences were found, either in ion-Mg or endothelial function, in the control group. In conclusion, the present study suggests that oral Mg improves endothelial function in diabetic elderly subjects. PMID:20736142

  14. Short-term improvement of masticatory function after implant restoration

    PubMed Central

    2015-01-01

    Purpose Dental implants present several advantages over other tooth replacement options. However, there has been little research on masticatory function in relation to implant treatment. Therefore, the aim of the present study was to evaluate the improvement of masticatory function two weeks after implant restoration. Methods Masticatory ability was evaluated with the subjective food intake ability (FIA) and objective mixing ability index (MAI) methods. Fifty-four subjects with first and second missing molars completed the study. The subjects were asked to complete a self-reported questionnaire about 30 different food items, and to chew wax samples 10 times both before and two weeks after implant restoration. A total of 108 waxes were analyzed with an image analysis program. Results Dental implant restoration for lost molar teeth on one side increased the FIA score by 9.0% (P<0.0001). The MAI score also increased, by 14.3% after implant restoration (P<0.0001). Comparison between the good and poor mastication groups, which were subdivided based on the median MAI score before implant restoration, showed that the FIA score of the poor group was enhanced 1.1-fold while its MAI score was enhanced 2.0-fold two weeks after an implant surgery. Conclusions Using the FIA and MAI assessment methods, this study showed that masticatory function was improved two weeks after implant restoration. In particular, the enhancement of masticatory function by implant restoration was greater in patients with relatively poor initial mastication than in those with good initial mastication. PMID:26734490

  15. Remote sensing of vegetation ecophysiological function for improved hydrologic prediction

    NASA Astrophysics Data System (ADS)

    Drewry, D.; Ruddell, B. L.

    2014-12-01

    Land surface hydrology in vegetated landscapes is strongly controlled by ecophysiological function. The coupling between photosynthesis, stomatal dynamics and leaf energy balance fundamentally links the hydrologic and carbon cycles, and provides a basis for examining the utility of observations of functional plant traits for hydrologic prediction. Here we explore the potential of solar induced fluorescence (SIF) and thermal infrared (TIR) remote sensing observations to improve the accuracy and reduce the uncertainty in hydrologic prediction. While SIF represents an emission of radiation associated with photosynthesis, TIR provides information on foliage temperature and is related to stomatal function and water stress. A set of remote observing system simulation experiments are conducted to quantify the value of remotely sensed observations of SIF and TIR when assimilated into a detailed vegetation biophysical model. The MLCan model discretizes a dense plant canopy to resolve vertical variation in photosynthesis, water vapor and energy exchange. Here we present extensions to MLCan that allow for direct computation of the canopy emission of both SIF and TIR. The detailed representation of the physical environment and biological functioning of structurally complex canopies makes MLCan an ideal simulation tool for exploring the impact of these two unique, and potentially synergistic observables. This work specifically addresses remote sensing capabilities on both recently launched (OCO-2) and near-term (ECOSTRESS) satellite platforms. We contrast the information gained through the assimilation of SIF and TIR observations to that of the assimilation of data related to physical states such as soil moisture and leaf area index.

  16. Pathogenicity of a subgroup C feline leukemia virus (FeLV) is augmented when administered in association with certain FeLV recombinants.

    PubMed

    Mathes, L E; Pandey, R; Chakrabarti, R; Hofman, F M; Hayes, K A; Stromberg, P; Roy-Burman, P

    1994-01-01

    There is evidence to suggest that infectious feline leukemia viruses (FeLVs) may be altered biologically because of homologous recombination with non-infectious endogenous FeLV (enFeLV) sequences in the infected cells. To evaluate the role of such recombination events in FeLV pathogenesis, a molecular clone of subgroup C FeLV, Sarma strain (FSC), was tested for induction of aplastic anemia in the absence or presence of mixtures of recombinants between FSC and an enFeLV element. In the recombinants, FSC sequences in the viral surface glycoprotein (SU) protein were variably replaced by the corresponding sequences of the enFeLV. The results showed that the virus mixtures varied in their infectivity to neonatal specific pathogen-free cats. One group of mixtures, although exhibiting relatively reduced infectivity, represented the most acute disease-inducing agents. The presence of recombinants in this mixture significantly accelerated the development of erythrocyte aplasia compared to cats infected with FSC alone. In addition, infected cells appeared to be distributed differently in various hematopoietic organs with respect to infection with FSC versus viral mixture. Viral recombinants which were present in this inoculum mixture, however, could not be detected in the plasma or infected tissues of the cats at the end stage of the disease, although their presence in the plasma at the early stages could be detected. Clearly, parental FSC outgrew the recombinants in the infected animals, since its detection was prominent at all stages of the progression of the disease. Therefore, we hypothesize that recombinants initially present in the infected animals, while only poorly replicated compared to FSC in the host, might have had the opportunity to infect certain target cells (potentially erythroid progenitor cells) and then disappeared with the associated cytopathic effect. PMID:8259654

  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. Intracoronary administration of cardiac stem cells in mice: a new, improved technique for cell therapy in murine models

    PubMed Central

    Li, Qianhong; Guo, Yiru; Ou, Qinghui; Chen, Ning; Wu, Wen-Jian; Yuan, Fangping; O’Brien, Erin; Wang, Tao; Luo, Li; Hunt, Gregory N.; Zhu, Xiaoping

    2013-01-01

    A model of intracoronary stem cell delivery that enables transgenesis/gene targeting would be a powerful tool but is still lacking. To address this gap, we compared intracoronary and intramyocardial delivery of lin−/c-kit+/GFP+ cardiac stem cells (CSCs) in a murine model of reperfused myocardial infarction (MI). Lin−/c-kit+/GFP+ CSCs were successfully expanded from GFP transgenic hearts and cultured with no detectable phenotypic change for up to ten passages. Intracoronary delivery of CSCs 2 days post-MI resulted in significant alleviation of adverse LV remodeling and dysfunction, which was at least equivalent, if not superior, to that achieved with intramyocardial delivery. Compared with intramyocardial injection, intracoronary infusion was associated with a more homogeneous distribution of CSCs in the infarcted region and a greater increase in viable tissue in this region, suggesting greater formation of new cardiomyocytes. Intracoronary CSC delivery resulted in improved function in the infarcted region, as well as in improved global LV systolic and diastolic function, and in decreased LV dilation and LV expansion index; the magnitude of these effects was similar to that observed after intramyocardial injection. We conclude that, in the murine model of reperfused MI, intracoronary CSC infusion is at least as effective as intramyocardial injection in limiting LV remodeling and improving both regional and global LV function. The intracoronary route appears to be superior in terms of uniformity of cell distribution, myocyte regeneration, and amount of viable tissue in the risk region. To our knowledge, this is the first study to report that intracoronary infusion of stem cells in mice is feasible and effective. PMID:21516491

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

    PubMed Central

    2010-01-01

    Background Maca (Lepidium meyenii) is an Andean plant of the brassica (mustard) family. Preparations from maca root have been reported to improve sexual function. The aim of this review was to assess the clinical evidence for or against the effectiveness of the maca plant as a treatment for sexual dysfunction. Methods We searched 17 databases from their inception to April 2010 and included all randomised clinical trials (RCTs) of any type of maca compared to a placebo for the treatment of healthy people or human patients with sexual dysfunction. The risk of bias for each study was assessed using Cochrane criteria, and statistical pooling of data was performed where possible. The selection of studies, data extraction, and validations were performed independently by two authors. Discrepancies were resolved through discussion by the two authors. Results Four RCTs met all the inclusion criteria. Two RCTs suggested a significant positive effect of maca on sexual dysfunction or sexual desire in healthy menopausal women or healthy adult men, respectively, while the other RCT failed to show any effects in healthy cyclists. The further RCT assessed the effects of maca in patients with erectile dysfunction using the International Index of Erectile Dysfunction-5 and showed significant effects. Conclusion The results of our systematic review provide limited evidence for the effectiveness of maca in improving sexual function. However, the total number of trials, the total sample size, and the average methodological quality of the primary studies were too limited to draw firm conclusions. More rigorous studies are warranted. PMID:20691074

  1. Traditional Japanese Medicine Daikenchuto Improves Functional Constipation in Poststroke Patients

    PubMed Central

    Numata, Takehiro; Takayama, Shin; Tobita, Muneshige; Ishida, Shuichi; Katayose, Dai; Shinkawa, Mitsutoshi; Oikawa, Takashi; Aonuma, Takanori; Kaneko, Soichiro; Tanaka, Junichi; Kanemura, Seiki; Iwasaki, Koh; Ishii, Tadashi; Yaegashi, Nobuo

    2014-01-01

    Poststroke patients with functional constipation, assessed by the Rome III criteria, from 6 hospitals were recruited in a study on the effects of the traditional Japanese medicine Daikenchuto (DKT) on constipation. Thirty-four patients (17 men and 17 women; mean age: 78.1 ± 11.6 years) were randomly assigned to 2 groups; all patients received conventional therapy for constipation, and patients in the DKT group received 15 g/day of DKT for 4 weeks. Constipation scoring system (CSS) points and the gas volume score (GVS) (the measure of the intestinal gas volume calculated from plain abdominal radiographs) were recorded before and after a 4-week observation period. The total score on the CSS improved significantly in the DKT group compared to the control (P < 0.01). In addition, scores for some CSS subcategories (frequency of bowel movements, feeling of incomplete evacuation, and need for enema/disimpaction) significantly improved in the DKT group (P < 0.01, P = 0.049, and P = 0.03, resp.). The GVS was also significantly reduced in the DKT group compared to the control (P = 0.03). DKT in addition to conventional therapy is effective in treating functional constipation in poststroke patients. This study was a randomized controlled trial and was registered in the UMIN Clinical Trial Registry (no. UMIN000007393). PMID:25089144

  2. 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.

  3. Does L-carnitine improve endothelial function in hemodialysis patients?

    PubMed Central

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

    2012-01-01

    Background: Atherosclerosis is the leading cause of death in hemodialysis patients. These patients are also very prone to L-carnitine deficiency due to kidney disease. In this clinical trial, we investigated the effect of oral L-carnitine on endothelial function of these patients. Materials ans Methods: We studied 31 adult chronic hemodialysis patients in our center and divided them into two groups. The first group (n = 20) received 1500 mg/dialysis interval (every other day) oral L-carnitine. The control group (n = 11) received placebo for one month. Ultrasonographic measurements of flow mediated dilation and carotid intima-media thickness were performed before and after one month of L-carnitine and placebo therapy. Results: This study showed that after one month of L-carnitine or placebo therapy there was no significant improvement in flow mediated dilation (p = 0.80 and p = 0.59, respectively) or decrease in carotid intima-media thickness (p = 0.12 and p = 0.50, respectively). Conclusions: Our study revealed that one month of oral L-carnitine therapy did not improve endothelial function in hemodialysis patients. Long-term studies with large sample size using intravenous form and higher doses of the drug are required to clarify the questionable role of L-carnitine in hemodialysis patients. PMID:23626603

  4. Improvement of renal function after opening occluded atherosclerotic renal arteries.

    PubMed

    Kanamori, Hiroshi; Toma, Masanao; Fukatsu, Atsushi

    2009-09-01

    Percutaneous transluminal renal angioplasty (PTRA) with stenting has been effective in the control of hypertension, renal function and pulmonary edema caused by atherosclerotic renal artery stenosis (ARAS). However, concerning the viability of renal function, this procedure has not been fully established, especially in the presence of renal atrophy or severe renal parenchymal disease. We report a dramatically improved case of acute renal failure caused by acute worsening ARAS treated by stenting. A 72-year-old female was admitted for accelerated renal dysfunction (serum ceatinine; 1.2-2.3 mg/dl) and hypertension (190/100 mmHg). At 10 days after admission, the patient's serum ceatinine increased to 6.7 mg/dl, her pulmonary edema was exaggerated and hemodialysis was required. Ultrasonography showed bilateral high-echoic kidneys, but no apparent finding of renal artery stenosis (RAS). At day 15, computed tomographic angiography indicated bilateral ostial RAS. Renal angiography demonstrated total occlusion of the right and severe (90%) disease in the left. ARAS was diagnosed by intravascular ultrasonography. The guidewire was inserted in both renal arteries, PTRA with stenting was performed in the right and a stent was directly implanted in the left. Immediately, each kidney enlarged to almost normal size, leading to satisfactory urination. She was released from hemodialysis the next day since her serum creatinine was normal and the pulmonary edema was improved. Although there is still no reliable prognostic factor including resistive index or kidney size, it is important that PTRA with stenting in ARAS should be considered in a case of accelerated renal dysfunction because of the possible improvement. PMID:19726830

  5. Qualification of uralane 5750 A/B (LV) for flight applications

    NASA Technical Reports Server (NTRS)

    Lewis, Donald F.; O'Donnell, Tim

    1991-01-01

    Uralane 5750 A/B (LV) is a POLYURETHANE which was to be considered for use as a thin CONFORMAL COATING on printed circuit boards for JPL flight projects. As part of the qualification process several properties of Uralane 5750 A/B (LV) were measured for the as-cured material and after various environmental exposures. The properties that were measured included outgassing i.e. Total Mass Loss (TML) and Vacuum Condensable Mass (VCM) and mass accumulation rates on cold surfaces, Static Elastic Modulus and coefficient of Thermal Expansion (CTE). The Uralane 5750 A/B (LV) that was tested consisted of sheets which varied in both thickness and curing procedures. The environmental exposures consisted of vacuum, thermal and combined thermal vacuum. The physical properties of Uralane 5750 A/B (LV) met the JPL requirements for flight in both the as-cured condition and after environmental exposures.

  6. Intestinal barrier function in neonatal foals: options for improvement.

    PubMed

    Vendrig, Johannes C; Fink-Gremmels, Johanna

    2012-07-01

    Gastrointestinal defence in the new-born is limited in comparison to adults, due to an immature epithelial barrier function and deficits in both innate and adaptive immune responses. Consequently, neonates (including foals) are at increased risk of disturbance to mucosal homeostasis during initial intestinal colonisation that may lead to excessive inflammation and bacterial translocation into the bloodstream, resulting in septicaemia. Bacterial recognition by Pattern Recognition Receptors (PRRs) and their downstream regulation of cytokine release have been shown to be pivotal for gastrointestinal mucosal homeostasis and the development of a functional intestinal barrier. Evidence suggests that selective PRR agonists limit the inflammatory responses and improve epithelial barrier function. Milk, and in particular colostrum, contain a broad array of oligosaccharides which seem to act as PRR agonists. This class of compounds forms a source for new dietary formulas that may orchestrate gut colonisation by the commensal flora in the early phase of life and so reduce the risks of inflammation and pathogen invasion. PMID:22377327

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

    PubMed

    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 Oβ knock-out (Oβ (-/-)) 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 Oβ 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 Oβ (-/-) 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

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

    SciTech Connect

    Pirus, D.

    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)

  9. Neutralising antibodies against the transmembrane protein of feline leukaemia virus (FeLV).

    PubMed

    Langhammer, S; Fiebig, U; Kurth, R; Denner, J

    2005-05-01

    Neutralising antibodies specific for feline leukaemia virus (FeLV) were induced by immunisation with recombinant FeLV transmembrane envelope protein p15E. Epitope mapping revealed two epitopes located in similar regions to those previously identified for the porcine endogenous retrovirus (PERV). One of the epitopes has partial homology and both are located in regions corresponding to epitopes recognised by neutralising antibodies in patients infected with HIV-1. PMID:15837241

  10. Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni

    PubMed Central

    Leite, Luiz Arthur Calheiros; Pimenta Filho, Adenor Almeida; Ferreira, Rita de Cássia dos Santos; da Fonseca, Caíque Silveira Martins; dos Santos, Bianka Santana; Montenegro, Silvia Maria Lucena; Lopes, Edmundo Pessoa de Almeida; Domingues, Ana Lúcia Coutinho; Owen, James Stuart; Lima, Vera Lucia de Menezes

    2015-01-01

    Background Schistosomiasis mansoni is a chronic liver disease, in which some patients (5–10%) progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients. Methodology/Principal Findings Forty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55). Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1. Conclusion/Significance This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status. PMID:26267788

  11. Inhibition of neutrophil activity improves cardiac function after cardiopulmonary bypass

    PubMed Central

    Abdel-Rahman, Ulf; Margraf, Stefan; Aybek, Tayfun; Lögters, Tim; Bitu-Moreno, José; Francischetti, Ieda; Kranert, Tilmann; Grünwald, Frank; Windolf, Joachim; Moritz, Anton; Scholz, Martin

    2007-01-01

    Background The arterial in line application of the leukocyte inhibition module (LIM) in the cardiopulmonary bypass (CPB) limits overshooting leukocyte activity during cardiac surgery. We studied in a porcine model whether LIM may have beneficial effects on cardiac function after CPB. Methods German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min reperfusion) without (group I; n = 6) or with LIM (group II; n = 6). The cardiac indices (CI) and cardiac function were analyzed pre and post CPB with a Swan-Ganz catheter and the cardiac function analyzer. Neutrophil labeling with technetium, scintigraphy, and histological analyses were done to track activated neutrophils within the organs. Results LIM prevented CPB-associated increase of neutrophil counts in peripheral blood. In group I, the CI significantly declined post CPB (post: 3.26 ± 0.31; pre: 4.05 ± 0.45 l/min/m2; p < 0.01). In group II, the CI was only slightly reduced (post: 3.86 ± 0.49; pre 4.21 ± 1.32 l/min/m2; p = 0.23). Post CPB, the intergroup difference showed significantly higher CI values in the LIM group (p < 0.05) which was in conjunction with higher pre-load independent endsystolic pressure volume relationship (ESPVR) values (group I: 1.57 ± 0.18; group II: 1.93 ± 0.16; p < 0.001). Moreover, the systemic vascular resistance and pulmonary vascular resistance were lower in the LIM group. LIM appeared to accelerate the sequestration of hyperactivated neutrophils in the spleen and to reduce neutrophil infiltration of heart and lung. Conclusion Our data provides strong evidence that LIM improves perioperative hemodynamics and cardiac function after CPB by limiting neutrophil activity and inducing accelerated sequestration of neutrophils in the spleen. PMID:17925040

  12. Cloning of the cellular receptor for feline leukemia virus subgroup C (FeLV-C), a retrovirus that induces red cell aplasia.

    PubMed

    Quigley, J G; Burns, C C; Anderson, M M; Lynch, E D; Sabo, K M; Overbaugh, J; Abkowitz, J L

    2000-02-01

    Feline leukemia virus-C (FeLV-C) causes red cell aplasia in cats, likely through its interaction with its cell surface receptor. We identified this receptor by the functional screening of a library of complementary DNAs (cDNA) from feline T cells. The library, which was cloned into a retroviral vector, was introduced into FeLV-C-resistant murine (NIH 3T3) cells. The gene conferring susceptibility to FeLV-C was isolated and reintroduced into the same cell type, as well as into FeLV-C-resistant rat (NRK 52E) cells, to verify its role in viral infection. The receptor cDNA is predicted to encode a protein of 560 amino acids with 12 membrane-spanning domains, termed FLVCR. FLVCR has significant amino acid sequence homology with members of the major facilitator superfamily and especially D-glucarate transporters described in bacteria and in C. elegans. As FeLV-C impairs the in vivo differentiation of burst-forming unit-erythroid to colony-forming unit-erythroid, we hypothesize that this transporter system could have an essential role in early erythropoiesis. In further studies, a 6-kb fragment of the human FLVCR gene was amplified by polymerase chain reaction from genomic DNA, using homologous cDNA sequences identified in the human Expressed Sequence Tags database. By radiation hybrid mapping, the human gene was localized to a 0.5-centiMorgan region on the long arm of chromosome 1 at q31.3. PMID:10648427

  13. Improving Project Management with Simulation and Completion Distribution Functions

    NASA Technical Reports Server (NTRS)

    Cates, Grant R.

    2004-01-01

    Despite the critical importance of project completion timeliness, management practices in place today remain inadequate for addressing the persistent problem of project completion tardiness. A major culprit in late projects is uncertainty, which most, if not all, projects are inherently subject to. This uncertainty resides in the estimates for activity durations, the occurrence of unplanned and unforeseen events, and the availability of critical resources. In response to this problem, this research developed a comprehensive simulation based methodology for conducting quantitative project completion time risk analysis. It is called the Project Assessment by Simulation Technique (PAST). This new tool enables project stakeholders to visualize uncertainty or risk, i.e. the likelihood of their project completing late and the magnitude of the lateness, by providing them with a completion time distribution function of their projects. Discrete event simulation is used within PAST to determine the completion distribution function for the project of interest. The simulation is populated with both deterministic and stochastic elements. The deterministic inputs include planned project activities, precedence requirements, and resource requirements. The stochastic inputs include activity duration growth distributions, probabilities for events that can impact the project, and other dynamic constraints that may be placed upon project activities and milestones. These stochastic inputs are based upon past data from similar projects. The time for an entity to complete the simulation network, subject to both the deterministic and stochastic factors, represents the time to complete the project. Repeating the simulation hundreds or thousands of times allows one to create the project completion distribution function. The Project Assessment by Simulation Technique was demonstrated to be effective for the on-going NASA project to assemble the International Space Station. Approximately $500 million per month is being spent on this project, which is scheduled to complete by 2010. NASA project stakeholders participated in determining and managing completion distribution functions produced from PAST. The first result was that project stakeholders improved project completion risk awareness. Secondly, using PAST, mitigation options were analyzed to improve project completion performance and reduce total project cost.

  14. Improved fibroblast functionalities by microporous pattern fabricated by microelectromechanical systems.

    PubMed

    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

  15. 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

  16. Hydrogen sulfide improves neural function in rats following cardiopulmonary resuscitation

    PubMed Central

    LIN, JI-YAN; ZHANG, MIN-WEI; WANG, JIN-GAO; LI, HUI; WEI, HONG-YAN; LIU, RONG; DAI, GANG; LIAO, XIAO-XING

    2016-01-01

    The alleviation of brain injury is a key issue following cardiopulmonary resuscitation (CPR). Hydrogen sulfide (H2S) is hypothesized to be involved in the pathophysiological process of ischemia-reperfusion injury, and exerts a protective effect on neurons. The aim of the present study was to investigate the effects of H2S on neural functions following cardiac arrest (CA) in rats. A total of 60 rats were allocated at random into three groups. CA was induced to establish the model and CPR was performed after 6 min. Subsequently, sodium hydrosulfide (NaHS), hydroxylamine or saline was administered to the rats. Serum levels of H2S, neuron-specific enolase (NSE) and S100β were determined following CPR. In addition, neurological deficit scoring (NDS), the beam walking test (BWT), prehensile traction test and Morris water maze experiment were conducted. Neuronal apoptosis rates were detected in the hippocampal region following sacrifice. After CPR, as the H2S levels increased or decreased, the serum NSE and S100β concentrations decreased or increased, respectively (P<0.0w. The NDS results of the NaHS group were improved compared with those of the hydroxylamine group at 24 h after CPR (P<0.05). In the Morris water maze experiment, BWT and prehensile traction test the animals in the NaHS group performed best and rats in the hydroxylamine group performed worst. At day 7, the apoptotic index and the expression of caspase-3 were reduced in the hippocampal CA1 region, while the expression of Bcl-2 increased in the NaHS group; and results of the hydroxylamine group were in contrast. Therefore, the results of the present study indicate that H2S is able to improve neural function in rats following CPR. PMID:26893650

  17. Dissociation between cardiomyocyte function and remodeling with beta-adrenergic receptor blockade in isolated canine mitral regurgitation.

    PubMed

    Pat, Betty; Killingsworth, Cheryl; Denney, Thomas; Zheng, Junying; Powell, Pamela; Tillson, Michael; Dillon, A Ray; Dell'Italia, Louis J

    2008-12-01

    The low-pressure volume overload of isolated mitral regurgitation (MR) is associated with increased adrenergic drive, left ventricular (LV) dilatation, and loss of interstitial collagen. We tested the hypothesis that beta1-adrenergic receptor blockade (beta1-RB) would attenuate LV remodeling after 4 mo of MR in the dog. beta1-RB did not attenuate collagen loss or the increase in LV mass in MR dogs. Using MRI and three-dimensional (3-D) analysis, there was a 70% increase in the LV end-diastolic (LVED) volume-to-LV mass ratio, a 23% decrease in LVED midwall circumferential curvature, and a >50% increase in LVED 3-D radius/wall thickness in MR dogs that was not attenuated by beta1-RB. However, beta1-RB caused a significant increase in LVED length from the base to apex compared with untreated MR dogs. This was associated with an increase in isolated cardiomyocyte length (171+/-5 microm, P<0.05) compared with normal (156+/-3 microm) and MR (165+/-4 microm) dogs. Isolated cardiomyocyte fractional shortening was significantly depressed in MR dogs compared with normal dogs (3.73+/-0.31 vs. 5.02+/-0.26%, P<0.05) and normalized with beta1-RB (4.73+/-0.48%). In addition, stimulation with the beta-adrenergic receptor agonist isoproterenol (25 nM) increased cardiomyocyte fractional shortening by 215% (P<0.05) in beta1-RB dogs compared with normal (56%) and MR (50%) dogs. In summary, beta1-RB improved LV cardiomyocyte function and beta-adrenergic receptor responsiveness despite further cell elongation. The failure to attenuate LV remodeling associated with MR could be due to a failure to improve ultrastructural changes in extracellular matrix organization. PMID:18849331

  18. Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction - MI3 Trial

    PubMed Central

    Nair, Velu; Madan, Hemant; Sofat, Sunil; Ganguli, Prosenjit; Jacob, M.J.; Datta, Rajat; Bharadwaj, Prashant; Sarkar, R.S.; Pandit, A.J.; Nityanand, Soniya; Goel, Pravin K.; Garg, Naveen; Gambhir, Sanjay; George, Paul V.; Chandy, Sunil; Mathews, Vikram; George, Oomen K.; Talwar, K.K.; Bahl, Ajay; Marwah, Neelam; Bhatacharya, Anish; Bhargava, Balram; Airan, Balram; Mohanty, Sujata; Patel, Chetan D.; Sharma, Alka; Bhatnagar, Shinjini; Mondal, A.; Jose, Jacob; Srivastava, A.

    2015-01-01

    Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 × 108 autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy. Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI). Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 × 108(n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study. Interpretation & conclusions: Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials. PMID:26354213

  19. Interventions to Improve the Physical Function of ICU Survivors

    PubMed Central

    Calvo-Ayala, Enrique; Farber, Mark O.; Ely, E. Wesley; Boustani, Malaz A.

    2013-01-01

    Background: ICU admissions are ever increasing across the United States. Following critical illness, physical functioning (PF) may be impaired for up to 5 years. We performed a systematic review of randomized controlled trials evaluating the efficacy of interventions targeting PF among ICU survivors. The objective of this study was to identify effective interventions that improve long-term PF in ICU survivors. Methods: MEDLINE, Excerpta Medica Database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Physiotherapy Evidence-Based Database (PEDro) were searched between 1990 and 2012. Two reviewers independently evaluated studies for eligibility, critically appraised the included studies, and extracted data into standardized evidence tables. Results: Fourteen studies met the inclusion criteria. Interventions included exercise/physical therapy (PT), parenteral nutrition, nurse-led follow-up, spontaneous awakening trials, absence of sedation during mechanical ventilation, and early tracheotomy. Nine studies failed to demonstrate efficacy on PF of the ICU survivors. However, early physical exercise and PT-based interventions had a positive effect on long-term PF. Conclusions: The only effective intervention to improve long-term PF in critically ill patients is exercise/PT; its benefit may be greater if started earlier. Further research in this area comparing different interventions and timing is needed. PMID:23949645

  20. Improving 3D Genome Reconstructions Using Orthologous and Functional Constraints

    PubMed Central

    Diament, Alon; Tuller, Tamir

    2015-01-01

    The study of the 3D architecture of chromosomes has been advancing rapidly in recent years. While a number of methods for 3D reconstruction of genomic models based on Hi-C data were proposed, most of the analyses in the field have been performed on different 3D representation forms (such as graphs). Here, we reproduce most of the previous results on the 3D genomic organization of the eukaryote Saccharomyces cerevisiae using analysis of 3D reconstructions. We show that many of these results can be reproduced in sparse reconstructions, generated from a small fraction of the experimental data (5% of the data), and study the properties of such models. Finally, we propose for the first time a novel approach for improving the accuracy of 3D reconstructions by introducing additional predicted physical interactions to the model, based on orthologous interactions in an evolutionary-related organism and based on predicted functional interactions between genes. We demonstrate that this approach indeed leads to the reconstruction of improved models. PMID:26000633

  1. Impact of Untreated Obstructive Sleep Apnea on Left and Right Ventricular Myocardial Function and Effects of CPAP Therapy

    PubMed Central

    Wiesen, Martin; Momcilovic, Diana; Pabst, Stefan; Nickenig, Georg; Skowasch, Dirk

    2013-01-01

    Background Obstructive sleep apnea (OSA) has deteriorating effect on LV function, whereas its impact on RV function is controversial. We aimed to determine the effect of OSA and continuous positive airway pressure (CPAP) treatment on left and right ventricular (LV, RV) function using transthoracic echocardiography (TTE) and 2 dimensional speckle tracking (2D ST) analysis of RV deformation capability. Methods and Results 82 patients with OSA and need for CPAP therapy were prospectively enrolled and underwent TTE at study inclusion and after 6 months of follow up (FU). Multivariate regression analysis revealed an independent association between baseline apical right ventricular longitudinal strain (RV-Sl), BMI and the severity of OSA (apical RV-Sl: P?=?0.0002, BMI: P?=?0.02). After CPAP therapy, LV functional parameters (LVEF: P<0.0001, LV performance index: P?=?0.03, stroke volume: P?=?0.042), and apical RV-Sl (P?=?0.001) improved significantly. The effect of CPAP therapy was related to severity of OSA (LVEF: AHI 514, 66.48.8%, 68.510.6% [P?=?ns]; AHI 1530?59.87.7%, 68.69.3% [P?=?0.002]; AHI>30?54.112.4%, 68.213.6%[P<0.0001]; apical RV-Sl: AHI 514: ?17.38.7%, ?16.010.8% [P?=?ns], AHI 1530: ?9.86.0%, ?15.410.9% [P?=?0.028], AHI>30: ?6.35.7%, ?17.911.2% [P<0.0001]). Conclusions OSA seems to have deteriorating effect on LV and RV function. We found a beneficial effect of CPAP on LV and RV functional parameters predominately in patients with severe OSA. 2D speckle tracking might be of value to determine early changes in global and regional right ventricular function. PMID:24146857

  2. 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.

  3. 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 PPARγ-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

  4. Impact of biogenic nanoscale metals Fe, Cu, Zn and Se on reproductive LV chickens

    NASA Astrophysics Data System (ADS)

    Khiem Nguyen, Quy; Dieu Nguyen, Duy; Kien Nguyen, Van; Thinh Nguyen, Khac; Chau Nguyen, Hoai; Tin Tran, Xuan; Nguyen, Huu Cuong; Tien Phung, Duc

    2015-09-01

    Using biogenic nanoscale metals (Fe, Cu, ZnO, Se) to supplement into diet premix of reproductive LV (a Vietnamese Luong Phuong chicken breed) chickens resulted in certain improvement of poultry farming. The experimental data obtained showed that the farming indices depend mainly on the quantity of nanocrystalline metals which replaced the inorganic mineral component in the feed premix. All four experimental groups with different quantities of the replacement nano component grew and developed normally with livability reaching 91 to 94%, hen’s bodyweight at 38 weeks of age and egg weight ranged from 2.53-2.60 kg/hen and 50.86-51.55 g/egg, respectively. All these farming indices together with laying rate, egg productivity and chick hatchability peaked at group 5 with 25% of nanoscale metals compared to the standard inorganic mineral supplement, while feed consumption was lowest. The results also confirmed that nanocrystalline metals Fe, Cu, ZnO and Se supplemented to chicken feed were able to decrease inorganic minerals in the diet premixes at least four times, allowing animals to more effectively absorb feed minerals, consequently decreasing environmental pollution risks.

