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Sample records for enhances cardiac commitment

  1. Silk fibroin scaffolds enhance cell commitment of adult rat cardiac progenitor cells.

    PubMed

    Di Felice, Valentina; Serradifalco, Claudia; Rizzuto, Luigi; De Luca, Angela; Rappa, Francesca; Barone, Rosario; Di Marco, Patrizia; Cassata, Giovanni; Puleio, Roberto; Verin, Lucia; Motta, Antonella; Migliaresi, Claudio; Guercio, Annalisa; Zummo, Giovanni

    2015-11-01

    The use of three-dimensional (3D) cultures may induce cardiac progenitor cells to synthesize their own extracellular matrix (ECM) and sarcomeric proteins to initiate cardiac differentiation. 3D cultures grown on synthetic scaffolds may favour the implantation and survival of stem cells for cell therapy when pharmacological therapies are not efficient in curing cardiovascular diseases and when organ transplantation remains the only treatment able to rescue the patient's life. Silk fibroin-based scaffolds may be used to increase cell affinity to biomaterials and may be chemically modified to improve cell adhesion. In the present study, porous, partially orientated and electrospun nanometric nets were used. Cardiac progenitor cells isolated from adult rats were seeded by capillarity in the 3D structures and cultured inside inserts for 21 days. Under this condition, the cells expressed a high level of sarcomeric and cardiac proteins and synthesized a great quantity of ECM. In particular, partially orientated scaffolds induced the synthesis of titin, which is a fundamental protein in sarcomere assembly.

  2. Running Ahead. Enhancing Teacher Commitment.

    ERIC Educational Resources Information Center

    Graham, Kathy C.

    1996-01-01

    Workplace factors that affect teacher commitment include teacher autonomy and efficacy, participation, feedback, collaboration, learning opportunities, and resources. The paper details five strategies to help teachers enhance their personal level of commitment (being responsive, getting involved, seeking feedback, developing a plan to maximize…

  3. Hepatocyte growth factor (HGF) enhances cardiac commitment of differentiating embryonic stem cells by activating PI3 kinase

    SciTech Connect

    Roggia, Cristiana; Ukena, Christian; Boehm, Michael; Kilter, Heiko . E-mail: kilter@med-in.uni-saarland.de

    2007-03-10

    Hepatocyte growth factor (HGF) is a pleiotropic cytokine promoting proliferation, migration and survival in several cell types. HGF and its cognate receptor c-Met are expressed in cardiac cells during early cardiogenesis, but data concerning its role in cardiac differentiation of embryonic stem cells (ESCs) and the underlying molecular mechanisms involved are limited. In the present study we show that HGF significantly increases the number of beating embryoid bodies of differentiating ESCs without affecting beating frequency. Furthermore, HGF up-regulates the expression of the cardiac-specific transcription factors Nkx 2.5 and GATA-4 and of markers of differentiated cardiomyocytes, i.e. {alpha}-MHC, {beta}-MHC, ANF, MLC2v and Troponin T. The HGF-induced increase in Nkx 2.5 expression was inhibited by co-treatment with the PI3 kinase inhibitors Wortmannin and LY294002, but not by its inactive homolog LY303511, suggesting an involvement of the PI3 kinase/Akt pathway in this effect. We conclude that HGF is an important growth factor involved in cardiac differentiation and/or proliferation of ESCs and may therefore be critical for the in vitro generation of pre- or fully differentiated cardiomyocytes as required for clinical use of embryonic stem cells in cardiac diseases.

  4. Small molecule cardiogenol C upregulates cardiac markers and induces cardiac functional properties in lineage-committed progenitor cells.

    PubMed

    Mike, Agnes K; Koenig, Xaver; Koley, Moumita; Heher, Philipp; Wahl, Gerald; Rubi, Lena; Schnürch, Michael; Mihovilovic, Marko D; Weitzer, Georg; Hilber, Karlheinz

    2014-01-01

    Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC), and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.

  5. Enhanced autophagy ameliorates cardiac proteinopathy

    PubMed Central

    Bhuiyan, Md. Shenuarin; Pattison, J. Scott; Osinska, Hanna; James, Jeanne; Gulick, James; McLendon, Patrick M.; Hill, Joseph A.; Sadoshima, Junichi; Robbins, Jeffrey

    2013-01-01

    Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To increase levels of basal autophagy, we generated an inducible Tg mouse expressing autophagy-related 7 (Atg7), a critical and rate-limiting autophagy protein. Hearts from these mice had enhanced autophagy, but normal morphology and function. We crossed these mice with CryABR120G mice, a model of DRC in which autophagy is significantly attenuated in the heart, to test the functional significance of autophagy activation in a proteotoxic model of heart failure. Sustained Atg7-induced autophagy in the CryABR120G hearts decreased interstitial fibrosis, ameliorated ventricular dysfunction, decreased cardiac hypertrophy, reduced intracellular aggregates and prolonged survival. To determine whether different methods of autophagy upregulation have additive or even synergistic benefits, we subjected the autophagy-deficient CryABR120G mice and the Atg7-crossed CryABR120G mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7-crossed CryABR120G cohort survived to 7 months. These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions. PMID:24177425

  6. Enhanced autophagy ameliorates cardiac proteinopathy.

    PubMed

    Bhuiyan, Md Shenuarin; Pattison, J Scott; Osinska, Hanna; James, Jeanne; Gulick, James; McLendon, Patrick M; Hill, Joseph A; Sadoshima, Junichi; Robbins, Jeffrey

    2013-12-01

    Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To increase levels of basal autophagy, we generated an inducible Tg mouse expressing autophagy-related 7 (Atg7), a critical and rate-limiting autophagy protein. Hearts from these mice had enhanced autophagy, but normal morphology and function. We crossed these mice with CryABR120G mice, a model of DRC in which autophagy is significantly attenuated in the heart, to test the functional significance of autophagy activation in a proteotoxic model of heart failure. Sustained Atg7-induced autophagy in the CryABR120G hearts decreased interstitial fibrosis, ameliorated ventricular dysfunction, decreased cardiac hypertrophy, reduced intracellular aggregates and prolonged survival. To determine whether different methods of autophagy upregulation have additive or even synergistic benefits, we subjected the autophagy-deficient CryABR120G mice and the Atg7-crossed CryABR120G mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7-crossed CryABR120G cohort survived to 7 months. These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions.

  7. Small Molecule Cardiogenol C Upregulates Cardiac Markers and Induces Cardiac Functional Properties in Lineage-Committed Progenitor Cells

    PubMed Central

    Mike, Agnes K.; Koenig, Xaver; Koley, Moumita; Heher, Philipp; Wahl, Gerald; Rubi, Lena; Schnürch, Michael; Mihovilovic, Marko D.; Weitzer, Georg; Hilber, Karlheinz

    2015-01-01

    Background/Aims Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited trans-differentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Methods Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC), and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Results Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. Conclusion CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy. PMID:24481283

  8. Brg1 modulates enhancer activation in mesoderm lineage commitment

    SciTech Connect

    Alexander, Jeffrey M.; Hota, Swetansu K.; He, Daniel; Thomas, Sean; Ho, Lena; Pennacchio, Len A.; Bruneau, B. G.

    2015-03-26

    The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histone modifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results in a failure of cardiomyocyte differentiation and broad deregulation of lineage-specific gene expression during mesoderm induction. We find that Brg1 co-localizes with H3K27ac at distal enhancers and is required for robust H3K27 acetylation at distal enhancers that are activated during mesoderm induction. Brg1 is also required to maintain Polycomb-mediated repression of non-mesodermal developmental regulators, suggesting cooperativity between Brg1 and Polycomb complexes. Thus, Brg1 is essential for modulating active and repressive chromatin states during mesoderm lineage commitment, in particular the activation of developmentally important enhancers. In conclusion, these findings demonstrate interplay between chromatin remodeling complexes and histone modifications that, together, ensure robust and broad gene regulation during crucial lineage commitment decisions.

  9. Brg1 modulates enhancer activation in mesoderm lineage commitment

    DOE PAGES

    Alexander, Jeffrey M.; Hota, Swetansu K.; He, Daniel; ...

    2015-03-26

    The interplay between different levels of gene regulation in modulating developmental transcriptional programs, such as histone modifications and chromatin remodeling, is not well understood. Here, we show that the chromatin remodeling factor Brg1 is required for enhancer activation in mesoderm induction. In an embryonic stem cell-based directed differentiation assay, the absence of Brg1 results in a failure of cardiomyocyte differentiation and broad deregulation of lineage-specific gene expression during mesoderm induction. We find that Brg1 co-localizes with H3K27ac at distal enhancers and is required for robust H3K27 acetylation at distal enhancers that are activated during mesoderm induction. Brg1 is also requiredmore » to maintain Polycomb-mediated repression of non-mesodermal developmental regulators, suggesting cooperativity between Brg1 and Polycomb complexes. Thus, Brg1 is essential for modulating active and repressive chromatin states during mesoderm lineage commitment, in particular the activation of developmentally important enhancers. In conclusion, these findings demonstrate interplay between chromatin remodeling complexes and histone modifications that, together, ensure robust and broad gene regulation during crucial lineage commitment decisions.« less

  10. Enhancing Commitment Improves Adherence to a Medical Regimen.

    ERIC Educational Resources Information Center

    Putnam, Dana E.; And Others

    1994-01-01

    Evaluated commitment-based intervention for improvement of adherence to 10-day antibiotic regimen. Subjects were 60 college students. Experimental subjects made verbal and written commitments for adherence and completed tasks designed to increase their investment in medication regimen. Controls performed similarly structured tasks unrelated to…

  11. Enhancing Commitment Improves Adherence to a Medical Regimen.

    ERIC Educational Resources Information Center

    Putnam, Dana E.; And Others

    1994-01-01

    Evaluated commitment-based intervention for improvement of adherence to 10-day antibiotic regimen. Subjects were 60 college students. Experimental subjects made verbal and written commitments for adherence and completed tasks designed to increase their investment in medication regimen. Controls performed similarly structured tasks unrelated to…

  12. Human C-kit+CD45- cardiac stem cells are heterogeneous and display both cardiac and endothelial commitment by single-cell qPCR analysis.

    PubMed

    Sandstedt, Joakim; Jonsson, Marianne; Dellgren, Göran; Lindahl, Anders; Jeppsson, Anders; Asp, Julia

    2014-01-03

    C-kit expressing cardiac stem cells have been described as multipotent. We have previously identified human cardiac C-kit+CD45- cells, but only found evidence of endothelial commitment. A small cardiac committed subpopulation within the C-kit+CD45- population might however be present. To investigate this at single-cell level, right and left atrial biopsies were dissociated and analyzed by FACS. Only right atrial biopsies contained a clearly distinguishable C-kit+CD45- population, which was single-cell sorted for qPCR. A minor portion of the sorted cells (1.1%) expressed early cardiac gene NKX2.5 while most of the cells (81%) expressed late endothelial gene VWF. VWF- cells were analyzed for a wider panel of genes. One group of these cells expressed endothelial genes (FLK-1, CD31) while another group expressed late cardiac genes (TNNT2, ACTC1). In conclusion, human C-kit+CD45- cells were predominantly localized to the right atrium. While most of these cells expressed endothelial genes, a minor portion expressed cardiac genes.

  13. The Inhibitory and Enhancing Influence of Pretest Commitment

    ERIC Educational Resources Information Center

    Calabrese, Frank J.; Lana, Robert E.

    1974-01-01

    Sixty subjects, 30 volunteers and 30 nonvolunteers, participated in an experiment examining pretest sensitization effects. Two interpretations of these effects--the commitment hypothesis and the demand interpretation--are explored. (Author)

  14. Pim1 Kinase Overexpression Enhances ckit(+) Cardiac Stem Cell Cardiac Repair Following Myocardial Infarction in Swine.

    PubMed

    Kulandavelu, Shathiyah; Karantalis, Vasileios; Fritsch, Julia; Hatzistergos, Konstantinos E; Loescher, Viky Y; McCall, Frederic; Wang, Bo; Bagno, Luiza; Golpanian, Samuel; Wolf, Ariel; Grenet, Justin; Williams, Adam; Kupin, Aaron; Rosenfeld, Aaron; Mohsin, Sadia; Sussman, Mark A; Morales, Azorides; Balkan, Wayne; Hare, Joshua M

    2016-12-06

    Pim1 kinase plays an important role in cell division, survival, and commitment of precursor cells towards a myocardial lineage, and overexpression of Pim1 in ckit(+) cardiac stem cells (CSCs) enhances their cardioreparative properties. The authors sought to validate the effect of Pim1-modified CSCs in a translationally relevant large animal preclinical model of myocardial infarction (MI). Human cardiac stem cells (hCSCs, n = 10), hckit(+) CSCs overexpressing Pim1 (Pim1(+); n = 9), or placebo (n = 10) were delivered by intramyocardial injection to immunosuppressed Yorkshire swine (n = 29) 2 weeks after MI. Cardiac magnetic resonance and pressure volume loops were obtained before and after cell administration. Whereas both hCSCs reduced MI size compared to placebo, Pim1(+) cells produced a ∼3-fold greater decrease in scar mass at 8 weeks post-injection compared to hCSCs (-29.2 ± 2.7% vs. -8.4 ± 0.7%; p < 0.003). Pim1(+) hCSCs also produced a 2-fold increase of viable mass compared to hCSCs at 8 weeks (113.7 ± 7.2% vs. 65.6 ± 6.8%; p <0.003), and a greater increase in regional contractility in both infarct and border zones (both p < 0.05). Both CSC types significantly increased ejection fraction at 4 weeks but this was only sustained in the Pim1(+) group at 8 weeks compared to placebo. Both hCSC and Pim1(+) hCSC treatment reduced afterload (p = 0.02 and p = 0.004, respectively). Mechanoenergetic recoupling was significantly greater in the Pim1(+) hCSC group (p = 0.005). Pim1 overexpression enhanced the effect of intramyocardial delivery of CSCs to infarcted porcine hearts. These findings provide a rationale for genetic modification of stem cells and consequent translation to clinical trials. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Enhanced sympathetic cardiac modulation in bruxism patients.

    PubMed

    Marthol, Harald; Reich, Sven; Jacke, Julia; Lechner, Karl-Heinz; Wichmann, Manfred; Hilz, Max Josef

    2006-08-01

    Sleep bruxism, an oral parafunction including teeth clenching and grinding, might be related to increased stress. To evaluate sympathetic cardiac activity in bruxism patients, we monitored cardiac autonomic modulation using spectral analysis of heart rate variability and compared results to those of age-matched healthy volunteers. In bruxism patients, sympathetic cardiac activity was higher than in volunteers. The increased sympathetic tone suggests increased stress and might be related to occlusal disharmonies.

  16. Enhancing Cardiac Triacylglycerol Metabolism Improves Recovery From Ischemic Stress

    PubMed Central

    Liu, Li; Goldberg, Ira J.

    2015-01-01

    Elevated cardiac triacylglycerol (TAG) content is traditionally equated with cardiolipotoxicity and suggested to be a culprit in cardiac dysfunction. However, previous work demonstrated that myosin heavy-chain–mediated cardiac-specific overexpression of diacylglycerol transferase 1 (MHC-DGAT1), the primary enzyme for TAG synthesis, preserved cardiac function in two lipotoxic mouse models despite maintaining high TAG content. Therefore, we examined whether increased cardiomyocyte TAG levels due to DGAT1 overexpression led to changes in cardiac TAG turnover rates under normoxia and ischemia-reperfusion conditions. MHC-DGAT1 mice had elevated TAG content and synthesis rates, which did not alter cardiac function, substrate oxidation, or myocardial energetics. MHC-DGAT1 hearts had ischemia-induced lipolysis; however, when a physiologic mixture of long-chain fatty acids was provided, enhanced TAG turnover rates were associated with improved functional recovery from low-flow ischemia. Conversely, exogenous supply of palmitate during reperfusion suppressed elevated TAG turnover rates and impaired recovery from ischemia in MHC-DGAT1 hearts. Collectively, this study shows that elevated TAG content, accompanied by enhanced turnover, does not adversely affect cardiac function and, in fact, provides cardioprotection from ischemic stress. In addition, the results highlight the importance of exogenous supply of fatty acids when assessing cardiac lipid metabolism and its relationship with cardiac function. PMID:25858561

  17. Stop Managing, Start Coaching! How Performance Coaching Can Enhance Commitment and Improve Productivity.

    ERIC Educational Resources Information Center

    Gilley, Jerry W.; Boughton, Nathaniel W.

    This book, which is intended for managers responsible for training and managing employees, outlines an approach to employee management and training that is based on the premise that, if managers are to enhance employees' commitment to the organization and improve productivity, they must first stop managing their employees and start coaching them.…

  18. Amniotic fluid stem cells morph into a cardiovascular lineage: analysis of a chemically induced cardiac and vascular commitment.

    PubMed

    Maioli, Margherita; Contini, Giovanni; Santaniello, Sara; Bandiera, Pasquale; Pigliaru, Gianfranco; Sanna, Raimonda; Rinaldi, Salvatore; Delitala, Alessandro P; Montella, Andrea; Bagella, Luigi; Ventura, Carlo

    2013-01-01

    Mouse embryonic stem cells were previously observed along with mesenchymal stem cells from different sources, after being treated with a mixed ester of hyaluronan with butyric and retinoic acids, to show a significant increase in the yield of cardiogenic and vascular differentiated elements. The aim of the present study was to determine if stem cells derived from primitive fetal cells present in human amniotic fluid (hAFSCs) and cultured in the presence of a mixture of hyaluronic (HA), butyric (BU), and retinoic (RA) acids show a higher yield of differentiation toward the cardiovascular phenotype as compared with untreated cells. During the differentiation process elicited by exposure to HA + BU + RA, genes controlling pluripotency and plasticity of stem cells, such as Sox2, Nanog, and Oct4, were significantly downregulated at the transcriptional level. At this point, a significant increase in expression of genes controlling the appearance of cardiogenic and vascular lineages in HA + BU + RA-treated cells was observed. The protein expression levels typical of cardiac and vascular phenotypes, evaluated by Western blotting, immunofluorescence, and flow cytometry, were higher in hAFSCs cultured in the presence of HA + BU + RA, as compared with untreated control cells. Appearance of the cardiac phenotype was further inferred by ultrastructural analysis using transmission and scanning electron microscopy. These results demonstrate that a mixture of HA + BU + RA significantly increased the yield of elements committed toward cardiac and vascular phenotypes, confirming what we have previously observed in other cellular types.

  19. Amniotic fluid stem cells morph into a cardiovascular lineage: analysis of a chemically induced cardiac and vascular commitment

    PubMed Central

    Maioli, Margherita; Contini, Giovanni; Santaniello, Sara; Bandiera, Pasquale; Pigliaru, Gianfranco; Sanna, Raimonda; Rinaldi, Salvatore; Delitala, Alessandro P; Montella, Andrea; Bagella, Luigi; Ventura, Carlo

    2013-01-01

    Mouse embryonic stem cells were previously observed along with mesenchymal stem cells from different sources, after being treated with a mixed ester of hyaluronan with butyric and retinoic acids, to show a significant increase in the yield of cardiogenic and vascular differentiated elements. The aim of the present study was to determine if stem cells derived from primitive fetal cells present in human amniotic fluid (hAFSCs) and cultured in the presence of a mixture of hyaluronic (HA), butyric (BU), and retinoic (RA) acids show a higher yield of differentiation toward the cardiovascular phenotype as compared with untreated cells. During the differentiation process elicited by exposure to HA + BU + RA, genes controlling pluripotency and plasticity of stem cells, such as Sox2, Nanog, and Oct4, were significantly downregulated at the transcriptional level. At this point, a significant increase in expression of genes controlling the appearance of cardiogenic and vascular lineages in HA + BU + RA-treated cells was observed. The protein expression levels typical of cardiac and vascular phenotypes, evaluated by Western blotting, immunofluorescence, and flow cytometry, were higher in hAFSCs cultured in the presence of HA + BU + RA, as compared with untreated control cells. Appearance of the cardiac phenotype was further inferred by ultrastructural analysis using transmission and scanning electron microscopy. These results demonstrate that a mixture of HA + BU + RA significantly increased the yield of elements committed toward cardiac and vascular phenotypes, confirming what we have previously observed in other cellular types. PMID:24101862

  20. Automatic segmentation and quantification of the cardiac structures from non-contrast-enhanced cardiac CT scans

    NASA Astrophysics Data System (ADS)

    Shahzad, Rahil; Bos, Daniel; Budde, Ricardo P. J.; Pellikaan, Karlijn; Niessen, Wiro J.; van der Lugt, Aad; van Walsum, Theo

    2017-05-01

    Early structural changes to the heart, including the chambers and the coronary arteries, provide important information on pre-clinical heart disease like cardiac failure. Currently, contrast-enhanced cardiac computed tomography angiography (CCTA) is the preferred modality for the visualization of the cardiac chambers and the coronaries. In clinical practice not every patient undergoes a CCTA scan; many patients receive only a non-contrast-enhanced calcium scoring CT scan (CTCS), which has less radiation dose and does not require the administration of contrast agent. Quantifying cardiac structures in such images is challenging, as they lack the contrast present in CCTA scans. Such quantification would however be relevant, as it enables population based studies with only a CTCS scan. The purpose of this work is therefore to investigate the feasibility of automatic segmentation and quantification of cardiac structures viz whole heart, left atrium, left ventricle, right atrium, right ventricle and aortic root from CTCS scans. A fully automatic multi-atlas-based segmentation approach is used to segment the cardiac structures. Results show that the segmentation overlap between the automatic method and that of the reference standard have a Dice similarity coefficient of 0.91 on average for the cardiac chambers. The mean surface-to-surface distance error over all the cardiac structures is 1.4+/- 1.7 mm. The automatically obtained cardiac chamber volumes using the CTCS scans have an excellent correlation when compared to the volumes in corresponding CCTA scans, a Pearson correlation coefficient (R) of 0.95 is obtained. Our fully automatic method enables large-scale assessment of cardiac structures on non-contrast-enhanced CT scans.

  1. Enhancing the commitment of nurses to the organisation by means of trust and monetary reward.

    PubMed

    Hsu, Chiu-Ping; Chiang, Chi-Yun; Chang, Chia-Wen; Huang, Heng-Chiang; Chen, Chia-Chen

    2015-07-01

    This study examines how trust and monetary reward influence nurses' job satisfaction and strengthen organisational commitment. Hospitals with high nurse retention rates typically have fewer medical errors and better quality care for patients. Therefore, health care administrators should provide a trustworthy workplace and a satisfactory reward system to retain experienced and skilled nurses. This study adopts the partial least squares method for parameter estimates and hypotheses based on 797 valid questionnaires from registered nurses in a Taiwan medical centre. All hypotheses were supported. The results show that the perceived trust of and rewards for registered nurses significantly influence their job satisfaction and organisational commitment. Although the impact of rewards is slightly stronger than that of trust among nurses on job satisfaction, the influence of trust among nurses is significantly higher than that of reward on organisational commitment. The results show that administrators should enhance trust among nurses, establish a fair and attractive reward system, and increase nurse job satisfaction to elevate their commitment to the organisation. To build a high level of organisational commitment, developing trust among nurses and increasing job satisfaction are more critical than compensating with monetary incentives alone. © 2013 John Wiley & Sons Ltd.

  2. The role of commitment strength in enhancing safe water consumption: mediation analysis of a cluster-randomized trial.

    PubMed

    Inauen, Jennifer; Tobias, Robert; Mosler, Hans-Joachim

    2014-11-01

    The objectives of this study were to investigate the importance of commitment strength in the theory of planned behaviour (TPB) and to test whether behaviour change techniques (BCTs) aimed at increasing commitment strength indeed promote switching to arsenic-safe wells by changing commitment strength. A cluster-randomized controlled trial with four arms was conducted to compare an information-only intervention to information plus one, two, or three commitment-enhancing BCTs. Randomly selected households (N = 340) of Monoharganj, Bangladesh, in seven geographically separate areas, whose members were drinking arsenic-contaminated water at baseline and had access to arsenic-safe wells, participated in this trial. The areas were randomly allocated to the four intervention arms. Water consumption behaviour, variables of the TPB, commitment strength, and socio-demographic characteristics were assessed at baseline and at 3-month follow-up by structured face-to-face interviews. Mediation analysis was used to investigate the mechanisms of behaviour change. Changes in commitment strength significantly increased the explanatory power of the TPB to predict well-switching. Commitment-enhancing BCTs - public self-commitment, implementation intentions, and reminders - increased the behaviour change effects of information by up to 50%. Mediation analyses confirmed that the BCTs indeed increased well-switching by increasing commitment strength. Unexpectedly, however, mediation via changes in behavioural intentions was the strongest mechanism of the intervention effects. Commitment is an important construct to consider in water- and health-related behaviour change and may be for other health behaviours as well. BCTs that alter behavioural intentions and commitment strength proved highly effective at enhancing the behaviour change effects of information alone. Statement of contribution What is already known on this subject? Millions of people drink contaminated water even if they

  3. Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase.

    PubMed

    Fischer, Kimberlee M; Cottage, Christopher T; Wu, Weitao; Din, Shabana; Gude, Natalie A; Avitabile, Daniele; Quijada, Pearl; Collins, Brett L; Fransioli, Jenna; Sussman, Mark A

    2009-11-24

    Despite numerous studies demonstrating the efficacy of cellular adoptive transfer for therapeutic myocardial regeneration, problems remain for donated cells with regard to survival, persistence, engraftment, and long-term benefits. This study redresses these concerns by enhancing the regenerative potential of adoptively transferred cardiac progenitor cells (CPCs) via genetic engineering to overexpress Pim-1, a cardioprotective kinase that enhances cell survival and proliferation. Intramyocardial injections of CPCs overexpressing Pim-1 were given to infarcted female mice. Animals were monitored over 4, 12, and 32 weeks to assess cardiac function and engraftment of Pim-1 CPCs with echocardiography, in vivo hemodynamics, and confocal imagery. CPCs overexpressing Pim-1 showed increased proliferation and expression of markers consistent with cardiogenic lineage commitment after dexamethasone exposure in vitro. Animals that received CPCs overexpressing Pim-1 also produced greater levels of cellular engraftment, persistence, and functional improvement relative to control CPCs up to 32 weeks after delivery. Salutary effects include reduction of infarct size, greater number of c-kit(+) cells, and increased vasculature in the damaged region. Myocardial repair is significantly enhanced by genetic engineering of CPCs with Pim-1 kinase. Ex vivo gene delivery to enhance cellular survival, proliferation, and regeneration may overcome current limitations of stem cell-based therapeutic approaches.

  4. REDD1 attenuates cardiac hypertrophy via enhancing autophagy.

    PubMed

    Liu, Chen; Xue, Ruicong; Wu, Dexi; Wu, Lingling; Chen, Cong; Tan, Weiping; Chen, Yili; Dong, Yugang

    2014-11-07

    Cardiac hypertrophy is a major risk factor of cardiovascular morbidity and mortality. Autophagy is established to be involved in regulating cardiac hypertrophy. REDD1, a stress-responsive protein, is proved to contribute in autophagy induction. However, the role of REDD1 in cardiac hypertrophy remains unknown. Our study demonstrated that REDD1 knockdown by RNAi exacerbated phenylephrine (PE)-induced cardiac hypertrophy, manifested by increased hypertrophic markers such as ANP and cell surface area. In addition, we discovered that ERK1/2 signaling pathway was involved in the effect of REDD1 on hypertrophy. Moreover, our study showed that REDD1 knockdown impaired autophagy in hypertrophied cardiomyocytes. mTOR, a signaling molecule governing autophagy induction, was activated by the knockdown of REDD1 under PE stress. Importantly, the pro-hypertrophic effect of REDD1 knockdown was significantly reversed by the autophagy enhancer rapamycin. Taken together, we firstly prove that REDD1 is essential for inhibiting cardiac hypertrophy by enhancing autophagy. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. miRNA-1 and miRNA-133a are involved in early commitment of pluripotent stem cells and demonstrate antagonistic roles in the regulation of cardiac differentiation.

    PubMed

    Izarra, Alberto; Moscoso, Isabel; Cañón, Susana; Carreiro, Candelas; Fondevila, Dolors; Martín-Caballero, Juan; Blanca, Vanessa; Valiente, Iñigo; Díez-Juan, Antonio; Bernad, Antonio

    2017-03-01

    miRNA-1 (miR-1) and miRNA-133a (miR-133a) are muscle-specific miRNAs that play an important role in heart development and physiopathology. Although both miRNAs have been broadly studied during cardiogenesis, the mechanisms by which miR-1 and miR-133a could influence linage commitment in pluripotent stem cells remain poorly characterized. In this study we analysed the regulation of miR-1 and miR-133a expression during pluripotent stem cell differentiation [P19.CL6 cells; embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)] and investigated their role in DMSO and embryoid body (EB)-mediated mesodermal and cardiac differentiation by gain- and loss-of-function studies, as well as in vivo, by the induction of teratomas. Gene expression analysis revealed that miR-1 and miR-133a are upregulated during cardiac differentiation of P19.CL6 cells, and also during ESC and iPSC EB differentiation. Forced overexpression of both miRNAs promoted mesodermal commitment and a concomitant decrease in the expression of neural differentiation markers. Moreover, overexpression of miR-1 enhanced the cardiac differentiation of P19.CL6, while miR-133a reduced it with respect to control cells. Teratoma formation experiments with P19.CL6 cells confirmed the influence of miR-1 and miR-133a during in vivo differentiation. Finally, inhibition of both miRNAs during P19.CL6 cardiac differentiation had opposite results to their overexpression. In conclusion, gene regulation involving miR-1 and miR-133a controls the mesodermal and cardiac fate of pluripotent stem cells. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Cardiac Output Monitoring Managing Intravenous Therapy (COMMIT) to Treat Emergency Department Patients with Sepsis

    PubMed Central

    Hou, Peter C.; Filbin, Michael R.; Napoli, Anthony; Feldman, Joseph; Pang, Peter S.; Sankoff, Jeffrey; Lo, Bruce M.; Dickey-White, Howard; Birkhahn, Robert H.; Shapiro, Nathan I.

    2016-01-01

    ABSTRACT Objective: Fluid responsiveness is proposed as a physiology-based method to titrate fluid therapy based on preload dependence. The objectives of this study were to determine if a fluid responsiveness protocol would decrease progression of organ dysfunction, and a fluid responsiveness protocol would facilitate a more aggressive resuscitation. Methods: Prospective, 10-center, randomized interventional trial. Inclusion criteria: suspected sepsis and lactate 2.0 to 4.0 mmol/L. Exclusion criteria (abbreviated): systolic blood pressure more than 90 mmHg, and contraindication to aggressive fluid resuscitation. Intervention: fluid responsiveness protocol using Non-Invasive Cardiac Output Monitor (NICOM) to assess for fluid responsiveness (>10% increase in stroke volume in response to 5 mL/kg fluid bolus) with balance of a liter given in responsive patients. Control: standard clinical care. Outcomes: primary—change in Sepsis-related Organ Failure Assessment (SOFA) score at least 1 over 72 h; secondary—fluids administered. Trial was initially powered at 600 patients, but stopped early due to a change in sponsor's funding priorities. Results: Sixty-four patients were enrolled with 32 in the treatment arm. There were no significant differences between arms in age, comorbidities, baseline vital signs, or SOFA scores (P > 0.05 for all). Comparing treatment versus Standard of Care—there was no difference in proportion of increase in SOFA score of at least 1 point (30% vs. 33%) (note bene underpowered, P = 1.0) or mean preprotocol fluids 1,050 mL (95% confidence interval [CI]: 786–1,314) vs. 1,031 mL (95% CI: 741–1,325) (P = 0.93); however, treatment patients received more fluids during the protocol (2,633 mL [95% CI: 2,264–3,001] vs. 1,002 mL [95% CI: 707–1,298]) (P < 0.001). Conclusions: In this study of a “preshock” population, there was no change in progression of organ dysfunction with a fluid responsiveness protocol

  7. Thrombolytic-Enhanced Extracorporeal Cardiopulmonary Resuscitation After Prolonged Cardiac Arrest

    PubMed Central

    Spinelli, Elena; Davis, Ryan P.; Ren, Xiaodan; Sheth, Parth S.; Tooley, Trevor R.; Iyengar, Amit; Sowell, Brandon; Owens, Gabe E.; Bocks, Martin L.; Jacobs, Teresa L.; Yang, Lynda J.; Stacey, William C.; Bartlett, Robert H.; Rojas-Peña, Alvaro; Neumar, Robert W.

    2016-01-01

    Objective To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation (ECPR) and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest. Design Laboratory investigation Setting University Laboratory Subjects Pigs Interventions Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation (ECPR) for 6 hours. Animals were allocated into two experimental groups: t-ECPR, which received Streptokinase 1 MU and c-ECPR which did not receive Streptokinase. In both groups the resuscitation protocol included the following physiologic targets: mean arterial pressure (MAP) > 70 mmHg, Cerebral perfusion pressure (CerPP) > 50 mmHg, PaO2 150 ± 50 mmHg, PaCO2 40 ± 5 mmHg and core temperature 33 ± 1 °C. Defibrillation was attempted after 30 minutes of ECPR. Measurements and Main Results A cardiac resuscitability score was assessed on the basis of: success of defibrillation; return of spontaneous heart beat; weanability form ECPR; and left ventricular systolic function after weaning. The addition of thrombolytic to ECPR significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40 ± 15% VS 18 ± 21 %). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of EEG signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages. Conclusions In a porcine model of prolonged cardiac arrest, thrombolytic-enhanced ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early EEG recovery and ischemic neuronal injury were

  8. Evaluating an Adjunctive Mobile App to Enhance Psychological Flexibility in Acceptance and Commitment Therapy.

    PubMed

    Levin, Michael E; Haeger, Jack; Pierce, Benjamin; Cruz, Rick A

    2017-11-01

    The primary aims of this study were to evaluate the feasibility and potential efficacy of a novel adjunctive mobile app designed to enhance the acquisition, strengthening, and generalization of acceptance and commitment therapy (ACT) skills being taught in therapy. A sample of 14 depressed/anxious clients receiving ACT used the ACT Daily app for 2 weeks in a pre-post, open trial design. Participants reported a high degree of program satisfaction. Clients significantly improved over the 2-week period on depression and anxiety symptoms as well as a range of psychological inflexibility measures. Analyses of mobile app data indicated effects of ACT Daily skill coaching on in-the-moment measures of inflexibility and symptoms, with unique effects found for acceptance and mindfulness. Adjunctive ACT mobile apps appear promising in enhancing therapy effects on psychological inflexibility and outcomes. A tailored skill coaching approach like ACT Daily based on randomly prompted assessments may be especially promising.

  9. RGD and BMP-2 mimetic peptide crosstalk enhances osteogenic commitment of human bone marrow stem cells.

    PubMed

    Bilem, I; Chevallier, P; Plawinski, L; Sone, E D; Durrieu, M C; Laroche, G

    2016-05-01

    Human bone marrow mesenchymal stem cells (hBMSCs) commitment and differentiation are dictated by bioactive molecules sequestered within their Extra Cellular Matrix (ECM). One common approach to mimic the physiological environment is to functionalize biomaterial surfaces with ECM-derived peptides able to recruit stem cells and trigger their linage-specific differentiation. The objective of this work was to investigate the effect of RGD and BMP-2 ligands crosstalk and density on the extent of hBMSCs osteogenic commitment, without recourse to differentiation medium. RGD peptide promotes cell adhesion via cell transmembrane integrin receptors, while BMP-2 peptide, corresponding to residues 73-92 of Bone Morphogenetic Protein-2, was shown to induce hBMSCs osteoblast differentiation. The immobilization of peptides on aminated glass was ascertained by X-ray Photoelectron Spectroscopy (XPS), the density of grafted peptides was quantified by fluorescence microscopy and the surface roughness was evaluated using Atomic Force Microscopy (AFM). The osteogenic commitment of hBMSCs cultured on RGD and/or BMP-2 surfaces was characterized by immunohistochemistry using STRO-1 as specific stem cells marker and Runx-2 as an earlier osteogenic marker. Biological results showed that the osteogenic commitment of hBMSCs was enhanced on bifunctionalized surfaces as compared to surfaces containing BMP-2, while on RGD surfaces cells mainly preserved their stemness character. These results demonstrated that RGD and BMP-2 mimetic peptides act synergistically to enhance hBMSCs osteogenesis without supplementing the media with osteogenic factors. These findings contribute to the development of biomimetic materials, allowing a deeper understanding of signaling pathways that govern the transition of stem cells towards the osteoblastic lineage. For a long time, scientists thought that the differentiation of Mesenchymal Stem Cells (MSCs) into bone cells was dictated by growth factors. This

  10. Conditional Cripto overexpression in satellite cells promotes myogenic commitment and enhances early regeneration

    PubMed Central

    Prezioso, Carolina; Iaconis, Salvatore; Andolfi, Gennaro; Zentilin, Lorena; Iavarone, Francescopaolo; Guardiola, Ombretta; Minchiotti, Gabriella

    2015-01-01

    Skeletal muscle regeneration mainly depends on satellite cells, a population of resident muscle stem cells. Despite extensive studies, knowledge of the molecular mechanisms underlying the early events associated with satellite cell activation and myogenic commitment in muscle regeneration remains still incomplete. Cripto is a novel regulator of postnatal skeletal muscle regeneration and a promising target for future therapy. Indeed, Cripto is expressed both in myogenic and inflammatory cells in skeletal muscle after acute injury and it is required in the satellite cell compartment to achieve effective muscle regeneration. A critical requirement to further explore the in vivo cellular contribution of Cripto in regulating skeletal muscle regeneration is the possibility to overexpress Cripto in its endogenous configuration and in a cell and time-specific manner. Here we report the generation and the functional characterization of a novel mouse model for conditional expression of Cripto, i.e., the Tg:DsRedloxP/loxPCripto-eGFP mice. Moreover, by using a satellite cell specific Cre-driver line we investigated the biological effect of Cripto overexpression in vivo, and provided evidence that overexpression of Cripto in the adult satellite cell compartment promotes myogenic commitment and differentiation, and enhances early regeneration in a mouse model of acute injury. PMID:26052513

  11. Conditional Cripto overexpression in satellite cells promotes myogenic commitment and enhances early regeneration.

    PubMed

    Prezioso, Carolina; Iaconis, Salvatore; Andolfi, Gennaro; Zentilin, Lorena; Iavarone, Francescopaolo; Guardiola, Ombretta; Minchiotti, Gabriella

    2015-01-01

    Skeletal muscle regeneration mainly depends on satellite cells, a population of resident muscle stem cells. Despite extensive studies, knowledge of the molecular mechanisms underlying the early events associated with satellite cell activation and myogenic commitment in muscle regeneration remains still incomplete. Cripto is a novel regulator of postnatal skeletal muscle regeneration and a promising target for future therapy. Indeed, Cripto is expressed both in myogenic and inflammatory cells in skeletal muscle after acute injury and it is required in the satellite cell compartment to achieve effective muscle regeneration. A critical requirement to further explore the in vivo cellular contribution of Cripto in regulating skeletal muscle regeneration is the possibility to overexpress Cripto in its endogenous configuration and in a cell and time-specific manner. Here we report the generation and the functional characterization of a novel mouse model for conditional expression of Cripto, i.e., the Tg:DsRed (loxP/loxP) Cripto-eGFP mice. Moreover, by using a satellite cell specific Cre-driver line we investigated the biological effect of Cripto overexpression in vivo, and provided evidence that overexpression of Cripto in the adult satellite cell compartment promotes myogenic commitment and differentiation, and enhances early regeneration in a mouse model of acute injury.

  12. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential

    PubMed Central

    Colangelo, Donato; Gregoletto, Luca; Reano, Simone; Pietronave, Stefano; Merlin, Simone; Talmon, Maria; Novelli, Eugenio; Diena, Marco; Nicoletti, Carmine; Musarò, Antonio; Filigheddu, Nicoletta; Follenzi, Antonia; Prat, Maria

    2015-01-01

    A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol. PMID:26375957

  13. Implementation of efficacy enhancement nursing interventions with cardiac elders.

    PubMed

    Hiltunen, Elizabeth F; Winder, Patricia A; Rait, Michelle A; Buselli, Elizabeth F; Carroll, Diane L; Rankin, Sally H

    2005-01-01

    Intervention strategies based on social cognitive theory and encompassing the bio-psycho-behavioral domains are proposed to enhance self-efficacy in men and women 65 years and older recovering from myocardial infarction and coronary artery bypass grafting. This paper describes a study in which the theory-based development of efficacy enhancement (EE) nursing interventions and their implementation and utilization with interventions from the Nursing Interventions Classification (NIC) were used with cardiac elders in the treatment group of the community-based randomized clinical, trial, "Improving Health Outcomes in Unpartnered Cardiac Elders." Advanced practice nurses (APNs) provided the nursing intervention to 110 participants (mean age = 76.2, SD = 6.0) for the first 12 weeks after discharge to home. After an initial introductory meeting in the acute-care setting, participant contacts by the APNs were made at a home visit and telephone calls at 2, 6, and 10 weeks. Results describe the number of participants receiving interventions at all contacts over 12 weeks, at specified contact points, and the intensity (nurse time) of the interventions. Verbal encouragement and mastery were EE interventions used with the greatest number of participants. Exercise promotion, energy management and active listening were NIC interventions used with the most participants. Variations in the use of interventions over 12 weeks and their intensities, suggest patterns of recovery in the elders. During rehabilitation EE interventions can be successfully implemented with men and women 65 years and older and individualized to the recovery trajectory. Nurses can integrate specific EE interventions with more general interventions from the bio-psycho-behavioral domains to enhance the recovery process for cardiac elders.

  14. Enhanced Glycolytic Metabolism Contributes to Cardiac Dysfunction in Polymicrobial Sepsis.

    PubMed

    Zheng, Zhibo; Ma, He; Zhang, Xia; Tu, Fei; Wang, Xiaohui; Ha, Tuanzhu; Fan, Min; Liu, Li; Xu, Jingjing; Yu, Kaijiang; Wang, Ruitao; Kalbfleisch, John; Kao, Race; Williams, David; Li, Chuanfu

    2017-05-01

    Cardiac dysfunction is present in >40% of sepsis patients and is associated with mortality rates of up to 70%. Recent evidence suggests that glycolytic metabolism plays a critical role in host defense and inflammation. Activation of Toll-like receptors on immune cells can enhance glycolytic metabolism. This study investigated whether modulation of glycolysis by inhibition of hexokinase will be beneficial to septic cardiomyopathy. Male C57B6/J mice were treated with a hexokinase inhibitor (2-deoxy-d-glucose [2-DG], 0.25-2 g/kg, n = 6-8) before cecal ligation and puncture (CLP) induced sepsis. Untreated septic mice served as control. Sham surgically operated mice treated with or without the 2-DG inhibitor served as sham controls. Cardiac function was assessed 6 hours after CLP sepsis by echocardiography. Serum was harvested for measurement of inflammatory cytokines and lactate. Sepsis-induced cardiac dysfunction was significantly attenuated by administration of 2-DG. Ejection fraction and fractional shortening in 2-DG-treated septic mice were significantly (P < .05) greater than in untreated CLP mice. 2-DG administration also significantly improved survival outcome, reduced kidney and liver injury, attenuated sepsis-increased serum levels of tumor necrosis factor α and interleukin 1β as well as lactate, and enhanced the expression of Sirt1 and Sirt3 in the myocardium, which play an important role in mitochondrial function and metabolism. In addition, 2-DG administration suppresses sepsis-increased expression of apoptotic inducers Bak and Bax as well as JNK phosphorylation in the myocardium. Glycolytic metabolism plays an important role in mediating sepsis-induced septic cardiomyopathy. The mechanisms may involve regulation of inflammatory response and apoptotic signaling.

  15. Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells

    PubMed Central

    Chimenti, Isotta; Pagano, Francesca; Cavarretta, Elena; Angelini, Francesco; Peruzzi, Mariangela; Barretta, Antonio; Greco, Ernesto; De Falco, Elena; Marullo, Antonino G. M.; Sciarretta, Sebastiano; Biondi-Zoccai, Giuseppe; Frati, Giacomo

    2016-01-01

    Β-blockers (BB) are a primary treatment for chronic heart disease (CHD), resulting in prognostic and symptomatic benefits. Cardiac cell therapy represents a promising regenerative treatment and, for autologous cell therapy, the patients clinical history may correlate with the biology of resident progenitors and the quality of the final cell product. This study aimed at uncovering correlations between clinical records of biopsy-donor CHD patients undergoing cardiac surgery and the corresponding yield and phenotype of cardiospheres (CSs) and CS-derived cells (CDCs), which are a clinically relevant population for cell therapy, containing progenitors. We describe a statistically significant association between BB therapy and improved CSs yield and CDCs phenotype. We show that BB-CDCs have a reduced fibrotic-like CD90 + subpopulation, with reduced expression of collagen-I and increased expression of cardiac genes, compared to CDCs from non-BB donors. Moreover BB-CDCs had a distinctive microRNA expression profile, consistent with reduced fibrotic features (miR-21, miR-29a/b/c downregulation), and enhanced regenerative potential (miR-1, miR-133, miR-101 upregulation) compared to non-BB. In vitro adrenergic pharmacological treatments confirmed cytoprotective and anti-fibrotic effects of β1-blocker on CDCs. This study shows anti-fibrotic and pro-commitment effects of BB treatment on endogenous cardiac reparative cells, and suggests adjuvant roles of β-blockers in cell therapy applications. PMID:27841293

  16. Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells.

    PubMed

    Chimenti, Isotta; Pagano, Francesca; Cavarretta, Elena; Angelini, Francesco; Peruzzi, Mariangela; Barretta, Antonio; Greco, Ernesto; De Falco, Elena; Marullo, Antonino G M; Sciarretta, Sebastiano; Biondi-Zoccai, Giuseppe; Frati, Giacomo

    2016-11-14

    Β-blockers (BB) are a primary treatment for chronic heart disease (CHD), resulting in prognostic and symptomatic benefits. Cardiac cell therapy represents a promising regenerative treatment and, for autologous cell therapy, the patients clinical history may correlate with the biology of resident progenitors and the quality of the final cell product. This study aimed at uncovering correlations between clinical records of biopsy-donor CHD patients undergoing cardiac surgery and the corresponding yield and phenotype of cardiospheres (CSs) and CS-derived cells (CDCs), which are a clinically relevant population for cell therapy, containing progenitors. We describe a statistically significant association between BB therapy and improved CSs yield and CDCs phenotype. We show that BB-CDCs have a reduced fibrotic-like CD90 + subpopulation, with reduced expression of collagen-I and increased expression of cardiac genes, compared to CDCs from non-BB donors. Moreover BB-CDCs had a distinctive microRNA expression profile, consistent with reduced fibrotic features (miR-21, miR-29a/b/c downregulation), and enhanced regenerative potential (miR-1, miR-133, miR-101 upregulation) compared to non-BB. In vitro adrenergic pharmacological treatments confirmed cytoprotective and anti-fibrotic effects of β1-blocker on CDCs. This study shows anti-fibrotic and pro-commitment effects of BB treatment on endogenous cardiac reparative cells, and suggests adjuvant roles of β-blockers in cell therapy applications.

  17. CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis.

    PubMed

    Ounzain, Samir; Micheletti, Rudi; Arnan, Carme; Plaisance, Isabelle; Cecchi, Dario; Schroen, Blanche; Reverter, Ferran; Alexanian, Michael; Gonzales, Christine; Ng, Shi Yan; Bussotti, Giovanni; Pezzuto, Iole; Notredame, Cedric; Heymans, Stephane; Guigó, Roderic; Johnson, Rory; Pedrazzini, Thierry

    2015-12-01

    Long noncoding RNAs (lncRNAs) are emerging as important regulators of developmental pathways. However, their roles in human cardiac precursor cell (CPC) remain unexplored. To characterize the long noncoding transcriptome during human CPC cardiac differentiation, we profiled the lncRNA transcriptome in CPCs isolated from the human fetal heart and identified 570 lncRNAs that were modulated during cardiac differentiation. Many of these were associated with active cardiac enhancer and super enhancers (SE) with their expression being correlated with proximal cardiac genes. One of the most upregulated lncRNAs was a SE-associated lncRNA that was named CARMEN, (CAR)diac (M)esoderm (E)nhancer-associated (N)oncoding RNA. CARMEN exhibits RNA-dependent enhancing activity and is upstream of the cardiac mesoderm-specifying gene regulatory network. Interestingly, CARMEN interacts with SUZ12 and EZH2, two components of the polycomb repressive complex 2 (PRC2). We demonstrate that CARMEN knockdown inhibits cardiac specification and differentiation in cardiac precursor cells independently of MIR-143 and -145 expression, two microRNAs located proximal to the enhancer sequences. Importantly, CARMEN expression was activated during pathological remodeling in the mouse and human hearts, and was necessary for maintaining cardiac identity in differentiated cardiomyocytes. This study demonstrates therefore that CARMEN is a crucial regulator of cardiac cell differentiation and homeostasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Enhancement of committed hematopoietic stem cell colony formation by nandrolone decanoate after sublethal whole body irradiation

    SciTech Connect

    Gallicchio, V.S.; Chen, M.G.; Watts, T.D.

    1984-11-01

    The ability of an anabolic steroid, nandrolone decanoate, to increase committed topoietic stem cell (CFU-gm, CFU-e, and BFU-e) colony formation after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation and on the next two days, each mouse was injected intraperitoneally with nandrolone decanoate (1.25 mg) in propylene glycol. Irradiated control mice received only propylene glycol. Compared to controls, drug-treated mice showed marked peripheral blood leukocytosis and more stable packed red cell volume. Drug-treated mice also demonstrated increased erythropoiesis, as CFU-e/BFU-e concentrations from both marrow (9% to 581%) and spleen (15% to 797%) were elevated. Granulopoiesis was increased similarly, as CFU-gm concentrations from marrow (38% to 685%) and spleen (9% to 373%) were elevated. These results demonstrate that nandrolone decanoate enhances hematopoietic stem cell recovery after sublethal whole body irradiation. This suggests that following hematopoietic suppression, nandrolone decanoate may stimulate the recovery of hematopoiesis at the stem cell level and in peripheral blood.

  19. Costs of cardiac rehabilitation and enhanced lifestyle modification programs.

    PubMed

    Lee, A James; Shepard, Donald S

    2009-01-01

    Inadequate payment to providers for traditional cardiac rehabilitation (CR) and lifestyle modification programs may contribute to low utilization, but little systematic evidence exists. This article estimates and compares the per-patient costs and revenues for 3 types of secondary prevention programs: the Dr Dean Ornish Program for Reversing Heart Disease (Ornish), the Benson-Henry Mind/Body Medical Institute's Cardiac Wellness Program (M/BMI), and CR. The authors developed an Excel spreadsheet template for the costs of a secondary prevention program and calibrated it to 7 programs that provided the necessary data. The calibration was based on budgets, cost accounting, statistical reports, and structured interviews (in person or by telephone). The 4 lifestyle programs (2 Ornish and 2 M/BMI) cost almost 4 times as much per patient as the 3 traditional CR programs (means of $7,176 and $1,828, respectively; difference P < .05). The Ornish program costs averaged more than twice those of M/BMI ($9,895 and $4,458, respectively; difference P < .10). Medicare-allowed charges (including co-payments) were $5,650 for Ornish, $4,800 for M/BMI, and about $32.50 per session or $683 overall for CR. Programs achieved the lowest costs per patient by carefully matching program capacity to demand. In none of the programs did net revenues cover costs. The findings suggest that 4 patients could attend a traditional CR program for the cost of 1 patient in an enhanced program.

  20. Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction

    PubMed Central

    Khan, Mohsin; Nickoloff, Emily; Abramova, Tatiana; Johnson, Jennifer; Verma, Suresh Kumar; Krishnamurthy, Prasanna; Mackie, Alexander Roy; Vaughan, Erin; Garikipati, Venkata Naga Srikanth; Benedict, Cynthia; Ramirez, Veronica; Lambers, Erin; Ito, Aiko; Gao, Erhe; Misener, Sol; Luongo, Timothy; Elrod, John; Qin, Gangjian; Houser, Steven R; Koch, Walter J; Kishore, Raj

    2015-01-01

    Rationale Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to various concerns. Recently, salutary effects of stem cells have been connected to exosome secretion. ESCs have the ability to produce exosomes however their effect in the context of the heart is unknown. Objective Determine the effect of ESC-derived exosome for the repair of ischemic myocardium and whether c-kit+ CPCs function can be enhanced with ESC exosomes Methods and Results This study demonstrates that mouse ESC derived exosomes (mES Ex) possess ability to augment function in infarcted hearts. mES Ex enhanced neovascularization, cardiomyocyte survival and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex augmented cardiac progenitor cell (CPC) survival, proliferation and cardiac commitment concurrent with increased c-kit+ CPCs in vivo 8 weeks after in vivo transfer along with formation of bonafide new cardiomyocytes in the ischemic heart. miRNA array revealed significant enrichment of miR290–295 cluster and particularly miR-294 in ESC exosomes. The underlying basis for the beneficial effect of mES Ex was tied to delivery of ESC specific miR-294 to CPCs promoting increased survival, cell cycle progression and proliferation. Conclusions mES Ex provide a novel cell free system that utilizes the immense regenerative power of ES cells while avoiding the risks associated with direct ES or ES derived cell transplantation and risk of teratomas. ESC exosomes possess cardiac regeneration ability and modulate both cardiomyocyte and CPC based repair programs in the heart. PMID:25904597

  1. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    SciTech Connect

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; May, Dalit; Johnson, Rory; Dauvillier, Jérôme; Pennacchio, Len A.; Pedrazzini, Thierry

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.

  2. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    DOE PAGES

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; ...

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

  3. Dynamic Enhancement of B-Mode Cardiac Ultrasound Image Sequences.

    PubMed

    Perperidis, Antonios; Cusack, David; White, Audrey; McDicken, Norman; MacGillivray, Tom; Anderson, Tom

    2017-07-01

    Limited contrast, along with speckle and acoustic noise, can reduce the diagnostic value of echocardiographic images. This study introduces dynamic histogram-based intensity mapping (DHBIM), a novel approach employing temporal variations in the cumulative histograms of cardiac ultrasound images to contrast enhance the imaged structures. DHBIM is then combined with spatial compounding to compensate for noise and speckle. The proposed techniques are quantitatively assessed (32 clinical data sets) employing (i) standard image quality measures and (ii) the repeatability of routine clinical measurements, such as chamber diameter and wall thickness. DHBIM introduces a mean increase of 120.9% in tissue/chamber detectability, improving the overall repeatability of clinical measurements by 17%. The integrated approach of DHBIM followed by spatial compounding provides the best overall enhancement of image quality and diagnostic value, consistently outperforming the individual approaches and achieving a 401.4% average increase in tissue/chamber detectability with an associated 24.3% improvement in the overall repeatability of clinical measurements. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction

    PubMed Central

    Trivieri, Maria Giovanna; Oudit, Gavin Y.; Sah, Rajan; Kerfant, Benoit-Gilles; Sun, Hui; Gramolini, Anthony O.; Pan, Yan; Wickenden, Alan D.; Croteau, Walburga; Morreale de Escobar, Gabriella; Pekhletski, Roman; St. Germain, Donald; MacLennan, David H.; Backx, Peter H.

    2006-01-01

    Thyroid hormone (TH) is critical for cardiac development and heart function. In heart disease, TH metabolism is abnormal, and many biochemical and functional alterations mirror hypothyroidism. Although TH therapy has been advocated for treating heart disease, a clear benefit of TH has yet to be established, possibly because of peripheral actions of TH. To assess the potential efficacy of TH in treating heart disease, type 2 deiodinase (D2), which converts the prohormone thyroxine to active triiodothyronine (T3), was expressed transiently in mouse hearts by using the tetracycline transactivator system. Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased Ca2+ transients and sarcoplasmic reticulum (SR) Ca2+ uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression as well as decreased Na+/Ca2+ exchanger, β-myosin heavy chain, and sarcolipin (SLN) expression. In pressure overload, targeted increases in D2 activity could not block hypertrophy but could completely prevent impaired contractility and SR Ca2+ cycling as well as altered expression patterns of SERCA2a, SLN, and other markers of pathological hypertrophy. Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function and altered gene expression after pressure overload. PMID:16595628

  5. Increasing the Institutional Commitment of College Students: Enhanced Measurement and Test of a Nomological Model

    ERIC Educational Resources Information Center

    Davidson, William B.; Beck, Hall P.; Grisaffe, Douglas B.

    2015-01-01

    Measurement shortcomings have hampered the understanding of institutional commitment (IC) in college students. Therefore, this study sought to (a) develop validated indices of IC and associated psychosocial attributes and (b) use these indices to test a nomological network of variables and their direct and indirect relationships to IC. Exploratory…

  6. Increasing the Institutional Commitment of College Students: Enhanced Measurement and Test of a Nomological Model

    ERIC Educational Resources Information Center

    Davidson, William B.; Beck, Hall P.; Grisaffe, Douglas B.

    2015-01-01

    Measurement shortcomings have hampered the understanding of institutional commitment (IC) in college students. Therefore, this study sought to (a) develop validated indices of IC and associated psychosocial attributes and (b) use these indices to test a nomological network of variables and their direct and indirect relationships to IC. Exploratory…

  7. Assessment of myocardial delayed enhancement with cardiac computed tomography in cardiomyopathies: a prospective comparison with delayed enhancement cardiac magnetic resonance imaging.

    PubMed

    Lee, Hye-Jeong; Im, Dong Jin; Youn, Jong-Chan; Chang, Suyon; Suh, Young Joo; Hong, Yoo Jin; Kim, Young Jin; Hur, Jin; Choi, Byoung Wook

    2016-11-22

    To evaluate the feasibility of cardiac CT for the evaluation of myocardial delayed enhancement (MDE) in the assessment of patients with cardiomyopathy, compared to cardiac MRI. A total of 37 patients (mean age 54.9 ± 15.7 years, 24 men) who underwent cardiac MRI to evaluate cardiomyopathy were enrolled. Dual-energy ECG-gated cardiac CT was acquired 12 min after contrast injection. Two observers evaluated cardiac MRI and cardiac CT at different kV settings (100, 120 and 140 kV) independently for MDE pattern-classification (patchy, transmural, subendocardial, epicardial and mesocardial), differentiation between ischemic and non-ischemic cardiomyopathy and MDE quantification (percentage MDE). Kappa statics and the intraclass correlation coefficient were used for statistical analysis. Among different kV settings, 100-kV CT showed excellent agreements compared to cardiac MRI for MDE detection (κ = 0.886 and 0.873, respectively), MDE pattern-classification (κ = 0.888 and 0.881, respectively) and differentiation between ischemic and non-ischemic cardiomyopathy (κ = 1.000 and 0.893, respectively) for both Observer 1 and Observer 2. The Bland-Altman plot between MRI and 100-kV CT for the percentage MDE showed a very small bias (-0.15%) with 95% limits of agreement of -7.02 and 6.72. Cardiac CT using 100 kV might be an alternative method to cardiac MRI in the assessment of cardiomyopathy, particularly in patients with contraindications to cardiac MRI.

  8. MicroRNA-1 transfected embryonic stem cells enhance cardiac myocyte differentiation and inhibit apoptosis by modulating the PTEN/Akt pathway in the infarcted heart.

    PubMed

    Glass, Carley; Singla, Dinender K

    2011-11-01

    microRNAs (miRs) have emerged as critical modulators of various physiological processes including stem cell differentiation. Indeed, miR-1 has been reported to play an integral role in the regulation of cardiac muscle progenitor cell differentiation. However, whether overexpression of miR-1 in embryonic stem (ES) cells (miR-1-ES cells) will enhance cardiac myocyte differentiation following transplantation into the infarcted myocardium is unknown. In the present study, myocardial infarction (MI) was produced in C57BL/6 mice by left anterior descending artery ligation. miR-1-ES cells, ES cells, or culture medium (control) was transplanted into the border zone of the infarcted heart, and 2 wk post-MI, cardiac myocyte differentiation, adverse ventricular remodeling, and cardiac function were assessed. We provide evidence demonstrating enhanced cardiac myocyte commitment of transplanted miR-1-ES cells in the mouse infarcted heart as compared with ES cells. Assessment of apoptosis revealed that overexpression of miR-1 in transplanted ES cells protected host myocardium from MI-induced apoptosis through activation of p-AKT and inhibition of caspase-3, phosphatase and tensin homolog, and superoxide production. A significant reduction in interstitial and vascular fibrosis was quantified in miR-1-ES cell and ES cell transplanted groups compared with control MI. However, no statistical significance between miR-1-ES cell and ES cell groups was observed. Finally, mice receiving miR-1-ES cell transplantation post-MI had significantly improved heart function compared with respective controls (P < 0.05). Our data suggest miR-1 drives cardiac myocyte differentiation from transplanted ES cells and inhibits apoptosis post-MI, ultimately giving rise to enhanced cardiac repair, regeneration, and function.

  9. Cbfβ governs osteoblast-adipocyte lineage commitment through enhancing β-catenin signaling and suppressing adipogenesis gene expression.

    PubMed

    Wu, Mengrui; Wang, Yiping; Shao, Jian-Zhong; Wang, Jue; Chen, Wei; Li, Yi-Ping

    2017-09-19

    The mechanism underlying how transcription factors regulate mesenchymal stem cell lineage commitment remains unclear. To determine the role of core-binding factor subunit beta (Cbfβ) in osteoblast lineage commitment, we generated three mouse models by deleting Cbfβ at different osteoblast lineage stages. We demonstrated that the Cbfβ(f/f)Prx1-Cre, Cbfβ(f/f)Col2α1-Cre, and Cbfβ(f/f)Osx-Cre mice exhibited severe osteoporosis with substantial accumulation of marrow adipocytes resembling aged bone from enhanced adipogenesis, indicating that mesenchymal stem cells and osteoblasts can be programed and reprogramed, respectively, into adipocytes. Consistently, Cbfβ-deficient calvarial cells and bone marrow mesenchymal stem cells displayed strong adipogenic potential, with 5- to ∼70-fold increased adipocyte gene expression, which can be rescued by Cbfβ overexpression. Canonical Wnt signaling was impeded in the Cbfβ-deficient cells, with ∼80% decrease of Wnt10b expression. Accordingly, ChIP and luciferase assays demonstrated that Cbfβ/RUNX2 binds to Wnt10b promoter driving Wnt10b expression. Furthermore, Wnt3a suppressed adipogenesis but did not rescue osteoblastogenesis in Cbfβ-deficient cells. Notably, mixing culture of Cbfβ-deficient with normal cells demonstrates that Cbfβ functions not only through WNT paracrine pathway but also through endogenous signaling. Further analysis shows that Cbfβ/RUNX2 inhibits c/ebpα expression at transcriptional level. Our results show that, besides its osteogenic role, Cbfβ governs osteoblast-adipocyte lineage commitment both cell nonautonomously through enhancing β-catenin signaling and cell autonomously through suppressing adipogenesis gene expression to maintain osteoblast lineage commitment, indicating Cbfβ may be a therapeutic target for osteoporosis.

  10. Disruption of cardiac cholinergic neurons enhances susceptibility to ventricular arrhythmias

    PubMed Central

    Jungen, Christiane; Scherschel, Katharina; Eickholt, Christian; Kuklik, Pawel; Klatt, Niklas; Bork, Nadja; Salzbrunn, Tim; Alken, Fares; Angendohr, Stephan; Klene, Christiane; Mester, Janos; Klöcker, Nikolaj; Veldkamp, Marieke W.; Schumacher, Udo; Willems, Stephan; Nikolaev, Viacheslav O.; Meyer, Christian

    2017-01-01

    The parasympathetic nervous system plays an important role in the pathophysiology of atrial fibrillation. Catheter ablation, a minimally invasive procedure deactivating abnormal firing cardiac tissue, is increasingly becoming the therapy of choice for atrial fibrillation. This is inevitably associated with the obliteration of cardiac cholinergic neurons. However, the impact on ventricular electrophysiology is unclear. Here we show that cardiac cholinergic neurons modulate ventricular electrophysiology. Mechanical disruption or pharmacological blockade of parasympathetic innervation shortens ventricular refractory periods, increases the incidence of ventricular arrhythmia and decreases ventricular cAMP levels in murine hearts. Immunohistochemistry confirmed ventricular cholinergic innervation, revealing parasympathetic fibres running from the atria to the ventricles parallel to sympathetic fibres. In humans, catheter ablation of atrial fibrillation, which is accompanied by accidental parasympathetic and concomitant sympathetic denervation, raises the burden of premature ventricular complexes. In summary, our results demonstrate an influence of cardiac cholinergic neurons on the regulation of ventricular function and arrhythmogenesis. PMID:28128201

  11. Efficient generation of human embryonic stem cell-derived cardiac progenitors based on tissue-specific enhanced green fluorescence protein expression.

    PubMed

    Szebényi, Kornélia; Péntek, Adrienn; Erdei, Zsuzsa; Várady, György; Orbán, Tamás I; Sarkadi, Balázs; Apáti, Ágota

    2015-01-01

    Cardiac progenitor cells (CPCs) are committed to the cardiac lineage but retain their proliferative capacity before becoming quiescent mature cardiomyocytes (CMs). In medical therapy and research, the use of human pluripotent stem cell-derived CPCs would have several advantages compared with mature CMs, as the progenitors show better engraftment into existing heart tissues, and provide unique potential for cardiovascular developmental as well as for pharmacological studies. Here, we demonstrate that the CAG promoter-driven enhanced green fluorescence protein (EGFP) reporter system enables the identification and isolation of embryonic stem cell-derived CPCs. Tracing of CPCs during differentiation confirmed up-regulation of surface markers, previously described to identify cardiac precursors and early CMs. Isolated CPCs express cardiac lineage-specific transcripts, still have proliferating capacity, and can be re-aggregated into embryoid body-like structures (CAG-EGFP(high) rEBs). Expression of troponin T and NKX2.5 mRNA is up-regulated in long-term cultured CAG-EGFP(high) rEBs, in which more than 90% of the cells become Troponin I positive mature CMs. Moreover, about one third of the CAG-EGFP(high) rEBs show spontaneous contractions. The method described here provides a powerful tool to generate expandable cultures of pure human CPCs that can be used for exploring early markers of the cardiac lineage, as well as for drug screening or tissue engineering applications.

  12. Efficient Generation of Human Embryonic Stem Cell-Derived Cardiac Progenitors Based on Tissue-Specific Enhanced Green Fluorescence Protein Expression

    PubMed Central

    Szebényi, Kornélia; Péntek, Adrienn; Erdei, Zsuzsa; Várady, György; Orbán, Tamás I.; Sarkadi, Balázs

    2015-01-01

    Cardiac progenitor cells (CPCs) are committed to the cardiac lineage but retain their proliferative capacity before becoming quiescent mature cardiomyocytes (CMs). In medical therapy and research, the use of human pluripotent stem cell-derived CPCs would have several advantages compared with mature CMs, as the progenitors show better engraftment into existing heart tissues, and provide unique potential for cardiovascular developmental as well as for pharmacological studies. Here, we demonstrate that the CAG promoter-driven enhanced green fluorescence protein (EGFP) reporter system enables the identification and isolation of embryonic stem cell-derived CPCs. Tracing of CPCs during differentiation confirmed up-regulation of surface markers, previously described to identify cardiac precursors and early CMs. Isolated CPCs express cardiac lineage-specific transcripts, still have proliferating capacity, and can be re-aggregated into embryoid body-like structures (CAG-EGFPhigh rEBs). Expression of troponin T and NKX2.5 mRNA is up-regulated in long-term cultured CAG-EGFPhigh rEBs, in which more than 90% of the cells become Troponin I positive mature CMs. Moreover, about one third of the CAG-EGFPhigh rEBs show spontaneous contractions. The method described here provides a powerful tool to generate expandable cultures of pure human CPCs that can be used for exploring early markers of the cardiac lineage, as well as for drug screening or tissue engineering applications. PMID:24734786

  13. Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes.

    PubMed

    Takahashi, Tomosaburo; Lord, Bernadette; Schulze, P Christian; Fryer, Ryan M; Sarang, Satinder S; Gullans, Steven R; Lee, Richard T

    2003-04-15

    Embryonic stem (ES) cells are capable of self-renewal and differentiation into cellular derivatives of all 3 germ layers. In appropriate culture conditions, ES cells can differentiate into specialized cells, including cardiac myocytes, but the efficiency is typically low and the process is incompletely understood. We evaluated a chemical library for its potential to induce cardiac differentiation of ES cells in the absence of embryoid body formation. Using ES cells stably transfected with cardiac-specific alpha-cardiac myosin heavy chain (MHC) promoter-driven enhanced green fluorescent protein (EGFP), 880 compounds approved for human use were screened for their ability to induce cardiac differentiation. Treatment with ascorbic acid, also known as vitamin C, markedly increased the number of EGFP-positive cells, which displayed spontaneous and rhythmic contractile activity and stained positively for sarcomeric myosin and alpha-actinin. Furthermore, ascorbic acid induced the expression of cardiac genes, including GATA4, alpha-MHC, and beta-MHC in untransfected ES cells in a developmentally controlled manner. This effect of ascorbic acid on cardiac differentiation was not mimicked by the other antioxidants such as N-acetylcysteine, Tiron, or vitamin E. Ascorbic acid induces cardiac differentiation in ES cells. This study demonstrates the potential for chemically modifying the cardiac differentiation program of ES cells.

  14. Embryonic stem cell-derived cardiomyocyte heterogeneity and the isolation of immature and committed cells for cardiac remodeling and regeneration.

    PubMed

    Boheler, Kenneth R; Joodi, Robert N; Qiao, Hui; Juhasz, Ondrej; Urick, Amanda L; Chuppa, Sandra L; Gundry, Rebekah L; Wersto, Robert P; Zhou, Rong

    2011-01-01

    Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs) are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance. Following transplantation into rodent hearts, bioluminescence imaging revealed that immature cells, but not more mature CMs, survived for at least one month following injection. These data and comparisons with more mature cells lead us to conclude that immature hypoxia resistant ESC-CMs can be isolated in mass in vitro and, following injection into heart, form grafts that may mediate long-term recovery of global and regional myocardial contractile function following infarction.

  15. Cardiac-specific PID1 overexpression enhances pressure overload-induced cardiac hypertrophy in mice.

    PubMed

    Liu, Yaoqiu; Shen, Yahui; Zhu, Jingai; Liu, Ming; Li, Xing; Chen, Yumei; Kong, Xiangqing; Song, Guixian; Qian, Lingmei

    2015-01-01

    PID1 was originally described as an insulin sensitivity relevance protein, which is also highly expressed in heart tissue. However, its function in the heart is still to be elucidated. Thus this study aimed to investigate the role of PID1 in the heart in response to hypertrophic stimuli. Samples of human failing hearts from the left ventricles of dilated cardiomyopathy (DCM) patients undergoing heart transplants were collected. Transgenic mice with cardiomyocyte-specific overexpression of PID1 were generated, and cardiac hypertrophy was induced by transverse aortic constriction (TAC). The extent of cardiac hypertrophy was evaluated by echocardiography as well as pathological and molecular analyses of heart samples. A significant increase in PID1 expression was observed in failing human hearts and TAC-treated wild-type mouse hearts. When compared with TAC-treated wild-type mouse hearts, PID1-TG mouse showed a significant exacerbation of cardiac hypertrophy, fibrosis, and dysfunction. Further analysis of the signaling pathway in vivo suggested that these adverse effects of PID1 were associated with the inhibition of AKT, and activation of MAPK pathway. Under pathological conditions, over-expression of PID1 promotes cardiac hypertrophy by regulating the Akt and MAPK pathway. © 2015 S. Karger AG, Basel.

  16. Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence

    PubMed Central

    Org, Tõnis; Duan, Dan; Ferrari, Roberto; Montel-Hagen, Amelie; Van Handel, Ben; Kerényi, Marc A; Sasidharan, Rajkumar; Rubbi, Liudmilla; Fujiwara, Yuko; Pellegrini, Matteo; Orkin, Stuart H; Kurdistani, Siavash K; Mikkola, Hanna KA

    2015-01-01

    Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms. We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm, to regulate the divergence of hematopoietic and cardiac lineages. Scl does not act as a pioneer factor but rather exploits a pre-established epigenetic landscape. As the blood lineage emerges, Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers, whereas cardiac enhancers are decommissioned by removal of active epigenetic marks. Our data suggest that, rather than recruiting corepressors to enhancers, Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors, such as Gata4 and Hand1, use for gene activation. Although hematopoietic Gata factors bind with Scl to both activated and repressed genes, they are dispensable for cardiac repression, but necessary for activating genes that enable hematopoietic stem/progenitor cell development. These results suggest that a unique subset of enhancers in lineage-specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated. PMID:25564442

  17. Ultrafine ambient particulate matter enhances cardiac ischemia and reperfusion injury

    EPA Science Inventory

    Epidemiological studies have demonstrated a consistent link between exposure to ambient particulate air pollutant (PM) and the incidence of cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of ambient PM. Mice were exposed to 1...