  5. Does Functional Outcome Improve with Time Postsurgery for Hirschsprung Disease?

    PubMed

    Aworanti, Olugbenga Michael; McDowell, Dermot Thomas; Martin, Ian Michael; Quinn, Feargal

    2016-04-01

    Purpose Constipation and incontinence are significant problems following pull-through surgery for Hirschsprung disease (HD). There is evidence that these problems improve with time. However, there is also evidence showing no improvements and furthermore, significant long-term data are lacking for the newer endorectal pull-through. We aim to determine if there is clinical evidence that show improvements in functional outcomes with time after an endorectal pull-through surgery for HD. Methods We utilized the validated pediatric incontinence and constipation scoring system (PICSS) to score 51 consecutive children 3 months to 15 years posttransabdominal or transanal endorectal pull-through for HD. Cases of total colonic aganglionosis and Down syndrome were excluded. PICSS scores below the age-specific lower limit 95% confidence interval scores represent incomplete continence or constipation, respectively. We performed linear regression to analyze the relationship between PICSS scores and the follow-up duration and then compared the demographics of children with and without incomplete continence and constipation, respectively. Significance was set at p < 0.05. Results The median age at PICSS interview was 71 months (range, 6-191 months). Incontinence scores obtained from 42 children older than 35 months showed a positive relationship with the follow-up duration (p = 0.03). Constipation scores obtained from 51 children were unrelated to follow-up duration (p = 0.486). When demographics were compared, the continent children had longer follow-up than those with incomplete continence (mean, 111.64 vs. 69.19 months; p = 0.051), however follow-up duration did not differ in the group of constipated children compared with the nonconstipated group (mean, 61.88 vs. 71.80 months; p = 0.321). Conclusion These findings suggest that after an endorectal pull-through, improved continence should be expected with time but constipation often continues to be an ongoing problem. PMID:25643245

  6. Improvement in renal functions with transcatheter aortic valve implantation

    PubMed Central

    Kele?, Telat; Ayhan, Hseyin; Durmaz, Tahir; Sar?, Cenk; Aslan, Abdullah Nabi; Erdo?an, Kemal E?ref; Kasapkara, Hac? Ahmet; Bilen, Emine; Bayram, Nihal Akar; Akay, Murat; Bozkurt, Engin

    2013-01-01

    Background & Objectives In recent years, emerging transcatheter aortic valve implantation (TAVI) has become an alternative for surgery. However, with advanced age, several co-morbid factors together with contrast agent usage can cause deterioration in renal function and increase in the risk of acute kidney injury (AKI) with poor prognosis in patients with AKI. Therefore, many patients cannot benefit from this treatment. In this study, we aim to examine the effects of TAVI on renal functions. Methods and Results Seventy patients, mean age of 77.6 years, underwent TAVI between July 2011 and December 2012. Estimated glomerular filtration rate (eGFR) was calculated by using the Cockcroft and Gault Formula. Patients were monitored for 48 h for urine output. Stage 1 AKI, according to the VARC-2 AKIN system, developed in only five (7.1%) of the patients after the procedure. There was a statistically significant increase between the mean 1st month eGFRs before (68.2 vs. 61.0, P < 0.01) and after (68.2 vs. 63.6, P < 0.05) the TAVI in the cohort. After TAVI (48.5 mL/min, P < 0.01) and the 1st month (52.1 mL/min, P < 0.01), the eGFR of the 36 (51.4%) patients diagnosed with chronic kidney disease before the procedure showed a statistically significant increase in renal functions. The hospital mortality rate was higher in the group which developed AKI (P < 0.01). First month eGFR showed a more statistically significant increase than pre-TAVI eGFR (62.8 and 69.8, P < 0.05, respectively) in AKI developing patients and this difference - though statistically not significant - continued into the sixth month. Conclusions In this study, we showed that the treatment of aortic stenosis through TAVI allows improvement of renal functions, and that AKI rates will be lower with careful patient selection, proper pre-procedural hydration, and careful use of contrast agent. PMID:24454323

  7. Lingo-1 inhibited by RNA interference promotes functional recovery of experimental autoimmune encephalomyelitis.

    PubMed

    Wang, Chun-Juan; Qu, Chuan-Qiang; Zhang, Jie; Fu, Pei-Cai; Guo, Shou-Gang; Tang, Rong-Hua

    2014-12-01

    Lingo-1 is a negative regulator of myelination. Repairment of demyelinating diseases, such as multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE), requires activation of the myelination program. In this study, we observed the effect of RNA interference on Lingo-1 expression, and the impact of Lingo-1 suppression on functional recovery and myelination/remyelination in EAE mice. Lentiviral vectors encoding Lingo-1 short hairpin RNA (LV/Lingo-1-shRNA) were constructed to inhibit Lingo-1 expression. LV/Lingo-1-shRNA of different titers were transferred into myelin oligodendrocyte glycoprotein-induced EAE mice by intracerebroventricular (ICV) injection. Meanwhile, lentiviral vectors carrying nonsense gene sequence (LVCON053) were used as negative control. The Lingo-1 expression was detected and locomotor function was evaluated at different time points (on days 1,3,7,14,21, and 30 after ICV injection). Myelination was investigated by luxol fast blue (LFB) staining.LV/Lingo-1-shRNA administration via ICV injection could efficiently down-regulate the Lingo-1 mRNA and protein expression in EAE mice on days 7,14,21, and 30 (P < 0.01), especially in the 5 × 10(8) TU/mL and 5 × 10(9) TU/mL LV/Lingo-1-shRNA groups. The locomotor function score in the LV/Lingo-1-shRNA treated groups were significantly lower than the untreated or LVCON053 group from day 7 on. The 5 × 10(8) TU/mL LV/Lingo-1-shRNA group achieved the best functional improvement (0.87 ± 0.11 vs. 3.05 ± 0.13, P < 0.001). Enhanced myelination/remyelination was observed in the 5 × 10(7) , 5 × 10(8) , 5 × 10(9) TU/mL LV/Lingo-1-shRNA groups by LFB staining (P < 0.05, P < 0.01, and P < 0.05).The data showed that administering LV/Lingo-1-shRNA by ICV injection could efficiently knockdown Lingo-1 expression in vivo, improve functional recovery and enhance myelination/remyelination. Antagonism of Lingo-1 by RNA interference is, therefore, a promising approach for the treatment of demyelinating diseases, such as MS/EAE. PMID:25045138

  8. Left and Right Ventricular Functional Dynamics Determined by Echocardiograms Before and After Lung Transplantation.

    PubMed

    Kato, Tomoko S; Armstrong, Hilary F; Schulze, P Christian; Lippel, Matthew; Amano, Atsushi; Farr, Maryjane; Bacchetta, Matthew; Bartels, Matthew N; Di Tullio, Marco R; Homma, Shunichi; Mancini, Donna

    2015-08-15

    Impaired cardiac function is considered a contraindication for lung transplantation (LT). Because right ventricular (RV) function is expected to improve after LT, poor left ventricular (LV) function is often the determinant for LT eligibility. However, the changes in cardiac function before and after LT have not yet been elucidated. Therefore, we reviewed echocardiograms obtained from 67 recipients before and after LT. In a subset of 49 patients, both RV and LV longitudinal strains based on 2-dimensional speckle tracking echocardiography were analyzed. The cardiopulmonary exercise tests were also reviewed. All patients showed significant improvements in their exercise capacity after LT. RV echo parameters improved in all patients after LT (RV fractional area change: 36.7 ± 5.6% to 41.5 ± 2.7%, RV strain: -15.5 ± 2.9% to -18.0 ± 2.1%, RV E/E': 8.4 ± 1.8 to 7.7 ± 1.8; all p <0.05). Overall, the left ventricular ejection fraction (LVEF) did not change (58.7 ± 6.0% to 57.5 ± 9.7%, p = 0.385); however, 20 patients (30%) showed >10% decrease in LVEF after LT (61.5 ± 6.1% to 47.3 ± 4.2%, p <0.001) and an increase in LV E/E' (11.8 ± 1.8 to 12.9 ± 2.2, p = 0.049). Multivariate logistic regression analysis revealed that pre-LT LV E/E' was associated with decrease in LVEF after LT (odds ratio 1.381, 95% confidence interval 1.010 to 1.947, p = 0.043). Furthermore, patients with strain data showed that lower pre-LT LV strain was independently associated with LVEF decrease after LT (odds ratio 1.293, 95% confidence interval 1.088 to 1.614, p = 0.002). Although RV function improves after LT, LV systolic and diastolic functions deteriorate in a sizable proportion of patients. Impaired LV diastolic function before transplant appears to increase the risk of LVEF deterioration after LT. PMID:26089014

  9. The Adverse Impact of Diabetes Mellitus on Left Ventricular Remodeling and Function in Patients with Severe Aortic Stenosis

    PubMed Central

    Lindman, Brian R.; Arnold, Suzanne V.; Madrazo, José A.; Zajarias, Alan; Johnson, Stephanie N.; Pérez, Julio E.; Mann, Douglas L.

    2011-01-01

    Background The diabetic heart exhibits increased left ventricular (LV) mass and reduced ventricular function. However, this relationship has not been studied in patients with aortic stenosis (AS), a disease process that causes LV hypertrophy and dysfunction through a distinct mechanism of pressure overload. The aim of this study was to determine how diabetes mellitus (DM) impacts LV remodeling and function in patients with severe AS. Methods and Results Echocardiograms were performed on 114 patients with severe AS [mean aortic valve area (AVA) 0.6 cm2] and included measures of LV remodeling and function. Multivariable linear regression models investigated the independent effect of DM on these aspects of LV structure and function. Compared to non-diabetics (n=60), diabetics (n=54) had increased LV mass, LV end-systolic dimension, LV end-diastolic dimension, and decreased LV ejection fraction (EF) and longitudinal systolic strain (p<0.01 for all). In multivariable analyses adjusting for age, sex, systolic BP, AVA, BSA, and coronary disease, DM was an independent predictor of increased LV mass (β=26g, p=0.01), LV end-systolic dimension (β=0.5cm, p=0.008), and LV end-diastolic dimension (β=0.3cm, p=0.025). After additionally adjusting for LV mass, DM was associated with reduced longitudinal systolic strain (β=1.9%, p=0.023) and a trend toward reduced EF (β=−5%, p=0.09). Among diabetics, insulin use (as a marker of disease severity) was associated with larger LV end-systolic dimension and worse LV function. LV mass was a strong predictor of reduced EF and systolic strain (p<0.001 for both). Conclusions DM has an additive adverse effect on hypertrophic remodeling—increased LV mass and larger cavity dimensions—and is associated with reduced systolic function in patients with AS beyond known factors of pressure overload. PMID:21357546

  10. Emulsion design to improve the delivery of functional lipophilic components.

    PubMed

    McClements, David Julian

    2010-01-01

    The food industry has used emulsion science and technology for many years to create a diverse range of food products, such as milk, cream, soft drinks, nutritional beverages, dressings, mayonnaise, sauces, dips, deserts, ice cream, margarine, and butter. The majority of these food products are conventional oil-in-water (O/W) or water-in-oil (W/O) type emulsions. Recently, there has been increasing interest within the food industry in either improving or extending the functional performance of foods using novel structured emulsions. This article reviews recent developments in the creation of structured emulsions that could be used by the food and other industries, including nanoemulsions, multiple emulsions, multilayer emulsions, solid lipid particles, and filled hydrogel particles. These structured emulsions can be produced from food-grade [generally recognized as safe (GRAS)] ingredients (e.g., lipids, proteins, polysaccharides, surfactants, and minerals), using simple processing operations (e.g., mixing, homogenizing, and thermal processing). The structure, production, performance, and potential applications of each type of structured emulsion system are discussed. PMID:22129337

  11. Stimulus Characteristics for Vestibular Stochastic Resonance to Improve Balance Function

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  12. 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

  13. Applying Quality Function Deployment Model in Burn Unit Service Improvement.

    PubMed

    Keshtkaran, Ali; Hashemi, Neda; Kharazmi, Erfan; Abbasi, Mehdi

    2014-10-13

    Quality function deployment (QFD) is one of the most effective quality design tools. This study applies QFD technique to improve the quality of the burn unit services in Ghotbedin Hospital in Shiraz, Iran. First, the patients' expectations of burn unit services and their priorities were determined through Delphi method. Thereafter, burn unit service specifications were determined through Delphi method. Further, the relationships between the patients' expectations and service specifications and also the relationships between service specifications were determined through an expert group's opinion. Last, the final importance scores of service specifications were calculated through simple additive weighting method. The findings show that burn unit patients have 40 expectations in six different areas. These expectations are in 16 priority levels. Burn units also have 45 service specifications in six different areas. There are four-level relationships between the patients' expectations and service specifications and four-level relationships between service specifications. The most important burn unit service specifications have been identified in this study. The QFD model developed in the study can be a general guideline for QFD planners and executives. PMID:23884047

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

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

    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 Γ-point were altered to reduce finite size effects: their eigenvalues corresponding to the acoustic modes were set to zero. This scheme was found to work well for simple Bravais lattices as long as only atoms within the last layer were treated as Green's function atoms. However, it failed to function as expected in all other cases. It turns out that a violation of the acoustic sum rule for the effective elastic coefficients at Γ (Kong, 2010 [3]) was responsible for this behavior. In the new version, the acoustic sum rule is enforced by adopting an iterative procedure, which is found to be physically more meaningful than the previous one. In addition, the new algorithm allows one to treat lattices with bases and the Green's function slab is no longer confined to one layer. New version program summaryProgram title: FixGFC/FixGFMD v1.12 Catalogue identifier: AECW_v1_1 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AECW_v1_1.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 206 436 No. of bytes in distributed program, including test data, etc.: 4 314 850 Distribution format: tar.gz Programming language: C++ Computer: All Operating system: Linux Has the code been vectorized or parallelized?: Yes. Code has been parallelized using MPI directives. RAM: Depends on the problem Classification: 7.7 External routines: LAMMPS ( http://lammps.sandia.gov/), MPI ( http://www.mcs.anl.gov/research/projects/mpi/), FFT ( http://www.fftw.org/) Catalogue identifier of previous version: AECW_v1_0 Journal reference of previous version: Comput. Phys. Comm. 180 (2009) 1004 Does the new version supersede the previous version?: Yes Nature of problem: Green's function molecular dynamics (GFMD) is a coarse-graining method that enables one to investigate the full elastic response of an interface between a semi-infinite solid and a contact while taking only the surface atoms in the solid into consideration. The effect of long-range elastic deformations on the surface atoms from the semi-infinite solid is replaced by effective elastic interactions, thus reducing the problem from three dimensions to two dimensions without compromising the physical essence of the problem. Solution method: See "Nature of problem". Reasons for new version: The basic theory underlying the new version is essentially the same as the previous one, while the special treatment to reduce the finite size effect on effective elastic coefficients at the Γ-point is now realized in a physically meaningful manner. Finite size effects are an important issue in molecular dynamics simulations, particularly for GFMD, they result in a violation of the acoustic sum rule (ASR) for the effective elastic coefficients measured at the Γ-point ( Φ). In the previous implementation, the effective elastic coefficients measured at the Γ-point were altered by setting their eigenvalues corresponding to the acoustic modes to zero. This scheme was found to work well for simple Bravais lattices as long as only atoms within the last layer were treated as Green's function atoms. However, it failed to function as expected in all other cases. We therefore adopt a new algorithm to enforce the ASR for Φ (Kong, 2010 [3]) which is implemented in this revision. Summary of revisions: Assuming the lattice under study consists of surface unit cells with n basis atoms labeled by k=1,2,…,n. When all atoms in the lattice are moved by the same amount, i.e., the crystal is rigidly translated, the force on any atom must be zero. This is known as the translational invariance, leading to the so-called acoustic sum rule: ∑Φ(Γ)=0 where Φ(Γ) is the kα,kβ component of the effective elastic coefficients at the Γ-point; we will denote it as Φ hereafter. α and β enumerate the Cartesian directions. In addition, Φ should be Hermitian (or symmetric, since at the Γ-point, the imaginary part of Φ is zero.) because of the commutative nature of the force constants: Φkα,kβΓ=Φkβ,kαΓ. These two properties are expected for Φ, yet the ASR is not satisfied during the measurement (done by FixGFC) because of the finite size effect. A scheme is therefore needed to enforce ASR on Φ afterwards, while the symmetric nature of Φ should be retained. We list below the detailed scheme adopted to enforce ASR implemented in the improved version of GFMD together with some other revisions to the code after the previous release. Restrictions: By adopting the new method to enforce the acoustic sum rule, the restriction that atoms in the Green's function slab must be in the same layer is lifted, while it is still necessary to ensure that the mean equilibrium positions of atoms in the Green's function slab satisfy the Born-von Karman boundary condition. In addition, only deformations within the harmonic regime are expected in the slab during Green's function molecular dynamics simulations. Additional comments: The new version is not compatible with the previous one: the contents in the binary file are different and therefore the effective elastic coefficients measured by the previous version of FixGFC cannot be used by the current version of FixGFMD. Running time: FixGFC varies from minutes to days, like a typical molecular dynamics simulation, depending on the system size, the number of processors used, and the complexity of the force field. FixGFMD varies from seconds to hours, depending on the system size and the number of processors used.

  15. Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure.

    PubMed

    Fukui, Miho; Goda, Akiko; Komamura, Kazuo; Nakabo, Ayumi; Masaki, Mitsuru; Yoshida, Chikako; Hirotani, Shinichi; Lee-Kawabata, Masaaki; Tsujino, Takeshi; Mano, Toshiaki; Masuyama, Tohru

    2016-02-01

    While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = -0.33, p < 0.05; r = -0.28, p < 0.05, respectively), and HR (r = -0.31, p < 0.05; r = -0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction. PMID:25351137

  16. 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

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

    PubMed Central

    2014-01-01

    Background In patients with anomalous left coronary artery from the pulmonary artery (ALCAPA) left ventricular (LV) dilatation and dysfunction evolves due to diminished myocardial perfusion caused by coronary steal phenomenon. Using late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) imaging, myocardial scarring has been shown in ALCAPA patients late after repair, however the incidence of scarring before surgery and its impact on postoperative course after surgical repair remained unknown. Methods 8 ALCAPA-patients (mean age 10.0 ± 5.8 months) underwent CMR before and early after (mean 4.9 ± 2.5 months) coronary reimplantation procedures. CMR included functional analysis and LGE for detection of myocardial scars. Results LV dilatation (mean LVEDVI 171 ± 94 ml/m2) and dysfunction (mean LV-EF 22 ± 10 %) was present in all patients and improved significantly after surgery (mean LVEDV 68 ± 42 ml/m2, p = 0.02; mean LV-EF 58 ± 19 %, p < 0.001). Preoperative CMR revealed myocardial scarring in 2 of the 8 patients and did not predict postoperative course. At follow-up CMR, one LGE-positive patient showed delayed recovery of LV function while myocardial scarring was still present in both patients. In two patients new-onset transmural scarring was found, although functional recovery after operation was sufficient. One of them showed a stenosis of the left coronary artery and required resurgery. Conclusions Despite diminished myocardial perfusion and severely compromised LV function, myocardial scarring was preoperatively only infrequently present. Improvement of myocardial function was independent of new-onset scarring while the impact of preoperative scarring still needs to be defined. PMID:24387660

  18. Human Cardiac Function Simulator for the Optimal Design of a Novel Annuloplasty Ring with a Sub-valvular Element for Correction of Ischemic Mitral Regurgitation.

    PubMed

    Baillargeon, Brian; Costa, Ivan; Leach, Joseph R; Lee, Lik Chuan; Genet, Martin; Toutain, Arnaud; Wenk, Jonathan F; Rausch, Manuel K; Rebelo, Nuno; Acevedo-Bolton, Gabriel; Kuhl, Ellen; Navia, Jose L; Guccione, Julius M

    2015-06-01

    Ischemic mitral regurgitation is associated with substantial risk of death. We sought to: (1) detail significant recent improvements to the Dassault Systèmes human cardiac function simulator (HCFS); (2) use the HCFS to simulate normal cardiac function as well as pathologic function in the setting of posterior left ventricular (LV) papillary muscle infarction; and (3) debut our novel device for correction of ischemic mitral regurgitation. We synthesized two recent studies of human myocardial mechanics. The first study presented the robust and integrative finite element HCFS. Its primary limitation was its poor diastolic performance with an LV ejection fraction below 20% caused by overly stiff ex vivo porcine tissue parameters. The second study derived improved diastolic myocardial material parameters using in vivo MRI data from five normal human subjects. We combined these models to simulate ischemic mitral regurgitation by computationally infarcting an LV region including the posterior papillary muscle. Contact between our novel device and the mitral valve apparatus was simulated using Dassault Systèmes SIMULIA software. Incorporating improved cardiac geometry and diastolic myocardial material properties in the HCFS resulted in a realistic LV ejection fraction of 55%. Simulating infarction of posterior papillary muscle caused regurgitant mitral valve mechanics. Implementation of our novel device corrected valve dysfunction. Improvements in the current study to the HCFS permit increasingly accurate study of myocardial mechanics. The first application of this simulator to abnormal human cardiac function suggests that our novel annuloplasty ring with a sub-valvular element will correct ischemic mitral regurgitation. PMID:25984248

  19. Diaphragmatic plication offers functional improvement in dyspnoea and better pulmonary function with low morbidity.

    PubMed

    Gazala, Sayf; Hunt, Ian; Bdard, Eric L R

    2012-09-01

    A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was as follows: In adults with unilateral diaphragmatic paralysis, does diaphragmatic plication offer functional improvement in dyspnoea, better pulmonary function tests (PFTs) and return to activity? A total of 126 papers were found using the reported search, of which 13 represented the best evidence to answer the clinical question. The authors, date and country of publication, patient group studied, surgical approach, study type, relevant outcomes and results of these articles are tabulated. Those articles reporting improvement in PFTs following plication, documented this benefit in the following parameters: mean forced vital capacity (range 17-40%), forced expiratory volume at 1 sec (range 21-27%), functional residual capacity (range 20-21%) and total lung capacity (range 16-19%). The percentage of postoperative improvement in shortness of breath as measured by a dyspnoea score was reported to be between 90 and 96% in the thoracotomy group and 100% in the Video Assisted Thoracoscopic Surgery (VATS) group, the dyspnoea score that was used in all the studies was a visual analogue scale between 0 and 10 where 0 is no dyspnoea and 10 is the worst dyspnoea a patient can have. One of the studies reported postoperative normalization in ventilation perfusion scan (VQ) scan parameters when compared with the preoperative mismatch. Complication rate was similar between the two groups, while the mortality rate was 4% in the thoracotomy group and 0% in the VATS group. The total number of patients included in all the studies combined was 161. All reports included in this review are observational studies (one cohort study and the remainder being case series); therefore, the risk of selection, information and publication biases are high and conclusions should be implemented with caution. We conclude that diaphragmatic plication can improve the functional status, shortness of breath and PFTs of patients with unilateral diaphragm paralysis. Patients undergoing a VATS approach appear to have more advantages in objective and subjective measures (including PFTs, dyspnoea score, length of hospital stay and postoperative complications). Further research with high-quality study designs is advised, focussing mainly on the long-term benefits and assessment of health-related quality of life. PMID:22691375

  20. Influence of naturally acquired feline leukemia virus (FeLV) infection on the phagocytic and respiratory burst activity of neutrophils and monocytes of peripheral blood.

    PubMed

    Hoffmann-Jagielska, M; Winnicka, A; Jagielski, D; Micu?, J; Zmudzka, M; Lechowski, R

    2005-01-01

    The purpose of this study was cytometric evaluation of phagocytic and oxidative burst activity of neutrophils and monocytes in cats naturally infected with FeLV. To conduct the study, the peripheral blood was obtained from 33 cats naturally infected with FeLV. The control group consisted of 30 FeLV-, FIV-, clinically healthy cats. The percentage of phagocytizing neutrophils of peripheral blood was lower in FeLV+ than in FeLV- cats. The percentage of neutrophils and monocytes in which an oxidative burst occurred was lower in FeLV+ than in FeLV-animals. Also an oxidative product formation in neutrophils after E. coli and PMA stimulation was lower in FeLV+ than in FeLV-animals. Obtained results allow to conclude that diminished phagocytic and oxidative burst activity of peripheral blood leukocytes may cause impairment of innate immunity in cats infected with FeLV. PMID:15989127

  1. Oral bisoprolol improves surgical field during functional endoscopic sinus surgery

    PubMed Central

    Jacob, Sumitha Mary; Chandy, Tony Thomson; Cherian, Verghese T

    2014-01-01

    Background: The success of functional endoscopic sinus surgery (FESS) depends on visual clarity of the surgical field, through the endoscope. The objective of this double-blind, randomized, controlled study was to determine if a pre-operative dose of bisoprolol (2.5 mg) would reduce the bleeding during FESS and improve the visualization of the operative field. Materials and Methods: Thirty American Society of Anesthesiologists I or II patients, scheduled for FESS were randomized to receive either a placebo (Group A) or 2.5 mg of bisoprolol (Group B) 90 min prior to the surgery. All the patients received standard anesthesia and monitoring. The aim was to maintain the mean arterial pressure (MAP) of 60-70 mmHg, by titrating dose of isoflurane and fentanyl. The concentration of isoflurane used was recorded every 15 min. At the end of the surgery, the volume of blood loss was measured and the surgeon was asked to grade the operative field as per the Fromme-Boezaart Scale. Result: The blood loss was significantly (P < 0.0001) more in the control group (398.67 ± 228.79 ml) as compared with that in the bisoprolol group (110.67 ± 45.35 ml). The surgical field was graded better in those who received bisoprolol as compared with those in the control group (P − 0.0001). The volume percent of isoflurane and the dose of fentanyl used was significantly lower in those who received bisoprolol. During the operative period, the MAPs were 70.0 ± 2.7 (Group A) and 62.6 ± 3.6 mmHg (Group B) and the heart rate was 99.8 ± 5.0/min (Group A) and 69.2 ± 4.4/min (Group B). These differences were statistically significant ( P − 0.001). Conclusion: This clinical trial has demonstrated that administration of a single pre-operative dose of bisoprolol (2.5 mg) can significantly reduce the blood loss during FESS and improve the visualization of the operating field. PMID:24574595

  2. Exercise training improves endothelial function in young prehypertensives

    PubMed Central

    Beck, Darren T; Casey, Darren P; Martin, Jeffrey S; Emerson, Blaze D; Braith, Randy W

    2015-01-01

    Prehypertensives exhibit marked endothelial dysfunction, a risk factor for future cardiovascular morbidity and mortality. However, the ability of exercise to ameliorate endothelial dysfunction in prehypertensives is grossly underinvestigated. This prospective randomized and controlled study examined the separate effects of resistance and endurance training on conduit artery endothelial function in young prehypertensives. Forty-three unmedicated prehypertensive (systolic blood pressure [SBP]=120–139 mmHg; diastolic blood pressure [DBP]=80–89 mmHg) but otherwise healthy men and women and 15 normotensive matched time-controls (NMTC); n = 15) between 18 and 35 y of age met screening requirements and participated in the study. Prehypertensive subjects were randomly assigned to either a resistance exercise training (PHRT; n = 15), endurance exercise training (PHET; n = 13) or time-control group (PHTC; n = 15). The treatment groups performed exercise training three days per week for eight weeks. The control groups did not initiate exercise programs throughout the study. Flow mediated dilation (FMD) of the brachial artery, biomarkers of enodothelial function and peripheral blood pressure were evaluated before and after exercise intervention or time-matched control. PHRT and PHET reduced resting SBP (9.6 ± 3.6 and 11.9 ± 3.4 mmHg, respectively; P < 0.05) and DBP (8.0 ± 5.1 and 7.2 ± 3.4 mmHg, respectively; P < 0.05). Exercise training improved brachial artery FMD absolute diameter, percent dilation and normalized percent dilation by 30%, 34% and 19% for PHRT, P < 0.05; and by 54%, 63% and 75% for PHET, P < 0.05; respectively. PHRT and PHET increased plasma concentrations of 6-keto prostaglandin F1α (19% and 22%, respectively; P < 0.05), NOx (19% and 23%, respectively; P < 0.05), and reduced endothelin-1 by (16% and 24%, respectively; P < 0.01). This study provides novel evidence that resistance and endurance exercise separately have beneficial effects on resting peripheral blood pressure, brachial artery FMD and endothelial-derived vasoactive agents in young prehypertensives. PMID:23760009

  3. Exercise training improves endothelial function in young prehypertensives.

    PubMed

    Beck, Darren T; Casey, Darren P; Martin, Jeffrey S; Emerson, Blaze D; Braith, Randy W

    2013-04-01

    Prehypertensives exhibit marked endothelial dysfunction, a risk factor for future cardiovascular morbidity and mortality. However, the ability of exercise to ameliorate endothelial dysfunction in prehypertensives is grossly underinvestigated. This prospective randomized and controlled study examined the separate effects of resistance and endurance training on conduit artery endothelial function in young prehypertensives. Forty-three unmedicated prehypertensive (systolic blood pressure [SBP]=120-139 mmHg; diastolic blood pressure [DBP]=80-89 mmHg) but otherwise healthy men and women and 15 normotensive matched time-controls (NMTC); n = 15) between 18 and 35 y of age met screening requirements and participated in the study. Prehypertensive subjects were randomly assigned to either a resistance exercise training (PHRT; n = 15), endurance exercise training (PHET; n = 13) or time-control group (PHTC; n = 15). The treatment groups performed exercise training three days per week for eight weeks. The control groups did not initiate exercise programs throughout the study. Flow mediated dilation (FMD) of the brachial artery, biomarkers of enodothelial function and peripheral blood pressure were evaluated before and after exercise intervention or time-matched control. PHRT and PHET reduced resting SBP (9.6 ± 3.6 and 11.9 ± 3.4 mmHg, respectively; P < 0.05) and DBP (8.0 ± 5.1 and 7.2 ± 3.4 mmHg, respectively; P < 0.05). Exercise training improved brachial artery FMD absolute diameter, percent dilation and normalized percent dilation by 30%, 34% and 19% for PHRT, P < 0.05; and by 54%, 63% and 75% for PHET, P < 0.05; respectively. PHRT and PHET increased plasma concentrations of 6-keto prostaglandin F1α (19% and 22%, respectively; P < 0.05), NO x (19% and 23%, respectively; P < 0.05), and reduced endothelin-1 by (16% and 24%, respectively; P < 0.01). This study provides novel evidence that resistance and endurance exercise separately have beneficial effects on resting peripheral blood pressure, brachial artery FMD and endothelial-derived vasoactive agents in young prehypertensives. PMID:23760009

  4. Strategies for improving the functionality of an affinity bioreactor.

    PubMed

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

    2005-12-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2000-01-01

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

  6. [Epidemiology of FeLV and FIV infection in the Federal Republic of Germany].

    PubMed

    Fuchs, A; Binzel, L; Lonsdorfer, M

    1994-06-01

    In a nationwide study 6101 cats were tested for presence of feline leukemia virus (FeLV) antigen and for feline immunodeficiency virus (FIV) antibodies utilizing enzyme linked immunosorbent assay (ELISA). 21.8% of the German cat population may be FeLV- and/or FIV-positive. Of the animals tested, 13.4% were found to be FeLV carriers, while 8.4% showed evidence of FIV infection. Infection with both viruses was identified in 2.1% of the cats tested. Of the animals showing clinical symptoms, nearly one cat in three was found to be carrying either one or both of the viruses. Male cats were more likely to be infected then were females, similarly as were free-roaming cats, compared with confined cats; domestic cats, compared with purebred cats; and cats > 6 years old, compared with younger cats. PMID:8048038

  7. Reassessment of feline leukaemia virus (FeLV) vaccines with novel sensitive molecular assays.

    PubMed

    Hofmann-Lehmann, Regina; Tandon, Ravi; Boretti, Felicitas S; Meli, Marina L; Willi, Barbara; Cattori, Valentino; Gomes-Keller, Maria A; Ossent, Pete; Golder, Matthew C; Flynn, J Norman; Lutz, Hans

    2006-02-20

    We previously described antigen negative, provirus positive cats. Subsequently, we hypothesized that efficacious FeLV vaccines cannot prevent minimal viral replication. Thus, we vaccinated cats with either a canarypox-vectored live or a killed virus vaccine and analyzed the challenge outcome with quantitative PCR and a newly established real-time RT-PCR. When judged by conventional parameters (antigenaemia, virus isolation), most of the vaccinated cats were, as expected, protected from persistent viraemia. However, all cats were found to be plasma viral RNA positive. The loads were significantly associated with the infection outcome. Thus, commonly used FeLV vaccines understood to be successful model antiretroviral vaccines protecting against FeLV-related diseases do not confer sterilizing immunity. PMID:16198454

  8. Landslide risk assessment in the Göta Älv river valley to limit consequences of climate change on society

    NASA Astrophysics Data System (ADS)

    Hedlund, Jonas; Lind, Bo; Tremblay, Marius; Zackrisson, Peter; Cederbom, Charlotte

    2010-05-01

    Higher temperatures, higher average precipitation and increased occurrence of extreme rainfall events are some expected climate changes in Sweden during the coming 70-100 years. Due to the changing climate the risk for floods, erosion and landslides are expected to increase. in large parts of the country. To prevent extensive floodings and damages of cities and infrastructure around Lake Vänern, it is necessary to allow controlled overflow from Lake Vänern through the river Göta Älv. An overflow in the river, in turn, leads to increased risk for erosion and landslides along the Göta Älv valley. In order to meet the upcoming climate changes and to handle the increasing flows through the river, we need to improve the knowledge of the stability of the entire river bank. The Swedish Government has commissioned the Swedish Geotechnical Institute (SGI) to investigate the landslide potential of the Göta Älv valley, taking the predicted climate changes into consideration. The investigated area includes the parts of Göta Älv that could be affected by the increased flows from Lake Vänern; areas where the increased flow will affect stability and where landslides could cause serious damages or damming of the river. The investigation area includes c. 90 km of the Göta Älv river plus tributaries in connection to Göta Älv. In the landslide risk analyses developed for Göta Älv, the likelihood of landslides and estimation of the subsequent consequences are included. The methodology involves mapping of landslide hazards and a judgement of the risk area on the basis of a risk matrix. The landslide risk analysis allows for an assessment of where geotechnical reinforcements would be necessary. A cost estimation for the required reinforcement measures is also provided. In areas where the estimated risk for a landslide is low (e.g. limited consequences), stability mapping in accordance with the model used by the Swedish Civil Contingencies Agency (MSB) is developed; mapping that extends beyond residential areas. The submarine river topography has been mapped by multi-ray sonar and automatic stations measuring slope-inclination, groundwater- and porewater pressure and water level has been installed around and in the river. However, there is a need for improving the mapping methods of the river, including data gathering and risk estimation. The outer and inner erosion potential of the Göta Älv is not fully known and more information regarding the river floor and shores are required. Hence, analysis and measures of erosion and sediment transportation, combined with the bathymetric and topographic conditions, are performed. Moreover, new methods for landslide risk analyses that include the impact of climate change on geotechnical conditions (e.g. porewater pressure) are evaluated.

  9. Improving Sensorimotor Function and Adaptation using Stochastic Vestibular Stimulation

    NASA Technical Reports Server (NTRS)

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

    2014-01-01

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

  10. Addition of substitution of simian virus 40 enhancer sequences into the Moloney murine leukemia virus (M-MuLV) long terminal repeat yields infectious M-MuLV with altered biological properties.

    PubMed Central

    Hanecak, R; Pattengale, P K; Fan, H

    1988-01-01

    Moloney murine leukemia virus (M-MuLV) is a replication-competent retrovirus which induces T-cell lymphoma in mice. The enhancer sequences present within the M-MuLV long terminal repeat (LTR) region of the proviral genome have been shown to influence the disease specificity of the virus strongly. We examined the contribution of the M-MuLV enhancers to the transcriptional activity and pathogenesis of M-MuLV by constructing LTRs containing heterologous enhancer elements. The simian virus 40 enhancer region (72- and 21-base-pair repeats) was inserted into the U3 region (at -150 base pairs) of the M-MuLV LTR (Mo + SV) and also into a deleted form of the LTR which lacks the M-MuLV enhancer sequences (delta Mo + SV). These chimeric LTRs were used to generate infectious M-MuLVs by transfection of corresponding proviral plasmids into mouse fibroblasts. The relative infectivities of Mo + SV and delta Mo + SV recombinant viruses as determined by rat XC cell plaque assay and reverse transcriptase assay were 60 to 70% of wild-type M-MuLV levels. To study the pathogenicity of these two recombinant viruses, we inoculated newborn NIH Swiss mice with either Mo + SV or delta Mo + SV M-MuLV. Both viruses induced disease more slowly than M-MuLV, which induces disease 2 to 4 months postinoculation. Mo + SV M-MuLV-inoculated animals became moribund at 3 to 13 months postinoculation, whereas delta Mo + SV M-MuLV-inoculated animals became moribund at 6 to 24 months postinoculation. The tumors induced by the two viruses were characterized histologically and molecularly. Mo + SV M-MuLV-induced tumors were primarily T-cell-derived lymphoblastic lymphomas containing extensive rearrangements of the T-cell receptor beta gene. In contrast, delta Mo + SV M-MuLV induced pre-B- and B-cell lymphoblastic lymphomas, B-cell-derived follicular-center cell lymphomas, and acute myeloid leukemia. The delta Mo + SV tumor DNAs from B-lineage tumors were typically rearranged at the immunoglobulin gene loci and contained germ line configurations of the T-cell receptor beta gene. Southern blot hybridization confirmed that the tumor DNAs contained the predicted Mo + SV M-MuLV or delta Mo + SV M-MuLV provirus. Images PMID:2836623

  11. 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.

  12. Improving Treatment Integrity through a Functional Approach to Intervention Support

    ERIC Educational Resources Information Center

    Liaupsin, Carl J.