  18. Ultrafine ambient particulate matter enhances cardiac ischemia and reperfusion injury

    EPA Science Inventory

    Epidemiological studies have demonstrated a consistent link between exposure to ambient particulate air pollutant (PM) and the incidence of cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of ambient PM. Mice were exposed to 1...

  19. Residual force enhancement is regulated by titin in skeletal and cardiac myofibrils.

    PubMed

    Shalabi, Nabil; Cornachione, Anabelle; de Souza Leite, Felipe; Vengallatore, Srikar; Rassier, Dilson E

    2017-03-15

    When a skeletal muscle is stretched while it contracts, the muscle produces a relatively higher force than the force from an isometric contraction at the same length: a phenomenon referred to as residual force enhancement. Residual force enhancement is puzzling because it cannot be directly explained by the classical force-length relationship and the sliding filament theory of contraction, the main paradigms in the muscle field. We used custom-built instruments to measure residual force enhancement in skeletal myofibrils, and, for the first time, in cardiac myofibrils. Our data report that residual force enhancement is present in skeletal muscles, but not cardiac muscles, and is regulated by the different isoforms of the titin protein filaments. When a skeletal muscle contracts isometrically, the muscle produces a force that is relative to the final isometric sarcomere length (SL). However, when the same final SL is reached by stretching the muscle while it contracts, the muscle produces a relatively higher force: a phenomenon commonly referred to as residual force enhancement. In this study, we investigated residual force enhancement in rabbit skeletal psoas myofibrils and, for the first time, cardiac papillary myofibrils. A custom-built atomic force microscope was used in experiments that stretched myofibrils before and after inhibiting myosin and actin interactions to determine whether the different cardiac and skeletal titin isoforms regulate residual force enhancement. At SLs ranging from 2.24 to 3.13 μm, the skeletal myofibrils enhanced the force by an average of 9.0%, and by 29.5% after hindering myosin and actin interactions. At SLs ranging from 1.80 to 2.29 μm, the cardiac myofibrils did not enhance the force before or after hindering myosin and actin interactions. We conclude that residual force enhancement is present only in skeletal muscles and is dependent on the titin isoforms. © 2016 The Authors. The Journal of Physiology © 2016 The

  20. Importance Of Delayed Enhanced Cardiac MRI In Idiopathic RVOT-VT: Differentiating Mimics Including Early Stage ARVC And Cardiac Sarcoidosis.

    PubMed

    Macias, Carlos; Nakamura, Keijiro; Tung, Roderick; Boyle, Noel G; Kalyanam, Shivkumar; Bradfield, Jason S

    2014-12-01

    A detailed understanding of cardiac anatomy and pathophysiology is necessary to optimize catheter ablation procedural success for patients with symptomatic ventricular tachycardia (VT)/premature ventricular contractions (PVCs) of outflow tract origin. Comprehensive imaging with cardiac magnetic resonance imaging (cMRI) is now at the forefront of procedural planning for complex ventricular arrhythmia ablation for patients with structural heart disease, but is increasingly used in patients with presumed "idiopathic" outflow VT/PVCs as well. cMRI with late gadolinium enhancement (LGE) can localize small regions of myocardial scar from previous myocardial infarction, fibrosis from non-ischemic cardiomyopathy, or edema/fibrosis from inflammatory disorders and help define targets for ablation. LGE, in combination with structural assessment, can help differentiate true idiopathic outflow VT/PVCs from those caused by early stage disease secondary to more significant pathology, such as arrhythmogenic right ventricular cardiomyopathy or cardiac sarcoidosis. We review the benefits of cMRI with LGE for patients with VT/PVCs of outflow origin.

  1. Notch Inhibition Enhances Cardiac Reprogramming by Increasing MEF2C Transcriptional Activity.

    PubMed

    Abad, Maria; Hashimoto, Hisayuki; Zhou, Huanyu; Morales, Maria Gabriela; Chen, Beibei; Bassel-Duby, Rhonda; Olson, Eric N

    2017-03-14

    Conversion of fibroblasts into functional cardiomyocytes represents a potential means of restoring cardiac function after myocardial infarction, but so far this process remains inefficient and little is known about its molecular mechanisms. Here we show that DAPT, a classical Notch inhibitor, enhances the conversion of mouse fibroblasts into induced cardiac-like myocytes by the transcription factors GATA4, HAND2, MEF2C, and TBX5. DAPT cooperates with AKT kinase to further augment this process, resulting in up to 70% conversion efficiency. Moreover, DAPT promotes the acquisition of specific cardiomyocyte features, substantially increasing calcium flux, sarcomere structure, and the number of spontaneously beating cells. Transcriptome analysis shows that DAPT induces genetic programs related to muscle development, differentiation, and excitation-contraction coupling. Mechanistically, DAPT increases binding of the transcription factor MEF2C to the promoter regions of cardiac structural genes. These findings provide mechanistic insights into the reprogramming process and may have important implications for cardiac regeneration therapies.

  2. Evaluation of apical subtype of hypertrophic cardiomyopathy using cardiac magnetic resonance imaging with gadolinium enhancement.

    PubMed

    Kebed, Kalie Y; Al Adham, Raed I; Bishu, Kalkidan; Askew, J Wells; Klarich, Kyle W; Araoz, Philip A; Foley, Thomas A; Glockner, James F; Nishimura, Rick A; Anavekar, Nandan S

    2014-09-01

    Apical hypertrophic cardiomyopathy (HC) is an uncommon variant of HC. We sought to characterize cardiac magnetic resonance imaging (MRI) findings among apical HC patients. This was a retrospective review of consecutive patients with a diagnosis of apical HC who underwent cardiac MRI examinations at the Mayo Clinic (Rochester, MN) from August 1999 to October 2011. Clinical and demographic data at the time of cardiac MRI study were abstracted. Cardiac MRI study and 2-dimensional echocardiograms performed within 6 months of the cardiac MRI were reviewed; 96 patients with apical HC underwent cardiac MRI examinations. LV end-diastolic and end-systolic volumes were 130.7 ± 39.1 ml and 44.2 ± 20.9 ml, respectively. Maximum LV thickness was 19 ± 5 mm. Hypertrophy extended beyond the apex into other segments in 57 (59.4%) patients. Obstructive physiology was seen in 12 (12.5%) and was more common in the mixed apical phenotype than the pure apical (19.3 vs 2.6%, p = 0.02). Apical pouches were noted in 39 (40.6%) patients. Late gadolinium enhancement (LGE) was present in 70 (74.5%) patients. LGE was associated with severe symptoms and increased maximal LV wall thickness. In conclusion, cardiac MRI is well suited for studying the apical form of HC because of difficulty imaging the cardiac apex with standard echocardiography. Cardiac MRI is uniquely suited to delineate the presence or absence of an apical pouch and abnormal myocardial LGE that may have implications in the natural history of apical HM. In particular, the presence of abnormal LGE is associated with clinical symptoms and increased wall thickness.

  3. Our Common Commitment. Enhancing Ethnic Minority Integration and Achievement in Arizona's Universities.

    ERIC Educational Resources Information Center

    Arizona Board of Regents, Phoenix.

    A report and recommendations of the Arizona Board of Regents' Ad Hoc Committee on University Access and Retention focuses on the enhancement of ethnic minority integration and achievement in Arizona's universities. Eight sections cover: introduction (the challenge for Arizona's universities); House Bill 2108; early outreach (linkages and…

  4. Similarity enhancement for automatic segmentation of cardiac structures in computed tomography volumes

    PubMed Central

    Vera, Miguel; Bravo, Antonio; Garreau, Mireille; Medina, Rubén

    2011-01-01

    The aim of this research is proposing a 3–D similarity enhancement technique useful for improving the segmentation of cardiac structures in Multi-Slice Computerized Tomography (MSCT) volumes. The similarity enhancement is obtained by subtracting the intensity of the current voxel and the gray levels of their adjacent voxels in two volumes resulting after preprocessing. Such volumes are: a.- a volume obtained after applying a Gaussian distribution and a morphological top-hat filter to the input and b.- a smoothed volume generated by processing the input with an average filter. Then, the similarity volume is used as input to a region growing algorithm. This algorithm is applied to extract the shape of cardiac structures, such as left and right ventricles, in MSCT volumes. Qualitative and quantitative results show the good performance of the proposed approach for discrimination of cardiac cavities. PMID:22256220

  5. CHIP enhances angiogenesis and restores cardiac function after infarction in transgenic mice.

    PubMed

    Xu, Cheng-Wei; Zhang, Tian-Peng; Wang, Hong-Xia; Yang, Hui; Li, Hui-Hua

    2013-01-01

    Carboxyl terminus of Hsp70-interacting protein (CHIP) is a chaperone/ubiquitin ligase that plays an important role in stress-induced apoptosis. However, the effect of CHIP on angiogenesis, cardiac function and survival 4 weeks after myocardial infarction (MI) remain to be explored. Wild-type (WT) and transgenic mice (TG) with cardiac-specific overexpression of CHIP were used for coronary artery ligation. The cardiac function, cardiomyocyte apoptosis, inflammation and angiogenesis were examined by echocardiography, histological analysis, real-time PCR and Western blot analysis. At 4 weeks of after coronary artery ligation, echocardiography demonstrated that cardiac remodeling and dysfunction were prevented in TG mice compared with WT mice. The infarct size, cardiomyocyte apoptosis and inflammation were significantly reduced in TG mice than in WT mice. The survival rate after MI in TG mice was higher than that of WT mice. Furthermore, the levels of p53 protein was markedly decreased, but the expression of HIF-1α and VEGF, and the formation of capillary and arteriole after MI were significantly enhanced in TG mice compared with WT mice. We report the first in vivo evidence that CHIP enhances angiogenesis, inhibits inflammation, restores cardiac function, and improves survival at 4 weeks after MI. The present study expands on previous results and defines a novel mechanism. Thus, increased CHIP level may provide a novel therapeutic approach for left ventricular dysfunction after MI. Copyright © 2013 S. Karger AG, Basel.

  6. Admission Laboratory Results to Enhance Prediction Models of Postdischarge Outcomes in Cardiac Care.

    PubMed

    Pine, Michael; Fry, Donald E; Hannan, Edward L; Naessens, James M; Whitman, Kay; Reband, Agnes; Qian, Feng; Schindler, Joseph; Sonneborn, Mark; Roland, Jaclyn; Hyde, Linda; Dennison, Barbara A

    Predictive modeling for postdischarge outcomes of inpatient care has been suboptimal. This study evaluated whether admission numerical laboratory data added to administrative models from New York and Minnesota hospitals would enhance the prediction accuracy for 90-day postdischarge deaths without readmission (PD-90) and 90-day readmissions (RA-90) following inpatient care for cardiac patients. Risk-adjustment models for the prediction of PD-90 and RA-90 were designed for acute myocardial infarction, percutaneous cardiac intervention, coronary artery bypass grafting, and congestive heart failure. Models were derived from hospital claims data and were then enhanced with admission laboratory predictive results. Case-level discrimination, goodness of fit, and calibration were used to compare administrative models (ADM) and laboratory predictive models (LAB). LAB models for the prediction of PD-90 were modestly enhanced over ADM, but negligible benefit was seen for RA-90. A consistent predictor of PD-90 and RA-90 was prolonged length of stay outliers from the index hospitalization.

  7. Cardiac hypertrophy is enhanced in PPAR alpha-/- mice in response to chronic pressure overload.

    PubMed

    Smeets, Pascal J H; Teunissen, Birgit E J; Willemsen, Peter H M; van Nieuwenhoven, Frans A; Brouns, Agnieszka E; Janssen, Ben J A; Cleutjens, Jack P M; Staels, Bart; van der Vusse, Ger J; van Bilsen, Marc

    2008-04-01

    Peroxisome proliferator-activated receptor-alpha (PPARalpha) is a nuclear receptor regulating cardiac metabolism that also has anti-inflammatory properties. Since the activation of inflammatory signalling pathways is considered to be important in cardiac hypertrophy and fibrosis, it is anticipated that PPARalpha modulates cardiac remodelling. Accordingly, in this study the hypothesis was tested that the absence of PPARalpha aggravates the cardiac hypertrophic response to pressure overload. Male PPARalpha-/- and wild-type mice were subjected to transverse aortic constriction (TAC) for 28 days. TAC resulted in a more pronounced increase in ventricular weight and left ventricular (LV) wall thickness in PPARalpha-/- than in wild-type mice. Compared with sham-operated mice, TAC did not affect cardiac function in wild-type mice, but significantly depressed LV ejection fraction and LV contractility in PPARalpha-/- mice. Moreover, after TAC mRNA levels of hypertrophic (atrial natriuretic factor, alpha-skeletal actin), fibrotic (collagen 1, matrix metalloproteinase-2), and inflammatory (interleukin-6, tumour necrosis factor-alpha, cyclo-oxygenase-2) marker genes were higher in PPARalpha-/- than in wild-type mice. The mRNA levels of genes involved in fatty acid metabolism (long-chain acyl-CoA synthetase, hydroxyacyl-CoA dehydrogenase) were decreased in PPARalpha-/- mice, but were not further compromised by TAC. The present findings show that the absence of PPARalpha results in a more pronounced hypertrophic growth response and cardiac dysfunction that are associated with an enhanced expression of markers of inflammation and extracellular matrix remodelling. These findings indicate that PPARalpha exerts salutary effects during cardiac hypertrophy.

  8. The Histone Methyltransferase Inhibitor BIX01294 Enhances the Cardiac Potential of Bone Marrow Cells

    PubMed Central

    Mezentseva, Nadejda V.; Yang, Jinpu; Kaur, Keerat; Iaffaldano, Grazia; Rémond, Mathieu C.; Eisenberg, Carol A.

    2013-01-01

    Bone marrow (BM) has long been considered a potential stem cell source for cardiac repair due to its abundance and accessibility. Although previous investigations have generated cardiomyocytes from BM, yields have been low, and far less than produced from ES or induced pluripotent stem cells (iPSCs). Since differentiation of pluripotent cells is difficult to control, we investigated whether BM cardiac competency could be enhanced without making cells pluripotent. From screens of various molecules that have been shown to assist iPSC production or maintain the ES cell phenotype, we identified the G9a histone methyltransferase inhibitor BIX01294 as a potential reprogramming agent for converting BM cells to a cardiac-competent phenotype. BM cells exposed to BIX01294 displayed significantly elevated expression of brachyury, Mesp1, and islet1, which are genes associated with embryonic cardiac progenitors. In contrast, BIX01294 treatment minimally affected ectodermal, endodermal, and pluripotency gene expression by BM cells. Expression of cardiac-associated genes Nkx2.5, GATA4, Hand1, Hand2, Tbx5, myocardin, and titin was enhanced 114, 76, 276, 46, 635, 123, and 5-fold in response to the cardiogenic stimulator Wnt11 when BM cells were pretreated with BIX01294. Immunofluorescent analysis demonstrated that BIX01294 exposure allowed for the subsequent display of various muscle proteins within the cells. The effect of BIX01294 on the BM cell phenotype and differentiation potential corresponded to an overall decrease in methylation of histone H3 at lysine9, which is the primary target of G9a histone methyltransferase. In summary, these data suggest that BIX01294 inhibition of chromatin methylation reprograms BM cells to a cardiac-competent progenitor phenotype. PMID:22994322

  9. The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells.

    PubMed

    Mezentseva, Nadejda V; Yang, Jinpu; Kaur, Keerat; Iaffaldano, Grazia; Rémond, Mathieu C; Eisenberg, Carol A; Eisenberg, Leonard M

    2013-02-15

    Bone marrow (BM) has long been considered a potential stem cell source for cardiac repair due to its abundance and accessibility. Although previous investigations have generated cardiomyocytes from BM, yields have been low, and far less than produced from ES or induced pluripotent stem cells (iPSCs). Since differentiation of pluripotent cells is difficult to control, we investigated whether BM cardiac competency could be enhanced without making cells pluripotent. From screens of various molecules that have been shown to assist iPSC production or maintain the ES cell phenotype, we identified the G9a histone methyltransferase inhibitor BIX01294 as a potential reprogramming agent for converting BM cells to a cardiac-competent phenotype. BM cells exposed to BIX01294 displayed significantly elevated expression of brachyury, Mesp1, and islet1, which are genes associated with embryonic cardiac progenitors. In contrast, BIX01294 treatment minimally affected ectodermal, endodermal, and pluripotency gene expression by BM cells. Expression of cardiac-associated genes Nkx2.5, GATA4, Hand1, Hand2, Tbx5, myocardin, and titin was enhanced 114, 76, 276, 46, 635, 123, and 5-fold in response to the cardiogenic stimulator Wnt11 when BM cells were pretreated with BIX01294. Immunofluorescent analysis demonstrated that BIX01294 exposure allowed for the subsequent display of various muscle proteins within the cells. The effect of BIX01294 on the BM cell phenotype and differentiation potential corresponded to an overall decrease in methylation of histone H3 at lysine9, which is the primary target of G9a histone methyltransferase. In summary, these data suggest that BIX01294 inhibition of chromatin methylation reprograms BM cells to a cardiac-competent progenitor phenotype.

  10. Control of cardiac-specific transcription by p300 through myocyte enhancer factor-2D.

    PubMed

    Slepak, T I; Webster, K A; Zang, J; Prentice, H; O'Dowd, A; Hicks, M N; Bishopric, N H

    2001-03-09

    The transcriptional integrator p300 regulates gene expression by interaction with sequence-specific DNA-binding proteins and local remodeling of chromatin. p300 is required for cardiac-specific gene transcription, but the molecular basis of this requirement is unknown. Here we report that the MADS (MCM-1, agamous, deficiens, serum response factor) box transcription factor myocyte enhancer factor-2D (MEF-2D) acts as the principal conduit for cardiac transcriptional activation by p300. p300 activation of the native 2130-base pair human skeletal alpha-actin promoter required a single hybrid MEF-2/GATA-4 DNA motif centered at -1256 base pairs. Maximal expression of the promoter in cultured myocytes and in vivo correlated with binding of both MEF-2 and p300, but not GATA-4, to this AT-rich motif. p300 and MEF-2 were coprecipitated from cardiac nuclear extracts by an oligomer containing this element. p300 was found exclusively in a complex with MEF-2D at this and related sites in other cardiac-restricted promoters. MEF-2D, but not other MEFs, significantly potentiated cardiac-specific transcription by p300. No physical or functional interaction was observed between p300 and other factors implicated in skeletal actin transcription, including GATA-4, TEF-1, or SRF. These results show that, in the intact cell, p300 interactions with its protein targets are highly selective and that MEF-2D is the preferred channel for p300-mediated transcriptional control in the heart.

  11. Employee self-enhancement motives and job performance behaviors: investigating the moderating effects of employee role ambiguity and managerial perceptions of employee commitment.

    PubMed

    Yun, Seokhwa; Takeuchi, Riki; Liu, Wei

    2007-05-01

    This study examined the effects of employee self-enhancement motives on job performance behaviors (organizational citizenship behaviors and task performance) and the value of these behaviors to them. The authors propose that employees display job performance behaviors in part to enhance their self-image, especially when their role is not clearly defined. They further argue that the effects of these behaviors on managerial reward recommendation decisions should be stronger when managers believe the employees to be more committed. The results from a sample of 84 working students indicate that role ambiguity moderated the effects of self-enhancement motives on job performance behaviors and that managerial perceptions of an employee's commitment moderated the effects of those organizational citizenship behaviors that are aimed at other individuals on managers' reward allocation decisions. 2007 APA, all rights reserved

  12. Cardiac Amyloidosis: Typical Imaging Findings and Diffuse Myocardial Damage Demonstrated by Delayed Contrast-Enhanced MRI

    SciTech Connect

    Sueyoshi, Eijun Sakamoto, Ichiro; Okimoto, Tomoaki; Hayashi, Kuniaki; Tanaka, Kyouei; Toda, Genji

    2006-08-15

    Amyloidosis is a rare systemic disease. However, involvement of the heart is a common finding and is the most frequent cause of death in amyloidosis. We report the sonographic, scintigraphic, and MRI features of a pathologically proven case of cardiac amyloidosis. Delayed contrast-enhanced MR images, using an inversion recovery prepped gradient-echo sequence, revealed diffuse enhancement in the wall of both left and right ventricles. This enhancement suggested expansion of the extracellular space of the myocardium caused by diffuse myocardial necrosis secondary to deposition of amyloid.

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

    PubMed Central

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

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

  14. Pharmacologic and genetic strategies to enhance cell therapy for cardiac regeneration.

    PubMed

    Kanashiro-Takeuchi, Rosemeire M; Schulman, Ivonne Hernandez; Hare, Joshua M

    2011-10-01

    Cell-based therapy is emerging as an exciting potential therapeutic approach for cardiac regeneration following myocardial infarction (MI). As heart failure (HF) prevalence increases over time, development of new interventions designed to aid cardiac recovery from injury are crucial and should be considered more broadly. In this regard, substantial efforts to enhance the efficacy and safety of cell therapy are continuously growing along several fronts, including modifications to improve the reprogramming efficiency of inducible pluripotent stem cells (iPS), genetic engineering of adult stem cells, and administration of growth factors or small molecules to activate regenerative pathways in the injured heart. These interventions are emerging as potential therapeutic alternatives and/or adjuncts based on their potential to promote stem cell homing, proliferation, differentiation, and/or survival. Given the promise of therapeutic interventions to enhance the regenerative capacity of multipotent stem cells as well as specifically guide endogenous or exogenous stem cells into a cardiac lineage, their application in cardiac regenerative medicine should be the focus of future clinical research. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure." Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Pharmacologic And Genetic Strategies To Enhance Cell Therapy For Cardiac Regeneration

    PubMed Central

    Kanashiro-Takeuchi, Rosemeire M.; Schulman, Ivonne Hernandez; Hare, Joshua M.

    2012-01-01

    Cell-based therapy is emerging as an exciting potential therapeutic approach for cardiac regeneration following myocardial infarction (MI). As heart failure (HF) prevalence increases over time, development of new interventions designed to aid cardiac recovery from injury are crucial and should be considered more broadly. In this regard, substantial efforts to enhance the efficacy and safety of cell therapy are continuously growing along several fronts, including modifications to improve the reprogramming efficiency of inducible pluripotent stem cells (iPS), genetic engineering of adult stem cells, and administration of growth factors or small molecules to activate regenerative pathways in the injured heart. These interventions are emerging as potential therapeutic alternatives and/or adjuncts based on their potential to promote stem cell homing, proliferation, differentiation, and/or survival. Given the promise of therapeutic interventions to enhance the regenerative capacity of multipotent stem cells as well as specifically guide endogenous or exogenous stem cells into a cardiac lineage, their application in cardiac regenerative medicine should be the focus of future clinical research. This article is part of a Special Issue entitled ‘Key Signaling Molecules Special Issue’. PMID:21645519

  16. Biventricular apical thrombi demonstrated by contrast-enhanced cardiac MRI following anteroapical STEMI and unsuccessful reperfusion therapy

    PubMed Central

    Keeble, William; VonderMuhll, Isabelle; Paterson, Ian

    2008-01-01

    Contrast-enhanced cardiac magnetic resonance imaging can define the territory and extent of myocardial infarction from patterns of late gadolinium enhancement. Following failure to reperfuse with thrombolytic therapy, a case of myocardial infarction is described in which ongoing symptoms and an electrocardiogram change led to a diagnostic dilemma. Cardiac magnetic resonance imaging confirmed an apical infarction, an aneurysm and acute pericarditis. In addition, late gadolinium enhancement unexpectedly revealed the presence of biventricular apical thrombi. The prevalence of cardiac thrombi and pulmonary emboli may be greater than generally appreciated. PMID:18685749

  17. Enhanced cardiac TBC1D10C expression lowers heart rate and enhances exercise capacity and survival

    PubMed Central

    Volland, Cornelia; Bremer, Sebastian; Hellenkamp, Kristian; Hartmann, Nico; Dybkova, Nataliya; Khadjeh, Sara; Kutschenko, Anna; Liebetanz, David; Wagner, Stefan; Unsöld, Bernhard; Didié, Michael; Toischer, Karl; Sossalla, Samuel; Hasenfuß, Gerd; Seidler, Tim

    2016-01-01

    TBC1D10C is a protein previously demonstrated to bind and inhibit Ras and Calcineurin. In cardiomyocytes, also CaMKII is inhibited and all three targeted enzymes are known to promote maladaptive cardiomyocyte hypertrophy. Here, in accordance with lack of Calcineurin inhibition in vivo, we did not observe a relevant anti-hypertrophic effect despite inhibition of Ras and CaMKII. However, cardiomyocyte-specific TBC1D10C overexpressing transgenic mice exhibited enhanced longevity. Ejection fraction and exercise capacity were enhanced in transgenic mice, but shortening of isolated cardiomyocytes was not increased. This suggests longevity resulted from enhanced cardiac performance but independent of cardiomyocyte contractile force. In further search for mechanisms, a transcriptome-wide analysis revealed expressional changes in several genes pertinent to control of heart rate (HR) including Hcn4, Scn10a, Sema3a and Cacna2d2. Indeed, telemetric holter recordings demonstrated slower atrial conduction and significantly lower HR. Pharmacological reduction of HR was previously demonstrated to enhance survival in mice. Thus, in addition to inhibition of stress signaling, TBC1D10C economizes generation of cardiac output via HR reduction, enhancing exercise capacity and survival. TBC1D10C may be a new target for HR reduction and longevity. PMID:27667030

  18. Noninvasive detection of cardiac amyloidosis using delayed enhanced MDCT: a pilot study.

    PubMed

    Deux, Jean-François; Mihalache, Cristian-Ionut; Legou, François; Damy, Thibaud; Mayer, Julie; Rappeneau, Stéphane; Planté-Bordeneuve, Violaine; Luciani, Alain; Kobeiter, Hicham; Rahmouni, Alain

    2015-08-01

    To evaluate myocardial enhancement of patients with cardiac amyloidosis (CA) using computed tomography (CT). Thirteen patients with CA and 11 control patients were examined with first-pass and delayed CT acquisition. A qualitative and quantitative analysis of images was performed. Myocardial attenuation, myocardial signal-to-noise ratio (SNRmyoc), blood pool SNR (SNRblood), contrast-to-noise ratio between blood pool and myocardium (CNRblood-myoc) and relative attenuation index (RAI) defined as variation of myocardial attenuation between delayed and first-pass acquisitions were calculated. Two false negative cases (15 %) and three false positive cases (27 %) were detected on qualitative analysis. SNRmyoc of patients with CA was significantly (p < 0.05) lower on first-pass (4.08 ± 1.9) and higher on delayed acquisition (7.10 ± 2.7) than control patients (6.1 ± 2.2 and 5.03 ± 1.8, respectively). Myocardial attenuation was higher in CA (121 ± 39 HU) than control patients (81 ± 17 HU) on delayed acquisition. CNRblood-myoc was significantly (p < 0.05) lower in CA (1.51 ± 0.7) than control patients (2.85 ± 1.2) on delayed acquisition. The RAI was significantly (p < 0.05) higher in CA (0.12 ± 0.25) than in control patients (-0.56 ± 0.21). Dual phase MDCT can detect abnormal myocardial enhancement in patients with CA. • CT can detect abnormal first-pass and delayed enhancement in cardiac amyloidosis. • Measurement of relative myocardial enhancement between acquisitions helps to detect cardiac amyloidosis. • CT may provide useful data to diagnose cardiac amyloidosis.

  19. Mice lacking thyroid hormone receptor Beta show enhanced apoptosis and delayed liver commitment for proliferation after partial hepatectomy.

    PubMed

    López-Fontal, Raquel; Zeini, Miriam; Través, Paqui G; Gómez-Ferrería, Mariana; Aranda, Ana; Sáez, Guillermo T; Cerdá, Concha; Martín-Sanz, Paloma; Hortelano, Sonsoles; Boscá, Lisardo

    2010-01-14

    The role of thyroid hormones and their receptors (TR) during liver regeneration after partial hepatectomy (PH) was studied using genetic and pharmacologic approaches. Roles in liver regeneration have been suggested for T3, but there is no clear evidence distinguishing the contribution of increased amounts of T3 from the modulation by unoccupied TRs. Mice lacking TRalpha1/TRbeta or TRbeta alone fully regenerated liver mass after PH, but showed delayed commitment to the initial round of hepatocyte proliferation and transient but intense apoptosis at 48h post-PH, affecting approximately 30% of the remaining hepatocytes. Pharmacologically induced hypothyroidism yielded similar results. Loss of TR activity was associated with enhanced nitrosative stress in the liver remnant, due to an increase in the activity of the nitric oxide synthase (NOS) 2 and 3, caused by a transient decrease in the concentration of asymmetric dimethylarginine (ADMA), a potent NOS inhibitor. This decrease in the ADMA levels was due to the presence of a higher activity of dimethylarginineaminohydrolase-1 (DDAH-1) in the regenerating liver of animals lacking TRalpha1/TRbeta or TRbeta. DDAH-1 expression and activity was paralleled by the activity of FXR, a transcription factor involved in liver regeneration and up-regulated in the absence of TR. We report that TRs are not required for liver regeneration; however, hypothyroid mice and TRbeta- or TRalpha1/TRbeta-deficient mice exhibit a delay in the restoration of liver mass, suggesting a specific role for TRbeta in liver regeneration. Altered regenerative responses are related with a delay in the expression of cyclins D1 and E, and the occurrence of liver apoptosis in the absence of activated TRbeta that can be prevented by administration of NOS inhibitors. Taken together, these results indicate that TRbeta contributes significantly to the rapid initial round of hepatocyte proliferation following PH, and improves the survival of the regenerating

  20. Mice Lacking Thyroid Hormone Receptor β Show Enhanced Apoptosis and Delayed Liver Commitment for Proliferation after Partial Hepatectomy

    PubMed Central

    López-Fontal, Raquel; Zeini, Miriam; Través, Paqui G.; Gómez-Ferrería, Mariana; Aranda, Ana; Sáez, Guillermo T.; Cerdá, Concha; Martín-Sanz, Paloma; Hortelano, Sonsoles; Boscá, Lisardo

    2010-01-01

    Background The role of thyroid hormones and their receptors (TR) during liver regeneration after partial hepatectomy (PH) was studied using genetic and pharmacologic approaches. Roles in liver regeneration have been suggested for T3, but there is no clear evidence distinguishing the contribution of increased amounts of T3 from the modulation by unoccupied TRs. Methodology/Principal Findings Mice lacking TRα1/TRβ or TRβ alone fully regenerated liver mass after PH, but showed delayed commitment to the initial round of hepatocyte proliferation and transient but intense apoptosis at 48h post-PH, affecting ∼30% of the remaining hepatocytes. Pharmacologically induced hypothyroidism yielded similar results. Loss of TR activity was associated with enhanced nitrosative stress in the liver remnant, due to an increase in the activity of the nitric oxide synthase (NOS) 2 and 3, caused by a transient decrease in the concentration of asymmetric dimethylarginine (ADMA), a potent NOS inhibitor. This decrease in the ADMA levels was due to the presence of a higher activity of dimethylarginineaminohydrolase-1 (DDAH-1) in the regenerating liver of animals lacking TRα1/TRβ or TRβ. DDAH-1 expression and activity was paralleled by the activity of FXR, a transcription factor involved in liver regeneration and up-regulated in the absence of TR. Conclusions/Significance We report that TRs are not required for liver regeneration; however, hypothyroid mice and TRβ– or TRα1/TRβ–deficient mice exhibit a delay in the restoration of liver mass, suggesting a specific role for TRβ in liver regeneration. Altered regenerative responses are related with a delay in the expression of cyclins D1 and E, and the occurrence of liver apoptosis in the absence of activated TRβ that can be prevented by administration of NOS inhibitors. Taken together, these results indicate that TRβ contributes significantly to the rapid initial round of hepatocyte proliferation following PH, and improves the

  1. miR-133a Enhances the Protective Capacity of Cardiac Progenitors Cells after Myocardial Infarction

    PubMed Central

    Izarra, Alberto; Moscoso, Isabel; Levent, Elif; Cañón, Susana; Cerrada, Inmaculada; Díez-Juan, Antonio; Blanca, Vanessa; Núñez-Gil, Iván-J.; Valiente, Iñigo; Ruíz-Sauri, Amparo; Sepúlveda, Pilar; Tiburcy, Malte; Zimmermann, Wolfram-H.; Bernad, Antonio

    2014-01-01

    Summary miR-133a and miR-1 are known as muscle-specific microRNAs that are involved in cardiac development and pathophysiology. We have shown that both miR-1 and miR-133a are early and progressively upregulated during in vitro cardiac differentiation of adult cardiac progenitor cells (CPCs), but only miR-133a expression was enhanced under in vitro oxidative stress. miR-1 was demonstrated to favor differentiation of CPCs, whereas miR-133a overexpression protected CPCs against cell death, targeting, among others, the proapoptotic genes Bim and Bmf. miR-133a-CPCs clearly improved cardiac function in a rat myocardial infarction model by reducing fibrosis and hypertrophy and increasing vascularization and cardiomyocyte proliferation. The beneficial effects of miR-133a-CPCs seem to correlate with the upregulated expression of several relevant paracrine factors and the plausible cooperative secretion of miR-133a via exosomal transport. Finally, an in vitro heart muscle model confirmed the antiapoptotic effects of miR-133a-CPCs, favoring the structuration and contractile functionality of the artificial tissue. PMID:25465869

  2. Heart-specific Rpd3 downregulation enhances cardiac function and longevity

    PubMed Central

    Kopp, Zachary A.; Hsieh, Jo-Lin; Li, Andrew; Wang, William; Bhatt, Dhelni T.; Lee, Angela; Kim, Sae Yeon; Fan, David; Shah, Veevek; Siddiqui, Emaad; Ragam, Radhika; Park, Kristen; Ardeshna, Dev; Park, Kunwoo; Wu, Rachel; Parikh, Hardik; Parikh, Ayush; Lin, Yuh-Ru; Park, Yongkyu

    2015-01-01

    Downregulation of Rpd3, a homologue of mammalian Histone Deacetylase 1 (HDAC1), extends lifespan in Drosophila melanogaster. Once revealed that long-lived fruit flies exhibit limited cardiac decline, we investigated whether Rpd3 downregulation would improve stress resistance and/or lifespan when targeted in the heart. Contested against three different stressors (oxidation, starvation and heat), heart-specific Rpd3 downregulation significantly enhanced stress resistance in flies. However, these higher levels of resistance were not observed when Rpd3 downregulation was targeted in other tissues or when other long-lived flies were tested in the heart-specific manner. Interestingly, the expressions of anti-aging genes such as sod2, foxo and Thor, were systemically increased as a consequence of heart-specific Rpd3 downregulation. Showing higher resistance to oxidative stress, the heart-specific Rpd3 downregulation concurrently exhibited improved cardiac functions, demonstrating an increased heart rate, decreased heart failure and accelerated heart recovery. Conversely, Rpd3 upregulation in cardiac tissue reduced systemic resistance against heat stress with decreased heart function, also specifying phosphorylated Rpd3 levels as a significant modulator. Continual downregulation of Rpd3 throughout aging increased lifespan, implicating that Rpd3 deacetylase in the heart plays a significant role in cardiac function and longevity to systemically modulate the fly's response to the environment. PMID:26399365

  3. Neurally released pituitary adenylate cyclase-activating polypeptide enhances guinea pig intrinsic cardiac neurone excitability.

    PubMed

    Tompkins, John D; Ardell, Jeffrey L; Hoover, Donald B; Parsons, Rodney L

    2007-07-01

    Intracellular recordings were made in vitro from guinea-pig cardiac ganglia to determine whether endogenous neuropeptides such as pituitary adenylate cyclase-activating polypeptide (PACAP) or substance P released during tetanic neural stimulation modulate cardiac neurone excitability and/or contribute to slow excitatory postsynaptic potentials (sEPSPs). When nicotinic and muscarinic receptors were blocked by hexamethonium and atropine, 20 Hz stimulation for 10 s initiated a sEPSP in all innervated neurones. In 40% of the cells, excitability was enhanced after termination of the sEPSP. This suggested that non-cholinergic receptor-mediated mechanisms contributed to the sEPSP and modulated neuronal excitability. Exogenous PACAP and substance P initiated a slow depolarization in the neurones whereas neuronal excitability was only increased by PACAP. When ganglia were treated with the PAC1 antagonist PACAP6-38 (500 nM), the sEPSP evoked by 20 Hz stimulation was reduced by approximately 50% and an enhanced excitability occurred in only 10% of the cells. These observations suggested that PACAP released from preganglionic nerve terminals during tetanic stimulation enhanced neuronal excitability and evoked sEPSPs. After addition of 1 nM PACAP to the bath, 7 of 9 neurones exhibited a tonic firing pattern whereas in untreated preparations, the neurons had a phasic firing pattern. PACAP6-38 (500 nM) diminished the increase in excitability caused by 1 nM PACAP so that only 4 of 13 neurones exhibited a tonic firing pattern and the other 9 cells retained a phasic firing pattern. These findings indicate that PACAP can be released by tetanic neural stimulation in vitro and increase the excitability of intrinsic cardiac neurones. We hypothesize that in vivo PACAP released during preganglionic firing may modulate neurotransmission within the intrinsic cardiac ganglia.

  4. [PPARα attenuates palmitate-induced endoplasmic reticulum stress in human cardiac cells by enhancing AMPK activity].

    PubMed

    Palomer, Xavier; Capdevila-Busquets, Eva; Garreta, Gerard; Davidson, Mercy M; Vázquez-Carrera, Manuel

    2014-01-01

    Endoplasmic reticulum (ER) stress has been linked to several cardiovascular diseases, such as atherosclerosis, heart failure and cardiac hypertrophy. ER stress impairs insulin signalling, thus contributing to the development of insulin resistance and diabetes. Since several studies have reported that PPARα may inhibit ER stress, the main aim of this study consisted in investigating whether activation of this nuclear receptor is able to prevent lipid-induced ER stress in cardiac cells, as well as studying the mechanisms involved. A cardiomyocyte cell line of human origin, AC16, was treated with palmitate in the presence or absence of several AMPK and PPARα pharmacological agonists and antagonists. For the in vivo studies, wild-type male mice were fed a standard diet, or a high-fat diet (HFD), for two months. At the end of the experiments, several ER stress markers were assessed in cardiac cells or in the mice hearts, using real-time RT-PCR and Western-blot analyses. The results demonstrate that both palmitate and the HFD induced ER stress in cardiac cells, since they upregulated the expression (ATF3, BiP/GRP78 and CHOP), splicing (sXBP1), and phosphorylation (IRE-1α and eIF2α) of several ER stress markers. Interestingly, treatment with the PPARα agonist Wy-14,643 prevented an increase in the majority of these ER stress markers in human cardiac cells by means of AMPK activation. These data indicate that PPARα activation by Wy-14,643 might be useful to prevent the harmful effects of ER stress and associated cardiovascular diseases in obese patients, and even during diabetic cardiomyopathy, by enhancing AMPK activity. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  5. Enhancement of early cardiac differentiation of dedifferentiated fat cells by dimethyloxalylglycine via notch signaling pathway.

    PubMed

    Li, Fuhai; Li, Zongzhuang; Jiang, Zhi; Tian, Ye; Wang, Zhi; Yi, Wei; Zhang, Chenyun

    2016-01-01

    Background: Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated. Objective: To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism. Methods: DFAT cells were prepared from 4 to 6 week-age mice and cultured under hypoxic conditions by adding Prolyl hydroxylase inhibitor and dimethyloxalylglycine (DMOG) into the culture media. To inhibit or block Notch signaling, γ-secretase inhibitor-II (GSI-II) and Notch1 siRNA (si-Notch1) were used. DFAT cell viability was detected using MTT assay. qRT-PCR, immunofluorescence microscopy and western blotting were used to evaluate the cardiac differentiation of DFAT cells and co-immunoprecipitation was used to study the interaction between HIF-1α and Notch signaling. Results: 0.6-mM DMOG failed to affect the viability of DFAT cells, but stimulated the cells to express early cardiac transcription factors including Islet1, Nkx2.5 and Gata4 in a time-dependent manner and increase the number of cTnT(+) cardiomyocytes (detected at the 28(th) day after stimulation). It was also demonstrated that DMOG was involved in HIF-1α and Notch signaling as well as HIF-1α-NICD complex formation. Conclusion: Hypoxia enhanced early cardiac differentiation of DFAT cells through HIF-1α and Notch signaling pathway.

  6. Enhancement of early cardiac differentiation of dedifferentiated fat cells by dimethyloxalylglycine via notch signaling pathway

    PubMed Central

    Li, Fuhai; Li, Zongzhuang; Jiang, Zhi; Tian, Ye; Wang, Zhi; Yi, Wei; Zhang, Chenyun

    2016-01-01

    Background: Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated. Objective: To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism. Methods: DFAT cells were prepared from 4 to 6 week-age mice and cultured under hypoxic conditions by adding Prolyl hydroxylase inhibitor and dimethyloxalylglycine (DMOG) into the culture media. To inhibit or block Notch signaling, γ-secretase inhibitor-II (GSI-II) and Notch1 siRNA (si-Notch1) were used. DFAT cell viability was detected using MTT assay. qRT-PCR, immunofluorescence microscopy and western blotting were used to evaluate the cardiac differentiation of DFAT cells and co-immunoprecipitation was used to study the interaction between HIF-1α and Notch signaling. Results: 0.6-mM DMOG failed to affect the viability of DFAT cells, but stimulated the cells to express early cardiac transcription factors including Islet1, Nkx2.5 and Gata4 in a time-dependent manner and increase the number of cTnT+ cardiomyocytes (detected at the 28th day after stimulation). It was also demonstrated that DMOG was involved in HIF-1α and Notch signaling as well as HIF-1α-NICD complex formation. Conclusion: Hypoxia enhanced early cardiac differentiation of DFAT cells through HIF-1α and Notch signaling pathway. PMID:27904680

  7. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

    PubMed

    Jin, Hong; Stojnic, Robert; Adryan, Boris; Ozdemir, Anil; Stathopoulos, Angelike; Frasch, Manfred

    2013-01-01

    The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP) from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

  8. Genome-Wide Screens for In Vivo Tinman Binding Sites Identify Cardiac Enhancers with Diverse Functional Architectures

    PubMed Central

    Jin, Hong; Stojnic, Robert; Adryan, Boris; Ozdemir, Anil; Stathopoulos, Angelike; Frasch, Manfred

    2013-01-01

    The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP) from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ∼50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites. PMID:23326246

  9. Cell-based delivery of dATP via gap junctions enhances cardiac contractility.

    PubMed

    Lundy, Scott D; Murphy, Sean A; Dupras, Sarah K; Dai, Jin; Murry, Charles E; Laflamme, Michael A; Regnier, Michael

    2014-07-01

    The transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is a promising strategy to treat myocardial infarction and reverse heart failure, but to date the contractile benefit in most studies remains modest. We have previously shown that the nucleotide 2-deoxyadenosine triphosphate (dATP) can substitute for ATP as the energy substrate for cardiac myosin, and increasing cellular dATP content by globally overexpressing ribonucleotide reductase (R1R2) can dramatically enhance cardiac contractility. Because dATP is a small molecule, we hypothesized that it would diffuse readily between cells via gap junctions and enhance the contractility of neighboring coupled wild type cells. To test this hypothesis, we performed studies with the goals of (1) validating gap junction-mediated dATP transfer in vitro and (2) investigating the use of R1R2-overexpressing hPSC-CMs in vivo as a novel strategy to increase cardiac function. We first performed intracellular dye transfer studies using dATP conjugated to fluorescein and demonstrated rapid gap junction-mediated transfer between cardiomyocytes. We then cocultured wild type cardiomyocytes with either cardiomyocytes or fibroblasts overexpressing R1R2 and saw more than a twofold increase in the extent and rate of contraction of wild type cardiomyocytes. Finally, we transplanted hPSC-CMs overexpressing R1R2 into healthy uninjured rat hearts and noted an increase in fractional shortening from 41±4% to 53±5% just five days after cell transplantation. These findings demonstrate that dATP is an inotropic factor that spreads between cells via gap junctions. Our data suggest that transplantation of dATP-producing hPSC-CMs could significantly increase the effectiveness of cardiac cell therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Semi-automated scar detection in delayed enhanced cardiac magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Morisi, Rita; Donini, Bruno; Lanconelli, Nico; Rosengarden, James; Morgan, John; Harden, Stephen; Curzen, Nick

    2015-06-01

    Late enhancement cardiac magnetic resonance images (MRI) has the ability to precisely delineate myocardial scars. We present a semi-automated method for detecting scars in cardiac MRI. This model has the potential to improve routine clinical practice since quantification is not currently offered due to time constraints. A first segmentation step was developed for extracting the target regions for potential scar and determining pre-candidate objects. Pattern recognition methods are then applied to the segmented images in order to detect the position of the myocardial scar. The database of late gadolinium enhancement (LE) cardiac MR images consists of 111 blocks of images acquired from 63 patients at the University Hospital Southampton NHS Foundation Trust (UK). At least one scar was present for each patient, and all the scars were manually annotated by an expert. A group of images (around one third of the entire set) was used for training the system which was subsequently tested on all the remaining images. Four different classifiers were trained (Support Vector Machine (SVM), k-nearest neighbor (KNN), Bayesian and feed-forward neural network) and their performance was evaluated by using Free response Receiver Operating Characteristic (FROC) analysis. Feature selection was implemented for analyzing the importance of the various features. The segmentation method proposed allowed the region affected by the scar to be extracted correctly in 96% of the blocks of images. The SVM was shown to be the best classifier for our task, and our system reached an overall sensitivity of 80% with less than 7 false positives per patient. The method we present provides an effective tool for detection of scars on cardiac MRI. This may be of value in clinical practice by permitting routine reporting of scar quantification.

  11. Genetic enhancement of ventricular contractility protects against pressure-overload-induced cardiac dysfunction.

    PubMed

    Du, Xiao-Jun; Fang, Lin; Gao, Xiao-Ming; Kiriazis, Helen; Feng, Xinheng; Hotchkin, Elodie; Finch, Angela M; Chaulet, Hervé; Graham, Robert M

    2004-11-01

    In response to pressure-overload, cardiac function deteriorates and may even progress to fulminant heart failure and death. Here we questioned if genetic enhancement of left ventricular (LV) contractility protects against pressure-overload. Transgenic (TG) mice with cardiac-restricted overexpression (66-fold) of the alpha(1A)-adrenergic receptor (alpha(1A)-AR) and their non-TG (NTG) littermates, were subjected to transverse aorta constriction (TAC)-induced pressure-overload for 12 weeks. TAC-induced hypertrophy was similar in the NTG and TG mice but the TG mice were less likely to die of heart failure compared to the non-TG animals (P <0.05). The hypercontractile phenotype of the TG mice was maintained over the 12-week period following TAC with LV fractional shortening being significantly greater than in the NTG mice (42+/-2 vs 29+/-1%, P <0.01). In the TG animals, 11-week beta-AR-blockade with atenolol neither induced hypertrophy nor suppressed the hypercontractile phenotype. The hypertrophic response to pressure-overload was not altered by cardiac alpha(1A)-AR overexpression. Moreover, the inotropic phenotype of alpha(1A)-AR overexpression was well maintained under conditions of pressure overload. Although the functional decline in contractility with pressure overload was similar in the TG and NTG animals, given that contractility was higher before TAC in the TG mice, their LV function was better preserved and heart failure deaths were fewer after induction of pressure overload.

  12. Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction.

    PubMed

    Protti, Andrea; Mongue-Din, Heloise; Mylonas, Katie J; Sirker, Alexander; Sag, Can Martin; Swim, Megan M; Maier, Lars; Sawyer, Greta; Dong, Xuebin; Botnar, Rene; Salisbury, Jon; Gray, Gillian A; Shah, Ajay M

    2016-01-01

    Bone marrow transplantation (BMT) is commonly used in experimental studies to investigate the contribution of BM-derived circulating cells to different disease processes. During studies investigating the cardiac response to acute myocardial infarction (MI) induced by permanent coronary ligation in mice that had previously undergone BMT, we found that BMT itself affects the remodelling response. Compared to matched naive mice, animals that had previously undergone BMT developed significantly less post-MI adverse remodelling, infarct thinning and contractile dysfunction as assessed by serial magnetic resonance imaging. Cardiac rupture in male mice was prevented. Histological analysis showed that the infarcts of mice that had undergone BMT had a significantly higher number of inflammatory cells, surviving cardiomyocytes and neovessels than control mice, as well as evidence of significant haemosiderin deposition. Flow cytometric and histological analyses demonstrated a higher number of alternatively activated (M2) macrophages in myocardium of the BMT group compared to control animals even before MI, and this increased further in the infarcts of the BMT mice after MI. The process of BMT itself substantially alters tissue macrophage phenotype and the subsequent response to acute MI. An increase in alternatively activated macrophages in this setting appears to enhance cardiac recovery after MI. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Locating AED Enabled Medical Drones to Enhance Cardiac Arrest Response Times.

    PubMed

    Pulver, Aaron; Wei, Ran; Mann, Clay

    2016-01-01

    Out-of-hospital cardiac arrest (OOHCA) is prevalent in the United States. Each year between 180,000 and 400,000 people die due to cardiac arrest. The automated external defibrillator (AED) has greatly enhanced survival rates for OOHCA. However, one of the important components of successful cardiac arrest treatment is emergency medical services (EMS) response time (i.e., the time from EMS "wheels rolling" until arrival at the OOHCA scene). Unmanned Aerial Vehicles (UAV) have regularly been used for remote sensing and aerial imagery collection, but there are new opportunities to use drones for medical emergencies. The purpose of this study is to develop a geographic approach to the placement of a network of medical drones, equipped with an automated external defibrillator, designed to minimize travel time to victims of out-of-hospital cardiac arrest. Our goal was to have one drone on scene within one minute for at least 90% of demand for AED shock therapy, while minimizing implementation costs. In our study, the current estimated travel times were evaluated in Salt Lake County using geographical information systems (GIS) and compared to the estimated travel times of a network of AED enabled medical drones. We employed a location model, the Maximum Coverage Location Problem (MCLP), to determine the best configuration of drones to increase service coverage within one minute. We found that, using traditional vehicles, only 4.3% of the demand can be reached (travel time) within one minute utilizing current EMS agency locations, while 96.4% of demand can be reached within five minutes using current EMS vehicles and facility locations. Analyses show that using existing EMS stations to launch drones resulted in 80.1% of cardiac arrest demand being reached within one minute Allowing new sites to launch drones resulted in 90.3% of demand being reached within one minute. Finally, using existing EMS and new sites resulted in 90.3% of demand being reached while greatly reducing

  14. Phenotypic expression in hypertrophic cardiomyopathy and late gadolinium enhancement on cardiac magnetic resonance.

    PubMed

    Caetano, Francisca; Botelho, Ana; Trigo, Joana; Silva, Joana; Almeida, Inês; Venâncio, Margarida; Pais, João; Sanches, Conceição; Leitão Marques, António

    2014-05-01

    The prognostic value of late gadolinium enhancement (LGE) for risk stratification of hypertrophic cardiomyopathy (HCM) patients is the subject of disagreement. We set out to examine the association between clinical and morphological variables, risk factors for sudden cardiac death and LGE in HCM patients. From a population of 78 patients with HCM, we studied 53 who underwent cardiac magnetic resonance. They were divided into two groups according to the presence or absence of LGE. Ventricular arrhythmias and morbidity and mortality during follow-up were analyzed. Patients with LGE were younger at the time of diagnosis (p=0.046) and more often had a family history of sudden death (p=0.008) and known coronary artery disease (p=0.086). On echocardiography they had greater maximum wall thickness (p=0.007) and left atrial area (p=0.037) and volume (p=0.035), and more often presented a restrictive pattern of diastolic dysfunction (p=0.011) with a higher E/É ratio (p=0.003) and left ventricular systolic dysfunction (p=0.038). Cardiac magnetic resonance supported the association between LGE and previous echocardiographic findings: greater left atrial area (p=0.029) and maximum wall thickness (p<0.001) and lower left ventricular ejection fraction (p=0.056). Patients with LGE more often had an implantable cardioverter-defibrillator (ICD) (p=0.015). At follow-up, no differences were found in the frequency of ventricular arrhythmias, appropriate ICD therapies or mortality. The presence of LGE emerges as a risk marker, associated with the classical predictors of sudden cardiac death in this population. However, larger studies are required to confirm its independent association with clinical events. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  15. Severe Left Ventricular Hypertrophy, Small Pericardial Effusion, and Diffuse Late Gadolinium Enhancement by Cardiac Magnetic Resonance Suspecting Cardiac Amyloidosis: Endomyocardial Biopsy Reveals an Unexpected Diagnosis

    PubMed Central

    Hofmann, Nina P.; Giusca, Sorin; Klingel, Karin; Nunninger, Peter; Korosoglou, Grigorios

    2016-01-01

    Left ventricular (LV) hypertrophy can be related to a multitude of cardiac disorders, such as hypertrophic cardiomyopathy (HCM), cardiac amyloidosis, and hypertensive heart disease. Although the presence of LV hypertrophy is generally associated with poorer cardiac outcomes, the early differentiation between these pathologies is crucial due to the presence of specific treatment options. The diagnostic process with LV hypertrophy requires the integration of clinical evaluation, electrocardiography (ECG), echocardiography, biochemical markers, and if required CMR and endomyocardial biopsy in order to reach the correct diagnosis. Here, we present a case of a patient with severe LV hypertrophy (septal wall thickness of 23 mm, LV mass of 264 g, and LV mass index of 147 g/m2), severely impaired longitudinal function, and preserved radial contractility (ejection fraction = 55%), accompanied by small pericardial effusion and diffuse late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR). Due to the imaging findings, an infiltrative cardiomyopathy, such as cardiac amyloidosis, was suspected. However, amyloid accumulation was excluded by endomyocardial biopsy, which revealed the presence of diffuse myocardial fibrosis in an advanced hypertensive heart disease. PMID:27247807

  16. Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

    PubMed

    Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

    2007-01-01

    Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

  17. An efficient method for accurate segmentation of LV in contrast-enhanced cardiac MR images

    NASA Astrophysics Data System (ADS)

    Suryanarayana K., Venkata; Mitra, Abhishek; Srikrishnan, V.; Jo, Hyun Hee; Bidesi, Anup

    2016-03-01

    Segmentation of left ventricle (LV) in contrast-enhanced cardiac MR images is a challenging task because of high variability in the image intensity. This is due to a) wash-in and wash-out of the contrast agent over time and b) poor contrast around the epicardium (outer wall) region. Current approaches for segmentation of the endocardium (inner wall) usually involve application of a threshold within the region of interest, followed by refinement techniques like active contours. A limitation of this method is under-segmentation of the inner wall because of gradual loss of contrast at the wall boundary. On the other hand, the challenge in outer wall segmentation is the lack of reliable boundaries because of poor contrast. There are four main contributions in this paper to address the aforementioned issues. First, a seed image is selected using variance based approach on 4D time-frame images over which initial endocardium and epicardium is segmented. Secondly, we propose a patch based feature which overcomes the problem of gradual contrast loss for LV endocardium segmentation. Third, we propose a novel Iterative-Edge-Refinement (IER) technique for epicardium segmentation. Fourth, we propose a greedy search algorithm for propagating the initial contour segmented on seed-image across other time frame images. We have experimented our technique on five contrast-enhanced cardiac MR Datasets (4D) having a total of 1097 images. The segmentation results for all 1097 images have been visually inspected by a clinical expert and have shown good accuracy.

  18. Myeloid Zinc Finger 1 (Mzf1) Differentially Modulates Murine Cardiogenesis by Interacting with an Nkx2.5 Cardiac Enhancer

    PubMed Central

    Doppler, Stefanie A.; Werner, Astrid; Barz, Melanie; Lahm, Harald; Deutsch, Marcus-André; Dreßen, Martina; Schiemann, Matthias; Voss, Bernhard; Gregoire, Serge; Kuppusamy, Rajarajan; Wu, Sean M.; Lange, Rüdiger; Krane, Markus

    2014-01-01

    Vertebrate heart development is strictly regulated by temporal and spatial expression of growth and transcription factors (TFs). We analyzed nine TFs, selected by in silico analysis of an Nkx2.5 enhancer, for their ability to transactivate the respective enhancer element that drives, specifically, expression of genes in cardiac progenitor cells (CPCs). Mzf1 showed significant activity in reporter assays and bound directly to the Nkx2.5 cardiac enhancer (Nkx2.5 CE) during murine ES cell differentiation. While Mzf1 is established as a hematopoietic TF, its ability to regulate cardiogenesis is completely unknown. Mzf1 expression was significantly enriched in CPCs from in vitro differentiated ES cells and in mouse embryonic hearts. To examine the effect of Mzf1 overexpression on CPC formation, we generated a double transgenic, inducible, tetOMzf1-Nkx2.5 CE eGFP ES line. During in vitro differentiation an early and continuous Mzf1 overexpression inhibited CPC formation and cardiac gene expression. A late Mzf1 overexpression, coincident with a second physiological peak of Mzf1 expression, resulted in enhanced cardiogenesis. These findings implicate a novel, temporal-specific role of Mzf1 in embryonic heart development. Thereby we add another piece of puzzle in understanding the complex mechanisms of vertebrate cardiac development and progenitor cell differentiation. Consequently, this knowledge will be of critical importance to guide efficient cardiac regenerative strategies and to gain further insights into the molecular basis of congenital heart malformations. PMID:25436607

  19. Visualization and enhancement patterns of radiofrequency ablation lesions with iodine contrast-enhanced cardiac C-arm CT

    NASA Astrophysics Data System (ADS)

    Girard-Hughes, Erin; Al-Ahmad, Amin; Moore, Teri; Lauritsch, Günter; Boese, Jan; Fahrig, Rebecca

    2009-02-01

    The purpose of this study was to evaluate whether contrast-enhanced C-arm CT (3D rotational angiography) can distinguish radiofrequency (RF) ablation lesions created in the left ventricle. Ablation lesions were created on the endocardial surface of the left ventricle of 6 swine using a 7 F RF ablation catheter with a 4 mm electrode. An ECGgated C-arm CT imaging protocol was used to acquire projection images during iodine contrast injection and every 5 min for up to 30 min, with no additional contrast. Reconstructed images were analyzed offline and the mean and standard deviation of the signal intensity of the ablation lesion, normal myocardium, and blood were measured. Eleven ablation lesions were visualized and the time-attenuation curve of the signal intensity was plotted. A mean signal intensity increase of 64.8 +/-33.6 HU was measured in the late enhancement of seven lesions compared to normal myocardium. This is the first study to demonstrate RF ablation lesion enhancement patterns similar to those seen for MR imaging using C-arm CT, an imaging modality that can provide valuable feedback during cardiac interventional procedures.

  20. Anatomically Constrained Neural Networks (ACNN): Application to Cardiac Image Enhancement and Segmentation.

    PubMed

    Oktay, Ozan; Ferrante, Enzo; Kamnitsas, Konstantinos; Heinrich, Mattias; Bai, Wenjia; Caballero, Jose; Cook, Stuart; de Marvao, Antonio; Dawes, Timothy; O'Regan, Declan; Kainz, Bernhard; Glocker, Ben; Rueckert, Daniel

    2017-09-26

    Incorporation of prior knowledge about organ shape and location is key to improve performance of image analysis approaches. In particular, priors can be useful in cases where images are corrupted and contain artefacts due to limitations in image acquisition. The highly constrained nature of anatomical objects can be well captured with learning based techniques. However, in most recent and promising techniques such as CNN based segmentation it is not obvious how to incorporate such prior knowledge. State-of-the-art methods operate as pixel-wise classifiers where the training objectives do not incorporate the structure and inter-dependencies of the output. To overcome this limitation, we propose a generic training strategy that incorporates anatomical prior knowledge into CNNs through a new regularisation model, which is trained end-to-end. The new framework encourages models to follow the global anatomical properties of the underlying anatomy (e.g. shape, label structure) via learnt non-linear representations of the shape. We show that the proposed approach can be easily adapted to different analysis tasks (e.g. image enhancement, segmentation) and improve the prediction accuracy of the state-of-the-art models. The applicability of our approach is shown on multi-modal cardiac datasets and public benchmarks. Additionally, we demonstrate how the learnt deep models of 3D shapes can be interpreted and used as biomarkers for classification of cardiac pathologies.

  1. Estradiol enhances effects of fructose rich diet on cardiac fatty acid transporter CD36 and triglycerides accumulation.

    PubMed

    Korićanac, Goran; Tepavčević, Snežana; Romić, Snježana; Živković, Maja; Stojiljković, Mojca; Milosavljević, Tijana; Stanković, Aleksandra; Petković, Marijana; Kamčeva, Tina; Žakula, Zorica

    2012-11-05

    Fructose rich diet increases hepatic triglycerides production and has deleterious cardiac effects. Estrogens are involved in regulation of lipid metabolism as well, but their effects are cardio beneficial. In order to study effects of fructose rich diet on the main heart fatty acid transporter CD36 and the role of estrogens, we subjected ovariectomized female rats to the standard diet or fructose rich diet, with or without estradiol (E2) replacement. The following parameters were analyzed: feeding behavior, visceral adipose tissue mass, plasma lipids, cardiac CD36 expression, localization and insulin regulation, as well as the profile of cardiac lipids. Results show that fructose rich diet significantly increased plasma triglycerides and decreased plasma free fatty acid (FFA) concentration, while E2 additionally emphasized FFA decrease. The fructose diet increased cardiac plasma membrane content of CD36 in the basal and insulin-stimulated states, and decreased its low density microsomes content. The E2 in fructose-fed rats raised the total cardiac protein content of CD36, its presence in plasma membranes and low density microsomes, and cardiac deposition of triglycerides, as well. Although E2 counteracts fructose in some aspects of lipid metabolism, and separately they have opposite cardiac effects, in combination with fructose rich diet, E2 additionally enhances CD36 presence in plasma membranes of cardiac cells and triglycerides accumulation, which paradoxically might promote deleterious effects of fructose diet on cardiac lipid metabolism. Taken together, the results presented in this work are of high importance for clinical administration of estrogens in females with a history of type 2 diabetes. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Cardiac Non-myocyte Cells Show Enhanced Pharmacological Function Suggestive of Contractile Maturity in Stem Cell Derived Cardiomyocyte Microtissues

    PubMed Central

    Ravenscroft, Stephanie M.; Pointon, Amy; Williams, Awel W.; Cross, Michael J.; Sidaway, James E.

    2016-01-01

    The immature phenotype of stem cell derived cardiomyocytes is a significant barrier to their use in translational medicine and pre-clinical in vitro drug toxicity and pharmacological analysis. Here we have assessed the contribution of non-myocyte cells on the contractile function of co-cultured human embryonic stem cell derived cardiomyocytes (hESC-CMs) in spheroid microtissue format. Microtissues were formed using a scaffold free 96-well cell suspension method from hESC-CM cultured alone (CM microtissues) or in combination with human primary cardiac microvascular endothelial cells and cardiac fibroblasts (CMEF microtissues). Contractility was characterized with fluorescence and video-based edge detection. CMEF microtissues displayed greater Ca2+ transient amplitudes, enhanced spontaneous contraction rate and remarkably enhanced contractile function in response to both positive and negative inotropic drugs, suggesting a more mature contractile phenotype than CM microtissues. In addition, for several drugs the enhanced contractile response was not apparent when endothelial cell or fibroblasts from a non-cardiac tissue were used as the ancillary cells. Further evidence of maturity for CMEF microtissues was shown with increased expression of genes that encode proteins critical in cardiac Ca2+ handling (S100A1), sarcomere assembly (telethonin/TCAP) and β-adrenergic receptor signalling. Our data shows that compared with single cell-type cardiomyocyte in vitro models, CMEF microtissues are superior at predicting the inotropic effects of drugs, demonstrating the critical contribution of cardiac non-myocyte cells in mediating functional cardiotoxicity. PMID:27125969

  3. Paracrine Engineering of Human Cardiac Stem Cells With Insulin-Like Growth Factor 1 Enhances Myocardial Repair.

    PubMed

    Jackson, Robyn; Tilokee, Everad L; Latham, Nicholas; Mount, Seth; Rafatian, Ghazaleh; Strydhorst, Jared; Ye, Bin; Boodhwani, Munir; Chan, Vincent; Ruel, Marc; Ruddy, Terrence D; Suuronen, Erik J; Stewart, Duncan J; Davis, Darryl R

    2015-09-11

    Insulin-like growth factor 1 (IGF-1) activates prosurvival pathways and improves postischemic cardiac function, but this key cytokine is not robustly expressed by cultured human cardiac stem cells. We explored the influence of an enhanced IGF-1 paracrine signature on explant-derived cardiac stem cell-mediated cardiac repair. Receptor profiling demonstrated that IGF-1 receptor expression was increased in the infarct border zones of experimentally infarcted mice by 1 week after myocardial infarction. Human explant-derived cells underwent somatic gene transfer to overexpress human IGF-1 or the green fluorescent protein reporter alone. After culture in hypoxic reduced-serum media, overexpression of IGF-1 enhanced proliferation and expression of prosurvival transcripts and prosurvival proteins and decreased expression of apoptotic markers in both explant-derived cells and cocultured neonatal rat ventricular cardiomyocytes. Transplant of explant-derived cells genetically engineered to overexpress IGF-1 into immunodeficient mice 1 week after infarction boosted IGF-1 content within infarcted tissue and long-term engraftment of transplanted cells while reducing apoptosis and long-term myocardial scarring. Paracrine engineering of explant-derived cells to overexpress IGF-1 provided a targeted means of improving cardiac stem cell-mediated repair by enhancing the long-term survival of transplanted cells and surrounding myocardium. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  4. Semi-automatic segmentation of nonviable cardiac tissue using cine and delayed enhancement magnetic resonance images

    NASA Astrophysics Data System (ADS)

    O'Donnell, Thomas P.; Xu, Ning; Setser, Randolph M.; White, Richard D.

    2003-05-01

    Post myocardial infarction, the identification and assessment of non-viable (necrotic) tissues is necessary for effective development of intervention strategies and treatment plans. Delayed Enhancement Magnetic Resonance (DEMR) imaging is a technique whereby non-viable cardiac tissue appears with increased signal intensity. Radiologists typically acquire these images in conjunction with other functional modalities (e.g., MR Cine), and use domain knowledge and experience to isolate the non-viable tissues. In this paper, we present a technique for automatically segmenting these tissues given the delineation of myocardial borders in the DEMR and in the End-systolic and End-diastolic MR Cine images. Briefly, we obtain a set of segmentations furnished by an expert and employ an artificial intelligence technique, Support Vector Machines (SVMs), to "learn" the segmentations based on features culled from the images. Using those features we then allow the SVM to predict the segmentations the expert would provide on previously unseen images.

  5. Enhanced apoptotic propensity in diabetic cardiac mitochondria: influence of subcellular spatial location

    PubMed Central

    Williamson, Courtney L.; Dabkowski, Erinne R.; Baseler, Walter A.; Croston, Tara L.; Alway, Stephen E.

    2010-01-01

    Cardiovascular complications, such as diabetic cardiomyopathy, account for the majority of deaths associated with diabetes mellitus. Mitochondria are particularly susceptible to the damaging effects of diabetes mellitus and have been implicated in the pathogenesis of diabetic cardiomyopathy. Cardiac mitochondria consist of two spatially distinct subpopulations, termed subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). The goal of this study was to determine whether subcellular spatial location is associated with apoptotic propensity of cardiac mitochondrial subpopulations during diabetic insult. Swiss Webster mice were subjected to intraperitoneal injection of streptozotocin or citrate saline vehicle. Ten weeks following injection, diabetic hearts displayed increased caspase-3 and caspase-9 activities, indicating enhanced apoptotic signaling (P < 0.05, for both). Mitochondrial size (forward scatter) and internal complexity (side scatter) were decreased in diabetic IFM (P < 0.05, for both) but not in diabetic SSM. Mitochondrial membrane potential (ΔΨm) was lower in diabetic IFM (P < 0.01) but not in diabetic SSM. Mitochondrial permeability transition pore (mPTP) opening was increased in diabetic compared with control IFM (P < 0.05), whereas no differences were observed in diabetic compared with control SSM. Examination of mPTP constituents revealed increases in cyclophilin D in diabetic IFM. Furthermore, diabetic IFM possessed lower cytochrome c and BcL-2 levels and increased Bax levels (P < 0.05, for all 3). No significant changes in these proteins were observed in diabetic SSM compared with control. These results indicate that diabetes mellitus is associated with an enhanced apoptotic propensity in IFM, suggesting a differential apoptotic susceptibility of distinct mitochondrial subpopulations based upon subcellular location. PMID:19966057

  6. The value of cardiac magnetic resonance and distribution of late gadolinium enhancement for risk stratification of sudden cardiac death in patients with hypertrophic cardiomyopathy.

    PubMed

    Klopotowski, Mariusz; Kukula, Krzysztof; Malek, Lukasz A; Spiewak, Mateusz; Polanska-Skrzypczyk, Magdalena; Jamiolkowski, Jacek; Dabrowski, Maciej; Baranowski, Rafal; Klisiewicz, Anna; Kusmierczyk, Mariusz; Jasinska, Anna; Jarmus, Ewelina; Kruk, Mariusz; Ruzyllo, Witold; Witkowski, Adam; Chojnowska, Lidia

    2016-07-01

    The presence of late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcome and the extent of LGE predicts the increased risk of sudden cardiac death (SCD). Limited data exist regarding the distribution of LGE. We attempted to verify whether the presence of LGE outside the interventricular insertion points carries additional risk for patients with HCM. In this prospective study, 328 patients with HCM, who underwent cardiac magnetic resonance (CMR) were enrolled. Five major risk factors for SCD were assessed in all patients. The median follow-up was 37 months. LGE was detected in 226 (68.9%) patients. In 70 (21.3%) patients it was present only at the interventricular insertion points - LGE (+) group, while in 156 (47.6%) it was noted in other locations - LGE (++) group. Primary endpoint defined as SCD or appropriate implantable cardioverter-defibrillator intervention occurred in 14 (4.3%) patients, one in LGE (+) and 13 in LGE (++). In multivariable analysis including five traditional risk factors and left ventricular ejection fraction <50%, only the presence of LGE outside the insertion points was a significant predictor of SCD/aborted SCD (HR 10.01, 95% CI 1.21-83.86, p=0.033). The performance of the multivariable sudden cardiac death risk model was improved by the addition of LGE (++) to the traditional risk factors (likelihood ratio p=0.005). The Kaplan-Meier curves showed better event-free survival in the LGE (-) and LGE (+) patient groups compared to the LGE (++) group. In HCM patients, presence of LGE outside interventricular insertion points is associated with increased risk of sudden cardiac death or its equivalent as well as overall mortality. Cardiac fibrosis as a substrate for SCD in HCM may be identified on CMR and serve as an imaging biomarker of increased risk. Copyright © 2016. Published by Elsevier Ltd.

  7. [Association between delayed enhancement on cardiac magnetic resonance imaging and arrhythmia in patients with hypertrophic cardiomyopathy].

    PubMed

    WANG, Jing; KONG, Xiang-quan; XU, Hai-bo; ZHOU, Guo-feng; LIU, Fang; SHI, Hao-jun; LIU, Ding-xi

    2010-09-01

    to observe the association between myocardial fibrosis, detected by delayed-enhancement (DE) cardiac magnetic resonance imaging (MRI) and arrhythmia in patients with hypertrophic cardiomyopathy (HCM). forty-eight untreated HCM patients who underwent Cine MR, DE-MRI, 24 h ambulatory Holter electrocardiogram and ECG examinations were recruited. Extent of myocardial fibrosis (fibrosis mass/total LV mass) was assessed using DE imaging. Association between arrhythmias including premature ventricular complexes (PVCS ≥ 200), supra-ventricular tachycardia (SVT), non-sustained ventricular tachycardia (NSVT), atrio-ventricular block (AVB) and intra-ventricular block (IVB) detected by Holter monitoring and ECG with regard to delayed enhancement (DE) on contrast enhanced CMR was analyzed. myocardial fibrosis was detected in 35 patients. Incidence of arrhythmia was significantly higher in patients with DE than in patients without DE (P < 0.05). Extent of myocardial fibrosis was significantly associated with the QRS duration (r = 0.33, P < 0.001). myocardial fibrosis detected by DE-CMR was associated with arrhythmia in patients with HCM. DE-CMR might be helpful to detect high-risk HCM patients prone to arrhythmia.

  8. Presence of Late Gadolinium Enhancement by Cardiac Magnetic Resonance Among Patients With Suspected Cardiac Sarcoidosis Is Associated With Adverse Cardiovascular Prognosis: A Systematic Review and Meta-Analysis.

    PubMed

    Hulten, Edward; Agarwal, Vikram; Cahill, Michael; Cole, Geoff; Vita, Tomas; Parrish, Scott; Bittencourt, Marcio Sommer; Murthy, Venkatesh L; Kwong, Raymond; Di Carli, Marcelo F; Blankstein, Ron

    2016-09-01

    Individuals with cardiac sarcoidosis have an increased risk of ventricular arrhythmia and death. Several small cohort studies have evaluated the ability of late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging (MRI) to predict adverse cardiovascular events. However, studies have yielded inconsistent results, and some analyses were underpowered. Therefore, we sought to systematically review and perform meta-analysis of the prognostic value of cardiac MRI for patients with known or suspected cardiac sarcoidosis. We systematically searched for cohort studies of patients with known sarcoidosis with suspected cardiac involvement who underwent cardiac MRI with LGE with at least 12 months of either prospective or retrospective follow-up data regarding post-MRI adverse cardiovascular outcomes. We identified 7 studies of 694 subjects (mean age 53; 42% men).One hundred and ninety-nine patients (29%) were LGE positive. All-cause mortality occurred in 19 LGE-positive versus 17 LGE-negative subjects (annualized incidence, 3.1% versus 0.6%). The pooled relative risk was 3.38 (95% confidence interval, 1.07-10.7; P=0.04). Cardiovascular mortality occurred in 10 LGE-positive versus 2 LGE-negative subjects (annualized incidence, 1.9% versus 0.3%; relative risk 10.7 [95% confidence interval, 1.34-86.3]; P=0.03). Ventricular arrhythmia occurred in 41 LGE-positive versus 0 LGE-negative subjects (annualized incidence, 5.9% versus 0%; relative risk 19.5 [95% confidence interval, 2.68-143]; P=0.003). A combined end point of death or ventricular arrhythmia occurred in 64 LGE-positive versus 18 LGE-negative subjects (annualized incidence, 8.8% versus 0.6%; relative risk 6.20 [95% confidence interval, 2.47-15.6]; P<0.001). There was no significant heterogeneity for any outcomes. LGE is associated with future cardiovascular death and ventricular arrhythmia among patients referred to MRI for known or suspected cardiac sarcoidosis. © 2016 American Heart Association, Inc.

  9. Amalaki rasayana, a traditional Indian drug enhances cardiac mitochondrial and contractile functions and improves cardiac function in rats with hypertrophy.

    PubMed

    Kumar, Vikas; Aneesh, Kumar A; Kshemada, K; Ajith, Kumar G S; Binil, Raj S S; Deora, Neha; Sanjay, G; Jaleel, A; Muraleedharan, T S; Anandan, E M; Mony, R S; Valiathan, M S; Santhosh, Kumar T R; Kartha, C C

    2017-08-17

    We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated. Histology, gene and protein expression analysis were done in heart tissues. Chemical composition of AR was analyzed by HPLC, HPTLC and LC-MS. AR intake improved (P < 0.05) cardiac function in aging rats and decreased LVH (P < 0.05) in AC rats as well as increased (P < 0.05) fatigue time in treadmill exercise in both groups. In heart tissues of AR administered rats of both the groups, SERCA2, CaM, Myh11, antioxidant, autophagy, oxidative phosphorylation and TCA cycle proteins were up regulated. ADRB1/2 and pCREB expression were increased; pAMPK, NF-kB were decreased. AR has thus a beneficial effect on myocardial energetics, muscle contractile function and exercise tolerance capacity.

  10. Hand-carried cardiac ultrasound enhances healthcare delivery in developing countries.

    PubMed

    Kobal, Sergio L; Lee, Steve S; Willner, Richard; Aguilar Vargas, Francisco E; Luo, Huai; Watanabe, Colin; Neuman, Yoram; Miyamoto, Takashi; Siegel, Robert J

    2004-08-15

    The availability of cardiac ultrasound is limited in developing countries. We evaluated the feasibility and diagnostic capability of a hand-carried cardiac ultrasound device in 126 patients (age 44 +/- 24 years) referred for consultation to a cardiology clinic in rural Mexico. The hand-carried cardiac ultrasound device identified 86 cardiac findings and obviated the need for further comprehensive echocardiographic evaluation in 90% of patients (113 of 126).

  11. Machine learning classification of cell-specific cardiac enhancers uncovers developmental subnetworks regulating progenitor cell division and cell fate specification

    PubMed Central

    Ahmad, Shaad M.; Busser, Brian W.; Huang, Di; Cozart, Elizabeth J.; Michaud, Sébastien; Zhu, Xianmin; Jeffries, Neal; Aboukhalil, Anton; Bulyk, Martha L.; Ovcharenko, Ivan; Michelson, Alan M.

    2014-01-01

    The Drosophila heart is composed of two distinct cell types, the contractile cardial cells (CCs) and the surrounding non-muscle pericardial cells (PCs), development of which is regulated by a network of conserved signaling molecules and transcription factors (TFs). Here, we used machine learning with array-based chromatin immunoprecipitation (ChIP) data and TF sequence motifs to computationally classify cell type-specific cardiac enhancers. Extensive testing of predicted enhancers at single-cell resolution revealed the added value of ChIP data for modeling cell type-specific activities. Furthermore, clustering the top-scoring classifier sequence features identified novel cardiac and cell type-specific regulatory motifs. For example, we found that the Myb motif learned by the classifier is crucial for CC activity, and the Myb TF acts in concert with two forkhead domain TFs and Polo kinase to regulate cardiac progenitor cell divisions. In addition, differential motif enrichment and cis-trans genetic studies revealed that the Notch signaling pathway TF Suppressor of Hairless [Su(H)] discriminates PC from CC enhancer activities. Collectively, these studies elucidate molecular pathways used in the regulatory decisions for proliferation and differentiation of cardiac progenitor cells, implicate Su(H) in regulating cell fate decisions of these progenitors, and document the utility of enhancer modeling in uncovering developmental regulatory subnetworks. PMID:24496624

  12. Machine learning classification of cell-specific cardiac enhancers uncovers developmental subnetworks regulating progenitor cell division and cell fate specification.

    PubMed

    Ahmad, Shaad M; Busser, Brian W; Huang, Di; Cozart, Elizabeth J; Michaud, Sébastien; Zhu, Xianmin; Jeffries, Neal; Aboukhalil, Anton; Bulyk, Martha L; Ovcharenko, Ivan; Michelson, Alan M

    2014-02-01

    The Drosophila heart is composed of two distinct cell types, the contractile cardial cells (CCs) and the surrounding non-muscle pericardial cells (PCs), development of which is regulated by a network of conserved signaling molecules and transcription factors (TFs). Here, we used machine learning with array-based chromatin immunoprecipitation (ChIP) data and TF sequence motifs to computationally classify cell type-specific cardiac enhancers. Extensive testing of predicted enhancers at single-cell resolution revealed the added value of ChIP data for modeling cell type-specific activities. Furthermore, clustering the top-scoring classifier sequence features identified novel cardiac and cell type-specific regulatory motifs. For example, we found that the Myb motif learned by the classifier is crucial for CC activity, and the Myb TF acts in concert with two forkhead domain TFs and Polo kinase to regulate cardiac progenitor cell divisions. In addition, differential motif enrichment and cis-trans genetic studies revealed that the Notch signaling pathway TF Suppressor of Hairless [Su(H)] discriminates PC from CC enhancer activities. Collectively, these studies elucidate molecular pathways used in the regulatory decisions for proliferation and differentiation of cardiac progenitor cells, implicate Su(H) in regulating cell fate decisions of these progenitors, and document the utility of enhancer modeling in uncovering developmental regulatory subnetworks.

  13. The effectiveness of acceptance and commitment therapy bibliotherapy for enhancing the psychological health of Japanese college students living abroad.

    PubMed

    Muto, Takashi; Hayes, Steven C; Jeffcoat, Tami

    2011-06-01

    International students often experience significant psychological distress but empirically tested programs are few. Broadly distributed bibliotherapy may provide a cost-effective approach. About half of the Japanese international students in a western university in the United States (N=70) were randomly assigned to a wait-list or to receive a Japanese translation of a broadly focused acceptance and commitment therapy (ACT) self-help book. Although recruited without regard to health status, the sample was highly distressed with nearly 80% exceeding clinical cutoffs on one or more measures. After a 2-months period for the first treatment group to read the book and a 2-month follow up, wait-list participants also received the book. Students receiving the book showed significantly better general mental health at post and follow up. Moderately depressed or stressed, and severely anxious students showed improvement compared to those not receiving the book. These patterns were repeated when the wait-list participants finally received the book. Improvements in primary outcomes were related to how much was learned about an ACT model from the book. Follow-up outcomes were statistically mediated by changes in psychological flexibility, but not vice versa and were moderated by level of initial flexibility. Overall, the data suggest that ACT bibliotherapy improved the mental health and psychological flexibility of Japanese international students. Copyright © 2011. Published by Elsevier Ltd.

  14. Overexpressing superoxide dismutase 2 induces a supernormal cardiac function by enhancing redox-dependent mitochondrial function and metabolic dilation.

    PubMed

    Kang, Patrick T; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J; Meszaros, J Gary; Chilian, William M; Chen, Yeong-Renn

    2015-11-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate×MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, "spilled" over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function.

  15. Overexpressing Superoxide Dismutase 2 Induces a Supernormal Cardiac Function by Enhancing Redox-dependent Mitochondrial Function and Metabolic Dilation*

    PubMed Central

    Kang, Patrick T.; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J.; Meszaros, J. Gary; Chilian, William M.; Chen, Yeong-Renn

    2015-01-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate × MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, “spilled” over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function. PMID:26374996

  16. Interactive Hierarchical-Flow Segmentation of Scar Tissue From Late-Enhancement Cardiac MR Images.

    PubMed

    Rajchl, Martin; Yuan, Jing; White, James A; Ukwatta, Eranga; Stirrat, John; Nambakhsh, Cyrus M S; Li, Feng P; Peters, Terry M

    2014-01-01

    We propose a novel multi-region image segmentation approach to extract myocardial scar tissue from 3-D whole-heart cardiac late-enhancement magnetic resonance images in an interactive manner. For this purpose, we developed a graphical user interface to initialize a fast max-flow-based segmentation algorithm and segment scar accurately with progressive interaction. We propose a partially-ordered Potts (POP) model to multi-region segmentation to properly encode the known spatial consistency of cardiac regions. Its generalization introduces a custom label/region order constraint to Potts model to multi-region segmentation. The combinatorial optimization problem associated with the proposed POP model is solved by means of convex relaxation, for which a novel multi-level continuous max-flow formulation, i.e., the hierarchical continuous max-flow (HMF) model, is proposed and studied. We demonstrate that the proposed HMF model is dual or equivalent to the convex relaxed POP model and introduces a new and efficient hierarchical continuous max-flow based algorithm by modern convex optimization theory. In practice, the introduced hierarchical continuous max-flow based algorithm can be implemented on the parallel GPU to achieve significant acceleration in numerics. Experiments are performed in 50 whole heart 3-D LE datasets, 35 with left-ventricular and 15 with right-ventricular scar. The experimental results are compared to full-width-at-half-maximum and Signal-threshold to reference-mean methods using manual expert myocardial segmentations and operator variabilities and the effect of user interaction are assessed. The results indicate a substantial reduction in image processing time with robust accuracy for detection of myocardial scar. This is achieved without the need for additional region constraints and using a single optimization procedure, substantially reducing the potential for error.

  17. Paracrine Engineering of Human Explant-Derived Cardiac Stem Cells to Over-Express Stromal-Cell Derived Factor 1α Enhances Myocardial Repair.

    PubMed

    Tilokee, Everad L; Latham, Nicholas; Jackson, Robyn; Mayfield, Audrey E; Ye, Bin; Mount, Seth; Lam, Buu-Khanh; Suuronen, Erik J; Ruel, Marc; Stewart, Duncan J; Davis, Darryl R

    2016-07-01

    First generation cardiac stem cell products provide indirect cardiac repair but variably produce key cardioprotective cytokines, such as stromal-cell derived factor 1α, which opens the prospect of maximizing up-front paracrine-mediated repair. The mesenchymal subpopulation within explant derived human cardiac stem cells underwent lentiviral mediated gene transfer of stromal-cell derived factor 1α. Unlike previous unsuccessful attempts to increase efficacy by boosting the paracrine signature of cardiac stem cells, cytokine profiling revealed that stromal-cell derived factor 1α over-expression prevented lv-mediated "loss of cytokines" through autocrine stimulation of CXCR4+ cardiac stem cells. Stromal-cell derived factor 1α enhanced angiogenesis and stem cell recruitment while priming cardiac stem cells to readily adopt a cardiac identity. As compared to injection with unmodified cardiac stem cells, transplant of stromal-cell derived factor 1α enhanced cells into immunodeficient mice improved myocardial function and angiogenesis while reducing scarring. Increases in myocardial stromal-cell derived factor 1α content paralleled reductions in myocyte apoptosis but did not influence long-term engraftment or the fate of transplanted cells. Transplantation of stromal-cell derived factor 1α transduced cardiac stem cells increased the generation of new myocytes, recruitment of bone marrow cells, new myocyte/vessel formation and the salvage of reversibly damaged myocardium to enhance cardiac repair after experimental infarction. Stem Cells 2016;34:1826-1835. © 2016 AlphaMed Press.

  18. Synchronized drumming enhances activity in the caudate and facilitates prosocial commitment--if the rhythm comes easily.

    PubMed

    Kokal, Idil; Engel, Annerose; Kirschner, Sebastian; Keysers, Christian

    2011-01-01

    Why does chanting, drumming or dancing together make people feel united? Here we investigate the neural mechanisms underlying interpersonal synchrony and its subsequent effects on prosocial behavior among synchronized individuals. We hypothesized that areas of the brain associated with the processing of reward would be active when individuals experience synchrony during drumming, and that these reward signals would increase prosocial behavior toward this synchronous drum partner. 18 female non-musicians were scanned with functional magnetic resonance imaging while they drummed a rhythm, in alternating blocks, with two different experimenters: one drumming in-synchrony and the other out-of-synchrony relative to the participant. In the last scanning part, which served as the experimental manipulation for the following prosocial behavioral test, one of the experimenters drummed with one half of the participants in-synchrony and with the other out-of-synchrony. After scanning, this experimenter "accidentally" dropped eight pencils, and the number of pencils collected by the participants was used as a measure of prosocial commitment. Results revealed that participants who mastered the novel rhythm easily before scanning showed increased activity in the caudate during synchronous drumming. The same area also responded to monetary reward in a localizer task with the same participants. The activity in the caudate during experiencing synchronous drumming also predicted the number of pencils the participants later collected to help the synchronous experimenter of the manipulation run. In addition, participants collected more pencils to help the experimenter when she had drummed in-synchrony than out-of-synchrony during the manipulation run. By showing an overlap in activated areas during synchronized drumming and monetary reward, our findings suggest that interpersonal synchrony is related to the brain's reward system.

  19. Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking.

    PubMed

    Anneken, Lars; Baumann, Stefan; Vigneault, Patrick; Biliczki, Peter; Friedrich, Corinna; Xiao, Ling; Girmatsion, Zenawit; Takac, Ina; Brandes, Ralf P; Kissler, Stefan; Wiegratz, Inka; Zumhagen, Sven; Stallmeyer, Birgit; Hohnloser, Stefan H; Klingenheben, Thomas; Schulze-Bahr, Eric; Nattel, Stanley; Ehrlich, Joachim R

    2016-02-14

    Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues. Published on behalf of the European Society of Cardiology. All rights

  20. Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking

    PubMed Central

    Anneken, Lars; Baumann, Stefan; Vigneault, Patrick; Biliczki, Peter; Friedrich, Corinna; Xiao, Ling; Girmatsion, Zenawit; Takac, Ina; Brandes, Ralf P.; Kissler, Stefan; Wiegratz, Inka; Zumhagen, Sven; Stallmeyer, Birgit; Hohnloser, Stefan H.; Klingenheben, Thomas; Schulze-Bahr, Eric; Nattel, Stanley; Ehrlich, Joachim R.

    2016-01-01

    Background Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. Methods and results We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. Conclusion Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues. PMID:26271031

  1. Pulmonary exposure of rats to ultrafine titanium dioxide enhances cardiac protein phosphorylation and substance P synthesis in nodose ganglia.

    PubMed

    Kan, Hong; Wu, Zhongxin; Young, Shih-Houng; Chen, Teh-Hsun; Cumpston, Jared L; Chen, Fei; Kashon, Michael L; Castranova, Vincent

    2012-11-01

    The inhalation of engineered nanoparticles stimulates the development of atherosclerosis and impairs vascular function. However, the cardiac effects of inhaled engineered nanoparticles are unknown. Here, we investigate the effects of ultrafine titanium dioxide (UFTiO(2)) on the heart, and we define the possible mechanisms underlying the measured effects. Pulmonary exposure of rats to UFTiO(2) increased the phosphorylation levels of p38 mitogen-activated protein kinase and cardiac troponin I, but not Akt, in the heart and substance P synthesis in nodose ganglia. Circulatory levels of pro-inflammatory cytokines, and blood cell counts and differentials were not significantly changed after pulmonary exposure. Separately, the incubation of cardiac myocytes isolated from naïve adult rat hearts in vitro with UFTiO(2) did not alter the phosphorylation status of the same cardiac proteins. In conclusion, the inhalation of UFTiO(2) enhanced the phosphorylation levels of cardiac proteins. Such responses are likely independent of systemic inflammation, but may involve a lung-neuron-regulated pathway.

  2. Trichostatin A enhances differentiation of human induced pluripotent stem cells to cardiogenic cells for cardiac tissue engineering.

    PubMed

    Lim, Shiang Y; Sivakumaran, Priyadharshini; Crombie, Duncan E; Dusting, Gregory J; Pébay, Alice; Dilley, Rodney J

    2013-09-01

    Human induced pluripotent stem (iPS) cells are a promising source of autologous cardiomyocytes to repair and regenerate myocardium for treatment of heart disease. In this study, we have identified a novel strategy to enhance cardiac differentiation of human iPS cells by treating embryoid bodies (EBs) with a histone deacetylase inhibitor, trichostatin A (TSA), together with activin A and bone morphogenetic protein 4 (BMP4). Over a narrow window of concentrations, TSA (1 ng/ml) directed the differentiation of human iPS cells into a cardiomyocyte lineage. TSA also exerted an additive effect with activin A (100 ng/ml) and BMP4 (20 ng/ml). The resulting cardiomyocytes expressed several cardiac-specific transcription factors and contractile proteins at both gene and protein levels. Functionally, the contractile EBs displayed calcium cycling and were responsive to the chronotropic agents isoprenaline (0.1 μM) and carbachol (1 μM). Implanting microdissected beating areas of iPS cells into tissue engineering chambers in immunocompromised rats produced engineered constructs that supported their survival, and they maintained spontaneous contraction. Human cardiomyocytes were identified as compact patches of muscle tissue incorporated within a host fibrocellular stroma and were vascularized by host neovessels. In conclusion, human iPS cell-derived cardiomyocytes can be used to engineer functional cardiac muscle tissue for studying the pathophysiology of cardiac disease, for drug discovery test beds, and potentially for generation of cardiac grafts to surgically replace damaged myocardium.

  3. Epicardial delivery of VEGF and cardiac stem cells guided by 3-dimensional PLLA mat enhancing cardiac regeneration and angiogenesis in acute myocardial infarction.

    PubMed

    Chung, Hye-Jin; Kim, Jong-Tae; Kim, Hee-Jung; Kyung, Hei-Won; Katila, Pramila; Lee, Jeong-Han; Yang, Tae-Hyun; Yang, Young-Il; Lee, Seung-Jin

    2015-05-10

    Congestive heart failure is mostly resulted in a consequence of the limited myocardial regeneration capacity after acute myocardial infarction. Targeted delivery of proangiogenic factors and/or stem cells to the ischemic myocardium is a promising strategy for enhancing their local and sustained therapeutic effects. Herein, we designed an epicardial delivery system of vascular endothelial growth factor (VEGF) and cardiac stem cells (CSCs) using poly(l-lactic acid) (PLLA) mat applied to the acutely infarcted myocardium. The fibrous VEGF-loaded PLLA mat was fabricated by an electrospinning method using PLLA solution emulsified VEGF. This mat not only allowed for sustained release of VEGF for 4weeks but boosted migration and proliferation of both endothelial cells and CSCs in vitro. Furthermore, sustained release of VEGF showed a positive effect on in vitro capillary-like network formation of endothelial cells compared with bolus treatment of VEGF. PLLA mat provided a permissive 3-dimensional (3D) substratum that led to spontaneous cardiomyogenic differentiation of CSCs in vitro. Notably, sustained stimulation by VEGF-loaded PLLA mat resulted in a substantial increase in the expression of proangiogenic mRNAs of CSCs in vitro. The epicardially implanted VEGF-loaded PLLA mat showed modest effects on angiogenesis and cardiomyogenesis in the acutely infarcted hearts. However, co-implantation of VEGF and CSCs using the PLLA mat showed meaningful therapeutic effects on angiogenesis and cardiomyogenesis compared with controls, leading to reduced cardiac remodeling and enhanced global cardiac function. Collectively, the PLLA mat allowed a smart cargo that enabled the sustained release of VEGF and the delivery of CSCs, thereby synergistically inducing angiogenesis and cardiomyogenesis in acute myocardial infarction. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. [Studies of three-dimensional cardiac late gadolinium enhancement MRI at 3.0 Tesla].

    PubMed

    Ishimoto, Takeshi; Ishihara, Masaru; Ikeda, Takayuki; Kawakami, Momoe

    2008-12-20

    Cardiac late Gadolinium enhancement MR imaging has been shown to allow assessment of myocardial viability in patients with ischemic heart disease. The current standard approach is a 3D inversion recovery sequence at 1.5 Tesla. The aims of this study were to evaluate the technique feasibility and clinical utility of MR viability imaging at 3.0 Tesla in patients with myocardial infarction and cardiomyopathy. In phantom and volunteer studies, the inversion time required to suppress the signal of interests and tissues was prolonged at 3.0 Tesla. In the clinical study, the average inversion time to suppress the signal of myocardium at 3.0 Tesla with respect to MR viability imaging at 1.5 Tesla was at 15 min after the administration of contrast agent (304.0+/-29.2 at 3.0 Tesla vs. 283.9+/-20.9 at 1.5 Tesla). The contrast between infarction and viable myocardium was equal at both field strengths (4.06+/-1.30 at 3.0 Tesla vs. 4.42+/-1.85 at 1.5 Tesla). Even at this early stage, MR viability imaging at 3.0 Tesla provides high quality images in patients with myocardial infarction. The inversion time is significantly prolonged at 3.0 Tesla. The contrast between infarction and viable myocardium at 3.0 Tesla are equal to 1.5 Tesla. Further investigation is needed for this technical improvement, for clinical evaluation, and for limitations.

  5. Pulsatile extracorporeal circulation during on-pump cardiac surgery enhances aortic wall shear stress.

    PubMed

    Assmann, Alexander; Benim, Ali Cemal; Gül, Fethi; Lux, Philipp; Akhyari, Payam; Boeken, Udo; Joos, Franz; Feindt, Peter; Lichtenberg, Artur

    2012-01-03

    Controversy on superiority of pulsatile versus non-pulsatile extracorporeal circulation in cardiac surgery still continues. Stroke as one of the major adverse events during cardiopulmonary bypass is, in the majority of cases, caused by mobilization of aortic arteriosclerotic plaques that is inducible by pathologically elevated wall shear stress values. The present study employs computational fluid dynamics to evaluate the aortic blood flow and wall shear stress profiles under the influence of antegrade or retrograde perfusion with pulsatile versus non-pulsatile extracorporeal circulation. While, compared to physiological flow, a non-pulsatile perfusion resulted in generally decreased blood velocities and only moderately increased shear forces (48 Pa versus 20 Pa antegradely and 127 Pa versus 30 Pa retrogradely), a pulsatile perfusion extensively enhanced the occurrence of turbulences, maximum blood flow speed and maximum wall shear stress (1020 Pa versus 20 Pa antegradely and 1178 Pa versus 30 Pa retrogradely). Under these circumstances arteriosclerotic embolism has to be considered. Further simulations and experimental work are necessary to elucidate the impact of our findings on the scientific discourse of pulsatile versus non-pulsatile extracorporeal circulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Subject-specific patch-based denoising for contrast-enhanced cardiac MR images

    NASA Astrophysics Data System (ADS)

    Ma, Lorraine; Ebrahimi, Mehran; Pop, Mihaela

    2016-03-01

    Many patch-based techniques in imaging, e.g., Non-local means denoising, require tuning parameters to yield optimal results. In real-world applications, e.g., denoising of MR images, ground truth is not generally available and the process of choosing an appropriate set of parameters is a challenge. Recently, Zhu et al. proposed a method to define an image quality measure, called Q, that does not require ground truth. In this manuscript, we evaluate the effect of various parameters of the NL-means denoising on this quality metric Q. Our experiments are based on the late-gadolinium enhancement (LGE) cardiac MR images that are inherently noisy. Our described exhaustive evaluation approach can be used in tuning parameters of patch-based schemes. Even in the case that an estimation of optimal parameters is provided using another existing approach, our described method can be used as a secondary validation step. Our preliminary results suggest that denoising parameters should be case-specific rather than generic.

  7. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

    PubMed

    Danoviz, Maria E; Nakamuta, Juliana S; Marques, Fabio L N; dos Santos, Leonardo; Alvarenga, Erica C; dos Santos, Alexandra A; Antonio, Ednei L; Schettert, Isolmar T; Tucci, Paulo J; Krieger, Jose E

    2010-08-10

    Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). 99mTc-labeled ASCs (1x10(6) cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

  8. Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

    PubMed Central

    Danoviz, Maria E.; Nakamuta, Juliana S.; Marques, Fabio L. N.; dos Santos, Leonardo; Alvarenga, Erica C.; dos Santos, Alexandra A.; Antonio, Ednei L.; Schettert, Isolmar T.; Tucci, Paulo J.; Krieger, Jose E.

    2010-01-01

    Background Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings 99mTc-labeled ASCs (1×106 cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by γ-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8±2.0 and 26.8±2.4% vs. 4.8±0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers. PMID:20711471

  9. Effect of heart rate on CT angiography using the enhanced cardiac model of the 4D NCAT

    NASA Astrophysics Data System (ADS)

    Segars, W. P.; Taguchi, K.; Fung, G. S. K.; Fishman, E. K.; Tsui, B. M. W.

    2006-03-01

    We investigate the effect of heart rate on the quality and artifact generation in coronary artery images obtained using multi-slice computed tomography (MSCT) with the purpose of finding the optimal time resolution for data acquisition. To perform the study, we used the 4D NCAT phantom, a computer model of the normal human anatomy and cardiac and respiratory motions developed in our laboratory. Although capable of being far more realistic, the 4D NCAT cardiac model was originally designed for low-resolution imaging research, and lacked the anatomical detail to be applicable to high-resolution CT. In this work, we updated the cardiac model to include a more detailed anatomy and physiology based on high-resolution clinical gated MSCT data. To demonstrate its utility in high-resolution dynamic CT imaging research, the enhanced 4D NCAT was then used in a pilot simulation study to investigate the effect of heart rate on CT angiography. The 4D NCAT was used to simulate patients with different heart rates (60-120 beats/minute) and with various cardiac plaques of known size and location within the coronary arteries. For each simulated patient, MSCT projection data was generated with data acquisition windows ranging from 100 to 250 ms centered within the quiet phase (mid-diastole) of the heart using an analytical CT projection algorithm. CT images were reconstructed from the projection data, and the contrast of the plaques was then measured to assess the effect of heart rate and to determine the optimal time resolution required for each case. The 4D NCAT phantom with its realistic model for the cardiac motion was found to provide a valuable tool from which to optimize CT cardiac applications. Our results indicate the importance of optimizing the time resolution with regard to heart rate and plaque location for improved CT images at a reduced patient dose.

  10. Rubicon deficiency enhances cardiac autophagy and protects mice from lipopolysaccharide-induced lethality and reduction in stroke volume.

    PubMed

    Zi, Zhenguo; Song, Zongpei; Zhang, Shasha; Ye, Yong; Li, Can; Xu, Mingqing; Zou, Yunzeng; He, Lin; Zhu, Hongxin

    2015-03-01

    : Rubicon has been suggested to suppress autophagosome maturation by negatively regulating PI3KC3/Vps34 activity. However, the physiological function of Rubicon remains elusive. We hypothesized that Rubicon deficiency enhances autophagic flux in the heart and affects cardiac function. Rubicon knockout (KO) mice were generated by piggyBac transposition. Loss of Rubicon was demonstrated at both mRNA and protein levels. Rubicon KO mice were born in Mendelian ratios. Autophagic flux, assessed by bafilomycin A1-induced changes in LC3 II protein abundance, was enhanced in the heart of Rubicon KO mice compared with wild-type (WT) controls. Hematoxylin-eosin staining and picrosirius red staining showed that Rubicon KO mice exhibited normal baseline cardiac morphology. Echocardiography revealed that ejection fraction and fractional shortening, 2 indices of cardiac function, were comparable between Rubicon KO mice at 2, 8, and 12 months of age (n = 6-8 for each age group) and the corresponding WT controls (n = 6-8 for each age group). In a mouse model of lipopolysaccharide (LPS)-induced sepsis, the survival time of LPS-treated Rubicon KO mice (n = 10) was prolonged compared with LPS-treated WT controls (n = 11). Echocardiography revealed that Rubicon deficiency partially normalized LPS-induced reduction in stroke volume and cardiac output 12 hours after LPS administration compared with LPS-treated WT controls (n = 6 for each group). Autophagic flux was enhanced in Rubicon-deficient hearts 12 hours after LPS treatment compared with LPS-treated WT controls. Real-time quantitative polymerase chain reaction suggested that proinflammatory cytokine expression was not significantly different between LPS-treated Rubicon KO mice and WT controls (n = 3 for each group). Our data demonstrate for the first time that Rubicon deficiency enhances autophagic flux in the heart and protects mice from lethality and reduction in stroke volume induced by LPS.

  11. Reduction of blood oxygen levels enhances postprandial cardiac hypertrophy in Burmese python (Python bivittatus).

    PubMed

    Slay, Christopher E; Enok, Sanne; Hicks, James W; Wang, Tobias

    2014-05-15

    Physiological cardiac hypertrophy is characterized by reversible enlargement of cardiomyocytes and changes in chamber architecture, which increase stroke volume and via augmented convective oxygen transport. Cardiac hypertrophy is known to occur in response to repeated elevations of O2 demand and/or reduced O2 supply in several species of vertebrate ectotherms, including postprandial Burmese pythons (Python bivittatus). Recent data suggest postprandial cardiac hypertrophy in P. bivittatus is a facultative rather than obligatory response to digestion, though the triggers of this response are unknown. Here, we hypothesized that an O2 supply-demand mismatch stimulates postprandial cardiac enlargement in Burmese pythons. To test this hypothesis, we rendered animals anemic prior to feeding, essentially halving blood oxygen content during the postprandial period. Fed anemic animals had heart rates 126% higher than those of fasted controls, which, coupled with a 71% increase in mean arterial pressure, suggests fed anemic animals were experiencing significantly elevated cardiac work. We found significant cardiac hypertrophy in fed anemic animals, which exhibited ventricles 39% larger than those of fasted controls and 28% larger than in fed controls. These findings support our hypothesis that those animals with a greater magnitude of O2 supply-demand mismatch exhibit the largest hearts. The 'low O2 signal' stimulating postprandial cardiac hypertrophy is likely mediated by elevated ventricular wall stress associated with postprandial hemodynamics.

  12. Myocardial Extracellular Volume Fraction with Dual-Energy Equilibrium Contrast-enhanced Cardiac CT in Nonischemic Cardiomyopathy: A Prospective Comparison with Cardiac MR Imaging.

    PubMed

    Lee, Hye-Jeong; Im, Dong Jin; Youn, Jong-Chan; Chang, Suyon; Suh, Young Joo; Hong, Yoo Jin; Kim, Young Jin; Hur, Jin; Choi, Byoung Wook

    2016-07-01

    Purpose To evaluate the feasibility of equilibrium contrast material-enhanced dual-energy cardiac computed tomography (CT) to determine extracellular volume fraction (ECV) in nonischemic cardiomyopathy (CMP) compared with magnetic resonance (MR) imaging. Materials and Methods This study was approved by the institutional review board; informed consent was obtained. Seven healthy subjects and 23 patients (six with hypertrophic CMP, nine with dilated CMP, four with amyloidosis, and four with sarcoidosis) (mean age ± standard deviation, 57.33 years ± 14.82; 19 male participants [63.3%]) were prospectively enrolled. Twelve minutes after contrast material injection (1.8 mL/kg at 3 mL/sec), dual-energy cardiac CT was performed. ECV was measured by two observers independently. Hematocrit levels were compared between healthy subjects and patients with the Mann-Whitney U test. In per-subject analysis, interobserver agreement for CT was assessed with the intraclass correlation coefficient (ICC), and intertest agreement between MR imaging and CT was assessed with Bland-Altman analysis. In per-segment analysis, Student t tests in the linear mixed model were used to compare ECV on CT images between healthy subjects and patients. Results Hematocrit level was 43.44% ± 1.80 for healthy subjects and 41.23% ± 5.61 for patients with MR imaging (P = .16) and 43.50% ± 1.92 for healthy subjects and 41.35% ± 5.92 for patients with CT (P = .15). For observer 1 in per-subject analysis, ECV was 34.18% ± 8.98 for MR imaging and 34.48% ± 8.97 for CT. For observer 2, myocardial ECV was 34.42% ± 9.03 for MR imaging and 33.98% ± 9.05 for CT. Interobserver agreement for ECV at CT was excellent (ICC = 0.987). Bland-Altman analysis between MR imaging and CT showed a small bias (-0.06%), with 95% limits of agreement of -1.19 and 1.79. Compared with healthy subjects, patients with hypertrophic CMP, dilated CMP, amyloidosis, and sarcoidosis had significantly higher myocardial ECV at dual

  13. Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by enhancing osteogenic commitment and differentiation.

    PubMed

    Scanlon, Vanessa; Walia, Bhavita; Yu, Jungeun; Hansen, Marc; Drissi, Hicham; Maye, Peter; Sanjay, Archana

    2017-02-01

    The periosteum contains multipotent skeletal progenitors that contribute to bone repair. The signaling pathways regulating the response of periosteal cells to fracture are largely unknown. Phosphatidylinositol-3 Kinase (PI3K), a prominent lipid kinase, is a major signaling protein downstream of several factors that regulate osteoblast differentiation. Cbl is an E3 ubiquitin ligase and a major adaptor protein that binds to the p85 regulatory subunit and modulates PI3K activity. Substitution of tyrosine 737 to phenylalanine (Y737F) in Cbl abolishes the interaction between Cbl and p85 subunit without affecting the Cbl's ubiquitin ligase function. Here, we investigated the role of PI3K signaling during the very early stages of fracture healing using Osterix(RFP) reporter mice. We found that the absence of PI3K regulation by Cbl resulted in robust periosteal thickening, with increased proliferation of periosteal cells. While the multipotent properties of periosteal progenitors to differentiate into chondrocytes and adipocytes did not change, osteogenic differentiation in the absence of Cbl-PI3K interaction was highly augmented. The increased stability and nuclear localization of Osterix observed in periosteal cells lacking Cbl-PI3K interaction may explain this enhanced osteogenic differentiation since the expression of Osterix transcriptional target genes including osteocalcin and BSP are increased in YF cells. Overall, our findings highlight a hitherto unexplored and novel role for Cbl and PI3K in modulating the osteogenic response of periosteal cells during the early stages of fracture repair.

  14. Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging Post-robotic Radiosurgical Pulmonary Vein Isolation (RRPVI): First Case in the World

    PubMed Central

    Azpiri, Jose; De La Peña, Cuauhtémoc; Cardona, Carlos; Hinojosa, Miguel; Zamarripa, Rafael; Assad, Jose

    2016-01-01

    Pulmonary vein isolation using robotic radiosurgery system CyberKnife is a new non-invasive treatment of atrial fibrillation, currently in clinical phase. Robotic radiosurgical pulmonary vein isolation (RRPVI) uses stereotactic, non-invasive (painless) pinpoint radiation energy delivery to a small, precise area to accomplish ablation. The purpose of this report is to describe the finding of an increase in the enhancement of the left atrium demonstrated with the use of cardiac magnetic resonance imaging using late gadolinium enhancement (LGE-CMR) as a result of RRPVI in the first case in the world in humans using CyberKnife as a treatment for paroxysmal atrial fibrillation (PAF). PMID:27660737

  15. Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging Post-robotic Radiosurgical Pulmonary Vein Isolation (RRPVI): First Case in the World.

    PubMed

    Monroy, Edgar; Azpiri, Jose; De La Peña, Cuauhtémoc; Cardona, Carlos; Hinojosa, Miguel; Zamarripa, Rafael; Assad, Jose

    2016-08-15

    Pulmonary vein isolation using robotic radiosurgery system CyberKnife is a new non-invasive treatment of atrial fibrillation, currently in clinical phase. Robotic radiosurgical pulmonary vein isolation (RRPVI) uses stereotactic, non-invasive (painless) pinpoint radiation energy delivery to a small, precise area to accomplish ablation. The purpose of this report is to describe the finding of an increase in the enhancement of the left atrium demonstrated with the use of cardiac magnetic resonance imaging using late gadolinium enhancement (LGE-CMR) as a result of RRPVI in the first case in the world in humans using CyberKnife as a treatment for paroxysmal atrial fibrillation (PAF).

  16. Vibration induced osteogenic commitment of mesenchymal stem cells is enhanced by cytoskeletal remodeling but not fluid shear.

    PubMed

    Uzer, Gunes; Pongkitwitoon, Suphannee; Ete Chan, M; Judex, Stefan

    2013-09-03

    Consistent across studies in humans, animals and cells, the application of vibrations can be anabolic and/or anti-catabolic to bone. The physical mechanisms modulating the vibration-induced response have not been identified. Recently, we developed an in vitro model in which candidate parameters including acceleration magnitude and fluid shear can be controlled independently during vibrations. Here, we hypothesized that vibration induced fluid shear does not modulate mesenchymal stem cell (MSC) proliferation and mineralization and that cell's sensitivity to vibrations can be promoted via actin stress fiber formation. Adipose derived human MSCs were subjected to vibration frequencies and acceleration magnitudes that induced fluid shear stress ranging from 0.04 Pa to 5 Pa. Vibrations were applied at magnitudes of 0.15 g, 1g, and 2g using frequencies of both 100 Hz and 30 Hz. After 14 d and under low fluid shear conditions associated with 100 Hz oscillations, mineralization was greater in all vibrated groups than in controls. Greater levels of fluid shear produced by 30 Hz vibrations enhanced mineralization only in the 2g group. Over 3d, vibrations led to the greatest increase in total cell number with the frequency/acceleration combination that induced the smallest level of fluid shear. Acute experiments showed that actin remodeling was necessary for early mechanical up-regulation of RUNX-2 mRNA levels. During osteogenic differentiation, mechanically induced up-regulation of actin remodeling genes including Wiskott-Aldrich syndrome (WAS) protein, a critical regulator of Arp2/3 complex, was related to the magnitude of the applied acceleration but not to fluid shear. These data demonstrate that fluid shear does not regulate vibration induced proliferation and mineralization and that cytoskeletal remodeling activity may play a role in MSC mechanosensitivity.

  17. High-sensitivity cardiac troponin assays: From improved analytical performance to enhanced risk stratification.

    PubMed

    Kozinski, Marek; Krintus, Magdalena; Kubica, Jacek; Sypniewska, Grazyna

    2017-05-01

    Implementation of cardiac troponin (cTn) assays has revolutionized the diagnosis, risk stratification, triage and management of patients with suspected myocardial infarction (MI). The Universal Definition of MI brought about a shift in the diagnostics of MI, from an approach primarily based on electrocardiography (ECG) to one primarily based on biomarkers. Currently, detection of a rise and/or fall in concentration or activity of myocardial necrosis biomarkers, preferentially cTns, with at least one value above the 99th percentile upper reference limit (URL), is the essential component for the diagnosis of MI. High-sensitivity cardiac troponin (hs-cTn) assays with their superior analytical performance were designed to further facilitate clinical decision making. The ability of hs-cTn assays to detect measurable cTn concentrations in at least 50% of healthy individuals, along with their improved precision (expressed as coefficient of variation ≤10% at the 99th percentile URL) associated with increased recognition of changing values, leads to enhanced risk stratification of patients with suspected MI, and also enables them to be used as prognostic tools potentially useful in other patient subsets. In this comprehensive review, we aim to integrate updated laboratory and clinical knowledge regarding hs-cTn assays in order to promote their optimal use in daily practice. We primarily focus on the role of hs-cTn assays in patients with suspected MI, discussing recommended diagnostic algorithms and result interpretation. Emphasis is also placed on the release of cTns following myocardial injury, the characteristics of antibodies used in available cTn immunoassays, and analytical performance of hs-cTn assays. In this paper, we also review potential challenges related to the selection of a healthy reference population in determining 99th percentile values, biological variation of hs-cTns, inequality between hs-cTn assays, and outline the current status of c

  18. Factors affecting radiographers' organizational commitment.

    PubMed

    Akroyd, Duane; Jackowski, Melissa B; Legg, Jeffrey S

    2007-01-01

    A variety of factors influence employees' attitudes toward their workplace and commitment to the organization that employs them. However, these factors have not been well documented among radiologic technologists. To determine the predictive ability of selected organizational, leadership, work-role and demographic variables on organizational commitment for a national sample of radiographers. Three thousand radiographers registered by the American Registry of Radiologic Technologists working full time in clinical settings were surveyed by mail regarding their commitment to their employers, leadership within the organization that employs them, employer support and demographic information. Overall, radiographers were found to have only a moderate level of commitment to their employers. Among the factors that significantly affected commitment were the radiographer's educational level, perceived level of organizational support, role clarity and organizational leadership. The results of this study could provide managers and supervisors with insights on how to empower and challenge radiographers and offer opportunities that will enhance radiographers' commitment to the organization, thus reducing costly turnover and improving employee performance.

  19. Omega-3 fatty acid supplementation enhances stroke volume and cardiac output during dynamic exercise.

    PubMed

    Walser, Buddy; Stebbins, Charles L

    2008-10-01

    Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have beneficial effects on cardiovascular function. We tested the hypotheses that dietary supplementation with DHA (2 g/day) + EPA (3 g/day) enhances increases in stroke volume (SV) and cardiac output (CO) and decreases in systemic vascular resistance (SVR) during dynamic exercise. Healthy subjects received DHA + EPA (eight men, four women) or safflower oil (six men, three women) for 6 weeks. Both groups performed 20 min of bicycle exercise (10 min each at a low and moderate work intensity) before and after DHA + EPA or safflower oil treatment. Mean arterial pressure (MAP), heart rate (HR), SV, CO, and SVR were assessed before exercise and during both workloads. HR was unaffected by DHA + EPA and MAP was reduced, but only at rest (88 +/- 5 vs. 83 +/- 4 mm Hg). DHA + EPA augmented increases in SV (14.1 +/- 6.3 vs. 32.3 +/- 8.7 ml) and CO (8.5 +/- 1.0 vs. 10.3 +/- 1.2 L/min) and tended to attenuate decreases in SVR (-7.0 +/- 0.6 vs. -10.1 +/- 1.6 mm Hg L(-1) min(-1)) during the moderate workload. Safflower oil treatment had no effects on MAP, HR, SV, CO or SVR at rest or during exercise. DHA + EPA-induced increases in SV and CO imply that dietary supplementation with these fatty acids can increase oxygen delivery during exercise, which may have beneficial clinical implications for individuals with cardiovascular disease and reduced exercise tolerance.

  20. Enhancing Cardiac Rehabilitation With Stress Management Training: A Randomized, Clinical Efficacy Trial.

    PubMed

    Blumenthal, James A; Sherwood, Andrew; Smith, Patrick J; Watkins, Lana; Mabe, Stephanie; Kraus, William E; Ingle, Krista; Miller, Paula; Hinderliter, Alan

    2016-04-05

    Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease. Despite considerable epidemiological evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR. One hundred fifty-one outpatients with coronary heart disease who were 36 to 84 years of age were randomized to 12 weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and coronary heart disease biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR made up the no-CR comparison group. All participants were followed up for up to 5.3 years (median, 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone (P=0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in coronary heart disease biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with those in the CR-alone group (18% versus 33%; hazard ratio=0.49; 95% confidence interval, 0.25-0.95; P=0.035), and both CR groups had lower event rates compared with the no-CR group (47%; hazard ratio=0.44; 95% confidence interval, 0.27-0.71; P<0.001). CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00981253. © 2016 American Heart Association, Inc.

  1. Enhancing Cardiac Rehabilitation With Stress Management Training: A Randomized Clinical Efficacy Trial

    PubMed Central

    Blumenthal, James A.; Sherwood, Andrew; Smith, Patrick J.; Watkins, Lana; Mabe, Stephanie; Kraus, William E.; Ingle, Krista; Miller, Paula; Hinderliter, Alan

    2016-01-01

    Background Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease (CHD). Despite considerable epidemiologic evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR. Methods and Results 151 outpatients with CHD aged 36 to 84 years were randomized to 12-weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and CHD biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR comprised a No-CR comparison group. All participants were followed for up to 5.3 years (median = 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone (P = 0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in CHD biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with CR alone (18% vs. 33%, HR = 0.49 [0.25, 0.95], P = 0.035) and both CR groups had lower event rates compared to the No-CR group (47%, HR = 0.44 [0.27, 0.71], P < .001). Conclusions CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR. Clinical Trial Registration Information www.Clinicaltrials.gov. Identifier: NCT00981253. PMID:27045127

  2. Impaired cardiac mitochondrial oxidative phosphorylation and enhanced mitochondrial oxidative stress in feline hypertrophic cardiomyopathy.

    PubMed

    Christiansen, Liselotte B; Dela, Flemming; Koch, Jørgen; Hansen, Christina N; Leifsson, Pall S; Yokota, Takashi

    2015-05-15

    Mitochondrial dysfunction and oxidative stress are important players in the development of various cardiovascular diseases, but their roles in hypertrophic cardiomyopathy (HCM) remain unknown. We examined whether mitochondrial oxidative phosphorylation (OXPHOS) capacity was impaired with enhanced mitochondrial oxidative stress in HCM. Cardiac and skeletal muscles were obtained from 9 domestic cats with spontaneously occurring HCM with preserved left ventricular systolic function and from 15 age-matched control cats. Mitochondrial OXPHOS capacities with nonfatty acid and fatty acid substrates in permeabilized fibers and isolated mitochondria were assessed using high-resolution respirometry. ROS release originating from isolated mitochondria was assessed by spectrofluorometry. Thiobarbituric acid-reactive substances were also measured as a marker of oxidative damage. Mitochondrial ADP-stimulated state 3 respiration with complex I-linked nonfatty acid substrates and with fatty acid substrates, respectively, was significantly lower in the hearts of HCM cats compared with control cats. Mitochondrial ROS release during state 3 with complex I-linked substrates and thiobarbituric acid-reactive substances in the heart were significantly increased in cats with HCM. In contrast, there were no significant differences in mitochondrial OXPHOS capacity, mitochondrial ROS release, and oxidative damage in skeletal muscle between groups. Mitochondrial OXPHOS capacity with both nonfatty acid substrates and fatty acid substrates was impaired with increased mitochondrial ROS release in the feline HCM heart. These findings provide new insights into the pathophysiology of HCM and support the hypothesis that restoration of the redox state in the mitochondria is beneficial in the treatment of HCM. Copyright © 2015 the American Physiological Society.

  3. Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction

    PubMed Central

    Nakajima, Kazuaki; Fujita, Jun; Matsui, Makoto; Tohyama, Shugo; Tamura, Noriko; Kanazawa, Hideaki; Seki, Tomohisa; Kishino, Yoshikazu; Hirano, Akinori; Okada, Marina; Tabei, Ryota; Sano, Motoaki; Goto, Shinya; Tabata, Yasuhiko; Fukuda, Keiichi

    2015-01-01

    Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×106 or 1x106 cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×106 CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved cardiac

  4. Fli-1 regulates the DN2 to DN3 thymocyte transition and promotes γδ T-cell commitment by enhancing TCR signal strength.

    PubMed

    Smeets, Monique F M A; Wiest, David L; Izon, David J

    2014-09-01

    Friend leukemia integration 1 (Fli-1) is a member of the Ets transcription factor family and is expressed during T-cell development; however, the role Fli-1 plays in early T-cell differentiation has not been elucidated. In this report, we demonstrate that in mouse, Fli-1 overexpression retards the CD4(-) CD8(-) double-negative (DN) to CD4(+) CD8(+) double-positive (DP) transition by deregulating normal DN thymocyte development. Specifically, Fli-1 expression moderates the DN2 and DN3 developmental transitions. We further show that Fli-1 overexpression partially mimics strong TCR signals in developing DN thymocytes and thereby enhances γδ T-cell development. Conversely, Fli-1 knockdown by small hairpin RNA reverses the lineage bias from γδ T cells and directs DN cells to the αβ lineage by attenuating TCR signaling. Therefore, Fli-1 plays a critical role in both the DN2 to DN3 transition and αβ/γδ lineage commitment.

  5. Hypoxia Enhances Differentiation of Hair Follicle-Associated-Pluripotent (HAP) Stem Cells to Cardiac-Muscle Cells.

    PubMed

    Shirai, Kyoumi; Hamada, Yuko; Arakawa, Nobuko; Yamazaki, Aiko; Tohgi, Natsuko; Aki, Ryoichi; Mii, Sumiyuki; Hoffman, Robert M; Amoh, Yasuyuki

    2017-03-01

    We have previously demonstrated that the neural stem-cell marker nestin is expressed in hair-follicle stem cells located in the bulge area which are termed hair-follicle-associated pluripotent (HAP) stem cells. HAP stem cells from mouse and human could form spheres in culture, termed hair spheres, which are keratin 15-negative and nestin-positive and could differentiate to neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. Subsequently, we demonstrated that nestin-expressing stem cells could effect nerve and spinal cord regeneration in mouse models. Recently, we demonstrated that HAP stem cells differentiated to beating cardiac muscle cells. We recently observed that isoproterenol directs HAP stem cells to differentiate to cardiac-muscle cells in large numbers in culture compared to HAP stem cells not supplemented with isoproterenol. The addition of activin A, bone morphogenetic protein 4, and basic fibroblast growth factor, along with isoproternal, induced the cardiac muscle cells to form tissue sheets of beating heart muscle cells. In the present study, we report that, under hypoxic conditions, HAP stem cells differentiated to troponin-positive cardiac-muscle cells at a higher rate that under normoxic conditions. Hypoxia did not influence the differentiation to other cell types. For future use of HAP stem cells for cardiac muscle regeneration, hypoxia should enhance the rate of differentiation thereby providing patients more opportunities to use their own HAP stem cells which are easily accessible, for this purpose. J. Cell. Biochem. 118: 554-558, 2017. © 2016 Wiley Periodicals, Inc.

  6. Resveratrol protects against lipopolysaccharide-induced cardiac dysfunction by enhancing SERCA2a activity through promoting the phospholamban oligomerization.

    PubMed

    Bai, Tao; Hu, Xinyue; Zheng, Yang; Wang, Shudong; Kong, Jian; Cai, Lu

    2016-10-01

    The bacterial endotoxin lipopolysaccharide (LPS) is a main culprit responsible for cardiac dysfunction in sepsis. This study examined whether resveratrol could protect against LPS-induced cardiac dysfunction by improving the sarcoplasmic endoplasmic reticulum Ca(2+)-ATPase (SERCA2a) activity. Echocardiographic parameters, cardiomyocyte contractile and Ca(2+) transient properties, markers for cardiac inflammation, cell death, and oxidative stress, SERCA2a activity, and the ratios of phospholamban (PLB) monomer to oligomer were measured. Cardiac function was decreased >50% after LPS challenge (6 mg/kg for 6 h), which was improved by resveratrol. There was neither difference in plasma tumor necrosis factor-α and troponin I levels nor in infiltration of CD45(+) cells in cardiac tissue between resveratrol-treated and untreated groups. In cardiomyocytes, LPS significantly decreased contractile amplitude, elongated relengthening time, diminished Ca(2+) transient, reduced SERCA2a activity, and increased superoxide generation. These pathological alterations were attenuated by resveratrol treatment. Immunoblot analysis showed that LPS-treated mice had increased levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and the monomer form of PLB, along with decreases in the levels of SERCA2a, the oligomer form of PLB and nuclear factor erythroid 2-related factor (Nrf-2). Resveratrol treatment upregulated SERCA2a, the oligomer form of PLB, and Nrf-2 expression and function, and downregulated MDA, 4-HNE, and the monomer form of PLB. Our data suggest that the activity of SERCA2a in endotoxemia is inhibited, possibly due to increases in the monomer form of PLB. Resveratrol protects the heart from LPS-induced injuries at least in part through promoting the oligomerization of PLB that leads to enhanced SERCA2a activity. Copyright © 2016 the American Physiological Society.

  7. Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction).

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-05-01

    Cardiac miRNAs (miR-1, miR133a, miR-208a/b, and miR-499) are abundantly expressed in the myocardium. They play a central role in cardiogenesis, heart function and pathology. While miR-1 and miR-133a predominantly control early stages of cardiogenesis supporting commitment of cardiac-specific muscle lineage from embryonic stem cells and mesodermal precursors, miR-208 and miR-499 are involved in the late cardiogenic stages mediating differentiation of cardioblasts to cardiomyocytes and fast/slow muscle fiber specification. In the heart, miR-1/133a control cardiac conductance and automaticity by regulating all phases of the cardiac action potential. miR-208/499 located in introns of the heavy chain myosin genes regulate expression of sarcomeric contractile proteins. In cardiac pathology including myocardial infarction (MI), expression of cardiac miRNAs is markedly altered that leads to deleterious effects associated with heart wounding, arrhythmia, increased apoptosis, fibrosis, hypertrophy, and tissue remodeling. In acute MI, circulating levels of cardiac miRNAs are significantly elevated making them to be a promising diagnostic marker for early diagnosis of acute MI. Great cardiospecific capacity of these miRNAs is very helpful for enhancing regenerative properties and survival of stem cell and cardiac progenitor transplants and for reprogramming of mature non-cardiac cells to cardiomyocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Enhanced open-loop but not closed-loop cardiac baroreflex sensitivity during orthostatic stress in humans.

    PubMed

    Akimoto, Toshinari; Sugawara, Jun; Ichikawa, Daisuke; Terada, Nobuyuki; Fadel, Paul J; Ogoh, Shigehiko

    2011-11-01

    The neural interaction between the cardiopulmonary and arterial baroreflex may be critical for the regulation of blood pressure during orthostatic stress. However, studies have reported conflicting results: some indicate increases and others decreases in cardiac baroreflex sensitivity (i.e., gain) with cardiopulmonary unloading. Thus the effect of orthostatic stress-induced central hypovolemia on regulation of heart rate via the arterial baroreflex remains unclear. We sought to comprehensively assess baroreflex function during orthostatic stress by identifying and comparing open- and closed-loop dynamic cardiac baroreflex gains at supine rest and during 60° head-up tilt (HUT) in 10 healthy men. Closed-loop dynamic "spontaneous" cardiac baroreflex sensitivities were calculated by the sequence technique and transfer function and compared with two open-loop carotid-cardiac baroreflex measures using the neck chamber system: 1) a binary white-noise method and 2) a rapid-pulse neck pressure-neck suction technique. The gain from the sequence technique was decreased from -1.19 ± 0.14 beats·min(-1)·mmHg(-1) at rest to -0.78 ± 0.10 beats·min(-1)·mmHg(-1) during HUT (P = 0.005). Similarly, closed-loop low-frequency baroreflex transfer function gain was reduced during HUT (P = 0.033). In contrast, open-loop low-frequency transfer function gain between estimated carotid sinus pressure and heart rate during white-noise stimulation was augmented during HUT (P = 0.01). This result was consistent with the maximal gain of the carotid-cardiac baroreflex stimulus-response curve (from 0.47 ± 0.15 beats·min(-1)·mmHg(-1) at rest to 0.60 ± 0.20 beats·min(-1)·mmHg(-1) at HUT, P = 0.037). These findings suggest that open-loop cardiac baroreflex gain was enhanced during HUT. Moreover, under closed-loop conditions, spontaneous baroreflex analyses without external stimulation may not represent open-loop cardiac baroreflex characteristics during orthostatic stress.

  9. Cardiac catheterization

    MedlinePlus

    Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization; CAD - cardiac catheterization; Coronary artery disease - cardiac catheterization; Heart valve - cardiac catheterization; Heart failure - ...

  10. Ankyrin-B reduction enhances Ca spark-mediated SR Ca release promoting cardiac myocyte arrhythmic activity

    PubMed Central

    Camors, Emmanuel; Mohler, Peter J.; Bers, Donald M.; Despa, Sanda

    2012-01-01

    Ankyrin-B (AnkB) loss-of-function may cause ventricular arrhythmias and sudden cardiac death in humans. Cardiac myocytes from AnkB heterozygous mice (AnkB+/−) show reduced expression and altered localization of Na/Ca exchanger (NCX) and Na/K-ATPase (NKA), key players in regulating [Na]i and [Ca]i. Here we investigate how AnkB reduction affects cardiac [Na]i, [Ca]i and SR Ca release. We found reduced NCX and NKA transport function but unaltered [Na]i and diastolic [Ca]i in myocytes from AnkB+/− vs. wild-type (WT) mice. Ca transients, SR Ca content and fractional SR Ca release were larger in AnkB+/− myocytes. The frequency of spontaneous, diastolic Ca sparks (CaSpF) was significantly higher in intact myocytes from AnkB+/− vs. WT myocytes (with and without isoproterenol), even when normalized for SR Ca load. However, total ryanodine receptor (RyR)-mediated SR Ca leak (tetracaine-sensitive) was not different between groups. Thus, in AnkB+/− mice SR Ca leak is biased towards more Ca sparks (vs. smaller release events), suggesting more coordinated openings of RyRs in a cluster. This is due to local cytosolic RyR regulation, rather than intrinsic RyR differences, since CaSpF was similar in saponin-permeabilized myocytes from WT and AnkB+/− mice. The more coordinated RyRs openings resulted in an increased propensity of pro-arrhythmic Ca waves in AnkB+/− myocytes. In conclusion, AnkB reduction alters cardiac Na and Ca transport and enhances the coupled RyR openings, resulting in more frequent Ca sparks and waves although the total SR Ca leak is unaffected. This could enhance the propensity for triggered arrhythmias in AnkB+/− mice. PMID:22406428

  11. Nuclear CaMKII enhances histone H3 phosphorylation and remodels chromatin during cardiac hypertrophy.

    PubMed

    Awad, Salma; Kunhi, Muhammad; Little, Gillian H; Bai, Yan; An, Woojin; Bers, Donald; Kedes, Larry; Poizat, Coralie

    2013-09-01

    Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in pathological cardiac hypertrophy, but the mechanisms by which it modulates gene activity in the nucleus to mediate hypertrophic signaling remain unclear. Here, we report that nuclear CaMKII activates cardiac transcription by directly binding to chromatin and regulating the phosphorylation of histone H3 at serine-10. These specific activities are demonstrated both in vitro and in primary neonatal rat cardiomyocytes. Activation of CaMKII signaling by hypertrophic agonists increases H3 phosphorylation in primary cardiac cells and is accompanied by concomitant cellular hypertrophy. Conversely, specific silencing of nuclear CaMKII using RNA interference reduces both H3 phosphorylation and cellular hypertrophy. The hyper-phosphorylation of H3 associated with increased chromatin binding of CaMKII occurs at specific gene loci reactivated during cardiac hypertrophy. Importantly, H3 Ser-10 phosphorylation and CaMKII recruitment are associated with increased chromatin accessibility and are required for chromatin-mediated transcription of the Mef2 transcription factor. Unlike phosphorylation of H3 by other kinases, which regulates cellular proliferation and immediate early gene activation, CaMKII-mediated signaling to H3 is associated with hypertrophic growth. These observations reveal a previously unrecognized function of CaMKII as a kinase signaling to histone H3 and remodeling chromatin. They suggest a new epigenetic mechanism controlling cardiac hypertrophy.

  12. The enhancement of cardiac toxicity by concomitant administration of Berberine and macrolides.

    PubMed

    Zhi, Duo; Feng, Pan-Feng; Sun, Jia-Liang; Guo, Fengfeng; Zhang, Rui; Zhao, Xin; Li, Bao-Xin

    2015-08-30

    As is well-known, hERG plays an essential role in phase III repolarization of cardiac action potentials. Blocking of hERG channels can lead to LQTS. Inhibition of the metabolism of CYPs activities may elevate plasma levels, to further increase accumulation of drug on cardiac. The elevated serum levels may however elicit unexpected toxicities. Therefore, the inhibition tests of hERG and CYP are central to the preclinical studies because they may lead to severe cardiac toxicity. Berberine is widely used as an antibacterial agent and often combined with macrolides to treat gastropathy. Our objective was to assess cardiac toxicity during the combined use of Berberine with macrolides. (1) Azithromycin reduced hERG currents by accelerated channel inactivation. (2) The combination of Berberine with Azithromycin reduced hERG currents, producing an inhibitive effect stronger than use of a single drug alone, due to the high binding affinity for the onset of inactivation. (3) When cells were perfused concomitantly with Berberine and Clarithromycin, they showed a stronger inhibitive effect on hERG currents by decreasing the time constant for the onset of inactivation. (4) The combined administration of Berberine with Clarithromycin had a powerful inhibitive effect on CYP3A activities than use of a single drug alone. Collectively, these results demonstrated that concomitant use of Berberine with macrolides may require close monitoring because of potential drug toxicities, especially cardiac toxicity.

  13. Taurine protects cardiac contractility in killifish, Fundulus heteroclitus, by enhancing sarcoplasmic reticular Ca(2+) cycling.

    PubMed

    Henry, Elenor F; MacCormack, Tyson J

    2017-05-23

    Intracellular taurine is abundant in many animals and it influences an array of physiological processes, including osmoregulation, metabolism, and cardiac contractility. Taurine is an important osmolyte in teleost hearts, but its role in stress tolerance, cardiac metabolism, and contractility has not been assessed. The goal of this study was to determine if ventricular taurine concentration changes in response to environmental stress and to characterize its influence on contractility. Cardiac taurine concentrations varied in killifish (Fundulus heteroclitus) but were generally maintained following acute environmental challenges. In isometrically contracting ventricular strips, supplemental taurine (40 mmol L(-1)) protected peak tension development (F max) at high stimulation frequencies, an effect abolished by treatment with ryanodine, a blocker of sarcoplasmic reticulum Ca(2+) release. In the presence of ryanodine, taurine-treated preparations were also better able to maintain F max at supraphysiological extracellular Ca(2+) levels, but a prior anoxia exposure abolished this effect. Taurine had no impact on basal F max during or after anoxia, but it provided additive protection to high-frequency contractility post-anoxia. Tissue oxygen consumption and extracellular glucose utilization were unaffected by taurine in non-contracting preparations, indicating that it does not impact energy metabolism. Overall, the results suggest that cardiac taurine levels are well maintained on acute time scales in this highly stress-tolerant species. Supplemental taurine has no effect on aerobic metabolism in vitro, but it significantly improved cardiac contractility in a manner dependent upon sarcoplasmic reticulum Ca(2+) cycling. The data indicate that taurine likely plays an important role in the regulation of cardiac performance in teleosts.

  14. Comparing group-based acceptance and commitment therapy (ACT) with enhanced usual care for adolescents with functional somatic syndromes: a study protocol for a randomised trial

    PubMed Central

    Kallesøe, Karen Hansen; Schröder, Andreas; Wicksell, Rikard K; Fink, Per; Ørnbøl, Eva; Rask, Charlotte Ulrikka

    2016-01-01

    Introduction Functional somatic syndromes (FSS) are common in adolescents, characterised by severe disability and reduced quality of life. Behavioural treatments such as acceptance and commitment therapy (ACT) has shown promising results in children and adolescents with FSS, but has focused on specific syndromes such as functional pain. The current study will compare the efficacy of group-based ACT with that of enhanced usual care (EUC) in adolescents with a range of FSS operationalised by the unifying construct of multiorgan bodily distress syndrome (BDS). Methods and analysis A total of 120 adolescents aged 15–19 and diagnosed with multiorgan BDS, of at least 12 months duration, will be assessed and randomised to either: (1) EUC: a manualised consultation with a child and adolescent psychiatrist and individualised treatment plan or (2) manualised ACT-based group therapy plus EUC. The ACT programme consists of 9 modules (ie, 27 hours) and 1 follow-up meeting (3 hours). The primary outcome is physical health, assessed by an Short Form Health Survey (SF-36) aggregate score 12 months after randomisation. Secondary outcomes include self-reported symptom severity, symptom interference, depression and anxiety, illness worry, perceived stress and global improvement; as well as objective physical activity and bodily stress response measured by heart rate variability, hair cortisol and inflammatory biomarkers. Process measures are illness perception, illness-related behaviour and psychological flexibility. Ethics and dissemination The study is conducted in accordance with Helsinki Declaration II. Approval has been obtained from the Science Ethics Committee of the Central Denmark Region and the Danish Data Protection. The results will be sought to be published according to the CONSORT statement in peer-reviewed journals. Discussion This is one of the first larger randomised clinical trials evaluating the effect of a group-based intervention for adolescents with a

  15. Resveratrol Co-Treatment Attenuates the Effects of HIV Protease Inhibitors on Rat Body Weight and Enhances Cardiac Mitochondrial Respiration

    PubMed Central

    Symington, Burger; Mapanga, Rudo F.; Norton, Gavin R.

    2017-01-01

    Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months). Body weights and weight gain, blood metabolite levels (total cholesterol, HDL, LDL, triglycerides), echocardiography and cardiac mitochondrial respiration were assessed in PI-treated rats ± various co-treatments. Our data reveal that PI treatment significantly lowered body weight and cardiac respiratory function while no significant changes were found for heart function and blood metabolite levels. Moreover, all co-treatments ameliorated the PI-induced decrease in body weight after 4 months of PI treatment, while RSV co-treatment enhanced cardiac mitochondrial respiratory capacity in PI-treated rats. This pilot study therefore provides novel hypotheses regarding RSV co-treatment that should be further assessed in greater detail. PMID:28107484

  16. Amino acid substitutions in the FXYD motif enhance phospholemman-induced modulation of cardiac L-type calcium channels.

    PubMed

    Guo, Kai; Wang, Xianming; Gao, Guofeng; Huang, Congxin; Elmslie, Keith S; Peterson, Blaise Z

    2010-11-01

    We have found that phospholemman (PLM) associates with and modulates the gating of cardiac L-type calcium channels (Wang et al., Biophys J 98: 1149-1159, 2010). The short 17 amino acid extracellular NH(2)-terminal domain of PLM contains a highly conserved PFTYD sequence that defines it as a member of the FXYD family of ion transport regulators. Although we have learned a great deal about PLM-dependent changes in calcium channel gating, little is known regarding the molecular mechanisms underlying the observed changes. Therefore, we investigated the role of the PFTYD segment in the modulation of cardiac calcium channels by individually replacing Pro-8, Phe-9, Thr-10, Tyr-11, and Asp-12 with alanine (P8A, F9A, T10A, Y11A, D12A). In addition, Asp-12 was changed to lysine (D12K) and cysteine (D12C). As expected, wild-type PLM significantly slows channel activation and deactivation and enhances voltage-dependent inactivation (VDI). We were surprised to find that amino acid substitutions at Thr-10 and Asp-12 significantly enhanced the ability of PLM to modulate Ca(V)1.2 gating. T10A exhibited a twofold enhancement of PLM-induced slowing of activation, whereas D12K and D12C dramatically enhanced PLM-induced increase of VDI. The PLM-induced slowing of channel closing was abrogated by D12A and D12C, whereas D12K and T10A failed to impact this effect. These studies demonstrate that the PFXYD motif is not necessary for the association of PLM with Ca(V)1.2. Instead, since altering the chemical and/or physical properties of the PFXYD segment alters the relative magnitudes of opposing PLM-induced effects on Ca(V)1.2 channel gating, PLM appears to play an important role in fine tuning the gating kinetics of cardiac calcium channels and likely plays an important role in shaping the cardiac action potential and regulating Ca(2+) dynamics in the heart.

  17. Delay and block of cardiac impulse caused by enhanced phase-4 depolarization in the His-Purkinje system.

    PubMed Central

    Kretz, A; Da Rous, H O; Palumbo, J R

    1975-01-01

    The underlying mechanism of bradycardia-dependent bundle-branch and paroxysmal atrioventricular block appears to be enhancement of phase-4 depolarization in a branch or in a natural or acquired monofascicular pathway. Clinical records of these forms of impaired conduction occurring in the bundle-branches, with either longer or shorter cardiac cycle lengths, are presented and analysed. These also include the combination of Mobitz typw I atrioventricular block with variable degrees of bundle-branch block, as a representative example of narrow ventricular escape beats firing in the zone where prominent diastolic depolarization is present. PMID:123463

  18. Amino acid substitutions in the FXYD motif enhance phospholemman-induced modulation of cardiac L-type calcium channels

    PubMed Central

    Guo, Kai; Wang, Xianming; Gao, Guofeng; Huang, Congxin; Elmslie, Keith S.

    2010-01-01

    We have found that phospholemman (PLM) associates with and modulates the gating of cardiac L-type calcium channels (Wang et al., Biophys J 98: 1149–1159, 2010). The short 17 amino acid extracellular NH2-terminal domain of PLM contains a highly conserved PFTYD sequence that defines it as a member of the FXYD family of ion transport regulators. Although we have learned a great deal about PLM-dependent changes in calcium channel gating, little is known regarding the molecular mechanisms underlying the observed changes. Therefore, we investigated the role of the PFTYD segment in the modulation of cardiac calcium channels by individually replacing Pro-8, Phe-9, Thr-10, Tyr-11, and Asp-12 with alanine (P8A, F9A, T10A, Y11A, D12A). In addition, Asp-12 was changed to lysine (D12K) and cysteine (D12C). As expected, wild-type PLM significantly slows channel activation and deactivation and enhances voltage-dependent inactivation (VDI). We were surprised to find that amino acid substitutions at Thr-10 and Asp-12 significantly enhanced the ability of PLM to modulate CaV1.2 gating. T10A exhibited a twofold enhancement of PLM-induced slowing of activation, whereas D12K and D12C dramatically enhanced PLM-induced increase of VDI. The PLM-induced slowing of channel closing was abrogated by D12A and D12C, whereas D12K and T10A failed to impact this effect. These studies demonstrate that the PFXYD motif is not necessary for the association of PLM with CaV1.2. Instead, since altering the chemical and/or physical properties of the PFXYD segment alters the relative magnitudes of opposing PLM-induced effects on CaV1.2 channel gating, PLM appears to play an important role in fine tuning the gating kinetics of cardiac calcium channels and likely plays an important role in shaping the cardiac action potential and regulating Ca2+ dynamics in the heart. PMID:20720179

  19. Taurine depresses cardiac contractility and enhances systemic heart glucose utilization in the cuttlefish, Sepia officinalis.