    2015-01-01

    A functional approach to intervention planning has been shown to be effective in reducing problem behaviors and promoting appropriate behaviors in children and youth with behavior disorders. When function-based intervention plans are not successful, it is often due to issues of treatment integrity in which teachers omit or do not sufficiently…

  13. SVM-based classification of LV wall motion in cardiac MRI with the assessment of STE

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

    In this paper, we propose an automated method to classify normal/abnormal wall motion in Left Ventricle (LV) function in cardiac cine-Magnetic Resonance Imaging (MRI), taking as reference, strain information obtained from 2D Speckle Tracking Echocardiography (STE). Without the need of pre-processing and by exploiting all the images acquired during a cardiac cycle, spatio-temporal profiles are extracted from a subset of radial lines from the ventricle centroid to points outside the epicardial border. Classical Support Vector Machines (SVM) are used to classify features extracted from gray levels of the spatio-temporal profile as well as their representations in the Wavelet domain under the assumption that the data may be sparse in that domain. Based on information obtained from radial strain curves in 2D-STE studies, we label all the spatio-temporal profiles that belong to a particular segment as normal if the peak systolic radial strain curve of this segment presents normal kinesis, or abnormal if the peak systolic radial strain curve presents hypokinesis or akinesis. For this study, short-axis cine- MR images are collected from 9 patients with cardiac dyssynchrony for which we have the radial strain tracings at the mid-papilary muscle obtained by 2D STE; and from one control group formed by 9 healthy subjects. The best classification performance is obtained with the gray level information of the spatio-temporal profiles using a RBF kernel with 91.88% of accuracy, 92.75% of sensitivity and 91.52% of specificity.

  14. Weakly coupled hyperbolic systems modeling the circulation of FeLV in structured feline populations.

    PubMed

    Fitzgibbon, W E; Langlais, M

    2000-05-01

    Global existence and regularity results are provided for weakly coupled first order hyperbolic systems modeling the propagation of the Feline Leukemia Virus (FeLV), a retrovirus of domestic cats (Felis catus). In a simple example we find a threshold parameter yielding endemic stationary states. PMID:10804261

  15. Right ventricular septal pacing- clinical and electrical predictors for LV contraction asynchrony

    PubMed Central

    Iorgulescu, C; Radu, DA; Constantinescu, D; Caldararu, C; Dorobantu, M

    2014-01-01

    Purpose: Prolonged pacing from the right ventricular apex (RV) is associated with the LV dyssynchrony leading to progressive left ventricular dysfunction and increased morbidity and mortality. Alternate RV pacing sites-in particular the mid- RV septum and the RV outflow tract (RVOT) septum were considered, but no clear benefit was proven till now for this pacing sites. This may be due to the heterogeneity of the RV septal positions and to the significant number of leads placed on the RV free wall. The aim of this study is to find a reliable method of septal lead placement and to identify those pacing sites which provide better LV electrical activation Methods: 50 consecutive patients referred for pacemaker implants due to AV block were included. Patients with history of heart failure or LVEF < 50% at the implant were excluded. All patients had RV leads placed in septal position. This was achieved with a double curved stilet with the distal curve aimed posteriorly. RV septum and RVOT were mapped during implant aiming for a narrow paced QRS with an axis as close to normal as possible. Pacing lead position was evaluated during the implant using fluoroscopy (AP and LAO 40 °) and than by 12 lead ECG and echo. IntraLV dyssynchrony was evaluated during pacing using SPWMD in short axis parasternal view and the TDI septal to lateral ∆ t. Paced QRS duration and axis were also recorded. The correlation was sought between lead position evaluated by Rx and by echo and between paced QRS duration and axis and LV dyssynchrony. Results: 92%(46) of the patients had the lead in septal position RV (32 in the mid-septal RV and 14 in RVOT), while 8% (4 pts) had the lead on the RVOT RV free wall as shown by echo. An anterior-oriented lead in the left anterior oblique fluoroscopic projection was specific for free wall position while positive QRS in DI in RVOT position was suggestive for free wall position on the ECG. No correlation was made between paced QRS axis and LV dyssynchrony while the QRS duration of > 160 ms was associated with significant LV dyssynchrony (SPWMD > 130 ms and to lateral septal ∆ t > 70 ms). Conclusions: RV lead placement on the RV septum can be reliably achieved using a specially curved stilet and the LAO projection for confirmation. The wide paced QRS is correlated with significant intra LV dyssynchrony and therefore the RV pacing site with the narrowest QRS should be sought. PMID:27057256

  16. Detection of Antibodies to the Feline Leukemia Virus (FeLV) Transmembrane Protein p15E: an Alternative Approach for Serological FeLV Detection Based on Antibodies to p15E

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-06-01

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

  18. Hypnotic Relaxation and Yoga to Improve Sleep and School Functioning

    ERIC Educational Resources Information Center

    Perfect, Michelle M.; Smith, Bradley

    2016-01-01

    Sleep insufficiency, defined as inadequate sleep duration, poor sleep quality, and daytime sleepiness, has been linked with students' learning and behavioral outcomes at school. However, there is limited research on interventions designed to improve the sleep of school-age children. In order to promote more interest on this critical topic, we

  19. Hypnotic Relaxation and Yoga to Improve Sleep and School Functioning

    ERIC Educational Resources Information Center

    Perfect, Michelle M.; Smith, Bradley

    2016-01-01

    Sleep insufficiency, defined as inadequate sleep duration, poor sleep quality, and daytime sleepiness, has been linked with students' learning and behavioral outcomes at school. However, there is limited research on interventions designed to improve the sleep of school-age children. In order to promote more interest on this critical topic, we…

  20. 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…

  1. Executive function needs to be targeted to improve social functioning with Cognitive Remediation Therapy (CRT) in schizophrenia.

    PubMed

    Penadés, Rafael; Catalán, Rosa; Puig, Olga; Masana, Guillem; Pujol, Núria; Navarro, Víctor; Guarch, Joana; Gastó, Cristóbal

    2010-05-15

    While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established, the relationship between cognitive and functional change in the context of treatments is far from clear. The current paper tries to identify which cognitive changes lead to improvements in daily functioning among persons with chronic schizophrenia who had current negative symptoms and evidenced neuropsychological impairments. In a previous work, Cognitive Remediation Therapy (CRT) was compared with a control therapy, involving similar length of therapist contact but different targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and functioning [Schizophrenia Research, 87 (2006) 323-331]. Subsequently, analyses of covariance (ANCOVA) were conducted with baseline and cognitive change scores as covariates to test whether cognitive change predicted change in functioning. Additionally, statistical tests to establish the mediation path with significant variables were performed. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present. PMID:20381164

  2. Overview of solid particle LV seeding techniques used at UTRC

    NASA Astrophysics Data System (ADS)

    Patrick, W. P.

    1985-10-01

    Due to the failure of existing seeders to meet the stringent specifications required for benchmark experiments in high pressure, high temperature, rapidly accelerating flowfields, an effort is made to improve an existing solid particle seeder. The goal is to produce a more monodisperse seed from the 0.3 micro alumina powder with more than 99 percent of the particles in the submicron range while maintaining a high seeding rate. Coiled-wire inserts are installed within the ends of the nitrogen injection lines in the primary seeder to produce swirling conical jets to vigorously agitate the seed bed. A secondary swirler, constructed from a 25 cm length of 3.8 cm ID steel pipe having threaded end caps, is connected to the output line of the primary seeder. The seeded nitrogen from the primary seeder is injected tangentially at near sonic velocity into the secondary swirler 9.4 cm above its base. Independently controlled auxiliary nitrogen used to increase the swirl in the secondary chamber is also injected tangentially 2.5 cm below the seeded nitrogen lines. Large seed particles are collected by bleeds in the swirler cap and directed overboard. The remaining seeded nitrogen is collected on the center line of the secondary swirler and ducted to the rig.

  3. Bayesian Estimation of Conditional Independence Graphs Improves Functional Connectivity Estimates.

    PubMed

    Hinne, Max; Janssen, Ronald J; Heskes, Tom; van Gerven, Marcel A J

    2015-11-01

    Functional connectivity concerns the correlated activity between neuronal populations in spatially segregated regions of the brain, which may be studied using functional magnetic resonance imaging (fMRI). This coupled activity is conveniently expressed using covariance, but this measure fails to distinguish between direct and indirect effects. A popular alternative that addresses this issue is partial correlation, which regresses out the signal of potentially confounding variables, resulting in a measure that reveals only direct connections. Importantly, provided the data are normally distributed, if two variables are conditionally independent given all other variables, their respective partial correlation is zero. In this paper, we propose a probabilistic generative model that allows us to estimate functional connectivity in terms of both partial correlations and a graph representing conditional independencies. Simulation results show that this methodology is able to outperform the graphical LASSO, which is the de facto standard for estimating partial correlations. Furthermore, we apply the model to estimate functional connectivity for twenty subjects using resting-state fMRI data. Results show that our model provides a richer representation of functional connectivity as compared to considering partial correlations alone. Finally, we demonstrate how our approach can be extended in several ways, for instance to achieve data fusion by informing the conditional independence graph with data from probabilistic tractography. As our Bayesian formulation of functional connectivity provides access to the posterior distribution instead of only to point estimates, we are able to quantify the uncertainty associated with our results. This reveals that while we are able to infer a clear backbone of connectivity in our empirical results, the data are not accurately described by simply looking at the mode of the distribution over connectivity. The implication of this is that deterministic alternatives may misjudge connectivity results by drawing conclusions from noisy and limited data. PMID:26540089

  4. Bayesian Estimation of Conditional Independence Graphs Improves Functional Connectivity Estimates

    PubMed Central

    Hinne, Max; Janssen, Ronald J.; Heskes, Tom; van Gerven, Marcel A.J.

    2015-01-01

    Functional connectivity concerns the correlated activity between neuronal populations in spatially segregated regions of the brain, which may be studied using functional magnetic resonance imaging (fMRI). This coupled activity is conveniently expressed using covariance, but this measure fails to distinguish between direct and indirect effects. A popular alternative that addresses this issue is partial correlation, which regresses out the signal of potentially confounding variables, resulting in a measure that reveals only direct connections. Importantly, provided the data are normally distributed, if two variables are conditionally independent given all other variables, their respective partial correlation is zero. In this paper, we propose a probabilistic generative model that allows us to estimate functional connectivity in terms of both partial correlations and a graph representing conditional independencies. Simulation results show that this methodology is able to outperform the graphical LASSO, which is the de facto standard for estimating partial correlations. Furthermore, we apply the model to estimate functional connectivity for twenty subjects using resting-state fMRI data. Results show that our model provides a richer representation of functional connectivity as compared to considering partial correlations alone. Finally, we demonstrate how our approach can be extended in several ways, for instance to achieve data fusion by informing the conditional independence graph with data from probabilistic tractography. As our Bayesian formulation of functional connectivity provides access to the posterior distribution instead of only to point estimates, we are able to quantify the uncertainty associated with our results. This reveals that while we are able to infer a clear backbone of connectivity in our empirical results, the data are not accurately described by simply looking at the mode of the distribution over connectivity. The implication of this is that deterministic alternatives may misjudge connectivity results by drawing conclusions from noisy and limited data. PMID:26540089

  5. Radionuclide left ventricular dV/dt for the assessment of cardiac function in patients with coronary disease.

    PubMed

    Bianco, J A; Makey, D G; Laskey, W K; Shafer, R B

    1979-01-01

    To investigate potential uses of left-ventricular (LV) systolic ejection rate (LV dV/dt) in the evaluation of LV function, we examined the effect of exercise, angiotensin, and leg raising on LV ejection fraction and LV dV/dt in patients with coronary-artery disease. The following observations were made: a) LV ejection fraction and dV/dt changed proportionately, but in opposite directions, during supine exercise; b) LV ejection fraction and dV/dt decreased to a similar extent during angiotensin infusions; and c) LV ejection fraction and dV/dt were unchanged by leg raising. The changes in peak and mean LV dV/dt were similar. Regardless of the physiologic state, peak LV dV/dt occurred during the first third of systole. These data imply that in this population there were no specific advantages of LV dV/dt over LV ejection fraction in the evaluation of LV performance. PMID:430171

  6. Improvement of Ejection Fraction After Coronary Artery Bypass Grafting Surgery in Patients with Impaired Left Ventricular Function

    PubMed Central

    Haxhibeqiri-Karabdic, Ilirijana; Hasanovic, Aida; Kabil, Emir; Straus, Slavenka

    2014-01-01

    ABSTRACT Objectives: The present study evaluates our experience with aorto-coronary bypass grafting in patients with severe dysfunction of left ventricle (LV) and low ejection fraction-EF(<35%). Revascularization of myocardium in this settings remains contraversial because of concerns over morbidity, mortality and quality of life. Material and Methodes: Forty patients with severe coronary artery disease and dysfunction of LV (low ejection fraction <35%) underwent coronary artery bypass grafting in period of 3 years. Preoperative diagnostic of 40 patients was consisted of anamnesis, clinical exam, non-invasive methods EHO, MR and invasive diagnostic methods-cateterization. The major indication for surgery was severe anginal pain, heart failure symptoms and low ejection fraction. Internal mammary artery was used in all operated patients. Results: Average age of patients who have been operated was 59,8. In the present study, 81,3% were male and 18,8% female. We found one-vessel disease present in 2,5% (1/40) of patients, two -vessel disease in 40% (16/40), three-vessel disease in 42,5% (17/40) and four -vessel disease in 15% (6/40) of patients. One bypass grafting we implanted in 2,5% patients, two bypasses in 42,5%, three bypasses in 45 5%, and four bypasses in 10% of patients. Left ventricular ejection fraction assessed preoperativly was 18%-27% and postoperatively was improved to 31, 08% in period of 30 days. Conclusion: In patients with left ventricular dysfunction, coronary artery bypass grafting can be performed safely with improvement in quality of life and in left ventricular ejection fraction. PMID:25568566

  7. Improvement of tactile roughness discrimination acuity correlates with perception of improved hand function in patients after hand surgery

    PubMed Central

    Fujimoto, Shuhei; Kon, Noriko

    2016-01-01

    [Purpose] The purpose of this study was to elucidate how well patients’ perceptions related to the improvements in their hand function during hospitalization. [Subjects] Sixteen patients who were hospitalized after hand surgery. [Methods] Using the Japanese Society for Surgery of the Hand edition of the Quick-Disabilities of the Arm, Shoulder, and Hand questionnaire; tactile roughness discrimination acuity, motor imagery, motor function, sensory function, and pain of the upper limb were assessed at admission and discharge. Spearman’s rank-order correlation coefficients were calculated using the differences in all assessment items at admission and discharge. A multiple regression analysis (stepwise method) was performed to investigate factors that correlated with improvements in Quick-Disabilities of the Arm, Shoulder, and Hand scores. [Results] The improvement of tactile roughness discrimination acuity was significantly associated with patient perception of improved hand function. [Conclusion] The results suggest that an improvement in tactile roughness discrimination acuity was most strongly correlated with patient perception of improved hand function. PMID:27190473

  8. Improved motion invariant imaging with time varying shutter functions

    NASA Astrophysics Data System (ADS)

    Webster, Steve; Dorrell, Andrew

    2011-01-01

    In motion invariant photography, blur is introduced by a structured movement of the camera during capture. The structured movement results in a uniform blur which simplifies deblur through post-processing for objects moving at different speeds in a single motion plane. However motion invariance depends on the camera speed exceeding the object speed (in the image plane) by a significant amount. This can lead to noisy image results and may be a problem for implementation of the method in practice. We propose the introduction of a time varying shutter transmittance to this recently proposed computational imaging method and demonstrate through simulation how this can improve both the degree of motion invariance and the reconstructed image quality, despite a reduction in optical efficiency. Improvements in the order 6dB are demonstrated for the reconstructed, deblurred images in the presence of moderate noise. The work has the potential to bring motion invariant photography closer to use in real camera product.

  9. Work function measurements using an improved thermionic projection microscope

    NASA Astrophysics Data System (ADS)

    Hinrichs, C. H.; Mackie, W. A.; Cohen, Ira; Alin, Jack; Schnitzler, Don; Noel, Ian

    1994-12-01

    A quantitative thermionic projection microscope, employing computer image processing, is described. In this system, thermionic emission from a single-crystal hemispherical cathode is projected onto a phosphor screen and the resulting image is digitized by means of a video camera. Single-plane effective work functions for the highest emitting planes of the cathode may be measured to within a tenth of an electron volt.

  10. Prohibitin overexpression improves myocardial function in diabetic cardiomyopathy.

    PubMed

    Dong, Wen-Qian; Chao, Min; Lu, Qing-Hua; Chai, Wei-Li; Zhang, Wei; Chen, Xue-Ying; Liang, Er-Shun; Wang, Ling-Bo; Tian, Hong-Liang; Chen, Yu-Guo; Zhang, Ming-Xiang

    2016-01-01

    Prohibitin (PHB) is a highly conserved protein implicated in various cellular functions including proliferation, apoptosis, tumor suppression, transcription, and mitochondrial protein folding. However, its function in diabetic cardiomyopathy (DCM) is still unclear. In vivo, type 2 diabetic rat model was induced by using a high-fat diet and low-dose streptozotocin. Overexpression of the PHB protein in the model rats was achieved by injecting lentivirus carrying PHB cDNA via the jugular vein. Characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. Rats with DCM showed severe insulin resistance, left ventricular dysfunction, fibrosis and apoptosis. PHB overexpression ameliorated the disease. Cardiofibroblasts (CFs) and H9c2 cardiomyoblasts were used in vitro to investigate the mechanism of PHB in altered function. In CFs treated with HG, PHB overexpression decreased expression of collagen, matrix metalloproteinase activity, and proliferation. In H9c2 cardiomyoblasts, PHB overexpression inhibited apoptosis induced by HG. Furthermore, the increased phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was significantly decreased and the inhibited phosphorylation of Akt was restored in DCM. Therefore, PHB may be a new therapeutic target for human DCM. PMID:26623724

  11. Prohibitin overexpression improves myocardial function in diabetic cardiomyopathy

    PubMed Central

    Dong, Wen-qian; Chao, Min; Lu, Qing-hua; Chai, Wei-li; Zhang, Wei; Chen, Xue-ying; Liang, Er-shun; Wang, Ling-bo; Tian, Hong-liang; Chen, Yu-guo; Zhang, Ming-xiang

    2016-01-01

    Prohibitin (PHB) is a highly conserved protein implicated in various cellular functions including proliferation, apoptosis, tumor suppression, transcription, and mitochondrial protein folding. However, its function in diabetic cardiomyopathy (DCM) is still unclear. In vivo, type 2 diabetic rat model was induced by using a high-fat diet and low-dose streptozotocin. Overexpression of the PHB protein in the model rats was achieved by injecting lentivirus carrying PHB cDNA via the jugular vein. Characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. Rats with DCM showed severe insulin resistance, left ventricular dysfunction, fibrosis and apoptosis. PHB overexpression ameliorated the disease. Cardiofibroblasts (CFs) and H9c2 cardiomyoblasts were used in vitro to investigate the mechanism of PHB in altered function. In CFs treated with HG, PHB overexpression decreased expression of collagen, matrix metalloproteinase activity, and proliferation. In H9c2 cardiomyoblasts, PHB overexpression inhibited apoptosis induced by HG. Furthermore, the increased phosphorylation of extracellular signal–regulated kinase (ERK) 1/2 was significantly decreased and the inhibited phosphorylation of Akt was restored in DCM. Therefore, PHB may be a new therapeutic target for human DCM. PMID:26623724

  12. Activation of PPARδ signaling improves skeletal muscle oxidative metabolism and endurance function in an animal model of ischemic left ventricular dysfunction.

    PubMed

    Zizola, Cynthia; Kennel, Peter J; Akashi, Hirokazu; Ji, Ruiping; Castillero, Estibaliz; George, Isaac; Homma, Shunichi; Schulze, P Christian

    2015-05-01

    Exercise intolerance in heart failure has been linked to impaired skeletal muscle oxidative capacity. Oxidative metabolism and exercise capacity are regulated by PPARδ signaling. We hypothesized that PPARδ stimulation reverts skeletal muscle oxidative dysfunction. Myocardial infarction (MI) was induced in C57BL/6 mice and the development of ventricular dysfunction was monitored over 8 wk. Mice were randomized to the PPARδ agonist GW501516 (5 mg/kg body wt per day for 4 wk) or placebo 8 wk post-MI. Muscle function was assessed through running tests and grip strength measurements. In muscle, we analyzed muscle fiber cross-sectional area and fiber types, metabolic gene expression, fatty acid (FA) oxidation and ATP content. Signaling pathways were studied in C2C12 myotubes. FA oxidation and ATP levels decreased in muscle from MI mice compared with sham- operated mice. GW501516 administration increased oleic acid oxidation levels in skeletal muscle of the treated MI group compared with placebo treatment. This was accompanied by transcriptional changes including increased CPT1 expression. Further, the PPARδ-agonist improved running endurance compared with placebo. Cell culture experiments revealed protective effects of GW501516 against the cytokine-induced decrease of FA oxidation and changes in metabolic gene expression. Skeletal muscle dysfunction in HF is associated with impaired PPARδ signaling and treatment with the PPARδ agonist GW501516 corrects oxidative capacity and FA metabolism and improves exercise capacity in mice with LV dysfunction. Pharmacological activation of PPARδ signaling could be an attractive therapeutic intervention to counteract the progressive skeletal muscle dysfunction in HF. PMID:25713305

  13. Tetrahydrobiopterin Improves Endothelial Function in Cardiovascular Disease: A Systematic Review

    PubMed Central

    Wang, Qiongying; Yang, Mina; Xu, Han; Yu, Jing

    2014-01-01

    Background. Tetrahydrobiopterin (BH4) is a cofactor of nitric oxide synthase (NOS). Nitric oxide (NO) bioavailability is reduced during the early stage of vascular diseases, such as coronary artery disease, hypercholesterolemia, hypertension, and diabetic vasculopathy, and even throughout the entire progression of atherosclerosis. Methods. A literature search was performed using electronic databases (up to January 31, 2014), including MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), using an established strategy. Results. Fourteen articles were selected with a total of 370 patients. Ten of the fourteen studies showed a significant improvement in the endothelial dysfunction of various cardiovascular disease groups with BH4 supplementation compared with the control groups or placebos. Three studies showed no positive outcome, and one study showed that low-dose BH4 had no effect but that high-dose BH4 did have a significantly different result. Conclusions. This review concludes that supplementation with BH4 and/or augmentation of the endogenous levels of BH4 will be a novel approach to improve the endothelial dysfunction observed in various cardiovascular diseases. BH4 might be considered to be a new therapeutic agent to prevent the initiation and progression of cardiovascular disease. PMID:25548592

  14. 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

  15. 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

  16. 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; Hper, 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 810 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

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

    SciTech Connect

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

    1984-11-01

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

  18. 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.

  19. Regular Football Practice Improves Autonomic Cardiac Function in Male Children

    PubMed Central

    Fernandes, Luis; Oliveira, Jose; Soares-Miranda, Luisa; Rebelo, Antonio; Brito, Joao

    2015-01-01

    Background: The role of the autonomic nervous system (ANS) in the cardiovascular regulation is of primal importance. Since it has been associated with adverse conditions such as cardiac arrhythmias, sudden death, sleep disorders, hypertension and obesity. Objectives: The present study aimed to investigate the impact of recreational football practice on the autonomic cardiac function of male children, as measured by heart rate variability. Patients and Methods: Forty-seven male children aged 9 - 12 years were selected according to their engagement with football oriented practice outside school context. The children were divided into a football group (FG; n = 22) and a control group (CG; n = 25). The FG had regular football practices, with 2 weekly training sessions and occasional weekend matches. The CG was not engaged with any physical activity other than complementary school-based physical education classes. Data from physical activity, physical fitness, and heart rate variability measured in time and frequency domains were obtained. Results: The anthropometric and body composition characteristics were similar in both groups (P > 0.05). The groups were also similar in time spent daily on moderate-to-vigorous physical activities (FG vs. CG: 114 ± 64 vs. 87 ± 55 minutes; P > 0.05). However, the FG performed better (P < 0.05) in Yo-Yo intermittent endurance test (1394 ± 558 vs. 778 ± 408 m) and 15-m sprint test (3.06 ± 0.17 vs. 3.20 ± 0.23 s). Also, the FG presented enhanced autonomic function. Significant differences were detected (P < 0.05) between groups for low frequency normalized units (38.0 ± 15.2 vs. 47.3 ± 14.2 n.u (normalized units)), high frequency normalized units (62.1 ± 15.2 vs. 52.8 ± 14.2 n.u.), and LF:HF ratio (0.7 ± 0.4 vs. 1.1 ± 0.6 ms2). Conclusions: Children engaged with regular football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest. PMID:26448848

  20. 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

  1. High prevalence of non-productive FeLV infection in necropsied cats and significant association with pathological findings.

    PubMed

    Suntz, M; Failing, K; Hecht, W; Schwartz, D; Reinacher, M

    2010-07-01

    Applying a combination of semi-nested PCR and immunohistology (IHC), the presence of exogenous feline leukemia virus infection was studied in 302 necropsied cats with various disorders. 9% showed the classical outcome of persistent productive FeLV infection which was represented by FeLV antigen expression in different organs. 152 cats (50%) harboured exogenous FeLV-specific proviral sequences in the bone marrow but did not express viral antigen. These cats were considered as horizontally but non-productively infected. Statistical evaluation showed a significant association of non-productive horizontal FeLV infection with a variety of parameters. Non-productively infected cats were statistically significantly older and more often originated from animal shelters than cats without exogenous FeLV infection. Furthermore, some pathological disorders like anemia, panleukopenia, and purulent inflammation showed significant association with non-productive FeLV infection. No significant association was found with lymphosarcoma, known for a long time to be induced by productive FeLV infection. PMID:20398945

  2. Envelope Proteins of White Spot Syndrome Virus (WSSV) Interact with Litopenaeus vannamei Peritrophin-Like Protein (LvPT)

    PubMed Central

    Xie, Shijun; Zhang, Xiaojun; Zhang, Jiquan; Li, Fuhua; Xiang, Jianhai

    2015-01-01

    White spot syndrome virus (WSSV) is a major pathogen in shrimp cultures. The interactions between viral proteins and their receptors on the surface of cells in a frontier target tissue are crucial for triggering an infection. In this study, a yeast two-hybrid (Y2H) library was constructed using cDNA obtained from the stomach and gut of Litopenaeus vannamei, to ascertain the role of envelope proteins in WSSV infection. For this purpose, VP37 was used as the bait in the Y2H library screening. Forty positive clones were detected after screening. The positive clones were analyzed and discriminated, and two clones belonging to the peritrophin family were subsequently confirmed as genuine positive clones. Sequence analysis revealed that both clones could be considered as the same gene, LV-peritrophin (LvPT). Co-immunoprecipitation confirmed the interaction between LvPT and VP37. Further studies in the Y2H system revealed that LvPT could also interact with other WSSV envelope proteins such as VP32, VP38A, VP39B, and VP41A. The distribution of LvPT in tissues revealed that LvPT was mainly expressed in the stomach than in other tissues. In addition, LvPT was found to be a secretory protein, and its chitin-binding ability was also confirmed. PMID:26692362

  3. FIV, FeLV, and FIPV: interpretation and misinterpretation of serological test results.

    PubMed

    Barr, M C

    1996-08-01

    Serological testing is a common method of diagnosis of felina viral infections, including feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), and feline infectious peritonitis virus (FIPV). Infections with these viruses can be difficult to diagnose by clinical signs alone and are sometimes clinically inapparent for months after initial exposure. Serological testing to confirm a tentative diagnosis or as a screening tool for infection can be invaluable. However, serological tests must be used only with a thorough understanding of the mechanisms and abilities of the tests, and with recognition of their potential inadequacies and misinterpretations. This report summarizes the assays available for FIV, FeLV, and FIPV, and discusses merits and pitfalls associated with each test. PMID:8942210

  4. 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

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

    PubMed

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

    2009-04-17

    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 long terminal repeat (LTR)-specific small non-coding RNA is produced from a feline leukemia virus (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 kappaB signaling. Taken together, our findings suggest a possible role for this LTR transcript in FeLV pathogenesis. PMID:19336234

  6. Resistance to RadLV-induced leukemia: non-participation of splenic natural killer cells

    SciTech Connect

    St.-Pierre, Y.; Hugo, P.; Lemieux, S.; Lussier, G.; Potworowski, E.F.

    1988-08-01

    The phenotypic expression of genetically determined resistance to radiation leukemia virus (RadLV)-induced leukemia in mice has been shown to reside in the bone marrow. Because the bone marrow contains precursors of natural killer (NK) cells, known to play a role in retrovirally induced infections, and because these cells have been suggested as participating in resistance to radiation-induced leukemia, it was pertinent to establish whether their levels differed in strains of mice susceptible and resistant to leukemia. We therefore tested splenic NK cell levels in C57BL/Ka (susceptible) and B10.A(5R) (resistant) mice before viral inoculation, immediately after viral inoculation, and throughout the preleukemic period and showed that they were not different. This indicates that splenic NK cell levels have no bearing on the resistance to RadLV-induced leukemia and that other immune or non-immune mechanisms must be sought.

  7. The potential role and mechanisms of FeLV vaccine-induced neoplasms.

    PubMed

    Macy, D W

    1995-11-01

    Vaccine-induced sarcomas are reported to occur in 1 in 10,000 or less cats vaccinated with feline leukemia virus (FeLV) vaccines. The potential of local vaccine site adjuvant-associated inflammation plays in the pathogenesis of these tumors is probably significant. However, it is believed that the feline leukemia antigens contained within these vaccines also play an important role in malignant transformation. PMID:8820597

  8. Functionally gradient hard carbon composites for improved adhesion and wear

    NASA Astrophysics Data System (ADS)

    Narayan, Roger Jagdish

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

  9. An Improved Green's Function for Ion Beam Transport

    NASA Technical Reports Server (NTRS)

    Tweed, J.; Wilson, J. W.; Tripathi, R. K.

    2003-01-01

    Ion beam transport theory allows testing of material transmission properties in the laboratory environment generated by particle accelerators. This is a necessary step in materials development and evaluation for space use. The approximations used in solving the Boltzmann transport equation for the space setting are often not sufficient for laboratory work and those issues are the main emphasis of the present work. In consequence, an analytic solution of the linear Boltzmann equation is pursued in the form of a Green's function allowing flexibility in application to a broad range of boundary value problems. It has been established that simple solutions can be found for the high charge and energy (HZE) by ignoring nuclear energy downshifts and dispersion. Such solutions were found to be supported by experimental evidence with HZE ion beams when multiple scattering was added. Lacking from the prior solutions were range and energy straggling and energy downshift with dispersion associated with nuclear events. Recently, we have found global solutions including these effects providing a broader class of HZE ion solutions.

  10. Vitamin D supplement improved testicular function in diabetic rats.

    PubMed

    Ding, Chenzhao; Wang, Qinzhu; Hao, Yue; Ma, Xiaojun; Wu, Lina; du, Mengmeng; Li, Wen; Wu, Yang; Guo, Feng; Ma, Siyuan; Huang, Fengjuan; Qin, Guijun

    2016-04-22

    This study was designed to investigate the role that 1,25(OH)2D3 plays against testicular lesion in diabetic rats and try to find its possible mechanism of the steroidogenesis and the spermatogenesis. In diabetic rats, prolonged hyperglycemia evaluated inflammatory cytokines, damaged sperm production function and redox balance, diminished serum testosterone. After treated with 1,25(OH)2D3 at two different doses respectively for 12 months, all the alternations were effectively normalized. 1,25(OH)2D3 showed inhibitory effect on excessive inflammatory biomarkers and adjusted the expression reproductive genes and testicular androgen synthesis. It also upregulated Bcl-2 expression, decreased Bax and COX-2 expression and inhibited active caspase cascade (caspase 8 and caspase 3), which may preserved the testicular cells under diabetic condition. It revealed that vitamin D supplement may protect the cells through suppressing inflammation factors and alleviating cell apoptotic death, as well as upregulating the expression of genes related to reproductive and testosterone synthesis. PMID:27003251

  11. An improved Green's function for ion beam transport

    NASA Technical Reports Server (NTRS)

    Tweed, J.; Wilson, J. W.; Tripathi, R. K.

    2004-01-01

    Ion beam transport theory allows testing of material transmission properties in the laboratory environment generated by particle accelerators. This is a necessary step in materials development and evaluation for space use. The approximations used in solving the Boltzmann transport equation for the space setting are often not sufficient for laboratory work and those issues are the main emphasis of the present work. In consequence, an analytic solution of the linear Boltzmann equation is pursued in the form of a Green's function allowing flexibility in application to a broad range of boundary value problems. It has been established that simple solutions can be found for high charge and energy (HZE) ions by ignoring nuclear energy downshifts and dispersion. Such solutions were found to be supported by experimental evidence with HZE ion beams when multiple scattering was added. Lacking from the prior solutions were range and energy straggling and energy downshift with dispersion associated with nuclear events. Recently, we have found global solutions including these effects providing a broader class of HZE ion solutions. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  12. Silymarin improves vascular function of aged ovariectomized rats.

    PubMed

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

    2014-06-01

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

  13. 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.

  14. Inhibition of late Na+ current, a novel target to improve diastolic function and electrical abnormalities in Dahl salt-sensitive rats.