    PubMed

    MacCormack, Tyson J; Callaghan, N I; Sykes, A V; Driedzic, W R

    2016-02-01

    Taurine is the most abundant amino acid in the blood of the cuttlefish, Sepia officinalis, where levels can exceed 200 mmol L(-1). In mammals, intracellular taurine modulates cardiac Ca(2+) handling and carbohydrate metabolism at much lower concentrations but it is not clear if it exerts similar actions in cephalopods. Blood Ca(2+) levels are high in cephalopods and we hypothesized that taurine would depress cardiac Ca(2+) flux and modulate contractility in systemic and branchial hearts of cuttlefish. Heart performance was assessed with an in situ perfused systemic heart preparation and contractility was evaluated using isometrically contracting systemic and branchial heart muscle rings. Stroke volume, cardiac output, and Ca(2+) sensitivity were significantly lower in systemic hearts perfused with supplemental taurine (100 mmol L(-1)) than in controls. In muscle ring preparations, taurine impaired relaxation at high contraction frequencies, an effect abolished by supra-physiological Ca(2+) levels. Taurine did not affect oxygen consumption in non-contracting systemic heart muscle, but extracellular glucose utilization was twice that of control preparations. Collectively, our results suggest that extracellular taurine depresses cardiac Ca(2+) flux and potentiates glucose utilization in cuttlefish. Variations in taurine levels may represent an important mechanism for regulating cardiovascular function and metabolism in cephalopods.

  20. Older Adults in Cardiac Rehabilitation: A New Strategy for Enhancing Physical Function.

    ERIC Educational Resources Information Center

    Rejeski, W. Jack; Foy, Capri Gabrielle; Brawley, Lawrence R.; Brubaker, Peter H.; Focht, Brian C.; Norris, James L., III; Smith, Marci L.

    2002-01-01

    Contrasted the effect of a group-mediated cognitive- behavioral intervention (GMCB) versus traditional cardiac rehabilitation (CRP) upon changes in objective and self-reported physical function of older adults after 3 months of exercise therapy. Both groups improved significantly. Adults with lower function at the outset of the intervention…

  1. Older Adults in Cardiac Rehabilitation: A New Strategy for Enhancing Physical Function.

    ERIC Educational Resources Information Center

    Rejeski, W. Jack; Foy, Capri Gabrielle; Brawley, Lawrence R.; Brubaker, Peter H.; Focht, Brian C.; Norris, James L., III; Smith, Marci L.

    2002-01-01

    Contrasted the effect of a group-mediated cognitive- behavioral intervention (GMCB) versus traditional cardiac rehabilitation (CRP) upon changes in objective and self-reported physical function of older adults after 3 months of exercise therapy. Both groups improved significantly. Adults with lower function at the outset of the intervention…

  2. TBX1 Represses Vegfr2 Gene Expression and Enhances the Cardiac Fate of VEGFR2+ Cells

    PubMed Central

    Lania, Gabriella; Ferrentino, Rosa; Baldini, Antonio

    2015-01-01

    The T-box transcription factor TBX1 has critical roles in maintaining proliferation and inhibiting differentiation of cardiac progenitor cells of the second heart field (SHF). Haploinsufficiency of the gene that encodes it is a cause of congenital heart disease. Here, we developed an embryonic stem (ES) cell-based model in which Tbx1 expression can be modulated by tetracycline. Using this model, we found that TBX1 down regulates the expression of VEGFR2, and we confirmed this finding in vivo during embryonic development. In addition, we found a Vegfr2 domain of expression, not previously described, in the posterior SHF and this expression is extended by loss of Tbx1. VEGFR2 has been previously described as a marker of a subpopulation of cardiac progenitors. Clonal analysis of ES-derived VEGFR2+ cells indicated that 12.5% of clones expressed three markers of cardiac lineage (cardiomyocyte, smooth muscle and endothelium). However, a pulse of Tbx1 expression was sufficient to increase the percentage to 20.8%. In addition, the percentage of clones expressing markers of multiple cardiac lineages increased from 41.6% to 79.1% after Tbx1 pulse. These results suggest that TBX1 plays a role in maintaining a progenitor state in VEGFR2+ cells. PMID:26382615

  3. Enhanced Cardiac Perception Is Associated with Increased Susceptibility to Framing Effects

    ERIC Educational Resources Information Center

    Sutterlin, Stefan; Schulz, Stefan M.; Stumpf, Theresa; Pauli, Paul; Vogele, Claus

    2013-01-01

    Previous studies suggest in line with dual process models that interoceptive skills affect controlled decisions via automatic or implicit processing. The "framing effect" is considered to capture implicit effects of task-irrelevant emotional stimuli on decision-making. We hypothesized that cardiac awareness, as a measure of interoceptive…

  4. Shared medical appointments after cardiac surgery-the process of implementing a novel pilot paradigm to enhance comprehensive postdischarge care.

    PubMed

    Harris, Marianne D

    2010-01-01

    To facilitate the physical and emotional needs of patients undergoing cardiac surgery and their families, our Cardiac Surgery Outpatient Clinic at Cleveland Clinic, a nonprofit multispecialty academic medical center in Cleveland, Ohio, decided to implement a trial of a novel care delivery paradigm called Shared Medical Appointments (SMAs). The purpose of this venture was to facilitate timely access to care 3 to 5 days after hospital discharge, include family members in the education process and the care of the patient, and provide a forum for support and shared learning among patients who have been through like surgical experiences. The clinic system, which performed 3,597 open heart surgeries and 213 robotically assisted cardiac surgeries in 2008, already used family education classes to provide instruction to the patients and family prior to surgery. Because this medium was an effective way to disseminate knowledge, we theorized that using an SMA would be an effective strategy to provide timely medical care after discharge and garner support, education, and increased access to timely medical care after discharge. Although there were many physicians in subspecialties performing these types of clinic visits at our institution since 2002, by the spring of 2007, a group of cardiothoracic nurses decided to perform a trial on this model in this cohort of patients and be a fully nurse-led SMA to provide comprehensive care after discharge. Preliminary patient satisfaction surveys have revealed that 92% of post-cardiac surgery patients rated the experience as good or excellent, and 82% would prefer an SMA for their next clinic visit rather than an individual visit. These data are consistent with physician-led SMA satisfaction surveys in our organization to date. Although still in its relative infancy, an SMA for this cohort appears to have merit in enhancing the support and education as well as providing for the complex medical needs of these patients.

  5. Enhanced Ca2+ binding of cardiac troponin reduces sarcomere length dependence of contractile activation independently of strong crossbridges.

    PubMed

    Korte, F Steven; Feest, Erik R; Razumova, Maria V; Tu, An-Yue; Regnier, Michael

    2012-10-01

    Calcium sensitivity of the force-pCa relationship depends strongly on sarcomere length (SL) in cardiac muscle and is considered to be the cellular basis of the Frank-Starling law of the heart. SL dependence may involve changes in myofilament lattice spacing and/or myosin crossbridge orientation to increase probability of binding to actin at longer SLs. We used the L48Q cardiac troponin C (cTnC) variant, which has enhanced Ca(2+) binding affinity, to test the hypotheses that the intrinsic properties of cTnC are important in determining 1) thin filament binding site availability and responsiveness to crossbridge activation and 2) SL dependence of force in cardiac muscle. Trabeculae containing L48Q cTnC-cTn lost SL dependence of the Ca(2+) sensitivity of force. This occurred despite maintaining the typical SL-dependent changes in maximal force (F(max)). Osmotic compression of preparations at SL 2.0 μm with 3% dextran increased F(max) but not pCa(50) in L48Q cTnC-cTn exchanged trabeculae, whereas wild-type (WT)-cTnC-cTn exchanged trabeculae exhibited increases in both F(max) and pCa(50). Furthermore, crossbridge inhibition with 2,3-butanedione monoxime at SL 2.3 μm decreased F(max) and pCa(50) in WT cTnC-cTn trabeculae to levels measured at SL 2.0 μm, whereas only F(max) was decreased with L48Q cTnC-cTn. Overall, these results suggest that L48Q cTnC confers reduced crossbridge dependence of thin filament activation in cardiac muscle and that changes in the Ca(2+) sensitivity of force in response to changes in SL are at least partially dependent on properties of thin filament troponin.

  6. High-quality anatomical structure enhancement for cardiac image dynamic volume rendering

    NASA Astrophysics Data System (ADS)

    Zhang, Qi; Eagleson, Roy; Guiraudon, Gerard M.; Peters, Terry M.

    2008-03-01

    Dynamic volume rendering of the beating heart is an important element in cardiac disease diagnosis and therapy planning, providing the clinician with insight into the internal cardiac structure and functional behavior. Most clinical applications tend to focus upon a particular set of organ structures, and in the case of cardiac imaging, it would be helpful to embed anatomical features into the dynamic volume that are of particular importance to an intervention. A uniform transfer function (TF), such as is generally employed in volume rendering, cannot effectively isolate such structures because of the lack of spatial information and the small intensity differences between adjacent tissues. Explicit segmentation is a powerful way to approach this problem, which usually yields a single binary mask volume (MV), where a unit value in a voxel within the MV acts as a tag label representing the anatomical structure of interest (ASOI). These labels are used to determine the TF employed to adjust the ASOI display. Traditional approaches for rendering such segmented volumetric datasets usually deliver unsatisfactory results, such as noninteractive rendering speed, low image quality, intermixing artifacts along the rendered subvolume boundaries, and speckle noise. In this paper, we introduce a new "color coding" approach, based on the graphics processing unit (GPU) accelerated raycasting algorithm and a pre-integrated voxel classification method, to address this problem. The mask tag labels derived from segmentation are first smoothed with a Gaussian filter, and multiple TFs are designed for each of the MVs and the source cardiac volume respectively, mapping the voxel's intensity to color and opacity at each sampling point along the casting ray. The resultant values are composited together using a boundary color adjustment technique, which acts as "coding" the segmented anatomical structure information into the rendered source volume of the beating heart. Our algorithm

  7. An automatic machine learning system for coronary calcium scoring in clinical non-contrast enhanced, ECG-triggered cardiac CT

    NASA Astrophysics Data System (ADS)

    Wolterink, Jelmer M.; Leiner, Tim; Takx, Richard A. P.; Viergever, Max A.; Išgum, Ivana

    2014-03-01

    Presence of coronary artery calcium (CAC) is a strong and independent predictor of cardiovascular events. We present a system using a forest of extremely randomized trees to automatically identify and quantify CAC in routinely acquired cardiac non-contrast enhanced CT. Candidate lesions the system could not label with high certainty were automatically identified and presented to an expert who could relabel them to achieve high scoring accuracy with minimal effort. The study included 200 consecutive non-contrast enhanced ECG-triggered cardiac CTs (120 kV, 55 mAs, 3 mm section thickness). Expert CAC annotations made as part of the clinical routine served as the reference standard. CAC candidates were extracted by thresholding (130 HU) and 3-D connected component analysis. They were described by shape, intensity and spatial features calculated using multi-atlas segmentation of coronary artery centerlines from ten CTA scans. CAC was identified using a randomized decision tree ensemble classifier in a ten-fold stratified cross-validation experiment and quantified in Agatston and volume scores for each patient. After classification, candidates with posterior probability indicating uncertain labeling were selected for further assessment by an expert. Images with metal implants were excluded. In the remaining 164 images, Spearman's p between automatic and reference scores was 0.94 for both Agatston and volume scores. On average 1.8 candidate lesions per scan were subsequently presented to an expert. After correction, Spearman's p was 0.98. We have described a system for automatic CAC scoring in cardiac CT images which is able to effectively select difficult examinations for further refinement by an expert.

  8. Reduced nitric oxide in the rostral ventrolateral medulla enhances cardiac sympathetic afferent reflex in rats with chronic heart failure.

    PubMed

    Zhu, Guo-Qing; Gao, Xing-Ya; Zhang, Feng; Wang, Wei

    2004-02-25

    The purpose of this study was to determine the effect of nitric oxide (NO) in the rostral ventrolateral medulla (RVLM) on the central integration of the cardiac sympathetic afferent reflex (CSAR) in normal rats and in rats with coronary ligation-induced chronic heart failure (CHF). Under alpha-chloralose and urethane anesthesia, mean arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were recorded at baseline and during elicitation of the CSAR evoked by electrical stimulation of the cardiac afferent sympathetic nerves in sino-aortic denervated and cervical vagotomized rats. A cannula was inserted into the left RVLM for microinjection of NO synthase inhibitor, S-methyl-L-thiocitruline (MeTC) or NO donor, S-nitroso-N-acetyl-penicillamine (SNAP). The CSAR was tested by electrical stimulation (5, 10, 20 and 30 Hz at 10 V for 1 ms) of the afferent cardiac sympathetic nerves. It was observed that (1) the responses of RSNA to stimulation were enhanced in rats with CHF; (2) MeTC (80 nmol) potentiated the responses of RSNA to stimulation in sham rats but not in rats with CHF; (3) SNAP (50 nmol) depressed the enhanced RSNA response to stimulation in CHF rats but had no effect in sham rats; and (4) MeTC increased the baseline RSNA and MAP only in sham rats, but SNAP inhibited the baseline RSNA and MAP in both sham and CHF rats. These results indicate that reductance of NO in the RVLM is involved in the augmentation of CSAR in CHF rats.

  9. Spatiotemporal Regulation of an Hcn4 Enhancer Defines a Role for Mef2c and HDACs in Cardiac Electrical Patterning

    PubMed Central

    Vedantham, Vasanth; Evangelista, Melissa; Huang, Yu; Srivastava, Deepak

    2012-01-01

    Regional differences in cardiomyocyte automaticity permit the sinoatrial node (SAN) to function as the leading cardiac pacemaker and the atrioventricular (AV) junction as a subsidiary pacemaker. The regulatory mechanisms controlling the distribution of automaticity within the heart are not understood. To understand regional variation in cardiac automaticity, we carried out an in vivo analysis of cis-regulatory elements that control expression of the hyperpolarization-activated cyclic-nucleotide gated ion channel 4 (Hcn4). Using transgenic mice, we found that spatial and temporal patterning of Hcn4 expression in the AV conduction system required cis-regulatory elements with multiple conserved fragments. One highly conserved region, which contained a myocyte enhancer factor 2C (Mef2C) binding site previously described in vitro, induced reporter expression specifically in the embryonic non-chamber myocardium and the postnatal AV bundle in a Mef2c-dependent manner in vivo. Inhibition of histone deacetylase (HDAC) activity in cultured transgenic embryos showed expansion of reporter activity to working myocardium. In adult animals, hypertrophy induced by transverse aortic constriction, which causes translocation of HDACs out of the nucleus, resulted in ectopic activation of the Hcn4 enhancer in working myocardium, recapitulating pathological electrical remodeling. These findings reveal mechanisms that control the distribution of automaticity among cardiomyocytes during development and in response to stress. PMID:23085412

  10. Contrast enhanced micro-computed tomography resolves the 3-dimensional morphology of the cardiac conduction system in mammalian hearts.

    PubMed

    Stephenson, Robert S; Boyett, Mark R; Hart, George; Nikolaidou, Theodora; Cai, Xue; Corno, Antonio F; Alphonso, Nelson; Jeffery, Nathan; Jarvis, Jonathan C

    2012-01-01

    The general anatomy of the cardiac conduction system (CCS) has been known for 100 years, but its complex and irregular three-dimensional (3D) geometry is not so well understood. This is largely because the conducting tissue is not distinct from the surrounding tissue by dissection. The best descriptions of its anatomy come from studies based on serial sectioning of samples taken from the appropriate areas of the heart. Low X-ray attenuation has formerly ruled out micro-computed tomography (micro-CT) as a modality to resolve internal structures of soft tissue, but incorporation of iodine, which has a high molecular weight, into those tissues enhances the differential attenuation of X-rays and allows visualisation of fine detail in embryos and skeletal muscle. Here, with the use of a iodine based contrast agent (I(2)KI), we present contrast enhanced micro-CT images of cardiac tissue from rat and rabbit in which the three major subdivisions of the CCS can be differentiated from the surrounding contractile myocardium and visualised in 3D. Structures identified include the sinoatrial node (SAN) and the atrioventricular conduction axis: the penetrating bundle, His bundle, the bundle branches and the Purkinje network. Although the current findings are consistent with existing anatomical representations, the representations shown here offer superior resolution and are the first 3D representations of the CCS within a single intact mammalian heart.

  11. Enhanced cardiac perception is associated with increased susceptibility to framing effects.

    PubMed

    Sütterlin, Stefan; Schulz, Stefan M; Stumpf, Theresa; Pauli, Paul; Vögele, Claus

    2013-07-01

    Previous studies suggest in line with dual process models that interoceptive skills affect controlled decisions via automatic or implicit processing. The "framing effect" is considered to capture implicit effects of task-irrelevant emotional stimuli on decision-making. We hypothesized that cardiac awareness, as a measure of interoceptive skills, is positively associated with susceptibility to the framing effect. Forty volunteers performed a risky-choice framing task in which the effect of loss versus gain frames on decisions based on identical information was assessed. The results show a positive association between cardiac awareness and the framing effect, accounting for 24% of the variance in the framing effect. These findings demonstrate that good interoceptive skills are linked to poorer performance in risky choices based on ambivalent information when implicit bias is induced by task-irrelevant emotional information. These findings support a dual process perspective on decision-making and suggest that interoceptive skills mediate effects of implicit bias on decisions.

  12. Enhancing ejection fraction measurement through 4D respiratory motion compensation in cardiac PET imaging.

    PubMed

    Tang, Jing; Wang, Xinhui; Gao, Xiangzhen; Segars, Paul; Lodge, Martin; Rahmim, Arman

    2017-03-02

    ECG gated cardiac PET imaging measures functional parameters such as left ventricle (LV) ejection fraction (EF), providing diagnostic and prognostic information for management of patients with coronary artery disease (CAD). Respiratory motion degrades spatial resolution and affects the accuracy in measuring the LV volumes for EF calculation. The goal of this study is to systematically investigate the effect of respiratory motion correction on the estimation of end-diastolic volume (EDV), end-systolic volume (ESV), and EF, especially on the separation of normal and abnormal EFs. We developed a respiratory motion incorporated 4D PET image reconstruction technique which uses all gated-frame data to acquire a motion-suppressed image. Using the standard XCAT phantom and two individual-specific volunteer XCAT phantoms, we simulated dual-gated myocardial perfusion imaging data for normally and abnormally beating hearts. With and without respiratory motion correction, we measured the EDV, ESV, and EF from the cardiac gated reconstructed images. For all the phantoms, the estimated volumes increased and the biases significantly reduced with motion correction compared with those without. Furthermore, the improvement of ESV measurement in the abnormally beating heart led to better separation of normal and abnormal EFs. The simulation study demonstrated the significant effect of respiratory motion correction on cardiac imaging data with motion amplitude as small as 0.7 cm. The larger the motion amplitude the more improvement respiratory motion correction brought about on the measurement of EF. Using data-driven respiratory gating, we also demonstrated the effect of respiratory motion correction on estimation of the above functional parameters from list mode patient data. Respiratory motion correction is shown to improve the accuracy of EF measurement in clinical cardiac PET imaging.

  13. Enhancing ejection fraction measurement through 4D respiratory motion compensation in cardiac PET imaging

    NASA Astrophysics Data System (ADS)

    Tang, Jing; Wang, Xinhui; Gao, Xiangzhen; Segars, W. Paul; Lodge, Martin A.; Rahmim, Arman

    2017-06-01

    ECG gated cardiac PET imaging measures functional parameters such as left ventricle (LV) ejection fraction (EF), providing diagnostic and prognostic information for management of patients with coronary artery disease (CAD). Respiratory motion degrades spatial resolution and affects the accuracy in measuring the LV volumes for EF calculation. The goal of this study is to systematically investigate the effect of respiratory motion correction on the estimation of end-diastolic volume (EDV), end-systolic volume (ESV), and EF, especially on the separation of normal and abnormal EFs. We developed a respiratory motion incorporated 4D PET image reconstruction technique which uses all gated-frame data to acquire a motion-suppressed image. Using the standard XCAT phantom and two individual-specific volunteer XCAT phantoms, we simulated dual-gated myocardial perfusion imaging data for normally and abnormally beating hearts. With and without respiratory motion correction, we measured the EDV, ESV, and EF from the cardiac-gated reconstructed images. For all the phantoms, the estimated volumes increased and the biases significantly reduced with motion correction compared with those without. Furthermore, the improvement of ESV measurement in the abnormally beating heart led to better separation of normal and abnormal EFs. The simulation study demonstrated the significant effect of respiratory motion correction on cardiac imaging data with motion amplitude as small as 0.7 cm. The larger the motion amplitude the more improvement respiratory motion correction brought about on the EF measurement. Using data-driven respiratory gating, we also demonstrated the effect of respiratory motion correction on estimating the above functional parameters from list mode patient data. Respiratory motion correction has been shown to improve the accuracy of EF measurement in clinical cardiac PET imaging.

  14. Diminazene aceturate enhances ACE2 activity and attenuates ischemia-induced cardiac pathophysiology

    PubMed Central

    Qi, YanFei; Zhang, Juan; Cole-Jeffrey, Colleen T; Shenoy, Vinayak; Espejo, Andrew; Hanna, Mina; Song, Chunjuan; Pepine, Carl J; Katovich, Michael J; Raizada, Mohan K

    2013-01-01

    Angiotensin-converting enzyme 2 (ACE2) plays a critical role against myocardial infarction (MI). We hypothesized that activation of intrinsic ACE2 would be protective against ischemia-induced cardiac pathophysiology. Diminazine aceturate (DIZE), a small molecule ACE2 activator has been used to evaluate this hypothesis. DIZE (15 mg/kg/day, s.c.) was injected two days prior to MI surgery and continued throughout the study-period. MI rats showed a 62% decrease in fractional shortening (FS,%) [control (Con): 51.1 ± 3.2; DIZE alone (D) : 52.1 ± 3.2; MI (M): 19.1± 3.0], a 55% decrease in contractility (dP/dtmax mmHg/s) (Con: 9480 ± 425.3; D: 9585 ± 597.4; M: 4251 ± 657.7), and a 27% increase in ventricular hypertrophy [VH, mg/mm (Con: 26.5 ± 1.5; D: 26.9 ± 1.4; M: 33.4± 1.1)]. DIZE attenuated the MI-induced decrease in FS by 89%, improved dP/dtmax by 92%, and reversed VH by 18%. MI also significantly increased ACE and angiotensin type 1 receptor levels while decreased ACE2 activity by 40% (Con: 246.2 ± 25.1; D: 254.2 ± 20.6; M: 148.9 ± 29.2, RFU/min), which was reversed by DIZE treatment. Thus, DIZE treatment decreased the infarct area, attenuated LV remodeling post-MI and restored normal balance of the cardiac renin angiotensin system. Additionally, DIZE treatment increased circulating endothelial progenitor cells, increased engraftment of cardiac progenitor cells and decreased inflammatory cells in peri-infarct cardiac regions. All of the beneficial effects associated with DIZE treatment were abolished by C-16, an ACE2 inhibitor. Collectively, DIZE and DIZE-like small molecules may represent promising new therapeutic agents for MI. PMID:23959549

  15. Comparing group-based acceptance and commitment therapy (ACT) with enhanced usual care for adolescents with functional somatic syndromes: a study protocol for a randomised trial.

    PubMed

    Kallesøe, Karen Hansen; Schröder, Andreas; Wicksell, Rikard K; Fink, Per; Ørnbøl, Eva; Rask, Charlotte Ulrikka

    2016-09-15

    Functional somatic syndromes (FSS) are common in adolescents, characterised by severe disability and reduced quality of life. Behavioural treatments such as acceptance and commitment therapy (ACT) has shown promising results in children and adolescents with FSS, but has focused on specific syndromes such as functional pain. The current study will compare the efficacy of group-based ACT with that of enhanced usual care (EUC) in adolescents with a range of FSS operationalised by the unifying construct of multiorgan bodily distress syndrome (BDS). A total of 120 adolescents aged 15-19 and diagnosed with multiorgan BDS, of at least 12 months duration, will be assessed and randomised to either: (1) EUC: a manualised consultation with a child and adolescent psychiatrist and individualised treatment plan or (2) manualised ACT-based group therapy plus EUC. The ACT programme consists of 9 modules (ie, 27 hours) and 1 follow-up meeting (3 hours). The primary outcome is physical health, assessed by an Short Form Health Survey (SF-36) aggregate score 12 months after randomisation. Secondary outcomes include self-reported symptom severity, symptom interference, depression and anxiety, illness worry, perceived stress and global improvement; as well as objective physical activity and bodily stress response measured by heart rate variability, hair cortisol and inflammatory biomarkers. Process measures are illness perception, illness-related behaviour and psychological flexibility. The study is conducted in accordance with Helsinki Declaration II. Approval has been obtained from the Science Ethics Committee of the Central Denmark Region and the Danish Data Protection. The results will be sought to be published according to the CONSORT statement in peer-reviewed journals. This is one of the first larger randomised clinical trials evaluating the effect of a group-based intervention for adolescents with a range of severe FSS. NCT02346071; Pre-results. Published by the BMJ

  16. Commitment to health theory.

    PubMed

    Kelly, Cynthia W

    2008-01-01

    This article introduces commitment to health as a middle-range. Commitment to health (CTH) is derived from Prochaska and DiClemente's (1983) Transtheoretical Model of Behavior Change. CTH theory is designed to predict the likelihood of behavior change between the action and maintenance stages of change. Commitment is defined as a freely chosen internal resolve to perform health behaviors, even when encumbered or inconvenienced by difficulties. Health is defined as the optimal level of well-being. Commitment is an independent continuous variable, but it can be categorized into three time-oriented categories: (1) low-level, (2) middle-level, and (3) high-level commitment. The higher the level of commitment, the more likely the individual will adopt long-term behavior change. This article presents the definitions, assumptions, and relational statements of CTH.

  17. Hydrogen Sulfide in Paraventricular Nucleus Enhances Sympathetic Activity and Cardiac Sympathetic Afferent Reflex in Chronic Heart Failure Rats

    PubMed Central

    Gan, Xian-Bing; Liu, Tong-Yan; Xiong, Xiao-Qing; Chen, Wei-Wei; Zhou, Ye-Bo; Zhu, Guo-Qing

    2012-01-01

    Background Intracerebroventricular infusion of NaHS, a hydrogen sulfide (H2S) donor, increased mean arterial pressure (MAP). This study was designed to determine the roles of H2S in the paraventricular nucleus (PVN) in modulating sympathetic activity and cardiac sympathetic afferent reflex (CSAR) in chronic heart failure (CHF). Methodology/Principal Findings CHF was induced by left descending coronary artery ligation in rats. Renal sympathetic nerve activity (RSNA) and MAP were recorded under anesthesia. CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. PVN microinjection of low doses of a H2S donor, GYY4137 (0.01 and 0.1 nmol), had no significant effects on RSNA, MAP and CSAR. High doses of GYY4137 (1, 2 and 4 nmol) increased baseline RSNA, MAP and heart rate (HR), and enhanced CSAR. The effects were greater in CHF rats than sham-operated rats. A cystathionine-β-synthase (CBS) inhibitor, hydroxylamine (HA) in PVN had no significant effect on the RSNA, MAP and CSAR. CBS activity and H2S level in the PVN were decreased in CHF rats. No significant difference in CBS level in PVN was found between sham-operated rats and CHF rats. Stimulation of cardiac sympathetic afferents with capsaicin decreased CBS activity and H2S level in the PVN in both sham-operated rats and CHF rats. Conclusions Exogenous H2S in PVN increases RSNA, MAP and HR, and enhances CSAR. The effects are greater in CHF rats than those in sham-operated rats. Endogenous H2S in PVN is not responsible for the sympathetic activation and enhanced CSAR in CHF rats. PMID:23166827

  18. Dietary nitrate improves cardiac contractility via enhanced cellular Ca²⁺ signaling.

    PubMed

    Pironti, Gianluigi; Ivarsson, Niklas; Yang, Jiangning; Farinotti, Alex Bersellini; Jonsson, William; Zhang, Shi-Jin; Bas, Duygu; Svensson, Camilla I; Westerblad, Håkan; Weitzberg, Eddie; Lundberg, Jon O; Pernow, John; Lanner, Johanna; Andersson, Daniel C

    2016-05-01

    The inorganic anion nitrate (NO3 (-)), which is naturally enriched in certain vegetables (e.g., spinach and beetroot), has emerged as a dietary component that can regulate diverse bodily functions, including blood pressure, mitochondrial efficiency, and skeletal muscle force. It is not known if dietary nitrate improves cardiac contractility. To test this, mice were supplemented for 1-2 weeks with sodium nitrate in the drinking water at a dose similar to a green diet. The hearts from nitrate-treated mice showed increased left ventricular pressure and peak rate of pressure development as measured with the Langendorff heart technique. Cardiomyocytes from hearts of nitrate-treated and control animals were incubated with the fluorescent indicator Fluo-3 to measure cytoplasmic free [Ca(2+)] and fractional shortening. Cardiomyocytes from nitrate-treated mice displayed increased fractional shortening, which was linked to larger Ca(2+) transients. Moreover, nitrate hearts displayed increased protein expression of the L-type Ca(2+) channel/dihydropyridine receptor and peak L-type Ca(2+) channel currents. The nitrate-treated hearts displayed increased concentration of cAMP but unchanged levels of cGMP compared with controls. These findings provide the first evidence that dietary nitrate can affect the expression of important Ca(2+) handling proteins in the heart, resulting in increased cardiomyocyte Ca(2+) signaling and improved left ventricular contractile function. Our observation shows that dietary nitrate impacts cardiac function and adds understanding to inorganic nitrate as a physiological modulator.

  19. Transforming growth factor-{beta}2 enhances differentiation of cardiac myocytes from embryonic stem cells

    SciTech Connect

    Kumar, Dinender . E-mail: Dinender.Kumar@uvm.edu; Sun, Baiming

    2005-06-24

    Stem cell therapy holds great promise for the treatment of injured myocardium, but is challenged by a limited supply of appropriate cells. Three different isoforms of transforming growth factor-{beta} (TGF-{beta}) -{beta}1, -{beta}2, and -{beta}3 exhibit distinct regulatory effects on cell growth, differentiation, and migration during embryonic development. We compared the effects of these three different isoforms on cardiomyocyte differentiation from embryonic stem (ES) cells. In contrast to TGF-{beta}1, or -{beta}3, treatment of mouse ES cells with TGF-{beta}2 isoform significantly increased embryoid body (EB) proliferation as well as the extent of the EB outgrowth that beat rhythmically. At 17 days, 49% of the EBs treated with TGF-{beta}2 exhibited spontaneous beating compared with 15% in controls. Cardiac myocyte specific protein markers sarcomeric myosin and {alpha}-actin were demonstrated in beating EBs and cells isolated from EBs. In conclusion, TGF-{beta}2 but not TGF-{beta}1, or -{beta}3 promotes cardiac myocyte differentiation from ES cells.

  20. Isolated right ventricular infarct presenting as ventricular fibrillation arrest and confirmed by delayed-enhancement cardiac MRI.

    PubMed

    Cavalcante, João L; Al-Mallah, Mouaz; Hudson, Michael

    2010-10-01

    Malignant ventricular arrhythmias resulting from isolated right ventricular myocardial infarction (RVMI) without left ventricular myocardial ischaemia or infarction occur rarely. We present a case of a 61 year-old male with acute onset of chest pain and ventricular fibrillation cardiac arrest requiring prompt defibrillation. Subsequent 15-lead EKG, showed ST-segment elevation in the anterior and right precordial leads without ST-segment elevation in the inferior leads. Angiography documented occlusion of a large RV marginal branch. Delayed enhancement cardiac magnetic resonance imaging (DE-CMR) with gadolinium performed two days post-infarct showed isolated RVMI. Patient remained symptom free and haemodynamically stable throughout his hospital stay. The clinical presentation of isolated RV infarct can be misleading and diagnosis difficult. EKG findings can resemble acute anterior wall myocardial infarction, while its course can be accompanied by life-threatening ventricular arrhythmias. This case uniquely combines this rare clinical sequence with DE-CMR images using gadolinium to confirm isolated RVMI. A brief review of RVMI presentation and associated EKG patterns is also discussed. Published by Elsevier B.V.

  1. Cardiac MRI and 3D contrast-enhanced MR angiography in pediatric and young adult patients with Turner syndrome.

    PubMed

    Yiğit, Hasan; Önder, Aşan; Özgür, Senem; Aycan, Zehra; Karademir, Selmin; Doğan, Vehbi

    2017-02-27

    This study aimed to describe the spectrum and frequency of cardiovascular abnormalities in pediatric and young adult patients with Turner syndrome (TS) using cardiac MRI and MR angiography. This prospective study consisted of 47 female patients of pediatric age and young adults with a karyotypically confirmed diagnosis of TS. All patients underwent cardiac MRI and contrast-enhanced MR angiography. A second examination after 9-26 months was performed for 28 of these patients. Elongation of the transverse aortic arch (ETA) was the most frequent abnormality with a rate of 37%. The rate of partial anomalous pulmonary venous connection (PAPVC) was 21.7%, bicuspid aortic valve (BAV) was 19.6%, coarctation was 6.5%, ascending aorta dilatation was 28.3%, and descending aorta dilatation was 15.2%. The diameters of the aorta and the rate of aortic dilatation per unit of time was greater in the patients with BAV (P < 0.05). ETA was less observed in the patients who were receiving growth hormone therapy (P < 0.05). The most common cardiovascular abnormalities in TS patients are aortic arch anomalies such as ETA and coarctation, aortic dilatation, PAPVCs, and BAV. The presence of BAV is an important risk factor for the aortic dilatation.

  2. CYP2J2 and its metabolites (epoxyeicosatrienoic acids) attenuate cardiac hypertrophy by activating AMPKα2 and enhancing nuclear translocation of Akt1.

    PubMed

    Wang, Bei; Zeng, Hesong; Wen, Zheng; Chen, Chen; Wang, Dao Wen

    2016-10-01

    Cytochrome P450 epoyxgenase 2J2 and epoxyeicosatrienoic acids (EETs) are known to protect against cardiac hypertrophy and heart failure, which involve the activation of 5'-AMP-activated protein kinase (AMPK) and Akt. Although the functional roles of AMPK and Akt are well established, the significance of cross talk between them in the development of cardiac hypertrophy and antihypertrophy of CYP2J2 and EETs remains unclear. We investigated whether CYP2J2 and its metabolites EETs protected against cardiac hypertrophy by activating AMPKα2 and Akt1. Moreover, we tested whether EETs enhanced cross talk between AMPKα2 and phosphorylated Akt1 (p-Akt1), and stimulated nuclear translocation of p-Akt1, to exert their antihypertrophic effects. AMPKα2(-/-) mice that overexpressed CYP2J2 in heart were treated with Ang II for 2 weeks. Interestingly, overexpression of CYP2J2 suppressed cardiac hypertrophy and increased levels of atrial natriuretic peptide (ANP) in the heart tissue and plasma of wild-type mice but not AMPKα2(-/-) mice. The CYP2J2 metabolites, 11,12-EET, activated AMPKα2 to induce nuclear translocation of p-Akt1 selectively, which increased the production of ANP and therefore inhibited the development of cardiac hypertrophy. Furthermore, by co-immunoprecipitation analysis, we found that AMPKα2β2γ1 and p-Akt1 interact through the direct binding of the AMPKγ1 subunit to the Akt1 protein kinase domain. This interaction was enhanced by 11,12-EET. Our studies reveal a novel mechanism in which CYP2J2 and EETs enhanced Akt1 nuclear translocation through interaction with AMPKα2β2γ1 and protect against cardiac hypertrophy and suggest that overexpression of CYP2J2 might have clinical potential to suppress cardiac hypertrophy and heart failure. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  3. The Dynamic Commitment Design.

    ERIC Educational Resources Information Center

    Grabosky, Fran

    1985-01-01

    Presents a model to remedy the problem of groups with poor cohesion, energy, and interaction. The Dynamic Commitment Design promotes group growth through the "fish-bowl" effect. Members currently committed to therapy who wish to make contact form the inner circle, while those wishing to withdraw move outside the circle. (BH)

  4. Critical service learning in community health nursing: enhancing access to cardiac health screening.

    PubMed

    Gillis, Angela; Mac Lellan, Marian A

    2013-04-23

    Critical service learning (CSL) offers promise for preparing community health nursing students to be advocates for social justice and social change. The purpose of this article is to describe a community based CSL project designed to provide cardiac health screening to an underserviced population, wherein nursing's role in social justice is integrated into nursing practice. First, the relationship between social justice and CSL is explored. Then, the CSL approach is examined and differentiated from the traditional service learning models frequently observed in the nursing curriculum. The CSL project is described and the learning requisites, objectives, requirements, and project outcomes are outlined. While not a panacea for system reform, CSL offers nursing students avenues for learning about social justice and understanding the social conditions that underlie health inequalities. Nurse educators may benefit from the new strategies for incorporating social justice into nursing curriculum; this paper suggests that CSL offers one possibility.

  5. Enhancing patient safety with intelligent intravenous infusion devices: experience in a specialty cardiac hospital.

    PubMed

    Wood, Jacqueline L; Burnette, Jeremy S

    2012-01-01

    The study objective was to evaluate patient safety, increase nursing satisfaction, and affect economic factors through implementation of intelligent intravenous (IV) infusion devices in a specialty cardiac hospital. Intelligent IV infusion devices have been shown to decrease medication errors associated with inpatient infusions. Intelligent IV infusion device evaluation and drug library creation were conducted by a multidisciplinary team within the hospital. Devices were then implemented into patient care, and the impact was analyzed over a 9-month period. Post-implementation data showed that compliance was approximately 100%. A total of 494 critical catches occurred over the study period, resulting in an estimated annual savings of $7,513,333. End-users became familiar with the new technology and recognized the increase in safety measures and time spent with patients. This evaluation suggests that intelligent IV infusion devices resulted in decreased costs and a safer environment for patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Enhancement of diuresis with metolazone in infant paediatric cardiac intensive care patients.

    PubMed

    Wise, Russell T; Moffett, Brady S; Akcan-Arikan, Ayse; Galati, Marianne; Afonso, Natasha; Checchia, Paul A

    2017-09-11

    Few data are available regarding the use of metolazone in infants in cardiac intensive care. Researchers need to carry out further evaluation to characterise the effects of this treatment in this population. This is a descriptive, retrospective study carried out in patients less than a year old. These infants had received metolazone over a 2-year period in the paediatric cardiac intensive care unit at our institution. The primary goal was to measure the change in urine output from 24 hours before the start of metolazone therapy to 24 hours after. Patient demographic variables, laboratory data, and fluid-balance data were analysed. The study identified 97 infants with a mean age of 0.32±0.25 years. Their mean weight was 4.9±1.5 kg, and 58% of the participants were male. An overall 63% of them had undergone cardiovascular surgery. The baseline estimated creatinine clearance was 93±37 ml/minute/1.73 m2. Initially, the participants had received a metolazone dose of 0.27±0.10 mg/kg/day, the maximum dose being 0.43 mg/kg/day. They had also received other diuretics during metolazone initiation, such as furosemide (87.6%), spironolactone (58.8%), acetazolamide (11.3%), bumetanide (7.2%), and ethacrynic acid (1%). The median change in urine output after metolazone was 0.9 ml/kg/hour (interquartile range 0.15-1.9). The study categorised a total of 66 patients (68.0%) as responders. Multivariable analysis identified acetazolamide use (p=0.002) and increased fluid input in the 24 hours after metolazone initiation (p0.05). Metolazone increased urine output in a select group of patients. Efficacy can be maximised by strategic selection of patients.

  7. Myosin regulatory light chain phosphorylation enhances cardiac β-myosin in vitro motility under load.

    PubMed

    Karabina, Anastasia; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta; Moore, Jeffrey R

    2015-08-15

    Familial hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and myofibrillar disarray, and often results in sudden cardiac death. Two HCM mutations, N47K and R58Q, are located in the myosin regulatory light chain (RLC). The RLC mechanically stabilizes the myosin lever arm, which is crucial to myosin's ability to transmit contractile force. The N47K and R58Q mutations have previously been shown to reduce actin filament velocity under load, stemming from a more compliant lever arm (Greenberg, 2010). In contrast, RLC phosphorylation was shown to impart stiffness to the myosin lever arm (Greenberg, 2009). We hypothesized that phosphorylation of the mutant HCM-RLC may mitigate distinct mutation-induced structural and functional abnormalities. In vitro motility assays were utilized to investigate the effects of RLC phosphorylation on the HCM-RLC mutant phenotype in the presence of an α-actinin frictional load. Porcine cardiac β-myosin was depleted of its native RLC and reconstituted with mutant or wild-type human RLC in phosphorylated or non-phosphorylated form. Consistent with previous findings, in the presence of load, myosin bearing the HCM mutations reduced actin sliding velocity compared to WT resulting in 31-41% reductions in force production. Myosin containing phosphorylated RLC (WT or mutant) increased sliding velocity and also restored mutant myosin force production to near WT unphosphorylated values. These results point to RLC phosphorylation as a general mechanism to increase force production of the individual myosin motor and as a potential target to ameliorate the HCM-induced phenotype at the molecular level.

  8. Non-contrast-enhanced MR angiography of the thoracic aorta using cardiac and navigator-gated magnetization-prepared three-dimensional steady-state free precession.

    PubMed

    Amano, Yasuo; Takahama, Katsuya; Kumita, Shinichiro

    2008-03-01

    To assess the usefulness of non-contrast-enhanced MR angiography using cardiac and navigator-gated magnetization-prepared three-dimensional (3D) steady-state free precession (SSFP) imaging for the diagnosis of diseases of the thoracic aorta. Twenty-two patients with diseases of the thoracic aorta were examined using a 1.5 Tesla unit. Non-contrast-enhanced MR angiography was done using parasagittal 3D SSFP combined with cardiac-gating and k-space weighted navigator-gating techniques, using T2-prepared and fat-suppression pulses. Imaging quality and the diagnostic capability of this technique were compared with the imaging quality of 2D SSFP or contrast-enhanced 3D MR angiography and with final diagnoses. Non-contrast-enhanced 3D MR angiography provided signal-to-noise and contrast-to-noise ratios of the thoracic aorta comparable to non-contrast-enhanced 2D or contrast-enhanced 3D MR angiography (P > 0.17). This imaging technique gave accurate diagnoses in 19 of the 22 patients. Non-contrast-enhanced MR angiography using cardiac and navigator-gated magnetization-prepared 3D SSFP technique was useful for the diagnosis of diseases of the thoracic aorta.

  9. Contractile force generation by 3D hiPSC-derived cardiac tissues is enhanced by rapid establishment of cellular interconnection in matrix with muscle-mimicking stiffness.

    PubMed

    Lee, Soah; Serpooshan, Vahid; Tong, Xinming; Venkatraman, Sneha; Lee, Meelim; Lee, Jaecheol; Chirikian, Orlando; Wu, Joseph C; Wu, Sean M; Yang, Fan

    2017-03-30

    Engineering 3D human cardiac tissues is of great importance for therapeutic and pharmaceutical applications. As cardiac tissue substitutes, extracellular matrix-derived hydrogels have been widely explored. However, they exhibit premature degradation and their stiffness is often orders of magnitude lower than that of native cardiac tissue. There are no reports on establishing interconnected cardiomyocytes in 3D hydrogels at physiologically-relevant cell density and matrix stiffness. Here we bioengineer human cardiac microtissues by encapsulating human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in chemically-crosslinked gelatin hydrogels (1.25 × 10(8)/mL) with tunable stiffness and degradation. In comparison to the cells in high stiffness (16 kPa)/slow degrading hydrogels, hiPSC-CMs in low stiffness (2 kPa)/fast degrading and intermediate stiffness (9 kPa)/intermediate degrading hydrogels exhibit increased intercellular network formation, α-actinin and connexin-43 expression, and contraction velocity. Only the 9 kPa microtissues exhibit organized sarcomeric structure and significantly increased contractile stress. This demonstrates that muscle-mimicking stiffness together with robust cellular interconnection contributes to enhancement in sarcomeric organization and contractile function of the engineered cardiac tissue. This study highlights the importance of intercellular connectivity, physiologically-relevant cell density, and matrix stiffness to best support 3D cardiac tissue engineering.

  10. Analysis of Fibroblast growth factor 15 cis-elements reveals two conserved enhancers which are closely related to cardiac outflow tract development.

    PubMed

    Saitsu, Hirotomo; Shiota, Kohei; Ishibashi, Makoto

    2006-09-01

    Fibroblast growth factor 15 (Fgf15) is expressed in the developing mouse central nervous system and pharyngeal arches. Fgf15 mutant mice showed defects of the cardiac outflow tract probably because of aberrant behavior of the cardiac neural crest cells. In this study, we examined cis-elements of the Fgf15 gene by transient transgenic analysis using lacZ as a reporter. We identified two enhancers: one directed lacZ expression in the hindbrain/spinal cord and the other in the posterior midbrain (pmb), rhombomere1 (r1) and pharyngeal epithelia. Interestingly, human genomic regions which are highly homologous to these two mouse enhancers showed almost the same enhancer activities as those of mice in transgenic mouse embryos, indicating that the two enhancers are conserved between humans and mice. We also showed that the mouse and human pmb/r1 enhancer can regulate lacZ expression in chick embryos in almost the same way as in mouse embryos. We found that the lacZ expression domain with this enhancer was expanded by ectopic Fgf8b expression, suggesting that this enhancer is regulated by Fgf8 signaling. Moreover, over-expression of Fgf15 resulted in up-regulation of Fgf8 expression in the isthmus/r1. These findings suggest that a reciprocal positive regulation exists between Fgf15 and Fgf8 in the isthmus/r1. Together with cardiac outflow tract defects in Fgf15 mutants, the conservation of enhancers in the hindbrain/spinal cord and pharyngeal epithelia suggests that human FGF19 (ortholog of Fgf15) is involved in early development and the distribution of cardiac neural crest cells and is one of the candidate genes for congenital heart defects.

  11. Comparison between (99m)Tc-diphosphonate imaging and MRI with late gadolinium enhancement in evaluating cardiac involvement in patients with transthyretin familial amyloid polyneuropathy.

    PubMed

    Minutoli, Fabio; Di Bella, Gianluca; Mazzeo, Anna; Donato, Rocco; Russo, Massimo; Scribano, Emanuele; Baldari, Sergio

    2013-03-01

    Cardiac involvement is not rare in systemic amyloidosis and is associated with poor prognosis. Both (99m)Tc-diphosphonate imaging and cardiac MRI with late gadolinium enhancement are considered valuable tools in revealing amyloid deposition in the myocardium; however, to our knowledge, no comparative study between the two techniques exists. We compared findings of these two techniques in patients with transthyretin-familial amyloid polyneuropathy (FAP). Eighteen patients with transthyretin-FAP underwent (99m)Tc-diphosphonate imaging and MRI with late gadolinium enhancement. Images were visually evaluated by independent readers to determine the presence of radiotracer accumulation or late gadolinium enhancement-positive areas at the level of cardiac chambers. Interobserver agreement ranged from moderate to very good for (99m)Tc-diphosphonate imaging findings and was very good for findings of MRI with late gadolinium enhancement. Left ventricle (LV) radiotracer uptake was found in 10 of 18 patients, whereas LV late gadolinium enhancement-positive areas were found in eight of 18 patients (χ(2) = 0.9; p = 0.343). One hundred fifty-nine LV segments showed (99m)Tc-diphosphonate accumulation, and 57 LV segments were late gadolinium enhancement positive (p < 0.0001). Radiotracer uptake was found in the right ventricle (RV) in eight patients and in both atria in five patients, whereas MRI showed that RV was involved in three patients and both atria in six patients; the differences were not statistically significant (RV, p = 0.07; atria, p = 1). Intermodality agreement between (99m)Tc-diphosphonate imaging and MRI ranged from fair to good. Our study shows that, although (99m)Tc-diphosphonate imaging and MRI with late gadolinium enhancement have similar capabilities to identify patients with myocardial amyloid deposition, cardiac amyloid infiltration burden can be significantly underestimated by visual analysis of MRI with late gadolinium enhancement compared with (99m

  12. Noncanonical EF-hand motif strategically delays Ca2+ buffering to enhance cardiac performance

    PubMed Central

    Wang, Wang; Barnabei, Matthew S; Asp, Michelle L; Heinis, Frazer I; Arden, Erik; Davis, Jennifer; Braunlin, Elizabeth; Li, Qi; Davis, Jonathan P; Potter, James D; Metzger, Joseph M

    2013-01-01

    EF-hand proteins are ubiquitous in cell signaling. Parvalbumin (Parv), the archetypal EF-hand protein, is a high-affinity Ca2+ buffer in many biological systems. Given the centrality of Ca2+ signaling in health and disease, EF-hand motifs designed to have new biological activities may have widespread utility. Here, an EF-hand motif substitution that had been presumed to destroy EF-hand function, that of glutamine for glutamate at position 12 of the second cation binding loop domain of Parv (ParvE101Q), markedly inverted relative cation affinities: Mg2+ affinity increased, whereas Ca2+ affinity decreased, forming a new ultra-delayed Ca2+ buffer with favorable properties for promoting cardiac relaxation. In therapeutic testing, expression of ParvE101Q fully reversed the severe myocyte intrinsic contractile defect inherent to expression of native Parv and corrected abnormal myocardial relaxation in diastolic dysfunction disease models in vitro and in vivo. Strategic design of new EF-hand motif domains to modulate intracellular Ca2+ signaling could benefit many biological systems with abnormal Ca2+ handling, including the diseased heart. PMID:23396207

  13. Endogenous hydrogen peroxide in paraventricular nucleus mediates sympathetic activation and enhanced cardiac sympathetic afferent reflex in renovascular hypertensive rats.

    PubMed

    Xu, Yao; Gao, Qing; Gan, Xian-Bing; Chen, Lei; Zhang, Lei; Zhu, Guo-Qing; Gao, Xing-Ya

    2011-12-01

    An enhancement of the cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic activation in renovascular hypertension. Angiotensin II in the paraventricular nucleus (PVN) augments the CSAR and increases sympathetic outflow and blood pressure. The present study aimed to determine whether endogenous hydrogen peroxide in the PVN mediated the enhanced CSAR, sympathetic activity and the effects of angiotensin II in the PVN in renovascular hypertension induced by the two-kidney, one-clip method (2K1C) in rats. At the end of the fourth week, the rats underwent sino-aortic and vagal denervation under general anaesthesia with urethane and α-chloralose. Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin. Microinjection of polyethylene glycol-catalase (PEG-CAT), an analogue of endogenous catalase, into the PVN decreased the RSNA and MAP and abolished the CSAR in both sham-operated and 2K1C rats. Microinjection into the PVN of the catalase inhibitor, aminotriazole, increased the RSNA and MAP and enhanced the CSAR. The effects of PEG-CAT or aminotriazole were greater in 2K1C rats than in sham-operated animals. The effects of angiotensin II in the PVN were abolished by pretreatment with PEG-CAT in both sham-operated and 2K1C rats; however, aminotriazole failed to potentiate the effects of angiotensin II. The catalase activity was decreased but the H(2)O(2) levels were increased in the PVN of 2K1C rats. These results indicate that endogenous H(2)O(2) in the PVN not only mediates the enhanced sympathetic activity and CSAR, but also the effects of angiotensin II in the PVN in renovascular hypertensive rats.

  14. Alzheimer's: From Caring to Commitment

    MedlinePlus

    ... Current Issue Past Issues Home Current issue contents Alzheimer's: From Caring to Commitment From Caring to Commitment ... Caring to Commitment During her sister’s battle with Alzheimer’s, Anne Murphy stayed by her side and continues ...

  15. Contrast-enhanced cardiac MRI before coronary artery bypass surgery: impact of myocardial scar extent on bypass flow.

    PubMed

    Hunold, Peter; Massoudy, Parwis; Boehm, Claudia; Schlosser, Thomas; Nassenstein, Kai; Knipp, Stephan; Eggebrecht, Holger; Thielmann, Matthias; Erbel, Raimund; Jakob, Heinz; Barkhausen, Jörg

    2008-12-01

    The aim of the study was to relate the extent of myocardial late gadolinium enhancement (LGE) in cardiac MRI to intraoperative graft flow in patients undergoing coronary artery bypass graft (CABG) surgery. Thirty-three CAD patients underwent LGE MRI before surgery using an inversion-recovery GRE sequence (turboFLASH). Intraoperative graft flow in Doppler ultrasonography was compared with the scar extent in each coronary vessel territory. One hundred and fourteen grafts were established supplying 86 of the 99 vessel territories. A significant negative correlation was found between scar extent and graft flow (r = -0.4, p < 0.0001). Flow in grafts to territories with no or small subendocardial scar was significantly higher than in grafts to territories with broad nontransmural or transmural scar (75 +/- 39 vs. 38 +/- 26 cc min(-1); p < 0.0001). In summary, the extent of myocardial scar as defined by contrast-enhanced MRI predicts coronary bypass graft flow. Beyond the probability of functional recovery, preoperative MRI might add value to surgery planning by predicting midterm bypass graft patency.

  16. Prognostic Implications of Left Ventricular Scar Determined by Late Gadolinium Enhanced Cardiac Magnetic Resonance in Patients With Atrial Fibrillation.

    PubMed

    Suksaranjit, Promporn; McGann, Christopher J; Akoum, Nazem; Biskupiak, Joseph; Stoddard, Gregory J; Kholmovski, Eugene G; Navaravong, Leenhapong; Rassa, Allen; Bieging, Erik; Chang, Lowell; Haider, Imran; Marrouche, Nassir F; Wilson, Brent D

    2016-10-01

    Left ventricular (LV) scar identified by late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR) is associated with adverse outcomes in coronary artery disease and cardiomyopathies. We sought to determine the prognostic significance of LV-LGE in atrial fibrillation (AF). We studied 778 consecutive patients referred for radiofrequency ablation of AF who underwent CMR. Patients with coronary artery disease, previous myocardial infarction, or hypertrophic or dilated cardiomyopathy were excluded. The end points of interest were major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of cardiovascular death, myocardial infarction, and ischemic stroke/transient ischemic attack. Of the 754 patients who met the inclusion criteria, 60% were men with an average age of 64 years. Most (87%) had a normal LV ejection fraction of ≥55%. LV-LGE was found in 46 patients (6%). There were 32 MACCE over the mean follow-up period of 55 months. The MACCE rate was higher for patients with LV-LGE (13.0% vs 3.7%; p = 0.002). In multivariate analysis, CHA2DS2-VASc score (hazard ratio [HR] 1.36, 95% CI 1.05 to 1.76), the presence of LV-LGE (HR 3.21, 95% CI 1.31 to 7.88), and the LV-LGE extent (HR 1.43, 95% CI 1.15 to 1.78) were independent predictors of MACCE. In addition, the presence of LV-LGE was an independent predictor for ischemic stroke/transient ischemic attack (HR 3.61, 95% CI 1.18 to 11.01) after adjusting for CHA2DS2-VASc score. In conclusion, the presence and extent of LV scar identified by LGE-CMR were independent predictors of MACCE in patients with AF. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells

    PubMed Central

    Zhu, Jing-jing; Zhang, Xin-xin; Miao, Yun-qiu; He, Shu-fang; Tian, Dan-mei; Yao, Xin-sheng; Tang, Jin-shan; Gan, Yong

    2017-01-01

    Acetylthevetin B (ATB), a cardiac glycoside from the seed of Thevetia peruviana (Pers) K Schum (yellow oleander), exhibits not only antitumor activity but also potential cardiac toxicity. In the present study, we attempted to enhance its antitumor action and decrease its adverse effects via chitosan-Pluronic P123 (CP) micelle encapsulation. Two ATB-loaded CP micelles (ATB-CP1, ATB-CP2) were prepared using an emulsion/solvent evaporation technique. They were spherical in shape with a particle size of 40–50 nm, showed a neutral zeta potential, and had acceptable encapsulation efficiency (>90%). Compared to the free ATB (IC50=2.94 μmol/L), ATB-loaded CP micelles exerted much stronger cytotoxicity against human lung cancer A549 cells with lower IC50 values (0.76 and 1.44 μmol/L for ATB-CP1 and ATB-CP2, respectively). After administration of a single dose in mice, the accumulation of ATB-loaded CP1 micelles in the tumor and lungs, respectively, was 15.31-fold and 9.49-fold as high as that of free ATB. A549 xenograft tumor mice treated with ATB-loaded CP1 micelles for 21 d showed the smallest tumor volume (one-fourth of that in the control group) and the highest inhibition rate (85.6%) among all the treatment groups. After 21-d treatment, no significant pathological changes were observed in hearts and other main tissues. In summary, ATB may serve as a promising antitumor chemotherapeutic agent for lung cancer, and its antitumor efficacy was significantly improved by CP micelles, with lower adverse effects. PMID:27917871

  18. Enhancing Predictive Accuracy of Cardiac Autonomic Neuropathy Using Blood Biochemistry Features and Iterative Multitier Ensembles.

    PubMed

    Abawajy, Jemal; Kelarev, Andrei; Chowdhury, Morshed U; Jelinek, Herbert F

    2016-01-01

    Blood biochemistry attributes form an important class of tests, routinely collected several times per year for many patients with diabetes. The objective of this study is to investigate the role of blood biochemistry for improving the predictive accuracy of the diagnosis of cardiac autonomic neuropathy (CAN) progression. Blood biochemistry contributes to CAN, and so it is a causative factor that can provide additional power for the diagnosis of CAN especially in the absence of a complete set of Ewing tests. We introduce automated iterative multitier ensembles (AIME) and investigate their performance in comparison to base classifiers and standard ensemble classifiers for blood biochemistry attributes. AIME incorporate diverse ensembles into several tiers simultaneously and combine them into one automatically generated integrated system so that one ensemble acts as an integral part of another ensemble. We carried out extensive experimental analysis using large datasets from the diabetes screening research initiative (DiScRi) project. The results of our experiments show that several blood biochemistry attributes can be used to supplement the Ewing battery for the detection of CAN in situations where one or more of the Ewing tests cannot be completed because of the individual difficulties faced by each patient in performing the tests. The results show that AIME provide higher accuracy as a multitier CAN classification paradigm. The best predictive accuracy of 99.57% has been obtained by the AIME combining decorate on top tier with bagging on middle tier based on random forest. Practitioners can use these findings to increase the accuracy of CAN diagnosis.

  19. Calcifications of the Thoracic Aorta on Extended Non-Contrast-Enhanced Cardiac CT

    PubMed Central

    Craiem, Damian; Chironi, Gilles; Casciaro, Mariano E.; Graf, Sebastian; Simon, Alain

    2014-01-01

    Background The presence of calcified atherosclerosis in different vascular beds has been associated with a higher risk of mortality. Thoracic aorta calcium (TAC) can be assessed from computed tomography (CT) scans, originally aimed at coronary artery calcium (CAC) assessment. CAC screening improves cardiovascular risk prediction, beyond standard risk assessment, whereas TAC performance remains controversial. However, the curvilinear portion of the thoracic aorta (TA), that includes the aortic arch, is systematically excluded from TAC analysis. We investigated the prevalence and spatial distribution of TAC all along the TA, to see how those segments that remain invisible in standard TA evaluation were affected. Methods and Results A total of 970 patients (77% men) underwent extended non-contrast cardiac CT scans including the aortic arch. An automated algorithm was designed to extract the vessel centerline and to estimate the vessel diameter in perpendicular planes. Then, calcifications were quantified using the Agatston score and associated with the corresponding thoracic aorta segment. The aortic arch and the proximal descending aorta, “invisible” in routine CAC screening, appeared as two vulnerable sites concentrating 60% of almost 11000 calcifications. The aortic arch was the most affected segment per cm length. Using the extended measurement method, TAC prevalence doubled from 31% to 64%, meaning that 52% of patients would escape detection with a standard scan. In a stratified analysis for CAC and/or TAC assessment, 111 subjects (46% women) were exclusively identified with the enlarged scan. Conclusions Calcium screening in the TA revealed that the aortic arch and the proximal descending aorta, hidden in standard TA evaluations, concentrated most of the calcifications. Middle-aged women were more prone to have calcifications in those hidden portions and became candidates for reclassification. PMID:25302677

  20. Estimating Commit Sizes Efficiently

    NASA Astrophysics Data System (ADS)

    Hofmann, Philipp; Riehle, Dirk

    The quantitative analysis of software projects can provide insights that let us better understand open source and other software development projects. An important variable used in the analysis of software projects is the amount of work being contributed, the commit size. Unfortunately, post-facto, the commit size can only be estimated, not measured. This paper presents several algorithms for estimating the commit size. Our performance evaluation shows that simple, straightforward heuristics are superior to the more complex text-analysis-based algorithms. Not only are the heuristics significantly faster to compute, they also deliver more accurate results when estimating commit sizes. Based on this experience, we design and present an algorithm that improves on the heuristics, can be computed equally fast, and is more accurate than any of the prior approaches.

  1. Autoantibodies enhance agonist action and binding to cardiac muscarinic receptors in chronic Chagas' disease.

    PubMed

    Hernandez, Ciria C; Nascimento, Jose H; Chaves, Elen A; Costa, Patricia C; Masuda, Masako O; Kurtenbach, Eleonora; Campos DE Carvalho, Antonio C; Gimenez, Luis E

    2008-01-01

    Chronic Chagasic patient immunoglobulins (CChP-IgGs) recognize an acidic amino acid cluster at the second extracellular loop (el2) of cardiac M(2)-muscarinic acetylcholine receptors (M(2)AChRs). These residues correspond to a common binding site for various allosteric agents. We characterized the nature of the M(2)AChR/CChP-IgG interaction in functional and radioligand binding experiments applying the same mainstream strategies previously used for the characterization of other allosteric agents. Dose-response curves of acetylcholine effect on heart rate were constructed with data from isolated heart experiments in the presence of CChP or normal blood donor (NBD) sera. In these experiments, CChP sera but not NBD sera increased the efficacy of agonist action by augmenting the onset of bradyarrhythmias and inducing a Hill slope of 2.5. This effect was blocked by gallamine, an M(2)AChR allosteric antagonist. Correspondingly, CChP-IgGs increased acetylcholine affinity twofold and showed negative cooperativity for [(3)H]-N-methyl scopolamine ([(3)H]-NMS) in allosterism binding assays. A peptide corresponding to the M(2)AChR-el2 blocked this effect. Furthermore, dissociation assays showed that the effect of gallamine on the [(3)H]-NMS off-rate was reverted by CChP-IgGs. Finally, concentration-effect curves for the allosteric delay of W84 on [(3)H]-NMS dissociation right shifted from an IC(50) of 33 nmol/L to 78 nmol/L, 992 nmol/L, and 1670 nmol/L in the presence of 6.7 x 10(- 8), 1.33 x 10(- 7), and 2.0 x 10(- 7) mol/L of anti-el2 affinity-purified CChP-IgGs. Taken together, these findings confirmed a competitive interplay of these ligands at the common allosteric site and revealed the novel allosteric nature of the interaction of CChP-IgGs at the M(2)AChRs as a positive cooperativity effect on acetylcholine action.

  2. Autoantibodies Enhance Agonist Action and Binding to Cardiac Muscarinic Receptors in Chronic Chagas’ Disease

    PubMed Central

    Hernández, Ciria C.; Nascimento, José H.; Chaves, Elen A.; Costa, Patrícia C.; Masuda, Masako O.; Kurtenbach, Eleonora; Campos de Carvalho, Antônio C.; Giménez, Luis E.

    2009-01-01

    Chronic Chagasic patient immunoglobulins (CChP-IgGs) recognize an acidic amino acid cluster at the second extracellular loop (el2) of cardiac M2-muscarinic acetylcholine receptors (M2AChRs). These residues correspond to a common binding site for various allosteric agents. We characterized the nature of the M2AChR/CChP-IgG interaction in functional and radioligand binding experiments applying the same mainstream strategies previously used for the characterization of other allosteric agents. Dose-response curves of acetylcholine effect on heart rate were constructed with data from isolated heart experiments in the presence of CChP or normal blood donor (NBD) sera. In these experiments, CChP sera but not NBD sera increased the efficacy of agonist action by augmenting the onset of bradyarrhythmias and inducing a Hill slope of 2.5. This effect was blocked by gallamine, an M2AChR allosteric antagonist. Correspondingly, CChP-IgGs increased acetylcholine affinity twofold and showed negative cooperativity for [3H]-N-methyl scopolamine ([3H]-NMS) in allosterism binding assays. A peptide corresponding to the M2AChR-el2 blocked this effect. Furthermore, dissociation assays showed that the effect of gallamine on the [3H]-NMS off-rate was reverted by CChP-IgGs. Finally, concentration-effect curves for the allosteric delay of W84 on [3H]-NMS dissociation right shifted from an IC50 of 33 nmol/L to 78 nmol/L, 992 nmol/L, and 1670 nmol/L in the presence of 6.7 × 10−8, 1.33 × 10−7, and 2.0 × 10−7 mol/L of anti-el2 affinity-purified CChP-IgGs. Taken together, these findings confirmed a competitive interplay of these ligands at the common allosteric site and revealed the novel allosteric nature of the interaction of CChP-IgGs at the M2AChRs as a positive cooperativity effect on acetylcholine action. PMID:18702010

  3. Hypoxic Preconditioning Enhances the Benefit of Cardiac Progenitor-Cell Therapy for Treatment of Myocardial Infarction by Inducing CXCR4 Expression

    PubMed Central

    Tang, Yao Liang; Zhu, Wuqiang; Cheng, Min; Chen, Lijuan; Zhang, John; Sun, Tao; Kishore, Raj; Phillips, M. Ian; Losordo, Douglas W.; Qin, Gangjian

    2009-01-01

    Myocardial infarction (MI) rapidly depletes the endogenous cardiac progenitor-cell pool, and the inefficient recruitment of exogenously administered progenitor cells limits the effectiveness of cardiac-cell therapy. Recent reports indicate that interactions between the CXC chemokine stromal-cell–derived factor 1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) critically mediate the ischemia-induced recruitment of bone-marrow—derived circulating stem/progenitor cells, but the expression of CXCR4 in cardiac progenitor cells is very low. Here, we studied the influence of hypoxia on CXCR4 expression in cardiac progenitor cells, on the recruitment of intravenously administered cells to ischemic heart tissue, and on the preservation of heart function in a murine MI model. We found that hypoxic preconditioning increased CXCR4 expression in cardiosphere-derived, Lin−/c-kit+ progenitor (CLK) cells and markedly augmented CLK-cell migration (in vitro) and recruitment (in vivo) to the ischemic myocardium. Four weeks after surgically induced MI, infarct size and heart function were significantly better in mice administered hypoxia-preconditioned CLK cells than in mice treated with cells cultured under normoxic conditions. Furthermore, these effects were largely abolished by the addition of a CXCR4 inhibitor, indicating that the benefits of hypoxic preconditioning are mediated by the SDF-1/CXCR4 axis, and that therapies targeting this axis may enhance cardiac-progenitor-cell—based regenerative therapy. PMID:19407239

  4. Committed dis(s)idents: participation in radical collective action fosters disidentification with the broader in-group but enhances political identification.

    PubMed

    Becker, Julia C; Tausch, Nicole; Spears, Russell; Christ, Oliver

    2011-08-01

    The present research examined the hypothesis that participation in radical, but not moderate, action results in disidentification from the broader in-group. Study 1 (N = 98) was a longitudinal study conducted in the context of student protests against tuition fees in Germany and confirmed that participation in radical collective action results in disidentification with the broader in-group (students) whereas participation in moderate collective action does not. Both types of action increased politicized identification. Study 2 (N = 175) manipulated the normativeness of different types of imagined collective actions in the same context and replicated this disidentification effect for radical actions, but only when this action mismatched the broader in-group's norms. This study also indicated that these effects were partially mediated by perceived lack of solidarity and perceived lack of commitment to the cause among the broader in-group. The implications of these findings for understanding radicalization within social movements are discussed.

  5. Alterations in action potential profile enhance excitation-contraction coupling in rat cardiac myocytes

    PubMed Central

    Sah, Rajan; Ramirez, Rafael J; Kaprielian, Roger; Backx, Peter H

    2001-01-01

    Action potential (AP) prolongation typically occurs in heart disease due to reductions in transient outward potassium currents (Ito), and is associated with increased Ca2+ transients. We investigated the underlying mechanisms responsible for enhanced Ca2+ transients in normal isolated rat ventricular myocytes in response to the AP changes that occur following myocardial infarction. Normal myocytes stimulated with a train of long post-myocardial infarction (MI) APs showed a 2.2-fold elevation of the peak Ca2+ transient and a 2.7-fold augmentation of fractional cell shortening, relative to myocytes stimulated with a short control AP. The steady-state Ca2+ load of the sarcoplasmic reticulum (SR) was increased 2.0-fold when myocytes were stimulated with trains of long post-MI APs (111 ± 21.6 μmol l−1) compared with short control APs (56 ± 7.2 μmol l−1). Under conditions of equal SR Ca2+ load, long post-MI APs still resulted in a 1.7-fold increase in peak [Ca2+]i and a 3.8-fold increase in fractional cell shortening relative to short control APs, establishing that changes in the triggering of SR Ca2+ release are largely responsible for elevated Ca2+ transients following AP prolongation. Fractional SR Ca2+ release calculated from the measured SR Ca2+ load and the integrated SR Ca2+ fluxes was 24 ± 3 and 11 ± 2 % following post-MI and control APs, respectively. The fractional release (FR) of Ca2+ from the SR divided by the integrated L-type Ca2+ flux (FR/∫FCa,L) was increased 1.2-fold by post-MI APs compared with control APs. Similar increases in excitation-contraction (E-C) coupling gains were observed establishing enhanced E-C coupling efficiency. Our findings demonstrate that AP prolongation alone can markedly enhance E-C coupling in normal myocytes through increases in the L-type Ca2+ current (ICa,L) trigger combined with modest enhancements in Ca2+ release efficiency. We propose that such changes in AP profile in diseased myocardium may contribute

  6. Embryonic stem cell-based cardiopatches improve cardiac function in infarcted rats.

    PubMed

    Vallée, Jean-Paul; Hauwel, Mathieu; Lepetit-Coiffé, Matthieu; Bei, Wang; Montet-Abou, Karin; Meda, Paolo; Gardier, Stephany; Zammaretti, Prisca; Kraehenbuehl, Thomas P; Herrmann, Francois; Hubbell, Jeffrey A; Jaconi, Marisa E

    2012-03-01

    Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.

  7. Mesenchymal Stem Cells with eNOS Over-Expression Enhance Cardiac Repair in Rats with Myocardial Infarction.

    PubMed

    Chen, Leilei; Zhang, Yuan; Tao, Liangliang; Yang, Zhijian; Wang, Liansheng

    2017-02-01

    Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic option for patients with acute myocardial infarction. We show here that the ectopic overexpression of endothelial nitric oxide synthases (eNOS), an endothelial form of NOS, could enhance the ability of MSCs in treating ischemic heart damage after the occlusion of the coronary artery. Adenoviral delivery of human eNOS gene into mouse bone marrow-derived MSCs (BM-MSCs) conferred resistance to oxygen glucose deprivation (OGD)-induced cell death in vitro, and elevated the bioavailability of nitric oxide when injected into the myocardium in vivo. In a rat model of acute myocardial infarction, the transplantation of eNOS-overexpressing BM-MSCs significantly reduced myocardial infarct size, corrected hemodynamic parameters and increased capillary density. We also found that the synergistic effects were consistently better than either treatment alone. These findings reveal a positive role of elevated eNOS expression in cardiac repair, and suggest the combination of eNOS and MSC transplant therapy as a potential approach for treating myocardial infarction.

  8. Diallyl trisulfide and diallyl disulfide ameliorate cardiac dysfunction by suppressing apoptotic and enhancing survival pathways in experimental diabetic rats.

    PubMed

    Huang, Yao-Te; Yao, Chun-Hsu; Way, Chia-Li; Lee, Kung-Wei; Tsai, Cheng-Yen; Ou, Hsiu-Chung; Kuo, Wei-Wen

    2013-02-01

    Cardiovascular disease is one of the major causes of mortality in diabetic patients. Mounting studies have shown that garlic exhibits, possibly through its antioxidant potential, diverse biological activities. In this study, we investigated the alleviating effects of garlic oil (GO) and its two major components, diallyl disulfide (DADS) and diallyl trisulfide (DATS), on diabetic cardiomyopathy in rats. Physiological cardiac parameters were obtained using echocardiography. Apoptotic cells were evaluated using TUNEL and DAPI staining. Protein expression levels were determined using Western blotting analysis. Our findings indicated that in diabetic rat hearts significantly decreased fractional shortening percentage, increased levels of nitrotyrosine, an elevated number of TUNEL-positive cells, enhanced levels of caspase 3 expression, and decreased PI3K-Akt signaling pathway activities were observed. Furthermore, all of these alterations were reversed following both GO and DATS (or DADS) administrations through increasing PI3K-Akt signaling pathway activities and inhibiting both the death receptor-dependent and the mitochondria-dependent apoptotic pathways. In conclusion, this study shows that DATS and DADS, with the efficacy order DATS > DADS, have the therapeutic potential for ameliorating diabetic cardiomyopathy. Furthermore, the therapeutic effects of GO on diabetic cardiomyopathy should be mainly from DATS and DADS.