    PubMed

    Chi, Liguo; Belardinelli, Luiz; Zeng, Aliya; Hirakawa, Ryoko; Rajamani, Sridharan; Ling, Haiyun; Dhalla, Arvinder K

    2016-05-15

    Late Na(+) current (INaL) is enhanced in myocytes of animals with chronic heart failure and patients with hypertrophic cardiomyopathy. To define the role of INaL in diastolic heart failure, the effects of GS-458967 (GS-967), a potent INaL inhibitor on mechanical and electrical abnormalities, were determined in an animal model of diastolic dysfunction. Dahl salt-sensitive (DSS) rats fed a high-salt (HS) diet for 8 wk, compared with a normal salt (NS) diet, had increased left ventricular (LV) mass (1,257 ± 96 vs. 891 ± 34 mg) and diastolic dysfunction [isovolumic relaxation time (IVRT): 26.8 ± 0.5 vs. 18.9 ± 0.2 ms; early transmitral flow velocity/early mitral annulus velocity (E/E') ratio: 25.5 ± 1.9 vs. 14.9 ± 0.9]. INaL in LV myocytes from HS rats was significantly increased to 0.41 ± 0.02 from 0.14 ± 0.02 pA/pF in NS rats. The action potential duration (APD) was prolonged to 136 ± 12 from 68 ± 9 ms in NS rats. QTc intervals were longer in HS vs. NS rats (267 ± 8 vs. 212 ± 2 ms). Acute and chronic treatment with GS-967 decreased the enhanced INaL to 0.24 ± 0.01 and 0.17 ± 0.02 pA/pF, respectively, vs. 0.41 ± 0.02 pA/pF in the HS group. Chronic treatment with GS-967 dose-dependently reduced LV mass, the increases in E/E' ratio, and the prolongation of IVRT by 27, 27, and 20%, respectively, at the 1.0 mg·kg(-1)·day(-1) dose without affecting blood pressure or LV systolic function. The prolonged APDs in myocytes and QTc of HS rats were significantly reduced with GS-967 treatment. These results indicate that INaL is a significant contributor to the LV diastolic dysfunction, hypertrophy, and repolarization abnormalities and thus, inhibition of this current is a promising therapeutic target for diastolic heart failure. PMID:26993228

  15. Dynamics of a feline retrovirus (FeLV) in host populations with variable spatial structure.

    PubMed

    Fromont, E; Pontier, D; Langlais, M

    1998-06-22

    The predictions of epidemic models are remarkably affected by the underlying assumptions concerning host population dynamics and the relation between host density and disease transmission. Furthermore, hypotheses underlying distinct models are rarely tested. Domestic cats (Felis catus) can be used to compare models and test their predictions, because cat populations show variable spatial structure that probably results in variability in the relation between density and disease transmission. Cat populations also exhibit various dynamics. We compare four epidemiological models of Feline Leukaemia Virus (FeLV). We use two different incidence terms, i.e. proportionate mixing and pseudo-mass action. Population dynamics are modelled as logistic or exponential growth. Compared with proportionate mixing, mass action incidence with logistic growth results in a threshold population size under which the virus cannot persist in the population. Exponential growth of host populations results in systems where FeLV persistence at a steady prevalence and depression of host population growth are biologically unlikely to occur. Predictions of our models account for presently available data on FeLV dynamics in various populations of cats. Thus, host population dynamics and spatial structure can be determinant parameters in parasite transmission, host population depression, and disease control. PMID:9684375

  16. Dynamics of a feline retrovirus (FeLV) in host populations with variable spatial structure.

    PubMed Central

    Fromont, E; Pontier, D; Langlais, M

    1998-01-01

    The predictions of epidemic models are remarkably affected by the underlying assumptions concerning host population dynamics and the relation between host density and disease transmission. Furthermore, hypotheses underlying distinct models are rarely tested. Domestic cats (Felis catus) can be used to compare models and test their predictions, because cat populations show variable spatial structure that probably results in variability in the relation between density and disease transmission. Cat populations also exhibit various dynamics. We compare four epidemiological models of Feline Leukaemia Virus (FeLV). We use two different incidence terms, i.e. proportionate mixing and pseudo-mass action. Population dynamics are modelled as logistic or exponential growth. Compared with proportionate mixing, mass action incidence with logistic growth results in a threshold population size under which the virus cannot persist in the population. Exponential growth of host populations results in systems where FeLV persistence at a steady prevalence and depression of host population growth are biologically unlikely to occur. Predictions of our models account for presently available data on FeLV dynamics in various populations of cats. Thus, host population dynamics and spatial structure can be determinant parameters in parasite transmission, host population depression, and disease control. PMID:9684375

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

    PubMed

    Kreja, L; Seidel, H J

    1985-08-01

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

  18. Viral Determinants of FeLV Infection and Pathogenesis: Lessons Learned from Analysis of a Natural Cohort

    PubMed Central

    Bolin, Lisa L.; Levy, Laura S.

    2011-01-01

    Detailed analysis has been performed over many years of a geographic and temporal cohort of cats naturally infected with feline leukemia virus (FeLV). Molecular analysis of FeLV present in the diseased tissues and application of those viruses to experimental systems has revealed unique isolates with distinctive disease potential, previously uncharacterized virus-receptor interactions, information about the role of recombinant viruses in disease induction, and novel viral and cellular oncogenes implicated in pathogenesis, among other findings. The studies have contributed to an understanding of the selective forces that lead to predominance of distinctive FeLV isolates and disease outcomes in a natural population. PMID:21994802

  19. Viral determinants of FeLV infection and pathogenesis: lessons learned from analysis of a natural cohort.

    PubMed

    Bolin, Lisa L; Levy, Laura S

    2011-09-01

    Detailed analysis has been performed over many years of a geographic and temporal cohort of cats naturally infected with feline leukemia virus (FeLV). Molecular analysis of FeLV present in the diseased tissues and application of those viruses to experimental systems has revealed unique isolates with distinctive disease potential, previously uncharacterized virus-receptor interactions, information about the role of recombinant viruses in disease induction, and novel viral and cellular oncogenes implicated in pathogenesis, among other findings. The studies have contributed to an understanding of the selective forces that lead to predominance of distinctive FeLV isolates and disease outcomes in a natural population. PMID:21994802

  20. Improved functional overview of protein complexes using inferred epistatic relationships

    PubMed Central

    2011-01-01

    Background Epistatic Miniarray Profiling(E-MAP) quantifies the net effect on growth rate of disrupting pairs of genes, often producing phenotypes that may be more (negative epistasis) or less (positive epistasis) severe than the phenotype predicted based on single gene disruptions. Epistatic interactions are important for understanding cell biology because they define relationships between individual genes, and between sets of genes involved in biochemical pathways and protein complexes. Each E-MAP screen quantifies the interactions between a logically selected subset of genes (e.g. genes whose products share a common function). Interactions that occur between genes involved in different cellular processes are not as frequently measured, yet these interactions are important for providing an overview of cellular organization. Results We introduce a method for combining overlapping E-MAP screens and inferring new interactions between them. We use this method to infer with high confidence 2,240 new strongly epistatic interactions and 34,469 weakly epistatic or neutral interactions. We show that accuracy of the predicted interactions approaches that of replicate experiments and that, like measured interactions, they are enriched for features such as shared biochemical pathways and knockout phenotypes. We constructed an expanded epistasis map for yeast cell protein complexes and show that our new interactions increase the evidence for previously proposed inter-complex connections, and predict many new links. We validated a number of these in the laboratory, including new interactions linking the SWR-C chromatin modifying complex and the nuclear transport apparatus. Conclusion Overall, our data support a modular model of yeast cell protein network organization and show how prediction methods can considerably extend the information that can be extracted from overlapping E-MAP screens. PMID:21605386

  1. Rescue of arterial function by angiotensin-(1-7): towards improvement of endothelial function by drug-eluting stents

    PubMed Central

    Langeveld, B.E.; Henning, R.H.; de Smet, B.J.G.L.; Zijlstra, F.; Driessen, A.; Tijsma, E.; van Gilst, W.H.; Roks, A

    2008-01-01

    Purpose: To explore the hypothesis that stent placement decreases dilator function of various arteries outside the stented segment and that angiotensin- (1-7) improves this function, and to assess the contribution of dilator signal compounds. A further objective was to test the hypothesis that on-stent delivery of Ang-(1-7) reduces neointima formation and improves endothelial function. Methods: Abdominal aortic stenting or sham operation was performed in the rat four weeks after stenting and treatment with intravenous saline or Ang-(1-7) infusion (24 ?g/kg/h); vasomotor function in isolated thoracic aorta and brachial and iliac artery was measured in organ baths. Furthermore, Ang-(1-7)-eluting stents were designed and placed in rat abdominal aorta. Neointima formation and aortic function were tested after four weeks. Results: Relaxation of the thoracic aorta to metacholine was decreased after stenting compared with shams due to a decrease in nitric oxide-mediated response (67% reduction in maximal NO-dependent response). Ang-(1-7) restored the response mainly through increased prostaglandin- and possibly also endothelial-derived hyperpolarising factor-mediated relaxation. Relaxation in the brachial artery decreased after stenting (maximal response dropped by 50%), whilst contractions to phenylephrine increased. Ang-(1-7) normalised vasomotor function. Iliac artery function remained unaltered after stenting but Ang-(1-7) increased maximal relaxations by 65%. Delivery of Ang-(1-7) by means of a drug-eluting stent improved endothelial function. Conclusion: Stenting differentially affects dilator and contractile function in various arterial beds. Ang-(1-7) both improves dilator function and normalises contractile function. Delivery of protective peptides such as Ang-(1-7) from the stent is a new therapy option that merits further development and exploration. (Neth Heart J 2008;16:293-8.) PMID:18827872

  2. Relationship between systolic and diastolic function with improvements in forward stroke volume following reduction in mitral regurgitation

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    Efforts to improve mitral regurgitation (MR) are often performed in conjunction with coronary revascularization. However, the independent effects of a reduced MR area (MRa) are difficult to quantify. Using a previously developed cardiovascular model, ventricular contractility (elastance 1-8 mmHg/ml) and relaxation (tau: 40-150 msec) were independently adjusted for four grades of MR orifice areas (0.0 to 0.8 cm2). Improvements in forward stroke volume (fSV) were determined for the permutations of reduced MRa. For all conditions, LV end-diastolic pressure and volumes ranged from 7.3-24.2 mmHg and 64.8-174.3 ml, respectively. Overall, fSV ranged from 36.0-89.4 (mean: 64.2 +/- 12.8) ml, improved between 6.4 and 35.3% (mean: 15.6 +/- 8.1%), and was best predicted by (r=0.97, p<0.01) %delta(fSV)[correction of fVS]=34[MRa initial] - 46[MRa final] -0.5[elastance]. Reduced MRa, independent of relaxation and minimally influence by contractility, yield improved fSVs.

  3. The number of regulatory T cells correlates with hemodynamic improvement in patients with inflammatory dilated cardiomyopathy after immunoadsorption therapy.

    PubMed

    Bulut, D; Creutzenberg, G; Mügge, A

    2013-01-01

    Inflammatory DCM (iDCM) may be related to autoimmune processes. An immunoadsorption (IA) has been reported to improve cardiac hemodynamics. The benefit of IA is probably related to the removal of autoantibodies. A recent study suggests additional effects of IA on the T cell-mediated immune reactions, especially on regulatory T cells (Tregs). In this prospective study, the correlation between the level of Tregs and improvement of myocardial contractility in response to IA in patients with iDCM was investigated. Patients (n = 18) with iDCM, reduced left ventricular (LV) ejection fraction (<35%), were enrolled for IA. Before and 6 months after IA, LV systolic function was assessed by echocardiography, and blood levels of Tregs were quantified by FACS analysis. Patients (n = 12) with chronic ischaemic heart failure and comparable reduced LV-EF served as controls. IA improved LV-EF in 12 of 18 patients at 6-month follow-up. These patients were classified as 'IA responder'. In 6 patients, LV-EF remained unchanged. At baseline, IA responder and non-responder subgroups showed similar values for C-reactive protein, white blood cells, lymphocytes and T helper cells, but they differ for the number of circulating Tregs (responder: 2.32 ± 1.38% versus non-responder: 4.86 ± 0.28%; P < 0.01). Tregs increased significantly in the IA responders, but remained unchanged in the IA non-responders. In patients with ischaemic cardiomyopathy, none of these values changed over time. A low level of Tregs in patients with chronic iDCM may characterize a subset of patients who do best respond to IA therapy. PMID:22998220

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

    SciTech Connect

    Harrison, I.P.; McKnight, A.

    2011-06-20

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

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

    PubMed Central

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

    2014-01-01

    Background Individuals with HIV infection and peripheral metabolic complications have impaired basal myocardial insulin sensitivity that is related to left ventricular (LV) diastolic dysfunction. It is unknown whether interventions shown to be effective in improving peripheral insulin sensitivity can improve basal myocardial insulin sensitivity and diastolic function in people with HIV and peripheral metabolic complications. Objective In a pilot study, we evaluated whether the peroxisome proliferator–activated receptor-gamma (PPAR-γ) agonist pioglitazone or combined endurance and resistance exercise training improves basal myocardial insulin sensitivity and diastolic function in HIV+ adults with peripheral metabolic complications. Design Twenty-four HIV+ adults with metabolic complications including peripheral insulin resistance were randomly assigned to 4 months of pioglitazone (PIO; 30 mg/d) or supervised, progressive endurance and resistance exercise training (EXS; 90–120 min/d, 3 d/wk). Basal myocardial substrate metabolism was quantified by radioisotope tracer methodology and positron emission tomography (PET) imaging, and LV function was measured by echocardiography. Results Twenty participants completed the study. Neither PIO nor EXS resulted in a detectable improvement in basal myocardial insulin sensitivity or diastolic function. Post hoc analyses revealed sample sizes of more than 100 participants are needed to detect significant effects of these interventions on basal myocardial insulin sensitivity and function. Conclusions PIO or EXS alone did not significantly increase basal myocardial insulin sensitivity or LV diastolic function in HIV+ individuals with peripheral metabolic complications. PMID:24334183

  6. Is blockade of the Renin-Angiotensin system able to reverse the structural and functional remodeling of the left ventricle in severe aortic stenosis?

    PubMed

    Helske-Suihko, Satu; Laine, Mika; Lommi, Jyri; Kaartinen, Maija; Werkkala, Kalervo; Kovanen, Petri T; Kupari, Markku

    2015-03-01

    : In experimental aortic stenosis (AS), blockade of the renin-angiotensin system attenuates AS-related left ventricular (LV) dysfunction and improves survival. We tested whether candesartan, an angiotensin II type 1 receptor blocker, favorably influences LV structure and function and improves exercise capacity in AS patients. Fifty-one patients with severe AS were randomized to receive candesartan (target dose 16 mg/d) or placebo. Eight patients discontinued treatment and the remaining 43 patients underwent echocardiography, walking test, and measurement of plasma N-terminal B-type natriuretic peptide (Nt-proBNP) before and after an average of 5-month treatment. No statistically significant changes in LV diameters, mass, or function were seen. The median 6-minute walking distance decreased from 390 to 368 m with candesartan (P = 0.003) and from 380 to 370 m with placebo (P = 0.523), reflecting natural progression of AS. Concomitantly, median Nt-proBNP increased from 319 to 414 ng/L with candesartan (P = 0.170) and from 413 to 561 ng/L with placebo (P = 0.035). No change with candesartan was statistically significantly different from the corresponding change with placebo. In conclusion, candesartan was well tolerated but had no favorable effects on the LV or effort tolerance. The benefits found in experimental AS of blocking the renin-angiotensin system could not be reproduced in patients with severe AS. PMID:25469804

  7. Resistance Training Congruent With Minimal Guidelines Improves Function in Older Adults: A Pilot Study

    PubMed Central

    Gennuso, Keith P.; Zalewski, Kathryn; Cashin, Susan E.; Strath, Scott J.

    2016-01-01

    Background To examine the effectiveness of the American College of Sports Medicine (ACSM) and the American Heart Association (AHA) resistance training (RT) guidelines to improve physical function and functional classification in older adults with reduced physical abilities. Methods Twenty-five at-risk older adults were randomized to a control (CON = 13) or 8-week resistance training intervention arm (RT = 12). Progressive RT included 8 exercises for 1 set of 10 repetitions at a perceived exertion of 5–6 performed twice a week. Individuals were assessed for physical function and functional classification change (low, moderate or high) by the short physical performance battery (SPPB) and muscle strength measures. Results Postintervention, significant differences were found between groups for SPPB—Chair Stand [F(1,22) = 9.14, P < .01, η = .29] and SPPB—Total Score [F(1,22) = 7.40, P < .05, η = .25]. Functional classification was improved as a result of the intervention with 83% of participants in the RT group improving from low to moderate functioning or moderate to high functioning. Strength significantly improved on all exercises in the RT compared with the CON group. Conclusions A RT program congruent with the current ASCM and AHA guidelines is effective to improve overall physical function, functional classification, and muscle strength for older adults with reduced physical abilities. PMID:23074076

  8. 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

  9. 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.

  10. Determination of early diastolic LV vortex formation time (T*) via the PDF formalism: a kinematic model of filling.

    PubMed

    Ghosh, Erina; Shmuylovich, Leonid; Kovacs, Sandor J

    2009-01-01

    The filling (diastolic) function of the human left ventricle is most commonly assessed by echocardiography, a non-invasive imaging modality. To quantify diastolic function (DF) empiric indices are obtained from the features (height, duration, area) of transmitral flow velocity contour, obtained by echocardiography. The parameterized diastolic filling (PDF) formalism is a kinematic model developed by Kovcs et. al. which incorporates the suction pump attribute of the left ventricle and facilitates DF quantitation by analysis of echocardiographic transmitral flow velocity contours in terms of stiffness (k), relaxation (c) and load (x(0)). A complementary approach developed by Gharib et. al., uses fluid mechanics and characterizes DF in terms of vortex formation time (T*) derived from streamline features formed by the jet of blood aspirated into the ventricle. Both of these methods characterize DF using a causality-based approach. In this paper, we derive T*'s kinematic analogue T*(kinematic) in terms of k, c and x(0). A comparison between T*(kinematic) and T*(fluid) (mechanic) obtained from averaged transmitral velocity and mitral annulus diameter, is presented. We found that T* calculated by the two methods were comparable and T*(kinematic) correlated with the peak LV recoil driving force kx(0). PMID:19964049

  11. 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.

  12. Precise improvement of ISAF reconstruction algorithm based on the computational radius of density function.

    PubMed

    Wang, Gongming; Xu, Fan

    2014-01-01

    The output of icosahedral symmetry-adapted functions (ISAF) reconstruction algorithm is a virus capsid, where the density function of every outside point is theoretically zero. However, original ISAF algorithm takes reconstructed map as a solid sphere and density function of every point in the whole sphere is calculated. The density functions outside virus capsid may not be always zero, which may sometimes produce noise. In this study, Fourier shell correlation (FSC) is used for proving that density function calculation of original ISAF algorithm can reduce reconstruction precision. Subsequently, the range of virus capsid is determined with radial density function curve and the original ISAF algorithm is improved by calculating density function inside virus capsid. The experimental results on Cryo-electron microscopy (Cryo-EM) data of cytoplasmic polyhedrosis virus (CPV) indicate that the improved ISAF algorithm can generate more details of virus capsid and achieve a higher resolution. PMID:25227095

  13. Rodent Biocompatibility Test Using the NASA Foodbar and Epoxy EP21LV

    NASA Technical Reports Server (NTRS)

    Tillman, J.; Steele, M.; Dumars, P.; Vasques, M.; Girten, B.; Sun, S. (Technical Monitor)

    2002-01-01

    Epoxy has been used successfully to affix NASA foodbars to the inner walls of the Animal Enclosure Module for past space flight experiments utilizing rodents. The epoxy used on past missions was discontinued, making it necessary to identify a new epoxy for use on the STS-108 and STS-107 missions. This experiment was designed to test the basic biocompatibility of epoxy EP21LV with male rats (Sprague Dawley) and mice (Swiss Webster) when applied to NASA foodbars. For each species, the test was conducted with a control group fed untreated foodbars and an experimental group fed foodbars applied with EP21LV. For each species, there were no group differences in animal health and no statistical differences (P<0.05) in body weights throughout the study. In mice, there was a 16% increase in heart weight in the epoxy group; this result was not found in rats. For both species, there were no statistical differences found in other organ weights measured. In rats, blood glucose levels were 15% higher and both total protein and globulin were 10% lower in the epoxy group. Statistical differences in these parameters were not found in mice. For both species, no statistical differences were found in other blood parameters tested. Food consumption was not different in rats but water consumption was significantly decreased 10 to 15% in the epoxy group. The difference in water consumption is likely due to an increased water content of the epoxy-treated foodbars. Finally, both species avoided consumption of the epoxy material. Based on the global analysis of the results, the few parameters found to be statistically different do not appear to be a physiologically relevant effect of the epoxy material, We conclude that the EP21LV epoxy is biocompatible with rodents.

  14. Vascular endothelium: functioning in norm, changes in atherosclerosis and current dietary approaches to improve endothelial function.

    PubMed

    Chistiakov, Dimitry A; Revin, Victor V; Sobenin, Igor A; Orekhov, Alexander N; Bobryshev, Yuri V

    2015-01-01

    The endothelium represents not only a simple cellular monolayer that lines the vascular tree in humans and other vertebrates. Depending on the location, the endothelium shows significant morphological and functional heterogeneity through differentiated expression of pro- and anticoagulant factors, presence and frequency of intercellular contacts, variable contractility, cell shape, and volume. Altogether, these properties are crucial for adjustment of the endothelial function and further maintenance of the adequate homeostasis in response in local microenvironmental changes. Endothelial cells (ECs) play a critical role in coordinated regulation of blood flow. This is achieved due to the capacity of ECs to create the active anti-thrombotic surface that supports blood fluidity and transfer of blood cells and biomolecules. However, in certain vascular regions that can occur in inflamed sites or in sites with high hydrodynamic shear stress, ECs could lost their anti-thrombotic properties and switch their normal quiescent phenotype towards the prothrombotic, proadhesion, and proinflammatory state. In such an athero-prone site, the proper endothelial function is impaired that increases risk for formation of the atherosclerotic plaque. The endothelial dysfunction not only precedes atherosclerosis but greatly contributes to atherogenesis in all disease stages. Healthy lifestyle and regular intake of correct antioxidant-rich diet such as fresh fruits, vegetables, olive oil, red wine, and tea have beneficial effects on endothelial function and could therefore reduce the cardiovascular risk. PMID:25723463

  15. 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)…

  16. LV motion and strain computation from tMRI based on meshless deformable models.

    PubMed

    Wang, Xiaoxu; Chen, Ting; Zhang, Shaoting; Metaxas, Dimitris; Axel, Leon

    2008-01-01

    We propose a novel meshless deformable model for in vivo Left Ventricle (LV) 3D motion estimation and analysis based on tagged MRI (tMRI). The meshless deformable model can capture global deformations such as contraction and torsion with a few parameters, while track local deformations with Laplacian representation. In particular, the model performs well even when the control points (tag intersections) are relatively sparse. We test the performance of the meshless model on a numeric phantom, as well as in vivo heart data of healthy subjects and patients. The experimental results show that the meshless deformable model can fully recover the myocardial motion and strain in 3D. PMID:18979800

  17. Key Residues in the Nicotinic Acetylcholine Receptor β2 Subunit Contribute to α-Conotoxin LvIA Binding*

    PubMed Central

    Zhangsun, Dongting; Zhu, Xiaopeng; Wu, Yong; Hu, Yuanyan; Kaas, Quentin; Craik, David J.; McIntosh, J. Michael; Luo, Sulan

    2015-01-01

    α-Conotoxin LvIA (α-CTx LvIA) is a small peptide from the venom of the carnivorous marine gastropod Conus lividus and is the most selective inhibitor of α3β2 nicotinic acetylcholine receptors (nAChRs) known to date. It can distinguish the α3β2 nAChR subtype from the α6β2* (* indicates the other subunit) and α3β4 nAChR subtypes. In this study, we performed mutational studies to assess the influence of residues of the β2 subunit versus those of the β4 subunit on the binding of α-CTx LvIA. Although two β2 mutations, α3β2[F119Q] and α3β2[T59K], strongly enhanced the affinity of LvIA, the β2 mutation α3β2[V111I] substantially reduced the binding of LvIA. Increased activity of LvIA was also observed when the β2-T59L mutant was combined with the α3 subunit. There were no significant difference in inhibition of α3β2[T59I], α3β2[Q34A], and α3β2[K79A] nAChRs when compared with wild-type α3β2 nAChR. α-CTx LvIA displayed slower off-rate kinetics at α3β2[F119Q] and α3β2[T59K] than at the wild-type receptor, with the latter mutant having the most pronounced effect. Taken together, these data provide evidence that the β2 subunit contributes to α-CTx LvIA binding and selectivity. The results demonstrate that Val111 is critical and facilitates LvIA binding; this position has not previously been identified as important to binding of other 4/7 framework α-conotoxins. Thr59 and Phe119 of the β2 subunit appear to interfere with LvIA binding, and their replacement by the corresponding residues of the β4 subunit leads to increased affinity. PMID:25713061

  18. 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.

  19. Using Wannier functions to improve solid band gap predictions in density functional theory.

    PubMed

    Ma, Jie; Wang, Lin-Wang

    2016-01-01

    Enforcing a straight-line condition of the total energy upon removal/addition of fractional electrons on eigen states has been successfully applied to atoms and molecules for calculating ionization potentials and electron affinities, but fails for solids due to the extended nature of the eigen orbitals. Here we have extended the straight-line condition to the removal/addition of fractional electrons on Wannier functions constructed within the occupied/unoccupied subspaces. It removes the self-interaction energies of those Wannier functions, and yields accurate band gaps for solids compared to experiments. It does not have any adjustable parameters and the computational cost is at the DFT level. This method can also work for molecules, providing eigen energies in good agreement with experimental ionization potentials and electron affinities. Our approach can be viewed as an alternative approach of the standard LDA+U procedure. PMID:27114185

  20. Using Wannier functions to improve solid band gap predictions in density functional theory

    PubMed Central

    Ma, Jie; Wang, Lin-Wang

    2016-01-01

    Enforcing a straight-line condition of the total energy upon removal/addition of fractional electrons on eigen states has been successfully applied to atoms and molecules for calculating ionization potentials and electron affinities, but fails for solids due to the extended nature of the eigen orbitals. Here we have extended the straight-line condition to the removal/addition of fractional electrons on Wannier functions constructed within the occupied/unoccupied subspaces. It removes the self-interaction energies of those Wannier functions, and yields accurate band gaps for solids compared to experiments. It does not have any adjustable parameters and the computational cost is at the DFT level. This method can also work for molecules, providing eigen energies in good agreement with experimental ionization potentials and electron affinities. Our approach can be viewed as an alternative approach of the standard LDA+U procedure. PMID:27114185

  1. An improved nearly-orthogonal structured mesh generation system with smoothness control functions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper presents an improved nearly-orthogonal structured mesh generation system with a set of smoothness control functions, which were derived based on the ratio between the Jacobian of the transformation matrix and the Jacobian of the metric tensor. The proposed smoothness control functions are...

  2. 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…

  3. 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...

  4. 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 ...

  5. Improving the work function of the niobium surface of SRF cavities by plasma processing

    NASA Astrophysics Data System (ADS)

    Tyagi, P. V.; Doleans, M.; Hannah, B.; Afanador, R.; McMahan, C.; Stewart, S.; Mammosser, J.; Howell, M.; Saunders, J.; Degraff, B.; Kim, S.-H.

    2016-04-01

    An in situ plasma processing technique using chemically reactive oxygen plasma to remove hydrocarbons from superconducting radio frequency cavity surfaces at room temperature has been developed at the spallation neutron source, at Oak Ridge National Laboratory. To understand better the interaction between the plasma and niobium surface, surface studies on small samples were performed. In this article, we report the results from those surface studies. The results show that plasma processing removes hydrocarbons from top surface and improves the surface work function by 0.5-1.0 eV. Improving the work function of RF surface of cavities can help to improve their operational performance.

  6. Improving the work function of the niobium surface of SRF cavities by plasma processing

    DOE PAGESBeta

    Tyagi, P. V.; Doleans, M.; Hannah, B.; Afanador, R.; McMahan, C.; Stewart, S.; Mammosser, J.; Howell, M.; Saunders, J.; Degraff, B.; et al

    2016-01-01

    An in situ plasma processing technique using chemically reactive oxygen plasma to remove hydrocarbons from superconducting radio frequency cavity surfaces at room temperature was developed at the spallation neutron source, at Oak Ridge National Laboratory. To understand better the interaction between the plasma and niobium surface, surface studies on small samples were performed. In this article, we report the results from those surface studies. The results show that plasma processing removes hydrocarbons from top surface and improves the surface work function by 0.5₋1.0 eV. Improving the work function of RF surface of cavities can help to improve their operational performance.

  7. Regional myocardial function after intracoronary bone marrow cell injection in reperfused anterior wall infarction - a cardiovascular magnetic resonance tagging study

    PubMed Central

    2011-01-01

    Background Trials have brought diverse results of bone marrow stem cell treatment in necrotic myocardium. This substudy from the Autologous Stem Cell Transplantation in Acute Myocardial Infarction trial (ASTAMI) explored global and regional myocardial function after intracoronary injection of autologous mononuclear bone marrow cells (mBMC) in acute anterior wall myocardial infarction treated with percutaneous coronary intervention. Methods Cardiovascular magnetic resonance (CMR) tagging was performed 2-3 weeks and 6 months after revascularization in 15 patients treated with intracoronary stem cell injection (mBMC group) and in 13 controls without sham injection. Global and regional left ventricular (LV) strain and LV twist were correlated to cine CMR and late gadolinium enhancement (LGE). Results In the control group myocardial function as measured by strain improved for the global LV (6 months: -13.1 ± 2.4 versus 2-3 weeks: -11.9 ± 3.4%, p = 0.014) and for the infarct zone (-11.8 ± 3.0 versus -9.3 ± 4.1%, p = 0.001), and significantly more than in the mBMC group (inter-group p = 0.027 for global strain, respectively p = 0.009 for infarct zone strain). LV infarct mass decreased (35.7 ± 20.4 versus 45.7 ± 29.5 g, p = 0.024), also significantly more pronounced than the mBMC group (inter-group p = 0.034). LV twist was initially low and remained unchanged irrespective of therapy. Conclusions LGE and strain findings quite similarly demonstrate subtle differences between the mBMC and control groups. Intracoronary injection of autologous mBMC did not strengthen regional or global myocardial function in this substudy. Trial registration ClinicalTrials.gov: NCT00199823 PMID:21414223

  8. Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of infection

    PubMed Central

    Major, Andrea; Cattori, Valentino; Boenzli, Eva; Riond, Barbara; Ossent, Peter; Meli, Marina Luisa; Hofmann-Lehmann, Regina; Lutz, Hans

    2009-01-01

    In felids, feline leukemia virus (FeLV) infection results in a variety of outcomes that range from abortive (virus readily eliminated and never detectable) to progressive infection (persistent viremia and viral shedding). Recently, a novel outcome was postulated for low FeLV infectious doses. Nave cats exposed to faeces of persistently infected cats seroconverted, indicating infection, but remained negative for provirus and p27 antigen in blood. FeLV provirus was found in some tissues but not in the bone marrow, infection of which is usually considered a necessary stage for disease progression. To investigate the impact of low FeLV doses on young cats and to test the hypothesis that low dose exposure may lead to an unknown pathogenesis of infection without involvement of the bone marrow, 21 cats were infected oronasally with variable viral doses. Blood p27, proviral and viral loads were followed until week 20 post-infection. Tissue proviral loads were determined as well. The immune response was monitored by measuring FeLV whole virus and p45 antibodies; and feline oncornavirus-associated cell membrane antigen (FOCMA) assay. One cat showed regressive infection (transient antigenemia, persistent provirus-positivity, and seroconversion) with provirus only found in some organs at sacrifice. In 7 of the 20 remaining cats FOCMA assay positivity was the only sign of infection, while all other tests were negative. Overall, the results show that FeLV low dose exposure can result in seroconversion during a presumed abortive infection. Therefore, commonly used detection methods do not detect all FeLV-infected animals, possibly leading to an underestimation of the prevalence of infection. PMID:19861115

  9. Exposure of cats to low doses of FeLV: seroconversion as the sole parameter of infection.

    PubMed

    Major, Andrea; Cattori, Valentino; Boenzli, Eva; Riond, Barbara; Ossent, Peter; Meli, Marina Luisa; Hofmann-Lehmann, Regina; Lutz, Hans

    2010-01-01

    In felids, feline leukemia virus (FeLV) infection results in a variety of outcomes that range from abortive (virus readily eliminated and never detectable) to progressive infection (persistent viremia and viral shedding). Recently, a novel outcome was postulated for low FeLV infectious doses. Nave cats exposed to faeces of persistently infected cats seroconverted, indicating infection, but remained negative for provirus and p27 antigen in blood. FeLV provirus was found in some tissues but not in the bone marrow, infection of which is usually considered a necessary stage for disease progression. To investigate the impact of low FeLV doses on young cats and to test the hypothesis that low dose exposure may lead to an unknown pathogenesis of infection without involvement of the bone marrow, 21 cats were infected oronasally with variable viral doses. Blood p27, proviral and viral loads were followed until week 20 post-infection. Tissue proviral loads were determined as well. The immune response was monitored by measuring FeLV whole virus and p45 antibodies; and feline oncornavirus-associated cell membrane antigen (FOCMA) assay. One cat showed regressive infection (transient antigenemia, persistent provirus-positivity, and seroconversion) with provirus only found in some organs at sacrifice. In 7 of the 20 remaining cats FOCMA assay positivity was the only sign of infection, while all other tests were negative. Overall, the results show that FeLV low dose exposure can result in seroconversion during a presumed abortive infection. Therefore, commonly used detection methods do not detect all FeLV-infected animals, possibly leading to an underestimation of the prevalence of infection. PMID:19861115

  10. Effects of remission speed and improvement of cognitive functions of depressed patients.

    PubMed

    Gudayol-Ferré, Esteve; Guàrdia-Olmos, Joan; Peró-Cebollero, Maribel

    2015-03-30

    Major depressive disorder (MDD) presents neuropsychological alterations which improve after the treatment, but it might be mediated by clinical variables. Our goal is to study whether the speed of remission of MDD bears any relation to the improvement of the patients' cognitive functioning after a successful treatment. We carried out clinical and neuropsychological assessments of 51 patients with MDD. After these procedures they underwent a 24-week treatment with fluoxetine, and were assessed again with the same battery used prior to treatment. They were arranged into three groups according to how rapid their symptoms remitted. The patients with a rapid remission presented improvements in working memory, speed of information processing, and some executive functions, unlike the other groups. Rapid remitters also improved in episodic memory and executive functions more than the other patients. PMID:25619432

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

    PubMed

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

    2011-05-01

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

  12. A replication-competent feline leukemia virus, subgroup A (FeLV-A), tagged with green fluorescent protein reporter exhibits in vitro biological properties similar to those of the parental FeLV-A.

    PubMed

    Chang, Z; Pan, J; Logg, C; Kasahara, N; Roy-Burman, P

    2001-09-01

    We previously established that lymphoid tumors could be induced in cats by intradermal injection of ecotropic feline leukemia virus (FeLV), subgroup A, plasmid DNA. In preparation for in vivo experiments to study the cell-to-cell pathway for the spread of the virus from the site of inoculation, the green fluorescent protein (GFP) transgene fused to an internal ribosome entry site (IRES) was inserted after the last nucleotide of the env gene in the ecotropic FeLV-A Rickard (FRA) provirus. The engineered plasmid was transfected into feline fibroblast cells for production of viruses and determination of GFP expression. The virions produced were highly infectious, and the infected cells could continue to mediate strong expression of GFP after long-term propagation in culture. Similar to parental virus, the transgene-containing ecotropic virus demonstrated recombinogenic activity with endogenous FeLV sequences in feline cells to produce polytropic recombinant FeLV subgroup B-like viruses which also contained the IRES-GFP transgene in the majority of recombinants. To date, the engineered virus has been propagated in cell culture for up to 8 months without diminished GFP expression. This is the first report of a replication-competent FeLV vector with high-level and stable expression of a transgene. PMID:11507228

  13. A Replication-Competent Feline Leukemia Virus, Subgroup A (FeLV-A), Tagged with Green Fluorescent Protein Reporter Exhibits In Vitro Biological Properties Similar to Those of the Parental FeLV-A

    PubMed Central

    Chang, Zongli; Pan, Judong; Logg, Christopher; Kasahara, Noriyuki; Roy-Burman, Pradip

    2001-01-01

    We previously established that lymphoid tumors could be induced in cats by intradermal injection of ecotropic feline leukemia virus (FeLV), subgroup A, plasmid DNA. In preparation for in vivo experiments to study the cell-to-cell pathway for the spread of the virus from the site of inoculation, the green fluorescent protein (GFP) transgene fused to an internal ribosome entry site (IRES) was inserted after the last nucleotide of the env gene in the ecotropic FeLV-A Rickard (FRA) provirus. The engineered plasmid was transfected into feline fibroblast cells for production of viruses and determination of GFP expression. The virions produced were highly infectious, and the infected cells could continue to mediate strong expression of GFP after long-term propagation in culture. Similar to parental virus, the transgene-containing ecotropic virus demonstrated recombinogenic activity with endogenous FeLV sequences in feline cells to produce polytropic recombinant FeLV subgroup B-like viruses which also contained the IRES-GFP transgene in the majority of recombinants. To date, the engineered virus has been propagated in cell culture for up to 8 months without diminished GFP expression. This is the first report of a replication-competent FeLV vector with high-level and stable expression of a transgene. PMID:11507228

  14. Feline leukaemia virus (FeLV) and feline immunodeficiency virus infections in cats in the Pisa district of Tuscany, and attempts to control FeLV infection in a colony of domestic cats by vaccination.