  9. Object identification accuracy under ultrasound enhanced virtual reality for minimally invasive cardiac surgery

    NASA Astrophysics Data System (ADS)

    Wiles, Andrew D.; Moore, John; Linte, Cristian A.; Wedlake, Christopher; Ahmad, Anis; Peters, Terry M.

    2008-03-01

    A 2D ultrasound enhanced virtual reality surgical guidance system has been under development for some time in our lab. The new surgical guidance platform has been shown to be effective in both the laboratory and clinical settings, however, the accuracy of the tracked 2D ultrasound has not been investigated in detail in terms of the applications for which we intend to use it (i.e., mitral valve replacement and atrial septal defect closure). This work focuses on the development of an accuracy assessment protocol specific to the assessment of the calibration methods used to determine the rigid transformation between the ultrasound image and the tracked sensor. Specifically, we test a Z-bar phantom calibration method and a phantomless calibration method and compared the accuracy of tracking ultrasound images from neuro, transesophageal, intracardiac and laparoscopic ultrasound transducers. This work provides a fundamental quantitative description of the image-guided accuracy that can be obtained with this new surgical guidance system.

  10. Cardiac gated ventilation

    SciTech Connect

    Hanson, C.W. III; Hoffman, E.A.

    1995-12-31

    There are several theoretic advantages to synchronizing positive pressure breaths with the cardiac cycle, including the potential for improving distribution of pulmonary and myocardial blood flow and enhancing cardiac output. The authors evaluated the effects of synchronizing respiration to the cardiac cycle using a programmable ventilator and electron beam CT (EBCT) scanning. The hearts of anesthetized dogs were imaged during cardiac gated respiration with a 50 msec scan aperture. Multi slice, short axis, dynamic image data sets spanning the apex to base of the left ventricle were evaluated to determine the volume of the left ventricular chamber at end-diastole and end-systole during apnea, systolic and diastolic cardiac gating. The authors observed an increase in cardiac output of up to 30% with inspiration gated to the systolic phase of the cardiac cycle in a non-failing model of the heart.

  11. A driving commitment.

    PubMed

    McGuire, S

    1995-01-01

    Italy's statistics institute, ISTAT, has announced in its annual report that the number of AIDS deaths is threatening to pass the number of deaths from traffic accidents. According to ISTAT, 4,370 Italians died from AIDS in 1994, while some 6,000 died on the country's roads. The report states that AIDS is the second leading cause of death after road accidents for young males, aged 18 to 29. Three years ago, Americans made a commitment to safer automobile engineering, better highway design, and increased penalties for drunken driving; consequently reducing both the total numbers and the per-capita incidence of traffic deaths, in spite of much more driving. A similar commitment to prevention and treatment efforts could have an equally dramatic impact on the incidence of AIDS and HIV transmission in the United States. However, that commitment will not likely emerge anytime soon given Congress's current plans for the budget.

  12. Commitment to Health Scale.

    PubMed

    Kelly, Cynthia W

    2005-01-01

    The Commitment to Health Scale (CHS) was developed to predict likelihood of clients being able to permanently adopt new health-promoting behaviors. Commitment is based on the association between starting new health behaviors and long-term performance of those behaviors. The CHS evolved from an examination of Prochaska and DiClemente's Stages of Change Algorithm, Decisional Balance Scale, and Strong and Weak Principle (Velicer, Rossi, Prochaska, & DiClemente, 1996). Scale items were assessed by classical and Rasch measurement methods. The research was performed in three separate studies at various locations in the United States and included approximately 1100 subjects. A new unidimensional variable was identified called Commitment to Health. Internal consistency reliability of the scale was .94 (Cronbach's alpha). External validity and reliability were assessed based on expected and observed ordering and between known groups. Scale scores predicted self-reported health behaviors and body mass index.

  13. Association of aortic wall thickness on contrast-enhanced chest CT with major cerebro-cardiac events.

    PubMed

    Tresoldi, Silvia; Di Leo, Giovanni; Zoffoli, Elena; Munari, Alice; Primolevo, Alessandra; Cornalba, Gianpaolo; Sardanelli, Francesco

    2014-11-01

    There is a significant association between aortic atherosclerosis and previous major cardiovascular events. Particularly, thoracic aortic atherosclerosis is closely related to the degree of coronary and carotid artery disease. Thus, there is a rationale for screening the thoracic aorta in patients who undergo a chest computed tomography (CT) for any clinical question, in order to detect patients at increased risk of cerebro-cardiovascular (CCV) events. To estimate the association between either thoracic aortic wall thickness (AWT) or aortic total calcium score (ATCS) and CCV events. One hundred and forty-eight non-cardiac patients (78 men; 67 ± 12 years) underwent chest contrast-enhanced multidetector CT (MDCT). The AWT was measured at the level of the left atrium (AWTref) and at the maximum AWT (AWTmax). Correlation with clinical CCV patients' history was estimated. The value of AWTmax and of a semi-quantitative ATCS as a marker for CCV events was assessed using receiver-operating characteristic curve (ROC) analysis and multivariate regression analysis. Out of 148 patients, 59% reported sedentary lifestyle, 44% hypertension, 32% smoking, 23% hypercholesterolemia, 13% family history of cardiac disease, 12% diabetes, and 10% BMI ≥ 30 kg/m(2); 9% reported myocardial infarction, 8% aortic aneurism, 8% myocardial revascularization, and 2% ischemic stroke. Twenty-six percent of patients had a medium-to-high ATCS. Both AWTmax and AWTref correlated with hypertension and age (P < 0.002). At the ROC analysis, a 4.8 mm threshold was associated to a 90% specificity and an odds ratio of 6.3 (AUC = 0.735). Assuming as threshold the AWTmax median value (4.3 mm) of patients who suffered from at least one CCV event in their history, a negative predictive value of 90%, a RR of 3.6 and an OR of 6.3 were found. At the multivariate regression analysis, AWTmax was the only independent variable associated to the frequency of CCV events. Patients with increased thoracic

  14. Extracellular Hb Enhances Cardiac Toxicity in Endotoxemic Guinea Pigs: Protective Role of Haptoglobin

    PubMed Central

    Baek, Jin Hyen; Zhang, Xiaoyuan; Williams, Matthew C.; Schaer, Dominik J.; Buehler, Paul W.; D’Agnillo, Felice

    2014-01-01

    Endotoxemia plays a major causative role in the myocardial injury and dysfunction associated with sepsis. Extracellular hemoglobin (Hb) has been shown to enhance the pathophysiology of endotoxemia. In the present study, we examined the myocardial pathophysiology in guinea pigs infused with lipopolysaccharide (LPS), a Gram-negative bacterial endotoxin, and purified Hb. We also examined whether the administration of the Hb scavenger haptoglobin (Hp) could protect against the effects observed. Here, we show that Hb infusion following LPS administration, but not either insult alone, increased myocardial iron deposition, heme oxygenase-1 expression, phagocyte activation and infiltration, as well as oxidative DNA damage and apoptosis assessed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunostaining, respectively. Co-administration of Hp significantly attenuated the myocardial events induced by the combination of LPS and Hb. These findings may have relevant therapeutic implications for the management of sepsis during concomitant disease or clinical interventions associated with the increased co-exposures to LPS and Hb, such as trauma, surgery or massive blood transfusions. PMID:24691127

  15. Technology enhanced practice for patients with chronic cardiac disease Home Implementation and Evaluation

    PubMed Central

    Brennan, Patricia Flatley; Casper, Gail R.; Burke, Laura J.; Johnson, Kathy A.; Brown, Roger; Valdez, Rupa S.; Sebern, Marge; Perez, Oscar A.; Sturgeon, Billie

    2010-01-01

    Objective This 3-year field experiment engaged 60 nurses and 282 patients in the design and evaluation of an innovative home care nursing model, technology enhanced practice (TEP). Method Nurses in the TEP conditions augmented usual care with a web-based resource (HeartCareII) that provided patients with self-management information, self-monitoring tools, and messaging services. Results Patients exposed to TEP demonstrated better quality of life and self-management of chronic heart disease during the first four weeks and were no more likely than patients in usual care to make unplanned visits to a clinician or the hospital. Both groups demonstrated the same long term symptom management and health status achievements. Conclusion This project provides new evidence that it is possible to purposefully create patient-tailored web resources within a hospital portal; that it is hard for nurses to modify their practice routines even with a highly-tailored web resource, and that the benefits of this intervention are more discernable in the early post-discharge stages of care. PMID:21092830

  16. Adenylyl cyclase type 6 overexpression selectively enhances beta-adrenergic and prostacyclin receptor-mediated inhibition of cardiac fibroblast function because of colocalization in lipid rafts.

    PubMed

    Liu, Xiaoqiu; Thangavel, Muthusamy; Sun, Shu Qiang; Kaminsky, Joseph; Mahautmr, Penden; Stitham, Jeremiah; Hwa, John; Ostrom, Rennolds S

    2008-06-01

    Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor beta and inhibited by agents that elevate 3',5'-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. The present study sought to define the localization of key G protein-coupled receptors with adenylyl cyclase type 6 (AC6) in lipid rafts of rat cardiac fibroblasts and to determine if this colocalization was functionally relevant. We found that cardiac fibroblasts produce cAMP in response to agonists for beta-adrenergic (isoproterenol), prostaglandin EP2 (butaprost), adenosine (adenosine-5'-N-ethylcarboxamide, NECA), and prostacyclin (beraprost) receptors. Overexpression of AC6 increased cAMP production stimulated by isoproterenol and beraprost but not by butaprost or NECA. A key function of fibroblasts is the production of collagen. Isoproterenol- and beraprostmediated inhibition of collagen synthesis was also enhanced by AC6 overexpression, while inhibition by butaprost and NECA were unaltered. Lipid raft fractions from cardiac fibroblasts contain the preponderance of beta-adrenergic receptors and AC6 but exclude EP2 receptors. While we could not determine the localization of native prostacyclin receptors, we were able to determine that epitope-tagged prostanoid IP receptors (IPR) expressed in COS7 cells did localize, in part, in lipid raft fractions. These findings indicate that IP receptors are expressed in lipid rafts and can activate raft-localized AC isoforms. AC6 is completely compartmentized in lipid raft domains where it is activated solely by coresident G protein-coupled receptors to regulate cardiac fibroblast function.

  17. Salmeterol enhances the cardiac response to gene therapy in Pompe disease.

    PubMed

    Han, Sang-Oh; Li, Songtao; Koeberl, Dwight D

    2016-05-01

    Enzyme replacement therapy (ERT) with recombinant human (rh) acid α-glucosidase (GAA) has prolonged the survival of patients. However, the paucity of cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle, where it is needed to take up rhGAA, correlated with a poor response to ERT by muscle in Pompe disease. Clenbuterol, a selective β2 receptor agonist, enhanced the CI-MPR expression in striated muscle through Igf-1 mediated muscle hypertrophy, which correlated with increased CI-MPR (also the Igf-2 receptor) expression. In this study we have evaluated 4 new drugs in GAA knockout (KO) mice in combination with an adeno-associated virus (AAV) vector encoding human GAA, 3 alternative β2 agonists and dehydroepiandrosterone (DHEA). Mice were injected with AAV2/9-CBhGAA (1E+11 vector particles) at a dose that was not effective at clearing glycogen storage from the heart. Heart GAA activity was significantly increased by either salmeterol (p<0.01) or DHEA (p<0.05), in comparison with untreated mice. Furthermore, glycogen content was reduced in the heart by treatment with DHEA (p<0.001), salmeterol (p<0.05), formoterol (p<0.01), or clenbuterol (p<0.01) in combination with the AAV vector, in comparison with untreated GAA-KO mice. Wirehang testing revealed that salmeterol and the AAV vector significantly increased performance, in comparison with the AAV vector alone (p<0.001). Similarly, salmeterol with the vector increased performance significantly more than any of the other drugs. The most effective individual drugs had no significant effect in absence of vector, in comparison with untreated mice. Thus, salmeterol should be further developed as adjunctive therapy in combination with either ERT or gene therapy for Pompe disease.

  18. Pentobarbital enhances GABAergic neurotransmission to cardiac parasympathetic neurons, which is prevented by expression of GABA(A) epsilon subunit.

    PubMed

    Irnaten, Mustapha; Walwyn, Wendy M; Wang, Jijiang; Venkatesan, Priya; Evans, Cory; Chang, Kyoung S K; Andresen, Michael C; Hales, Tim G; Mendelowitz, David

    2002-09-01

    Pentobarbital decreases the gain of the baroreceptor reflex on the order of 50%, and this blunting is caused nearly entirely by decreasing cardioinhibitory parasympathetic activity. The most likely site of action of pentobarbital is the gamma-aminobutyric acid type A (GABA(A)) receptor. The authors tested whether pentobarbital augments the inhibitory GABAergic neurotransmission to cardiac parasympathetic neurons, and whether expression of the GABA(A) epsilon subunit prevents this facilitation. The authors used a novel approach to study the effect of pentobarbital on identified cardiac parasympathetic preganglionic neurons in rat brainstem slices. The cardiac parasympathetic neurons in the nucleus ambiguus were retrogradely prelabeled with a fluorescent tracer and were visually identified for patch clamp recording. The effects of pentobarbital on spontaneous GABAergic synaptic events were tested. An adenovirus was used to express the epsilon subunit of the GABA(A) receptor in cardiac parasympathetic neurons to examine whether this transfection alters pentobarbital-mediated changes in GABAergic neurotransmission. Pentobarbital increased the duration but not the frequency or amplitude of spontaneous GABAergic currents in cardiac parasympathetic neurons. Transfection of cardiac parasympathetic neurons with the epsilon subunit of the GABA(A) receptor prevented the pentobarbital-evoked facilitation of GABAergic currents. Pentobarbital, at clinically relevant concentrations, prolongs the duration of spontaneous inhibitory postsynaptic currents that impinge on cardiac parasympathetic neurons. This action would augment the inhibition of cardiac parasympathetic neurons, reduce parasympathetic cardioinhibitory activity, and increase heart rate. Expression of the GABA(A) receptor epsilon subunit in cardiac parasympathetic neurons renders the GABA receptors insensitive to pentobarbital.

  19. Peptide-enhanced mRNA transfection in cultured mouse cardiac fibroblasts and direct reprogramming towards cardiomyocyte-like cells

    PubMed Central

    Lee, Kunwoo; Yu, Pengzhi; Lingampalli, Nithya; Kim, Hyun Jin; Tang, Richard; Murthy, Niren

    2015-01-01

    The treatment of myocardial infarction is a major challenge in medicine due to the inability of heart tissue to regenerate. Direct reprogramming of endogenous cardiac fibroblasts into functional cardiomyocytes via the delivery of transcription factor mRNAs has the potential to regenerate cardiac tissue and to treat heart failure. Even though mRNA delivery to cardiac fibroblasts has the therapeutic potential, mRNA transfection in cardiac fibroblasts has been challenging. Herein, we develop an efficient mRNA transfection in cultured mouse cardiac fibroblasts via a polyarginine-fused heart-targeting peptide and lipofectamine complex, termed C-Lipo and demonstrate the partial direct reprogramming of cardiac fibroblasts towards cardiomyocyte cells. C-Lipo enabled the mRNA-induced direct cardiac reprogramming due to its efficient transfection with low toxicity, which allowed for multiple transfections of Gata4, Mef2c, and Tbx5 (GMT) mRNAs for a period of 2 weeks. The induced cardiomyocyte-like cells had α-MHC promoter-driven GFP expression and striated cardiac muscle structure from α-actinin immunohistochemistry. GMT mRNA transfection of cultured mouse cardiac fibroblasts via C-Lipo significantly increased expression of the cardiomyocyte marker genes, Actc1, Actn2, Gja1, Hand2, and Tnnt2, after 2 weeks of transfection. Moreover, this study provides the first direct evidence that the stoichiometry of the GMT reprogramming factors influence the expression of cardiomyocyte marker genes. Our results demonstrate that mRNA delivery is a potential approach for cardiomyocyte generation. PMID:25834424

  20. Peptide-enhanced mRNA transfection in cultured mouse cardiac fibroblasts and direct reprogramming towards cardiomyocyte-like cells.

    PubMed

    Lee, Kunwoo; Yu, Pengzhi; Lingampalli, Nithya; Kim, Hyun Jin; Tang, Richard; Murthy, Niren

    2015-01-01

    The treatment of myocardial infarction is a major challenge in medicine due to the inability of heart tissue to regenerate. Direct reprogramming of endogenous cardiac fibroblasts into functional cardiomyocytes via the delivery of transcription factor mRNAs has the potential to regenerate cardiac tissue and to treat heart failure. Even though mRNA delivery to cardiac fibroblasts has the therapeutic potential, mRNA transfection in cardiac fibroblasts has been challenging. Herein, we develop an efficient mRNA transfection in cultured mouse cardiac fibroblasts via a polyarginine-fused heart-targeting peptide and lipofectamine complex, termed C-Lipo and demonstrate the partial direct reprogramming of cardiac fibroblasts towards cardiomyocyte cells. C-Lipo enabled the mRNA-induced direct cardiac reprogramming due to its efficient transfection with low toxicity, which allowed for multiple transfections of Gata4, Mef2c, and Tbx5 (GMT) mRNAs for a period of 2 weeks. The induced cardiomyocyte-like cells had α-MHC promoter-driven GFP expression and striated cardiac muscle structure from α-actinin immunohistochemistry. GMT mRNA transfection of cultured mouse cardiac fibroblasts via C-Lipo significantly increased expression of the cardiomyocyte marker genes, Actc1, Actn2, Gja1, Hand2, and Tnnt2, after 2 weeks of transfection. Moreover, this study provides the first direct evidence that the stoichiometry of the GMT reprogramming factors influence the expression of cardiomyocyte marker genes. Our results demonstrate that mRNA delivery is a potential approach for cardiomyocyte generation.

  1. Commitment to Peace.

    ERIC Educational Resources Information Center

    Montessori, Renilde

    1995-01-01

    This reprint from a 1985 issue of "The NAMTA Journal" discusses the ideas of Maria Montessori and Erich Fromm in relation to world peace and the role of education in promoting peace. Also examines the nature of conflict, war, and peace, and the need to commit oneself to peace. (MDM)

  2. Committed Sport Event Volunteers

    ERIC Educational Resources Information Center

    Han, Keunsu; Quarterman, Jerome; Strigas, Ethan; Ha, Jaehyun; Lee, Seungbum

    2013-01-01

    The purpose of this study was to investigate the relationships among selected demographic characteristics (income, education and age), motivation and commitment of volunteers at a sporting event. Three-hundred and five questionnaires were collected from volunteers in a marathon event and analyzed using structural equation modeling (SEM). Based on…

  3. Commitment to Peace.

    ERIC Educational Resources Information Center

    Montessori, Renilde

    1995-01-01

    This reprint from a 1985 issue of "The NAMTA Journal" discusses the ideas of Maria Montessori and Erich Fromm in relation to world peace and the role of education in promoting peace. Also examines the nature of conflict, war, and peace, and the need to commit oneself to peace. (MDM)

  4. The Vocational Commitment Index

    ERIC Educational Resources Information Center

    Weis, Susan F.; Hubbard, Constance F.

    1973-01-01

    The Index is the result of an effort made to examine all components of vocational commitment and to translate this information into an instrument which could be used to assess the relationship of an individual to a vocation.. The predictive ability of the 74-item device requires further research. (Author/AG)

  5. From controlled to committed.

    PubMed

    Hess, J C

    1996-02-01

    Most of us agree that people are our most important resource. Yet we spend a minimal amount of time learning more about human behavior, communication, and how our attitudes and behavior impact employee performance. Instead we rely on traditional methods of negative reinforcement in an attempt to control our areas of responsibility. While these methods can render some short-term success, managers and organizations that succeed during these times of change and fierce competition will be those that take the time to understand and capture the power of a committed workforce. The committed workforce is energized, not simply compliant, as a result of having basic human needs for achievement satisfied, belonging to a group, and receiving recognition for its contributions. Committed workers typically describe the manager as one who has the ability to give them a great degree of control over their area of influence. We all know that we don't change our leadership style like we change clothes. Old habits die hard. it takes a personal commitment and lots of practice to rid outselves of habits and behavior that no longer serve our departments and facilities. This commitment, however, is crucial to survival. As managers, we must cope with increasing ambiguity and uncertainty in the workplace. To survive these challenges, we must improve our interpersonal skills and ability to successfully bring out the best in others. I believe that success will continue for managers who not only increase their knowledge and technical ability, but who also inspire their workers to move forward with a collective sense of enthusiasm and purpose.

  6. Physically active lifestyle enhances vagal-cardiac function but not central autonomic neural interaction in elderly humans.

    PubMed

    Shi, Xiangrong; Schaller, Frederick A; Tierney, Nancy; Chanthavong, Patrick; Chen, Shande; Raven, Peter B; Smith, Michael L

    2008-02-01

    The cause of the age-related impairment of arterial baroreflex function remains ill-defined; moreover, it is unknown whether this impairment results from aging per se or from an inactive lifestyle associated with aging. In this study, we sought to: 1) determine whether elderly individuals who maintained an active lifestyle had an enhanced carotid baroreflex function as compared with their sedentary counterparts; and 2) determine whether this difference was due in part to altered function of the arterial baroreceptor and/or altered central modulation. Eight healthy, sedentary (SED, 68+/-2 yr) and eight physically active (ACT, 68+/-1 yr) elderly men with peak O(2) consumption 25.5+/-1.2 vs 35.7+/-2.4 ml/min/kg (P<0.01), respectively, were assessed with carotid baroreceptor (CBR) function using 5s pulses of neck pressure or suction (ranging from +40 to -80 Torr) delivered to the carotid sinus region at rest and during lower body negative pressure (LBNP) of -15 and -40 Torr. Changes in heart rate (HR) and mean arterial pressure (MAP) were assessed for CBR-HR and CBR-MAP gains, respectively. Overall CBR-HR gains in a range of approximately 120 mmHg of carotid sinus pressure were greater (P<0.01) in ACT than SED at rest and during LBNP. The derived peak CBR-HR slopes between ACT and SED at rest were -0.32+/-0.07 vs -0.11+/-0.02 bpm/mmHg (P=0.007), respectively. However, there was no statistical difference (P=0.37) in CBR-MAP gains between the groups. Neither CBR-MAP (P=0.08) nor CBR-HR (P=0.41) gain was augmented by LBNP in the elderly. Active lifestyle enhances the CBR-HR reflex sensitivity as a result of the improved vagal-cardiac function in elderly people. Aging is associated with an absence of central autonomic interaction in the control of blood pressure regardless of physical fitness.

  7. The H29D Mutation Does Not Enhance Cytosolic Ca2+ Activation of the Cardiac Ryanodine Receptor.

    PubMed

    Xiao, Zhichao; Guo, Wenting; Yuen, Siobhan M Wong King; Wang, Ruiwu; Zhang, Lin; Van Petegem, Filip; Chen, S R Wayne

    2015-01-01

    The N-terminal domain of the cardiac ryanodine receptor (RyR2) harbors a large number of naturally occurring mutations that are associated with stress-induced ventricular tachyarrhythmia and sudden death. Nearly all these disease-associated N-terminal mutations are located at domain interfaces or buried within domains. Mutations at these locations would alter domain-domain interactions or the stability/folding of domains. Recently, a novel RyR2 mutation H29D associated with ventricular arrhythmia at rest was found to enhance the activation of single RyR2 channels by diastolic levels of cytosolic Ca2+. Unlike other N-terminal disease-associated mutations, the H29D mutation is located on the surface of the N-terminal domain. It is unclear how this surface-exposed H29D mutation that does not appear to interact with other parts of the RyR2 structure could alter the intrinsic properties of the channel. Here we carried out detailed functional characterization of the RyR2-H29D mutant at the molecular and cellular levels. We found that the H29D mutation has no effect on the basal level or the Ca2+ dependent activation of [3H]ryanodine binding to RyR2, the cytosolic Ca2+ activation of single RyR2 channels, or the cytosolic Ca2+- or caffeine-induced Ca2+ release in HEK293 cells. In addition, the H29D mutation does not alter the propensity for spontaneous Ca2+ release or the thresholds for Ca2+ release activation or termination. Furthermore, the H29D mutation does not have significant impact on the thermal stability of the N-terminal region (residues 1-547) of RyR2. Collectively, our data show that the H29D mutation exerts little or no effect on the function of RyR2 or on the folding stability of the N-terminal region. Thus, our results provide no evidence that the H29D mutation enhances the cytosolic Ca2+ activation of RyR2.

  8. The H29D Mutation Does Not Enhance Cytosolic Ca2+ Activation of the Cardiac Ryanodine Receptor

    PubMed Central

    Xiao, Zhichao; Guo, Wenting; Yuen, Siobhan M. Wong King; Wang, Ruiwu; Zhang, Lin; Van Petegem, Filip; Chen, S. R. Wayne

    2015-01-01

    The N-terminal domain of the cardiac ryanodine receptor (RyR2) harbors a large number of naturally occurring mutations that are associated with stress-induced ventricular tachyarrhythmia and sudden death. Nearly all these disease-associated N-terminal mutations are located at domain interfaces or buried within domains. Mutations at these locations would alter domain-domain interactions or the stability/folding of domains. Recently, a novel RyR2 mutation H29D associated with ventricular arrhythmia at rest was found to enhance the activation of single RyR2 channels by diastolic levels of cytosolic Ca2+. Unlike other N-terminal disease-associated mutations, the H29D mutation is located on the surface of the N-terminal domain. It is unclear how this surface-exposed H29D mutation that does not appear to interact with other parts of the RyR2 structure could alter the intrinsic properties of the channel. Here we carried out detailed functional characterization of the RyR2-H29D mutant at the molecular and cellular levels. We found that the H29D mutation has no effect on the basal level or the Ca2+ dependent activation of [3H]ryanodine binding to RyR2, the cytosolic Ca2+ activation of single RyR2 channels, or the cytosolic Ca2+- or caffeine-induced Ca2+ release in HEK293 cells. In addition, the H29D mutation does not alter the propensity for spontaneous Ca2+ release or the thresholds for Ca2+ release activation or termination. Furthermore, the H29D mutation does not have significant impact on the thermal stability of the N-terminal region (residues 1–547) of RyR2. Collectively, our data show that the H29D mutation exerts little or no effect on the function of RyR2 or on the folding stability of the N-terminal region. Thus, our results provide no evidence that the H29D mutation enhances the cytosolic Ca2+ activation of RyR2. PMID:26405799

  9. Effects of endurance exercise training on heart rate variability and susceptibility to sudden cardiac death: protection is not due to enhanced cardiac vagal regulation.

    PubMed

    Billman, George E; Kukielka, Monica

    2006-03-01

    Low heart rate variability (HRV) is associated with an increased susceptibility to ventricular fibrillation (VF). Exercise training can increase HRV (an index of cardiac vagal regulation) and could, thereby, decrease the risk for VF. To test this hypothesis, a 2-min coronary occlusion was made during the last min of a 18-min submaximal exercise test in dogs with healed myocardial infarctions; 20 had VF (susceptible), and 13 did not (resistant). The dogs then received either a 10-wk exercise program (susceptible, n=9; resistant, n=8) or an equivalent sedentary period (susceptible, n=11; resistant, n=5). HRV was evaluated at rest, during exercise, and during a 2-min occlusion at rest and before and after the 10-wk period. Pretraining, the occlusion provoked significantly (P<0.01) greater increases in HR (susceptible, 54.9+/-8.3 vs. resistant, 25.0+/-6.1 beats/min) and greater reductions in HRV (susceptible, -6.3+/-0.3 vs. resistant, -2.8+/-0.8 ln ms2) in the susceptible dogs compared with the resistant animals. Similar response differences between susceptible and resistant dogs were noted during submaximal exercise. Training significantly reduced the HR and HRV responses to the occlusion (HR, 17.9+/-11.5 beats/min; HRV, -1.2+/-0.8, ln ms2) in the susceptible dogs; similar response reductions were noted during exercise. In contrast, these variables were not altered in the sedentary susceptible dogs. Posttraining, VF could no longer be induced in the susceptible dogs, whereas four sedentary susceptible dogs died during the 10-wk control period, and the remaining seven animals still had VF when tested. Atropine decreased HRV but only induced VF in one of eight trained susceptible dogs. Thus exercise training increased cardiac vagal activity, which was not solely responsible for the training-induced VF protection.

  10. Functional flexibility in women's commitment-skepticism bias.

    PubMed

    Brown, Christina M; Olkhov, Yevgeniy M

    2015-04-02

    If a woman overestimates her romantic partner's commitment, the cost to her fitness-reproduction without an investing partner-can be considerable. Error Management Theory predicts that women have an evolved bias to be skeptical of men's commitment in a relationship, which reduces the likelihood of making a costly false positive error. However, because error probabilities are inversely related, this commitment-skepticism bias simultaneously increases the likelihood of missed opportunities, or false negatives. False positives when gauging a partner's commitment are the more costly error for women, but missing an opportunity to secure a genuinely high-quality mate can also be quite costly. We predicted and found that women's mating cognitions are functionally flexible, such that women do not exhibit the commitment-skepticism bias when faced with behavioral evidence that a male partner is willing to commit (Study 1). This suggests that relationship-enhancing behaviors are one contextual cue that may lessen the bias. However, not all relationship-enhancing behaviors are equally diagnostic of a person's true commitment intent. When comparing men and women's commitment thresholds, we found that women require more behavioral evidence than men do to feel certain of their partner's commitment to them (Study 2).

  11. JS-K, a GST-activated nitric oxide donor prodrug, enhances chemo-sensitivity in renal carcinoma cells and prevents cardiac myocytes toxicity induced by Doxorubicin.

    PubMed

    Qiu, Mingning; Ke, Longzhi; Zhang, Sai; Zeng, Xin; Fang, Zesong; Liu, Jianjun

    2017-08-01

    Doxorubicin, a highly effective and widely used anthracycline antibiotic in multiple chemotherapy regimens, has been limited by its cardiotoxicity. The aim of this study is to investigate the effect of nitric oxide donor prodrug JS-K on proliferation and apoptosis in renal carcinoma cells and cardiac myocytes toxicity induced by Doxorubicin and to explore possible p53-related mechanism in renal carcinoma cells. The effect of JS-K on anti-cancer activity of Doxorubicin was investigated in renal carcinoma cells via detecting cell proliferation, cytotoxicity, cell death and apoptosis and expressions of apoptotic-related proteins. Effect of p53 on the combination of JS-K and Doxorubicin was determined using p53 inhibitor Pifithrin-α and p53 activator III. Furthermore, the effect of JS-K on cardiac myocytes toxicity of Doxorubicin was investigated in H9c2 (2-1) cardiac myocytes via measuring cell growth, cell death and apoptosis, expressions of proteins involved in apoptosis and intracellular reactive oxygen species. We demonstrated that JS-K could increase Doxorubicin-induced renal carcinoma cell growth suppression and apoptosis and could increase expressions of proteins that are involved in apoptosis. Additionally, Pifithrin-α reversed the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis; conversely, the p53 activator III exacerbated the promoting effect of JS-K on Doxorubicin-induced renal carcinoma cell apoptosis. Furthermore, JS-K protected H9c2 (2-1) cardiac myocytes against Doxorubicin-induced toxicity and decreased Doxorubicin-induced reactive oxygen species production. JS-K enhances the anti-cancer activity of Doxorubicin in renal carcinoma cells by upregulating p53 expression and prevents cardiac myocytes toxicity of Doxorubicin by decreasing oxidative stress.

  12. Complementary Prognostic Values of Stress Myocardial Perfusion and Late Gadolinium Enhancement Imaging by Cardiac Magnetic Resonance in Patients with Known or Suspected Coronary Artery Disease

    PubMed Central

    Steel, Kevin; Broderick, Ryan; Gandla, Vijay; Larose, Eric; Resnic, Frederick; Jerosch-Herold, Michael; Brown, Kenneth A.; Kwong, Raymond Y.

    2009-01-01

    BACKGROUND Recent studies have demonstrated the significant prognostic value of stress CMR myocardial perfusion imaging (CMRMPI). Apart from characterizing reversible perfusion defect (RevPD) from flow-limiting coronary stenosis, CMR late enhancement imaging (LGE) is currently the most sensitive method in detecting subendocardial infarction (MI). We therefore tested the hypothesis that, characterization of these 2 processes from coronary artery disease (CAD) by CMR can provide complementary prognostic values. Methods and Results We performed CMRMPI followed by LGE imaging on 254 patients referred with symptoms of myocardial ischemia. At a median follow up of 17 months, 49 cardiac events (MACE) occurred including 12 cardiac deaths, 16 acute myocardial infarction (MI), and 21 cardiac hospitalizations. RevPD and LGE both maintained a > 3-fold association with cardiac death or acute MI (Death/MI) when adjusted to each other and to the effects of patient age and gender (adjusted HR 3.31, P=0.02 and 3.43, P=0.01, respectively). In patients without a history of MI who had negative RevPD, LGE presence was associated with >11-fold hazards increase to Death/MI. Patients with neither RevPD nor LGE had a 98.1% negative annual event rate for Death/MI. For association with MACE, RevPD was the strongest multivariable variable in the best overall model (HR 10.92, P<0.0001). Conclusions CMR imaging provides robust risk-stratification of patients who presents with symptoms of ischemia. Characterization of RevPD and LGE by CMR provides strong and complementary prognostic implication towards cardiac death or acute MI. PMID:19770399

  13. Staff nurse commitment, work relationships, and turnover intentions: a latent profile analysis.

    PubMed

    Gellatly, Ian R; Cowden, Tracy L; Cummings, Greta G

    2014-01-01

    The three-component model of organization commitment has typically been studied using a variable-centered rather than a person-centered approach, preventing a more complete understanding of how these forms of commitment are felt and expressed as a whole. Latent profile analysis was used to identify qualitatively distinct categories or profiles of staff nurses' commitment. Then, associations of the profiles with perceived work unit relations and turnover intentions were examined. Three hundred thirty-six registered nurses provided data on affective, normative, and continuance commitment, perceived work unit relations, and turnover intentions. Latent profile analysis of the nurses' commitment scores revealed six distinct profile groups. Work unit relations and turnover intentions were compared in the six profile-defined groups. Staff nurses with profiles characterized by high affective commitment and/or high normative commitment in relation to other components experienced stronger work unit relations and reported lower turnover intentions. Profiles characterized by high continuance commitment relative to other components or by low overall commitment experienced poorer work unit relations, and the turnover risk was higher. High continuance commitment in combination with high affective and normative commitment was experienced differently than high continuance commitment in combination with low affective and normative commitment. Healthcare organizations often foster commitment by using continuance commitment-enhancing strategies (e.g., offer high salaries and attractive benefits) that may inadvertently introduce behavioral risk. This work suggests the importance of changing the context in which continuance commitment occurs by strengthening the other two components.

  14. A Commitment to Excellence

    PubMed Central

    Budin, Wendy C.

    2012-01-01

    In this column, the editor of The Journal of Perinatal Education describes two international credentialing programs, the Magnet Recognition Program and the Baby-Friendly Hospital Initiative. Both require an ongoing commitment to excellence. The editor also describes the contents of this issue, which offer a broad range of resources, research, and inspiration for childbirth educators in their efforts to promote, support, and protect natural, safe, and healthy birth. Wendy C. BudinEditor

  15. [Psychosomatic aspects of cardiac arrhythmias].

    PubMed

    Siepmann, Martin; Kirch, Wilhelm

    2010-07-01

    Emotional stress facilitates the occurrence of cardiac arrhythmias including sudden cardiac death. The prevalence of anxiety and depression is increased in cardiac patients as compared to the normal population. The risk of cardiovascular mortality is enhanced in patients suffering from depression. Comorbid anxiety disorders worsen the course of cardiac arrhythmias. Disturbance of neurocardiac regulation with predominance of the sympathetic tone is hypothesized to be causative for this. The emotional reaction to cardiac arrhythmias is differing to a large extent between individuals. Emotional stress may result from coping with treatment of cardiac arrhythmias. Emotional stress and cardiac arrhythmias may influence each other in the sense of a vicious circle. Somatoform cardiac arrhythmias are predominantly of psychogenic origin. Instrumental measures and frequent contacts between physicians and patients may facilitate disease chronification. The present review is dealing with the multifaceted relationships between cardiac arrhythmias and emotional stress. The underlying mechanisms and corresponding treatment modalities are discussed.

  16. Insulin-like Growth Factor-I and Slow, Bi-directional Perfusion Enhance the Formation of Tissue-Engineered Cardiac Grafts

    PubMed Central

    Cheng, Mingyu; Moretti, Matteo; Engelmayr, George C.

    2009-01-01

    Biochemical and mechanical signals enabling cardiac regeneration can be elucidated using in vitro tissue-engineering models. We hypothesized that insulin-like growth factor-I (IGF) and slow, bi-directional perfusion could act independently and interactively to enhance the survival, differentiation, and contractile performance of tissue-engineered cardiac grafts. Heart cells were cultured on three-dimensional porous scaffolds in medium with or without supplemental IGF and in the presence or absence of slow, bi-directional perfusion that enhanced transport and provided shear stress. Structural, molecular, and electrophysiologic properties of the resulting grafts were quantified on culture day 8. IGF had independent, beneficial effects on apoptosis (p < 0.01), cellular viability (p < 0.01), contractile amplitude (p < 0.01), and excitation threshold (p < 0.01). Perfusion independently affected the four aforementioned parameters and also increased amounts of cardiac troponin-I (p < 0.01), connexin-43 (p < 0.05), and total protein (p < 0.01) in the grafts. Interactive effects of IGF and perfusion on apoptosis were also present (p < 0.01). Myofibrillogenesis and spontaneous contractility were present only in grafts cultured with perfusion, although contractility was inducible by electrical field stimulation of grafts from all groups. Our findings demonstrate that multi-factorial stimulation of tissue-engineered cardiac grafts using IGF and perfusion resulted in independent and interactive effects on heart cell survival, differentiation, and contractility. PMID:18759675

  17. Robust relativistic bit commitment

    NASA Astrophysics Data System (ADS)

    Chakraborty, Kaushik; Chailloux, André; Leverrier, Anthony

    2016-12-01

    Relativistic cryptography exploits the fact that no information can travel faster than the speed of light in order to obtain security guarantees that cannot be achieved from the laws of quantum mechanics alone. Recently, Lunghi et al. [Phys. Rev. Lett. 115, 030502 (2015), 10.1103/PhysRevLett.115.030502] presented a bit-commitment scheme where each party uses two agents that exchange classical information in a synchronized fashion, and that is both hiding and binding. A caveat is that the commitment time is intrinsically limited by the spatial configuration of the players, and increasing this time requires the agents to exchange messages during the whole duration of the protocol. While such a solution remains computationally attractive, its practicality is severely limited in realistic settings since all communication must remain perfectly synchronized at all times. In this work, we introduce a robust protocol for relativistic bit commitment that tolerates failures of the classical communication network. This is done by adding a third agent to both parties. Our scheme provides a quadratic improvement in terms of expected sustain time compared with the original protocol, while retaining the same level of security.

  18. Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats

    PubMed Central

    Lv, Y.; Liu, B.; Wang, H.P.; Zhang, L.

    2016-01-01

    The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats. PMID:27254663

  19. 24 CFR 200.46 - Commitment issuance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Requirements for Application, Commitment, and Endorsement... Eligibility Requirements for Existing Projects Commitment Applications § 200.46 Commitment issuance....

  20. Keratin mediated attachment of stem cells to augment cardiomyogenic lineage commitment.

    PubMed

    Ghosh, Lopamudra Das; Ravi, Venkatraman; Sanpui, Pallab; Sundaresan, Nagalingam R; Chatterjee, Kaushik

    2017-03-01

    The objective of this work was to develop a simple surface modification technique using keratin derived from human hair for efficient cardiomyogenic lineage commitment of human mesenchymal stem cells (hMSCs). Keratin was extracted from discarded human hair containing both the acidic and basic components along with the heterodimers. The extracted keratin was adsorbed to conventional tissue culture polystyrene surfaces at different concentration. Keratin solution of 500μg/ml yielded a well coated layer of 12±1nm thickness with minimal agglomeration. The keratin coated surfaces promoted cell attachment and proliferation. Large increases in the mRNA expression of known cardiomyocyte genes such as cardiac actinin, cardiac troponin and β-myosin heavy chain were observed. Immunostaining revealed increased expression of sarcomeric α-actinin and tropomyosin whereas Western blots confirmed higher expression of tropomyosin and myocyte enhancer factor 2C in cells on the keratin coated surface than on the non-coated surface. Keratin promoted DNA demethylation of the Atp2a2 and Nkx2.5 genes thereby elucidating the importance of epigenetic changes as a possible molecular mechanism underlying the increased differentiation. A global gene expression analysis revealed a significant alteration in the expression of genes involved in pathways associated in cardiomyogenic commitment including cytokine and chemokine signaling, cell-cell and cell-matrix interactions, Wnt signaling, MAPK signaling, TGF-β signaling and FGF signaling pathways among others. Thus, adsorption of keratin offers a facile and affordable yet potent route for inducing cardiomyogenic lineage commitment of stem cells with important implications in developing xeno-free strategies in cardiovascular regenerative medicine.

  1. What is the role of procedural justice in civil commitment?

    PubMed

    McKenna, B G; Simpson, A I; Coverdale, J H

    2000-08-01

    To determine best practice management strategies in the clinical application of civil commitment. All relevant literature on the topics of 'civil commitment', 'coercion' and 'procedural justice' were located on MEDLINE and PsychLIT databases and reviewed. Literature on the use of Ulysses contracts and advance directives in mental health treatment was integrated into the findings. Best practice evidence that guides management strategies is limited to the time of enactment of civil commitment. Management strategies involve enhancing the principles of procedural justice as a means of limiting negative patient perception of commitment. In the absence of evidence-based research beyond this point of enactment, grounds for the application of the principles of procedural justice are supported by reference to ethical considerations. Ulysses contracts provide an additional method for strengthening procedural justice. Procedural justice principles should be routinely applied throughout the processes of civil commitment in order to enhance longer term therapeutic outcomes and to blunt paternalism.

  2. MiRNA-Sequence Indicates That Mesenchymal Stem Cells and Exosomes Have Similar Mechanism to Enhance Cardiac Repair

    PubMed Central

    Zhang, Yu; Lan, Beibei; Wang, Juanjuan; Zhang, Zhiwei; Zhang, Lulu; Xiao, Pengli; Meng, Qingyou; Geng, Yong-jian; Yu, Xi-yong

    2017-01-01

    Mesenchymal stem cells (MSCs) repair infarcted heart through paracrine mechanism. We sought to compare the effectiveness of MSCs and MSC-derived exosomes (MSC-Exo) in repairing infarcted hearts and to identify how MSC-Exo mediated cardiac repair is regulated. In a rat myocardial infarction model, we found that MSC-Exo inhibited cardiac fibrosis, inflammation, and improved cardiac function. The beneficial effects of MSC-Exo were significantly superior compared to that of MSCs. To explore the potential mechanisms underlying MSC-Exo's effects, we performed several in vitro experiments and miRNA-sequence analysis. MSC-Exo stimulated cardiomyocyte H9C2 cell proliferation, inhibited apoptosis induced by H2O2, and inhibited TGF-β induced transformation of fibroblast cell into myofibroblast. Importantly, novel miRNA sequencing results indicated that MSC-Exo and MSCs have similar miRNA expression profile, which could be one of the reasons that MSC-Exo can replace MSCs for cardiac repair. In addition, the expression of several miRNAs from MSC-Exo was significantly different from that of MSCs, which may explain why MSC-Exo has better therapeutic effect than MSCs. In conclusion, this study demonstrates that MSC-Exo could be used alone to promote cardiac repair and are superior to MSCs in repairing injured myocardium. PMID:28203568

  3. Observing joint action: Coordination creates commitment.

    PubMed

    Michael, John; Sebanz, Natalie; Knoblich, Günther

    2016-12-01

    Previous research has shown that interpersonal coordination enhances pro-social attitudes and behavior. Here, we extend this research by investigating whether the degree of coordination observed in a joint action enhances the perception of individuals' commitment to the joint action. In four experiments, participants viewed videos of joint actions. In the low coordination condition, two agents made independent individual contributions to a joint action. In the high coordination condition, the individual contributions were tightly linked. Participants judged whether and for how long the observed agents would resist a tempting outside option and remain engaged in the joint action. The results showed that participants were more likely to expect agents to resist outside options when observing joint actions with a high degree of coordination. This indicates that observing interpersonal coordination is sufficient to enhance the perception of commitment to joint action. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Observing Joint Action: Coordination Creates Commitment

    PubMed Central

    Michael, John; Sebanz, Natalie; Knoblich, Günther

    2016-01-01

    Previous research has shown that interpersonal coordination enhances pro-social attitudes and behavior. Here, we extend this research by investigating whether the degree of coordination observed in a joint action enhances the perception of individuals’ commitment to the joint action. In four experiments, participants viewed videos of joint actions. In the low coordination condition, two agents made independent individual contributions to a joint action. In the high coordination condition, the individual contributions were tightly linked. Participants judged whether and for how long the observed agents would resist a tempting outside option and remain engaged in the joint action. The results showed that participants were more likely to expect agents to resist outside options when observing joint actions with a high degree of coordination. This indicates that observing interpersonal coordination is sufficient to enhance the perception of commitment to joint action. PMID:27610745

  5. Enhanced Cardiac Akt/Protein Kinase B Signaling Contributes to Pathological Cardiac Hypertrophy in Part by Impairing Mitochondrial Function via Transcriptional Repression of Mitochondrion-Targeted Nuclear Genes

    PubMed Central

    Wende, Adam R.; O'Neill, Brian T.; Bugger, Heiko; Riehle, Christian; Tuinei, Joseph; Buchanan, Jonathan; Tsushima, Kensuke; Wang, Li; Caro, Pilar; Guo, Aili; Sloan, Crystal; Kim, Bum Jun; Wang, Xiaohui; Pereira, Renata O.; McCrory, Mark A.; Nye, Brenna G.; Benavides, Gloria A.; Darley-Usmar, Victor M.; Shioi, Tetsuo; Weimer, Bart C.

    2014-01-01

    Sustained Akt activation induces cardiac hypertrophy (LVH), which may lead to heart failure. This study tested the hypothesis that Akt activation contributes to mitochondrial dysfunction in pathological LVH. Akt activation induced LVH and progressive repression of mitochondrial fatty acid oxidation (FAO) pathways. Preventing LVH by inhibiting mTOR failed to prevent the decline in mitochondrial function, but glucose utilization was maintained. Akt activation represses expression of mitochondrial regulatory, FAO, and oxidative phosphorylation genes in vivo that correlate with the duration of Akt activation in part by reducing FOXO-mediated transcriptional activation of mitochondrion-targeted nuclear genes in concert with reduced signaling via peroxisome proliferator-activated receptor α (PPARα)/PGC-1α and other transcriptional regulators. In cultured myocytes, Akt activation disrupted mitochondrial bioenergetics, which could be partially reversed by maintaining nuclear FOXO but not by increasing PGC-1α. Thus, although short-term Akt activation may be cardioprotective during ischemia by reducing mitochondrial metabolism and increasing glycolysis, long-term Akt activation in the adult heart contributes to pathological LVH in part by reducing mitochondrial oxidative capacity. PMID:25535334

  6. SNR enhancement of highly-accelerated real-time cardiac MRI acquisitions based on non-local means algorithm.

    PubMed

    Naegel, Benoît; Cernicanu, Alexandru; Hyacinthe, Jean-Noël; Tognolini, Maurizio; Vallée, Jean-Paul

    2009-08-01

    Real-time cardiac MRI appears as a promising technique to evaluate the mechanical function of the heart. However, ultra-fast MRI acquisitions come with an important signal-to-noise ratio (SNR) penalty, which drastically reduces the image quality. Hence, a real-time denoising approach would be desirable for SNR amelioration. In the clinical context of cardiac dysfunction assessment, long acquisitions are required and for most patients the acquisition takes place with free breathing. Hence, it is necessary to compensate respiratory motion in real-time. In this article, a real-time and interactive method for sequential registration and denoising of real-time MR cardiac images is presented. The method has been experimented on 60 fast MRI acquisitions in five healthy volunteers and five patients. These experiments assessed the feasibility of the method in a real-time context.

  7. Creating prodynorphin-expressing stem cells alerted for a high-throughput of cardiogenic commitment.

    PubMed

    Maioli, Margherita; Asara, Yolande; Pintus, Antonella; Ninniri, Stefania; Bettuzzi, Saverio; Scaltriti, Maurizio; Galimi, Francesco; Ventura, Carlo

    2007-03-01

    The development of cell therapy for the rescue of damaged heart muscle is a major area of inquiry. Within this context, the establishment of a cardiogenic cell line may remarkably facilitate the molecular dissection of cardiac fate specification, a low-efficiency and still poorly understood process, paving the way for novel approaches in the use of stem cells for cardiac repair. We used GTR1 cells, a derivative of mouse R1 embryonic stem cells bearing the puromycin-resistance gene driven by the cardiomyocyte-specific alpha-myosin heavy chain promoter, affording a gene trapping selection of a virtually pure population of embryonic stem cell-derived cardiomyocytes. Third-generation lentiviral vectors were used to overexpress the prodynorphin gene, previously shown to orchestrate a dynorphinergic system acting as a major conductor of embryonic stem cell cardiogenesis. Lentiviral prodynorphin transduction remarkably enhanced the transcription of GATA-4 and Nkx-2.5, two cardiac lineage-promoting genes, resulting in a dramatic increase in the number of spontaneously beating cardiomyocytes. Transduced cells also exhibited a subcellular redistribution patterning of protein kinase C-beta, -delta and -epsilon, a major requirement in cardiac lineage commitment. This activation resulted from a sustained increase in the transcription of targeted protein kinase C genes. Prodynorphin transduction was selective in nature and failed to activate genes responsible for skeletal myogenesis or neuronal specification. The cell line developed in this study provides a powerful in vitro model of cardiomyogenesis that may help clarify the cascade of transcriptional activation and signaling networks that push multipotent cells to take on the identity of a cardiac myocyte.

  8. Organizational commitment of military physicians.

    PubMed

    Demir, Cesim; Sahin, Bayram; Teke, Kadir; Ucar, Muharrem; Kursun, Olcay

    2009-09-01

    An individual's loyalty or bond to his or her employing organization, referred to as organizational commitment, influences various organizational outcomes such as employee motivation, job satisfaction, performance, accomplishment of organizational goals, employee turnover, and absenteeism. Therefore, as in other sectors, employee commitment is crucial also in the healthcare market. This study investigates the effects of organizational factors and personal characteristics on organizational commitment of military physicians using structural equation modeling (SEM) on a self-report, cross-sectional survey that consisted of 635 physicians working in the 2 biggest military hospitals in Turkey. The results of this study indicate that professional commitment and organizational incentives contribute positively to organizational commitment, whereas conflict with organizational goals makes a significantly negative contribution to it. These results might help develop strategies to increase employee commitment, especially in healthcare organizations, because job-related factors have been found to possess greater impact on organizational commitment than personal characteristics.

  9. Contrast-Enhanced High-Pitch Computed Tomography in Pediatric Patients Without Electrocardiography Triggering and Sedation: Comparison of Cardiac Image Quality With Conventional Multidetector Computed Tomography.

    PubMed

    Esser, Michael; Gatidis, Sergios; Teufel, Matthias; Ketelsen, Inés; Nikolaou, Konstantin; Schäfer, Jürgen F; Tsiflikas, Ilias

    2017-01-01

    The aim of this study was to compare image quality of anatomical cardiac details without electrocardiography triggering, sedation, or heart rate-regulating drugs in contrast-enhanced pediatric chest computed tomography (CT), using high-pitch CT (HPCT) versus conventional pitch-mode technique (multidetector CT [MDCT]). After written informed consent, 55 patients (median age, 11 years; range, 3-17 years) were prospectively included in this institutional review board-approved study. Patients underwent clinically indicated, contrast-enhanced MDCT or HPCT of the chest.Image quality was assessed evaluating morphological criteria on a 3-point scale (from 1, high, to 3, low detail) and summed up in a global score (from 4, best, to 12, poor image quality). Artifacts were analyzed correspondingly (from 3, low, to 9, severe artifacts). Effective dose and size-specific dose estimate were calculated for all scans. Cardiac image quality was higher in HPCT than in MDCT (7.1 [1.6] vs 8.8 [1.9], P < 0.001). Nevertheless, HPCT showed limitations in image quality, especially concerning the heart valves (2.5 [0.6] and 1.7 [0.5]) and coronary arteries (1.8 [0.6). Artifact score (3.4 [0.6 vs 5.1 [0.9, P < 0.001), effective dose (1.6 [1.3] vs 2.3 [1.6] mSv, P = 0.047), and size-specific dose estimate (2.5 [1.7] vs 4.1 [2.3] mGy, P = 0.002) were lower in HPCT compared with those in MDCT. In pediatric patients, contrast-enhanced HPCT of the chest provides high image quality without electrocardiography triggering or sedation, although image quality is somewhat limited for a detailed depiction of cardiac anatomy.

  10. Synergy between intention recognition and commitments in cooperation dilemmas.

    PubMed

    Han, The Anh; Santos, Francisco C; Lenaerts, Tom; Pereira, Luís Moniz

    2015-03-20

    Commitments have been shown to promote cooperation if, on the one hand, they can be sufficiently enforced, and on the other hand, the cost of arranging them is justified with respect to the benefits of cooperation. When either of these constraints is not met it leads to the prevalence of commitment free-riders, such as those who commit only when someone else pays to arrange the commitments. Here, we show how intention recognition may circumvent such weakness of costly commitments. We describe an evolutionary model, in the context of the one-shot Prisoner's Dilemma, showing that if players first predict the intentions of their co-player and propose a commitment only when they are not confident enough about their prediction, the chances of reaching mutual cooperation are largely enhanced. We find that an advantageous synergy between intention recognition and costly commitments depends strongly on the confidence and accuracy of intention recognition. In general, we observe an intermediate level of confidence threshold leading to the highest evolutionary advantage, showing that neither unconditional use of commitment nor intention recognition can perform optimally. Rather, our results show that arranging commitments is not always desirable, but that they may be also unavoidable depending on the strength of the dilemma.

  11. Synergy between intention recognition and commitments in cooperation dilemmas

    NASA Astrophysics Data System (ADS)

    Han, The Anh; Santos, Francisco C.; Lenaerts, Tom; Pereira, Luís Moniz

    2015-03-01

    Commitments have been shown to promote cooperation if, on the one hand, they can be sufficiently enforced, and on the other hand, the cost of arranging them is justified with respect to the benefits of cooperation. When either of these constraints is not met it leads to the prevalence of commitment free-riders, such as those who commit only when someone else pays to arrange the commitments. Here, we show how intention recognition may circumvent such weakness of costly commitments. We describe an evolutionary model, in the context of the one-shot Prisoner's Dilemma, showing that if players first predict the intentions of their co-player and propose a commitment only when they are not confident enough about their prediction, the chances of reaching mutual cooperation are largely enhanced. We find that an advantageous synergy between intention recognition and costly commitments depends strongly on the confidence and accuracy of intention recognition. In general, we observe an intermediate level of confidence threshold leading to the highest evolutionary advantage, showing that neither unconditional use of commitment nor intention recognition can perform optimally. Rather, our results show that arranging commitments is not always desirable, but that they may be also unavoidable depending on the strength of the dilemma.

  12. More than Tiny Sacks: Stem Cell Exosomes as Cell-free Modality for Cardiac Repair

    PubMed Central

    Kishore, Raj; Khan, Mohsin

    2015-01-01

    Stem cell therapy provides immense hope for regenerating the pathological heart yet has been marred by issues surrounding the effectiveness, unclear mechanisms and survival of the donated cell population in the ischemic myocardial milieu. Poor survival and engraftment coupled to inadequate cardiac commitment of the adoptively transferred stem cells compromises the improvement in cardiac function. Various alternative approaches to enhance the efficacy of stem cell therapies and to overcome issues with cell therapy have been employed with varied success. Cell free components such as exosomes enriched in proteins, mRNAs and miRs characteristic of parental stem cells represent a potential approach for treating cardiovascular diseases. Recently, exosomes from different kinds of stem cells have been effectively employed to promote cardiac function in the pathological heart. The aim of this review is to summarize current research efforts on stem cell exosomes including their potential benefits and limitations in order to develop a potentially viable therapy for cardiovascular problems. PMID:26838317

  13. Commitment and energy conservation

    SciTech Connect

    Pallak, M.S.; Cook, D.A.; Sullivan, J.J.

    1980-01-01

    The authors discuss the process of becoming committed to energy conservation research, then describe practical issues of field research and several data sets on household energy conservation. Their results show that taking a stand affected behavior in reducing the levels of natural gas and electricity usage, with the effect continuing even after the study ended. Although based on the assumption that homeowners were initially favorable toward energy conservation, the studies suggest that energy-related behavior is malleable and amenable to approaches familiar to psychologists. The study indicates that feedback on energy use during peak seasons could help to avoid power shortages. 16 references, 6 tables.

  14. [Acceptance and commitment therapy].

    PubMed

    Ducasse, D; Fond, G

    2015-02-01

    Acceptance and commitment therapy (ACT) is a third generation of cognitive-behavioral therapies. The point is to help patients to improve their psychological flexibility in order to accept unavoidable private events. Thus, they have the opportunity to invest energy in committed actions rather than struggle against their psychological events. (i) To present the ACT basic concepts and (ii) to propose a systematic review of the literature about effectiveness of this kind of psychotherapy. (i) The core concepts of ACT come from Monestès (2011), Schoendorff (2011), and Harris (2012); (ii) we conducted a systematic review of the literature using the PRISMA's criteria. The research paradigm was « acceptance and commitment therapy AND randomized controlled trial ». The bases of the MEDLINE, Cochrane and Web of science have been checked. Overall, 61 articles have been found, of which, after reading the abstracts, 40 corresponded to the subject of our study. (I) Psychological flexibility is established through six core ACT processes (cognitive defusion, acceptance, being present, values, committed action, self as context), while the therapist emphasizes on experiential approach. (II) Emerging research shows that ACT is efficacious in the psychological treatment of a wide range of psychiatric problems, including psychosis, depression, obsessive-compulsive disorder, trichotillomania, generalized anxiety disorder, post-traumatic stress disorder, borderline personality disorder, eating disorders. ACT has also shown a utility in other areas of medicine: the management chronic pain, drug-dependence, smoking cessation, the management of epilepsy, diabetic self-management, the management of work stress, the management of tinnitus, and the management of multiple sclerosis. Meta-analysis of controlled outcome studies reported an average effect size (Cohen's d) of 0.66 at post-treatment (n=704) and 0.65 (n=580) at follow-up (on average 19.2 weeks later). In studies involving

  15. Noncoronary Measures Enhance the Predictive Value of Cardiac CT Above Traditional Risk Factors and CAC Score in the General Population.

    PubMed

    Mahabadi, Amir A; Lehmann, Nils; Möhlenkamp, Stefan; Pundt, Noreen; Dykun, Iryna; Roggenbuck, Ulla; Moebus, Susanne; Jöckel, Karl-Heinz; Erbel, Raimund; Kälsch, Hagen

    2016-10-01

    The aim of this study was to determine whether noncoronary measures from cardiac computed tomography (CT) may enhance the prognostic value of this imaging technology. When cardiac CT is performed for quantification of coronary artery calcium (CAC) score, information on other cardiac and thoracic structures is available. Participants without known cardiovascular disease from the prospective population based Heinz Nixdorf Recall study underwent noncontrast cardiac CT for CAC score quantification. From CT, epicardial adipose tissue (EAT) volume, left ventricular and left atrial (LA) axial area index, ascending and descending aortic diameters, as well as aortic valve, mitral ring, and thoracic aortic calcification (TAC) were assessed. Incident cardiovascular events included myocardial infarction, stroke, and cardiovascular death. The prognostic value of CT-derived parameters was assessed by Cox regression analysis, receiver operating characteristics, and net reclassification improvement. From 3,630 subjects (59 ± 8 years of age, 46% male), 241 (6.6%) developed a cardiovascular event during 9.9 ± 2.6 years of follow-up. In multivariable Cox regression analysis including Framingham Risk Score, CAC (as log[CAC + 1]), and CT parameters, LA index (hazard ratio [HR]: 1.22 [95% confidence interval [CI]: 1.05 to 1.41] per SD; p = 0.010) and EAT volume (HR: 1.15 [95% CI: 1.01 to 1.30] per SD; p = 0.031) were significantly associated with incident events. In addition, presence of TAC showed an elevated event rate (HR: 1.33 [95% CI: 0.97 to 1.81]; p = 0.08), whereas all other CT-derived parameters showed no relevant association. The LA index, EAT volume, and presence of TAC together improved the prediction of events over Framingham Risk Score and CAC in receiver operating characteristics analysis (area under the curve: 0.749 to 0.764; p = 0.011), and let to a significant net reclassification improvement (HR: 38.0%; 95% CI: 25.1% to 50.8%). Assessment of LA index, EAT

  16. Cell therapy with embryonic stem cell-derived cardiomyocytes encapsulated in injectable nanomatrix gel enhances cell engraftment and promotes cardiac repair.

    PubMed

    Ban, Kiwon; Park, Hun-Jun; Kim, Sangsung; Andukuri, Adinarayana; Cho, Kyu-Won; Hwang, Jung Wook; Cha, Ho Jin; Kim, Sang Yoon; Kim, Woan-Sang; Jun, Ho-Wook; Yoon, Young-Sup

    2014-10-28

    A significant barrier to the therapeutic use of stem cells is poor cell retention in vivo. Here, we evaluate the therapeutic potential and long-term engraftment of cardiomyocytes (CMs) derived from mouse embryonic stem cells (mESCs) encapsulated in an injectable nanomatrix gel consisting of peptide amphiphiles incorporating cell adhesive ligand Arg-Gly-Asp-Ser (PA-RGDS) in experimental myocardial infarction (MI). We cultured rat neonatal CMs in PA-RGDS for 7 days and found that more than 90% of the CMs survived. Next, we intramyocardially injected mouse CM cell line HL-1 CMs with or without PA-RGDS into uninjured hearts. Histologic examination and flow cytometry analysis of digested heart tissues showed approximately 3-fold higher engraftment in the mice that received CMs with PA-RGDS compared to those without PA-RGDS. We further investigated the therapeutic effects and long-term engraftment of mESC-CMs with PA-RGDS on MI in comparison with PBS control, CM-only, and PA-RGDS only. Echocardiography demonstrated that the CM-only and CM+PA-RGDS groups showed higher cardiac function at week 2 compared to other groups. However, from 3 weeks, higher cardiac function was maintained only in the CM+PA-RGDS group; this was sustained for 12 weeks. Confocal microscopic examination of the cardiac tissues harvested at 14 weeks demonstrated sustained engraftment and integration of mESC-CMs into host myocardium in the CM+PA-RGDS group only. This study for the first time demonstrated that PA-RGDS encapsulation can enhance survival of mESC-derived CMs and improve cardiac function post-MI. This nanomatrix gel-mediated stem cell therapy can be a promising option for treating MI.

  17. Transcription enhancer factor 1 interacts with a basic helix-loop-helix zipper protein, Max, for positive regulation of cardiac alpha-myosin heavy-chain gene expression.

    PubMed Central

    Gupta, M P; Amin, C S; Gupta, M; Hay, N; Zak, R

    1997-01-01

    The M-CAT binding factor transcription enhancer factor 1 (TEF-1) has been implicated in the regulation of several cardiac and skeletal muscle genes. Previously, we identified an E-box-M-CAT hybrid (EM) motif that is responsible for the basal and cyclic AMP-inducible expression of the rat cardiac alpha-myosin heavy chain (alpha-MHC) gene in cardiac myocytes. In this study, we report that two factors, TEF-1 and a basic helix-loop-helix leucine zipper protein, Max, bind to the alpha-MHC EM motif. We also found that Max was a part of the cardiac troponin T M-CAT-TEF-1 complex even when the DNA template did not contain an apparent E-box binding site. In the protein-protein interaction assay, a stable association of Max with TEF-1 was observed when glutathione S-transferase (GST)-TEF-1 or GST-Max was used to pull down in vitro-translated Max or TEF-1, respectively. In addition, Max was coimmunoprecipitated with TEF-1, thus documenting an in vivo TEF-1-Max interaction. In the transient transcription assay, overexpression of either Max or TEF-1 resulted a mild activation of the alpha-MHC-chloramphenicol acetyltransferase (CAT) reporter gene at lower concentrations and repression of this gene at higher concentrations. However, when Max and TEF-1 expression plasmids were transfected together, the repression mediated by a single expression plasmid was alleviated and a three- to fourfold transactivation of the alpha-MHC-CAT reporter gene was observed. This effect was abolished once the EM motif in the promoter-reporter construct was mutated, thus suggesting that the synergistic transactivation function of the TEF-1-Max heterotypic complex is mediated through binding of the complex to the EM motif. These results demonstrate a novel association between Max and TEF-1 and indicate a positive cooperation between these two factors in alpha-MHC gene regulation. PMID:9199327

  18. Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats.

    PubMed

    Dolinsky, Vernon W; Jones, Kelvin E; Sidhu, Robinder S; Haykowsky, Mark; Czubryt, Michael P; Gordon, Tessa; Dyck, Jason R B

    2012-06-01

    Exercise training (ET) improves endurance capacity by increasing both skeletal muscle mitochondrial number and function, as well as contributing to favourable cardiac remodelling.Interestingly, some of the benefits of regular exercise can also be mimicked by the naturally occurring polyphenol, resveratrol (RESV). However, it is not known whether RESV enhances physiological adaptations to ET. To investigate this, male Wistar rats were randomly assigned to a control chow diet or a chow diet that contained RESV (4 g kg⁻¹ of diet) and subsequently subjected to a programme of progressive treadmill running for 12 weeks. ET-induced improvements in exercise performance were enhanced by 21% (P <0.001) by the addition of RESV to the diet. In soleus muscle, ET+RESV increased both the twitch (1.8-fold; P <0.05) and tetanic(1.2-fold; P <0.05) forces generated during isometric contraction, compared to ET alone. In vivo echocardiography demonstrated that ET+RESV also increased the resting left ventricular ejection fraction by 10% (P <0.05), and reduced left ventricular wall stress compared to ET alone.These functional changes were accompanied by increased cardiac fatty acid oxidation (1.2-fold;P <0.05) and favourable changes in cardiac gene expression and signal transduction pathways that optimized the utilization of fatty acids in ET+RESV compared to ET alone. Overall, our findings provide evidence that the capacity for fatty acid oxidation is augmented by the addition of RESV to the diet during ET, and that this may contribute to the improved physical performance of rats following ET.

  19. Elevated InsP3R expression underlies enhanced calcium fluxes and spontaneous extra-systolic calcium release events in hypertrophic cardiac myocytes.

    PubMed

    Harzheim, Dagmar; Talasila, Amarnath; Movassagh, Mehregan; Foo, Roger S-Y; Figg, Nichola; Bootman, Martin D; Roderick, H Llewelyn

    2010-01-01

    Cardiac hypertrophy is associated with profound remodeling of Ca(2+) signaling pathways. During the early, compensated stages of hypertrophy, Ca(2+) fluxes may be enhanced to facilitate greater contraction, whereas as the hypertrophic heart decompensates, Ca(2+) homeostatic mechanisms are dysregulated leading to decreased contractility, arrhythmia and death. Although ryanodine receptor Ca(2+) release channels (RyR) on the sarcoplasmic reticulum (SR) intracellular Ca(2+) store are primarily responsible for the Ca(2+) flux that induces myocyte contraction, a role for Ca(2+) release via the inositol 1,4,5-trisphosphate receptor (InsP(3)R) in cardiac physiology has also emerged. Specifically, InsP(3)-induced Ca(2+) signals generated following myocyte stimulation with an InsP(3)-generating agonist (e.g., endothelin, ET-1), lead to modulation of Ca(2+) signals associated with excitation-contraction coupling (ECC) and the induction of spontaneous Ca(2+) release events that cause cellular arrhythmia. Using myocytes from spontaneously hypertensive rats (SHR), we recently reported that expression of the type 2 InsP(3)R (InsP(3)R2) is significantly increased during hypertrophy. Notably, this increased expression was restricted to the junctional SR in close proximity to RyRs. There, enhanced Ca(2+) release via InsP(3)Rs serves to sensitize neighboring RyRs causing an augmentation of Ca(2+) fluxes during ECC as well as an increase in non-triggered Ca(2+) release events. Although the sensitization of RyRs may be a beneficial consequence of elevated InsP(3)R expression during hypertrophy, the spontaneous Ca(2+) release events are potentially of pathological significance giving rise to cardiac arrhythmia. InsP(3)R2 expression was also increased in hypertrophic hearts from patients with ischemic dilated cardiomyopathy and aortically-banded mice demonstrating that increased InsP(3)R expression may be a general phenomenon that underlies Ca(2+) changes during hypertrophy.

  20. Cardiac catheterization - discharge

    MedlinePlus

    Catheterization - cardiac - discharge; Heart catheterization - discharge: Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization discharge; CAD - cardiac catheterization discharge; Coronary artery disease - cardiac catheterization ...

  1. Experimental unconditionally secure bit commitment

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Cao, Yuan; Curty, Marcos; Liao, Sheng-Kai; Wang, Jian; Cui, Ke; Li, Yu-Huai; Lin, Ze-Hong; Sun, Qi-Chao; Li, Dong-Dong; Zhang, Hong-Fei; Zhao, Yong; Chen, Teng-Yun; Peng, Cheng-Zhi; Zhang, Qiang; Cabello, Adan; Pan, Jian-Wei

    2014-03-01

    Quantum physics allows unconditionally secure communication between parties that trust each other. However, when they do not trust each other such as in the bit commitment, quantum physics is not enough to guarantee security. Only when relativistic causality constraints combined, the unconditional secure bit commitment becomes feasible. Here we experimentally implement a quantum bit commitment with relativistic constraints that offers unconditional security. The commitment is made through quantum measurements in two quantum key distribution systems in which the results are transmitted via free-space optical communication to two agents separated with more than 20 km. Bits are successfully committed with less than 5 . 68 ×10-2 cheating probability. This provides an experimental proof of unconditional secure bit commitment and demonstrates the feasibility of relativistic quantum communication.

  2. A unit commitment expert system

    SciTech Connect

    Mokhtari, S.; Singh, J.; Wollenberg, B.

    1987-02-01

    An expert system based consultant has been developed to assist power system operators in scheduling the operation of generating units. First, problems with existing unit commitment algorithms were identified. Then the knowledge of an experienced power system operator and a unit commitment programming expert were combined to create an expert system rule base. To use the expert system as a unit commitment consultant the operator provides information in response to questions. The expert system uses this information along with the rules either to ask for more information or to reach a conclusion. The expert system answers the most frequent questions raised by system operators and improves the unit commitment solution results by indicating how to adjust input data. It concludes the operational constraints not included in the unit commitment base algorithm and results in a more efficient program execution. Numerical examples and test results show that this approach can obtain a better and operationally more acceptable unit commitment solution.

  3. Utility and efficacy of a smartphone application to enhance the learning and behavior goals of traditional cardiac rehabilitation: a feasibility study.