    PubMed

    Bandecchi, P; Dell'Omodarme, M; Magi, M; Palamidessi, A; Prati, M C

    2006-04-22

    The seroprevalence of feline immunodeficiency virus (FIV) in 203 apparently healthy domestic cats living in the district of Pisa, central Italy, was 11.3 per cent, and the prevalence of feline leukaemia virus (FeLV) was 8.4 per cent. The prevalence of FIV depended significantly on the lifestyle and age of the cats; cats living outdoors were more likely to be FIV-positive than cats living indoors, and the proportion of FIV-positive cats increased with age. In contrast, there was no significant relationship between these variables and the prevalence of FeLV. There was no significant relationship between the cats' seropositivity for FIV and FeLV. The results of a five-year field study to control FeLV infection by vaccination in a colony of 30 domestic adult cats naturally exposed to the infection suggest that the vaccination was effective in FIV-negative cats, but failed to protect FIV-positive cats against FeLV. PMID:16632529

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

    PubMed

    Courchamp, F; Suppo, C; Fromont, E; Bouloux, C

    1997-06-22

    We present a deterministic model of the dynamics of two microparasites simultaneously infecting a single host population. Both microparasites are feline retroviruses, namely Feline Immunodeficiency Virus (FIV) and Feline Leukaemia Virus (FeLV). The host is the domestic cat Felis catus. The model has been tested with data generated by a long-term study of several natural cat populations. Stability analysis and simulations show that, once introduced in a population, FIV spreads and is maintained, while FeLV can either disappear or persist. Moreover, introduction of both viruses into the population induces an equilibrium state for individuals of each different pathological class. The viruses never induce the extinction of the population. Furthermore, whatever the outcome for the host population (persistence of FIV only, or of both viruses), the global population size at the equilibrium state is only slightly lower than it would have been in the absence of the infections (i.e. at the carrying capacity), indicating a low impact of the viruses on the population. Finally, the impact of the diseases examined simultaneously is higher than the sum of the impact of the two diseases examined separately. This seems to be due to a higher mortality rate when both viruses infect a single individual. PMID:9225475

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

    PubMed Central

    Courchamp, F; Suppo, C; Fromont, E; Bouloux, C

    1997-01-01

    We present a deterministic model of the dynamics of two microparasites simultaneously infecting a single host population. Both microparasites are feline retroviruses, namely Feline Immunodeficiency Virus (FIV) and Feline Leukaemia Virus (FeLV). The host is the domestic cat Felis catus. The model has been tested with data generated by a long-term study of several natural cat populations. Stability analysis and simulations show that, once introduced in a population, FIV spreads and is maintained, while FeLV can either disappear or persist. Moreover, introduction of both viruses into the population induces an equilibrium state for individuals of each different pathological class. The viruses never induce the extinction of the population. Furthermore, whatever the outcome for the host population (persistence of FIV only, or of both viruses), the global population size at the equilibrium state is only slightly lower than it would have been in the absence of the infections (i.e. at the carrying capacity), indicating a low impact of the viruses on the population. Finally, the impact of the diseases examined simultaneously is higher than the sum of the impact of the two diseases examined separately. This seems to be due to a higher mortality rate when both viruses infect a single individual. PMID:9225475

  17. Generation and role of defective proviruses in cytopathic feline leukemia virus (FeLV-FAIDS) infections.

    PubMed

    de Noronha, C M; Reinhart, T A; Mullins, J I

    1996-01-01

    Cytopathic feline leukemia virus (FeLV) infections of feline T-cell line (FeT-cell) cultures led to the accumulation and maintenance of threefold more proviruses with deletions within the polymerase gene (pol) than minimally cytopathic FeLV infections. Over 60% of the viral DNA from cytopathic infections bore deletions in pol. Characterization of DNA sequences adjoining the deletions revealed that the junctions were most often flanked by RNA splice donor and acceptor consensus motifs. A thymidine-to-cytidine mutation introduced at the +2 position of one RNA splice donor-like motif inhibited formation of the two most prevalent viral DNA species with deletions, confirming the origin of many proviruses with deletions from reverse transcription of aberrantly spliced viral RNA species. An example of deletion by misalignment was also characterized. Viral inocula obtained from cells recovered after cytopathic infections were attenuated in their ability to cause cytopathic effects (CPE) and were able to confer superinfection resistance to nave FeT-cells, despite maintaining envelope gene (env) sequences with full cytopathic potential. This suggested that viral genomes with deletions, rather than being required for cytopathicity, play a role in protecting cells from CPE. Indeed, expression of a molecularly cloned provirus bearing one of the characterized deletions attenuated CPE in FeT-cells caused by superinfecting cytopathic virus. PMID:8523548

  18. 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

  19. The Frequency of Occurrence and Nature of Recombinant Feline Leukemia Viruses in the Induction of Multicentric Lymphoma by Infection of the Domestic Cat with FeLV-945

    PubMed Central

    Ahmad, Shamim; Levy, Laura S.

    2010-01-01

    During feline leukemia virus (FeLV) infection in the domestic cat, viruses with a novel envelope gene arise by recombination between endogenous FeLV-related elements and the exogenous infecting species. These recombinant viruses (FeLV-B) are of uncertain disease association, but have been linked to the induction of thymic lymphoma. To assess the role of FeLV-B in the induction of multicentric lymphoma and other non-T-cell disease, the frequency of occurrence and nature of FeLV-B was examined in diseased tissues from a large collection of FeLV-infected animals. Diseased tissues were examined by Southern blot and PCR amplification to detect the presence of FeLV-B. Further analysis was performed to establish the recombination junctions and infectivity of FeLV-B in diseased tissues. The results confirmed the frequent association of FeLV-B with thymic lymphoma but showed infrequent generation, low levels and lack of infectivity of FeLV-B in non-T-cell diseases including multicentric lymphoma. PMID:20451235

  20. The frequency of occurrence and nature of recombinant feline leukemia viruses in the induction of multicentric lymphoma by infection of the domestic cat with FeLV-945.

    PubMed

    Ahmad, Shamim; Levy, Laura S

    2010-08-01

    During feline leukemia virus (FeLV) infection in the domestic cat, viruses with a novel envelope gene arise by recombination between endogenous FeLV-related elements and the exogenous infecting species. These recombinant viruses (FeLV-B) are of uncertain disease association, but have been linked to the induction of thymic lymphoma. To assess the role of FeLV-B in the induction of multicentric lymphoma and other non-T-cell disease, the frequency of occurrence and nature of FeLV-B were examined in diseased tissues from a large collection of FeLV-infected animals. Diseased tissues were examined by Southern blot and PCR amplification to detect the presence of FeLV-B. Further analysis was performed to establish the recombination junctions and infectivity of FeLV-B in diseased tissues. The results confirmed the frequent association of FeLV-B with thymic lymphoma but showed infrequent generation, low levels and lack of infectivity of FeLV-B in non-T-cell diseases including multicentric lymphoma. PMID:20451235

  1. 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

  2. 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

  3. Improved Sensing Behaviors in Reduced Graphene Oxide Functionalized with Ni(OH)2 Nanoparticles.

    PubMed

    Na, Han Gil; Kwon, Yong Jung; Cho, Hong Yeon; Kang, Sung Yong; Jung, Taek Kyun; Lee, Hyo-Soo; Kim, Hyoun Woo

    2015-11-01

    In this paper, we detail improvements in the sensing properties of reduced graphene oxide (RGO), which were achieved through functionalization. The functionalization process utilizes graphene oxide suspensions, generating nanoparticles on the RGO surface mainly comprised of Ni(OH)2 phase. Raman spectra indicate that functionalization increases the degree of disorder in RGOs. NO2 gas sensing tests reveal an approximate increase of 154% in the sensor response of the RGOs after functionalization. Possible mechanisms for improving sensing responses via functionalization are discussed. The enhancement is due to the spillover effect, to the increase of the sensor surface by the catalytic particles, to the reduction of RGO conduction volume through the generation of depletion region, and to the resistance modulation of the heterojunctions. PMID:26726632

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

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  5. Influence of a quality improvement learning collaborative program on team functioning in primary healthcare.

    PubMed

    Kotecha, Jyoti; Brown, Judith Belle; Han, Han; Harris, Stewart B; Green, Michael; Russell, Grant; Roberts, Sharon; Webster-Bogaert, Susan; Fournie, Meghan; Thind, Amardeep; Reichert, Sonja M; Birtwhistle, Richard

    2015-09-01

    Quality improvement (QI) programs are frequently implemented to support primary healthcare (PHC) team development and to improve care outcomes. In Ontario, Canada, the Quality Improvement and Innovation Partnership (QIIP) offered a learning collaborative (LC) program to support the development of interdisciplinary team function and improve chronic disease management, disease prevention, and access to care. A qualitative study using a phenomenological approach was conducted as part of a mixed-method evaluation to explore the influence of the program on team functioning in participating PHC teams. A purposive sampling strategy was used to identify PHC teams (n = 10), from which participants of different professional roles were selected through a purposeful recruitment process to reflect maximum variation of team roles. Additionally, QI coaches working with the interview participants and the LC administrators were also interviewed. Data were collected through semistructured telephone interviews that were audiotaped and transcribed verbatim. Thematic analysis was conducted through an iterative and interpretive approach. The shared experience of participating in the program appeared to improve team functioning. Participants described increased trust and respect for each other's clinical and administrative roles and were inspired by learning about different approaches to interdisciplinary care. This appeared to enhance collegial relationships, collapse professional silos, improve communication, and increase interdisciplinary collaboration. Teamwork involves more than just physically grouping healthcare providers from multiple disciplines and mandating them to work together. The LC program provided opportunities for participants to learn how to work collaboratively, and participation in the LC program appeared to enhance team functioning. PMID:25799255

  6. Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus.

    PubMed

    Guo, Min; Mi, Jia; Jiang, Qiu-Ming; Xu, Jin-Mei; Tang, Ying-Ying; Tian, Geng; Wang, Bin

    2014-09-01

    Diabetes mellitus and depressive disorders are both common chronic diseases that increase functional disability and social burden. Cognitive impairment is a potentially debilitating feature of depression. Previous evidence indicates that the antidiabetic drug metformin could be suitable for diabetic patients with cognitive impairment. However, there is no direct evidence from clinical studies that metformin treatment improves cognitive function in diabetic patients suffering from depression. In the present study, 58 participants diagnosed with depression and type 2 diabetes mellitus (T2DM) were recruited and divided into two groups, one treated with metformin and the other treated with placebo for 24 weeks. Cognitive function, depressive behaviour and diabetes improvement were evaluated. Chronic treatment with metformin for 24 weeks improved cognitive performance, as assessed by the Wechsler Memory Scale-Revised, in depressed patients with T2DM. In addition, metformin significantly improved depressive performance and changed the glucose metabolism in depressed patients with diabetes. Depressive symptoms were negatively correlated with cognitive performance in metformin-treated participants. Furthermore, associations were observed between the parameters of blood glucose metabolism and the depression phenotype. These findings suggest that chronic treatment with metformin has antidepressant behavioural effects and that improved cognitive function is involved in the therapeutic outcome of metformin. The results of the present study also raise the possibility that supplementary administration of antidiabetic medications may enhance the recovery of depression, comorbid with T2DM, through improvements in cognitive performance. PMID:24862430

  7. The effect of losartan and amlodipine on left ventricular diastolic function and atherosclerosis in Japanese patients with mild-to-moderate hypertension (J-ELAN) study.

    PubMed

    Yamamoto, Kazuhiro; Ozaki, Hitoshi; Takayasu, Ken; Akehi, Noriyuki; Fukui, Sugao; Sakai, Akihiko; Kodama, Mineo; Shimonagata, Tsuyoshi; Kobayashi, Keiji; Ota, Mitsushige; Horiguchi, Yasunori; Ebisuno, Shoji; Katsube, Yoshiki; Yamazaki, Tsutomu; Ohtsu, Hiroshi; Hori, Masatsugu

    2011-03-01

    This study was a prospective, randomized, open, blinded endpoint study to assess the effects of angiotensin II type 1 receptor blocker, losartan, compared with calcium channel blocker, amlodipine, on left ventricular (LV) diastolic function and atherosclerosis of the carotid artery in Japanese patients with mild-to-moderate hypertension, LV hypertrophy, diastolic dysfunction and preserved systolic function. Fifty-seven patients were randomly assigned to losartan- or amlodipine-based treatment groups and were followed up for 18 months. Blood pressure was similarly reduced by both regimens. Losartan shortened the transmitral E-wave deceleration time, and amlodipine reduced LV mass index; however, there was no significant difference in the percent changes of these indices between the two groups. Mean carotid intima-media thickness (mean IMT) as well as plaque score significantly increased in the amlodipine-based regimen (pre: 1.050.26 mm, follow-up: 1.230.33 mm, P=0.0015), but not in the losartan-based regimen (pre: 1.080.35 mm, follow-up: 1.160.52 mm, P=non-significant). The percent increase in mean IMT in the amlodipine-based regimen tended to be large compared with the losartan-based regimen (amlodipine: 19.823.7%, losartan: 6.923.3%, P=0.06). Under similar reduction of blood pressure, losartan is likely effective in protecting the progression of atherosclerosis of the carotid artery compared with amlodipine. Losartan may improve LV diastolic function, and amlodipine may attenuate LV hypertrophy; however, this study cannot make consecutive remarks about the superiority of either treatment regimen in the effects on cardiac function and geometry. This study has been registered at http://www.umin.ac.jp/ctr/listj/ (identifier C000000319). PMID:21124328

  8. Antibodies neutralizing feline leukaemia virus (FeLV) in cats immunized with the transmembrane envelope protein p15E.

    PubMed

    Langhammer, Stefan; Hbner, Janine; Kurth, Reinhard; Denner, Joachim

    2006-02-01

    The feline leukaemia virus (FeLV) vaccines that are currently in wide use are generally poor inducers of virus-neutralizing antibodies, although such antibodies appear after recovering from challenge. However, the presence of neutralizing antibodies in cats recovering from natural FeLV infection clearly correlates with resistance to subsequent infection and passive transfer of antibodies can protect other animals. After demonstrating the induction of neutralizing antibodies in rats and goats immunized with the transmembrane envelope protein p15E of FeLV, cats were immunized with the same antigen. High titres of neutralizing antibodies specific for FeLV were induced and epitope mapping revealed a pattern of recognition similar to that seen following immunization of rats and goats. These epitopes are highly related to epitopes recognized after immunization with porcine endogenous retrovirus (PERV) p15E and to epitopes recognized by neutralizing antibodies in patients infected with human immunodeficiency virus type 1. The ability of p15E to induce neutralizing antibodies in cats suggests that it should be included in the next generation of vaccines. In contrast, sera from FeLV-infected animals usually fail to recognize the neutralization-relevant epitopes in p15E. Since homologous epitope sequences are present in feline endogenous retroviruses, it appears that tolerance against these sequences is not induced. PMID:16423059

  9. Isolation of a novel subgroup B feline leukemia virus from a cat infected with FeLV-A.

    PubMed

    Boomer, S; Gasper, P; Whalen, L R; Overbaugh, J

    1994-11-01

    Proviruses were cloned directly from a cat that developed neurological disorders approximately 28 months after inoculation with a molecularly cloned, minimally pathogenic subgroup A feline leukemia virus (FeLV-A). In addition to FeLV-A proviruses that were nearly identical to the inoculated virus, we detected a subgroup B-like variant in brain, bone marrow, and lymph node that apparently had acquired the major portion of its extracellular envelope gene (gp70) from endogenous FeLV-related sequences. A similar recombinant was also detected, by PCR, at low levels in bone marrow from an early time postinfection (2.5 months). A full-length proviral variant with this recombinant structure cloned from brain tissue encoded a replication-defective virus. A chimera encoding the 5' gag-pol portion of FeLV-A and the 3' env-LTR portion of the defective brain-derived clone was replication-competent and had the extended host range properties of FeLV-B. PMID:7941350

  10. Antibodies neutralizing feline leukaemia virus (FeLV) in cats immunized with the transmembrane envelope protein p15E

    PubMed Central

    Langhammer, Stefan; Hbner, Janine; Kurth, Reinhard; Denner, Joachim

    2006-01-01

    The feline leukaemia virus (FeLV) vaccines that are currently in wide use are generally poor inducers of virus-neutralizing antibodies, although such antibodies appear after recovering from challenge. However, the presence of neutralizing antibodies in cats recovering from natural FeLV infection clearly correlates with resistance to subsequent infection and passive transfer of antibodies can protect other animals. After demonstrating the induction of neutralizing antibodies in rats and goats immunized with the transmembrane envelope protein p15E of FeLV, cats were immunized with the same antigen. High titres of neutralizing antibodies specific for FeLV were induced and epitope mapping revealed a pattern of recognition similar to that seen following immunization of rats and goats. These epitopes are highly related to epitopes recognized after immunization with porcine endogenous retrovirus (PERV) p15E and to epitopes recognized by neutralizing antibodies in patients infected with human immunodeficiency virus type 1. The ability of p15E to induce neutralizing antibodies in cats suggests that it should be included in the next generation of vaccines. In contrast, sera from FeLV-infected animals usually fail to recognize the neutralization-relevant epitopes in p15E. Since homologous epitope sequences are present in feline endogenous retroviruses, it appears that tolerance against these sequences is not induced. PMID:16423059

  11. Exergames: neuroplastic hypothesis about cognitive improvement and biological effects on physical function of institutionalized older persons

    PubMed Central

    Monteiro-Junior, Renato Sobral; Vaghetti, César Augusto Otero; Nascimento, Osvaldo José M.; Laks, Jerson; Deslandes, Andrea Camaz

    2016-01-01

    Exergames can be considered a dual task because the games are performed by a man-videogame interface, requiring cognitive and motor functions simultaneously. Although the literature has shown improvements of cognitive and physical functions due to exergames, the intrinsic mechanisms involved in these functional changes have still not been elucidated. The aims of the present study were (1) to demonstrate the known biological mechanisms of physical exercise regarding muscle adaptation and establish a relationship with exergames; and (2) to present a neurobiological hypothesis about the neuroplastic effects of exergames on the cognitive function of institutionalized older persons. These hypotheses are discussed. PMID:27073355

  12. Exergames: neuroplastic hypothesis about cognitive improvement and biological effects on physical function of institutionalized older persons.

    PubMed

    Monteiro-Junior, Renato Sobral; Vaghetti, César Augusto Otero; Nascimento, Osvaldo José M; Laks, Jerson; Deslandes, Andrea Camaz

    2016-02-01

    Exergames can be considered a dual task because the games are performed by a man-videogame interface, requiring cognitive and motor functions simultaneously. Although the literature has shown improvements of cognitive and physical functions due to exergames, the intrinsic mechanisms involved in these functional changes have still not been elucidated. The aims of the present study were (1) to demonstrate the known biological mechanisms of physical exercise regarding muscle adaptation and establish a relationship with exergames; and (2) to present a neurobiological hypothesis about the neuroplastic effects of exergames on the cognitive function of institutionalized older persons. These hypotheses are discussed. PMID:27073355

  13. 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

  14. Laminoplasty improves respiratory function in elderly patients with cervical spondylotic myelopathy.

    PubMed

    Yanaka, K; Noguchi, S; Asakawa, H; Nose, T

    2001-10-01

    Respiratory insufficiency after acute cervical trauma is well documented, but the relationship between respiratory function and chronic lesions, such as cervical spondylosis, has received scant attention. This clinical study investigated the effect of cervical spondylosis on respiratory function in 12 patients over 65 years of age who underwent expansive laminoplasty. Functional and neurological status were assessed using the Japanese Orthopaedic Association (JOA) scale and Neurosurgical Cervical Spine Scale (NCSS). To assess the effect of laminoplasty on respiratory function in patients with cervical spondylotic myelopathy, lung volumes including vital capacity, tidal volume (TV), inspiratory reserve volume, expiratory reserve volume, inspiratory capacity, and forced expiratory volume were measured by spirometer before surgery and 6 months after surgery. The arterial blood gas values were also measured before and after surgery. All patients showed functional improvement after surgery, and neurological examination 6 months after surgery revealed a significant improvement in both JOA scale and NCSS scores (p < 0.001). There were no significant differences in most lung volumes, but TV (p = 0.039) at 6 months after surgery showed a significant increase compared to before surgery. PCO2 also showed a significant reduction after surgery (p = 0.047). This limited study revealed that laminoplasty improved respiratory function in patients over 65 years of age with cervical spondylotic myelopathy. Lung volume measurement may be one method to estimate spinal cord function after a surgical procedure. PMID:11760383

  15. Cardiac function is preserved following 4 weeks of voluntary wheel running in a rodent model of chronic kidney disease

    PubMed Central

    Kuczmarski, James M.; Martens, Christopher R.; Kim, Jahyun; Lennon-Edwards, Shannon L.

    2014-01-01

    The purpose of this investigation was to determine the effect of 4 wk of voluntary wheel running on cardiac performance in the 5/6 ablation-infarction (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary wheel running would be effective in preserving cardiac function in AI. Male Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI. Animals were maintained over a total period of 8 wk following AI and sham surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk voluntary wheel-running intervention/sedentary control period. Cardiac performance was assessed using an isolated working heart preparation. Left ventricular (LV) tissue was used for biochemical tissue analysis. In addition, soleus muscle citrate synthase activity was measured. AI-WR rats performed a low volume of exercise, running an average of 13 2 km, which resulted in citrate synthase activity not different from that in sham animals. Isolated AI-SED hearts demonstrated impaired cardiac performance at baseline and in response to preload/afterload manipulations. Conversely, cardiac function was preserved in AI-WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO) synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In addition, LV H2O2 in AI-WR was similar to that of sham and associated with increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2. The findings of the current study suggest that a low-volume exercise intervention is sufficient to maintain cardiac performance in rats with CKD, potentially through a mechanism related to improved redox homeostasis and increased NO. PMID:25059238

  16. 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

  17. Left Ventricular Remodeling and Function in Children with Biventricular Circulation After Fetal Aortic Valvuloplasty.

    PubMed

    Friedman, Kevin G; Freud, Lindsay; Escobar-Diaz, Maria; Banka, Puja; Emani, Sitaram; Tworetzky, Wayne

    2015-10-01

    Fetal aortic valvuloplasty (FAV) has shown promise in averting the progression of fetal aortic stenosis to hypoplastic left-heart syndrome. Altered loading conditions due to valvar disease, intrinsic endomyocardial abnormalities, and procedures that alter endomyocardial mechanics may place patients with biventricular circulation (BiV) after FAV at risk of abnormal LV remodeling and function. Using the most recent echo data on BiV patients after technically successful FAV (n = 34), we evaluated LV remodeling pattern, risk factors for pathologic LV remodeling, and the association between LV remodeling pattern and LV function. Median age at follow-up was 4.7 years (range 1.0-12.5). Cardiac interventions were common. At latest follow-up, no patient had hypoplastic LV. Nineteen patients (55 %) had dilated LV, and five (16 %) patients had severely dilated LV. LV remodeling patterns were as follows: 12 (35 %) normal ventricle, 11 (32 %) mixed hypertrophy, 8 (24 %) eccentric hypertrophy or remodeling, and 3 (9 %) concentric hypertrophy. Univariate factors associated with pathologic LV remodeling were long-standing AR, ≥2 cardiac interventions, EFE resection, and aortic or mitral regurgitation ≥ moderate at most recent follow-up. In multivariate analysis, only long-standing AR fraction remained associated with pathologic remodeling. Pathologic LV remodeling was associated with depressed ejection fraction, lower septal E´, and higher E/E´. Pathologic LV remodeling, primarily eccentric or mixed hypertrophy, is common in BiV patients after FAV and is related to LV loading conditions imposed by valvar disease. Pathologic remodeling is associated with both systolic and diastolic dysfunction in this population. PMID:25972285

  18. Transduction of feline hematopoietic cells by oncoretroviral vectors pseudotyped with the subgroup A feline leukemia virus (FeLV-A).

    PubMed

    Josephson, N C; Sabo, K M; Abkowitz, J L

    2000-07-01

    The domestic cat is an outbred species with many identified analogues of human genetic diseases. Therefore, it has the potential to serve as a large animal model for evaluating the feasibility of hematopoietic stem cell gene therapy. This study compared gene transfer rates into feline hematopoietic progenitors by oncoretroviral vectors pseudotyped with the subgroup A feline leukemia virus (FeLV-A), the gibbon ape leukemia virus (GALV), and the murine amphotropic virus. Gene transfer rates were superior with the FeLV-A pseudotypes, which were then tested for their ability to transduce a cat hematopoietic repopulating cell. At more than 1 year posttransplantation, persistent marking was seen in both lymphoid and myeloid lineages of a myeloablated domestic cat that had received autologous marrow cells transduced with an FeLV-A pseudotyped vector. PMID:10899828

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

    PubMed

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

    2013-07-01

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

  20. Cardiac-Specific YAP Activation Improves Cardiac Function and Survival in an Experimental Murine MI Model

    PubMed Central

    Lin, Zhiqiang; von Gise, Alexander; Zhou, Pingzhu; Gu, Fei; Ma, Qing; Jiang, Jiangming; Yau, Allan L.; Buck, Jessica N.; Gouin, Katryna A.; van Gorp, Pim R. R.; Zhou, Bin; Chen, Jinghai; Seidman, Jonathan G.; Wang, Da-zhi; Pu, William T.

    2014-01-01

    Rationale Yes-Associated Protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte (CM) proliferation. Objective We hypothesized that YAP activation after myocardial infarction would preserve cardiac function and improve survival. Methods and Results We used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted CM proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the adult murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing CM apoptosis. Rather, AAV9:hYAP stimulated adult CM proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated expression of cell cycle genes and promoted a less mature cardiac gene expression signature. Conclusions Cardiac specific YAP activation after MI mitigated myocardial injury, improved cardiac function, and enhanced survival. These findings suggest that therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI. PMID:24833660

  1. A novel α4/7-conotoxin LvIA from Conus lividus that selectively blocks α3β2 vs. α6/α3β2β3 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 α3β2-subtype-selective nicotinic acetylcholine receptor (nAChR) ligand. A novel α4/7-conotoxin, α-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. α-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 α-CTxLvIA was for α3β2 nAChRs (IC50 8.7 nM), where blockade was reversible within 2 min. IC50 values were >100 nM at α6/α3β2β3, α6/α3β4, and α3β4 nAChRs, and ≥3 μM at all other subtypes tested. α3β2 vs. α6β2 subtype selectivity was confirmed for human-subunit nAChRs with much greater preference (300-fold) for α3β2 over α6β2 nAChRs. This is the first α-CTx reported to show high selectivity for human α3β2 vs. α6β2 nAChRs. α-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, α3β2 nAChR antagonist α-CTx PeIA probably reside within the three residues, which differ in loop 2, given their otherwise similar 3D structures. α4/7-CTx LvIA is a new, potent, selective α3β2 nAChR antagonist, which will enable detailed studies of α3β2 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 α4/7-conotoxin LvIA from Conus lividus that selectively blocks α3β2 vs. α6/α3β2β3 nicotinic acetylcholine receptors. PMID:24398291

  2. Novel invasion determinant of enteropathogenic Escherichia coli plasmid pLV501 encodes the ability to invade intestinal epithelial cells and HEp-2 cells.

    PubMed Central

    Fletcher, J N; Embaye, H E; Getty, B; Batt, R M; Hart, C A; Saunders, J R

    1992-01-01

    An Escherichia coli K-12 transformant carrying 96.5-kb plasmid pLV501 from enteropathogenic E. coli (EPEC) strain K798 is able to produce the same characteristic attaching-effacing lesions in a rabbit ileal biopsy explant model as its parent strain. Cloned EcoRI-SalI DNA restriction fragments from this plasmid failed to reproduce the attaching-effacing lesions, but one recombinant plasmid, pLV527, containing 4.5 kb of pLV501 DNA, conferred on E. coli DH1 transformants the ability to invade enterocytes in the rabbit explant model. DH1(pLV527) was also able to adhere to and invade HEp-2 cells. The relative invasive ability of DH1(pLV527) was quantified by recovery of internalized bacteria following gentamicin treatment of infected HEp-2 monolayers. DH1(pLV527) was 1,000-fold more invasive than DH1 carrying pBR322 or a recombinant plasmid which had no physiological effect on ileal biopsy explants but was less invasive than an enteroinvasive E. coli strain or a transformant carrying the cloned invasion genes of Shigella flexneri. Invasion by DH1(pLV501) could also be detected but occurred at a level 30 times lower than that by DH1(pLV527). Colony-hybridization of the pLV527 insert against a panel of 49 EPEC and related strains revealed that only 11 contained pLV527-hybridizing sequences; thus, the invasion determinant is not an essential component of the attachment-effacement pathogenic mechanism. One pLV527-hybridizing strain displayed both attachment-effacement and invasiveness in the rabbit ileal biopsy explant model. No significant hybridization was observed to non-EPEC invasive pathogenic enteric bacteria, indicating that the invasion determinant encoded on pLV527 is distinct from those used by these organisms. Images PMID:1587591

  3. Exercise effects on cardiac size and left ventricular diastolic function: relationships to changes in fitness, fatness, blood pressure and insulin resistance

    PubMed Central

    Stewart, K J; Ouyang, P; Bacher, A C; Lima, S; Shapiro, E P

    2006-01-01

    Objectives To determine exercise training effects on cardiac size and left ventricular (LV) diastolic function and relationships of exercise induced changes in physiological and body composition parameters with cardiac parameters. Design Prospective, randomised controlled trial. Subjects Men and women (63.6 (5.7) years, body mass index 29.5 (4.4) kg/m2) with untreated hypertension (systolic blood pressure (BP) 130–159 or diastolic BP 85–99 mm Hg). Main outcome measures Cardiac size and LV diastolic function, peak oxygen uptake (Vo2), muscle strength, general and abdominal fatness, and insulin resistance. Interventions 6 months of exercise training versus usual care. Results When analysed by group at six months, cardiac size and LV diastolic function did not differ between exercisers (n  =  51) and controls (n  =  53), whereas exercisers had significantly higher peak Vo2 (28 v 24 ml/kg/min) and strength (383 v 329 kg), and lower fatness (34% v 37%), diastolic BP (73 v 75 mm Hg) and insulin resistance (quantitative insulin sensitivity check index 0.35 v 0.34) versus controls (all p ⩽ 0.05). By regression analysis, among six month changes, increased peak Vo2 and reduced abdominal fat were associated with increased cardiac size. Increased peak Vo2 and reduced abdominal fat, BP and insulin resistance were associated with improved LV diastolic function. r Values ranged from 0.20 to 0.32 (p ⩽ 0.05). Conclusions When examined by group assignment, exercise had no effect on cardiac size or LV diastolic function. When individual variations in six month changes were examined, participants attaining the greatest increases in fitness and reductions in abdominal fatness, insulin resistance and BP showed a modest trend towards physiological hypertrophy characterised by increased cardiac size and improved LV diastolic function. These results suggest that decreased abdominal fatness may have a role in improving cardiovascular health. PMID:16308413

  4. The non-specificity of the left/right ventricular amplitude ratio (LV/RV) for mitral insufficiency

    SciTech Connect

    Preston, D.F.; Reinsel, M.S.; Martin, N.L.; Robinson, R.G.

    1984-01-01

    The purpose of this study was to determine the specificity of the LV/RV for mitral insufficiency. One hundred and sixty patients underwent MUGA studies as part of their diagnostic evaluation. Phase analysis was performed. In the amplitude image, the LV/RV was measured. Patients were divided into 11 clinical groups based on chart review after adequate follow-up. The groups were compared by Duncan's Multiple Comparsion Test. Patients with mitral insufficiency (N = 12, mean LV/RV = 2.36), those with idiopathic myocardiopathy (8, 2.29) and those with normal hearts having lung disease on chest x-ray (22, 1.78) formed a group which at the p < .05 level were not different from one another. Patients with idiopathic myocardiography, normal hearts with lung disease on chest x-ray, normal hearts with lung disease (23, 1.71) formed a second group which partially overlapped with both the first and third groups. The third group consisted of normal hearts with lung disease, normal hearts not taking adriamycin (18, 1.53), normal hearts taking adriamycin (22, 1.50), congestive heart failure (19, 1.50), arteriosclerotic heart disease, normal hearts (15, 1.29), chronic obstructive pulmonary disease and acute myocardial infarction. The LV/RV is not specific for mitral insufficiency. Idiopathic myocardiography, and normal hearts with lung disease on chest x-ray (metastases, cancer of the lung, infiltrates, fibrosis, and/or COPD) cannot be differentiated on a statistical basis. The mitral insufficiency group had the greatest values of LV/RV. It appears that decreased RV amplitude seen with diseases causing strain on the right ventricle will result in elevated LV/RV ratios.

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

    PubMed

    Shi, Benyun; Liu, Jiming

    2012-10-01

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

  6. Thermal and rheological properties improvement of drilling fluids using functionalized carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Fazelabdolabadi, Babak; Khodadadi, Abbas Ali; Sedaghatzadeh, Mostafa

    2015-08-01

    The application of functionalized/unfunctionalized (multi-walled) carbon nanotubes (CNT) was investigated in the context of formulating nano-based drilling fluids from water/oil-based fluid templates. CNT functionalization was attempted by applying hydrophilic functional groups onto the surface of the nanotubes via acid treatment. Experimental data were collected for thermal conductivity, viscosity/yield point, and filtrate amount in all samples. The time evolution of thermal conductivity was studied, as well as the effects of temperature and CNTs volume fraction on the parameter. Scanning electron microscopy (SEM) was used to monitor CNTs dispersion quality. The thermal conductivity results unveil considerable enhancements, by as much as 23.2 % (1 % vol. functionalized CNT) in CNT-water-based case at ambient temperature, with extended improvement of 31.8 % at an elevated temperature of 50 °C. Corresponding results for the CNT-oil-based case exhibit an improvement in thermal conductivity by 40.3 % (unfunctionalized) and 43.1 % (functionalized) and 1 % volume fraction of CNT. The rheological results follow an analogous improvement trend. For the CNT-oil-based case, the filtration tests conducted at 138 °C and 500 (psi) show a 16.67 % reduction in filtrate amount (1 % vol. CNT). The time evolution of thermal conductivity was found to nearly equalize (at an amount of 9.7 %) after 100 h of sample preparation in both functionalized and unfunctionalized CNT-oil-based cases.

  7. Seroprevalence of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in shelter cats on the island of Newfoundland, Canada

    PubMed Central

    Munro, Hannah J.; Berghuis, Lesley; Lang, Andrew S.; Rogers, Laura; Whitney, Hugh

    2014-01-01

    Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses found within domestic and wild cat populations. These viruses cause severe illnesses that eventually lead to death. Housing cats communally for long periods of time makes shelters at high risk for virus transmission among cats. We tested 548 cats from 5 different sites across the island of Newfoundland for FIV and FeLV. The overall seroprevalence was 2.2% and 6.2% for FIV and FeLV, respectively. Two sites had significantly higher seroprevalence of FeLV infection than the other 3 sites. Analysis of sequences from the FeLV env gene (envelope gene) from 6 positive cats showed that 4 fell within the FeLV subtype-A, while 2 sequences were most closely related to FeLV subtype-B and endogenous feline leukemia virus (en FeLV). Varying seroprevalence and the variation in sequences at different sites demonstrate that some shelters are at greater risk of FeLV infections and recombination can occur at sites of high seroprevalence. PMID:24688176

  8. Difficulties in demonstrating long term immunity in FeLV vaccinated cats due to increasing age-related resistance to infection

    PubMed Central

    2012-01-01

    Background Feline leukaemia virus (FeLV) is a pathogen causing fatal illness in cats worldwide, and as such there is a high demand for products to protect against disease. The duration of immunity provided by an inactivated FeLV vaccine, Versifel FeLV, when administered to cats of the target age was determined. Kittens received two vaccinations when aged 7 to 9 weeks old, and were subsequently challenged up to 36 months later with the FeLV-A Glasgow isolate. Results In all studies, all of the younger aged control kittens showed persistent FeLV p27 antigenaemia confirming that the challenge virus was severe and efficacious. In contrast, the control cats did not show the required level of persistent antigenaemia, with a maximum of 45% cats affected in the middle duration study and only 10% in the longer study. However, apart from one animal in the short duration study, all of the cats vaccinated with Versifel FeLV were negative for persistent antigenaemia and can be considered treatment successes. Conclusion In conclusion, we have shown that although age-related resistance to infection with a virulent FeLV challenge is evident from as early as 10 months of age, vaccination with Versifel FeLV may aid in the protection of cats from FeLV related disease up to three years after primary vaccination as kittens. PMID:22839692

  9. Molecular characterization of LvAV in response to white spot syndrome virus infection in the Pacific white shrimp (Litopenaeus vannamei).

    PubMed

    He, Shulin; Song, Lei; Qian, Zhaoying; Hou, Fujun; Liu, Yongjie; Wang, Xianzong; Peng, Zhangming; Sun, Chengbo; Liu, Xiaolin

    2015-07-01

    Litopenaeus vannamei is the most important farmed shrimp species globally, but its production is affected by several factors, including infectious disease. White spot syndrome virus (WSSV), in particular, causes significant shrimp losses. To understand the shrimp's immune response against WSSV, we cloned LvAV from L. vannamei and analyzed its expression pattern in different tissues, in addition to its expression following infection. We employed dsRNA and recombinant (r)LvAV to explore the potential role of LvAV in shrimp immunity when infected with WSSV. We find that LvAV is a C-type Lectin composed of 176 amino acids with a signal peptide and a specific C-type Lectin-type domain (CTLD). It shares 81% amino acid similarity with PmAV, an antiviral-like C-type Lectin from Penaeus monodom, and it is highly expressed in the hepatopancreas. Its expression is affected by infection with both WSSV and V. parahaemolyticus. Significantly, injection with rLvAV slowed WSSV replication, while injection with LvAV dsRNA initially led to enhanced virus propagation. Surprisingly, LvAV dsRNA subsequently led to a dramatic decrease in viral load in the later stages of infection, suggesting that LvAV may be subverted by WSSV to enhance viral replication or immune avoidance. Our results indicate that LvAV plays an important, but potentially complex role in the Pacific white shrimp's immune defense. PMID:25735872

  10. Seroprevalence of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in shelter cats on the island of Newfoundland, Canada.

    PubMed

    Munro, Hannah J; Berghuis, Lesley; Lang, Andrew S; Rogers, Laura; Whitney, Hugh

    2014-04-01

    Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses found within domestic and wild cat populations. These viruses cause severe illnesses that eventually lead to death. Housing cats communally for long periods of time makes shelters at high risk for virus transmission among cats. We tested 548 cats from 5 different sites across the island of Newfoundland for FIV and FeLV. The overall seroprevalence was 2.2% and 6.2% for FIV and FeLV, respectively. Two sites had significantly higher seroprevalence of FeLV infection than the other 3 sites. Analysis of sequences from the FeLV env gene (envelope gene) from 6 positive cats showed that 4 fell within the FeLV subtype-A, while 2 sequences were most closely related to FeLV subtype-B and endogenous feline leukemia virus (en FeLV). Varying seroprevalence and the variation in sequences at different sites demonstrate that some shelters are at greater risk of FeLV infections and recombination can occur at sites of high seroprevalence. PMID:24688176

  11. Structure and self assembly of a retrovirus (FeLV) proline rich neutralization domain.

    PubMed

    Fontenot, J D; Tjandra, N; Ho, C; Andrews, P C; Montelaro, R C

    1994-02-01

    The 60 amino acid proline-rich neutralization domain of the external surface unit glycoprotein of feline leukemia virus was chemically synthesized in total and in fragments. We examined the ability of these retroviral peptides to form ordered conformations using 1H-NMR, circular dichroism spectroscopy, and intrinsic viscosity measurements. One dimensional nuclear magnetic resonance spectroscopy revealed that the 60 amino acid peptide could form a stable, folded structure that was long-lived, as shown by the ability to protect amide-protons in D20. Peptides corresponding to the N-terminal 42, N-terminal 20 amino acids, and middle 20 amino acid sections could also form stable structures. The C-terminal segment did not protect any protons in D20. Interestingly, self assembly of the N-terminal 42 and C-terminal 16 amino acid peptides into a structure very close to that of the 60 amino acid domain was observed. The circular dichroism results reveals a large negative cotton effect at 198 nm that is characteristic of the proline-rich beta-turn helixes which consist predominantly of trans-proline. The intrinsic viscosity results suggest a non-random coil structure that is rod shaped. Our conclusion is that PRN60 forms a beta-turn helix and that this region of FeLV-gp70 is a separate folding domain of the retroviral surface unit glycoprotein. The unique conformational properties of PRN60 and its critical role as the predominant target for neutralizing antibody responses suggest that this peptide is a reasonable candidate for producing a synthetic peptide vaccine for FeLV. PMID:8204217

  12. 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

  13. Curva de rotação óptica de ESO-LV 5100550

    NASA Astrophysics Data System (ADS)

    Carvalho, D. B.; Soares, D. S. L.

    2003-08-01

    ESO-LV 5100550 é o membro mais fraco do par de galáxias austral SBG 357 (Soares et al. 1995). É classificada no catálogo RC3 como uma espiral ordinária de tipo inicial (early-type); porém, uma análise morfológica sugere que ela tenha uma grande barra. O objetivo do estudo é determinar sua cinemática de tal modo que possamos inferir mais a respeito de sua dinâmica, provavelmente perturbada, já que se espera que esteja sob forte influência da companheira ESO-LV 5100560. Apresentarei resultados parciais determinados a partir de espectros obtidos com o instrumento Double Spectrograph montado no telescópio Hale do Monte Palomar, EUA. As observações foram realizadas por D.S.L. Soares, P.M.V. Veiga e T.E. Nordgren, em 1998. Foram tomados espectros de fenda longa posicionada sobre a linha dos nodos do disco e ao longo da suposta barra. Os dados foram reduzidos com uso do pacote IRAF. Obtivemos o perfil de velocidades radiais na linha de visada ao longo das fendas e calculamos o desvio para o vermelho cosmológico do sistema, com base no espectro central. Determinamos as curvas de rotação deprojetadas, com base em cálculos para os valores teóricos esperados das componentes de velocidades puramente circulares em um disco inclinado. A inclinação do disco, dado fundamental nesta deprojeção, foi estimada através da média das elipticidades das isofotas mais externas.

  14. iPFPi: A System for Improving Protein Function Prediction through Cumulative Iterations.

    PubMed

    Taha, Kamal; Yoo, Paul D; Alzaabi, Mohammed

    2015-01-01

    We propose a classifier system called iPFPi that predicts the functions of un-annotated proteins. iPFPi assigns an un-annotated protein P the functions of GO annotation terms that are semantically similar to P. An un-annotated protein P and a GO annotation term T are represented by their characteristics. The characteristics of P are GO terms found within the abstracts of biomedical literature associated with P. The characteristics of Tare GO terms found within the abstracts of biomedical literature associated with the proteins annotated with the function of T. Let F and F/ be the important (dominant) sets of characteristic terms representing T and P, respectively. iPFPi would annotate P with the function of T, if F and F/ are semantically similar. We constructed a novel semantic similarity measure that takes into consideration several factors, such as the dominance degree of each characteristic term t in set F based on its score, which is a value that reflects the dominance status of t relative to other characteristic terms, using pairwise beats and looses procedure. Every time a protein P is annotated with the function of T, iPFPi updates and optimizes the current scores of the characteristic terms for T based on the weights of the characteristic terms for P. Set F will be updated accordingly. Thus, the accuracy of predicting the function of T as the function of subsequent proteins improves. This prediction accuracy keeps improving over time iteratively through the cumulative weights of the characteristic terms representing proteins that are successively annotated with the function of T. We evaluated the quality of iPFPi by comparing it experimentally with two recent protein function prediction systems. Results showed marked improvement. PMID:26357323

  15. Bilateral Improvements in Lower Extremity Function After Unilateral Balance Training in Individuals With Chronic Ankle Instability

    PubMed Central

    Hale, Sheri A.; Fergus, Andrea; Axmacher, Rachel; Kiser, Kimberly

    2014-01-01

    Context: Bilateral improvements in postural control have been reported among individuals with acute lateral ankle sprains and individuals with chronic ankle instability (CAI) when only the unstable ankle is rehabilitated. We do not know if training the stable ankle will improve function on the unstable side. Objective: To explore the effects of a unilateral balance-training program on bilateral lower extremity balance and function in individuals with CAI when only the stable limb is trained. Design: Cohort study. Setting: University clinical research laboratory. Patients or Other Participants: A total of 34 volunteers (8 men, 26 women; age = 24.32 ± 4.95 years, height = 167.01 ± 9.45 cm, mass = 77.54 ± 23.76 kg) with CAI were assigned to the rehabilitation (n = 17) or control (n = 17) group. Of those, 27 (13 rehabilitation group, 14 control group) completed the study. Intervention(s): Balance training twice weekly for 4 weeks. Main Outcome Measure(s): Foot and Ankle Disability Index (FADI), FADI Sport (FADI-S), Star Excursion Balance Test, and Balance Error Scoring System. Results: The rehabilitation and control groups differed in changes in FADI-S and Star Excursion Balance Test scores over time. Only the rehabilitation group improved in the FADI-S and in the posteromedial and anterior reaches of the Star Excursion Balance Test. Both groups demonstrated improvements in posterolateral reach; however, the rehabilitation group demonstrated greater improvement than the control group. When the groups were combined, participants reported improvements in FADI and FADI-S scores for the unstable ankle but not the stable ankle. Conclusions: Our data suggest training the stable ankle may result in improvements in balance and lower extremity function in the unstable ankle. This further supports the existence of a centrally mediated mechanism in the development of postural-control deficits after injury, as well as improved postural control after rehabilitation. PMID:24568231

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

    PubMed

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

    2013-01-01

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

  17. Systemic and coronary hemodynamic actions and left ventricular functional effects of levosimendan in conscious dogs.

    PubMed

    Harkin, C P; Pagel, P S; Tessmer, J P; Warltier, D C

    1995-08-01

    We examined the effects of levosimendan, a new myofilament Ca2+ sensitizer with phosphodiesterase (PDE)-inhibiting properties, on systemic and coronary hemodynamics and left ventricular (LV) systolic and diastolic function in conscious dogs with intact and blocked autonomic nervous system (ANS) reflexes. Twenty experiments were conducted in 10 dogs chronically instrumented for measurement of aortic and LV pressure, the peak rate of increase and decrease in LV pressure (+dP/dtmax and -dP/dtmin), subendocardial segment length, diastolic coronary blood flow (CBF) velocity, and cardiac output (CO). The slope (Mw) of the regional preload recruitable stroke work relation was used to assess myocardial contractility. Diastolic function was evaluated by -dP/dtmin, a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity during rapid ventricular filling (dL/dtmax), and a regional chamber stiffness constant (Kp). Dogs were randomly assigned to receive levosimendan (0.5, 1.0, 2.0, and 4.0 micrograms.kg-1.min-1) with or without ANS blockade. On separate experimental days, systemic and coronary hemodynamics and LV pressure-segment length diagrams and waveforms were recorded after 10-min equilibration at each dose in the conscious ANS-intact or ANS-blocked state. Levosimendan increased heart rate (HR), CO, mean and diastolic CBF velocity, and pressure-work index (PWI, an estimate of myocardial oxygen consumption) and decreased LV end-diastolic pressure (EDP), systemic vascular resistance (SVR), end-systolic and end-diastolic segment length, and mean and diastolic coronary vascular resistance (CVR) in dogs with intact ANS function. Levosimendan-induced increases in HR and PWI and decreases in SVR were attenuated by ANS blockade. Levosimendan caused equivalent dose-dependent increases in Mw in ANS-intact and ANS-blocked dogs, consistent with a positive inotropic effect independent of ANS activity. Levosimendan decreased tau (e.g., 35 +/- 1 ms during control to 29 +/- 1 ms at the high dose) and increased the magnitude of LV -dP/dtmin in dogs with intact but not blocked ANS reflexes, suggesting that relaxation was enhanced by favorable changes in systemic hemodynamics or ANS activation and direct effects of this drug on lusitropic state. Levosimendan also increased dL/dtmax to a greater degree in ANS-intact dogs, indicating that improvement of rapid ventricular filling was also partially dependent on ANS tone. No changes in Kp were observed in either experimental group. The results indicate that levosimendan decreases preload and afterload and has positive inotropic and lusitropic properties. The actions of levosimendan on diastolic function are largely mediated by the ANS. PMID:7475041

  18. EXERCISE IMPROVES SEXUAL FUNCTION IN WOMEN TAKING ANTIDEPRESSANTS: RESULTS FROM A RANDOMIZED CROSSOVER TRIAL

    PubMed Central

    Lorenz, Tierney Ahrold; Meston, Cindy May

    2014-01-01

    Background In laboratory studies, exercise immediately before sexual stimuli improved sexual arousal of women taking antidepressants [1]. We evaluated if exercise improves sexual desire, orgasm, and global sexual functioning in women experiencing antidepressant-induced sexual side effects. Methods Fifty-two women who were reporting antidepressant sexual side effects were followed for 3 weeks of sexual activity only. They were randomized to complete either three weeks of exercise immediately before sexual activity (3×/week) or 3 weeks of exercise separate from sexual activity (3×/week). At the end of the first exercise arm, participants crossed to the other. We measured sexual functioning, sexual satisfaction, depression, and physical health. Results Exercise immediately prior to sexual activity significantly improved sexual desire and, for women with sexual dysfunction at baseline, global sexual function. Scheduling regular sexual activity significantly improved orgasm function; exercise did not increase this benefit. Neither regular sexual activity nor exercise significantly changed sexual satisfaction. Conclusions Scheduling regular sexual activity and exercise may be an effective tool for the behavioral management of sexual side effects of antidepressants. PMID:24754044

  19. Playing piano can improve upper extremity function after stroke: case studies.

    PubMed

    Villeneuve, Myriam; Lamontagne, Anouk

    2013-01-01

    Music-supported therapy (MST) is an innovative approach that was shown to improve manual dexterity in acute stroke survivors. The feasibility of such intervention in chronic stroke survivors and its longer-term benefits, however, remain unknown. The objective of this pilot study was to estimate the short- and long-term effects of a 3-week piano training program on upper extremity function in persons with chronic stroke. A multiple pre-post sequential design was used, with measurements taken at baseline (week0, week3), prior to (week6) and after the intervention (week9), and at 3-week follow-up (week12). Three persons with stroke participated in the 3-week piano training program that combined structured piano lessons to home practice program. The songs, played on an electronic keyboard, involved all 5 digits of the affected hand and were displayed using a user-friendly MIDI program. After intervention, all the three participants showed improvements in their fine (nine hole peg test) and gross (box and block test) manual dexterity, as well as in the functional use of the upper extremity (Jebsen hand function test). Improvements were maintained at follow-up. These preliminary results support the feasibility of using an MST approach that combines structured lessons to home practice to improve upper extremity function in chronic stroke. PMID:23533954

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

    PubMed Central

    Villeneuve, Myriam; Lamontagne, Anouk

    2013-01-01

    Music-supported therapy (MST) is an innovative approach that was shown to improve manual dexterity in acute stroke survivors. The feasibility of such intervention in chronic stroke survivors and its longer-term benefits, however, remain unknown. The objective of this pilot study was to estimate the short- and long-term effects of a 3-week piano training program on upper extremity function in persons with chronic stroke. A multiple pre-post sequential design was used, with measurements taken at baseline (week0, week3), prior to (week6) and after the intervention (week9), and at 3-week follow-up (week12). Three persons with stroke participated in the 3-week piano training program that combined structured piano lessons to home practice program. The songs, played on an electronic keyboard, involved all 5 digits of the affected hand and were displayed using a user-friendly MIDI program. After intervention, all the three participants showed improvements in their fine (nine hole peg test) and gross (box and block test) manual dexterity, as well as in the functional use of the upper extremity (Jebsen hand function test). Improvements were maintained at follow-up. These preliminary results support the feasibility of using an MST approach that combines structured lessons to home practice to improve upper extremity function in chronic stroke. PMID:23533954

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

    ERIC Educational Resources Information Center

    Henning, Diane; Pickett, Anita

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

  2. Improving Students' Representational Flexibility in Linear-Function Problems: An Intervention

    ERIC Educational Resources Information Center

    Acevedo Nistal, A.; Van Dooren, W.; Verschaffel, L.

    2014-01-01

    This study evaluates the effects of an intervention aimed at improving representational flexibility in linear-function problems. Forty-nine students aged 13-16 participated in the study. A pretest-intervention-posttest design with an experimental and control group was used. At pretest, both groups solved a choice test, where they could freely…

  3. 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...

  4. 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…

  5. 42 CFR 493.2001 - Establishment and function of the Clinical Laboratory Improvement Advisory Committee.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Establishment and function of the Clinical Laboratory Improvement Advisory Committee. 493.2001 Section 493.2001 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Consultations §...

  6. A new function of rapid eye movement sleep: improvement of muscular efficiency.

    PubMed

    Cai, Zi-Jian

    2015-05-15

    Previously I demonstrated that the slow wave sleep (SWS) functioned to adjust the emotional balance disrupted by emotional memories randomly accumulated during waking, while the rapid eye movement (REM) sleep played the opposite role. Many experimental results have unambiguously shown that various emotional memories are processed during REM sleep. In this article, it is attempted to combine this confirmed function of REM sleep with the atonic state unique to REM sleep, and to integrate a new theory suggesting that improvement of muscular efficiency be a new function of REM sleep. This new function of REM sleep is more advantageous than the function of REM sleep in emotional memories and disinhibited drives to account for the phylogenetic variations of REM sleep, especially the absence of REM sleep in dolphins and short duration of REM sleep in birds in contrary to that in humans and rodents, the absence of penile erections in REM sleep in armadillo, as well as the higher voltage in EEG during REM sleep in platypus and ostrich. Besides, this new function of REM sleep is also advantageous to explain the association of REM sleep with the atonic episodes in SWS, the absence of drastic menopausal change in duration of REM sleep, and the effects of ambient temperature on the duration of REM sleep. These comparative and experimental evidences support the improvement of muscular efficiency as a new and major function of REM sleep. PMID:25770701

  7. Vagal activation by sham feeding improves gastric motility in functional dyspepsia.

    PubMed

    Lunding, J A; Nordström, L M; Haukelid, A-O; Gilja, O H; Berstad, A; Hausken, T

    2008-06-01

    Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 degrees C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude x frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 +/- 1.2 vs 4.4 +/- 1.0 min(-1), P = 0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding (P = 0.04 and P = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score (r = -0.59, P = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia. PMID:18248581

  8. Review of functional markers for improving cooking, eating, and the nutritional qualities of rice

    PubMed Central

    Lau, Wendy C. P.; Rafii, Mohd Y.; Ismail, Mohd R.; Puteh, Adam; Latif, Mohammad A.; Ramli, Asfaliza

    2015-01-01

    After yield, quality is one of the most important aspects of rice breeding. Preference for rice quality varies among cultures and regions; therefore, rice breeders have to tailor the quality according to the preferences of local consumers. Rice quality assessment requires routine chemical analysis procedures. The advancement of molecular marker technology has revolutionized the strategy in breeding programs. The availability of rice genome sequences and the use of forward and reverse genetics approaches facilitate gene discovery and the deciphering of gene functions. A well-characterized gene is the basis for the development of functional markers, which play an important role in plant genotyping and, in particular, marker-assisted breeding. In addition, functional markers offer advantages that counteract the limitations of random DNA markers. Some functional markers have been applied in marker-assisted breeding programs and have successfully improved rice quality to meet local consumers’ preferences. Although functional markers offer a plethora of advantages over random genetic markers, the development and application of functional markers should be conducted with care. The decreasing cost of sequencing will enable more functional markers for rice quality improvement to be developed, and application of these markers in rice quality breeding programs is highly anticipated. PMID:26528304

  9. Review of functional markers for improving cooking, eating, and the nutritional qualities of rice.

    PubMed

    Lau, Wendy C P; Rafii, Mohd Y; Ismail, Mohd R; Puteh, Adam; Latif, Mohammad A; Ramli, Asfaliza

    2015-01-01

    After yield, quality is one of the most important aspects of rice breeding. Preference for rice quality varies among cultures and regions; therefore, rice breeders have to tailor the quality according to the preferences of local consumers. Rice quality assessment requires routine chemical analysis procedures. The advancement of molecular marker technology has revolutionized the strategy in breeding programs. The availability of rice genome sequences and the use of forward and reverse genetics approaches facilitate gene discovery and the deciphering of gene functions. A well-characterized gene is the basis for the development of functional markers, which play an important role in plant genotyping and, in particular, marker-assisted breeding. In addition, functional markers offer advantages that counteract the limitations of random DNA markers. Some functional markers have been applied in marker-assisted breeding programs and have successfully improved rice quality to meet local consumers' preferences. Although functional markers offer a plethora of advantages over random genetic markers, the development and application of functional markers should be conducted with care. The decreasing cost of sequencing will enable more functional markers for rice quality improvement to be developed, and application of these markers in rice quality breeding programs is highly anticipated. PMID:26528304

  10. B cell-specific lentiviral gene therapy leads to sustained B-cell functional recovery in a murine model of X-linked agammaglobulinemia.

    PubMed

    Kerns, Hannah M; Ryu, Byoung Y; Stirling, Brigid V; Sather, Blythe D; Astrakhan, Alexander; Humblet-Baron, Stephanie; Liggitt, Denny; Rawlings, David J

    2010-03-18

    The immunodeficiency disorder, X-linked agammaglobulinemia (XLA), results from mutations in the gene encoding Bruton tyrosine kinase (Btk). Btk is required for pre-B cell clonal expansion and B-cell antigen receptor signaling. XLA patients lack mature B cells and immunoglobulin and experience recurrent bacterial infections only partially mitigated by life-long antibody replacement therapy. In pursuit of definitive therapy for XLA, we tested ex vivo gene therapy using a lentiviral vector (LV) containing the immunoglobulin enhancer (Emu) and Igbeta (B29) minimal promoter to drive B lineage-specific human Btk expression in Btk/Tec(-/-) mice, a strain that reproduces the features of human XLA. After transplantation of EmuB29-Btk-LV-transduced stem cells, treated mice showed significant, albeit incomplete, rescue of mature B cells in the bone marrow, peripheral blood, spleen, and peritoneal cavity, and improved responses to T-independent and T-dependent antigens. LV-treated B cells exhibited enhanced B-cell antigen receptor signaling and an in vivo selective advantage in the peripheral versus central B-cell compartment. Secondary transplantation showed sustained Btk expression, viral integration, and partial functional responses, consistent with long-term stem cell marking; and serial transplantation revealed no evidence for cellular or systemic toxicity. These findings strongly support pursuit of B lineage-targeted LV gene therapy in human XLA. PMID:20093406

  11. Fluorescently Labeled Peptide Increases Identification of Degenerated Facial Nerve Branches during Surgery and Improves Functional Outcome

    PubMed Central

    Hussain, Timon; Mastrodimos, Melina B.; Raju, Sharat C.; Glasgow, Heather L.; Whitney, Michael; Friedman, Beth; Moore, Jeffrey D.; Kleinfeld, David; Steinbach, Paul; Messer, Karen; Pu, Minya; Tsien, Roger Y.; Nguyen, Quyen T.

    2015-01-01

    Nerve degeneration after transection injury decreases intraoperative visibility under white light (WL), complicating surgical repair. We show here that the use of fluorescently labeled nerve binding probe (F-NP41) can improve intraoperative visualization of chronically (up to 9 months) denervated nerves. In a mouse model for the repair of chronically denervated facial nerves, the intraoperative use of fluorescent labeling decreased time to nerve identification by 40% compared to surgeries performed under WL alone. Cumulative functional post-operative recovery was also significantly improved in the fluorescence guided group as determined by quantitatively tracking of the recovery of whisker movement at time intervals for 6 weeks post-repair. To our knowledge, this is the first description of an injectable probe that increases visibility of chronically denervated nerves during surgical repair in live animals. Future translation of this probe may improve functional outcome for patients with chronic denervation undergoing surgical repair. PMID:25751149

  12. Lactulose enhances neuroplasticity to improve cognitive function in early hepatic encephalopathy

    PubMed Central

    Yang, Nan; Liu, He; Jiang, Yao; Zheng, Ji; Li, Dong-mei; Ji, Chao; Liu, Yan-yong; Zuo, Ping-ping

    2015-01-01

    Lactulose is known to improve cognitive function in patients with early hepatic encephalopathy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cognitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy. PMID:26604907

  13. Improving function in age-related macular degeneration: design and methods of a randomized clinical trial.

    PubMed

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

    2011-03-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD's prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population. PMID:20974293

  14. IMPROVING CORRELATION FUNCTION FITTING WITH RIDGE REGRESSION: APPLICATION TO CROSS-CORRELATION RECONSTRUCTION

    SciTech Connect

    Matthews, Daniel J.; Newman, Jeffrey A. E-mail: janewman@pitt.edu

    2012-02-01

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

  15. Improvement of mechanical heart function by trimetazidine in db/db mice

    PubMed Central

    Li, Yuan-jing; Wang, Pei-hua; Chen, Chen; Zou, Ming-hui; Wang, Dao-wen

    2010-01-01

    Aim: To investigate the influence of trimetazidine, which is known to be an antioxidant and modulator of metabolism, on cardiac function and the development of diabetic cardiomyopathy in db/db mouse. Methods: Trimetazidine was administered to db/db mice for eight weeks. Cardiac function was measured by inserting a Millar catheter into the left ventricle, and oxidative stress and AMP-activated protein kinase (AMPK) activity in the myocardium were evaluated. Results: Untreated db/db mice exhibited a significant decrease in cardiac function compared to normal C57 mice. Oxidative stress and lipid deposition were markedly increased in the myocardium, concomitant with inactivation of AMPK and increased expression of peroxisome proliferator-activated receptor coactivator-1α (PGC-1α). Trimetazidine significantly improved systolic and diastolic function in hearts of db/db mice and led to reduced production of reactive oxygen species and deposition of fatty acid in cardiomyocytes. Trimetazidine also caused AMPK activation and reduced PGC-1α expression in the hearts of db/db mice. Conclusion: The data suggest that trimetazidine significantly improves cardiac function in db/db mice by attenuating lipotoxicity and improving the oxidation status of the heart. Activation of AMPK and decreased expression of PGC-1α were involved in this process. Furthermore, our study suggests that trimetazidine suppresses the development of diabetic cardiomyopathy, which warrants further clinical investigation. PMID:20383170

  16. Increasing Muscle Mass Improves Vascular Function in Obese (db/db) Mice

    PubMed Central

    Qiu, Shuiqing; Mintz, James D.; Salet, Christina D.; Han, Weihong; Giannis, Athanassios; Chen, Feng; Yu, Yanfang; Su, Yunchao; Fulton, David J.; Stepp, David W.

    2014-01-01

    Background A sedentary lifestyle is an independent risk factor for cardiovascular disease and exercise has been shown to ameliorate this risk. Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training. The relationship between muscle mass and vascular function is poorly defined. The aims of the current study were to determine whether increasing muscle mass by genetic deletion of myostatin, a negative regulator of muscle growth, can influence vascular function in mesenteric arteries from obese db/db mice. Methods and Results Myostatin expression was elevated in skeletal muscle of obese mice and associated with reduced muscle mass (30% to 50%). Myostatin deletion increased muscle mass in lean (40% to 60%) and obese (80% to 115%) mice through increased muscle fiber size (P<0.05). Myostatin deletion decreased adipose tissue in lean mice, but not obese mice. Markers of insulin resistance and glucose tolerance were improved in obese myostatin knockout mice. Obese mice demonstrated an impaired endothelial vasodilation, compared to lean mice. This impairment was improved by superoxide dismutase mimic Tempol. Deletion of myostatin improved endothelial vasodilation in mesenteric arteries in obese, but not in lean, mice. This improvement was blunted by nitric oxide (NO) synthase inhibitor l‐NG‐nitroarginine methyl ester (l‐NAME). Prostacyclin (PGI2)‐ and endothelium‐derived hyperpolarizing factor (EDHF)‐mediated vasodilation were preserved in obese mice and unaffected by myostatin deletion. Reactive oxygen species) was elevated in the mesenteric endothelium of obese mice and down‐regulated by deletion of myostatin in obese mice. Impaired vasodilation in obese mice was improved by NADPH oxidase inhibitor (GKT136901). Treatment with sepiapterin, which increases levels of tetrahydrobiopterin, improved vasodilation in obese mice, an improvement blocked by l‐NAME. Conclusions Increasing muscle mass by genetic deletion of myostatin improves NO‐, but not PGI2‐ or EDHF‐mediated vasodilation in obese mice; this vasodilation improvement is mediated by down‐regulation of superoxide. PMID:24965025

  17. Towards improved local hybrid functionals by calibration of exchange-energy densities

    SciTech Connect

    Arbuznikov, Alexei V. E-mail: martin.kaupp@tu-berlin.de; Kaupp, Martin E-mail: martin.kaupp@tu-berlin.de

    2014-11-28

    A new approach for the calibration of (semi-)local and exact exchange-energy densities in the context of local hybrid functionals is reported. The calibration functions are derived from only the electron density and its spatial derivatives, avoiding spatial derivatives of the exact-exchange energy density or other computationally unfavorable contributions. The calibration functions fulfill the seven more important out of nine known exact constraints. It is shown that calibration improves substantially the definition of a non-dynamical correlation energy term for generalized gradient approximation (GGA)-based local hybrids. Moreover, gauge artifacts in the potential-energy curves of noble-gas dimers may be corrected by calibration. The developed calibration functions are then evaluated for a large range of energy-related properties (atomization energies, reaction barriers, ionization potentials, electron affinities, and total atomic energies) of three sets of local hybrids, using a simple one-parameter local-mixing. The functionals are based on (a) local spin-density approximation (LSDA) or (b) Perdew-Burke-Ernzerhof (PBE) exchange and correlation, and on (c) Becke-88 (B88) exchange and Lee-Yang-Parr (LYP) correlation. While the uncalibrated GGA-based functionals usually provide very poor thermochemical data, calibration allows a dramatic improvement, accompanied by only a small deterioration of reaction barriers. In particular, an optimized BLYP-based local-hybrid functional has been found that is a substantial improvement over the underlying global hybrids, as well as over previously reported LSDA-based local hybrids. It is expected that the present calibration approach will pave the way towards new generations of more accurate hyper-GGA functionals based on a local mixing of exchange-energy densities.

  18. 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

  19. 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

  20. 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

  1. Analysis and improvement of a chaos-based Hash function construction

    NASA Astrophysics Data System (ADS)

    Deng, Shaojiang; Li, Yantao; Xiao, Di

    2010-05-01

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

  2. Improved imaging with phase-weighted common conversion point stacks of receiver functions

    NASA Astrophysics Data System (ADS)

    Frassetto, A.; Zandt, G.; Gilbert, H.; Owens, T. J.; Jones, C. H.

    2010-07-01

    Broad-band array studies frequently stack receiver functions to improve their signal-to-noise ratio while mapping structures in the crust and upper mantle. Noise may produce spurious secondary arrivals that obscure or mimic arrivals produced by P-to-S conversions at large contrasts in seismic impedance such as the Moho. We use a Hilbert transform to calculate phase-weights, which minimize the constructive stacking of erroneous signal in receiver function data sets. We outline this approach and demonstrate its application through synthetic data combined with different types of noise, a previously published example of signal-generated noise, and a large data set from the Sierra Nevada EarthScope Project. These examples show that phase-weighting reduces the presence of signal-generated noise in receiver functions and improves stacked data sets.

  3. New casting material and improved functional design for lower femoral fracture bracing.

    PubMed

    Vaughan-Lane, T; Meggitt, B F

    1980-12-01

    A new water setting light plastic plaster material, Crystona, is presented and its plaster room characteristics compared with plaster of Paris. Plaster of Paris is considered better as the "acute fracture splinting material" in the Accident Service setting. Crystona, however, has considerable advantages as the "dynamic bracing material" in the post-acute fracture period and is demonstrated in the functional bracing of femoral shaft fractures. An improved functional cast brace design is presented, the "Knee Hinge Cylinder Brace" with a simple waist belt suspension to a hinged tube cast without the foot in the treatment of distal half femoral fractures. Using Crystona and the cylinder brace design, the cast weight has been reduced by half and the functional limb bracing improved with free mobilization of the knee, ankle and foot. The prescription, application technique and early clinical experiences are presented. PMID:7220245

  4. N-acetylcysteine amide preserves mitochondrial bioenergetics and improves functional recovery following spinal trauma.