    PubMed

    Forman, Daniel E; LaFond, Karen; Panch, Trishan; Allsup, Kelly; Manning, Kenneth; Sattelmair, Jacob

    2014-01-01

    Most eligible patients do not participate in traditional clinic-based cardiac rehabilitation (CR) despite well-established benefits. Novel approaches to overcome logistic obstacles and increase efficiencies of learning, behavior modification, and exercise surveillance may increase CR participation. In an observational study, the feasibility and utility of a mobile smartphone application for CR, Heart Coach (HC), were assessed as part of standard care. Ultimately, innovative CR models incorporating HC may facilitate better CR usage and value. Twenty-six patients enrolled in CR installed HC. Over the next 30 days, they were prompted by HC to complete a daily "task list" that included medications, walking, education (text and videos), and surveys. Cardiac rehabilitation providers monitored each patient's progress through a HC-based Web dashboard and also sent them personalized feedback and support. Completion of the tasks and feedback (qualitative and quantitative) from patients and clinicians were tracked. Patients engaged with HC 90% of days during the study period, with uniformly favorable impact on compliance and adherence. Eighty-three percent of patients reported a positive/very positive HC experience. Providers reported that HC enhanced their provision of therapy by improving communication, clinical insight, patient participation, and program efficiency. Integrating a mobile care delivery platform into CR was feasible, safe, and agreeable to patients and clinicians. It enhanced patient perceptions of CR care and physician perceptions of the CR caregiving process. Mobile-enabled technologies hold promise to extend the quality and reach of CR, and to better achieve contemporary accountable care goals.

  4. Dual-enhancement cardiac computed tomography for assessing left atrial thrombus and pulmonary veins before radiofrequency catheter ablation for atrial fibrillation.

    PubMed

    Hur, Jin; Pak, Hui-Nam; Kim, Young Jin; Lee, Hye-Jeong; Chang, Hyuk-Jae; Hong, Yoo Jin; Choi, Byoung Wook

    2013-07-15

    Noninvasive imaging that provides anatomic information while excluding intracardiac thrombus would be of significant clinical value for patients referred for catheter ablation of atrial fibrillation (AF). This study assessed the diagnostic performance of a dual-enhancement single-phase cardiac computed tomography (CT) protocol for thrombus and circulatory stasis detection in AF patients before catheter ablation. We studied 101 consecutive symptomatic AF patients (71 men and 30 women; mean age, 61.8 years) who were scheduled to have catheter ablation. All patients had undergone pre-AF ablation CT imaging and transesophageal echocardiography on the same day. CT was performed with prospective electrocardiographic gating, and scanning began 180 seconds after the test bolus. Mean left atrial appendage (LAA)/ascending aorta Hounsfield unit (HU) ratios were measured on CT images. Among the 101 patients, 9 thrombi and 18 spontaneous echo contrasts were detected by transesophageal echocardiography. The overall sensitivity, specificity, positive predictive value, and negative predictive value of CT for the detection of thrombi in the LAA were 89%, 100%, 100%, and 99%, respectively. The mean LAA/ascending aorta HU ratios were significantly different between thrombus and circulatory stasis (0.17 vs 0.33, p = 0.002). Dual-enhancement single-scan cardiac CT is a sensitive modality for detecting and differentiating LAA thrombus and circulatory stasis.

  5. Simulated Microgravity and 3D Culture Enhance Induction, Viability, Proliferation and Differentiation of Cardiac Progenitors from Human Pluripotent Stem Cells

    PubMed Central

    Jha, Rajneesh; Wu, Qingling; Singh, Monalisa; Preininger, Marcela K.; Han, Pengcheng; Ding, Gouliang; Cho, Hee Cheol; Jo, Hanjoong; Maher, Kevin O.; Wagner, Mary B.; Xu, Chunhui

    2016-01-01

    Efficient generation of cardiomyocytes from human pluripotent stem cells is critical for their regenerative applications. Microgravity and 3D culture can profoundly modulate cell proliferation and survival. Here, we engineered microscale progenitor cardiac spheres from human pluripotent stem cells and exposed the spheres to simulated microgravity using a random positioning machine for 3 days during their differentiation to cardiomyocytes. This process resulted in the production of highly enriched cardiomyocytes (99% purity) with high viability (90%) and expected functional properties, with a 1.5 to 4-fold higher yield of cardiomyocytes from each undifferentiated stem cell as compared with 3D-standard gravity culture. Increased induction, proliferation and viability of cardiac progenitors as well as up-regulation of genes associated with proliferation and survival at the early stage of differentiation were observed in the 3D culture under simulated microgravity. Therefore, a combination of 3D culture and simulated microgravity can be used to efficiently generate highly enriched cardiomyocytes. PMID:27492371

  6. Integrated management of cardiac failure: the cardiac failure clinic.

    PubMed

    Loisance, Daniel

    2011-03-01

    The prevalence of the risk factors and the risk of cardiac failure are both increasing in China. This might be the consequence of the changes of the life conditions (emigration to the urban areas, changes in the diet and life style, lack of physical exercise, etc.). The wide range of clinical presentations of cardiac failure (acute or chronic) and of therapeutic approaches (medical or surgical) makes necessary the integration within the same structure of the various experts involved in the diagnosis and the treatment of cardiac diseases. Technologic and human resources required to offer all the options represent a multifaceted commitment which should be focused optimally in dedicated centers. In these centers, collaboration should replace competition between the medical and the surgical cardiac specialists. Development of team work should permit to optimize the cost efficacy of the treatments. Most of all, such a structure will facilitate the translation of innovative therapies between the research centers and clinical facilities.

  7. MR imaging of cardiac masses.

    PubMed

    Syed, Imran S; Feng, Dali; Harris, Scott R; Martinez, Matthew W; Misselt, Andrew J; Breen, Jerome F; Miller, Dylan V; Araoz, Philip A

    2008-05-01

    Cardiac MR imaging is the preferred method for assessment of cardiac masses. A comprehensive cardiac MR imaging examination for a cardiac mass consists of static morphologic images using fast spin-echo sequences, including single-shot techniques, with T1 and T2 weighting and fat suppression pulses as well as dynamic imaging with cine steady-state free precession techniques. Further tissue characterization is provided with perfusion and delayed enhancement imaging. Specific cardiac tumoral characterization is possible in many cases. When specific tumor characterization is not possible, MR imaging often can demonstrate aggressive versus nonaggressive features that help in differentiating malignant from benign tumors.

  8. Induced apnea enhances image quality and visualization of cardiopulmonary anatomic during contrastenhanced cardiac computerized tomographic angiography in children.

    PubMed

    Chakravarthy, Murali; Sunilkumar, Gubbihalli; Pargaonkar, Sumant; Hosur, Rajathadri; Harivelam, Chidananda; Kavaraganahalli, Deepak; Srinivasan, Pradeep

    2015-01-01

    The purpose of our study was to determine the effect of induced apnea on quality of cardiopulmonary structures during computerized tomographic (CT) angiography images in children with congenital heart diseases. Pediatric patients with congenital heart defects undergoing cardiac CT angiography at our facility in the past 3 years participated in this study. The earlier patients underwent cardiac CT angiography without induced apnea and while, later, apnea was induced in patients, which was followed by electrocardiogram gated cardiac CT angiography. General anesthesia was induced using sleep dose of intravenous propofol. After the initial check CT, on request by the radiologist, apnea was induced by the anesthesiologist by administering 1 mg/kg of intravenous suxamethonium. Soon after apnea ensued, the contrast was injected, and CT angiogram carried out. CT images in the "apnea group" were compared with those in "nonapnea group." After the completion of the procedure, the patients were mask ventilated with 100% oxygen till the spontaneous ventilation was restored. We studied 46 patients, of whom 36 with apnea and yet another 10 without. The quality of the image, visualization of structures such as cardiac wall, outflow tracts, lung field, aortopulmonary shunts, and coronary arteries were analyzed and subjected to statistical analysis (Mann-Whitney U, Fischer's exact test and Pearson's Chi-square test). In the induced apnea group, overall image quality was considered excellent in 89% (n = 33) of the studies, while in the "no apnea group," only 30% of studies were excellent. Absent or minimal motion artifacts were seen in a majority of the studies in apnea group (94%). In the nonapnea group, the respiratory and body motion artifacts were severe in 50%, moderate in 30%, and minimal in 20%, but they were significantly lesser in the apnea group. All the studied parameters were statistically significant in the apnea group in contrast to nonapnea group (P < 0.000). The image

  9. Potent enhancement of (/sup 3/H)nitrendipine binding in rat cerebral cortical and cardiac homogenates: a putative mechanism for the action of MDL 12,330A

    SciTech Connect

    Lee, H.R.; Jaros, J.A.; Roeske, W.R.; Wiech, N.L.; Ursillo, R.; Yamamura, H.I.

    1985-06-01

    (/sup 3/H)Nitrendipine ((/sup 3/H)NTD), a specific high-affinity calcium channel antagonist, was used to label dihydropyridine binding sites associated with calcium channels in rat cerebral cortical and cardiac homogenates. A novel lactamimide compound, MDL 12,330A, has been shown previously to have negative inotropic and chronotropic effects in isolated working guinea-pig hearts and these effects are reversed by the administration of calcium. MDL 12,330A is potent in enhancing (/sup 3/H)NTD binding in membranes prepared from the cerebral cortex and the heart, with EC50 values of 6.1 X 10(-8) and 3.4 X 10(-8) M, respectively, at 37 degrees C. This allosteric effect by MDL 12,330A is similar to that produced by a known calcium channel antagonist, d-cis diltiazem, which has been shown previously to enhance (/sup 3/H)NTD binding at 37 degrees C. The extent of enhancement by MDL 12,330A depends on incubation temperature (37 degrees C greater than 25 degrees C greater than 0 degrees C). The mechanism of this enhancement by MDL 12,330A is due to a decrease in the dissociation rate constant of the dihydropyridine-calcium channel supramolecular complex. MDL 12,330A is the most potent drug thus far examined which demonstrates the enhancement of (/sup 3/H)NTD binding.

  10. Using internal marketing to improve organizational commitment and service quality.

    PubMed

    Tsai, Yafang; Wu, Shih-Wang

    2011-12-01

    The purpose of this article was to explore the structural relationships among internal marketing, organizational commitment and service quality and to practically apply the findings. Internal marketing is a way to assist hospitals in improving the quality of the services that they provide while executing highly labour-intensive tasks. Through internal marketing, a hospital can enhance the organizational commitment of its employees to attain higher service quality. This research uses a cross-sectional study to survey nursing staff perceptions about internal marketing, organizational commitment and service quality. The results of the survey are evaluated using equation models. The sample includes three regional hospitals in Taiwan. Three hundred and fifty questionnaires were distributed and 288 valid questionnaires were returned, yielding a response rate of 82.3%. The survey process lasted from 1 February to 9 March 2007. The data were analysed with SPSS 12.0, including descriptive statistics based on demographics. In addition, the influence of demographics on internal marketing, organizational commitment and service quality is examined using one-way anova. The findings reveal that internal marketing plays a critical role in explaining employee perceptions of organizational commitment and service quality. Organizational commitment is the mediator between internal marketing and service quality. The results indicate that internal marketing has an impact on both organizational commitment and service quality. Internal marketing should be emphasized to influence frontline nursing staff, thereby helping to create better organizational commitment and service quality. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

  11. Patients' and nurses' views on providing psychological support within cardiac rehabilitation programmes: a qualitative study.

    PubMed

    Turner, Katrina M; Winder, Rachel; Campbell, John L; Richards, David A; Gandhi, Manish; Dickens, Chris M; Richards, Suzanne

    2017-09-01

    To explore patients' and nurses' views on the feasibility and acceptability of providing psychological care within cardiac rehabilitation services. In-depth interviews analysed thematically. 18 patients and 7 cardiac nurses taking part in a pilot trial (CADENCE) of an enhanced psychological care intervention delivered within cardiac rehabilitation programmes by nurses to patients with symptoms of depression. Cardiac services based in the South West of England and the East Midlands, UK. Patients and nurses viewed psychological support as central to good cardiac rehabilitation. Patients' accounts highlighted the significant and immediate adverse effect a cardiac event can have on an individual's mental well-being. They also showed that patients valued nurses attending to both their mental and physical health, and felt this was essential to their overall recovery. Nurses were committed to providing psychological support, believed it benefited patients, and advocated for this support to be delivered within cardiac rehabilitation programmes rather than within a parallel healthcare service. However, nurses were time-constrained and found it challenging to provide psychological care within their existing workloads. Both patients and nurses highly value psychological support being delivered within cardiac rehabilitation programmes but resource constraints raise barriers to implementation. Consideration, therefore, should be given to alternative forms of delivery which do not rely solely on nurses to enable patients to receive psychological support during cardiac rehabilitation. ISCTRN34701576. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Organizational Commitment and Nurses' Characteristics as Predictors of Job Involvement.

    PubMed

    Alammar, Kamila; Alamrani, Mashael; Alqahtani, Sara; Ahmad, Muayyad

    2016-01-01

    To predict nurses' job involvement on the basis of their organizational commitment and personal characteristics at a large tertiary hospital in Saudi Arabia. Data were collected in 2015 from a convenience sample of 558 nurses working at a large tertiary hospital in Riyadh, Saudi Arabia. A cross-sectional correlational design was used in this study. Data were collected using a structured questionnaire. All commitment scales had significant relationships. Multiple linear regression analysis revealed that the model predicted a sizeable proportion of variance in nurses' job involvement (p < 0.001). High organizational commitment enhances job involvement, which may lead to more organizational stability and effectiveness.

  13. Organizational Climate and Teacher Commitment

    ERIC Educational Resources Information Center

    Douglas, Stephen Michael

    2010-01-01

    This study examined the relationship of school climate and teacher commitment in elementary schools in Alabama. A total of 67 elementary schools were surveyed and 1353 teachers voluntarily participated in the study. The instruments used in this study were the Organizational Climate Index (OCI) and the Organizational Commitment Questionnaire (OCQ).…

  14. Organizational Climate and Teacher Commitment

    ERIC Educational Resources Information Center

    Douglas, Stephen Michael

    2010-01-01

    This study examined the relationship of school climate and teacher commitment in elementary schools in Alabama. A total of 67 elementary schools were surveyed and 1353 teachers voluntarily participated in the study. The instruments used in this study were the Organizational Climate Index (OCI) and the Organizational Commitment Questionnaire (OCQ).…

  15. The Measurement of Organizational Commitment.

    ERIC Educational Resources Information Center

    Mowday, Richard T.; And Others

    1979-01-01

    This paper summarizes a stream of research aimed at developing and validating a measure of employee commitment to work organizations. The instrument, developed by Porter and his colleagues, is called the Organizational Commitment Questionnaire. Satisfactory test-retest reliabilities and internal consistency reliabilities were found. (Author)

  16. NADPH Oxidase/ROS-Dependent VCAM-1 Induction on TNF-α-Challenged Human Cardiac Fibroblasts Enhances Monocyte Adhesion

    PubMed Central

    Lin, Chih-Chung; Yang, Chien-Chung; Wang, Chen-Yu; Tseng, Hui-Ching; Pan, Chih-Shuo; Hsiao, Li-Der; Yang, Chuen-Mao

    2016-01-01

    The inflammation-dependent adhesion molecule expressions are characterized in cardiovascular diseases and myocardial tissue infiltrations. Several pro-inflammatory cytokines are elevated in the acute myocardial injury and infarction. Tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, is raised in the injury tissues and inflammatory regions and involved in the pathogenesis of cardiac injury, inflammation, and apoptosis. In fibroblasts, TNF-α-triggered expression of vascular cell adhesion molecule (VCAM)-1 aggravated the heart inflammation. However, the mechanisms underlying TNF-α-mediated VCAM-1 expression in cardiac fibroblasts remain unclear. Here, the primary cultured human cardiac fibroblasts (HCFs) were used to investigate the effects of TNF-α on VCAM-1 expression. The molecular evidence, including protein, mRNA, and promoter analyses, indicated that TNF-α-induced VCAM-1 gene expression is mediated through the TNFR-dependent manner. Activation of TNF-α/TNFR system triggered PKCα-dependent NADPH oxidase (Nox)/reactive oxygen species (ROS) signal linking to MAPK cascades, and then led to activation of the transcription factor, AP-1. Moreover, the results of mRNA and promoter assay demonstrated that c-Jun/AP-1 phosphorylated by TNF-α turns on VCAM-1 gene expression. Subsequently, up-regulated VCAM-1 on the cell surface of TNF-α-challenged HCFs increased the number of monocytes adhering to these cells. These results indicated that in HCFs, activation of AP-1 by PKCα-dependent Nox/ROS/MAPKs cascades is required for TNF-α-induced VCAM-1 expression. To clarify the mechanisms of TNF-α-induced VCAM-1 expression in HCFs may provide therapeutic strategies for heart injury and inflammatory diseases. PMID:26858641

  17. Combined administration of mesenchymal stem cells overexpressing IGF-1 and HGF enhances neovascularization but moderately improves cardiac regeneration in a porcine model.

    PubMed

    Gómez-Mauricio, Guadalupe; Moscoso, Isabel; Martín-Cancho, María-Fernanda; Crisóstomo, Verónica; Prat-Vidal, Cristina; Báez-Díaz, Claudia; Sánchez-Margallo, Francisco M; Bernad, Antonio

    2016-07-16

    Insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) are among the most promising growth factors for promoting cardiorepair. Here, we evaluated the combination of cell- and gene-based therapy using mesenchymal stem cells (MSC) genetically modified to overexpress IGF-1 or HGF to treat acute myocardial infarction (AMI) in a porcine model. Pig MSC from adipose tissue (paMSC) were genetically modified for evaluation of different therapeutic strategies to improve AMI treatment. Three groups of infarcted Large White pigs were compared (I, control, non-transplanted; II, transplanted with paMSC-GFP (green fluorescent protein); III, transplanted with paMSC-IGF-1/HGF). Cardiac function was evaluated non-invasively using magnetic resonance imaging (MRI) for 1 month. After euthanasia and sampling of the animal, infarcted areas were studied by histology and immunohistochemistry. Intramyocardial transplant in a porcine infarct model demonstrated the safety of paMSC in short-term treatments. Treatment with paMSC-IGF-1/HGF (1:1) compared with the other groups showed a clear reduction in inflammation in some sections analyzed and promoted angiogenic processes in ischemic tissue. Although cardiac function parameters were not significantly improved, cell retention and IGF-1 overexpression was confirmed within the myocardium. The simultaneous administration of IGF-1- and HGF-overexpressing paMSC appears not to promote a synergistic effect or effective repair. The combined enhancement of neovascularization and fibrosis in paMSC-IGF-1/HGF-treated animals nonetheless suggests that sustained exposure to high IGF-1 + HGF levels promotes beneficial as well as deleterious effects that do not improve overall cardiac regeneration.

  18. Experimental Unconditionally Secure Bit Commitment

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Cao, Yuan; Curty, Marcos; Liao, Sheng-Kai; Wang, Jian; Cui, Ke; Li, Yu-Huai; Lin, Ze-Hong; Sun, Qi-Chao; Li, Dong-Dong; Zhang, Hong-Fei; Zhao, Yong; Chen, Teng-Yun; Peng, Cheng-Zhi; Zhang, Qiang; Cabello, Adán; Pan, Jian-Wei

    2014-01-01

    Quantum physics allows for unconditionally secure communication between parties that trust each other. However, when the parties do not trust each other such as in the bit commitment scenario, quantum physics is not enough to guarantee security unless extra assumptions are made. Unconditionally secure bit commitment only becomes feasible when quantum physics is combined with relativistic causality constraints. Here we experimentally implement a quantum bit commitment protocol with relativistic constraints that offers unconditional security. The commitment is made through quantum measurements in two quantum key distribution systems in which the results are transmitted via free-space optical communication to two agents separated with more than 20 km. The security of the protocol relies on the properties of quantum information and relativity theory. In each run of the experiment, a bit is successfully committed with less than 5.68×10-2 cheating probability. This demonstrates the experimental feasibility of quantum communication with relativistic constraints.

  19. Alcohol breeds empty goal commitments.

    PubMed

    Sevincer, A Timur; Oettingen, Gabriele

    2009-08-01

    According to alcohol-myopia theory (C. M. Steele & R. A. Josephs, 1990), alcohol leads individuals to disproportionally focus on the most salient aspects of a situation and to ignore peripheral information. The authors hypothesized that alcohol leads individuals to strongly commit to their goals without considering information about the probability of goal attainment. In Study 1, participants named their most important interpersonal goal, indicated their expectations of successfully attaining it, and then consumed either alcohol or a placebo. In contrast to participants who consumed a placebo, intoxicated participants felt strongly committed to their goals despite low expectations of attaining them. In Study 2, goal-directed actions were measured over time. Once sober again, intoxicated participants with low expectations did not follow up on their strong commitments. Apparently, when prospects are bleak, alcohol produces empty goal commitments, as commitments are not based on individuals' expectations of attaining their goals and do not foster goal striving over time.

  20. Contexts as Shared Commitments

    PubMed Central

    García-Carpintero, Manuel

    2015-01-01

    Contemporary semantics assumes two influential notions of context: one coming from Kaplan (1989), on which contexts are sets of predetermined parameters, and another originating in Stalnaker (1978), on which contexts are sets of propositions that are “common ground.” The latter is deservedly more popular, given its flexibility in accounting for context-dependent aspects of language beyond manifest indexicals, such as epistemic modals, predicates of taste, and so on and so forth; in fact, properly dealing with demonstratives (perhaps ultimately all indexicals) requires that further flexibility. Even if we acknowledge Lewis (1980)'s point that, in a sense, Kaplanian contexts already include common ground contexts, it is better to be clear and explicit about what contexts constitutively are. Now, Stalnaker (1978, 2002, 2014) defines context-as-common-ground as a set of propositions, but recent work shows that this is not an accurate conception. The paper explains why, and provides an alternative. The main reason is that several phenomena (presuppositional treatments of pejoratives and predicates of taste, forces other than assertion) require that the common ground includes non-doxastic attitudes such as appraisals, emotions, etc. Hence the common ground should not be taken to include merely contents (propositions), but those together with attitudes concerning them: shared commitments, as I will defend. PMID:26733087

  1. Contexts as Shared Commitments.

    PubMed

    García-Carpintero, Manuel

    2015-01-01

    Contemporary semantics assumes two influential notions of context: one coming from Kaplan (1989), on which contexts are sets of predetermined parameters, and another originating in Stalnaker (1978), on which contexts are sets of propositions that are "common ground." The latter is deservedly more popular, given its flexibility in accounting for context-dependent aspects of language beyond manifest indexicals, such as epistemic modals, predicates of taste, and so on and so forth; in fact, properly dealing with demonstratives (perhaps ultimately all indexicals) requires that further flexibility. Even if we acknowledge Lewis (1980)'s point that, in a sense, Kaplanian contexts already include common ground contexts, it is better to be clear and explicit about what contexts constitutively are. Now, Stalnaker (1978, 2002, 2014) defines context-as-common-ground as a set of propositions, but recent work shows that this is not an accurate conception. The paper explains why, and provides an alternative. The main reason is that several phenomena (presuppositional treatments of pejoratives and predicates of taste, forces other than assertion) require that the common ground includes non-doxastic attitudes such as appraisals, emotions, etc. Hence the common ground should not be taken to include merely contents (propositions), but those together with attitudes concerning them: shared commitments, as I will defend.

  2. Enhanced carotid-cardiac baroreflex response and elimination of orthostatic hypotension 24 hours after acute exercise in paraplegics

    NASA Technical Reports Server (NTRS)

    Engelke, K. A.; Shea, J. D.; Doerr, D. F.; Convertino, V. A.

    1992-01-01

    To test the hypothesis that an acute bout of maximal exercise can ameliorate orthostatic hypotension consequent to prolonged wheelchair confinement, we evaluated heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure responses during 15 minutes of 70 degrees head-up tilt (HUT) in 10 paraplegic subjects 24 hours after arm crank exercise designed to elicit maximal effort, and during a control (no exercise) conditions. Additionally, the carotid baroreceptor stimulus-cardiac response relationship was determined by measurement of R-R interval during external application of graded pressures to the carotid sinuses. One week separated the treatment conditions. The maximum slope of the carotid-cardiac baroreflex response was increased (p = 0.049) by exercise (6.2 +/- 1.7 msec/mmHg) compared to control (3.3 +/- 0.6). During control HUT, HR increased from 61 +/- 1 to 90 +/- 7 bpm (p = 0.001) while SBP decreased from 118 +/- 5 to 106 +/- 9 mmHg (p = 0.025). During HUT 24 hours after exercise, HR increased from 60 +/- 2 to 90 +/- 4 bpm (p = 0.001), but the reduction in SBP was essentially eliminated (116 +/- 5 to 113 +/- 5 mmHg).

  3. Gene therapy delivery systems for enhancing viral and nonviral vectors for cardiac diseases: current concepts and future applications.

    PubMed

    Katz, Michael G; Fargnoli, Anthony S; Williams, Richard D; Bridges, Charles R

    2013-11-01

    Gene therapy is one of the most promising fields for developing new treatments for the advanced stages of ischemic and monogenetic, particularly autosomal or X-linked recessive, cardiomyopathies. The remarkable ongoing efforts in advancing various targets have largely been inspired by the results that have been achieved in several notable gene therapy trials, such as the hemophilia B and Leber's congenital amaurosis. Rate-limiting problems preventing successful clinical application in the cardiac disease area, however, are primarily attributable to inefficient gene transfer, host responses, and the lack of sustainable therapeutic transgene expression. It is arguable that these problems are directly correlated with the choice of vector, dose level, and associated cardiac delivery approach as a whole treatment system. Essentially, a delicate balance exists in maximizing gene transfer required for efficacy while remaining within safety limits. Therefore, the development of safe, effective, and clinically applicable gene delivery techniques for selected nonviral and viral vectors will certainly be invaluable in obtaining future regulatory approvals. The choice of gene transfer vector, dose level, and the delivery system are likely to be critical determinants of therapeutic efficacy. It is here that the interactions between vector uptake and trafficking, delivery route means, and the host's physical limits must be considered synergistically for a successful treatment course.

  4. Gene Therapy Delivery Systems for Enhancing Viral and Nonviral Vectors for Cardiac Diseases: Current Concepts and Future Applications

    PubMed Central

    Katz, Michael G.; Fargnoli, Anthony S.; Williams, Richard D.

    2013-01-01

    Abstract Gene therapy is one of the most promising fields for developing new treatments for the advanced stages of ischemic and monogenetic, particularly autosomal or X-linked recessive, cardiomyopathies. The remarkable ongoing efforts in advancing various targets have largely been inspired by the results that have been achieved in several notable gene therapy trials, such as the hemophilia B and Leber's congenital amaurosis. Rate-limiting problems preventing successful clinical application in the cardiac disease area, however, are primarily attributable to inefficient gene transfer, host responses, and the lack of sustainable therapeutic transgene expression. It is arguable that these problems are directly correlated with the choice of vector, dose level, and associated cardiac delivery approach as a whole treatment system. Essentially, a delicate balance exists in maximizing gene transfer required for efficacy while remaining within safety limits. Therefore, the development of safe, effective, and clinically applicable gene delivery techniques for selected nonviral and viral vectors will certainly be invaluable in obtaining future regulatory approvals. The choice of gene transfer vector, dose level, and the delivery system are likely to be critical determinants of therapeutic efficacy. It is here that the interactions between vector uptake and trafficking, delivery route means, and the host's physical limits must be considered synergistically for a successful treatment course. PMID:24164239

  5. Enhanced carotid-cardiac baroreflex response and elimination of orthostatic hypotension 24 hours after acute exercise in paraplegics

    NASA Technical Reports Server (NTRS)

    Engelke, K. A.; Shea, J. D.; Doerr, D. F.; Convertino, V. A.

    1992-01-01

    To test the hypothesis that an acute bout of maximal exercise can ameliorate orthostatic hypotension consequent to prolonged wheelchair confinement, we evaluated heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure responses during 15 minutes of 70 degrees head-up tilt (HUT) in 10 paraplegic subjects 24 hours after arm crank exercise designed to elicit maximal effort, and during a control (no exercise) conditions. Additionally, the carotid baroreceptor stimulus-cardiac response relationship was determined by measurement of R-R interval during external application of graded pressures to the carotid sinuses. One week separated the treatment conditions. The maximum slope of the carotid-cardiac baroreflex response was increased (p = 0.049) by exercise (6.2 +/- 1.7 msec/mmHg) compared to control (3.3 +/- 0.6). During control HUT, HR increased from 61 +/- 1 to 90 +/- 7 bpm (p = 0.001) while SBP decreased from 118 +/- 5 to 106 +/- 9 mmHg (p = 0.025). During HUT 24 hours after exercise, HR increased from 60 +/- 2 to 90 +/- 4 bpm (p = 0.001), but the reduction in SBP was essentially eliminated (116 +/- 5 to 113 +/- 5 mmHg).

  6. Acceptance and Commitment: Implications for Prevention Science

    PubMed Central

    Biglan, Anthony; Hayes, Steven C.; Pistorello, Jacqueline

    2009-01-01

    Recent research in behavior analysis and clinical psychology points to the importance of language processes having to do with the control of negative cognition and emotion and the commitment to valued action. Efforts to control unwanted thoughts and feelings, also referred to as experiential avoidance, appear to be associated with a diverse array of psychological and behavioral difficulties. Recent research shows that interventions that reduce experiential avoidance (EA) and help people to identify and commit to the pursuit of valued directions is beneficial for ameliorating diverse problems in living. These developments have the potential to improve the efficacy of many preventive interventions. This paper reviews the basic findings in these areas and points to some ways in which these developments could enhance the impact of preventive interventions. PMID:18690535

  7. Differentiation between acute and chronic myocardial infarction by means of texture analysis of late gadolinium enhancement and cine cardiac magnetic resonance imaging.

    PubMed

    Larroza, Andrés; Materka, Andrzej; López-Lereu, María P; Monmeneu, José V; Bodí, Vicente; Moratal, David

    2017-07-01

    The purpose of this study was to differentiate acute from chronic myocardial infarction using machine learning techniques and texture features extracted from cardiac magnetic resonance imaging (MRI). The study group comprised 22 cases with acute myocardial infarction (AMI) and 22 cases with chronic myocardial infarction (CMI). Cine and late gadolinium enhancement (LGE) MRI were analyzed independently to differentiate AMI from CMI. A total of 279 texture features were extracted from predefined regions of interest (ROIs): the infarcted area on LGE MRI, and the entire myocardium on cine MRI. Classification performance was evaluated by a nested cross-validation approach combining a feature selection technique with three predictive models: random forest, support vector machine (SVM) with Gaussian Kernel, and SVM with polynomial kernel. The polynomial SVM yielded the best classification performance. Receiver operating characteristic curves provided area-under-the-curve (AUC) (mean±standard deviation) of 0.86±0.06 on LGE MRI using 72 features; AMI sensitivity=0.81±0.08 and specificity=0.84±0.09. On cine MRI, AUC=0.82±0.06 using 75 features; AMI sensitivity=0.79±0.10 and specificity=0.80±0.10. We concluded that texture analysis can be used for differentiation of AMI from CMI on cardiac LGE MRI, and also on standard cine sequences in which the infarction is visually imperceptible in most cases. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Commitment Contracts and Team Incentives

    PubMed Central

    White, Justin S.; Dow, William H.; Rungruanghiranya, Suthat

    2013-01-01

    Background Treatment for tobacco dependence is not available in many low-resource settings, especially in developing countries. Purpose To test the impact of a novel mix of monetary and social incentives on smoking abstinence in rural communities of Thailand. Design An RCT of commitment contracts and team incentives for rural smokers to quit smoking. Smokers were not blinded to treatment status, although the assessor of the biochemical urine test was. Setting/participants All adult smokers living in the study area were eligible to participate; 215 adult smokers from 42 villages in Nakhon Nayok province, Thailand participated. Fourteen smokers who lacked teammates were dropped. Intervention 201 smokers were assigned to a two-person team, and then randomly assigned by team (in a 2:1 ratio) with computer-generated random numbers to receive smoking-cessation counseling (control group) or counseling plus offer of a commitment contract, team incentives, and text message reminders for smoking cessation at 3 months (intervention group). Main outcome measures The primary outcome was biochemically-verified 7-day abstinence at 6 months, assessed on an intention-to-treat basis. Secondary outcomes include biochemically-verified abstinence at 3 months, self-reported abstinence at 14 months, and the incremental cost per quitter of the intervention, nicotine gum, and varenicline in Thailand. Data were collected in 2010–2011 and analyzed in 2012. Results The trial enrolled 215 (10.5%) of 2055 smokers. The abstinence rate was 46.2% (61/132) in the intervention group and 14.5% (10/69) in the control group (adjusted OR 7.5 [3.0–18.6]) at 3 months; 44.3% (58/131) and 18.8% (13/69) at the primary end point of 6 months (adjusted OR 4.2 [1.8–9.7]); and 42.0% (55/131) and 24.6% (17/69) at 14 months (adjusted OR 2.2 [1.0–4.8]). The purchasing-power–parity-adjusted incremental cost per quitter from the intervention is $281 (95% CI=$187, $562), less than for nicotine gum ($1780 [95

  9. Newly graduated nurses' occupational commitment and its associations with professional competence and work-related factors.

    PubMed

    Numminen, Olivia; Leino-Kilpi, Helena; Isoaho, Hannu; Meretoja, Riitta

    2016-01-01

    -up studies of newly graduated nurses' commitment, its relationship with quality care, managers' role in enhancing commitment and evaluation of the impact of interventions on improving commitment need further studying. © 2015 John Wiley & Sons Ltd.

  10. Fibroblast Growth Factor-9 Enhances M2 Macrophage Differentiation and Attenuates Adverse Cardiac Remodeling in the Infarcted Diabetic Heart

    PubMed Central

    Singla, Dinender K.; Singla, Reetu D.; Abdelli, Latifa S.; Glass, Carley

    2015-01-01

    Inflammation has been implicated as a perpetrator of diabetes and its associated complications. Monocytes, key mediators of inflammation, differentiate into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages upon infiltration of damaged tissue. However, the inflammatory cell types, which propagate diabetes progression and consequential adverse disorders, remain unclear. The current study was undertaken to assess monocyte infiltration and the role of fibroblast growth factor-9 (FGF-9) on monocyte to macrophage differentiation and cardioprotection in the diabetic infarcted heart. Db/db diabetic mice were assigned to sham, myocardial infarction (MI), and MI+FGF-9 groups. MI was induced by permanent coronary artery ligation and animals were subjected to 2D transthoracic echocardiography two weeks post-surgery. Immunohistochemical and immunoassay results from heart samples collected suggest significantly increased infiltration of monocytes (Mean ± SEM; MI: 2.02% ± 0.23% vs. Sham 0.75% ± 0.07%; p<0.05) and associated pro-inflammatory cytokines (TNF-α, MCP-1, and IL-6), adverse cardiac remodeling (Mean ± SEM; MI: 33% ± 3.04% vs. Sham 2.2% ± 0.33%; p<0.05), and left ventricular dysfunction (Mean ± SEM; MI: 35.4% ± 1.25% vs. Sham 49.19% ± 1.07%; p<0.05) in the MI group. Importantly, treatment of diabetic infarcted myocardium with FGF-9 resulted in significantly decreased monocyte infiltration (Mean ± SEM; MI+FGF-9: 1.39% ± 0.1% vs. MI: 2.02% ± 0.23%; p<0.05), increased M2 macrophage differentiation (Mean ± SEM; MI+FGF-9: 4.82% ± 0.86% vs. MI: 0.85% ± 0.3%; p<0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean ± SEM; MI+FGF-9: 11.59% ± 1.2% vs. MI: 33% ± 3.04%; p<0.05), and improved cardiac function (Fractional shortening, Mean ± SEM; MI+FGF-9: 41.51% ± 1.68% vs. MI: 35.4% ± 1.25%; p<0.05). In conclusion, our data suggest FGF-9 possesses novel therapeutic potential in its ability to

  11. [Study of optimal flip angle for inversion-recovery gradient echo method in delayed contrast-enhanced cardiac magnetic resonance imaging].

    PubMed

    Ogawa, Masashi; Matsumura, Yoshio; Tsuchihashi, Toshio

    2013-04-01

    Delayed contrast-enhanced cardiac magnetic resonance imaging (MRI) is a valuable tool for detecting myocardial infarction and assessing myocardial viability. The standard viability MRI technique is the inversion-recovery gradient echo (IR-GRE) method. Several previous studies have demonstrated that this imaging technique provides superior image quality at high magnetic field strengths, e.g., 3.0 T. However, there are numerous possible flip angles. We investigated the optimal flip angle of IR-GRE in delayed contrast-enhanced cardiac MRI. Phantoms were made that modeled infarcted myocardium and normal myocardium after administration of contrast agent. To determine optimal flip angle, we compared the contrast-to-noise ratio (CNR) among these phantoms and evaluated the degree of artifacts induced by increased flip angle. The flip angle that showed the highest CNR for 2D IR-GRE and 3D IR-GRE was 30°/15° at 1.5 T and 25°/15° at 3.0 T. The flip angle that showed the highest CNR was independent of R-R interval. Streak artifacts induced by increased flip angle tended to occur more readily at 3.0 T than 1.5 T. The optimal flip angle for 2D IR-GRE and 3D IR-GRE at 1.5 T was 30° and 15°, respectively. At 3.0 T, taking into account the results for both CNR and streak artifacts, we concluded the optimal flip angle of 2D IR-GRE to be 15-20°.

  12. Reporters and Their Professional and Organizational Commitment.

    ERIC Educational Resources Information Center

    Becker, Lee B.; And Others

    1979-01-01

    Secondary analyses of data gathered in a national study of United States journalists yielded information about variables that predict professional and organizational commitment. The factors selected for analysis were found to explain organizational commitment better than professional commitment. (GT)

  13. Self-determination in sport commitment.

    PubMed

    Zahariadis, Panayotis; Tsorbatzoudis, Haralambos; Alexandris, Konstantinos

    2006-04-01

    The study tested utility of self-determination and sport commitment theories to understanding young athletes' sport commitment. 343 young athletes (M= 13.5 yr., SD= +/- 1.1) from soccer, basketball, volleyball, handball, and water polo teams volunteered to participate. All completed the Sport Motivation Scale and the Sport Commitment Questionnaire. Pearson correlations showed a strong relationship between commitment and intrinsic motivation scores. In contrast, extrinsic motivation scores were not significantly correlated to commitment, whereas amotivation scores showed a negative correlation to commitment. Path analysis resulted in strong positive association of intrinsic motivation and commitment. Amotivation had small negative relation to commitment. According to the model tested, social constraints and involvement opportunities were not significant contributors to sport commitment. An alternative model supported the mediating role of enjoyment to psychological commitment. The results showed that high self-determination is supportive of sport commitment, whereas low self-determination reduces sport commitment.

  14. Insulin-like growth factor-1 enhances ventricular hypertrophy and function during the onset of experimental cardiac failure.

    PubMed Central

    Duerr, R L; Huang, S; Miraliakbar, H R; Clark, R; Chien, K R; Ross, J

    1995-01-01

    To determine whether additional hypertrophy would be beneficial or maladaptive in cardiac failure, the effects of insulin-like growth factor (IGF-1) were investigated in rats with left ventricular (LV) dysfunction. In normal rats, 3 mg/kg per d of recombinant human IGF-1 for 14 d augmented LV wt (32%) and increased LV/body wt ratio (P < 0.01). 2 d after coronary occlusion, rats were randomized to IGF-1 (3 mg/kg per d) or placebo. After 2 wk, IGF-1-treated rats showed significant increases in LV wt (13%) and LV wt/tibial length ratio, but LV/body wt ratio was unchanged. By microangiography, compared with controls (n = 12) IGF-1-treated rats (n = 16) showed increased LV end-diastolic volume (19%) and stroke volume (31%) (both significant normalized to tibial length, but not to body wt). Average infarct size did not differ between groups. The LV ejection fraction (EF) was not significantly different between groups, but estimated cardiac output was higher in treated rats; there was a significant interaction for the EF between infarct size and treatment (P = 0.029) and a trend for EF to be higher in treated rats with large infarctions (EF 33.4 vs 25.1% in controls). Myocyte cross-sectional areas in noninfarcted LV zones tended to be larger in treated rats (232.1 vs 205.4 microns 2; P = 0.10), but there was no difference in capillary density and collagen content did not differ between groups. In conclusion, IGF-1 administration caused hypertrophy of the normal heart in vivo. When stimulated by IGF-1, the severely dysfunctional heart in evolving myocardial infarction is capable of undergoing additional hypertrophy with evidence of improved function, suggesting a beneficial effect. Further investigation of the potential role of growth factor therapy in heart failure appears warranted. PMID:7860746

  15. Integrated cardiac magnetic resonance imaging with coronary magnetic resonance angiography, stress-perfusion, and delayed-enhancement imaging for the detection of occult coronary artery disease in asymptomatic individuals.

    PubMed

    Song, Kyoung Doo; Kim, Sung Mok; Choe, Yeon Hyeon; Jung, Wooin; Lee, Sang-Chol; Chang, Sung-A; Choi, Yoon Ho; Sung, Jidong

    2015-06-01

    To evaluate the feasibility of using coronary magnetic resonance angiography (CMRA) with stress-perfusion and delayed-enhancement MRI as a screening tool for the detection of coronary artery disease (CAD) in asymptomatic subjects. Three hundred and forty-one self-referred asymptomatic subjects were enrolled in this study. Cardiac MR imaging was performed using a 1.5-T scanner with a 32-channel cardiac coil. Coronary artery stenosis, regional wall motion abnormalities, myocardial perfusion abnormalities, and delayed myocardial enhancement were analyzed. The occurrence of new chest pain and cardiac events was assessed in 332 subjects (97.3 %) over an average 29 ± 6 months (range, 18-39 months) follow-up period. A total of 3296 (82.4 %) of 4000 coronary artery segments examined exhibited diagnostic image quality on combined whole-heart and volume-targeted CMRA. Combined MRI detected significant CADs in 13 (3.8 %) of 341 subjects. Among these, 11 subjects (84.6 %) had both coronary artery stenosis (≥50 % by diameter) on CMRA and stress-perfusion defects in corresponding areas. Five of the 13 subjects showed evidence of old myocardial infarctions on delayed-enhancement MRI. Three subjects (0.9 %) underwent percutaneous coronary intervention after CAD was detected on cardiac MRI. There were no cardiac events during the follow-up period in subjects who complied with follow-up. Normal stress-perfusion and delayed-enhancement MRI lead to excellent outcomes when used to predict future cardiac events in asymptomatic subjects. Coronary MRA correlates well with stress-perfusion MRI for detecting significant CAD and helps exclude CAD in asymptomatic individuals.

  16. Communication, Leadership, and Organizational Commitment.

    ERIC Educational Resources Information Center

    Eblen, Anna L.

    1987-01-01

    Analyzes the relationship of leadership style and communication behavior to employee commitment. Finds that leaders' stylistic qualities and socially skilled communication play a part in predicting how subordinates feel about their organization. (MS)

  17. Committed warming inferred from observations

    NASA Astrophysics Data System (ADS)

    Mauritsen, Thorsten; Pincus, Robert

    2017-09-01

    Due to the lifetime of CO2, the thermal inertia of the oceans, and the temporary impacts of short-lived aerosols and reactive greenhouse gases, the Earth’s climate is not equilibrated with anthropogenic forcing. As a result, even if fossil-fuel emissions were to suddenly cease, some level of committed warming is expected due to past emissions as studied previously using climate models. Here, we provide an observational-based quantification of this committed warming using the instrument record of global-mean warming, recently improved estimates of Earth’s energy imbalance, and estimates of radiative forcing from the Fifth Assessment Report of the Intergovernmental Panel on Climate Change. Compared with pre-industrial levels, we find a committed warming of 1.5 K (0.9-3.6, 5th-95th percentile) at equilibrium, and of 1.3 K (0.9-2.3) within this century. However, when assuming that ocean carbon uptake cancels remnant greenhouse gas-induced warming on centennial timescales, committed warming is reduced to 1.1 K (0.7-1.8). In the latter case there is a 13% risk that committed warming already exceeds the 1.5 K target set in Paris. Regular updates of these observationally constrained committed warming estimates, although simplistic, can provide transparent guidance as uncertainty regarding transient climate sensitivity inevitably narrows and the understanding of the limitations of the framework is advanced.

  18. The Role of Cardiac Side Population Cells in Cardiac Regeneration

    PubMed Central

    Yellamilli, Amritha; van Berlo, Jop H.

    2016-01-01

    The heart has a limited ability to regenerate. It is important to identify therapeutic strategies that enhance cardiac regeneration in order to replace cardiomyocytes lost during the progression of heart failure. Cardiac progenitor cells are interesting targets for new regenerative therapies because they are self-renewing, multipotent cells located in the heart. Cardiac side population cells (cSPCs), the first cardiac progenitor cells identified in the adult heart, have the ability to differentiate into cardiomyocytes, endothelial cells, smooth muscle cells, and fibroblasts. They become activated in response to cardiac injury and transplantation of cSPCs into the injured heart improves cardiac function. In this review, we will discuss the current literature on the progenitor cell properties and therapeutic potential of cSPCs. This body of work demonstrates the great promise cSPCs hold as targets for new regenerative strategies. PMID:27679798

  19. Antimicrobial innovation: combining commitment, creativity and coherence.

    PubMed

    van der Meer, Jos W M; Fears, Robin; Davies, Sally C; ter Meulen, Volker

    2014-10-01

    Enhanced antibiotic innovation depends on many things--defining and validating new and better targets, resourcing and facilitating high-quality preclinical and clinical research, streamlining regulation and solving market problems so as to provide incentives to the private sector. Further detail is provided in our recent report (see further information). Acting on these critical steps in concert to provide long-term solutions requires that urgent attention be paid to tackling policy disconnects. Sustaining the political commitment depends on raising the visibility of the problems and their solutions worldwide. The academies of science in the EU recognize their continuing responsibility to help do this.

  20. Enhancing kidney function with thrombolytic therapy following donation after cardiac death: a multicenter quasi-blinded prospective randomized trial.

    PubMed

    Woodside, Kenneth J; Goldfarb, David A; Rabets, John C; Sanchez, Edmund Q; Lebovitz, Daniel J; Schulak, James A; Fung, John J; Eghtesad, Bijan

    2015-12-01

    Kidneys from donors after cardiac death (DCD) are at risk for inferior outcomes, possibly due to microthrombi and additional warm ischemia. We describe an organ procurement organization-wide trial utilizing thrombolytic tissue plasminogen activator (tPA) during machine pulsatile perfusion (MPP). A kidney from each recovered kidney pair was prospectively randomized to receive tPA (50 mg Alteplase) or no tPA (control) in the MPP perfusate. From 2011 to 2013, 24 kidneys were placed with enrolled recipients from 19 DCD kidney donors. There were no significant differences for absolute values of flow or resistance while undergoing MPP between the groups, nor rates of achieving discrete flow and resistance targets. While there was a trend toward lower creatinine and higher glomerular filtration rates in the tPA group at 3, 6, 9, and 12 months, these differences were not significant. Delayed graft function (DGF) rates were 41.7% in the tPA group vs. 58.4% in the control group (OR 0.51, 95%CI 0.10-2.59, p = 0.68). Death-censored graft survival was similar between the groups. In this pilot study, encouraging trends are seen in kidney allograft function independent of MPP parameters following DCD kidney transplantation for those kidneys receiving thrombolytic tPA and MPP, compared with standard MPP. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Enhanced effect of VEGF165 on L-type calcium currents in guinea-pig cardiac ventricular myocytes.

    PubMed

    Xing, Wenlu; Gao, Chuanyu; Qi, Datun; Zhang, You; Hao, Peiyuan; Dai, Guoyou; Yan, Ganxin

    2017-01-01

    The mechanisms of vascular endothelial growth factor 165 (VEGF165) on electrical properties of cardiomyocytes have not been fully elucidated. The aim of this study is to test the hypothesis that VEGF165, an angiogenesis-initiating factor, affects L-type calcium currents (ICa,L) and cell membrane potential in cardiac myocytes by acting on VEGF type-2 receptors (VEGFR2). ICa,L and action potentials (AP) were recorded by the whole-cell patch clamp method in isolated guinea-pig ventricular myocytes treated with different concentrations of VEGF165 proteins. Using a VEGFR2 inhibitor, we also tested the receptor of VEGF165 in cardiomyocytes. We found that VEGF165 increased ICa,L in a concentration-dependent manner. SU5416, a VEGFR2 inhibitor, almost completely eliminated VEGF165-induced ICa,L increase. VEGF165 had no significant influence on action potential 90 (APD90) and other properties of AP. We conclude that in guinea-pig ventricular myocytes, ICa,L can be increased by VEGF165 in a concentration-dependent manner through binding to VEGFR2 without causing any significant alteration to action potential duration. Results of this study may further expound the safety of VEGF165 when used in the intervention of heart diseases.

  2. Contrast-enhanced specific absorption rate-efficient 3D cardiac cine with respiratory-triggered radiofrequency gating.

    PubMed

    Henningsson, Markus; Chan, Raymond H; Goddu, Beth; Goepfert, Lois A; Razavi, Reza; Botnar, Rene M; Schaeffter, Tobias; Nezafat, Reza

    2013-04-01

    To investigate the use of radiofrequency (RF) gating in conjunction with a paramagnetic contrast agent to reduce the specific absorption rate (SAR) and increase the blood-myocardium contrast in balanced steady-state free precession (bSSFP) 3D cardiac cine. RF gating was implemented by synchronizing the RF-excitation with an external respiratory sensor (bellows), which could additionally be used for respiratory gating. For reference, respiratory-gated 3D cine images were acquired without RF gating. Free-breathing 3D cine images were acquired in eight healthy subjects before and after contrast injection (Gd-BOPTA) and compared to breath-hold 2D cine. RF-gated 3D cine reduced the SAR by nearly 40% without introducing significant artifacts while providing left ventricle (LV) measurements similar to those obtained with 2D cine. The contrast-to-noise ratio (CNR) was significantly higher for 3D cine compared to 2D cine, both before and after contrast injection; however, no statistically significant CNR increase was observed for the postcontrast 3D cine compared to the precontrast acquisitions. Respiratory-triggered RF gating significantly reduces SAR in 3D cine acquisitions, which may enable a more widespread clinical use of 3D cine. Furthermore, CNR of 3D bSSFP cine is higher than of 2D and administration of Gd-BOPTA does not improve the CNR of 3D cine. Copyright © 2012 Wiley Periodicals, Inc.

  3. Determination of cardiac ejection fraction and left ventricular volume: contrast-enhanced ultrafast cine MR imaging vs IV digital subtraction ventriculography.

    PubMed

    Matsumura, K; Nakase, E; Haiyama, T; Takeo, K; Shimizu, K; Yamasaki, K; Kohno, K

    1993-05-01

    To assess the accuracy of contrast-enhanced, single breath-hold cine MR imaging in the calculation of left ventricular volume and ejection fraction, we compared values obtained by using this method with those obtained by using IV digital subtraction angiography (IV-DSA). All patients (n = 28) had conventional cine and contrast-enhanced ultrafast cine MR imaging. For ultrafast cine MR imaging, a phase-rewind gradient-echo (rewind-SMASH) sequence was used: TR, 8 msec (standard excitation and acquisition block of 6 msec with phase rewind pulse of 2 msec); TE, 3.2 msec; a 128 x 96 matrix (pile encode factor, 6; k-space segment, 16); a 200-mm field of view; and one excitation. Values for left ventricular volume and ejection fraction obtained with ultrafast cine MR imaging correlated well with those obtained with IV-DSA (end-diastolic volume, y = 0.986x - 7.79, r = .985; end-systolic volume, y = 0.863x + 0.71, r = .984; ejection fraction, y = 0.877x + 6.44, r = .887). In the calculation of left ventricular volume by the area-length method, manual tracing of the left ventricular cavity was more difficult when the conventional cine method was used than when the enhanced ultrafast cine method was used. Our results show that cardiac multiphase study with horizontal long-axis, first-pass, contrast-enhanced, single breath-hold, cine MR imaging is an accurate and highly reproducible method of evaluating left ventricular volume and ejection fraction.

  4. Differentiation of pre-ablation and post-ablation late gadolinium-enhanced cardiac MRI scans of longstanding persistent atrial fibrillation patients

    NASA Astrophysics Data System (ADS)

    Yang, Guang; Zhuang, Xiahai; Khan, Habib; Haldar, Shouvik; Nyktari, Eva; Li, Lei; Ye, Xujiong; Slabaugh, Greg; Wong, Tom; Mohiaddin, Raad; Keegan, Jennifer; Firmin, David

    2017-03-01

    Late Gadolinium-Enhanced Cardiac MRI (LGE CMRI) is an emerging non-invasive technique to image and quantify preablation native and post-ablation atrial scarring. Previous studies have reported that enhanced image intensities of the atrial scarring in the LGE CMRI inversely correlate with the left atrial endocardial voltage invasively obtained by electro-anatomical mapping. However, the reported reproducibility of using LGE CMRI to identify and quantify atrial scarring is variable. This may be due to two reasons: first, delineation of the left atrium (LA) and pulmonary veins (PVs) anatomy generally relies on manual operation that is highly subjective, and this could substantially affect the subsequent atrial scarring segmentation; second, simple intensity based image features may not be good enough to detect subtle changes in atrial scarring. In this study, we hypothesized that texture analysis can provide reliable image features for the LGE CMRI images subject to accurate and objective delineation of the heart anatomy based on a fully-automated whole heart segmentation (WHS) method. We tested the extracted texture features to differentiate between pre-ablation and post-ablation LGE CMRI studies in longstanding persistent atrial fibrillation patients. These patients often have extensive native scarring and differentiation from post-ablation scarring can be difficult. Quantification results showed that our method is capable of solving this classification task, and we can envisage further deployment of this texture analysis based method for other clinical problems using LGE CMRI.

  5. Multi-atlas propagation based left atrium segmentation coupled with super-voxel based pulmonary veins delineation in late gadolinium-enhanced cardiac MRI

    NASA Astrophysics Data System (ADS)

    Yang, Guang; Zhuang, Xiahai; Khan, Habib; Haldar, Shouvik; Nyktari, Eva; Li, Lei; Ye, Xujiong; Slabaugh, Greg; Wong, Tom; Mohiaddin, Raad; Keegan, Jennifer; Firmin, David

    2017-02-01

    Late Gadolinium-Enhanced Cardiac MRI (LGE CMRI) is a non-invasive technique, which has shown promise in detecting native and post-ablation atrial scarring. To visualize the scarring, a precise segmentation of the left atrium (LA) and pulmonary veins (PVs) anatomy is performed as a first step—usually from an ECG gated CMRI roadmap acquisition—and the enhanced scar regions from the LGE CMRI images are superimposed. The anatomy of the LA and PVs in particular is highly variable and manual segmentation is labor intensive and highly subjective. In this paper, we developed a multi-atlas propagation based whole heart segmentation (WHS) to delineate the LA and PVs from ECG gated CMRI roadmap scans. While this captures the anatomy of the atrium well, the PVs anatomy is less easily visualized. The process is therefore augmented by semi-automated manual strokes for PVs identification in the registered LGE CMRI data. This allows us to extract more accurate anatomy than the fully automated WHS. Both qualitative visualization and quantitative assessment with respect to manual segmented ground truth showed that our method is efficient and effective with an overall mean Dice score of 0.91.

  6. Company, country, connections: counterfactual origins increase organizational commitment, patriotism, and social investment.

    PubMed

    Ersner-Hershfield, Hal; Galinsky, Adam D; Kray, Laura J; King, Brayden G

    2010-10-01

    Four studies examined the relationship between counterfactual origins--thoughts about how the beginning of organizations, countries, and social connections might have turned out differently--and increased feelings of commitment to those institutions and connections. Study 1 found that counterfactually reflecting on the origins of one's country increases patriotism. Study 2 extended this finding to organizational commitment and examined the mediating role of poignancy. Study 3 found that counterfactual reflection boosts organizational commitment even beyond the effects of other commitment-enhancing appeals and that perceptions of fate mediate the positive effect of counterfactual origins on commitment. Finally, Study 4 temporally separated the counterfactual manipulation from a behavioral measure of commitment and found that counterfactual reflection predicted whether participants e-mailed social contacts 2 weeks later. The robust relationship between counterfactual origins and commitment was found across a wide range of companies and countries, with undergraduates and M.B.A. students, and for attitudes and behaviors.

  7. The β-arrestin-biased ligand TRV120023 inhibits angiotensin II-induced cardiac hypertrophy while preserving enhanced myofilament response to calcium

    PubMed Central

    Monasky, Michelle M.; Taglieri, Domenico M.; Henze, Marcus; Warren, Chad M.; Utter, Megan S.; Soergel, David G.; Violin, Jonathan D.

    2013-01-01

    In the present study, we compared the cardioprotective effects of TRV120023, a novel angiotensin II (ANG II) type 1 receptor (AT1R) ligand, which blocks G protein coupling but stimulates β-arrestin signaling, against treatment with losartan, a conventional AT1R blocker in the treatment of cardiac hypertrophy and regulation of myofilament activity and phosphorylation. Rats were subjected to 3 wk of treatment with saline, ANG II, ANG II + losartan, ANG II + TRV120023, or TRV120023 alone. ANG II induced increased left ventricular mass compared with rats that received ANG II + losartan or ANG II + TRV120023. Compared with saline controls, ANG II induced a significant increase in pCa50 and maximum Ca2+-activated myofilament tension but reduced the Hill coefficient (nH). TRV120023 increased maximum tension and pCa50, although to lesser extent than ANG II. In contrast to ANG II, TRV120023 increased nH. Losartan blocked the effects of ANG II on pCa50 and nH and reduced maximum tension below that of saline controls. ANG II + TRV120023 showed responses similar to those of TRV120023 alone; compared with ANG II + losartan, ANG II + TRV120023 preserved maximum tension and increased both pCa50 and cooperativity. Tropomyosin phosphorylation was lower in myofilaments from saline-treated hearts compared with the other groups. Phosphorylation of cardiac troponin I was significantly reduced in ANG II + TRV120023 and TRV120023 groups versus saline controls, and myosin-binding protein C phosphorylation at Ser282 was unaffected by ANG II or losartan but significantly reduced with TRV120023 treatment compared with all other groups. Our data indicate that TRV120023-related promotion of β-arrestin signaling and enhanced contractility involves a mechanism promoting the myofilament response to Ca2+ via altered protein phosphorylation. Selective activation of β-arrestin-dependent pathways may provide advantages over conventional AT1R blockers. PMID:23873795

  8. Preconditioning c-Kit-positive Human Cardiac Stem Cells with a Nitric Oxide Donor Enhances Cell Survival through Activation of Survival Signaling Pathways.

    PubMed

    Teng, Lei; Bennett, Edward; Cai, Chuanxi

    2016-04-29

    Cardiac stem cell therapy has shown very promising potential to repair the infarcted heart but is severely limited by the poor survival of donor cells. Nitric oxide (NO) has demonstrated cytoprotective properties in various cells, but its benefits are unknown specifically for human cardiac stem cells (hCSCs). Therefore, we investigated whether pretreatment of hCSCs with a widely used NO donor, diethylenetriamine nitric oxide adduct (DETA-NO), promotes cell survival. Results from lactate dehydrogenase release assays showed a dose- and time-dependent attenuation of cell death induced by oxidative stress after DETA-NO preconditioning; this cytoprotective effect was abolished by the NO scavenger. Concomitant up-regulation of several cell signaling molecules after DETA-NO preconditioning was observed by Western blotting, including elevated phosphorylation of NRF2, NFκB, STAT3, ERK, and AKT, as well as increased protein expression of HO-1 and COX2. Furthermore, pharmaceutical inhibition of ERK, STAT3, and NFκB activities significantly diminished NO-induced cytoprotection against oxidative stress, whereas inhibition of AKT or knockdown of NRF2 only produced a minor effect. Blocking PI3K activity or knocking down COX2 expression did not alter the protective effect of DETA-NO on cell survival. The crucial roles of STAT3 and NFκB in NO-mediated signaling pathways were further confirmed by stable expression of gene-specific shRNAs in hCSCs. Thus, preconditioning hCSCs with DETA-NO promotes cell survival and resistance to oxidative stress by activating multiple cell survival signaling pathways. These results will potentially provide a simple and effective strategy to enhance survival of hCSCs after transplantation and increase their efficacy in repairing infarcted myocardium. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Cardiac Sarcoidosis.

    PubMed

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo

    2015-12-01

    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  10. Lipid emulsion enhances cardiac performance after ischemia-reperfusion in isolated hearts from summer-active arctic ground squirrels.

    PubMed

    Salzman, Michele M; Cheng, Qunli; Deklotz, Richard J; Dulai, Gurpreet K; Douglas, Hunter F; Dikalova, Anna E; Weihrauch, Dorothee; Barnes, Brian M; Riess, Matthias L

    2017-03-31

    Hibernating mammals, like the arctic ground squirrel (AGS), exhibit robust resistance to myocardial ischemia/reperfusion (IR) injury. Regulated preference for lipid over glucose to fuel metabolism may play an important role. We tested whether providing lipid in an emulsion protects hearts from summer-active AGS better than hearts from Brown Norway (BN) rats against normothermic IR injury. Langendorff-prepared AGS and BN rat hearts were perfused with Krebs solution containing 7.5 mM glucose with or without 1% Intralipid™. After stabilization and cardioplegia, hearts underwent 45-min global ischemia and 60-min reperfusion. Coronary flow, isovolumetric left ventricular pressure, and mitochondrial redox state were measured continuously; infarct size was measured at the end of the experiment. Glucose-only AGS hearts functioned significantly better on reperfusion than BN rat hearts. Intralipid™ administration resulted in additional functional improvement in AGS compared to glucose-only and BN rat hearts. Infarct size was not different among groups. Even under non-hibernating conditions, AGS hearts performed better after IR than the best-protected rat strain. This, however, appears to strongly depend on metabolic fuel: Intralipid™ led to a significant improvement in return of function in AGS, but not in BN rat hearts, suggesting that year-round endogenous mechanisms are involved in myocardial lipid utilization that contributes to improved cardiac performance, independent of the metabolic rate decrease during hibernation. Comparative lipid analysis revealed four candidates as possible cardioprotective lipid groups. The improved function in Intralipid™-perfused AGS hearts also challenges the current paradigm that increased glucose and decreased lipid metabolism are favorable during myocardial IR.

  11. Comparison of two- and three-dimensional unenhanced and contrast-enhanced echocardiographies versus cineventriculography versus cardiac magnetic resonance for determination of left ventricular function.

    PubMed

    Hoffmann, Rainer; von Bardeleben, Stephan; Barletta, Giuseppe; Pasques, Agnes; Kasprzak, Jaroslaw; Greis, Christian; Becher, Harald

    2014-01-15

    Contrast enhancement has been shown to improve detection of regional wall motion abnormalities (RWMA) in 2-dimensional (2D) echocardiography. This study determined the use of contrast enhancement in the setting of 3-dimensional (3D) echocardiography for definition of left ventricular RWMA compared with 2D echocardiography, cineventriculography, and cardiac magnetic resonance (CMR). In 63 patients, unenhanced and contrast-enhanced (SonoVue; Bracco Imaging S.p.A., Milan, Italy) 2D and 3D echocardiographies, CMR, and cineventriculography were performed. Hypokinesia in ≥1 segment defined the presence of RWMA. Interreader agreement (IRA) between 2 blinded off-site readers on presence of RWMA was determined within each imaging technique. Intermethod agreement among imaging techniques was analyzed. A standard of truth for the presence of RWMA was obtained by an independent expert panel decision. IRA on presence of RWMA expressed as Cohen's κ coefficient was 0.27 for unenhanced 3D echocardiography, 0.40 for unenhanced 2D echocardiography, 0.57 for CMR, and 0.51 for cineventriculography. The use of contrast increased IRA on RWMA to 0.42 for 3D echocardiography and to 0.56 for 2D echocardiography. Agreement with CMR on RWMA increased for 3D echocardiography when contrast enhancement was used (κ 0.40 vs 0.22 for unenhanced 3D echocardiography). Similarly, agreement of 2D echocardiography with CMR on RWMA increased with contrast enhancement (κ 0.50 vs 0.32). Accuracy to detect expert panel-defined RWMA was highest for CMR (84%) followed by 2D contrast echocardiography (78%) and 3D contrast echocardiography (76%). It was lesser for 2D and 3D unenhanced echocardiographies. In conclusion, analysis of RWMA is characterized by considerable interreader variability even using high-quality imaging techniques. IRA on RWMA is lower with 3D echocardiography compared with 2D echocardiography. IRA on RWMA and accuracy to detect panel-defined RWMA improve with contrast enhancement

  12. Our commitment to quality

    SciTech Connect

    1995-05-01

    The Office of Science Education and Technical Information (OSETI) provides leadership in leveraging the Department of Energy`s (DOE) unique scientific and technical resources to enhance the United States (U.S.) global competitiveness and the development of a diverse, well-educated, scientifically literate workforce. The Office provides scientific and technical information management policy, guidance, and services, as well as education program assistance, to a wide range of customers to help the Department contribute to the Nation`s welfare. OSETI was established in July 1993 within the Science and Technology cluster. The Office has two subcomponents, the Office of Scientific and Technical Information (OSTI), located in Oak Ridge, Tennessee, and the Office of Science Education Programs (OSEP), located in Washington, D.C. (see organization chart on page 5). OSTI, the larger of the two offices, has 164 full-time equivalent (FTE) federal staff and 100 contractor employees, while OSEP has 21 federal and 5 contractor employees.

  13. Cardiac arrest

    MedlinePlus

    ... or low levels can cause cardiac arrest. Severe physical stress. Anything that causes a severe stress on your body can lead to cardiac arrest. This can include trauma, electrical shock, or major blood loss. Recreational drugs. Using certain drugs, such as cocaine ...

  14. The impact of work rewards on radiographers' organizational commitment.

    PubMed

    Akroyd, D; Mulkey, W; Utley-Smith, Q

    1995-01-01

    Organizational commitment is an affective work outcome that has been used to predict work-related behaviors such as turnover, absenteeism and intent-to-leave. There has been little research in organizational commitment for the allied health professions and no empirical studies in the radiologic sciences. The purpose of this study was to examine the predictive value of selected intrinsic and extrinsic work reward variables--involvement, significance, autonomy, general working conditions, supervision and salary--on staff radiographers' organizational commitment. In this study of 600 full-time staff radiographers in North and South Carolina, supervision (for ages 20-37 years) and involvement (for ages 38-66 years) were significant predictors of organizational commitment. The results of the study indicate that healthcare organizations should provide potential supervisors with managerial training, especially for radiographers who move to supervisory positions based on clinical skills and years of experience. In the long run, such programs are much less expensive than costs associated with replacing employees who leave the organization because of low organizational commitment. Also, management strategies and programs to redesign and enhance job tasks may help maintain or increase organizational commitment.

  15. Enhanced Ca²+ influx through cardiac L-type Ca²+ channels maintains the systolic Ca²+ transient in early cardiac atrophy induced by mechanical unloading.

    PubMed

    Schwoerer, A P; Neef, S; Broichhausen, I; Jacubeit, J; Tiburcy, M; Wagner, M; Biermann, D; Didié, M; Vettel, C; Maier, L S; Zimmermann, W H; Carrier, L; Eschenhagen, T; Volk, T; El-Armouche, A; Ehmke, H

    2013-12-01

    Cardiac atrophy as a consequence of mechanical unloading develops following exposure to microgravity or prolonged bed rest. It also plays a central role in the reverse remodelling induced by left ventricular unloading in patients with heart failure. Surprisingly, the intracellular Ca(2+) transients which are pivotal to electromechanical coupling and to cardiac plasticity were repeatedly found to remain unaffected in early cardiac atrophy. To elucidate the mechanisms underlying the preservation of the Ca(2+) transients, we investigated Ca(2+) cycling in cardiomyocytes from mechanically unloaded (heterotopic abdominal heart transplantation) and control (orthotopic) hearts in syngeneic Lewis rats. Following 2 weeks of unloading, sarcoplasmic reticulum (SR) Ca(2+) content was reduced by ~55 %. Atrophic cardiac myocytes also showed a much lower frequency of spontaneous diastolic Ca(2+) sparks and a diminished systolic Ca(2+) release, even though the expression of ryanodine receptors was increased by ~30 %. In contrast, current clamp recordings revealed prolonged action potentials in endocardial as well as epicardial myocytes which were associated with a two to fourfold higher sarcolemmal Ca(2+) influx under action potential clamp. In addition, Cav1.2 subunits which form the pore of L-type Ca(2+) channels (LTCC) were upregulated in atrophic myocardium. These data suggest that in early cardiac atrophy induced by mechanical unloading, an augmented sarcolemmal Ca(2+) influx through LTCC fully compensates for a reduced systolic SR Ca(2+) release to preserve the Ca(2+) transient. This interplay involves an electrophysiological remodelling as well as changes in the expression of cardiac ion channels.

  16. Conscientious commitment to women's health.

    PubMed

    Dickens, Bernard M; Cook, Rebecca J

    2011-05-01

    Conscientious commitment, the reverse of conscientious objection, inspires healthcare providers to overcome barriers to delivery of reproductive services to protect and advance women's health. History shows social reformers experiencing religious condemnation and imprisonment for promoting means of birth control, until access became popularly accepted. Voluntary sterilization generally followed this pattern to acceptance, but overcoming resistance to voluntary abortion calls for courage and remains challenging. The challenge is aggravated by religious doctrines that view treatment of ectopic pregnancy, spontaneous abortion, and emergency contraception not by reference to women's healthcare needs, but through the lens of abortion. However, modern legal systems increasingly reject this myopic approach. Providers' conscientious commitment is to deliver treatments directed to women's healthcare needs, giving priority to patient care over adherence to conservative religious doctrines or religious self-interest. The development of in vitro fertilization to address childlessness further illustrates the inspiration of conscientious commitment over conservative objections.

  17. Launch Commit Criteria Monitoring Agent

    NASA Technical Reports Server (NTRS)

    Semmel, Glenn S.; Davis, Steven R.; Leucht, Kurt W.; Rowe, Dan A.; Kelly, Andrew O.; Boeloeni, Ladislau

    2005-01-01

    The Spaceport Processing Systems Branch at NASA Kennedy Space Center has developed and deployed a software agent to monitor the Space Shuttle's ground processing telemetry stream. The application, the Launch Commit Criteria Monitoring Agent, increases situational awareness for system and hardware engineers during Shuttle launch countdown. The agent provides autonomous monitoring of the telemetry stream, automatically alerts system engineers when predefined criteria have been met, identifies limit warnings and violations of launch commit criteria, aids Shuttle engineers through troubleshooting procedures, and provides additional insight to verify appropriate troubleshooting of problems by contractors. The agent has successfully detected launch commit criteria warnings and violations on a simulated playback data stream. Efficiency and safety are improved through increased automation.

  18. Cardiac metastases

    PubMed Central

    Bussani, R; De‐Giorgio, F; Abbate, A; Silvestri, F

    2007-01-01

    Tumours metastatic to the heart (cardiac metastases) are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Although primary cardiac tumours are extremely uncommon (various postmortem studies report rates between 0.001% and 0.28%), secondary tumours are not, and at least in theory, the heart can be metastasised by any malignant neoplasm able to spread to distant sites. In general, cardiac metastases are considered to be rare; however, when sought for, the incidence seems to be not as low as expected, ranging from 2.3% and 18.3%. Although no malignant tumours are known that diffuse preferentially to the heart, some do involve the heart more often than others—for example, melanoma and mediastinal primary tumours. This paper attempts to review the pathophysiology of cardiac metastatic disease, epidemiology and clinical presentation of cardiac metastases, and pathological characterisation of the lesions. PMID:17098886

  19. Hydroxychloroquine Protects against Cardiac Ischaemia/Reperfusion Injury In Vivo via Enhancement of ERK1/2 Phosphorylation

    PubMed Central

    Bourke, Lauren; McCormick, James; Taylor, Valerie; Pericleous, Charis; Blanchet, Benoit; Costedoat-Chalumeau, Nathalie; Stuckey, Daniel; Lythgoe, Mark F.; Stephanou, Anastasis; Ioannou, Yiannis

    2015-01-01

    An increasing number of investigations including human studies demonstrate that pharmacological ischaemic preconditioning is a viable way to protect the heart from myocardial ischaemia/reperfusion (I/R) injury. This study investigated the role of hydroxychloroquine (HCQ) in the heart during I/R injury. In vitro and in vivo models of myocardial I/R injury were used to assess the effects of HCQ. It was found that HCQ was protective in neonatal rat cardiomyocytes through inhibition of apoptosis, measured by TUNEL and cleaved caspase-3. This protection in vitro was mediated through enhancement of ERK1/2 phosphorylation mediated by HCQ in a dose-dependent fashion. A decrease in infarct size was observed in an in vivo model of myocardial I/R injury in HCQ treated animals and furthermore this protection was blocked in the presence of the ERK1/2 inhibitor U0126. For the first time, we have shown that HCQ promotes a preconditioning like protection in an in vivo simulated rat myocardial I/R injury model. Moreover, it was shown that HCQ is protective via enhanced phosphorylation of the pro-survival kinase ERK1/2. PMID:26636577

  20. Learning organizations, internal marketing, and organizational commitment in hospitals.

    PubMed

    Tsai, Yafang

    2014-04-04

    Knowledge capital is becoming more important to healthcare establishments, especially for hospitals that are facing changing societal and industrial patterns. Hospital staff must engage in a process of continual learning to improve their healthcare skills and provide a superior service to their patients. Internal marketing helps hospital administrators to improve the quality of service provided by nursing staff to their patients and allows hospitals to build a learning culture and enhance the organizational commitment of its nursing staff. Our empirical study provides nursing managers with a tool to allow them to initiate a change in the attitudes of nurses towards work, by constructing a new 'learning organization' and using effective internal marketing. A cross-sectional design was employed. Two hundred questionnaires were distributed to nurses working in either a medical centre or a regional hospital in Taichung City, Taiwan, and 114 valid questionnaires were returned (response rate: 57%). The entire process of distribution and returns was completed between 1 October and 31 October 2009. Hypothesis testing was conducted using structural equation modelling. A significant positive correlation was found between the existence of a 'learning organization', internal marketing, and organizational commitment. Internal marketing was a mediator between creating a learning organization and organizational commitment. Nursing managers may be able to apply the creation of a learning organization to strategies that can strengthen employee organizational commitment. Further, when promoting the creation of a learning organization, managers can coordinate their internal marketing practices to enhance the organizational commitment of nurses.