    PubMed

    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

    2014-07-01

    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-acetylcysteine amide (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 600mg/kg) at 15min and 6h post-injury. After 24h 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 300mg/kg (n=4/group). For synaptic and non-synaptic mitochondria, only 300mg/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 6weeks 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

  5. Levomilnacipran Extended-Release Treatment in Patients With Major Depressive Disorder: Improvements in Functional Impairment Categories

    PubMed Central

    Gommoll, Carl P.; Chen, Changzheng; Greenberg, William M.; Ruth, Adam

    2015-01-01

    Objective: In this post hoc analysis, improvement in functional impairment in patients with major depressive disorder (MDD) treated with levomilnacipran extended release (ER) was evaluated by assessing shifts from more severe to less severe functional impairment categories on individual Sheehan Disability Scale (SDS) subscales. Method: SDS data were pooled from 5 phase II/III studies conducted between December 2006 and March 2012 of levomilnacipran ER versus placebo in adult patients with MDD (DSM-IV-TR criteria). Proportions of patients shifting from moderate-extreme baseline impairment (score ≥ 4) to mild-no impairment (score ≤ 3) at end of treatment were assessed for each SDS subscale. Proportions of patients shifting from marked-extreme (score ≥ 7) baseline impairment to moderate-no (score ≤ 6) or mild-no impairment (score ≤ 3) at end of treatment, and shifts in which patients worsened from moderate-no to marked-extreme impairment, were also evaluated. Results: A significantly higher proportion of patients treated with levomilnacipran ER than placebo-treated patients improved from more severe categories of functional impairment at baseline to less severe impairment categories across all SDS subscales: work/school, social life, and family life/home responsibilities (P < .01). Depending on the SDS subscale, 48%–55% of levomilnacipran ER–treated patients with moderate-extreme impairment at baseline improved to mild or no impairment, compared with no more than 40% of placebo patients on any subscale. Almost half (42%–47%) of levomilnacipran ER–treated patients versus only about one-third (29%–34%) of placebo patients improved from marked-extreme to mild or no impairment across functional domains. Conclusions: These results suggest that functional improvement was observed across the SDS functional domains. To our knowledge, this is the first such categorical analysis of functional improvement, as measured by the SDS, for an antidepressant. Trial Registration: ClinicalTrials.gov identifiers: NCT00969709, NCT01377194, NCT00969150, and NCT01034462 and EudraCT identifier: 2006–002404-34 PMID:26644957

  6. Conversion of human fibroblasts to tissue macrophages by the Snyder-Theilen feline sarcoma virus (ST:FeSV(FeLV)): productive infection by Leishmania major.

    PubMed

    Kopelovich, L

    1994-12-01

    The decisive role of macrophages in T-cell differentiation is best exemplified by cutaneous leishmaniasis. During infection, Leishmania attach to macrophages, the only site of replication for the parasite. We have recently demonstrated the conversion of human fibroblasts to tissue macrophages (TM) by transduction with the Snyder-Theilen feline sarcoma virus (ST:FeSV-(FeLV)). Since Leishmania have tropism only for macrophages, we have used the parasite to ascertain the functional phenotype of the ST:FeSV-induced TM. Here, we have demonstrated the productive infection of the ST:FeSV-induced TM by L. major. These results point to the utility of ST:FeSV-induced TM in studies that concern the role of human macrophages in T-cell differentiation during the course of infection by Leishmania. PMID:7721332

  7. Influence of Intraaortic Balloon Pump Counterpulsation on Transesophageal Echocardiography Derived Determinants of Diastolic Function

    PubMed Central

    Rosenberger, Peter; Schmid, Eckhard; Memtsoudis, Stavros G.; Angermair, Johannes; Tuli, Jayshree K.; Shernan, Stanton K.

    2015-01-01

    Introduction Intraaortic balloon pump counterpulsation (IABP) is often used in patients with acute coronary syndrome for its favourable effects on left ventricular (LV) systolic function and coronary perfusion. However, the effects of IABP on LV diastolic function have not been comprehensively investigated. Acute diastolic dysfunction has been linked to increased morbidity and mortality. The aim of this study was to examine the influence of IABP on LV diastolic dysfunction using standard TEE derived parameters. Methods Intraoperative TEE was performed in 10 patients (mean age 65 ± 11 yrs) undergoing urgent coronary artery bypass graft surgery (CABG), who had received an IABP preoperatively. TEE derived measures of diastolic dysfunction included early to late transmitral Doppler inflow velocity ratio (E/A), deceleration time (Dt), pulmonary venous systolic to diastolic Doppler velocity ratio (S/D), transmitral propagation velocity (Vp), and the ratio of early to late mitral annular tissue Doppler velocities (e’/a’). Statistical analyses included the Wilcoxon Sign-Rank test, and a p<0.05 was considered significant. Results Transmitral inflow E/A ratios increased significantly from 0.86 to 1.07 (p < 0.05), while Dt decreased significantly from 218 to 180 ms (p < 0.05) with the use of IABP. Significant increases in Vp (34 cm/s to 43 cm/s; p < 0.05), and e’/a’ (0.58 to 0.71; p < 0.05) suggested a favourable influence of intraaortic counterpulsation on diastolic function. Conclusion The use of perioperative IABP significantly improves TEE derived parameters of diastolic function consistent with a favourable impact on LV relaxation in cardiac surgery patients undergoing CABG. PMID:25739068

  8. Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure.

    PubMed Central

    Komamura, K; Shannon, R P; Pasipoularides, A; Ihara, T; Lader, A S; Patrick, T A; Bishop, S P; Vatner, S F

    1992-01-01

    We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition. Images PMID:1601992

  9. Alterations in left ventricular diastolic function in conscious dogs with pacing-induced heart failure

    NASA Technical Reports Server (NTRS)

    Komamura, K.; Shannon, R. P.; Pasipoularides, A.; Ihara, T.; Lader, A. S.; Patrick, T. A.; Bishop, S. P.; Vatner, S. F.

    1992-01-01

    We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition.

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

    NASA Technical Reports Server (NTRS)

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

    2012-01-01

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

  11. Percutaneous Mitral Valve Repair in Mitral Regurgitation Reduces Cell-Free Hemoglobin and Improves Endothelial Function

    PubMed Central

    Rammos, Christos; Zeus, Tobias; Balzer, Jan; Kubatz, Laura; Hendgen-Cotta, Ulrike B.; Veulemans, Verena; Hellhammer, Katharina; Totzeck, Matthias; Luedike, Peter; Kelm, Malte; Rassaf, Tienush

    2016-01-01

    Background and Objective Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO). NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR) suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR) approach has been shown to lead to significant clinical benefits. We here sought to investigate the role of endothelial function in MR and the potential impact of PMVR. Methods and Results Twenty-seven patients with moderate-to-severe MR treated with the MitraClip® device were enrolled in an open-label single-center observational study. Patients underwent clinical assessment, conventional echocardiography, and determination of endothelial function by measuring flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound at baseline and at 3-month follow-up. Patients with MR demonstrated decompartmentalized hemoglobin and reduced endothelial function (cell-free plasma hemoglobin in heme 28.9±3.8 μM, FMD 3.9±0.9%). Three months post-procedure, PMVR improved ejection fraction (from 41±3% to 46±3%, p = 0.03) and NYHA functional class (from 3.0±0.1 to 1.9±1.7, p<0.001). PMVR was associated with a decrease in cell free plasma hemoglobin (22.3±2.4 μM, p = 0.02) and improved endothelial functions (FMD 4.8±1.0%, p<0.0001). Conclusion We demonstrate here that plasma from patients with MR contains significant amounts of cell-free hemoglobin, which is accompanied by endothelial dysfunction. PMVR therapy is associated with an improved hemoglobin decompartmentalization and vascular function. PMID:26986059

  12. Development and validation of an evaporation duct model. Part II: Evaluation and improvement of stability functions

    NASA Astrophysics Data System (ADS)

    Ding, Juli; Fei, Jianfang; Huang, Xiaogang; Cheng, Xiaoping; Hu, Xiaohua; Ji, Liang

    2015-06-01

    This study aims to validate and improve the universal evaporation duct (UED) model through a further analysis of the stability function ( ψ). A large number of hydrometeorological observations obtained from a tower platform near Xisha Island of the South China Sea are employed, together with the latest variations in ψ function. Applicability of different ψ functions for specific sea areas and stratification conditions is investigated based on three objective criteria. The results show that, under unstable conditions, ψ function of Fairall et al. (1996) (i.e., Fairall96, similar for abbreviations of other function names) in general offers the best performance. However, strictly speaking, this holds true only for the stability (represented by bulk Richardson number R iB) range -2.6 ⩽ R iB < -0.1; when conditions become weakly unstable (-0.1 ⩽ R iB < -0.01), Fairall96 offers the second best performance after Hu and Zhang (1992) (HYQ92). Conversely, for near-neutral but slightly unstable conditions (-0.01 ⩽ R iB < 0.0), the effects of Edson04, Fairall03, Grachev00, and Fairall96 are similar, with Edson04 being the best function but offering only a weak advantage. Under stable conditions, HYQ92 is the optimal and offers a pronounced advantage, followed by the newly introduced SHEBA07 (by Grachev et al., 2007) function. Accordingly, the most favorable functions, i.e., Fairall96 and HYQ92, are incorporated into the UED model to obtain an improved version of the model. With the new functions, the mean root-mean-square (rms) errors of the modified refractivity ( M), 0-5-m M slope, 5-40-m M slope, and the rms errors of evaporation duct height (EDH) are reduced by 21.65%, 9.12%, 38.79%, and 59.06%, respectively, compared to the classical Naval Postgraduate School model.

  13. Phenomenological and biological correlates of improved cognitive function in hospitalized elderly medical inpatients.

    PubMed

    Adamis, Dimitrios; Meagher, David; Treloar, Adrian; Dunne, Colum; Larvin, Michael; Martin, Finbarr C; Macdonald, Alastair J D

    2014-01-01

    Deterioration of cognitive ability is a recognized outcome following acute illness in older patients. Levels of circulating cytokines and APOE genotype have both been linked with acute illness-related cognitive decline. In this observational longitudinal study, consecutive admissions to an elderly medical unit of patients aged ≥70 years were assessed within 3 days and re-assessed twice weekly with a range of scales assessing cognitive function, functional status and illness severity. Cytokines and APOE genotype were measured in a subsample. Improvement was defined as either a 20% or three points increase in mini mental state examination (MMSE). From the 142 participants 55 (39%) experienced cognitive improvement, of which 30 (54.5%) had delirium while 25 had non-delirious acute cognitive disorder. Using bivariate statistics, subjects with more severe acute illness, lower insulin-like growth factor-I (IGF-I) levels and more severe delirium were more likely to experience a ≥20% improvement in MMSE scores. When the criterion of cognitive improvement was a 3 point improvement in MMSE, those with more severe delirium, females and older were more likely to be improved. Longitudinal analysis using any criterion of improvement indicated that improvement was significantly (p<.05) predicted by higher levels of IGF-I, lower levels of IL-1 (alpha and beta), lack of APOE epsilon 4 allele, and female gender. In conclusion, cognitive recovery during admission is not exclusively linked to delirium status, but reflects a range of factors. The character and relevance of non-delirious acute cognitive disorder warrants further study. PMID:25189345

  14. DEVELOPMENT AND USE OF IMMUNOCHEMICAL METHODS FOR ENVIRONMENTAL CONTAMINANTS AT THE U.S. EPA, NERL, HERB-LV

    EPA Science Inventory

    The HERB-LV has developed several immunoassay methods for environmental and human exposure studies. Immunoassays to detect low levels (<10 ng/mL) chlorpyrifos in track-in dirt and house dust have been developed for indoor exposure surveys. An immunoassay for the urinary metabol...

  15. [A new intervention program for improvement of cognitive functions of senile dementia patients].

    PubMed

    Kawashima, Ryuta

    2005-01-01

    We proposed a new intervention program, the concept of which is derived from the knowledge of both brain science and clinical studies. We set up a hypothesis that activation of the association cortices by cognitive tasks may well improve the function of these cortices. To choose effective cognitive tasks for activation of the association cortices, we reviewed previous neuroimaging studies. Then, we prepared two tasks in arithmetic and Japanese language, which were systematized basic problems in reading and arithmetic, for the training program. Sixteen experimental and 16 control subjects participated. The subjects of the experimental group were asked to perform a training program using learning tasks in reading and arithmetic. The function of the frontal cortex of the subjects was assessed by FAB (frontal assessment battery at bedside). After six months of training, the FAB score of the experimental group showed a statistically significant improvement. We also observed the restoration of communication and independence, and improvement in relationships with the clinical staff in the experimental group. Our results indicate that learning tasks of reading aloud and arithmetic calculation can be used for cognitive rehabilitation, which improves frontal functions of dementia patients. PMID:16509427

  16. Anti-VEGF treatment improves neurological function and augments radiation response in NF2 schwannoma model.

    PubMed

    Gao, Xing; Zhao, Yingchao; Stemmer-Rachamimov, Anat O; Liu, Hao; Huang, Peigen; Chin, ShanMin; Selig, Martin K; Plotkin, Scott R; Jain, Rakesh K; Xu, Lei

    2015-11-24

    Hearing loss is the main limitation of radiation therapy for vestibular schwannoma (VS), and identifying treatment options that minimize hearing loss are urgently needed. Treatment with bevacizumab is associated with tumor control and hearing improvement in neurofibromatosis type 2 (NF2) patients; however, its effect is not durable and its mechanism of action on nerve function is unknown. We modeled the effect anti-VEGF therapy on neurological function in the sciatic nerve model and found that it improves neurological function by alleviating tumor edema, which may further improve results by decreasing muscle atrophy and increasing nerve regeneration. Using a cranial window model, we showed that anti-VEGF treatment may achieve these effects via normalizing the tumor vasculature, improving vessel perfusion, and delivery of oxygenation. It is known that oxygen is a potent radiosensitizer; therefore, we further demonstrated that combining anti-VEGF with radiation therapy can achieve a better tumor control and help lower the radiation dose and, thus, minimize radiation-related neurological toxicity. Our results provide compelling rationale for testing combined therapy in human VS. PMID:26554010

  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. 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

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

    PubMed

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

    2015-06-01

    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

  1. 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

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

    PubMed Central

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

    2011-01-01

    There has been increasing empirical evidence for the enhancing effects of Dejian Mind-Body Intervention (DMBI), a traditional Chinese Shaolin healing approach, on human frontal brain activity/functions, including patients with autism who are well documented to have frontal lobe problems. This study aims to compare the effects of DMBI with a conventional behavioural/cognitive intervention (CI) on enhancing the executive functions and memory of a nine-year-old boy with low-functioning autism (KY) and to explore possible underlying neural mechanism using EEG theta cordance. At post-one-month DMBI, KY's inhibitory control, cognitive flexibility, and memory functioning have significantly improved from “severely-to-moderately impaired” to “within-normal” range. This improvement was not observed from previous 12-month CI. Furthermore, KY showed increased cordance gradually extending from the anterior to the posterior brain region, suggesting possible neural mechanism underlying his cognitive improvement. These findings have implicated potential applicability of DMBI as a rehabilitation program for patients with severe frontal lobe and/or memory disorders. PMID:21584249

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

    PubMed Central

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

    2013-01-01

    Type 2 diabetes (T2D) has emerged as a major threat to human health in most parts of the world. Therapeutic strategies aimed at improving pancreatic ? cell function are predicted to prove beneficial for the treatment of T2D. In the present study, we demonstrate that drug-mediated, chronic, and selective activation of ? cell Gq signaling greatly improve ? cell function and glucose homeostasis in mice. These beneficial metabolic effects were accompanied by the enhanced expression of many genes critical for ? cell function, maintenance, and differentiation. By employing a combination of in vivo and in vitro approaches, we identified a novel ? cell pathway through which receptor-activated Gq leads to the sequential activation of ERK1/2 and IRS2 signaling, thus triggering a series of events that greatly improve ? cell function. Importantly, we found that chronic stimulation of a designer Gq-coupled receptor selectively expressed in ? cells prevented both streptozotocin-induced diabetes and the metabolic deficits associated with the consumption of a high-fat diet in mice. Since ? cells are endowed with numerous receptors that mediate their cellular effects via activation of Gq-type G proteins, our findings provide a rational basis for the development of novel antidiabetic drugs targeting this class of receptors. PMID:23478411

  4. A Piano Training Program to Improve Manual Dexterity and Upper Extremity Function in Chronic Stroke Survivors

    PubMed Central

    Villeneuve, Myriam; Penhune, Virginia; Lamontagne, Anouk

    2014-01-01

    Objective: Music-supported therapy was shown to induce improvements in motor skills in stroke survivors. Whether all stroke individuals respond similarly to the intervention and whether gains can be maintained over time remain unknown. We estimated the immediate and retention effects of a piano training program on upper extremity function in persons with chronic stroke. Methods: Thirteen stroke participants engaged in a 3-week piano training comprising supervised sessions (9 × 60 min) and home practice. Fine and gross manual dexterity, movement coordination, and functional use of the upper extremity were assessed at baseline, pre-intervention, post-intervention, and at a 3-week follow-up. Results: Significant improvements were observed for all outcomes at post-intervention and follow-up compared to pre-intervention scores. Larger magnitudes of change in manual dexterity and functional use of the upper extremity were associated with higher initial levels of motor recovery. Conclusion: Piano training can result in sustainable improvements in upper extremity function in chronic stroke survivors. Individuals with a higher initial level of motor recovery at baseline appear to benefit the most from this intervention. PMID:25202258

  5. Stretch-induced increase in cardiac contractility is independent of myocyte Ca2+ while block of stretch channels by streptomycin improves contractility after ischemic stunning

    PubMed Central

    Rhodes, Samhita S; Camara, Amadou K S; Aldakkak, Mohammed; Heisner, James S; Stowe, David F

    2015-01-01

    Stretching the cardiac left ventricle (LV) enhances contractility but its effect on myoplasmic [Ca2+] is controversial. We measured LV pressure (LVP) and [Ca2+] as a function of intra-LV stretch in guinea pig intact hearts before and after 15 min global stunning ± perfusion with streptomycin (STM), a stretch-activated channel blocker. LV wall [Ca2+] was measured by indo-1 fluorescence and LVP by a saline-filled latex balloon inflated in 50 μL steps to stretch the LV. We implemented a mathematical model to interpret cross-bridge dynamics and myofilament Ca2+ responsiveness from the instantaneous relationship between [Ca2+] and LVP ± stretching. We found that: (1) stretch enhanced LVP but not [Ca2+] before and after stunning in either control (CON) and STM groups, (2) after stunning [Ca2+] increased in both groups although higher in STM versus CON (56% vs. 39%), (3) STM-enhanced LVP after stunning compared to CON (98% vs. 76% of prestunning values), and (4) stretch-induced effects on LVP were independent of [Ca2+] before or after stunning in both groups. Mathematical modeling suggested: (1) cooperativity in cross-bridge kinetics and myofilament Ca2+ handling is reduced after stunning in the unstretched heart, (2) stunning results in depressed myofilament Ca2+ sensitivity in the presence of attached cross-bridges regardless of stretch, and (3) the initial mechanism responsible for increased contractility during stretch may be enhanced formation of cross-bridges. Thus stretch-induced enhancement of contractility is not due to increased [Ca2+], whereas enhanced contractility after stunning in STM versus CON hearts results from improved Ca2+ handling and/or enhanced actinomyosin cross-bridge cycling. PMID:26290532

  6. 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 μg/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.

  7. Enhanced response inhibition during intensive meditation training predicts improvements in self-reported adaptive socioemotional functioning.

    PubMed

    Sahdra, Baljinder K; MacLean, Katherine A; Ferrer, Emilio; Shaver, Phillip R; Rosenberg, Erika L; Jacobs, Tonya L; Zanesco, Anthony P; King, Brandon G; Aichele, Stephen R; Bridwell, David A; Mangun, George R; Lavy, Shiri; Wallace, B Alan; Saron, Clifford D

    2011-04-01

    We examined the impact of training-induced improvements in self-regulation, operationalized in terms of response inhibition, on longitudinal changes in self-reported adaptive socioemotional functioning. Data were collected from participants undergoing 3 months of intensive meditation training in an isolated retreat setting (Retreat 1) and a wait-list control group that later underwent identical training (Retreat 2). A 32-min response inhibition task (RIT) was designed to assess sustained self-regulatory control. Adaptive functioning (AF) was operationalized as a single latent factor underlying self-report measures of anxious and avoidant attachment, mindfulness, ego resilience, empathy, the five major personality traits (extroversion, agreeableness, conscientiousness, neuroticism, and openness to experience), difficulties in emotion regulation, depression, anxiety, and psychological well-being. Participants in Retreat 1 improved in RIT performance and AF over time whereas the controls did not. The control participants later also improved on both dimensions during their own retreat (Retreat 2). These improved levels of RIT performance and AF were sustained in follow-up assessments conducted approximately 5 months after the training. Longitudinal dynamic models with combined data from both retreats showed that improvement in RIT performance during training influenced the change in AF over time, which is consistent with a key claim in the Buddhist literature that enhanced capacity for self-regulation is an important precursor of changes in emotional well-being. PMID:21500899

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

    PubMed Central

    Dieruf, Kathy; Ewer, Lynette; Boninger, David

    2008-01-01

    Background/Objective: People with spinal cord injury (SCI) may spend several decades using a wheelchair as their primary means of mobility. Secondary injury and a decline in independence over time are common with manual wheelchair users who, in turn, may require increased assistance as time passes. The Natural-Fit contoured handrim has been shown to improve symptoms and function in people with SCI who use manual wheelchairs and who have experienced upper extremity pain. The objective of this study was to determine the factors associated with improved symptoms and functions. Participants: 87 people who purchased the ergonomic wheelchair handrims. Participants were predominately men, with a median age of 51 to 55 years, median level of injury T10 to T12, median time in a wheelchair of 15 years, and they had used the contoured rims for 1 to 2 years. Methods: This was a mail survey of 217 people who purchased the rims. The survey was mailed out from the manufacturer and was anonymously returned to the physical therapy department of a university. A $10 incentive was offered for returning the survey. Results: The majority of participants reported improvements in upper extremity symptoms, ease of wheelchair propulsion, and functional status. Longer use of the rims was associated with reported improvement in ease of wheelchair propulsion and reduction in pain in hands and wrists. Conclusion: If a simple modification of the wheelchair can help bring about significant changes in the users' symptoms and function, this modification should be incorporated by people who use manual wheelchairs before decline in function begins. Proactive intervention may alleviate symptoms, help the person maintain maximal independence, and prolong the length of time the individual remains independent. PMID:19086716

  9. Using Low Levels of Stochastic Vestibular Stimulation to Improve Balance Function

    PubMed Central

    Goel, Rahul; Kofman, Igor; Jeevarajan, Jerome; De Dios, Yiri; Cohen, Helen S.; Bloomberg, Jacob J.; Mulavara, Ajitkumar P.

    2015-01-01

    Low-level stochastic vestibular stimulation (SVS) has been associated with improved postural responses in the medio-lateral (ML) direction, but its effect in improving balance function in both the ML and anterior-posterior (AP) directions has not been studied. In this series of studies, the efficacy of applying low amplitude SVS in 0–30 Hz range between the mastoids in the ML direction on improving cross-planar balance function was investigated. Forty-five (45) subjects stood on a compliant surface with their eyes closed and were instructed to maintain a stable upright stance. Measures of stability of the head, trunk, and whole body were quantified in ML, AP and combined APML directions. Results show that binaural bipolar SVS given in the ML direction significantly improved balance performance with the peak of optimal stimulus amplitude predominantly in the range of 100–500 μA for all the three directions, exhibiting stochastic resonance (SR) phenomenon. Objective perceptual and body motion thresholds as estimates of internal noise while subjects sat on a chair with their eyes closed and were given 1 Hz bipolar binaural sinusoidal electrical stimuli were also measured. In general, there was no significant difference between estimates of perceptual and body motion thresholds. The average optimal SVS amplitude that improved balance performance (peak SVS amplitude normalized to perceptual threshold) was estimated to be 46% in ML, 53% in AP, and 50% in APML directions. A miniature patch-type SVS device may be useful to improve balance function in people with disabilities due to aging, Parkinson’s disease or in astronauts returning from long-duration space flight. PMID:26295807

  10. RNA Interference for Functional Genomics and Improvement of Cotton (Gossypium sp.).

    PubMed

    Abdurakhmonov, Ibrokhim Y; Ayubov, Mirzakamol S; Ubaydullaeva, Khurshida A; Buriev, Zabardast T; Shermatov, Shukhrat E; Ruziboev, Haydarali S; Shapulatov, Umid M; Saha, Sukumar; Ulloa, Mauricio; Yu, John Z; Percy, Richard G; Devor, Eric J; Sharma, Govind C; Sripathi, Venkateswara R; Kumpatla, Siva P; van der Krol, Alexander; Kater, Hake D; Khamidov, Khakimdjan; Salikhov, Shavkat I; Jenkins, Johnie N; Abdukarimov, Abdusattor; Pepper, Alan E

    2016-01-01

    RNA interference (RNAi), is a powerful new technology in the discovery of genetic sequence functions, and has become a valuable tool for functional genomics of cotton (Gossypium sp.). The rapid adoption of RNAi has replaced previous antisense technology. RNAi has aided in the discovery of function and biological roles of many key cotton genes involved in fiber development, fertility and somatic embryogenesis, resistance to important biotic and abiotic stresses, and oil and seed quality improvements as well as the key agronomic traits including yield and maturity. Here, we have comparatively reviewed seminal research efforts in previously used antisense approaches and currently applied breakthrough RNAi studies in cotton, analyzing developed RNAi methodologies, achievements, limitations, and future needs in functional characterizations of cotton genes. We also highlighted needed efforts in the development of RNAi-based cotton cultivars, and their safety and risk assessment, small and large-scale field trials, and commercialization. PMID:26941765

  11. Towards improved exact exchange functionals relying on G W quasiparticle methods for parametrization

    NASA Astrophysics Data System (ADS)

    Zólyomi, V.; Kürti, J.

    2015-07-01

    We use fully self-consistent GW calculations on diamond and silicon carbide to reparametrize the Heyd-Scuseria-Ernzerhof (HSE) exact exchange density functional for use in band structure calculations of semiconductors and insulators. We show that the thus modified functional is able to calculate the band structure of bulk Si, Ge, GaAs, and CdTe with good quantitative accuracy at a significantly reduced computational cost as compared to G W methods, and also gives significantly improved band gap predictions in wide-gap ionic crystals as compared to the HSE06 parametrization. We discuss the limitations of this functional in low dimensions by calculating the band structures of single-layer hexagonal BN and MoS2, and by demonstrating that the diameter scaling of curvature induced band gaps in single-walled carbon nanotubes is still physically incorrect using our functional; we consider possible remedies to this problem.

  12. Use of global functions for improvement in efficiency of nonlinear analysis. [in computer structural displacement estimation

    NASA Technical Reports Server (NTRS)

    Almroth, B. O.; Stehlin, P.; Brogan, F. A.

    1981-01-01

    A method for improving the efficiency of nonlinear structural analysis by the use of global displacement functions is presented. The computer programs include options to define the global functions as input or let the program automatically select and update these functions. The program was applied to a number of structures: (1) 'pear-shaped cylinder' in compression, (2) bending of a long cylinder, (3) spherical shell subjected to point force, (4) panel with initial imperfections, (5) cylinder with cutouts. The sample cases indicate the usefulness of the procedure in the solution of nonlinear structural shell problems by the finite element method. It is concluded that the use of global functions for extrapolation will lead to savings in computer time.

  13. RNA Interference for Functional Genomics and Improvement of Cotton (Gossypium sp.)

    PubMed Central

    Abdurakhmonov, Ibrokhim Y.; Ayubov, Mirzakamol S.; Ubaydullaeva, Khurshida A.; Buriev, Zabardast T.; Shermatov, Shukhrat E.; Ruziboev, Haydarali S.; Shapulatov, Umid M.; Saha, Sukumar; Ulloa, Mauricio; Yu, John Z.; Percy, Richard G.; Devor, Eric J.; Sharma, Govind C.; Sripathi, Venkateswara R.; Kumpatla, Siva P.; van der Krol, Alexander; Kater, Hake D.; Khamidov, Khakimdjan; Salikhov, Shavkat I.; Jenkins, Johnie N.; Abdukarimov, Abdusattor; Pepper, Alan E.

    2016-01-01

    RNA interference (RNAi), is a powerful new technology in the discovery of genetic sequence functions, and has become a valuable tool for functional genomics of cotton (Gossypium sp.). The rapid adoption of RNAi has replaced previous antisense technology. RNAi has aided in the discovery of function and biological roles of many key cotton genes involved in fiber development, fertility and somatic embryogenesis, resistance to important biotic and abiotic stresses, and oil and seed quality improvements as well as the key agronomic traits including yield and maturity. Here, we have comparatively reviewed seminal research efforts in previously used antisense approaches and currently applied breakthrough RNAi studies in cotton, analyzing developed RNAi methodologies, achievements, limitations, and future needs in functional characterizations of cotton genes. We also highlighted needed efforts in the development of RNAi-based cotton cultivars, and their safety and risk assessment, small and large-scale field trials, and commercialization. PMID:26941765

  14. 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

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

    PubMed

    Easterling, Caryn

    2008-09-01

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

  16. Nitric oxide-donating statin improves multiple functions of circulating angiogenic cells

    PubMed Central

    Mangialardi, G; Monopoli, A; Ongini, E; Spinetti, G; Fortunato, O; Emanueli, C; Madeddu, P

    2011-01-01

    BACKGROUND AND PURPOSE Statins, a major component of the prevention of cardiovascular disease, aid progenitor cell functions in vivo and in vitro. Statins bearing a NO-releasing moiety were developed for their enhanced anti-inflammatory/anti-thrombotic properties. Here, we investigated if the NO-donating atorvastatin (NCX 547) improved the functions of circulating angiogenic cells (CACs). EXPERIMENTAL APPROACH Circulating angiogenic cells (CACs) were prepared from peripheral blood monocytes of healthy volunteers and type-2 diabetic patients and were cultured in low (LG) or high glucose (HG) conditions, in presence of atorvastatin or NCX 547 (both at 0.1 µM) or vehicle. Functional assays (outgrowth, proliferation, viability, senescence and apoptosis) were performed in presence of the endothelial NOS inhibitor L-NIO, the NO scavenger c-PTIO or vehicle. KEY RESULTS Culturing in HG conditions lowered NO in CACs, inhibited outgrowth, proliferation, viability and migration, and induced cell senescence and apoptosis. NCX 547 fully restored NO levels and functions of HG-cultured CACs, while atorvastatin prevented only apoptosis in CACs. The activity of Akt, a pro-survival kinase, was increased by atorvastatin in LG-cultured but not in HG-cultured CACs, whereas NCX 547 increased Akt activity in both conditions. L-NIO partially blunted and c-PTIO prevented NCX 547-induced improvements in CAC functions. Finally, NCX 547 improved outgrowth and migration of CACs prepared from patients with type 2 diabetes. CONCLUSIONS AND IMPLICATIONS NCX 547 was more effective than atorvastatin in preserving functions of CACs. This property adds to the spectrum of favourable actions that would make NO-releasing statins more effective agents for treating cardiovascular disease. PMID:21486281

  17. Evolution of the genetic code by incorporation of amino acids that improved or changed protein function.

    PubMed

    Francis, Brian R

    2013-10-01

    Fifty years have passed since the genetic code was deciphered, but how the genetic code came into being has not been satisfactorily addressed. It is now widely accepted that the earliest genetic code did not encode all 20 amino acids found in the universal genetic code as some amino acids have complex biosynthetic pathways and likely were not available from the environment. Therefore, the genetic code evolved as pathways for synthesis of new amino acids became available. One hypothesis proposes that early in the evolution of the genetic code four amino acids-valine, alanine, aspartic acid, and glycine-were coded by GNC codons (N = any base) with the remaining codons being nonsense codons. The other sixteen amino acids were subsequently added to the genetic code by changing nonsense codons into sense codons for these amino acids. Improvement in protein function is presumed to be the driving force behind the evolution of the code, but how improved function was achieved by adding amino acids has not been examined. Based on an analysis of amino acid function in proteins, an evolutionary mechanism for expansion of the genetic code is described in which individual coded amino acids were replaced by new amino acids that used nonsense codons differing by one base change from the sense codons previously used. The improved or altered protein function afforded by the changes in amino acid function provided the selective advantage underlying the expansion of the genetic code. Analysis of amino acid properties and functions explains why amino acids are found in their respective positions in the genetic code. PMID:23743924

  18. Improved prediction of accessible surface area results in efficient energy function application.

    PubMed

    Iqbal, Sumaiya; Mishra, Avdesh; Hoque, Md Tamjidul

    2015-09-01

    An accurate prediction of real value accessible surface area (ASA) from protein sequence alone has wide application in the field of bioinformatics and computational biology. ASA has been helpful in understanding the 3-dimensional structure and function of a protein, acting as high impact feature in secondary structure prediction, disorder prediction, binding region identification and fold recognition applications. To enhance and support broad applications of ASA, we have made an attempt to improve the prediction accuracy of absolute accessible surface area by developing a new predictor paradigm, namely REGAd(3)p, for real value prediction through classical Exact Regression with Regularization and polynomial kernel of degree 3 which was further optimized using Genetic Algorithm. ASA assisting effective energy function, motivated us to enhance the accuracy of predicted ASA for better energy function application. Our ASA prediction paradigm was trained and tested using a new benchmark dataset, proposed in this work, consisting of 1001 and 298 protein chains, respectively. We achieved maximum Pearson Correlation Coefficient (PCC) of 0.76 and 1.45% improved PCC when compared with existing top performing predictor, SPINE-X, in ASA prediction on independent test set. Furthermore, we modeled the error between actual and predicted ASA in terms of energy and combined this energy linearly with the energy function 3DIGARS which resulted in an effective energy function, namely 3DIGARS2.0, outperforming all the state-of-the-art energy functions. Based on Rosetta and Tasser decoy-sets 3DIGARS2.0 resulted 80.78%, 73.77%, 141.24%, 16.52%, and 32.32% improvement over DFIRE, RWplus, dDFIRE, GOAP and 3DIGARS respectively. PMID:26092374

  19. Plasma electrophoretogram in feline immunodeficiency virus (FIV) and/or feline leukaemia virus (FeLV) infections.

    PubMed

    Mir, G; Domnech, A; Escolar, E; Collado, V M; Tejerizo, G; De Las Heras, A; Gmez-Luca, E

    2007-05-01

    The electrophoretogram of 89 cats, including those infected by feline immunodeficiency virus (FIV+), feline leukaemia virus (FeLV+) and non-infected, showed statistically significant differences in several of the fractions. FIV+ cats had very high protein values (mean, 8.10 g/dl), mostly because of hypergammaglobulinemia (mean, 2.81 g/dl) as compared with non-infected animals and FeLV+. In addition, in these FIV+ animals, the albumin/globulins ratio (A/G) was very low (mean, 0.72). Statistically significant differences in A/G and alpha2-globulin fraction were observed in FeLV+ group (A/G mean, 0.88 +/- 0.08; alpha2-globulin, mean, 0.84 +/- 0.07 g/dl) when compared with non-infected group (A/G mean, 1.06 +/- 0.08; alpha2-globulin mean, 0.68 +/- 0.04 g/dl). The alpha1-globulin fraction was higher in double infected animals (FIV and FeLV positive, F-F) (3.55 g/dl), than in FeLV+ or FIV+ cats (3.10 and 3.07 g/dl respectively), but no statistical conclusions may be drawn from this fact because of the low number of F-F animals. This technique may help to assess the initial clinical status of retrovirus-infected cats, and the clinical course of these chronic diseases, specifically during and after suitable therapy. PMID:17493167

  20. 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

  1. Antisecretory therapy with no improvement in functional level in Ménière's disease.

    PubMed

    Ingvardsen, Charlotte J; Klokker, Mads

    2016-03-01

    Conclusion Antisecretory factor-inducing (AF) specially processed cereals (SPC) were not shown to significantly improve the functional level in patients with MD. Objectives The aim of this study was to evaluate the effect of AF-inducing SPC in patients suffering from Ménière's disease (MD). Methods A randomized double-blinded, placebo-controlled cross-over study was conducted. All patients had a 2 months intake of SPC and control cereal with a 2 months washout period in between. The severity of MD was classified according to the American Academy of Otolaryngology-Head and Neck Surgery (AOO-HNS) functional scale, and the frequency of attacks was registered. Results Thirty-two patients completed the study. No carryover effect was found. In both functional level and frequency of attacks no significant effect of SPC was found. Seventeen patients showed improvement in functional level when treated with SPC (mean improvement = 0.9 points) and 14 when treated with placebo (mean improvements = 0.7 points). No patients showed worsening in functional level during treatment with SPC, but three showed worsening when treated with placebo. Seventeen patients reported fewer attacks when treated with SPC, and 22 when treated with placebo. Three patients reported more frequent attacks when treated with SPC, and three when treated with placebo. A non-parametric comparison and a parametric analysis supported the findings. PMID:26635204

  2. miR-27b overexpression improves mitochondrial function in a Sirt1-dependent manner.

    PubMed

    Zhou, Xihong; Zuo, Shengnan; Xin, Wu

    2015-12-01

    Resveratrol improves mitochondrial function, and recent evidences demonstrate that miRNAs play important roles in certain effects of resveratrol. In the current study, we found that a microRNA, miR-27b, was significantly induced in a dose-dependent way in skeletal muscle and C2C12 myoblast treated with resveratrol. Our results showed that overexpression of miR-27b could mimic the effects of resveratrol on improving mitochondrial function and glucose uptake in skeletal muscle cells. Subsequently, we found that FOXO1 was a potential target of miR-27b, and the effects of resveratrol on mitochondrial function were significantly affected after inhibition of miR-27b. Moreover, the effects of miR-27b on mitochondrial function were lost after inhibition of Sirt1, although miR-27b and FOXO1 expression were not influenced. Taken together, these data suggested that overexpression of miR-27b could benefit mitochondrial function, while the effects of overexpressed miR-27b were Sirt1-dependent. PMID:26452502

  3. Coherent Functional Modules Improve Transcription Factor Target Identification, Cooperativity Prediction, and Disease Association

    PubMed Central

    Karczewski, Konrad J.; Snyder, Michael; Altman, Russ B.; Tatonetti, Nicholas P.

    2014-01-01

    Transcription factors (TFs) are fundamental controllers of cellular regulation that function in a complex and combinatorial manner. Accurate identification of a transcription factor's targets is essential to understanding the role that factors play in disease biology. However, due to a high false positive rate, identifying coherent functional target sets is difficult. We have created an improved mapping of targets by integrating ChIP-Seq data with 423 functional modules derived from 9,395 human expression experiments. We identified 5,002 TF-module relationships, significantly improved TF target prediction, and found 30 high-confidence TF-TF associations, of which 14 are known. Importantly, we also connected TFs to diseases through these functional modules and identified 3,859 significant TF-disease relationships. As an example, we found a link between MEF2A and Crohn's disease, which we validated in an independent expression dataset. These results show the power of combining expression data and ChIP-Seq data to remove noise and better extract the associations between TFs, functional modules, and disease. PMID:24516403

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

    PubMed Central

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

    2013-01-01

    Motivation: Computational biologists have demonstrated the utility of using machine learning methods to predict protein function from an integration of multiple genome-wide data types. Yet, even the best performing function prediction algorithms rely on heuristics for important components of the algorithm, such as choosing negative examples (proteins without a given function) or determining key parameters. The improper choice of negative examples, in particular, can hamper the accuracy of protein function prediction. Results: We present a novel approach for choosing negative examples, using a parameterizable Bayesian prior computed from all observed annotation data, which also generates priors used during function prediction. We incorporate this new method into the GeneMANIA function prediction algorithm and demonstrate improved accuracy of our algorithm over current top-performing function prediction methods on the yeast and mouse proteomes across all metrics tested. Availability: Code and Data are available at: http://bonneaulab.bio.nyu.edu/funcprop.html Contact: shasha@courant.nyu.edu or bonneau@cs.nyu.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23511543

  5. 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 (ΔΨm), 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. PMID:26180820

  6. The Small Molecule Wnt Signaling Modulator ICG-001 Improves Contractile Function in Chronically Infarcted Rat Myocardium

    PubMed Central

    Nguyen, Cu; Kloner, Robert A.; Kahn, Michael

    2013-01-01

    The adult mammalian heart has limited capability for self-repair after myocardial infarction. Therefore, therapeutic strategies that improve post-infarct cardiac function are critically needed. The small molecule ICG-001 modulates Wnt signaling and increased the expression of genes beneficial for cardiac regeneration in epicardial cells. Lineage tracing experiments, demonstrated the importance of ?-catenin/p300 mediated transcription for epicardial progenitor contribution to the myocardium. Female rats given ICG-001 for 10 days post-occlusion significantly improved ejection fraction by 8.4%, compared to controls (P<0.05). Taken together, Wnt modulation via ?-catenin/CBP inhibition offers a promising therapeutic strategy towards restoration of myocardial tissues and an enhancement of cardiac functions following infarction. PMID:24069374

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

    PubMed

    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 (ΔΨ 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. PMID:26180820

  8. Treatment-related improvement in neuropsychological functioning in suicidal depressed patients: paroxetine vs. bupropion

    PubMed Central

    Gorlyn, Marianne; Keilp, John; Burke, Ainsley; Oquendo, Maria; Mann, J. John; Grunebaum, Michael

    2015-01-01

    Neuropsychological dysfunction is associated with risk for suicidal behavior, but it is unknown if antidepressant medication treatment is effective in reducing this dysfunction, or if specific medications might be more beneficial. A comprehensive neuropsychological battery was administered at baseline and after eight weeks of treatment within a randomized, double-blind clinical trial comparing paroxetine and bupropion in study of patients with DSM-IV major depressive disorder and either past suicide attempt or current suicidal thoughts. Change in neurocognitive performance was compared between assessments and between medication groups. Treatment effects on Hamilton Depression Rating Scale and Scale for Suicidal Ideation were compared with neurocognitive improvement. Neurocognitive functioning improved after treatment in all patients, without clear advantage for either medication. Improvement in memory performance was associated with a reduction in suicidal ideation independent of the improvement of depression severity. Overall, antidepressant medication improved neurocognitive performance in patients with major depression and suicide risk. Reduced suicidal ideation was best predicted by a combination of the independent improvements in both depression symptomatology and verbal memory. Targeted treatment of neurocognitive dysfunction in these patients may augment standard medication treatment for reducing suicidal behavior risk. PMID:25555415

  9. 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

  10. A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy.

    PubMed

    Whitehead, Nicholas P; Kim, Min Jeong; Bible, Kenneth L; Adams, Marvin E; Froehner, Stanley C

    2015-10-13

    Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases. PMID:26417069

  11. A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy

    PubMed Central

    Whitehead, Nicholas P.; Kim, Min Jeong; Bible, Kenneth L.; Adams, Marvin E.; Froehner, Stanley C.

    2015-01-01

    Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases. PMID:26417069

  12. Executive Functions and the Improvement of Thinking Abilities: The Intervention in Reading Comprehension

    PubMed Central

    García-Madruga, Juan A.; Gómez-Veiga, Isabel; Vila, José Ó.

    2016-01-01

    In this paper, we propose a preliminary theory of executive functions that address in a specific way their relationship with working memory (WM) and higher-level cognition. It includes: (a) four core on-line WM executive functions that are involved in every novel and complex cognitive task; (b) two higher order off-line executive functions, planning and revision, that are required to resolving the most complex intellectual abilities; and (c) emotional control that is involved in any complex, novel and difficult task. The main assumption is that efficiency on thinking abilities may be improved by specific instruction or training on the executive functions necessary to solving novel and complex tasks involved in these abilities. Evidence for the impact of our training proposal on WM's executive functions involved in higher-level cognitive abilities comes from three studies applying an adaptive program designed to improve reading comprehension in primary school students by boosting the core WM's executive functions involved in it: focusing on relevant information, switching (or shifting) between representations or tasks, connecting incoming information from text with long-term representations, updating of the semantic representation of the text in WM, and inhibition of irrelevant information. The results are consistent with the assumption that cognitive enhancements from the training intervention may have affected not only a specific but also a more domain-general mechanism involved in various executive functions. We discuss some methodological issues in the studies of effects of WM training on reading comprehension. The perspectives and limitations of our approach are finally discussed. PMID:26869961

  13. Executive Functions and the Improvement of Thinking Abilities: The Intervention in Reading Comprehension.

    PubMed

    García-Madruga, Juan A; Gómez-Veiga, Isabel; Vila, José Ó

    2016-01-01

    In this paper, we propose a preliminary theory of executive functions that address in a specific way their relationship with working memory (WM) and higher-level cognition. It includes: (a) four core on-line WM executive functions that are involved in every novel and complex cognitive task; (b) two higher order off-line executive functions, planning and revision, that are required to resolving the most complex intellectual abilities; and (c) emotional control that is involved in any complex, novel and difficult task. The main assumption is that efficiency on thinking abilities may be improved by specific instruction or training on the executive functions necessary to solving novel and complex tasks involved in these abilities. Evidence for the impact of our training proposal on WM's executive functions involved in higher-level cognitive abilities comes from three studies applying an adaptive program designed to improve reading comprehension in primary school students by boosting the core WM's executive functions involved in it: focusing on relevant information, switching (or shifting) between representations or tasks, connecting incoming information from text with long-term representations, updating of the semantic representation of the text in WM, and inhibition of irrelevant information. The results are consistent with the assumption that cognitive enhancements from the training intervention may have affected not only a specific but also a more domain-general mechanism involved in various executive functions. We discuss some methodological issues in the studies of effects of WM training on reading comprehension. The perspectives and limitations of our approach are finally discussed. PMID:26869961

  14. Inscapes: A movie paradigm to improve compliance in functional magnetic resonance imaging.

    PubMed

    Vanderwal, Tamara; Kelly, Clare; Eilbott, Jeffrey; Mayes, Linda C; Castellanos, F Xavier

    2015-11-15

    The examination of functional connectivity in fMRI data collected during task-free "rest" has provided a powerful tool for studying functional brain organization. Limitations of this approach include susceptibility to head motion artifacts and participant drowsiness or sleep. These issues are especially relevant when studying young children or clinical populations. Here we introduce a movie paradigm, Inscapes, that features abstract shapes without a narrative or scene-cuts. The movie was designed to provide enough stimulation to improve compliance related to motion and wakefulness while minimizing cognitive load during the collection of functional imaging data. We compare Inscapes to eyes-open rest and to age-appropriate movie clips in healthy adults (Ocean's Eleven, n=22) and a pilot sample of typically developing children ages 3-7 (Fantasia, n=13). Head motion was significantly lower during both movies relative to rest for both groups. In adults, movies decreased the number of participants who self-reported sleep. Intersubject correlations, used to quantify synchronized, task-evoked activity across movie and rest conditions in adults, involved less cortex during Inscapes than Ocean's Eleven. To evaluate the effect of movie-watching on intrinsic functional connectivity networks, we examined mean functional connectivity using both whole-brain functional parcellation and network-based approaches. Both inter- and intra-network metrics were more similar between Inscapes and Rest than between Ocean's Eleven and Rest, particularly in comparisons involving the default network. When comparing movies to Rest, the mean functional connectivity of somatomotor, visual and ventral attention networks differed significantly across various analyses. We conclude that low-demand movies like Inscapes may represent a useful intermediate condition between task-free rest and typical narrative movies while still improving participant compliance. Inscapes is publicly available for download at headspacestudios.org/inscapes. PMID:26241683

  15. 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

  16. Family history of Alzheimer’s disease limits improvement in cognitive function after bariatric surgery

    PubMed Central

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

    2014-01-01

    Background/Objective: Bariatric surgery can reverse cognitive impairments associated with obesity. However, such benefits may be attenuated in individuals with a predisposing risk for cognitive impairment such as family history of Alzheimer’s disease. Methods: In all, 94 bariatric surgery participants completed a computerized cognitive test battery before and 12 weeks after surgery. Family history of Alzheimer’s disease was obtained through self-report. Results: In the overall sample, cognitive function improved in memory and attention/executive function 12 weeks post-surgery. Repeated measures showed similar rates of improvements in attention/executive function between patients with and without a family history of Alzheimer’s disease. In contrast, only individuals without a family history of Alzheimer’s disease exhibited post-operative improvements in memory. A family history of Alzheimer’s disease was associated with greater post-surgery rates of cognitive impairment. Conclusions: Family history of Alzheimer’s disease may limit post-surgery cognitive benefits. Future studies should examine whether weight loss can modify the course of cognitive decline in patients at-risk for Alzheimer’s disease. PMID:26770731

  17. Parent, Teacher, and Student Perspectives on How Corrective Lenses Improve Child Wellbeing and School Function.

    PubMed

    Dudovitz, Rebecca N; Izadpanah, Nilufar; Chung, Paul J; Slusser, Wendelin

    2016-05-01

    Objectives Up to 20 % of school-age children have a vision problem identifiable by screening, over 80 % of which can be corrected with glasses. While vision problems are associated with poor school performance, few studies describe whether and how corrective lenses affect academic achievement and health. Further, there are virtually no studies exploring how children with correctable visual deficits, their parents, and teachers perceive the connection between vision care and school function. Methods We conducted a qualitative evaluation of Vision to Learn (VTL), a school-based program providing free corrective lenses to low-income students in Los Angeles. Nine focus groups with students, parents, and teachers from three schools served by VTL explored the relationships between poor vision, receipt of corrective lenses, and school performance and health. Results Twenty parents, 25 teachers, and 21 students from three elementary schools participated. Participants described how uncorrected visual deficits reduced students' focus, perseverance, and class participation, affecting academic functioning and psychosocial stress; how receiving corrective lenses improved classroom attention, task persistence, and willingness to practice academic skills; and how serving students in school rather than in clinics increased both access to and use of corrective lenses. Conclusions for Practice Corrective lenses may positively impact families, teachers, and students coping with visual deficits by improving school function and psychosocial wellbeing. Practices that increase ownership and use of glasses, such as serving students in school, may significantly improve both child health and academic performance. PMID:26649878

  18. Luteolin improves the impaired nerve functions in diabetic neuropathy: behavioral and biochemical evidences.

    PubMed

    Li, Ming; Li, Qiang; Zhao, Qingsong; Zhang, Jinchao; Lin, Jiang

    2015-01-01

    Peripheral neuropathies are a major cause of morbidity in patients with diabetes mellitus. Up to now, drugs for improving the impaired nerve functions has been lacking for diabetic neuropathy. The antioxidant and neuroprotective effects of luteolin make it an attractive candidate for diabetic neuropathy. The present study was designed to investigate the putative beneficial effect of luteolin on diabetic neuropathy. Diabetic rats were intraperitoneally treated with daily luteolin (50 mg/kg, 100 mg/kg and 200 mg/kg) or vehicle for 3 weeks from the 28(th) day after streptozotocin injection. Behavioral, electrophysiological and biochemical studies were performed to evaluate the effect of luteolin on the impaired nerve functions in diabetic neuropathy. It was found that luteolin dose dependently alleviated abnormal sensation, improved nerve conduction velocities and nerve blood flow in diabetic rats. Biochanical analysis showed that luteolin significantly lowered the reactive oxygen species production and malondialdehyde level, as well as increased antioxidants activities in a dose dependent manner. In addition, luteolin significantly up-regulated the protein levels of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in diabetic nerves. Taken together, luteolin is capable of improving diabetes-induced deficit in motor and sensory functions, which could be attributable, at least in part, to its Nrf2-dependent antioxidant capacity. The findings in the present study highlight the therapeutic value of luteolin for diabetic neuropathy. PMID:26617718

  19. Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure.

    PubMed

    Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

    2014-12-01

    Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF. PMID:25023328

  20. Luteolin improves the impaired nerve functions in diabetic neuropathy: behavioral and biochemical evidences

    PubMed Central

    Li, Ming; Li, Qiang; Zhao, Qingsong; Zhang, Jinchao; Lin, Jiang

    2015-01-01

    Peripheral neuropathies are a major cause of morbidity in patients with diabetes mellitus. Up to now, drugs for improving the impaired nerve functions has been lacking for diabetic neuropathy. The antioxidant and neuroprotective effects of luteolin make it an attractive candidate for diabetic neuropathy. The present study was designed to investigate the putative beneficial effect of luteolin on diabetic neuropathy. Diabetic rats were intraperitoneally treated with daily luteolin (50 mg/kg, 100 mg/kg and 200 mg/kg) or vehicle for 3 weeks from the 28th day after streptozotocin injection. Behavioral, electrophysiological and biochemical studies were performed to evaluate the effect of luteolin on the impaired nerve functions in diabetic neuropathy. It was found that luteolin dose dependently alleviated abnormal sensation, improved nerve conduction velocities and nerve blood flow in diabetic rats. Biochanical analysis showed that luteolin significantly lowered the reactive oxygen species production and malondialdehyde level, as well as increased antioxidants activities in a dose dependent manner. In addition, luteolin significantly up-regulated the protein levels of nuclear factor-E2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) in diabetic nerves. Taken together, luteolin is capable of improving diabetes-induced deficit in motor and sensory functions, which could be attributable, at least in part, to its Nrf2-dependent antioxidant capacity. The findings in the present study highlight the therapeutic value of luteolin for diabetic neuropathy. PMID:26617718

  1. Exercise training improves vascular function in adolescents with type 2 diabetes.

    PubMed

    Naylor, Louise H; Davis, Elizabeth A; Kalic, Rachelle J; Paramalingam, Niru; Abraham, Mary B; Jones, Timothy W; Green, Daniel J

    2016-02-01

    The impact of exercise training on vascular health in adolescents with type 2 diabetes has not been previously studied. We hypothesized that exercise training would improve micro- and macrovascular health in adolescents with type 2 diabetes. Thirteen adolescents (13-21 years, 10F) with type 2 diabetes were recruited from Princess Margaret Hospital. Participants were randomized to receive either an exercise program along with standard clinical care (n = 8) or standard care alone (n = 5). Those in the intervention group received 12 weeks of gym-based, personalized, and supervised exercise training. Those in the control group were instructed to maintain usual activity levels. Assessments were conducted at baseline and following week 12. The exercise group was also studied 12 weeks following the conclusion of their program. Assessments consisted of conduit artery endothelial function (flow-mediated dilation, FMD) and microvascular function (cutaneous laser Doppler). Secondary outcomes included body composition (dual-energy X-ray absorptiometry, DXA), glycemic control (whole body insulin sensitivity, M) assessed using the euglycemic-hyperinsulinemic clamp protocol, cardiorespiratory fitness (V˙O2peak), and muscular strength (1RM). Exercise training increased FMD (P < 0.05), microvascular function (P < 0.05), total lean mass (P < 0.05), and muscle strength (P < 0.001). There were no changes in cardiorespiratory fitness, body weight, BMI, or M. In the control group, body weight (P < 0.01), BMI (P < 0.01), and total fat mass (P < 0.05) increased. At week 24, improvements in vascular function were reversed. This study indicates that exercise training can improve both conduit and microvascular endothelial function and health, independent of changes in insulin sensitivity in adolescents with type 2 diabetes. PMID:26887327

  2. Cognitive Training for Improving Executive Function in Chemotherapy-Treated Breast Cancer Survivors

    PubMed Central

    Kesler, Shelli; Hosseini, S. M. Hadi; Heckler, Charles; Janelsins, Michelle; Palesh, Oxana; Mustian, Karen; Morrow, Gary

    2013-01-01

    Difficulties with thinking and problem solving are very common among breast cancer survivors. We tested a computerized cognitive training program for 41 breast cancer survivors. The training program was associated with significant improvements in thinking and problem-solving skills. Our findings demonstrate potential for our online, home-based cognitive training program to improve cognitive difficulties among breast cancer survivors. Background A majority of breast cancer (BC) survivors, particularly those treated with chemotherapy, experience long-term cognitive deficits that significantly reduce quality of life. Among the cognitive domains most commonly affected include executive functions (EF), such as working memory, cognitive flexibility, multitasking, planning, and attention. Previous studies in other populations have shown that cognitive training, a behavioral method for treating cognitive deficits, can result in significant improvements in a number of cognitive skills, including EF. Materials and Methods In this study, we conducted a randomized controlled trial to investigate the feasibility and preliminary effectiveness of a novel, online EF training program in long-term BC survivors. A total of 41 BC survivors (21 active, 20 wait list) completed the 48 session training program over 12 weeks. The participants were, on average, 6 years after therapy. Results Cognitive training led to significant improvements in cognitive flexibility, verbal fluency and processing speed, with marginally significant downstream improvements in verbal memory as assessed via standardized measures. Self-ratings of EF skills, including planning, organizing, and task monitoring, also were improved in the active group compared with the wait list group. Conclusions Our findings suggest that EF skills may be improved even in long-term survivors by using a computerized, home-based intervention program. These improvements may potentially include subjective EF skills, which suggest a transfer of the training program to real-world behaviors. PMID:23647804

  3. Zygotic LvBMP5-8 is required for skeletal patterning and for left-right but not dorsal-ventral specification in the sea urchin embryo.

    PubMed

    Piacentino, Michael L; Chung, Oliver; Ramachandran, Janani; Zuch, Daniel T; Yu, Jia; Conaway, Evan A; Reyna, Arlene E; Bradham, Cynthia A

    2016-04-01

    Skeletal patterning in the sea urchin embryo requires coordinated signaling between the pattern-dictating ectoderm and the skeletogenic primary mesenchyme cells (PMCs); recent studies have begun to uncover the molecular basis for this process. Using an unbiased RNA-Seq-based screen, we have previously identified the TGF-ß superfamily ligand, LvBMP5-8, as a skeletal patterning gene in Lytechinus variegatus embryos. This result is surprising, since both BMP5-8 and BMP2/4 ligands have been implicated in sea urchin dorsal-ventral (DV) and left-right (LR) axis specification. Here, we demonstrate that zygotic LvBMP5-8 is required for normal skeletal patterning on the left side, as well as for normal PMC positioning during gastrulation. Zygotic LvBMP5-8 is required for expression of the left-side marker soxE, suggesting that LvBMP5-8 is required for left-side specification. Interestingly, we also find that LvBMP5-8 knockdown suppresses serotonergic neurogenesis on the left side. While LvBMP5-8 overexpression is sufficient to dorsalize embryos, we find that zygotic LvBMP5-8 is not required for normal DV specification or development. In addition, ectopic LvBMP5-8 does not dorsalize LvBMP2/4 morphant embryos, indicating that, in the absence of BMP2/4, BMP5-8 is insufficient to specify dorsal. Taken together, our data demonstrate that zygotic LvBMP5-8 signaling is essential for left-side specification, and for normal left-side skeletal and neural patterning, but not for DV specification. Thus, while both BMP2/4 and BMP5-8 regulate LR axis specification, BMP2/4 but not zygotic BMP5-8 regulates DV axis specification in sea urchin embryos. PMID:26905309

  4. Complete set of mitochondrial pan-edited mRNAs in Leishmania mexicana amazonensis LV78

    PubMed Central

    Maslov, Dmitri A.

    2010-01-01

    Editing of mRNA transcribed from the mitochondrial cryptogenes ND8 (G1), ND9 (G2), G3, G4, ND3 (G5), RPS12 (G6) was investigated in Leishmania mexicana amazonensis, strain LV78, by amplification of the cDNA, cloning and sequencing. For each of these genes, extensively and partially edited transcripts were found to be relatively abundant compared to the respective pre-edited molecules. Moreover, the editing patterns observed in a majority of transcripts of each gene were consistent among themselves which allowed for inferring consensus editing sequences. The open reading frames contained in the consensus sequences were predicted to encode polypeptides that were highly similar to their counterparts in other species of Trypanosomatidae. Several kinetoplast DNA minicircles from this species available in the public domain were found to contain genes for guide RNAs which mediate editing of some of the mRNAs. The results indicate that the investigated strain of L. m. amazonensis has preserved its full editing capacity in spite of the long-term maintenance in culture. This property differs drastically from the other Leishmania species which lost some or all of the G1–G5 mRNA editing ability in culture. PMID:20546801

  5. LV MPI Change for Detection of Acute Cellular Rejection in Pediatric Heart Transplantation

    PubMed Central

    Flanagan, Ryan; Cain, Nicole; Tatum, Gregory; DeBrunner, Mark G.; Drant, Stacey; Feingold, Brian

    2013-01-01

    Endomyocardial biopsy (EMB), the gold standard for diagnosis of acute cellular rejection (ACR), poses unique risks in children. Limited cross- sectional data has associated left ventricular myocardial performance index (LVMPI) with ACR. We hypothesize that a relative change in MPI from baseline without ACR to the time of ACR will better detect ACR than an absolute threshold LVMPI value. We identified 40 children with ACR ≥60 days post-transplant matching them by age and time from transplantation to 40 children without ACR. There was a significant increase in LVMPI at time of ACR vs. baseline (0.59±0.17 vs. 0.41±0.11; p<0.001). There was no difference in LVMPI between baseline and follow-up (0.41±0.11 vs. 0.42±0.11; p=0.65). An absolute increase in LVMPI of ≥0.47 had 82.5% sensitivity and 85% specificity for ACR whereas an increase in LVMPI from baseline of ≥20.4% was 90% sensitive and 100% specific. Serial measurement of LVMPI appears to be a sensitive and specific marker of ACR. LV MPI shows good inter-observer agreement and increases at the time of EMB proven ACR with subsequent resolution to baseline measurements upon EMB proven resolution of ACR. Future studies in larger, prospective cohorts should be undertaken to validate these findings. PMID:24118848

  6. 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

  7. Chondroitinase gene therapy improves upper limb function following cervical contusion injury

    PubMed Central

    James, Nicholas D.; Shea, Jessie; Muir, Elizabeth M.; Verhaagen, Joost; Schneider, Bernard L.; Bradbury, Elizabeth J.

    2015-01-01

    Chondroitin sulphate proteoglycans (CSPGs) are known to be important contributors to the intensely inhibitory environment that prevents tissue repair and regeneration following spinal cord injury. The bacterial enzyme chondroitinase ABC (ChABC) degrades these inhibitory molecules and has repeatedly been shown to promote functional recovery in a number of spinal cord injury models. However, when used to treat more traumatic and clinically relevant spinal contusion injuries, findings with the ChABC enzyme have been inconsistent. We recently demonstrated that delivery of mammalian-compatible ChABC via gene therapy led to sustained and widespread digestion of CSPGs, resulting in significant functional repair of a moderate thoracic contusion injury in adult rats. Here we demonstrate that chondroitinase gene therapy significantly enhances upper limb function following cervical contusion injury, with improved forelimb ladder performance and grip strength as well as increased spinal conduction through the injury site and reduced lesion pathology. This is an important addition to our previous findings as improving upper limb function is a top priority for spinal injured patients. Additionally great importance is placed on replication in the spinal cord injury field. That chondroitinase gene therapy has now been shown to be efficacious in contusion models at either thoracic or cervical level is an important step in the further development of this promising therapeutic strategy towards the clinic. PMID:26044197

  8. Long-chain omega-3 fatty acids improve brain function and structure in older adults.

    PubMed

    Witte, A Veronica; Kerti, Lucia; Hermannstädter, Henrike M; Fiebach, Jochen B; Schreiber, Stephan J; Schuchardt, Jan Philipp; Hahn, Andreas; Flöel, Agnes

    2014-11-01

    Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) may be beneficial for the aging brain. We tested in a prospective interventional design whether high levels of supplementary LC-n3-FA would improve cognition, and addressed potential mechanisms underlying the effects. Sixty-five healthy subjects (50-75 years, 30 females) successfully completed 26 weeks of either fish oil (2.2 g/day LC-n3-FA) or placebo intake. Before and after the intervention period, cognitive performance, structural neuroimaging, vascular markers, and blood parameters were assayed. We found a significant increase in executive functions after LC-n3-FA compared with placebo (P = 0.023). In parallel, LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal, temporal, parietal, and limbic areas primarily of the left hemisphere, and on carotid intima media thickness and diastolic blood pressure. Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor, and negatively with changes in peripheral fasting insulin. This double-blind randomized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults, and elucidates underlying mechanisms. Our findings suggest novel strategies to maintain cognitive functions into old age. PMID:23796946

  9. Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE.

    PubMed

    De Martino, Federico; Zimmermann, Jan; Muckli, Lars; Ugurbil, Kamil; Yacoub, Essa; Goebel, Rainer

    2013-01-01

    Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE. PMID:23533682

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

    PubMed Central

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

    2013-01-01

    Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE. PMID:23533682

  11. Improving the accuracy of MTF measurement at low frequencies based on oversampled edge spread function deconvolution.

    PubMed

    Zhou, Zhongxing; Gao, Feng; Zhao, Huijuan; Zhang, Lixin; Ren, Liqiang; Li, Zheng; Ghani, Muhammad U; Hao, Ting; Liu, Hong

    2015-01-01

    The modulation transfer function (MTF) of a radiographic system is often evaluated by measuring the system's edge spread function (ESF) using edge device. However, the numerical differentiation procedure of the traditional slanted edge method amplifies noises in the line spread function (LSF) and limits the accuracy of the MTF measurement at low frequencies. The purpose of this study is to improve the accuracy of low-frequency MTF measurement for digital x-ray imaging systems. An edge spread function (ESF) deconvolution technique was developed for MTF measurement based on the degradation model of slanted edge images. Specifically, symmetric oversampled ESFs were constructed by subtracting a shifted version of the ESF from the original one. For validation, the proposed MTF technique was compared with conventional slanted edge method through computer simulations as well as experiments on two digital radiography systems. The simulation results show that the average errors of the proposed ESF deconvolution technique were 0.11% ± 0.09% and 0.23% ± 0.14%, and they outperformed the conventional edge method (0.64% ± 0.57% and 1.04% ± 0.82% respectively) at low-frequencies. On the experimental edge images, the proposed technique achieved better uncertainty performance than the conventional method. As a result, both computer simulation and experiments have demonstrated that the accuracy of MTF measurement at low frequencies can be improved by using the proposed ESF deconvolution technique. PMID:26410662

  12. Changes in Mitral Annular Ascent with Worsening Echocardiographic Parameters of Left Ventricular Diastolic Function

    PubMed Central

    2016-01-01

    Background. While the mitral annular plane systolic excursion (MAPSE) has been suggested as a surrogate measurement of left ventricular ejection fraction, less is known about the relative value of mitral annular ascent (MAa). Methods. Our database was queried for complete transthoracic echocardiograms performed for any clinical indication. Baseline echocardiographic measurements were compared to determine any correlation between MAa and traditional Echo-Doppler echocardiographic measures to characterize left ventricular diastolic dysfunction (LVDD). Results. Patients with normal LV diastolic function were younger (41 ± 13 years) than patients with LVDD (stage 1: 61 ± 13 years; stage 2: 57 ± 14 years; and stage 3: 66 ± 17 years; p = 0.156). LV ejection fraction decreased in patients with stage 2 LVDD (63 ± 17%) and was further reduced in patients with stage 3 LVDD (28 ± 21; p = 0.003). Discussion. While a vigorous MAa excursion was seen in patients with stage 1 LVDD, MAa significantly decreased in stage 2 and stage 3 LVDD patients. Our results highlight the importance of atrioventricular coupling, as MAa motion seems to reflect changes in left atrial pressure. Additional studies are now required to better examine atrioventricular interactions and electromechanical coupling that might improve our assessment of LV diastolic function. PMID:27051558

  13. Improvement of liver function parameters in patients with type 2 diabetes treated with thiazolidinediones.

    PubMed

    Ono, Masaya; Ikegami, Hiroshi; Fujisawa, Tomomi; Nojima, Koji; Kawabata, Yumiko; Nishino, Masanori; Taniguchi, Hidenori; Itoi-Babaya, Michiko; Babaya, Naru; Inoue, Kaori; Ogihara, Toshio

    2005-04-01

    To increase our understanding of the effect of thiazolidinediones, a new class of antidiabetic drugs, on liver function as well as glycemic control, we investigated liver function before, during, and after treatment with troglitazone and pioglitazone. A total of 32 patients with type 2 diabetes were studied. Glycemic control and liver function were measured before, during, and after 4 to 12 weeks of treatment with troglitazone or pioglitazone. Glycemic control was assessed by fasting levels of plasma glucose, hemoglobin A 1c , and serum insulin, and liver function was assessed by asparatate aminotransferase (AST), alanine aminotransferase (ALT), and gamma -glutamyl transpeptidase ( gamma-GTP). Homeostasis model assessment for insulin resistance was used as an index of insulin resistance. During treatment with troglitazone, fasting plasma glucose and hemoglobin A 1c levels and homeostasis model assessment for insulin resistance were significantly decreased. Serum AST, ALT, and gamma-GTP levels were significantly decreased during treatment (AST, -17.4%; ALT, -27.2%; gamma-GTP, -47.9%) and returned to pretreatment levels after 4 weeks of withdrawal of the drug. A similar tendency was observed during treatment with pioglitazone (AST, -4.7%; ALT, -16.4%; gamma-GTP, -30.8%). These data suggest that, in contrast to the deterioration of liver function reported in a small subset of patients treated with troglitazone, treatment with thiazolidinediones was associated with a decrease in serum transaminases in most patients. The improvement in liver function parameters known to be associated with fatty liver in the present study, together with an improvement in fatty liver reported for another class of insulin sensitizers, biguanides, suggests that thiazolidinediones may have a beneficial effect on fatty liver. PMID:15798962

  14. 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

  15. [An oral function improvement program utilizing health behavior theories ameliorates oral functions and oral hygienic conditions of pre-frail elderly persons].

    PubMed

    Hideo, Sakaguchi

    2014-06-01

    Oral function improvement programs utilizing health behavior theories are considered to be effective in preventing the need for long-term social care. In the present study, an oral function improvement program based upon health behavior theories was designed, and its utility was assessed in 102 pre-frail elderly persons (33