  1. Detection of cardiac biomarkers exploiting surface enhanced Raman scattering (SERS) using a nanofluidic channel based biosensor towards coronary point-of-care diagnostics

    NASA Astrophysics Data System (ADS)

    Benford, Melodie E.; Wang, Miao; Kameoka, Jun; Coté, Gerard L.

    2009-02-01

    According to the World Health Organization, cardiovascular disease is the most common cause of death in the world. In the US, over 115 million people visit the emergency department (ED), 5 million of which may have acute coronary syndrome (ACS). Cardiac biomarkers can provide early identification and diagnosis of ACS, and can provide information on the prognosis of the patient by assessing the risk of death. In addition, the biomarkers can serve as criteria for admission, indicate possibility of re-infarction, or eliminate ACS as a diagnosis altogether. We propose a SERSbased multi-marker approach towards a point-of-care diagnostic system for ACS. Using a nanofluidic device consisting of a microchannel leading into a nanochannel, we formed SERS active sites by mechanically aggregating gold particles (60 nm) at the entrance to the nanochannel (40nm×1μm). The induced capillary flow produces a high density of aggregated nanoparticles at this precise region, creating areas with enhanced electromagnetic fields within the aggregates, shifting the plasmon resonance to the near infrared region, in resonance with incident laser wavelength. With this robust sensing platform, we were able to obtain qualitative information of brain natriuretic peptide (biomarker of ventricular dysfunction or pulmonary stress), troponin I (biomarker of myocardial necrosis), and C-reactive protein (biomarker of inflammation potentially caused by atherosclerosis).

  2. Matters relating to commitments criteria for joint implementation

    SciTech Connect

    1995-11-01

    This paper discusses issues pertaining to commitments criteria for joint implementation activities. In cases where emissions limitations are mentioned, this should be taken to refer to policies and measures to protect and enhance greenhouse gas sinks and reservoirs, with equivalent results.

  3. Commitment of Licensed Social Workers to Aging Practice

    ERIC Educational Resources Information Center

    Simons, Kelsey; Bonifas, Robin; Gammonley, Denise

    2011-01-01

    This study sought to identify client, professional, and employment characteristics that enhance licensed social workers' commitment to aging practice. A series of binary logistic regressions were performed using data from 181 licensed, full-time social workers who reported aging as their primary specialty area as part of the 2004 NASW's national…

  4. Commitment of Licensed Social Workers to Aging Practice

    ERIC Educational Resources Information Center

    Simons, Kelsey; Bonifas, Robin; Gammonley, Denise

    2011-01-01

    This study sought to identify client, professional, and employment characteristics that enhance licensed social workers' commitment to aging practice. A series of binary logistic regressions were performed using data from 181 licensed, full-time social workers who reported aging as their primary specialty area as part of the 2004 NASW's national…

  5. Cardiac cachexia.

    PubMed

    Anker, Stefan D; Steinborn, Wolfram; Strassburg, Sabine

    2004-01-01

    Chronic heart failure (CHF) remains an important and increasing public health care problem. It is a complex syndrome affecting many body systems. Body wasting (i.e., cardiac cachexia) has long been recognised as a serious complication of CHF. Cardiac cachexia is associated with poor prognosis, independently of functional disease severity, age, and measures of exercise capacity and cardiac function. Patients with cardiac cachexia suffer from a general loss of fat tissue, lean tissue, and bone tissue. Cachectic CHF patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. The pathophysiologic alterations leading to cardiac cachexia remain unclear, but there is increasing evidence that metabolic, neurohormonal and immune abnormalities may play an important role. Cachectic CHF patients show raised plasma levels of epinephrine, norepinephrine, and cortisol, and they show high plasma renin activity and increased plasma aldosterone level. Several studies have also shown that cardiac cachexia is linked to raised plasma levels of tumour necrosis factor alpha and other inflammatory cytokines. The degree of body wasting is strongly correlated with neurohormonal and immune abnormalities. The available evidence suggests that cardiac cachexia is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis. A complex imbalance of different body systems may cause the development of body wasting.

  6. 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

  7. 24-Hour Relativistic Bit Commitment

    NASA Astrophysics Data System (ADS)

    Verbanis, Ephanielle; Martin, Anthony; Houlmann, Raphaël; Boso, Gianluca; Bussières, Félix; Zbinden, Hugo

    2016-09-01

    Bit commitment is a fundamental cryptographic primitive in which a party wishes to commit a secret bit to another party. Perfect security between mistrustful parties is unfortunately impossible to achieve through the asynchronous exchange of classical and quantum messages. Perfect security can nonetheless be achieved if each party splits into two agents exchanging classical information at times and locations satisfying strict relativistic constraints. A relativistic multiround protocol to achieve this was previously proposed and used to implement a 2-millisecond commitment time. Much longer durations were initially thought to be insecure, but recent theoretical progress showed that this is not so. In this Letter, we report on the implementation of a 24-hour bit commitment solely based on timed high-speed optical communication and fast data processing, with all agents located within the city of Geneva. This duration is more than 6 orders of magnitude longer than before, and we argue that it could be extended to one year and allow much more flexibility on the locations of the agents. Our implementation offers a practical and viable solution for use in applications such as digital signatures, secure voting and honesty-preserving auctions.

  8. Higher Education and Social Commitment.

    ERIC Educational Resources Information Center

    Nasution, S.; Virasai, Banphot, Eds.

    The proceedings of the Regional Institute of Higher Education and Development's seminar and the meaning and implications of social commitment in higher education are reported. The welcoming address (S. Nasution) and the opening address (Y. B. Dato' Murad bin Mohd. Noor) welcome the participants and set the tone for the discussions to follow. The…

  9. Hampshire Country School Staff Commitments.

    ERIC Educational Resources Information Center

    Hampshire Country School, Rindge, NH.

    Intended for professional personnel of the Hampshire Country School, which treats gifted children with immobilizing emotional dysfunctions, the handbook specifies staff commitments. The Code of Ethics, adapted from the National Education Association Code as supplemented by The Council for Exceptional Children, sets forth four principles:…

  10. Physical Education Teachers' Organizational Commitment

    ERIC Educational Resources Information Center

    Demir, Hayri

    2013-01-01

    The aim of this study was to determine physical education teachers' organizational commitment levels. The sample consisted of 204 physical education teachers working in the city center of Konya in the 2011 to 2012 academic year. The respondents were randomly selected in this research. Data collected for this research by using the Scale for…

  11. Higher Education and Social Commitment.

    ERIC Educational Resources Information Center

    Nasution, S.; Virasai, Banphot, Eds.

    The proceedings of the Regional Institute of Higher Education and Development's seminar and the meaning and implications of social commitment in higher education are reported. The welcoming address (S. Nasution) and the opening address (Y. B. Dato' Murad bin Mohd. Noor) welcome the participants and set the tone for the discussions to follow. The…

  12. Commitment Profiles and Employee Turnover

    ERIC Educational Resources Information Center

    Stanley, Laura; Vandenberghe, Christian; Vandenberg, Robert; Bentein, Kathleen

    2013-01-01

    We examined how affective (AC), normative (NC), perceived sacrifice (PS), and few alternatives (FA) commitments combine to form profiles and determine turnover intention and turnover. We theorized that three mechanisms account for how profiles operate, i.e., the degree to which membership is internally regulated, the perceived desirability and…

  13. School Climate and Teacher Commitment

    ERIC Educational Resources Information Center

    Smith, Larry Don

    2009-01-01

    This study examined the relationship between school climate and teacher commitment. The study focused on elementary schools in Northeast Alabama. Thirty-four elementary schools consisting of 522 teachers took part in the study. The teachers completed two survey instruments: the Organizational Climate Index (OCI) and the Organizational Commitment…

  14. Acceptance and Commitment Therapy: Introduction

    ERIC Educational Resources Information Center

    Twohig, Michael P.

    2012-01-01

    This is the introductory article to a special series in Cognitive and Behavioral Practice on Acceptance and Commitment Therapy (ACT). Instead of each article herein reviewing the basics of ACT, this article contains that review. This article provides a description of where ACT fits within the larger category of cognitive behavior therapy (CBT):…

  15. The Measurement of Vocational Commitment.

    ERIC Educational Resources Information Center

    Weis, Susan F.; Hubbard, Constance F.

    Recent efforts toward career education and the rise in occupationally oriented programs on the secondary and postsecondary level encourage a close examination of the nature of the relationship between people and their vocations. A 74 item device, the Vocational Commitment Index was developed to assess this relationship. Based upon a theoretically…

  16. Cheat sensitive quantum bit commitment.

    PubMed

    Hardy, Lucien; Kent, Adrian

    2004-04-16

    We define cheat sensitive cryptographic protocols between mistrustful parties as protocols which guarantee that, if either cheats, the other has some nonzero probability of detecting the cheating. We describe an unconditionally secure cheat sensitive nonrelativistic bit commitment protocol which uses quantum information to implement a task which is classically impossible; we also describe a simple relativistic protocol.

  17. Acceptance and Commitment Therapy: Introduction

    ERIC Educational Resources Information Center

    Twohig, Michael P.

    2012-01-01

    This is the introductory article to a special series in Cognitive and Behavioral Practice on Acceptance and Commitment Therapy (ACT). Instead of each article herein reviewing the basics of ACT, this article contains that review. This article provides a description of where ACT fits within the larger category of cognitive behavior therapy (CBT):…

  18. Regulatory Foci and Organizational Commitment

    ERIC Educational Resources Information Center

    Markovits, Yannis; Ullrich, Johannes; van Dick, Rolf; Davis, Ann J.

    2008-01-01

    We use regulatory focus theory to derive specific predictions regarding the differential relationships between regulatory focus and commitment. We estimated a structural equation model using a sample of 520 private and public sector employees and found in line with our hypotheses that (a) promotion focus related more strongly to affective…

  19. Physical Education Teachers' Organizational Commitment

    ERIC Educational Resources Information Center

    Demir, Hayri

    2013-01-01

    The aim of this study was to determine physical education teachers' organizational commitment levels. The sample consisted of 204 physical education teachers working in the city center of Konya in the 2011 to 2012 academic year. The respondents were randomly selected in this research. Data collected for this research by using the Scale for…

  20. Faculty Organizational Commitment and Citizenship

    ERIC Educational Resources Information Center

    Lawrence, Janet; Ott, Molly; Bell, Alli

    2012-01-01

    Building on a theoretical framework that links characteristics of individuals and their work settings to organizational commitment (OC) and citizenship behavior, this study considers why faculty may be disengaging from institutional service. Analyses of survey data collected from a state system of higher education suggest that job characteristics,…

  1. Idiosyncratic Deals and Organizational Commitment

    ERIC Educational Resources Information Center

    Ng, Thomas W. H.; Feldman, Daniel C.

    2010-01-01

    This article examines the relationship between idiosyncratic deals and organizational commitment. In particular, it examines how two individual differences which reflect self-worth (core self-evaluations and age) moderate that relationship. We predicted that employees with feelings of high self-worth will expect and will feel entitled to these…

  2. Predictors of Child Caregiver Commitment.

    ERIC Educational Resources Information Center

    Webb, Nancy Carnahan; Lowther, Malcolm

    This study examined the relationship between child caregiver commitment and the caregiver's personal characteristics and work experience, the characteristics of the job, and the quality of the child care center. Questionnaires that included several measurement instruments were sent to 381 full-time child caregivers in 94 centers. Caregiver…

  3. Idiosyncratic Deals and Organizational Commitment

    ERIC Educational Resources Information Center

    Ng, Thomas W. H.; Feldman, Daniel C.

    2010-01-01

    This article examines the relationship between idiosyncratic deals and organizational commitment. In particular, it examines how two individual differences which reflect self-worth (core self-evaluations and age) moderate that relationship. We predicted that employees with feelings of high self-worth will expect and will feel entitled to these…

  4. Faculty Organizational Commitment and Citizenship

    ERIC Educational Resources Information Center

    Lawrence, Janet; Ott, Molly; Bell, Alli

    2012-01-01

    Building on a theoretical framework that links characteristics of individuals and their work settings to organizational commitment (OC) and citizenship behavior, this study considers why faculty may be disengaging from institutional service. Analyses of survey data collected from a state system of higher education suggest that job characteristics,…

  5. The Relationships between Collegiate DECA Commitment, Mentoring and College Students' Perceived Career Commitment

    ERIC Educational Resources Information Center

    Duke, Linda

    2013-01-01

    This study investigated relationships between student's Collegiate DECA commitment, psychological capital, mentoring, and perceived career commitment. Proposed relationships were supported with several psychological theories and frameworks including Organizational Commitment, Psychological Capital, and Social Identity Theory. Data was…

  6. The Relationships between Collegiate DECA Commitment, Mentoring and College Students' Perceived Career Commitment

    ERIC Educational Resources Information Center

    Duke, Linda

    2013-01-01

    This study investigated relationships between student's Collegiate DECA commitment, psychological capital, mentoring, and perceived career commitment. Proposed relationships were supported with several psychological theories and frameworks including Organizational Commitment, Psychological Capital, and Social Identity Theory. Data was…

  7. Late gadolinium enhancement on cardiac magnetic resonance predicts coronary vasomotor abnormality and myocardial lactate production in patients with chronic heart failure.

    PubMed

    Uemura, Tomoaki; Yamamuro, Megumi; Kaikita, Koichi; Takashio, Seiji; Utsunomiya, Daisuke; Hirakawa, Kyoko; Nakayama, Mina; Sakamoto, Kenji; Yamamoto, Eiichiro; Tsujita, Kenichi; Kojima, Sunao; Hokimoto, Seiji; Yamashita, Yasuyuki; Ogawa, Hisao

    2016-12-01

    Myocardial fibrosis and microvascular dysfunction are key determinants of outcome in heart failure (HF); we examined their relationship in patients with HF. Our study included 61 consecutive patients with HF but without coronary stenosis. All underwent gadolinium-enhanced cardiac magnetic resonance to evaluate late gadolinium enhancement (LGE) and an acetylcholine (ACh) provocation test to evaluate microvascular dysfunction. During the ACh provocation test, we sampled blood simultaneously from the coronary sinus and aortic root to compare lactate concentrations. We quantified coronary blood flow volume using an intracoronary Doppler-tipped guidewire. We detected LGE in 34 patients (LGE-positive); 27 were LGE-negative. Coronary blood flow volume increased significantly after the ACh provocation test only in LGE-negative patients (before vs. after ACh, 47.5 ± 36.8 vs. 69.2 ± 48.0 ml/min, respectively; p = 0.004). The myocardial lactate extraction ratio (LER) significantly decreased after the ACh test in both groups (LGE-negative, p = 0.001; LGE-positive, p < 0.001), significantly more so in the LGE-positive group (p = 0.017). Multivariate logistic regression analysis showed that a post-ACh LER < 0 (indicating myocardial lactate production) was a significant predictor of LGE-positivity (odds ratio 4.54; 95 % confidence interval 1.38-14.93; p = 0.013). In the LGE-positive group, an LGE volume greater than the median significantly predicted a post-ACh LER of <0 (p = 0.042; odds ratio 6.02; 95 % confidence interval 1.07-33.86). ACh-provoked coronary vasomotor abnormality is closely correlated with myocardial fibrosis in patients with HF but without organic coronary stenosis. Coronary vasomotor abnormalities in fibrotic myocardium may worsen HF.

  8. Development Trajectories and Predictors of the Role Commitment of Nursing Preceptors.

    PubMed

    Wang, Wei-Fang; Hung, Chich-Hsiu; Li, Chung-Yi

    2017-08-31

    The commitment of nursing preceptors to their role is an important driving force that supports their clinical teaching and affects teaching quality. Role commitment undergoes dynamic development and thus changes over time. Existing studies have utilized only cross-sectional study designs and have not analyzed the changes in commitment trajectories with related factors. This study aimed to investigate the development trajectories of the commitment of preceptors and to examine the predictors between the trajectories of role commitment among nursing preceptors. A single-group, repeated-measures design was adopted, and 59 participants completed the Commitment to the Preceptor Role Scale and the Preceptor's Perception of Support Scale. The latent class growth analysis method was used to estimate the trajectory class patterns. The Wilcoxon rank-sum test, a nonparametric method, was used to compare the differences in demographic characteristics between the trajectories of commitment among nursing preceptors. Predictors were examined using binary logistic regression analysis. The two-class model was the best-fitting model to describe the trajectories of nursing preceptor commitment. The two classes in this model were "low commitment," which accounted for 90.3% of all the participants, and "high commitment," which accounted for 9.7%. A significant difference was found between the two classes in terms of motivation for being a preceptor (p = .048). Neither demographic characteristics nor organizational support had a predictive effect on the trajectories of commitment development. This study found a low level of role commitment among new preceptors. Moreover, internal motivation was found to be a significant factor affecting the trajectories of this commitment. Therefore, institutions should foster an appropriate environment to enhance the role identity of preceptors as well as cultivate and stimulate their commitment to this role.

  9. Cardiac Cephalgia

    PubMed Central

    Wassef, Nancy; Ali, Ali Turab; Katsanevaki, Alexia-Zacharoula; Nishtar, Salman

    2014-01-01

    Although most of the patients presenting with ischemic heart disease have chest pains, there are other rare presenting symptoms like cardiac cephalgia. In this report, we present a case of acute coronary syndrome with an only presentation of exertional headache. It was postulated as acute presentation of coronary artery disease, due to previous history of similar presentation associated with some chest pains with previous left coronary artery stenting. We present an unusual case with cardiac cephalgia in a young patient under the age of 50 which was not reported at that age before. There are four suggested mechanisms for this cardiac presentation. PMID:28352454

  10. Cardiac rhabdomyosarcoma

    PubMed Central

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical staining confirmed cardiac rhabdomyosarcoma with metastatic spread to the lungs. Difficulty in diagnosing and treating cardiac tumours is discussed. PMID:20428274

  11. Cardiac Lymphoma.

    PubMed

    Jeudy, Jean; Burke, Allen P; Frazier, Aletta Ann

    2016-07-01

    Lymphoma of the heart and pericardium may develop in up to 25% of patients with disseminated nodal disease, but primary cardiac lymphoma is rare. The majority are diffuse large B-cell lymphomas, which arise in immunocompetent older individuals, men twice as often as women. Subsets are found in immunocompromised patients, including those with HIV-AIDS or allograft recipients. Cardiac lymphomas tend to arise in the wall of the right heart, especially right atrium, with contiguous infiltration of epicardium and pericardium. Pericardial implants and effusions are common. The disease is often multifocal in the heart, but cardiac valves are usually spared. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Who Wants to Become a Teacher? Typology of Student-Teachers' Commitment to Teaching

    ERIC Educational Resources Information Center

    Moses, Ikupa; Berry, Amanda; Saab, Nadira; Admiraal, Wilfried

    2017-01-01

    Understanding student-teachers' decisions to enter and stay in the teaching profession after graduation could help teacher educators to find appropriate procedures to enhance commitment to teaching. This study classified student-teachers based on their levels of commitment to teaching, and described these types based on student-teachers'…

  13. Transcriptional, epigenetic and retroviral signatures identify regulatory regions involved in hematopoietic lineage commitment

    PubMed Central

    Romano, Oriana; Peano, Clelia; Tagliazucchi, Guidantonio Malagoli; Petiti, Luca; Poletti, Valentina; Cocchiarella, Fabienne; Rizzi, Ermanno; Severgnini, Marco; Cavazza, Alessia; Rossi, Claudia; Pagliaro, Pasqualepaolo; Ambrosi, Alessandro; Ferrari, Giuliana; Bicciato, Silvio; De Bellis, Gianluca; Mavilio, Fulvio; Miccio, Annarita

    2016-01-01

    Genome-wide approaches allow investigating the molecular circuitry wiring the genetic and epigenetic programs of human somatic stem cells. Hematopoietic stem/progenitor cells (HSPC) give rise to the different blood cell types; however, the molecular basis of human hematopoietic lineage commitment is poorly characterized. Here, we define the transcriptional and epigenetic profile of human HSPC and early myeloid and erythroid progenitors by a combination of Cap Analysis of Gene Expression (CAGE), ChIP-seq and Moloney leukemia virus (MLV) integration site mapping. Most promoters and transcripts were shared by HSPC and committed progenitors, while enhancers and super-enhancers consistently changed upon differentiation, indicating that lineage commitment is essentially regulated by enhancer elements. A significant fraction of CAGE promoters differentially expressed upon commitment were novel, harbored a chromatin enhancer signature, and may identify promoters and transcribed enhancers driving cell commitment. MLV-targeted genomic regions co-mapped with cell-specific active enhancers and super-enhancers. Expression analyses, together with an enhancer functional assay, indicate that MLV integration can be used to identify bona fide developmentally regulated enhancers. Overall, this study provides an overview of transcriptional and epigenetic changes associated to HSPC lineage commitment, and a novel signature for regulatory elements involved in cell identity. PMID:27095295

  14. Association of Left Atrial Local Conduction Velocity With Late Gadolinium Enhancement on Cardiac Magnetic Resonance in Patients With Atrial Fibrillation.

    PubMed

    Fukumoto, Kotaro; Habibi, Mohammadali; Ipek, Esra Gucuk; Zahid, Sohail; Khurram, Irfan M; Zimmerman, Stefan L; Zipunnikov, Vadim; Spragg, David; Ashikaga, Hiroshi; Trayanova, Natalia; Tomaselli, Gordon F; Rickard, John; Marine, Joseph E; Berger, Ronald D; Calkins, Hugh; Nazarian, Saman

    2016-03-01

    Prior studies have demonstrated regional left atrial late gadolinium enhancement (LGE) heterogeneity on magnetic resonance imaging. Heterogeneity in regional conduction velocities is a critical substrate for functional reentry. We sought to examine the association between left atrial conduction velocity and LGE in patients with atrial fibrillation. LGE imaging and left atrial activation mapping were performed during sinus rhythm in 22 patients before pulmonary vein isolation. The locations of 1468 electroanatomic map points were registered to the corresponding anatomic sites on 469 axial LGE image planes. The local conduction velocity at each point was calculated using previously established methods. The myocardial wall thickness and image intensity ratio defined as left atrial myocardial LGE signal intensity divided by the mean left atrial blood pool intensity was calculated for each mapping site. The local conduction velocity and image intensity ratio in the left atrium (mean ± SD) were 0.98 ± 0.46 and 0.95 ± 0.26 m/s, respectively. In multivariable regression analysis, clustered by patient, and adjusting for left atrial wall thickness, conduction velocity was associated with the local image intensity ratio (0.20 m/s decrease in conduction velocity per increase in unit image intensity ratio, P<0.001). In this clinical in vivo study, we demonstrate that left atrial myocardium with increased gadolinium uptake has lower local conduction velocity. Identification of such regions may facilitate the targeting of the substrate for reentrant arrhythmias. © 2016 American Heart Association, Inc.

  15. Characterization of t1 relaxation and blood-myocardial contrast enhancement of NC100150 injection in cardiac MRI.

    PubMed

    Wagenseil, J E; Johansson, L O; Lorenz, C H

    1999-11-01

    A new ultrasmall superparamagnetic iron oxide (Clariscan; NC100150 Injection) was studied in domestic farm pigs. The T1 effects were characterized for blood and myocardium and the blood-myocardial contrast was measured in T1-weighted cine images. The contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were measured at baseline and contrast doses of 1 and 5 mg Fe/kg body weight (bw) at end diastole and late systole. The T1 values for blood and myocardium were reduced by 97 and 43%, respectively, from baseline to 5 mg Fe/kg bw. The CNR was significantly improved with contrast at end diastole and late systole. The maximum improvement shown was 202% at 5 mg Fe/kg bw in late systole. The percent SNR enhancement was significantly higher in blood than myocardium at late systole. NC100150 Injection is an effective T1 shortening agent and can be used to improve blood-myocardial contrast in cine images of the heart. J. Magn. Reson. Imaging 1999;10:784-789.

  16. Knowledge-based segmentation of the heart from respiratory-gated CT datasets acquired without cardiac contrast-enhancement

    NASA Astrophysics Data System (ADS)

    Dey, Joyoni; Pan, Tin-Su; Choi, David J.; Smyczynski, Mark; Pretorius, Hendrik; King, Michael A.

    2006-03-01

    Respiratory motion degrades image quality in PET and SPECT imaging. Patient specific information on the motion of structures such as the heart if obtained from CT slices from a dual-modality imaging system can be employed to compensate for motion during emission reconstruction. The CT datasets may not be contrast enhanced. Since each patient may have 100-120 coronal slices covering the heart, an automated but accurate segmentation of the heart is important. We developed and implemented an algorithm to segment the heart in non-contrast CT datasets. The algorithm has two steps. In the first step we place a truncated-ellipse curve on a mid-slice of the heart, optimize its pose, and then track the contour through the other slices of the same dataset. During the second step the contour points are drawn to the local edge points by minimizing an distance measure. The segmentation algorithm was tested on 10 patients and the boundaries were determined to be accurate to within 2 mm of the visually ascertained locations of the borders of the heart. The segmentation was automatic except for initial placement of the first truncated-ellipse and for having to re-initialize the contour for 3 patients for less than 3% (1-3 slices) of the coronal slices of the heart. These end-slices constituted less than 0.3% of the heart volume.

  17. Cardiac Rehabilitation

    MedlinePlus

    ... surgery, coronary artery bypass grafting, or percutaneous coronary intervention. Cardiac rehab involves adopting heart-healthy lifestyle changes to address risk factors for cardiovascular disease. To help you adopt lifestyle changes, this program ...

  18. Cardiac Rehabilitation

    MedlinePlus

    ... eating a heart-healthy diet, keeping a healthy weight and quitting smoking. The goals of cardiac rehabilitation include establishing an individualized plan to help you regain strength, preventing your condition from worsening, reducing your ...

  19. Nuclear cardiac

    SciTech Connect

    Slutsky, R.; Ashburn, W.L.

    1982-01-01

    The relationship between nuclear medicine and cardiology has continued to produce a surfeit of interesting, illuminating, and important reports involving the analysis of cardiac function, perfusion, and metabolism. To simplify the presentation, this review is broken down into three major subheadings: analysis of myocardial perfusion; imaging of the recent myocardial infarction; and the evaluation of myocardial function. There appears to be an increasingly important relationship between cardiology, particularly cardiac physiology, and nuclear imaging techniques. (KRM)

  20. Targeted Delivery of Human VEGF Gene via Complexes of Magnetic Nanoparticle-Adenoviral Vectors Enhanced Cardiac Regeneration

    PubMed Central

    Ou, Lailiang; Wang, Weiwei; Delyagina, Evgenya; Lux, Cornelia; Sorg, Heiko; Riehemann, Kristina

    2012-01-01

    This study assessed the concept of whether delivery of magnetic nanobeads (MNBs)/adenoviral vectors (Ad)–encoded hVEGF gene (AdhVEGF) could regenerate ischaemically damaged hearts in a rat acute myocardial infarction model under the control of an external magnetic field. Adenoviral vectors were conjugated to MNBs with the Sulfo-NHS-LC-Biotin linker. In vitro transduction efficacy of MNBs/Ad–encoded luciferase gene (Adluc) was compared with Adluc alone in human umbilical vein endothelial cells (HUVECs) under magnetic field stimulation. In vivo, in a rat acute myocardial infarction (AMI) model, MNBs/AdhVEGF complexes were injected intravenously and an epicardial magnet was employed to attract the circulating MNBs/AdhVEGF complexes. In vitro, compared with Adluc alone, MNBs/Adluc complexes had a 50-fold higher transduction efficiency under the magnetic field. In vivo, epicardial magnet effectively attracted MNBs/AdhVEGF complexes and resulted in strong therapeutic gene expression in the ischemic zone of the infarcted heart. When compared to other MI-treated groups, the MI-M+/AdhVEGF group significantly improved left ventricular function (p<0.05) assessed by pressure-volume loops after 4 weeks. Also the MI-M+/AdhVEGF group exhibited higher capillary and arteriole density and lower collagen deposition than other MI-treated groups (p<0.05). Magnetic targeting enhances transduction efficiency and improves heart function. This novel method to improve gene therapy outcomes in AMI treatment offers the potential into clinical applications. PMID:22844395

  1. Cardiac cameras.

    PubMed

    Travin, Mark I

    2011-05-01

    Cardiac imaging with radiotracers plays an important role in patient evaluation, and the development of suitable imaging instruments has been crucial. While initially performed with the rectilinear scanner that slowly transmitted, in a row-by-row fashion, cardiac count distributions onto various printing media, the Anger scintillation camera allowed electronic determination of tracer energies and of the distribution of radioactive counts in 2D space. Increased sophistication of cardiac cameras and development of powerful computers to analyze, display, and quantify data has been essential to making radionuclide cardiac imaging a key component of the cardiac work-up. Newer processing algorithms and solid state cameras, fundamentally different from the Anger camera, show promise to provide higher counting efficiency and resolution, leading to better image quality, more patient comfort and potentially lower radiation exposure. While the focus has been on myocardial perfusion imaging with single-photon emission computed tomography, increased use of positron emission tomography is broadening the field to include molecular imaging of the myocardium and of the coronary vasculature. Further advances may require integrating cardiac nuclear cameras with other imaging devices, ie, hybrid imaging cameras. The goal is to image the heart and its physiological processes as accurately as possible, to prevent and cure disease processes.

  2. Organizational commitment, work environment conditions, and life satisfaction among Iranian nurses.

    PubMed

    Vanaki, Zohreh; Vagharseyyedin, Seyyed Abolfazl

    2009-12-01

    Employee commitment to the organization is a crucial issue in today's health-care market. In Iran, few studies have sought to evaluate the factors that contribute to forms of commitment. The aim of this study was to investigate the relationship between nurses' organizational commitment, work environment conditions, and life satisfaction. A cross-sectional design was utilized. Questionnaires were distributed to all the staff nurses who had permanent employment (with at least 2 years of experience in nursing) in the five hospitals affiliated to Birjand Medical Sciences University. Two hundred and fifty participants returned completed questionnaires. Most were female and married. The correlation of the total scores of nurses' affective organizational commitment and work environment conditions indicated a significant and positive relationship. Also, a statistically significant relationship was found between affective organizational commitment and life satisfaction. The implementation of a comprehensive program to improve the work conditions and life satisfaction of nurses could enhance their organizational commitment.

  3. Organizational trust and empowerment in restructured healthcare settings. Effects on staff nurse commitment.

    PubMed

    Laschinger, H K; Finegan, J; Shamian, J; Casier, S

    2000-09-01

    In today's dramatically restructured healthcare work environments, organizational trust is an increasingly important element in determining employee performance and commitment to the organization. The authors used Kanter's model of workplace empowerment to examine the effects of organizational trust and empowerment on two types of organizational commitment. A predictive, nonexperimental design was used to test Kanter's theory in a random sample of 412 Canadian staff nurses. Empowered nurses reported higher levels of organizational trust, which in turn resulted in higher levels of affective commitment. However, empowerment did not predict continuance commitment--that is, commitment to stay in the organization based on perceived lack of other job opportunities. Because past research has linked affective commitment to employee productivity, these results suggest that fostering environments that enhance perceptions of empowerment and organizational trust will have positive effects on organizational members and increase organizational effectiveness.

  4. Mesodermal iPSC–derived progenitor cells functionally regenerate cardiac and skeletal muscle

    PubMed Central

    Quattrocelli, Mattia; Swinnen, Melissa; Giacomazzi, Giorgia; Camps, Jordi; Barthélemy, Ines; Ceccarelli, Gabriele; Caluwé, Ellen; Grosemans, Hanne; Thorrez, Lieven; Pelizzo, Gloria; Muijtjens, Manja; Verfaillie, Catherine M.; Blot, Stephane; Janssens, Stefan; Sampaolesi, Maurilio

    2015-01-01

    Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles. PMID:26571398

  5. Activation of GATA4 gene expression at the early stage of cardiac specification

    PubMed Central

    Yilbas, Ayse E.; Hamilton, Alison; Wang, Yingjian; Mach, Hymn; Lacroix, Natascha; Davis, Darryl R.; Chen, Jihong; Li, Qiao

    2014-01-01

    Currently, there are no effective treatments to directly repair damaged heart tissue after cardiac injury since existing therapies focus on rescuing or preserving reversibly damaged tissue. Cell-based therapies using cardiomyocytes generated from stem cells present a promising therapeutic approach to directly replace damaged myocardium with new healthy tissue. However, the molecular mechanisms underlying the commitment of stem cells into cardiomyocytes are not fully understood and will be critical to guide this new technology into the clinic. Since GATA4 is a critical regulator of cardiac differentiation, we examined the molecular basis underlying the early activation of GATA4 gene expression during cardiac differentiation of pluripotent stem cells. Our studies demonstrate the direct involvement of histone acetylation and transcriptional coactivator p300 in the regulation of GATA4 gene expression. More importantly, we show that histone acetyltransferase (HAT) activity is important for GATA4 gene expression with the use of curcumin, a HAT inhibitor. In addition, the widely used histone deacetylase inhibitor valproic acid enhances both histone acetylation and cardiac specification. PMID:24790981

  6. Development of Bipotent Cardiac/Skeletal Myogenic Progenitors from MESP1+ Mesoderm.

    PubMed

    Chan, Sunny Sun-Kin; Hagen, Hannah R; Swanson, Scott A; Stewart, Ron; Boll, Karly A; Aho, Joy; Thomson, James A; Kyba, Michael

    2016-01-12

    The branchiomeric skeletal muscles co-evolved with new chambers of the heart to enable predatory feeding in chordates. These co-evolved tissues develop from a common population in anterior splanchnic mesoderm, referred to as cardiopharyngeal mesoderm (CPM). The regulation and development of CPM are poorly understood. We describe an embryonic stem cell-based system in which MESP1 drives a PDGFRA+ population with dual cardiac and skeletal muscle differentiation potential, and gene expression resembling CPM. Using this system, we investigate the regulation of these bipotent progenitors, and find that cardiac specification is governed by an antagonistic TGFβ-BMP axis, while skeletal muscle specification is enhanced by Rho kinase inhibition. We define transcriptional signatures of the first committed CPM-derived cardiac and skeletal myogenic progenitors, and discover surface markers to distinguish cardiac (PODXL+) from the skeletal muscle (CDH4+) CPM derivatives. These tools open an accessible window on this developmentally and evolutionarily important population. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Activation of GATA4 gene expression at the early stage of cardiac specification

    NASA Astrophysics Data System (ADS)

    Yilbas, Ayse; Hamilton, Alison; Wang, Yingjian; Mach, Hymn; Lacroix, Natascha; Davis, Darryl; Chen, Jihong; LI, Qiao

    2014-03-01

    Currently, there are no effective treatments to directly repair damaged heart tissue after cardiac injury since existing therapies focus on rescuing or preserving reversibly damaged tissue. Cell-based therapies using cardiomyocytes generated from stem cells present a promising therapeutic approach to directly replace damaged myocardium with new healthy tissue. However, the molecular mechanisms underlying the commitment of stem cells into cardiomyocytes are not fully understood and will be critical to guide this new technology into the clinic. Since GATA4 is a critical regulator of cardiac differentiation, we examined the molecular basis underlying the early activation of GATA4 gene expression during cardiac differentiation of pluripotent stem cells. Our studies demonstrate the direct involvement of histone acetylation and transcriptional coactivator p300 in the regulation of GATA4 gene expression. More importantly, we show that histone acetyltransferase (HAT) activity is important for GATA4 gene expression with the use of curcumin, a HAT inhibitor. In addition, the widely used histone deacetylase inhibitor valproic acid enhances both histone acetylation and cardiac specification.

  8. How do different types of community commitment influence brand commitment? The mediation of brand attachment.

    PubMed

    Zhang, Ning; Zhou, Zhi-min; Su, Chen-ting; Zhou, Nan

    2013-11-01

    Although previous research indicates that participation in a brand community may foster consumer loyalty to the brand in question, research has seldom examined the mediating effect of community commitment on brand commitment. Drawing from the typologies of organizational commitment, we divide community commitment into three components: continuance community commitment (continuance CC), affective community commitment (affective CC), and normative community commitment (normative CC). We then assess the mediating role of brand attachment in the relationship between these three components and brand commitment. We test the hypotheses using a sample of online mobile phone brand communities in China. The empirical results reveal that brand attachment exerts an indirect (but not mediated) effect on the relationship between continuance CC and brand commitment and on the relationship between normative CC and brand commitment. We also find that it exerts a partial mediating effect on the relationship between affective CC and brand commitment. The findings contribute to the branding literature and have important implications for brand community management.

  9. Cardiac rehabilitation after myocardial infarction.

    PubMed

    Contractor, Aashish S

    2011-12-01

    Cardiac rehabilitation/secondary prevention programs are recognized as integral to the comprehensive care of patients with coronary heart disease (CHD), and as such are recommended as useful and effective (Class I) by the American Heart Association and the American College of Cardiology in the treatment of patients with CHD. The term cardiac rehabilitation refers to coordinated, multifaceted interventions designed to optimize a cardiac patient's physical, psychological, and social functioning, in addition to stabilizing, slowing, or even reversing the progression of the underlying atherosclerotic processes, thereby reducing morbidity and mortality. Cardiac rehabilitation, aims at returning the patient back to normal functioning in a safe and effective manner and to enhance the psychosocial and vocational state of the patient. The program involves education, exercise, risk factor modification and counselling. A meta-analysis based on a review of 48 randomized trials that compared outcomes of exercise-based rehabilitation with usual medical care, showed a reduction of 20% in total mortality and 26% in cardiac mortality rates, with exercise-based rehabilitation compared with usual medical care. Risk stratification helps identify patients who are at increased risk for exercise-related cardiovascular events and who may require more intensive cardiac monitoring in addition to the medical supervision provided for all cardiac rehabilitation program participants. During exercise, the patients' ECG is continuously monitored through telemetry, which serves to optimize the exercise prescription and enhance safety. The safety of cardiac rehabilitation exercise programs is well established, and the occurrence of major cardiovascular events during supervised exercise is extremely low. As hospital stays decrease, cardiac rehabilitation is assuming an increasingly important role in secondary prevention. In contrast with its growing importance internationally, there are very few

  10. 7 CFR 3550.70 - Conditional commitments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... into the required agreements; (4) Be financially responsible and have the ability to finance or obtain... approval of an affirmative marketing plan. (b) Limitations. Conditional commitments for new or... as bad weather, materials shortages, or marketing difficulties. Conditional commitments may...

  11. 7 CFR 3550.70 - Conditional commitments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... approval of an affirmative marketing plan. (b) Limitations. Conditional commitments for new or... RHS-approved plans, specifications, and regulations and priced within the lesser of the property's... as bad weather, materials shortages, or marketing difficulties. Conditional commitments may be...

  12. Practical implications of understanding the influence of motivations on commitment to voluntary urban conservation stewardship.

    PubMed

    Asah, Stanley T; Blahna, Dale J

    2013-08-01

    Although the word commitment is prevalent in conservation biology literature and despite the importance of people's commitment to the success of conservation initiatives, commitment as a psychological phenomenon and its operation in specific conservation behaviors remains unexplored. Despite increasing calls for conservation psychology to play a greater role in meeting conservation goals, applications of the psychological sciences to specific conservation behaviors, illustrating their utility to conservation practice, are rare. We examined conservation volunteers' motivations and commitment to urban conservation volunteering. We interviewed key informant volunteers and used interview findings to develop psychometric scales that we used to assess motivations and commitment to volunteer. We surveyed 322 urban conservation volunteers and used factor analysis to reveal how volunteers structure their motivations and commitment to volunteer for urban conservation activities. Six categories of motivations and 2 categories of commitment emerged from factor analysis. Volunteers were motivated by desires to help the environment, defend and enhance the ego, career and learning opportunities, escape and exercise, social interactions, and community building. Two forms of commitment, affective and normative commitment, psychologically bind people to urban conservation volunteerism. We used linear-regression models to examine how these categories of motivations influence volunteers' commitment to conservation volunteerism. Volunteers' tendency to continue to volunteer for urban conservation, even in the face of fluctuating counter urges, was motivated by personal, social, and community functions more than environmental motivations. The environment, otherwise marginally important, was a significant motivator of volunteers' commitment only when volunteering met volunteers' personal, social, and community-building goals. Attention to these personal, social, and community

  13. Positive Feedback of NDT80 Expression Ensures Irreversible Meiotic Commitment in Budding Yeast

    PubMed Central

    Tsuchiya, Dai; Yang, Yang; Lacefield, Soni

    2014-01-01

    In budding yeast, meiotic commitment is the irreversible continuation of the developmental path of meiosis. After reaching meiotic commitment, cells finish meiosis and gametogenesis, even in the absence of the meiosis-inducing signal. In contrast, if the meiosis-inducing signal is removed and the mitosis-inducing signal is provided prior to reaching meiotic commitment, cells exit meiosis and return to mitosis. Previous work has shown that cells commit to meiosis after prophase I but before entering the meiotic divisions. Since the Ndt80 transcription factor induces expression of middle meiosis genes necessary for the meiotic divisions, we examined the role of the NDT80 transcriptional network in meiotic commitment. Using a microfluidic approach to analyze single cells, we found that cells commit to meiosis in prometaphase I, after the induction of the Ndt80-dependent genes. Our results showed that high-level expression of NDT80 is important for the timing and irreversibility of meiotic commitment. A modest reduction in NDT80 levels delayed meiotic commitment based on meiotic stages, although the timing of each meiotic stage was similar to that of wildtype cells. A further reduction of NDT80 resulted in the surprising finding of inappropriately uncommitted cells: withdrawal of the meiosis-inducing signal and addition of the mitosis-inducing signal to cells at stages beyond metaphase I caused return to mitosis, leading to multi-nucleate cells. Since Ndt80 enhances its own transcription through positive feedback, we tested whether positive feedback ensured the irreversibility of meiotic commitment. Ablating positive feedback in NDT80 expression resulted in a complete loss of meiotic commitment. These findings suggest that irreversibility of meiotic commitment is a consequence of the NDT80 transcriptional positive feedback loop, which provides the high-level of Ndt80 required for the developmental switch of meiotic commitment. These results also illustrate the

  14. Leadership and change commitment in the life insurance service context in Taiwan: the mediating-moderating role of job satisfaction.

    PubMed

    Yang, Yi-Feng

    2011-06-01

    The effects of transformational leadership and satisfaction were studied along with their interconnected effects (mediation and moderation) on commitment to change in the life insurance industry in two samples, sales managers and salespersons. A multiple mediated-moderated regression approach showed mediation and moderation to have statistically significant main effects on change commitment. Transformational leadership and satisfaction made a more important contribution to change commitment while job satisfaction had a mediating and moderating role that could enhance the relationships between leadership and change commitment. This information is of importance in building successful change commitment associations with customers.

  15. Spermatogenesis: The Commitment to Meiosis

    PubMed Central

    Griswold, Michael D.

    2015-01-01

    Mammalian spermatogenesis requires a stem cell pool, a period of amplification of cell numbers, the completion of reduction division to haploid cells (meiosis), and the morphological transformation of the haploid cells into spermatozoa (spermiogenesis). The net result of these processes is the production of massive numbers of spermatozoa over the reproductive lifetime of the animal. One study that utilized homogenization-resistant spermatids as the standard determined that human daily sperm production (dsp) was at 45 million per day per testis (60). For each human that means ∼1,000 sperm are produced per second. A key to this level of gamete production is the organization and architecture of the mammalian testes that results in continuous sperm production. The seemingly complex repetitious relationship of cells termed the “cycle of the seminiferous epithelium” is driven by the continuous commitment of undifferentiated spermatogonia to meiosis and the period of time required to form spermatozoa. This commitment termed the A to A1 transition requires the action of retinoic acid (RA) on the undifferentiated spermatogonia or prospermatogonia. In stages VII to IX of the cycle of the seminiferous epithelium, Sertoli cells and germ cells are influenced by pulses of RA. These pulses of RA move along the seminiferous tubules coincident with the spermatogenic wave, presumably undergoing constant synthesis and degradation. The RA pulse then serves as a trigger to commit undifferentiated progenitor cells to the rigidly timed pathway into meiosis and spermatid differentiation. PMID:26537427

  16. Spermatogenesis: The Commitment to Meiosis.

    PubMed

    Griswold, Michael D

    2016-01-01

    Mammalian spermatogenesis requires a stem cell pool, a period of amplification of cell numbers, the completion of reduction division to haploid cells (meiosis), and the morphological transformation of the haploid cells into spermatozoa (spermiogenesis). The net result of these processes is the production of massive numbers of spermatozoa over the reproductive lifetime of the animal. One study that utilized homogenization-resistant spermatids as the standard determined that human daily sperm production (dsp) was at 45 million per day per testis (60). For each human that means ∼1,000 sperm are produced per second. A key to this level of gamete production is the organization and architecture of the mammalian testes that results in continuous sperm production. The seemingly complex repetitious relationship of cells termed the "cycle of the seminiferous epithelium" is driven by the continuous commitment of undifferentiated spermatogonia to meiosis and the period of time required to form spermatozoa. This commitment termed the A to A1 transition requires the action of retinoic acid (RA) on the undifferentiated spermatogonia or prospermatogonia. In stages VII to IX of the cycle of the seminiferous epithelium, Sertoli cells and germ cells are influenced by pulses of RA. These pulses of RA move along the seminiferous tubules coincident with the spermatogenic wave, presumably undergoing constant synthesis and degradation. The RA pulse then serves as a trigger to commit undifferentiated progenitor cells to the rigidly timed pathway into meiosis and spermatid differentiation.

  17. Young Children's Understanding of Joint Commitments

    ERIC Educational Resources Information Center

    Grafenhain, Maria; Behne, Tanya; Carpenter, Malinda; Tomasello, Michael

    2009-01-01

    When adults make a joint commitment to act together, they feel an obligation to their partner. In 2 studies, the authors investigated whether young children also understand joint commitments to act together. In the first study, when an adult orchestrated with the child a joint commitment to play a game together and then broke off from their joint…

  18. Professionalism as a Form of Work Commitment.

    ERIC Educational Resources Information Center

    Morrow, Paula C.; Goetz, Joe F., Jr.

    1988-01-01

    Evaluated concept of professionalism as a form of work commitment using a modified version of Hall's (1968) multidimensional measure of professionalism on 325 accountants in public practice. Examined three forms of work commitment--job involvement, organizational commitment, and work ethic endorsement--and four professional behaviors. Suggests the…

  19. Professionalism as a Form of Work Commitment.

    ERIC Educational Resources Information Center

    Morrow, Paula C.; Goetz, Joe F., Jr.

    1988-01-01

    Evaluated concept of professionalism as a form of work commitment using a modified version of Hall's (1968) multidimensional measure of professionalism on 325 accountants in public practice. Examined three forms of work commitment--job involvement, organizational commitment, and work ethic endorsement--and four professional behaviors. Suggests the…

  20. Commitment among Arab Adolescents in Israel.

    ERIC Educational Resources Information Center

    Ben-Ari, Adital Tirosh; Azaiza, Faisal

    1998-01-01

    Examines 662 Arab adolescents' commitments to their own self-development, family, Arab people, and village along with the order in which these commitments are structured. Reveals that the two prevalent patterns of adolescent commitment, individualistic and collectivistic, demonstrate the adolescents' struggle with these value systems and the…

  1. The Commitment Process for Psychiatric Patients

    PubMed Central

    Shore, James H.

    1978-01-01

    Recent changes in commitment legislation for the mentally ill have had an important impact on the role of physicians in treating these patients. New commitment laws emphasize civil rights at the expense of right-to-treatment concepts, sometimes causing neglect of severely psychotic persons. Only four western states have a high rating of conformity with a model commitment statute. PMID:636410

  2. 24 CFR 200.47 - Firm commitments.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Requirements for Application, Commitment, and Endorsement... Eligibility Requirements for Existing Projects Commitment Applications § 200.47 Firm commitments. A valid firm... completion of construction or substantial rehabilitation of the project; or (2) Upon completion of...

  3. Organizational and Client Commitment among Contracted Employees

    ERIC Educational Resources Information Center

    Coyle-Shapiro, Jacqueline A-M.; Morrow, Paula C.

    2006-01-01

    This study examines affective commitment to employing and client organizations among long-term contracted employees, a new and growing employment classification. Drawing on organizational commitment and social exchange literatures, we propose two categories of antecedents of employee commitment to client organizations. We tested our hypotheses…

  4. Anchors of Religious Commitment in Adolescents

    ERIC Educational Resources Information Center

    Layton, Emily; Dollahite, David C.; Hardy, Sam A.

    2011-01-01

    This study explores adolescent religious commitment using qualitative data from a religiously diverse (Jewish, Christian, Muslim) sample of 80 adolescents. A new construct, "anchors of religious commitment," grounded in interview data, is proposed to describe what adolescents commit to as a part of their religious identity. Seven anchors of…

  5. Low-dose dobutamine adds incremental value to late gadolinium enhancement cardiac magnetic resonance in the prediction of adverse remodelling following acute myocardial infarction.

    PubMed

    Scott, Anne E; Semple, Scott I K; Redpath, Thomas W; Hillis, Graham S

    2013-09-01

    To examine the relative and combined value of late gadolinium enhancement (LGE) and low-dose dobutamine (LDD) cardiac magnetic resonance (CMR) to predict 'adverse remodelling' (AR) following acute myocardial infarction (AMI). Forty-five patients with AMI were recruited. CMR was performed 2-4 days after presentation and at 6 months. Ventricular wall motion and volume were recorded at rest and following dobutamine infusion. Measures of first pass perfusion, persistent microvascular obstruction (PMO), and LGE were obtained following contrast administration. Quantitation was performed using the MEDIS 6.2 software. Regression analysis was employed to determine the univariables and multivariate models most predictive of AR at 6 months. The incremental and relative value of LDD over LGE was investigated. The most predictive univariable was 'volume of PMO' (r = 0.51, r2 = 0.26, P < 0.001). The optimal 'combined' multivariate model, utilizing data from all components, was highly predictive of AR (r = 0.82, r2 = 0.67, P < 0.001). The optimal model using parameters only from the LGE component also predicted remodelling (r = 0.65, r2 = 42.0, P = 0.001) but with less accuracy. In contrast, the optimal model using variables from the LDD component alone predicted remodelling with a similar accuracy to the optimal combined model (r = 0.82, r2 = 0.67, P < 0.001). A comprehensive CMR examination accurately predicts AR following AMI. LDD is superior to LGE CMR in this respect. These data suggest that LDD not only adds incremental value to LGE in the prediction of remodelling post-AMI but also may be utilized alone with the same predictive power.

  6. Influence of Patient Goals of Care on Performance Measures in Patients Hospitalized for Heart Failure: An Analysis of the Enhanced Feedback For Effective Cardiac Treatment (EFFECT) Registry.

    PubMed

    McAlister, Finlay A; Wang, Julie; Donovan, Linda; Lee, Douglas S; Armstrong, Paul W; Tu, Jack V

    2015-05-01

    Pay for performance programs compare metrics that are risk-adjusted, but goals of care are not considered in current models. We conducted this study to explore the associations between do not resuscitate (DNR) designations, quality of care, and outcomes. Retrospective cohort study with chart review for inpatient quality metrics, 30 day mortality, and readmissions or death within 30 days of discharge in 96 Ontario hospitals participating in the Enhanced Feedback For Effective Cardiac Treatment (EFFECT) study in 2004/05. Of 8339 patients (mean age 77 years) with new heart failure, 1220 (15%) had DNR documented at admission (admission DNR, varying from 0% to 36% between hospitals) and 892 (11%) were switched from full resuscitation to DNR during their index hospitalization (later DNR). Death at 30 days was more common in patients with admission DNR (27%) or later DNR (35%) than full resuscitation (3%)-admission DNR was a stronger predictor (adjusted OR 8.6, 95% confidence interval 6.8-10.7) than any of the variables currently included in heart failure 30 day mortality risk models. Hospital-level rankings differed considerably if DNR patients were excluded: 22 of the 39 EFFECT hospitals in the top and bottom quintiles for 30 day mortality rates (the usual thresholds for rewards/penalties in current performance-based reimbursement schemes) would not have been in those same quintiles if admission DNR patients were excluded. Alternate goals of care are frequent and important confounders in heart failure comparative studies. Philosophy of care discussions should be considered for inclusion as a potential quality of care indicator. © 2015 American Heart Association, Inc.

  7. Highly sensitive detection of human cardiac myoglobin using a reverse sandwich immunoassay with a gold nanoparticle-enhanced surface plasmon resonance biosensor.

    PubMed

    Gnedenko, Oksana V; Mezentsev, Yury V; Molnar, Andrey A; Lisitsa, Andrey V; Ivanov, Alexis S; Archakov, Alexander I

    2013-01-08

    A highly sensitive reverse sandwich immunoassay for the detection of human cardiac myoglobin (cMb) in serum was designed utilizing a gold nanoparticle (AuNP)-enhanced surface plasmon resonance (SPR) biosensor. First, a monoclonal anti-cMb antibody (Mab1) was covalently immobilized on the sensor surface. AuNPs were covalently conjugated to the second monoclonal anti-cMb antibody (Mab2) to form an immuno-gold reagent (Mab2-AuNP). The reverse sandwich immunoassay consists of two steps: (1) mixing the serum sample with Mab2-AuNP and incubation for the formation of cMb/Mab2-AuNP complexes and (2) sample injection over the sensor surface and evaluation of the Mab1/cMb/Mab2-AuNP complex formation, with the subsequent calculation of the cMb concentration in the serum. The biosensor signal was amplified approximately 30-fold compared with the direct reaction of cMb with Mab1 on the sensor surface. The limit of detection of cMb in a human blood serum sample was found to be as low as 10 pM (approx. 0.18 ng mL(-1)), and the inter-assay coefficient of variation was less than 3%. Thus, the developed SPR-based reverse sandwich immunoassay has a sensitivity that is sufficient to measure cMb across a wide range of normal and pathological concentrations, allowing an adequate estimation of the disease severity and the monitoring of treatment.

  8. Zinc supplementation enhances the effectiveness of St. Thomas' Hospital No. 2 cardioplegic solution in an in vitro model of hypothermic cardiac arrest.

    PubMed

    Powell, S R; Aiuto, L; Hall, D; Tortolani, A J

    1995-12-01

    The present study was done to assess the effectiveness of a zinc-supplemented cardioplegic solution in an in vitro model of hypothermic arrest. Isolated hearts were perfused in the nonworking mode. All hearts were subjected to 2 hours of hypothermic arrest, at 10 degrees C, followed by 60 minutes of recovery. In protocol 1, arrest was initiated with infusion of cardioplegic solution with or without 30 mumol/l zinc for 5 minutes, which was then reinfused for 5 minutes every 15 minutes during arrest. In protocol 2, arrest was initiated with infusion of cardioplegic solution with or without 40 mumol/L zinc for 10 minutes. Cardioplegic solution (without zinc) was then reinfused for 5 minutes before the hearts were rewarmed. In protocol 1 hearts, peak postischemic left ventricular developed systolic pressure was 106 +/- 5 mm Hg and 80 +/- 3 mm Hg in zinc-treated versus control hearts, respectively (p < 0.05 by repeated-measures analysis of variance). In protocol 2 hearts, recovery of postischemic left ventricular developed systolic pressure peaked at 74 +/- 4 mm Hg and 46 +/- 8 mm Hg in zinc-treated and control hearts, respectively (p 0.05, repeated-measures analysis of variance). Similar effects were observed for the left ventricular rate of relaxation (p < 0.05, repeated-measures analysis of variance). Except for some minor effects, lactate dehydrogenase release was not affected by zinc supplementation. The present study demonstrates that zinc supplementation further enhances the normally observed preservation of postarrest cardiac function and suggests possible clinical utility for this metal as an additive to standard crystalloid cardioplegic solutions.

  9. Quantification of left ventricular size and function using contrast-enhanced real-time 3D imaging with power modulation: comparison with cardiac MRI.

    PubMed

    Coon, Patrick D; Pollard, Heidi; Furlong, Kathleen; Lang, Roberto M; Mor-Avi, Victor

    2012-11-01

    In patients with optimal images, real-time 3-D echocardiography (RT3DE) allows accurate evaluation of left ventricular (LV) volumes and ejection fraction (EF). However, in patients with poor acoustic windows, lower correlations were reported despite the use of contrast. We hypothesized that power modulation (PM) RT3DE imaging that uses low mechanical indices and provides uniform LV opacification could overcome this problem. Accordingly, we sought to: (i) Test the feasibility of quantification of LV volumes and EF from contrast-enhanced (CE) PM RT3DE images, (ii) validate this technique against cardiac magnetic resonance (CMR) reference and (iii) test its clinical value by quantifying the improvement in accuracy and reproducibility. We studied 20 patients who underwent CMR, harmonic nonenhanced RT3DE and CE PM RT3DE imaging on the same day. All images were analyzed to obtain end-systolic and end-diastolic LV volumes (EDV, ESV) and calculate EF. To determine the reproducibility of each RT3DE technique, imaging was repeated in the same setting by a second sonographer. In addition, patients were divided according to the quality of their RT3DE images into two groups, for which agreement with CMR and reproducibility were calculated separately. CE PM RT3DE imaging improved the accuracy of EDV, ESV and EF measurements in patients with poor acoustic windows without significantly affecting those in patients with optimal images. In addition, CE PM RT3DE imaging improved the reproducibility of the measurements, as reflected by a twofold decrease in intermeasurement variability. Importantly, the variability in CE PM RT3DE-derived volumes and EF was under 10%, irrespective of image quality. This methodology may become the new standard for LV size and function, which will be particularly important in patients with poor acoustic windows or contraindications to CMR. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights

  10. Left Atrial Volume as a Predictor of Left Ventricular Functional Recovery in Patients With Dilated Cardiomyopathy and Absence of Delayed Enhancement in Cardiac Magnetic Resonance.

    PubMed

    Moon, Jeonggeun; Shim, Chi Young; Kim, Young-Jin; Park, Sungha; Kang, Seok-Min; Chung, Namsik; Ha, Jong-Won

    2016-04-01

    Improvement of left ventricular (LV) systolic dysfunction can occur in patients with dilated cardiomyopathy (DCM), and it is more frequently observed if patients have no delayed enhancement (DE) in cardiac magnetic resonance imaging (CMR). However, even in the absence of DE, not all patients have functional recovery. We retrospectively investigated the predictors of LV functional recovery in patients with DCM who had no DE in CMR. A total of 136 patients with DCM underwent CMR. Among them, 44 (29 male, age 55 ± 14 years) showed no DE and these patients composed the study population. The study patients were divided into 2 groups according to the occurrence of functional recovery defined as an increase in LV ejection fraction to a level of ≥50% and net increase in ejection fraction of 20% or more: group 1 (n = 14) with functional recovery and group 2 (n = 30) without functional recovery. In patients who showed functional recovery, left atrial volume index (LAVI [26 ± 8 mL/m(2) vs 45 ± 18 mL/m(2)]) and LV end-diastolic dimension (62 ± 6 mm vs 67 ± 7 mm) were significantly smaller when compared with those without functional recovery (P <.05 for all). In Cox multiple regression analysis, LAVI was the only significant parameter associated with LV functional recovery (hazard ratio 0.932, 95% confidence interval 0.877-0.991, P = .024). LAVI < 38 mL/m(2) had 100% specificity in predicting the improvement of LV systolic dysfunction. In DCM patients who had no DE in CMR, LAVI predicts LV functional recovery with high specificity. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Tripartite Motif 8 Contributes to Pathological Cardiac Hypertrophy Through Enhancing Transforming Growth Factor β-Activated Kinase 1-Dependent Signaling Pathways.

    PubMed

    Chen, Lijuan; Huang, Jia; Ji, Yan-Xiao; Mei, Fanghua; Wang, Pi-Xiao; Deng, Ke-Qiong; Jiang, Xi; Ma, Genshan; Li, Hongliang

    2017-02-01

    Tripartite motif (TRIM) 8 functions as an E3 ubiquitin ligase, interacting with and ubiquitinating diverse substrates, and is implicated in various pathological processes. However, the function of TRIM8 in the heart remains largely uncharacterized. This study aims to explore the role of TRIM8 in the development of pathological cardiac hypertrophy. Mice and isolated neonatal rat cardiomyocytes overexpressing or lacking TRIM8 were examined in several experiments. The effect of aortic banding-induced cardiac hypertrophy was analyzed by echocardiographic, pathological and molecular analyses. Our results indicated that the TRIM8 overexpression in hearts exacerbated the cardiac hypertrophy triggered by aortic banding. In contrast, the development of pathological cardiac hypertrophy was profoundly blocked in TRIM8-deficient hearts. Mechanistically, our study suggests that TRIM8 may elicit cardiodetrimental effects by promoting the activation of transforming growth factor β-activated kinase 1 (TAK1)-p38/JNK signaling pathways. Similar results were observed in cultured neonatal rat cardiomyocytes treated with angiotensin II. The rescue experiments using the TAK1-specific inhibitor 5z-7-ox confirmed the requirement of TAK1 activation in TRIM8-mediated pathological cardiac hypertrophy. Furthermore, TRIM8 contributed to TAK1 activation by binding to and promoting TAK1 ubiquitination. In conclusion, our study demonstrates that TRIM8 plays a deleterious role in pressure overload-induced cardiac hypertrophy by accelerating the activation of TAK1-dependent signaling pathways.

  12. Late Gadolinium Enhancement on Cardiac MRI Correlates with QT Dynamicity Represented by QT/RR Relationship in Patients with Ventricular Arrhythmias.

    PubMed

    Sakamoto, Naka; Sato, Nobuyuki; Talib, Ahmed Karim; Sugiyama, Eitaro; Minoshima, Akiho; Tanabe, Yasuko; Fujino, Takayuki; Takeuchi, Toshiharu; Akasaka, Kazumi; Saijo, Yasuaki; Kawamura, Yuichiro; Hasebe, Naoyuki

    2016-03-01

    The distribution of late gadolinium enhancement (LGE) on the cardiac MRI (CMR) indicates myocardial fibrosis and provides information of possible reentry substrates. QT dynamicity reflecting repolarization abnormalities has gained attention as a potential prognostic predictive factor. To clarify the correlation between the LGE distribution on CMR and QT dynamicity represented by the QT/RR relationship. CMR and QT/RR analyses using Holter monitoring were performed in 34 patients (24 males, 60 ± 11 years) with ventricular tachycardia (VT) and/or ventricular fibrillation (VF). The LGE on CMR was scored using a 4-point score in 17 left ventricular segments. The sum of the LGE scores was calculated for each patient. The QT/RR slope and daytime/nighttime QT/RR ratio (day/night ratio) were calculated. The correlation between the slope or the day/night QT/RR ratio and late enhancement findings was analyzed. All patients were divided into 23 LGE positive (LGE(+)) and 11 LGE negative (LGE(-)) patients. The slopes of the QTe/RR and QTa /RR were significantly steeper in the LGE(+) than in LGE(-) patients (0.21 ± 0.03 vs 0.13 ± 0.02; P < 0.001, 0.19 ± 0.03 vs 0.13 ± 0.02; P < 0.001, respectively), and both slopes were significantly correlated with the total LGE scores (r = 0.83, P < 0.001; r = 0.71, P < 0.001, respectively). In the LGE(+) patients, the QTe day/night (1.37 ± 0.38 vs 0.91 ± 0.33; P = 0.002) and QTa day/night ratios (1.33 ± 0.26 vs 1.06 ± 0.30; P = 0.011) were significantly greater than those in the LGE(-) patients. The LGE distribution was closely related to the QT dynamicity, suggesting that a combination of these markers can be a powerful tool for understanding the background pathophysiology. © 2015 Wiley Periodicals, Inc.

  13. Microvascular obstruction on delayed enhancement cardiac magnetic resonance imaging after acute myocardial infarction, compared with myocardial (201)Tl and (123)I-BMIPP dual SPECT findings.

    PubMed

    Mori, Hiroaki; Isobe, Satoshi; Sakai, Shinichi; Yamada, Takashi; Watanabe, Naoki; Miura, Manabu; Uchida, Yasuhiro; Kanashiro, Masaaki; Ichimiya, Satoshi; Okumura, Takahiro; Murohara, Toyoaki

    2015-08-01

    The hypo-enhanced regions within the hyper-enhanced infarct areas detected by cardiac magnetic resonance (CMR) imaging reflect microvascular obstruction (MO) after acute myocardial infarction (AMI). The combined myocardial thallium-201 ((201)Tl)/iodine-123-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid ((123)I-BMIPP) dual single-photon emission computed tomography (SPECT) is a useful tool for detecting myocardial reversibility after AMI. We evaluated whether MO could be an early predictor of irreversible myocardial damage in comparison with (201)Tl and (123)I-BMIPP dual SPECT findings in AMI patients. Sixty-two patients with initial AMI who successfully underwent coronary revascularization were enrolled. MO was defined by CMR imaging. Patients were divided into 2 groups as follows: MO group (n=32) and non-MO group (n=30). Scintigraphic defect scores were calculated using a 17-segment model with a 5-point scoring system. The mismatch score (MMS) was calculated as follows: the total sum of (Σ) (123)I-BMIPP defect score minus Σ(201)Tl defect score. The percentage mismatch score (%MMS) was calculated as follows: MMS/(Σ(123)I-BMIPP score)×100 (%). The percentage infarct size (%IS) was significantly greater in the MO group than in the non-MO group (32.2±13.8% vs. 18.3±12.1%, p<0.001). The %MMS significantly correlated with the %IS and the percentage MO (r=-0.26, p=0.03; r=-0.45, p<0.001, respectively). The %MMS was significantly greater in the non-MO group than in the MO group (45.4±42.4% vs. 13.3±28.0%, p=0.001), and was an independent predictor for MO (OR 0.97, 95%CI 0.94-0.99, p=0.02). Our results reconfirm that, in comparison with myocardial dual scintigraphy, MO is an important structural abnormality. CMR imaging is useful for the early detection of irreversible myocardial damage after AMI. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. The Sense of Commitment: A Minimal Approach

    PubMed Central

    Michael, John; Sebanz, Natalie; Knoblich, Günther

    2016-01-01

    This paper provides a starting point for psychological research on the sense of commitment within the context of joint action. We begin by formulating three desiderata: to illuminate the motivational factors that lead agents to feel and act committed, to pick out the cognitive processes and situational factors that lead agents to sense that implicit commitments are in place, and to illuminate the development of an understanding of commitment in ontogeny. In order to satisfy these three desiderata, we propose a minimal framework, the core of which is an analysis of the minimal structure of situations which can elicit a sense of commitment. We then propose a way of conceptualizing and operationalizing the sense of commitment, and discuss cognitive and motivational processes which may underpin the sense of commitment. PMID:26779080

  15. Fast kVp-switching dual energy contrast-enhanced thorax and cardiac CT: A phantom study on the accuracy of iodine concentration and effective atomic number measurement.

    PubMed

    Papadakis, Antonios E; Damilakis, John

    2017-09-01

    To assess the effect of vessel diameter and exposure parameters on the estimation accuracy of concentration and effective atomic number (Zeff ) of iodine (I) in contrast-enhanced thorax and cardiac dual-energy CT using a modern fast kVp-switching CT scanner. A standard semi-anthropomorphic cardiac CT phantom devised to simulate the human chest at three different body habitus i.e., medium-sized, large-sized, and obese, was scanned using a fast kVp-switching Revolution-GSI GE CT scanner. Five cylindrical, 10 mm diameter, vials were filled with solutions prepared by diluting I contrast at five concentrations (2.5, 5, 10, 15, and 20 mg I/ml). To simulate small vessels, pipette tips with a diameter ranging from 5 mm to 0.5 mm were employed. The vials and pipette tips were accommodated within the semi-anthropomorphic phantom. CT acquisitions were performed in the fast kVp-switching dual-energy mode at six different CTDIw values. Acquisitions were also performed at 80, 100, 120, and 140 kVp. Images were acquired at 64 × 0.625 mm beam collimation and reconstructed at 2.5 mm using all available reconstruction filter kernels. Virtual monochromatic spectral (VMS) images, iodine concentration (IMeas ), and Zeff maps were reconstructed. Hounsfield unit as a function of energy (HUkeV ) in VMS and single-kVp (HUkVp ), IMeas and Zeff were measured at each CTDIw . The effect of vessel diameter on IMeas and Zeff was investigated. Measured HUkeV and Zeff were compared to theoretically estimated values and IMeas were compared to nominal (INom ) values. In 10 mm diameter vessels, HUkeV values were accurate to 18% for the medium-sized, 22% for the large-sized and 39% for the obese phantoms. IMeas was underestimated by up to 10% for the medium-sized, 26% for the large-sized and 33% for the obese phantom. IMeas error decreased with increasing CTDIw from ±0.799 mg/ml at 8.61 mGy to ±0.082 mg/ml at 32.01 mGy. The percentage difference between measured and theoretically estimated Zeff

  16. Commitment of Cultural Minorities in Organizations: Effects of Leadership and Pressure to Conform.

    PubMed

    Rupert, Joyce; Jehn, Karen A; van Engen, Marloes L; de Reuver, Renée S M

    2010-03-01

    PURPOSE: In this study, we investigated the commitment of cultural minorities and majorities in organizations. We examined how contextual factors, such as pressure to conform and leadership styles, affect the commitment of minority and majority members. DESIGN/METHODOLOGY/APPROACH: A field study was conducted on 107 employees in a large multinational corporation. FINDINGS: We hypothesize and found that cultural minorities felt more committed to the organization than majority members, thereby challenging the existing theoretical view that cultural minorities will feel less committed. We also found that organizational pressure to conform and effective leadership increased the commitment of minorities. IMPLICATIONS: Our findings indicate that organizational leaders and researchers should not only focus on increasing and maintaining the commitment of minority members, but should also consider how majority members react to cultural socialization and integration processes. The commitment of minority members can be further enhanced by effective leadership. ORIGINALITY/VALUE: In this study, we challenge the existing theoretical view based on similarity attraction theory and relational demography theory, that cultural minorities would feel less committed to the organization. Past research has mainly focused on minority groups, thereby ignoring the reaction of the majority to socialization processes. In this study, we show that cultural minorities can be more committed than majority members in organizations. Therefore, the perceptions of cultural majority members of socialization processes should also be considered in research on cultural diversity and acculturation.

  17. Commitment accounting for CO2 emissions

    NASA Astrophysics Data System (ADS)

    Davis, S. J.; Socolow, R. H.

    2013-12-01

    Long-lived energy infrastructure that burns fossil fuels represents a multi-decade 'commitment' to emit CO2. Today's global power sector, alone, represents hundreds of billions of tons of still unrealized 'committed emissions' of CO2. And every year, substantial new commitments to future emissions are made, as new power plants are built. The socioeconomic inertia of these commitments is a major barrier to climate change mitigation. Here, we quantify these annual commitments by a bottom-up analysis of all power plants commissioned between 1950 and 2011; assigning emission commitments to the year when each generator came on line. We find, assuming 40-year commitments, that the global commitment to future emissions from the world's generators in 2011 (the most recent year in our analysis) was 318 Gt CO2, of which 216 Gt CO2 were commitments from the world's coal-fired generators and 134 Gt CO2 were commitments from China's generators. Annual new global commitments exceeded 15 Gt CO2 per year in every year since 2000. Moreover, between 2005-2010 (the latest year of available emissions data), new global commitments were more than twice as large as actual emissions from all power plants. Country-specific ratios of new committed emissions to actual emissions, averaged over 1990-2010 were 4.1 for China, 2.6 for India, 0.9 for the EU, and 0.6 for the US. We urge that the reporting of annual CO2 emissions, already widely institutionalized, be augmented by 'commitment accounting' which makes these future emissions salient. Annual committed emissions and annual emissions of primary power infrastructure. New committed emissions (light green) have grown from approximately 4 Gt CO2 per year in 1960 to roughly 10 Gt CO2 per year between 1970-1995, and then to more than 15 Gt CO2 per year since 2000. Throughout this period, new committed emissions have exceeded annual emissions (blue curve, source: IEA). Although the commitments made 30-40 years ago have largely been realized (dark

  18. Measuring government commitment to vaccination.

    PubMed

    Glassman, Amanda; Zoloa, Juan Ignacio; Duran, Denizhan

    2013-04-18

    Vaccination is among the most cost-effective health interventions and has attracted ever greater levels of funding from public and private donors. However, some countries, mainly populous lower-middle income countries, are lagging behind on vaccination financing and performance. In this paper, we discuss the rationale for investing in vaccination and construct a metric to measure government commitment to vaccination that could promote accountability and better tracking of performance. While noting the limitations of available data, we find that populous middle-income countries, which stand to gain tremendously from increased vaccination uptake, perform poorly in terms of their vaccination outcomes.

  19. Our Commitment to Bioenergy Sustainability

    SciTech Connect

    2015-06-18

    The U.S. Department of Energy’s Bioenergy Technologies Office (BETO) is committed to developing the resources, technologies, and systems needed to support a thriving bioenergy industry that protects natural resources and ad- vances environmental, economic, and social benefits. BETO’s Sustainability Technology Area proactively identifies and addresses issues that affect the scale-up potential, public acceptance, and long-term viability of advanced bioenergy systems; as a result, the area is critical to achieving BETO’s overall goals.

  20. Cardiac Rehabilitation

    MedlinePlus

    ... your risk of future heart problems, and to improve your health and quality of life. Cardiac rehabilitation programs increase ... exercise routine at home or at a local gym. You may also continue to ... health concerns. Education about nutrition, lifestyle and weight loss ...

  1. Human embryonic stem cells and cardiac repair.

    PubMed

    Zhu, Wei-Zhong; Hauch, Kip D; Xu, Chunhui; Laflamme, Michael A

    2009-01-01

    The muscle lost after a myocardial infarction is replaced with noncontractile scar tissue, often initiating heart failure. Whole-organ cardiac transplantation is the only currently available clinical means of replacing the lost muscle, but this option is limited by the inadequate supply of donor hearts. Thus, cell-based cardiac repair has attracted considerable interest as an alternative means of ameliorating cardiac injury. Because of their tremendous capacity for expansion and unquestioned cardiac potential, pluripotent human embryonic stem cells (hESCs) represent an attractive candidate cell source for obtaining cardiomyocytes and other useful mesenchymal cell types for such therapies. Human embryonic stem cell-derived cardiomyocytes exhibit a committed cardiac phenotype and robust proliferative capacity, and recent testing in rodent infarct models indicates that they can partially remuscularize injured hearts and improve contractile function. Although the latter successes give good reason for optimism, considerable challenges remain in the successful application of hESCs to cardiac repair, including the need for preparations of high cardiac purity, improved methods of delivery, and approaches to overcome immune rejection and other causes of graft cell death. This review will describe the phenotype of hESC-derived cardiomyocytes and preclinical experience with these cells and will consider strategies to overcoming the aforementioned challenges.

  2. Aortic and Hepatic Contrast Enhancement During Hepatic-Arterial and Portal Venous Phase Computed Tomography Scanning: Multivariate Linear Regression Analysis Using Age, Sex, Total Body Weight, Height, and Cardiac Output.

    PubMed

    Masuda, Takanori; Nakaura, Takeshi; Funama, Yoshinori; Higaki, Toru; Kiguchi, Masao; Imada, Naoyuki; Sato, Tomoyasu; Awai, Kazuo

    We evaluated the effect of the age, sex, total body weight (TBW), height (HT) and cardiac output (CO) of patients on aortic and hepatic contrast enhancement during hepatic-arterial phase (HAP) and portal venous phase (PVP) computed tomography (CT) scanning. This prospective study received institutional review board approval; prior informed consent to participate was obtained from all 168 patients. All were examined using our routine protocol; the contrast material was 600 mg/kg iodine. Cardiac output was measured with a portable electrical velocimeter within 5 minutes of starting the CT scan. We calculated contrast enhancement (per gram of iodine: [INCREMENT]HU/gI) of the abdominal aorta during the HAP and of the liver parenchyma during the PVP. We performed univariate and multivariate linear regression analysis between all patient characteristics and the [INCREMENT]HU/gI of aortic- and liver parenchymal enhancement. Univariate linear regression analysis demonstrated statistically significant correlations between the [INCREMENT]HU/gI and the age, sex, TBW, HT, and CO (all P < 0.001). However, multivariate linear regression analysis showed that only the TBW and CO were of independent predictive value (P < 0.001). Also, only the CO was independently and negatively related to aortic enhancement during HAP and to liver parenchymal enhancement when the contrast material injection protocol was adjusted for the TBW (P < 0.001). By multivariate linear regression analysis only the TBW and CO were significantly correlated with aortic and liver parenchymal enhancement; the age, sex, and HT were not. The CO was the only independent factor affecting aortic and liver parenchymal enhancement at hepatic CT when the protocol was adjusted for the TBW.

  3. Spirituality and Autonomic Cardiac Control

    PubMed Central

    Berntson, Gary G.; Norman, Greg J.; Hawkley, Louise C.; Cacioppo, John T.

    2009-01-01

    Background Spirituality has been suggested to be associated with positive health, but potential biological mediators have not been well characterized. Purpose and Methods The present study examined, in a population based sample of middle-aged and older adults, the potential relationship between spirituality and patterns of cardiac autonomic control, which may have health significance. Measures of parasympathetic (high-frequency heart rate variability) and sympathetic (pre-ejection period) cardiac control were obtained from a representative sample of 229 participants. Participants completed questionnaires to assess spirituality (closeness to and satisfactory relation with God). Personality, demographic, anthropometric, health behavior, and health status information was also obtained. A series of multivariate regression models was used to examine the relations between spirituality, the autonomic measures, and two derived indexes-- cardiac autonomic balance (CAB, reflecting parasympathetic to sympathetic balance) and cardiac autonomic regulation (CAR, reflecting total autonomic control). Results Spirituality, net of demographics or other variables, was found to be associated with enhanced parasympathetic as well as sympathetic cardiac control (yielding a higher CAR); but was not associated with CAB. Although the number of cases was small (N=11), both spirituality and CAR were significant negative predictors of the prior occurrence of a myocardial infarction. Conclusions In a population based sample, spirituality appears to be associated with a specific pattern of cardiac autonomic regulation, characterized by a high level of cardiac autonomic control, irrespective of the relative contribution of the two autonomic branches. This pattern of autonomic control may have health significance. PMID:18357497

  4. Chronic ischemic mitral regurgitation and papillary muscle infarction detected by late gadolinium-enhanced cardiac magnetic resonance imaging in patients with ST-segment elevation myocardial infarction.

    PubMed

    Bouma, Wobbe; Willemsen, Hendrik M; Lexis, Chris P H; Prakken, Niek H; Lipsic, Erik; van Veldhuisen, Dirk J; Mariani, Massimo A; van der Harst, Pim; van der Horst, Iwan C C

    2016-12-01

    Both papillary muscle infarction (PMI) and chronic ischemic mitral regurgitation (CIMR) are associated with reduced survival after myocardial infarction. The influence of PMI on CIMR and factors influencing both entities are incompletely understood. We sought to determine the influence of PMI on CIMR after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and to define independent predictors of PMI and CIMR. Between January 2011 and May 2013, 263 patients (mean age 57.8 ± 11.5 years) underwent late gadolinium-enhanced cardiac magnetic resonance imaging and transthoracic echocardiography 4 months after PCI for STEMI. Infarct size, PMI, and mitral valve and left ventricular geometric and functional parameters were assessed. Univariate and multivariate analyses were performed to identify predictors of PMI and CIMR (≥grade 2+). PMI was present in 61 patients (23 %) and CIMR was present in 86 patients (33 %). In patients with PMI, 52 % had CIMR, and in patients without PMI, 27 % had CIMR (P < 0.001). In multivariate analyses, infarct size [odds ratio (OR) 1.09 (95 % confidence interval 1.04-1.13), P < 0.001], inferior MI [OR 4.64 (1.04-20.62), P = 0.044], and circumflex infarct-related artery [OR 8.21 (3.80-17.74), P < 0.001] were independent predictors of PMI. Age [OR 1.08 (1.04-1.11), P < 0.001], infarct size [OR 1.09 (1.03-1.16), P = 0.003], tethering height [OR 19.30 (3.28-113.61), P = 0.001], and interpapillary muscle distance [OR 3.32 (1.31-8.42), P = 0.011] were independent predictors of CIMR. The risk of PMI is mainly associated with inferior infarction and infarction in the circumflex coronary artery. Although the prevalence of CIMR is almost doubled in the presence of PMI, PMI is not an independent predictor of CIMR. Tethering height and interpapillary muscle distance are the strongest independent predictors of CIMR.

  5. Outpatient civil commitment: a dangerous charade or a component of a comprehensive institution of civil commitment?

    PubMed

    Schopp, Robert F

    2003-01-01

    This article examines three criticisms frequently directed toward preventive commitment as one form of outpatient commitment. These criticisms contend that preventive commitment (a) abandons the dangerousness criteria for civil commitmnet, (b) promotes unwarranted inpatient commitment of those who do not meet civil commitment criteria, and (c) undermines important individual liberties by diluting the right to refuse treatment. Understanding and evaluating these criticisms requires analysis of the intersection among empirical, conceptual, and justificatory claims. According to the analysis presented here, advocates of preventive commitment can defend a legitimate role for preventive commitment. This analysis applies to preventive commitment as a dispositional alternative within a comprehensive institution of civil commitment involving distinct parens patriae and police power components.

  6. Learning organizations, internal marketing, and organizational commitment in hospitals

    PubMed Central

    2014-01-01

    Background Knowledge capital is becoming more important to healthcare establishments, especially for hospitals that are facing changing societal and industrial patterns. Hospital staff must engage in a process of continual learning to improve their healthcare skills and provide a superior service to their patients. Internal marketing helps hospital administrators to improve the quality of service provided by nursing staff to their patients and allows hospitals to build a learning culture and enhance the organizational commitment of its nursing staff. Our empirical study provides nursing managers with a tool to allow them to initiate a change in the attitudes of nurses towards work, by constructing a new ‘learning organization’ and using effective internal marketing. Methods A cross-sectional design was employed. Two hundred questionnaires were distributed to nurses working in either a medical centre or a regional hospital in Taichung City, Taiwan, and 114 valid questionnaires were returned (response rate: 57%). The entire process of distribution and returns was completed between 1 October and 31 October 2009. Hypothesis testing was conducted using structural equation modelling. Results A significant positive correlation was found between the existence of a ‘learning organization’, internal marketing, and organizational commitment. Internal marketing was a mediator between creating a learning organization and organizational commitment. Conclusion Nursing managers may be able to apply the creation of a learning organization to strategies that can strengthen employee organizational commitment. Further, when promoting the creation of a learning organization, managers can coordinate their internal marketing practices to enhance the organizational commitment of nurses. PMID:24708601

  7. 78 FR 58149 - Continuation of the National Emergency With Respect to Persons Who Commit, Threaten To Commit, or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-20

    ... Emergency With Respect to Persons Who Commit, Threaten To Commit, or Support Terrorism #0; #0; #0... the National Emergency With Respect to Persons Who Commit, Threaten To Commit, or Support Terrorism On... persons who commit, threaten to commit, or support terrorism, pursuant to the International...

  8. 76 FR 58999 - Continuation of the National Emergency With Respect to Persons Who Commit, Threaten To Commit, Or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-22

    ... Emergency With Respect to Persons Who Commit, Threaten To Commit, or Support Terrorism #0; #0; #0... the National Emergency With Respect to Persons Who Commit, Threaten To Commit, Or Support Terrorism On... persons who commit, threaten to commit, or support terrorism, pursuant to the International...

  9. Leadership and satisfaction in change commitment.

    PubMed

    Yang, Yi-Feng

    2011-06-01

    Managerial transformational leadership skills may directly influence banking counter staff toward change commitment and improve job satisfaction and service quality, or the influence instead may be mediated by change commitment. For a sample comprised of 246 managers from four large Taiwanese banks, the following path relationships were tested: (1) the association of transformational leadership with change commitment, (2) the association of change commitment with job satisfaction, and (3) the direct or indirect (through the mediation of change commitment) effect of transformational leadership on job satisfaction. Regression was utilized to gain insight into the effects of transformational leadership and change commitment on job satisfaction. Transformational leadership may foster change by providing psychological support to the banking counter staff, enabling them to use their skills to meet the needs of individual customers in response to complex environments.

  10. On the justification for civil commitment.

    PubMed

    Høyer, G

    2000-01-01

    This paper explores some of the controversies in the debate regarding the justification of civil commitment. The sometimes conflicting values reflected in the mental health legislation, human rights principles, moral philosophy and psychiatric professional standards are discussed. In spite of the often substantial use of civil commitment in many countries, there are almost no scientifically sound studies addressing the outcome of coercive treatment. The paper establishes that the traditional arguments in favour of civil commitment, like lack of insight and competence as well as the effectiveness of civil commitment, are poorly founded. The paper concludes that there seems to be a general agreement that civil commitment of patients who are dangerous to themselves or others should be the responsibility of the mental health care system, while civil commitment for treatment purposes is more controversial and hard to justify.

  11. An examination of the role of perceived support and employee commitment in employee-customer encounters.

    PubMed

    Vandenberghe, Christian; Bentein, Kathleen; Michon, Richard; Chebat, Jean-Charles; Tremblay, Michel; Fils, Jean-François

    2007-07-01

    The authors examined the relationships between perceived organizational support, organizational commitment, commitment to customers, and service quality in a fast-food firm. The research design matched customer responses with individual employees' attitudes, making this study a true test of the service provider-customer encounter. On the basis of a sample of matched employee-customer data (N = 133), hierarchical linear modeling analyses revealed that perceived organizational support had both a unit-level and an employee-level effect on 1 dimension of service quality: helping behavior. Contrary to affective organizational commitment, affective commitment to customers enhanced service quality. The 2 sub-dimensions of continuance commitment to the organization--perceived high sacrifice and perceived lack of alternatives--exerted effects opposite in sign: The former fostered service quality, whereas the latter reduced it. The implications of these findings are discussed within the context of research on employee-customer encounters.

  12. Moderating effects of nurses' organizational support on the relationship between job satisfaction and organizational commitment.

    PubMed

    Chang, Ching-Sheng

    2015-06-01

    The aim was to investigate whether job satisfaction enhances organizational commitment among nursing personnel while exploring whether organizational support perception has a moderating effect on the relationship between their job satisfaction and organizational commitment. A cross-sectional survey was sent to 400 nurses; 386 valid questionnaires were collected, with a valid response rate of 96.5%. According to the research findings, nurses' job satisfaction has a positive and significant influence on organizational commitment. Results also indicated that the moderating effect of nurses' organizational support perception on the relationship between their job satisfaction and organizational commitment was stronger for high organizational support perception than it was for low organizational support perception. This study suggests that organizational support perception will develop a sense of belonging, and this will help improve nurses' job satisfaction and organizational commitment. This kind of relationship is rarely discussed in the research literature, and it can be applied for human resources management of nursing staff.

  13. Commitment, Careers, and Retention in Organizations.

    DTIC Science & Technology

    1980-11-01

    validation of a measure of employee commitment to organizations. This instrument has been used to carry out several studies relating to both the antecedents...validating a measure of employee commitment to work organizations. The instrument, developed by Porter and his colleagues, is called the Organizational...34 Employee Commitment and Organizational Effectiveness." Invited speaker, University of Washington, November 1978. Steers, R. M. "Facilitating

  14. Factors Affecting Organizational Commitment in Navy Corpsmen.

    PubMed

    Booth-Kewley, Stephanie; Dell'Acqua, Renée G; Thomsen, Cynthia J

    2017-07-01

    Organizational commitment is a psychological state that has a strong impact on the likelihood that employees will remain with an organization. Among military personnel, organizational commitment is predictive of a number of important outcomes, including reenlistment intentions, job performance, morale, and perceived readiness. Because of the unique challenges and experiences associated with military service, it may be that organizational commitment is even more critical in the military than in civilian populations. Despite the essential role that they play in protecting the health of other service members, little is known about the factors that influence Navy Corpsmen's organizational commitment. This study investigated demographic and psychosocial factors that may be associated with organizational commitment among Corpsmen. Surveys of organizational commitment and possible demographic and psychosocial correlates of organizational commitment were completed by 1,597 male, active duty Navy Corpsmen attending Field Medical Training Battalion-West, Camp Pendleton, California. Bivariate correlations and hierarchical multiple regression analyses were used to determine significant predictors of organizational commitment. Of the 12 demographic and psychosocial factors examined, 6 factors emerged as significant predictors of organizational commitment in the final model: preservice motivation to be a Corpsman, positive perceptions of Corpsman training, confidence regarding promotions, occupational self-efficacy, social support for a Corpsman career, and lower depression. Importantly, a number of the factors that emerged as significant correlates of organizational commitment in this study are potentially modifiable. These factors include confidence regarding promotions, positive perceptions of Corpsman training, and occupational self-efficacy. It is recommended that military leaders and policy-makers take concrete steps to address these factors, thereby strengthening

  15. Tissue Doppler imaging in cardiac sarcoidosis.

    PubMed

    Smedema, J P

    2008-07-01

    A middle-aged African lady, who presented with ventricular tachycardias, mitral valve regurgitation and congestive heart failure, was diagnosed with cardiac sarcoidosis. Tissue Doppler imaging demonstrated abnormalities suggestive of myocardial scar, which was confirmed by contrast-enhanced cardiac magnetic resonance.

  16. Commitment, pro-relationship behavior, and trust in close relationships.

    PubMed

    Wieselquist, J; Rusbult, C E; Foster, C A; Agnew, C R

    1999-11-01

    The present work advances and tests an interdependence-based model of the associations among commitment, pro-relationship behavior, and trust. Findings from two longitudinal studies revealed good support for model predictions. Commitment-inspired acts such as accommodation and willingness to sacrifice provide diagnostic information regarding a partner's pro-relationship motives. Individuals come to trust their partners when they perceive that their partners have enacted pro-relationship behaviors, departing from their direct self-interest for the good of the relationship. The results of mediation analyses are consistent with a model of mutual cyclical growth in which (a) dependence promotes strong commitment, (b) commitment promotes pro-relationship acts, (c) pro-relationship acts are perceived by the partner, (d) the perception of pro-relationship acts enhances the partner's trust, and (e) trust increases the partner's willingness to become dependent on the relationship. Auxiliary analyses revealed that self-reported attachment style does not account for substantial variance beyond the features of interdependence that form the basis for the present model.

  17. Cardiac emergencies.

    PubMed

    Barata, Isabel Araujo

    2013-08-01

    The diagnosis and management of pediatric cardiac emergencies can be challenging and complicated. Early presentations are usually the result of ductal-dependent lesions and appear with cyanosis and shock. Later presentations are the result of volume overload or pump failure and present with signs of congestive heart failure. Acquired diseases also present as congestive heart failure or arrhythmias. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Cardiac lipoma

    PubMed Central

    Ismail, Imtiaz; Al-Khafaji, Khalid; Mutyala, Monica; Aggarwal, Saurabh; Cotter, William; Hakim, Hosam; Khosla, Sandeep; Arora, Rohit

    2015-01-01

    Lipomas of the heart are encapsulated tumors that are composed primarily of mature fat cells. Cardiac lipomas can originate either from subendocardium (approximately 50%), subpericardium (25%), or from the myocardium (25%) and may be located more frequently in left ventricle or right atrium. We report a 74-year-old female who presented with dyspnea on exertion and was found to have 5×5 cm mass occupying most of the right atrium on a transesophageal echocardiogram. PMID:26486106

  19. Cardiac Surgery

    PubMed Central

    Weisse, Allen B.

    2011-01-01

    Well into the first decades of the 20th century, medical opinion held that any surgical attempts to treat heart disease were not only misguided, but unethical. Despite such reservations, innovative surgeons showed that heart wounds could be successfully repaired. Then, extracardiac procedures were performed to correct patent ductus arteriosus, coarctation of the aorta, and tetralogy of Fallot. Direct surgery on the heart was accomplished with closed commissurotomy for mitral stenosis. The introduction of the heart-lung machine and cardiopulmonary bypass enabled the surgical treatment of other congenital and acquired heart diseases. Advances in aortic surgery paralleled these successes. The development of coronary artery bypass grafting greatly aided the treatment of coronary heart disease. Cardiac transplantation, attempts to use the total artificial heart, and the application of ventricular assist devices have brought us to the present day. Although progress in the field of cardiovascular surgery appears to have slowed when compared with the halcyon times of the past, substantial challenges still face cardiac surgeons. It can only be hoped that sufficient resources and incentive can carry the triumphs of the 20th century into the 21st. This review covers past developments and future opportunities in cardiac surgery. PMID:22163121

  20. Cardiac optogenetics.

    PubMed

    Entcheva, Emilia

    2013-05-01

    Optogenetics is an emerging technology for optical interrogation and control of biological function with high specificity and high spatiotemporal resolution. Mammalian cells and tissues can be sensitized to respond to light by a relatively simple and well-tolerated genetic modification using microbial opsins (light-gated ion channels and pumps). These can achieve fast and specific excitatory or inhibitory response, offering distinct advantages over traditional pharmacological or electrical means of perturbation. Since the first demonstrations of utility in mammalian cells (neurons) in 2005, optogenetics has spurred immense research activity and has inspired numerous applications for dissection of neural circuitry and understanding of brain function in health and disease, applications ranging from in vitro to work in behaving animals. Only recently (since 2010), the field has extended to cardiac applications with less than a dozen publications to date. In consideration of the early phase of work on cardiac optogenetics and the impact of the technique in understanding another excitable tissue, the brain, this review is largely a perspective of possibilities in the heart. It covers the basic principles of operation of light-sensitive ion channels and pumps, the available tools and ongoing efforts in optimizing them, overview of neuroscience use, as well as cardiac-specific questions of implementation and ideas for best use of this emerging technology in the heart.

  1. Cardiac optogenetics

    PubMed Central

    2013-01-01

    Optogenetics is an emerging technology for optical interrogation and control of biological function with high specificity and high spatiotemporal resolution. Mammalian cells and tissues can be sensitized to respond to light by a relatively simple and well-tolerated genetic modification using microbial opsins (light-gated ion channels and pumps). These can achieve fast and specific excitatory or inhibitory response, offering distinct advantages over traditional pharmacological or electrical means of perturbation. Since the first demonstrations of utility in mammalian cells (neurons) in 2005, optogenetics has spurred immense research activity and has inspired numerous applications for dissection of neural circuitry and understanding of brain function in health and disease, applications ranging from in vitro to work in behaving animals. Only recently (since 2010), the field has extended to cardiac applications with less than a dozen publications to date. In consideration of the early phase of work on cardiac optogenetics and the impact of the technique in understanding another excitable tissue, the brain, this review is largely a perspective of possibilities in the heart. It covers the basic principles of operation of light-sensitive ion channels and pumps, the available tools and ongoing efforts in optimizing them, overview of neuroscience use, as well as cardiac-specific questions of implementation and ideas for best use of this emerging technology in the heart. PMID:23457014

  2. Revealing ontological commitments by magic.

    PubMed

    Griffiths, Thomas L

    2015-03-01

    Considering the appeal of different magical transformations exposes some systematic asymmetries. For example, it is more interesting to transform a vase into a rose than a rose into a vase. An experiment in which people judged how interesting they found different magic tricks showed that these asymmetries reflect the direction a transformation moves in an ontological hierarchy: transformations in the direction of animacy and intelligence are favored over the opposite. A second and third experiment demonstrated that judgments of the plausibility of machines that perform the same transformations do not show the same asymmetries, but judgments of the interestingness of such machines do. A formal argument relates this sense of interestingness to evidence for an alternative to our current physical theory, with magic tricks being a particularly pure source of such evidence. These results suggest that people's intuitions about magic tricks can reveal the ontological commitments that underlie human cognition.

  3. When a patient commits suicide.

    PubMed

    Marshall, K A

    1980-01-01

    Suicide is a tragic and upsetting event which sometimes occurs when a person is in some form of therapy. This paper advocates a process after a patient commits suicide which allows for a thorough and orderly working through of the event by involved treatment personnel. The primary focus of this process is neither identification of responsibility nor of cause. The primary goals are to air issues and attitudes, identify factors contributing to the suicide, and most particularly to allow for the thorough expression of residual feelings and issues by the treatment personnel affected. Therapists who utilized this process were able to deal satisfactorily with grief and guilt issues after experiencing patient suicides. A case example illustrates the use of this process.

  4. Combination Treatment With Antihypertensive Agents Enhances the Effect of Qiliqiangxin on Chronic Pressure Overload-induced Cardiac Hypertrophy and Remodeling in Male Mice.

    PubMed

    Ye, Yong; Gong, Hui; Wang, Xingxu; Wu, Jian; Wang, Shijun; Yuan, Jie; Yin, Peipei; Jiang, Guoliang; Li, Yang; Ding, Zhiwen; Zhang, Weijing; Zhou, Jingmin; Ge, Junbo; Zou, Yunzeng

    2015-06-01

    We previously showed that Qiliqiangxin (QL) capsules could ameliorate cardiac hypertrophy and remodeling in a mouse model of pressure overload. Here, we compared the effects of QL alone with those of QL combined with the following 3 types of antihypertensive drugs on cardiac remodeling and dysfunction induced by pressure overload for 4 weeks in mice: an angiotensin II type 1 receptor (AT1-R) blocker (ARB), an angiotensin-converting enzyme inhibitor (ACEI), and a β-adrenergic receptor (β-AR) blocker (BB). Adult male mice (C57B/L6) were subjected to either transverse aortic constriction or sham operation for 4 weeks, and the drugs (or saline) were orally administered through gastric tubes. Cardiac function and remodeling were evaluated through echocardiography, catheterization, histology, and analysis of hypertrophic gene expression. Cardiomyocyte apoptosis and autophagy, AT1-R and β1-AR expression, and cell proliferation-related molecules were also examined. Although pressure overload-induced cardiac remodeling and dysfunction, hypertrophic gene reprogramming, AT1-R and β1-AR expression, and ERK phosphorylation were significantly attenuated by QL alone, QL + ARB, QL + ACEI, and QL + BB, the attenuation was stronger in the combination treatment groups. Moreover, apoptosis was reduced to a larger extent by each combination treatment than by QL alone, whereas autophagy was more strongly attenuated by either QL + ARB or QL + ACEI. None of the treatments significantly upregulated ErbB2 or ErbB4 phosphorylation, and none significantly downregulated C/EBPβ expression. Therefore, the effects of QL on chronic pressure overload-induced cardiac remodeling may be significantly increased when QL is combined with an ARB, an ACEI, or a BB.

  5. Overexpression of ryanodine receptor type 1 enhances mitochondrial fragmentation and Ca2+-induced ATP production in cardiac H9c2 myoblasts.

    PubMed

    O-Uchi, Jin; Jhun, Bong Sook; Hurst, Stephen; Bisetto, Sara; Gross, Polina; Chen, Ming; Kettlewell, Sarah; Park, Jongsun; Oyamada, Hideto; Smith, Godfrey L; Murayama, Takashi; Sheu, Shey-Shing

    2013-12-01

    Ca(+) influx to mitochondria is an important trigger for both mitochondrial dynamics and ATP generation in various cell types, including cardiac cells. Mitochondrial Ca(2+) influx is mainly mediated by the mitochondrial Ca(2+) uniporter (MCU). Growing evidence also indicates that mitochondrial Ca(2+) influx mechanisms are regulated not solely by MCU but also by multiple channels/transporters. We have previously reported that skeletal muscle-type ryanodine receptor (RyR) type 1 (RyR1), which expressed at the mitochondrial inner membrane, serves as an additional Ca(2+) uptake pathway in cardiomyocytes. However, it is still unclear which mitochondrial Ca(2+) influx mechanism is the dominant regulator of mitochondrial morphology/dynamics and energetics in cardiomyocytes. To investigate the role of mitochondrial RyR1 in the regulation of mitochondrial morphology/function in cardiac cells, RyR1 was transiently or stably overexpressed in cardiac H9c2 myoblasts. We found that overexpressed RyR1 was partially localized in mitochondria as observed using both immunoblots of mitochondrial fractionation and confocal microscopy, whereas RyR2, the main RyR isoform in the cardiac sarcoplasmic reticulum, did not show any expression at mitochondria. Interestingly, overexpression of RyR1 but not MCU or RyR2 resulted in mitochondrial fragmentation. These fragmented mitochondria showed bigger and sustained mitochondrial Ca(2+) transients compared with basal tubular mitochondria. In addition, RyR1-overexpressing cells had a higher mitochondrial ATP concentration under basal conditions and showed more ATP production in response to cytosolic Ca(2+) elevation compared with nontransfected cells as observed by a matrix-targeted ATP biosensor. These results indicate that RyR1 possesses a mitochondrial targeting/retention signal and modulates mitochondrial morphology and Ca(2+)-induced ATP production in cardiac H9c2 myoblasts.

  6. Is nurse managers' leadership style related to Japanese staff nurses' affective commitment to their hospital?

    PubMed

    Kodama, Yoshimi; Fukahori, Hiroki; Sato, Kana; Nishida, Tomoko

    2016-10-01

    To determine if nurse managers' leadership style is related to Japanese staff nurses' affective commitment to their hospital. In Western countries, nurse managers' transformational leadership style has been found to increase staff nurses' affective commitment to their hospital. However, there are few studies examining this relationship in the context of acute care hospitals in Japan. Staff nurses completed measures of their nurse managers' perceived leadership style and factors related to their own affective commitment. The association between affective commitment and perception of leadership style was assessed with multiple logistic regression. Of 736 questionnaires distributed, 579 (78.9%) were returned, and data from 396 (53.8%) fully completed questionnaires were analysed. The intellectual stimulation aspect of transformational leadership positively increased staff nurses' affective commitment (odds ratio: 2.23). Nurse managers' transactional and laissez-faire leadership styles were not related to affective commitment among staff nurses. The intellectual stimulation aspect of transformational leadership may increase the retention of staff nurses through enhanced affective commitment. To increase staff nurses' affective commitment to their hospital, we suggest that hospital administrators equip nurse managers with intellectual stimulation skills. © 2016 John Wiley & Sons Ltd.

  7. Project on Elite Athlete Commitment (PEAK): IV. identification of new candidate commitment sources in the sport commitment model.

    PubMed

    Scanlan, Tara K; Russell, David G; Scanlan, Larry A; Klunchoo, Tatiana J; Chow, Graig M

    2013-10-01

    Following a thorough review of the current updated Sport Commitment Model, new candidate commitment sources for possible future inclusion in the model are presented. They were derived from data obtained using the Scanlan Collaborative Interview Method. Three elite New Zealand teams participated: amateur All Black rugby players, amateur Silver Fern netball players, and professional All Black rugby players. An inductive content analysis of these players' open-ended descriptions of their sources of commitment identified four unique new candidate commitment sources: Desire to Excel, Team Tradition, Elite Team Membership, and Worthy of Team Membership. A detailed definition of each candidate source is included along with example quotes from participants. Using a mixed-methods approach, these candidate sources provide a basis for future investigations to test their viability and generalizability for possible expansion of the Sport Commitment Model.

  8. Employee organizational commitment and hospital performance.

    PubMed

    Baird, Kevin M; Tung, Amy; Yu, Yanjie

    2017-09-15

    There is widespread evidence of the purported benefits of employee organizational commitment (EOC) and its impact on both individual and organizational performance. This study contributes to this literature by providing a unique insight into this relationship, focusing on the interrelationship between EOC with hospital performance and the role of the provision of adequate facilities in eliciting EOC. The aim of this study was to introduce and empirically examine a new theoretical model in which it is argued that the performance of hospitals with regard to the provision of adequate facilities (medical facilities, support facilities, and staff resources) influences the level of EOC, which in turn influences hospital performance with regard to patient care and operational effectiveness. To examine the interrelationships between the provision of adequate facilities, EOC, and hospital performance, the study utilizes a survey of hospital managers. The findings support the theoretical model, with the provision of support facilities and staff resources positively indirectly associated with both patient care and operational effectiveness through their impact on EOC. The findings highlight the importance of providing adequate facilities and EOC within hospitals and suggest that CEOs and general managers should try to enhance the provision of such resources in an attempt to elicit EOC within their hospitals. The findings suggest that managers should try to enhance their provision of adequate facilities in order to elicit EOC and enhance hospital performance. With regard to medical facilities, they should consider and incorporate the latest technology and up-to-date equipment. They should also provide adequate staff resources, including appropriate numbers of beds, nurses, and doctors, to prevent "fatigue" (West, 2001, p. 41) and provide adequate support facilities.

  9. More Than Tiny Sacks: Stem Cell Exosomes as Cell-Free Modality for Cardiac Repair.

    PubMed

    Kishore, Raj; Khan, Mohsin

    2016-01-22

    Stem cell therapy provides immense hope for regenerating the pathological heart, yet has been marred by issues surrounding the effectiveness, unclear mechanisms, and survival of the donated cell population in the ischemic myocardial milieu. Poor survival and engraftment coupled to inadequate cardiac commitment of the adoptively transferred stem cells compromises the improvement in cardiac function. Various alternative approaches to enhance the efficacy of stem cell therapies and to overcome issues with cell therapy have been used with varied success. Cell-free components, such as exosomes enriched in proteins, messenger RNAs, and miRs characteristic of parental stem cells, represent a potential approach for treating cardiovascular diseases. Recently, exosomes from different kinds of stem cells have been effectively used to promote cardiac function in the pathological heart. The aim of this review is to summarize current research efforts on stem cell exosomes, including their potential benefits and limitations to develop a potentially viable therapy for cardiovascular problems. © 2016 American Heart Association, Inc.

  10. Evaluation of Known or Suspected Cardiac Sarcoidosis.

    PubMed

    Blankstein, Ron; Waller, Alfonso H

    2016-03-01

    Sarcoidosis is a multisystem disorder of unknown cause, and cardiac sarcoidosis affects at least 25% of patients and accounts for substantial mortality and morbidity from this disease. Cardiac sarcoidosis may present with heart failure, left ventricular systolic dysfunction, AV block, atrial or ventricular arrhythmias, and sudden cardiac death. Cardiac involvement can be challenging to detect and diagnose because of the focal nature of the disease, as well as the fact that clinical criteria have limited diagnostic accuracy. Nevertheless, the diagnosis of cardiac sarcoidosis can be enhanced by integrating both clinical and imaging findings. This article reviews the various roles that different imaging modalities provide in the evaluation and management of patients with known or suspected cardiac sarcoidosis. © 2016 American Heart Association, Inc.

  11. Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells.

    PubMed

    Freire-Pritchett, Paula; Schoenfelder, Stefan; Várnai, Csilla; Wingett, Steven W; Cairns, Jonathan; Collier, Amanda J; García-Vílchez, Raquel; Furlan-Magaril, Mayra; Osborne, Cameron S; Fraser, Peter; Rugg-Gunn, Peter J; Spivakov, Mikhail

    2017-03-23

    Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells.

  12. Patterns of CMR measured longitudinal strain and its association with late gadolinium enhancement in patients with cardiac amyloidosis and its mimics.

    PubMed

    Williams, Lynne K; Forero, Julian F; Popovic, Zoran B; Phelan, Dermot; Delgado, Diego; Rakowski, Harry; Wintersperger, Bernd J; Thavendiranathan, Paaladinesh

    2017-08-07

    Regional variability of longitudinal strain (LS) has been previously described with echocardiography in patients with cardiac amyloidosis (CA), however, the reason for this variability is not completely evident. We sought to describe regional patterns in LS using feature-tracking software applied to cardiovascular magnetic resonance (CMR) cine images in patients with CA, hypertrophic cardiomyopathy (HCM), and Anderson-Fabry's disease (AFD) and to relate these patterns to the distribution of late gadolinium enhancement (LGE). Patients with CA (n = 45) were compared to LV mass indexed matched patients with HCM (n = 19) and AFD (n = 19). Peak systolic LS measurements were obtained using Velocity Vector Imaging (VVI) software on CMR cine images. A relative regional LS ratio (RRSR) was calculated as the ratio of the average of the apical segmental LS divided by the sum of the average basal and mid-ventricular segmental LS. LGE was quantified for the basal, mid, and apical segments using a threshold of 5SD above remote myocardium. A regional LGE ratio was calculated similar to RRSR. Patients with CA had significantly had worse global LS (-15.7 ± 4.6%) than those with HCM (-18.0 ± 4.6%, p = 0.046) and AFD (-21.9 ± 5.1%, p < 0.001). The RRSR was higher in patients with CA (1.00 ± 0.31) than in AFD (0.79 ± 0.24; p = 0.018) but not HCM (0.84 ± 0.32; p = 0.114). In CA, a regional difference in LGE burden was noted, with lower LGE in the apex (31.5 ± 19.1%) compared to the mid (38.2 ± 19.0%) and basal (53.7 ± 22.7%; p < 0.001 for both) segments. The regional LGE ratio was not significantly different between patients with CA (0.33 ± 0.15) and AFD (0.47 ± 0.58; p = 0.14) but lower compared to those with HCM (0.72 ± 0.43; p < 0.0001). LGE percentage showed a significant impact on LS (p < 0.0001), with a 0.9% decrease in absolute LS for every 10% increase in LGE percentage. The presence of marked "relative apical sparing

  13. Identity Style, Parental Authority, and Identity Commitment.

    ERIC Educational Resources Information Center

    Berzonsky, Michael D.

    2004-01-01

    The role that parental authority patterns and social-cognitive identity styles may play in establishing identity commitments was investigated. The results indicated that family authority and identity style variables combined accounted for 50% of the variation in strength of identity commitment. As hypothesized, the relationship between parental…

  14. Education on the Internet: Anonymity vs. Commitment.

    ERIC Educational Resources Information Center

    Dreyfus, Hubert L.

    1998-01-01

    Argues that learning a skill requires the kind of commitment which is undermined by the Press (the Public) and the Internet, citing Soren Kierkegaard's "The Present Age", and states that learning by apprenticeship is impossible in cyberspace. Includes: aesthetic sphere--commitment to the enjoyment of sheer information; ethical…

  15. Analyzing Teaching Commitment: Theoretical and Empirical Dimensions.

    ERIC Educational Resources Information Center

    Tyree, Alexander K., Jr.

    Classical commitment studies are either sociologically oriented or based in the psychological empirical research tradition. A review of the literature reveals agreement on the multidimensionality and the contextual complexity of commitment, two principles which guide the hypotheses of the present study. This study uses the Administrator and…

  16. Predictors of Commitment to Athletic Training Education

    ERIC Educational Resources Information Center

    Weiss, Windee M.; Neibert, Peter J.

    2013-01-01

    Context: In order for athletic training students to be successful in any athletic training education program (ATEP), a certain level of commitment to the program and profession is required. Objective: The purpose of this study was to explore the applicability of the sport commitment model (SCM) to an ATEP by applying the SCM in an academic setting…

  17. Sexually Violent Predators and Civil Commitment Laws

    ERIC Educational Resources Information Center

    Beyer Kendall, Wanda D.; Cheung, Monit

    2004-01-01

    This article analyzes the civil commitment models for treating sexually violent predators (SVPs) and analyzes recent civil commitment laws. SVPs are commonly defined as sex offenders who are particularly predatory and repetitive in their sexually violent behavior. Data from policy literature, a survey to all states, and a review of law review…

  18. Predicting the Social Commitments of College Students.

    ERIC Educational Resources Information Center

    Lavelle, Ellen; O'Ryan, Leslie W.

    2001-01-01

    Investigates the nature of social beliefs and commitments during the college years in relation to developmental orientations as measured by the Dakota Inventory of Student Orientations. Results support Creative-Reflective scale scores as predictive of commitment to the more humanitarian issues such as race and women's rights, whereas…

  19. The Social Construction of Marital Commitment

    ERIC Educational Resources Information Center

    Byrd, Stephanie Ellen

    2009-01-01

    This paper articulates a theoretical framework for understanding how individuals orient themselves toward marital commitment. Using a life history interview methodology and interpretive framework, it examines the orientations toward marital commitment for a sample of women and men, single and married, between the ages of 28 and 35 (N = 75).…

  20. Education on the Internet: Anonymity vs. Commitment.

    ERIC Educational Resources Information Center

    Dreyfus, Hubert L.

    1998-01-01

    Argues that learning a skill requires the kind of commitment which is undermined by the Press (the Public) and the Internet, citing Soren Kierkegaard's "The Present Age", and states that learning by apprenticeship is impossible in cyberspace. Includes: aesthetic sphere--commitment to the enjoyment of sheer information; ethical…

  1. Juvenile Court Commitment Rates: The National Picture.

    ERIC Educational Resources Information Center

    Sosin, Michael

    There is less geographic variation in the commitment rate of juvenile offenders than is commonly assumed. Apparently, judges across the country develop a similar standard of what percentage of youths they face should be committed. This standard may be similar across the country because it represents broadly shared ideals. However, there is much…

  2. 24 CFR 200.47 - Firm commitments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Requirements for Application, Commitment, and Endorsement... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Firm commitments. 200.47 Section 200.47 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued...

  3. 24 CFR 200.46 - Commitment issuance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... DEVELOPMENT GENERAL INTRODUCTION TO FHA PROGRAMS Requirements for Application, Commitment, and Endorsement... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Commitment issuance. 200.46 Section 200.46 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued...

  4. Psychology & employee commitment. Promoting physician loyalty.

    PubMed

    Lakin, J D

    1998-01-01

    Physician and staff loyalty has become more important and more difficult to maintain. Group managers should realize that not all forms of commitment are equal and should actively work to build commitment to the organization, not just to the practice of medicine.

  5. Overview of the Core Commitments Initiative

    ERIC Educational Resources Information Center

    McTighe Musil, Caryn

    2013-01-01

    This chapter provides an overview of the Core Commitments Initiative conducted by the Association of American Colleges and Universities (AAC&U). Core Commitments was intended to reinvigorate the conversation about personal and social responsibility within higher education, and served as the impetus for this "New Directions" volume.

  6. Making Commitments to Racial Justice Actionable

    ERIC Educational Resources Information Center

    Diab, Rasha; Ferrel, Thomas; Godbee, Beth; Simpkins, Neil

    2013-01-01

    In this article, we articulate a framework for making our commitments to racial justice actionable, a framework that moves from narrating confessional accounts to articulating our commitments and then acting on them through both self-work and work-with-others, a dialectic possibility we identify and explore. We model a method for moving beyond…

  7. Overview of the Core Commitments Initiative

    ERIC Educational Resources Information Center

    McTighe Musil, Caryn

    2013-01-01

    This chapter provides an overview of the Core Commitments Initiative conducted by the Association of American Colleges and Universities (AAC&U). Core Commitments was intended to reinvigorate the conversation about personal and social responsibility within higher education, and served as the impetus for this "New Directions" volume.

  8. Involuntary Outpatient Commitment of the Mentally Ill.

    ERIC Educational Resources Information Center

    Wilk, Ruta J.

    1988-01-01

    Examines the issue of involuntary outpatient commitment, and its implications for social workers working in the health system. Describes a nationwide movement to establish a new system of involuntary outpatient commitment to address the failure of deinstitutionalization, mandating mental health treatment in the community for persons ineligible for…

  9. Commitment: A Behavioral Approach to Job Involvement

    ERIC Educational Resources Information Center

    Wiener, Yoash; Gechman, Arthur S.

    1977-01-01

    Work commitment behaviors were defined as a special class of socially acceptable work behaviors exceeding formal and/or normative expectations relevant to work. For a sample of 54 female elementary school teachers, work commitment measures demonstrated moderate correlations with two attitudinal measures of job involvement and a job satisfaction…

  10. Predictors of Commitment to Athletic Training Education

    ERIC Educational Resources Information Center

    Weiss, Windee M.; Neibert, Peter J.

    2013-01-01

    Context: In order for athletic training students to be successful in any athletic training education program (ATEP), a certain level of commitment to the program and profession is required. Objective: The purpose of this study was to explore the applicability of the sport commitment model (SCM) to an ATEP by applying the SCM in an academic setting…

  11. The way to a man's heart is through his stomach: much 'diaphragmatic' attenuation is likely gastric, and effervescent granules enhance cardiac imaging.

    PubMed

    Munn, Samson

    2004-12-01

    Avoidance of falsely positive results depends on distinguishing reality from artifact, in turn depending on images of highest quality. In radionuclide cardiac imaging, an inferior wall artifactual defect, so called "diaphragmatic attenuation", is particularly common and vexing. Despite the historically held view, analysis and review of the literature suggest the defect is likely not diaphragmatic but rather primarily due to attenuation by nearby stomach wall. The explanation is based on gravity and anatomy. With this improved understanding, effervescent granules were given as a clinical, nonresearch measure to nine patients during myocardial scanning. It was observed that two-thirds demonstrated moderate or marked lessening of attenuation. An additional benefit is lessening of artifact by extracardiac activity. These benefits may also apply to other sorts of cardiac radionuclide imaging. The significance of this new imaging method is discussed and various avenues of research are proposed.

  12. Biomechanics of Cardiac Function

    PubMed Central

    Voorhees, Andrew P.; Han, Hai-Chao

    2015-01-01

    The heart pumps blood to maintain circulation and ensure the delivery of oxygenated blood to all the organs of the body. Mechanics play a critical role in governing and regulating heart function under both normal and pathological conditions. Biological processes and mechanical stress are coupled together in regulating myocyte function and extracellular matrix structure thus controlling heart function. Here we offer a brief introduction to the biomechanics of left ventricular function and then summarize recent progress in the study of the effects of mechanical stress on ventricular wall remodeling and cardiac function as well as the effects of wall mechanical properties on cardiac function in normal and dysfunctional hearts. Various mechanical models to determine wall stress and cardiac function in normal and diseased hearts with both systolic and diastolic dysfunction are discussed. The results of these studies have enhanced our understanding of the biomechanical mechanism in the development and remodeling of normal and dysfunctional hearts. Biomechanics provide a tool to understand the mechanism of left ventricular remodeling in diastolic and systolic dysfunction and guidance in designing and developing new treatments. PMID:26426462

  13. Nursing Assistants' Job Commitment: Effect of Nursing Home Organizational Factors and Impact on Resident Well-Being

    ERIC Educational Resources Information Center

    Bishop, Christine E.; Weinberg, Dana Beth; Leutz, Walter; Dossa, Almas; Pfefferle, Susan G.; Zincavage, Rebekah M.

    2008-01-01

    Purpose: The purpose of this study was to investigate (a) whether certified nursing assistants (CNAs) are more committed to nursing home jobs when they perceive their jobs as enhanced (greater autonomy, use of knowledge, teamwork), and (b) whether CNA job commitment affects resident satisfaction. Design and Methods: A qualitative exploration of…

  14. Nursing Assistants' Job Commitment: Effect of Nursing Home Organizational Factors and Impact on Resident Well-Being

    ERIC Educational Resources Information Center

    Bishop, Christine E.; Weinberg, Dana Beth; Leutz, Walter; Dossa, Almas; Pfefferle, Susan G.; Zincavage, Rebekah M.

    2008-01-01

    Purpose: The purpose of this study was to investigate (a) whether certified nursing assistants (CNAs) are more committed to nursing home jobs when they perceive their jobs as enhanced (greater autonomy, use of knowledge, teamwork), and (b) whether CNA job commitment affects resident satisfaction. Design and Methods: A qualitative exploration of…

  15. Lack of Inducible NO Synthase Reduces Oxidative Stress and Enhances Cardiac Response to Isoproterenol in Mice With Deoxycorticosterone Acetate–Salt Hypertension

    PubMed Central

    Sun, Ying; Carretero, Oscar A.; Xu, Jiang; Rhaleb, Nour-Eddine; Wang, Fangfei; Lin, Chunxia; Yang, James J.; Pagano, Patrick J.; Yang, Xiao-Ping

    2015-01-01

    Although NO derived from endothelial NO synthase (eNOS) is thought to be cardioprotective, the role of inducible NO synthase (iNOS) remains controversial. Using mice lacking iNOS (iNOS−/−), we studied (1) whether development of hypertension, cardiac hypertrophy, and dysfunction after deoxycorticosterone acetate (DOCA)–salt would be less severe compared with wild-type controls (WT; C57BL/6J), and (2) whether the cardioprotection attributable to lack of iNOS is mediated by reduced oxidative stress. Mice were uninephrectomized and received either DOCA-salt (30 mg/mouse SC and 1% NaCl+0.2% KCl in drinking water) or vehicle (tap water) for 12 weeks. Systolic blood pressure (SBP) was measured weekly. Left ventricular (LV) ejection fraction (EF) by echocardiography and cardiac response to isoproterenol (50 ng/mouse IV) were studied at the end of the experiment. Expression of eNOS and iNOS as well as the oxidative stress markers 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation) and nitrotyrosine (a marker for peroxynitrite) were determined by Western blot and immunohistochemical staining, respectively. DOCA-salt increased SBP and LV weight similarly in both strains and decreased EF in WT but not in iNOS−/−. Cardiac contractile and relaxation responses to isoproterenol were greater, 4-HNE and nitrotyrosine levels were lower, and eNOS expression tended to be higher in iNOS−/−. We conclude that lack of iNOS leads to better preservation of cardiac function, which may be mediated by reduced oxidative stress and increased eNOS; however, it does not seem to play a significant role in preventing DOCA-salt–induced hypertension and hypertrophy. PMID:16286571

  16. About Cardiac Arrest

    MedlinePlus

    ... Thromboembolism Aortic Aneurysm More About Cardiac Arrest Updated:Mar 10,2017 What is cardiac arrest? Cardiac arrest is the abrupt loss of heart function in a person who may or may not have diagnosed heart ...

  17. Fibrillar Type I Collagen Enhances the Differentiation and Proliferation of Myofibroblasts by Lowering α2β1 Integrin Expression in Cardiac Fibrosis

    PubMed Central

    Hong, Jian; Chu, Ming; Qian, Lijun; Wang, Junhong; Guo, Yan

    2017-01-01

    Many studies have shown that α2β1 integrin plays an important role in the development of cardiac fibrosis. However, the mechanism of how α2β1 integrin regulates the differentiation and proliferation of myofibroblasts in cardiac fibrosis through fibrillar collagen (FC) remains uncertain. We established that FC mimicked the 3-dimensional extracellular matrix (ECM) of fibroblasts from post-myocardial infarction (MI) patients in vivo. This allowed us to explore the differentiation and proliferation of cardiac fibroblasts on FC. Here, we report that low expression of α2β1 integrin increased protein kinase B (AKT) activation and α-smooth muscle actin (α-SMA) expression. This occurred due to the instability of phosphatase and tensin homolog (PTEN) in myofibroblasts on FC. We also demonstrated that FC reduced protein phosphatase type 2A (PP2A) activity of myofibroblasts, which was coincident with low α2β1 integrin expression and activation of AKT, but not mitogen-activated protein kinase (ERK). In addition, knock-down of both β1 integrin and PP2A in fibroblasts promoted differentiation and proliferation via AKT activation and increased α-SMA expression. In summary, our study demonstrated that low α2β1 integrin expression regulated its downstream targets PTEN and AKT via crosstalk with PP2A, a critical cell signaling pathway that permits aberrant differentiation and proliferation of myofibroblasts on FC. PMID:28251149

  18. Enhanced Cardiac Differentiation of Human Cardiovascular Disease Patient-Specific Induced Pluripotent Stem Cells by Applying Unidirectional Electrical Pulses Using Aligned Electroactive Nanofibrous Scaffolds.

    PubMed

    Mohammadi Amirabad, Leila; Massumi, Mohammad; Shamsara, Mehdi; Shabani, Iman; Amari, Afshin; Mossahebi Mohammadi, Majid; Hosseinzadeh, Simzar; Vakilian, Saeid; Steinbach, Sarah K; Khorramizadeh, Mohammad R; Soleimani, Masoud; Barzin, Jalal

    2017-03-01

    In the embryonic heart, electrical impulses propagate in a unidirectional manner from the sinus venosus and appear to be involved in cardiogenesis. In this work, aligned and random polyaniline/polyetersulfone (PANI/PES) nanofibrous scaffolds doped by Camphor-10-sulfonic acid (β) (CPSA) were fabricated via electrospinning and used to conduct electrical impulses in a unidirectional and multidirectional fashion, respectively. A bioreactor was subsequently engineered to apply electrical impulses to cells cultured on PANI/PES scaffolds. We established cardiovascular disease-specific induced pluripotent stem cells (CVD-iPSCs) from the fibroblasts of patients undergoing cardiothoracic surgeries. The CVD-iPSCs were seeded onto the scaffolds, cultured in cardiomyocyte-inducing factors, and exposed to electrical impulses for 1 h/day, over a 15-day time period in the bioreactor. The application of the unidirectional electrical stimulation to the cells significantly increased the number of cardiac Troponin T (cTnT+) cells in comparison to multidirectional electrical stimulation using random fibrous scaffolds. This was confirmed by real-time polymerase chain reaction for cardiac-related transcription factors (NKX2.5, GATA4, and NPPA) and a cardiac-specific structural gene (TNNT2). Here we report for the first time that applying electrical pulses in a unidirectional manner mimicking the unidirectional wave of electrical stimulation in the heart, could increase the derivation of cardiomyocytes from CVD-iPSCs.

  19. [Infanticide committed by the mother].

    PubMed

    Marleau, J D; Roy, R; Laporte, L; Webanck, T; Poulin, B

    1995-04-01

    Using data gathered at the Institut Philippe Pinel in Montréal, we shall describe the sociodemographic and psychiatric profile of a sample of 17 women who have killed (n = 14) or attempted to kill (n = 3) one of their children. Our data indicate that women who have committed this type of offence generally come from a disadvantaged socioeconomic environment. Most have a psychiatric history (evaluation and/or hospitalization). Review of the offence demonstrates that most women do not use a weapon to kill their child; the preferred methods are strangulation or drowning. Most of these offences may be classified as extended suicide or altruistic acts. Several of the women present with a severe personality disorder and an additional depressive episode in the context of the offence. We hope our study will help clarify understanding of filicide and assist in the development of certain prevention axes. These results indicate that the population at large and various intervenors in our society (family physicians, psychiatrists, criminologists, social workers, pediatricians, psychologists, gynecologists) must become increasingly vigilant and avoid trivialization of signals such as verbalization of homicidal thoughts about the child or recourse to certain disorganized behaviours.

  20. Prosodic form and parsing commitments.

    PubMed

    Watt, S M; Murray, W S

    1996-03-01

    This paper examines the question of whether there are effects of prosody on the syntactic parsing of temporarily ambiguous sentences containing complement verbs. It reports the results of five experiments employing cross-modal response tasks where the visually presented target word was either an ¿appropriate' or an ¿inappropriate' continuation in terms of the prosodic form of the preceeding auditory sentence fragment. Two experiments employing cross-modal naming only showed indications of sensitivity to syntactic and appropriateness manipulations when coupled with a simultaneous appropriateness judgment task. In contrast, the experiments employing cross-modal lexical decision showed greater sensitivity to syntactic and appropriateness effects. However, while the results from these studies replicated our earlier auditory parsing results and provided support for the suggestion that there are differences in visual and auditory parsing processes and for a ¿constituent-based, ' ¿minimal commitment' type auditory parser, none of the studies demonstrated an effect of prosodic form on the parsing process.

  1. An Internet- and mobile-based tailored intervention to enhance maintenance of physical activity after cardiac rehabilitation: short-term results of a randomized controlled trial.

    PubMed

    Antypas, Konstantinos; Wangberg, Silje C

    2014-03-11

    An increase in physical activity for secondary prevention of cardiovascular disease and cardiac rehabilitation has multiple therapeutic benefits, including decreased mortality. Internet- and mobile-based interventions for physical activity have shown promising results in helping users increase or maintain their level of physical activity in general and specifically in secondary prevention of cardiovascular diseases and cardiac rehabilitation. One component related to the efficacy of these interventions is tailoring of the content to the individual. Our trial assessed the effect of a longitudinally tailored Internet- and mobile-based intervention for physical activity as an extension of a face-to-face cardiac rehabilitation stay. We hypothesized that users of the tailored intervention would maintain their physical activity level better than users of the nontailored version. The study population included adult participants of a cardiac rehabilitation program in Norway with home Internet access and a mobile phone. The participants were randomized in monthly clusters to a tailored or nontailored (control) intervention group. All participants had access to a website with information regarding cardiac rehabilitation, an online discussion forum, and an online activity calendar. Those using the tailored intervention received tailored content based on models of health behavior via the website and mobile fully automated text messages. The main outcome was self-reported level of physical activity, which was obtained using an online international physical activity questionnaire at baseline, at discharge, and at 1 month and 3 months after discharge from the cardiac rehabilitation program. Included in the study were 69 participants. One month after discharge, the tailored intervention group (n=10) had a higher median level of overall physical activity (median 2737.5, IQR 4200.2) than the control group (n=14, median 1650.0, IQR 2443.5), but the difference was not significant

  2. How Do Different Types of Community Commitment Influence Brand Commitment? The Mediation of Brand Attachment

    PubMed Central

    Zhang, Ning; Su, Chen-ting; Zhou, Nan

    2013-01-01

    Abstract Although previous research indicates that participation in a brand community may foster consumer loyalty to the brand in question, research has seldom examined the mediating effect of community commitment on brand commitment. Drawing from the typologies of organizational commitment, we divide community commitment into three components: continuance community commitment (continuance CC), affective community commitment (affective CC), and normative community commitment (normative CC). We then assess the mediating role of brand attachment in the relationship between these three components and brand commitment. We test the hypotheses using a sample of online mobile phone brand communities in China. The empirical results reveal that brand attachment exerts an indirect (but not mediated) effect on the relationship between continuance CC and brand commitment and on the relationship between normative CC and brand commitment. We also find that it exerts a partial mediating effect on the relationship between affective CC and brand commitment. The findings contribute to the branding literature and have important implications for brand community management. PMID:23768073

  3. The roles of want to commitment and have to commitment in explaining physical activity behavior.

    PubMed

    Gabriele, Jeanne M; Gill, Diane L; Adams, Claire E

    2011-03-01

    Several theories and models have been proposed to explain decisions in changing and adopting behavior but few address the intricacies of behavioral maintenance. The current study assesses the utility of the Investment Model, which identifies satisfaction, investments, and involvement alternatives as predictors of commitment and continued behavior, in predicting physical activity behavior. Participants (N = 267) completed questionnaires about physical activity and commitment. Structural equation modeling assessed relationships among 2 types of exercise commitment (want to or enthusiastic commitment, have to or obligatory commitment), 3 commitment determinants (satisfaction, investments, and alternatives), and physical activity (minutes of physical activity, stage of behavior change). Want to commitment, but not have to commitment, was related to stage of exercise behavior change and time spent in physical activity. Satisfaction and investments were positively related to want to commitment; whereas, satisfaction, investments, and alternatives were positively related to have to commitment. The model explained 68% and 23% of the variance in time spent in physical activity and stage of behavior change, respectively. This study provides support for the application of the Investment Model to physical activity and suggests that want to commitment may be important for explaining and predicting sustained physical activity behavior.

  4. The Impact of Trust on Organization Commitment

    NASA Technical Reports Server (NTRS)

    Robinson, Kimberly; Stinson, Thomas N. (Technical Monitor)

    2002-01-01

    As the global economy continues to spawn competitive forces, organizations have sought to become more competitive by cutting costs, eliminating non-value added work, and using more automation. Jobs have become broader and more flexible leading to a leaner workforce with higher-level knowledge and skills and more responsibility for day-to-day decisions. More than ever, organizations depend on employees as the innovators and designers of products and processes and as a source of strategic advantage. Therefore employee commitment among knowledge workers is needed to maintain organizational viability. It would seem that stronger relationships due to greater dependency, involvement, and investment would develop between employers and high-technology workers resulting in more committed employees. However, the opposite has been evidenced as key knowledge workers are changing jobs frequently. This may be due to a perceived lack of commitment by management to its employees. The notion of exchange may dominate the development of organizational commitment whereby an individual decides what to give a firm (commitment, extra effort, better performance, etc.) based on what the firm gives them (e.g., trust and security). It is the relationship between an employee's organizational commitment and the responding level of trust in the organization that is examined in this paper. An experiment is described that will seek to identify this relationship. Preliminary results are expected to show a positive relationship whereby employee commitment is positively correlated with organizational trust.

  5. The Impact of Trust on Organization Commitment

    NASA Technical Reports Server (NTRS)

    Robinson, Kimberly; Stinson, Thomas N. (Technical Monitor)

    2002-01-01

    As the global economy continues to spawn competitive forces, organizations have sought to become more competitive by cutting costs, eliminating non-value added work, and using more automation. Jobs have become broader and more flexible leading to a leaner workforce with higher-level knowledge and skills and more responsibility for day-to-day decisions. More than ever, organizations depend on employees as the innovators and designers of products and processes and as a source of strategic advantage. Therefore employee commitment among knowledge workers is needed to maintain organizational viability. It would seem that stronger relationships due to greater dependency, involvement, and investment would develop between employers and high-technology workers resulting in more committed employees. However, the opposite has been evidenced as key knowledge workers are changing jobs frequently. This may be due to a perceived lack of commitment by management to its employees. The notion of exchange may dominate the development of organizational commitment whereby an individual decides what to give a firm (commitment, extra effort, better performance, etc.) based on what the firm gives them (e.g., trust and security). It is the relationship between an employee's organizational commitment and the responding level of trust in the organization that is examined in this paper. An experiment is described that will seek to identify this relationship. Preliminary results are expected to show a positive relationship whereby employee commitment is positively correlated with organizational trust.

  6. 3 CFR - Continuation of the National Emergency With Respect to Persons Who Commit, Threaten To Commit, or...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... to Persons Who Commit, Threaten To Commit, or Support Terrorism Presidential Documents Other... Persons Who Commit, Threaten To Commit, or Support Terrorism On September 23, 2001, by Executive Order... commit, or support terrorism, pursuant to the International Emergency Economic Powers Act (50 U.S.C....

  7. 3 CFR - Continuation of the National Emergency With Respect to Persons Who Commit, Threaten to Commit, or...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... to Persons Who Commit, Threaten to Commit, or Support Terrorism Presidential Documents Other... Persons Who Commit, Threaten to Commit, or Support Terrorism On September 23, 2001, by Executive Order... commit, or support terrorism, pursuant to the International Emergency Economic Powers Act (50 U.S.C....

  8. 3 CFR - Continuation of the National Emergency With Respect to Persons Who Commit, Threaten To Commit, or...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... to Persons Who Commit, Threaten To Commit, or Support Terrorism Presidential Documents Other... Persons Who Commit, Threaten To Commit, or Support Terrorism On September 23, 2001, by Executive Order... commit, or support terrorism, pursuant to the International Emergency Economic Powers Act (50 U.S.C....

  9. 3 CFR - Continuation of the National Emergency With Respect to Persons Who Commit, Threaten To Commit, or...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... to Persons Who Commit, Threaten To Commit, or Support Terrorism Presidential Documents Other... Persons Who Commit, Threaten To Commit, or Support Terrorism On September 23, 2001, by Executive Order... commit, or support terrorism, pursuant to the International Emergency Economic Powers Act (50 U.S.C....

  10. 75 FR 57159 - Continuation of the National Emergency With Respect to Persons Who Commit, Threaten to Commit, or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-20

    ... Emergency With Respect to Persons Who Commit, Threaten to Commit, or Support Terrorism On September 23, 2001... commit, threaten to commit, or support terrorism, pursuant to the International Emergency Economic Powers... grave acts of terrorism and threats of terrorism committed by foreign terrorists, including...

  11. Escalation of Commitment in the Surgical ICU.

    PubMed

    Braxton, Carla C; Robinson, Celia N; Awad, Samir S

    2017-04-01

    Escalation of commitment is a business term that describes the continued investment of resources into a project even after there is objective evidence of the project's impending failure. Escalation of commitment may be a contributor to high healthcare costs associated with critically ill patients as it has been shown that, despite almost certain futility, most ICU costs are incurred in the last week of life. Our objective was to determine if escalation of commitment occurs in healthcare settings, specifically in the surgical ICU. We hypothesize that factors previously identified in business and organizational psychology literature including self-justification, accountability, sunk costs, and cognitive dissonance result in escalation of commitment behavior in the surgical ICU setting resulting in increased utilization of resources and cost. A descriptive case study that illustrates common ICU narratives in which escalation of commitment can occur. In addition, we describe factors that are thought to contribute to escalation of commitment behaviors. Escalation of commitment behavior was observed with self-justification, accountability, and cognitive dissonance accounting for the majority of the behavior. Unlike in business decisions, sunk costs was not as evident. In addition, modulating factors such as personality, individual experience, culture, and gender were identified as contributors to escalation of commitment. Escalation of commitment occurs in the surgical ICU, resulting in significant expenditure of resources despite a predicted and often known poor outcome. Recognition of this phenomenon may lead to actions aimed at more rational decision making and may contribute to lowering healthcare costs. Investigation of objective measures that can help aid decision making in the surgical ICU is warranted.

  12. Education: Commodity, Come-On, or Commitment?

    NASA Astrophysics Data System (ADS)

    Moore, John W.

    2000-07-01

    July 4, and the glass art shown on pages 812-816, remind us that freedom is fragile. Through their governments, citizens of democracies have traditionally made strong commitments to education on grounds that without it individuals would not be able to act responsibly and to make wise decisions in voting booths and public meetings. All citizens have a stake in everyone's education, because a better-educated citizenry benefits all of society. In this country such a commitment has produced a system of public schools and public universities that offers opportunities to many who otherwise could not afford a level of education commensurate with their talents. But there are signs that this commitment to public education is flagging. Many students, teachers, and administrators view education as merely a way to enhance personal prosperity. How often have you heard the statistic that a college education pays for itself through increased earning power, even if it costs $20,000-30,000 per year? Investing in education pays off just as investing in the stock market does, provided you wait long enough. Attending a better school gets you a better job and a better income. In other words, a certified level of education is a commodity-something that is useful and can be turned to commercial advantage. Viewing education as a commodity has several consequences. First, if education is a means to better employment rather than better citizenship, why should anyone pay for it other than the person who benefits? Why should I pay taxes to help someone else get a better job when I could be spending the money for my own benefit? Education as a commodity makes such attitudes reasonable, though not commendable, and the result is lessened support for public education. Second, those who supply education as an economic good should be rewarded, and those who are much better at educating should be rewarded much more. Hence the fear of Arthur Levine, president of Teachers College, Columbia University

  13. A Green Tea Catechin Normalizes the Enhanced Ca2+ Sensitivity of Myofilaments Regulated by a Hypertrophic Cardiomyopathy Associated Mutation in Human Cardiac Troponin I (K206I)

    PubMed Central

    Warren, Chad M.; Karam, Chehade N.; Wolska, Beata M.; Kobayashi, Tomoyoshi; de Tombe, Pieter P.; Arteaga, Grace M.; Bos, J. Martijn; Ackerman, Michael J.; Solaro, R. John

    2015-01-01

    Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease characterized by thickening of ventricular walls and decreased left ventricular chamber volume. The majority of HCM-associated mutations are found in genes encoding sarcomere proteins. Herein, we set out to functionally characterize a novel HCM-associated mutation (K206I-TNNI3), and elucidate the mechanism of dysfunction at the level of myofilament proteins. Methods and Results The male index case was diagnosed with HCM after an out-of-hospital cardiac arrest which was followed by comprehensive clinical evaluation, transthoracic echocardiography, and clinical genetic testing. To determine molecular mechanism(s) of the mutant human cardiac troponin I (K206I), we tested the Ca2+ dependence of thin filament-activated myosin-S1-ATPase activity in a reconstituted, regulated, actomyosin system comparing wildtype human troponin complex, 50% mix of K206I/wildtype, or 100% K206I. We also exchanged native troponin detergent extracted fibers with reconstituted troponin containing either wildtype or a 65% mix of K206I/wildtype, and measured force generation. The Ca2+ sensitivity of the myofilaments containing the K206I variant was significantly increased, and when treated with 20 μM EGCG (green tea) was restored back to wildtype levels in ATPase and force measurements. The K206I mutation impairs the ability of the troponin I to inhibit ATPase activity in the absence of Ca-hcTnC (calcium-bound-human cardiac troponin C). The ability of Ca-hcTnC to neutralize the inhibition of K206I was greater than with wildtype TnI. Conclusions Compromised interactions of K206I with actin and hcTnC may lead to impaired relaxation and HCM. PMID:26553696

  14. Genetic-based unit commitment algorithm

    SciTech Connect

    Maifeld, T.T.; Sheble, G.B.

    1996-08-01

    This paper presents a new unit commitment scheduling algorithm. The proposed algorithm consist of using a genetic algorithm with domain specific mutation operators. The proposed algorithm can easily accommodate any constraint that can be true costed. Robustness of the proposed algorithm is demonstrated by comparison to a Lagrangian relaxation unit commitment algorithm on three different utilities. Results show the proposed algorithm finds good unit commitment schedules in a reasonable amount of computation time. Included in the appendix is an explanation of the true costing approach.

  15. Cardiac sarcoidosis: challenges in clinical practice.

    PubMed

    Bakker, Anne L; Grutters, Jan C; Keijsers, Ruth G; Post, Martijn C

    2017-09-01

    To address the current recommendations for screening, diagnosis, and treatment of cardiac sarcoidosis and the difficulties to put these recommendations into clinical practice. The incidence of cardiac sarcoidosis appears to be higher than earlier reported, probably because of improved imaging techniques. Late gadolinium enhancement with cardiac MRI (LGE-CMR) and fluorodeoxyglucose positron emission tomography obtained a central role in the diagnostic algorithm and monitoring of disease activity. New techniques are being investigated: T1 and T2 mapping for early detection in CMR, a sarcoid-specific tracer in PET, integrated positron emission tomography/MRI scanners, and assessment of scar with LGE in cardiac computed tomography. Isolated cardiac sarcoidosis is an increasingly recognized phenotype, but still an enormous challenge in clinical practice. The prognostic value of (and extent of) LGE-CMR should be taken into account for risk assessment and internal cardiac defbrillator therapy, even in patients with preserved left ventricular function. Unfortunately, randomized controlled trials to guide immunosuppressive therapy are still lacking. A multidisciplinary approach to diagnose and treat cardiac sarcoidosis patients in specialized centers is strongly recommendable. Cardiac sarcoidosis is increasingly recognized because of improved imaging techniques; however, treatment of cardiac sarcoidosis is still mainly based on expert opinion.

  16. Change-related expectations and commitment to change of nurses: the role of leadership and communication.

    PubMed

    Portoghese, Igor; Galletta, Maura; Battistelli, Adalgisa; Saiani, Luisa; Penna, Maria Pietronilla; Allegrini, Elisabetta

    2012-07-01

    The purpose of this study was to test a theoretical model linking the impact of expectations on commitment to change and to explore whether change-related communication is a mediating variable between leader-member exchange and expectations. Expectations for change outcomes are an important condition to increase nurses' commitment to change. To understand the role of leadership and communication in expectations development is crucial to promote commitment to change. A predictive, non-experimental design was used in a random sample of 395 nurses. Structural equation modelling was used to analyse the hypothesized model. Positive expectations had a direct effect on affective commitment to change, whereas negative expectation had a direct effect on continuance commitment to change. Leader-member exchange and communication influenced nurse's expectations about change. Communication partially mediated the relationship between Leade